Unitized Experiments in Organic Chemistry

Unitized Experiments in Organic Chemistry
UNITIZED EXPERIMENTS
IN ORGANIC CHEMISTRY
by
RAY Q. BREWSTER
CALVIN A. VANDERWERF
AND
WILLIAM E. McEWEN
Professors of Chemistry
University of Kansas
D. VAN NOSTRAND COMPANY, INC.
PRINCETON, NEW JERSEY
TORONTO
LONDON
NEW YORK
Preface
teacher to keep the laboratory work completely synchronized with the lectures, provides a high degree of
flexibility. Once the student has completed these early
experiments, he should be prepared to perform the
remaining experiment, both those on aliphatic and those
on aromatic compounds, in any order the teacher may
wish to follow.
Further flexibility is made possible by the inclusion
of more units than can be performed normally in a
two-semester course so that the instructor may exercise considerable selection. For a one-semester course,
we have found highly successful the plan of assigning
different experiments to different groups, with an opportunity provided for comparison of results. In this
way, each student is given an insight into the experimental aspects of many more experiments than he can
perform personally.
Every experiment has been carefully tested with hundreds of students under close supervision by the authors
and we believe that all are eminently workable. Special
emphasis has been placed on clear, accurate, and reliable experimental directions, given in sufficient detail
to lead to successful and satisfying results in the hands
of even the most inexperienced beginner; at the same
time special skill and technique will be rewarded with
sufficiently superior results to stimulate and challenge
the best of students. Hazards and pitfalls have been
either eliminated or properly recognized and pointed
out. Often alternative procedures are described to allow
for differences in equipment available to students at different institutions.
Students in the beginning courses in organic chemistry lack the experience to organize their work efficiently on their own. The present manual is based on
the philosophy that at this stage the very best training
for the future is that which shows the student how his
work can be organized for maximum productivity.
Over the years, the authors have been led to the
conviction that by far the most successful experiments
in organic chemistry are those whose results the student
can submit as an actual preparation or report as a numerical answer or an unknown. The interest and enthusiasm with which our own students have received
the present manual have confirmed that conviction.
Unitized Experiments in Organic Chemistry represents an embodiment of the conviction that a tremendous amount of organic chemistry can be taught—and
learned—in the laboratory. Not only the techniques,
skills, and philosophy involved in organic synthesis, but,
if the experiments are well designed, much of the fundamental theory and factual material of organic chemistry,
as well, can be mastered by the student during the several hours a week which he spends in the laboratory.
This can be achieved for an entire class only if every
student, the best as well as the poorest, works to capacity, thoughtfully and productively, and only if the
lectures and laboratory work are coordinated into a
single integrated unit. These are the goals which we
hope the present manual will aid the teacher in achieving.
Carefully tested time schedules, along with thoughtprovoking questions, are provided with each experiment
to challenge the student to maximum efficiency. Optional experiments are provided for superior students
who are able to complete the regular work in less than
the allotted time.
Every experiment has been designed, not only to
teach the basic skills and techniques of organic laboratory work, but also to clothe in flesh and blood the
skeleton of words to which lectures and textbooks are
necessarily restricted. Each day's experiment is preceded by an introduction which places the work of the
day in proper context in the scheme of organic chemistry and encourages the student to think about the
important principles that are being illustrated. Together, the discussion and experimental work constitute a complete, finished unit which affords the student
2 real sense of accomplishment and leaves him with a
sharply defined picture of what the day's assignment
s designed to teach.
The first eight units cover the theory and practice
of the most important fundamental techniques employed in the organic chemistry laboratory. Each discussion is followed immediately by an experimental
section designed to drive home the underlying principles involved. The discussions are, however, sharply
divided from the experimental sections so that the student may refer to them continuously without being
forced to re-read detailed instructions for a specific
experiment. The early introduction of these units on
techniques, which may be performed in regular order
or assigned individually at such times as will enable the
RAY Q. BREWSTER
CALVIN A. VANDERWERF
WILLIAM E. MCEWEN
lii
Contents
Preface
Foreword to the Student
Safe Working Procedures and Avoidance of Accidents
iii
ix
xi
EXPERIMENT
1 Calibration of a Thermometer
2 I. Melting Points
II. Sublimation
3 Boiling Points—Distillation—Fractional Distillation
4 Crystallization
5 I. Extraction
II. Drying Agents
6 Steam Distillation
7 Adsorption Chromatography
8 Qualitative Tests for the Elements
9 Preparation and Properties of Methane
10 Preparation of Ethane by Means of the Grignard Reaction
11 Properties of Kerosene
12 Ethylene and Ethylene Bromide
13 The Amylenes: 2-Methyl-2-Butene and 2-Pentene
14 Preparation and Properties of Acetylene
15 Chemistry of the Alcohols
16 I. Ethyl Iodide
II. Tertiary Butyl Chloride
17 I. Ethyl Bromide
II. Properties of Alkyl Halides .
18 Ethyl Ether
. . .
19 Preparation of Cyclopentanone
20 I. Preparation of n-Butyraldehyde (Butanal)
II. Some Reactions of Aldehydes and Ketones
21 I. Derivatives of Aldehydes and Ketones
.
.
II. Identification of an Unknown Carbonyl Compound
22 Dimethylglyoxime
23 I. Preparation of Chloroform
II. Properties of Chloroform
III. The Iodoform Test
24 Preparation of a Carboxylic Acid (Benzoic Acid) by the Grignard
Method
25 Formic Acid
26 I. Ethyl Acetate
.
.
.
II. Preparation of Soap and Glycerol
27 Preparation and Properties of Acetyl Chloride
28 I. Preparation of Acetic Anhydride
II. Preparation of Acetamide
29 Preparation and Properties of Methylamine
30 Preparation and Properties of Acetonitrile . . .
31 Some Chemical Properties of Ethylene Glycol and Glycerol
32 Oxalic Acid
33 I. Preparation of Ethyl Acetoacetate (Part A)
II. Alkylation of Ethyl Malonate (Part A)
34 I. Preparation of Ethyl Acetoacetate (Part B)
II. Alkylation of Ethyl Malonate (Part B)
1
4
7
11
18
25
29
32
35
41
44
46
48
49
52
54
56
59
60
62
62
64
67
69
70
73
74
75
77
78
78
80
83
86
87
88
90
91
93
95
96
98
100
101
102
103
CONTENTS
EXPERIMENT
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
I. w-Caproic Acid (Part A)
104
II. Reactions of Ethyl Acetoacetate
104
I. n-Caproic Acid (Part B)
106
II. Preparation of Adipic Acid
.
106
I. Diethyl Adipate (Azeotropic Esterification) .
108
II. Properties of Lactic, Tartaric, and Citric Acids
109
Proteins
111
Amino Acids
.
113
Preparation and Properties of Urea
115
I. Preparation and Resolution of D,L-s-Octyl Hydrogen Phthalate
118
II. Optical Properties of Some Common Carbohydrates
119
I. Preparation of /?-D( + )-Glucose Pentaacetate
120
II. Preparation of Dextrorotatory 2-Octanol
120
Chemical Properties of Some Common Carbohydrates
122
Polysaccharides . . .
124
Properties of Aromatic Hydrocarbons
127
Bromobenzene
129
Iodobenzene
131
Aromatic Nitro Compounds
. . .
132
Preparation of Aniline by Reduction of Nitrobenzene
134
Aniline and Some of Its Derivatives .
136
Identification of an Unknown Amino Compound
138
I. Preparation of Sulfanilic Acid
140
II. Preparation of Acetanilide
140
I. p-Bromoacetanilide and Its Hydrolysis to p-Bromoaniline .
141
II. Separation of a Mixture of Benzene, Nitrobenzene, and Aniline 141
p-Nitroacetanilide and p-Nitroaniline
142
I. m-Nitroaniline
143
II. p-Nitrosodimethylaniline
143
I. Thiocarbanilides
145
II. Phenyl Isothiocyanate
.
.
145
Azobenzene, Hydrazobenzene, and Benzidine
147
Sulfanilamide
149
I. Chlorobenzene by the Sandmeyer Reaction
151
II. Toluene by Deamination of p-Toluidine
152
I. Preparation of Diazoaminobenzene
153
II. Rearrangement of Diazoaminobenzene to Aminoazobenzene
153
Preparation and Properties of Phenol
155
I. Preparation of Phenetole
157
II. Solid Derivatives of Phenol
157
Preparation of o- and p-Nitrophenol .
.
159
Identification of an Unknown Phenolic Compound
161
Properties of Benzaldehyde
162
Preparation of Acetophenone by a Friedel and Crafts Reaction
163
Preparation of Benzophenone by a Friedel and Crafts Reaction.
165
Benzophenone Oxime and Its Rearrangement to Benzanilide
167
Preparation of Triphenylcarbinol by a Grignard Reaction
168
Benzoin, Benzil, and Benzilic Acid
169
Preparation of Cinnamic Acid—the Perkin Reaction
171
Quinones
172
Benzoic Acid
174
Oxidation of /?-Nitrotoluene to p-Nitrobenzoic Acid .
.176
Aromatic Hydroxy Acids (Salicylic Acid, Aspirin, and Tannic Acid) 178
Qualitative Organic Analysis
179
Dyes and Dyeing
182
Malachite Green, Phenolphthalein, and Fluorescein
184
CONTENTS
vii
EXPERIMENT
79
80
81
I. 3-Aminophthalhydrazide ("Luminol")
II. Chemiluminescence
. . .
Heterocyclic Compounds—Phenylmethylpyrazolone, Furfural, and
Pyridine
.
.
.
Preparation of Quinoline by the Skraup Synthesis
Special Reagents
Index
187
188
189
191
192
193
Foreword to the Student
The practice of organic chemistry is both an art and
a science. Complete elucidation of the structures of such
complex compounds as, for example, the anti-anemia
factor folic acid* and the steroidal hormone aldosterone,2 on total samples of 500 and 57 mg., respectively, is sheer artistry. But underlying such brilliant
work, and indispensable to it, is a thorough mastery of
the fundamental scientific principles upon which the
separation, purification, identification, and reactions of
organic compounds are based.
r*r"Y
COOH
CH 2 CH 2 CHNHC^f V - N H C H 2
I
|| \=/
COOH
0
Folic acid
,NH 2
T
OH
OH CH2OH
Aldosterone
It is the purpose of your laboratory work in organic
chemistry both to train you in the art and to school you
in the scientific principles upon which the art is founded.
It may perhaps be possible for you to muddle through
the laboratory phase of your course in organic chemistry and achieve results of a sort without a clear understanding of what you are doing and why you are doing
it. But truly distinguished achievement, characterized
by rapid, efficient performance of each experiment with
isolation of a high purity product in maximum yield,
will require on your part a real understanding of the
principles which underlie all laboratory techniques and
Above all, it is important that you study the experiment of the day carefully before coming to the laboratory. In advance (1) master the theoretical principles
involved, (2) in your notebook list in condensed form
the equipment and chemicals (with amounts) required,
so that a single trip to the stockroom or balance will
suffice, and (3) write your own outline of the procedure
in a form you can follow rapidly and write the balanced
equations for the reactions involved.
In the laboratory, work with an open, inquiring mind,
recording at once, not what you think is supposed to
happen, but what you actually observe. A good scientist is, first of all, a careful observer. As you work, ask
yourself questions; if, after a determined effort you cannot answer them, do not hesitate to ask your instructor.
Many of the most provocative and interesting questions
in organic chemistry are raised by beginning students.
Your experiments will be graded on the quality and
quantity of your product, your technique, your notebook report, and your understanding of the practice
and principles involved in the experiment as revealed
by oral or written quizzes which your instructor will
give from time to time. The quality of your product is
judged from physical appearance and from such physical constants as melting point, boiling point, density,
and refractive index. The quantity is expressed as the
"percentage yield."
The percentage yield for any reaction represents the
extent, expressed in per cent, to which the reactants
were converted into the isolated product. It is calculated
as follows:
where the actual yield = the weight or volume (for a
gas) of product actually isolated
and the theoretical yield = the weight or volume (for
a gas) of product that would be formed from the
starting materials used if the reaction proceeded 100
per cent as indicated by the balanced equation.
For example, let us calculate the percentage yield of
the
ester, ethyl acetate, if 33.6 g. were isolated from the
E. L. R. Stokstad, B. L. Hutchings, S. H. Mowat,
J. H. Boothe, C. W. Waller, R. B. Angier, J. Semb and reaction of 35.0 g. of acetic acid with 75.0 g. of ethyl
Y. SubbaRow, J. Am. Chem. Soc, 70, 5 and 10 (1948). alcohol. According to the balanced equation (see Ex2
S. A. Simpson, J. F. Tait, A. Wettstein, R. Neher, periment 26),
1
J. von Euw, O. Schindler and T. Reichstein, Experientia, 10, 132 (1954); Helv. Chim. Acta, 37, 1163,
1200 (1954); Ann. Reports, 1954, 223.
procedures. Such achievement does not just happen. It
will be possible only if you plan your work carefully in
advance and work purposefully during each laboratory
period.
O
O
CH3—C—OH + C2H6OH ^± CH3—C—OC2H6 + HOH
60.1 g.
(1 mole)
46.1 g.
(1 mole)
88.1 g.
(1 mole)
FOREWORD TO THE STUDENT
theoretically 60.1 g. (1 mole) of acetic acid reacts with
46.1 g. (1 mole) of ethyl alcohol to yield 88.1 g. (1
mole) of ethyl acetate.
Hence the theoretical yield of ethyl acetate from 35.0
g. of acetic acid is
that the iodine, by far the most expensive of the reagents, is the limiting reagent. From 25.0 g. of iodine,
the theoretical yield of ethyl iodide is
O o f : )( 935 - 9 «•) = 30 - 7 *
If the actual yield of ethyl iodide is 21.0 g., then the
and from 75.0 g. of ethyl alcohol,
/ 7 6 £ g A (88.1 g.) = 143.3 g.
\46-l g j
In other words, the ethyl alcohol is present in theoretical excess, and the acetic acid is the limiting reagent
in determining the theoretical yield. No matter how
great an excess of ethyl alcohol is added, the maximum
yield of ethyl acetate that can be obtained from 35.0 g.
of acetic acid is 51.3 g. This, then, is the theoretical
yield of ethyl acetate. The percentage yield is equal to
(if|:) (100%) -655%
Esterification is an equilibrium reaction and addition
of an excess of the cheaper reagent, ethyl alcohol,
through the mass action effect, increases the weight of
ethyl acetate produced per unit weight of the more
costly reactant, acetic acid.
You may prefer to solve problems of this type by
calculating the number of moles of the limiting reactant
used and of the product isolated. Thus, in the synthesis
of ethyl acetate, we see from the equation that, for
every 1 mole of acetic acid which reacts, 1 mole of
ethyl acetate is formed. But 35.0 g. of acetic acid is
only
35.0 g.
= 0.582 mole of acetic acid
60.1 g./mole
and the theoretical yield of ethyl acetate is therefore
0.582 mole of ethyl acetate.
The actual yield of ethyl acetate, 33.6 g., is
33.6 g.
= 0.381 mole of ethyl acetate
88.1 g./mole
The percentage yield is therefore
© = H - «**
If, in the synthesis of ethyl iodide (Experiment 16),
3.5 g. of phosphorus, 25.0 g. of iodine, and 19.7 g.
of ethyl alcohol are used, it can be calculated from the
balanced equation for the over-all reaction
2P
61.96 g.
(2 moles)
+
3I2
+
761.5 g.
(3 moles)
6CH3—CH2OH->
276.4 g.
(6 moles)
6C2H6I + 2H3PO3
935.9 g.
(6 moles)
percentage yield = (|Jy| 1 )(100%) = 68.4%
Working the same problem on a mole basis, we can
see from the equation that 3 moles of iodine yield theoretically 6 moles of ethyl iodide, or 1 mole of iodine
yields 2 moles of ethyl iodide. But 25.0 g. of iodine
is only
25.0 g.
= 0.0985 mole of iodine
253.84 g./mole
and yields theoretically (2) (0.0985) = 0.197 mole of
ethyl iodide.
The actual yield of ethyl iodide, 21.0 g., is
.,PP '—j—r- = 0.135 mole of ethyl
J iodide
155.98 g./mole
The percentage yield is then
The percentage yield obtained in a given reaction is
an indication both of the suitability of the reaction for
synthetic purposes and of the skill and technique of the
investigator. Many organic reactions are reversible,
most are accompanied by competing side reactions
which lead to the formation of by-products, and
almost all are relatively slow as compared, for example, to the familiar reaction of sodium hydroxide
solution with hydrochloric acid or of silver nitrate with
sodium chloride in solution. For these reasons, careful
control of such factors as time of reaction, temperature,
solvent, concentration, pH, product removal, and judicious use of catalysts are of the utmost importance in
organic reactions. But even under optimum experimental conditions, very few organic reactions afford the
desired product in 100 per cent yield.
For every reaction there is an inherent limitation on
possible yield imposed by the nature of the reaction
itself and competition from side reactions. Other factors being equal, a reaction in which a maximum yield
of 95 per cent may be achieved is certainly to be preferred above one in which the maximum attainable
yield is 25 per cent. But the percentage of this limiting yield that is actually realized in a given case depends
upon the personal factor; it is at this point that the skill,
technique, and ingenuity of the experimenter come into
play. Nothing will be more personally rewarding or
gratifying to you in the organic laboratory than the
type of intelligent and skilled workmanship which exploits each reaction to its fullest extent.
Safe Working Procedures ;
All too often chemical laboratories are the scene of
accidents—mostly minor ones but some of serious nature. These so-called accidents do not merely happen;
they are caused by improper or careless procedures.
Close observance of the precautions, given in the following list, will prevent directly most such mishaps and
indirectiy will aid the student in acquiring those habits
of safety which will be of inestimable value to him not
only in the laboratory but elsewhere as well.
1. Avoid cuts and lacerations
Cuts from broken pieces of glass tubing are among
the most frequent accidents in the laboratory. These
may be avoided by observing the following rules when
inserting a glass tube or thermometer into the hole in
a stopper:
a) Bore the hole in the stopper to a suitable size.
b) Lubricate the tube with water, soap solution, or
glycerol.
c) Protect your hands with a towel.
d) Rotate the tube slowly and apply pressure gently.
e) Do not use one arm of a bent tube as a lever for
application of excessive pressure, but grip the sidearm close to the cork or stopper.
f) Soften a cork stopper in the cork roller before boring a hole in it. The rolling aids in boring a smooth
hole which fits the tube securely. The same rules
apply to the removal of a tube from a stopper.
2. Guard against fire
Remember that many solvents used in the organic
chemistry laboratory are flammable. Observe the following precautions:
a) Flammable solvents of boiling point less than 100°
should be distilled, heated, or evaporated on the
steam bath, not over a Bunsen burner. This includes
methanol, ethanol, acetone, benzene, petroleum
ether, ligroin, etc.
b) Flammable solvents should be contained in flasks
rather than in open beakers.
c) Keep flasks containing flammable solvents away
from your own and also from your neighbor's Bunsen burner.
d) Bottles of flammable solvents should not be on your
work bench near a lighted burner. Keep them on the
side shelf.
e) Do not pour flammable liquids into the waste crocks.
Avoidance of Accidents
3. Extinguishing fires
The laboratory is provided with fire extinguishers, a
fire blanket, an emergency shower, a bucket of sand,
and perhaps other items.
a) Know the location and use of these pieces of equipment.
b) Remember that burning sodium reacts with carbon
tetrachloride with explosive vigor. Smother sodium
fires with dry sand or sodium carbonate, scrape the
material into a pan and carry it out of doors.
4. Protect your eyes
a) Wear goggles whenever you are performing an experiment in which there is danger of spattering.
b) Wearing protective spectacles in the laboratory at
all times is an excellent safety measure.
c) Avoid looking into the open mouth of a test tube
or flask in which a reaction is being conducted.
5. Shun explosive mixtures
Strong oxidizing agents and easily oxidized material
(reducing agents) must be mixed with extreme caution and in small amounts. Never add nitric acid to a
flask containing alcohol. The reaction is so violent that
a bad explosion may result.
6. General Procedures
a) Absorb escaping obnoxious gases in water or other
suitable medium or conduct the experiment in a
fume hood.
b) Keep the gas and water valves closed except when
these utilities are needed.
c) Insoluble waste such as filter papers, match stems,
and kindred items must be thrown into the waste
jars—not into the sinks.
d) Ordinary rubber stoppers are never used on apparatus where they can be subjected to the action of
organic solvents. Most such solvents attack the rubber and cause contamination of the product.
e) Never work in the laboratory alone. A minor mishap that may be of little consequence if some one
is at hand to help you, may be serious if you are
alone.
f) Do not swing a graduated cylinder or similar piece
of glassware in a circular arc to dry it by centrifugal
force. Such spattering of your neighbors is inexcusable.
xii
SAFE WORKING PROCEDURES
g) Do not put scraps of metallic sodium into the sinks
or waste jars. Cover them with kerosene and ask
the instructor for the local arrangements for disposing of them.
h) Be neat in your work. If you spill something, clean
it up.
i) Never heat an enclosed system and never completely
close an assembly of apparatus in which a gas is
being evolved; always provide a vent of suitable
size.
j) Work with bromine, phosphorous trichloride, acetyl
chloride, benzoyl chloride, and other obnoxious materials in the hood. Each laboratory has its own provisions for handling such substances. Ask the instructor for directions.
k) Much of the sloppiness of laboratory tables is
caused by a too rapid stream of water flowing
through the condenser; a gentle stream is usually
sufficient.
Writing Your Laboratory Notebook
We have stated in the Foreword and repeat here for emphasis that before
coming to the laboratory you should:
(a) Read carefully the discussion and directions for the experiment in this
manual.
(b) In your textbook, turn to the subject of the experiment and study the
presentation given there.
(c) Write up the experiment in your notebook using the following outline
and omitting only the observations and answers to questions that inherently cannot be supplied until the work has been done.
Careful observance of this plan for your laboratory work is the very essence
of meaningful experimentation. By following such a prearranged plan you will
have no trouble in completing the laboratory work according to the time schedule
given with the experiment. On the contrary, you will wonder why the schedule
is so slow.
Outline Reporting a Laboratory Preparation
EXPERIMENT NO.
Title
Materials
Theoretical Yield
Actual Yield
Percentage Yield
Boiling Range (or M.P.)
B.P. or M.P. (from Handbook)
Density (from Handbook)
Equations
Procedure. State or outline, briefly but clearly, the working methods so that the
experiment may be repeated from your notebook without reference to the Manual. All statements should be impersonal. In many instances one page of your
notebook will suffice for the report of the preparation of an organic compound.
The description of the chemical properties of a compound, or a series of related
compounds can usually be given best by short statements accompanied by chemical equations.
Answers to questions
Temperatures are in degrees centigrade.
A time schedule, in minutes, is given for completing each
assignment within the three-hour laboratory period. This
schedule is given in bold-face numbers in the margins.
EXPERIMENT 1
Calibration of a Thermometer
Introduction. Throughout your laboratory course in
organic chemistry, you will be measuring temperatures
—melting points, boiling points, reaction temperatures,
Dath temperatures, etc.—by means of a thermometer.
For some purposes, you will wish to know only the
ipproximate temperature, but often you will desire an
*xact reading. An ordinary mercury thermometer can
be used for measuring temperatures from approximately
- 3 8 ° to 360° (mercury boils at 356.6° at 760 mm.
pressure). This range will be adequate for your needs.
Laboratory thermometers, however, differ widely in
accuracy. The very best are calibrated according to the
ipecifications of the U. S. Bureau of Standards. For
such precision thermometers, the maximum tolerance is
[).5~ for temperatures up to 100° and 1.0° up to 250°.
Ordinary laboratory thermometers are less reliable; a
riven thermometer may be quite accurate or may, especially at higher temperatures, be in error by as much
as V or 4°.
For this reason, you will find it worthwhile to calibrate your own thermometer. For practical purposes,
it is best to do so under conditions as nearly identical
as possible to those under which the thermometer will
be used. Any required corrections can then be applied
to all of your precise readings throughout the course.
In the calibration of a thermometer its readings at a
series of known temperatures are determined. The
known temperatures are either (1) read from a standard comparison thermometer immersed in a bath along
with the thermometer being calibrated or (2) provided
by pure substances at some transition point, such as
the melting point (solid-liquid transition point) or
boiling point (liquid-vapor transition point).
The most convenient solid-liquid system is ice-water
at 0°. Others are listed in Table 1. Pressure effects are
negligible and can be disregarded.
A few of the many substances whose boiling points
at 760 mm. pressure may be used as reference temperatures are listed in Table 1. For other pressures, a
correction must be applied. When the pressure is not
too far from 760 mm., the approximate correction for
every 10 mm. of difference in pressure may be calculated by dividing the boiling point on the absolute scale
by a factor of 1020 for associated liquids and 850 for
nonassociated liquids. For example, at 740 mm. the
boiling point of water, which is highly associated, is
approximately (373°/1020)(2) = 0 . 7 ° lower than at
760 mm. Nitrobenzene, which is nonassociated, boils
approximately 483°/850 = 0.6° higher at 770 than at
760 mm.
Whenever a transition temperature is used as a reference standard, it is extremely important that equilibrium conditions are realized at the bulb of the thermometer. For solid-liquid systems (melting points) this
sometimes requires vigorous stirring. For liquid-vapor
systems (boiling points) the bulb of the thermometer
should be above the surface of the boiling liquid (which
is likely to be superheated) and wet with condensed
liquid in equilibrium with vapor.
Experimental
1. Ice-Water at 0°. Fill a 600-ml. beaker with finely
chopped ice and add distilled water to within 6 cm. of
the top of the beaker. Stir the mixture vigorously with
a stirring rod for a few moments. Then insert your
thermometer into the mixture so that the zero point is
just above the surface and note and record the minimum reading obtainable.
2. Melting Point of Benzoic Acid at 122.5°. Add
about 10 g. of C.p. benzoic acid to a 6-inch test tube.
Mount the test tube on a ring stand above a wire gauze
on a ring and heat gently until all of the benzoic acid
has melted. In a cork of proper size to fit a 6-inch test
tube, bore a hole to accommodate your thermometer.
Then suspend the thermometer (by means of a clamp
attached to the cork) into the liquid so *hat the top
of the bulb extends a centimeter or two below the surface of the liquid (Figure l a ) . Allow the liquid to cool,
TABLE 1. REFERENCE TEMPERATURES FOR CALIBRATION OF THERMOMETERS
Compound
Water-ice
Diphenylamine
fonzoic acid
^aliovlic acid
Succinic acid
J.5-Dinitrobenzoic acid
>-N itrobenzoic acid
f-p-Tolyurea
V,Ar-Diacetylbenzidine
M.P., °C,
at 760 mm.
Compound
Acetone
Benzene
Water
Chlorobenzene
Bromobenzene
Aniline
Nitrobenzene
Biphenyl
Acetanilide
0.0
53.5
122.5
158.3
189.0
205.0
239.0
268.0
317.0
1
B.P., °C,
at 760 mm.
56.1
80.2
100.0
132.0
156.2
184.5
210.9
254.9
305.0
0-20
20-90
2
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
(o)
ft)
stirring vigorously about the bulb by raising and lowering an aluminum or nichrome wire (Note l ) 1 looped
so as to fit loosely around the thermometer bulb.
When about one half of the benzoic acid has solidified, observe the thermometer reading, still stirring vigorously. Record the temperature and calculate the thermometer correction from the known m.p. (122.5°) of
benzoic acid (Note 2). Clean and dry the test tube
thoroughly before it is used in another determination.
Repeat with two or three other solids whose melting
points are listed in Table 1 and are distributed somewhat uniformly over the entire temperature range (Note
3). Calculate the required thermometer correction at
each melting point temperature.
3. Water-Water Vapor at 100°. Place about 6 ml.
of distilled water and a boiling chip (see p. 11) in a
clean, dry 6-inch Pyrex test tube. Mount the test tube
on a ring stand above a wire gauze on a ring and by
means of a vented one-holed cork suspend a thermometer in the tube so that the bulb is about 3 cm.
above the surface of the water (Figure l b ) .
Heat the tube until the water boils gently. You will
then observe a sharply defined ring of condensate around
the wall of the test tube indicating where condensation
of the ascending vapor begins. This ring rises as heating is increased. Apply heat until the condensation ring
is about 2 cm. above the bulb of the thermometer, and
the bulb is wet with condensed vapor. Continue gentle
boiling until the thermometer reading is constant; then
observe and record the temperature (Note 2) and the
atmospheric pressure.
ff9
Pit
W
w
(a)
(b).
FIG. 1. Apparatus for the calibration of a thermometer.
x
Notes are listed at end of the experiment.
+4
q
O
o
1
n
U
1
9
9
-4
50°
75°
100°
125°
150°
175°
200°
225°
250°
275°
300°
325°
90-110
CALIBRATION O F A T H E R M O M E T E R
110-160
Repeat this process for three additional pure compounds listed in Table 1 (Note 3 ) . Select these compounds so that they supplement the reference temperatures provided by your melting-point calibrations. Calculate the corrections which must be applied to the
readings at different temperatures. Then plot in the
figure provided on page 2 a correction curve for your
thermometer for use throughout this course.
NOTES
1. Copper and iron wire corrodes somewhat in the
molten acid. You may prefer to make a glass stirrer by
bending a circular or triangular loop at the end of a length
of 5- or 6-mm. glass rodding or sealed glass tubing. If
so, be certain to use a wing-tip on your burner. Be careful not to touch the glass at the heated section and always
lay the heated glass on a wire gauze or a strip of asbestos
paper—never on the desk top.
2. The method described here simulates sufficiently
closely the conditions actually used in the determination
of boiling points and melting points so that the stem
correction (see p. 7) is automatically included in the
calibration.
3
3. Three students may wish to cooperate, each calibrating all three thermometers at one temperature.
QUESTIONS
1. What is meant by an associated liquid? What type
of bonds are ordinarily involved in the association of the
molecules of liquids?
2. What advantage would result from the calibration
of a thermometer in such a way that the boiling vapor surrounded the entire mercury column of the thermometer?
What is the practical advantage of the method you used?
3. Even if your thermometer is not accurate, it will
give the same reading at the same temperature consistently.
What, then, is the purpose in calibrating it?
4. Calculate the approximate boiling point of benzene
at 710 mm.; of acetanilide at 724 mm.; of chlorobenzene
at 775 mm. What would be the corresponding temperature
readings on your thermometer?
5. Suggest how temperatures below - 4 0 ° and above
360° may be measured.
6. Can you suggest any explanation for the fact that a
change in pressure has a greater effect on the boiling point
of a nonassociated liquid than it does on that of an associated liquid?
EXPERIMENT 2
I. Melting Points
II. Sublimation
I. MELTING POINTS
A. Theory
a. Definition of Melting Point. No physical constant
of solids is more widely used by organic chemists than
the melting point. In a practical sense, the melting point
of a crystalline solid is simply the temperature at which
the solid changes to a liquid under a pressure of one
atmosphere. For a pure substance, the change is usually
quite sharp and the temperature is characteristic and
not significantly affected by moderate changes in pressure. Hence, the melting point is a convenient constant
commonly used in the identification of solids. In addition, because the melting point is almost always markedly altered by the presence of impurities,1 it is a valuable criterion of purity.
The liquid form of a pure substance, when cooled in
such a way that supercooling is prevented, solidifies at
the same temperature at which the pure solid phase
melts. For a pure substance, then, the melting and
freezing points are identical. The melting (and freezing)
point of a substance is best defined as the temperature
at which the liquid and solid phases can exist in equilibrium with each other under a total pressure of one
atmosphere.
b. Vapor Pressure-Temperature Diagram. The reason for the constancy and sharpness of the melting point
of a pure crystalline substance can be shown by means
of a generalized vapor pressure-temperature diagram
which is developed in Figure 2. AB (Figure 2a) gives
the experimentally determined vapor pressure of a pure
solid, x, at temperatures from TA to TB. BC (Figure
2a) shows the vapor pressures for pure liquid x at
temperatures from TB to r c . 2 At TB, the vapor pressures of both solid and liquid phases of pure x are equal
to PB\ in other words, the vapor pressure curves for
solid and liquid intersect at B. TB is therefore the melting point of x.
Now, let us evaluate the effect of a small amount of
an impurity, y (which is soluble in liquid x), on the
melting point of x. At the precise moment when the
last minute crystal of x is melting, all of the impurity y
1
In order to affect the melting point of a solid substance,
the impurity must be at least somewhat soluble in the liquid
melt. In practice, this condition is almost always met.
2
The extension of the liquid curve, BD, shows the vapor
pressure of supercooled liquid x at temperatures from TB to
TD. The line BD is dotted because it represents a metastable
condition which can exist only in the absence of any solid
phase. If solid x is added to the supercooled liquid, immediate
crystallization of x occurs, and the heat of crystallization raises
the temperature to TB, where solid and liquid phases can exist
in equilibrium.
will be dissolved in essentially all of x. But the presence
of this dissoved impurity will lower the vapor pressure
due to liquid x throughout the whole temperature range,
as shown by curve Bxd. It is clear, then, that the vapor
Vopor Pressure
FIG. 2a. Generalized vapor pressure-temperature diagram.
pressure of solid x becomes equal to that of the liquid
at temperature TBl, which is below the melting point
(TB) of pure x.
In other words, in the presence of this amount of
impurity, y, the temperature at which the last trace of
x melts is lowered to TBl, and the effect of the impurity
y is clearly to lower the melting point of x, just as salt
or alcohol lowers the melting point of ice.
c. Eutectic Point. Continued addition of higher percentages of y progressively lowers the melting point of
JC. Finally, however, a limiting situation is reached in
which y is present in a concentration just sufficient to
saturate the solvent liquid x even as the last trace of x
melts. The temperature at which this occurs is shown
on the graph as TE. It may be thought of as the temperature at which a saturated solution of y in liquid x
(the eutectic composition) is in equilibrium with solid x.
Any additional y does not dissolve and hence cannot
depress the melting point of x below TE. This limiting
temperature is known as the eutectic temperature. The
eutectic temperature is the temperature below which a
mixture of x and y cannot exist as a liquid under one
atmosphere pressure. It follows, also, that a mixture of
x and y having the eutectic composition melts con-
MELTING POINTS
stantly at the eutectic temperature, as if it were a pure
compound.
d. Effect of an Impurity on Melting Range. In order
to evaluate the effect of an impurity on the meltingpoint range of a pure substance, let us consider the
effect of heating the mixture of x with a small amount
of impurity y in which the last trace of x melted at TBl.
To establish the range, we must know where the mixture
will begin to melt. If stirring is sufficiently thorough to
assure equilibrium conditions while the solid mixture is
heated, as soon as a minute amount of liquid x is
formed, it will become saturated with dissolved y, to
form a liquid phase of eutectic composition. But such
a saturated solution of eutectic composition is in equilibrium with solid x at the eutectic temperature, TE> and
melting would therefore actually begin at TE.
As heating is continued, more x melts and more y
dissolves at the eutectic temperature until there is
enough liquid x to dissolve all of y. Then as more x
melts, the liquid becomes less concentrated in impurity
y and the melting point rises, as shown along curve EB,
until the whole mixture is liquid at TBv Hence, if perfect equilibrium conditions are maintained, the melting
point range for such a mixture would be from TE to
TBl.
In theory, for any mixture of x with impurity y, melting will begin at TE and will be complete at some temperature below TB. Theoretically, as the concentration
of impurity y is increased progressively, the upper limit
of the melting-point range is lowered, and therefore the
range itself is decreased.
In practice, however, equilibrium conditions are almost never achieved and, in addition, the melt is not
observed until an appreciable amount has been formed.
If only a small amount of impurity is present, the
amount of liquid formed at the eutectic is very small;
in fact, liquid may not be observed until considerably
above the eutectic temperature.
Therefore, as actually observed, a nearly pure solid
shows a narrow melting range with an upper limit near
the true melting point. A rather impure solid usually
gives a broad melting range with the maximum temperature attained considerably below the true melting
point. Hence, the purification of a solid is often followed by melting point; a sharp melting point, which
remains constant from one recrystallization to another,
even when different solvents are used, is a good indication of purity.
e. Temperature-Composition Diagram. Another way
of looking at melting-point theory may be helpful, especially in expanding our definition of the eutectic point.
Figure 2b is a generalized equilibrium temperaturecomposition diagram for a typical two-component system such as we have been discussing.3 The curve BE
'The system is understood to be one in which the components are completely miscible in the liquid phase and the solid
phases consist of pure components.
5
represents the temperature at which solutions of y in
x* of different concentrations are in equilibrium with
solid x. Pure x melts and freezes at the temperature
corresponding to B. For any other mixture of composi-
Solid x + Eutectic
oP'"
|100% x
0%y
• Solid y + Eutectic
!
I
Composition CE
100%y |
0%x
FIG. 2b. Generalized temperature-composition diagram.
tion between 100 per cent x and that represented at E,
the curve indicates the temperature at which the first
trace of x will crystallize when the liquid mixture is
cooled or the last trace of x will melt when the solid
mixture is heated.
Similarly, FE represents the temperature at which
solutions of x in y of different concentrations are in
equilibrium with solid y. At the point of intersection
of the two curves, E, both solid components can exist
in equilibrium with a liquid solution of the definite
composition CE. This point is, once again, the eutectic
point, and the corresponding temperature TE is the
eutectic temperature. In a broad sense, we might think
of the liquid at the eutectic point either as a saturated
solution of solute y in solvent x or of solute x in solvent
y. Cooling of the eutectic liquid will bring about crystallization of both x and y at a constant temperature, the
eutectic temperature, and at a constant composition,
the eutectic composition.
If a liquid mixture of x and y of the composition and
at the temperature represented by P is cooled, when
the temperature represented by P' is reached, pure x
will begin to crystallize. As cooling is continued, more
x will crystallize; the solution will then become more
concentrated in y and the temperature will drop, both
as indicated by curve BE.
As soon as the eutectic temperature and composition
* The designation of one component as solvent and the other
as solute is actually arbitrary.
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
6
are reached, both x and y will crystallize at constant
(eutectic) composition and at constant (eutectic) temperature until the entire mass is solidified. The temperature and composition of the solid are then those
represented by P". Further cooling simply lowers the
temperature of the solid mass to some point P'".
Now if the solid mixture of x and y, as represented
at P'", is heated, the system will retrace the route just
oudined, provided perfect equilibrium conditions are
maintained. Melting will begin at TE and will be complete at the temperature corresponding to P'. In practice, however, unless a sample is very impure, the first
sign of melting is not observed until the temperature is
considerably above TE.
B. Experimental Determination
of Melting Points
a. Apparatus and Procedure. To determine the melting point of a solid, you will introduce a small sample
into a capillary tube, attach the capillary to the stem of
a thermometer, heat the bath slowly, and observe the
temperatures at which melting begins and is complete.
Because at least some time is required for the melting
to occur and because the heating is uniform, even a
pure substance will show a melting-point range, as
measured in this manner. As a rule, however, pure
samples will melt sharply, with an observed range of
only 0.5°-1.0°.
The sample of solid should be dry and finely divided.
If necessary, it should be ground with mortar and pestle
or powdered on a piece of filter paper with a small
spatula. For economy, and in order to ensure a reliable
melting point, only enough solid to fill the capillary to
a height corresponding to the length of the thermometer
bulb should be used. The temptation is always to use
too much.
The melting-point tubes should be thin-walled capillary tubes, 1-2 mm. in diameter, sealed at one end.
They may be made from glass tubing or test tubes 10-15
mm. in diameter. The glass must be heated until quite
soft and then drawn, slowly at first, then quite rapidly,
until it is of the desired diameter.
A good trick is to seal off (with the flame) the long
capillary at intervals so as to give individual tubes of
twice the desired length, sealed at both ends. They may
then be cut into half, just before use, by means of a
file or small piece of carborundum, to give two tubes
of desired length. This method avoids contamination
of the inside of the tubes with moisture or dust.
To fill the melting-point tube, invert it and scoop up
a small amount of the solid with the open end of the
tube. Then revert the tube and tamp the solid to the
bottom by (1) gently rubbing with a file, (2) tapping
the tube on the desk gently while holding it with your
thumb and forefinger or (3) dropping the tube through
a 2-ft. length of glass tubing onto the desk. Repeat this
entire process until the desired amount of sample has
been introduced. The melting tube can be held to the
thermometer by capillary attraction or by means of a
narrow band of rubber tubing placed above the surface
of the liquid bath.
(5)
Vent
Mo
n
Vent
Vent
Vent
1.5 X 80 m m
(d)
(a)
FIG. 3. Various types of melting point baths, (a) Simple
beaker, (b) Kjeldahl flask, (c) Double liquid bath, (d)
Thiele apparatus.
MELTING POINTS
Liquids that may be used for the bath should be high
boiling and stable; glycerol, paraffin oil, cottonseed oil,
butyl phthalate, and silicone oil are popular. Glycerol
is highly hygroscopic and should be stored in a stoppered bottle; the other liquids may be left in the apparatus.
Various baths (Figure 3) for melting-point determinations are designed for uniform heating. The simplest bath consists of a beaker (100 ml.) mounted on
a wire gauze above a small burner (Figure 3a). The
thermometer may be suspended in the liquid by means
of a clamp and a fitted one-holed cork, a small lengthwise section of which is cut away so that the thermometer scale is visible throughout. The liquid is stirred
by the up-and-down motion of a wire, looped to encircle the thermometer bulb and provided with a convenient handle.
A Kjeldahl or similar type long-necked, roundbottomed flask (Figure 3b) may be substituted for the
beaker; in this case convection currents provide uniform heating of the thermometer bulb, and the stopper
bearing the thermometer is fitted loosely into the neck
of the flask. Still other baths are the Thiele apparatus
(Figure 3d), which depends upon convection currents
for uniform heating, and the double liquid bath (Figure 3c).
To save time, it is wise to heat the bath rapidly until
the temperature is about 10° below the melting point
of the sample. Then heating should be slow so that the
bath temperature rises uniformly and not faster than
2Z per minute.
If you do not know the melting point of the solid, you
will find it time-saving to fill two capillaries and take a
rough, preliminary melting point with rapid heating on
one sample. Then allow the bath to cool to about 30°
below the melting point, insert the second capillary, and
make an accurate determination.
b. Mixed Melting Points. You should always observe
and record the melting-point range, from the temperature of first softening to the temperature of complete
liquefaction. In the identification of an unknown compound, you will find it useful to run a mixed meltingpoint determination. If a pure unknown x is suspected
of being a known compound y, a melting point is run
on a mixture of x with a small amount of y. If x and y
are identical, the mixture will melt sharply at the same
temperature as pure x. If the x and y are different, the
mixture will, as a rule, melt unsharply below the melting point of x.5 This test is based upon the principles
discussed under the Theory Section of this Experiment.
c. Stem Correction. For readings of above 100°, the
mercury in the stem of the thermometer above the bath
5
This will not necessarily be true when solid x and solid y
are soluble in each other. Fortunately for our purposes, such
cases, which are in theory more complex than the general type
we have been discussing, are not frequently encountered in
organic laboratory work.
7
is considerably cooler than that in the bulb. For this
reason, the observed temperature is slightly lower than
the actual bath temperature, and if your thermometer
has not been calibrated (see Experiment 1) a "stem
correction" should be added.
An approximate correction for stem correction can
be calculated from the formula:
Stem correction (°C.) = (0.000154) / (T0 - Tm)
in which the constant 0.000154 = the apparent coefficient of expansion of mercury in glass,
/ = the length of exposed thread in degrees,
T0 = observed temperature,
Tm = median temperature of exposed thread.
This last value, Tm, is taken as the temperature read
on a second thermometer hung along the exposed stem.
II. SUBLIMATION
Occasionally one encounters a solid, such as hexachloroethane, C13C—CC13, or solid carbon dioxide (Dry
Ice), whose vapor pressure reaches 760 mm. before the melting point is attained; i.e., below the temperature at which the vapor pressure of the solid substance becomes equal to that of its liquid modification.
For such solids, the vapor pressure-temperature curve
(AM in Figure 4a) shows a pressure of 760 mm. at a
Temperature
FIG.
4a.
Generalized vapor pressure—temperature diagram of a solid which sublimes readily.
temperature below TM, or, stated in another way, the
vapor pressure, PM, at the melting point, TM, is above
760 mm.
When such a solid is heated under one atmosphere
pressure, as soon as a vapor pressure of 760 mm. is
reached, the solid will pass directly from the solid to
the vapor phase at constant temperature. Now, if the
vapors are cooled, they will pass back directly into the
8
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
solid phase. This total process of direct conversion of
a solid to vapor and back again is called sublimation.
It is a most useful and increasingly important method
for the purification of organic compounds.
A study of Figure 4a will show that many solids
which melt at atmospheric pressure can be sublimed
successfully under vacuum. Theoretically, in order to
sublime any solid, we need only reduce the external
pressure to some value below the pressure PM, the vapor
pressure at the melting point. In fact, a wide variety
of solids which ordinarily melt when heated at atmospheric pressure may still be made to sublime under
reduced pressure.
In order to see how this is possible, let us inspect the
vapor pressure-temperature diagram for camphor (Figure 4b). AB represents the vapor pressure of solid
atmosphere pressure. Suppose that solid camphor in an
evaporating dish were maintained at 175° with a condensing surface kept at 25° just above it. At 175° the
vapor pressure of camphor is 320 mm.; at 25° it is only
0.7 mm. Then camphor would sublime from the beaker
to the condensing surface, because the vapor, leaving
the surface of the solid camphor at 175° and 320 mm.
pressure, would be cooled at the condensing surface to
25°, where its vapor pressure cannot exceed 0.7 mm.
Thus the bulk of the camphor vapor would be converted
directly into solid camphor.
Various types of apparatus, from simple to highly
elaborate, have been devised for carrying out the purification of solids by sublimation, both at atmospheric
and reduced pressure. One of the simplest consists of
an evaporating or a Petri dish covered with an icecooled watch glass. This will be used in today's experiment on the sublimation of camphor. Other organic
solids, besides camphor and hexachloroethane, which
can be sublimed fairly readily, are anthracene and various quinones.
Experimental
80
120
160
200
1208
C
Temperature, °C
FIG. 4b. Vapor pressure—temperature diagram of camphor.
camphor from 0 to 179°; BC represents the vapor pressure of liquid camphor from 179° to 208°; BD represents the melting point of camphor at various pressures. Point B (179° and a pressure of 370 mm.) represents the normal melting point of camphor.6
When heated at atmospheric pressure, camphor melts
at 179° and boils at 208°. But if the external pressure
is reduced below 370 mm. (and this can very easily
be accomplished by means of a water or mechanical
pump), solid camphor will pass directly into the vapor
phase. Hence sublimation would be carried out readily
at any pressure below 370 mm.
But the sublimation could also be carried out at one
6
Actually 179° is the melting point of camphor at 370 mm.
pressure. The melting point at 760 mm. would differ from this
value very slightly because increased pressures change the melting point to only a small extent. The behavior of camphor is
unusual in that there is no break in the vapor pressure curve
in the transition from liquid to solid camphor at the melting
point.
1. Melting Points
The purpose of this experiment is to determine the
melting points of a series of compounds and then to
carry out the partial identification of an organic compound by means of mixed melting-point tests.
Arrange a Thiele tube melting-point apparatus as
shown in Figure 3d. Make a small lengthwise slit in the
stopper used for supporting the thermometer so that
the stem is exposed throughout. Add cottonseed 7 oil to
a level just above the top of the side arm.
Obtain from the side shelf small samples of five of
the compounds whose melting points are listed in Table
2. If necessary, powder the sample by means of a mortar and pestle or by crushing on a small filter paper with
a spatula.
Introduce a small amount of the first sample into a
melting-point tube. Attach the tube to the thermometer
by means of a small rubber band cut from rubber tubing so that the filled portion of the tube is alongside
the thermometer bulb (the two should be approximately
equal in length). Be sure that the rubber band is well
above the surface of the liquid.
Heat rapidly until the temperature is within 10° of
the recorded melting point for the sample. Then heat
slowly so that the temperature of the bath rises uniformly at a rate of not more than 2° per minute. Observe and record the melting-point range, from the time
the sample first softens and pulls away from the walls
of the capillary until it becomes a clear liquid. Determine and record the melting-point ranges for the four
other samples in the same way.
7
Any of the common vegetable oils available at a grocery
store may be used.
0-20
20-45
45-90
SUBLIMATION
TABLE 2
M.P., °C.
Compound
•\cpt-ftpilifip
R^Tizoir
Phthalic anhydride
Urea
frans-Cinnamic acid
Phenacetin
...
9*-13#
fl^-id
*
115
123
128
131
132
133
135
Apply to the instructor for an unknown, which may
be one of the 14 compounds listed in Table 2, or some
other compound. Determine the melting-point range of
your unknown. Then select from the list in Table 2
each compound which may possibly be identical with
your unknown. As a general rule, all compounds whose
melting points are within 5° of that observed for an
unknown are considered as possibilities.
Now run a mixed melting point with your unknown
and each of these known compounds. To do so, make
an intimate mixture of a small quantity of your unknown with roughly one fifth as much of the known
sample, either by means of small mortar and pestle or
by crushing the material on filter paper with a small
spatula. Determine and record the melting-point range.
If the compounds are identical, the melting point of
the unknown will be unchanged. If the compounds are
different, the known sample will constitute an impurity
in the unknown and, except in unusual cases, the mixture will melt lower and over a broader range. Sometimes it is helpful to run melting points on the pure and
the mixed samples simultaneously, one on either side
of the thermometer, so that their melting behavior may
be compared directly.
On the basis of the mixed melting-point determinations, decide which, if any, of the known compounds
corresponds to your unknown. Report the melting point
of your unknown, and, if possible, its identity.
Since the melting-point apparatus will be used frequently in future experiments, it may be advisable, if
possible, to store it in assembled form.
IL SeMimation
Purification of Camphor by Sublimation. Take from
the side shelf or prepare a 1-g. sample of an intimate
mixture of roughly 19 parts of camphor with 1 part
of succinic acid. Determine simultaneously and compare the melting points of camphor,8 alone, and the
camphor-succinic acid mixture, kecord these values.
Fill a third melting-point tube with a sample of the
camphor-succinic acid mixture and set it aside for comparison with the sublimed material.
13*-16#
Place the remainder of the sample in a small evapo6
For solids, such as camphor, which sublime readily, the
melting point is best determined in a sealed capillary.
Compound
1
Benzoin
o-Chlorobenzoic acid
3-Nitrosalicylic acid
Anthranilic acid
Adipic acid
Salicylic acid
Benzanilide
M.P., °C.
137
140
144
146
152
158
161
rating or Petri dish supported over a wire gauze on a
ring stand. Place over the dish a watch glass containing a few pieces of crushed ice. Gently heat the bottom of the dish, keeping the temperature below the
temperature at which any liquid is formed.
After a significant amount of camphor has collected
on the bottom of the watch glass, very gently pour out
the water and ice, and scrape off the camphor with a
spatula. Wrap the sample tightly in a small piece of
filter paper and allow it to dry until the next period.
Then determine simultaneously and compare the melting points of the sublimed material and of the camphorsuccinic acid mixture. Record the values.
QUESTIONS
1. What effect would each of the following have on
the observed melting point and melting point range of a
sample:
(a) Use of a thick-walled melting point tube.
(b) Use of a 3-5 mm. capillary tube.
(c) Rapid heating.
(d) Use of so much sample that the filled portion of
the capillary tube extends considerably beyond the thermometer bulb.
(e) Presence of a pin-hole in the bottom of the capillary
tube which allows the bath liquid to enter the capillary.
(f) Poor circulation of the bath liquid.
2. Can you suggest any reason why it might be advisable to run a mixed melting point on samples of
two different compositions before concluding that the two
compounds used were identical?
3. Which gives more accurate melting points, the capillary tube method or the equilibrium method used in the
calibration of your thermometer (Experiment 1)? Explain.
4. Ordinarily you will determine melting points in glass
apparatus. This means that glass constitutes an impurity
in the system. Why does the glass have no noticeable effect
on the melting points? Does sand lower the melting point
of ice appreciably? Why or why not?
5. A student suspected that an unknown was undergoing a chemical change at its melting point. Suggest a
simple method for testing his hypothesis.
6. How do you explain that acetone and ethyl alcohol
lower the melting point of ice as well as the boiling point
of water, whereas salt and sugar raise the boiling point
and lower the melting point?
10
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
7. How can liquid carbon dioxide and liquid hexachloroethane be obtained?
8. Cite specific data to prove that camphor may be
separated from succinic acid by sublimation.
9. An organic compound has a melting point of 156°;
its vapor pressure at that temperature is 231 mm. How
can it be sublimed?
10. (For Specially Interested Students) According to
Raoult's Law, addition of one mole of any nonionizing
solute to 1000 g. of solvent lowers the melting point of
the solvent by a constant value, characteristic of that
solvent, called the freezing-point constant, Kf, for that
solvent. This constitutes the basis for a convenient method
for the determination of the molecular weights of organic
compounds in solvents such as benzene and camphor. The
molecular weight (M) of any compound, x, may be calculated from the equation
*
M = 1000 K/w
ATW
where Kf is the freezing-point constant of the solvent, and
AT is the observed freezing-point depression observed for
a solution which contains w g. of x dissolved in W g. of
solvent. Derive this equation.
EXPERIMENT 3
Boiling Points—Distillation—Fractional Distillation
Introduction
of equilibrium between liquid and vapor at the bulb.
In tne distillation of water, rubber stoppers may be
used throughout. For many organic liquids which cause
swelling of rubber, neoprene or tightly fitting cork
stoppers are usually preferred.
Almost all liquids tend to superheat (rise to a temperature somewhat above the boiling point) to some
extent.1 This is a metastable condition and is interrupted
periodically by a sudden violent surge of vapor from
the liquid called bumping. When this occurs, the vapor
is superheated, also, and the observed boiling point
may be high. All this may be largely avoided by the
addition of 2 or 3 small boiling cnips to the distilling
flask.
Various types of commercially available carborundum2 or nard, porous porcelain or tile chips are
suitable for the purpose, or the boiling stones may be
made by chipping of a porous plate with a hammer or
pair of pliers. The small pores of the boiling stones
provide a site for the formation of bubble nuclei and
tnereby induce even boiling. If the boiling liquid drops
A. Simple Distillation
Distillation is the most common and most important
method for the purification of liquids. For the separation of a liquid from nonvolatile impurities, it is the
obvious method of choice.
A simple distillation apparatus, such as that pictured
in Figure 5, is used for this purpose. The entire apparatus should be mounted securely to ring stands by
means of clamps. The latter should preferably be supplied with rubber or asbestos sleeves to reduce thermal
and mechanical shock to the glass.
The liquid is distilled from the distilling flask which
rests on a wire gauze supported by means of a ring.
A fraction of the vapor condenses on the thermometer
and on the walls of the flask, but most of the vapor
passes through the side arm of the flask into the condenser where it is condensed by means of an ascending
stream of cold water in the jacket of the condenser. The
condensate is conveniently channeled into a receiving
FIG. 5. Simple distillation apparatus.
flask by means of a curved adapter. The nonvolatile material is left as a residue in the distilling flask.
The top of the thermometer bulb should extend just
to the lower level of the side arm (see Figure 5, inset)
so that the entire bulb is definitely bathed in a flow of
vapor. Distillation should always be conducted slowly
but steadily so that the thermometer bulb at all times
bears a drop of condensate. This favors the maintenance
below its boiling point at any time, liquid fills the pores
of the boiling aid and it is no longer effective. The
liquid should definitely be cooled below its boiling point
1
Water freed from all dissolved air has been superheated to
137° at 1 atmosphere before it boileid.
2
No. 12 carborundum stones available from the Carborundum Company, Niagara Falls, N. Y., are inexpensive and effective.
11
12
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
before the addition of a fresh chip; addition of a
boiling stone to a superheated liquid initiates boiling
that may proceed with violence.
A layer of solid at the bottom of the distillation flask
may be the cause of violent bumping during a distillation, especially if intense local heating at the bottom
of the flask is used. Heating of a flask in which a solid
has deposited should always be carried out in a liquid
bath of some type.
If a liquid is contaminated with a volatile impurity,
separation of the two may usually still be effected by
distillation. In fact, theoretically any two substances
which do not have identical vapor pressures over the
entire temperature range at which they are stable are
separable by distillation. Practical achievement of the
theoretical possibility is limited only by the patience
of the investigator and his skill and ingenuity in the
design and use of the proper equipment.
As a general rule, a mixture of any two components
which boil at least 80° apart may be separated by a
single simple distillation. For materials whose boiling
points differ by 30° to 80°, separation may still be effected by repeated simple distillations.
Such mixtures are much more conveniently separated
by fractional distillation, and, in fact, efficient fractionating equipment is used continually in industrial work
and in research laboratories for the separation of liquids
which boil but a few degrees or even a fraction of a
degree apart. In order to understand the principles
underlying such separation, we should review some of
the theory of the relationship between vapor pressure
and boiling point.
B. Boiling Points of Pure Liquids
Any given liquid, when admitted into a closed evacuated space, evaporates until the vapor attains a certain
definite pressure, which depends only upon the temperature. This pressure, which is the pressure exerted
by the vapor in equilibrium with the liquid, is the vapor
pressure of the liquid at that temperature. As the temperature increases, the vapor pressure of a typical
liquid, x, increases regularly as shown by the generalized vapor pressure-temperature curve BC, in Figure 6.
At the temperature, Tp, where the vapor pressure
reaches 760 mm., x begins to boil and Tp is called the
normal boiling point of x. Every liquid which does not
decompose before its vapor pressure reaches 760 mm.
has its own characteristic boiling point. In general, the
boiling point of a substance depends upon the mass of
its molecules and the strength of the attractive forces
between them. For a given homologous series, the boiling points of the member compounds rise fairly regularly with increasing molecular weight.
Polar liquids tend to boil higher than nonpolar liquids
of the same molecular weight, and associated polar
liquids usually boil considerably higher than nonassociated polar compounds. Thus ethyl alcohol, C2H5OH,
c" c
c'
Temperature
FIG. 6. Generalized vapor pressure diagrams for a pure
liquid (BC), for a solution in which the solute is less volatile than the solvent (B'C), and for a solution in which
the solute is more volatile than the solvent (B"C).
boils considerably higher (78.8°) than methyl ether,
CH3—O—CH3 ( - 2 3 . 7 ° ) , which is somewhat polar
but nonassociated, and both boil higher3 than propane,
C3H8, (—42.1°), which is both nonpolar and nonassociated.
The boiling point is a characteristic constant that is
widely used in the identification of liquids. Because of
its marked dependence upon pressure and its rather
erratic response to impurities, however, it is generally
less reliable and useful in characterization and as a
criterion of purity than is the melting point for solids.
C. Boiling Points of Solutions
The normal boiling point of any solution is the
temperature at which the total vapor pressure of the
solution is equal to 760 mm. The effect of any solute,
v, on the boiling point of x will depend, then, upon
the nature of v. If y is less volatile than x, then the
total vapor pressure of the solution is lower, at any
given temperature, than the vapor pressure of pure x.
Such a case is represented by curve B'C, in which
the experimentally determined values for the vapor
pressures of a solution are plotted against temperature.
The vapor pressure of the solution does not reach
760 mm. until a temperature Tp> is attained. In other
words, the presence of the less volatile solute raises the
boiling point of x from Tp to Tp>. A solution of sugar
or salt in water is a familiar example of this type of
solution.
3
The comparison is being made between compounds of approximately the same molecular weight.
BOILING POINTS—DISTILLATION—FRACTIONAL DISTILLATION
On the other hand, if y is more volatile than x, then
the total vapor pressure of the solution is higher than
that of pure x, as shown by curve B"C"\ The vapor
pressure of such a solution reaches 760 mm. at temperature 7>; hence the effect of the more volatile solute
is to lower the boiling point of x from Tp to Tv». A
solution of acetone in water is an example of this type.
In any solution of two liquids x and y, the molecules
of x are diluted by molecules of y, and, conversely, the
molecules of y are diluted by molecules of x. You would
therefore expect the vapor pressure due to x to be less
than that of pure x; in fact, you might predict that the
partial pressure due to x would be proportional to the
molecular concentration of x.
Similarly, the partial pressure of y might be expected
to be proportional to the molecular concentration of y.
This is, in fact, the relationship which holds for socalled ideal solutions. It is expressed in Raoult's Law:
the partial pressure of a component in a solution at a
given temperature is equal to the vapor pressure of the
pure substance multiplied by its mole fraction in solution. In symbols, for a solution of components x and
Px = P . W ,
where Px = the partial pressure of x in solution,
Px° = the vapor pressure of pure x at that temperature,
Nx = the mole fraction of x in the solution.
Similarly,
Pu = Pv°Ny
where Pv = the partial pressure of y in the solution,
Py° = the vapor pressure of pure y at that temperature,
Nv = the mole fraction of y in solution.
The total pressure, PT, of the solution would be
the sum of the partial pressures of x and y.
13
At 87.7° the partial pressure of benzene in a 2:1
molar mixture of benzene and toluene is 637 mm.
and that of toluene is 123 mm. Therefore at 87.7°,
the total vapor pressure would be 760 mm., and the
solution would begin to boil. The vapor which is in
equilibrium with a solution containing 66§ mole per
cent benzene and 33J mole per cent toluene is
637/760 or 83.8 mole per cent benzene and 123/760
or 16.2 mole per cent toluene. In other words, the
vapor is richer than the liquid in the more volatile
component, benzene.
As applied to fractional distillation, two important
practical generalizations emerge from Raoult's Law:
(1) the boiling points of all solutions of x and y will
lie between the boiling points of x and y, and (2)
the vapor will always be richer in the lower boiling
component than the liquid with which it is in equilibrium.
D. Temperature-Composition Diagram
for Solutions which Follow Raoult's Law
These facts are represented graphically in Figure 7
which shows a typical temperature-composition diagram. This diagram is a temperature-composition plot
PT = P* + PV
For example, at 25° the vapor pressure of benzene
is 94 mm. and that of toluene is 29 mm. In a solution
containing 2 moles of benzene and 1 mole of toluene,
therefore, the partial pressure, Px, of benzene is calculated as follows:
Px = (94 mm.) (f)
Px = 63 mm.
For the partial pressure of toluene, Py:
Pv = (29 mm.) (J)
Pv = 10 mm.
and for the total pressure, PT,
Pv
= 63 mm. + 10 mm.
PT = PX +
PT
PT = 73 mm.
100% Benzene
0 % Toluene
80
60
40
-«—Mole percent benzene
Mole percent toluene
20
Benzene 0 %
Toluene 100%
*•
Composition
FIG. 7. Temperature-composition diagram of the system
benzene-toluene.
of the experimentally determined values for the system
benzene-toluene, but it is representative of the plot for
all solutions which are described by Raoult's Law.
Boiling points (ordinates) are plotted against composition expressed as mole fractions (abscissae). Pure
benzene boils at 80.1° (point A) and pure toluene
(100 per cent y) at 110.6° (point £ ) . All mixtures
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
14
of the two boil at intermediate temperatures, as shown
by the liquid (lower) curve. This curve shows the
temperature at which a mixture of benzene and toluene
of any given composition begins to boil. The vapor
(upper) curve represents the composition of the vapor
in equilibrium with the liquid at any given temperature.
For example, consider the changes which occur when
a 20 mole per cent benzene—80 mole per cent toluene
solution (represented by point P) is heated. At 101.6°,
corresponding to point Lu the liquid begins to boil. The
first trace of vapor which is formed is, of course, in
equilibrium with the liquid at 101.6°. It has the composition 38 mole ppr cent benzene—62 mole per cent
toluene, as represented by point Vi, and is therefore
considerably richer than the liquid in benzene.
As the distillation proceeds, the concentration of
toluene in the liquid phase and the boiling point increase
continuously, following the values represented by LxB.
Finally, at the end of the distillation, the liquid phase is
pure B boiling at 110.6°. Similarly, the vapor becomes
progressively richer in toluene also, following VxB.
Always, however, it is richer in benzene than is the
liquid with which it is in equilibrium, as shown by the
points of intersection of any horizontal line with the
vapor and liquid curves.
Obviously, a single simple distillation could never
separate a 20:80 molar mixture of benzene and toluene
into the pure components. But now consider what
would be accomplished if the first trace of vapor formed
by distillation of the mixture were cooled and condensed. It would, of course, form liquid corresponding
to point L 2 of composition 38 mole per cent benzene
—62 mole per cent toluene at 94.5°.
Now, if liquid L 2 were distilled, the first trace of
vapor formed would have the composition 59 mole
per cent benzene—41 mole per cent toluene (point V2)
and when cooled would condense to liquid at 88°
(point L 3 ). This, in turn, may be further enriched in
benzene as indicated on the graph.
£. Fractional Distillation
Obviously, by repeated simple distillation with combination and recombination of various distillate and
condensate fractions, one could eventually separate a
mixture of benzene and toluene into pure benzene and
pure toluene. Ultimately, the distillate would become
pure low-boiling component (benzene) and the residue
pure high-boiling component (toluene).
Fractional distillation is simply a technique for accomplishing a whole series of such miniature separations in a single, continuous operation. In principle,
a fractional distillation column provides an extensive
surface for heat interchange, at equilibrium conditions,
between ascending vapor and descending condensate.
This makes possible a whole series of partial vaporizations and partial condensations along the length of
the column.
In a simple packed4 column, such as shown in Figure
8 a, for example, there is a continuous interchange of
4
The packing may consist of any of a wide variety of inert
materials with extensive surface area—glass beads or helices,
metal helices, carborundum or porcelain stones, etc.
It
1
Wh
o
o
Wt
'1
(a)
(c)
FIG. 8. Typical distilling columns, (a) Simple packed
column, (b) Vigreux column, (c) Young tube, (d) Bubble
plate column.
(d)
BOILING POINTS—DISTILLATION—FRACTIONAL DISTILLATION
heat between the cooler descending condensate and
the warmer ascending vapor at the surface of the packing. As the condensate at any point in the column accepts heat from the vapor, part is revaporized, and the
vapor formed is richer in the more volatile component
than the condensate. At the same time, as the vapor
loses heat to the condensate, part of it condenses, the
condensate being richer than the vapor with which it is
in equilibrium in the high boiling component. Hence,
the vapor eventually appearing and being removed at
the top of the column is pure low-boiling component;
the residue in the flask is pure high-boiling material.
Throughout the entire length of the column, there is
a temperature gradient from the boiling point of y to
the boiling point of x. This gradient represents a whole
series of separate equilibria between liquid and vapor
with the concentration of x in the equilibrium mixtures
increasing progressively from bottom to top in the
column.
Other simple types of fractionating columns are
pictured in Figure 8. The Vigreux column (b) has
indentations to provide increased surface, the Young
tube (c) has a glass or metal spiral wound around a
central core, and the bubble plate column (d) has
small liquid traps spaced at regular intervals. Elaborate
vacuum jacketed and externally heated columns (to
prevent heat loss to the outside and thereby confine
heat interchange to the liquid-vapor system) are in
wide use in industry and in research laboratories.
Such columns accomplish the equivalent of several
hundred separate simple distillations and are effective
even in the separation of liquids whose boiling points
differ by only a fraction of a degree. In these columns,
most of the condensate from the condenser is allowed
to trickle back over the packing in the column, with
only a small fraction being taken off as distillate. The
ratio of condensate returned to the column to that removed is called the reflux ratio. Efficiency of fractionation increases with increase in reflux ratio.
F. Temperature-Composition Curves
for Nouideal Systems
Unfortunately, many systems are not ideal (their
vapor pressure-composition behavior is not that described by Raoult's Law). Some liquid pairs form
minimum boiling mixtures. Ethyl alcohol (b.p. 78.3°)
and water, for example, form a minimum boiling mixture (95.57 per cent by weight alcohol and 4.43 per
cent water) which boils constantly at 78.2°, a value
below the boiling point of either water or alcohol.
Water and formic acid (b.p. 100.8°), on the other
hand, form a maximum boiling mixture (22.5 per cent
by weight water and 77.5 per cent formic acid), which
distills constantly at 107.1°, a temperature above the
boiling point of either component.
Boiling point-composition curves of such systems are
interpreted simply as if they consisted of two separate
100%x V2V,
15
100% y
Composition
FIG. 9. Temperature-composition curve for a system
which forms a minimum boiling mixture.
systems. Figure 9, for example, shows a typical temperature-composition diagram for a system of two components, x and y, which form a minimum boiling mixture, represented at M, with composition CM and boiling
point, TM. The minimum boiling mixture distills completely at constant temperature since, at the boiling
point, the vapor has the same composition as the liquid.
Fractional distillation of any mixture of composition
from pure x to CM is separated eventually into distillate
of composition CM (constant boiling mixture) and residue pure x. Similarly, any mixture of composition from
CM to pure y will separate into distillate of composition
CM (constant boiling mixture) and residue pure y. In
other words, this system behaves throughout the whole
composition range as if the minimum boiling mixture
is the low-boiling component.
Conversely, a system which forms a maximum boiling mixture behaves throughout its whole composition
range as if the maximum boiling mixture is the high-boiling component. Figure 10 represents a typical system of
100% y
100% x
Composition
FIG.
10. Temperature-composition diagram for a system
which forms a maximum boiling mixture.
16
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
this type, in which x and y form a maximum boiling
mixture, with composition CM and boiling point TM.
Fractional distillation of any mixture from composition
pure x to CM separates the mixture eventually into a
distillate of pure x and residue of composition CM
(constant boiling mixture). Similarly, any mixture of
composition from CM to pure y is separated eventually
into a distillate of pure y and residue of the constant
boiling mixture,
Constant boiling mixtures are called azeotropic
(Greek: to boil unchanged) mixtures. The composition,
as well as the boiling point, of an azeotropic mixture
varies somewhat with changes in the external pressure.
Often azeotropic mixtures can be separated into their
pure components by a type of distillation in which a
third component which alters the vapor pressure ratio
in the azeotrope is added (see Experiment 37).
G. Vacuum Distillation
Many substances cannot be purified by distillation at
ordinary pressures because they decompose below their
normal boiling points. Others have boiling points that
make distillation inconvenient or even difficult. Often
such liquids (and solids, also) can still be distilled if
the distillation is conducted under reduced pressure.
A liquid begins to boil at the temperature at which
its vapor pressure becomes equal to the external pressure. A study of Figure 6 will show that the boiling
point of a liquid decreases regularly with decrease in
the external pressure. Hence, by the use of a special
apparatus for the distillation (including fractional distillation) of liquids under reduced pressure, from just
below atmospheric pressure to pressures of 10~ 8 mm.,
chemists have been able to distill most organic liquids
and many solids. Such distillation at pressures below
atmospheric pressure is called vacuum distillation. A
simple apparatus for vacuum distillation is shown in
Figure 28 (Experiment 33).
Experimental
In this experiment you will compare the efficiency
of (1) simple distillation without a column, (2) distillation through an unpacked column, and (3) distillation
through a packed column. Students will work in groups
of three. One student in each trio will conduct the distillation described below with the simple apparatus
(Figure 5), the second using an unpacked air condenser or fractionating column (Figure 8), and the
third an air condenser or fractionating column packed
with a copper sponge. In order to pack the condenser
or column, pull out an ordinary dime-store copper
sponge (such as a "Chore Girl") to a strand about 3
ft. long and work it into the column with a quarter-inch
dowel.
At the end of the experiment, compare your results
with those obtained by each of the other two students
in your trio.
Introduce into a 150-ml. distilling flask, or a 200-ml.
round-bottomed flask, 35 ml. of water and 35 ml. of
acetone and 2 or 3 small boiling chips. Clamp the
distilling flask securely to a ring stand above a wire
gauze supported on a ring. Arrange the rest of the apparatus as specified in the previous paragraph, according to your assignment in your trio. Rubber stoppers
or tightly fitting corks should be used throughout. Force
a gentle stream of water from the tap up through the
condenser by means of a rubber tube from the tap
to the water inlet. The emergent stream of water should
be conducted to the drain by a length of rubber tubing
attached to the water outlet. Number and label five
small flasks for collecting various fractions as follows:
I 56°-62°
II 62°-72°
III 72°-82°
IV 82°-95°
V Residue
Heat the flask by means of a low flame so that the
condensate collects steadily, without interruption, at
the rate of approximately 1 drop a second. Change
the receivers rapidly at the specified temperature intervals. When the temperature reaches 95°, interrupt the
distillation and cool the distillation flask, allowing any
condensate in the fractionating column to trickle back
into the flask.
Measure with the graduated cylinder the volumes of
distillate obtained in each fraction, and of the residue
in the flask. Record these volumes and draw a distillation curve by plotting the volume of distillate vs.
the temperature. The first fraction is essentially pure
acetone, the residue pure water. You may wish to test
a small sample of each fraction on a watch glass to
see if it will burn. Record the data obtained by each
of your two partners and compare the three sets of
data.
Now, if you have been assigned the simple distillation
without use of a column, introduce into the empty distilling flask the contents of receiver II and reassemble
the apparatus for distillation. Distill until the temperature reaches 72°, adding the fraction distilling from
56°-62° to receiver I, and that from 62°-72° to receiver
II.
Again interrupt the distillation, allow the distilling
flask to cool below 50°, and pour into it, by means of
a small funnel, the contents of receiver III. Resume the
distillation and add the various fractions to receivers
I, II, III, as indicated by the thermometer reading.
Stop the distillation at 82°, allow the flask to cool
somewhat, and introduce the contents of receiver IV.
Repeat the distillation, adding each fraction to the appropriate receiver. When the temperature reaches 95°,
cease the distillation and add residue in the flask to
receiver V. Again measure and record the total volume
of each fraction.
BOILING POINTS—DISTILLATION—FRACTIONAL DISTILLATION
QUESTIONS
1. Summarize the data for the distillation of the
acetone-water mixture obtained by each member of your
trio. Explain the differences in the results.
2. Why does not all of the liquid in the distilling flask
vaporize at once when the boiling point is reached?
3. Why should a distilling flask not be filled much more
than half full?
4. What is the disadvantage of using a distilling flask
whose capacity is four or five times or more the volume of
the liquid being distilled?
5. Draw a general temperature-composition diagram
similar to that of Figure 7, but with a boiling point of
56.6° for component x and of 100° for component y.
This diagram now represents, at least approximately, the
acetone-water system. At approximately what temperature
will a 1:1 molar mixture of acetone and water begin to
distill? A 3:1 molar mixture? A 1:3 molar mixture? What
is the approximate composition of an acetone-water mixture which begins to distill at 70°? At 80°?
17
6. If liquids x and y both have a boiling point of 160°
and do not form an azeotrope, what will be the boiling
point of a mixture of x and y? In a general sense, how
does this fact limit the value of boiling points as a criterion
for determining the purity of liquids?
7. An organic liquid decomposes at 80°. Its vapor pressure at that temperature is 36 mm. How would you distill
the liquid?
8. If the thermometer bulb is not kept moist with condensate during a distillation, will the boiling-point reading
tend to be high or low? Explain.
9. Why does condensate continually flow back into the
distillation flask from a fractionating column that does not
have a reflux condenser? Does this have any effect on the
distillation? Explain.
10. If the rate of distillation through a packed column
is too rapid, flooding occurs (liquid is forced up through
the column). What effect would flooding have on the
efficiency of distillation?
EXPERIMENT 4
Crystallization
Introduction
General Methods of Crystallization. Since the days
of the earliest alchemists, solids have been purified by
crystallization from suitable solvents. Today this technique still stands as the most useful method for the
purification of solid substances.
As commonly practiced, purification by crystallization depends upon the fact that most solids are
more soluble in hot than in cold solvents. The solid to
be purified is dissolved in the hot solvent at its boiling point, the hot mixture is filtered to remove all
insoluble impurities, and then crystallization is allowed
to proceed as the solution cools. In the ideal case, all
of the desired substance separates in nicely crystalline
form and all the soluble impurities remain dissolved
in the mother liquor. Finally, the crystals are collected
on a filter and dried. If a single crystallization operation
does not yield a pure substance, the process may be
repeated with the same or another solvent.
The great beauty of crystallization as a purification
technique lies in the fact that the orientation of molecules in a crystal lattice is an extremely delicate and
selective process. Only infrequently do different substances crystallize in the same lattice. At times, the
desired solid can be crystallized selectively from a solution also saturated with other solid impurities simply
by the careful introduction of a tiny seed crystal. In
such cases, the molecules of the desired compound leave
the solution to take positions in the crystal lattice, while
the mother liquor remains saturated, or even becomes
supersaturated, with respect to the foreign materials.
A solid solute may, of course, be crystallized by
spontaneous evaporation of solvent from a saturated
solution. Occasionally, this is used as a method of
purification. Evaporation should proceed very slowly
to avoid formation of a crust of impure solid at the
evaporating surface. In general, this method is less
effective than the classical crystallization technique.
Selection of Solvent. Similia similibus solvunter (like
dissolves like) was a watchword among the alchemists
and medieval iatrochemists. It is still perhaps the best
three-word summary of solvent behavior; a detailed
study of the relationship between structure and solvent
action becomes highly complex. In the final analysis,
the best way to find a suitable recrystallization solvent
for a given substance is by experimental trial (see Experimental section). A few helpful and reasonably valid
generalizations may, however, speed the process. The
most useful of the common organic crystallization solvents, together with some of their properties, are listed
in Table 3.
No nonionic compound dissolves appreciably in
water unless its molecules are ionized in water solution
or can co-associate with water molecules through hydrogen bonding.1 Thus, hydrocarbons and their halogen
derivatives are virtually insoluble in water. Compounds
1
The hydrogen bonds or hydrogen bridges with which we
are concerned in dealing with the water solubilities of organic
compounds are almost exclusively those in which hydrogen
links oxygen atoms to oxygen or nitrogen atoms.
TABLE 3. COMMON RECRYSTALLIZATION SOLVENTS
Formula
Solvent
Pfit,rn1fiiim
77.2
78.1
80.2
-84
-116
5.5
Acetic acid
CH3—C—OH
0
118.1
16.6
Dimethylformamide
Nitrobenzene
H—C—N(CH3)2
C6H6N02
153.0
210.9
-61
5.7
18
++++
++ + +
++ +
++++
0
++
++
++
++++
+
+1
\
CHCI3
CH3OH
CCI4
0
CH3—C—OC2H5
C2H6OH
CeHe
0
<0
-116
-95
<0
<0
-98
<0
Fire
Hazard
+
Ethyl acetate
95% ethyl alcohol
Benzene
(caoaco
CrJ3.2n+2
35-65
34.6
56.1
60-80
61.3
64.7
76.7
Miscibility
with Water
l+ l
(Cffi)*)
Ether
Acetone
Ligroin
Chloroform
Methyl alcohol
Carbon tetrachloride
Freezing
Point, °C.
l l+ l l+ l
Mixture of
CsHi2 and CeHu
pf,W
Boiling
Point, °C.
+
+
0
CRYSTALLIZATION
whose molecules contain functional groups [such as
H
O
I
II
alcohol (OH), aldehyde (—C=0), 2 ketone (R—C—R),
O
O
II
II
carboxylic acid (—C—OH), and amide (—C—NH2)
groups], which can form hydrogen bonds with water,
are soluble in water unless the ratio of the total number
of carbon atoms to such functional groups in the molecule exceeds 4 or 5. Then the solubility falls off
O
rapidly. Thus, acetamide (CH3—C—NH2) is soluble in
0
II
water, but caproamide (CH3—(CH2)4—C—NH2) is
not. In fact, it is a very general rule that as any homologous series is ascended, the solubilities and all other
physical properties of the members tend to approach
those of the parent hydrocarbon.
Most organic compounds which lack a hydrogenbonding hydrogen atom dissolve readily in ether,
benzene, ligroin, and other typical nonassociated solvents, simply by a process of molecular mixing. Organic
compounds, which themselves are associated in the
liquid state, are likewise reasonably soluble in such
solvents, unless (1) they have two or more hydrogenbonding functional groups per molecule, approaching a
ratio of one such group for each carbon atom, or (2)
unless they are solids with high melting points. Thus,
n-propyl alcohol (CH3CH2CH2OH) and caproic acid
(CH3—(CH2)4—COOH) are soluble in ether, but
* For the purposes of discussing solubility behavior, we may
conveniently divide solutes into three classes: (1) those that
are associated in the liquid state; (2) those that are not associated but can co-associate with water; and (3) those that are
neither associated themselves nor capable of co-associating with
water.
Aldehydes, ketones, esters, and tertiary amines (RaN), and
similar oxygen- and nitrogen-containing compounds, can coassociate with water, even though they, themselves, are nonassociated because of the lack of a hydrogen-bonding hydrogen. In the co-association of such nonassociated compounds
with water, the hydrogen-bonding hydrogen must be supplied
by the water molecules. With aldehydes, for example, the
H
O
bonding would be represented as R—C=0—H
H.
On the other hand, compounds such as alcohols, carboxylic
adds, amides, and primary and secondary amines (RNH2 and
R*NH), whose molecules possess hydrogen-bonding hydrogen
atoms, are themselves associated in the liquid state, and can
also co-associate with water. Theoretically, at least, such coassociation can proceed through the hydrogen of water or
through the hydrogen attached to oxygen or nitrogen in the
organic molecule.
Finally, hydrocarbons and their simple halogen derivatives
are neither associated nor can they co-associate with water.
19
glycerol (HOCH2—CHOH—CH2OH), with one hydroxyl group for each of the three carbon atoms,
O
O
adipic acid (HO—C— (CH2)4—C—OH), with a melting
point of 153°, and glucose (HOCH2(CHOH)4CHO),
with five hydoxyl groups per six carbon atoms, are not.
Ether and benzene are quite similar in solvent action.
Ether is, in general, a better solvent than benzene for
associated compounds, and both are better than petroleum ether and ligroin. Petroleum ether is similar to
ligroin, but has somewhat weaker solvent action.
The associated hydroxylic solvents, such as methyl
alcohol, ethyl alcohol, and acetic acid (all three of
which are completely miscible with water), are somewhat intermediate between water and ether (and
benzene) in solvent properties. They are generally
somewhat weaker solvents than ether and considerably
stronger than water toward the hydrocarbons and their
halogen derivatives. Toward organic compounds which
are capable of association or co-association, they are
powerful solvents. The solvent power of the three varies
in the same order as their boiling points: acetic acid >
ethyl alcohol > methyl alcohol. As a solvent, acetone is
similar to ethyl alcohol, but more powerful.
The chlorinated hydrocarbons chloroform and carbon
tetrachloride are excellent solvents for nonassociated
substances. Because of their high chlorine content they
are relatively expensive.
Often a substance is found to be too soluble in one
solvent and too insoluble in another for satisfactory
crystallization. Then solvent pairs, such as methyl
alcohol-water, ethyl alcohol-water, ether-acetone, and
benzene-ligroin, are frequently effective. The compound is dissolved (at or slightly below the boiling
point) in the solvent in which it is very soluble and
the hot solvent in which it is sparingly soluble is added
drop wise until a slight turbidity is produced. Then just
enough of the first solvent is added to clear the turbidity,
and the solution is allowed to cool in the usual manner.
An ideal crystallization solvent should have a high
temperature coefficient toward the substance to be
purified; i.e., it should dissolve a large amount of the
substance at its boiling point and only a small amount
at room temperature or slightly below. It should have
a low temperature coefficient toward the impurities.
Furthermore, upon cooling it should readily yield well
formed crystals of the purified compound, from which
it should be easily removable. It should not react with
the solute, and it should be perfectfy safe to use (nonflammable). Of course, it should be inexpensive. If
water meets all of the solubility and recrystallization requirements, it is usually the solvent of choice.
Preparation of the Solution. As a rule, the objective
is to dissolve the solute in a minimum amount of solvent
at the boiling point. The following procedure is recommended: place the finely divided material in an Erlen-
20
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
3
meyer flask of suitable size. Add a boiling chip and
cover the solid with what is judged to be an insufficient
volume of the selected solvent.
Warm to boiling on a steam bath (or, for high-boiling
solvents, on a hot plate, covered with a layer of asbestos paper), constantly stirring the mixture by swirling the flask. To the boiling solution, add more solvent
in small portions with stirring. Allow sufficient time
between additions to give the solute a chance to dissolve. Continue the addition of solvent, until all the
solute has dissolved4 at the boiling temperature.
Decolorizing. Frequently the solution is colored by
high-molecular weight organic impurities, which may
occur in nature along with a desired natural product
or may be formed as decomposition products or byproducts in a synthetic process. Boiling for 5 or 10
minutes with a few grams per liter of a highly adsorbent
(activated) charcoal such as Norit, Darco, or Nuchar
will usually remove the color.
The amount of charcoal should be kept to a minimum, for some of the desired product is invariably
adsorbed, also. It has frequently been observed that
charcoal is considerably more effective in solvents which
are associated (particularly water) than in nonassociated solvents. Less charcoal is required if it is added
in portions.
Filtration of the Hot Solution? The hot solution
should be filtered in such a way that none of the solute
crystallizes on the filter paper or in the funnel. This
usually requires rapid filtration with a minimum of
evaporation through a previously warmed6 short-stem
funnel fitted with a doubly folded filter paper (folded
in half, and that half again folded in half). (See Figure
11a for the complete assembly.)
Sometimes, however, special techniques are required.
A fluted filter paper (Figure l i b ) may be used to increase the rate of filtration. If slight cooling of the solution causes heavy crystallization, either a deliberate
excess of solvent or a special hot water funnel heater
(Figure l i e ) may be employed. The funnel should not,
8
An Erlenmeyer flask is much preferred over a beaker. It is
more convenient to handle, and loss of solvent by evaporation
or boiling, with its attendant fire hazard, is minimized. With a
highly volatile solvent (especially one that is flammable) it is
frequently advisable to use a reflux condenser—very difficult
with a beaker. Finally, an Erlenmeyer flask is ideally shaped
for removal, by means of a suitable spatula, of solid material
adhering to the walls.
* Occasionally a sizable amount of insoluble impurity may
accumulate. If you suspect this to be the case, decant the solution from the solid material, and test its solubility in fresh
solvent.
5
The purpose of this step is to remove insoluble impurities;
if the solution is perfectly clear, it may be omitted.
8
The funnel and filter paper may be warmed in either of two
ways: (1) a small amount of boiling solvent may be poured
through the filter paper just in advance of the filtration, or (2)
a small amount of the solvent may be boiled in the receiving
flask until the funnel and filter paper are bathed with the hot
vapor.
however, be heated above the boiling point of the solvent. If excess solvent is added, it may be removed
by concentration of the filtrate to the volume originally
required to dissolve the material.
If thefiltrationis slowed by the clogging of the pores
of the filter paper by a colloidal or gelatinous impurity,
a filter aid should be added directly to the liquid or
placed on the filter paper in a Buchner or Hirsch funnel
in the form of a 2- to 3-mm. pad. Common filter aids
such as Hyflo and Filter-eel are forms of diatomaceous
earth which adsorb the undesirable colloidal material.
They are also effective in preventing decolorizing charcoal from passing through the filter paper into the filtrate.
Cooling, The aim of the cooling process is to bring
about the crystallization of the maximum amount of
desired material with a minimum amount of impurity.
The process should be carried out in an Erlenmeyer
flask, covered with a watch glass in order to avoid
evaporation. Usually medium-sized crystals are preferred, because large crystals are likely to include considerable amounts of solvent, which carries impurities
with it and complicates the drying process; small crystals, with their large surface area, on the other hand,
often adsorb significant amounts of impurities.
The size of the crystals is controlled by the rate of
crystallization; rapid growth favors small crystals, and
slow growth gives large crystals. Since most organic
compounds do not tend to form large crystals, a slow
to moderate rate of cooling is usually best. Supersaturation of the solution causes a high initial rate of
crystallization. This may be avoided by occasional
scratching of the inner surface of the glass (in order to
provide tiny fragments of glass as nuclei for crystallization) or, better, by periodic addition of a tiny seed
crystal.
The mixture should be allowed to stand with occasional shaking until crystallization is complete. As a
precautionary measure, the filtrate obtained may be set
aside for later observation.
Collecting the Crystals. The major aim here is the
removal of a maximum amount of mother liquor from
the crystals with a minimum amount of evaporation.
This is usually accomplished with a Buchner funnel
fitted by means of a rubber stopper into a clean filter
flask connected through a safety bottle (or trap) to a
water pump (see Figure l i d for a drawing of the complete apparatus).
All connections should be made with heavy-walled
(pressure) tubing. Filter flasks of 500-ml. capacity or
less should be clamped to a ring stand for support. The
smallest funnel which will accommodate all of the crystals comfortably with no danger of overflow should be
used. For very small samples, a Hirsch funnel (Figure
l i e ) is recommended.
The safety bottle serves to trap any tap water which
may flow back into the system when there is a sudden
CRYSTALLIZATION
21
FIG. 11. (a) Assembly for filtering a hot solution, (b)
Folding aflutedfilterpaper, (c) Special hot water funnel
heater, (d) Biichner funnel assembly for filtration under
reduced pressure, (e) Hirsch funnel. For aflutedfilter
paper, first fold the paper in half (1). Next, fold in half
again. Then open out the last crease so as to have a halfcircle; then fold each edge toward the center, making two
additional creases in the same direction. This divides the
paper into 4 equal sections (2). Then divide each section
by a crease still in the same direction. This gives 8 equal
sections (3). Divide each section in two by a crease in the
opposite direction, thus making 16 sections (4), and 32
sections when thefilterpaper is opened (5).
drop in water pressure. You will notice that the trap is
fitted so that any water present will be removed when
suction is applied. The screw clamp on the safety bottle
provides a convenient means of controlling the vacuum
when low boiling solvents are filtered and of releasing
the vacuum quickly.
The filter paper should cover the entire perforated
plate but its diameter should be slightly less than that
of the plate. It should be flat so that no solid material
can pass under its edge. This is accomplished by wetting
the paper with solvent and applying suction. Then, with
no suction, or at best only slight suction, to avoid needless evaporation, the mixture (or first portion of it) is
poured into the funnel. Then the full (or maximum desired) vacuum is applied. Use of a glass rod or spatula
will make possible the rapid transfer of the bulk of the
crystals to the funnel. Any remaining crystals are
washed into the funnel by means of small aliquots of
cold filtrate.
Just as soon as the filter cake is rigid enough, it is
pressed down carefully but firmly by means of a cork
or an inverted bottle stopper. When the flow of liquid
stops, the suction is discontinued. If the filtrate is of
value, it should be transferred to another vessel at this
point.
The crystals are then washed to remove all adhering
solution (which, of course, contains soluble impurities).
With the suction released (screw clamp open), the
crystals are covered with a small portion of fresh, cold
solvent.
It may be advisable to stir the mixture carefully with
a spatula or flattened stirring rod to insure uniform
wetting of the crystals. Then suction is applied and the
crystals tamped down as before. This process may be
22
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
repeated several times, after the screw clamp has been The sample is placed in a small boat (A) in the drying
reopened, but always with small portions of cold sol- chamber (B) which is continuously heated by refluxing
vent.
vapors from the liquid in the flask (C). The drying
Finally, if the solvent is high boiling, an ultimate chamber is connected by means of a ground glass joint
washing with a small amount of a low-boiling solvent to the desiccant chamber (D) and both may be evacin which the crystals are insoluble or only sparingly uated through stopcock E. The desiccant usually consoluble may be recommended.
sists of phosphoric anhydride (mixed with charcoal or
Frequently the original mother liquor (filtrate) may distributed on glass wool) when water is to be rebe concentrated and further crystals obtained. These moved, and of silica gel or thin slivers of paraffin for
are, however, almost always somewhat less pure than organic solvents.
the crystals which first separate.
In drying solids above room temperature one must
Drying of the Crystals. As the final step of the take into account that samples that are still moist with
crystallization procedure, the crystals must be freed of solvent melt considerably below the melting point of
adhering solvent by drying. The Buchner funnel is the pure material.
inverted over three or four layers of coarse-grained
Experimental
smooth-surfaced filter paper and the crystals transferred
with the aid of a clean spatula. Several additional sheets A. Selection of a Crystallizing Solvent
of the paper are placed on top of the crystals and most
Make solubility tests in each of the following solof the solvent squeezed out by firm pressing.
vents
on each of the compounds listed in Table 4: water,
The crystals are then transferred to a clean watch
glass or crystallizing dish and covered with a sheet of benzene, and ligroin.
filter paper to keep out dust particles. They may be air
TABLE 4. SOLIDS FOR CRYSTALLIZATION TESTS
dried at room temperature or in a vacuum desiccator
(Figure 12a) over a desiccant which is effective in the
Substance
Formula
Chemical Type
removal of the solvent used.7 Small samples are often Benzoic acid
C6H6COOH.
Carboxylic acid. Moledried on pieces of unglazed porcelain plates; such
cules can associate
A hydrocarbon
C14H10
porous plates cannot be cleaned, however, and the same Anthracene
Resorcinol
CflH4(OH)2
A dihydroxyl compound
piece cannot be used for different substances.
+
An ionic compound
Sodium
benzoate
C6H
COO-Na
6
Drying at higher temperatures may be accomplished
(salt)
in an oven, by means of a stream of hot air from a
C17H36COOH
A high molecular
Stearic acid
heater, such as an ordinary hair dryer, or, for small
weight carboxylic
samples, in an Abderhalden drying pistol (Figure 12b).
acid
7
For water, calcium chloride, concentrated sulfuric acid,
silica gel, and sodium hydroxide are widely used. Sulfuric acid
is effective also for ether, and silica gel or freshly cut shavings
of paraffin, for benzene, toluene, ether, carbon tetrachloride,
and chloroform.
Observe and record the degree of solubility in each
solvent, hot and cold. Select the best solvent or solvent
pair for each of the substances. Record the general
crystal form—needles, prisms, or platelets.
(b)
FIG. 12.
Drying apparatus, (a) Vacuum desiccator, (b)
Abderhalden drying pistol.
0-110
CRYSTALLIZATION
23
Carry out the solubility tests as follows: with a small a watch glass or crystallizing dish, and allow them to
spatula transfer an amount roughly estimated to be 0.1 stand, covered with a sheet of filter paper, until the
g. of the finely divided solid to a small (10 x 75 mm.) next period. During the next period, weigh the purified
test tube and add the solvent drop by drop with con- acetanilide and determine its melting point. Record
tinuous shaking. Stir with a fire polished 4-mm. stir- your results.
ring rod. After 1 ml. of solvent has been added, observe the mixture carefully.
C. Decolorization of Brown Sugar
130-150
If all the solid has dissolved in the cold solvent, the
Dissolve 10 g. of dark brown sugar in 75 ml. of
solvent is unsuitable. If not all of the solid has dissolved, warm the mixture gently to the boiling point water. Save a small portion of the solution for comwith stirring. If all of the solid dissolves, you can de- parison purposes; add to the remainder 1 g. of decolorclare it readily soluble in the hot solvent. If not all dis- izing charcoal (Note 2), and boil for 5 minutes. Add
solves, add more solvent in 0.5-ml. portions until all of 0.5 g. of Hyflo or Filter-eel as a filter aid. Then filter
the solid dissolves at the boiling point or until a total the hot solution and compare the color of the filtrate
of 3 ml. of solvent is present. If some of the solid still with that of the untreated material. Record your reremains undissolved at the boiling point, you can judge sults.
it sparingly soluble in that solvent and you should try
another crystallizing solvent. If all of the solid does D. Crystallization of an Unknown (For Specially
Interested Students)
dissolve in a total of less than 3 ml. of the hot solvent,
you can declare the material at least moderately soluble
Obtain a weighed sample of an unknown impure
in that solvent.
solid from your instructor. Determine its melting point.
In every case, when a solution of solid in a hot sol- Select a suitable crystallization solvent, and purify the
vent is obtained, slowly cool the solution, scratching material. Dry and weigh the purified material and dethe sides of the test tube with a small stirring rod. termine its melting point. Record and report to your
Observe the ease and amount of crystal formation. Note instructor the percentage recovery and the melting
and record the approximate proportions of solute and points of the impure and purified samples.
solvent which give the best results. On this basis, select
the most suitable crystallization solvent for each substance.
NOTES
If no single solvent appears to be particularly suitable, try mixed solvents as described in the Introduc1. If crude acetanilide is not available, a synthetic mixtion (p. 19) using the relative amounts of solid and ture of 9 parts of acetanilide, 1 part of oxalic acid, and
solvent specified above.
0.1 part of carbon may be used.
2. A very active grade of decolorizing charcoal is necessary for good results. You may find it advisable to heat
110-170 B. Recrystallization of Acetanilide
your charcoal in an evaporating dish over a Bunsen burner
Place 2 g. of crude acetanilide (Note 1) in a 125-ml. prior to use.
Erlenmeyer flask. Dissolve the acetanilide in a minimum amount of boiling water (the material contains
impurities which will appear as insoluble solids, but
QUESTIONS
the dark oil which forms is indicative of undissolved
acetanilide). Add an additional 5 ml. of water at the
1. A solid (JC) is soluble in water to the extent of 1 g.
boiling point and filter the hot solution through a short- per 100 g. of water at room temperature and 10 g. per
stem funnel, which has been previously heated in a jet 100 g. of water at the boiling point. How would you
of steam, into a 125-ml. Erlenmeyer flask. Allow the purify x from a mixture of 10 g. of x with 0.1 g. of
solution to cool undisturbed in a bath of cold water for impurity y, completely insoluble in water, and 1 g. of
impurity z, having the same solubility characteristics in
30 minutes.
water as JC? How much absolutely pure x could be obtained
after one recrystallization from water?
[Proceed to Part C]
How much pure x could be obtained after one reWhen the solution is cool, collect the crystals by suc- crystallization from a mixture of 10 g. of x with 9 of z?
tion filtration and wash with two separate 5-ml. por- What does this suggest in a general way about the use of
tions of cold water, each time pressing the crystals crystallization as a purification technique?
2. Why is it important to minimize evaporation during
firmly with an inverted glass stopper or a cork. Transfer the filtration of the hot solution?
the crystals to a layer of three or four sheets of coarse3. When you are collecting a solid by suction filtration,
grained filter paper. Place a layer of two or three addi- why do you always break the suction before turning off
tional sheets of filter paper above the crystals and press the water pump?
them firmly to remove water. Transfer the crystals to
4. Ethyl iodide, CH3CH2I is polar, but, unlike such
24
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
polar liquids as ethyl alcohol and acetic acid, is insoluble
in water. Explain.
5. Suggest a good solvent for each of the following:
O
II
naphthalene (C 10 H 8 ); sodium butyrate (C 3 H 7 C—0~,Na+);
propyl amine (C 3 H 7 NH 2 ); arabinose (HOCH2CHOHCHOHCHOHCHO); cetyl alcohol (C 16 H 33 OH).
6. What properties of activated charcoal make it a good
adsorbing agent?
7. Predict which compound is more soluble in ether
O
O
II II
and benzene, oxalic acid (HO—C—C—OH) or glyoxal
O
O
II II
(H—-C—C—H); ethylene diamine (H 2 N—CH 2 —CH 2 —
NH 2 ) or tetramethyl ethylene diamine [(CH 3 ) 2 N—CH 2 —
CH 2 —N(CH 3 ) 2 ].
EXPERIMENT 5
I. Extraction
II. Drying Agents
0
I. EXTRACTION
A. Theory
1. Definitions. No technique is more widely used for
the separation of an organic product from its reaction
mixture or for the isolation of naturally occurring organic substances than extraction. We may define extraction as the separation of a component from a mixture by means of a solvent.
In practice, extraction is usually employed to separate an organic compound from an aqueous solution or
suspension. The process then consists of shaking the
water solution or suspension with a water-immiscible
organic solvent and allowing the layers to separate. The
various solutes present then distribute themselves between the aqueous and organic layers according to their
relative solubilities.
Thus inorganic salts, which are almost entirely insoluble in the common organic extraction solvents, will
appear exclusively in the water layer, and nonhydrogenbonding organic compounds, such as hydrocarbons and
their halogen derivatives, which are essentially insoluble
in water, in the organic solvent layer. A single extraction will usually suffice to effect a clean separation between compounds of these two types.
2. Distribution Coefficient. For organic compounds,
such as alcohols, aldehydes, ketones, acids, esters,
amines, etc., which form hydrogen bonds with water
and therefore are usually at least partially soluble in
water, as well as in organic solvents, repeated extractions may be required to remove essentially all of the
compound from the water layer. When a water solution of any substance is shaken with an organic solvent
O, in which that substance is at least somewhat soluble,
it dissolves partially in each solvent. It will, in fact, distribute itself between the water and solvent O so that
concentrations1 (C0 and Cw) in the two solvent layers
are roughly proportional to its solubilities (S0 and Sw)
in the two solvents at the given temperature. The ratio
of the concentrations of solute in the two solvents at
equilibrium is called the distribution coefficient, KD.2
O
acid (HO—C—(CH 2 ) 6 —C—OH) is 0.56 g. per 100
ml. of ethyl ether and 0.14 g. per 100 ml. of water.
This means that when suberic acid is distributed between the solvents ether and water at 15°, its concentration in the ether layer will be 0.56/0.14 or 4.0 times
that in the water layer, and the KD = 4.0. If a solution
of 40.0 mg. of suberic acid in 50 ml. of water is extracted with 50 ml. of ether, the weight (x) of suberic
acid removed by the ether can be calculated as follows:
50 ml.
= 4
40 mg. — x
50 ml.
bx = 160 mg.
x = 32 mg.
In other words, the single extraction with 50 ml. of
ether would remove 32 mg. of the suberic acid, leaving
8 mg. in the water layer. It is apparent that suberic acid
can be separated readily from any ether insoluble contaminant by repeated extraction of a water solution
with ether.
You can prove for yourself by straightforward calculations using the distribution coefficient equation that
a double extraction with 25-ml. aliquots of ether would
be considerably more effective than the single extraction with 50 ml. In general, for a given total volume
of extracting solvent, the efficiency increases with the
number of separate extractions used. In practice, however, this factor must always be weighed against the
time and labor involved in repeated extractions and the
inconveniences introduced when the aliquot of extracting solvent used becomes too small for easy handling.
As a rule of thumb, when the solute is considerably
more soluble in the extracting solvent than in water, a
volume of solvent approximately one third that of the
solution is used for each extraction.
Other important organic extracting solvents are benzene (C 6 H 6 ), petroleum ether (low molecular weight
alkanes), methylene chloride (CH2C12), chloroform
(CHC13), carbon tetrachloride (CC14), and di-isopropyl
ether [(CH 3 —CH) 2 0]. The choice of solvent depends
Co
So
Cw Sw
For example, at 15° the solubility of solid suberic
KD =
I
1
Expressed here as weight of solute per unit volume of
solvent.
* If the solute is completely miscible with one or both of the
solvents, the distribution coefficient cannot, of course, be calculated from solubility data. It can still be determined experimentally, at least in dilute solution. In concentrated solutions,
the two solvent phases may become miscible with each other.
CH 3
upon the solubility of the substance to be extracted in
that solvent and upon the ease with which the solvent
can later be removed from the solute.
Ethyl ether, because of its powerful solvent action
25
26
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
toward most organic compounds and its low boiling
point (35°), is the most widely used extraction solvent. Its high volatility and extremeflammability,however, constitute a dangerous fire hazard which must
always be considered in its use.
B. Practice
1. Equipment and Procedure. The apparatus used
for carrying out extractions is a separatory funnel,
shown in Figure 13. You will use your separatory fun-
through the stopcock and pour the upper layer from
the top of the funnel to avoid contamination. The exact
number of extractions required in any given case will
depend upon the distribution coefficient and the relative volumes of solvent and water. You can determine
the completeness of any extraction by evaporating a
small portion of the last extract and noting the amount
of residue.
The relative positions of the water and organic layers
will, of course, depend upon their relative densities.
You can determine whether a given layer is aqueous or
organic by testing the solubility of a few drops in water.
When carrying out a new reaction, you will find it a
wise policy to save all layers until you have isolated the
final product in the expected yield. Then clean up.
2. Emulsions. Frequently, especially when working
with alkaline solutions, you will be plagued by the formation of emulsions during extraction. You can often
break up an emulsion by (1) gently swirling the funnel
while holding it in an upright position, (2) stirring the
FIG. 13 a. Proper method for holding a separatory funnel.
nels so frequently in the weeks to come that you will
save time by checking at once to see that they are in
good working condition. The stopper and stopcock
should fit tightly and should be absolutely leakproof.
Both should be lubricated with a thin film of stopcock
grease before each use.
When carrying out an extraction, always hold the
funnel securely with both hands, one hand at the top
so that the stopper rests at the base of your index
finger, the other hand in position for ready opening
and closing of the stopcock (Figure 13a). Invert the
funnel, and immediately open the stopcock to relieve
excess pressure. Shake gently for 1-2 seconds and open
the stopcock again. When further pressure is no longer
built up in the funnel, close the stopcock securely, and
then shake vigorously for a minute or two. Vent the
funnel again by means of the stopcock and then place
the funnel upright, with stopcock securely closed, in an
iron ring fitted with several strips of slit rubber tubing
for protecting the funnel against breaking (Figure 13b).
Remove the stopper and allow the mixture to separate into two well defined layers. Always keep a large
beaker under the separatory funnel so that all the contents of the funnel will be saved in case of an accident.
In separating layers, drain off the bottom layer
FIG. 13b. Ring support for separatory funnel.
emulsified layer vigorously with a glass rod, (3) saturating the aqueous layer with salt, or (4) centrifuging.
Method 3, saturating the aqueous layer with salt, has
a double advantage; it decreases the solubility of most
organic solutes and of extraction solvents such as ether
in the water layer. This is called the salting-out effect.
3. Extraction with Acids and Alkalies. Frequently
the cleanest separations of organic compounds can be
effected by use of acid or alkaline solutions which convert the compound to be extracted to a water-soluble,
ether-insoluble salt. A 5 or 10 per cent solution of sodium hydroxide, for example, converts carboxylic acids,
EXTRACTION
O
R—C—OH, to their sodium salts, R—C—O", Na+.
Phenolic compounds undergo similar salt formation
with sodium hydroxide solution. Hence, a sodium hydroxide solution can be used to extract a carboxylic
acid or phenolic compound from its solution in an organic solvent, or, conversely, an organic solvent can
be used to remove organic impurities from a carboxylic
acid or phenol dissolved in aqueous sodium hydroxide.
27
tion of basic substances from mixtures or in the removal
of basic impurities. The dilute acid converts the base
such as ammonia or an organic amine (R 3 N) 3 into the
water-soluble chloride salt (R3NH+, CI"). Conversely,
organic impurities may be removed from amines by
extraction from a dilute acid solution with organic solvents.
Sodium salts of carboxylic acids and phenolic compounds are readily reconverted to the parent compounds by treatment with sulfuric acid. The chlorides
FIG. 14. Continuous extraction apparatus, (a) For solvents lighter than water, (b) For solvents heavier than
water, (c) Soxhlet extraction apparatus for solids.
Aqueous solutions of sodium bicarbonate likewise
convert carboxylic acids to their sodium salts, but are
not sufficiently alkaline to form salts of phenolic compounds. This provides an elegant method for the separation of a carboxylic acid and a phenolic compound.
First the acid may be extracted from solution in an
organic solvent by means of extraction with sodium
bicarbonate solution, and then the phenol, with sodium
hydroxide solution.
Inorganic acids are regularly removed from organic
solvents by extraction with sodium hydroxide, sodium
carbonate, or sodium bicarbonate solutions.
Dilute hydrochloric acid is often used in the extrac-
of amines revert to the original amine upon addition of
sodium hydroxide solution.
4. Continuous Extraction. Often, when the system
being extracted forms intractable emulsions, or when
the organic solute being extracted is more soluble in
water than in the organic solvent, it is advisable to
switch to a method of continuous extraction.
Two types of apparatus have been devised which,
in effect, make possible the automatic treatment of
water solutions with an almost infinite number of separate extractions with minute aliquots of extracting solvent. One type (Figure 14a) is used for solvents lighter
3
R may be a hydrogen atom or an alkyl group.
28
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
than water and the second (Figure 14b) for solvents
heavier than water. In each case, the solvent is distilled
continuously from the flask on the left. The drops of
condensate trickle up (Figure 14a) or down (Figure
14b) through the solution and are finally returned,
along with extracted solute, to the distilling flask, where
the solute collects.
For the repeated and exhaustive extraction of a solid
by hot liquid, the solid mixture is placed in the thimble
(A) of a Soxhlet Extraction Apparatus (Figure 14c).
The extracting solvent is boiled gently, the vapor passes
through the side tube (B), and the condensate drops
onto the solid and slowly leaches out soluble material.
Other Soxhlet extractors are constructed so that the
solvent first fills the extraction chamber, and the solution which is formed is then siphoned into the distilling
flask, this process being repeated automatically until
the extraction is completed. Soxhlet extraction is particularly useful for the isolation of naturally occurring
products from animal and plant tissues that have high
water content and for leaching organic compounds from
inorganic salts.
Experimental
0-40
40-100
A. Extraction of Crystal Violet
1. Simple Extraction. Dissolve a small crystal of
crystal violet about the size of a pin-head in 60 ml. of
water. Divide the solution into two equal parts. Place
a clean, dry, and properly lubricated 125-ml. separatory
funnel on a ring support and add to it (stopcock closed)
the first portion of the crystal violet solution and 30 ml.
of chloroform. Insert the stopper securely in the funnel,
invert the funnel, and open the stopcock to relieve excess pressure. Close the stopcock, shake the funnel
gently for a moment, and again open the stopcock to
relieve excess pressure.
Repeat this process until no pressure builds up within
the funnel during the shaking period. Then close the
stopcock, shake vigorously for 1 minute, and finally
place the funnel upright in the ring support. Remove
the stopper from the top of the funnel and allow the
mixture to separate into two sharply defined layers.
(This will require several minutes. Use this time, in
every case, to prepare the solution and to set up the
melting point apparatus for Part B of this experiment.)
Drain off the chloroform (lower) layer into a test
tube and pour the aqueous layer through the top of the
funnel into a second test tube. Cork each test tube and
set them aside for future reference.
2. Multiple Extraction. Extract the second portion
of the crystal violet solution with three separate 10-ml.
portions of chloroform. Combine the three chloroform
extracts in a third test tube and pour the extracted
water solution through the top of the funnel into a
fourth test tube. Compare the intensity of color in the
two chloroform solutions and then in the two aqueous
solutions. Record your results.
B. Extraction with Sodium Hydroxide Solution
100-135
Dissolve in 35 ml. of ether (be certain that there
are no flames in the laboratory) 0.7 g. of benzoic
acid (C 6 H 5 COOH) and 0.7 g. of p-dichlorobenzene
(C6H4C12). Extract this solution with a single 15-ml.
portion of fresh 10 per cent sodium hydroxide solution.
Drain off the aqueous (lower) layer and pour the ether
solution through the top of the funnel into a small
Erlenmeyer flask.
Add to the ether solution three or four granules of
calcium chloride (see the discussion on drying agents
following this experiment) and shake the mixture occasionally until no turbidity remains. Then decant the
ether solution in a tared (previously weighed) watch
glass and set it aside (preferably in the hood) to allow
the ether to evaporate while you begin Part C of this
experiment. As soon as all the ether has evaporated,
weigh the residue. Then determine its melting point.
Pure p-dichlorobenzene melts at 53°. Record your results.
If you have time you may wish to devise your own
method for isolating the benzoic acid quantitatively
from the aqueous layer.
C. The Salting-Out Effect
Prepare a solution of 8 g. of /-butyl alcohol
[(CH 3 ) 3 COH] in 40 ml. of water and divide the solution into two equal portions. Extract the first with 25 g.
of chloroform. Weigh the chloroform solution and calculate the weight of f-butyl alcohol extracted.
To the second portion of f-butyl alcohol solution, add
25 g. of chloroform. Then dissolve in the water solution 10 g. of potassium carbonate. Finally, extract the
aqueous layer with the 25 g. of chloroform as before,
and compare the weights of r-butyl alcohol extracted in
the two cases.
D. Bonus Experiment for Specially
Interested Students
Obtain from your instructor a 3-g. sample of a mixture4 of benzoic acid, 0-naphthol (Ci 0 H 7 OH) and
p-dichlorobenzene. Devise a method for separating the
mixture into the three pure components by extraction.
After your instructor has approved your method, try it
and record your results. Some of the pertinent properties of the three compounds are as follows:
4
Prepared by melting a mixture containing equal weights of
the three components on a steam bath and then cooling, breaking up the solid with a spatula as it crystallizes.
135-170
DRYING AGENTS
Benzoic acid,
CsHsCOOH
3-Xaphthol,
C10H7OH
p-Dichlorobenzene,
C6H4C12
M.P.
Kion
Solubility
in Water
at 20°
123°
6.3 X lO"5
0.25 g./lOO g.
123°
7 X 10"9
0.10 g./lOO g.
53°
—
Insol.
QUESTIONS
\ ^ water
for
caffeine in
12. What practical advantage does an extraction solvent
that is heavier than water have over one that is lighter
than water?
13. Why should the stopper always be removed from a
separatory funnel whenever a liquid is being drained
through the stopcock?
14. (For Specially Interested Students) For efficiency in
continuous extractions with solvents lighter than water, it
is important that the extraction chamber should not be
much larger than required to accommodate the solution to
be extracted. Can you explain why this is true?
II. DRYING A G E N T S
1. On the basis of the extraction of crystal violet by
the two methods, compare the efficiency of extraction with
a single 30-ml. portion of solvent to that with three 10-ml.
portions.
2. Aniline, C 6 H 5 NH 2 , is very slightly soluble in water;
the solution turns red litmus blue. Outline a method for the
separation of a mixture of aniline, /?-naphthol, and p-dichlorobenzene into the pure components.
3. What is the effect of the addition of potassium carbonate on the solubility of f-butyl alcohol and of ether in
water? What effect does this have on the experimentally
determined distribution coefficient, CEy for f-butyl alcohol?
4. What advantages does di-isopropyl ether have over
ethyl ether as an extraction solvent?
5. Explain why the pressure in a stoppered funnel containing a water solution-ether mixture increases when it
is first shaken. Why does the pressure no longer increase
after several extractions have been performed?
6. Chloroform is an excellent solvent for extracting
caffeine from water. The distribution coefficient, KD
/QhWorixA
29
chloroform-water at 25° is 10.
/
What relative volumes of chloroform-water should be used
for the extraction of 90 per cent of the caffeine from a
water solution in a single extraction?
7. When a solution containing 4.0 g. of ^-butyric
acid in 100 ml. of water is extracted with 50 ml. of benzene at 15°, 2.4 g. of the acid is transferred to the benzene
layer. What is the distribution coefficient for n-butyric
acid in benzene-water at 15°?
8. The distribution coefficient, KD (
ether
Y between
\ k water/
ether and water for aspirin (acetylsalicylic acid) at
room temperature is 3.5. What weight of aspirin would be
extracted by a single extraction with 60 ml. of water of
a solution of 5 g. of aspirin in 100 ml. of ether? Calculate
the weight of aspirin which would be removed by three
extractions with 20-ml. portions of ether.
9. What volume of ether would be required to extract
0.95 g. of aspirin from a solution of 1 g. of aspirin in 100
ml. of water in a single extraction?
10. Would carbon tetrachloride be a good solvent for
extracting ethyl alcohol from water? (Consult a handbook.) Explain.
11. What effect does partial miscibility of the two solvents used have on the efficiency of extraction? Explain.
1. Importance of Drying
Small amounts of moisture sharply inhibit the crystallization of many solids. In addition, many liquids,
when distilled in the presence of water, react chemically
(are hydrolyzed) with water or distill (or steam distill)
with the water at temperatures far removed from their
true boiling points. For these reasons, the usual final
step just before the crystallization of a solid, or the distillation of a liquid, is the removal of water through
some drying process. 5 As a rule, this is best accomplished while the organic compound is in solution
(often in an extraction solvent).
2. Drying by Mechanical Means
Drying may be accomplished by mechanical or chemical means. Suspended water in an emulsion can often
be removed mechanically by distillation, freezing, filtration, or centrifugation, and water dissolved in a
liquid, by distillation or freezing. Sometimes a moist
solid or high-boiling liquid which is only slightly soluble in water is dried by addition of a low-boiling solvent
immiscible with water (usually benzene) and distillation
of the resulting mixture.
When benzene is used, its steam distills with the
water at 69.3°. After all of the water has been removed,
dry benzene distills at 80°. The dried material is then
usually distilled, if it is a liquid, or isolated directly,
if it is a solid.
3. Chemical Drying Agents
Chemical drying is even more widely used than mechanical drying. A good chemical drying agent or desiccant should (1) be compatible with the substance to be
dried; ( 2 ) have a high intensity, i.e., remove water
completely or nearly completely; (3) have a high capacity, i.e., remove a large amount of water per unit
weight of desiccant; (4) dry rapidly; and (5) be removed easily from the dried substance.
5
The removal of water from a reaction mixture is, of course,
effective in driving to completion a reversible reaction in
which water is one of the products. This is often accomplished
by distillation, with water as one compound of a constantboiling mixture. Effective use of this device is illustrated in
Experiment 37.
30
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
Chemical drying agents may be divided broadly into
two classes: (1) those which react chemically with
water by a nonreversible process giving rise to a new
water-free compound and (2) those that combine reversibly with water, either by hydrate formation or by
adsorption. In some cases, the dividing line between
these two classes is not sharp.
4. Nonreversible Drying Reactions
Phosphoric anhydride (P 4 Oi 0 ), sodium, calcium hydride, and calcium oxide (quicklime) belong to the
former class. The capacity of such drying agents depends upon the stoichiometry of their reaction with
water, and their intensity, upon the equilibrium point
in the system,
Drying Agent + Water ^± New Compound
For desiccants of this type, the reaction products with
water are quite stable at higher temperatures, and the
dried material is frequently distilled directly from the
desiccant.
Phosphoric anhydride reacts with water to form one
of a variety of phosphoric acids, depending upon the
ratio of anhydride to water. It removes water extremely
efficiently and rapidly. It is, however, difficult to handle
and expensive; it channels badly and tends to form a
syrupy coating on the surface. It is employed only when
extreme desiccation is required and only after preliminary drying with a less expensive desiccant of high
capacity. Phosphoric anhydride is used for hydrocarbons and their simple halogenated derivatives, ethers,
and nitriles, but never for alcohols, ketones, amines,
and acids.
Metallic sodium reacts with water to form sodium
hydroxide and hydrogen. It is highly effective, especially
when drawn out in the form of a fine wire, but can be
used only for ethers, alkanes, and aromatic hydrocarbons. Its use should always be preceded by a preliminary drying with calcium chloride, magnesium sulfate, or phosphoric anhydride. Sodium must be used
with great caution. It should never be allowed to come
into contact with water because a violent explosion may
result. Scrap sodium may be destroyed by addition in
small portions to a large quantity of ethyl or methyl
alcohol.
Calcium hydride is a powerful, high-capacity desiccant which reacts with water irreversibly to form calcium hydroxide and hydrogen:
CaH2 + 2H 2 0 - • Ca(OH)2 + 2H2 T
From the equation, it can be seen that 42 g. of calcium
hydride reacts quantitatively with 36 g. of water. Its
effectiveness increases markedly with increase in temperature. Calcium hydride is recommended for the
removal of traces of moisture from gases and from
ethers and tertiary amines (R3N).
Calcium oxide is commonly used for the drying of
low molecular weight alcohols. The alcohol is refluxed
with calcium oxide and finally removed by distillation
from the calcium oxide-calcium hydroxide mixture.
5. Drying by Hydrate Formation
Most chemical drying agents function by combining
reversibly with water to form hydrates. Their capacity
depends upon the stoichiometry of the hydrate-forming
reactions, and their intensity, upon the equilibrium
vapor pressure of the system
Desiccant + Water +± Hydrate
at the drying temperature.
Calcium sulfate (Drierite), for example, as ordinarily
used forms a hydrate containing only a half mole of
water per mole of sulfate:
CaS0 4 + £H 2 0 <± CaSO40.5H2O
On this basis, it has very low capacity, 1 g. of the
desiccant removing only about 0.066 g. of water. However, the vapor pressure of the system calcium sulfate
-calcium sulfate hemihydrate is only 0.004 mm. at
25°; this means that water is removed from any liquid
phase in equilibrium with the calcium sulfate system
until the partial pressure of water in the liquid phase is
only 0.004 mm. Thus calcium sulfate has remarkably
high intensity as a desiccant.
Most of the common hydrate-forming desiccants give
a series of hydrates, depending upon the ratio of water
to desiccant present. Thus anhydrous magnesium sulfate can add water to form hydrates containing 1, 2, 4,
5, 6, and 7 moles of water per mole of sulfate. The
equilibrium vapor pressure of the various hydrate systems involved, of course, increases with the degree of
hydration, from 1 mm. (25°) for the system
MgS04 (anhyd.) + H 2 0 <± MgS0 4 H 2 0
to 11.5 mm. for the system
MgS0 4 -6H 2 0 + H 2 0 <=* MgS0 4 -7H 2 0
Hence, with magnesium sulfate, different capacities
and intensities of drying can be realized, depending
upon the ratio of drying agent to water. If at least 1
mole of the sulfate per mole of water is added, the
demonstrated capacity will be low but the intensity will
be relatively high. If 1 mole of magnesium sulfate per
6-7 moles of water is present, the capacity will be high
but the observed intensity low. The equilibrium vapor
pressure of hydrate systems also increases rapidly with
increasing temperature; hence desiccants which form
hydrates are most effective at low temperatures.
The facts constitute the principles which underly the
common practices in the use of hydrate-forming desiccants. In the first place, such a desiccant is almost always removed, either by filtration or decantation, prior
to distillation, or a large part of the water of hydration
will be driven off with the distilling product. Similarly,
DRYING AGENTS
at times drying is carried out at very low temperatures
in order to exploit the maximum intensity of the drying
agent. Frequent agitation helps to hasten attainment of
equilibrium, thereby speeding the removal of water.
When a large amount of water is to be removed by a
desiccant which forms several hydrates, it is not advisable to attempt intense drying in a single step by
the addition of a large amount of desiccant. Preferably,
drying should be conducted in stages, with one portion
of desiccant being removed before the next is added. In
this way, the bulk of the water is removed through the
formation of a higher hydrate, and the final traces of
water yield to the full drying power of the lowest hydrate. Similarly, it is often advantageous to remove the
bulk of the water with an inexpensive primary desiccant of large capacity, such as sodium sulfate, and then
to complete the process with an agent of high intensity,
such as calcium sulfate.
6. Common Hydrate-forming Drying Agents
A list of some of the common hydrate-forming drying agents with their important characteristics, application, and limitations follows:
Anhydrous calcium chloride is widely used because
it has high capacity and is relatively cheap. It is rather
slow, however, and not unusually efficient. It is particularly useful for preliminary drying, but is recommended only for hydrocarbons and their halogen derivatives and for ethers. It is usually unsuitable for acidic
compounds, such as carboxylic acids and phenols, because it often contains some lime, and for alcohols,
phenols, ketones, amines, amino acids, amides, and
some aldehydes and esters, because of the formation of
complexes.
Neutral anhydrous salts, such as anhydrous sodium
sulfate, magnesium sulfate, and calcium sulfate, are
inert and insoluble in organic liquids and can be used
for all types of compounds. Sodium sulfate is cheap and
has a high capacity, since at temperatures below 33°
it forms hydrates up to a decahydrate, Na2SQ4 •
31
10H 2 O. It is slow, however, and because of its low
intensity is almost useless for solvents such as benzene,
toluene, and chloroform in which water solubility is
low. It is recommended as a preliminary drying agent
for the removal of large amounts of water, especially
from ether solutions.
Anhydrous magnesium sulfate is an excellent allpurpose desiccant with good capacity and good intensity. It is cheap and fairly rapid.
Anhydrous calcium sulfate (Drierite) is extremely
rapid and efficient, but has low capacity (at maximum
intensity it absorbs only 6.6 per cent of its weight of
water). It is often used after a primary desiccant such
as sodium sulfate.
Anhydrous sodium hydroxide and particularly anhydrous potassium hydroxide are the reagents of choice
for the drying of amines. Because of their strong basicity, they find little other use as desiccants, except in
desiccators where they do not come into contact with
the material being dried.
Anhydrous potassium carbonate has moderate intensity and capacity. It is used to some extent for ketones,
esters, alcohols, and amines (when a strongly alkaline
reagent is to be avoided), especially as a preliminary
drying agent. It is the reagent of choice for salting out
(see p. 26) water-soluble alcohols, amines, and ketones.
7. Adsorbing Agents
Two of the most common desiccants which function
by adsorption of water at the surface are a specially
treated form of silica called silica gel 6 and a series of
highly porous crystalline sodium and calcium aluminosilicates that have been heated to remove water of hydration called molecular sieves.7 These agents are extremely effective in removing water vapor from gases.
• Available from the Davison Chemical Company, Baltimore,
Maryland.
7
Supplied by the Linde Division of Union Carbide Corporation.
EXPERIMENT 6
Steam E stillation
Introduction
A. Principle of Steam Distillation
Steam distillation is an ingenious technique for the
separation of slightly volatile water-insoluble substances
from nonvolatile materials. It makes possible the convenient purification of many high-boiling substances by
low-temperature distillation. Steam distillation is particularly valuable when the desired substance boils
above 100° at atmospheric pressure and decomposes
at or below its boiling point. In such cases, it takes the
place of vacuum distillation and is much more convenient.
In order to appreciate how this is possible, we must
consider the distillation behavior of two-phase systems
consisting of two immiscible liquids. In Experiment 3,
we discussed the distillation of solutions. The behavior
of two-phase systems is quite different, but equally important.
In a mixture of two completely immiscible liquids, x
and y, each liquid exerts its own characteristic vapor
pressure independently of the other. Thus the total
vapor pressure, PT, may be calculated as follows:
Pv (at T)
where Px = the vapor pressure at x at temperature T
and Py = the vapor pressure of y at temperature T.
PT = PX +
The vapor pressures are totally independent of the relative amounts of x and y present in the mixtures.
The boiling point of the mixture will be the temperature at which the total pressure, PT, is equal to
760 mm. Unless either Px or Py = 0, this temperature
will be lower than the boiling point of both x and y.
Now, since gases exert pressures (at a given temperature) in proportion to the concentration of the
molecules, it follows that the ratio of vapor pressures
of x and y at the boiling point of the mixture is the
numerical ratio in which the molecules of x and y distill from the mixture. In other words, the composition
of the vapor may be calculated as follows:
Ny
Py
where Nx/Ny is the molar ratio of x to y in the vapor.
The ratio of weights of x and y in the vapor will depend not only upon the ratio of moles but also upon
the molecular weights of x and y, and this weight ratio,
wx/Wy, is as follows:
Wx _ MXNX _ MXPX
Wy " MyNy ~ MyPy
where Mx and My are the molecular weights of x and
y, respectively.
Stated in words, this important equation tells us that
in the distillation of a mixture of two immiscible liquids,
the relative weights of the two liquids which are collected in the receiver are directly proportional both (1)
to the vapor pressures of the liquids at the distillation
temperature and (2) to their molecular weights. Furthermore, the mixture will distill at a constant temperature as long as at least some of each component is
present.
These facts constitute the basis for the purification
and separation of substances by steam distillation.
There are many relatively high-boiling organic compounds which with water will distill in a favorable
weight concentration below 100°. This is true because
of their relatively high molecular weight compared to
water.
B. Steam Distillation of Bromobenzene
To illustrate this in a practical way, let us consider
the distillation of a mixture of water and bromobenzene,
C6H5Br, which is almost completely immiscible with
water. At 95.3° the vapor pressure of water is 641 mm.
and that of bromobenzene is 119 mm. The vapor pressure of the mixture is therefore 760 mm. (641 mm. +
119 mm.). Hence, a mixture of water and bromobenzene will distill at 95.3° and the molar ratio of bromobenzene to water in the distillate will be only 119/641.
But the molecular weight of bromobenzene is 157 compared to 18 for water. Therefore the theoreticalx ratio
of bromobenzene to water in the distillate will be as
follows:
Wt. of bromobenzene _ 119 X 157 =
Wt. of water
~ 641 X 18
1
*
Despite the much lower vapor pressure of bromobenzene, on a weight basis it will distill 1.6 times as
fast as water—all because of its much greater molecular
weight.
C. Applications of Steam Distillation
This process—the distillation of a somewhat volatile, insoluble substance with water—is called steam
distillation. For successful steam distillation, the insoluble substance to be distilled should have a vapor
pressure of at least 5-10 mm. at 100°. Besides serving
as a convenient substitute for vacuum distillation, steam
distillation is particularly useful when a relatively small
amount of material is to be separated from a large bulk
of solid or tarry material, which makes ordinary distillation, filtration, and extraction difficult or impractical (see the preparation of aniline in Experiment 49).
x
The actual value will be less than the theoretical, because
the two liquids are not completely immiscible in each other.
STEAM DISTILLATION
Thus steam distillation is often used in the isolation
of natural products and of reaction products which are
contaminated with large amounts of tarry by-products.
It is also useful in the separation of desired slightly
volatile organic compounds from (1) aqueous mixtures containing inorganic salts; (2) from other organic
compounds which are not appreciably volatile with
steam (see the separation of o-nitrophenol from p-nitrophenol in Experiment 63); and (3) when the distilled
material is a solid and would clog the condenser were
it not washed down with water.
If the water-insoluble phase in a steam distillation
contains two components, the two different phases
(water and organic) distill according to the principles
of steam distillation. In other words, the molar ratio
of the two phases in the distillate is the same as that
of the vapor pressures of the two phases. The components of the organic phase, however, distill relative to
each other according to the principles of ordinary distillation (see Experiment 3); i.e., the distillate is richer
than the residue in the more volatile component.
Most organic compounds which are distilled with
steam are not completely insoluble in water, especially
at the distillation temperature. This decreases somewhat the calculated efficiency of the process. The addition of sodium chloride to saturate the aqueous phase
has the double advantage of decreasing the solubility
of the organic compound in the aqueous phase and of
decreasing the vapor pressure of the water relative to
that of the organic phase.
D. Apparatus and Procedure
A typical apparatus for steam distillation is shown
in Figure 15. Steam is admitted from the flask A
equipped with a safety tube B into the steam distilla-
33
tion flask E, through delivery tube D, which is bent so
that it extends to the bottom of the tilted flask. The
distillate passes through the bent tube F into the condenser G, where it is channeled by means of a curved
adapter H, into the receiving flask I.
All connections are made as short as possible to keep
condensation to a minimum. All glass tubing should be
at least 7 mm. in diameter to permit the distillation to
be carried out as rapidly as the capacity of the condenser permits. The rubber stoppers should fit snugly
and should be inserted tightly. The distillation flask
should be clamped to a ring stand and also supported
by a wire gauze supported on a ring. It should not be
more than half filled with liquid and may be heated
with a small flame to prevent excessive condensation
during the distillation.
As an alternative method of generating steam a metal
can or flask, A', provided with a 2-ft. safety tube, B',
may be used. A pinch of zinc dust, which slowly reacts
with the water to liberate hydrogen, prevents bumping
in the generator. Use of a Fischer burner or two Bunsen burners may be necessary to keep the flow of steam
up to capacity. The moment generation of steam is
stopped or interrupted, pinch-cock C must be opened
(CAUTION! Steam is released.) to prevent the contents of flask E from sucking back into the generator.
If live steam is available at the laboratory table, the
steam line should be connected to the distillation flask
E through a trap J or K; K is easily constructed from
an adapter. The screw clamp is adjusted carefully so
that a small liquid seal is maintained to prevent the
escape of steam.
An improved type of steam-distillation head is pictured in Figure 15L. It is compact and convenient and
greatly reduces the likelihood that liquid from the flask
will splash over into the steam distillate.
c
FIG. 15. Steam distillation apparatus.
34
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
Experimental
0-70
70-110
A. Steam Distillation of Bromobenzene
Assemble a steam distillation apparatus as shown in
Figure 15. If live steam is available, connect the steam
outlet to the steam inlet tube through a trap. If not,
assemble a steam generator (Figure 15).
Place a mixture of 25 ml. of water and 30 ml. of
bromobenzene in the distillation flask. Insert all the
stoppers tightly. Place a lighted burner (small flame)
under the flask. Then pass a steady stream of steam
into the flask, steam distilling as rapidly as the condenser capacity will allow. Collect exactly 25 ml. of distillate as measured by means of a graduated cylinder.
Then change receivers and collect a second 25-ml. fraction of distillate. Compare the volumes of bromobenzene in each of the two fractions. Record your data.
B. Steam Distillation of a Mixture of
Benzene and Xylene
Add to the distillation flask 20 ml. of water, 15 ml.
of benzene (C 6 H 6 , b.p. 80.0°), and 15 ml. of xylene
(mixture of C6H4(CH3)2 isomers, b.p. 135°). Steam
distill the mixture, collecting two separate 25-ml. fractions of distillate. Measure and record the volume of
the upper (hydrocarbon) layer in each fraction. Note
how they compare.
C. Steam Distillation of a Mixture of
p-Dichlorobenzene and Salicylic Acid
110-170
By means of a mortar and pestle or by rubbing the
materials on a filter paper with a spatula, prepare
an intimate mixture of 3.5 g. of salicylic acid (HO—
C6H4—COOH) and 1.5 g. of p-dichlorobenzene
(C6H4C12). Take a melting point on a small sample of
the mixture. Then transfer the remainder of the mixture, along with 25 ml. of water, to the distillation flask
and steam distill.
Run water through the condenser only occasionally,
if necessary to condense the steam. Any sudden rise
of the water level in the safety tube is a danger signal
indicating that the condenser may be plugged. If this
occurs, drain all of the water from the condenser until
the plug is removed. Continue the distillation until the
distillate is clear.
Filter the distillate and press the solid between several sheets of filter paper to remove the water. Weigh
the dried sample. Wrap the solid in a piece of filter
paper and set it aside until the next period. At that
time, determine its melting point. Record your data.
Transfer the residue from the steam distillation to
a small Erlenmeyer flask, cool it in ice, and add 5 ml.
of concentrated hydrochloric acid. Filter the ice-cold
mixture by suction filtration, and press the solid between several sheets of filter paper for drying. Weigh
the dried material and then set it aside until the next
period. At that time, determine its melting point. Submit both the recovered p-dichlorobenzene and salicylic
acid to your instructor, properly bottled and labeled.
QUESTIONS
1. Compare the volumes of the organic layers in the
first two fractions from the bromobenzene distillation. Do
the same for the two fractions in the benzene-xylene distillation. How do you account for the difference?
2. How cleanly does steam distillation separate p-dichlorobenzene and salicylic acid? Cite experimental evidence to
support your statement.
3. What is the purpose of adding hydrochloric acid to
the residue from the steam distillation before filtration?
Why is it important to have the mixture ice-cold when it
is filtered?
4. Judging from the results with salicylic acid, can you
describe in general terms the nature of functional groups
which tend to decrease the volatility of compounds in
steam?
5. At 90.3° the vapor pressure of chlorobenzene,
C6H5C1, is 230 mm. and of water, 530 mm. Calculate the
weight percentage of chlorobenzene in the distillate when
it is steam distilled at atmospheric pressure.
6. What advantages would co-distillation with mercury
have over steam distillation? What disadvantages?
7. (For Specially Interested Students) The International
Critical Tables give the following values for the vapor
pressure of nitrobenzene (C 6 H 5 N0 2 ): 80°, 7.5 mm.; 90°,
12.9 mm.; 100°, 20.8 mm.; 110°, 32.5 mm. From these
data, draw a vapor pressure-temperature curve that will
show the vapor pressure of nitrobenzene at intermediate
temperatures. From this curve and the vapor pressure
values for water, calculate both the boiling point of a
mixture of nitrobenzene and water (at the pressure in your
laboratory) and the ratio by weight in which they should
distill. Devise the best experimental conditions for checking
these results in the laboratory. After you have your instructor's approval, carry out the experiment. Record your
results.
EXPERIMENT 7
Adsorption Chromatography
Introduction. The technique of adsorption chromaTheoretically, the smaller the particle size the greater
tography may be illustrated by a description of how two will be the degree of separation of the mixture being
dyes, methyl orange and methylene blue, are separated treated. However, there is a practical point which also
when a solution of the dyes is passed through a column needs to be considered; the smaller the particle size, the
of powdered alumina contained in a vertical glass tube. slower will be the rate of flow of solution or solvent
At first the two dyes are adsorbed at the top of the col- through the column. Therefore a compromise is reumn, giving this region a nearly uniform purple color. quired. The adsorbent should be neither too coarse nor
However, when the flow of solution is discontinued and too fine; the average particle size should be about 8-12
pure solvent is allowed to flow (percolate) through the microns in diameter. Where a required adsorbent is
column, a process known as development occurs.
available only as a fine powder, the rate of flow of soluThe methyl orange is held tenaciously at the top of tion or solvent may be increased by mixing the adthe column while the methylene blue begins to separate sorbent with filter-aid, such as Hyflo Super-eel (Johnsand move down the column. As development continues, Manville Company). Application of gentle suction
the separation becomes more pronounced until there (about 680 mm. pressure) or of pressure also accelresults a pure orange zone in the upper part of the erates the rate of flow of solvent through the column.
column and a pure blue zone in the lower part of the
The most widely used of all adsorbents is alumina
column. This pattern is called a chromatogram.
(A1 2 0 3 ). The most powerfully adsorbing variety is
At this point the passage of solvent through the prepared by heating commercial activated alumina at
alumina could be discontinued, the moist adsorbent red heat for a period of about 4 hours and then cooling
pushed out of the glass tube, the colored zones sepa- it in an evacuated desiccator. However, alumina actirated mechanically, and the individual dyes washed vated in this manner is usually too strong an adsorbent;
(elated) from the respective portions of adsorbent by it is difficult to remove adsorbed material from the
use of a suitable solvent. However, it is usually more column. Material more suitable for general use can be
convenient to continue the passage of fresh solvent obtained by heating commercial alumina for a shorter
through the intact column until the blue and orange period of time at a lower temperature or by deliberately
zones have been successively eluted from the adsorbent. adding water to the dehydrated powder prepared at
Evaporation of the respective fractions of filtrate afford the higher temperature.
pure methylene blue and pure methyl orange.
The adsorbent power of a given material depends not
This simple experiment illustrates all of the essential only on the material itself but also on the solvent used
steps of a process which is in constant use in labora- in the preparation of the chromatogram. Therefore,
tories throughout the world to effect separation of mix- it is not possible to provide a rigorous classification of
tures of compounds, both organic and inorganic, which relative adsorbent powers of different substances. Howin many instances can be separated in other ways only ever, a rough classification is as follows: strong adwith extreme difficulty. It should not be inferred from sorbents—alumina of low water content, activated carthe experiment just described that only mixtures of bon and fuller's earth; intermediate adsorbents—calcolored substances can be separated by the technique cium carbonate, calcium phosphate, magnesia and
of adsorption chromatography. Even mixtures of com- slaked lime; weak adsorbents—sucrose, inulin, starch
pletely colorless compounds may be separated in this and talc.
Solvents. As already mentioned, adsorption depends
manner, but, as might be expected, the details of the
operation need to be modified, depending on the nature upon both the nature of the solvent and the adsorbent.
of the substances being handled. Some of these details In any given separation of a mixture of compounds
can best be treated under the headings of adsorbents, by the chromatographic procedure, it is likely that different solvents will be used for placing the solute on
solvents, and apparatus.
Adsorbents. There are several considerations which the column, developing the chromatogram, and eluting
govern the choice of adsorbent for a given chromato- the adsorbed materials. Although only one adsorbent
graphic separation. It should be insoluble in the sol- is ordinarily used for a given separation, there are
vents to be used for the separation, and it must neither cases where the simultaneous use of two or more adreact with the substances to be separated nor act as a sorbents is advantageous. In fact, in one of the excatalyst for their decomposition, rearrangement, or isom- periments which may be carried out today, the use of
erization. It should have a uniform composition, re- three different adsorbents—sucrose, calcium carbonate,
gardless of the source, and it should be colorless when and alumina—is required.
zones containing colored compounds are to be located
It is common practice to use a relatively nonpolar
visually.
solvent to place the mixture of compounds to be sepa35
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
36
ated on the column, then to use a somewhat polar solvent to develop the chromatogram and an even more
polar solvent to elute the adsorbed materials. Of course,
this is subject to wide variation, depending on the nature
portion to retain the adsorbent in the tube; and (2) a
filter flask. The tube may be connected to the filter flask
by means of a bored cork or a one-holed rubber stopper,
as shown in Figure 16a. A tube that is distinctly longer
Reservoir
r Solvent
or
L
Solution
Cork Stopper
^—Solution
— Sucrose
Paper
discs
C=5"::<l
ft=^0
Adsorbent—
-Adsorbent
rn
Sintered
glass disc
•v.3
'///\
.Glass Wool
plug
1> Joint
with hooks
and
rubber bands
-Calcium Carbonate
K
«—Alumina
/ C o t t o n plug
^-Copper gauze
(b)
FIG. 16. Chromatographic adsorption apparatus, (a) Apparatus for adsorption chromatography with removal of
products by elution. (b) Two-piece chromatographic
column which permits ready extrusion of the adsorbent,
(c) Adsorption apparatus with open-ended column for
extrusion of adsorbent.
of the mixture to be separated. An approximate order
of increasing polarity of common solvents is as follows:
petroleum ether, carbon tetrachloride, cyclohexane, carbon disulfide, ether, acetone, benzene, esters of organic
acids, chloroform, alcohols, water, pyridine, organic
acids, and mixtures of acids or bases with water, alcohol, or pyridine.1 In a representative chromatographic
separation process, the mixture may be placed on the
column as a solution in petroleum ether, the chromatogram developed with benzene and the different bands
eluted with ethanol. Of course, finer shadings of development and elution are attained by using appropriate
mixed solvents, such as petroleum ether-benzene,
benzene-ethanol, etc.
Apparatus. In its simplest form, the only two pieces
of apparatus needed for chromatography are: (1) a
length of glass tubing drawn out at the lower end, with
a plug of glass wool placed at the top of the constricted
1
Although the given order of increasing solvent polarities
does not correspond exactly to an order of either increasing
dielectric constants or dipole moments, common criteria of
the "polarity" of a solvent, it does give a good measure of
the increasing abilities of these solvents to elute adsorbed
compounds from a variety of adsorbents.
than its column of adsorbent may function as its own
reservoir, or an extra reservoir may be fitted to the
top of the tube.
Refinements in the apparatus might include a perforated porcelain or sintered glass disc sealed into, the
tube just above the constriction, the presence of a
stopcock in the drawn out portion of the tube just
above the segment that fits into the filter flask through
the stopper, and the use of ground glass joints throughout. If the column of adsorbent is to be pushed out of
the tube and cut into segments following the development of the chromatogram, it is desirable to use a tube
having no constriction; the glass wool plug and column
of adsorbent may be held in place by a copper gauze
folded over the bottom of the tube (Figure 16c) or
by the use of a two-piece column, equipped with ground
glass joints, in which there is a constriction and disc
in the lower portion and all of the adsorbent is held
in the upper portion (Figure 16b).
The sizes of chromatographic columns range from
those which are designed to contain about 20 micrograms of adsorbent to those which can hold 20 pounds
of adsorbent. The proportions of columns may vary
ADSORPTION CHROMATOGRAPHY
considerably, but a length:breadth ratio of 5:1 is
generally satisfactory. The ratio of adsorbent to material being adsorbed is always generous; it is not at all
uncommon to use about 50 g. of adsorbent per gram
of material being adsorbed. One of the most important
aspects of column chromatography is the packing of
the column. In order to give satisfactory results, the
adsorbent must be packed uniformly in the column,
air bubbles and channels being rigorously excluded.
There are several satisfactory methods for filling
chromatographic columns. One wet method consists of
filling the column with solvent and sprinkling in the
adsorbent, which is then allowed to settle until the
proper height has been built up. The glass wool (or
cotton) plug should be thoroughly wetted with solvent
before this procedure is initiated; otherwise air bubbles
form in the column. Another wet method consists of
preparing a slurry of solvent and adsorbent and pouring this into the column and allowing it to settle. If
the column contains a stopcock at the bottom, this can
be opened slightly during the settling process. The slow
flow of solvent through the column tends to increase
the uniformity of the packing process. Another useful
device is to place a rubber stopper over the end of a
glass rod, and then tap the stopper gently along the
walls of the chromatographic tube as the adsorbent is
settling.
A satisfactory dry method for packing a column involves the addition of sufficient adsorbent to fill 1-2 cm.
of the column and then tamping this down gently before
adding another like portion of adsorbent. A cork having a diameter slightly less than the inner diameter of
the tube serves as a convenient ramrod. The cork is
attached to a glass rod which is slightly longer than the
column. An even more simple way to attain uniform
packing is to add small quantities of adsorbent to the
tube and then to tap the bottom of the tube gently on
the laboratory bench. It is important that the top portion
of the adsorbent be level and remain so during the
development of the chromatogram. It is a good idea to
protect the surface by placing a disc of filter paper or
a J-cm. layer of filter-aid at the top of the column. Once
the column has been wetted, it should not be permitted
to become dry again, for this causes the adsorbent to
shrink away from the glass walls and to form channels.
37
1.
2.
3.
4.
5.
Carboxylic acids
Alcohols, amines, and thiols
Aldehydes, ketones and esters
Organic halides
Unsaturated hydrocarbons; the greater the degree
of unsaturation, the greater the adsorbability
6. Saturated hydrocarbons.
Chromatography of Colorless Substances
Although colorless compounds can form well defined
bands on a chromatographic adsorption column, special
methods must be employed in order to locate these
bands and to effect a clean separation of the components
of a mixture. The use of an ultraviolet lamp has proved
to be the most generally useful method for locating
bands of adsorbed material. Its use depends upon the
fact that many substances which are colorless in ordinary light show strong fluorescence in ultraviolet light.
When such compounds are adsorbed on a column, the
bands stand out strongly if the column is irradiated
with ultraviolet light in a partially darkened room. The
use of ultraviolet light is also advantageous when dark
adsorbents, such as activated carbon or fuller's earth,
are used. The zones of fluorescent materials in the
chromatogram are readily apparent under the ultraviolet
radiation. Relatively inexpensive ultraviolet lamps may
be purchased from a variety of chemical supply companies.
Colorless substances which are not fluorescent may
be detected in other ways. For example, a reagent with
which the adsorbed compounds form a color may be
painted as a streak up the side of an extruded column.
As an illustration of this technique, a dilute solution
of potassium permanganate may be painted up the side
of an extruded column on which two or more alkenes
have been adsorbed. Where the oxidant comes in contact with an alkene, the purple color disappears and
the brown color of manganese dioxide becomes apparent. The column can then be cut into appropriate
sections, the surface layer of oxidized alkene and manganese dioxide scraped off, and the alkene eluted from
the adsorbent.
Purely empirical methods can also be used to locate
the different fractions of an adsorbed mixture. For example, the column can be eluted with a series of solvents of gradually increasing polarity and the filtrate
(percolate) collected in small batches. Evaporation of
Adsorbability of Organic Compounds
the solvent from each of these fractions will give the
The adsorbability of organic compounds is primarily organic compound which has been eluted. After the
influenced by the nature and number of the polar groups compound has been identified by means of its melting
present in their molecules. It is not possible to provide point or some other property, it can be combined with
a list of relative adsorbabilities of the various classes identical material obtained from the neighboring fracof organic compounds that is applicable to all types tions.
of adsorbents and solvents, but the following series is
arranged roughly in the order of decreasing adsorbabili- Uses of Column Adsorption Chromatography
ties; i.e., the more strongly adsorbed compounds are
The use of adsorption chromatography which has
listed at the top.
been emphasized in the previous discussion has been
38
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
the separation of mixtures into the pure individual
components. However, there are other valuable applications of column chromatography. These include:
(1) the purification of compounds by removal of small
amounts of contaminants; (2) the determination of the
homogeneity of chemical substances; (3) the comparison of compounds thought to be identical; and (4)
the concentration of materials from dilute solutions
such as those obtained when natural products are extracted from the roots, bark, or leaves of a plant or
tree by extraction with a large volume of organic solvent.
Other Types of Column Chromatography
Column chromatography is not limited to adsorption
chromatography. Other methods in common use are
partition chromatography and ion exchange chromatography. In partition chromatography, separation of the
components of a mixture depends upon the faet that,
as a rule, different compounds distribute themselves in
different ratios (have different partition eoefflcients)
between two different solvents. The praettee of column
chromatography is much the same whether separations
are based on differential adsorption or on partition, In
the latter procedure adsorbent powers are replaced by
materials, such as silica gel or cellylose, which contain
significant amounts of bound water. The solvent used
in partition chromatography is usually one in which
water has a limited solubility and which itself is partially
soluble in water; n-butyl alcohol is frequently used as
the solvent.
When a mixture of compounds, such as the amino
acids obtained on hydrolysis of a protein, is dissolved in
the solvent and passed through the column, the components pf the solute distribute themselves between the
water in the stationary phase and the solvent, which
is the moving phase. The more hydrophilic components
of the solute are held more strongly on the column,
and the more lipophilic solutes come through the
column first. Paper chromatography represents a special
case of partition chromatography and is discussed further in Experiment 39, page 113;
As the name implies, ion exchange chromatography
makes use of special resins which, under appropriate
circumstances, have the power of replacing ions present
in a solution in contact with them by ions originally
a part of their own structures. The technique of column
ion exchange chromatography is very similar to that
used in differential adsorption or partition chromatography.
Background Material for Today's Experiments
Two separate experiments are presented as the assignment for today. It is recommended that half the
class perform one separation and half the other separation, provided that all of the required materials are
available. Alternatively, one experiment may be as-
signed to all of the students, and the second reserved as
a bonus experiment for the more advanced students.
In the first experiment any one of three pairs of
dyes are to be separated by chromatography. Activated
alumina is used as the adsorbent and 95 per cent ethanol
as the solvent for developing the chromatogram. By this
procedure, water-soluble fluorescein may be separated
from methylene blue, methyl orange from methylene
blue, or methyl orange from Victoria Blue B.
In the second experiment, the naturally occurring
pigments of fresh green leaves (for example, spinach
leaves) or of grass are to be extracted by a mixture
of petroleum ether, benzene, and methanol, and then
a petroleum ether-benzene concentrate of the pigments
is to be chromatographed on a column containing three
different adsorbents—sucrose, calcium carbonate, and
alumina (Figure 16c). After development of the chromatogram with petroleum ether-benzene, the following
bands appear on the column:
Top: olive-green (chlorophyll-b)
Upper middle: blue-green (chlorophyll-a)
Lower middle: yellow (xanthophylls)
Bottom: pink-orange (carotenes).
Experimental
I. SEPARATION OF DYESTUFFS
Procedure. Set up a column of the general type
shown in Figure 16a. The dimensions of the column
should be about 1.8 x 30 cm. Tamp a plug of glass
wool firmly into the constricted portion of the glass
tube and cover it with a layer of sand not more than
5 mm. thick. Tap the tube gently to level off the sand,
and slowly add, with continual tapping of the tube, an
intimate mixture of 28 g. of activated adsorption
alumina (Aluminum Company of America) and 2 g.
of Hyflo Super-eel (Johns-Manville).
Cut a piece of filter paper so that it has the same
diameter as the inner part of the glass tube and place
it on top of the adsorbent. Now wash the column with
95 per cent ethanol, and apply sufficient suction by
means of the water aspirator for the rate of flow of
solvent through the column to be about 15 drops per
minute. The 95 per cent ethanol is continually added
so that the top of the column never runs dry.
After the proper flow rate has been attained, allow
the solvent to come within about 1 mm. of the top of
the adsorbent, then add the dye solution all at once.
When the dye solution, in turn, gets within 1 mm. of
the top of the column of adsorbent, rinse the top part
of the tube with about 2 ml. of 95 per cent ethanol.
Carry out one of the following separations.
Separation of Water-Soluble Fluorescein and Methylene Blue. Pour a solution containing 5 mg. of watersoluble fluorescein and 5 mg. of methylene blue in 4 ml.
of 95 per cent ethanol into the column, and, after the
0-45
45-160
ADSORPTION CHROMATOGRAPHY
tube has been rinsed with 95 per cent ethanol, continue to add the same solvent until the band of methylene blue has separated from the tightly held band of
fluorescein. Add sufficient 95 per cent ethanol to elute
all of the methylene blue from the column. When the
eluate dropping into the filter flask is colorless, empty
the flask and begin to use water as the eluent. The
water-soluble fluorescein immediately migrates down
the column.
Separation of Methyl Orange from Methylene Blue.
Use a solution containing 1 mg. of methyl orange and
5 mg. of methylene blue in 2.2 ml. of 95 per cent
ethanol. Develop the chromatogram with 95 per cent
ethanol, and elute the methylene blue with the same
solvent. Use water to elute the methyl orange after all
of the methylene blue has passed into the filter flask.
Separation of Methyl Orange from Victoria Blue B.
Use 2.2 ml. of a 95 per cent ethanol solution containing 1 mg. of methyl orange and 5 mg. of Victoria
Blue B. Develop the chromatogram with 95 per cent
ethanol, and elute the Victoria Blue B with the same
solvent. Methyl orange again exhibits the stronger
adsorption affinity and remains near the top of the
column of adsorbent. Elute the methyl orange with
water after all of the Victoria Blue B has passed through
the column.
II. SEPARATION OF LEAF PIGMENTS
Procedure. Chop four spinach leaves or a handful of
grass into a fine mash, and soak the mash for 3 hours
in a mixed solvent consisting of 90 ml. of petroleum
ether (boiling point 60°-80°), 10 ml. of benzene, and
30 ml. of methanol.
While the mash is being extracted, assemble the apparatus shown in Figure 16c. Wire on the lower end
of the clean 20 x 1.7 cm. column a piece of clean
copper gauze, and push a small cotton plug to the bottom of the column. Prepare a slurry of 8 g. of adsorption alumina in 15 ml. of petroleum ether (boiling point
60°-80°) and pour this into the column (Note 1). Allow
the alumina to settle while you tap the tube continuously. Rinse down the inside of the tube carefully with
the same solvent, and, after the alumina has settled,
drop afitteddisc of filter paper on top of the adsorbent.
The presence of liquid above the adsorbent allows the
disc to settle properly without trapping air.
When the solvent level has fallen to within about
2 cm. of the top of the alumina, pour a slurry of 5.3 g.
of calcium carbonate in 30 ml. of petroleum ether into
the column. Tap the column, wash it down with fresh
solvent, and add a paper disc as before. Finally pour
into the column a slurry of 7 g. of powdered sucrose in
20 ml. of petroleum ether. Once again, tap the tube,
wash it down with solvent, and add a disc offilterpaper.
Fit the reservoir into the top of the column, and allow
petroleum ether to flow through the column as the
39
solution of leaf pigments is being treated so that it can
be added to the column. Do not allow the top of the
column of adsorbent to become dry.
Filter with suction the mixture of leaves or grass
and the ternary solvent, and wash the extract with four
50-ml. portions of water to remove the methanol. Dry
the solution over anhydrous sodium sulfate for about
15 minutes, filter the mixture, and concentrate the
filtrate to about 1 ml. in a partial vacuum. This can
best be accomplished by placing the filtrate in a large
filter flask, setting a solid rubber stopper in the mouth
of the flask, and attaching the side outlet of the flask
to the aspirator with heavy-walled rubber tubing. Then
heat the flask on the steam bath and shake it constantly
to prevent the solution from bumping.
Pour the concentrated solution of pigment onto the
chromatographic column and develop the chromatogram
with petroleum ether (boiling point 40°-60°) (Note 2).
Note the eventual appearance of four distinct adsorption
bands. The olive-green band of chlorophyll-b will be
found on the sucrose, the blue-green band of chlorophyll-a either on the sucrose or the calcium carbonate,
the yellow band of xanthophylls on the calcium carbonate, and the pink-orange band of carotenes on the
alumina.
After the chromatogram has been developed fully,
apply suction to the receiver and drain the column
nearly dry. Carefully push the column of adsorbents out
of the glass tube onto a sheet of paper with the aid of
a glass rod flattened at one end. Cut the colored bands
from the extruded column of adsorbents and elute each
with 10 ml. of a 2 per cent solution of methanol in
ether.
It is obvious that all of the operations described in
this section cannot be completed within 3 hours. However, if you can at least carry the operation to the stage
of development of the chromatogram, which you can
do in the allotted time only by preparing the solution
of leaf pigments and drying the adsorbents in advance
of the regularly scheduled laboratory period, you will
have learned the essential details of the chromatographic method.
NOTES
1. Some students report that they obtain better results
in this experiment when the column is packed with dry
absorbents rather than with slurries. When the dry adsorbents are employed, paper discs are not used to separate
the three different adsorbents. Instead, the tube is tapped
on the desk as each adsorbent is added, and, after all of
one variety has been put into the column, the material is
tamped lightly with a cork stopper attached to a rod before the next adsorbent is added. All 3 adsorbents should
be heated at 100° for several hours before being used.
2. At this point, the rate of flow of solvent out of the
column should be decreased to about 10 drops per minute.
40
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
QUESTIONS
1. If a mixture of naphthacene, anthracene, and naphthalene was chromatographed on alumina, then eluted,
which material would come through the column first?
Which last?
2. An unknown dyestuff is thought to be methylene
blue. How might its identity be verified by a procedure
making use of the chromatographic technique?
3. Suppose that an initial attempt to separate a particular mixture of organic compounds by chromatography
on calcium carbonate, with chloroform as the solvent,
failed. What steps might be taken to achieve satisfactory
results in subsequent runs; i.e., what changes in solvent
and/or adsorbent might prove helpful?
4. Define or describe each of the following terms: (a)
development; (b) elution; (c) percolation; (d) adsorption; (e) adsorbent; (f) micron; (g) filter-aid; (h) fluorescence; (i) resin.
5. What are some of the considerations that govern
the choice of adsorbent for a given chromatographic separation?
6. Describe two wet methods and one dry method for
filling a chromatographic column.
7. What are some of the methods used for the location of adsorption bands when colorless compounds are
subjected to chromatographic adsorption?
8. What are some of the applications of column adsorption chromatography?
9. What is an anion exchange resin? A cation exchange
resin?
10. What do the words "hydrophilic" and "lipophilic"
mean? Why are the more hydrophilic components of a
mixture held more tightly on a column of silica gel or
cellulose than are the more lipophilic components when
butanol is used as the solvent?
EXPERIMENT 8
Qualitative Tests for the Elements
Introduction
Fe++ + 2CN-->Fe(CN) 2
Principles of Organic Chemistry Analysis. In the
characterization of any unknown organic compound,
a knowledge of the elementary constituents is essential.
Before the usual qualitative tests can be applied, however, the elements must be converted from the covalent
form in which they usually occur in organic compounds
into ions or simple compounds for which routine tests
are available. The elements which commonly occur in
organic compounds along with carbon, hydrogen, and
oxygen, and with which we are primarily concerned,
are nitrogen, sulfur, and the halogens.
A preliminary ignition over a free flame of a 0.1 -g.
sample of the unknown in a crucible cover or on the
tip of a spatula is revealing. If the sample burns with
a luminous flame leaving little,1 if any, residue, the
unknown is almost certainly organic (contains carbon).
Evidence of water (usually in the form of condensed
vapor) confirms the presence of hydrogen. No test is
ordinarily made for oxygen.
A somewhat more refined adaptation of the oxidative
decomposition consists of heating a 0.1-g. sample of
the unknown with 1-2 g. of fine copper oxide powder
in a small test tube. Carbon is converted to carbon
dioxide, which can be detected by precipitation of
barium carbonate with a solution of barium hydroxide,
and hydrogen, to water, which condenses in the cool
portion of the tube.
The method for the detection of sulfur, nitrogen, and
halogens depends upon the fact that fusion of an organic
compound containing these elements converts them to
easily identifiable ions.
Na+ + Fe+++ + Fe(CN)2 + 4CN~ - •
NaFe^^Fe^ClSQe]
'
' ' '
'
[NaX
Detection of Sulfur, Nitrogen, and Halogens. Sulfur
is converted to sulfide ion, which forms a black precipitate of lead sulfide with lead acetate in a solution
acidified with acetic acid:
Pb++ + S- -» PbS (Black)
Nitrogen appears in the fusion product as cyanide
ion. Upon addition first of ferrous sulfate and then of
ferric chloride, both under controlled pH, the characteristic bright color of Prussian blue appears:
1
Metallic salts of organic acids leave a small amount of ash,
but are not confused with inorganic salts which, almost without exception, do not burn. Since the number of metallic elements commonly found in organic compounds is small, a few
simple tests, beginning with a flame test, on the residue will
usually reveal the nature of the metal present.
("Soluble" Prussian blue)
Halogens are converted in every case to the corresponding halide, which, upon addition of silver nitrate
solution, forms a precipitate of silver halide, insoluble
in nitric acid. Distinctions among chloride, bromide,
and iodide ions are made by the usual methods of
inorganic qualitative analysis.
The Beilstein Test. A preliminary test for the possible presence of halogen, called the Beilstein2 test,
can be made directly on the original unknown. In this
test, a small sample of the unknown is burned on a
previously ignited copper spiral in the oxidizing portion
of a hot flame. Any halogen present is converted to the
corresponding copper11 halide, which imparts a bluishgreen color to the mantle of the flame as it volatilizes.
The appearance of this color cannot be interpreted as
positive evidence of halogen, for the test is extremely
sensitive and minute traces of halogen-containing impurities will suffice to give the test.
In addition, some organic acids and some nitrogencontaining compounds, such as pyridine and quinoline,
produce the colored flame. However, unless the unknown is so volatile that it evaporates completely before
the wire can be heated sufficiently to effect decomposition, a negative test indicates the absence of any
halogen except fluorine (CuF2 is not volatile).
Experimental
Described below are the best simple procedures for
the ignition test, the sodium fusion, and the detection
of sulfur, nitrogen, and halogens. Perform each test
on a known sample (Note 1) containing all three,
until you obtain an excellent test for each. Then obtain
two unknowns from your instructor and ignite each and
test for sulfur, nitrogen, and halogens. Report for each
unknown the elements present and as much additional
information about the chemical nature of the unknown
as you can, on the basis of the tests. After your report
has been accepted, use the remainder of the period
to answer the questions at the end of this experiment.
Ignition Test. Place about 0.1 g. of the material on
a small crucible cover or on the tip of a spatula and
heat (use tongs for crucible cover) in the oxidizing
portion of a small flame. Observe the following phenomena: (1) melting, (2) character of the flame, (3)
2
Named after the discoverer Friedrich Konrad Beilstein
(1838-1906), who also compiled the first editions of the famous Beilstein Handbuch der Organischen Chemie.
42
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
evidence of water vapor, (4) residue left after heating
to red heat, and (5) reaction of residue with red litmus
and with hydrochloric acid.
The melting behavior indicates the possibility of making a melting-point determination on the sample. A
flame indicates that the compound is volatile or forms
volatile decomposition products, and a very sooty flame
suggests unsaturation (probably aromatic). Condensation of water vapor on a cool glass tube held above
the burning sample confirms the presence of hydrogen.
Finally, a residue indicates the presence of a metal,
an alkaline metal if the residue is basic to litmus and
a heavy metal if it is insoluble in hydrochloric acid.
The Sodium Fusion. (CAUTION! Sodium is dangerous and should be treated with respect. It should always
be handled with forceps, never directly with the fingers.
It should be dried with filter paper and cut with a sharp
knife or scissors. Sodium scrap or residues should be
destroyed by treatment with a large volume of ethyl
alcohol. Never allow sodium to come into contact with
water. The sodium fusion is sometimes accompanied
by a sharp report or explosion. Wear goggles or safety
glasses. Be certain that the fusion tube is not pointed
toward anyone.)
Place a piece of clean sodium the size of a small pea
(about 4 mm. in diameter) in a 150 x 12 mm. (5-inch)
Pyrex test tube that is held in a vertical position by
means of a clamp lined with asbestos sleeves. Heat
the lower part of the tube with a hot flame until the
sodium melts and sodium vapors rise about 3 cm. in
the tube. Then remove the flame and quickly but carefully allow 4 drops of the unknown (or about 0.2 g.
if it is a solid) to fall directly into the sodium vapor
without touching the sides of the tube. Then heat the
tube to redness for at least 1 minute and finally allow
it to cool to room temperature.
Add 3 ml. of ethyl alcohol dropwise, and break up
the charred solid with a stirring rod to be sure that all
unreacted sodium is destroyed. Then half-fill the test
tube with distilled water, boil gently for several minutes,
and,finally,filterthe hot mixture and retain the alkaline
filtrate as a stock solution for subsequent tests (Note 2).
The Sulfur Test. Acidify 2 ml. of the stock solution
with dilute acetic acid and add 5 drops of lead acetate
solution. A black precipitate of lead sulfide indicates
the presence of sulfur. The brown color of the liquid
may obscure the black of the precipitate, so, if you
are in doubt, filter.
The Nitrogen Test. To 3 ml. of the filtrate, add 5
drops of a fresh 5 per cent solution of ferrous sulfate
and 5 drops of a 10 per cent solution of potassium
fluoride (Note 3). Boil the resulting mixture gently for
5 seconds, allow the suspension of iron hydroxides to
cool, and then add 2 drops of a 5 per cent solution of
ferric chloride. Finally add sufficient dilute (25 per
cent) sulfuric acid to dissolve the insoluble iron hy-
droxides and to make the solution distinctly acid to
litmus.
If nitrogen (as cyanide ion from the fusion) is present,
a brilliant blue solution or suspension of Prussian blue
will appear. Formation of a greenish-blue color suggests that nitrogen is present but that the fusion was
incomplete.
The Test for Halogens. Acidify 3 ml. of the stock
solution with dilute nitric acid. If sulfur or nitrogen,
or both, are present, boil in a small test tube for 3-4
minutes to expel all hydrogen sulfide and hydrogen
cyanide. Add 4 or 5 drops of silver nitrate.
A white or yellow precipitate which darkens rapidly
upon exposure to light indicates the presence of halogen. If the precipitate is colorless and is soluble in
fresh concentrated ammonium hydroxide, it is silver
chloride. If it is pale yellow and difficultly soluble, it
is probably silver bromide. If it is bright yellow and
completely insoluble, it is silver iodide. When two or
three different halogens are present, standard methods
of inorganic qualitative analysis are used for their detection.
Carry out a preliminary test for halogen on a sample
of the original unknown as follows: make a small loop,
2 to 3 mm. in diameter, at one end of a piece of short
copper wire and insert the other end into a cork to
serve as a holder. Heat the coil in the hot portion of a
Bunsen flame until it imparts no color to the flame.
Allow the wire to cool, dip it into a small portion of
the original unknown, and heat in the edge of a Bunsen
flame. A green color indicates the probability of the
presence of halogen. If no green color is formed, no
chlorine, bromine, or iodine-containing compound other
than an extremely volatile liquid can be present.
NOTES
1. A 1:1 mixture of thiocarbanilide and p-chloroaniline
or p-dichlorobenzene makes a convenient "known" for
sulfur, nitrogen, and halogen tests.
2. With this procedure, the same test tube can be used
for many sodium fusions. It should be retained and used
only for this purpose, as it will soon become etched and
discolored.
3. Potassium fluoride increases the sensitivity of the
Prussian blue test. It forms an unusually stable complex
with ferric ion, thereby preventing the ferric ion concentration from reaching a level at which insoluble ferric
ferrocyanide, rather than the desired soluble Prussian blue,
would be formed, and also minimizing the formation of
ferricyanide ion.
QUESTIONS
1. In inorganic chemistry, detection of the elements
(usually in the form of ions) present in an unknown is
QUALITATIVE TESTS FOR THE ELEMENTS
almost always sufficient to provide complete characterization of an unknown. With organic compounds, this is not
the case. For example, how completely is a compound
characterized if it is shown to contain only carbon and
hydrogen? Or if, by quantitative analysis, it is shown to
contain 85.7 per cent carbon and 14.3 per cent hydrogen
by weight?
Of what value, then, is a qualitative and quantitative
elementary analysis in the characterization of an organic
compound?
2. Why must hydrogen cyanide and hydrogen sulfide be
expelled before a test is made for halide ion?
3. An unknown leaves a residue upon ignition. Predict
the solubility in ether and benzene of tne original unknown.
An aqueous solution of the residue turns red litmus
43
blue. Predict the solubility in water of the original unknown.
4. An unknown is found to contain carbon, hydrogen,
and oxygen only. Can the unknown be an amine or a
mercaptan? Name several additional homologous series
which are eliminated as possibilities.
5. What elements are found in organic compounds isolated from natural sources? What additional elements may
occur in synthetic compounds?
6. How can the presence of oxygen in an organic compound be proved?
7. Write a balanced equation for the oxidation of Z)-glucose, C 6 H 12 O e , with copper oxide.
8. Write equations for the reactions which can occur
between carbon dioxide and a solution of barium hydroxide.
EXPERIMENT 9
Preparation and Properties of Methane
o
Fuse
(A)
CH 3 —C-ONa + NaOH
(B)
CHCI3 + 3Zn + 3HOH -* CH4 +3Zn(OH)Cl
(C)
AI4C3 + 12HC1 -* 3CH4 + 4A1C13
Introduction. Methane is the simplest of all organic
compounds. It is the first member of the family of
hydrocarbons called the methane, paraffin, or alkane
series. In fact, all the other members of this series may
be considered as derivatives of methane in which one
or more of the methane hydrogen atoms have been replaced by alkyl groups.
Methane constitutes 50 to 97 per cent of natural gas
and is formed in nature by bacterial decomposition of
cellulose in the absence of oxygen.
In this experiment, you will prepare methane by
> CH4 + Na 2 C0 3
this experiment are characteristic of the alkanes as a
group.
A. Preparation of Methane by Pyrolysis
of Sodium Acetate
Mix thoroughly in a mortar 8.2 g. (0.1 mole) of
anhydrous (fused) sodium acetate (Note 1) and 10 g.
of soda lime (Note 2). Introduce the mixture rapidly
into a large (8-inch) test tube fitted with a rubber
stopper and glass delivery tube as shown in Figure
17a. Be sure to tilt the test tube downward so that
0-60
FIG. 17. Apparatus for the synthesis of methane, (a) By
pyrolysis of sodium acetate, (b) By reduction of chloroform, (c) By hydrolysis of aluminum carbide.
three simple laboratory methods: (a) the decarboxylation of acetic acid, (b) the reduction of a halogenated
methane (chloroform), and (c) the reaction of certain
metallic carbides, such as aluminum carbide, with an
acid. In nature, acetic acid is decarboxylated at room
temperature through the action of certain microorganisms.
O
CH3—C—OH -> CH4 + C0 2
In the laboratory, drastic conditions, such as the
pyrolysis of a salt of acetic acid, are required to bring
about the reaction.
The chemical properties observed for methane in
44
adsorbed water driven from the mixture upon heating
will not run back into the heated portion of the tube
and break it.
Heat the test tube on all sides with a free flame,
cautiously at first, and then more strongly, in order to
maintain a steady evolution of methane. (Hold the
burner in your hand and play the flame over the tube.)
After the air in the test tube has been displaced, collect (over water) 5 gas bottles of methane and store
the gas for later use by keeping the bottles inverted
over water. Always remove the delivery tube from the
water trough before discontinuing the heating.
Now test the methane as follows:
(a) Apply a flame to the mouth of one of the bottles
of methane. Observe the character of the reaction and
60-80
PREPARATION AND PROPERTIES OF METHANE
of the flame. Note any indication of the nature of the
products of the reaction. Record your observations.
(b) Allow a second bottle of methane to stand upright and uncovered for about 15 seconds. Again, apply a flame to the mouth of the bottle. Note the
character of the reaction and of the flame.
(c) Shake about 2 ml. of a 0.3 per cent solution of
potassium permanganate in a third bottle of methane.
Observe whether or not the permanganate color is discharged.
(d) To each of the remaining bottles of methane,
add 4 or 5 drops of a 5 per cent solution of bromine
in carbon tetrachloride. Stopper one of the bottles and
place it in your desk and leave the other in a bright
light (preferably sunlight). After a few minutes, observe
the results. Blow your breath across the mouth of each
of the bottles. Note and record any differences in the
two cases.
B. Preparation of Methane
by Reduction of Chloroform
Introduce 10 g. of zinc dust into a small round-bottomed flask mounted on a ring stand and add 10 ml.
of ethyl alcohol and 10 ml. of water. Fit the flask with
a rubber stopper and delivery tube for collection of
the gas over water (Figure 17b). Add to the mixture
5 ml. of chloroform and 1 ml. of a 10 per cent copper
sulfate solution (Note 3). The reaction may require
several minutes to start. If it becomes too rapid, cool
the flask in a pan of cold water. Collect two bottles of
the gas by upward displacement of air and two by
downward displacement. Test for methane in each bottle by methods suggested in A. Note and record the
results.
C. Preparation of Methane by Hydrolysis
of Aluminum Carbide
Place 8 g. of aluminum carbide in a 250-ml. distilling flask fitted with a dropping funnel and glass delivery
tube (Figure 17c). Drop a total of 20 ml. of dilute
hydrochloric acid (Note 4) upon the aluminum carbide
to generate the gas. Collect several bottles of the gas as
before. Run tests designed to show that the collected gas
has all the properties observed for methane in A.
D. Preparation of Absolute Ether
If each student is to prepare his own absolute ether
for Experiment 10 (see p. 46), use the remainder of
the period for this purpose.
NOTES
O
1. If the sodium acetate is hydrated (CH3—C—ONa*
3H 2 0), it must first be dehydrated. To do this, place about
45
15 g. of the hydrated crystals in an iron dish or porcelain
evaporating dish on a ring stand and heat directly with the
flame of a Bunsen or Fisher burner. (Goggles!) The salt
will melt almost at once. Continue to heat, stirring constantly with a glass rod; it is advisable to steady the dish by
holding it with tongs. As the water of crystallization is
driven off, the salt will resolidify. Heat further until the
anhydrous sodium acetate begins to melt, being careful not
to overheat, as indicated by darkening of the material. The
anhydrous salt should be gray in color and flaky. Finally,
weigh 8 g. of the fused salt for use.
2. Soda lime is a granular mixture of sodium hydroxide
and calcium oxide. It is much more easily stored and
handled in finely divided form than is sodium hydroxide
alone.
3. The zinc and copper sulfate react to form a zinccopper couple which is much more effective in the reduction than zinc alone.
4. This synthesis can be carried out as a simple hydrolysis, with water functioning as the acid in place of hydrochloric acid, but the reaction is then much slower and the
reacting mixture must be heated.
QUESTIONS
1. In the preparation of methane by pyrolysis of sodium acetate, why must the delivery tube be removed from
the water trough before the heating is discontinued?
2. Calculate the relative densities of methane and air.
If you were to collect methane by displacement of air,
would you use upward or downward displacement of air?
3. Write balanced equations for the combustion of
methane; the reaction of methane with bromine in the
light; the combustion of pentane; the reaction of pentane
with bromine in the light.
4. How can you magnify the effect observed when you
blow your breath across the mouth of a tube containing
methane and bromine?
5. Derive a generalized equation for the complete combustion of any alkane, CnH2n + 26. If you were trying to make a highly explosive mixture of oxygen and methane, approximately in what ratio
would you mix the gases?
What volume of oxygen would be required for the
complete combustion of 5 liters of methane? Of pentane?
7. What general name is applied to the reaction of
alkanes with halogens? What is the function of the light?
8. Can you explain why hydrochloric acid reacts more
rapidly with aluminum carbide than does water?
9. What volume of methane at standard conditions
could be obtained theoretically from 8.2 g. of sodium
acetate? This is called the theoretical yield for the reaction.
An actual yield of 1.12 1. of methane (standard conditions) would represent what percentage of the theoretical
yield? This value is called the percentage yield.
Construct an equation which shows how the percentage
yield for any reaction may be calculated.
10. Write a balanced equation for the synthesis of
ethane by each of the general methods illustrated in today's
experiment that is applicable.
EXPERIMENT 10
Preparation of Ethane by Means of the Grignard Reaction
CHsBr + Mg -> C2H5MgBr
QHsMgBr + H 2 0 -> CH3—CH3 + MgBr(OH)
Introduction. Perhaps the most versatile synthetic
reagents in all of organic chemistry are the alkyl magnesium halides, RMgX. This class of compounds has
been named the Grignard reagent, after the renowned
French chemist, Victor Grignard, who was awarded
the Nobel Prize in chemistry (1912) for his pioneer
work in this field. Grignard reagents have been used for
the synthesis of compounds of almost every homologous
series, and their use in research is widespread.
The synthesis of an alkane via the Grignard reagent
actually constitutes a two-step reduction of an alkyl
halide to an alkane. In the first step, the Grignard
reagent is prepared by the reaction of an alkyl halide
with metallic magnesium in anhydrous ether. In the
second step, the Grignard reagent is hydrolyzed to yield
the alkane and the basic magnesium halide.
In this experiment, the Grignard reagent you will
prepare and hydrolyze is ethylmagnesium bromide.
Preparation of a Grignard reagent is a critical test of
your experimental technique. If conditions are proper,
the reaction proceeds readily in good yield; if not, the
reaction may proceed sluggishly or not at all.
Grignard reagents react with compounds containing
even weakly acidic hydrogen to form the corresponding alkane. Ethylmagnesium bromide is frequently used
in a quantitative test to determine the amount of socalled "active" (weakly acidic) hydrogen present in
a compound (Zerewitinoff determination). The volume
of ethane liberated in reaction of ethylmagnesium
bromide affords a convenient measure of the amount
of active hydrogen present in the compound. Such
weakly acidic hydrogen as that present in water and
alcohols may be determined quantitatively in this
fashion.
ignite in air.) Cork the flask and allow it to stand for
1 hour with occasional shaking. Then distill on a steam
bath (or if an open flame is used, see Figure 21 for
precautions against fire) through a clean, dry condenser, transfer to a clean dry bottle, and store for at
least 24 hours over a few thin shavings of sodium or
a few lengths of sodium wire from a sodium press. It
is advisable to test the ether for gas evolution with
fresh sodium before use.
Preparation of Ethylmagnesium Bromide
Fit a clean, dry 250-ml. round-bottomed flask with
a dry condenser for reflux, using a clean, well-fitting
cork. Attach a drying tube with soda lime to the top of
the condenser (Figure 18a). Be certain that a brisk
Absolute Ether
[To have been prepared during previous period.]
The ether that is used in the preparation of the
Grignard reagent (ethylmagnesium bromide) must be
made absolute, i.e., free from both water and alcohol
(Note 1). In order to accomplish this (Note 2), shake
150 ml. of commercial ether with a cold solution of
20 g. of calcium chloride in 20 g. of water. Separate the
ether (top) layer from the water layer and dry the ether
for several hours (overnight) over 20 g. of calcium
chloride.
Decant the ether from the calcium chloride into a
250-ml. Erlenmeyer flask. Add 10 g. of phosphoric
anhydride. (Weigh the phosphoric anhydride rapidly,
as it readily absorbs moisture from the air, and handle
it only in glass apparatus, as it may cause filter paper to
FIG. 18. Apparatus for the preparation of ethane, (a)
For the synthesis of the Grignard reagent, (b) For the
hydrolysis of the Grignard reagent.
stream of cold water is circulating through the condenser.
At this point, complete the bending of all tubing
required for the hydrolysis of the ethylmagnesium
bromide as described in the next section (see Figure
46
0-90
PREPARATION OF ETHANE
47
18b) and extinguish all flames before proceeding. Then cylinder, carefully measuring the total volume of water
prepare an ice bath for use in case control of the re- required. This is, of course, the volume of ethane
action becomes necessary. Next place 1.9 g. (0.08 evolved as measured at the observed temperature and
mole) of magnesium turnings, a crystal of iodine, 15 ml. pressure. Convert this volume to standard conditions.
of absolute ether, and 6.5 ml. (9.5 g., 0.087 mole) of Now calculate the percentage yield. Record all of your
ethyl bromide directly into the flask and quickly re- data and calculations.
place the condenser. Force a brisk stream of cold water
from the tap through the condenser. More ether will
/
be added as the reaction begins, but at the outset the
NOTES /
concentration of the ethyl bromide is kept high to
1. The reaction is difficult to start in the presence of
promote easy starting.
Watch the mixture carefully. Sudden appearance of water or alcohol, and the yield is reduced materially.
2. The nearly anhydrous ether supplied by the Carbide
cloudiness in the liquid and ebullition at the surface
of the magnesium are signs that the reaction has begun. and Carbon Chemical Corporation is sufficiently anhydrous to be subjected to the treatment with metallic sodium
At this point, add an additional 15 ml. of absolute directly without prior processing.
ether through the top of the condenser. (If you have
difficulty in initiating the reaction, warm the outside of
the flask with your hand and swirl the flask gently.
QUESTIONS
If necessary, scratch one of the magnesium turnings
against the side of the flask with a glass stirring rod
1. What effect would the following have on the calcuand add an extra crystal of iodine.)
lated percentage yield:
(a) Failure to correct the ethane volume for the effect
Once the reaction has begun, allow it to proceed
under as lively reflux as can be accommodated by the of water vapor?
(b) Entrainment in the ethane of ether vapor which is
condenser. If reflux is too vigorous, it may be necessary
carried
over to the collecting bottle?
to cool the flask for a moment by means of the ice
(c) Loss of ethane because of loose fittings?
bath. When spontaneous reflux ceases, reflux on a steam
(d) Weighing of 1.4 instead of 2.4 g. of magnesium?
or water bath for about 25 minutes. The reaction is
2. Assuming that a drop of water weighs 0.05 g., what
complete when only a few small remnants of mag- volume of ethane measured at standard conditions should
nesium or magnesium contaminants remain.
be evolved for each drop of water added as long as excess
Grignard reagent remains? What volume as measured in
Preparation of Ethane by Hydrolysis
your experiment?
of the Ethylmagnesium Bromide
3. Write balanced equations for the reaction of ethylInsert in the top of the condenser a well fitting, two- magnesium bromide with ammonia; methyl alcohol
holed rubber stopper fitted with a 125-ml. dropping (CH3OH); acetic acid (CH3COOH); hydrogen sulfide.
funnel and a delivery tube leading to a deep pneumatic On the basis of electronic structure, account for the reaction of the Grignard reagent, RMgX, with compounds contrough (Figure 18b). Prepare in the pneumatic trough taining
even very weakly acidic hydrogen.
an inverted, water-filled, 2000-ml. wide-mouth bottle
4. Can you propose a possible mechanism for the catafor collection of a gas by displacement of water.
lytic action of iodine in the preparation of the Grignard
Place the reaction flask in the ice bath and wait reagent?
until temperature equilibrium is established. Be certain
5. A compound has the molecular formula C4H10O2.
that there is a brisk flow of cold water through the Reaction of 0.45 g. of the compound with excess ethylcondenser. Then by means of the dropping funnel add magnesium bromide affords 253 ml. of ethane as meas(DROPWISE!) a total of 20 ml. of water (or until ured over water at 20° and a pressure of 740 mm. of
ethane evolution ceases), collecting the evolved ethane mercury.
What statements can you make about the hydrogen
in the 2000-ml. bottle. Read the temperature of the
atoms in the compound?
water and the barometric pressure. Then adjust the
6. How does the over-all transformation effected in the
height of the collecting bottle so that the water level preparation of an alkane from an akyl halide via the
inside the bottle is equal to that outside, place a watch Grignard reagent compare with that accomplished in the
glass firmly at the mouth, and invert the bottle.
reduction of an alkyl halide by means of zinc dust and
Fill the bottle with water by means of a graduated water?
EXPERIMENT 11
I. Properties of Kerosene
II. Assemble Apparatus for Experiment 12
and record the solubilities as very soluble, slightly
soluble, or insoluble.
Introduction. Most petroleum products are not pure
compounds but are mixtures obtained as a certain
fraction collected over a particular temperature range
in the fractional distillation of petroleum. This is the
case for kerosene, which consists largely of a mixture
of alkanes in the C12 to Cie range. Kerosene is used
as a fuel for oil stoves and in Diesel engines and tractors. As homologs of methane, the hydrocarbons which
make up kerosene exhibit the same general chemical
properties as does methane; some of these are more
easily studied for the liquid kerosene than they are
for the gas methane. Several of those investigated in
today's experiment will explain how the name paraffin
("little affinity") came to be applied to members of
this series.
[The study of kerosene will require only about half
of the period. The other half is to be spent in assembling
the apparatus to be used in the synthesis of ethylene
bromide (Experiment 12).]
I. PROPERTIES OF KEROSENE
0-30
60-75
D. Substitution Reaction on Kerosene
Add 3 ml. of kerosene to each of two test tubes.
Then pour into each enough bromine in carbon tetrachloride solution to give the mixture a pronounced
bromine color. Insert a cork into each test tube. Place
one in a dark cupboard or drawer at once, the other
in direct sunlight or in the light of a 200-watt bulb.
After 3 minutes, compare the two mixtures as to color
and effect on moist litmus paper.
75-90
II. ASSEMBLE APPARATUS FOR EXPERIMENT
A. Distillation of Kerosene
12
QUESTIONS
Place 15 ml. of kerosene and 2 boiling chips in a
small distilling flask clamped to a ring stand and supported by a wire gauze on a ring. Attach to it a condenser fitted with a curved adapter leading into a small
receiving flask. Heat the distilling flask gently with a
free flame so that the kerosene distills at the rate of
1-2 drops per second. Record the distillation range.
All the tests described below should be run on the
distillate.
30-60
C. Reactivity of Kerosene toward Sodium Hydroxide
and Potassium Permanganate
Add 5 drops of kerosene first to 3 ml. of dilute
sodium hydroxide solution and then to 5 drops of
aqueous potassium permanganate in separate test tubes.
Shake vigorously and inspect each mixture carefully
for evidence of reaction.
B. Solubility of Kerosene
Test the solubility of the distilled kerosene in water,
ether, ethyl alcohol, ligroin, concentrated sulfuric acid,
and concentrated nitric acid. In each case, place 5
drops of kerosene in a small, dry test tube and add the
specified solvent dropwise until complete solution occurs or until a total of 3 ml. has been added. Observe
48
1. What distillation range did you observe for the kerosene sample?
What is the distillation range for a typical sample of
gasoline? When your grandfather was a boy, almost every
state in the United States had a law in the books imposing
severe penalties for the adulteration of kerosene with gasoline. Can you explain why?
Is the exact method used for distillation of the kerosene
suitable for the distillation of gasoline? Of petroleum
ether? Explain.
2. What is the behavior of alkane hydrocarbons toward
each of the following at room temperature: (a) concentrated sulfuric acid; (b) concentrated nitric acid; (c)
aqueous potassium permanganate; (d) dilute sodium hydroxide solution?
3. Do the alkane hydrocarbons have any significant acid
or basic character in a broad sense? Explain.
4. Write a balanced equation for the reaction of a typical constituent of kerosene with bromine in the light.
EXPERIMENT 12
Ethylene and Ethylene Bromide
H2S0<
CH3—CH2OH - 160<
— * CH 2 =CH 2 + H 2 0
CH 2 =CH 2 -|- Br2
Introduction. Complete dehydration of alcohols
(elimination of one molecule of water from*one molecule
of alcohol) constitutes a simple laboratory method for
the preparation of alkenes. The dehydration may be
effected by heating of the alcohol in the presence of
an acid catalyst. For a single batch operation, it is
most convenient to heat the alcohol in a flask with a
nonvolatile protonic acid, such as sulfuric or phosphoric
acid.
-> BrCH2—CH2Br
can be passed through it at 350°-400°. The alkene
product, together with water, is collected in suitable
condensers connected to the column. The yield of alkene is, in general, considerably higher in this process
than for the protonic acid catalytic reaction, where partial dehydration of the alcohol (elimination of one molecule of water between two molecules of alcohol) to form
an ether is an inevitable and troublesome side reaction.
When sulfuric acid is used as the catalyst, the hot
FIG. 19. Apparatus for the synthesis of ethylene and of
ethylene bromide.
The relative ease of dehydration of alcohols is tertiary
> secondary > primary. Primary alcohols, such as
ethyl alcohol, are dehydrated only at elevated temperatures. Many tertiary alcohols, on the other hand, are
dehydrated by acids even at room temperature. This
fact must be borne in mind whenever an attempt is
made to carry out other reactions on tertiary alcohols
in the presence of strong acids.
For continuous or repeated batch operation, it is
timesaving in the long run to use a column packed
with coarse granules of the Lewis acid catalyst activated
alumina1 and heated so that the vaporized alcohol
concentrated acid also oxidizes some of the organic
material. The acid is reduced to sulfur dioxide, which
can often be recognized by its odor as a contaminant of
the olefin product.
As a by-product of the cracking still, ethylene is an
inexpensive and tremendously important raw material.
Its usefulness depends largely upon the ease with which
it undergoes addition reactions to form products of
great commercial importance. The addition of bromine
to ethylene is selected as a typical addition reaction of
the olefin.
1
Activated alumina is aluminum oxide which has been
treated so that it has an optimum porosity and an optimum
amount of water for maximum activity as a dehydration catalyst.
A. Ethylene Bromide
Assemble the apparatus as shown in Figure 19. The
generator should be a 2000-ml. round-bottomed flask,
49
0-120
50
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
the wash bottles and the Erlenmeyer flask at the end of
the train 250 ml. in size, and the safety tube about 2 ft.
long. Use rubber stoppers throughout the entire assembly and be sure that all connections are tight.
Fit the generator flask, by means of a three-holed
rubber stopper, with a thermometer, delivery tube, and
dropping funnel. Be certain that the end of the thermometer bulb extends to within 2 inches of the bottom
of the flask. If necessary, extend the dropping funnel by
attaching a glass tube, preferably one that is constricted
slightly at the tip, to it by means of a rubber sleeve.
Be certain that the two sections of glass from the
dropping funnel and extension tube meet within the
sleeve. Adjust the height of the dropping funnel so that
the rubber sleeve is located in the neck of the generator
flask when the rubber stopper is inserted.
Make smooth, strong bends in the glass tubing and
fire polish the ends of each piece of glass by heating in
the hot portion of a Bunsen flame. When inserting glass
tubing into rubber stoppers, always use glycerol liberally as a lubricant and protect each hand by means
of a towel. Note carefully how far each tube extends
into the wash bottles, test tube, and Erlenmeyer flask.
Fill each wash bottle about one-third full and the
safety bottle to a height of 2 cm. with 10 per cent
sodium hydroxide solution. Extend the safety tube into
the solution at least 1 cm. Add about 150 ml. of 10 per
cent sodium hydroxide to the Erlenmeyer flask following the test tubes in the train. Mount the generator flask
securely over a wire gauze on a ring stand with the
neck of the flask carefully clamped to the stand.
After the entire apparatus has been assembled, remove the rubber stopper from the generator flask and
cautiously charge the flask directly with 40 ml. of ethyl
alcohol, 80 ml. of concentrated sulfuric acid, and 3 g.
of diatomaceous earth or other finely divided siliceous
earth (Note 1). Then replace the stopper, making sure
that it fits tightly. From the bromine bottle in the hood,
measure 13 ml. (40 g., 0.25 mole) of bromine and
divide it approximately equally between two 8-inch
test tubes. Do not allow the bromine vapor to escape
into the laboratory (Note 2). Cover the bromine in
each tube with 5 ml. of water, place the tubes in a large
beaker containing water with a small amount of ice,
and insert the rubber stoppers bearing the bent glass
tubes as shown in Figure 19.
Now transfer the bromine tubes to the laboratory
desk and connect the second tube as shown in Figure
19 with a 250-ml. Erlenmeyer flask which contains 10
per cent sodium hydroxide solution for the absorption
of any escaping bromine vapors. The tube leading into
the flask should be inserted through a cotton plug and
should terminate about 1 cm. above the surface of the
solution. In the bromine tubes, it is critical that the
inlet tubes extend below the surface of the bromine
itself.
Arrange the trough for the collection of 4 bottles of
ethylene. Heat the generating flask strongly on the wire
gauze until the evolution of gas begins. This occurs at
about 160°, but a smooth evolution of gas is more important than the exact temperature, which will vary
somewhat with the mesh of the siliceous earth. Avoid,
however, heating above 200°.
When the air has been expelled from the apparatus,
collect 4 bottles of ethylene by displacement of water
for use in Section B. Store the ethylene by placing the
filled bottles mouth down in the trough. When all the
bottles are full, quickly disconnect the apparatus at A,
set the trough and bottles aside, and connect the bromine tubes of either type shown into the train. Allow
the ethylene to bubble through the bromine, with occasional shaking of the bromine tubes, until the bromine
color is discharged. This operation will require about
40 minutes.
[While it is in progress, you may make the short tests
in Section B.]
During this period, be sure that a steady and continuous flow of ethylene is maintained and shake the bromine tubes occasionally. It may be necessary to replenish the generator flask by adding through the dropping funnel a cooled solution of ethyl alcohol—sulfuric
acid (prepared by adding 20 ml. of concentrated sulfuric acid to 20 ml. of ethyl alcohol with stirring and
cooling by means of an ice bath).
When the decolorization of the bromine is complete,
disconnect the tubes containing the ethylene bromide
from the rest of the train and allow the generator flask,
still connected to the wash bottles, to cool. Then wash
the cooled contents of the flask down the sink with liberal quantities of water.
Transfer the contents of the test tubes (ethylene bro- 120-150
mide and water) to a small separatory funnel. Wash
the ethylene bromide once with 50 ml. of water. To
accomplish this, add the water to the funnel, stopper
the funnel, invert carefully, and open the stopcock momentarily to relieve any pressure which may develop.
Shake, gently at first, stopping to open the stopcock at
frequent intervals. Finally shake vigorously, then mount
the separatory funnel on a ring stand, and carefully tap
off the ethylene bromide into a small Erlenmeyer flask,
separating it cleanly from the water layer. Discard the
water layer by pouring it out of the top of the funnel,
thus keeping the aqueous layer from the stem of the
funnel where it could contaminate the ethylene bromide.
Repeat the washing process with 50 ml. of cold 10
per cent sodium hydroxide solution, and finally with a
second 50-ml. portion of water, separating the layers
carefully in each case. Drain off the ethylene bromide
layer from the final washing into a small Erlenmeyer
flask, and add 1-2 g. of granular anhydrous calcium
chloride.
Stopper the flask and set it aside, except for occasional shaking, while you clear away the apparatus on
ETHYLENE AND ETHYLENE BROMIDE
the desk and fit a small distilling flask with a dry thermometer and a dry water-jacketed condenser for final
distillation of the product. Use tightfitting rubber stoppers. Be certain that the top of the thermometer bulb
extends just to the lower end of the side arm of the
distilling flask and that the end of the side arm extends
into the condenser at least a centimeter beyond the
end of the rubber stopper.
When the ethylene bromide is dry, as indicated by
absence of turbidity, decant it from the calcium chloride (Note 3) into the distilling flask, and clamp the
distilling flask to a ring stand over a wire gauze mounted
on a ring.
Distill the ethylene bromide slowly, with a slow
stream of water passing through the condenser, collecting the portion boiling at 127°-135° separately in a
tared flask. If any lower boiling material is obtained,
you may dry it over fresh calcium chloride and redistill
it, adding the fraction boiling at 127°-135° to the main
portion, in order to improve your yield. Weigh your
ethylene bromide and calculate the percentage yield.
Record your results and submit your product in a properly labeled bottle to your instructor.
100-120 B. Properties of Ethylene
a. Flammability. Test the flammability of ethylene
by bringing a flame to the mouth of one of the bottles.
You can keep the ethylene burning steadily at the
mouth of the bottle by pouring water into the bottle
while the gas is burning. Note whether or not the flame
is luminous. Record all observations and results.
b. Explosive Properties. Remove one of the bottles
of ethylene from the trough, hold its mouth down for
15 seconds, and then bring a flame to the mouth. Note
the results.
c. Baeyer's Test for Unsaturation. To the third bottle
of ethylene add 2 ml. of 0.3 per cent potassium permanganate solution and shake. Observe the results.
d. Reaction with Iodine. To the final bottle of ethylene, add 2 drops of alcoholic iodine solution and shake
vigorously. Note the results.
150-170 C. Regeneration of Ethylene from Ethylene Bromide
Place 3 g. of granular zinc in a hard glass test tube
fitted with a delivery tube for collection of a gas over
water. Add a mixture of 3 ml. of ethylene bromide and
3 ml. of n-amyl alcohol. Heat the tube gently to start
the reaction and, after the air has been driven from the
apparatus, collect several small bottles of the gas. Devise and conduct tests designed to reveal the identity of
the gas. Record the results.
NOTES
1. The acid-catalyzed dehydration of olefins is promoted by many finely divided insoluble siliceous materials,
such as kieselguhr, fuller's earth, diatomaceous earth, and
powdered pumice.
51
2. Procedures for safe handling of bromine vary somewhat among different laboratories. Ask your instructor for
the procedure to be followed. If bromine should accidentally be spilled on the hands, wash at once with water and
then with alcohol. Apply moistened sodium bicarbonate
and glycerol to the area. Minor burns may not require
further treatment, but report the accident to the instructor
in any case.
3. If considerable ethylene bromide is occluded by the
calcium chloride, shake the calcium chloride with a few
ml. of chloroform, allow it to settle, and decant the chloroform solution into the distilling flask.
QUESTIONS
1. What could be used in place of sulfuric acid in the
generating flask?
2. What is the purpose of the wash bottles?
3. What is the function of the safety tube?
4. What size distilling flask did you use for the distillation of the ethylene bromide? Why?
5. Did you observe any by-product in the preparation
of ethylene? How do you account for its formation?
6. If you could not complete the entire experiment on
the preparation of ethylene bromide in one period, at what
stage would you interrupt it?
7. What effect would each of the following have on
the observed yield of ethylene bromide?
(a) Allowing the bromine to become too warm.
(b) Use throughout the experiment of equipment
which is much larger than necessary.
(c) The use, by mistake, of only 20 g. of bromine.
(d) Distillation of the ethyl bromide directly from the
calcium chloride.
(e) Extremely rapid bubbling of the ethylene through
the bromine.
(f) Loss of ethylene through a leak in the system.
8. Why is chloroform preferred to ether as a solvent
for removing occluded product from a desiccant?
9. Explain exactly how the various steps in the purification and isolation of the ethylene bromide are designed
to eliminate all possible contaminants.
10. Write balanced equations for the complete and the
partial combustion of ethylene.
11. Compare ethylene with methane in the following
respects: (a) nature of the flame when the gas is burned;
(b) reaction with bromine; (c) reaction toward aqueous
potassium permanganate. Write balanced equations for the
reactions involved in (b) and (c).
12. Write balanced equations to show exactly how the
addition of halogens to alkenes differs from the substitution of halogens in alkanes.
13. Assume that you had two bottles, each containing a
colorless gas, one methane and one ethene, from which the
labels were lost. How could you determine which bottle
contained methane and which contained ethene? Write
balanced equations for all reactions involved.
14. (For Specially Interested Students) Calculate the
percentage increase in volume which occurs in the quantitative conversion of bromine to ethylene bromide. If you
used 100 g. of bromine in the synthesis, what would be
the preferred size of the separatory funnel to be used in
washing the product?
EXPERIMENT 13
The Amylenes: 2-Methyl-2-Butene and 2-Pentene
CH3
CH3
H2S04
CH3—CH2—C—CH3 -—> CH 3 —CH=C—CH 3 + H 2 0
100'
OH
H 2 S0 4
CH3—CH2—CH2—CH—CH3 —-> CH 3 —CH 2 —CH=CH—CH 3 + H 2 0
100*
OH
Introduction. Amylene is a generic term applied to
the alkenes of formula C5Hi0. All of the amylenes are
well known, readily available compounds. In this experiment, you will prepare two of the amylenes from
common amyl alcohols, f-amyl alcohol (2-methyl-2butanol) and s-amyl alcohol (2-pentanol).
Each of the two dehydration reactions theoretically
could proceed in two ways to give two products, but the
major product obtained in each case is that represented
by the equation. This is in keeping with the general rule
that in the acid-catalyzed dehydration of alcohols which
can give rise to two isomeric olefins, the hydrogen atom
will be removed from the adjacent (to the —OH bearing carbon) carbon atom which bears the fewer hydrogen atoms to give the more highly branched olefin. The
greater ease of dehydration of tertiary vs. secondary
alcohols is here illustrated by the fact that less concentrated sulfuric acid is required to dehydrate f-amyl
alcohol than j-amyl alcohol.
The amylenes add bromine vigorously and with the
evolution of considerable heat. You should consider this
fact in planning an experimental procedure for the
addition of bromine to either 2-methyl-2-butene or
2-pentene. The acid-catalyzed addition of water to each
of these olefins follows the direction predicted for normal addition of unsymmetrical reagents to unsymmetrical alkenes.
0-100
A. 2-Methyl-2-butene
[Prepare reagents and apparatus for C and D.]
Transfer the cooled product to a small separatory funnel and add 15 ml. of cold 10 per cent sodium hydroxide solution. Invert the funnel, open the stopcock to
release the pressure, then close the stopcock and shake
vigorously, stopping occasionally to release the pressure.
Tap off and discard the lower aqueous layer and pour
the alkene through the mouth of the separatory funnel
into a small, dry, Erlenmeyer flask. Add about 2 g. of
anhydrous calcium chloride and allow the flask to stand
with cooling and occasional shaking. When the hydrocarbon is dry, as indicated by absence of turbidity,
transfer it into a small distilling flask fitted with a thermometer, and a dry condenser attached as before to a
curved adapter. Distill over a water bath collecting the
fraction boiling at 37°-43° in a small tared collecting
bottle packed in ice. Pure 2-methyl-2-butene is reported
to boil at 38.5° at 760 mm. Record the data and calculate the percentage yield.
NOTES
1. For efficient heating it is advisable to wrap a towel
around the flask and extend the towel over the top of the
steam bath. Escaping steam is then used effectively to heat
the flask.
2. The amylenes are all low boiling and highly flammable, so efficient condensation is critical.
3. This requires about 25 minutes if heating is efficient.
Prepare a 2:1 sulfuric acid mixture by adding cau- B. (Alternative Procedure) 2-Pentene
tiously, in small portions, 27 ml. of concentrated sulfuric acid to 54 ml. of cold water in a 200-ml. roundFollow the procedure described in A exactly except to
bottomed flask. Cool the flask by swirling it gently in substitute 54 ml. of s-amyl alcohol for the f-amyl alcoan ice bath or a stream of cold water between each addi- hol and to use 1:1 sulfuric acid prepared by adding 54
tion. Then add 54 ml. (44 g., 0.50 mole) of f-amyl ml. of water to 54 ml. of concentrated sulfuric acid.
alcohol with cooling and shaking. Mount the flask over Collect the fraction boiling at 34°-41°. Pure 2-butene
a steam bath (Note 1) on a ring stand and attach it to boils at 36.5° at 760 mm.
an efficient condenser arranged for distillation. Fit the
condenser with a curved adapter which leads through C. Hydration of the Amylene
a cotton plug into a 250-ml. Erlenmeyer receiving flask
Add 2 ml. of concentrated sulfuric acid to 2 ml. of
packed in ice (Note 2).
Heat the flask strongly with steam until alkene is no water in a test tube and cool in ice. Then add 4 ml. of
your amylene and shake vigorously with cooling. If a
longer obtained in the distillate (Note 3).
52
0-100
100-120
THE AMYLENES: 2-Methyl-2-Butene and 2-Pentene
layer of the alcohol does not appear, saturate the solution with sodium chloride to salt out the alcohol. Observe the properties of the alcohol and compare it with
the alcohol from which you prepared the amylene.
120-170 D. Amylene Bromide
Now weigh the remaining amylene and from it prepare the corresponding bromide by the addition of bromine. Devise your own experimental procedure in detail, keeping in mind the obnoxious odor and hazards of
bromine and the fact that the reaction is a vigorous one.
Obtain approval of your procedure from your instructor
before you begin. Report the yield and physical constants of the dibromide exactly as you observe them.
53
QUESTIONS
1. Write structural formulas for all of the possible
amylenes. Indicate for each the alcohol from which that
isomer could best be prepared.
2. Write equations for the hydration of 2-methyl-2butene and 2-pentene. What is the function of the sulfuric
acid?
3. List the various isomeric amyl alcohols, as completely as you can, in order of decreasing ease of dehydration.
4. The cycle alkene -* dibromide -> alkene is frequently
carried out in research for very good reasons. Can you
suggest two?
5. List your reasons for carrying out the addition of bromine to your amylene and isolating the dibromide by the
exact procedure which you used.
EXPERIMENT 14
Preparation and Properties of Acetylene
CaCs + 2 H 2 0 -> H G = C H + Ca(OH) 2
Introduction. Acetylene is the first and only commercially important member of the alkyne series of hydrocarbons. In general, alkynes may be prepared conveniently by any of three general methods:
1. Alkylation of acetylene or of a monoalkylated
acetylene by reaction of an alkylating agent (alkyl halide or sulfate) with the sodium salt.
RX + N a C ^ C H -» R C = C H
R'X + R C ^ C N a -> R C ^ C R '
2. Elimination of 2 moles of hydrogen halide from a
suitable dihalide with potassium hydroxide or sodamide.
or
or
RCHX—CHXR'
+ 2KOH ->
RCH2—CX2R'
R _ C = C — R ' + 2KBr + 2H 2 0
RCX2—CH2R'
3. Elimination of 4 halogen atoms, two from each
of two adjacent carbon atoms, from a tetrahalide, by
means of zinc.
(in alcohol)
RCXr -CX2R' + Zn
• R C ^ C R ' + 2ZnX2
These methods are applicable to the preparation of
acetylene, but, as one of the most important intermediates in the chemical industry, acetylene is produced much more cheaply by the hydrolysis of calcium
carbide.1 The hydrolysis may be viewed simply as a
protolysis reaction in which a weak diprotic acid (acetylene) is formed from its conjugate base (acetylide ion)
which accepts 2 protons from a stronger acid (water).
In this sense, calcium carbide is a salt of the very weak
acid acetylene and should properly be called calcium
acetylide.
Acetylene is most conveniently prepared in the laboratory by the calcium carbide method. The product
is contaminated with traces of hydrides of phosphorus,
arsenic, and sulfur, which give it the characteristic odor;
pure acetylene is practically odorless.
In this experiment, you will prepare acetylene by the
carefully controlled hydrolysis of calcium carbide and
study some of its properties. Today's assignment completes our laboratory study of alkanes, alkenes, and
alkynes and therefore marks an especially appropriate
time for a review drill on aliphatic hydrocarbons.
0-50
Preparation of Acetylene
Fit a dry 100-ml. distilling flask with a cork carrying
a small dropping funnel and clamp the flask securely
on a ring stand. Attach to the side arm a delivery tube
1
Calcium carbide itself is manufactured by the reaction of
calcium oxide with coke at temperatures of 2000° in an electric furnace.
54
arranged for collection of the acetylene over water. Add
10 g. of calcium carbide in the form of small lumps to
the flask and 20 ml. of water to the dropping funnel.
Insert the cork tightly into the distilling flask. Check to
be certain that there is no flame within 8 ft. of your
acetylene generator (Note 1). Then allow the water to
flow slowly, drop by drop, onto the calcium carbide.
As soon as a sample of the gas collected over water
in a test tube (Note 2) burns quietly when ignited,
collect five full 100-ml. wide-mouth bottles of acetylene.
In a sixth bottle displace approximately 1/20 its volume of water. Then bubble acetylene into 5 ml. of benzene in a test tube for 2 minutes. Stopper the solution
for later study. Finally, allow a slow stream of acetylene
to bubble into 5 ml. of concentrated sulfuric acid in a
small test tube. Note whether or not it dissolves.
Properties of Acetylene
a. Flammability. Ignite a bottle of acetylene, under
a hood if possible; in order to keep the gas burning
smoothly, pour a stream of water into the bottle while
the gas burns. Note the character of the flame. Record
all of your observations.
b. Reaction with Bromine. In the hood, add 2 drops
of bromine to a second bottle of acetylene and shake
vigorously for a minute. Note the result. Examine the
contents of the bottle for evidence of chemical change.
Compare the behavior of acetylene with that of methane
and ethylene.
c. Baeyer Test for Unsaturation. Test the action of
potassium permanganate on acetylene by adding a few
ml. of a 0.3 per cent solution to the third bottle of
acetylene. Observe the result. Test the material in the
bottle with litmus paper.
d. Acidity of Acetylene. To the benzene solution of
acetylene, add a small piece of sodium about half the
size of a pea. Observe the results. Transfer the material
to a watch glass and allow the benzene to evaporate.
Examine the residue. Add a few drops of water to it
and observe the results. Test the solution with litmus
paper.
e. Reaction with Ammoniacal Cuprous Chloride.
Add 2 ml. of ammoniacal cuprous chloride solution to
a fourth bottle of acetylene. Note the formation of red
cuprous acetylide. Remove the precipitate rapidly by
filtration and heat it cautiously (Note 3) on a spatula.
/. Reaction with Ammoniacal Silver Nitrate. Add 3
ml. of ammoniacal silver nitrate solution to a fourth
bottle of acetylene. Note the formation of a white precipitate of silver acetylide. Remove the precipitate rapidly by filtration and heat it cautiously (Note 3) on a
spatula.
50-80
PREPARATION AND PROPERTIES OF ACETYLENE
g. Explosion with Air. Remove the sixth, partially
filled bottle from the collecting trough, allowing air
to displace the water. Then ignite the mixture. Note the
character of the reaction and of the products.
NOTES
1. Acetylene-air mixtures are explosive over a wide
range—from 2.5 to 80 per cent of acetylene in air. For
methane the explosive range is from 5.3 to 14 per cent
methane and for ethylene 3.0 to 34 per cent.
2. Do not allow the acetylene to escape freely into the
air. Acetylene is a poisonous gas. If feasible, use a hood.
When you have finished the experiment, take the generating flask to the hood and add water until the excess carbide is completely decomposed. Add dilute hydrochloric
acid to dissolve the bulk of the residue and wash the material down the sink in the hood with a liberal supply of
water.
3. Cuprous and silver acetylide are extremely explosive
when dry.
QUESTIONS
1. Write balanced equations for the complete combustion of acetylene to caroon dioxide and water and for incomplete combustion in the presence of insufficient oxygen.
Compare the character of the flame of burning acetylene
with that of methane and of ethane. What causes a flame
to be luminous? Does this test suggest an important use
of acetylene in former days?
2. Compare the balanced equations for the complete
combustion of ethane, ethylene, and acetylene. Can you
suggest any reason, in addition to its high energy content,
why acetylene is the best of the three gases for use in
welding?
3. Which is more explosive, a mixture of ethylene and
air or a mixture of acetylene and air? Why?
4. Write balanced equations for the possible reactions
of acetylene with bromine. Predict some of the physical
properties of acetylene tertabromide (1,1,2,2-tetrabromoethane). Check your predictions in a handbook.
5. Write balanced equations for possible reactions
which occur when acetylene is treated with aqueous permanganate. How do you account for the effect of the reaction mixture on litmus?
6. Write a balanced equation for the reaction of acetylene with sodium. Name the product.
55
To what general class of compounds does it belong?
Is the anion a weaker or stronger base than hydroxide ion?
On what evidence do you base your answer? Is acetylene
a stronger or weaker acid than water? Explain.
Would 1-hexyne give a positive test with sodium?
2-hexyne?
7. Write balanced equations for the reaction of acetylene with ammoniacal cuprous chloride and with ammoniacal silver nitrate.
Of the two general types of acetylene derivatives,
R—C=C—H and R—C=C—R\ which would be expected to give a positive test with these reagents? What
structural feature is required for reaction?
8. In what sense is acetylene a protonic acid? Can you
explain why its reactions with ammoniacal copper chloride and silver nitrate are considered as reactions of an
acid?
9. What volume of acetylene measured at standard
conditions could be obtained from 10 g. of pure calcium
carbide?
10. Describe by means of balanced equations how ethylene and acetylene differ from methane in their behavior
toward (a) concentrated sulfuric acid; (b) bromine; (c)
aqueous permanganate. What structural feature of ethylene and acetylene is responsible for their reactivity?
11. Describe by means of balanced equations how acetylene differs from methane and ethylene in its behavior toward (a) metallic sodium; (b) ammoniacal cuprous chloride; (c) ammoniacal silver nitrate. What structural feature of acetylene is responsible for its reactivity toward
these reagents?
12. Assume that you had in the laboratory stock bottles
of heptane, 1-heptene, and 1-heptyne, all of which had
lost their labels. What series of reactions would you use
to ascertain which of the three possible compounds each
bottle contained? If you are ahead of schedule in your
laboratory work, perhaps your instructor would like to
assign you this, or a similar project, as a test of your reasoning and experimental ability.
How would the problem be complicated if there were
four bottles, with 2-heptyne as an added possibility? Could
you still solve the problem?
13. Now assume that you had a single bottle containing
a mixture of equal amounts of each of the three compounds
heptane, 1-heptene, and 1-hexyne. How would you proceed to separate the mixture into pure individual components, isolating each in its original form?
How would the separation be complicated if 2-heptyne
were also present in the mixture? How could this difficulty
be solved?
80-160
EXPERIMENT 15
Chemistry of the Alcohols
Introduction. Like water, which may be regarded as
the first member of the alcohol series, alcohols are in a
general sense both acids and bases. This dual character
is revealed by the tendency of alcohol molecules to associate through hydrogen bonding; it is this tendency
which accounts for the fact that alcohols in general boil
at considerably higher temperatures than hydrocarbons
of the same molecular weight.
With water molecules, alcohol molecules co-associate
through hydrogen bonding, and, as a result, the lower
molecular weight alcohols are completely miscible with
water. As acids, the alcohols react with active metals
such as sodium with evolution of hydrogen. The relative rates of reaction of alcohols in such reactions, in
which only the hydrogen of the hydroxyl group is removed leaving behind both electrons of the pair through
which it was originally bonded to the oxygen, are in
the order primary > secondary > tertiary.
As bases, the alcohols accept a proton from strong
H
mineral acids to form alkyl oxonium ions, R—0
/
\
+,
H
comparable to the hydronium ion formed from water.
Depending upon the conditions, especially the temperature, the protolysis may be followed by any of a number of other reactions: (1) complete dehydration to an
alkene, (2) partial dehydration to an ether, or (3)
displacement of the water molecule from the alkyl
oxonium ion by an anion to form an alkyl halide, an
alkyl nitrate, an alkyl hydrogen sulfate, or similar
product. For all of these reactions, in which the hydroxyl group of the alcohol is ultimately removed, taking with it both electrons of the pair through which it
was originally bonded to carbon, the relative rate of
reactions are in the order tertiary > secondary > primary.
Primary and secondary alcohols are also moderately
active reducing agents and are oxidized by many of the
common chemical oxidizing agents. The structure of
tertiary alcohols makes it impossible for them to undergo oxidation except under conditions sufficiently
severe (strong oxidizing agents and high temperatures)
to bring about oxidative cleavage of a carbon-carbon
bond. In strong acid solution, a tertiary alcohol may
sometimes give a positive test with oxidizing agents because of the reducing action of the alkene formed by
dehydration of the tertiary alcohol.
In general, the rate of oxidation of alcohols varies,
not only with the nature and concentration both of the
alcohol and of the oxidizing agent, but also with the
temperature and the acidity or alkalinity of the solu-
tions. Potassium permanganate is a favorite oxidizing
agent for test purposes, because the changes, especially
in color, that accompany its reduction are so easily
observed. It is effective in acid, alkaline, and neutral
solutions, but its strength as an oxidizing agent can be
controlled over broad limits by regulation of the pH.
Solubility Tests
Add 10 ml. of 95 per cent ethyl alcohol to 10 ml. of
water in a test tube. Then saturate the solution with
potassium carbonate. Observe the results. Determine
approximately the weights of n-butyl alcohol, .y-butyl
alcohol, and f-butyl alcohol which can be dissolved in
5 ml. of water. Record all of your observations and
results.
0-35
Acid Properties of Alcohols
Add a small piece of sodium about the size of a pea
to 5 ml. of absolute ethyl alcohol (Note 1) in a small
test tube. When the reaction is over, add an equal volume of absolute ether and observe the results. Now
transfer the mixture to a watch glass and allow the ether
and excess ethyl alcohol to evaporate. Note the character of the residue. Add to it about 3 ml. of water. Test
the resulting solution with litmus and note its odor.
To each of three 8-inch test tubes, add 5 ml. of dry
n-butyl, s-butyl, and f-butyl alcohol, respectively. To
each add a small piece of sodium about the size of a
pea, and compare the rates of reaction. Warm if necessary to complete the reaction.
35-60
Comparative Rates of Reaction with
Hydrochloric Acid
Place 3 ml. of n-butyl, ^-butyl, and /-butyl alcohol
in each of three 8-inch test tubes, respectively. Add to
each 10 ml. of concentrated hydrochloric acid. Watch
carefully for evidence of reaction.
60-100
[Proceed to next experiment.]
Select those tubes in which the solutions are still clear
and homogeneous after 10 minutes of standing at room
temperature and place them in a beaker of boiling water
for 15 minutes, and observe any changes which occur.
Oxidation of Alcohols
a. With Potassium Permanganate at Different pH's.
Prepare a solution for testing by adding 5 ml. of methyl
alcohol to 45 ml. of water. Pour 5-ml. portions into
each of three test tubes. Make one portion alkaline with
1 drop of 10 per cent sodium hydroxide solution, acidify the second with 1 drop of a 10 per cent sulfuric acid
solution, and leave the third neutral. Now add to each
solution 2 drops of a 0.3 per cent solution of potassium
permanganate. Allow the mixtures to stand for 2 min-
75-85
CHEMISTRY OF THE ALCOHOLS
85-100
utes. Then warm, if necessary, to effect reaction. Observe the order in which reduction of the permanganate
occurs.
b. Comparison of a Primary, Secondary, and Tertiary Alcohol. Prepare the oxidizing solution by dissolving 5 g. of sodium dichromate in 50 ml. of water and
adding 5 ml. of concentrated sulfuric acid. Pour 10 ml.
of this solution into an 8-inch test tube and add 2 ml.
of n-butyl alcohol. Shake the tube and note any rise in
temperature or change in color. Repeat, using 2 ml.
of s-butyl alcohol and finally with 2 ml. of f-butyl alcohol.
100-170 Tests for Water in Alcohol
a. With Anhydrous Copper Sulfate. Add about 0.5
g. of anhydrous copper sulfate (Note 2) to 5 ml. of 95
per cent alcohol in a dry test tube and shake vigorously.
Repeat with 5 ml. of absolute alcohol.
b. With Calcium Carbide. Heat a piece of calcium
carbide half the size of a pea gently in a Bunsen flame
to drive off any occluded moisture. Immediately introduce the calcium carbide into about 5 ml. of absolute
alcohol in a test tube. Repeat, using 5 ml. of 95 per cent
alcohol. Note any differences.
[Proceed to c]
If no difference is observed after 10 minutes, stopper
the test tubes with cork stoppers and observe again after
an hour.
c. With Paraffin Oil. Add one drop of paraffin (mineral oil) to 5-ml. samples of absolute alcohol and 95
per cent alcohol, respectively. Note the difference. Test
similarly the relative solubilities of ammonium chloride,
anhydrous sodium sulfate, acetanilide, naphthalene, and
sucrose in absolute and in 95 per cent alcohol.
130-160 Distinguishing Tests for Ethyl and
Methyl Alcohols (Note 3)
Acetate Test. Add 1 ml. of concentrated sulfuric acid
(Note 4) to a mixture of 1 ml. of absolute ethyl alcohol
and 1 ml. of glacial acetic acid in a test tube, and warm
gently {do not boil). Cool below 20° and add to 5 ml.
of a cold brine solution. Note the characteristic odor of
the ester ethyl acetate.
Repeat with pure methyl alcohol, and note the odor
of methyl acetate.
For interest, repeat this test with pure n-amyl alcohol.
Salicylate Test. Add 1 ml. of concentrated sulfuric
acid to a mixture of 1 ml. of pure methyl alcohol and
about 0.25 g. of salicylic acid (Note 5). Warm gently
for a few minutes, then cool, and pour into 10 ml. of
cold water contained in a small beaker. Note the odor
of methyl salicylate.
[Repeat with absolute ethyl alcohol.]
"Solid Alcohol" Mix 45 ml. of 96 per cent alcohol
with 5 ml. of a saturated aqueous solution of calcium
57
acetate by pouring the two solutions simultaneously
into a small beaker. Allow the mixture to stand until it
gels. Then inspect it. Place a small amount of the material in an iron dish and burn it. This is a form of solid
alcohol or canned heat.
NOTES
1. If absolute ethyl alcohol is not available it may be prepared by refluxing 95 per cent alcohol (2.5 parts) with
lumps of fresh quicklime (1 part) for at least 1 hour and
then distilling the alcohol directly from the calcium oxidecalcium hydroxide mixture.
2. If it is not available, anhydrous copper sulfate can
be prepared by heating the blue hydrate very gently in an
evaporating dish until all of the water of crystallization is
removed.
3. The iodoform test (p. 78) should be noted as an
additional test to distinguish ethyl alcohol, which gives a
positive iodoform test, from methyl alcohol, which does
not.
4. The sulfuric acid acts as a catalyst for the esterification reaction and also, in the concentration used here, increases the yield of ester by reducing the effective concentration of the product water available for participation in
the reverse reaction.
5. Salicylic acid is an aromatic carboxylic acid which
has the formula:
H
A
/ \
H—C
C—COOH
||
|
H—C
C—OH
(C«H4(OH)—COOH)
V
I
H
QUESTIONS
1. Write a formula to indicate the probable structure
of co-associated ethyl alcohol-water molecules in a solution
of ethyl alcohol in water. How does potassium carbonate
function in decreasing the solubility? Can you suggest any
reason why a divalent anion should be particularly effective?
2. Of the three isomeric butyl alcohols tested—primary, secondary, tertiary—which is most soluble in water?
Which is the least soluble? Does this order generally hold
for a series of isomeric primary, secondary, and tertiary
alcohols? Can you offer an explanation of this fact?
3. Write a balanced equation for the reaction of sodium with ethyl alcohol. Does this reaction occur more
or less readily than that of sodium with water? What type
of compound is sodium ethoxide?
Write a balanced equation for the reaction that occurs
when sodium ethoxide is placed in water.
What do these reactions indicate concerning the relative strengths of water and ethyl alcohol as acids and of
58
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
hydroxide and ethoxide ions as bases? Would it be possible
for ethoxide ions to exist in appreciable concentration in
water (in the form of a soluble salt)? Explain.
4. Compare the rate of reaction toward sodium of
primary, secondary, and tertiary butyl alcohols. Can you
account for the observed order of reactivity on the basis
of structure? Which of the three alcohols is most acidic?
5. Write balanced equations for the reaction of tertiary and of secondary butyl alcohol with hydrochloric
acid. How do you account for the fact that the butyl alcohols are much more soluble in water than the corresponding chlorides? Can you explain the observed order of reactivity of the alcohols toward hydrochloric acid on the basis
of structure?
6. At what general pH range is potassium permanganate the strongest oxidizing agent toward methyl alcohol? Does this agree with what you know about the relative
oxidation potentials of potassium permanganate in acid
and basic solutions? Write balanced equations for the reactions involved.
7. Compare the relative ease of oxidation of primary,
secondary, and tertiary butyl alcohols toward acid dichromate. Could this order be predicted in part?
8. In general, is absolute or 95 per cent ethyl alcohol
a better solvent for ionic substances? For covalent nonpolar substances?
9. Write balanced equations for the esterification of
acetic acid and of salicylic acid with methyl and ethyl
alcohols.
Could f-butyl esters be made satisfactorily by this
method?
Identify the odors of the esters you prepared which
were familiar to you from previous experience.
10. Judging from its behavior with calcium acetate,
would you predict that ethyl alcohol could be dried satisfactorily with calcium chloride as the desiccant? You might
be interested in trying it.
EXPERIMENT 16
I. Ethyl Iodide
(i)
2P + 3I2
(2)
3C2H5OH + PI 3
2PI3
• 3QH5I + H3PO3
II. Tertiary Butyl Chloride
(CH3)3COH + HC1 -» (CH 3 ) 3 Ca + H 2 0
Introduction. Conversion of an alcohol to the corresponding alkyl halide by means of a phosphorus trihalide or a hydrohalic acid constitutes a convenient
laboratory synthesis of alkyl halides.
Primary, secondary, and tertiary alcohols all react
readily with phosphorus halides to yield the corresponding alkyl halides. For the synthesis of alkyl chlorides,
phosphorus trichloride is customarily used directly, but
for bromides and iodides, it is convenient to generate
the phosphorus tribromide or triodide in situ, by treatment of phosphorus with bromine or iodine. '
All three classes of alcohols react with hydrohalic
acids to form alkyl halides, but, as you have already
observed in Experiment 15, at markedly different rates.
Tertiary alcohols react rapidly at room temperature,
secondary alcohols more slowly, and primary alcohols
require elevated temperatures. This difference in reaction rate is the basis for the Lucas1 test for primary,
secondary and tertiary alcohols, in which the alcohol to
be tested is treated with concentrated hydrochloric acid
(usually in the presence of the catalyst zinc chloride).
Tertiary alcohols form an upper layer of the insoluble
halide almost instantaneously at room temperature, secondary alcohols within 5-10 minutes, but primary alcohols react only at higher temperatures. This pronounced
difference in reactivity is illustrated by a comparison
of the severity of reaction conditions required to synthesize tertiary butyl chloride in this experiment and
ethyl bromide in the next experiment.
For the hydrohalic acids, the rate of the reaction follows the order HI > HBr > HC1 > HF. Thus, the
strongest acid, hydriodic acid, reacts with a given alcohol to produce the corresponding alkyl halide most
readily, and the weakest acid, hydrogen fluoride, least
rapidly.
In general, the rate of reactivity of any group of corresponding halides follows the order RI > RBr > RC1.
Thus, ethyl iodide is more reactive toward most reagents than is ethyl bromide, with ethyl chloride the
least reactive of all three.
To make efficient use of your time, first assemble the
apparatus for both Parts I and II of this assignment.
While you are refluxing the ethyl iodide reaction mix1
Named for Howard Lucas, emeritus professor of
at the California Institute of Technology.
ture in Part I, proceed with the synthesis of tertiary
butyl chloride in Part II.
I. ETHYL IODIDE
Place 3.5 g. (0.11 mole) of red phosphorus (Note 1)
and 25 ml. (0.43 mole) of ethanol (preferably absolute) in a 200-ml. flask and fit the flask with a watercooled reflux condenser as shown in Figure 20a. Detach the flask from the condenser and gradually add 25
g. (0.1 mole) of iodine in portions of 2-3 g. each. After
each addition of iodine, shake the flask and reattach it
to the reflux condenser if necessary to prevent loss of
alcohol by evaporation. If the reaction becomes too
rapid, cool the flask in cold water.
After all the iodine has been added and the mixture
no longer heats spontaneously, attach the flask to the
reflux condenser and reflux the mixture for 30 minutes
on a water bath to complete the reaction.
[Proceed to Part II.]
Remove the flask and cool it in cold water. By means
of a bent glass tube connect the flask and condenser for
distillation (Figure 20b) and distill to dryness. Transfer
the crude iodide to a small separatory funnel and add
enough 3 per cent sodium hydroxide solution so that all
of the free iodine is removed by shaking, as evidenced
by the discharge of the iodine color.
Separate the bottom ethyl iodide layer from the alkaline solution and wash it with 25 ml. of water by shaking a mixture of the two in the separatory funnel. Separate the ethyl iodide layer as carefully as possible and
dry it in a small flask over 8-12 granules of anhydrous
calcium chloride. During this time wash the condenser,
rinse it with a little acetone, and clamp it in a vertical
position to dry.
Decant the ethyl iodide from the calcium chloride
into a small distilling flask and redistill it. Carefully
note and record the distillation range. Collect the pure
product in a tared (previously weighed) bottle. Determine its weight and calculate the percentage yield. Save
at least a few ml. of the ethyl iodide for tests in Experiment 17.
Other Alkyl Iodides. (For Specially Interested Students)
As optional experiments, other alkyl iodides
chemistry
may be made by this general method simply by substi59
0-150
60
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
FIG. 20. Apparatus for the preparation of ethyl iodide.
(a) For refluxing of reaction mixture, (b) For distillation
of ethyl iodide, (c) For collection of product.
tuting 0.4 mole of the appropriate alcohol for the ethyl
alcohol. The normal boiling points of some common
alkyl iodides are as follows:
Methyl iodide . . . . 43°
n-Propyl iodide . . . 102°
Isopropyl iodide
89°
n-Butyl iodide . . . . 130
s-Butyl iodide . . . . 119
72-Amyl iodide . . . . 155
If methyl iodide is prepared, the receiving flask should
be well cooled in ice during the distillation to prevent
loss by evaporation. For storage, the methyl iodide
should be sealed in a glass tube.
NOTE
1. For safety, red phosphorus is often kept in a moist
condition while stored. In such a case, dry the phosphorus
by pressing it between the two halves of a piece of folded
filter paper before weighing out 3.5 g. for use in today's
experiment.
Neither phosphorus nor iodine should be allowed to
come into contact with the skin. Both stain the skin badly
and may cause severe burns.
40-170
II. TERTIARY BUTYL CHLORIDE
Add to a 250-ml. separatory funnel, 37 g. (0.50
mole) of r-butyl alcohol and 125 ml. of C.p. (Note 1)
concentrated hydrochloric acid. Gently swirl the unstoppered funnel for approximately 1 minute. Then
stopper the funnel, invert it, and open the stopcock
momentarily to release excess pressure. Shake the funnel for about 4 minutes, venting it at intervals. Then
mount the funnel on a ring stand and allow it to stand
until the two layers have separated and are completely
clear.
Drain off the lower aqueous layer and discard it. Add
50 ml. of saturated sodium bicarbonate solution to the
crude tertiary butyl chloride in the separatory funnel.
Gently swirl the unstoppered funnel several times until
vigorous effervescence ceases. Then stopper the funnel,
invert carefully, and open the stopcock momentarily to
relieve the pressure. Shake, gently at first, opening the
stopcock at frequent intervals. Then shake vigorously,
still opening the stopcock intermittently. Finally remove
the lower bicarbonate layer, wash the f-butyl chloride
remaining in the funnel with 40 ml. of water, and carefully draw off the lower water layer.
Transfer the crude f-butyl chloride into a small Erlenmeyer flask and dry over 8-12 granules of calcium
chloride (Note 2) until it becomes clear. Decant the
liquid into a small dry distilling flask and distill through
a dry condenser. Collect the fraction boiling at 48°-52°
as r-butyl chloride, refractionating any lower boiling
distillate. Because of the low boiling point of f-butyl
chloride, it is well to cool the receiving flask in ice
water. Save at least a few ml. of the f-butyl chloride for
tests in Experiment 17.
NOTES
1. For a good yield of f-butyl chloride, the concentration of hydrochloric acid is critical. The usual C.p. (36-38
per cent) acid is sufficiently concentrated to give good
results, whereas the technical acid is not.
2. You can speed the drying process markedly by intermittent shaking of the flask.
QUESTIONS
1. How do you account on a theoretical basis for the
relative rates of reactivity of primary, secondary, and tertiary alcohols toward hydrohalic acids? For the relative
reactivity of HI, HBr, and HC1 toward alcohols?
TERTIARY BUTYL CHLORIDE
2. Which of the reactants constitutes the basis for your
calculation of the theoretical yield of ethyl iodide? Why?
3. Calculate the percentage yield realized by a student
who obtained 5.0 g. of ethyl iodide by reaction of 3.5 g. of
red phosphorus and 25 g. of iodine with excess ethanol.
What might you conclude about his experimental technique?
4. Would you expect f-butyl alcohol to be more or less
expensive than isobutyl? Why?
61
5. Look up the melting point and the boiling point of
r-butyl alcohol. What observation would you make about
the size of the temperature range in which r-butyl alcohol
exists as a liquid? Can you offer any explanation for this
fact?
6. Explain how the various steps in the purification and
isolation of ethyl iodide are designed to remove all possible
contaminants.
EXPERIMENT 17
I. Ethyl Bromide
(i)
H 2 S0 4 + NaBr
(2)
C2H5OH + HBr
> HBr + NaHS0 4
C2H5Br + H 2 0
II. Properties of Alkyl Halides
Introduction. Perhaps the most convenient way to
prepare a primary alkyl bromide is to heat the corresponding alcohol with a mixture of sodium or potassium
bromide and sulfuric acid. The bromide-sulfuric acid
combination serves a double function: (1) it liberates
the hydrogen bromide for the reaction, and (2) it forms
with the alcohol a mixture which boils above the temperature required for fairly rapid reaction of hydrogen
bromide with even a primary alcohol.
0-120
I. PREPARATION OF ETHYL BROMIDE
Measure 60 ml. (47.3 g., 1.03 moles) of ethyl alcohol into a 1-liter round-bottomed flask. Add cautiously
with stirring and cooling 50 ml. of concentrated sulfuric
acid. With further shaking and cooling add 69.5 g.
(0.500 mole) of crystalline sodium bromide (NaBr •
2H 2 0) which has been previously ground to a fine
powder with a mortar and pestle. Mount the flask securely above a wire gauze on a ring stand. By means of
a rubber stopper, curved tube, and second rubber stopper, fit the flask for distillation with a condenser carrying an adapter which dips just below the surface (Note
1) of some ice water in a 250-ml. beaker (Figure 20b,
but with receiver c). Heat gently at first and then
more strongly, finally distilling as rapidly as possible
without undue frothing. You will be able to observe
droplets of ethyl bromide forming in the water and
settling to the bottom of the beaker. Continue heating
until a water insoluble oil is no longer obtained. The
reaction mixture will foam considerably throughout the
distillation but settles to a quietly simmering liquid as
the reaction comes to an end and no more volatile material is formed.
Pour the crude ethyl bromide and ice water into a
separatory funnel, and tap off the lower ethyl bromide
layer into a small Erlenmeyer flask. Immediately cool
the flask in an ice bath. Slowly add 10 ml. of concentrated sulfuric acid and shake gently (Note 2). Transfer the mixture to a small separatory funnel and carefully add a single drop of water. Observe the behavior
of the water in order to determine which is the sulfuric
acid and which the ethyl bromide layer. Separate the
layers (Note 3) and wash the ethyl bromide, first with
25 ml. of water, then with 15 ml. of dilute sodium
hydroxide solution and again with 25 ml. of water.
Dry the ethyl bromide over about 10 granules of
calcium chloride in a small Erlenmeyer flask with occasional shaking to hasten the process (Note 4). Decant
62
the liquid into a small, dry distilling flask, add 2 or 3
boiling chips, fit the flask by means of rubber stoppers
with a thermometer and dry condenser, and distill. Collect the distillate in a small Erlenmeyer flask packed in
ice in a beaker. Collect separately the portion distilling
at 37°-40° and redistill any higher or lower boiling
fractions. Submit your product to your instructor at
once for storage in a refrigerator.
Allow the residue in the reaction flask to cool until
it can be handled conveniently, then dispose of it by
pouring it directly into the sink and washing it down
with a large excess of cold water.
NOTES
1. If the adapter dips too far below the surface of the
water, it may be possible for water to rise into the condenser tube and into the reaction flask with disastrous
results.
2. This treatment is designed to remove the ethyl ether
which is formed as a by-product in the reaction. Usually
there is sufficient ethyl ether to dilute the sulfuric acid to
the extent that the sulfuric acid-ethyl ether mixture forms
the less dense top layer. If the amount of ether is small,
however, the ethyl bromide may appear as the top layer.
3. In order to distinguish the interface, you may find it
necessary to view the funnel from several different angles.
4. Disappearance of turbidity indicates that the ethyl
bromide is dry.
II. PROPERTIES OF ALKYL HALIDES
1. Shake a few drops of ethyl bromide with 2 ml. of
distilled water and add 2 drops of silver nitrate solution. Repeat with a few drops of ethyl iodide, f-butyl
chloride, and n-butyl chloride. Allow each mixture to
stand for at least 15 minutes.
[Proceed to parts 2 and 3.]
Observe the rate at which a precipitate appears.
2. Expose a few drops of ethyl iodide to a bright
light. Observe the results.
3. Dissolve approximately 1 g. of sodium iodide in
7 ml. of acetone. To 1 ml. of the solution in a small
test tube, add 2 drops of ethyl bromide with vigorous
shaking. Allow the mixture to stand for 3 minutes at
room temperature. If no precipitate forms, place the
test tube in a beaker of water at 50° for 6 minutes.
Again observe whether or not a precipitate has formed.
Repeat with isopropyl bromide and /-butyl chloride.
120-170
PROPERTIES OF ALKYL HALIDES
QUESTIONS
1. Would the method used in today's experiment be suitable for the synthesis of secondary and tertiary bromides?
Explain.
2. Propose a function of the sulfuric acid in the preparation of ethyl bromide based on a preliminary reaction of
the acid with ethyl alcohol. Write a series of equations to
show all the steps involved in the over-all reaction for
such a mechanism. Actually, the ethyl bromide may be
formed in part through this route.
3. Write a balanced equation for the formation of ethyl
ether as a by-product in this reaction. Assume that 8.0 g.
63
of ethyl ether were formed. What would then be the maximum yield of ethyl bromide that could have been formed?
4. What is the relation of ethyl bromide to ethane?
Write balanced equations for the synthesis of ethane from
ethyl bromide and from ethyl chloride. Could isobutane
be obtained from f-butyl chloride in good yield by this
method?
5. Compare the rates of reaction of primary, secondary,
and tertiary halides with silver nitrate solution. With sodium iodide in acetone. Can you propose any reason for
the differences? Write general equations for the reactions
involved.
EXPERIMENT 18
Ethyl Ether
2C 2 H 6 OH-^UC
2H6
140-150°
H5 + H20
Introduction. Ethyl ether may be synthesized conveniently in good yield from ethyl alcohol by partial
dehydration (removal of one molecule of water between
two molecules of alcohol) in the presence of a nonvolatile acid such as sulfuric acid as catalyst. In practice, the ether is distilled directly from the reaction
mixture and temperature control is critical. Some ethylene is inevitably formed as a by-product, and complete dehydration of the alcohol to an alkene is an
unavoidable competitive reaction that limits the applicability of this method to alcohols which are not easily
dehydrated to alkenes.
In general, low-boiling, diprimary ethers can be synthesized readily in good yield by catalytic partial dehydration of primary alcohols. If the ether formed boils
above the temperature at which sulfuric acid effects
complete dehydration of the alcohol to olefin, the ether
may still be synthesized successfully if it is removed by
distillation under reduced pressure.
In the preparation of disecondary ethers from secondary alcohols by this method, the yields are greatly re-
dehydration of ethyl alcohol over the Lewis acid catalyst aluminum oxide at temperatures of 240°-260°.
Ethyl ether is highly volatile and extremely flammable; therefore it is dangerous if handled improperly.
You will, however, encounter no difficulty if you perform this experiment carefully and thoughtfully.
Like most ethers, ethyl ether upon exposure to air
reacts with oxygen to form peroxides of undetermined
structure which explode violently when ether is distilled
to dryness and the residue heated excessively. Ether
which has been stored with access to air should be tested
for peroxides before use. Peroxides should be removed
by shaking with any one of a variety of reducing agents
such as, for example, acidified ferrous sulfate solution.
Iron wire is often added to containers of commercial
ether to inhibit peroxide formation.
FIG. 21a. Assembly for the preparation of ethyl ether.
FIG. 21b. Assembly for fractional distillation of ethyl
ether product mixture.
duced because of the ease with which sulfuric acid
dehydrates secondary alcohols to alkenes. With tertiary
alcohols, complete dehydration to alkenes is almost
quantitative; hence ditertiary ethers cannot be prepared
by this process.
As a cheap, nonvolatile acid, sulfuric acid is a widely
used catalyst for ether synthesis. It does, however, suffer
from the fact that when hot and concentrated it is an
oxidizing agent, and considerable oxidation of organic
material occurs at the expense of the sulfuric acid. Commercially, ethyl ether is widely produced by partial
the end of the thermometer bulb extends to within one
inch of the bottom of the flask.
If necessary, extend the dropping funnel by attaching a glass tube, preferably one that is constricted
slightly at the tip, to it by means of a rubber sleeve.
Be certain that the two sections of glass from the dropping funnel and tube meet within the sleeve. Adjust the
height of the dropping funnel so that the rubber sleeve
is located in the neck of the distilling flask when the
rubber stopper is inserted. Attach a rubber stopper to
the side arm of the distilling flask to connect the flask
A. Preparation of Ether
Fit a 500-ml. distilling flask by means of a two-holed
rubber stopper with a thermometer and dropping funnel as shown in Figure 21a (Note 1). Be certain that
64
0-110
ETHYL ETHER
with a condenser provided with a suction flask receiver
as shown in Figure 21a.
Remove the rubber stopper bearing the thermometer
and dropping funnel and disengage the distilling flask
from the condenser. Then pour 94 ml. (72 g., 1.50
moles) of 96 per cent ethyl alcohol into the flask. Add
carefully, in 5-ml. portions, a total of 40 ml. of C.p.
concentrated sulfuric acid, shaking the flask and cooling it in a stream of cold water after each addition.
Then place the flask on a sand bath mounted on a ring
stand, insert the stopper with the thermometer and dropping funnel, attach the condenser, and surround the
receiver with a pan of crushed ice.
Attach to the side arm of the receiver a length of
rubber tubing which extends almost to the floor. Be
certain that this receiver is not near your neighbor's
burner and keep your own burner away from your
neighbor's receiver.
Heat the flask on the sand bath until the thermometer
registers 140°-145°. Maintain this temperature as
nearly as possible and admit slowly through the addition funnel 104 ml. (80 g., 1.65 moles) of 96 per cent
ethyl alcohol. Heat for an additional 5 minutes after all
of the alcohol has been added, in order to drive off the
last of the ether. Extinguish the flame and arrange an
apparatus for fractional distillation as shown in Figure
21b, using a 250-ml. round-bottomed flask. For the
fractionation column, use a column or air condenser
packed with copper sponge, as in Experiment 3.
110-170 Transfer the crude ether to the flask, add 2 or 3 boiling chips and also 2 g. of solid sodium hydroxide to
convert the dissolved sulfur dioxide to sodium sulfite,
and distill over a steam bath.
Collect fractions as follows: I, 34°-42° (ether);
II, 42°-55°; III, 53°-75°; IV, 75°-82° (alcohol); V,
82°-95°; and VI, residue, largely water. Refractionate
fractions II, III, and IV to separate them into the three
principal components: (1) ether, 34°-42°; (2) alcohol,
75°-82°; and (3) water (residue). Measure the volume
of the alcohol fraction, weigh it, and calculate its density.
From handbook tables, find the alcohol concentration
in alcohol-water solutions of that density and calculate
the weight of recovered alcohol. Calculate the percentage yield, both on the basis of the total alcohol used
during the experiment and on the basis of that actually
consumed during the reaction (not recovered).
NOTE
1. Insert the thermometer and dropping funnel into the
rubber stopper with great care. Protect each hand by means
of a towel. Lubricate the holes in the stopper liberally with
glycerol. Hold the glass piece to be inserted near the
stopper and push very gently while rotating the stopper.
Never use brute force. Be sure that the end of the glass
tube is fire polished.
65
B. Properties of Ether (Optional, for
Specially Interested Students)
Ether as a Solvent and Solute—Salting Out Effect.
1. Test the solubility of each of the following by
determining the volume or weight (Note 1) which can
be dissolved in 3 ml. of ether: (1) kerosene, (2) benzene, (3) paraffin, (4) iodine, (5) carbon tetrachloride,
(6) cottonseed oil, (7) alcohol, (8) water, (9) sodium
chloride, and (10) ammonium chloride.
2. Determine what volume of ether can be dissolved
in 10 ml. of water.
3. Add 5 ml. of cold sulfuric acid to 2 ml. of icecold ether in a small test tube. Stir vigorously, keeping
the test tube in an ice bath. Finally pour the material
onto about 15 g. of cracked ice. Note the results.
4. Introduce 5 ml. of ether into a graduated cylinder
and add 5-ml. portions of water until the ether is dissolved, noting the total amount of water added. Then
add 15 g. of sodium chloride and shake until the salt is
dissolved. Note the results.
Test for Peroxides in Ether. Add 1 ml. of a 10 per
cent solution of potassium iodide to 10 ml. of water in
a small test tube and acidify the solution with a few
drops of dilute sulfuric acid. Add 2 ml. of commercial
ether from the side shelf and shake the tube for a moment. Add a few drops of starch paste indicator or a
strip of starch-iodide paper and shake. Appearance of
a blue color (Note 2) indicates the presence of peroxides in the ether.
NOTES
1. You can do this conveniently by starting with a
known volume or weight of solute, adding it in small portions, and subtracting the amount which remains unused
after the ether has been saturated.
2. The typical blue color is characteristic of the product
formed when the so-called amylose fraction of starch absorbs iodine.
QUESTIONS
1. Write balanced equations for the various reactions
which ethyl alcohol may undergo with sulfuric acid. What
factors determine which reaction predominates under a
given set of conditions?
If the desired product is ethyl ether, what is indicated
about the reaction conditions used if (a) a large amount
of ethylene is formed, or (b) a large amount of ethyl
alcohol is recovered?
2. Write a balanced equation for a likely side reaction
in the ether synthesis of which sulfur dioxide is one of the
products. What does the production of much sulfur dioxide
indicate about the yield that may be expected in the reaction?
3. What properties of ethyl ether make it a good extrac-
66
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
tion solvent? Which of the properties are undesirable for
this purpose?
4. What simple method for distinguishing between
ethers and alkanes is suggested by the behavior of ethyl
ether toward cold, concentrated sulfuric acid? Write a balanced equation for the reaction. What property of ethers
is involved in this reaction? What is the effect of the addition of water?
EXPERIMENT 19
Preparation of Cyclopentanone
CH2—CH2—COOH
Ba(OH)j
CH2—CH2
\
285-295 <l
CH2—CH2—COOH
CH2
Introduction. As you observed in Experiment 9, pyrolysis of the carboxylate salt of a monovalent metal
(RCOOM) effects complete decarboxylation (loss of
1 mole of C0 2 for each mole of acid) to the corresponding alkane, RH. Decarboxylation of the carboxylate
0
salts [(R—C—0)2M] of divalent metals (such as calcium, barium, manganese, thorium, and cerium'), on
the other hand, gives partial decarboxylation (loss of
1 mole of C0 2 from 2 moles of acid) to the corresponding ketone.
O
In fact, symmetrical ketones, R—C—R, may be prepared conveniently by the pyrolysis of the calcium,
barium, or manganese salt of the appropriate acid,
O
CH2
/
c=o + co2 + H2O
Calcium, barium, and manganese salts of the 6-carbon
(adipic acid) and the 7-carbon (pimelic acid) dicarboxylic acids are partially decarboxylated to give good
yields of the cyclic ketones, cyclopentanone and cyclohexanone, respectively. This illustrates the familiar rule
of organic chemistry that 5- and 6-membered carbon
rings are readily formed. The yields of larger ring ketones formed by the pyrolysis of higher molecular
weight dicarboxylic acids fall off rapidly as the value
0
O
of n in HO—C—(CH2)n—C—OH increases.
In this experiment, you will prepare cyclopentanone
from adipic acid. In recent years, adipic acid has
achieved tremendous commercial importance as a starting material in the production of one type of nylon
(Nylon 66).
II
Preparation of Cyclopentanone
0
Mix 28.3 g. (0.400 mole) of powdered adipic acid
intimately with 2.0 g. of finely-powdered barium hydroxide in a mortar. Place the mixture in a 50-ml. distilling flask fitted with a thermometer reaching to within
4 mm. of the bottom of the flask. Connect the flask
with a condenser fitted with a curved adapter leading
through a cotton plug into a receiver (small Erlenmeyer flask) packed in ice. Heat the flask carefully
with a small flame held close to the flask; if necessary,
agitate the flask to shake the solid into the melted acid.
When all of the solid has melted, heat more rapidly
until the thermometer reaches 285°.
R—C—OH. In practice, the ketone formed is allowed
to distill directly from the reaction mixture. For many
years, calcium acetate, formed by addition of lime to
pyroligneous acid, constituted the principal source of
acetone.
It is possible to prepare an unsymmetrical ketone,
R—C—R' by heating a mixture of the salts of two acids,
0
0
II
II
(R—C—OH and R'—C—OH), or even an aldehyde,
O
II
R—C—H, if one of the acids is formic
acid
0-30
30-130
[Assemble apparatus for Experiment 20 and answer
drill questions.]
At this temperature, decarboxylation occurs and cyclopentanone, accompanied by water and a little adipic
acid, distills slowly. Heat to maintain the temperature
at 285°-295° as long as a liquid distills (Note 1) and
until only a small amount of dry residue remains in the
distilling flask.
O
O
Transfer the two-phase distillate to a small separatory 130-170
funnel and slowly add just enough solid potassium
II
II
R—C—R', the two symmetrical ketones, R—C—R and carbonate to saturate the aqueous layer. Draw off the
aqueous layer and add about 0.5 g. of anhydrous potasO
sium
carbonate to the cyclopentanone in the separatory
II
R'—C—R', are formed along with the desired product. funnel. Swirl the funnel occasionally, until the cyclo67
(
»
) In such cases, however, the decarboxy\H—C—OH/.
lation may occur in three ways to give a mixture of
three different carbonyl compounds, and the yield of
the desired unsymmetrical ketone or aldehyde is low.
Thus, in the synthesis of the unsymmetrical ketone,
68
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
pentanone is clear. Then decant the ketone through the
mouth of the separatory funnel (Note 2) into a small
distilling flask, and distill with a small free flame over a
wire gauze. Collect the cyclopentanone distilling at
129°-131°. Calculate the percentage yield and store the
product in a labeled bottle for testing in the next experiment.
NOTES
1. You will find it possible during this period to assemble your apparatus in preparation for the synthesis of
H-butyraldehyde to be carried out at the beginning of the
next period, and to work on the questions at the end of
this experiment.
2. Filter through a small funnel if necessary.
QUESTIONS
1. Assume that you were assigned the project of synthesizing ethyl ^-propyl ketone by the pyrolysis of a mixture of barium salts. Write the formulas for the two carboxylic acids you would use. In what ratio by weight would
you mix them?
What three ketones would you expect to find in the
product mixture? On a statistical basis, in what mole ratio
should they be formed? In what weight ratio?
2. What is the role of the barium hydroxide in the synthesis of cyclopentanone?
3. Propose another method for the preparation of cyclopentanone. Write the balanced equation for the reaction.
4. If 12 g. of water were formed in the partial decarboxylation of a certain weight of adipic acid, what would
be the maximum weight of cyclopentanone that could be
obtained?
5. What purposes does the potassium carbonate wash
serve in this experiment?
EXPERIMENT 20
I. Preparation of w-Butyraldehyde (Butanal)
II. Some Reactions of Aldehydes and Ketones
3CH3CH2CH2CH2OH + Na 2 Cr 2 0 7 + 4H 2 S0 4 -* 3CH3CH2CH2CHO + Na 2 S0 4 + Cr 2 (S0 4 ) 3 + 7 H 2 0
H
Introduction. Aliphatic aldehydes, R — C = 0 , can be
prepared from primary alcohols, R—CH 2 —OH, and
O
II
aliphatic ketones, R—C—R', from secondary alcohols,
R—CHOH—R', by carefully controlled oxidation.
The preferred reagent is an aqueous solution of sodium
or potassium dichromate and sulfuric acid. Because of
the extreme ease with which aldehydes are oxidized
further to carboxylic acids (an aldehyde is much more
easily oxidized than the alcohol from which it is
formed), an aldehyde must be removed from the reaction mixture as rapidly as it is produced. Fortunately,
because of the greater volatility of aldehydes as compared with alcohols, this can be accomplished by distillation of the aldehyde.
It is an interesting generalization that aldehydes,
whose molecules lack the hydrogen atom required for
association through hydrogen bonding, always boil
lower than the corresponding alcohols and acids, the
molecules of both of which are extensively associated
through hydrogen bonding.
Ketones are more resistant to oxidation than are
aldehydes and primary and secondary alcohols. In their
synthesis from secondary alcohols, they can be retained
in the heated oxidizing medium with almost no loss
due to further oxidation.
The oxidation of primary and secondary alcohols
with dichromate is highly exothermic, and the reaction
is usually controlled by gradual addition of either the
alcohol or dichromate.
You will be interested in noting that the net effect
of the reaction from the standpoint of the alcohol
molecule is simply the removal of two hydrogen atoms.
This suggests that a catalytic dehydrogenation would
accomplish the same result and this is, indeed, the
case. In fact, a number of aldehydes and ketones are
produced commercially by dehydrogenation of the corresponding alcohols over copper-zinc catalysts at 200°350°.
The markedly superior ease of oxidation of aldehydes
constitutes the basis for a convenient means of distinguishing between aldehydes and ketones. A number
of mild oxidizing reagents, which are reduced only by
aldehydes and a few other easily oxidized types of
organic compounds, and are unaffected by ketones and
alcohols, have been developed. Among such oxidizing reagents, which are commonly used to test for
aldehydes, are Tollens' reagent and Fehling's solution.
Tollens' reagent is essentially a solution of Ag(NH3)2OH,
and Fehling's solution, of Cu(OH) 2 in which the cupric
ion is complexed with tartrate ion.
SchhTs reagent is a sensitive reagent for the detection
of aldehydes. The test is based, not upon the reducing
action of aldehydes, but upon a complex reaction to
form a red-purple solution which aldehydes undergo
with the almost colorless compound formed by addition of sulfurous acid to the pink dye fuchsin.
I. PREPARATION OF H-BUTYRALDEHYDE
FROM n-BUTYL ALCOHOL
Fit a 1.5-liter, round-bottomed flask (Note 1) with
a rubber stopper carrying a dropping funnel and a
fractionating column leading to a condenser and receiving flask, as shown in Figure 22. Disconnect the
reaction flask, introduce into it 260 ml. of water, 149 g.
(0.50 mole) of sodium dichromate, and a few boiling
chips. Add cautiously, with cooling under a water tap,
120 ml. of concentrated sulfuric acid. Mount the flask
securely on a ring stand above a wire gauze, and set
up the distillation assembly. Add 37 g. (0.50 mole)
of n-butyl alcohol to the dropping funnel (stopcock
closed!).
Heat the reaction mixture moderately so that a drop
of n-butyl alcohol introduced from the dropping funnel
reacts vigorously when it strikes the mixture. Continue
to introduce the alcohol, at the rate of about a drop a
second, regulating the flow so that distillation takes
place regularly and the temperature, as registered by
the thermometer, is 75°-90° (Note 2).
From time to time loosen the clamp somewhat and
shake the flask gently to insure good mixing of the
reactants. When all of the alcohol has been added, heat
the mixture with a small flame as long as material distills
below 90°.
The two-phase distillate consists of an upper layer
of aldehyde with a considerable amount of alcohol and
a small lower layer of water. Transfer it to a small
separatory funnel and drain off the water. Add 4 g. of
anhydrous magnesium sulfate directly to the aldehyde
in the funnel and swirl the mixture occasionally. When
the liquid is dry, as indicated by disappearance of
turbidity, decant it through the mouth of the funnel,
filtering if necessary, into a small round-bottomed flask.
Distill through a short fractionating column, collecting
the fraction boiling at 72°-76° in a tared bottle. Weigh
the product and calculate the yield.
69
0-100
70
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
FIG. 22. Assembly for the synthesis of butyraldehyde.
II. SOME REACTIONS OF ALDEHYDES AND KETONES
(Test Tube Experiments)
100-125 A. Oxidation of Aldehydes and Ketones
( i ) With Permanganate. To a few drops of a dilute
(10 per cent) (Note 3) aqueous solution of formaldehyde, add 1 or 2 drops of a 0.3 per cent solution of
potassium permanganate. Repeat with dilute (about
10 per cent) solutions of acetaldehyde, acetone, and
cyclopentanone. If no reaction is observed in 1 minute,
add a drop of sodium hydroxide solution. Note the
results.
Repeat, using permanganate solution acidified with
dilute sulfuric acid.
(2) With Tollens' Reagent. Place 5 ml. of Tollens'
reagent in a clean test tube and add a few drops of
formaldehyde solution. Repeat with acetaldehyde, acetone, and cyclopentanone. Observe the results both
before and after the solution is warmed.
(3) With Fehling's Solution. To 3 ml. of Fehling's
solution Part I, add Part II slowly until the initially
formed light-blue precipitate of copper hydroxide dissolves as the dark-blue complex tartrate ion upon shaking. Add 3 drops of formaldehyde solution. Boil gently
for 2 minutes. Repeat with solutions of n-butyraldehyde, acetone, and cyclopentanone.
125-135 B. Color Test with SchifFs Reagent
To 4 ml. of SchifFs reagent add a few drops of the
dilute formaldehyde solution. Repeat with acetaldehyde
solution and with pure acetone and cyclopentanone.
Note the results.
C. Addition Reaction with Sodium Bisulfite
Shake 1 ml. of butyraldehyde with 5 ml. of a freshly
prepared saturated solution of sodium bisulfite. Cool.
Note the results.
Repeat with acetaldehyde solution, acetone, cyclopentanone, and diethyl ketone.
D. Aldehyde Resins
Heat about 2 ml. of a solution of acetaldehyde with
an equal volume of dilute sodium hydroxide solution.
Repeat with acetone. Note any differences.
E. Reactions of Aldehydes with Ammonia
Add 2 ml. of concentrated ammonium hydroxide to
5 ml. of formalin. Evaporate the mixture to dryness on
a water bath in the hood. Note the appearance of the
product.
NOTES
1. A two-necked flask would be most convenient, if
available,
2. If the alcohol is introduced at the proper rate, heating will probably be unnecessary while the alcohol is being
added.
3. Ordinary formalin is a 40 per cent aqueous solution
of formaldehyde.
QUESTIONS
1. Suggest some possible by-products in the oxidation
of w-butyl alcohol to n-butyraldehyde. How are they re-
SOME REACTIONS OF ALDEHYDES AND KETONES
71
moved by the purification procedure? What would be the and H-butyraldehyde. How is a positive test with each of
probable effect of allowing the reaction temperature to go these reagents recognized in a practical way?
too high?
6. Assume that a certain reagent reacts chemically with
2. Can you suggest why sodium dichromate is used in organic compound A and not with B. Does this in itself
make the reagent a good reagent for distinguishing beplace of potassium dichromate?
3. rc-Butyraldehyde is an oxidation product of rc-butyl tween A and B in simple, clear-cut fashion? Explain.
7. Is sodium bisulfite a perfectly general reagent for
alcohol and a reduction product of ^-butyric acid, yet it is
more easily oxidized than the alcohol and more easily the detection of a carbonyl function? What general types
reduced than the acid. Can you recall any analogy from of carbonyl compounds form sodium bisulfite addition
products?
inorganic chemistry?
4. Write balanced equations for the oxidation of for8. Propose a mechanism for the addition of sodium
maldehyde and of acetaldehyde with potassium perman- bisulfite to n-butyraldehyde.
ganate in neutral and acid solution.
9. Could H-butyraldehyde be obtained by the catalytic
What is the effect of the addition of alkali on the oxi- hydration of 1-butyne? Explain.
dizability of ketones with permanganate? Can you suggest
10. Write balanced equations for the reactions involved
an explanation?
in chemical tests you would use to distinguish between:
5. Write balanced equations for the reactions of Tol(a) Acetone and acetaldehyde.
lens' reagent and of Fehling's solution with formaldehyde
(b) Methyl ethyl ketone and di-isopropyl ketone.
EXPERIMENT 21
I. Derivatives of Aldehydes and Ketones
II. Identification of an Unknown Carbonyl Compound
CH3
CH3
\
C = 0 + H 2 NOH
/
CH3
CH3
C=NOH + H20
/
Acetoxime
CH3
\
B.
CH,
CH3
\
C = 0 + H2N—NH—CeH6
/
CH 8
C=N—NH—CeH 6 + H 2 0
/
Acetone phenylhydrazone
NO a
CH3
\
C = 0 + H2N—NH—/
CH3
\ — N 0 2 -•
CH3
02N
C=N—NH—(
\-N0
2
+ H20
CH3
Acetone 2,4-dinitrophenylhydrazone
CH3
\
o
CH3
o
C=N—NH—C—NH 2 + H 2 0
C = 0 + H 2 N—NH—C—NH 2
/
CH 3
CH 3
Acetone semicarbazone
for use in identification of the unknown. An ideal
derivative should be a crystalline, easily purified solid
with a sharp melting point which can be prepared
readily from the unknown in one direct and unambiguous step. It should possess properties distinctly
different from those of the parent compound and should
single out uniquely one compound from among all possibilities.
Carbonyl expounds (aldehydes and ketones) are
noteworthy for the number of excellent and conveniently prepared derivatives available for use in their
identification. In this experiment, several of the best
derivatives of aldehydes and ketones will be studied
—oximes, phenylhydrazones, 2,4-dinitrophenylhydrazones, and semicarbazones. You will observe from the
equations that the over-all reaction in the preparation
of each of these types of derivations involves the elimination of the elements of water between a molecule of
the carbonyl compound and a molecule of the reagent.
The oxygen of the water molecule is supplied by the
carbonyl group and the two hydrogen atoms by the
terminal NH2-group of the reagent molecule.
The phenylhydrazones, 2,4-dinitrophenylhydrazones,
and semicarbazones of most aldehydes and ketones are
solids. Conversion of the carbonyl compound to each
Introduction. One of the most frequently encountered
problems in organic chemical research is that of identifying an unknown compound. In attacking this problem, organic chemists, to some extent at least, follow a
systematic procedure which involves the following
steps:
1. Purification of unknown.
2. Qualitative (and sometimes quantitative) analysis
for elements.
3. Determination of solubility behavior and other
important physical constants.
4. Determination of functional groups present in
molecule or of the homologous series to which the
unknown belongs.
5. Survey of literature for the purpose of compiling
a list of all possibilities (based on data obtained in
steps 2-4).
6. Preparation of derivatives.
7. Synthesis of the unknown for comparison purposes by an unequivocal method.
Step 6 (the preparation of derivatives) usually establishes the identity of the unknown with certainty,
and step 7 (synthesis) is regarded as conclusive confirmatory evidence. The term "derivative" as used here
refers simply to a compound prepared from an unknown
72
DERIVATIVES OF ACETONE
of these derivatives not only effects a large increase in
molecular weight but also introduces at least one hydrogen atom capable of forming hydrogen bonds. The
molecular weight increase on conversion to oximes is
only 15 units; hence it is not surprising that a number
of oximes are liquids.
Hydroxylamine, phenylhydrazine, and semicarbazide
are not very stable in the free form and are usually
stored in the laboratory in the form of their hydrochloride salts. In each case, a basic reagent is used to
liberate the free base for reaction with the carbonyl
compound. The reaction of 2,4-dinitrophenylhydrazine
with aldehydes and ketones is catalyzed by strong
mineral acids.
In today's experiment you will prepare several typical
derivatives of the model carbonyl compound acetone.
Then you will begin the identification of an unknown
carbonyl compound. Determination of the melting point
of some of the acetone derivatives and complete identification of one (or possibly two) unknown carbonyl
compounds will require the next laboratory period, as
well.
I. DERIVATIVES OF ACETONE
0-35
A. Acetoxime. Dissolve 0.7 g. of hydroxylamine
hydrochloride in 1.5 ml. of water in a small Erlenmeyer
flask. Place the flask in an ice bath and add slowly a
cold solution of 0.5 g. of sodium hydroxide in 1 ml.
of water. Then, with the flask still in the ice bath,
add slowly 1 g. (25 drops) of acetone (Note 1).
The crystals of acetoxime will separate completely
within 10-15 minutes (Note 2). Then filter the crystals
(Note 3) by means of a small Hirsch (p. 21) or
Biichner funnel, and recrystallize from petroleum ether
73
(b.p. 40°-60°). Dry rapidly (Note 4) on filter paper or
in a desiccator and determine the melting point. Record
the results.
B. Acetone Phenylhydrazone. Add 0.4 g. (10 drops)
of acetone dissolved in 5 ml. of 95 per cent ethyl alcohol
to 5 ml. of a stock solution of phenylhydrazine hydrochloride (Note 5). Shake the mixture until a clear
solution is obtained (Note 1). Heat the mixture
on a steam bath for 10 minutes (Note 2). Then cool
in an ice bath and filter the crystals (Note 3).
Recrystallize the phenylhydrazone as follows: dissolve it in hot 95 per cent ethyl alcohol, add water to
the hot solution until a faint turbidity persists, then
add just enough 95 per cent alcohol to give a clear solution, and finally cool and filter the mixture.
C. Acetone 2,4-Dinitrophenylhydrazone. Add 2 ml.
of concentrated sulfuric acid to a solution of approximately 0.4 g. of 2,4-dinitrophenylhydrazine in 3 ml. of
water contained in a small Erlenmeyer flask. Swirl the
flask until solution is complete and then add 10 ml. of
95 per cent ethanol to the warm solution. Dissolve
0.5 g. (25 drops) of acetone in 10 ml. of 95 per cent
ethanol. Add the 2,4-dinitrophenylhydrazine solution,
and allow the resulting mixture to stand at room temperature. Crystallization of the acetone 2,4-dinitrophenylhydrazone usually occurs almost immediately; other
carbonyl compounds may require 5-6 minutes, or even
several hours (Note 2). When crystallization is complete, cool the mixture in an ice bath and filter. Recrystallize from 95 per cent ethanol, dry, and determine
the melting point of the acetone 2,4-dinitrophenylhydrazone.
D. Acetone Semicarbazone. In an 8-inch test tube,
dissolve 1 g. of semicarbazide hydrochloride and 1.5 g.
TABLE 5. CARBONYL UNKNOWNS AND MELTING POINTS OF DERIVATIVES (°C.)
2,4-DinitroCompound
Water
Solubility
B.P.
Sp. Gr.
56
0.79
n-Butyraldehyde
CH3CH2CH2CHO
Methyl ethyl ketone CH3CH2COCH3
Diethyl ketone
CH3CH2COCH2CH3
Furfural
C4H3OCHO
Crotonaldehyde.
CH3CH=CHCHO
Benzaldehyde
CeHsCHO
74
80
102
161
103
179
0.82
0.81
0.81
1.16
0.85
1.05
Completely
miscible
4 g./lOO g.
37 g./lOO g.
4.7 g./lOO g.
9 g./lOO g.
18 g./lOO g.
0.3 g./lOO g.
Cyclohexanone
2-Heptanone
n-Heptaldehyde
Acetophenone
2-Octanone
Salicylaldehyde
Cinnamaldehyde
156
151
156
202
173
197
252
0.95
0.83
0.82
1.03
0.82
1.15
1.10
2.1 g./lOO g.
Insol.
Insol.
Insol.
Insol.
1.72 g./lOO g.
Insol.
Acetone
Formula
CH3COCH3
CeHioO
CH3(CH2)4COCH3
CH3(CH2)5CHO
CCHBCOCHS
CH3(CH2)5COCH3
C6H5(OH)CHO
C6H6CH=CHCHO
1
Oxime
60
Oil
Oil
69
89
119
35
(dec.)
91
Oil
57
59
Oil
63
139
SemiphenylPhenylhydrazone hydrazone carbazone
42
128
190
Oil
Oil
Oil
97
56
158
123
126
156
229
190
237
106
187
139
202
199
224
81
207
Oil
105
Oil
143
168
162
89
108
250
58
252
255
(dec.)
167
127
109
199
123
231
215
25-60
40-75
60-100
74
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
of sodium acetate in 10 ml. of water, add 1 g. (25
drops) of acetone, and shake vigorously (Note 1).
Place the test tube in a beaker of boiling water for
5 minutes and let it cool. Transfer the tube to an ice
bath and scratch the sides with a glass stirring rod. Cool
until crystallization is complete. Filter the crystals, wash
with a few ml. of water, and recrystallize from 95 per
cent alcohol. Dry and determine the melting point of
the semicarbazone.
100-360
II. IDENTIFICATION OF AN UNKNOWN
CARBONYL COMPOUND
While the various acetone derivatives are drying,
obtain a sample of an unknown from your instructor
and begin its identification. Proceed as far as you can
this period, and complete the identification during the
next period. If you work especially efficiently, you may
be able to solve two carbonyl unknowns by the end of
the second period. Your unknown may be any aldehyde
or ketone listed in Table 5, or a noncarbonyl compound.
Test for the carbonyl group by means of the phenylhydrazine and 2,4-dinitrophenyIhydrazine reactions described in Section I for acetone. In each case, substitute
your unknown for the acetone. If the test is positive,
save the phenylhydrazones formed for later use as one
of your derivatives. If your unknown is not a carbonyl
compound, obtain a second unknown.
Now by means of physical constants, any tests in
Experiment 20 which will be helpful, the iodoform test
(Experiment 23) if it will be useful, and appropriate
derivatives, identify your unknown. The derivatives may
in every case be prepared by the procedures given in
Section I. Merely substitute your unknown for the acetone.
When you have completed the identification, submit
your derivatives to your instructor, along with your
report.
NOTES
1. If the unknown does not dissolve completely or if
the solution is turbid at this point, add just enough 95
per cent alcohol to give a clear solution.
2. During this period, proceed with the preparation of
the next derivative.
3. If no solid separates on cooling add 3 volumes of
water and cool again.
4. Acetoxime has a rather high vapor pressure and
evaporates readily in the air.
5. The stock solution of phenylhydrazine hydrochloride
can be prepared as follows: add 45.0 g. of crystalline
sodium acetate to a solution containing 25.0 g. of colorless
phenylhydrazine hydrochloride in 250 ml. of water. Stir
until all the sodium acetate has dissolved and store in an
amber bottle.
If the phenylhydrazine hydrochloride is dark it should
be decolorized. Dissolve the phenylhydrazine hydrochloride
in six times its weight of water, add a small amount of
decolorizing charcoal, and heat at the boiling point for
10 minutes. Then filter the hot solution, add a volume of
concentrated hydrochloric acid equal to one third that of
the solution, cool in an ice bath, and filter.
QUESTIONS
1. After a study of Table 5, explain why it is often
necessary to prepare more than one derivative in the
identification of an aldehyde or ketone.
2. Propose a mechanism for the reaction of hydroxylamine, phenylhydrazine, 2,4-dinitrophenylhydrazine, and
semicarbazide with carbonyl compounds. How do these
reactions differ in mechanism from the addition of ammonia to acetaldehyde?
3. Point out one important advantage in using low
boiling petroleum ether as a solvent for recrystallization.
4. Which of the various derivatives of aldehydes and
ketones do you prefer in general? Why?
EXPERIMENT 22
Dimethylglyoxime
(1)
C2H5OH + N a N 0 2 + H 2 S0 4
(2)
C2H5ONO + H 2 0
(3)
CH3—CH2—C—CH3 + H — O — N = 0
II
II II
HON
O
Introduction. Dimethylglyoxime is of special interest
because of its wide use as a reagent for the qualitative
and quantitative analysis of nickel. It is actually the
dioxime of the diketone called biacetyl or dimethyl
0
glyoxal (CH3—C—C—CH3) but may be more cheaply
prepared from the readily available ketone 2-butanone
(methyl ethyl ketone). The key step is the nitrosation
of methyl ethyl ketone with nitrous acid to produce the
monoxime of biacetyl. This step illustrates a fairly
general reaction of a methylene (CH2) group adjacent
to a carbonyl group, which is frequently used to oxidize
a carbonyl compound to a 1,2-dicarbonyl compound.
The monoxime of biacetyl is then treated with hydroxylamine to form the dioxime, dimethylglyoxime.
In this experiment you will introduce the nitrous acid
into the reaction mixture indirectly by passing gaseous
ethyl nitrite into an acidified solution of methyl ethyl
ketone. The ethyl nitrite is hydrolyzed in the acid
medium to nitrous acid and ethyl alcohol.
0-30
H — O — N = 0 + QHsOH
CH 3 —C—O-CH3 + H 2 0
HON
CH 3 —O-C—CH 3 + H 2 NOH
0
HCl
II II
O
(4)
> QHgONO + NaHS0 4 + H 2 0
A. Preparation of Dimethylglyoxime
Assemble the apparatus as shown in Figure 23. The
filter flask, which is to serve as the ethyl nitrite generator, should be 1 liter in size, and the distilling flask,
which will be the actual reaction vessel, 125 ml. The
O
CH3—C—C—CH3 + H 2 0
II II
HON
NOH
two bottles of 5 per cent sodium hydroxide solution
serve to remove excess ethyl nitrite (Note 1). As an
alternative means of absorbing excess ethyl nitrite the
two bottles may be replaced by the type of trap shown
at the extreme right in Figure 23.
To the ethyl nitrite generator (filter flask) add a
solution of 40 g. of commercial sodium nitrite, 300 ml.
of water, and 15 ml. of 95 per cent ethyl alcohol. Place
in the reaction flask (distilling flask) 45 ml. (36 g.,
0.50 mole) of methyl ethyl ketone and 3 ml. of concentrated C.p. hydrochloric acid.
Add to the dropping funnel (be certain that the
stopcock is closed!) a solution of 15 ml. of 95 per
cent ethyl alcohol in 300 ml. of water which has been
acidified with 25 ml. of concentrated sulfuric acid. Be
certain that all stoppers are inserted tightly. Then allow
the solution in the dropping funnel to drop into the
generating flask at the rate of about 1 drop per second
so that all of it is introduced during the course of 45-50
minutes. Shake the generating flask frequently during
this period.
The heat of reaction soon warms the mixture in the
distilling flask to above 40°; raise or lower the cooling
bath as needed to maintain the temperature between
45°-55° until all of the ethyl nitrite has been absorbed.
During this period prepare a solution of hydroxylamine
by dissolving 28 g. (0.4 mole) of hydroxylamine hydro-
Gentle stream of
water from tap.
FIG. 23. Ethyl nitrite generator and ethyl nitrite-methyl
ethyl ketone reaction flask.
75
30-100
76
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
chloride and 33 g. (0.40 mole) of sodium acetate in
300 ml. of water in a 1-liter beaker.
100-130
When all of the ethyl nitrite has been absorbed by
the methyl ethyl ketone, pour the biacetyl monoxime
solution from the distilling flask into the beaker containing the hydroxylamine solution, with constant stirring. Heat the mixture over a wire gauze on a ring
stand to 75° with constant stirring. Remove the burner,
and continue to stir for an additional 15 minutes. Then
place a large sheet of filter paper over the beaker to
keep out dust and store the material overnight to allow
the dimethylglyoxime to crystallize.
[Use the balance of the period to assemble the apparatus for Experiment 23.]
Collect the crystalline product on a filter, wash with
four 25-ml. portions of cold water and then with 15 ml.
of ice-cold acetone, and finally dry on filter paper or
in an oven at 80°. The yield is about 35 g. of dimethylglyoxime, melting at 235°-240°. Calculate the percentage yield (Note 2) and determine the melting point
for reporting to your instructor. This product is suitable
for most laboratory purposes but may be recrystallized
from glacial acetic acid if a very pure material is desired.
B. Properties of Dimethylglyoxime
(Optional for specially interested students; to be
performed during the next laboratory period.)
Solubility in Alkali Dissolve 1 g. of dimethylglyoxime
in 10 ml. of warm 5 per cent sodium hydroxide solution
and divide the solution into two parts. Pour one part
into 10 ml. of 95 per cent ethyl alcohol. The sodium
salt of dimethylglyoxime crystallizes from the alcohol solution as the octahydrate, (CH 3 —C—C—CH 3 -8H 2 0),
II II
Na+,-ON
NO-,Na+
upon cooling.
Dilute the second half of the alkaline solution with
5 ml. of water and then acidify with dilute hydrochloric
acid. Observe the results.
Tests with Metallic Salts. Dissolve a small crystal
of a nickel salt in a few ml. of water, add 1 ml. of
sodium acetate solution, and then a few drops of 1
per cent solution of dimethylglyoxime in alcohol. Observe the results. Repeat the test several times, each
time diluting the solution of the nickel salts in order
to test the sensitivity of the test.
Repeat with copper and cobalt salts. Add the alcoholic solution of dimethylglyoxime to a dilute freshly
prepared solution of a ferrous salt and introduce a few
drops of ammonium hydroxide. Observe the results.
NOTES
1. The delivery tube leading into the first bottle should
extend just below the surface of the sodium hydroxide
solution. Ethyl nitrite, like the other lower molecular
weight alkyl nitrites, is a vasodilator (an agent which
causes dilation of the blood vessels). Isoamyl nitrite, because of this property, is used for treatment of angina
pectoris. Inhalation of these nitrites soon produces marked
flushing, throbbing in the head, and occasionally nausea.
The fume absorber may be replaced by two wash bottles
in series containing an alkaline solution of ethyl alcohol
or may be dispensed with if the experiment is performed
in an efficient hood.
2. It is standard practice, in a multi-step synthesis, to
base the yield on the major organic starting material. In
this case, for example, the yield should be based on 0.5
mole of methyl ethyl ketone, even though only 0.4 mole of
hydroxylamine hydrochloride is later used. At that stage,
there is less than 0.4 mole of the biacetyl monoxime,
formed in the prior step, available for reaction with the
hydroxylamine.
QUESTIONS
1. Show the structure of the compound which precipitates when nickel ion is heated with dimethylglyoxime.
What name is given to this general type of compound?
2. How can you account, on the basis of structure, for
the acidity of oximes?
EXPERIMENT 23
I. Preparation of Chloroform
o
II
(1)
(2)
(1) + (2)
o
II
CH3—C—CH3 + 3C12 + 3 0 H " - • CH3—C—CC13 + 3C1" + 3H 2 0
O
CH3—C—CC13 +
O
+ CHC13
OH" -> CH3-
O
O
II
II
CH3—C—CH3 + 3C12 + 4 0 H " -> CH3—C—O"
+ CHC13 + 3H 2 0
II. Properties of Chloroform
III. The Iodoform Test
Introduction. Chloroform is produced commercially
by the chlorination of methane and methyl chloride, by
the reduction of carbon tetrachloride with iron and
water, and by the action of bleaching powder on
acetaldehyde or acetone. In today's experiment, the last
of the three methods, with acetone as the starting material, is utilized as a convenient laboratory synthesis
of chloroform.
The reaction proceeds in two stages. In the first
stage, one of the methyl groups is fully substituted by
chlorine1 to produce trichloroacetone. In alkaline solution the substitution of three chlorine proceeds
readily, with each successive chlorine substituting more
easily than the one before. The second stage of the
synthesis is the alkaline cleavage of the trichloroacetone
to form chloroform and sodium acetate.
The preparation of chloroform by the reaction of
acetone with chlorine in alkaline solution is an example
of an important general type of reaction known as the
haloform reaction. Whenever (1) an aldehyde or a
ketone containing a CH 3 —C— grouping, or (2) an
alcohol which is oxidized by the reagent to give such
an aldehyde or ketone, is treated with an alkaline solution of a halogen, the corresponding haloform is
formed. This is the haloform reaction.
O
Specifically, this includes the following groups of
compounds:2
H
Aldehydes CH 3 —C=0
Acetaldehyde only
O
Ketones
R—C—CH3
AH methyl ketones
Primary
alcohols
CH3—CH2OH
Ethyl alcohol (which is
oxidized to acetaldehyde; only
Secondary
alcohols
OH
|
R—C—CH3
H
All methyl carbinols
(which are oxidized
to methyl ketones).
When the halogen used is iodine, the haloform obtained, iodoform or tri-iodomethane (CHI 3 ), is readily
identified by its characteristic odor and bright yellow
color and by its melting point of 119°-120°. Formation
of iodoform upon treatment of an unknown with iodine
and sodium hydroxide is the basis for the iodoform test,
an important diagnostic test for the structures shown
above. It has played an important role in the development of organic chemistry and is widely used in research
today.
I. PREPARATION OF CHLOROFORM
II
In general, compounds which contain the CH 3 —C—
grouping joined to a hydrogen or carbon atom, as well
as compounds which give such a structure upon oxidation, undergo the haloform reaction.
Weigh 100 g. of fresh high test bleaching powder,
such as HTH or Perchloron (Note 1) into a 600-ml.
beaker and add 300 ml. of water. Stir the mixture into a
thin slurry and pour it into a 1-liter round-bottomed
flask. Fit a reflux condenser to the flask and mount the
1
Bleaching powder is a mixture whose composition may be
represented roughly by the formula CaCl(OCl). In water, it
gives chlorine and calcium hydroxide: CaCl(OCl) + H z O->
Cla + Ca(OH) 2 . It therefore constitutes a ready source of chlorine in alkaline solution.
2
It is understood throughout that the methyl group may
already be partially halogenated in every case. Thus, CH2X—
CHO, CHXSr—CHO, and CXs—CHO, as well as CHU—CHO,
would undergo the haloform reaction with Xa in alkaline solution.
77
0-70
78
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
assembly on a ring stand. Add through the condenser
a total of 37 ml. (0.5 mole) of acetone in 2-ml.
portions, shaking the flask gently with a rotary motion
after each addition. Cool the flask occasionally in cold
water if the reaction becomes too vigorous. After all
of the acetone has been added, continue to shake the
O
water in a small separatory funnel and then allow the
layers to separate. Observe and record the results.
Test chloroform for flammability.
III. THE IODOFORM TEST 3
For acetaldehyde and methyl ketones
O
R—C—CH3 + 3I2 + 3NaOH - •
R—C—CI3 + 3NaI + 3H20
O
O
II
II
R—C—CI3
O
+
NaOH -> CHI3 + R—C—ONa
O
II
II
R—C—CH3 + 3I2 + 4NaOH -> CHI3 + R—C—ONa + 3NaI + 3H20
For ethyl alcohol and secondary methyl carbinols
OH
R—C—CH3 +
H
O
II
O
I2 + 2NaOH - •
R—C—CH3 + 2NaI + 2H20
O
II
R—C—CH3 + 3I2 + 4NaOH -> CHI3 + R—C—ONa + 3NaI + 3H2Q
OH
O
I
II
R—C—CH3 + 4I2 + 6NaOH -> CHI3 + R—C—ONa + 5NaI + 5H20
H
flask at frequent intervals for an additional 10 minutes.
Run the iodoform test on (1) acetaldehyde, (2)
Arrange the apparatus for steam distillation, as acetone, (3) methyl ethyl ketone, (4) methyl alcohol,
shown in Figure 15, page 33. Begin the steam distil- (5) ethyl alcohol, (6) isopropyl alcohol, and (7)
lation and continue until droplets of chloroform can n-propyl alcohol as follows:
no longer be observed in the distillate. Transfer the
Add 4 drops of the substance to be tested to 5 ml.
distillate to a small separatory funnel, draw off the of water (in the case of acetaldehyde, merely use the
lower chloroform layer into a small Erlenmeyer flask, water solution as it comes from the shelf) in a small
and wash it once with 20 ml. of water. Dry the moist test tube. Make the solution alkaline by the addition
chloroform over anhydrous calcium chloride with fre- of 12 drops of 10 per cent sodium hydroxide solution.
quent gentle shaking for several minutes.
Then add to the mixture, a drop at a time, the iodine
Decant the dry chloroform from the desiccant into a in potassium iodide reagent until the solution remains
small distilling flask and distill into a tared bottle, ob- straw-colored after a minute of shaking. In a positive
serving and recording the boiling point range. Weigh test the brown iodine color disappears and yellow iodothe chloroform and calculate the percentage yield. The form is precipitated.
recorded boiling point of chloroform is 61.2° at 760
Note the odor of the solution and also whether a
mm. and its specific gravity 1.49.
precipitate forms. If no precipitate develops, warm the
solution to about 60° and allow it to stand for a minute.
If the solution becomes colorless, add more iodine solution and repeat the warming.
NOTE
Isolate the iodoform in at least one case as follows:
1. Best results are obtained if fresh bleaching powder add 3 ml. of chloroform, stopper the test tube and
specified to have at least "70 per cent available chlorine"
shake vigorously to extract the iodoform in the lower
is used.
chloroform layer, withdraw this layer with a capillary
II. PROPERTIES OF CHLOROFORM
dropping tube, transfer to a small test tube, and remove
the chloroform by evaporation on a steam bath.
Test the solubility of each of the following in chloro8
form: ether, ethyl alcohol, water, rubber, vaseline.
R (in the general formulas in this section) = a hydrogen
Shake 4 ml. of chloroform with 4 ml. of bromine atom or an alkyl group.
THE IODOFORM TEST
Recrystallize the iodoform from a 1:1 mixture of
methanol and water, dry in a desiccator, and determine
the melting point.
QUESTIONS
1. How many grams of chloroform could be obtained
theoretically from 100 g. of acetaldehyde? Of acetone?
Of ethyl alcohol?
2. What important general commercial use of chloroform is suggested by its properties? What properties make
chloroform a useful extraction solvent?
79
3. Write a general equation for the preparation of a
carboxylic acid, RCOOH, from a ketone by means of the
haloform reaction. If your interest was only in the preparation of the acid, what halogen would you use? Why?
4. Write a balanced equation for the iodoform reaction
as run on 2-butanol (s-butyl alcohol).
5. Which of the following will give a positive iodoform
test: 1-pentanol, 2-pentanol, 3-pentanol, diethyl ketone,
methyl n-butyl ketone, dimethyl ether, acetic acid? Write
balanced equations for the reactions.
6. What weight of iodoform might be obtained theoretically from 1 g. of acetaldehyde?
EXPERIMENT 24
Preparation of a Carboxylic Acid (Benzoic Acid)
by the Grignard Method
CeHeBr + Mg Eth.
— CeH6MgBr
(i)
O
(2)
C6H5MgBr + C 0 2
-» CeHB—C—OMgBr
O
O
(3)
C6H5—C—OMgBr + HC1
> G6H5—C—OH + MgClBr
the preparation of a Grignard reagent. Actually, the
ether plays a more important role in the reaction than
merely that of solvent. Ether molecules combine with
the various components of a Grignard reagent to form
complex etherates. For example, one of the components
present in phenylmagnesium bromide-ether solution is
the complex shown below:
Introduction. Some of the common methods for the
preparation of carboxylic acids include the oxidation of
alcohols, hydrolysis of nitriles and the carbonation of
Grignard reagents. The latter procedure will be illustrated in today's experiment.
Owing to the fact that a solid carboxylic acid is much
easier to isolate and purify than a liquid acid, benzoic
acid, m.p. 121°, rather than a liquid aliphatic acid,
has been selected for this assignment. It will be prepared by treatment of phenylmagnesium bromide with
solid carbon dioxide (Dry Ice) and subsequent acidification of the reaction mixture by the addition of
hydrochloric acid.
The Grignard reagent, phenylmagnesium bromide, is
to be prepared at the start of the present period by
reaction of bromobenzene with metallic magnesium.
The entire sequence of steps employed in this synthesis
of benzoic acid is shown in the equations at the top of
the page.
Since most of the common aliphatic carboxylic acids
are liquids at room temperature, such acids are purified
by distillation. If one were to prepare such an acid by
the Grignard method, not only would the purification
by distillation have to be carried out, but also it would
be necessary to prepare at least one solid derivative of
the acid in order to identify the product in a reasonably
certain manner. Hence the entire experiment could
not conveniently be completed in a regular 3-hour
laboratory period.
However, in the actual practice of organic chemistry
in industrial or institutional laboratories, where there
are no arbitrary time limits for completing an experiment, the syntheses of certain aliphatic carboxylic acids
can better be achieved by the Grignard process than by
other methods. For example, trimethylacetic acid,
(CH 3 ) 3 CCOOH, is readily prepared from r-butyl chloride, (CH3)3CC1, by the Grignard method, whereas
the nitrile route would be of no use whatsoever; treatment of f-butyl chloride with sodium cyanide gives
sodium chloride, hydrogen cyanide and isobutylene
rather than trimethylacetonitrile, (CH 3 ) 3 CCN.
Anhydrous ether is generally used as the solvent in
C2H5—O—C2H6
C6H6—Mg—Br
C2H5—0—C2H5
As implied in the previous paragraph, a Grignard
reagent is actually an equilibrium mixture of different
molecular species. One of the equilibria thought to
exist in any Grignard reagent is shown in the following
equation, which has been simplified in that the ether
molecules coordinated with the magnesium are not
shown:
2RMgX <=> R2Mg + MgX2
Addition of anhydrous dioxane to an ether solution
of a Grignard reagent causes RMgX and MgX2 to
precipitate, leaving R2Mg in solution. Occasionally, for
certain specific reactions, it is preferable to use the
filtrate from such a mixture rather than the Grignard
mixture itself; i.e., there are certain Grignard reactions
in which the use of R2Mg is preferable to the use of
the equilibrium mixture of RMgX, MgX2 and R2Mg.
However, no such complication exists in today's experiment.
Grignard reagents can be prepared successfully only
in a completely anhydrous medium and in an atmosphere that is free of oxygen. The presence of water
causes hydrolysis of the reagent, and the presence of
oxygen causes loss of the reagent by oxidation.
RMgX + H 2 0 -> RH + Mg(OH)X
2RMgX + 0 2 -> 2ROMgX
Therefore, in carrying out a Grignard reaction, one
must take care to dry the apparatus and all of the
80
PREPARATION OF A CARBOXYLIC ACID (BENZOIC ACID)
reagents (magnesium metal, ether, and organic halide)
carefully and also to provide an inert atmosphere over
the reaction mixture. The latter condition is best realized by passing highly purified nitrogen over the surface
of the liquid.
However, in today's experiment, the oxygen-free
atmosphere will be attained by keeping the ether solution warm during the preparation of the Grignard
reagent. Ether is so highly volatile (boiling point 35°)
that a blanket of ether vapor over the warm solution
keeps the reagent reasonably well insulated from contact
with the air.
0-30
30-60
G6-90
**-130
Preparation of a Carboxylic Acid
Fit a dry (Note 1), 500-ml. round-bottomed flask
with a dry, water-cooled condenser, using a clean and
well-fitting cork; a drying tube filled with calcium
chloride is attached to the top of the condenser. (See
Figure 18, page 46.) In the flask place 8.0 g. of dry
magnesium turnings, a few small crystals of iodine,
20 ml. of anhydrous ether (Note 2), and 10 ml. (15 g.)
of anhydrous bromobenzene (Note 3). If reaction does
not start immediately, warm the flask on the steam bath
so that the ether refluxes gently and then remove the
bath. This will usually initiate the reaction. The disappearance of the iodine color, the production of a
cloudiness in the solution, and gentle boiling of the
ether are all indications that the reaction has started
(Note 4).
Replace the drying tube by a separatory funnel containing a solution of 26 ml. (38 g.) of bromobenzene
in 140 ml. of ether; fit the separatory funnel into the
top of the condenser by use of a cork which has been
grooved on each side by rubbing a triangular file vertically along the sides. Place the calcium chloride drying
tube in the mouth of the separatory funnel. Allow
the bromobenzene solution to run into the flask at such
a rate that the ether refluxes vigorously because of the
exothermic nature of the reaction. (Begin to answer
the questions at the end of this unit of work.)
When all of the solution of bromobenzene has been
introduced into the reaction flask, replace the separatory
funnel by the calcium chloride tube and heat the mixture
under gentle reflux on the steam bath for 30 minutes
(continue with the questions). By the end of this period,
the solution should be somewhat cloudy and almost all
of the magnesium should have gone into solution.
Place about 80 g. of crushed solid carbon dioxide
(Note 5) in a large beaker and decant the ether solution of the Grignard reagent slowly and steadily onto
the carbon dioxide; be sure to leave any unreacted
magnesium metal behind in the round-bottomed flask.
Stir the mixture with a glass rod as the Grignard solution is being added to the Dry Ice. The reaction is
vigorous, and the mixture sets to a stiff mass. Continue
stirring the mixture until all of the excess of carbon
dioxide has evaporated. Add about 200 g. of crushed
81
ice and then 60 ml. of 6 M hydrochloric acid. Stir the
mixture until most of the solid mass has disintegrated.
Pour the mixture into a separatory funnel, and wash
the last of the material from the beaker into the funnel
with the aid of several small portions of ordinary ether.
Draw off the lower aqueous layer and discard it. Wash
the ether layer with two 25-ml. portions of water, and
discard the wash solutions. Extract the ether solution
with two 100-ml. portions of 5 per cent sodium hydroxide solution and collect the alkaline solution in a
clean Erlenmeyer flask. Warm the alkaline solution with
about 1 g. of decolorizing carbon and filter the mixture
with suction. If necessary, filter the solution a second
time to remove the last of the carbon. Cool the filtrate
in ice and acidify it with 6 M hydrochloric acid. Collect the precipitate of benzoic acid on a Biichner funnel
by suction filtration. Recrystallize about 1 g. of the
acid from hot water and determine its melting point. 130-160
Dry the remainder of the acid by spreading it out
on filter paper or a paper towel and allowing it to
stand in the air for the remainder of the period. In the
meantime place the ether remaining in the separatory
funnel in a bottle which will be provided by the instructor.
Weigh the benzoic acid and calculate the yield.
160-170
NOTES
1. The flask should be dried in an oven at about 100°
for several minutes before the apparatus is assembled.
The condenser, apparently dry, should be rinsed with a
little absolute ether.
2. Anhydrous ether should be prepared by one of the
methods described in Experiment No. 10 (page 46).
3. The bromobenzene, if not already dry, must be dried
over anhydrous calcium chloride and redistilled before it
can be used.
4. If the reaction does not start after this treatment, add
some more iodine and crush an iodine crystal together
with a magnesium turning against the wall of the flask by
use of a stirring rod that has aflattenedend. If the reaction
still does not start, it will be necessary for you to try
the whole procedure again, this time taking even greater
care than before to dry the apparatus and all the reagents.
5. The solid carbon dioxide should not be handled with
the fingers. Place a few lumps on a towel with the aid of
tongs, wrap the towel around the solid and pound the
towel and its contents with some blunt object such as a
mallet or block of wood to powder the Dry Ice.
QUESTIONS
1. In what way does carbon dioxide resemble an
aldehyde, ketone, or ester?
2. Write a detailed mechanism for the condensation
of phenylmagnesium bromide with carbon dioxide.
3. Write equations to show what products are formed
in the reaction of ethylmagnesium bromide with each of
the following reagents:
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
82
(a)
(b)
(c)
(d)
H20
C 2 H 5 OH
02
acetone
(e)
(f)
(g)
(h)
ethyl acetate
acetaldehyde
C02
capronitrile
4. Would a Grignard reagent be formed on treatment
of 4-bromo-l-butanol with magnesium in anhydrous ether?
Explain your answer.
5. In the electrolysis of a Grignard solution, ions containing magnesium migrate to both the anode and cathode.
How can this result be explained?
6. Write equations to show how f-amyl chloride can
be converted to dimethylethylacetic acid.
7. Name several types of organometallic reagents other
than Grignard reagents.
8. Describe an analytical method making use of a
Grignard reagent whereby the number of "active hydrogen" atoms in a molecule may be determined.
9. Write equations to show how primary, secondary,
and tertiary alcohols may be produced by the action of
Grignard reagents on aldehydes or ketones.
10. A student was instructed to prepare triethylcarbinol
by treatment of ethyl propionate with ethylmagnesium
bromide. Inadvertently he used methyl propionate rather
than the ethyl ester. How would this affect his results?
11. When alcohols are prepared by a Grignard reaction,
ammonium chloride solution rather than hydrochloric acid
is ordinarily used to hydrolyze the reaction mixture. Why
is this the case?
12. Which is more reactive toward a given Grignard
reagent, a ketone or an ester? Explain your answer.
EXPERIMENT 25
Formic Acid
o
II
3CH3OH + 2Na 2 Cr 2 0 7 + 8H 2 S0 4 -» 3H—C—OH + 2Cr 2 (S0 4 ) 3 + 2Na 2 S0 4 + 11H 2 0
0-10
Introduction. The first member of a homologous
series frequently possesses some properties that are not
characteristic of the series as a whole. This is particularly true of formic acid. Examination of its structure reveals that it is, in a sense, both an aldehyde and
a carboxylic acid. The aldehyde properties are reflected
in the ease of oxidation of formic acid by mild reagents
such as Tollens' solution or mercuric chloride. The
acid properties are apparent in the acidity of the compound. (Ka = 2.1 x 10- 4 at 25°) and in its ability to
form esters with alcohols and salts with suitable bases.
The latter property tends to mask certain of the properties of the aldehyde function.
For example, reagents such as hydroxylamine and
phenylhydrazine form salts with formic acid rather than
the oxime or phenylhydrazone, respectively. The large
resonance energy and consequent stability of the formate anion precludes further reaction with a second
molecule of hydroxylamine or phenylhydrazine.
Other unusual chemical properties of formic acid
include its sulfuric acid-catalyzed decomposition to
water and carbon monoxide and also its inability to
form the acid chloride, formyl chloride, on treatment
with phosphorus trichloride; hydrogen chloride and carbon monoxide are formed instead, presumably by decomposition of the unstable and nonisolable acid chloride.
As a part of today's assignment, formic acid will be
prepared in two different ways. One of these involves
the oxidation of methanol with sodium dichromate and
sulfuric acid in which, as might well be expected, the
yield is low owing to the ease of oxidation of the desired product. In the second method of preparation of
formic acid, glyceryl monooxalate is first formed by reaction of glycerol with oxalic acid. On being heated to
a temperature of 90°-115°, glyceryl monooxalate loses
carbon dioxide to form glyceryl monoformate. Hydrolysis of the latter compound affords formic acid.
Preliminary Operation. Before beginning the preparation of formic acid by oxidation of methanol, make
preparations for the oxalic acid-glycerol method by
placing about 60 g. of commercial oxalic acid in an
oven maintained at 110°. The oxalic acid will be anhydrous by the time that it is needed.
of methanol dropwise, with continuous shaking of the
flask. After the initial spontaneous reaction has subsided, attach a glass tube 50 cm. in length to the distilling flask to serve as a reflux condenser (see Figure
24a), and set the flask in a beaker of hot water for 5
FIG. 24a. Use of a glass tube as an air condenser in the
oxidation of methanol.
minutes. Attach the flask to a condenser and distill
25-30 ml. of the liquid. The distillate consists of an
aqueous solution of formic acid and may be used for
the tests described below.
Formic Acid as a Reducing Agent
(a) Reduction of Tollens' Solution. Add about 1
ml. of the formic acid solution to 5 ml. of Tollens'
reagent. Warm the solution gently and note the result.
Write the equation for the reaction.
(b) Reduction of Mercuric Chloride. Heat 5 ml. of
the formic acid solution with an equal volume of a saturated solution of mercuric chloride. What is the initial
white precipitate? Why does it gradually darken? Write
the equation for the reaction.
Decomposition of Formic Acid
(CAUTION: Carbon monoxide, a poisonous gas,
is evolved in this experiment. Carry out the experiment
in the hood.) Warm 1 g. of sodium formate with 5 ml.
of concentrated sulfuric acid. Note the result, and write
the equation for the reaction. Why must sodium formate
be used in this experiment rather than the aqueous solution of formic acid prepared earlier?
30-50
50-60
60-70
70-80
I. PREPARATION OF FORMIC ACID FROM METHANOL
10-30
Salts of Formic Acid
(a) Hydrolysis of Sodium Formate. Dissolve 1 g. of
sodium formate in 5 ml. of water, and test the solution
with litmus paper. Explain the result.
Procedure. Place a solution containing 16 g. of sodium dichromate, 50 ml. of water, and 10 ml. of concentrated sulfuric acid in a 125-ml. distilling flask and
immerse the flask in a pan of cold water. Add 10 ml.
83
80-90
84
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
90-100
(b) Preparation of Lead Formate. Boil 10 ml. of
formic acid solution with about 2 g. of litharge (PbO)
for 2 minutes and filter the hot solution rapidly. Lead
formate crystallizes as the filtrate cools. Write the equation for the reaction between formic acid and PbO.
100-120
Answer the questions at the end of today's assignment as anhydrous glycerol is being prepared for the
next experiment.
immersed in the reaction mixture. Support the flask by
clamping it loosely at the neck, and connect it with a
water-cooled condenser as shown in Figure 24b.
Heat the flask gendy by waving a slightly luminous
flame of the Bunsen burner beneath it, and agitate the
flask frequently in order to obtain a uniform melt. The
use of a wire gauze is not necessary. Raise the temperature of the reaction mixture to 110°-115° and main-
II. FORMIC ACID FROM OXALIC ACID BY THE AID OF GLYCEROL
H
H
H—C—OH
I
0
O
II
H—C—OH
II
-H 2 O
H—C—OH + HO—C—C—OH
I
»H—C—OH
O O
I
I
H—C—OH
I
II
H—C—O
II
C—C—OH
I
H
H
Glyceryl monooxalate
-CO*
H
H—C—OH
H
I
O
H—C—OH + H—C—OH *
I
H—C—OH
H
Procedure. Heat 50 ml. of glycerol in an evaporating
100-120 dish or a beaker until a thermometer inserted in the
liquid registers a temperature of 180°. By this time,
most of the water present in ordinary glycerol will have
120-140 been driven off. When the vessel has cooled somewhat
transfer the anhydrous glycerol to a 500-ml. distilling
flask and add 50 g. of the oxalic acid that has been drying in the oven since the start of the period. Fit the flask
with a stopper and thermometer, the bulb of which is
FIG. 24b. Distillation assembly for the preparation of
formic acid from glycerol monooxalate.
H—C—OH
hydrol
I
H—C—OH
O
I
II
H—C—O
I
C—H
H
Glyceryl monoformate
tain that temperature for about 7 minutes. Evolution
of carbon dioxide begins at about 90°, and a large volume of the gas is given off during the period of heating
at 110°-115°. Finally, apply heat at such a rate that the
temperature of the reaction mixture rises from 115° to
130° during the course of 15 minutes.
During this period of time about 20 ml. of aqueous 140-155
formic acid (approximately 50 per cent formic acid)
collects in the receiver. To obtain a rough measure of
the amount of formic acid present in the distillate, dis- 155-165
solve 10 ml. of the distillate in 50 ml. of water, add a
few drops of phenolphthalein indicator and determine
how many ml. of 10 per cent sodium hydroxide solution are needed to neutralize the solution. Inasmuch as
the result is only an approximate one in this crude titration, the use of a graduated cylinder suffices for the
measurement of volumes.
QUESTIONS
1. What is the approximate pH of a 0.01 M solution
of formic acid in water at 25°?
2. Calculate the approximate pH of a 0.01 M solution
of sodium formate in water at 25°.
3. Would it be proper to say that glycerol functions
FORMIC ACID
as a catalyst for the conversion of oxalic acid to formic
acid? Explain.
4. Why is less than the theoretical quantity of sodium
dichromate used in the preparation of formic acid from
methanol?
5. Is it likely that the aqueous distillate from the oxi-
85
dation of methanol contains some formaldehyde? How
would it be possible to separate formaldehyde from formic
acid?
6. How may pure formic acid be obtained from an
aqueous solution of the acid?
EXPERIMENT 26
I. Ethyl Acetate
o
CH 3 —C—OH + QHsOH
HJSO.
> CH 3 —€—OQHs + H a O
II. Preparation of Soap and Glycerol
o
CH2—o—c—R
CH 2 —OH
o
CH—O—C—R + 3 N a O H
> CH—OH + 3R—C—ONa
O
CH,
Introduction. The reaction of a carboxylic acid with
an alcohol to produce an ester plus water is known as
the Fischer esterification reaction. A mineral acid, usually sulfuric acid or hydrochloric acid, is used as a
catalyst. Since the reaction is reversible the law of mass
action is applicable. This law states that when equilibrium is attained in a reversible reaction at constant
temperature, the product of the concentration of the
substances formed, divided by the product of the concentration of the reacting substances, each concentration being, raised to that power which is the coefficient
of the substance in the chemical equation, is a constant.
CH 2 —OH
and, although they too are fats, are usually referred to
as oils. The alkaline hydrolysis of any fat results in the
formation of glycerol and a soap; hence, the terms
"alkaline hydrolysis" and "saponification" have become
synonomous.
I. ETHYL ACETATE
Procedure. Into a 500-ml. round-bottomed flask place
0-20
60 g. (1 mole) of glacial acetic acid and 75 ml. of 95
per cent ethanol. Then, with constant shaking of the
flask, slowly add 10 ml. of concentrated sulfuric acid.
Connect the flask to a water cooled reflux condenser
and heat the mixture under reflux for 30 minutes on the
20-50
steam
bath.
RCOOH + ROH T± RCOOR + H 2 0
[During the period of refluxing proceed with Part II.]
K = t e s t e r •> v-Avater
At the end of the period of refluxing, cool the flask 50-100
^acid X ^alcohol
and its contents (Note 1) and rearrange the flask and
For most Fischer esterification reactions, K has a condenser for distillation, the connection being made
value of approximately four (K = 4). Thus, if equal by a bent glass tube about 7 mm. in diameter. A filter
concentrations of alcohol and carboxylic acid are used, flask, whose side arm is joined to a rubber tube leading
the yield of ester, under equilibrium conditions, is about over the edge of the laboratory bench as shown in Fig67 per cent. This yield may be improved either by use ure 21 (page 64), is used as a receiver (Note 2). Put
of an excess of one of the reactants or by removal of a few boiling chips (Note 3) in the flask and distill the
the water as it is formed.
ethyl acetate from the steam bath. A small residue of
Today's experiment consists of the preparation of dilute sulfuric acid remains in the flask. The distillate
ethyl acetate from acetic acid and ethyl alcohol, sul- (Note 4) is shaken with sodium carbonate solution unfuric acid being used as the catalyst. While the reaction til the upper layer is no longer acid to litmus. Separate
mixture is being heated under reflux and also during the the upper layer and wash it with a cool solution of 40 g.
period that the product is being treated with anhydrous of calcium chloride in 40 ml. of water. Dry the prodmagnesium sulfate prior to distillation, one of the fats uct for 30 minutes over anhydrous magnesium sulfate
100-130
will be subjected to alkaline hydrolysis. It may be well (Note 5).
to explain here that fats belong to the family of esters.
[While the product is being dried, continue with Part
Ordinary solid fats, such as tallow, consist chiefly of
II.]
esters of glycerol with saturated carboxylic acids of high
After the product has been dried over anhydrous 130-170
molecular weight. The glyceryl esters of unsaturated
carboxylic acids are liquids at ordinary temperature magnesium sulfate, filter the liquid through a dry filter
86
P R E P A R A T I O N O F SOAP AND G L Y C E R O L
and distill it (Note 6 ) . Collect the portion boiling from
75°-78° separately. The fractions of higher and lower
boiling point are fractionated again, the portion of boiling point 75°-78° being collected and added to the first
lot (Note 7 ) . Weigh your product and calculate the
percentage yield based upon the amount of acetic acid
used (Note 8 ) .
In preparation for Part II of Experiment 28, the
production of acetamide, place 50 ml. of ethyl acetate
and 70 ml. of concentrated ammonium hydroxide in an
Erlenmeyer flask and stopper the flask. The mixture
should be permitted to stand for at least 48 hours before
an attempt is made to isolate acetamide.
NOTES
1. If the flask and its contents are not cooled sufficiently,
there will be some loss of material by evaporation.
2. Ethyl acetate is highly flammable. Therefore any
vapors should be conducted off the table and toward the
floor.
3. Broken pieces of clay plate may be used.
4. The distillate consists mainly of ethyl acetate, but
impurities such as water, alcohol, ether, acetic acid and
sulfurous acid are also present.
5. If no anhydrous magnesium sulfate is on hand, it
can be prepared by heating 20 g. of Epsom salts in an
evaporating dish.
6. It would be preferable to use a small column, such
as a Vigreux column (see page 14), for this distillation.
7. Pure ethyl acetate boils at 77°. However, ethyl acetate
forms an azeotrope of minimum boiling point with water
and also with ethanol. Furthermore, the three-component
system, ethyl acetate-ethanol-water, forms a ternary azeotrope of minimum boiling point. The compositions (in
percentage by weight) of these three azeotropes and their
boiling points are as follows:
Ethyl Acetate 93.9%—Water 6.1%, b.p. 70.4°
Ethyl Acetate 69.1%—Ethanol 30.9%, b.p. 71.8°
Ethyl Acetate 83.3%—Ethanol 8.9%—Water 7.8%, b.p.
70.3°
The necessity for removing water and ethanol from the
crude ethyl acetate is obvious. If your product should
distill at 70°-72°, dry it again with anhydrous magnesium
sulfate and refractionate it.
8. Ordinarily the yield is about 50 g.
II.
24MO
46-100
PREPARATION OF SOAP AND GLYCEROL
Procedure. Weigh 25 g. of cottonseed oil, lard, or
other fat, into a beaker and add to it 25 ml. of ethyl
alcohol and 6 g. of sodium hydroxide dissolved in 25
ml. of water. Set the beaker in a pan of hot water placed
on a wire gauze over a Bunsen burner (Note 1 ) . Heat the
87
water occasionally in order to maintain its temperature
at 80°-90° (Note 2 ) . Stir the mixture frequently and
continue heating for at least an hour.
[In the meantime, proceed with Part I.]
If so much of the water and alcohol should evaporate
that the contents of the flask become almost solid, add a
little distilled water. After this period of heating add
200 ml. of saturated salt solution. Cool the mixture
and filter it through a double thickness of cheesecloth.
Rinse the soap on the filter with 50 ml. of cold water
and preserve the filtrate and washings for the recovery
of glycerol. Press the soap into a small evaporating dish
which will serve as a mold.
Recovery of Glycerol. Separate the salt solution,
which contains the glycerol, from particles of soap by
filtration. Neutralize or slightly acidify the filtrate with
hydrochloric acid and evaporate it to dryness. Remove
the glycerol from the salt by extraction with 20 ml. of
absolute ethyl alcohol. Decant the alcohol solution from
the salt and evaporate the alcohol on the steam bath.
A small residue of glycerol remains.
NOTES
1. The apparatus should be mounted on a ring stand,
all of the equipment being adequately supported.
2. Keep the flame of the Bunsen burner well removed
from the ethyl acetate being prepared in Part I.
QUESTIONS
1. Write the equation for the preparation of soap, assuming that the fat is pure glyceryl stearate.
2. How would you expect an aqueous solution of soap
to react toward litmus?
3. What happens if a soap solution is treated with
solutions of copper sulfate, magnesium sulfate, or calcium
chloride?
4. If soap is dissolved in hot water, then cooled and
acidified with hydrochloric acid, what is the nature of the
precipitate which forms?
5. Name three acids which can usually be obtained
from soap.
6. Give a qualitative explanation for the ability of
soap to bring about formation of an emulsion of water
and oil.
7. What excess of one mole of ethanol was used in
the preparation of ethyl acetate? Why is an excess of one
of the reagents employed?
8. Suggest several ways in which the equilibrium reaction of a Fischer esterification may be shifted to the
right.
100-130
EXPERIMENT 27
Preparation and Properties of Acetyl Chloride
o
II
o
II
3CH3—C—OH + PC13 -> 3CH3—C—CI + H3PO3
Introduction. Carboxylic acids may be converted to
acid chlorides by treatment with phosphorus pentachloride, phosphorus trichloride, or thionyl chloride. Equations for the three reactions are given below:
0
R—C—OH + PClg
O
3R—C—OH + PCI3
0
O
R—C—CI + POCI3 + HC1
0
II
3R—C—CI + H3PO3
O
R—C—OH + SOCI2 - • R—C—CI + S0 2 + HC1
Inasmuch as the acid chlorides are generally purified
by distillation from the reaction mixture, the choice of
reagent for the preparation of a particular acid chloride
is dictated, at least in part, by the ease of separation of
the acid chloride from the reagent or by-products.
For example, when phosphorus pentachloride is used
as the reagent, the inorganic by-product is phosphorus
oxychloride, which has a boiling point of 107°. The
the corresponding acid chloride if the latter should have
a boiling point close to 107°.
Similarly, thionyl chloride, having a boiling point
of 79°, would not be used to prepare an acid chloride having about the same boiling point. Although
the inorganic by-products are gases, the resulting acid
chloride must be separated from unreacted thionyl chloride by fractional distillation.
In the major part of today's experiment, acetyl chloride will be prepared by the action of phosphorus trichloride on acetic acid. In the purification step, acetyl
chloride (boiling point 52°) is readily separated from
a small amount of unreacted phosphorus trichloride
(boiling point 76°) and orthophosphorous acid (decomposes at 200°) by distillation. The reactions of
acetyl chloride with water, alcohols, and amines will be
investigated in a qualitative manner during the latter
part of the laboratory period.
I. PREPARATION OF ACETYL CHLORIDE
Procedure. Assemble the apparatus as shown in Figure 25. The escaping hydrogen chloride must be abGentle Stream of WaterFume•*=
FIG. 25. Apparatus for the preparation and distillation of
acetyl chloride with absorption of hydrogen chloride (three
different types of trap shown).
major purification problem, therefore, is the separation
of the acid chloride from phosphorus oxychloride by
fractional distillation. Obviously, phosphorus pentachloride would not be used to convert a carboxylic acid to
sorbed by a suitable trap such as A, B, or C. If type A
is used be sure that the glass tubes leading into the botties or flasks terminate about 1 cm. above the surface
of the sodium hydroxide solution; otherwise there is
88
0-30
PREPARATION AND
30-70
70-130
danger that the solution might be sucked back into the
acetyl chloride causing a violent reaction. A similar
precaution applies to type B. In type C the stream of
water entering the top of the vertical tube must not
exceed the rate of flow from the bottom of the tube.
The idea is simply to keep a moving film of water spread
over a large surface for absorption of the hydrogen
chloride.
In all cases a tube of calcium chloride protects the
acetyl chloride in the receiving flask from the moist
vapors in the absorption apparatus. Note also that the
pan of water completely covers the bulb of the distilling
flask.
To 60 g. (1 mole, 58 ml.) of glacial acetic acid contained in the 500-ml. distilling flask add slowly from
the dropping funnel 30 ml. of phosphorus trichloride
and shake the flask to mix the reactants. Warm the
water bath to 40°-50° until the evolution of hydrogen
chloride ceases. By this time the liquid will have separated into two layers. Heat the water bath to boiling
and continue the heating until all of the acetyl chloride
has distilled. Redistill the acid chloride and collect the
fraction boiling from 50°-60°. Weigh the distillate and
calculate the percentage yield.
While the acetyl chloride is being purified by distillation, answer some of the questions at the end of the
assignment.
II. PROPERTIES OF ACETYL CHLORIDE
Procedure. Carry out the following experiments in
the hood.
(7) Hydrolysis. Carefully add 1 ml. of acetyl chlo130-135 ride to 5 ml. of water. Record your observations, and
write the equation for the reaction.
(2) Esterification. Cautiously add 1 ml. of acetyl
OF ACETYL CHLORIDE
89
chloride to 2 ml. of ethyl alcohol. Pour the resulting 135-140
solution into 50 ml. of water and note the odor. Write
the equation for the reaction.
Carry out the same procedure with amyl alcohol in 140-145
place of ethyl alcohol. Equation.
(5) Reaction with Aniline. Slowly mix 1 ml. of
acetyl chloride with an equal volume of aniline. When 145-160
the initially vigorous reaction has subsided, add 15 ml.
of water to the tube and shake the mixture vigorously.
To crystallize the precipitate which has formed heat the
contents of the tube to boiling, filter, and allow the filtrate to cool. Collect the crystals by filtration, press out
a few mg. on a clay plate and determine the melting
point. What is the product? Write the equation for the
reaction.
QUESTIONS
1. Would it be wise to prepare benzoyl chloride (boiling
point 199°) by reaction of benzoic acid with phosphorus
trichloride? Would the use of phosphorus pentachloride be
more satisfactory? Explain your answers.
2. Look up in a handbook or elsewhere the boiling,
sublimation, or decomposition points of phosphorus pentachloride, phosphorus oxychloride, phosphorus trichloride,
orthophosphorous acid, and thionyl chloride.
3. In the preparation of acid chlorides, why is it not
practical to destroy excess of reagents (phosphorus pentachloride, phosphorus trichloride, and thionyl chloride) by
pouring the reaction mixtures into water?
4. Write equations for the reactions of acetyl chloride
with each of the following reagents:
(a) w-amylamine
(b) diethylamine
(c) n-butyl alcohol
(d) ethanolamine
EXPERIMENT 28
I. Preparation of Acetic Anhydride
o
o
o
o
II
II
II
II
CH 3 —C—CI + CH 3 —C—ONa -> CH 3 —C—O—C—CH 3 + NaCl
II. Preparation of Acetamide
o
II
o
II
CH3—C—OC2H5 + NH 3 -> CH3—C—NH2 + C2H5OH
Introduction. The anhydrides of carboxylic acids are
usually obtained in the laboratory by reaction of the
acid chlorides with the sodium salts of the acids. Acid
anhydrides are useful acylating agents.
O
O
0
II
II
II
0
II
R—C—CI + R—C—ONa - • R—C—0—C—R + NaCl
They undergo reaction with alcohols to produce esters,
with ammonia or amines to produce amides, and with
aromatic hydrocarbons, in the presence of anhydrous
aluminum chloride, to give ketones.
In the experiment to be carried out during this laboratory period, acetic anhydride will be prepared by
reaction of acetyl chloride with sodium acetate. After
the acetic anhydride has been purified by distillation,
some of the characteristic reactions of acid anhydrides
will be studied in a qualitative manner. At the same
time, acetamide will be prepared according to the directions given in Part II, and some of the characteristic
properties of the amide will be tested.
into the distilling bulb and pour 20 ml. (22 g.) of
acetyl chloride into the dropping funnel. Immerse the
bulb of the distilling flask in cold water and allow about
one fourth of the acetyl chloride to flow slowly into it.
Do not allow the mixture to become hot enough to boil.
Agitate the mixture as much as possible, and, after a
few minutes, disconnect the flask from the condenser
and shake it carefully to obtain a uniform mixture.
When the reaction has subsided, add another portion of
acetyl chloride, cooling the flask and shaking it as before.
When all of the acetyl chloride has been added, arrange the apparatus as shown in Figure 26b. The dis-
I. ACETIC ANHYDRIDE
0-30
Procedure. Fit a 500-ml. distilling flask with a condenser and dropping funnel as shown in Figure 26a.
FIG.
FIG. 26b. Apparatus for distillation of acetic anhydride
with absorption of volatile acids.
tillate is protected from the moist vapors of the 5 per
cent solution of sodium hydroxide in the absorption
bottle by a tube of calcium chloride.
Heat the flask with a slightly luminous flame until
all of the acetic anhydride has distilled. The distillate
consists of acetic anhydride containing a little acetyl
chloride. Transfer the distillate to a clean distilling flask
and mix it with 2 g. of fused sodium acetate and redistill it in order to convert any remaining acetyl chloride
to the anhydride. Use a thermometer during the second
distillation to determine the boiling point of the liquid
(Note 1). Weigh your product and calculate the percentage yield on the basis of the acetyl chloride used.
26a. Reflux assembly for preparation of acetic anhydride.
[Proceed to Part II of today's assignment. While the
acetamide is being purified by distillation, carry out the
qualitative experiments described below.]
Notice that there is no stopper in the top of the condenser. Introduce 35 g. of freshly fused sodium acetate
90
30-60
60-160
91
Properties of Acetic Anhydride
The following short experiments show the characteristic properties of acetyl chloride.
(7) Comparative Ease of Hydrolysis of Acetyl Chloride, Acetic Anhydride, and Ethyl Acetate. Place 1 ml.
of acetyl chloride, acetic anhydride and ethyl acetate
into each of three dry test tubes, respectively. Add 5 ml.
of water cautiously to each tube. Compare the violence
of the reaction in each case. Write equations for the
reactions.
(2) Reaction of Acetic Anhydride with Ethyl Alcohol. Add 1 ml. of acetic anhydride to 5 ml. of ethyl
alcohol. After 2 minutes pour the solution into 50 ml.
of water and note the odor. Write an equation for the
reaction.
(3) Reaction of Acetic Anhydride with Aniline.
Slowly add 1 ml. of acetic anhydride to 2 ml. of aniline.
Add 15 ml. of water to the tube and shake it vigorously.
Note the formation of a solid product. Recrystallize
this solid by heating the contents of the tube to boiling,
then filter and allow the filtrate to cool. Collect the
crystalline product by filtration and determine its melting point (Note 2). Write an equation for the reaction.
II. ACETAMIDE
60-120
Procedure. Transfer the reaction mixture of ethyl
acetate and ammonia water from Part I of Experiment
26 to a 500-ml. distilling flask (Note 3). Add a few
boiling chips, and connect the receiver in such a way
that the escaping ammonia gas will be absorbed in dilute sulfuric acid solution, Figure 25, page 88 (Note
4). (The calcium chloride tube shown in Figure 25 is
not needed in the present experiment.)
Distill the liquid, using a water condenser, until the
thermometer reading reaches 180°. At this point, interrupt the distillation, replace the water condenser with
an air condenser, and use a small flask as a receiver.
It will also be of advantage to transfer the acetamide
solution to a 100-ml. distilling bulb before carrying out
the rest of the distillation. Proceed with the distillation,
heating the flask directly with a slightly luminous Bunsen flame, and collect the distillate in two fractions: I,
150°-210° and II, 210°-225°. The second fraction is
mainly acetamide (Note 5). The liquid collected between 150° and 210° should be refractionated and the
acetamide thus obtained added to the first lot.
Throughout the distillation any acetamide that solidifies in the condenser should be removed by warming
the tube. Otherwise the flask may burst if the tube becomes clogged. Crystallize a small portion of the acetamide from chloroform and determine its melting point
(Note 6). Determine the percentage yield of the product. Note the odor of your sample of acetamide. This
odor is due to the presence of an impurity, as pure
acetamide is odorless. Save the bulk of your acetamide
for Experiment 29.
Properties of Acetamide
The following qualitative tests are designed to demonstrate some of the characteristic reactions and properties 120-160
of amides in general and acetamide in particular.
(1) Hydrolysis in Acid Solution. Boil about 1 g. of
acetamide with 10 ml. of a 10 per cent solution of sulfuric acid. Test the vapor with litmus paper. Write the
equation for the reaction.
(2) Hydrolysis in Alkaline Solution. Boil about 1 g.
of acetamide with 10 ml. of a 10 per cent solution of
sodium hydroxide. Test the escaping gas with litmus
paper. Write the equation for the reaction.
(5) Reaction of Acetamide with Nitrous Acid. Dissolve 1 g. of acetamide in 10 ml. of water. Acidify the
solution by the addition of 1 ml. of concentrated hydrochloric acid and add dropwise a 5 per cent solution of sodium nitrite. Note the evolution of a gas. Write
the equation for the reaction.
(4) Test with Litmus. Test a solution of acetamide
in water with litmus paper. How do you explain your
observed result?
NOTES
1. The boiling point of acetic anhydride is about 137°
at atmospheric pressure.
2. The melting point of acetanilide is 114°.
3. This should be a homogeneous solution after the
48-hour reaction period.
4. As an alternative method of absorbing the ammonia,
a trap such as B or C of Figure 25 on page 88 may be
used.
5. The boiling point of acetamide is 222°.
6. The melting point of acetamide is 82°.
QUESTIONS
1. Why is an excess of sodium acetate employed in the
preparation of acetic anhydride? How many grams of sodium acetate in excess of the theoretical quantity were
used in today's experiment?
2. Complete the following outline equations:
n-C«H»OH
n-C4HoOH
>
I
>
n-C4H»NH2
i
n-C 4 H 9 NH2
I
>
/
O
CH3 C—CI
>
0\
\CH3—C/20
(C 2 H S ) 2 NH
I
__
•
(CiHi)iNH
I
•
Benzene
Benzene
(AlCls)
(Aids)
3. Explain why acetyl chloride is more reactive than
acetic anhydride in each of the reactions given in your
answer to question 2.
92
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
4. Would it be reasonable to look upon both acetyl
chloride and acetic anhydride as being essentially acid
anhydrides?
5. Write a detailed mechanism for the reaction of ethyl
acetate with ammonia to produce acetamide plus ethanol.
6. Why is acetamide essentially neutral? Keep in mind
the fact that ammonia and amines are basic compounds;
i.e., aqueous solutions of these compounds turn litmus
paper blue.
7. Does the evolution of ammonia on boiling an amide
with sodium hydroxide solution serve as a qualitative test
to distinguish amides from all other classes of neutral
compounds which contain nitrogen? Explain.
EXPERIMENT 29
Preparation and Properties of Methylamine
CH3—C—NH2 + Br2 + 4NaOH -> CH 3 —NH 2 + Na2COs + 2NaBr + 2 H 2 0
Introduction. Primary aliphatic amines are frequently
prepared from acid amides by application of the Hofmann hypobromite reaction. A molecular rearrangement occurs in one step of the overall process; specifically, an alkyl group migrates from the carbon atom to
which it is bonded to an adjacent electron-deficient nitrogen atom. The steps in the accepted mechanism for
the Hofmann hypobromite reaction are shown below:
Fit a 500-ml. distilling flask with a thermometer,
dropping funnel, and condenser as shown in Figure 27.
0
(a) R—C—NH2 + NaOH + Br2 -»
O H
R—C—N—Br + H 2 0 + NaBr
O H
I
(b) R—C—N—Br + NaOH
r n
T Na+ + H 0
LR—C—N—BrJ
(c) l_R—C—N—BrJ Na+-
2
(R—C—N) + NaBr
0
(non-isolable)
(d) R—C—N -> R — N = C = 0
(e) R — N = C = 0 + 2NaOH -> R—NH2 + Na2C03
During the latter part of the distillation of methylamine, some characteristic reactions of primary aliphatic
amines will be investigated.
I. PREPARATION OF METHYLAMINE
0-30
Procedure. CAUTION: Bromine vapor must not be
allowed to escape into the laboratory. Await the instructor's directions.
Into a 500-ml. round-bottomed flask place 15 g. of
acetamide and 12 ml. (37 g.) of bromine. Add to
this mixture a cold solution of 10 g. of sodium hydroxide in 120 ml. of water in portions of about 5 ml.
at a time. After each addition wait until the reaction
ceases before adding more alkali. The flask should be
shaken and cooled continuously in cold water. When all
of the alkali has been added, the liquid should have a
bright yellow color due to the formation of acetobromoamide, CH3CONHBr. If any precipitate should
form during this process, add a little water to bring it
into solution because it might clog the dropping funnel
in the next part of the experiment.
FIG. 27. Apparatus for preparation of methylamine, the
gaseous product being collected in water or dilute hydrochloric acid.
Pour into the distilling flask a solution of 25 g. of
sodium hydroxide in 150 ml. of water. Transfer the
solution of acetobromoamide prepared as described
above to the separatory funnel and allow it to drop
slowly into the sodium hydroxide solution. Meanwhile
shake the flask frequently and warm its contents to a
temperature of 80°-90°. The reaction is exothermic and
the application of heat should be stopped if the solution
begins to boil.
When all of the acetobromoamide solution has been
added, introduce a few chips of unglazed porcelain and
heat the flask gently over an asbestos gauze. Methylamine escapes as a gas along with water vapor and a
little ammonia. During the first 5 minutes of the distillation collect the methylamine in 25 ml. of distilled water.
Continue the distillation, absorbing the remainder of
the methylamine in 25 ml. of dilute (1-1) hydrochloric
acid solution.
[During this latter period of distillation and also while
the hydrochloric acid solution is being evaporated to
dryness (see below), begin Part II of the assignment.]
60-120
When the distillate plus the original hydrochloric 120-160
acid solution amounts to 100 ml., the distillation is
93
94
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
stopped, and the hydrochloric acid solution is evaporated to dryness on the water bath. Transfer the residue of methylamine hydrochloride, which also contains
some ammonium chloride, to a small flask fitted with
a glass tube about 60 cm. in length which serves as an
air condenser, and boil it for 2 minutes with 25 ml. of
absolute ethanol. Remove the solution of methylamine
hydrochloride (methylammonium chloride) from the
undissolved ammonium chloride by filtration. Evaporation of the alcohol on the steam bath leaves the methylamine hydrochloride as a white solid.
II. PROPERTIES OF METHYLAMINE
60-160
Procedure. Make use of the 25 ml. of methylamine
solution obtained from the first part of the distillate of
Part I for the following experiments.
1. Tests for Primary Amines
The following reactions represent convenient qualitative tests for the detection of primary amines in general. Of course, the specific reactions will be carried out
on methylamine.
(a) Nitrous Acid. To 5 ml. of the methylamine solution contained in a test tube add sufficient dilute hydrochloric acid to make the solution acid to litmus. Add
dropwise about 2 ml. of a 5 per cent solution of sodium
nitrite. If no gas evolution is observed, warm the test
tube gently. Write the equation for the reaction.
(b) Isocyanide Reaction. Add 3 ml. of a 10 per cent
solution of sodium hydroxide and 2 drops of chloroform to 1 ml. of the methylamine solution contained
in a test tube. Warm the mixture and note the odor.
Write the equation for the reaction.
(c) Complex Ion Formation with Cupric Ion. To 3
ml. of copper sulfate solution add 1 ml. of methylamine
solution. Note the change in color of the copper sulfate
solution. Write the equation for the reaction.
2. Methylamine as a Base
Amines in general are moderately strong organic
bases. The following experiments illustrate this property of methylamine.
(a) Behavior of Aqueous Solution Toward Litmus.
Place a drop of the methylamine solution on a strip of
red litmus paper. Note the color change. Write the
equation for the reaction of methylamine with water.
(b) Reaction with Hydrogen Chloride. Wet a glass
rod with the methylamine solution and bring the rod
close to an open bottle of concentrated hydrochloric
acid. Note the result, and write the equation for the
reaction.
(c) Reaction with Ferric Chloride. To 3 ml. of ferric
chloride solution add methylamine solution until a precipitate appears. Write the equation for the reaction.
[During the remaining part of the laboratory period
answer the questions that follow.]
QUESTIONS
1. What volume (S.T.P.) of methylamine gas is theoretically obtainable from 14.75 g. of acetamide by application of the Hofmann hypobromite reaction?
2. If the theoretical amount of methylamine obtainable
from 14.75 g. of acetamide by the Hofmann hypobromite
reaction were dissolved in sufficient distilled water to bring
the total volume of the solution to 100 ml., what would
be the molar concentration of methylamine in this solution?
3. What volume of 0.5 M hydrochloric acid solution
would be required to neutralize the 100 ml. of solution
described in question 2?
4. Write balanced equations for the preparation of
isopropylamine from isobutyramide and of aniline from
benzamide by the Hofmann hypobromite reaction.
5. What is the approximate pH of a 0.1 M solution of
ethylamine at 25°? KB = 5.6 X 10~4.
6. What qualitative tests may be used to distinguish
among primary, secondary, and tertiary aliphatic amines?
7. In what way does an aqueous solution of a quaternary
ammonium hydroxide differ from an aqueous solution of
a primary, secondary, or tertiary amine?
8. How may a water-insoluble amine be isolated when
it is present in a mixture with several neutral, water-insoluble organic compounds?
EXPERIMENT 30
Preparation and Properties of Acetonitrile
o
II
2CH3—C—NH2 + P 2 0 5 -* 2 C H 3 — f e N + H4P2O7 (Note 1)
Introduction. Nitriles are neutral compounds that may
be prepared by reaction of primary alkyl halides with
sodium cyanide or by dehydration of acid amides. The
latter procedure will be followed in the experiment for
today.
0
II
R—C—NH2
p2o.
* R—C=NT
A nitrile may be hydrolyzed either in acid or alkaline
medium to the carboxylic acid and ammonia. It is also
possible in an acid-catalyzed hydrolysis of a nitrile to
stop the reaction at an intermediate stage, thus permitting isolation of the acid amide. Reduction of nitriles
affords primary amines. Several of these typical reactions will be carried out in a qualitative manner in Part
II of this day's assignment.
I. PREPARATION OF ACETONITRILE
0-30
30-60
60-90
Procedure. Place 30 g. of phosphoric anhydride
(Note 2) in a dry, 125-ml. distilling flask, and add 20
g. of dry acetamide. Mix the compounds as thoroughly
as possible by shaking the flask. Attach a water-cooled
condenser to the side arm and heat the flask gently with
a small, slightly luminous flame. The mixture tends to
foam during this operation. After the mixture has been
heated in this manner for about 5 minutes, gradually
raise the temperature until the nitrile distills. To the
distillate add one half of its volume of water and about
10 g. of potassium carbonate in small portions, with
swirling and cooling of the flask and its contents in a
pan of water. Decant the mixture of liquids into a separatory funnel. Draw off the lower aqueous layer and
discard it.
Transfer the upper layer of acetonitrile to a small distilling flask, add about 1 g. of phosphoric anhydride, 2
or 3 boiling chips, and then distill the liquid. Collect
the distillate having a boiling point range of 77°-82°
(Note 3) in a weighed bottle. Determine the weight of
the distillate and calculate the percentage yield.
II. PROPERTIES OF ACETONITRILE
1. Hydrolysis of Acetonitrile
(a) Acid Solution. To 10 ml. of a 25 per cent sul- 90-115
furic acid solution add 1 ml. of acetonitrile and heat
the solution to boiling. Test the escaping vapor with
litmus paper. Cool the solution and make it alkaline
by addition of sodium hydroxide solution. Heat the
solution and test the escaping gas with litmus paper.
Write equations for the reactions described above.
(b) Alkaline Solution. Add 1 ml. of acetonitrile to 115-125
10 ml. of a 10 per cent sodium hydroxide solution.
Heat the solution and test the escaping gas with litmus
paper. Write the equation for the reaction.
2. Reduction of Acetonitrile
125-140
To 10 ml. of commercial absolute ethanol add 1 ml.
of acetonitrile. Add a piece of sodium about one half
the size of a pea. When the reaction subsides and the
sodium has gone into solution, cool the mixture and add
a second piece of sodium. After the sodium has dissolved, apply the isocyanide test for a primary amine to
the resulting solution (see page 94). Write equations
for the reactions described above.
[During the remainder of the laboratory period answer
the questions that follow.]
QUESTIONS
1. Write equations to show how n-butyl alcohol may be
converted into (a) n-butyronitrile and (b) n-valeronitrile.
2. Give both "nitrile" and "cyanide" names to each of
the following compounds:
(d) CH3CH(CH3)CH2CN
(a) CH3CH2CH2CN
CH3
CH3
(e) CH3CH2s—CH—1•CN
(b) CH3—CH—CN
(f) CH3— (CH2)*-CN
(c) (CH3)3C—CN
3. Can trimethylacetonitrile be prepared by reaction of
f-butyl chloride with sodium cyanide? Write equations
for an alternative method of preparation of the nitrile
NOTES
from f-butyl chloride.
4. How may lactic acid be prepared from acetaldehyde?
1. Actually a mixture of phosphoric acids is produced,
5. Would it be best to employ the nitrile route or the
but the major component is pyrophosphoric acid, H 4 P 2 0 7 .
2. Phosphoric anhydride can cause a bad burn if it Grignard route for the conversion of 4-chloro-l-butanol
gets on the skin. In case of accident, wash the area well to 5-hydroxy-pentanoic acid? Explain.
6. Write equations to show how n-propyl alcohol may
with water and apply a paste of sodium bicarbonate.
3. The boiling point of acetonitrile is 81°. The yield be converted to (a) n-butylamine, (b) ethylamine, and
(c) ^-propylamine.
usually amounts to about 8-10 g.
95
AENT 31
Some Chemical Properties of Ethylene Glycol and Glycerol
0-20
20-40
Introduction. Many of the chemical properties of are not already at that temperature. Draw the ethyl
1,2-diols are simply the properties to be expected of al- alcohol into a 10-ml. pipette up to the mark and then
cohols in general. However, there are other reactions determine the number of seconds required for the alcowhich are specific for the 1,2-diol unit. For example, hol to flow from the pipette. Use a stop watch, if one
the formation of esters by the action of acid chlorides, is available, or use a watch having a second hand to time
acid anhydrides, or carboxylic acids under the catalytic the flow. Make a duplicate observation. Wash the pipinfluence of mineral acids and the liberation of hydro- ette with water and acetone and dry it either by blowing
gen with formation of the corresponding alkoxide salts air through it from the compressed air line or by warmon treatment with metallic sodium represent reactions ing it gently over the Bunsen burner while drawing air
common to most alcohols, whereas the oxidative cleav- through it by means of a tube attached to the aspirator.
age of 1,2-diols to aldehydes and/or ketones by the ac- Repeat the experiment, first with ethylene glycol and
tion of periodic acid or lead tetraacetate and the forma- then with glycerol. Record the relative viscosities of
tion of relatively highly acidic complexes with boric these three liquids.
acid represent specific reactions of the 1,2-diol group.
(c) Ethylene Glycol as an "Antifreeze" Compound.
45-65
The outstanding physical properties of 1,2-diols are Fill a 500-ml. beaker with an intimate mixture of salt
their relatively high boiling points, viscosities, and solu- and crushed ice and stir the mixture for a few minutes.
bilities in water. All of these characteristics are a direct The temperature of this freezing mixture will be between
consequence of hydrogen bonding. In order to separate - 1 5 ° and - 2 0 ° . Add 2 ml. of ethylene glycol to 8 ml.
the diol molecules in the process of distillation, it is of water contained in a test tube and set the tube in the
necessary to supply sufficient heat to overcome the elec- freezing bath for several minutes. Does the solution
trostatic attraction, mainly owing to hydrogen bonding, freeze? Try several other concentrations and record
your observations.
between the molecules.
(d) Action of Metallic Sodium. Add a piece of so65-75
Thus it is apparent why glycols (diols) have decidedly higher boiling points than most other organic com- dium about the size of a small pea to 3 ml. of ethylene
pounds of about the same molecular weight. Glycols glycol. Note the result. Write the equation for the reachave higher boiling points than simple alcohols of about tion. To destroy any unreacted sodium, add a few ml.
the same molecular weight because glycols, having two of alcohol, wait until the reaction subsides, then pour
hydroxyl groups per molecule, can enter into a greater the mixture into the sink.
(e) Action of Acetyl Chloride. In the hood add 2
75-85
degree of hydrogen bonding than the simple alcohols.
The relatively high viscosity of glycols reflects the ml. of acetyl chloride dropwise to an equal volume of
fact that two glycol molecules can slide by one another ethylene glycol. Pour the product into 50 ml. of water
only with difficulty owing to the making and breaking contained in a small beaker. Note the sweet odor of
of hydrogen bonds in the process of flow; the hydroxyl ethylene glycol diacetate. Write the equation for the
groups attached to the glycol molecule can be likened reaction.
(/) Benzoylation (Schotten-Baumann Reaction).
85-105
to small hooks which, by forming hydrogen bonds, tend
to catch the similar hooks attached to the other mole- Carry out this experiment in the hood. Dissolve 2 ml.
cules and thus impede the passage of one molecule past of ethylene glycol in 8 ml. of 10 per cent sodium hythe other. The relatively high solubility of glycols in droxide solution contained in a test tube and add a
water is the consequence of the favorable decrease in total of 2 ml. of benzoyl chloride in 0.5-ml. portions,
energy (increase in stability) of the system when glycol with shaking of the tube for about a minute after each
molecules are attracted to water molecules with forma- addition. Pour the reaction mixture into 10 ml. of cold
water and collect the solid ester by filtration. Crystaltion of hydrogen bonds.
lize the ester from 50 per cent ethanol and determine
I. PROPERTIES OF ETHYLENE GLYCOL
its melting point. Look up the melting point of ethylene
Procedure. Distill 50 ml. of commercial ethylene gly- glycol dibenzoate and record this value also. Write the
col (or Eveready, Prestone or Zerex) from a 125-ml. equation for the reaction.
(g) Oxidation to Oxalic Acid. Add 3 drops (no 105-115
distilling flask connected to an air condenser. Collect
the portion boiling from 185°-200° for use in the fol- more) of ethylene glycol to 3 ml. of concentrated nitric
acid contained in a test tube. Carry the tube to the
lowing experiments:
(a) Taste. Taste a drop of ethylene glycol. How hood and warm the solution until the evolution of brown
fumes begins. Remove the flame and allow the reaction
would you classify the taste?
(b) Viscosity. Pour 15-ml. samples of ethyl alcohol, to proceed spontaneously. When the evolution of oxides
ethylene glycol, and glycerol into small beakers and of nitrogen ceases, pour the solution into 10 ml. of
allow the samples to attain room temperature if they water and neutralize it with ammonium hydroxide solu-
ETHYLENE GLYCOL AND GLYCEROL
tion. Add a few drops of calcium chloride solution and
note the result. Write equations for the three reactions
involved in this experiment.
115-130
(h) Cleavage by Action of Periodic Acid. Dissolve
0.1 g. of para-periodic acid (H 5 I0 6 ) in 20 ml. of distilled water. Place 2 ml. of this reagent in a small test
tube, add 1 drop of concentrated nitric acid, and shake
the solution thoroughly. Add 1 drop of ethylene glycol
to the solution and shake the tube for 15 seconds. Then
add 2 drops of 3 per cent silver nitrate solution. The
instantaneous formation of a white precipitate of silver
iodate (AgI0 3 ) indicates that the ethylene glycol has
been cleaved to two molecules of formaldehyde by the
periodic acid, which is thereby reduced to iodic acid.
Repeat this test with glycerol and D( + )-glucose. Write
equations for the sequence of reactions starting with
periodic acid and ethylene glycol.
II. PROPERTIES OF GLYCEROL
130-140
(a) Solubility. Test the solubility of glycerol in water,
ether, and petroleum ether. Record your results. How
does glycerol compare with ethylene glycol with regard to its solubility in these solvents?
140-150
(b) Formation of a Complex with Boric Acid. Add
a few drops of phenolphthalein indicator solution to
5 ml. of 1 per cent borax solution, and note the color.
Add 1 ml. of glycerol to the solution and note the
change in color. Explain this result by writing equations
for the reactions taking place.
97
(c) Dehydration of Glycerol. Add 6 drops of glycerol 150-160
to 1 g. of potassium hydrogen sulfate contained in a
test tube. Heat the mixture strongly and note the odor.
Write the equation for the reaction.
QUESTIONS
1. Complete and balance each of the following equations:
OH OH
(a) CH3—CH—CH—CH3 + HI0 4 ->
(b) HO—CH2—CH2—OH + Pb(OCOCH3)4-»
O
(c) HO—CH2—CH2—CH2OH + 2CH3—C—CI ->
OH OH
(d) 2CH3—CH—CH—CH3 + H3BO3 - •
O
(e) HO—CH2—CH2—CH2—CH2—OH + 2CeH5—C—CI
+ 2NaOH ->
2. Write equations to show three different methods for
effecting the conversion of cyclohexene to adipaldehyde.
3. In analytical chemistry, titration of boric acid with
standard sodium hydroxide solution can be carried out
satisfactorily only if a considerable quantity of mannitol,
glycerol, glucose, or other polyhydric alcohol is added to
the boric acid solution. Why is this true?
32
Oxali Acid
0-10
Introduction. Oxalic acid is one of the oldest known
carboxylic acids. Gay-Lussac obtained the sodium salt
of the acid in 1829 by fusing sawdust with sodium
hydroxide, and Scheele prepared the acid in 1776 by
the oxidation of cane sugar with nitric acid. Both procedures were used for the commercial manufacture of
oxalic acid in the nineteenth century, but most of the
acid used today is manufactured by heating sodium
formate to drive off hydrogen and then liberating oxalic
acid from the resulting sodium salt by the action of
mineral acid. Oxalic acid crystallizes from aqueous solution as a dihydrate, and it is thought that the dihydrate
is actually ortho-oxalic acid. Oxalic acid forms both
normal and acid salts with alkali metal hydroxides.
Potassium acid oxalate and oxalic acid dihydrate combine to form a crystalline compound known as potassium tetroxalate, KHC2O4H2C2O42H2O. Either oxalic
acid dihydrate or potassium tetroxalate may be used
in quantitative analysis for the standardization of potassium permanganate solution.
Oxalic acid readily forms esters with the simple
alcohols. Most of these esters are liquids, but the methyl
ester, which is to be prepared as a part of today's assignment, is a solid. Hydrogen chloride is used as the
catalyst in this esterification reaction. The carbon atoms
of the carbonyl groups present in methyl oxalate are
highly electrophilic in reactivity, and accordingly nucleophilic substitution reactions occur rapidly. For example, methyl oxalate is converted to oxamide almost
instantaneously on treatment with ammonia.
Procedure. Place an evaporating dish containing 60 g.
of oxalic acid dihydrate in an oven maintained at 100°
and allow it to remain there for about Wi hours. Anhydrous oxalic acid obtained in this manner will be
used for the preparation of methyl oxalate.
I. PREPARATION OF SODIUM OXALATE
FROM SODIUM FORMATE
10-30
Place 1 g. of sodium formate in a test tube and
heat the tube until the crystals melt and decompose
with evolution of hydrogen. When the evolution of
hydrogen ceases, cool the tube and dissolve the fused
mass in water. To about 2 ml. of the solution add a
few drops of calcium chloride solution and acidify it
by the addition of acetic acid. Note the result. As a
control experiment, add calcium chloride solution and
acetic acid to aqueous sodium formate solution. Write
equations for the preparation of sodium oxalate and
calcium oxalate by the procedure described above.
II. PREPARATION OF OXALIC ACID FROM SUCROSE
30-70
To 50 ml. of concentrated nitric acid (sp. gr. 1.42)
contained in a 1-liter flask add 10 g. of sucrose (cane
or beet sugar). Support the flask on a ring stand in
the hood. Warm the mixture gently with the slightly
luminous flame of the Bunsen burner, removing the
flame when the evolution of brown fumes begins. Allow
the reaction to proceed spontaneously until it is ended.
Transfer the acid solution to an evaporating dish and
heat it on the steam bath in the hood until the solution
has evaporated to about one third of its original volume.
[Proceed with the next part of today's assignment
while the solution is being concentrated.]
Set the solution aside until the next laboratory period,
when a deposit of crystalline oxalic acid will have
formed. Collect the solid by filtration through a porcelain funnel or a glass funnel fitted with a perforated
porcelain plate (Witt plate). Crystallize the solid from
the least possible quantity of hot water and determine
the melting point of the product.
III. PROPERTIES OF OXALIC ACID
(a) Reducing Action of Oxalic Acid. Dissolve about
0.5 g. of oxalic acid in 5 ml. of water and add 3 drops
of concentrated sulfuric acid. Then add a few drops
of a dilute aqueous solution of potassium permanganate
and warm the solution. Record your observations. Write
the equation for the reaction.
(b) Decomposition of Oxalic Acid. Heat 2 g. of
oxalic acid with 5 ml. of concentrated sulfuric acid in
the hood. What gases are evolved? Write the equation
for the reaction.
70-80
80-90
IV. PREPARATION OF METHYL OXALATE
To 50 ml. of methanol contained in a 250-ml. Erlenmeyer flask add 45 g. (0.5 mole) of the oxalic acid
that has been drying in the oven since the start of the
period. Equip the flask with a two-holed rubber stopper
bearing two bent glass tubes, one extending only a few
millimeters below the stopper and the other extending
to within 1 cm. of the surface of the methanol-oxalic
acid mixture. Gaseous hydrogen chloride, generated in
a filter flask by dropping concentrated sulfuric acid
onto a slurry of sodium chloride and concentrated
hydrochloric acid, is passed through the longer tube into
the Erlenmeyer flask. Shake the flask frequently to
facilitate dissolution of the hydrogen chloride.
The smaller tube extending into the Erlenmeyer flask
serves as an exit tube. Although most of the hydrogen
chloride is absorbed by the methanol solution, some
of the gas escapes through the exit tube. Therefore,
that tube should be connected by rubber tubing to a
suitable apparatus for the absorption of excess hydrogen chloride (see page 88). As the introduction of
hydrogen chloride proceeds, the Erlenmeyer flask and
its contents become warm and the oxalic acid passes
into solution. Absorption of the gas is continued until
90-150
OXALIC ACID
the solution is practically saturated or at least until the
flask has increased 10 g. in weight.
Filter the hot solution into a second Erlenmeyer flask,
and allow the filtrate to stand for 10 minutes. Then
place the flask in a pan of ice and water, and stir the
solution as methyl oxalate crystallizes. When the mixture has been thoroughly chilled, collect the crystals
in a Buchner funnel and press them out with a large,
flat-topped glass stopper. Place the crystals in a beaker,
stir with 25 ml. of ice-cold methanol and again filter
the mixture and press out the crystals.
Most of the hydrogen chloride has now been removed and the methyl oxalate is recrystallized from
50 ml. of hot methanol by cooling in ice. Once again,
collect the crystals by filtration, press them out, and
finally dry them on a clay plate or between pieces of
filter paper. Weigh the dried material, and, inasmuch
as methyl oxalate is somewhat volatile, transfer the
compound to a stoppered bottle. Determine the melting
point of your product. The recorded melting point is
54°. Calculate the percentage yield.
V. CONVERSION OF METHYL OXALATE TO OXAMIDE
Dissolve about 1 g. of methyl oxalate in a few ml.
150-160 of methanol and add about 1 ml. of concentrated am-
99
monium hydroxide solution. What do you observe?
Write the equation for the reaction.
QUESTIONS
1. Can you suggest an explanation for the fact that the
carbonyl group carbon atoms of methyl oxalate have a
high degree of electrophilic reactivity (i.e., add bases
rapidly)?
2. If titration of a dilute sulfuric acid solution containing 0.6165 g. of oxalic acid requires 17.70 ml. of potassium permanganate solution, what is the molarity of the
permanganate solution?
3. Write a sequence of equations to show how oxalic
acid may be prepared from carbon monoxide, sodium
hydroxide, and sulfuric acid as the fundamental starting
materials.
4. Why does oxalic acid tend to form a hydrate?
5. Propose a mechanism for the acid-catalyzed decomposition of oxalic acid.
6. What are two types of salts that may be formed on
reaction of oxalic acid with an amine?
7. Which would be larger, the first or the second ionization constant of oxalic acid? Why?
8. How may diethyl phenylmalonate be prepared from
ethyl oxalate and ethyl phenylacetate as the organic starting materials?
EXPERIMENT 33
I. Preparation of Ethyl Acetoacetate (Part A)
o
o
2CH3—C—OCjHs
o
II H ||
' ' CH3—C—C—C—OQHs
+ C2H6OH
Na0C H
H
II. Alkylation of Ethyl Malonate (Part A)
COOCjHe
COOQHs
COOQHs
I
I
_
CjH»ONa , ,
-• H — CI : , __
Na+,
COOC2H5
Introduction. ^-Ketoesters may be prepared by application of the Claisen condensation reaction. Usually
it is necessary to employ esters having at least two
a-hydrogen atoms when a sodium alkoxide is used as
the catalyst. The condensation always takes place at
the a-carbon, as shown in the following equation.
O
2RCH2-C-0-R-^^
O R
II
0
I II
RCH2—C—CH—C—0—R + R—OH
C«H.Br
H—C—C4H9
I
COOC2H5
sary to use high-grade absolute ethanol. This will be
prepared during today's period and utilized during the
next laboratory period. A convenient method for the
preparation of anhydrous ethanol is to treat commercial
absolute ethanol with sodium metal and then with diethyl phthalate. After the solution has been heated for
a short time, pure ethanol can be distilled from the
mixture. When sodium metal dissolves in commercial
absolute ethanol, the small amount of water present is
converted to sodium hydroxide with evolution of hydrogen, and some ethanol is converted to sodium ethoxide,
also with hydrogen evolution. The sodium hydroxide
produced saponifies diethyl phthalate to give sodium
phthalate and sodium ethyl phthalate, which are nonvolatile, and ethanol. Pure ethanol can be distilled from
this mixture, leaving behind the various sodium salts
and any unchanged diethyl phthalate (boiling point
298°).
You will note that the condensation of two molecules of ethyl acetate yields a /?-ketoester in which a
methylene group (CH2) is located between two carbonyl (CO) groups. A methylene group so placed is
particularly reactive and is called an "active methylene
group"; likewise its two hydrogen atoms are referred
I. PREPARATION OF ETHYL ACETOACETATE (PART A)
to as "acid methylene hydrogen atoms."
The two classic examples of compounds containing
Procedure. Place 200 ml. of commercial ethyl acetate
0-20
an "acid methylene group" are ethyl acetoacetate and in a separatory funnel and shake the ester with an equal
ethyl malonate, compounds being studied in today's as- volume of 5 per cent sodium carbonate solution (Note
signment. In each compound an acidic hydrogen atom 1). After removal of the sodium carbonate solution,
of the methylene group may be replaced by sodium, shake the ethyl acetate with 50 ml. of saturated calcium
yielding a sodio derivative whose sodium atom, in turn, chloride solution, then dry the ester over anhydrous
20-80
may be replaced by an alkyl group through reaction potassium carbonate for an hour.
with an alkyl halide. Hence the two-step process results
[While the ethyl acetate is being dried, proceed with
in the formation of an alkyl derivative of the compound
Part II.]
containing the acid methylene group and is known as an
alkylation reaction. In Part II of today's experiment
Decant the ethyl acetate from the drying agent and 80-120
and also in the assignment for the next laboratory distill it, taking care that all of the apparatus used is
period, such an alkylation reaction is illustrated by the completely dry. Weigh the purified ester (Note 2) and
preparation of the n-butyl derivative of ethyl malonate pour it into a 500-ml. round-bottomed flask equipped
(ethyl n-butylmalonate).
with a water-cooled reflux condenser and a calcium
chloride drying tube.
(a) CH2(C02C2H5)2 + NaOC2H6 ->
Place 2 or 3 lumps of clean sodium having a com- 120-160
NaCH(C02C2H5)2 + C2HBOH
bined weight of 16 g. in a beaker and cover the metal
(b) NaCH(C02C2HB)2 + C4H9Br->
with kerosene. Cut off about a 2-g. piece of sodium,
C4H9CH(C02C2H6)2 + NaBr dry it with a paper towel or a piece of filter paper, and
In order to prepare ethyl sodiomalonate, it is neces- cut it into thin slices. As quickly as possible, discon100
ALKYLATION OF ETHYL MALONATE (PART A )
nect the flask of ethyl acetate from the condenser and
add the slices of sodium (Note 3 ) . Join the flask to
the condenser once again and wait until the reaction
subsides before adding another 2-g. quantity of sliced
sodium. All of the metal may be added to the ester
in the course of about 20 minutes.
After the initial vigorous reaction has diminished,
place the flask with its attached condenser on the steam
bath and heat it for the remainder of the period. At
the end of the laboratory period, remove the apparatus
from the steam bath, and allow the reaction mixture
to stand until the next laboratory period. Leave the
flask attached to the reflux condenser but shut off the
stream of water through the condenser.
NOTES
1. The sodium carbonate solution neutralizes any acetic
acid present in the ethyl acetate. Since carbon dioxide is
liberated in the neutralization reaction, be prepared to
release the pressure in the separatory funnel at frequent
intervals while shaking the mixture.
2. At this stage, the ethyl acetate is free of acetic acid
and water, but it does contain some ethyl alcohol. The
presence of this alcohol is necessary in order to initiate
the reaction. Sodium reacts with the alcohol to produce
sodium ethoxide, the catalyst for the reaction.
3. Owing to the increased surface area, thin shavings
of sodium may inflame if left in contact with air for too
long a time. If this should happen, smother the metal with
dry sand, scrape the material into a pan and take it out
of doors. Do not use a fire extinguisher! Of course, the
main portion of sodium should be kept in the beaker of
kerosene and portions removed and sliced only as needed.
II. ALKYLATION OF ETHYL MALONATE (PART
A)
Procedure. To 300 ml. of commercial absolute
ethanol contained in a 500-ml. round-bottomed flask
add 3 g. of sodium, in small pieces. After all of the
sodium has dissolved, add 10 g. of diethyl phthalate
to the solution, connect the flask to a water-cooled
101
reflux condenser, the top of which bears a calcium
chloride tube to exclude moisture, and heat the mixture
on the steam bath for about 30 minutes (don't forget
the standard procedure of adding 1 or 2 boiling chips).
Distill the ethanol into a dry bottle, the distillate being
protected from moisture by a calcium chloride tube,
and stopper the bottle tightly. Save the anhydrous
ethanol for the next laboratory period. Continue with
Part I as the ethanol is being distilled.
QUESTIONS
1. Write equations for the Claisen condensation of
ethyl propionate; of ethyl n-butyrate.
2. Would it be a good idea to use sodium methoxide
to catalyze the Claisen condensation of ethyl acetate?
Explain.
3. At the completion of the experiment, before the
hydrolysis step, does ethyl acetoacetate exist mainly as
the free /?-ketoester or as some derivative? Of what significance is this?
4. Write a detailed mechanism for the Claisen condensation as applied to ethyl acetate.
5. One method for preparing absolute ethanol was
given in Part II of today's assignment. What are some
other methods?
6. Why does the Claisen condensation fail when applied to ethyl isobutyrate, with sodium ethoxide as the
catalyst? How might a successful reaction be brought
about?
7. What is the easiest way to prepare absolute methanol? Why isn't the same method used for the preparation
of absolute ethanol?
8. What is the commercial method for the manufacture
of ethyl acetoacetate?
9. How might a /?-aldehydoester be prepared by a
Claisen condensation reaction? In general, under what
circumstances are "mixed" Claisen condensation reactions
useful in synthesis?
10. What is the product of the sodium ethoxide-catalyzed reaction of acetone with ethyl acetate? May the
same compound be prepared under conditions of acidcatalysis? What acid catalyst could be used?
EXPERIMENT 34
I. Preparation of Ethyl Acetoacetate (Part B)
II. Alkylation of Ethyl Malonate (Part B)
Introduction. During the previous laboratory period
the Claisen condensation of ethyl acetate was carried
out. Today, the product, ethyl acetoacetate, will be isolated and purified by distillation.
The absolute ethanol prepared last time will be
utilized today for the preparation of a sodium ethoxide
solution, which, in turn, will be used to prepare ethyl
sodiomalonate. The latter reagent, on treatment with
n-butyl bromide, affords ethyl n-butylmalonate.
I. PREPARATION OF ETHYL ACETOACETATE (PART B)
0-40
Procedure. The reaction mixture left from the previous period should contain a large quantity of precipitate
consisting of sodium ethoxide and the sodium salt of
ethyl acetoacetate. Some unreacted sodium will probably also be present. Add 5 ml. of the anhydrous
ethanol prepared during the previous period and heat
the mixture under reflux for 30 minutes.
[Proceed with Part II.]
40-70
Cool the mixture somewhat, then add, in small
portions, a total of 25 ml. of anhydrous ethyl alcohol,
with swirling of the contents of the flask, and watch
for any evidence of unused sodium. If metallic sodium
is present in the reaction mixture, wait until it dissolves before proceeding with the next step. When there
appears to be no further evidence of the metal, add a
few drops of a 50 per cent solution of acetic acid and
swirl the mixture. If, in spite of the previous treatment,
any sodium comes to the surface at this point, stir the
mixture thoroughly and do not add any more acetic
acid solution until the metal dissolves.
Gradually add 50 per cent acetic acid solution
until all of the precipitate has dissolved and the resulting solution is faintly acidic to litmus. About 110 ml.
of the acetic acid solution will be required. Add to the
mixture an equal volume of saturated sodium chloride
solution and separate the upper layer of mixed esters
(ethyl acetoacetate and unreacted ethyl acetate) from
the lower aqueous layer.
Dry the ester layer over calcium chloride for about
10 minutes, filter the liquid into a 125-ml. distilling
flask, add some boiling chips and distill the liquid
in the usual manner (Note 1). Collect three fractions:
I, up to 95°; II, 95°-175°; III, 175°-185°. The last
fraction consists of ethyl acetoacetate (Note 2) and
the first fraction is mainly ethyl acetate. Redistill the
intermediate fraction in order to obtain additional ethyl
acetoacetate (Note 3).
After the ethyl acetoacetate has been purified by distillation, continue with Part II of the laboratory assignment.
NOTES
1. It would be preferable to distill the ethyl acetoacetate
at reduced pressure in order to minimize thermal decomposition of the ester, but, in order to save time, the distillation is carried out at atmospheric pressure in this
experiment. An assembly of apparatus for vacuum distillation is shown in Figure 28.
2. The boiling point of ethyl acetoacetate is 181°.
3. The yield of ethyl acetoacetate should be about
10-15 g.
FIG. 28. Apparatus for distillation at reduced pressure.
102
70-80
80-130
ALKYLATION OF ETHYL MALONATE (PART B)
II. ALKYLATION OF ETHYL MALONATE (PART B )
10-40
Procedure. Pour 150 ml. of the absolute ethanol prepared during the last period into a dry 500-ml. roundbottomed flask and attach a reflux condenser equipped
with a calcium chloride drying tube. Weigh out 5.8 g.
of clean sodium in a small beaker containing sufficient
kerosene to cover the metal. Add the sodium, in small
pieces, through the condenser tube, to the ethanol at
such a rate that the alcohol solution refluxes gently.
When all of the sodium has dissolved, cool the solution
to about 50°, and add, in the course of 5 minutes,
40 ml. (44 g.) of ethyl malonate. Warm the solution of
ethyl sodiomalonate on the steam bath and, through
the condenser, add dropwise from a separatory funnel
27 ml. (34.3 g.) of w-butyl bromide in the course of
10 minutes. Add some boiling chips to the reaction
40-130 mixture and allow it to reflux for 90 minutes (Note 1).
130-160
Filter the hot solution to remove sodium bromide,
and then distill off as much ethanol as possible from
the steam bath. Cool the residue by running tap water
over the flask, add 100 ml. of water and 3 ml. of concentrated hydrochloric acid to the contents of the flask,
and pour the mixture into a separatory funnel. Discard
the aqueous layer, wash the organic layer with a small
amount of water, and pour the crude ethyl n-butylmalonate into a bottle containing anhydrous magnesium
sulfate.
At a subsequent laboratory period purify the dried
ethyl rt-butylmalonate by one of the following methods,
as directed by the instructor:
(a) Distill the ester at atmospheric pressure collecting the fraction boiling at 210°-240°. This involves
some thermal decomposition of the ester.
(b) Distill the ester at diminished pressure provided
a sufficient number of sets of apparatus is available.
(c) The laboratory instructor will distill several collected lots of the ester at diminished pressure as a
demonstration experiment.
The ethyl n-butylmalonate will be used in Experiment 35 for the preparation of n-caproic acid.
103
NOTE
1. Violent bumping may occur when sodium bromide
precipitates during the course of the refluxing.
QUESTIONS
1. Write equations to show how the following compounds may be prepared from ethyl malonate and any
alkyl halides containing not more than four carbon atoms
per molecule.
(a) CH3CH2CH2CH2CH2COOH
CH3
(b) CH3CH2CH2CH2—CH—COOH
(c) HOOCCH2CH2CH2CH2CH2CH2COOH
2. Can ethyl phenylmalonate be prepared by reaction
of ethyl sodiomalonate with bromobenzene? Explain.
3. Using any materials that have been studied throughout this course write equations for six common nucleophilic
displacement reactions involving fundamentally different
bases as the displacing agents.
4. Write equations to show how the following compounds may be prepared from ethyl acetoacetate and any
alkyl halides containing not more than four carbon atoms
per molecule.
O
(a) CH3CCH2CH2CHaCH2CH3
(b) CH3CH2CH2CH*CH2COOH
5. What is barbital? How may barbital be prepared
from ethyl malonate as one of the main starting materials?
6. The crude ethyl acetoacetate prepared in Part I of
today's assignment is dried over anhydrous calcium chloride prior to being distilled. If, through careless handling,
some water containing dissolved calcium chloride should
remain with the ethyl acetoacetate, what reaction will occur as the mixture is heated?
7. What volume (S.T,P.) of carbon dioxide would be
evolved on acid-catalyzed hydrolysis of 15 g. of ethyl
acetoacetate?
EXPERIMENT 35
I. w-Caproic Acid (Part A)
CH3(CH2)3CH(COOCsH5)2
NaOH
HjSOi
heat
• CH3(CHs)3CH(COONa)2 - = S CH8(CH2)sCH(COOH)
CH3(CH2)4COOH + C 0 2
II. Reactions of Ethyl Acetoacetate
Introduction. Malonic acid, an alkylmalonic acid, or
a dialkylmalonic acid, when heated, undergoes decarboxylation to give acetic acid, an alkylacetic acid or
a dialkylacetic acid, respectively. Thus, alkylation of
ethyl malonate, followed by saponification of the product and decarboxylation of the corresponding malonic
acid, provides a general method for the preparation of
an alkylacetic acid or a dialkylacetic acid.
RCH(COOR)2 ^
RCH(COONa)2 5?!2j
heat
RCH(COOH) 2 R2C(COOR)2 ^ 5 R2C(COONa)2
RCH2COOH
H2SO4
heat
R2C(COOH)2 - = + R2CHCOOH
In today's work the ethyl n-butylmalonate prepared
in Experiment 34 will be hydrolyzed to n-butylmalonic
acid which, by removal of one mole of carbon dioxide,
yields n-caproic acid.
At one point, in which the production of the specimen of n-caproic acid will require little attention for
about an hour, the properties of ethyl acetoacetate will
be studied.
0-30
30-90
90-120
range the apparatus for distillation, and distill off about
65 ml. of water and ethyl alcohol. Cool the distillation
residue to room temperature, then attach a reflux condenser to theflaskand place it on a wire gauze. Through
the condenser tube slowly add a solution of 33 ml. of
cold, concentrated sulfuric acid in 65 ml. of water.
Foaming of the reaction mixture can be kept under
control by slow addition of the sulfuric acid and shaking of the flask. Add some boiling chips and heat the 120-180
mixture under reflux for the remainder of the period.
Allow the mixture to stand until the next laboratory
period.
[While the acid solution is being heated under reflux,
finish Part II of today's assignment and answer the
questions at the end of Part II.]
II. REACTIONS OF ETHYL ACETOACETATE
Introduction. In the molecular structure of ethyl
acetoacetate, as in that of ethyl malonate, a reactive
methylene (CH2) group is located between two carbonyl groups. In each substance reaction with sodium
ethoxide followed by the addition of an alkyl halide
I. PREPARATION OF H-CAPROIC Aero (PART A)
successively replaces one or both of the two methylene
hydrogen atoms by alkyl groups. The monoalkylation
NaOH
CH3CH2CH2CH2CH(COOC2HB)2
of ethyl malonate has been illustrated in our former
H S0
CH3CH2CH2CH2CH(COONa)2 2 4 preparation of ethyl n-butylmalonate which is being
converted into n-caproic acid in today's experiment.
heat
CH3CH2CH2CH2CH(COOH)2
Ethyl acetoacetate may be alkylated in a similar manCH3CH2CH2CH2CH2COOH ner yielding an alkylated ester which is useful not only
Procedure. Place 30 g. of potassium hydroxide in a for the synthesis of acids but of certain ketones as well.
Hydrolysis of ethyl acetoacetate with dilute alkali
500-ml. round-bottomed flask, add 30 ml. of water and
shake the mixture until the potassium hydroxide dis- (5 per cent) gives sodium acetoacetate, which undersolves. Add 30 g. of ethyl n-butylmalonate to the hot goes decarboxylation to furnish acetone (ketone split).
alkaline solution in small portions, with thorough shak- Use of concentrated alkali (30 per cent) gives two
ing of the flask. The reaction is usually vigorous, and moles of sodium acetate (acid split). Since ethyl sodiosome of the ethanol formed in the saponification re- acetoacetate is readily prepared and undergoes alkylaaction boils off. To avoid spattering of the alkaline tion with appropriate alkyl halides, and since the subsolution upon the skin, hold the flask in a towel, be stituted acetoacetic esters also undergo the ketone split
sure to add the ester in small portions, and shake the with dilute alkali or the acid split with concentrated
flask thoroughly after each addition. After all the ester alkali, alkylacetic acids or alkyl-substituted acetones are
has been added, place the flask on a wire gauze, attach readily prepared from ethyl acetoacetate.
/3-Ketoesters in general, and ethyl acetoacetate in
a reflux condenser, and boil the mixture for an hour.
particular, exist as tautomeric mixtures of the keto and
[While the mixture is being heated under reflux, pro- enol forms. The enol form of ethyl acetoacetate underceed with Part II.]
goes characteristic reactions with ferric chloride, amAdd 80 ml. of water to the reaction mixture, rear- moniacol copper sulfate and bromine water.
104
30-35
REACTIONS OF ETHYL ACETOACETATE
Short Experiments with Ethyl Acetoacetate
(a) Ferric Chloride Test. Add a drop of ethyl
acetoacetate to 10 ml. of water contained in a test tube
and shake the mixture. Then add a drop of ferric
chloride solution. Record your observation.
35-45
(b) Formation of the Copper Salt. To 10 ml. of ammoniacal copper sulfate solution contained in a test
tube add 1 ml. of ethyl acetoacetate, and shake the
mixture vigorously. The precipitation of the copper salt
begins in about 1 minute, and the amount of salt becomes quite abundant after about 4 minutes.
45-50
(c) Bromine Water. Add 1 ml. of ethyl acetoacetate
to 10 ml. of water contained in a test tube, and shake
the mixture. To the resulting suspension add 10 ml. of
bromine water and shake the mixture for a minute.
Record your observations and explain the result by
writing the equation for the reaction.
50-60
(d) Cleavage to Produce Acetic Acid. Add 5 ml. of
ethyl acetoacetate to 15 ml. of a 30 per cent aqueous
sodium hydroxide solution contained in a small roundbottomed flask. Ethyl sodioacetoacetate usually precipitates a short time after the reagents are mixed.
Attach a reflux condenser to the flask and place the
60-90 flask on a wire gauze. Heat the mixture under reflux
for 30 minutes. If the precipitate does not dissolve when
the flask is heated, add a small quantity of water. Cool
120-135 the flask, add 15 ml. of water and acidify the solution
by addition of 30 per cent sulfuric acid. Arrange the
condenser for distillation and collect 15 ml. of distillate.
135-160 Note the odor of the distillate, and test it with litmus
105
paper. Neutralize the distillate with dilute sodium hydroxide solution and evaporate the solution to dryness.
Note the residue. Write the equation for this type of
cleavage of ethyl acetoacetate.
(e) Cleavage to Produce Acetone. Place 5 ml. of
ethyl acetoacetate and 25 ml. of 10 per cent sodium
hydroxide solution in a small flask equipped with a
reflux condenser and boil the mixture for 15 minutes.
Cool the flask, arrange the condenser for distillation
and collect about 10 ml. of distillate. Note the odor
of the distillate. Test for acetone in the distillate by the
addition of a drop of a freshly prepared solution of
sodium nitroprusside and a drop of ammonium hydroxide. The appearance of a red-violet coloration
indicates the presence of acetone. Write the equation
for the cleavage reaction.
QUESTIONS
1. How may the keto and enol forms of ethyl acetoacetate be isolated in pure form?
2. List the properties of the keto and enol forms of
ethyl acetoacetate.
3. Suggest an analytical procedure for determining the
concentration of enol in a keto-enol tautomeric mixture.
4. What is the theoretical volume of carbon dioxide
liberated on hydrolysis and decarboxylation of 30 g. of
ethyl H-butylmalonate?
5. Can f-butylacetic acid be prepared by alkylation
of ethyl sodiomalonate, followed by hydrolysis and decarboxylation of the corresponding malonic acid? Explain.
120-160
EXPERIMENT 36
I. rc-Caproic Acid (Part B)
II. Preparation of Adipic Acid
C
/
\
H2C
CH.2
1
1
H2C
+ 2 K M n 0 4 - • KOOC—(CH2)4—COOK + 2 M n 0 2 + H 2 0
CH2
\
C
H2
/
Introduction. The preparation of n-caproic acid,
begun in Experiment 35, by saponification of ethyl
w-butylmalonate and decarboxylation of the corresponding malonic acid will be completed today. Inasmuch as
n-caproic acid is a liquid, a portion of it may be converted to the anilide, a solid derivative, in some subsequent period. The reactions used to prepare the
anilide are summarized in the following equations:
0-10
10-70
Filter the solution into a 500-ml. distilling flask, attach 110-130
a water-cooled condenser, and distill off the benzene.
Transfer the residue to a small distilling flask, attach 130-150
an air-cooled condenser and distill the liquid. Collect
the portion boiling from 196°-206° (Note 1) in a
tared bottle and determine the amount of n-caproic
acid obtained. Calculate the percentage yield of product.
Stopper the bottle and save the compound for some
(a)
future period when the anilide can be prepared.
CH3CH2CH2CH2CH2COOH + SOCl2 ->
CH3CH2CH2CH2CH2C0C1 + S0 2 + HC1
n-Caproanilide (Optional). In a small flask mix 3 g.
of fl-caproic acid with 4.5 ml. of pure thionyl chloride,
(b)
attach a reflux condenser and boil the solution under
CH3CH2CH2CH2CH2C0C1 + 2C6H6NH2->
CH3CH2CH2CH2CH2CONHC6H6 + C 6 H 6 NH 2 HC1 reflux for 30 minutes. Cool the liquid, dissolve it in
30 ml. of anhydrous benzene, and pour the solution
As Part II of the laboratory assignment, adipic acid
in portions, with shaking, into a solution of 6 ml. of
will be prepared by oxidation of cyclohexanone with
aniline in 50 ml. of anhydrous benzene. Warm the sopotassium permanganate. This experiment illustrates
lution on the steam bath for a few minutes, pour the
the opening of a ring by oxidation. Adipic acid, which
liquid into a separatory funnel and wash it successively
may also be prepared by oxidation of cyclohexanol with
hot nitric acid, is used commercially in the manufacture with small amounts of 5 per cent hydrochloric acid, 5
per cent sodium hydroxide solution, and water. Distill
of one type of Nylon (Nylon 66).
the benzene from the solution and crystallize the residue
from 70 per cent ethanol. Collect the crystals and
I. PREPARATION OF W-CAPROIC ACID (PART B)
determine the melting point of the n-caproanilide (Note
Procedure. Heat the acid mixture which has been 2).
standing since the last laboratory period to boiling and
reflux for an additional hour..
[While the solution is being heated under reflux proceed with Part II.]
70-90
90-110
[Meanwhile continue with Part II.]
NOTES
1. The boiling point of zz-caproic acid is 202°.
Cool the hot acid solution to room temperature, pour
2.
The melting point ofrc-caproanilideis 95°.
the mixture into a separatory funnel, draw off the lower
sulfuric acid solution, and pour the upper layer of
II. PREPARATION OF ADIPIC ACID
rt-caproic acid into a 500-ml. Erlenmeyer flask. Extract
Procedure. To a solution of 15 g. of potassium
the sulfuric acid solution with three 100-ml. portions
of benzene and combine the benzene extracts with the permanganate in 130 ml. of water contained in a
original n-caproic acid layer. Wash the resulting so- 250-ml. Erlenmeyer flask add 5 g. of cyclohexanone
lution with about 20 ml. of water, then dry the benzene and 1 ml. of 10 per cent potassium hydroxide solution.
solution over anhydrous magnesium sulfate for 20 min- Place a thermometer in the reaction mixture and observe the rise in temperature. When the temperature
utes.
106
10-25
PREPARATION OF ADIPIC ACID
25-45
70-90
reaches 50°, immerse the flask in cold water until the
temperature drops to 45°.
Keep the mixture at a temperature of 45°-50° for
20 minutes by alternately cooling the flask to 45° in
water and allowing it to warm up to 50° again outside
the water bath. Place the flask on a wire gauze and
heat the contents to the boiling point, then cool slightly,
add a few crystals of sodium bisulfite and filter the mixture with suction. Wash the precipitate with two 30-ml.
portions of water and concentrate the combined filtrate
and wash solution to about 40 ml. by boiling in an
evaporating dish. Allow the solution to cool slightly,
add a small amount of decolorizing carbon and filter the
hot solution, collecting the filtrate in an Erlenmeyer
flask.
Acidify the hot filtrate with concentrated hydrochloric acid and allow it to stand in a bath of ice and
water for 15-20 minutes. Collect the crystals of adipic
acid by suction filtration and determine the melting
point of the compound (Note 1). After the crystals
have been dried, determine their weight (Note 2) and
calculate the percentage yield.
107
(b) CH3CH2CH2OH + Na2Cr207 + H2S04
>
O
CH3CH2—C—OH + Cr2(S04)3 + Na2S04 + H20
(c) HOCH2—(CH2)3—CH2OH + K M n 0 4 ^ >
KOH
O
0
KO—C—(CH2)4—C—OH + Mn02 + H20
(d)
+ Na2Cr207 + H2S04
•
+ Na2S04 + Cr2(S04)3 + H20
(e)
+ KMn04
NOTES
1. The melting point of adipic acid is 152°.
2. The weight of adipic acid obtained in this experiment
is usually about 3 g.
QUESTIONS
1. Balance each of the following equations and show
your method for doing so.
(a) CH3—CH=CH—CH3 + K M n 0 4 - ^
CH3—CH—CH—CH3 + KOH + Mn02
AH
OH
KO—C—(CH2)4—C—OK + Mn02 + KOH
2. Write equations to show how Nylon-66 may be prepared from adipic acid and hexamethylenediamine.
3. Write equations to show the preparation of Nylon-6
from cyclohexanone.
4. What is the purpose in adding a small amount of
sodium bisulfite before the initial filtration of the above
preparation?
5. What are the commercial sources of cyclohexanol?
6. Would it make any difference if sodium hydroxide
solution rather than potassium hydroxide solution was used
to catalyze the oxidation reaction described in the above
preparation?
EXPERIMENT 37
I. Diethyl Adipate (Azeotropic Esterification)
II. Properties of Lactic, Tartaric, and Citric Acids
Introduction. As mentioned previously (Experiment
26), the Fischer esterification is an equilibrium reaction,
and the yield of ester is usually about 67 per cent if
equimolar quantities of alcohol and carboxylic acid
are caused to react and no scheme is used to displace
the equilibrium to the right.
O
H
0
[H + ]
II
R—C—OH + R—OH -4 R—C—O—R + H 2 0
However, the yield of ester can be made to approach
100 per cent by the simple expedient of removing water
as it is formed. Most often this is accomplished by a
process of azeotropic distillation. A third compound is
added to the mixture of alcohol and carboxylic acid
such that an azeotrope of minimum boiling point, including water as one of the components, will be formed.
The reaction is carried out in aflaskjoined to a distilling
column. As water is formed in the esterification process,
the azeotrope of minimum boiling point is distilled
through the column, thus displacing the esterification
equilibrium to the right.
A typical boiling point-composition curve for a
binary azeotrope of minimum boiling point is shown
in Figure 9, page 15. If a solution of composition Lx
is heated to the temperature Tl9 the mixture will begin
to boil, and the composition of the vapor which first
distills is Vi. If distillation is permitted to continue for
a short period of time, the temperature of the liquid
in the distilling flask rises from Ti to T2 and the distillate possesses the composition ranging from Ki to V2.
If the distillate were redistilled, the vapor would approach the composition of the system of minimum boiling point. Therefore fractional distillation with the aid
of a column will afford a distillate of composition CM,
the residue in the distilling flask approaching the composition A as the distillation progresses. A similar situation would prevail if the starting liquid had a composition falling in the right-hand portion of the curve
shown in Figure 9. A few examples of binary azeotropic
mixtures of minimum boiling point are given below:
Per Cent by
1st
Component
Water
(b.p. 100°)
Water
(b.p. 100°)
Ethanol
(b.p. 78.3°)
Ethanol
(b.p. 78.3°)
2nd
Component
Ethanol
(b.p. 78.3°)
Pyridine
(b.p. 115.5°)
Ethyl Acetate
(b.p. 77.2°)
Toluene
(b.p. 110.6°)
Ternary azeotropes of minimum boiling point are
also known. Although the phase diagram for such a
system, being 3-dimensional, is necessarily more complex than that shown in Figure 9 for a binary mixture,
the principles involved in a fractional distillation are
the same.
In today's experiment, diethyl adipate will be prepared from adipic acid and ethanol, with toluene serving as the agent for azeotropic removal of water. Inasmuch as a ternary azeotrope containing toluene, ethanol,
and water is formed, it will be necessary to treat the
initial distillate with anhydrous potassium carbonate
in order to remove most of the water and then to
filter the mixture and return the filtrate to the reaction
flask; otherwise excessive quantities of toluene and
ethanol would have to be employed.
While the ternary azeotrope is being removed by
distillation and also during the purification of diethyl
adipate by distillation, certain of the properties of some
common hydroxyacids will be examined.
I. DIETHYL ADIPATE (AZEOTROPIC ESTERIFICATION)
HOOC— (CH2)4—COOH + 2C2H6OH -*
C2H5OOC—(CH2)4—COOC2H6 + 2H20
Procedure. Place 73 g. (0.5 mole) of adipic acid,
180 ml. (142 g., 3.1 moles) of absolute ethanol, 90 ml.
of toluene, and 1 ml. of concentrated sulfuric acid in a
500-ml. round-bottomed flask. Attach a short Vigreux
or packed column (Note 1) to the flask and connect
a water-cooled condenser set for distillation to the head
of the column. Partially immerse the flask in an oil
bath and raise the temperature of the bath to 115°.
As the temperature of the bath is raised, adipic acid
dissolves in the reaction mixture, and the ternary azeotrope of ethanol, toluene, and water begins to distill at
a temperature of 75°. Collect the distillate in a flask
containing 75 g. of anhydrous potassium carbonate.
0-30
30-60
[While the distillation is in progress, work on Part II
of the assignment for today.]
Continue the distillation until the thermometer at
Weight of
B.p. of
Azeotropic 1st Component the top of the column attains a reading of 78°. At this
Mixture in the Mixture point, discontinue heating the oil bath. When the dis-
60-80
tillation ceases, shake the distillate which has been
collected with the anhydrous potassium carbonate for
1-2 minutes, then filter the mixture through a Buchner
funnel with suction, and return the filtrate to the distilling flask. Connect the column with its attached condenser to the flask once again, raise the temperature of
the oil bath to about 110°, and continue the distillation
80-100
78.15°
4.4
92.6°
43.0
71.8°
31.0
76.7°
68.0
108
PROPERTIES OF LACTIC, TARTARIC, AND CITRIC ACIDS
until the overhead vapor attains a temperature of 78°80°.
[Continue with Part II of the assignment.]
100-120
Discontinue heating the oil bath, allow the solution in
the flask to cool somewhat, then transfer the liquid to
a distilling flask, attach a water-cooled condenser, and,
with heating of the flask by the oil bath, remove the
120-170 solvents by distillation. Replace the water-cooled condenser by an air condenser and purify the diethyl
adipate by distillation.
[Continue with Part II.]
Use the slightly luminous flame of the Bunsen burner
to heat the flask in the latter operation. Collect the
material boiling from 225°-240° (Note 2). Weigh the
ester and calculate the percentage yield.
NOTES
1. A Vigreux column about 1 foot long or a packed
column of the same length containing glass beads or
helices is adequate for this operation.
2. The recorded b.p. of diethyl adipate is 239° at
760 mm. pressure. Less charring of the ester would result
if the distillation were carried out in vacuo (see Figure
28, page 102). It is recommended that the distillation be
conducted at 20 mm. pressure if suitable apparatus for
conducting such a vacuum distillation is available. The
recorded b.p. of diethyl adipate at 20 mm. pressure is 138°.
II.
PROPERTIES OF LACTIC, TARTARIC,
AND CITRIC ACIDS
H O
O
II
1 II
H—C—C—OH
C—OH
OH
O
1 II
CH3—C—- C - -OH
1
H
I
I
H—C—OH
1
0
H—C—OH
II
HO—C—C—OH
0
C—OH
II
O
II
H—C—C—OH
1
H
Lactic acid
30-35
35-45
raeso-Tartaric
. acid
Citric acid
Properties of Lactic Acid
(a) Action on Litmus. Dilute 1 ml. of syrupy lactic
acid with 5 ml. of water and test the solution with
litmus paper. What is the result?
(b) Ferric Chloride Test for an a-Hydroxy Acid.
To the dilute solution of lactic acid prepared as described above add 1 drop of ferric chloride solution.
Compare the color with that produced in a test with
water alone. The color is best observed by looking
down through the test tube against a white background.
109
In this test ferric ion is reduced to the ferrous state.
To show the presence of ferrous ion, warm the tube
and its contents and add a few drops of potassium
ferricyanide solution. Record your observations.
(c) Decomposition with Sulfuric Acid. Add 7 ml. of
syrupy lactic acid to 20 ml. of 30 per cent sulfuric
acid contained in a distilling flask. Fit the flask with a
water-cooled condenser and distill the liquid until about
8 ml. of distillate has been obtained. Divide the distillate into two portions. Test one portion for acetaldehyde with Tollens' solution without the application of
heat and test the other portion for formic acid by warming it with a solution of mercuric chloride and sodium
acetate. Write the equation for the acid-catalyzed cleavage of lactic acid.
45-60
Properties of Tartaric Acid
(a) Ferric Chloride Test. Dissolve 1 g. of tartaric
80-90
acid in 100 ml. of water. To 10 ml. of this solution
add 1 drop of ferric chloride solution. Note the depth of
the color on looking down through the test tube. Prepare a control solution by adding 1 drop of ferric
chloride solution to 10 ml. of a 2 per cent acetic acid
solution. Record your observations.
(b) Potassium Salts of Tartaric Acid. To 5 ml. of 90-100
a cold saturated solution of tartaric acid in water add
a solution of potassium hydroxide dropwise until a precipitate forms. Then add more potassium hydroxide
solution until the precipitate dissolves. Write equations
for the two reactions. What is cream of tartar?
(c) Reducing Action of Tartrates. Determine 120-130
whether Rochelle salt will reduce Tollens' solution.
What is Rochelle salt?
(d) Preparation of Fehling's Solution. To 2 ml. of 130-140
copper sulfate solution add sodium hydroxide solution
until a heavy precipitate forms. Now add a solution of
Rochelle salt until the precipitate dissolves. Write
equations for these reactions.
(e) Tartar Emetic. Dissolve 5 g. of potassium hydro- 140-150
gen tartrate in 50 ml. of water. Add approximately 1 g.
of antimony trioxide and boil the solution for 2-3 minutes. Filter the mixture, concentrate the filtrate to about
one third of its original volume, and set it aside. What
product eventually crystallizes from the solution?
Properties of Citric Acid
(a) The Use of Ferric Ammonium Citrate in Blue
Print Paper. Add 10 ml. of a 5 per cent aqueous solution of ferric ammonium citrate to an equal volume
of a 5 per cent solution of potassium ferricyanide and
moisten a sheet of filter paper with this solution. Dry
the sheet in an oven at 100° for about 20 minutes.
150-155
[Proceed with the next portion of the assignment.]
When the paper is dry expose it to sunlight under a
sheet of cardboard or heavy paper in which a design
has been cut. After 3 minutes dip the paper in water.
175-180
110
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
Record your observations and explain what reactions
have taken place.
155-160
(b) Thermal Decomposition. Heat 0.5 g. of citric
acid in a test tube and note the odor. Write structural
formulas and names of three possible organic decomposition products.
160-165
(c) Reducing Power of Citrates. Determine whether
citric acid will reduce Tollens' reagent.
165-175
(d) Solubility of Calcium Citrate. Dissolve 0.5 g. of
citric acid in about 10 ml. of cold water and add a small
amount of a thick aqueous suspension of lime. Shake
the tube for about 2 minutes, then remove undissolved
material by filtration. Heat the filtrate to boiling and
note the result. Is calcium citrate more soluble in hot
or cold water?
QUESTIONS
1. Select any point on the solution curve of the right-
hand portion of Figure 9 and explain briefly what would
happen if a solution of that composition were subjected to
fractional distillation.
2. Are azeotropic mixtures of maximum boiling point
known? Give the names of the components, the boiling
point of the azeotropic mixture, and the per cent composition of several such mixtures.
3. Would the composition and boiling point of an azeotropic mixture vary as the Aressure over the liquid is
changed?
4. Name one important industrial procedure for the
purification of a common organic compound that involves
an azeotropic distillation.
5. What are several methods that may be used for
separating the components of azeotropic mixtures?
6. Compare the behavior of a-, /?- and y-hydroxy-acids
on heating.
7. How may ethyl acetonedicarboxylate be prepared
from citric acid?
8. Of what biochemical importance is lactic acid?
EXPERIMENT 38
Proteins
Introduction. The three classes of foods—proteins,
fats, and carbohydrates—are so interdependent in
animal and plant metabolism that it is impossible to
list them in any order of importance. However, there
can be no question about the relative structural complexities of the three classes of foods; proteins are by
far the most complex. In elementary composition the
fats and carbohydrates are compounds of carbon, hydrogen, and oxygen; whereas proteins always contain
nitrogen in addition to these elements, and often contain sulfur and phosphorus as well. Protein molecules
have high molecular weights; values range from about
40,000-45,000 for egg albumin and gliadin up to
40,000,000 reported for the tobacco mosaic virus.
In today's experiments the protein gliadin will be
isolated from wheat flour, and an aqueous solution of
albumin will be prepared from egg white. Certain color
reactions, coagulation tests, and precipitation reactions,
characteristic of proteins in general, will be carried out
on these proteins and also on milk casein and gelatin.
The acid-catalyzed hydrolysis of a protein to its
component amino acids requires a long period of refluxing. In preparation for some experiments on amino
acids, to be conducted during the next laboratory
period, the hydrolysis of a sample of gelatin will be
begun during this period and allowed to continue until
the next period.
the gummy mass of gluten, cut it into small pieces,
mix the pieces with 200 ml. of 70 per cent ethanol,
heat the mixture on the steam bath for a few minutes,
and filter the hot solution. Repeat the operation, then
combine the filtrates and evaporate the solution to a
volume of 100 ml. Cool this solution, add with stirring
10 ml. of 10 per cent sodium chloride solution to "salt
out" the protein, allow the precipitate to settle, and
wash it twice by decantation with 95 per cent ethanol.
The residue is the protein, gliadin.
Preparation of an Albumin Solution
Prepare an aqueous solution of egg albumin by beating the white of an egg for a short time, then mixing
it with five times its volume of water. Filter the mixture
through cheesecloth and save the filtrate for the various
tests described below.
Coagulation of Albumin
Place about 2 ml. of egg-white solution in each of five
test tubes. Heat one tube gradually and note the approximate temperature at which coagulation takes
place. To another tube add 4 ml. of ethanol. To a third
add a few drops of concentrated hydrochloric acid, to
the fourth nitric acid, and to the fifth concentrated
sodium hydroxide solution. Note the cases in which
coagulation occurs.
Acid-Catalyzed Hydrolysis of Gelatin
Add 20 g. of gelatin to 100 ml. of 25 per cent sulfuric
0-20
acid contained in a round-bottomed flask. Place the
flask on a wire gauze, attach a water-cooled reflux
condenser to the flask, and support the apparatus on
a ring stand. Heat the solution under reflux with a
20-155 Bunsen burner for the remainder of the period while
155-165 you are carrying out other experiments, then cool the
solution somewhat, replace the water-cooled condenser
with an air-condenser, and heat the mixture at about
90° in the multiple unit bath shown in Figure 31, page
139, until the next laboratory period.
15-30
30-90
Isolation of Gliadin from Wheat Flour
Gradually add sufficient water to 1000 g. of highgrade wheat flour to make a stiff dough. Allow the
dough to "age" by standing at room temperature for an
hour.
[Proceed with the next section.]
Knead the dough in your hands under a stream of
90-105
cold water until the wash water no longer has a turbid
appearance and the residue is a gummy mass. The material obtained in this way is called "gluten" and consists
of a mixture of different proteins from the wheat.
To obtain the protein gliadin in fairly pure form from
105-130
30-45
45-60
Precipitation of a Protein by Cations
Introduce into six test tubes the following solutions:
I. 5 ml. of water.
II. 5 ml. of egg-white solution.
III. 5 ml. of water and 4 drops of 10 per cent hydrochloric acid.
IV. 5 ml. of egg-white solution and 4 drops of 10 per
cent hydrochloric acid.
V. 5 ml. of water and 4 drops of 10 per cent sodium
hydroxide solution.
VI. 5 ml. of egg-white solution and 4 drops of 10 per
cent sodium hydroxide solution.
Next introduce into each tube 2 ml. of 10 per cent
copper sulfate solution and note the results. The control experiments in which no protein is used are necessary to determine whether the observed effect in each
case is actually due to the precipitation of the protein
or rather to precipitation of the metal hydroxide. Is
the precipitate formed in tube VI simply copper hydroxide? How is the difference in the behavior of acidic,
neutral, and alkaline solutions of proteins toward cation
precipitants accounted for? What factor is important
in determining the effectiveness of a cation precipitant,
aside from the atomic weight of the cation?
111
60-75
112
75-90
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
Precipitation of Proteins by Anions
Prepare solutions identical with II, IV,
previous section. To each add 2 drops
ferricyanide solution and note in which
cipitate forms most readily. Explain this
and VI of the
of potassium
tube the preresult.
Action of Formaldehyde on Proteins
130-150
Place a little gliadin in a 20 per cent formaldehyde
solution and allow it to stand for 15 minutes.
[Proceed with the following experiments.]
150-155 Remove the gliadin and compare its solubility in 70 per
cent ethanol with that of untreated gliadin. Indicate how
formaldehyde reacts with amino groups in proteins.
Biuret Color Reaction for Proteins
135-140
Add to an egg-white solution an equal volume of 10
per cent sodium hydroxide solution. Then add 1 drop
of a 1 per cent copper sulfate solution. Note the color
produced.
Formaldehyde Color Reaction for Proteins
140-145
To a small amount of egg-white solution contained
in a test tube add 1 drop of dilute formaldehyde solution. Pour concentrated sulfuric acid down the tube in
such a manner that it forms a separate layer in the bottom of the tube. What do you observe? Repeat the test
with a gelatin solution. Note the result.
Millon's Test for Proteins
145-150
Add 5 drops of Millon's reagent to an egg-white
solution, heat, and note the color. A protein when tested
in this manner gives a reddish-orange color provided
that a tyrosine, phenylalanine, or tryptophane moiety is
present; otherwise the test is negative. Repeat the test
with gelatin. What are your conclusions?
Xanthoproteic Reaction for Proteins
Add a small piece of wool or silk to about 1 ml. of 165-170
concentrated nitric acid contained in a test tube and
heat the tube. Note the color of the material. Make the
mixture alkaline by the addition of sodium hydroxide
solution and note the change in color.
QUESTIONS
1. What is the essential chemical reaction involved in
Millon's test?
2. Describe Heller's ring test. What is its main use?
3. What is a conjugated protein?
4. Casein is known to contain phosphorus in addition
to the other common elements found in proteins. Does
this fact indicate that casein is a conjugated protein?
5. What is the total number of isomers, including optical
isomers, possible for a tripeptide containing the alanine,
phenylalanine, and tryptophane moieties?
6. Hemoglobin contains 0.335 per cent of iron. What is
the minimum possible molecular weight of hemoglobin?
The actual molecular weight is four times this value.
7. Why does nitric acid produce a yellow color when
it comes in contact with the skin?
8. Why is egg white frequently used as an antidote for
various poisons?
EXPERIMENT 39
Amino Acids
Introduction. The hydrolysis of gelatin, started last
period, should have been completed by now. However,
in order to make sure of this point, the hydrolysate
should be subjected to the biuret test at the start of this
period. If the test is positive, indicating the presence of
protein molecules, the solution must be refluxed for an
additional period of time. Following completion of the
hydrolysis, studies will be made of the buffer action of
amino acids. Also, the action of nitrous acid on amino
acids and the ninhydrin color test of such acids will be
investigated. Ninhydrin is the common name for triketohydrindene hydrate, which undergoes reaction with an
amino acid to form a blue compound according to the
following equation:
o
II
C
<
OH
NH 2
I
\ /
C
+ R—C—COOH
.O/ \
I
C
OH
Ninhydrin
H
OH
/
C=N—C
C
O
\
\ / \
f R-CHO
j | \ + \ C0 2
/ V
l 3H20
C
O
tion. Well defined spots appear wherever the reagent
comes in contact with an amino acid.
Acid-Catalyzed Hydrolysis of Gelatin
(Continued from Experiment No. 38)
Apply the biuret test (page 112) to the gelatin solution that has been heated in the multiple unit bath since
the last period. If the test is positive, indicating the presence of unhydrolyzed protein, heat the solution under
reflux for the remainder of this period and proceed
with another laboratory assignment according to the
directions of your laboratory instructor. If the test is
negative, however, continue with this experiment. Dilute the solution to about 300 ml. and add enough of
a solution of barium hydroxide [Ba(OH) 2 -7H 2 0] in
hot water to neutralize all of the sulfuric acid originally
used. Use litmus paper to detect the end point of the
neutralization.
When the hot solution containing much barium sulfate is approximately neutral, filter it through a porcelain funnel using hardened filter paper: Test the filtrate with litmus paper and adjust the pH as nearly as
possible to a value of seven. Add a small amount of
decolorizing charcoal, heat the mixture to boiling, filter
and evaporate the filtrate to dryness in an evaporating
dish. The residue consists of a mixture of amino acids
including glycine, L( — )-hydroxyproline, L ( - ) - p r o line, L( + )-arginine, L( + )-alanine, L(-)-leucine,
L( + )-lysine, L( + )-glutamic acid, L( —)-aspartic acid,
L( —^-phenylalanine, L( —)-cystine and L( —)-tyrosine.
While the solution is being evaporated to dryness, answer the questions at the end of this experiment.
The ninhydrin test represents an important part of Paper Chromatography of Amino Acids
the analysis of the components of a protein hydrolysate
With the aid of a pipette, place about 0.2 ml. of
by the technique of paper chromatography. The amino
acids present in the hydrolysate are partitioned between freshly prepared 80 per cent phenol in the bottom of a
water absorbed on the cellulose of the paper and an 25 x 200 mm. test tube without wetting the walls of
organic solvent, only partially soluble in water, which the tube. Cut a piece of Whatman No. 1 filter paper
is caused to travel along the strip of paper by either into a 0.5 x 8 inch strip and fold it along its long axis.
ascending or descending flow. The absorbed water rep- Use a clean spatula to crease the paper and handle only
resents the stationary phase and the organic solvent the upper 1 inch of the paper with the fingers. Cut the
the moving phase. Butanol or phenol may be used as paper and crease it on a clean paper towel or sheet of
writing paper in order to avoid contact with the laborathe organic solvent.
The more hydrophilic the amino acid, the more it tory desk.
Moisten the bottom of a clean glass rod in a dilute
tends to be retained in the stationary phase; the more
lipophilic the acid, the greater is its tendency to travel aqueous solution of the amino acids obtained by hywith the moving organic phase. The ratio of the dis- drolysis of gelatin and touch the rod to the strip of filter
tance traveled by the amino acid to that traveled by the paper about £ inch from the bottom. Cut off the top
organic solvent is called the Rf value, a constant inch of the paper strip, the part that has been touched
characteristic of each amino acid. When the chromato- with the ringers, and with the aid of forceps lower the
graphic separation of the amino acids has been com- strip into the test tube containing the 80 per cent phenol
pleted, the location of the various amino acids is deter- solution so that only the bottom and top of the strip
mined by spraying the dried paper with ninhydrin solu- touch the test tube. Cork the tube, place it in an Erlen113
0-15
15-30
30-60
60-75
114
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
75-135
meyer flask at a slight angle, and allow it to stand for
an hour.
Meanwhile, proceed with the remaining parts of
today's assignment and continue with the questions at
the end of this unit of work.
135-155
Remove the strip of paper from the test tube with
the aid of forceps and measure the distance that the
solvent front has traveled along the strip of paper. Wash
the paper with a stream of acetone from a polyethylene
wash bottle, and hang it from a hook made from a piece
of wire and attached to a clamp on the ring stand.
155-165
Allow it to dry for 15 minutes, then spray it lightly
with a solution prepared by dissolving 0.4 g. of ninhydrin and 1.5 ml. of pyridine in 100 ml. of 95 per cent
ethanol. The paper should be made moist but not so
wet that it drips. Spots indicating the positions of the
various amino acids usually begin to appear within 5
to 10 minutes.
Of the amino acids found in gelatin hydrolysate,
L ( —) -proline, L (—) -phenylalanine, and L ( + ) -arginine
will have traveled the farthest along the paper strip,
while L (—) -cystine, L (—) -aspartic acid, L ( + ) -glutamic
acid, and glycine will have traveled the least distance.
Assume that the spot farthest removed from the point
at which the rhixture of amino acids was applied to the
paper represents L( —) -proline, and then calculate the
Rf value for this amino acid. Your result will be only
approximate inasmuch as a more carefully designed
experiment than the one described here would have to
be carried out before accurate Rf values could be measured. The reported Rf value for L( —)-proline is 0.85.
75-90
90-115
Ninhydrin Reaction for Proteins and Amino Acids
Although the ninhydrin test is applied in the development of the paper chromatogram of the previous experiment, it is desirable to make a few preliminary test
tube experiments with the reagent. The contents of a
0.1-g. vial of ninhydrin is dissolved in 30 ml. of water.
Two drops of this solution are added to 2-3 ml. of the
solution to be tested and the mixture is heated to boiling
for about a minute. Cool the solution and note the result. Make the test on a solution of the amino acids
obtained by hydrolysis of gelatin and on gelatin itself.
Buffer Action of Amino Acids
Add a drop of congo red indicator solution to 5 ml.
of distilled water contained in a test tube and also to
5 ml. of a 1 per cent aqueous solution of the amino
acids obtained by hydrolysis of gelatin. Is there any
marked difference in the colors of the two solutions?
Add approximately 0.1 iV hydrochloric acid to each
tube drop by drop and note the difference in behavior.
Repeat the experiment with phenolphthalein as the indicator and O.liV sodium hydroxide solution. How are
the results explained?
Action of Nitrous Acid on Amino Acids
Add 1 ml. of a 5 per cent aqueous solution of sodium 115-130
nitrite to 5 ml. of an ice-cold solution which contains
5 per cent of hydrochloric acid and 2 per cent of the
amino acid mixture obtained by the hydrolysis of gelatin. As a control experiment add the same amount of
sodium nitrite solution to 5 ml. of ice-cold 5 per cent
hydrochloric acid. Note the results. Write equations for
the action of nitrous acid on glycine and alanine.
QUESTIONS
1. Write structural formulas for each of the amino acids
listed as being among the hydrolysis products of gelatin.
2. Write equations to show how ninhydrin may be
synthesized from phthalic acid and ethyl acetate as the
organic starting materials.
3. Rf values vary with the solvent system and type of
filter paper employed. Therefore the Rf values given below
for various amino acids represent values for one particular
system only: glycine, 0.42; alanine, 0.59; a-aminobutyric
acid, 0.70; norleucine, 0.81; ornithine, 0.67; lysine, 0.71;
arginine, 0.76; serine, 0.43; threonine, 0.51; tyrosine, 0.62;
aspartic acid, 0.32; glutamic acid, 0.40. Plot each of these
Rf values as ordinate vs. molecular weights of the amino
acids as abscissa. Do the various amino acids seem to fall
into certain natural groups in this plot? Draw any conclusions you can with regard to the relationship between
Rf values and structures of the amino acids.
4. Would you expect the Rf value of ornithine to be
higher or lower than the Rf value of its conjugate acid?
Explain. Answer the same question with regard to aspartic
acid and its conjugate base.
5. Would you expect lysine hydrochloride and lysine
perchlorate to give different Rf values in the type of experiment carried out as a part of today's assignment?
EXPERIMENT 40
Preparation and Properties of Urea
(NH 4 ) 2 S0 4 + 2 K O C N ^ 2 N H 4 O C N + K 2 S0 4
O
NH 4 OCN -> H 2 N—C—NH 2
Introduction. Urea is an important chemical, both
with respect to its industrial uses and its role in biological processes. The compound is also of interest in
the history of organic chemistry inasmuch as Wohler's
synthesis of urea in 1828 represented an early synthesis
of a typically organic compound from inorganic reagents. The first part of today's laboratory assignment
consists of a synthesis of urea which is quite similar to
Wohler's original preparation of the compound. The
second part of the period will be devoted to a study of
the properties of urea including: (1) hydrolysis reactions conducted under various conditions; (2) the formation of a salt with nitric acid; (3) degradation reactions with nitrous acid and sodium hypobromite; (4)
thermal decomposition to isocyanic acid which forms
biuret by further reaction with urea; (5) trimerization
of isocyanic acid; and (6) formation of a resin by the
action of formaldehyde on urea.
0-15
15-45
A. Preparation of Urea from Potassium Cyanate
and Ammonium Sulfate
Place 10 g. of potassium cyanate and 35 g. of ammonium sulfate in an evaporating dish, and dissolve
the salts in 25 ml. of hot water. Evaporate the solution
to dryness on the steam bath.
[During this interim answer some of the questions at
the end of today's assignment.]
45-75
75-85
85-95
The residue consists mainly of a mixture of urea, which
is soluble in absolute ethanol, and potassium sulfate,
which is insoluble in alcohol. Place the solid material
in an Erlenmeyer flask, add 25 ml. of absolute alcohol,
and heat the mixture on the steam bath until the solvent
begins to boil. Decant the liquid into a filter funnel.
Repeat the alcohol extraction of the residue and combine the filtrates. Evaporate the solution to dryness, and
determine the weight and the melting point of the
crystalline residue. Calculate the per cent yield of
product.
line and note the odor of the vapor above the solution.
Test the vapor with litmus paper. Write the equation for
the reaction.
C. Formation of Urea Nitrate
To a solution of 2 g. of urea in a small amount of
water add a few ml. of concentrated nitric acid. What is
the precipitate which forms? Write the equation for the
reaction.
95-100
D. Reaction of Urea with Nitrous Acid
Add 1 ml. of 5 per cent sodium nitrite solution to an 100-110
ice-cold solution of about 0.1 g. of urea in 5 ml. of 5
per cent hydrochloric acid. Note the evolution of a gas.
As a control experiment add the same amount of sodium
nitrite to 5 ml. of ice-cold 5 per cent hydrochloric acid
alone. Is there any gas evolution in this experiment?
Write the equation for the reaction of urea with nitrous
acid.
E. Reaction of Urea with Sodium Hypobromite
Add a small amount of sodium hypobromite solution 110-120
to about 5 ml. of a dilute aqueous solution of urea.
Note the evolution of a gas. If sodium hypobromite
solution is not available in the laboratory, it may be
prepared by adding bromine to a 10 per cent sodium
hydroxide solution until a yellow color persists. Write
the equation for the reaction of urea with sodium hypo- •
bromite.
F. Biuret and Cyanuric Acid
Place 1 g. of urea in a test tube and heat the tube 120-135
and its contents until evolution of gas has almost ceased
and the mass has resolidified. What is the gas? Cool the
tube and stir the contents with 5 ml. of cold water to
dissolve the biuret which resulted from the pyrolysis
reaction. Cyanuric acid, which is also present, is less
soluble. Filter the mixture, make the filtrate alkaline by
addition of 10 per cent sodium hydroxide solution, and
add 2 drops of 1 per cent copper sulfate solution. What
B. Hydrolysis of Urea
do you observe?
Wash the insoluble portion of the pyrolysis mixture
(1) In Alkaline Solution. Add 5 ml. of 5 per cent
sodium hydroxide solution to about 0.5 g. of urea con- with another 5 ml. of water, then dissolve the residual
tained in a test tube, and warm the solution gently. Note cyanuric acid in the minimum amount of boiling water.
the odor of the escaping gas. Write the equation for the Add 1 ml. of an ammoniacal solution of copper sulfate.
Note the formation of a precipitate of copper cyanurate.
reaction.
Write two equations for the pyrolysis of urea, one
(2) In Acid Solution. Dissolve about 0.5 g. of urea
in 5 ml. of 5 per cent hydrochloric acid and boil the showing the formation of biuret and die other showing
solution for about 2 minutes. Make the solution alka- the formation of cyanuric acid.
115
116
135-160
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
G. Urea Resin
Prepare in an 8-inch test tube a solution containing
3 g. of urea and 5 ml. of concentrated hydrochloric acid
in 30 ml. of water. Place a few drops of methyl orange
indicator in the solution in order to color it, then add
3 ml. of formalin and mix the reagents by shaking the
tube. Allow the tube to stand for several minutes. What
is your observation? Write an equation for a partial
reaction.
QUESTIONS
1. Write equations to show how urea may be prepared
from ammonia and each of the following reagents: (a)
phosgene, (b) ethyl carbonate, (c) ethyl carbamate, (d)
ethyl chloroformate, (e) carbon dioxide.
2. Write equations to show how urea and any other
needed reagents may be used for the synthesis of each of
the following compounds: (a) semicarbazide, (b) parabanic acid, (c) barbituric acid, (d) amytal, (e) phenobarbetal, (f) uric acid, (g) guanidine.
3. In the formation of the conjugate acid of urea, why
is it more likely that the proton becomes bonded to oxygen
rather than to nitrogen?
4. Would you expect guanidine or urea to be the
stronger base? Why does but one proton add to these
bases? Justify your answers.
5. How may urea be prepared from calcium cyanamide?
EXPERIMENT 41
I. Preparation and Resolution of D,L-s-Octyl Hydrogen Phthalate
o
OH
C
I
I
CHs
O -»
\A
/
H
X
v
O
C—OH
C
/
H
/\/
1
A C1 d
.
n
l(—)-Brucine- HC1
C—O—CH(CH2)6CH3
(b)
C—O—C—(CH2)6—CH3
/\/ \
(a) CH3—C—(CH2)6—CH3 +
O
CH3
-* D' . A c i d ( - ) - B r u c i n e S a l t - ^ / ° - i
+ (—)-Brucine X
C—OH
-> L-Acid(—)-Brucine Salt
O
>•< . x „
.
„_.
l(-) -Brucine • H Q
(D,L)
II. Optical Properties of Some Common Carbohydrates
Introduction. One of the classical methods for resolution of a racemate is to convert the enantiomorphs to
diastereoisomers by reaction with a suitable optically
active compound, separate the diastereoisomers by frac-
tional crystallization, then regenerate the individual
enantiomorphs. In the experiments for today and the
next period, this classical general scheme is adapted to
the resolution of a D,L-alcohol as shown below:
0
0
C—OR
(a) R—O—H +
/ \ / V0\ .
(D,L)
C
(
S
C—OH
II
II
0
0
(D,L)
0
II
C—OR
C—0 ,(—)-amine-H
0
II
C—OR
0
D-Acid • (— )-amine salt
Diastereoisomer A
+ (—)-amine-
(b)
>
0
C—OH
II
0
O—OR
(D,L)
C—0 ,(-)-amine-H
0
L-Acid-(— )-amine salt
Diastereoisomer B
117
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
118
(c) Diastereoisomers A and B are separated by fractional crystallization.
0
0
C—OR
C—OR
+ HC1-
+ (-)-amine-H , CI
•(
C—O ,(—)-amine-H
C—OH
II
0
0
Diastereoisomer A
(D)
o
C—OR
(e)
/
COONa
+ 2NaOH^ROH +
\
distill
(D)
C—OH
^
^
COONa
0
(D)
(f) The same procedure as shown in (d) and (e) is used for the isolation of the L-alcohol.
The D,L-alcohol which is to be resolved is 2-octanol,
and the resolving agent is the levorotatory alkaloid
(— )-brucine, which is obtained from the bark of Strychnos nux vomica. The structure of brucine is shown
below. Despite its structural complexity, the functional
groups present in the molecule are easily recognizable.
Note that one nitrogen atom (1) is part of a tertiary
amino group, whereas the other nitrogen atom (2) belongs to an acid amide group.
CH 3 0
N(l)
(—)-Brucine
CH3O
0=1
V
I. PREPARATION AND RESOLUTION OF
D,L-J-OCTYL HYDROGEN PHTHALATE
0-70
(a) Preparation of D,L-s-Octyl Hydrogen Phthalate
Procedure. Mix 32.5 g. of anhydrous D,L-2-octanol,
37 g. of pure phthalic anhydride (Note 1) and 20 g. of
anhydrous pyridine (Note 2) in a 125-ml. Erlenmeyer
flask, and heat the mixture on the steam bath for an
hour. The flask should be stoppered after the contents
have attained the temperature of the bath.
[While the flask is being heated, proceed with Part B
of today's laboratory assignment.]
70-120
Dissolve the viscous mass in an equal volume of
acetone and add slowly, with stirring, 28 ml. of concentrated hydrochloric acid diluted with an equal volume of crushed ice. If an oil separates before all of
the hydrochloric acid solution has been added, add
sufficient acetone to make a homogeneous solution.
Pour the solution into a 1000-ml. steam distillation
flask, add water until an oil separates, and subject the
mixture to steam distillation until the distillate is no
longer cloudy. Pour the contents of the steam distillation flask, containing the octyl hydrogen phthalate,
into an Erlenmeyer flask and allow the mixture to cool.
Collect the solid D,L-.y-octyl hydrogen phthalate by
suction filtration, wash it with water, grind it in a
mortar with water, filter again, wash it with a small
amount of alcohol, then with a small amount of ether
and allow the solid to dry in the air.
(b) Resolution of D,L-$-Octyl Hydrogen Phthalate by
the Use of (—)-Brucine
Procedure. To a solution of 70 g. of D,L-^-octyl hy- 120-165
drogen phthalate in 150 ml. of warm acetone contained
in a 500-ml. round-bottomed flask add 108 g. of
( — )-brucine tetrahydrate. Attach a reflux condenser to
the flask and heat the mixture on the steam bath until
a clear solution results. Upon cooling, one of the diastereoisomers [(H-)-Acid-(-)-Brucine Salt] separates
in crystalline form. Collect the solid by suction filtration
and wash it with about 60 ml. of cold acetone. Save
the filtrate and the wash solution.
Transfer the crystalline material to an Erlenmeyer
flask and cover the solid with acetone. Add slowly,
with stirring, a small excess of 6 N hydrochloric acid
(about 30 ml.). If necessary, add more acetone to keep
the solution clear. Add ice water until precipitation of
the dextrorotatory enantiomorph of s-octyl hydrogen phthalate is complete. Collect the solid by suction
filtration, wash it with cold water and allow it to dry
in the air.
OPTICAL PROPERTIES O F SOME COMMON
CARBOHYDRATES
119
Distill about half of the solvent from the original
filtrate plus wash solution and pour the residue into
30 ml. of 6 N hydrochloric acid. Add about 150 ml.
of cold water and collect the resulting precipitate by
suction filtration. This is the somewhat crude levorotatory enantiomorph of s-octyl hydrogen phthalate.
Wash this solid with cold water and allow it to dry in
the air.
Crystallize the two crude enantiomorphs from 90
per cent acetic acid and determine the melting points
of the two samples. If the melting points are not sharp
and within one degree of 75°, recrystallize the samples
from 90 per cent acetic acid. Repeat this procedure
until both enantiomorphs melt sharply at about 75°.
It will probably be necessary to complete the purification of the two enantiomorphs during the next
laboratory period. The enantiomorphs have specific
rotations, [«] D , in absolute ethanol of about 44° and
—44°, respectively.
D( + )-glucose and D ( - ) - f r u c t o s e . Inasmuch as the
specific rotation of D ( - ) - f r u c t o s e is greater than that
of D ( + )-glucose, the course of the hydrolysis can be
followed by observation of inversion of rotation of the
solution.
Procedure. Prepare 100 ml. of a 10 per cent solution
of sucrose in water as accurately as possible without
the use of an analytical balance. Determine its rotation
in a polarimeter and calculate the specific rotation.
To 50 ml. of the solution add 5 ml. of concentrated
hydrochloric acid, dilute the solution to 100 ml. and
heat the solution on the steam bath for 20 minutes.
Determine the rotation of this solution and calculate
the approximate specific rotation. These results will be
only approximations owing to the inexperience of the
student taking the polarimetric measurements and also
to the lack of precision in the preparation of the solutions. Write the equation for the hydrolysis of sucrose.
NOTES
1. In order to avoid congestion in the use of the polarimeter, it might be necessary for the instructor to limit
the number of students carrying out this experiment during any one laboratory period.
NOTE
1. Phthalic anhydride can be freed of phthalic acid by
extraction with chloroform. The anhydride is soluble but
the acid is insoluble.
2. Pyridine dried over anhydrous barium oxide is suitable for use in this experiment. The laboratory instructor
should prepare for the experiment by drying a good grade
of pyridine over several successive batches of barium oxide
for several days prior to the present laboratory period.
II. O P T I C A L PROPERTIES
OF SOME C O M M O N CARBOHYDRATES
1. Mutarotation of Glucose
10-30
A freshly prepared aqueous solution of <*-D( + ) glucose, the common crystalline form of glucose, undergoes a change in rotatory power rather slowly. However, basic substances act as catalysts for bringing about
equilibration of <*-D( + )-glucose with some of its tautomers. In this experiment the addition of a small amount
of ammonia to a solution of a-D( + )-glucose causes the
solution to change its rotatory power at a moderately
rapid rate.
Procedure. Add sufficient water to 10 g. of « - D ( + ) glucose to prepare 100 ml. of solution. Fill a
1-decimeter polarimeter tube with this solution and
determine the rotation. Add 1 drop of concentrated
ammonium hydroxide to 50 ml. of the original solution,
fill the polarimeter tube and determine the rotation of
this solution. Take several readings at intervals of a
minute or two. Does the polarimeter reading remain
constant? Does it increase or decrease? Write equations
to show the structural changes which «-D( + )-glucose
undergoes on standing in solution (Note 1).
2. Acid-Catalyzed Hydrolysis of Sucrose
Sucrose (which is dextrorotatory) undergoes acidcatalyzed hydrolysis to produce equimolar amounts of
QUESTIONS
1. Give one-sentence definitions or descriptions of each
of the following terms: (a) resolution, (b) racemization,
(c) enantiomorphs, (d) diastereoisomers, (e) meso form,
(f) specific rotation, and (g) racemic mixture or compound.
2. Why is it usually impossible to separate enantiomorphs
by conventional techniques such as fractional crystallization
or fractional distillation? Under what circumstances may a
resolution sometimes be effected following recrystallization
of certain racemates?
3. How many and what types of stereoisomers exist for
each of the following compounds?
OH
(a) CH3—CH—CH2—CH2—CH3
CH3
CH3
(b) CH3—CH—CH2—CH—CH2—CH3
(c) CH 3 —CH=CH—CH 2 —CH 3
OH
(d) CH3—CH=CH—CH2—CH—CH3
CH3 CH3
(e) CH3—CH2—CH—CH—CH2—CH3
Br Br Br O
I
I
I
II
(f) CH3—CH—CH—CH—C—OH
4. Will an L-alcohol undergo Fischer esterification with
each of two enantiomorphic carboxylic acids at equal
speeds? Explain.
5. What is the difference between conformers and
optical or geometrical isomers?
30-70
EXPERIMENT 42
I. Preparation of j3-D(+)-Glucose Pentaacetate
II. Preparation of Dextrorotatory 2-Octanol
Introduction. Esters may be prepared by reaction of
alcohols with acid anhydrides. Since glucose contains
five alcoholic groups per molecule, it is possible to
prepare a pentaacetate by reaction with acetic anhydride. The use of a catalyst is of importance, not
only in increasing the speed of the reaction, but also
in influencing the stereochemical course of the reaction.
For example, the use of sodium acetate to catalyze the
reaction between D( + )-glucose and acetic anhydride
leads to the formation of /?-D( + )-glucose pentaacetate,
whereas the use of zinc chloride leads to the formation
of «-D( + )-glucose pentaacetate.
In today's work while the mixture of D( + )-glucose,
acetic anhydride and sodium acetate is being heated,
one of the enantiomorphs, the dextrorotatory 2-octyl
hydrogen phthalate, prepared during the preceding
laboratory period, will be saponified and the corresponding optically active alcohol isolated. If time was insufficient to complete the purification of the two hydrogen phthalate esters during the last period, begin or
repeat the recrystallization step before starting with
Part I of today's experiment.
I. PREPARATION OF /?-D( + ) -GLUCOSE PENTAACETATE
CH2OH
H
1/
C
r
HO
I
c
an air condenser, and heat the mixture on the steam
bath for an hour, with occasional shaking of the flask.
20-80
[While the mixture is being heated, proceed with
Part II.]
To about 400 ml. of crushed ice and water contained
in a beaker slowly add the hot reaction mixture with
stirring. Stir occasionally, and allow the mixture to
stand for 40 minutes.
80-90
90-130
[Continue with Part II.]
Filter the solid with suction, wash it with small
amounts of cold water, alcohol, and ether, and recrystallize about 1 g. of the material from hot water.
Determine the melting point of the purified material
(Note 2). Weigh the air-dried solid and calculate the
per cent yield.
130-160
NOTES
1. If anhydrous sodium acetate is not available in the
laboratory, prepare some according to the directions given
on page 45.
2. Pure /?-D(+)-glucose pentaacetate melts at 132°.
II. PREPARATION OF DEXTROROTATORY 2-OCTANOL
0
H
0
0
O
H
OH
si
C—
\ ) + 5CH3—C—0—C—CH3
C—O—CH—(CH2)B—CH3
H
OH
I,
-C
+ 2NaOH •
(
H
OH
a-D(+)-Glucose
I
c
1/ ' I
o c H
CH3—C—0
C—OH
O
Dextrorotatory isomer
CH2OCOCH3
H
CH3
O
o
O—COCH3
C + 5CH3COOH
'I
OH
C—ONa
CH 3 —C—(CH 2 )^CH 3 +
H
^C—ONa
H
OCOCH3 H
siH
\y
OCOCH3
Dextrorotatory isomer
/3-D(+)-Glucose
c pentaacetate
c
Procedure. Place 20 g. of dextrorotatory j-octyl hyProcedure. Place 10 g. of dry «-D( + )-glucose and
6 g. of anhydrous sodium acetate (Note 1) in a mortar drogen phthalate and a solution of 8 g. of sodium
and mix the two compounds thoroughly by grinding hydroxide in 20 ml. of water in a round-bottomed
them with the pestle. Transfer the mixture to a round- flask equipped with a reflux condenser and boil the
bottomed flask, add 50 ml. of acetic anhydride, attach solution for 15 minutes. Add 150 ml. of water and re120
I
0-20
20-35
35-50
PREPARATION OF DEXTROROTATORY 2-OCTANOL
arrange the apparatus for distillation. Collect distillate
until it is no longer turbid.
Extract the distillate with two 50-ml. portions of
ether, and dry the ether extract over anhydrous magnesium sulfate for 15 minutes. Filter the solution and
remove the ether by distillation. Weigh the residue and
dilute it to a volume of 30 ml. by addition of ethanol.
Determine the rotation of this solution in a polarimeter.
Calculate the approximate specific rotation of the solution.
Levorotatory 2-octanol could be obtained by treatment of the levorotatory hydrogen phthalate in the same
manner as described previously for the dextrorotatory
enantiomorph. However, there is insufficient time to
carry out this experiment, and, in any event, this
would represent an uninstructive repetition of work
already done.
121
QUESTIONS
1. Write structural formulas for sucrose octaacetate and
a-D (+) -glucose pentaacetate.
2. Write the Fischer projection formula for /3-D(+)glucose pentaacetate.
3. Draw the most stable conformation for / ? - D ( + ) glucose pentaacetate. Are the acetoxyl groups axial or
equatorial?
4. Write out a detailed mechanism for the saponification of s-octyl hydrogen phthalate. Are any of the
bonds to the asymmetric carbon atom broken in the saponification step? Does the optically active alcohol obtained
from one of the enantiomorphic hydrogen phthalates have
the same absolute configuration as the half ester?
5. Write out the mechanism for the reaction of 2-octanol
with phthalic anhydride. Would you expect to obtain an
optically active hydrogen phthalate ester by reaction of
dextrorotatory 2-octanol with phthalic anhydride?
EXPERIMENT 43
Chemical Properties of Some Common Carbohydrates
Introduction. Over the years, phenylhydrazine has
proved to be a very valuable reagent in the characterization of many carbohydrates and in stereochemical
studies of the sugars. Both uses of the reagent are
illustrated in today's major experiment, which consists
of the preparation of phenylosazones of D( + )-glucose
and D(-)-fructose. As supplementary experiments, the
relative ease of oxidation of D( + )-glucose, sucrose,
maltose, and lactose will be studied. In addition, both
the acid-catalyzed and enzymatic hydrolysis of sucrose
will be investigated.
Fasten melting point tubes containing the two samples
of phenylosazone to the thermometer and carry out 135-160
both melting point determinations at the same time.
Since phenylosazones melt with decomposition, and
since the decomposition range varies markedly, depending on the rate of heating of the melting point bath,
the bath should be heated at a standard rate, viz., 0.5°
per second. Mix equal amounts of the two samples and
determine the decomposition point of the mixture.
Record your conclusions in your notebook.
I. PHENYLOSAZONES OF D( + ) -GLUCOSE AND D ( - ) -FRUCTOSE
CHO
H-
-OH
H— —OH
CH2OH
+ 3C6H6NHNH2 -> HO—| -H
20-50
60-75
75-135
C=0
2
3C6H6NHNH2 + HO—I —H
3
-OH
H- I—OH
4
H-
-OH
H-
-OH
5
CH2OH
6
CH2OH
+ C6H6NH2 + NH 3 + 2H 2 0
Procedure. Heat about 600 ml. of water to its boiling
point in a large beaker. While the water is being heated,
introduce 20-ml. portions of 5 per cent solutions of
D( + )-glucose and D( —)-fructose into each of two large
test tubes. To each solution add either 2 ml. of phenylhydrazine, 3 g. of sodium acetate, and 3 ml. of glacial
acetic acid or 3 g. of phenylhydrazine hydrochloride
plus 3 g. of sodium acetate. Stir the solutions. As soon
as the water in the beaker begins to boil, extinguish the
burner and place the test tubes in the hot water. Allow
them to stand in the hot water for 30 minutes.
[Proceed with the next part of the assignment for
today.]
50-60
1
H
D(+)-Glucose
0-20
I
C=N—NH—C 6 H 6
H- I—OH
HO—| -H
CH2OH
CH=N—NH—C 6 H 6
During this time crystals of the phenylosazone appear and increase in amount as the mixtures cool. Collect the crystals on a filter and with a low-power
microscope examine the shapes of the crystals from
the two reaction mixtures. Do the two batches of crystals have the same appearance?
Crystallize the two batches of phenylosazone from
hot 50 per cent ethanol. In this case it is better to
sacrifice yields in order to obtain small amounts of
pure product for melting point determinations. Collect
the crystals by filtration and allow them to dry on a
porous clay plate for 20 to 30 minutes.
D(—)-Fructose
II. EASE OF OXIDATION OF D( + )-GLUCOSE
(a) With Permanganate. Place a few ml. of a 10 per
cent glucose solution in a test tube and add a few drops
of 0.3 per cent potassium permanganate solution. Does
oxidation occur at room temperature or must the mixture be warmed in order for the reaction to take place?
Repeat the experiment with a 10 per cent glucose solution to which has been added 1 drop of 10 per cent
sodium hydroxide solution. What is your observation?
(b) With Tollens' Reagent. Determine whether
glucose, in dilute solution, is oxidized by Tollens'
reagent. What is the relative ease of oxidation as compared with any typical aliphatic aldehyde? What complicating situation exists?
(c) With Fehling's Solution. Add a few drops of 10
per cent glucose solution to 6 ml. of Fehling's solution
(3 ml. each of solutions A and B) and heat. Record
your observations.
20-30
30-40
40-50
III. REDUCING ACTION OF DISACCHARIDES
Add a few drops of dilute solutions of sucrose, maltose, and lactose to separate test tubes each containing
5 ml. of Fehling's solution. Place the tubes in boiling
water and note the results. Carry out similar tests with
Tollens' reagent. Record your observations.
75-90
IV. HYDROLYSIS OF SUCROSE
[Proceed with the short experiments given in Parts II,
(<0 Conditions Favoring Hydrolysis. Place three test
III and IV.]
tubes, each containing 5 ml. of a 5 per cent solution of
122
90-110
CHEMICAL PROPERTIES OF SOME COMMON CARBOHYDRATES
sucrose, in a beaker of hot water and to these add equal
volumes of (1) water, (2) 10 per cent hydrochloric
acid, and (3) 10 per cent sodium hydroxide solution.
Heat the tubes for 5 minutes, then test a portion of
each reaction mixture with Fehling's solution. What are
your conclusions?
110-135
(b) Enzymatic Hydrolysis. Prepare a suspension of
baker's yeast by adding a few drops of water to one
eighth of a small cake of compressed yeast, macerating
the mixture, then adding 10 ml. of water. Add 5 ml.
of the suspension to an equal volume of 5 per cent
sucrose solution, and, as a control, add 5 ml. of water
to the second portion of the suspension. Warm the
two mixtures to about 35° in a beaker of warm water
and allow them to stand at that temperature for 15
minutes.
[Begin to answer the questions at the end of this assignment.]
Test a portion of each suspension with Fehling's solution. What are your observations? The control ex-
123
periment is carried out to check whether the yeast
itself contains a reducing agent.
QUESTIONS
1. May D-gluconic acid be prepared by oxidation of
D(+)-glucose with either Fehling's solution or Tollens'
reagent? What is the reagent usually used for the preparation of D-gluconic acid?
2. Write structural formulas for sucrose, maltose, and
lactose. Which of these disaccharides would be expected to
exhibit mutarotation?
3. What conclusions may be drawn as to the relative
configurations of carbon atoms numbered 3, 4, and 5 in
both D(+)-glucose and D(-)-fructose as a result of the
phenylosazone preparation?
4. What products would be obtained on treatment of
maltose with methanol and a catalytic amount of hydrogen chloride? Answer the same question for lactose. Equations.
5. Write the structural formula of a typical acetal. How
would this acetal behave toward (1) water, (2) dilute
hydrochloric acid, and (3) dilute sodium hydroxide solution?
EXPERIMENT 44
Polysaccharides
Introduction. Starch is widely distributed in plants
and is stored in grains and tubers as a food supply for
the germinating seed. All types of starch give a blue
color with iodine, and this serves as a sensitive qualitative test either for starch or for iodine. Acid-catalyzed
hydrolysis of starch converts it through several grades
of dextrin to maltose and finally to D( + )-glucose. The
iodine test is used to follow the extent of hydrolysis
since the coloration changes progressively from blue
to faint red as the molecular weight of the organic
molecule decreases. In fact, the dextrins of low molecular weight, maltose, and D( + )-glucose show no coloration with iodine.
The functional groups found in starch and cellulose
are hydroxyl and acetal groups. As shown in the structures, these molecules differ in configuration, starch
having the a-glucoside and cellulose the /?-glucoside
configuration. They also differ in size, cellulose having a
much larger average molecular weight than starch.
C-
I.
C-
-0
I
1/
H
O
O
I
C
H
I
c—0
O
H
OH
si
C
H
I
C
OH
i-i
0
/
C
H/
-O
-O
H
H
OH
H
/ \
\
/
C
OH
0-25
CH2OH
H
\
/
H
ns.
OH
.1
H . /c
.1
c—c
0
I
A segment of the starch molecule
CH2OH
1/ " I
Prepare a starch solution by mixing thoroughly 2 g.
of starch with 10 ml. of water and then pouring this
mixture into 200 ml. of boiling water. Save part of the
solution for later experiments.
\l
I.
c—cOH
H
-c
I
OH
H
(a) Iodine Test for Starch
H
C
\
C
H
The following tests show some of the easily observed
properties of starch and cellulose.
H
H
H
OH
Experimental
CH2OH
CH2OH
H
ordinated with several of the oxygen atoms of the hydroxyl groups of cellulose.
When paper (cellulose) is treated with 80 per cent
sulfuric acid, the surface of the paper is altered and
the resulting product resembles parchment. Although
the exact chemistry of this process is obscure, the
changes in the surface molecules probably involve both
hydrolysis and dehydration.
0
I
H
OH
CH2OH
OH
I
| \
H
H \ |
/
H
H
C
C
0
-0
CH2OH
A segment of the cellulose molecule
c—o
'I
H
OH
H
.1
I.
c—c
I
V
0
'I
H
I
H
OH
Add a drop of a very dilute aqueous solution (strawcolored) of iodine in potassium iodide to a few ml. of
the starch solution. Note the color of the solution.
Heat the colored solution to boiling and observe the
effect. Also note the effect produced by cooling the
solution. Add a few drops of sodium thiosulfate solution
to the cooled solution and note the result. Explain.
The chemical properties of starch and cellulose reflect the properties of the individual functional groups
present. Acid-catalyzed hydrolysis represents a typical
property of acetals. The formation of cellulose nitrate,
cellulose acetate, and cellulose xanthate illustrate the
ester-forming property of the alcoholic hydroxyl groups
present in the polymer.
Cellulose dissolves in cupric ammonia hydroxide so(b) Starch and Fehling's Solution
lution (Schweitzer's reagent) and is reprecipitated when
Test the reducing action of Fehling's solution on 3
acid is added to the solution. Probably the solution
contains complex ions in which each copper ion is co- ml. of starch solution and record the result.
124
25-30
POLYSACCHARIDES
30-50
50-65
65-85
85-105
(c) Hydrolysis of Starch
Add 1 ml. of concentrated hydrochloric acid to
25 ml. of starch solution. Boil the solution and withdraw about 1 ml. at frequent intervals for an iodine
test. Record the color of the test solutions at the various
intervals.
When the solution no longer gives a color with iodine,
neutralize it and test a portion with Fehling's solution.
Write structural formulas for the end products (a disaccharide and a monosaccharide) of the hydrolysis of
starch.
Repeat the experiment, adding 5 ml. of 10 per cent
sodium hydroxide solution instead of hydrochloric acid
as the catalyst. Are the results the same?
(d) Enzymatic Hydrolysis of Starch
Collect about 10 ml. of saliva. Its flow may be accelerated by chewing paraffin. Filter the saliva through
a previously moistened filter paper and add 5 ml. of
the filtrate to 50 ml. of starch solution. Watch for
changes in the appearance of the starch solution, and
also test 1-ml. samples of the solution from time to
time with iodine. Note the period of time required for
essentially complete hydrolysis of the starch solution
(negative iodine test).
Test the solution with Fehling's solution at this time.
Is the principal end product the same in both the
enzymatic and acid-catalyzed hydrolysis? Do different
samples of saliva show equal activity in catalysis of
starch hydrolysis? (Consult your neighbors about their
results.)
(e) Dialysis of a Starch Solution
The purpose of this experiment is to determine
whether starch in solution will pass through a parchment paper membrane. The same test will be made
with a glucose solution. Select 2-3 pieces of parchment
paper about 5 cm. square and allow them to soak in
water several minutes. Add to a large test tube 10 ml.
of starch solution and carefully cover the mouth of
the tube with parchment paper, holding it fast with a
number of windings of string. Dry the outside of the
parchment paper with a piece of filter paper and clamp
the test tube to a ring stand in the inverted position
for a few minutes to test whether it leaks. If it does
leak, repeat the procedure with a different piece of
parchment paper.
Rinse the outside of the tube and paper with distilled
water, then clamp the tube in a beaker of distilled
water in the inverted position and adjust it such that
the level of water in the beaker coincides with that of
the solution in the test tube. Carry out exactly the
same procedure with a test tube containing 10 ml. of
a 5 per cent solution of D( + )-glucose.
Allow the two tubes to remain in the separate beakers
of distilled water until the next period. At that time,
test the contents of the beakers for starch and glucose,
125
respectively. How might you effect separation of the
components of a starch-glucose mixture?
(f) Cellulose Nitrate-Collodion
Add 10 ml. of concentrated sulfuric acid to 10 ml. of
concentrated nitric acid contained in a small beaker
and heat the mixed acid solution on the steam bath.
Add about 0.5 g. of cotton and allow it to remain in
contact with the acid solution for 3 minutes. Remove
the partially nitrated cotton (cellulose) from the acid
with a stirring rod and press the cotton against the wall
of the beaker in order to free it of as much of the acid
solution as possible. Next, wash the nitrated cotton
with a large amount of water, squeeze out as much of
the water as possible, and allow the material to dry.
While it is drying, proceed with the remaining parts
of today's assignment.
Digest the nitrated cotton with 20 ml. of a mixture
of equal volumes of ether and alcohol, decant, and
allow a portion of the solution to evaporate on a watch
glass. Note the appearance of the residual film and test
its flammability on a very small portion. Record your
observations.
105-115
155-160
(g) Cellulose Acetate
To a solution of 6 ml. of acetic anhydride and 2 115-125
drops of concentrated sulfuric acid in 20 ml. of glacial
acetic acid, contained in a small Erlenmeyer flask, add
0.5 g. of cotton and wet it as thoroughly as possible
with the solution. Stopper the flask and allow the reaction mixture to stand until the next laboratory period.
By this time the cotton will have been converted to
cellulose acetate, which is soluble in the reaction
medium.
Pour the solution in a thin stream into 500 ml. of
water and collect the resulting precipitate by filtration.
Dry the precipitate by pressing it between pieces of
filter paper. Dissolve a small portion of the solid in
chloroform and allow the solution to evaporate on a
watch glass. Note the appearance of the film and test
a small portion for its flammability. How do you account for its behavior as contrasted with that of cellulose nitrate?
(h) Cellulose Xanthate-Viscose
To 5 ml. of 20 per cent sodium hydroxide solution 125-135
contained in a test tube add a small wad of cotton. Wet
the cotton thoroughly and warm the solution for about
3 minutes. Remove the cotton with a stirring rod, and
squeeze out as much as possible of the solution. The
fingers should be protected from the alkaline solution
by the use of rubber cots or gloves. Place the cotton in
another test tube and add 5 ml. of carbon disulfide.
Stopper the tube and allow the mixture to stand until
the next laboratory period.
Remove the cotton from the orange-colored solution
and squeeze out the liquid. Allow the carbon disulfide
126
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
to evaporate from the cotton wad, then add it to about
10 ml. of a 10 per cent sodium hydroxide solution.
Shake the mixture until a fairly homogeneous suspension is obtained. Pour the viscous liquid in a thin
stream into dilute hydrochloric acid. Record your observations.
135-150
150-155
(i) Action of Schweitzer's Reagent on Cellulose
To 100 ml. of a 5 per cent copper sulfate solution
add 5 ml. of 10-20 per cent ammonium chloride solution, then add sodium hydroxide solution as long as
a precipitate forms. Wash the precipitate by decantation
with 500 ml. of water three times. Collect the precipitate
in a cotton-cloth filter and wash it until the wash water
is free of sulfates.
Dissolve as much of the solid copper hydroxide as
possible in 10 ml. of concentrated ammonium hydroxide
solution (sp. gr. 0.90). This solution is Schweitzer's
reagent. Dissolve some filter paper (cellulose) in the
solution and then pour the cellulose solution into dilute
hydrochloric acid. Why does acid cause the reprecipitation of the cellulose?
(j) Parchment Paper
Carefully pour 40 ml. of concentrated sulfuric acid
into 20 ml. of water. Cool the solution thoroughly and
place it in an evaporating dish. Immerse a piece of filter
paper in the solution and allow it to remain there 10-12
seconds. Remove the paper, rinse it with running water,
neutralize the remaining traces of acid by dipping the
paper in dilute ammonium hydroxide solution, then
wash it again with running water. The resulting material
is parchment paper. How does it differ from the paper
used in its preparation?
QUESTIONS
1. What are some of the lines of evidence for the structures of starch and cellulose?
2. Write a structural formula for cellobiose. How is cellobiose related to cellulose? How does cellobiose differ
from maltose?
3. What is glycogen? Where is it found? It acts also as
a reservoir for what inorganic group of importance in
biological processes?
4. What is inulin? Where is it found?
5. Write partial equations to show the conversion of
cellulose to cellulose trinitrate, cellulose triacetate and cellulose xanthate.
6. What is ethyl cellulose and how may it be prepared?
7. How may jG-cellulose be differentiated from a-cellulose?
8. What is Pyroxylin? Celluloid? Collodion? Cellophane?
9. Of what use is cellulose to termites and other insects?
EXPERIMENT 45
Properties of Aromatic Hydrocarbons1
A. PREPARATION OF BENZENE BY THE DECARBOXYLATION OF SODIUM BENZOATE
O
(|^V-C—ONa + NaOH
0-40
In a 6-inch evaporating dish place 10 g. (0.25 mole)
of sodium hydroxide and 20 ml. of water. Warm the
dish gently over the Bunsen burner until the sodium
hydroxide has dissolved and then add 12 g. (0.1 mole)
of benzoic acid. While stirring the solution continuously,
evaporate it to dryness by gentle application of heat
from the burner. (CAUTION: Wear your goggles.)
Transfer the dry mixture of sodium benzoate and
sodium hydroxide to a 25 x 200 mm. test tube which
is connected to a delivery tube and condenser as shown
in Figure 29. Heat the tube with the Bunsen burner
+ Na2C03
3. Flammability. Ignite a few drops of benzene in a
small evaporating dish. Note the character of the flame
and the appearance of the dish when the flame dies.
4. Reaction with Bromine. Pour about 5 ml. of
benzene into a test tube, take the tube to the hood
and, after adding 2 or 3 drops of bromine, pour one
half of the solution into another test tube. Into one
of the tubes introduce 2 or 3 small iron tacks and
observe the difference in the rates of reaction in the
two tubes. If the reaction does not begin at once, set
the tubes in the beaker of warm water. The comparative
55-60
60-70
FIG. 29. Apparatus for decarboxylation of an acid.
until no more liquid is collected in the receiver. Separate
the upper layer of benzene from the layer of water,
dry it over a little calcium chloride, and determine
the yield of benzene by measuring its volume in a
graduated cylinder. The density of benzene at 20° is
0.879. Note the boiling point of benzene by the method
described in Experiment 1 upon the calibration of a
thermometer.
B. PROPERTIES OF BENZENE
40-50
50-55
1. Solubility. Test the solubility of 2-ml. portions
of benzene, obtained from the side shelf, in water,
ethanol, gasoline, and ether.
2. Benzene as a Solvent. Determine the solubility
of a small amount of iodine, paraffin wax, and of cottonseed oil in a few ml. of benzene.
rates of reaction may be judged by blowing your breath
across the mouth of each tube. What is the gas evolved?
Write the equation for the reaction of benzene with
bromine.
5. Permanganate Test. Shake a few drops of benzene
with dilute potassium permanganate solution. Compare
the behavior of benzene in this test with that of an
alkene.
6. Suljonation of Benzene. Add 1 ml. of benzene
to 5 ml. of concentrated sulfuric acid contained in a
test tube. Does the benzene dissolve in the cold acid?
Heat the tube in a beaker of water at 70° and shake
it frequently for 10 minutes or until a clear solution
is obtained.
[During this heating period go on to the nitration of
benzene, section 7.]
1
Ii this experiment is assigned on the opening day of a
Cool the tube and pour its contents carefully into
semester when the students are checking the apparatus in their 2 5-30 ml. of cold water. Write the equation for the
desks, it will be well to omit certainLportions
.
- ,
, U1 , . 7
portionsofofthe
theexperiment
experiment f i™» .«*•.«
because sufficient time will not be available for performing all formation of the water-soluble derivative of benzene
that has been produced.
of the tests described.
127
70-75
75-80
128
80-90
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
7. Nitration of Benzene. In a large test tube cautiously add 2 ml. of concentrated sulfuric acid to 3 ml.
of concentrated nitric acid. Then introduce 1 ml. of
benzene dropwise. Note the exothermic character of the
reaction. Shake the tube 2-3 minutes and pour the contents into about 25 ml. of cold water. What is the heavy
oil that separates? Write the equation for the reaction.
C. NAPHTHALENE
90-95
8. Sublimation. Place about 2 g. of flake naphthalene into a test tube. Heat the lower end of the
tube gently over the Bunsen burner and note the result.
95-100
9. Bromination. To 0.5 g. of naphthalene add, at
the hood, 1-2 drops of bromine. Does a catalyst appear
to be necessary? Equation. Compare this experiment
with the bromination of benzene.
100-120
10. Sulfonation. Add about 0.2 g. of naphthalene
to 5 ml. of concentrated sulfuric acid contained in a
test tube and heat the mixture with frequent shaking
of the tube in a beaker of boiling water for about 15
minutes.
[During this time go on to section 11.]
At the end of the heating period cool the tube and
pour its contents into 25-30 ml. of cold water. Does
a precipitate of unchanged naphthalene separate? What
derivative of naphthalene has been obtained? What
variation in the product results if the sulfonation has
been conducted at a higher temperature (180°-190°)?
120-130
11. Nitration. To a solution of 3 ml. of concentrated
nitric acid and 3 ml. of concentrated sulfuric acid
(nitrating acid) contained in a large test tube, add about
0.05 g. of naphthalene. Shake the tube and note the
evolution of heat. When the lower part of the tube has
cooled to 50°-60° (i.e., not uncomfortably hot to the
hand), add another small portion of naphthalene and
continue in this manner until 0.2 g. of naphthalene has
been added.
Maintain a temperature of 50°-60° for about 3
minutes and then cool the tube and pour its contents
into 40-50 ml. of cold water contained in a small
beaker. The a-nitronaphthalene, some of which usually
separates in the nitration tube, is obtained as a pale
yellow solid. Equation.
12. Naphthalene Picrate. Add about 0.1 g. of naph- 130-140
thalene to 5 ml. of a saturated solution of picric acid
in ethanol, heat the mixture in hot water until a clear
solution is obtained and then set the tube into an
ice bath. A double compound of the composition
Ci 0 H 8 -C 6 H 2 (OH)(NO 2 ) 3 is obtained.
Naphthalene, anthracene, and various other aromatic
hydrocarbons (but not benzene) form fairly stable addition compounds of this type. In some instances the
compounds are sufficiently stable to permit their identification by their melting points and "mixed melting
points" with known samples.
D. FAMILIARITY WITH OTHER HYDROCARBONS
On the supply shelf the storekeeper will have placed
specimens of other aromatic hydrocarbons, such as
toluene, ethylbenzene, xylene, cumene, mesitylene, anthracene, phenanthrene, and perhaps others. Each bottle
will be labeled with the name and boiling point, or
melting point, of the material that it contains. Make
note of these physical properties as well as the appearance and odor of each specimen. Write the formula
for each of the compounds presented.
QUESTIONS
1. How does the method for the preparation of benzene
used in today's experiment compare with that used for the
production of methane in Experiment 9?
2. What other solvent you have used does benzene resemble in its solvent properties? For what kinds of compounds is benzene a good crystallization solvent? What are
its advantages as a crystallization solvent? Its disadvantages?
3. What structural characteristic of benzene accounts for
the fact that benzene burns with a luminous flame?
4. Is benzene more or less unsaturated than 1,3-hexadiene?
5. In reaction with bromine and with potassium permanganate, does benzene behave more like an alkane or
like an alkene? How do you account for this fact?
6. Is naphthalene more or less reactive than benzene
toward bromine and sulfuric acid? How can you explain
this fact?
140-150
EXPERIMENT 46
Bromobenzene
2Fe + 3Br2 -> 2FeBr'3
(1)
(2)
(3)
••
:Br:
••
:Br:
••
••
: B r : Fe + : B r : Br :
•• ••
•• ••
:Br:
: Br : Fe : Br :
»']
:Br:
C6H6 + [FeBr 4 ]- [Br]+ -> C6H6Br + HBr + FeBr3
Introduction. A substitution reaction in benzene may
be described as one in which a substituting reagent
makes an electrophilic attack upon the aromatic nucleus. In today's experiment the attacking agent is
probably a bromine cation derived from an iron polybromide. The ferric bromide, formed on the surface
of the iron wire, is an effective catalyst for the reaction.
After its regeneration, as shown in the last equation,
it may react again according to the second equation.
150mm
structor will indicate what type of trap is to be used.
The hydrobromic acid collected may be utilized as
described later in this experiment. The 500-ml. flask
must be dry; if it should be wet, rinse it once with
alcohol and then three times with small portions of
benzene.
When the apparatus has been assembled, remove the
flask to the hood and introduce into it first 35 ml. of
benzene and then 40 g. (0.25 mole, 13.5 ml.) of
bromine according to a procedure which the instructor
Procedure
will describe (Note 1). Return the flask immediately
The apparatus, consisting of a 500-ml. flask, con- to your desk and drop into it 4 or 5 iron tacks (Note
denser, and absorption trap, is assembled as shown in 2) and attach it at once to the condenser. Do not surFigure 30. The hydrogen bromide evolved during the round the flask, as yet, with the bath of cold water
unless a vigorous reaction should begin at once. If
the reaction is slow in starting, warm the bottom of
the flask gently with a very small flame of the Bunsen
burner.
As soon as the evolution of hydrogen bromide ber
)
1
comes
rather brisk, bring the bath of cold water up
A
around the flask and support the bath with an iron ring.
When the, rate of reaction, which at first is often fairly
rapid, subsides, the bath may be heated gradually in
order to maintain a satisfactory rate.
r
During this time the absorption trap may require
some attention to see that it is operating effectively. A
38 mm
little bromine and benzene will usually be carried along
with the hydrogen bromide into the trap. Any intense
red color in the condenser, however, indicates that the
reaction is going too fast and the temperature of the
. bath should be lowered by the addition of cold water
or a few pieces of ice. Within 15-20 minutes the rate
of reaction ordinarily decreases sufficiently to permit
the bath to be heated to about 50°, at which temperaFIG. 30. Apparatus for the preparation of bromobenzene ture the completion of the reaction, evidenced by the
absence of red vapors above the liquid, will be attained
and collection of the evolved hydrogen bromide.
in about 10 minutes.
reaction must not be allowed to escape into the room
Remove the stopper and tube from the top of the
and is absorbed in a suitable trap. Home-made traps condenser and pour 150 ml. of water through the consuch as those shown in Figure 30, are easily con- denser into the flask. The water absorbs hydrogen
structed from 38-40 mm. tubing and may be kept in bromide which would otherwise escape into the room.
the storeroom to lend to students. Such devices, as Remove,the flask from the condenser, shake it well,
compared with absorption bottles fitted with tubes and and separate the layer of bromobenzene which, of
two-holed stoppers, save a great deal of time. The in- course, contains some benzene because an excess of
129
15-50
h
50-85
130
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
0.25 mole of benzene was used. Transfer the bromobenzene to a flask for steam distillation, add enough
sodium hydroxide solution to make the well shaken
liquid faintly but distinctly alkaline and purify the
bromobenzene by distillation in steam (see page 32).
The steam distillation should be conducted as rapidly
as the capacity of the condenser will permit; often this
is about 15 ml. per minute; hence, 10-15 minutes of
distillation will be sufficient to distill all of the bromobenzene with 150-200 ml. of water. (During this time
prepare for the final distillation of the bromobenzene.)
85-110
Separate the bromobenzene from the water and dry
it for a few minutes over calcium chloride or other
drying agent. Decant the liquid from the drying agent
and distill it using a short fractionating column or a
flask with a long neck. The fraction boiling at 150°160° may be collected. The recorded boiling point of
bromobenzene at normal barometric pressure is 156°.
The yield is 25-30 g.
110-130
Some p-dibromobenzene is always formed in this
process, although the amount is usually small. The
high-boiling residue, if any, remaining in the distilling
flask consists chiefly of p-dibromobenzene and a little
more of the solid often collects in the condenser tube
during the distillation with steam. Both of these portions
may be combined and recrystallized from a little hot
ethanol. p-Dibromobenzene is a white crystalline material melting at 87°.
130-140
Wash and dry your glassware and clean your desk.
Leave your working space in proper order for the
students in the next laboratory class.
Utilization of the Hydrobromic Acid. The by-product
of hydrobromic acid obtained in this experiment may
well be saved for some future time and then purified for general laboratory use. If 30-40 ml. of water is
placed in each of the absorption bottles, the solution
in the first bottle will attain a high concentration; that
in the second bottle will, of course, be more dilute.
At the end of the experiment, pour the contents of
the first bottle into the large container that the store-
keeper will provide labeled "Concentrated Hydrobromic Acid" and the contents of the second bottle
into the container labeled "Dilute Hydrobromic Acid."
In order to purify the acid, add sodium sulfite to
the more concentrated solution to reduce any free
bromine to hydrogen bromide and fractionally distill
the solution. The boiling point of the constant-boiling
acid is 125°-125.5° at 758 mm. This acid has a specific
gravity of 1.486 and contains 46.83 per cent of hydrogen bromide. The dilute solution may be saved for
later repetitions of this experiment, at which time you
can enrich the dilute acid in its hydrogen bromide content by placing some of it into the first absorption
bottle.
NOTES
1. Details of safe procedures for dispensing bromine differ somewhat among various laboratories; hence, the instructor will prescribe the method that is to be followed.
2. A small coil of iron wire of about the same surface
area as the tacks may also be used as a catalyst. Often
somewhat rusty wire or tacks have better catalytic value
than does iron having a bright polished surface.
QUESTIONS
1. Predict the relative rates of reaction of bromine, chlorine, and iodine with benzene. Give reasons for the predicted orders.
2. Calculate the maximum weight of bromobenzene that
could be formed in today's experiment if a total of 5.0 g.
of dibromobenzenes were formed in the reaction.
3. At a price of 31^/lb. for benzene and 39//lb. for
bromine, what was your cost for starting materials per
pound of bromobenzene? Compare this with the commercial price for bromobenzene of $3.12/lb.
4. A compound of formula CxHyBT contains 73.4% of
bromine. Can this compound be a bromine substitution
product of an aromatic hydrocarbon? If so, of which hydrocarbon? Of an aliphatic hydrocarbon? If so, which one?
EXPERIMENT 47
Iodobenzene
2CeH6 + I2 + 2 H N 0 3 -> 2C6H5I + 2 N 0 2 + 2 H 2 0
Introduction. Iodine, the least active of the halogens,
does not replace readily one or more of the hydrogen
atoms of benzene. The addition of an oxidizing agent,
such as nitric acid, however, will bring about the
formation of iodobenzene according to the equation.
Note that all of the iodine goes into the production of
iodobenzene.
Procedure
A 250-ml. standard-taper flask is connected with a
reflux condenser the top of which is fitted to an absorption trap to absorb oxides of nitrogen that are
evolved in this experiment. A large flask containing
100 ml. of 15 per cent sodium hydroxide solution will
prove effective (see trap A, Figure 32, page 163).
Into the standard-taper flask are placed 12.7 g.
(0.1 g. atomic weight) of iodine, 20 ml. of benzene
(what excess over 0.1 mole?), 2 ml. of pyridine, and
20 ml. of nitric acid. The contents of the flask are then
heated to boiling under reflux until the violet color of
the iodine has disappeared. Additional quantities of
nitric acid will be required and at intervals of 15 minutes the tube and stopper at the top of the condenser
are removed momentarily for the introduction of 10 ml.
of nitric acid. Ordinarily two such additions of nitric
acid are sufficient and the reaction is completed in a
total time of about 40 minutes.
When the color of the free iodine has disappeared,
the burner is extinguished and the flask is cooled in
cold water. The heavy layer containing the iodobenzene
(D = 1.824) and the excess benzene is separated from
the acid layer, washed with water and dilute alkali,
dried over calcium chloride, and distilled. Yield about
15 g. B.p. 188°.
Iodobenzene-dichloride
Obtain from the side shelf 10 ml. of a saturated solution of chlorine in carbon tetrachloride. Add to this
solution 2 ml. of iodobenzene and set the test tube
containing the reactants in ice. Result? Equation. What
product may be obtained by the reaction of iodobenzene-dichloride with sodium hydroxide solution?
Equation.
QUESTIONS
1. Rate the hydrohalic acids in order of their strengths
as reducing agents.
2. What reaction would occur if iodobenzene were refluxed with constant boiling hydriodic acid? How do you
explain the role of nitric acid in improving the yield of
iodobenzene in today's experiment?
3. Could the method used for the preparation of iodobenzene be used for the preparation of bromobenzene?
Would there be the same advantage costwise? (Bromine is
quoted at 39^/lb. and resublimed iodine at $2.00/lb.)
4. Would you expect much diiodobenzene to be formed
in today's experiment? Explain.
5. An unknown iodine-containing organic compound has
a boiling point of 176°. Can it be an aromatic compound?
6. Which compound forms a Grignard reagent more
readily, bromobenzene or iodobenzene? Which was used in
Experiment 24? Why?
131
90-100
ENT 48
Aromatic Nitre ) Compounds
^
~ -
.
<•>_«.• ^>
H2SO4
CeH6 + HNO3
Introduction. Ease of nitration is a characteristic
property of aromatic hydrocarbons and of many of their
derivatives. In some instances, such as the reaction with
phenol (Experiment 63), the nitration is accomplished
readily with dilute nitric acid; other compounds, including benzene, bromobenzene, and many others, require
the use of concentrated nitric acid (D = 1.42) mixed
with approximately an equal volume of concentrated
sulfuric acid. The use of this solution of the two strong
acids, often called nitrating acid, is illustrated by the
nitration of benzene in the following experiment.
I. NITRATION OF BENZENE
0-20
20-45
45-75
Prepare the nitrating acid by adding 30 ml. of concentrated sulfuric acid to 30 ml. of concentrated nitric
acid (D = 1.42) contained in a 500-ml. flask. Measure
22.5 ml. of benzene (19.5 g., 0.25 mole) in the graduated cylinder and add 2-3 ml. of it to the nitrating acid.
Shake the flask vigorously with a rotatory motion (Note
1) in order to mix the reactants thoroughly. Note the
rise in temperature by resting the flask in the palm of
your hand (Note 2).
If the temperature rises above 60° the flask should
be cooled in a pan of cold water. As soon as the reaction following the first addition of benzene has subsided, add another 2-3 ml. portion of benzene and
shake the flask vigorously as before. Cool the flask in
cold water as required to maintain a temperature of
50°-60° and continue the nitration in this manner until
all of the benzene has been used.
When all of the benzene has been added to the
nitrating acid, shake the flask continuously and
thoroughly for 10 minutes by the clock (Note 3). If
the temperature falls below the 50°-60° range, the
flask should be warmed gently over a low flame of the
Bunsen burner or in a pan of hot water. At the conclusion of this 10-minute period, cool the flask and
pour the contents into a separatory funnel for separation
of the two layers. The acid layer may be discarded
(Note 4 ) ; the nitrobenzene is washed once with water,
once with 5 per cent sodium hydroxide solution, and
then finally with water.
Dry the nitrobenzene over 2-3 g. of calcium chloride
for about 15 minutes while you prepare for its distillation. Distill the nitrobenzene using a small distilling
flask and an air-cooled condenser. The first portion of
the distillate, consisting of unchanged benzene and
perhaps a little water, is discarded. Collect the portion
boiling at 200°-215°, but do not go above this temperature nor distill to dryness because the small quantity
of residue contains dinitrobenzene which may decom-
» C 6 H 5 N0 2 + H 2 0
pose violently at high temperature. The normal boiling
point of nitrobenzene is 210°. Yield 15-20 g.
II. ACTION OF ALKALI
UPON NITROETHANE AND NITROBENZENE
From the bottle on the side shelf pour about 1 ml.
of nitroethane into a test tube, add 10 ml. of 10 per
cent sodium hydroxide solution, and shake the tube
vigorously. Repeat this experiment in another test tube,
replacing the nitroethane with 1 ml. of the nitrobenzene
that you have prepared. In which tube does the nitro
compound dissolve in the alkali? Acidify the solution
with hydrochloric acid and set the tube aside for a few
minutes. Does the nitro compound separate from the
solution? Write the equations for the reactions involved.
75-95
III. SOLID NITRO COMPOUNDS
FOR PURPOSES OF IDENTIFICATION
Introduction. Many aromatic nitro compounds are
solids which may be identified by their melting points
and by "mixed melting points" with known specimens.
As illustrations of such procedures, bromobenzene and
nitrobenzene, liquids at ordinary temperatures, may be
converted respectively into p-nitrobromobenzene and
m-dinitrobenzene.
Suggestion. It is often advantageous for one student
to make one of these compounds while his neighbor
prepares the other. They may then compare notes and
exchange data.
Option I. m-Dinitrobenzene. Add 1 ml. of nitrobenzene to a little nitrating acid made by mixing 5 ml.
of concentrated sulfuric acid with 5 ml. of concentrated
nitric acid contained in a 25 x 200 mm. test tube. Note
that heat is evolved. Heat the tube over the burner
nearly to the boiling point as indicated by the evolution
of oxides of nitrogen. Keep the contents of the tube
hot, but not actually boiling, for 2-3 minutes, then cool
the tube and pour its contents into 75-100 ml. of cold
water containing a few pieces of ice.
Stir the mixture well, collect the m-dinitrobenzene
on a small Hirsch funnel, and recrystallize the material
from a little hot alcohol. Bring the crystals again onto
the filter, press out the solvent as well as possible, and
dry a portion of the purified product upon a fragment
of unglazed dry plate. Observe its melting point. The
recorded melting point is 90°. Equation.
Option II. p-Nitrobromobenzene. Prepare the "nitrating acid" by adding 5 ml. of concentrated sulfuric acid
to 5 ml. of concentrated nitric acid contained in a
25 x 200 mm. test tube, and then add 1 ml. of bromobenzene. The reaction, when the tube is shaken, is suf-
95-140
95-140
AROMATIC NITRO COMPOUNDS
ficiently exothermic that no heat need be applied from
the Bunsen burner or steam bath. Within a few minutes,
as the tube cools somewhat, crystals of /7-nitrobromobenzene appear first upon the upper part of the tube
and then throughout the reacting mixture.
Pour the contents of the tube into 75-100 ml. of
cold water, collect the crystals on a small Hirsch filter,
and recrystallize them from a little hot alcohol. Dry
some of the recrystallized product upon a fragment of
unglazed clay plate and take its melting point. The recorded melting point is 127°. Equation.
NOTES
1. A rotatory motion of the flask permits vigorous shaking and mixing of the contents of the flask and has the
added advantage of avoiding spattering.
2. A thermometer may be used to measure the temperature but, in this instance, the sensitivity of the hand will
serve almost equally well because the desired temperature
of 50°-60° is about as hot as can be borne without discomfort.
133
3. Vapors of nitric acid and of nitrobenzene are irritating to the skin. Hence it is convenient to fit the mouth
of the flask with a one-holed cork stopper bearing a piece
of 6-mm. glass tubing 10-12 inches in length to carry such
vapors away from the hand.
4. Be careful to save the layer containing the nitrobenzene. Which layer should be soluble in water?
QUESTIONS
1. Compare the boiling points (see handbook) of w-butylbenzene, nitrobenzene, and benzoic acid, all of which
have approximately the same molecular weight. How do
you account for the difference?
2. A comparison of the conditions for the nitration of
bromobenzene and of nitrobenzene, as in today's experiment, clearly shows that the former compound nitrates
more rapidly than the latter. How do you account for this
difference?
3. What is the Victor Meyer method for the preparation
of a nitroalkane? Is this method adaptable to the production of nitrobenzene? Of phenylnitromethane?
EXPERIMENT 49
Preparation of Aniline by Reduction of Nitrobenzene
(1)
(2)
2C6H 5 N0 2 + 3Sn + 14HC1 -> 2C 6 H 5 NH 3 + ,C1- + 3SnCl4 + 4H 2 0
C 6 H 5 NH 3 + , CI" + NaOH -> C6H5NH2 + NaCl + H 2 0
Introduction. From among the various procedures
that may be used for the reduction of nitro compounds
to amines, the one selected for today's experiment
makes use of tin and hydrochloric acid as the reducing
agent. As a second step, aniline is liberated from its
hydrochloride by the addition of alkali.
In commercial practice the reduction is accomplished
by iron and steam. A small quantity of acid is usually
employed at the start of the process.
C6H6N02 + 2Fe + 4H 2 0 -> C6HBNH2 + 2Fe(OH)3
0-45
45-90
Procedure
Into a 1-liter flask which later is to be used for
steam distillation, introduce 20 ml. (24.6 g., 0.2 mole)
of nitrobenzene and 50 g. of granulated tin. Measure
90 ml. of concentrated hydrochloric acid in the graduated cylinder and pour about 10 ml. of the acid into the
flask containing the tin and nitrobenzene. An exothermic reaction soon begins, and it is necessary to
cool the flask in cold water to prevent loss of material
by boiling. Avoid excessive cooling as the reducing reaction proceeds more rapidly at a higher than at a
lower temperature. Aim to keep the contents of the
flask hot but below the boiling point.
As soon as the rate of reaction subsides, add another
5-10 ml. portion of the hydrochloric acid, shake the
flask thoroughly, and cool it as required to prevent
boiling. Continue the addition of the acid in this way
with almost constant shaking of the flask until all of
the hydrochloric acid has been used. Heat the flask
on the steam bath for 20 minutes. During this interval
shake the flask frequently, prepare the solution of
sodium hydroxide described below, and get ready for
the distillation with steam.
contents are not alkaline, more sodium hydroxide must
be added (Note 1).
Subject the contents of the flask to distillation with
steam (Note 2). (See Figure 15, page 33.) At first
oily drops of aniline collect in the receiver but toward
the end of the distillation the small quantity of aniline
coming over may be dissolved by the water (Note 3).
Collect 250-300 ml. of distillate, add 40-50 g. of
sodium chloride, and stir the mixture until the salt dissolves (Note 4).
[During the steam distillation, turn to the list of questions and answer as many of them as time allows.]
Transfer the distillate to a separatory funnel and remove directly as much of the aniline as possible. Return the water solution to the funnel and extract any
remaining quantity of aniline by shaking the solution
with 20 ml. of benzene. Separate the benzene layer
and combine it with the aniline previously obtained.
Dry the benzene solution of aniline, contained in a
small Erlenmeyer flask, by shaking it with about 5 g.
of solid sodium hydroxide.
As soon as the apparatus for the final distillation of
the aniline is ready, decant the benzene solution of
aniline from the drying agent into a small distilling flask
and distill it. Discard the benzene fraction (b.p. 75°90°) and collect the aniline (b.p. 180°-186°) separately. The intermediate fraction (b.p. 90°-180°)
should be refractionated and any aniline obtained from
it may be combined with the first lot. Yield about 15 g.
Pure freshly distilled aniline is nearly colorless. It
darkens on exposure to the light and air. A trace of
nitrobenzene that escapes reduction in this experiment
often imparts an orange tint to the preparation. Add 1
ml. of nitrobenzene to 1 ml. of nearly colorless aniline
and note the red color produced.
Liberation of the Aniline and Its Removal
by Steam Distillation
Weigh 40 g. of sodium hydroxide (commercial
NOTES
flake) into a 400-ml. beaker.and add to it 200 ml. of
water. Cool this solution to about 30° in a pan of cold
1. It is not necessary that the precipitate of stannous
water. Remove the reaction flask from the steam bath and stannic hydroxides be dissolved in excess alkali.
2. Conduct the steam distillation as rapidly as the capacand cool it in cold water until the temperature of the
contents is not higher than 50°, then add a small portion ity of the condenser will permit. Steam must not be allowed
of the sodium hydroxide solution, shake the flask well, to escape into the room, however, because the aniline vapor
it is highly toxic. If the condenser has a
and cool it so that no steam escapes. Add successive accompanying
capacity of 12-15 ml. per minute, the distillation can be
small portions of the alkali, cooling the flask as required, completed in about 20 minutes.
until all of the sodium hydroxide solution has been in3. The solubility of aniline is about 3.5 g. in 100 ml. of
troduced.
water at room temperature or 6.3 g. of aniline in 100 ml.
Shake the flask thoroughly and remove a drop of the of water at the boiling point.
4. Aniline, like many other organic compounds, is less
liquid on a glass rod for a test on litmus paper. If the
134
90-120
PREPARATION OF ANILINE BY REDUCTION OF NITROBENZENE
soluble in saturated salt solution than in water. Aniline
(D = 1.02) sinks in water but floats on the salt solution.
QUESTIONS
1. In the commercial method of making aniline using
iron and steam as the reducing agent, would the addition
of a base be needed to liberate the aniline? Explain.
2. In our laboratory procedure how many grams of tin
will be required to reduce 1 mole of nitrobenzene (a) if
the tin is oxidized to the tetravalent (stannic) state; (b)
if the tin is oxidized only to the divalent (stannous) condition?
135
3. Write the formula for (a) the double salt of aniline
hydrochloride and stannic chloride; (b) the double salt of
aniline hydrochloride and platinic chloride.
4. What is the molecular weight of an amine whose
hydrochloride and platinic chloride gave a double salt containing 31.4 per cent of platinum?
5. If nitrobenzene is reduced with hydrogen with the
aid of a platinum or nickel catalyst, what volume of hydrogen, measured at 0° and 760 mm. pressure, will be
required for the reduction of 0.5 mole of nitrobenzene?
6. Under what conditions of temperature and pressure
may aniline be made from chlorobenzene?
EXPERIMENT 50
Aniline and Some of Its Derivatives
I. PROPERTIES OF ANILINE
0-20
A. Basic Character of Aniline
(a) Action on Indicators. Shake a few drops of aniline with 10 ml. of distilled water and test the action
of the solution with litmus paper or with phenolphthalein indicator solution. How does aniline compare with
ammonia in basicity?
(b) Ferric Chloride Test. Shake a few drops of aniline with 5 ml. of water and add 2 ml. of ferric chloride
solution. Is aniline sufficiently basic to give a precipitate of ferric hydroxide? Equation.
(c) Formation of Aniline Hydrochloride. On a watch
glass mix 1 drop of aniline with 1 drop of concentrated
hydrochloric acid. Equation.
(d) Formation of Aniline Acid Sulfate. Add a drop
of concentrated sulfuric acid to a drop of aniline on a
watch glass. Equation.
20-35
B. Reaction of Aniline with Oxidizing Agents
(a) Bleaching Powder Test. Shake 0.5 g. of bleaching powder with 5 ml. of water to which 1 drop of
aniline has been added. Note the formation of an intense purple color.
(b) Dichrornate Test. Dissolve a drop of aniline in
3-4 ml. of concentrated sulfuric acid in a porcelain
evaporating dish and add a few drops of a solution of
sodium dichromate. Note the intense blue coloration
produced upon mixing the solutions.
35-45
45-75
C. Isocyanide Test for Aniline
To 3-4 drops of aniline contained in a test tube add
5 ml. of 10 per cent sodium hydroxide solution and a
few drops of chloroform. Warm the tube over the Bunsen burner and note carefully the nauseating odor of
phenyl isocyanide. Cf. Chloroform, p. 77. Equation.
(Flush the contents of the tube down the drain in the
hood.)
II.
FAMILIARITY WITH OTHER AROMATIC
AMINO COMPOUNDS
On the supply shelf will be found small samples of
important amino compounds, such as the toluidines
(o, m, p ) , the nitroanilines (o, m, p)9 ochloroaniline
and other halogenated derivatives of aniline, some of
the xylidines (aminodimethylbenzenes), and any others
that the instructor may select. Note the appearance and
odor of each of these specimens. Write the structural
formula for each of them.
75-150
III.
SOLID DERIVATIVES OF ANILINE
A. Acetanilide
The acetyl derivative of aniline, acetanilide, is easily
obtained by the acetylation of aniline with acetyl chloride or acetic anhydride.
(a) Use of Acetyl Chloride. Place 1 ml. of aniline
into a dry test tube and cautiously add 2 ml. of acetyl
chloride in portions of a few drops at a time. Equation.
Note the vigor of the reaction. Dissolve the crude
acetanilide in 20-25 ml. of hot water, filter and allow
the filtrate to cool. Collect the recrystallized product on
a filter, dry some of the crystals on a piece of unglazed
clay plate, and determine their melting point.
(b) Use of Acetic Anhydride. Add about 2 ml. of
acetic anhydride to 1 ml. of aniline as in paragraph
(a). Note that the reaction is less vigorous than that
observed when acetyl chloride was used. Equation. Dissolve the crude acetanilide in about 25 ml. of boiling
water and set the solution aside to crystallize. If the
melting point was observed in paragraph (a), it need
not be repeated here.
B. Benzanilide
The benzoyl derivative of aniline, benzanilide, is easily prepared by the time-honored Schotten-Baumann
method consisting of benzoylation in alkaline medium.
To 1 ml. of aniline contained in a large test tube add
10 ml. of 10 per cent sodium hydroxide solution and
1.5 ml. of benzoyl chloride. Equation. (The benzoyl
chloride is so highly irritating to the eyes and nose that
it should be used in the hood.) Shake the tube vigorously, collect the benzanilide on a filter, wash it with
water, and recrystallize it from a little hot alcohol.
Determine its melting point. The recorded melting point
is 161°.
C. Carbanilide (Diphenylurea)
Dissolve 1 ml. of aniline in 7-8 ml. of benzene and
add 1 ml. of phenyl isocyanate from the small bottle "of
this reagent which is kept in the hood because of its
strong lachrymatory property. Crystals of carbanilide
separate almost immediately. Equation. When recrystallized from hot alcohol, the product melts at 240°.
D. Thiocarbanilide (Diphenylthiourea)
Dissolve 1 ml. of aniline in about 10 ml. of ethanol
and add 1 ml. of phenyl isothiocyanate. Crystals of thiocarbanilide separate within a few minutes. Equation.
The material may be recrystallized from hot alcohol.
M.p. 154°.
£. Hinsberg Reaction
[Aniline and other liquid amino compounds may be
Into three separate test tubes introduce 3 or 4 drops
converted readily into solid derivatives which may be
identified by their melting points and mixed melting of aniline, monomethylaniline, and dimethylaniline, respectively, and add 5 ml. of water to each tube. Take
points with known samples.]
136
ANILINE AND SOME OF ITS DERIVATIVES
the tubes to the hood and add to each of them a few
drops of benzenesulfonyl chloride. Note the reaction,
or lack of it, that occurs in each tube. In the tube (or
tubes) in which a solid product was formed, determine
137
if the product is soluble in alkali. How does the use of
benzenesulfonyl chloride (Hinsberg reaction) serve to
distinguish among primary, secondary, and tertiary
amines? Write equations for the reactions involved.
EXPERIMENT 51
Identification of an Unknown Amino Compound
Introduction. The amino compound given to you will
be one of those shown in Table 7. The identification of
a compound selected from such a limited list may be
obvious from its appearance, odor, boiling point, or
other easily observed property. Your purpose in this experiment, however, is to prove the identity of the unknown given to you by making solid derivatives of the
compound, comparing the melting points of these derivatives with those shown in Table 6, and,finally,making mixed melting point tests with known samples.
acetyl derivative of your unknown and the acetyl derivative of the known sample have the same melting point
and if an intimate mixture of the two shows no depression of the melting point, it is highly probable that the
two specimens are identical (Note 2). Clinch the argument, however, by making similar comparisons of the
individual and "mixed" melting points of a second
derivative.
If the melting points of two or more derivatives of
your unknown and the corresponding derivatives of a
TABLE 6. MELTING POINTS OF DERIVATIVES OF COMMON AROMATIC AMINO COMPOUNDS
Boiling
Point
Amino Compound
Aniline
Methylaniline
Ethylaniline
o-Toluidine
ra-Toluidine
p-Toluidine
o-Chloroaniline
p-Chloroaniline
p-Bromoaniline
o-Anisidine
p-Anisidine
o-Phenetidine
p-Phenetidine
184
195
204
200
203
m.p. 44
209
231
m.p. 66
225
244
229
254
Acetyl Deriv.
RNHCOCH3
Benzoyl Deriv.
RNHCOC6H5
114
102
53
110
66
153
88
179
168
88
132
79
137
161
63
60
145
125
158
99
187
202
60
154
104
173
Procedure
0-170
Note the boiling point, or melting point, of your
unknown. If it is an oily liquid of dark color, distill it.
Determine the presence or absence of halogen by the
Beilstein (copper wire) test (page 42). Make at least
two derivatives of your unknown by the methods given
in Part III of Experiment 50. Recrystallize these derivatives at least once (twice will be better) and observe
their melting points.
Compare the melting points that you have obtained
with those of the corresponding derivatives of the compounds in Table 6 and decide upon the probable identity of your unknown. Since the melting points of various compounds are often nearly the same, it may be
necessary to make a third derivative of the unknown in
question.
When you have arrived at the probable identity of
your unknown, ask the instructor for a small sample
of this compound and make at least two derivatives of
it for melting point tests (Note 1). If, for example the
Urea
Thiourea
(with C6H6NCO) (with C6HBNCS)
RNHCONHC6H6 RNHCSNHCeHfi
238
104
91
196
173
212
182
237
245
144
193
173
187
154
87
89
139
92
142
165
152
158
136
157
142
137
known sample have the same melting points individually and show no depression of the melting point when
intimately mixed, the two compounds may be considered identical and you are ready to make your report
to the instructor.
NOTES
1. Your instructor may be able to supply small quantities of known samples of derivatives for the mixed melting
point tests.
2. See page 4 for a discussion of eutectic mixtures.
QUESTIONS
1. What structural features account for the fact that the
various derivatives of the liquid amines are solids?
2. Which of the various types of amine derivatives do
you find most satisfactory? Why?
138
EXPERIMENT 52
I. Preparation of Sulfanilic Acid
HN—S0 2 OH
NH,
HS'
sv
HNH
[HS0 4 ]SO2OH
II. Preparation of Acetanilide
o
H
NH
/
+ (CH 3 —CO) 2 0
-a
Introduction. The usual methods of preparation of
some organic compounds specify that the reactants be
heated for 6-8 hours—a requirement that is highly inconvenient for laboratory classes. The difficulty may be
circumvented, however, by any of several procedures.
One method of operation that gives very good results
employs a large heating bath such as is shown in Figure
31. Each student, at one laboratory period, may mix
H ||
N—C—CH3
+ CH3COOH
class. A group of student volunteers can easily arrange
a schedule of hours so that the temperature of the bath
may be adequately controlled throughout the heating
period. When the class returns to the laboratory the
product of the reaction may be isolated without loss of
time.
Another device, intended for individual use, is also
shown in Figure 31. The reaction tube may be made
$ 34/45\ hi I $24/40
Air Space
JZ
FIG.
=\\
31. Convenient devices for heating tubes at 150190°C.
the reactants in a large tube, or small flask, and place by sealing a piece of glass tubing onto a standard taper
the tube along with others in the bath where the com- joint, or an ordinary 25 x 200 mm. test tube passing
bined lot may be heated before the next meeting of the through a large hole in a cork stopper will serve equally
139
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
140
well. Such a large hole in the cork is not easily made
and, as a substitute, a stopper may be improvised by
wrapping the tube with a narrow strip of asbestos paper.
The temperature at which the reacting materials contained in the tube are heated is controlled automatically
by the boiling point of the liquid placed in the flask.
Regardless of the type of apparatus used it is often
desirable to shorten the period of time during which
the reactants are heated. Some sacrifice in yield may
be made in order to complete an experiment in a single
laboratory period. Such an exchange of yield for time
is suggested in today's preparation of sulfanilic acid.
In the production of acetanilide, the mixture of aniline
and acetic acid may be boiled for 6-8 hours as in commercial practice but, again to save time, the addition of
some acetic anhydride to the aniline-acetic acid solution
is proposed as a means of acetylating the aniline rapidly.
I. PREPARATION OF SULFANILIC ACID
0-10
The instructor will designate the type of apparatus to
be used. Pour 9 ml. (9.3 g.; 0.1 mole) of aniline into
the reaction tube and cautiously add 12 ml. of concentrated sulfuric acid. The solid aniline acid sulfate
formed will melt when the tube is heated.
Heating the Aniline Acid Sulfate
10-120
Option A. If the large bath of molten paraffin wax is
used, heat the tube in the bath at a temperature of
180°-190° for about 2 hours counting from the time
the bath has attained a temperature of at least 170°.
[Go on to Part II.]
Option B. Place about 75 ml. of ethylene glycol into
the two-necked flask (Figure 31), insert the reaction
tube, and attach a reflux condenser. Heat the flask over
the Bunsen burner at such a rate that the glycol boils
steadily and condensate drips from the condenser. Continue the heating process for nearly 2 hours, during
which time the specimen of acetanilide (Part II) may
be prepared as the sulfanilic acid experiment will require little or no attention.
120-170
Isolation of the Sulfanilic Acid. After the preparation
of acetanilide has been completed, remove the tube
containing the sulfanilic acid from the hot bath and
allow it to cool partially before pouring the contents of
the tube into a beaker containing 50-60 g. of crushed
ice and a little water. Collect the crystals of crude sulfanilic acid on a Biichner funnel and recrystallize them
from boiling water using a little carbon for decolorization. Set the resulting hot solution in a pan of ice and,
when crystallization appears to be complete, bring the
product onto the suction filter. Press out as much water
as possible. Dry the crystals by rinsing them with alcohol and ether as described for drying the specimen of
acetanilide (Part II, following). Weigh the product and
calculate the yield. Do not attempt to determine the
melting point. Sulfanilic acid chars at 280°-300° without melting.
II. PREPARATION OF ACETANILIDE
Into a 200-ml. flask introduce 9 ml. (0.1 mole) of
aniline, 15 ml. of glacial acetic acid, and 15 ml. of
acetic anhydride. Note that heat is evolved owing to
the reaction of the acetic anhydride and aniline. Attach
the flask to a reflux condenser and heat the solution to
boiling for 10 minutes. At the end of this time, cool
the flask somewhat under the water faucet and pour its
contents into a beaker containing about 50 ml. of water
and 40-50 g. of ice. Stir the mixture well and collect
the crystals of acetanilide upon a Biichner funnel.
Rinse the crystals on the filter with a little cold water
and transfer them to a 600-ml. beaker for recrystallization. Add 200 ml. of water and heat the mixture until
the water is boiling. If all of the acetanilide does not
dissolve, add another 50 ml. of water and again heat to
boiling (Note 1). Remove the beaker from the flame,
allow the contents to cool for a moment, and add 1-2
grams of decolorizing carbon (Note 2). Again heat the
solution to boiling, stir well, and filter through a funnel
fitted with a hot-water, or steam, jacket (see page 21).
Chill the filtrate in ice, collect the crystals on a Biichner funnel, and press out as much water as possible.
Shut off the suction pump and stir the crystals on the
filter with 5 ml. of cold ethanol. Suck the alcohol through
the filter, again shut off the pump, and stir the crystals
gently with 10 ml. of ether. Draw the ether through the
filter and spread the crystals on a sheet of paper to dry
in the air. As an alternative procedure to the rinsing with
alcohol and ether, the moist acetanilide may be dried
in an oven at 50°-60°. Yield 8-10 g. M.p. 115°.
Use this intervening period of time for answering
some of the questions at the end of this experiment.
NOTES
1. The solubility of acetanilide is 5.55 per cent at 100°;
3.45 per cent at 80°; 0.84 per cent at 50°; 0.46 per cent
at 20°.
2. The addition of finely divided carbon (or other substance, for that matter) to the solution at the boiling point
often causes the solution to boil over.
QUESTIONS
1. May acetanilide be considered N-phenylacetamide?
May acetamide be made by heating ammonium acetate?
May acetanilide be made by heating phenylammonium acetate? What is the commercial method for the manufacture
of acetanilide?
2. How do you account for the extremely high melting
point of sulfanilic acid? Write the formula for the acid as
it largely exists.
3. How does the structural formula of sulfanilic acid
compare with that of sulfanilamide?
EXPERIMENT 53
I. ^-Bromoacetanilide and Its Hydrolysis to ^-Bromoaniline
HN—COCH3
HN—COCH3
HNH
H20
I
Br
II. Separation of a Mixture of Benzene, Nitrobenzene, and Aniline
0-30
30-80
Procedure. In a 250-ml. flask add 13.5 g. (0.1 mole)
of acetanilide (Experiment 52) to 50 ml. of glacial
acetic acid. Note that the heat of solution is negative.
Warm the flask slightly, if necessary, to bring the last
of the acetanilide into solution and then, at a temperature not above 40°, add slowly with constant shaking
of the flask a solution of 16 g. (0.1 mole, 5.5 ml.) of
bromine dissolved in 20 ml. of glacial acetic acid.
(Handle the bromine in the hood.) Note that the solution becomes warm, that hydrogen bromide is evolved,
and that the red color of the free bromine gradually
fades.
Within 7 or 8 minutes the bromination is complete
and the solution (along with any p-bromoacetanilide
which may have separated) is poured into about 300
ml. of cold water containing a little ice. If any yellow
or orange color persists, because of excess bromine,
discharge it by adding sodium bisulfite solution until
the precipitate is white. Equation. Collect the p-bromoacetanilide on a Buchner funnel. Remove a small part
of the material (a few tenths of a gram) for recrystallization from alcohol and determination of its melting
point. Use the main portion for hydrolysis to p-bromoaniline.
Hydrolysis. Transfer the p-bromoacetanilide from the
Buchner funnel to a 500-ml. flask and add 150 ml. of
water and 50 ml. of concentrated hydrochloric acid. Fit
the flask with a reflux condenser and boil the liquid
for 30 minutes. At the conclusion of this time, cool the
flask, make the contents alkaline by the addition of a
20 per cent solution of sodium hydroxide, and remove
the p-bromoaniline by distillation in steam.
[Begin Part II.]
If the p-bromoaniline solidifies in the tube of the condenser, shut off the water temporarily until the solid
melts. The solidified p-bromoaniline in the receiver is
collected on the Buchner funnel and dried between
folded pieces of paper towel. Weigh the product, determine its melting point, and calculate the percentage
yield.
II.
SEPARATION OF A M I X T U R E OF B E N Z E N E ,
NITROBENZENE, AND A N I L I N E
Into the separatory funnel pour 20 ml. of benzene,
15 ml. of nitrobenzene, and 15 ml. of aniline. The solution now contains one basic compound (aniline) and
two neutral compounds of widely different boiling
points; hence, their separation may be accomplished
easily.
Devise a method for the separation of the mixture
into its three components and submit your method in
diagrammatic form to the instructor. If he approves the
method, proceed with the separation.
QUESTIONS
1. Write equations to show:
(a) how p-bromoaniline may be made from bromobenzene
(b) how ra-Z>romoaniline may be made from nitrobenzene
(c) how /7-chloroaniline may be made from acetanilide.
2. Write equations showing the reaction of p-bromoaniline with each of the following reagents and name the
chief product formed in each reaction:
(b) acetic anhydride
(a) acetyl chloride
(d) ethyl chlorocarbonate
(c) benzoyl chloride
(e) phenyl isocyanate
(f) phenyl isothiocyanate
(h) bromine water
(g) benzenesulfonyl
chloride
3. Write the formula and name of the compound that
may be hydrolyzed to:
(a) formic acid (1 mole) and /?-bromoaniline (1 mole)
(b) n-butyric acid (1 mole) and aniline (1 mole)
(c) benzoic acid (1 mole) and aniline (1 mole)
(d) acetic acid (1 mole) and p-chloroaniline (1 mole)
(e) aniline (1 mole), C 0 2 (1 mole), and ethanol (1
mole)
4. List the following compounds in order of decreasing
basicity: aniline, /7-chloroaniline, p-toluidine, p-methoxyaniline, p-nitroaniline, picramide, diphenylamine, and triphenylamine. Could each of these amines be separated from
benzene and nitrobenzene by the method you used for aniline? Explain.
141
60-140
EXPERIMENT 54
^-Nitroacetanilide and ^?-Nitroaniline
HN—COCH3
HN—COCH3
I
O
NH 3 +,C1-
I
NH 2
I
HNOs f i ^ l
H20
N02
f [ ^ 1
N02
I. NITRATION OF ACETANILIDE
Introduction. The direct nitration of aniline and most
other aromatic amino compounds usually produces a
tarry mixture of nitrated and oxidized substances from
which the desired product can be isolated only with
difficulty and in poor yield. The nitration of the acyl
derivatives of the amino compounds, however, proceeds
smoothly and the subsequent removal of the acyl group
by hydrolysis gives the nitrated product both in good
yield and in a satisfactory state of purity.
Procedure. Pour 30 ml. of concentrated sulfuric acid
into a small beaker and add 13.5 g. (0.1 mole) of
acetanilide in small portions with constant stirring. As
soon as all, or nearly all, of the acetanilide has dissolved, set the beaker in a pan of crushed ice and add
from a dropping funnel a solution of 12 ml. of nitric
acid in 12 ml. of concentrated sulfuric acid in portions
of but a few drops at a time. Stir the reacting mixture
gently with a thermometer and add the nitrating acid
so slowly that the temperature does not exceed 35°.
When all of the nitrating acid has been added, remove
the beaker from the ice bath and let it stand at room
temperature for 15 minutes.
Pour the solution of nitrated acetanilide into a
600-ml. beaker containing 200 ml. of water and about
50 g. of ice. Stir the mixture well and collect the precipitated p-nitroaniline on the Biichner funnel. Wash it
on the funnel twice with 100-ml. portions of cold water,
press out as much water as possible, and remove about
0.5 g. of the p-nitroacetanilide for recrystallization from
hot alcohol and determination of the melting point.
II. HYDROLYSIS OF P-NITROACETANILIDE TO
p-NlTROANILINE
Transfer the moist cake of p-nitroacetanilide from the
Biichner funnel to a 600-ml. beaker and stir it into a
thin paste with 200 ml. of water. Pour the mixture into
a 500-ml. flask, using a little water for rinsing purposes,
add 75 ml. of concentrated hydrochloric acid, and fit
the flask with a reflux condenser. Heat the flask over
the Bunsen burner to maintain active boiling of the contents for 30-40 minutes.
[During this interval give your attention to the questions at the end of this experiment.]
I
NaOH
( f ^ l
N02
At the end of this 30-minute period of hydrolysis,
cool the flask and contents somewhat under the water
faucet and pour the contents into an 800-ml. beaker.
Add 75-100 g. of crushed ice and precipitate the p-nitroaniline by making the solution alkaline through the
addition of ammonium hydroxide solution. (Because of
the low basicity of p-nitroaniline some of it usually
separates from the diluted acidic solution before any
ammonium hydroxide is added.)
Bring the precipitate of p-nitroaniline onto the Biichner funnel, wash it with water, press out as much water
as possible, and dry the material in an oven at 60°-70°.
Recrystallize about 0.5 g. of the moist p-nitroaniline by
dissolving it in 40-50 ml. of boiling water. Add a little
decolorizing carbon and filter the hot solution through
a fluted filter paper in a heated funnel. If the solution
is allowed to cool slowly, the p-nitroaniline separates
in long needle-shaped crystals melting at 146°.
Stains on Hands and Clothing. Avoid getting any of
the p-nitroaniline solution on your clothing because
the yellow stains cannot easily be removed without
bleaching the original dye in the cloth. Colored spots
on your hands may be removed by application of a thin
paste of bleaching powder in water. Follow this treatment by an alcohol rub to get rid of the odor of chlorine.
QUESTIONS
1. How do you explain the observation that:
(a) Direct nitration of aniline ordinarily is an unsatisfactory procedure.
(b) In the direct nitration of aniline some m-nitroaniline is obtained.
(c) In the nitration of phenyltrimethylammonium sulfate the nitro group enters the meta position almost exclusively.
2. May p-nitroacetanilide be considered N-p-nitrophenylacetamide?
3. As a rule are amides easily hydrolyzed? Is the hydrolysis of p-nitroacetanilide comparable to the hydrolysis of
acetamide?
4. How do you account for the low basicity of p-nitroaniline?
142
EXPERIMENT 55
I. 7w-Nitroaniline
NH 2
N02
N O
+ 3NH 4 SH + H 2 0
NO,
+ 3S + 3NH 4 OH
II. ^-Nitrosodimethylaniline
CH 3 —N—CH 3
CH 3 —N—CH 3
+ H20
+ HO—N=O
NO
I. R E D U C T I O N O F m-DiNiTROBENZENE
TO m-NlTROANILINE
0-60
nearly so. Cool the flask under the water faucet and add
about 250 ml. of cold water. The precipitate consists of
m-nitroaniline, sulfur, and any remaining unreduced
m-dinitrobenzene. Bring the precipitate onto the Biichner funnel and wash it 2-3 times with small amounts of
water to remove the red alkaline solution. Transfer the
yellow precipitate to a 600-ml. beaker, add 250 ml. of
water with 50 ml. of concentrated hydrochloric acid,
and heat the mixture to boiling in order to dissolve the
m-nitroaniline.
Separate the solution from the undissolved sulfur and
any m-dinitrobenzene that may have escaped reduction
by filtration through a funnel equipped with a hot-water
jacket (page 21, Figure l i e ) . Cool the filtrate thoroughly in ice, and precipitate the m-nitroaniline by the
addition of a 10 per cent solution of sodium hydroxide
(Note 1). The m-nitroaniline is precipitated as a bright
yellow solid. Recrystallize about 0.5 g. of the material
from a little boiling water and dry the main portion in
the oven at 60°. Yield 6-7 g. M.p. 114°.
Stains on Hands and Clothing. Avoid getting m-nitroaniline on your clothing as the stains cannot easily be
removed without bleaching the original color of the
cloth. Remove spots from your hands by application of
bleaching powder and water followed by an alcohol rub.
Introduction. Strong reducing agents, such as metals
with acids, reduce both nitro groups in m-dinitrobenzene
producing m-phenylenediamine. Milder reducing agents,
of which ammonium hydrosulfide is an example, attack
but one of the nitro groups yielding m-nitroaniline.
The preparation of the ammonium hydrosulfide reagent
by passing hydrogen sulfide gas into ammonium hydroxide solution is inconvenient; hence, in this experiment, a solution of ammonium chloride and sodium
sulfide is employed.
Procedure. Place 8.4 g. (0.05 mole) of m-dinitrobenzene into a 500-ml. flask, add 50-60 ml. of 95 per
cent ethanol, and warm the flask on the steam bath
until the solid dissolves. Meanwhile prepare a solution
of 10 g. of ammonium chloride in 25 ml. of hot water
and another solution of 10 g. of sodium sulfide (anhydrous commercial flake, or the equivalent quantity of
the crystalline material, Na«jS • 9H 2 0) in 25 ml. of hot
water. At a temperature of 50°-60°, slowly add the ammonium chloride solution to the alcoholic solution of
m-dinitrobenzene. This will cause some precipitation,
but all of the precipitated m-dinitrobenzene may be
redissolved by heating the flask on the steam bath. Add
a little more alcohol if necessary to obtain complete
solution.
NOTE
Remove the hot alcoholic solution from the steam
bath and introduce the sodium sulfide solution in por1. m-Nitroaniline is such a weak base that some of it
tions of not more than 1 or 2 ml. at a time at intervals separates as the solution cools, even before any sodium
of 10-15 seconds. Hold the hot flask with a towel and hydroxide is added.
shake it continuously during the addition of the sodium
II. /7-NlTROSODIMETHYLANILINE
sulfide solution, which requires 2-3 minutes. The reacIntroduction. From the study of aliphatic compounds
tion is exothermic and no heat need be applied during
this time. After all of the sodium sulfide solution has it will be recalled that (1) aliphatic primary amines
been added, return the flask to the steam bath for an- react with nitrous acid to give alcohols with evolution
of nitrogen, (2) secondary amines and nitrous acid
other 5 minutes.
Reduction of the nitro group is now complete, or yield oily nitroso compounds, and (3) tertiary amines
143
144
60-120
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
merely form salts, the trialkylammonium nitrites. In a
tertiary amine, such as dimethylaniline, however, substitution on the benzene ring occurs so easily that
/7-nitrosodimethylaniline is obtained rapidly. Hence, it
is obvious that the common statement that "tertiary
amines do not have any visible reaction with nitrous
acid" needs to be reconsidered in the light of the group,
aliphatic or aromatic, that may be attached to the amino
nitrogen atom.
Procedure. In a small beaker dissolve 3 ml. of dimethylaniline in 10 ml. of concentrated hydrochloric
acid and 10 ml. of water. Add a small quantity of
crushed ice to cool the solution to 0° and then, with
constant stirring of the solution, add 2 g. of sodium
nitrite dissolved in a little water. Keep the temperature
of the solution at 0°-10°. The orange-colored crystals
that separate are p-nitrosodimethylaniline hydrochloride. Collect the crystals on the Buchner or Hirsch funnel, remove as much of the liquid as possible, and return the hydrochloride to a small beaker for liberation
of the free base by the addition of ammonium hydroxide.
Bring the green crystals of p-nitrosodimethylaniline
onto the suction funnel and rinse them with a little
water. After pressing out as much of the water as possible, dissolve the product in ether and set the beaker
containing the ethereal solution aside to evaporate
slowly. The recorded melting point of the green foliated
crystals is 85°.
QUESTIONS
1. If a 90 per cent yield is obtained in each step of the
following sequence of operations, what weight of ra-nitroaniline will be obtained from 78 g. (1 mole) of benzene?
C6H6 -+
C 6 HBN0 2
-• m-C6H4(N02)2 -* m-02N—C6H4—NH2
2. Write equations to show how m-nitroaniline will react with (a) acetic anhydride, (b) benzoyl chloride, (c)
Sn + HC1.
3. Upon bromination of m-nitroaniline, the bromine
atoms would be expected to enter what positions?
EXPERIMENT 56
I. Thiocarbanilides
H
CeHs—NH2 + CS2
s
H
s
H
-» CsHs—N—C—SH -252E; C 6 H 5 _ N _ C — N _ C e H 6 + H 2 S
Phenyldithiocarbamic acid
Thiocarbanilide
(Diphenylthiourea)
II. Phenyl Isothiocyanate
s H
I II I
H
(1)
2C 6 H 6 —N—C—N—C 6 H 5 + HC1
H
(2)
S
QH.—N-
H
C=N—C 6 H 5 CI" + C 6 H 5 — N = C = S
+ H2S
/
LCeHe—NH
H
-N—C 6 H 5 + HC1
I. THIOCARBANILIDE
0-40
CeHe—NH
\
-> CeHe—NH3+,C1- + C6H 6 —N=C=S
ml. of cold alcohol. Stir the material on the filter gently
with a glass rod and suck out the alcohol. Repeat this
rinsing process using 10 ml. of ether.
Spread the crystals on a sheet of paper to dry in the
air. This method of drying is convenient but involves
some loss because of the solubility of the thiocarbanilide.
As an alternative procedure, the material, after washing
with water, may be dried in an oven at 60°-70°. Yield
28-30 g. Recrystallize a small portion from hot ethanol
for observation of the melting point. The recorded melting point is 154°.
Introduction. The reaction between aniline and carbon disulfide at room temperature is slow and must be
allowed to proceed for several days in order to afford
a reasonable yield of thiocarbanilide. When the reactants are boiled under reflux, a yield, satisfactory for
laboratory purposes, can be obtained in a few hours.
The reaction apparently proceeds in stages. In alkaline
solution, however, as used in the following experiment,
the reaction is so rapid that a specimen of thiocarbanilide may be obtained quickly.
II. PHENYL ISOTHIOCYANATE
Procedure. In a 500-ml. flask place 28 g. (0.3 mole,
Introduction. The reaction of thiocarbanilide (di27.5 ml.) of aniline and 20 ml. of carbon disulfide.
Then gradually add in small portions a cooled solu- phenylthiourea) with boiling hydrochloric acid proceeds
tion of 15 g. of sodium hydroxide in 40 ml. of water. partially according to both of the above equations.
Shake the flask continuously and cool it in cold water Usually reaction (1) leading to the formation of phenyl
if the contents should begin to boil. Continue the vig- isothiocyanate and triphenylguanidine hydrochloride
orous shaking of the flask for about 10 minutes after all predominates.
of the alkaline solution has been added. By this time
Procedure. In a 500-ml. flask place 22.8 (0.1 mole)
the contents will have become almost solid with the of thiocarbanilide, 100 ml. of concentrated hydrochloseparation of thiocarbanilide.
ric acid, and 50 ml. of water. Fit the flask with a reflux
Add 200 ml. of cold water to the orange-colored condenser and boil the mixture until the solid thiocarmixture and collect the crystals on a Biichner funnel. banilide has been replaced by the oily phenyl isothioTo wash the product on the filter shut off the suction, cyanate (about 45 minutes). Disconnect the flask from
fill the funnel nearly full of water, stir the mixture well, the condenser and add 125 ml. of water. Introduce a
but gently to avoid tearing the filter paper, suck the wash few boiling chips and join the flask to the condenser by
water through the funnel, and repeat the process two or a bent piece of glass tubing for downward distillation.
three times until the press cake is nearly free of alkali.
Heat the flask over the Bunsen burner and distill
Transfer the product into a 600-ml. beaker, stir it into a about 175 ml. of water which carries with it the phenyl
slurry with 100-150 ml. of water, and add hydrochloric isothiocyanate and some hydrogen chloride. Add to the
acid until the mixture is acidic to litmus.
distillate about 20 ml. of carbon tetrachloride to aid
Put the thiocarbanilide, now in the form of nearly in collecting the oily phenyl isothiocyanate, separate the
white flakes, onto the Biichner funnel and wash the lower layer, dry it over a little calcium chloride and
product with water to remove excess acid and a little distill it. The carbon tetrachloride boils at 77° and the
aniline hydrochloride. Press out as much water as pos- phenyl isothiocyanate at 220°. Yield 6-7 g.
sible, shut off the pump, and wet the crystals with 10
Isolation of the Triphenylguanidine. The triphenyl145
40-140
146
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
guanidine, as its hydrochloride salt remains in the distillation flask partly in solution and partly in the solid
state. Some of the solid matter is unchanged starting material (thiocarbanilide). To isolate the triphenylguanidine, pour the contents of the flask into a 600-ml.
beaker and dilute the acidic solution with water until
the beaker is half full (about 300 ml. total volume of
liquid).
Heat the water to boiling in order to dissolve the triphenylguanidine hydrochloride and filter, while still hot,
through a large fluted filter paper in order to remove
the undissolved thiocarbanilide (see Figure l i b , page
21). Cool the filtrate to about 50° and make the solution alkaline by the addition of 10 per cent sodium
hydroxide solution. The triphenylguanidine is precipitated as a white solid. Note that the hot mixture has
an odor of aniline. How is the presence of aniline to be
explained?
Add a little ice to the beaker to lower the temperature of its contents to 30°-40° and collect the triphenylguanidine on a Buchner funnel. After recrystallization
from hot 60 per cent ethanol, it melts at 143°.
Use of Phenyl lsothiocyanate as a Reagent for
Amines. If the usefulness of phenyl isothiocyanate in
the identification of amines has not been studied pre-
viously (Section D, Part III, Experiment 50), that short
test should be made now.
QUESTIONS
1. Write the structural formulas for the following compounds, all of which are related to urea:
(a) monophenylurea
(b) iV,W-diphenylurea (symmetrical diphenylurea)
(c) N,N-diphenylurea (unsymmetrical diphenylurea)
(d) urethane (ethyl carbamate)
(e) thiourea
(f) Af,iV'-diphenylthiourea
(g) carbodiphenylimide
(h) Af-phenylurethane (ethyl phenylcarbamate)
(i) guanidine
(j) iV,Ar,Af-triphenylguanidine
(k) ethyl phenyldithiocarbamate
Which of the above is thiocarbanilide? Which of the
above is carbanilide? Which of the above are isomers?
2. What three compounds may be made from aniline
and phosgene by suitable control of concentrations and
temperature?
3. Ethyl phenylthiocarbamate can be prepared by refluxing of a solution of phenyl isothiocyanate in ethanol for
several hours. Write the equation for the reaction.
EXPERIMENT 57
Azobenzene, Hydrazobenzene,1 and Benzidine
H
2C 6 H 5 —N0 2 — > ' C 6 H 5 —N=N—C 6 H 5 —
C 6 H 5 —N—N—C 6 H 5 -?-* H2N-
Introduction. You will probably recall that azobenzene and hydrazobenzene are among the reduction products of nitrobenzene and that the rearrangement of hydrazobenzene yields benzidine. The reduction process is
conducted commercially by warming nitrobenzene with
zinc dust and sodium hydroxide solution, although the
rate of reaction is so slow that 15-20 hours may be required for conversion of the nitrobenzene to hydrazobenzene. For laboratory purposes magnesium turnings
and absolute methanol may be used to prepare either
azobenzene or hydrazobenzene in much less time. The
product obtained depends upon the quantity of magnesium used and also upon the length of time during
which the reduction is continued.
After the hydrazobenzene has been obtained, you
can convert it into benzidine hydrochloride by warming
it with a dilute solution of hydrochloric acid. The free
benzidine is then liberated from its salt by the addition
of alkali.
0-10
15-60
60-100
H
A-A
-NH 2
ture well to facilitate the separation of the azobenzene.
Collect the red precipitate of azobenzene on a Buchner
funnel and recrystallize the material from a little ethyl
alcohol. The yield of azobenzene, m.p. 68°, is 2.5-3.0 g.
II. PREPARATION OF HYDRAZOBENZENE
Pour 3 g. (2.6 ml., 0.025 mole) of nitrobenzene into
a dry 250-ml. flask and add 50 ml. of commercial absolute methanol along with a small crystal of iodine. Then
add 3 g. of clean magnesium turnings and connect the
flask to a reflux condenser. A vigorous exothermic reaction begins quickly and is allowed to proceed unchecked
unless the boiling solution reaches nearly to the neck
of the flask, in which event the flask is momentarily
surrounded by cold water.
In about 10 minutes the separation of magnesium
methoxide becomes so extensive that the contents of the
flask tend to set to a thick paste. Add, through the top
of the condenser, an additional 25 ml. of absolute methanol, shake the flask, and allow the reaction to proceed
I. PREPARATION OF AZOBENZENE
as before.
[The preparations of azobenzene and of hydrazobenWithin another 10-15 minutes the rate of reaction
zene may be conducted almost concurrently. As soon becomes slow and the flask is heated in a pan of hot
as Part I is well started, begin Part II.]
water at 75°-85°. A bath temperature of 80°-85° proIn a dry 250-ml. flask place 6.15 g. (5.1 ml., 0.05 duces gentle bumping which is advantageous as it helps
mole) of nitrobenzene, 125 ml. of commercial absolute to stir the thick suspension. Above 85° the bumping
methanol, and a small crystal of iodine. Weigh 6.0 g. usually becomes excessive. Add another 2-g. portion of
of magnesium turnings on a piece of paper, add one magnesium turnings (usually these will drop through
half of the magnesium to the solution of nitrobenzene, the condenser) and continue heating the flask and shakand attach the flask to a water-cooled reflux condenser. ing it occasionally during the next 20 minutes or a little
The exothermic reaction, which begins at once, causes longer if you are busy with the production of the specimen of azobenzene.
the solution to boil.
Disconnect the flask from the condenser and stir the
[Begin Part II.]
hot contents into a slurry so that the thick suspension
In 7-8 minutes the rate of ebullition will have sub- may be poured into a 400-ml. beaker. Add 100 ml. of
sided somewhat and the remainder of the magnesium water, part of which is used in rinsing the flask, and
turnings may be introduced into the flask. Again attach slowly acidify the suspension by the addition of glacial
the flask to the reflux condenser and allow the spon- acetic acid. About 25-30 ml. of the acid will be required.
As the magnesium methoxide dissolves, a white (or
taneous reaction to proceed until boiling nearly ceases
(about 15 minutes). Thereafter heat the flask in a pan pale yellow) residue of hydrazobenzene remains which,
of hot water at 70°-80° for an additional 30 minutes. for the most part, floats on the surface of the liquid.
(At a higher temperature, excessive bumping occurs.) A small quantity of excess magnesium settles to the
Pour the orange-colored contents of the flask into a bottom of the beaker. Pour the water solution and susbeaker containing 100 g. of ice and 100 ml. of water pended hydrazobenzene onto the suction filter, leaving
and add hydrochloric acid until the mixture is acidic to the magnesium granules, in so far as is possible, in the
litmus. Set the beaker in an ice bath and stir the mix- beaker.
Wash the product on the Buchner funnel well with
x
The preparation of azobenzene and of hydrazobenzene
water
to remove magnesium salts and avoid drawing
given here is modeled after that described by A. I. Vogel,
much air through the filter cake in order to minimize
A. Watling, and J. Watling, /. Chem. Educ, 35, 40 (1958).
147
15-40
40-55
55-75
75-100
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
148
atmospheric oxidation of the hydrazobenzene (colorless
when pure) to red azobenzene. We shall not recrystallize the hydrazobenzene for determination of its melting point nor make a direct measurement of the yield.
The latter may be derived from the weight of benzidine
sulfate obtained in Part III.
III.
100-125
BENZIDINE
Transfer the moist hydrazobenzene to a 250-ml.
beaker and add 100 ml. of water plus 15 ml. of concentrated hydrochloric acid. Warm the mixture to 40°-50°
and stir it for a few minutes. The hydrazobenzene rearranges rather rapidly to benzidine and passes into solution as benzidine hydrochloride. Usually a small quantity of orange-red azobenzene remains undissolved. This
is removed by filtration and the filtrate containing benzidine hydrochloride is used in sections (a), (b), and (c)
of this experiment.
Dilute the solution with distilled water to a volume
of 150 ml. and stir the solution well to assure its uniform concentration. Reserve 25 ml. of this solution for
tests (b) and (c).
(a) Benzidine Sulfate. To 125 ml. of the solution of
benzidine hydrochloride add 5 ml. of concentrated sulfuric acid and set the solution in an ice bath for a few
minutes. Collect the white, slightly soluble benzidine
sulfate on a small Buchner or Hirsch funnel, rinse it on
the filter with two 5-ml. portions of ethyl alcohol, then
with a little ether, and spread the material on a sheet of
filter paper to dry in the air.
Weigh the benzidine sulfate and calculate the yield,
assuming the salt obtained to be the double acid sulfate,
[H3N—C6H4—C6H4—NH3]++, 2HS0 4 ". Remember
that this weight of salt is from 5/6 of your benzidine
hydrochloride; hence, in calculating the yield the weight
of salt obtained should be multiplied by 6/5.
(b) Benzidine as a Reagent for Free Chlorine. To
50 ml. of water contained in a 25 x 200 mm. test tube
add 2 or 3 drops of your solution of benzidine hydrochloride. Shake the tube to mix the solutions well and
then add 1 or 2 drops of chlorine water. A green coloration is produced. If the color is orange or red, the solutions are too concentrated. Dilute them and repeat the
test.
o-Tolidine, which is commonly used as a colorimetric reagent for free chlorine in municipal water supplies, is structurally similar to benzidine and gives a
yellow color the intensity of which is a measure of the
concentration of chlorine in the water.
(c) Precipitation of Benzidine. Add a 5 per cent
solution of sodium hydroxide to the remainder of your
solution of benzidine hydrochloride until the solution is
alkaline to litmus. Collect the gray precipitate of benzidine upon a filter, recrystallize it from a small amount
of ethyl alcohol, and observe its melting point. The recorded melting point of benzidine is 128°.
QUESTIONS
1. (a) What is the formula for o-tolidine? (b) How
would you make it?
2. What is the importance of benzidine and related compounds to the manufacture of dyes for cotton cloth?
EXPERIMENT 58
Sulfanilamide
O
H
O H
O H
CH3C—N—C6H4—S02OH + C1S0 2 0H -> CH3C—N—C6H4—S02C1 + H 2 S0 4
O H
(2)
H
II I
CH 3 C—N—CeH,—S0 2 —NH 2 + H 2 0 -> CH3COOH + p-H 2 N—C 6 H 4 —S0 2 NH 2
Introduction. The preparation of sulfanilamide involves three successive steps: (1) The sulfonation of
acetanilide and subsequent formation of p-acetaminobenzenesulfonyl chloride, (2) the conversion of the sulfonyl chloride to p-acetaminobenzenesulfonamide, and
(3) the removal of the acetyl group by hydrolysis.
0-70
70-120
O H
CH3C—N—C6H4-^S02C1 + 2NH 3 - • CH 3 C—N—CeH,—S0 2 NH 2 + NH4C1
O
(3)
H
CH3C—N—C6H5 + C1S0 2 0H -> CH3C—N—C6H4-^S02OH + HC1
(la)
(lb)
O
Step I. p-Acetaminobenzenesulfonyl Chloride
In a 100-ml. flask place 20 ml. of chlorosulfonic acid
and cool it to 15° in cold water. (CAUTION: chlorosulfonic acid causes bad burns on the skin. Handle it
with care.) Add to the acid in the flask 7 g. (approximately 0.05 mole) of dry acetanilide in small portions.
Stir the mixture with a stirring rod and add the acetanilide slowly so that the temperature does not rise
above 25°.
When all, or nearly all, of the acetanilide has dissolved, fit the flask with a stopper, through which is
inserted a piece of glass tubing about 2 feet long to
exclude moisture, and heat the flask on a steam bath
for 45 minutes. At the end of this time pour the contents of the flask slowly and cautiously into a 400-ml.
beaker which is half filled with ice and water. The
p-acetaminobenzenesulfonyl chloride separates as a
gummy mass which soon solidifies. It is broken into
lumps, collected on a Buchner funnel, dried as much as
possible by suction, and used immediately in the next
step.
sulfuric acid (15-20 per cent) until the solution is acidic
to Congo red paper. Allow the flask to stand in the ice
bath for 5 minutes and collect the crystals of the amide
upon a Buchner funnel. Wash the crystals with a little
water, dry them as much as possible by suction, and
proceed to step III.
In order to verify the identity of the product, recrystallize a small portion of it from alcohol and determine
its melting point. p-Acetaminobenzenesulfonamide melts
at 219°.
Step III. p-Aminobenzenesulfonamide
Weigh the p-acetaminobenzenesulfonamide and place
it in a small flask. Add to the amide twice its weight of
dilute hydrochloric acid (one volume of acid to one volume of water) and boil the mixture gently under a reflux condenser for 20 minutes. At the end of this time
dilute the solution with an equal quantity of water and
transfer it to a beaker. Add solid sodium carbonate in
small quantities at a time until the solution, after thorough stirring, is barely alkaline to litmus.
A precipitate of sulfanilamide forms during the neutralization and grows when the beaker is chilled in
ice. Collect the product on a suction filter, wash it with
a little water, and dry it on paper or on a piece of porous
clay plate. The yield is about 4 g. Dissolve the sulfanilamide in about fifteen times its weight of boiling
water, decolorize the solution with a little charcoal,
filter, and chill the filtrate in ice. The sulfanilamide separates in needle-shaped crystals which melt at 163°.
Note that sulfanilamide will dissolve in either dilute
acid or dilute alkali.
Step II. p-AcetaminobenzenesuIfonainide
Place the acid chloride obtained in step I into a
100-ml. flask and add 25 ml. of concentrated ammonium hydroxide solution. The reaction begins at once
and is exothermic. Stir the mixture to produce a thin
paste and heat the flask on the steam bath or in a pan
QUESTIONS
of boiling water for 10 minutes. (At this point the preparation may be set aside until the next laboratory pe1. Why must sulfanilic acid be acetylated before the
riod if necessary.)
sulfonic acid group is converted into the sulfonyl chloride?
2. What explanation would you offer for the observaChill the flask in an ice bath and slowly add dilute
149
120-170
150
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
tion that sulfanilic acid undergoes acetylation with acetic
anhydride slowly, whereas the acetylation of sodium sulfanilate proceeds rapidly?
3. How do you account for the amphoteric nature of
sulfanilamide?
4. In consideration of the fact that /?-acetaminobenzenesulfonamide contains the amide of a carboxylic acid as
well as the amide of a sulfonic acid, how do you explain
the observation that the former is hydrolyzed far more
rapidly than the latter?
EXPERIMENT 59
I. Chlorobenzene by the Sandmeyer Reaction
C 6 H 6 —N=N+, CI-
CuCl
• C6H5—CI + N.
II. Toluene by the Deamination of ^-Toluidine
(1)
^TW
+ N a N 0 2 + HCl -» CH 3
/ V - N = N +
Q - + H C = 0 + 2NaOH
CH 3 —f
(2) CH,
J—NH2
CHS
^ V - N•N=N+,
^ l CI" +
Jr~\
NaCl + 2H 2 0
H + NaCl + N 2 + HC—ONa + H 2 0
water during the course of 2 or 3 minutes. Let the solution stand in the ice bath for about 10 minutes while
The Cuprous Chloride Solution
you prepare for the steam distillation.
Prepare a solution of cuprous chloride by one of the
When the apparatus for steam distillation has been
following methods as directed by the instructor.
assembled, give your attention to the cuprous chloride
(a) From Copper Sulfate. In a 1-liter flask dissolve solution. If procedure (a) has been followed, carefully
80 g. of pulverized copper sulfate (CuS0 4 • 5H 2 0) in pour off and discard the supernatant solution and wash
about 300 ml. of hot water and add 30 g. of sodium the white precipitate of cuprous chloride by decantation
chloride. In a 400-ml. beaker prepare a solution of 18 with water. Then dissolve the cuprous chloride in 100g. of sodium bisulfite and 12 g. of sodium hydroxide in 125 ml. of concentrated hydrochloric acid and 30-40
150 ml. of water and add this solution (reducing agent) ml. of water. Cool the solution, contained in a 1-liter
in small portions to the hot solution of copper sulfate (or 2-liter) flask, to 0°-10° in an ice bath. If method
during the course of 2 or 3 minutes. Throughout this (b) or (c) was used, add a sufficient quantity of contime shake the flask containing the copper sulfate con- centrated hydrochloric acid to dissolve any precipitate
tinuously. Close the mouth of the flask loosely with a of cuprous chloride that may have formed, pour the
stopper to minimize oxidation and set the flask aside solution into a 1-liter (or 2-liter) flask and cool it in
while you diazotize the aniline.
ice.
The Main Reaction. With almost continuous shaking
(b) From Copper Carbonate. In a 500-ml. flask
place 20 g. of copper carbonate with 100 ml. of water and cooling of the flask containing the cuprous chloand dissolve the copper carbonate by the gradual addi- ride, slowly add the solution of benzenediazonium
tion of 75 ml. of concentrated hydrochloric acid. Then chloride. A voluminous precipitate of a double salt of
add 20 g. of copper turnings (Note 1), cover the mouth cuprous chloride-benzenediazonium chloride is formed
of the flask with a watch glass, and heat the solution to which loses nitrogen as the temperature rises. When all
the boiling point for 15 minutes while you diazotize of the diazo solution has been added, warm the flask
gently to aid in the decomposition of the double salt.
the aniline (Note 2).
(c) From Cupric Chloride. Dissolve 28 g. of cupric The heat should be applied slowly in order to avoid
chloride (CuCl2 • 2H 2 0) in 100 ml. of water and 75 excessive foaming in connection with the loss of nitroml. of concentrated hydrochloric acid and heat the solu- gen. When the temperature has risen to approximately
tion with 20 g. of copper turnings as in section (b) 50°, all of the solid will have been replaced by an oily
layer of chlorobenzene which is then removed by disabove.
tillation with steam.
Diazotization of the Aniline
Chlorobenzene has a high vapor pressure at temPour 22.5 ml. (23.2 g., 0.25 mole) of aniline into peratures near the boiling point of water and is carried
a 400-ml. beaker and dissolve it by the addition of 50 over so rapidly that the collection of 125-150 ml. of
ml. of water and 75 ml. of concentrated hydrochloric distillate is sufficient. Add a little sodium hydroxide
acid. Cool the solution to about 5° by setting the beaker solution to the distillate to dissolve any phenol that may
in a pan of ice and by adding about 50 g. of ice to the have been formed, separate the chlorobenzene, wash it
solution. Diazotize the aniline by adding, in small por- once with water, dry it over a little calcium chloride,
tions, a solution of 18 g. of sodium nitrite in a little and distill it. The yield is 16-18 g.; b.p. 132°.
151
I. CHLOROBENZENE
0-15
15-40
40-130
152
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
NOTES
1. If copper turnings are not available, copper shot or
pieces of copper foil may be used. In any event the metal
should be in such form that it is well covered by the solution. Avoid pouring residual copper shot into the sinks
because it clogs the drain pipes.
2. The solution should simmer only. Vigorous boiling
results in the loss of acid from the flask where it is needed
and in the acidification of the atmosphere which cannot be
tolerated.
II. TOLUENE BY DEAMINATION OF P-TOLUIDINE
60-75
75-100
Diazotization of the p-Toluidine. As soon as the
steam distillation in Part I is well started, diazotize 27 g.
(0.25 mole) of p-toluidine in the following manner:
Dissolve the p-toluidine, contained in a beaker, in 75
ml. of concentrated hydrochloric acid and 200 ml. of
water. Cool the solution to 0°-5° in an ice bath and add
about 100 g. of ice to the solution. Slowly add a solution of 18 g. of sodium nitrite in a little water and set
the solution aside while you prepare the alkaline solution of formaldehyde.
Reduction of p-Toluenediazonium Chloride with Alkaline Formaldehyde Solution. In a 2-liter flask fitted
with a mechanical stirrer dissolve 50 g. of commercial
sodium hydroxide in 300 ml. of water and add 300 g.
of crushed ice. Start the stirrer (or, if mechanical stirrers are not available, shake the flask) and add 50 ml.
of formalin (37 per cent formaldehyde). Then intro-
duce the p-toluenediazonium chloride in a slow stream
into the stirred alkaline solution of formaldehyde. The
rapid escape of nitrogen causes considerable frothing.
The toluene, produced by the reaction, quickly separates from the solution as an upper layer. Remove the
stirring motor, add a few boiling chips and, by means
of stoppers and a bent tube, connect the flask to a condenser for distillation of the toluene. The introduction
of steam is unnecessary; simply boil the mixture over
the Bunsen burner and collect about 150 ml. of the
toluene-water distillate.
[While the toluene is being distilled from the reaction 100-130
mixture, complete the preparation of the chlorobenzene.]
Separate the upper layer of toluene, wash it once 130-170
with water, dry it over a little calcium chloride and distill it. Yield 15-18 g.; b.p. 110°.
QUESTIONS
1. How do you account for the presence of small
amounts of phenol in the chlorobenzene prepared in Part I?
2. What products other than hydrocarbons may be obtained by reduction of diazonium salts under various conditions?
3. Write equations showing how reactions of diazonium
salts may be used in the preparation of p-bromotoluene,
iodobenzene, benzoic acid, p-toluic acid, o-iodotoluene,
and phenylhydrazine.
EXPERIMENT 60
I. Preparation of Diazoaminobenzene
(1)
C«H6—NH2 + N a N 0 2 + 2HC2
> C«H 6 —N=N+ CI" + NaCl + 2 H 2 0
H
(2)
Q H 6 — N = N + CI" + C 6 H 6 —NH 2
> C»H 6 —N=N—N—C«H 6 + H d
II. Rearrangement of Diazoaminobenzene to Aminoazobenzene
I. DIAZOAMINOBENZENE
Diazotization of Aniline. In a 400-ml. beaker dissolve 9.3 g. (9 ml, 0.1 mole) of aniline in 10 ml. of
concentrated hydrochloric acid and 50 ml. of water.
Cool the solution to 0°-5° by the introduction of 50-75
g. of ice and diazotize half of the aniline by the addition
of 3.5 g. (0.05 mole) of sodium nitrite dissolved in a
little water. Set the solution aside for about 15 minutes
while you prepare some aniline hydrochloride that will
be needed in Part II (Note 1).
15-30
30-60
[Prepare the aniline hydrochloride as described in
Part II.]
Coupling of Benzenediazonium Chloride with Aniline.
Return to the original experiment and add to the solution, now containing approximately 0.5 mole of aniline
and 0.5 mole of benzenediazonium chloride, a solution
of 25 g. of sodium acetate in 100 ml. of water. A voluminous precipitate of diazoaminobenzene is formed.
Stir the mixture until the precipitate is well coagulated
and then collect the precipitate on a Buchner filter.
Remove as much liquid as possible by suction and wash
the solid twice on the filter with small quantities of
water.
Again remove the water by suction and press the
crystals with the flat top of a large glass stopper in order
to obtain a compact cake of diazoaminobenzene that is
fairly dry. Remove about 0.5 g. of the diazoaminobenzene for recrystallization from ethanol and observation
of the melting point. The recorded melting point is 98°.
Silver Salt. Dissolve about 0.1 g. of diazoaminobenzene in ethanol and add 1 ml. of an alcoholic solution
of silver nitrate. The orange-colored precipitate has the
composition C 6 H 5 —N=N—N(Ag)—C fl H 5 .
II.
15-30
AMINOAZOBENZENE
Introduction. For the conversion of diazoaminobenzene to aminoazobenzene, the former compound is dissolved in aniline and warmed with aniline hydrochloride,
which is the acidic agent.
Preparation of Aniline Hydrochloride. In a 100-ml.
beaker stir 10 ml. of aniline with 25 ml. of concentrated
hydrochloric acid. Cool the mixture in ice until a thick
paste is obtained. Thin the paste by addition of 10-15
ml. of ether and collect the crystals of aniline hydrochloride on a small Buchner funnel. Suck the crystals
as dry as possible, rinse them on the filter with about
10 ml. of ether and spread them out on a sheet of
paper to dry in the air.
Conversion of Diazoaminobenzene to Aminoazobenzene. Transfer the moist solid cake containing the
major portion of the diazoaminobenzene to a 250-ml.
beaker, add the crystals of aniline hydrochloride prepared above, and 10-15 ml. of aniline. Stir the mixture
well and heat the beaker in boiling water or on the
steam bath for 30 minutes to bring about the molecular
rearrangement. At the end of this time remove the
beaker from the steam bath, cool the contents to 40°50°, add 25 ml. of glacial acetic acid, and pour the
well stirred solution into 200 ml. of cold water for
precipitation of the aminoazobenzene (Note 2).
Stir the mixture well until the aminoazobenzene settles readily leaving a clear supernatant liquid. Bring
the solid material onto the Buchner funnel and wash
it twice with water. After removing as much water as
possible by suction, press the crystals well with the
flat top of a glass stopper.
Recrystallize the crude brown product by transferring
it from the Buchner funnel to a 250-ml. flask that is
fitted with a stopper bearing a piece of glass tubing
about 18 inches long and proceeding in the following
manner:
Introduce 100 ml. of ligroin (b.p. 90°-100°) into
the flask, replace the stopper and tube, and heat the
flask on the steam bath to dissolve as much of the
solid material as possible. (CAUTION: Keep clear of
lighted Bunsen burners; do not give mishap a chance!)
Remove the flask from the steam bath, allow the dark
solid material to settle for a moment and decant the
clear solution into a 250-ml. beaker, being careful to
retain all dark material in the flask. The clear solution
in the beaker quickly deposits small aggregates of
153
154
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
orange-colored needle-shaped crystals of aminoazobenzene when cooled in ice.
As soon as crystallization appears to be complete
(about 3 minutes), the crystals are collected on the
suction filter and the filtrate returned to the flask for
a second extraction of the crude material by heating
on the steam bath, decanting, and cooling as before.
Repeat this extraction process as long as a worthwhile
yield of crystals is obtained. Combine the various crops
of crystals, dry them, and observe the melting point.
The recorded melting point is 127°. Yield 5-6 g.
NOTES
1. Aniline and benzenediazonium chloride do not combine in strongly acidic solution. In order to bring about
the combination with the formation of diazoaminobenzene,
the acidity of the solution is diminished by the addition of
sodium acetate. In the present experiment the concentration of hydrochloric acid is so low that some diazoaminobenzene may separate even before the sodium acetate is
added. This, of course, does no harm.
2. Both aniline and aminoazobenzene are basic and,
consequently, form salts with acids. The aminoazobenzene
is a weaker base than aniline, however, and its acetate is
so nearly completely hydrolyzed in dilute water solution
that the free base precipitates. Aniline, a stronger base,
remains in solution as its salt with acetic acid.
QUESTIONS
1. Which of the following amines may be diazotized?
(a)
(c)
(e)
(g)
(i)
ethylamine
trimethylamine
p-toluidine
diphenylamine
/7-nitroaniline
(b)
(d)
(f)
(h)
(j)
ethylenediamine
aniline
benzylamine
dimethylaniline
2,4-dichloroaniline
2. Write equations to show the diazoamino compound
formed when (a) benzenediazonium chloride reacts with
/7-bromoaniline and (b) when p-bromobenzenediazonium
chloride reacts with aniline. How do you account for the
fact that the two products are indistinguishable?
3. How would you separate a mixture of aniline and
aminoazobenzene?
4. What products will be formed by strong reduction of
aminoazobenzene (as with metal and acid)?
EXPERIMENT 61
Preparation and Properties of Phenol
(1)
(2)
C6H5—NH2 + NaN0 2 + 2H 2 S0 4
CeHs—N=N+, H S 0 4 - + H 2 0 — • C6H5—OH + N 2 + H 2 S0 4
lution vigorously with 20 ml. of carbon tetrachloride.
Introduction. Today's experiment for the production Ten ml. of concentrated hydrochloric acid added to
of phenol involves (1) the diazotization of aniline and the contents of the funnel at this point will break the
emulsion and aid in the rapid settling of the carbon
(2) the hydrolysis of the benzenediazonium salt.
[CAUTION: Phenol, except in dilute solution, causes tetrachloride.
Remove the lower layer of carbon tetrachloride which
burns on the skin. Should any concentrated phenol
come in contact with the hands wash them at once contains some phenol, extract the aqueous solution
with a second 20-ml. portion of carbon tetrachloride,
with alcohol and with water.]
Procedure. Into a 1-liter flask pour 300 ml. of water and combine the two extracts with the phenol that
and 30 ml. of concentrated sulfuric acid. Then, with was separated directly. Should there be a small upper
continuous shaking of the flask, add 28 g. (27.5 ml., layer of water on the carbon tetrachloride solution,
0.3 mole) of aniline in small portions so that the remove it with a separatory funnel and dry the lower
precipitate of aniline acid sulfate, (C 6 H 5 NH3)+HS04-, layer over a little anhydrous magnesium sulfate.
Distill the solution collecting three fractions: (1)
will be finely divided.
Cool the solution to 25°-30° by rotating the flask up to 100°, consisting chiefly of carbon tetrachloride,
in a bath of ice and water and then introduce into the (2) 100°-170°, a small fraction containing both phenol
flask 200-250 g. of crushed ice to bring the temperature and carbon tetrachloride, and (3) 170°-182°, phenol.
of the solution below 10°. Diazotize the aniline by the Redistillation of the second fraction will give a little
portion-wise addition of 22 g. of sodium nitrite dis- more phenol which is added to the main portion. The
solved in 100 ml. of water. Shake the flask well during product should solidify when placed in a bath of cold
the addition of the sodium nitrite, which will require water. Yield 16-18 g.
The tarry material remaining in the flask in which
about 3 minutes.
Let the solution stand for 10 minutes to allow time the main reaction was conducted may be removed by
for the diazotization reaction to proceed, then warm the washing with warm sodium hydroxide solution.
flask over the Bunsen burner until a thermometer imII. PROPERTIES OF PHENOL
mersed in the liquid records a temperature of 45°-50°.
AND OTHER PHENOLIC COMPOUNDS
At this point the burner is removed, as the exothermic
1. Solubility in Water. Pour about 5 ml. of molten
hydrolysis of the diazonium salt during the next 10-12
minutes will cause a slow rise in the temperature of the phenol, obtained from the side shelf, into a large test
liquid to about 70°. During this process, stir the con- tube and add an equal volume of water. Insert a
tents of the flask gently with a stirring rod to facili- thermometer and warm the contents of the tube to about
tate a smooth and continuous evolution of nitrogen. 70°, at which temperature the water and phenol are
After most of the nitrogen has escaped, allow the completely miscible. Stir the solution gently with the
liquid to attain a temperature of 70°, either auto- thermometer and allow it to cool slowly, noting the
matically or with a little help from the Bunsen burner, temperature at which clouding occurs.
[Note: At room temperature phenol is soluble in waadd a few boiling chips, connect the flask with a condenser for distillation and collect 350 ml. of distillate ter to the extent of about 10 per cent and water in
phenol to about 27 per cent. The solubilities increase as
(30-35 minutes of distillation).
the temperature rises; the recorded temperature for com[During this half hour perform the short experiments plete miscibility is 65.3°, or higher.]
given in Part II.]
2. Solubility in Alkali. Add a little phenol to dilute
Extraction of the Phenol from the Distillate. To the (5 per cent) sodium hydroxide solution and note the
phenolic distillate add 100 g. of clean salt (NaCl) and ready solubility of sodium phenoxide. Equation.
3. Color Reaction with Ferric Chloride. Add a drop
stir the mixture until the salt dissolves. Note that some
phenol is "salted out" as it is less soluble in brine than of phenol to 25 ml. of water. To a portion of this soin pure water. Pour the liquid into a separatory funnel lution add a few drops of ferric chloride solution and
and separate directly as much of the phenolic layer note the purple coloration produced. Dilute the original
solution of phenol and make repeated trials to show
as possible.
Return the aqueous solution to the separatory funnel the delicacy of this test for phenol. Many other phenolic
and extract the dissolved phenol by shaking the so- compounds show similar color reactions.
155
I. PREPARATION OF PHENOL
0-90
55-90
90-140
• C 6 H 6 —N=N+, H S O r + NaHS0 4 + 2H 2 0
50-60°
156
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
4. Reaction with Bromine Water. Dissolve 1 or 2
drops of phenol in a little water and add bromine water
until a yellow coloration in the well-shaken mixture
indicates that a slight excess of bromine is present.
Remove the excess bromine by the addition of a little
sodium bisulfite. The white precipitate of 2,4,6-tribromophenol (m.p. 96°) has such low solubility that
it is often used not only as a qualitative test for phenol
but also as a quantitative measure of the amount of
phenol present. Equation.
5. Comparative Reducing Power of Phenol, Resorcinol, Hydroquinone, and Pyrogallol. Dissolve 0.2 g.
of phenol in 10 ml. of water and test the reducing
power of this solution upon Tollens' reagent. Repeat
the experiment replacing the phenol, in turn, by resorcinol, hydroquinone, and pyrogallol. Results? How do
the increased number of hydroxyl groups and their
relative positions influence the reducing power of the
phenolic compounds? Do the polyhydric phenols have
greater solubility in water than does phenol?
QUESTIONS
1. Write equations to show the preparation of:
(a) phenol from chlorobenzene
(b) phenol from benzenesulfonic acid
(c) p-cresol from p-toluidine
(d) guaiacol (monomethylether of catechol) from
0-anisidine.
2. Write the formula and name for the chief product
formed by the reaction of phenol with each of the following reagents:
(a) NaOH solution
(b) CH3COCl
(c) (CH3CO)20
(d) C6H5COCl
(e) (C3H7CO)20
(f) dil. HN0 3
(g) bromine water
(h) C6H5N2+, Cl~
(i) NaOH + C2H5I
3. To what approximate dilution does the ferric chloride
test for phenol appear to be sensitive? Propose a structure
for the colored product.
4. (For Specially Interested Students) Is phenol a
stronger or a weaker acid than carbonic acid? Propose and
carry out an experiment designed to prove your answer.
EXPERIMENT 62
I. Preparation of Phenetole
C6H6—OH + (C 2 H 5 ) 2 S0 4 + 2NaOH -> C6H5—O—C2H5 + C ^ — O H + Na 2 S0 4 + H 2 0
II. Solid Derivatives of Phenol
Introduction. Aromatic ethers such as diphenyl ether
or phenyl ethyl ether (phenetole) are not easily obtained in good yield by heating a phenolic compound,
or a mixture of a phenol and an alcohol, with sulfuric
acid or other dehydrating agent. The laboratory procedure usually followed for the preparation of such an
ether is a variation of the method devised by Williamson
for the production of aliphatic ethers.
In today's experiment we shall use the Williamson
method for the preparation of phenetole by heating a
solution of sodium phenoxide with diethyl sulfate. In the
Ullmann variation of the Williamson reaction, the alkaline salt of a phenol is heated with an aromatic halide
in which the halogen is activated by the presence of
one or more nitro groups in the molecule. Thus, when
potassium phenoxide is heated with p-nitrochlorobenzene, usually in the presence of copper powder as a
catalyst, phenyl 4-nitrophenyl ether is obtained.
Further modifications of the Ullmann process employ, as the active halogen compound, 4-nitrofluorobenzene or 2,4-dinitrochlorobenzene. The use of the
latter of these nitrated aromatic halides is illustrated
in section (d) of Part II in today's assignment.
t-25
II. SOLID DERIVATIVES OF PHENOLIC COMPOUNDS
Introduction. For the identification of an unknown
phenolic compound it is advantageous to prepare
several of its solid derivatives so that the identity of
the phenolic compound in question may be established
(1) by the melting points of these crystalline compounds, and (2) by their "mixed melting points" with
known samples. Four derivatives of phenolic compounds which, in most instances, are well crystallized
solids that may be prepared easily are (a) the bromine
substitution product, (b) the benzoyl derivative, (c)
the substituted ester of carbamic acid (urethane type)
made by reaction of the phenol with phenyl isocyanate,
and (d) the substituted diphenyl ether obtained from
the phenol and 2,4-dinitrochlorobenzene.
(a) The Bromine Derivative. Reaction of a phenolic
compound with bromine water, or bromine in acetic
acid solution, results in substitution of bromine atoms
at positions ortho and para to the hydroxyl group unless those positions are firmly held by other substituents.
For example, trisubstitution readily occurs in phenol
yielding 2,4,6-tribromophenol, whereas but two bromine atoms are substituted in p-cresol. In the latter
instance, the bromine atoms occupy the two positions
I. PREPARATION OF PHENETOLE
ortho to the hydroxyl group. No reaction occurs elseProcedure. In a 200-ml. flask dissolve 16 g. of sodium where in the p-cresol molecule because the positions
hydroxide in 50 ml. of water and add 18.8 g. (0.2 meta to the hydroxyl group are not activated and the
mole, about 18 ml.) of molten phenol or the equivalent methyl group is securely attached to the benzene ring
quantity of the 90 per cent liquid phenol. To this so- at the para position.
A feebly held substituent, such as the carboxyl group
lution add 30.8 g. (0.2 mole, 27 ml.) of diethyl sulfate
in portions of 2 or 3 ml. at a time and shake the flask in salicylic acid, is replaced by bromine; thus salicylic
well after each addition. If the mixed liquids should acid and bromine water give a precipitate of 2,4,6begin to boil, cool the flask in cold water. Note that tribromophenol with elimination of carbon dioxide.
Tribromophenol. Dissolve 0.5 g. of phenol in 10 ml.
the reaction is rapid and that a layer of pleasant-smelling phenetole (phenyl ethyl ether) quickly rises to the of water and add bromine water to the solution until
surface of the liquid. In order to bring the reaction the color of the solution indicates that a slight excess of
nearly to completion, connect the flask with a reflux bromine is present. Add a little sodium bisulfite solution to remove the excess bromine. Remove the precondenser and boil the liquid for 10 minutes.
At the conclusion of this period cool the flask and cipitate of 2,4,6-tribromophenol by filtration, wash it
pour the contents into a separatory funnel for removal with water, and recrystallize it from a little hot ethyl
of the upper layer of phenetole. Extract any small alcohol. The purified crystals should melt at 96°.
(b) The Benzoyl Derivative (Production of Phenyl
amount of phenetole remaining in the alkaline solution
by shaking the solution with 15-20 ml. of carbon tetra- Benzoate by the Schotten-Baumann Reaction). Dischloride and combine this extract with the phenetole solve approximately 1 g. of phenol in 10 ml. of water
previously separated. Dry the combined lot with a few with the addition of 10 ml. of a 10 per cent solution
grams of magnesium sulfate, decant from the drying of sodium hydroxide. Add 10-12 drops of benzoyl
agent, and distill the liquid, collecting the portion boil- chloride and shake the tube for a few minutes. The
ing from 165°-172°. The yield is usually about 18-20 g. odor of benzoyl chloride soon disappears and a pre157
60-85
85-110
158
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
cipitate of phenyl benzoate forms. Equation. Remove
the precipitate by filtration. After recrystallization from
a little hot ethyl alcohol the product melts at 70°.
(c) The Substituted Ester of Carbamic Acid {A
compound of the Urethane Type). Phenyl isocyanate
reacts with a phenol more slowly than does an amino
compound, and usually a little anhydrous aluminum
chloride must be added as a catalyst. The following
procedure for the combination of phenyl isocyanate
with p-cresol is a typical illustration of the method to
be used.
110-140
Dissolve 5 g. of p-cresol in 40 ml. of dry benzene
and, at the hood, add 4 g. of phenyl isocyanate (a
powerful lachrymator) and 5 g. of anhydrous aluminum
chloride. Heat is evolved and it may be necessary to
cool the flask somewhat. Let the reaction proceed for
10 minutes and then pour the mixture cautiously into
100 ml. of ice water. Separate the benzene layer, cool
it in ice, and precipitate the ester by the addition of
ligroin. Collect the solid ester on a filter and recrystallize it from ligroin, m.p. 114°.
140-160
(d) The Ether of 2,4-Dinitrophenol. Dissolve 0.3 g.
of phenol in 10 ml. of ethanol and add 10 drops of
10 per cent sodium hydroxide solution and 0.5 g. of
2,4-dinitrochlorobenzene. Heat the solution to boiling
for a few minutes. If the phenyl 2,4-dinitrophenyl ether
separates as an oil, add a little more alcohol to bring
it into solution in the boiling solvent and set the tube
aside until the product crystallizes. After recrystallization from a small amount of ethanol, the ether melts
at 71°. Many other phenols react in a similar manner
though sometimes at a slower rate; consequently the
period of heating the reactants may vary from 2 to 20
minutes.
QUESTIONS
1. Write the formula for the following ethers and esters
of phenolic compounds:
(a) anisole (phenyl methyl ether)
(b) phenetole (phenyl ethyl ether)
(c) hydroquinone dimethyl ether
(d) resorcinol diethyl ether
(e) hydroquinone dibenzoate
(f) 4-chlorophenyl 4-nitrophenyl ether
(g) benzyl phenyl ether
(h) 2,4-dichlorophenyl 2,4-dinitrophenyl ether
2. Suggest convenient means for preparing each of the
above ethers.
3. May alkyl halides be used in place of alkyl sulfates
in the production of ethers of phenolic compounds?
4. Write the equation for the reaction of phenol with
phenyl isocyanate. Why does phenol react more slowly
than an amine? Name the product. Does it exist to any
appreciable extent in tautomeric forms? Can you suggest
why, or why not?
EXPERIMENT 63
Preparation of o- and ^-Nitrophenol
OH
OH
OH
N02
+ H20
N02
Introduction. The nitration of phenol with concen- Bunsen burner to remove water by distillation until
trated nitric and sulfuric acids leads to the formation the contents of the flask do not exceed 250 ml. in
of 2,4,6-trinitrophenol (picric acid). Nitration of the volume. Heat the liquid to the boiling point and filter
phenol with dilute nitric acid, alone, introduces but it through a fluted filter paper. To the hot filtrate add
one nitro group and gives a satisfactory method for the 2 g. of decolorizing carbon, again heat to boiling, and
laboratory preparation of ortho- and para-nitrophenol. filter to remove the carbon.
The o-nitrophenol is separated from its para isomer by
Place an empty 400-ml. beaker into an ice bath and
distillation in steam.
add to it a few ml. of the hot solution. Stir the chilled
Procedure. In a 100-ml. graduated cylinder measure solution with a glass rod to induce crystallization of
25 ml. of concentrated nitric acid and fill the cylinder the p-nitrophenol. Such rapid cooling brings about crysto the 100-ml. mark with water. In a small beaker tallization of the p-nitrophenol and thus avoids the
weigh 18.6 g. (0.2 mole) of molten phenol and add separation of the material as a dark oil which usually
2-3 ml. of water to keep the phenol liquid or, as an occurs if the solution is allowed to cool slowly.
When crystallization of the first small portion of the
alternative, if the storekeeper supplies the 90 per cent
"liquid phenol," use 20 ml. of it. Pour the diluted nitric p-nitrophenol has been attained, add another 2-5 ml.
acid into a 500-ml. flask and add about 2 ml. of the portion of the hot solution and stir briskly as before.
Continue adding small amounts of the hot solution to
liquid phenol.
The immediate nitration reaction is marked by the the chilled beaker in this manner until the entire
appearance of a dark coloration in the solution and by quantity of solution has been used. Collect the crystals
the evolution of heat. Cool the solution if necessary to of p-nitrophenol on the BUchner funnel and dry them in
keep the temperature below 60° and so regulate the ad- an oven at about 60°. If further purification is desired,
dition of small portions of the phenol and the cooling of recrystallize the product from hot benzene. (CAUTION!
the flask that the temperature of the solution is main- Use a steam bath. Guard against fire.) The recorded
melting point of p-nitrophenol is 114°.
tained as nearly as possible in the 45°-55° range.
Weigh the o-nitrophenol and p-nitrophenol sepaAfter the introduction of the phenol, which requires
about 5 minutes, the flask is shaken well (or stirred rately and calculate the yield of each isomer.
mechanically) for an additional 10 minutes. Cool the
COMPARATIVE ACIDITY OF PHENOL
flask until the temperature of the mixture is 25°-30°
AND NlTROPHENOLS
and pour the contents of the flask into a small sepaPrepare aqueous solutions of phenol, o-nitrophenol,
ratory funnel where the lower oily layer is withdrawn
into another flask for steam distillation. The upper p-nitrophenol, 2,4-dinitrophenol, and 2,4,6-trinitrophenol (picric acid) by shaking about 0.5 g. of each
aqueous layer may be discarded.
The heavy oily layer, consisting chiefly of 0-nitro- phenolic compound with 10 ml. of water. Test each
phenol, p-nitrophenol, and some tarry oxidation prod- water solution with litmus paper. Result? Add a little
ucts of indefinite composition, is subjected to distil- solid sodium bicarbonate to each solution. In which
lation in steam until all of the 0-nitrophenol has been tubes is carbon dioxide evolved? Rate these phenolic
carried over into the receiver. This will require the compounds in the order of their acidity.
collection of about 400 ml. of distillate. If the o-nitrophenol (m.p. 45°) does not solidify at once in the
receiver, it will do so upon the addition of a little ice.
QUESTIONS
p-Nitrophenol. The p-nitrophenol, almost nonvolatile
1. How do you account for the observation that o-nitroin steam, remains in the distillation flask partly in so- phenol distills with steam far more rapidly than does
lution in the hot water and partly as a dark-colored p-nitrophenol?
oil. Add sufficient water to the flask to bring the total
2. Starting from o-nitrophenol or p-nitrophenol and such
volume of liquid to 200-250 ml. or, if the volume of inorganic reagents as may be needed, show by outline
liquid is greater than 250 ml., heat the flask with the equations how it would be possible to obtain:
159
160
(a) onitroanisole
(b) oanisidine
(c) guaiacol
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
(d) p-nitrophenetole
(e) p-phenetidine
(f) hydroquinone mono-ethyl
ether
3. How may 2,4,6-trinitrophenol (picric acid) be made
(a) from phenol, (b) from chlorobenzene? What is picryl
chloride?
EXPERIMENT 64
phenol and make its derivatives. The mixed melting
point test applied to your known and unknown derivatives will prove the identity of your sample and you may
make your report to the instructor.
IDENTIFICATION OF AN UNKNOWN
PHENOLIC COMPOUND
Obtain from the instructor an unknown phenolic
compound (which will be one of those in the following
table) and make two derivatives of it by the procedures
given in Experiment 60. Also, determine whether a
halogen is present by application of the Beilstein test
(page 4 2 ) . The unknown may be in the form of
a pure substance or as a dilute water solution. In the
later case, prepare only the benzoyl and bromine derivatives.
No attempt should be made to use phenyl isocyanate
with a water solution since it reacts almost instantly
with water to give diphenyl urea. (Remember that
phenyl isocyanate is a powerful lachrymator. Keep it
in the hood.)
The most probable identity of your unknown may be
deduced from the melting points of its derivatives. Then
obtain from the storeroom a known sample of this
UNKNOWN REPORT
M.p.
or B.p.
Unknown
Possibility
Possibility
Possibility
Possibility
Presence
of Halogen
1
2
3
4
MELTING POINTS OF DERIVATIVES
Unknown
Possibility
Possibility
Possibility
Possibility
Conclusion
Bromine
Benzoyl
Urethane
Ether
TABLE 3. MELTING POINTS OF DERIVATIVES OF PHENOLIC COMPOUNDS
Phenol
Phenol
o-Chlorophenol. . . .
p-Chlorophenol....
p-Bromophenol....
2,4-Dichlorophenol.
o-Cresol
m-Cresol
p-Cresol
Guaiacol
p-Nitrophenol
Benzoyl
Derivative
70
b.p. 315
86
102
97
b.p. 307
54
71
56
142
Ester with
CeHsNCO
Bromine
Derivative
2,4-Dinitrophenyl Ether
126
121
138
144
112
145
122
114
136
123
96
76
92
96
68
57
82
49
94
141
71
99
126
137
119
90
74
93
128
114
[Begin Section 8 of Experiment 65.]
161
EXPERIMENT 65
Properties of Benzaldehyde
Introduction. Benzaldehyde has many properties that
are analogous to those of aliphatic aldehydes, such as
acetaldehyde, but it also has other properties in which
it differs from most of its aliphatic counterparts. This
latter type of behavior, in large part, centers around
the fact that benzaldehyde—-like formaldehyde, trimethylacetaldehyde, and other tertiary aldehydes—has
no hydrogen atom on the alpha carbon. The following
experiments illustrate several of these properties.
[Note: Section 8 of this experiment should have been
started at the previous laboratory period.]
0-10
10-15
15-30
30-40
40-50
50-70
1. Solubility. Test the solubility of benzaldehyde in
water, alcohol, and ether.
2. Atmospheric Oxidation. By means of a glass rod
spread a drop of benzaldehyde into a thin film on a
glass plate or watch glass. Examine the material at
the end of the laboratory period or at the time of the
next laboratory session. Result?
3. Addition Product with Sodium Bisulfite. Shake
1 ml. of benzaldehyde with 5 ml. of a saturated solution
of sodium bisulfite for a few minutes and then cool the
mixture in an ice bath. What is the crystalline product?
Equation.
4. Reaction with Phenylhydrazine. Dissolve a few
drops of benzaldehyde in 5 ml. of ethanol and add a
few drops of phenylhydrazine. Result? Equation.
5. Reaction with Ammonia. Shake a few drops of
benzaldehyde with 10 ml. of concentrated ammonium
hydroxide solution, close the mouth of the test tube
with a stopper, and examine the material an hour or
two later. If no crystals of hydrobenzamide have
formed, let the tube stand until the next laboratory
period. Equation. Compare this behavior with the
analogous reactions of ammonia with formaldehyde;
with acetaldehyde.
6. Condensation with Acetone. To 20 ml. of ethanol
contained in a small flask, add 2 ml. of acetone, 4 ml. of
benzaldehyde, and 10 ml. of a 5 per cent solution of
sodium hydroxide. Fit the flask with a reflux condenser
(an air-condenser will serve) and boil the solution
gently for 5 minutes. Cool the flask and collect the dibenzalacetone (C 6 H 5 CH=CH—CO—CH=CHC 6 H 5 )
on a filter. When purified by recrystallization from
ethanol, the crystals melt at 111°. The production of
dibenzalacetone is often used for the identification of
either acetone or benzaldehyde. Equation.
7. Reducing Action. Test the reducing power of
benzaldehyde upon Tollens' reagent and Fehling's solution. Results? Compare with acetaldehyde.
8. Auto-oxidation and Reduction (Cannizzaro Reaction). In a 100-ml. bottle, fitted with a cork stopper,
shake 15 g. of benzaldehyde with a solution of 15 g.
of sodium hydroxide in 12 ml. of water until a permanent emulsion is produced. Set the bottle aside until
the next laboratory period.
Add a sufficient quantity of water to dissolve the
crystals of sodium benzoate which have separated and
extract the benzyl alcohol by shaking the liquid twice
with ether. About 25 ml. of ether should be used for
each extraction.
Separate the ether layer from the alkaline solution
(which is saved for isolation of the benzoic acid) and
dry it over anhydrous sodium sulfate. Distill the ether
from the water bath and then distill the residual benzyl
alcohol with the direct flame of a Bunsen burner. Benzyl
alcohol boils at 206°.
Obtain the benzoic acid by carefully acidifying the
alkaline solution with hydrochloric acid. Remove the
benzoic acid by filtration and purify it by recrystallization from hot water. Write the equation for the reaction involved in this experiment and calculate the
percentage yield of each product.
QUESTIONS
1. Write equations to show how benzaldehyde may be
prepared from
(a) benzyl chloride
(c) benzoic acid
(b) benzal chloride
(d) by a Friedel and Crafts
reaction
2. Show how sodium bisulfite may be used to purify
benzaldehyde.
3. Write equations to show how benzaldehyde will react
with the following reagents:
162
(a) hydroxylamine
(c) phosphorus pentachloride
(e) ethyl acetate
(basic cat.)
(g) phenylmagnesium
bromide
(b) semicarbazide
(d) acetaldehyde
(basic cat.)
(f) ethyl butyrate
(basic cat.)
(h) aniline
70-80
80-110
EXPERIMENT 66
Preparation of Acetophenone by a Friedel and Crafts Reaction
o
CeHe ~r CH3
AlCls
Introduction. A typical example of the Friedel
and Crafts reaction, employing anhydrous aluminum
chloride as the catalyst, ordinarily involves the reaction
between an aromatic hydrocarbon and an active halogen
compound. For the production of a ketone such as
acetophenone, benzene may be allowed to react with
acetyl chloride or, since acetyl chloride is rather too
vigorous in its reactivity, the acid chloride may be replaced with the less active acetic anhydride.
The benzene used must be well dried over calcium
chloride. The acetic anhydride should have a boiling
range of 137°-140° to insure freedom from significant
quantities of acetic acid. The anhydrous aluminum
chloride should be in small lumps or in the form of a
coarse powder, should fume in moist air, and should
make a hissing sound upon the addition of a little water.
0-25
Procedure
Connect a 500-ml. flask to a reflux condenser, dropping funnel and one of the traps for absorption of escaping hydrogen chloride as shown in Figure 32. In the use
» C 6 H 5 —C—CH 3 + CH 3 —C—OH
trap and back up into the reaction flask where the
presence of water may cause a vigorous (or even violent) reaction. Remember that all laboratory work requires care and thoughtfulness.
When the apparatus is assembled, disconnect the
flask and put into it 40 g. of anhydrous aluminum
chloride and 65 ml. of dry benzene. (Weigh the aluminum chloride rapidly to avoid absorption of atmospheric
moisture and be sure to replace the cap on the stock
bottle.) Join the flask to the condenser and, during a
period of about 10 minutes, add through the dropping
funnel 20.4 g. (about 19.6 ml., 0.2 mole) of acetic
anhydride. From time to time, loosen the clamp on the
flask and shake the flask in order to mix the reactants
thoroughly. If the heat of the reaction causes the benzene to boil, decrease the rate of addition of the acetic
anhydride and, if necessary, bring a cooling bath up
around the flask.
After all of the acetic anhydride has been added and
the vigor of the reaction has diminished, heat the flask
on the steam bath for 20 minutes. Then remove the
Gentle Stream
of Water-
FIG. 32. Apparatus for a Friedel and Crafts reaction with
absorption of escaping hydrogen chloride.
of a trap such as types B or C in which water from the steam bath, cool the flask in cold water, and pour its
line is employed, care must be exercised in regulating the contents slowly into a 600-ml. beaker which contains
rate of flow to a small gentle stream. The pressure on 75 ml. of concentrated hydrochloric acid and about
the water line can easily force water into the trap faster 150 g. of crushed ice.
than it will flow through the exit tube causing the
If any precipitate of basic aluminum salt remains
water, if the flow is not properly regulated, to fill the after the mixture is well stirred, add enough hydro163
25-70
164
70-140
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
chloric acid to bring it into solution. The beaker now
contains an acidic aqueous solution of aluminum
chloride and an upper layer consisting of benzene and
acetophenone.
By means of the separatory funnel remove the upper
layer and extract the aqueous layer with 30-40 ml. of
benzene. Combine the two benzene solutions and wash
them once with dilute sodium hydroxide solution and
then with water. Dry the solution of benzene and acetophenone over magnesium sulfate, decant from the drying agent and distill the liquid.
Benzene (b.p. 80°) does not distill rapidly from the
steam bath but, with reasonable care, may be distilled
with the aid of the burner. (Some laboratories have
special arrangements for the distillation of benzene.
If so, the instructor will give the necessary directions.)
The acetophenone boils at 202°. Yield 16-20 g.
QUESTIONS
See questions following Experiment 67.
EXPERIMENT 67
Preparation of Benzophenone by a Friedel and Crafts Reaction
(1)
2CeH6 + CC14
Aids
• C6H5—€C12—CeHg + 2HC1
O
(2)
QH5—CC12—C6H5 + H 2 0
Introduction. The reaction between benzene and carbon tetrachloride, in the presence of anhydrous aluminum chloride, may proceed in three stages as shown
in equations I, II, and III.
0-25
25-65
II
> C6H5—C—C6HB + 2HC1
drogen chloride within 2 minutes, warm the flask gently
with the Bunsen burner. Once the reaction has started,
add more of the benzene-carbon tetrachloride solution
at intervals of a few minutes in order to maintain a
gentle and continuous evolution of hydrogen chloride.
I. C6H6 + CCI4 ^ t C6H6CC13 + HC1
The temperature of the reaction flask should be at
30°-40°; i.e., just perceptibly warm to the hand. If
II. C6H6CC13 + C 6 H 6 ^ C6H6—CC12—C6H6 + HC1 the temperature rises above this point, cool the flask
by bringing a pan of cold water up around it. About
IIA. CeHg—CC12—C6H6 + H 2 0
>
15 minutes will be required for the addition of all of
O
the reactants. Thereafter heat the flask on the steam
II
C6HB—C—C6H5 + 2HC1 bath, or in a pan of hot water, for 20 minutes in order
to bring the formation of benzophenone dichloride
nearly to completion.
III. (C6H6)2CC12 + C 6 H 6 ^ (C6H6)3CC1 + HC1
The next step is the removal of the anhydrous alu65-85
Under ordinary conditions it is difficult to stop the re- minum chloride by addition of water. Anhydrous aluaction at the completion of the first stage (equation I) minum chloride reacts with water so vigorously that
but the process may be terminated conveniently at the water must be added to the cooled reaction mixthe end of the second or third stage by control of the ture in small portions. Therefore, replace the steam
quantity of benzene used. If an excess of benzene is bath by a bath of ice and water and pour 50 ml. of
avoided, as is true in today's experiment, the production water into the dropping funnel. Allow the water to
of diphenyldichloromethane, commonly called benzo- drop slowly into the flask and shake the flask frequently
phenone dichloride (equation II), may be easily by removing the cooling bath momentarily and also
achieved. Hydrolysis of the dichloride (equation II A) loosening the clamp.
provides a convenient method for the preparation of
The heat of hydration of the aluminum chloride may
benzophenone.
cause the carbon tetrachloride to boil gently. When all
[Note: Both the carbon tetrachloride and benzene of the water has been added and the exothermic hyused for this experiment must have been dried previ- drolysis process has been completed, transfer all the
ously over calcium chloride for several hours.]
material to a larger flask for steam distillation (Note 1).
Distillation with steam not only removes the excess 85-130
Procedure
carbon tetrachloride and any remaining benzene but
A dry 500-ml. flask is fitted with a dry reflux con- also accomplishes the hydrolysis of benzophenone didenser, dropping funnel, and trap for the absorption of chloride to benzophenone as shown in equation IIA.
escaping hydrogen chloride as shown in Figure 32. The Although the benzene and carbon tetrachloride are retrap may be any of those illustrated. (CAUTION: If moved rapidly, the steam distillation should extend over
trap B or C is used, be sure that the flow of water is a period of 45-50 minutes for completion of the hyregulated so that water cannot be sucked back into the drolysis of the dichloride to the ketone (Note 1).
The flask is then cooled and the contents poured 130-170
reaction flask, because water will react with the aninto a large separatory funnel where the upper layer
hydrous aluminum chloride in a violent manner.)
Into the flask place 35 g. of anhydrous aluminum of benzophenone is separated. The aqueous layer is
chloride and 50 ml. of dry carbon tetrachloride. Pour returned to the separatory funnel for the extraction of
a solution of 30 ml. of dry carbon tetrachloride and any remaining benzophenone with 25-30 ml. of ben30 ml. of dry benzene into the dropping funnel. Allow zene. The benzene extract is combined with the main
5-10 ml. of the benzene-carbon tetrachloride solution portion of benzophenone and the resulting solution
to run into the reaction flask and shake the flask gently dried over magnesium sulfate, separated from the drying
(loosen the clamp momentarily, if necessary) in order agent, and distilled.
After removal of the benzene, the residual benzoto mix the reactants.
If the reaction does not begin with evolution of hy- phenone may be distilled at atmospheric pressure, al165
166
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
though distillation under diminished pressure is to be
preferred (see Figure 28, page 102). Its boiling point
is 305.9° at 760 mm., and 185° at 15 mm. Yield 2025 g.
On cooling, the benzophenone usually solidifies to
the stable rhombic crystalline form (called the a. form)
melting at 48.1°. There are two other modifications,
known as /? and y, which melt at 26.5° and 45.8°,
respectively. If your specimen does not solidify on cooling, add a crystal of the stable rhombic form and allow the material to stand.
NOTE
1. If the preparation cannot be completed in one laboratory period, the mouth of the flask may be closed
tightly with a stopper and set aside at either of these points.
QUESTIONS
1. What ketone will be produced in reactions of the
Friedel-Crafts type by the following pairs of reactants?
(a) benzene and benzoyl chloride
(b) benzene and p-bromobenzoyl chloride
(c) bromobenzene and acetic anhydride
(d) toluene and /7-nitrobenzoyl chloride
2. Which of the following alcohols or ketones will give
the haloform reaction?
(a) C6H6—CO—C6H6
(b) p-CH3C6H4—CO—C6H6
(c) C6HB—CO—CH3
(d) CH30—C6H4—CO—CH3
(e) C6H5—CH2—CH2OH
(f) C6H5—CHOH—CH3
3. Is benzophenone dichloride hydrolyzed relatively
easily or difficultly? How can you account for its behavior
on the basis of its structure?
EXPERIMENT 68
Benzophenone Oxime and Its Rearrangement to Benzanilide
(1)
(C6H 5 ) 2 C=0 + H 2 NOH
> (C 6 H 5 ) 2 C=NOH + H 2 0
O
(2)
(C 6 H 5 ) 2 C=NOH —
I. PREPARATION OF THE OXIME
0-70
70-75
To a solution of 5.4 g. (0.03 mole) of benzophenone
and 6 g. of hydroxylamine hydrochloride in 75 ml. of
ethanol contained in a 500-ml. flask, add a solution of
10 g. of sodium hydroxide in 50 ml. of water. Attach
the flask to a reflux condenser and boil the solution
gently for 40 minutes. Remove the flask from the condenser, add 300 ml. of cold water, and remove any
unchanged benzophenone by filtration. Add a few lumps
of ice to the filtrate and acidify it with dilute sulfuric
acid to precipitate the benzophenone oxime.
Collect the oxime on a Biichner filter, press it as dry
as possible, spread it into a thin layer so that it will dry
quickly, and place it in an oven at 70°-80°. The dry
oxime, of which the yield is about 5 g., will be needed in
Part II of this experiment. Recrystafiize a small portion
of the product from ethanol and determine its melting
point. The recorded melting point is 141°.
Test the solubility of benzophenone oxime in dilute
sodium hydroxide solution. If it dissolves, acidify the
solution with hydrochloric acid. Is there a precipitate?
II. BECKMANN REARRANGEMENT OF A KETOXIME
75-150
The phosphorus pentachloride used in this experiment should be weighed as rapidly as possible because
of the irritating odor and also because of its reaction
with moisture of the air. Weigh 5 g. of the phosphorus
pentachloride from the bottle in the hood and enclose
the 5-g. portion in a glass-stoppered weighing bottle
such as is used in quantitative analysis.
In a small flask dissolve 4.0 g. of benzophenone
oxime in 50 ml. of absolute ethyl ether (previously
H
CeHg—C-N—CeH 5
dried over sodium). Cool the flask in an ice bath and
add about 1 g. of the phosphorus pentachloride. When
the heat of reaction subsides add another small portion
of the phosphorus pentachloride and continue in this
manner until all of the material has been added.
Mix the reactants well with a glass rod, remove most
of the ether by heating the flask on the steam bath,
and pour the residue onto a little crushed ice contained
in a mortar. Grind the lumps to a powder under water
and collect the solid benzanilide on a filter. Wash it
with water and recrystallize it from alcohol. Yield about
3 g. M.p. 161°.
QUESTIONS
1. Are oximes soluble in dilute alkali? Cf. acetoxime,
page 72, and dimethylglyoxime, page 75.
2. Write formulas to represent the syn and and forms of
benzaldoxime. Show how one may be distinguished from
the other.
3. May benzophenone oxime exist as syn and anti isomers?
4. Name and show the structures of the substituted
amides obtained by the Beckmann rearrangement of the
following oximes:
167
NOH
a.
CHa-^3
°
C^~Br
HON
b.
CH 3 -<(3
C
^>-Br
EXPERIMENT 69
Preparation of Triphenylcarbinol by a Grignard Reaction
OMgBr
CeHsMgBr +
(C^CO
-> C6H5—C—C6H5
OH
acid
CeH.5—C—CeHs
I
CeHs
Introduction. Grignard reagents react with ketones to
form tertiary alcohols. In the present experiment phenylmagnesium bromide and benzophenone (diphenyl
ketone) are used for the preparation of triphenylcarbinol. The absolute ether used in the process is prepared as described on page 46.
0-60
Preparation of the Grignard Reagent. Attach a
500-rnl. flask to a water-jacketed reflux condenser and
fit the top of the condenser with a stopper and dropping
funnel. Also file a rather deep groove in the stopper
at the top of the condenser to serve as an air vent.
Into the distilling flask put 2.4 g. (0.1 g. atomic wt.)
of clean magnesium turnings and add 50 ml. of absolute ether. Pour 15.7 g. (0.1 mole) of dry bromobenzene (or 0.1 mole of iodobenzene) and 50 ml. of dry
ether into the dropping funnel. Allow about 10 ml.
of the solution in the dropping funnel to run into the
flask and wait for the reaction to begin.
If the reaction does not begin within a few minutes,
add a crystal of iodine. If this fails, warm the flask
gently in warm water.
When the reaction has begun, the remainder of the
solution in the dropping funnel is added at such a rate
that the heat of reaction causes vigorous refluxing of the
ether. After all of the bromobenzene solution has been
added, heat the flask in a bath of warm water at 40°50° for 20-30 minutes, during which time practically
all of the magnesium dissolves. The ether should boil
steadily but not so rapidly that ether vapor escapes
from the top of the condenser.
60-110
Condensation of the Grignard Reagent with Benzophenone. Remove the flask from the bath of warm water
and cool it to 10°-15° in cold water. Through the
dropping funnel at the top of the condenser slowly
add, with constant shaking of the reaction flask, a solution of 18.2 g. (0.1 mole) of benzophenone in 50 ml.
of dry benzene. Allow the mixture to stand at room
temperature for 5 minutes and then heat it on the
water bath for 20 minutes to bring the reaction nearly
to completion. After cooling, pour the contents of the
flask onto 100 g. of ice, stirring well during the addition,
and add 15 ml. of concentrated hydrochloric acid to
dissolve the basic magnesium bromide.
110-170
Return the material to the round-bottomed flask and
distill as much of the ether and benzene as is possible
1
CeHs
on the steam bath. Then subject the residue to distillation with steam in order to remove the biphenyl and
unchanged bromobenzene. (Write the equation for the
side reaction by which biphenyl might be formed.)
During the steam distillation the triphenylcarbinol
usually solidifies. Cool the distillation flask and collect
the triphenylcarbinol on a filter. For purification, dissolve the crude product in hot alcohol (see page 94)
and cool the solution in ice until crystallization is complete. The yield is 12-15 g. M.p. 164°.
QUESTIONS
1. Write equations to show the products that are obtainable by the reaction of phenylmagnesium bromide with
each of the following reagents. (Note: It is to be understood that at the end of the main reaction dilute acid may
be added for liberation of the final product.)
(a)
(c)
(e)
(g)
(i)
H20
NH3
HCHO
C6H6CHO
HCOOC2H6
(k) C6H5COOC2H5
(b) C2H5OH
(d) (C2H6)2NH
(f) CH3CHO
(h) CH3COCH3
(j) CH3COOC2H5
CH2
(1)
O
/
CH2
2. From the list of reagents given in question 1, select
the one (or more than one) that converts a Grignard reagent, RMgX, into
(a)
(b)
(c)
(d)
(e)
(f)
(g)
the hydrocarbon, RH
the primary alcohol, RCH2OH
the secondary alcohol, RCHOHR'
the tertiary alcohol, RC(OH)(R')R"
the aldehyde, RCHO
the ketone, RCOR
the primary alcohol, RCH2CH2OH
3. Explain the role of ether in the formation of the
Grignard reagent.
168
EXPERIMENT 70
Benzoin, Benzil, and Benzilic Acid
H
HO
QH 6 —C=0
CHs—C=0
C*H6
Benzoin
Benzil
Potassium
benzilate
Introduction. When benzaldehyde is boiled in alcoholic solution with a little potassium cyanide as catalyst,
two molecules of benzaldehyde condense to give one
molecule of benzoin. Oxidation of benzoin yields benzil
(one of the most common a-diketones) which, in turn,
undergoes molecular rearrangement in alkaline solution
to give a salt of benzilic acid.
0-55
O
I. THE PREPARATION OF BENZOIN
A and B). Result? The benzoin is oxidized to benzil.
Note that benzoin and fructose are related in molecular
structure since each contains the —CO—CHOH—
grouping.
II. OXIDATION OF BENZOIN TO BENZIL
Place 6 g. benzoin in a small flask and add 20 ml.
of concentrated nitric acid (D = 1.42). Connect the
flask to a trap to absorb oxides of nitrogen (Figure 33)
In a 250-ml. flask place 10.6 g. (0.1 mole, 10.1 ml.)
of benzaldehyde, 35 ml. of ethanol and 1.5 g. of potassium cyanide. (Handle the cyanide with care.) Attach
the flask to a water-cooled reflux condenser the top of
which is fitted with an absorption trap to prevent the
possibility of any hydrogen cyanide escaping into the
room. (The reaction liberates no hydrocyanic acid but
it is wise to make certain that none can escape.)
A trap such as type B shown in Figure 32 is convenient, or as an alternative effective measure, any escaping gas may be led over the surface of 10 per cent
sodium hydroxide solution contained in an absorption
bottle. Boil the solution of reactants gently for 40
minutes and then set the flask in a bath of ice and
water for crystallization of the benzoin.
[During this 40-minute interval give your attention to
the questions at the end of this experiment.]
The nearly solid mass of crystals of benzoin in the
flask is transferred onto a Biichner funnel and any material remaining in the flask washed into the funnel
with 100-150 ml. of water. Remove as much water as
possible from the crystals by suction and rinse the
crystals of benzoin, first, with a little cold alcohol and
then with 10 ml. of ether. When spread on a clean
sheet of paper the benzoin will dry quickly in the air.
For oxidation to benzil the product need not be recrystallized. Yield 7-8 g.
FIG.
33. An assembly suitable for the oxidation of benzoin to benzil.
and heat the flask in boiling water, or on the steam
bath, for 10-12 minutes. The evolution of brown fumes,
very rapid at first, becomes much slower after the first
five minutes of heating. After the flask has been in the
boiling water for 10-12 minutes, disconnect the delivery
tube, cool the flask in a bath of ice and water, and
pour the contents into 150 ml. of water containing a
few small pieces of ice. Stir the mixture well and break
up with a spatula any lumps of benzil in order to wash
out the nitric acid.
[After Part II is underway, perform the following tests
Bring the yellow crystalline benzil onto the Biichner
with a small portion of benzoin that has been reserved
funnel
and wash it with a little water. Shut off the
for this purpose.]
suction pump and stir the benzil gently on the filter
Recrystallization. Recrystallize a small portion of the with a little cold alcohol. Suck the alcohol through the
benzoin from hot alcohol for observation of its melting filter and spread the benzil onto a sheet of paper to
dry for a few minutes in the air. (CAUTION: Do not
point.
Reaction with Fehling's Solution. Dissolve 0.5 g. of attempt to obtain rapid drying of the benzil by washing
benzoin in a little ethanol and warm the solution with the product with ether because much benzil will be
10 ml. of Fehling's solution (5 ml. each of Solutions lost due to its ready solubility in ether.) Yield 5 g.
169
55-85
170
85-120
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
III. REARRANGEMENT OF BENZIL TO BENZILIC ACID
In a small flask place 4 g. of benzil, 5 g. of potassium
hydroxide, 10 ml. of ethanol, and 10 ml. of water.
Attach a reflux condenser and heat the contents of the
flask to boiling for 15 minutes. Pour the hot liquid into
a 250-ml. beaker and add 100 ml. of water. A little
unchanged benzil usually separates at this point in
the form of a colloidal suspension. As an aid in removing the residual benzil, add 1 g. of decolorizing carbon,
stir well, and filter the liquid to remove the carbon.
Precipitate the benzilic acid from the filtrate in the
following manner: place 50-75 g. of crushed ice into a
400-ml. beaker and add 15 ml. of concentrated hydrochloric acid. Now add to the ice and acid 10-15 ml.
of the solution of potassium benzilate and stir the mixture until the benzilic acid which sometimes separates
in colloidal form becomes crystalline. Then gradually,
with continuous stirring, add the remainder of the potassium benzilate solution. Finally collect the benzilic acid
on the Buchner filter. Yield about 3 g. After recrystallization from boiling water, it melts at 150°.
QUESTIONS
1. Write formulas for the following compounds:
(a) hydrobenzoin
(c) benzilmonoxime
(b) desoxybenzoin
(d) benzildioxime
2. Does hydrobenzoin have a structural relationship to
ethylene glycol?
3. May desoxybenzoin be named easily as a ketone?
4. Write formulas for the geometrical isomers that you
would consider possible for (a) benzilmonoxime, (b) benzildioxime.
5. Write a balanced equation for the oxidation of benzoin to benzil with concentrated nitric acid.
6. If benzoin is produced from benzaldehyde in 92 per
cent yield, and if benzil is produced from benzoin in 96
per cent yield, what weight of benzaldehyde would be
needed to prepare one mole of benzil?
7. What is the mechanism of the benzoin condensation?
Why is the cyanide ion a specific catalyst for the reaction?
8. How may benzoin be degraded to a mixture of benzaldehyde and benzonitrile? Would this degradation reaction be of any use in establishing the structures of mixed
benzoins?
9. How may p'-methylbenzoin be prepared? How may
it be isomerized to p-methylbenzoin?
10. Write structural formulas for furoin and furil. How
may these compounds be prepared?
EXPERIMENT 71
Preparation of Cinnamic
H
O
[—the Perkin Reaction
O
H
I
H
O
I II
O
II
—> CSHB—C^C^C—O—C—CH 3 + H 2 0
Mixed anhydride of
acetic and cinnamic acids
H
(2)
H
O
O
H
I
C 6 H 5 —C=C—C—O—C—CH 3 + H 2 0
H
O
I II
O
II
—• C,sH6—C=C—C—OH + CH3—C—OH
Cinnamic acid
Introduction. The Perkin reaction is one of the many
base-catalyzed condensation reactions which are encountered in the/Study of organic chemistry. The present
experiment, in which benzaldehyde is condensed with
acetic anhydride under the influence of sodium acetate
(actually the acetate ion) as the basic catalyst, is a
typical example of this reaction.
The reacting materials must be heated in a bath at
170°-180° for 6-8 hours. Such a long period of heating, though necessary, is inconvenient for laboratory
classes. Tfte authors recommend that the reaction be
conducted in a large tube fitted with a stopper and an
air-condenser and that the collected lot of tubes from
all members of the class be heated at one time in a
large paraffin bath such as that illustrated in Figure
31, page 139. If the tubes are placed in the bath at
one laboratory session, the bath may then be heated
by volunteers working in relays so that the reaction is
complete and the product ready for isolation at the
next laboratory session.
Procedure
In a large test tube, or small flask, place 10.6 g.
(0.1 mole, 10.1 ml.) of benzaldehyde, 11 ml. (slight
excess of 0.1 mole) of acetic anhydride, 12 g. of fused
powdered sodium acetate, and 1 ml. of pyridine which
has been shown to be a catalyst for this reaction. After
mixing the reactants well with a glass rod, attach an
air-cooled reflux condenser and heat the tube in a bath
of molten paraffin wax at 140°-150° for 2 hours. Thereafter raise the temperature of the bath to 170°-180°
and maintain this temperature for 4-5 hours.
At the end of the heating period allow the tube to
cool and, with the aid of 200-250 ml. of water, transfer
the contents of the tube to a 1000-ml. flask for removal of unchanged benzaldehyde by steam distillation.
After the excess benzaldehyde has been eliminated
(125-150 ml. of distillate), make the contents of the
distilling flask alkaline with sodium hydroxide solution
and shake the flask well to dissolve any cinnamic acid
that may be present as an oil.
Filter the hot solution from any tarry matter, cool
the filtrate in ice, and precipitate the cinnamic acid by
addition of hydrochloric acid. Collect the cinnamic acid
on the Biichner filter and recrystallize it from 8001000 ml. of boiling water. Yield 9 g. M.p. 133°.
QUESTIONS
1. Write formulas for the following substances: (a)
cw-cinnamic acid, (b) fraws-cinnamic acid, (c) ethyl cinnamate.
2. Write equations to show the base-catalyzed condensation of benzaldehyde with the following reagents: (a)
n-butyric anhydride (with sodium butyrate), (b) acetophenone, (c) ethyl n-butyrate.
3. Starting from phenol show how one may prepare
salicylaldehyde and how, by a reaction of the Perkin type,
this aldehyde may be used for the production of coumarin.
4. From cinnamic acid, show how one may prepare:
(a) styrene, (b) dihydrocinnamic acid, (c) cinnamoyl
chloride.
5. Ten grams of cinnamic acid will add what weight of
bromine?
6. Write equations to show how ethyl malonate may be
used for the preparation of dihydrocinnamic acid.
171
EXPERIMENT 72
Fuinones
I. PREPARATION OF /?-BENZOQUINONE
3HO—{
0-40
V - O H + HBr0 3 -> SO==/==\=0
Introduction. One of the most convenient methods for
the preparation of a small sample of p-benzoquinone
consists of the oxidation of hydroquinone. Various oxidizing agents may be employed; the one selected for
today's experiment is bromic acid.
Procedure. A mixture of 10 g. of hydroquinone, 5.5 g.
of potassium bromate, 100 ml. of water, and 5 ml. of
normal sulfuric acid (Note 1) is warmed to 60° in a
200-ml. flask. The solids dissolve and the reaction starts
promptly giving first nearly black, crystalline quinhydrone as an intermediate product. Without further heating, the temperature rises slowly to about 75°. After
10-15 minutes the oxidation is complete, the dark color
giving way to the clear bright yellow of quinone (Note
2).
The mixture is then heated to 80° to dissolve the
quinone completely, next cooled to 0°, filtered, and
washed free of potassium bromide with a little ice water and dried. The yield is nearly quantitative and the
quinone is crystalline and exceptionally pure. M.p. 115°.
III.
+ HBr + 3H 2 0
Quinone has a quite noticeable vapor pressure at room
temperature, hence it should be dried as quickly as possible, to avoid loss by volatilization, and transferred to
a stoppered bottle.
II. QUINHYDRONE
40*50
Shake about 0.5 g. of quinone with 10 ml. of water
and add a solution of 0.5 g. of hydroquinone in 10-15
ml. of water. The greenish-black crystals of quinhydrone
are formed by an addition reaction between the two
original compounds, supposedly by hydrogen bonding.
O—H<-0
O—H<-0
In electrochemistry the quinhydrone electrode is used
in the measurement of hydrogen ion concentration.
ANTHRAQUINONE
• + Na2Cr207 + 4H2S04 - '
+ N a m + Cr2(S04)3 + 5H 2 0
9,10-Anthraquinone
50-120
In striking contrast to benzene or naphthalene, an- tion of acetic acid. Finally, wash the crystals with a
thracene may be directly oxidized to a quinone. Into little water and spread them upon a sheet of paper to
a 500-ml. flask fitted with a short reflux condenser place dry in the air. The yield is about 5 g.
Recrystallize a small portion of the anthraquinone
5 g. of a good grade of anthracene and 50 ml. of glacial
acetic acid. Heat the solution to the boiling point with from alcohol and determine its melting point. The rethe Bunsen burner and, during the course of 10-12 min- corded melting point is 273°. Anthraquinone may also
utes, add dropwise from a dropping funnel mounted on be purified readily by sublimation.
Reduction to Oxanthranol. Boil a trace of anthra- 120-135
a ring at the top of the condenser, a solution of 13 g.
of sodium dichromate, 15 ml. of water, 5 ml. of con- quinone for 1 minute with a little zinc dust and 10 ml.
centrated sulfuric acid, and 35 ml. of glacial acetic acid. of 3 per cent sodium hydroxide solution. Filter the soluKeep the solution at the boiling point during the addition of the dichromate solution and maintain this temperature for 10 minutes after all of the oxidizing agent
has been added. Extinguish the burner and allow the
flask to stand without the external application of heat
for 20 minutes.
H
OH
At the end of this period cool the flask in cold water
to bring about crystallization of the anthraquinone. Col- tion and blow air through it. Anthraquinone is reduced
lect the crystals on a small Buchner or Hirsch funnel by the zinc to oxanthranol which forms a red solution
and wash them twice with 20 ml. of a 30 per cent solu- in alkali and which is easily reoxidized to anthraqui172
173
QUINONES
none. The preceding test is frequently used for the
identification of anthraquinone.
an orange color due to the liberation of free bromine
(HBr0 3 + 5HBr-> 3Br2 + 3H 2 0).
NOTES
QUESTIONS
1. A normal solution of sulfuric acid of sufficient accuracy for this purpose may be made by adding 3 ml. of
concentrated sulfuric acid (£> = 1.84) to 100 ml. of water.
2. If too much sulfuric acid is used the temperature of
the reacting mixture rises to 80° or 85°, the oxidation is
complete in 1 or 2 minutes, and the sample of quinone has
1. What advantage does bromic acid possess as an oxidizing agent?
2. Compare the melting point and volatility of quinone
with the corresponding properties of hydroquinone. How
do you account for the differences?
3. Write the formula for vitamin Kx.
EXPERIMENT 73
Benzoic Acid
I. PREPARATION OF BENZOIC ACID FROM BENZYL CHLORIDE
C6H6CH2C1 + Na 2 C0 3 + H 2 0 -> C6H6CH2OH + NaHC0 3 + NaCl
3C6HBCH2OH + 4KMn0 4 + -> 3C6HBCOOK + 4Mn0 2 + KOH + 4H 2 0
II. PREPARATION OF BENZOIC ACID AND BROMOFORM BY THE HALOFORM REACTION
0
O Br
II
II I
C6H6C—CH3 + 3Br2 + 3NaOH -> C6H5C—C—Br + 3NaBr + 3H 2 0
I
O Br
II
I
Br
O
II
C6H6—C—C—Br + NaOH -> C6H6—C—ONa + CHBr3
Br
I. BENZOIC ACID FROM BENZYL CHLORIDE
0-20
80-130
II. THE HALOFORM REACTION
Introduction. The direct oxidation of toluene to benIntroduction. It will be recalled that ketones in which
zoic acid is slow by most laboratory procedures; hence, one group is methyl show the haloform reaction (cf.
benzyl chloride is a more convenient starting material acetone, page 77). In the present experiment acetoas it is hydrolyzable to benzyl alcohol which undergoes phenone (phenyl methyl ketone) yields bromoform and
oxidation rapidly.
benzoic acid as shown in the equations:
Procedure. In a 500-ml. flask place 8 g. of anhydrous
Procedure. Prepare a solution of bromine in sodium
sodium carbonate and 12 g. of potassium permanga- hydroxide as follows: In a 250-ml. flask dissolve 4 g.
nate with 200 ml. of water. Add 6.3 g. (5.8 ml., 0.05 of sodium hydroxide in 50 ml. of water, add about
mole) of benzyl chloride, fit the flask with a reflux con- 50 g. of crushed ice, then introduce 2 ml. of bromine
denser, and boil the mixture for 1 hour. (Note: Benzyl and shake the flask until the bromine dissolves. (Brochloride is irritating to the eyes. Measure the needed mine is always handled in the hood. Ask the inquantity with a small graduated cylinder from the sup- structor about local laboratory provisions for dispensply bottle which is kept in the hood.)
ing this reagent.) Add 2 ml. of acetophenone and shake
The brown precipitate of manganese dioxide, which the flask well for 6-8 minutes. Note that heat is evolved
gradually accumulates in the flask, sometimes settles to and that about 1 ml. of liquid bromoform settles to the
the bottom where it causes excessive bumping. Usually bottom of the flask.
this trouble can be overcome by shaking the flask freTransfer the contents of the flask to a separatory
quently. Continue boiling the mixture for 50-60 min- funnel, withdraw the small lower layer of bromoform
utes while you prepare another specimen of benzoic and give it to the instructor—the combined lot from all
acid from acetophenone by the haloform reaction as members of the class may be worth saving. The soluoutlined in Part II.
tion of sodium benzoate in the separatory funnel is turDisconnect the flask from the condenser and remove bid due to the presence of suspended droplets of bromoit to the hood where the precipitate of manganese diox- form. Pour the liquid into a beaker, stir it with 1 g. of
ide is removed by filtration through a large sheet of decolorizing carbon which collects the particles of brofluted filter paper. Rinse the precipitate with 50 ml. of moform, and then remove the carbon by filtration. Add
hot water and combine the washings with the main a little ice to the filtrate and acidify it with dilute sulportion. Chill the filtrate, containing the potassium furic acid.
benzoate, to 20° or lower in a bath of ice and water
Usually the solution acquires a yellow or orange color
and acidify the solution with dilute sulfuric acid. Col- at this point due to the presence of a slight excess of
lect the precipitate of benzoic acid, which may be col- bromine. This is removed by the addition of a little
ored somewhat by unchanged permanganate, on a Biich- sodium bisulfite and the white precipitate of benzoic
ner funnel and recrystallize it from hot water. The acid is collected on a filter. Yield about 1 g. After resolubility of benzoic acid in water: At 0° = 1.7 g./liter; crystallization from 15-20 ml. of boiling water, benzoic
at 20° = 2.9 g./liter; at 50° = 9.5 g./liter; at 95° = acid melts at 122°.
68.9 g./liter. Weigh your product and calculate the
yield. Pure benzoic acid melts at 122°.
174
20-80
ACID
QUESTIONS
1. The concentration of a saturated solution of benzoic
acid at 25° is approximately 0.03 M. The ionization constant (KA) of benzoic acid at 25° is 6.4 X 10~ 5 . Calculate (a) the hydrogen ion concentration in the solution,
(b) the pH of the solution and (c) the pKA value for
benzoic acid.
2. Write equations showing how benzoic acid may be
converted into the following derivatives:
(a) calcium benzoate
(b) ethyl benzoate
(c) benzoyl chloride
(d) benzanilide
(e) benzamide
(f) benzoyl peroxide
(g) m-nitrobenzoic acid
(h) ra-bromobenzoic acid
3. What products may be obtained by the strong oxidation (as with Na 2 Cr 2 0 7 and H 2 S0 4 ) of the following
compounds?
175
(b) C6H5CH2CH3
(a) C6H5CH3
(c) C 6 H 5 CH(CH 3 ) 2
(d) C 6 H 5 CH=CH 2
(e) C 6 H 5 CH=CHC 6 H 5
(f) C6H5CHC1CH3
(g) C6H5COCH3
(h) C6H5COC2Hs
(i) C6H5CHOHCOOH
4. Which of the following compounds will give the haloform reaction?
(a) C 6 H 5 CC1 3
(b) C 6 H 5 CHOHCH 3
(c) C 6 H 5 COCH 3
(d) C 6 H 5 CH 2 COCH 3
(e) C 6 H 5 CH 2 CHOHCH 3 (f) C 6 H 5 CHOHCH 2 CH 3
5. (a) What volume (in ml.) of normal base solution
will be required for the neutralization of 1 g. of benzoic
acid? (b) Calculate the neutralization equivalent (its equivalent weight as determined by neutralization with a standardized solution of base) of benzoic acid.
6. What is the neutralization equivalent of an acid (a)
if 1 g. requires 16.67 ml. of normal base; (b) if 1 g. of
acid requires 12.05 ml. of normal base?
EXPERIMENT 74
Oxidation of ^-Nitrotoluene to jb-Nitrobenzoic Acid
O
0 2 N—/
V - C H + Na2Cr207 + 4H2S04 -> 0 2 N - /
= /
0-60
60-120
^
H + Na 2 S0 4 + Cr 2 (S0 4 ) 3 + 5H 2 0
H
(d) Procaine (novocaine)
(e) anthranilic acid from phthalimide
2. Substances which show the Cannizzaro reaction
(auto-oxidation and reduction in alkaline solution) include:
(a) formaldehyde
(b) acetaldehyde
(c) isobutyraldehyde
(d) trimethylacetaldehyde
(e) acetone
(f) benzaldehyde
(g) anisaldehyde
(h) benzophenone
(i) phenyl p-bromophenyl (j) benzyl phenyl ketone
ketone
3. Which of the ketones listed in question 2 will form
oximes capable of existing as syn and anti isomers?
4. Which of the following substances will show the haloform reaction?
(a) benzaldehyde
(b) acetaldehyde
(c) phenylacetaldehyde
(d) acetone
(e) sec-butyl alcohol
(f) methyl ethyl ketone
(g) acetophenone
(h) benzyl methyl ketone
(i) phenyl ethyl ketone (j) a-phenylethyl alcohol
5. Which of the compounds listed in Group II may be
made by a base catalyzed condensation of benzaldehyde
with one of the reactants shown in Group I?
Group I
(a) acetaldehyde
(b) acetophenone
(c) acetone
(d) ethyl acetate
(e) ethyl w-butyrate
Group II
(f) C6H5CH=CHCOCH=CH—C6H5
(g) C6H5CH=CH—CH2CH2COOC2H5
(h) C6H5CH=CHCOOC2H5
(i) C6H5CH2COOC2H5
(j) C6H5CH=CHCOC6H5
6. In which of the following compounds will the action
of phosphorus pentachloride replace one oxygen atom by
two chlorine atoms; in which is the oxygen atom replaced
by but one chlorine atom?
(a) acetophenone
(b) benzophenone
(c) p-benzoquinone
(d) phenyl p-tolyl ketone
7. What compounds are obtained by the condensation
of benzaldehyde with:
(a) nitromethane
(b) nitroethane
(c) 1-nitropropane
8. Mark the following statements true or false.
(a) Hydrolysis of a compound such as RCHC12 yields
an aldehyde.
(b) Metallic sodium is similar to a free radical in that
it has an "odd" or "unpaired" electron.
(c) A specimen of mandelic acid prepared from benzaldehyde by the addition of HCN and hydrolysis of the
nitrile is optically active.
(d) The reduction of a Schiff base yields a primary
amine.
176
Introduction. The direct oxidation of toluene to benzoic acid occurs so slowly with the usual laboratory
reagents that the experiment is not easily adaptable to
use in laboratory classes where time is limited. The introduction of a para nitro group, however, causes the
oxidation of the methyl group to proceed readily; hence,
p-nitrotoluene is easily oxidized to p-nitrobenzoic acid.
At this juncture a review of the chemistry of several
series of aromatic compounds will be helpful. Such a
review is provided by the Questions at the end of the
experiment.
Procedure. In a 2-liter flask, fitted with a mechanical
stirrer, are placed 60 g. of sodium dichromate, 150 ml.
of water, and 20.5 g. (0.15 mole) of p-nitrotoluene.
The stirrer is started and 95 ml. of concentrated sulfuric acid is added dropwise from a dropping funnel
during the course of 10 minutes. The heat of dilution
of the sulfuric acid causes the p-nitrotoluene to melt
and a highly exothermic reaction soon begins. It will be
necessary to cool the flask at this point if the contents
begin to boil.
When the spontaneous reaction has subsided the flask
is heated on the steam bath for 30 minutes or in a pan
of boiling water for 1 hour with continuous stirring.
The mixture is then cooled in ice to 20° and 400 ml.
of water is added. The cooled solution is filtered with
suction and the crude p-nitrobenzoic acid washed on
the filter with two 50-ml. portions of water.
The crude acid is then transferred from the funnel to
a beaker and warmed with 100 ml. of 10 per cent sulfuric acid solution for removal of the chromium salts.
After cooling, the p-nitrobenzoic acid is again collected
on a filter. It is then returned to the beaker, dissolved in
5 per cent sodium hydroxide solution, and filtered from
any chromium hydroxide and unchanged p-nitrotoluene.
The filtrate, which should have only a pale greenishyellow color, is acidified with 10 per cent sulfuric acid
solution. Better results are usually obtained by running
the alkaline solution into the dilute sulfuric acid rather
than by the use of the reverse procedure. The precipitated acid is brought onto the Biichner filter, washed,
and dried. Yield about 18 g. M.p. 235°-238°.
QUESTIONS
1. Write equations to show how you would obtain:
(a) ra-nitrobenzoic acid from toluene
(b) m-aminobenzoic acid from toluene
(c) p-aminobenzoic acid from toluene
OXIDATION OF p-NITROTOLUENE TO p-NITROBENZOIC ACID
(e) Cinnamic acid may be made from benzaldehyde by
use of the Perkin reaction.
(f) Condensation of benzaldehyde with nitromethane
yields a product which upon reduction may give /?-phenylethylamine.
(g) The molecule of benzoin has a structural resemblance to that of fructose and, like fructose, reduces
Fehling's solution.
(h) Cinnamic acid can exist in both a cis and a trans
modification.
(i) o-Hydroxycinnamic acid easily forms a lactone
known as "coumarin."
(j) Phenylacetaldehyde is an isomer of acetophenone.
177
(k) Aromatic ketones are often made by use of the
Friedel and Crafts reaction.
(1) Acetophenone shows the haloform reaction.
(m) The Beckmann rearrangement of syn-pheny\-ptolylketoxime gives a product which yields p-toluidine and
benzoic acid upon hydrolysis.
(n) Vitamin Kx is related to 1,4-naphthoquinone.
(o) Quinhydrone is a reduction product of hydroquinone.
(p) Quinone shows reactions of the Diels-Alder type.
(q) Oxidation of benzoin givesfirstbenzil and then benzoic acid.
EXPERIMENT 75
Aromatic Hydroxy Acids
(Salicylic Acid, Aspirin, and Tannic Acid)
0-35
I. PREPARATION OF SALICYLIC ACID FROM OIL OF WINTERGREEN
COOH
COOCH;
+ H 2 O ^ U f |]
+ CH3OH
then acid \x
OH
In a 250-ml. flask mix 5 g. of oil of wintergreen
(methyl salicylate) with a solution of 10 g. of sodium
hydroxide in 50 ml. of water. The sodium salt of the
phenolic group in the methyl salicylate, which usually
separates at this point, dissolves when the mixture is
warmed. Attach the flask to a reflux condenser and heat
the contents of the flask to boiling for 15 minutes for
hydrolysis of the ester.
Pour the solution into a beaker, cool it well in an ice
bath and acidify it with dilute sulfuric acid. Collect the
precipitated salicylic acid on a Biichner funnel and dry
it in the oven or spread it out on a sheet of paper to dry
in the air. After recrystallization from hot water, salicylic acid melts at 157°.
35-60
II.
PROPERTIES OF SALICYLIC ACID
A. Properties of the Carboxyl Group
7. Decarboxylation. In a test tube heat salicylic acid
with an equal weight of soda lime. Note the odor
evolved. Equation.
2. Esterification. Formation of Methyl Salicylate. Mix
1 g. of salicylic acid with 2 ml. of methyl alcohol and
2 ml. of concentrated sulfuric acid. Warm the mixture
gently and note the odor. The odor is sometimes more
apparent if the liquid is poured into 25 ml. of cold
water. Equation.
60-130
OH
separation of aspirin appears to be nearly complete.
Dilute the crystalline paste with 10 ml. of cold glacial
acetic acid, cool the mixture in cold water, and collect
the crystals on a Biichner funnel. Wash the product on
the filter with a little cold water and transfer it to a
small beaker for recrystallization from boiling water.
Determine the melting point of the recrystallized sample. Pure aspirin melts at 135°.
Suspend about 0.1 g. of your preparation in water
and add 1-2 ml. of ferric chloride solution. Would you
expect aspirin to give any coloration with ferric chloride? If any coloration develops with ferric chloride, to
what is it due?
III.
PROPERTIES OF TANNIC ACID
7. Fehling's Solution. Warm 5 ml. of a solution of
tannic acid with 10 ml. of Fehling's solution (5 ml.
each of solutions A and B). Result. Repeat the test
using Tollens' reagent in place of Fehling's solution.
Does the reducing power of a phenolic compound increase or decrease with increasing number of hydroxyl
groups? Compare with phenol, hydroquinone, and pyrogallol.
2. Ferric Chloride. Add a few drops of ferric chloride
solution to 5 ml. of a dilute solution of tannic acid. Does
the coloration produced have any connection with the
colors produced by phenols and ferric chloride (page
155)?
3. Ferrous Sulfate. To a dilute solution of tannic
acid add a few drops of a freshly prepared solution of
ferrous sulfate. Is any color produced? Dip a strip of
filter paper into the solution and expose it to the oxidizing action of the air. Does a color develop? How is this
principle used in the iron inks?
B. Properties Due to the Phenolic Group
7. Ferric Chloride Test. To a dilute solution of salicylic acid in water add a few drops of ferric chloride
solution. Result. Does phenol give a similar coloration?
2. Reaction with Bromine. Dissolve 0.2 g. of salicylic acid in a little warm water and add bromine water
until the liquid has a faint yellow color. The precipitate
is 2,4,6-tribromophenol. Explain this reaction. Does
salicylic acid resemble a phenol or a carboxylic acid in
QUESTIONS
this reaction?
1. Write equations showing how:
3. Preparation of Acetylsalicylic Acid (Aspirin).
(a) Salicylic acid may be made from phenol by the
Into a small flask introduce in the order named 5 g. of
Kolbe
method and by the Reimer-Tiemann process.
salicylic acid, 10 ml. of acetic anhydride, and 1-2 ml.
(b) p-Anisic acid (p-methoxybenzoic acid) may be
of concentrated sulfuric acid. Stir the mixture and note made from p-nitrophenol.
the rise in temperature. All of the salicylic acid dissolves
(c) Salol (phenyl salicylate) may be prepared from
rapidly and crystals of aspirin soon begin to form.
salicylic acid.
Continue stirring the contents of the flask for a few
2. Would you expect salicylic acid to be steam-distillaminutes until the temperature falls somewhat and the ble? Explain.
178
*
130-150
EXPERIMENT 76
Qualitative Organic Analysis
Introduction. Although the subject of the identifica- 5 per cent sodium hydroxide, and 5 per cent hydrochlotion of organic compounds by application of a syste- ric acid, and that contains no nitrogen, test its solubility
matic scheme of qualitative organic analysis is* covered in concentrated sulfuric acid.
In the following chart are given the various types of
in a full course at the senior or graduate student level
in most schools, there is much to be gained by making compounds that belong to the different solubility classes:
a preliminary study of this phase of organic chemistry
I. Water-soluble Compounds
in thefirstcourse in the subject. Of course, the approach
A. Soluble in Ether.—Aliphatic alcohols, aldehydes,
must be simplified greatly in order to be applicable to
ketones, carboxylic acids, esters, amines, amides
one or two laboratory periods.
and nitriles of low molecular weight, and a few
The laboratory instructor will furnish each student
phenols
B. Insoluble in Ether.—Glycols, amine salts, salts of
with a 10-15 g. sample of an unknown compound,
carboxylic acids
either liquid or solid, which is to be identified during
the course of one or two periods. In order to limit the II. Water-insoluble Compounds
A. Soluble in 5 per cent Sodium Hydroxide
scope of the problem, the unknown will belong to one
1. Soluble in 5 per cent Sodium Bicarbonate.—
of the following classes of monofunctional compounds:
Carboxylic acids, nitrophenols
aliphatic or aromatic aldehydes, ketones, carboxylic
2. Insoluble in 5 per cent Sodium Bicarbonate.—
acids, esters, amines, amides of the type RCONH2,
Phenols
nitriles, salts of carboxylic acids, and salts of amines;
B. Soluble in 5 per cent Hydrochloric Acid.—Amines
aliphatic alcohols including simple glycols; aromatic
C. Insoluble in Dilute Hydrochloric Acid or Sodium
hydrocarbons, halides, nitro compounds and phenols.
Hydroxide
1. Contains Nitrogen.—Amides, nitriles, nitro comThe unknowns will be given to the student in the
pounds
form in which they are received from the chemical sup2. Contains No Nitrogen
ply companies; i.e., they will be of good quality but not
a. Soluble in Cold, Concentrated Sulfuric
necessarily 100 per cent pure compounds. The steps
Acid.—Alcohols, aldehydes, ketones, and
given below for the identification of each unknown
esters of relatively high molecular weight
should be followed in the order given, and notes should
b. Insoluble in Cold, Concentrated Sulfuric Acid.
be taken after each experiment.
—Aromatic halides, hydrocarbons
Purification. If the unknown is a solid, determine its
Tests for Functional Groups. Depending on the inmelting point, then recrystallize it according to the directions given in Experiment 4, and again determine formation gathered in the previous tests, carry out one
its melting point. Repeat this procedure until the melt- or more of the following tests for detecting the presence
4ag point reaches a constant value. If the unknown is a of functional groups.
A. Aldehydes and Ketones. To 3 ml. of 2,4-dinitroliquid, purify it by distillation, and, at the same time,
determine its boiling point. (CAUTION: Some organic phenylhydrazine reagent (Note 1) add a few mg. of the
liquids decompose when heated at too high a tempera- compound to be tested and shake vigorously. The
ture. Never heat an unknown compound to dryness.) 2,4-dinitrophenylhydrazones of all aldehydes and keElemental Analysis. Test the unknown to determine tones are relatively insoluble and usually give an immewhether it contains nitrogen, halogen, or a metal. Use diate precipitate. If the test with this reagent is positive,
carry out tests with Tollens' reagent (Experiment 20)
the procedure given in Experiment 8.
Solubility Classification. Place 0.2 ml. of a liquid un- and Fehling's solution (Experiment 20). Also try the
known or 0.1 g. of a solid unknown in a small test tube iodoform reaction (Experiment 23). The 2,4-dinitroand add, in portions, with shaking, 3 ml. of water. If phenylhydrazone can be used, also, as a derivative.
B. Alcohols. Carry out tests with acetyl chloride
the compound proves to be soluble, repeat the test with
(Experiment 27), benzoyl chloride plus sodium hyether as the solvent.
If the compound is insoluble in water, test its solu- droxide solution (Experiment 31), and metallic sodium
bility in 5 per cent sodium hydroxide solution. Any (Experiment 31). Apply the Lucas test (Experiment
compound that is found to be soluble in sodium hy- 16) and the iodoform test (Experiment 23) if the above
droxide solution should next be tested for its solubility tests are positive.
C. Esters. Saponify the compound with sodium hyin 5 per cent sodium bicarbonate solution. Carry out
these tests in the same manner as described for the test droxide solution and identify the carboxylic acid and
alcohol produced (Experiment 26).
with water.
D. Nitriles and Amides. Add about 0.2 g. of the comIf the compound is insoluble in sodium hydroxide solution, test its solubility in 5 per cent hydrochloric acid. pound to be tested to 5 ml. of 10 per cent sodium hyFinally, for any unknown that is insoluble in water, droxide solution contained in a test tube, and heat the
179
180
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
mixture to boiling. Note the odor of the vapor. Test the
vapor with litmus paper. Both nitriles and amides of the
type RCONH2 evolve ammonia in this test.
E. Aromatic Nitro Compounds. Dissolve about 0.5
g. of the compound in 10 ml. of 50 per cent ethanol,
then add 0.5 g. of ammonium chloride and 0.5 g. of
zinc dust. Mix the reagents by shaking, then heat the
mixture to boiling. Cool the mixture for 5 minutes, filter
it, and test the filtrate with Tollens' reagent. The unknown is reduced by zinc dust and ammonium chloride
to a hydrazine, a hydroxylamine, or an aminophenol.
All of these compounds are oxidized by Tollens' reagent, which, in turn, is reduced and gives a silver mirror.
Salts. The metal salt of a carboxylic acid can be decomposed by hydrochloric acid and the liberated carboxylic acid collected byfiltrationor separated by ether
extraction. The salt of an amine and an acid can be
decomposed by sodium hydroxide solution and the liberated amine collected byfiltrationor separated by ether
extraction.
Glycols. Determine whether the compound is a 1,2diol by application of the periodic acid test (Experiment
31).
Amines. Determine whether the amine is primary,
secondary, or tertiary by application of the Hinsberg
reaction (Experiment 50).
Phenols. Try the ferric chloride (Experiment 61) and
bromine water (Experiment 61) tests.
Preparation of Solid Derivatives. After the functional
group in the unknown has been identified, at least one
solid derivative and preferably two or more should be
prepared in order to complete the identification. Some
of the more useful solid derivatives for the various
classes of compounds are listed below:
Aldehydes and Ketones. Prepare the semicarbazone
(Experiment 21), the oxime and/or the phenylhydrazone and 2,4-dinitrophenylhydrazone. Purify these and
all other derivatives described subsequently by crystallization from a suitable solvent, and determine the melting points.
Alcohols and Glycols. To 1 g. of 3,5-dinitrobenzoyl
chloride (Note 2) add about 1 g. of the unknown and
heat the mixture on the steam bath for 20 minutes. Add
10 ml. of water and collect the solid ester by filtration.
Wash the solid with dilute sodium carbonate solution
and then with water. Crystallize the ester from petroleum ether and determine its melting point.
Carboxylic Acids. Prepare the anilide or p-toluidide
(Experiment 36).
Esters. Saponify the ester, isolate the alcohol (or
phenol) and acid, and prepare solid derivatives of each.
Amides and Nitriles. Hydrolyze the compound (Experiment 30), isolate the acid, and prepare a solid derivative.
Amines. Prepare the acetyl or benzoyl derivative (Experiment 50).
Phenols. Prepare the 2,4-dinitrophenyl ether (Experi-
ment 62), benzoate (Experiment 62), or polybromo
derivative (Experiment 62).
Aromatic Hydrocarbons or Halides. Prepare the
mono- or dinitro-derivative (Experiment 48).
Salts. Decompose amine salts with sodium hydroxide
solution, isolate the free amine, and prepare a solid
derivative. Decompose metal salts of carboxylic acids
with hydrochloric acid, isolate the free acid, and prepare a solid derivative.
Nitro Compounds. Reduce these to primary amines
(Experiment 49) and prepare solid derivatives of the
amines.
Literature Search. With knowledge of the melting
point or boiling point of the unknown, the type of functional group present, and the melting point of at least
one solid derivative, you should be able to identify the
unknown by looking up tables of compounds and their
derivatives in one or more of the following books:
Shriner, Fuson, and Curtin, Identification of Organic
Compounds, Wiley.
Kamm, Qualitative Organic Analysis, Wiley.
McElvain, The Characterization of Organic Compounds,
Macmillan.
Cheronis and Entriken, Semimicro Qualitative Organic
Analysis, Crowell.
Huntress and Mulliken, Identification of Pure Organic
Compounds, Wiley.
NOTES
1. To prepare the reagent, dissolve 2 g. of 2,4-dinitrophenylhydrazine in 15 ml. of concentrated sulfuric acid,
then add this solution, with stirring, to 150 ml. of 95 per
cent ethanol. Finally, dilute the solution to 500 ml. by addition of distilled water and filter. The filtrate is used as
the test reagent.
2. If necessary, prepare 3,5-dinitrobenzoyl chloride as
follows: Add 1 g. of 3,5-dinitrobenzoic acid and 1 drop
of pyridine to 3 ml. of thionyl chloride and heat the mixture under reflux for 30 minutes. Remove excess thionyl
chloride by distillation, and use the residue for making
solid derivatives of alcohols.
QUESTIONS
1. The following observations are frequently made in
the examination of unknowns. In each case, state what
deduction may be made as to the nature of the compound
being tested.
(a) A compound gives an orange precipitate when
treated with 2,4-dinitrophenylhydrazine reagent, but it does
not reduce Tollens' reagent.
(b) A compound gives a positive test with 2,4-dinitrophenylhydrazine reagent, and it reduces Tollens' reagent;
however, it gives a negative test with Fehling's solution.
(c) An unknown is found to contain nitrogen. It is insoluble in water, 5 per cent hydrochloric acid, and 5 per
QUALITATIVE ORGANIC ANALYSIS
cent sodium hydroxide solution. It does not undergo hydrolysis in hot sodium hydroxide solution. When an ethanol
solution of the compound is treated with zinc dust and
ammonium chloride and the resulting mixture filtered, the
filtrate is found to reduce Tollens' reagent.
(d) An unknown contains nitrogen, and it is insoluble
in water, 5 per cent sodium hydroxide solution, and 5 per
cent hydrochloric acid. When boiled in 10 per cent sodium
hydroxide solution, ammonia is evolved.
(e) A compound is insoluble in water and 5 per cent
sodium bicarbonate solution, but it is soluble in 5 per cent
sodium hydroxide solution. It gives a pronounced color
with ferric chloride.
(f) A compound is insoluble in water, 5 per cent sodium
hydroxide solution, and 5 per cent hydrochloric acid, but
it is soluble in concentrated sulfuric acid. The compound
undergoes hydrolysis when heated with sodium hydroxide
solution.
(g) Elemental analysis of a compound shows that it
contains bromine. The compound is insoluble in water, 5
per cent sodium hydroxide solution, 5 per cent hydrochloric acid and concentrated sulfuric acid.
(h) An unknown undergoes reaction with acetyl chloride to give a sweet smelling derivative, and it also gives a
positive iodoform test. However, it gives a negative test
with 2,4-dinitrophenylhydrazine reagent.
181
(i) Each of two different pleasant-smelling, water-insoluble organic compounds gradually dissolves when refluxed with sodium hydroxide solution with disappearance
of the characteristic odor. In the case of the first compound,
distillation of the resulting solution affords as the distillate,
along with water, a compound which, when isolated free
of water, reacts with acetyl chloride and gives a positive
iodoform test, but does not give a positive Lucas test at
room temperature.
In the case of the second compound, distillation of the
basic solution affords pure water.
2. The compound C 9 H n ON (A) is insoluble in dilute
hydrochloric acid but soluble in a dilute sodium hydroxide
solution. Phosphorus pentachloride converts A into an isomeric compound (B) which is no longer soluble in alkali.
Hydrolysis of A with 10 per cent sulfuric acid gives
C9H10O (C) which is soluble only in concentrated sulfuric
acid. C is converted into benzoic acid by vigorous oxidation, yields iodoform when treated with iodine in alkaline
solution, and reacts with phenylhydrazine. B is converted
by hydrolysis with 10 per cent sulfuric acid into acetic
acid and C7H9N (D). D is soluble in water, gives a basic
reaction, and is converted by nitrous acid into C 7 H 8 0 (E)
which yields benzoic acid when oxidized. What are the
structures of A, B, C, D, and E? Show by means of equations the reactions involved. Identify any "name" reactions.
UNKNOWN REPORT
Physical Examination
a. Physical State
b. Color
c. Odor
Physical Constants
a. Melting point
b. Boiling point
Elemental Analyses
Elements present other than carbon and hydrogen .
Solubility Behavior
Compound is soluble in
Classification Tests
Observation
Inference
Reagent
a.
b.
c..
d. .
e.
f. .
6. Possibilities. After you have determined the melting point or boiling point of the unknown and what functional group
is present, list all of the compounds of that class which have a m.p. or b.p. within ±5° of that you have observed.
Possibilities
a. Unknown
b. ZIZZZ
c.
d
e.
f
g7. Conclusion
B.P. or M.P.
Derivatives and Their Melting Points
EXPERIMENT 77
Dyes and Dyeing
I. PREPARATION OF METHYL ORANGE ( A N AZO D Y E )
(1) 20z^-\~\-NH3
+ NasCOa->2Na03S-/
\ — N H 2 + H 2 C0 3
(2) N a O i S - Y V - N H i + ONONa + 2HC1 -+ OS—f
(3) 03S-
/VH= •N=N+ +
H
f~\
V - N = N + + 2H 2 0 + 2NaCl
•N(CH3)2+, CI" + 2NaOH •
Na03S—/
V - N=N—/
Introduction. The preparation of an azo dye consists Tests with Methyl Orange
of the following operations:
(a) Helianthin. To 0.2 g. of methyl orange add 10
1. The diazotization of an aromatic substance con- ml. of water and 1 ml. of concentrated hydrochloric
taining a primary amino group.
acid. Warm the solution and then cool it. The red
2. The preparation of a solution of some aromatic crystals (inner salt) that separate are known as "helianamino compound in dilute acid, or a solution of a thin."
phenolic substance in dilute alkali.
The indicator action of methyl orange may be illus3. The mixing of the above solutions when the reac- trated by the following formulas:
tion (called coupling) takes place with the formation
HCl
of the dye. Before coupling can occur, the solution must
•N=NNa03S-N(CH3)2^=t
be alkaline or only slightly acidic.
NaOH
In the preparation of methyl orange, sulfanilic acid is
Yellow
diazotized (step 1); dimethyl aniline is dissolved in
H
dilute hydrochloric acid (step 2 ) ; and the two solutions
are "coupled" (step 3).
=N(CH3)2
•N—N=<
o 3 sProcedure. Dissolve 5 g. of sulfanilic acid and 2 g.
Red
of sodium carbonate in 100 ml. of water. Cool the solution to 0° by the addition of 150 g. of ice and add 2 g.
(b) Cleavage of Methyl Orange by Reduction. To
of sodium nitrite dissolved in 15 ml. of water. A solu- 0.1 g. of methyl orange, contained in a small Erlention of 4 ml. of concentrated hydrochloric acid in 25 meyer flask, add 30 ml. of water, 5 ml. of glacial acetic
ml. of cold water is then slowly introduced. This process acid, and 3-4 g. of zinc dust. Keep the solution warm
is known as diazotization.
for a few minutes and observe the gradual loss of color.
Dissolve 3 ml. of dimethylaniline in 5 ml. of con- Equation.
centrated hydrochloric acid diluted with 15 ml. of water.
All azo dyes undergo cleavage at the —N=N—
Cool this solution with ice and pour it into the diazo- bonding upon reduction to give two amino compounds
tized sulfanilic acid with continuous stirring. This proc- whose identification provides valuable information toess is known as "coupling" and is used for the prepara- ward the identification of an azo dye of unknown struction of all "azo" dyes.
ture.
Some coupling occurs in the dilute acid solution and
II. DYEING CLOTH
the dye thus formed imparts a red color to the solution.
Complete the coupling process and, at the same time,
convert the dye into its yellow sodium salt by the addi- A. Direct Dyeing of Wool and Silk
In 400-ml. beakers prepare (1) a solution of 0.2 g. of
tion of approximately 40 ml. of a 10 per cent solution
Malachite Green in 200 ml. of water, and (2) a soluof sodium hydroxide.
At this point the solution is faintly basic to litmus tion of 0.2 g. of Crystal Violet (or Methyl Violet) in
paper. Add 30 g. of clean salt (NaCl), heat the con- 200 ml. of water.
Heat the two solutions to boiling and immerse in each
tents of the beaker nearly to the boiling point, and set
the solution aside (or in an ice bath) to cool. The dye a piece of cotton cloth, one of wool, and one of silk,
separates in orange colored crystals which are collected each of which is 2-3 inches square. After 2 minutes
on the Biichner funnel, pressed well, rinsed with a small remove the cloth with a glass rod; avoid getting the dye
quantity of ethanol and dried in the oven or spreatl out solution on your hands or dripping it upon the laboraon paper to dry in the air. Do not attempt to take the tory table, and wash out the excess dye in a gentle
stream of water at the sink. Is the color "fast" in each
melting point of the dye. Yield 8-9 g.
182
y v
0-50
^ N ( C H 3 ) 2 + NaCl + 2H 2 0
50-55
/ v
55-65
65-85
DYES AND DYEING
sample? Dry the samples on a string tied between two
iron stands and fasten them in your notebook with
pieces of Scotch tape. Save the dye solutions for Part B.
85-105
B. Dyeing Cotton with the Aid of a Mordant
Prepare a solution of 1.0 g. of tannic acid in 200 ml.
of water and immerse in it two small pieces of cotton
cloth. Let the cloth remain in the solution at room temperature while you prepare a solution of 0.2 g. of tartar
emetic in 200 ml. of water. By means of a glass rod
remove the pieces of cloth from the solution of tannic
acid to an empty beaker and, with the aid of a spatula,
press out as much of the tannic acid solution as possible.
Fasten the tannic acid in the pieces of cloth by dipping them in the solution of tartar emetic and again pressing out the excess solution as before. Now immerse one
piece of the mordanted cloth in the Malachite Green
dye bath, the other in the Crystal Violet bath. Dye the
cloth at or near the boiling point of the solutions for 2
minutes and wash and dry the samples of dyed cloth as
in Part A. Does the mordant aid in fixing the dye in
the fiber? Fasten the specimens in your notebook.
105-130 C. Dyeing with Indigo-A Vat Dye
The "vat" dyes, of which indigo is the classic example, are insoluble in water but become soluble upon
reduction to the "leuco" dye. The "leuco" forms of such
dyes may or may not be colorless; for example, the solution of leuco-indigo (often called indigo-white) is green.
Cloth impregnated with the solution of the "leuco" dye
develops a "fast" color when oxidized in the air.
183
ml. of water. Stopper the flask to exclude air and shake
it gently 2-3 minutes. Note that the solution acquires a
dark-green color as the indigo dissolves. Dilute the solution with 50 ml. of water.
From a piece of cotton cloth, cut a strip 2 inches wide
by 10 inches long. Hold the strip at one end and dip
the lower half or two thirds of the cloth into the leucoindigo for 10-15 seconds and then hang the cloth on a
support to oxidize in the air. After a few minutes wash
the cloth under the tap. Is the blue color fast? Fasten
a sample of the dyed cloth in your notebook.
Reduction and Reoxidation of a Dye
In a 1-liter flask dissolve 10 g. of glucose and 10 g.
of sodium hydroxide in 500 ml. of water. To the wellshaken solution add 1 or 2 ml. of a solution of methylene blue in order to impart a distinct blue color to the
solution.
When this solution is allowed to stand quietly for
about 1 minute, the blue color disappears because the
dye is reduced to its leuco form by the alkaline solution
of glucose. When the flask is shaken vigorously so that
the dye may be oxidized by good contact with the air,
the blue color reappears, only to fade again when the
flask is allowed to remain at rest. This "now you see it,
now you don't" demonstration may be repeated many
times.
Cleaning the Glassware
Dye stains may be removed from the glassware by
brushing with a thin paste made of bleaching powder
and water. Remove any dye spots from your hands
likewise by application of a little of this paste; finally
remove the odor of chlorine from your hands by washing them with a little alcohol.
red'n.
c=c
^
H
oxid.
QUESTIONS
1. What structural formula would you assign to a dye
made by diazotizing the amine listed in column A and
coupling it with the compound opposite it in column B.
\
||
o
Indigo
(Insoluble in water)
H
N
C^C
)
\
c
I
OH
Leuco-indigo
(Soluble in water)
Procedure. In a small Erlenmeyer flask place 0.1 g.
of blue indigo powder (or 0.5 g. of the 20 per cent
indigo paste), 0.1 g. of sodium hydrosulfite (Na2S 2 0 4 ),
2 pellets of sodium hydroxide (about 0.15 g.), and 10
(a) /7-aminodimethylaniline
(b) a-naphthylamine
(c) sulfanilic acid
(d) sulfanilic acid
(e) benzidine
/?-naphthol
a-naphthol
p-cresol
resorcinol
4-amino-1 -naphthalenesulfonic acid
2. What structural formula would you assign to an azo
dye which upon reduction gave:
(a) aniline (1 mole) and p-aminophenol (1 mole)
(b) sulfanilic acid (1 mole) and l-amino-2-naphthol
(1 mole)
(c) benzidine (1 mole) and 3,4-diamino-l-naphthalenesulfonic acid (2 moles)
EXPERIMENT 78
Malachite Green, Phenolphthalein, and Fluorescein
I. PREPARATION OF MALACHITE GREEN
CH3
/
^ - o
+ 2H
CH3
y~vv
H
y~V-N—CH3
™i {^yc
•N
^=^
+ H2O
\^V-N—CH,
CH3
CHa
Leuco Base of Malachite Green
CH8
H
//~Vi-CH3
f V-N—CHa
CH3
Leuco Base of
Malachite Green
0-60
CHa
OK/-\-l-CK3
\ ^ > - N - C H ,
CHa
^V-N—CHa
HCl
fVc-
CI"
\
I
CH3
Carbinol Base of
Malachite Green
N—CH3
CHa
Malachite Green
(A salt)
Introduction. It has been said that in giving an exam- lation until 125 ml. of water has been collected. This
ination in Organic Chemistry one should not ask a stu- distillation "boils out," or steam distills, the excess benzdent to write the answers to a series of questions, but aldehyde and dimethylaniline. The leuco base of Malarather should send him to the laboratory to prepare a chite Green remains in the flask as a gummy blue-green
specimen of Malachite Green. If the student can make mass. The prefix leuco- means "white" but the leuco
this dye without getting it all over the laboratory as well form of a dye may or may not be colorless; its color,
as himself, he is an excellent chemist. Many students however, if far less intense than that of the correspondhave failed so woefully on such a test that in many uni- ing dye.
versities the experiment, though highly instructive, is
Oxidation of the Leuco Base to the Dye. Add 3 ml. of
often omitted from the list of assignments.
concentrated hydrochloric acid to the contents of the
The procedure that follows is short and only a modi- distilling flask and shake the mixture for 30 seconds to
cum of care is needed to ensure that not so much as one dissolve as much of the leuco base as possible. Add 150
drop of the dye solution will be spilled on one's clothing ml. of tap water, shake well, and then add 3 g. of lead
dioxide (Pb0 2 ). Note the immediate deepening of the
or upon the laboratory table.
Procedure. Place 4 ml. each of benzaldehyde and color. Shake the flask for 2 minutes to mix the materials
dimethylaniline along with 2 or 3 g. of coarsely pow- well and then add about 3 g. of sodium sulfate to predered fused zinc chloride into a 250- or 500-ml. dis- cipitate the lead as lead sulfate.
Heat the solution nearly to boiling and filter part of
tilling flask. (The sticks of fused zinc chloride should
be broken quickly in a dry mortar because the mate- the solution (about 15 ml.) into a large test tube. Add
rial rapidly absorbs water from the air. Keep the bottle a piece of woolen cloth to this solution and heat it until
it boils for 1 minute. Remove the cloth with a glass rod
of zinc chloride closed.)
Lower a thermometer into the flask so that the bulb and wash it at the water tap. Dry the cloth and fasten
rests on the bottom. Warm the flask with a small semi- it in your notebook with Scotch tape. Pour all solutions
luminous flame of the Bunsen burner until the ther- of the dye directly into the drain pipe in the sink and
mometer registers a temperature of 130°-140°. Main- wash the dye down the drain.
Cleaning the Glassware. To clean the glassware protain this temperature by intermittent application or removal of heat for 10 minutes by the clock. The flask now ceed in the following manner:
(1) Wash the flask several times with water at the
contains the leuco base of Malachite Green along with
the zinc chloride and some unchanged benzaldehyde sink, pouring the dye solution directly into the drain
pipe.
and dimethylaniline.
(2) Pour 20 ml. of concentrated hydrochloric acid
Allow the flask to cool somewhat and add 150 ml. of
water measured from a graduated cylinder. Connect into the flask, rotate the flask to wet the sides well, and
the flask with a condenser and remove water by distil- add 150 ml. of water. Heat this solution nearly to boil184
MALACHITE GREEN, PHENOLPHTHALEIN, AND FLUORESCEIN
ing and shake the flask to dissolve as much as possible
of the dye remaining on the upper part of the flask.
Wash the flask well at the sink.
(3) Remove the remaining dye by total immersion
of the flask in the crock of bleaching solution, which
will be placed near the sink. (The bleaching solution
contains CaOCl2 + Na 2 C0 3 .) After several minutes remove the flask with the old pair of tongs provided for
the purpose and wash the flask well with water.
185
(4) The test tube and funnel may be washed with
water at the sink and then immersed in the bleaching
solution.
(5) Remove any spots of dye on your hands by application of a little of the bleaching solution and allowing it to remain for one or two minutes. Wash well and
remove the odor of chlorine from your hands by an
alcohol rub.
Introduction. Malachite Green, prepared in Part I,
II. PHENOLPHTHALEIN
O
f V-OH
0 ^
V-OH
c
Phenolphthalein (colorless)
Lactone of the carbinol base
•\=
o
/ V -0~,Na+
C—0-,Na+
C—0-,Na+
0
0
Carbinol base
(Disodium salt)
60-80
is a typical example of the triphenylmethane dyes. The
phthalein dyes are so closely related structurally to those
of the triphenylmethane classification that the two types
may well be studied collectively. Note that the colorless
form of phenolphthalein may be considered the lactone
of the carbinol base of the dye.
Procedure. In a test tube mix 0.3-0.4 g. of phenol
with about 0.2 g. of phthalic anhydride. Add 3-4 drops
II
Phenolphthalein (red)
of concentrated sulfuric acid, stir the mixture with a
stirring rod, and heat the mass to a temperature of
approximately 160° for 2-3 minutes. The substances
will react with gentle ebullition. Pour the hot melt into
50-60 ml. of water. Make a portion of the solution alkaline and then reacidify it. Does the solution give the
change of color that is characteristic of phenolphthalein?
0 - , Na+
Fluorescein (acidic)
Fluorescein (sodium salt)
186
80-100
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
Introduction. If resorcinol (m-dihydroxybenzene) replaces phenol in the preceding experiment, the dye
formed, known as fluorescein, contains in its molecular
structure an oxygen linkage between the two phenolic
nuclei. Solutions of fluorescein have a greenish-yellow
fluorescence.
Procedure. Repeat the above experiment replacing
the phenol with resorcinol. After the reaction mixture
has been poured into water, make the solution alkaline
and examine the solution by direct and by reflected
light.
QUESTIONS
1. Show how Michler's ketone and phenylmagnesium
bromide may be used for the preparation of Malachite
Green.
2. Show how Michler's ketone may be condensed with
dimethylaniline in the production of Crystal Violet.
3. (a) What may be formed by the reduction of Malachite Green; (b) by the reaction of Malachite Green with
sodium hydroxide solution?
4. (a) Compare the formula of Crystal Violet with
that of Pararosaniline. (b) Show how Pararosaniline may
be converted into the parent hydrocarbon, triphenylmethane.
5. Write structural formulas for:
(a) 4-hydroxytriphenylmethane
(b) 4,4'-dihy droxy triphenylmethane
(c) 4,4',4"-trihydroxytriphenylmethane
(d) eosin
(e) mercurochrome
EXPERIMENT 79
I. 3-Aminophthalhydrazide (^Luminol")
o
NH 3 +
||
O + |
,S0 4 = + 2CH3—C—ONa + H 2 0 - •
NH 3 +
NO
O
II
c—o-
+NH 3
0
+ Na 2 S0 4 + 2CH 3 —C—OH
C—O- +NH 3
II. Chemiluminescence
Introduction. All chemical reactions proceed with the
evolution or absorption of energy. In most instances the
energy evolved or absorbed is in the form of heat, although many experimenters from time to time have
noticed that visible radiation was produced when various chemical reactions were conducted in a darkened
room. In most instances of this kind the intensity of the
light emitted is low. The oxidation of 3-aminophthalhydrazide in alkaline solution, however, gives one of
the most brilliant displays of chemiluminescence on
record and has the added advantages that, in contrast
to certain other compounds which exhibit this phenomenon, the materials are easily obtained, are safe to handle, and are used in very dilute solutions.
Today's experiment is a small-scale adaptation of the
procedure given by Huntress, Stanley, and Parker.1
These authors not only describe the preparation of
3-aminophthalhydrazide but also present a discussion of
chemiluminescence that will be of interest.
I. 3-AMINOPHTHALHYDRAZIDE
("LUMINOL")
Procedure. Into a 25 x 200 ml. test tube introduce
1 g. of 3-nitrophthalic anhydride, 0.7 g. of hydrazine
sulfate, 1 g. of hydrated sodium acetate, and 4 ml. of
water. Support the tube at an angle of about 45° on an
iron stand by means of a clamp and heat the mixture
to boiling. Note that the escaping steam carries with it
the vapors of acetic acid.
The hot suspension now contains hydrazine 3-nitrophthalate. The composition of the salt formed by
hydrazine and 3-nitrophthalic acid apparently is not
known with certainty. The structure shown in the equation is one possibility.
In order to convert the salt (hydrazine 3-nitrophthalate) to 3-nitrophthalhydrazide (belonging to the amide
family of compounds), a temperature considerably
above the boiling point of water is required. To attain
this temperature introduce 5 ml. of glycerol and a boiling chip, insert a thermometer whose bulb rests on the
bottom of the tube, and heat the tube to remove water.
No stopper is used; the mouth of the tube is left open
to facilitate the escape of steam.
Boil the contents of the tube rather vigorously but
do not apply heat so rapidly that excessive bumping
occurs. Stir the contents of the tube with a stirring
rod and note the rise in temperature. After a temperature of 120° is attained the thermometer reading
rises quickly to 200°. At this point heat the tube gently
and intermittently so that a temperature of 200°-220°
is maintained for 3 or 4 minutes. During this period the
contents of the tube acquire an orange-yellow color.
Allow the tube to cool to about 100° and add 40 ml.
of water. Warm the tube over the Bunsen burner to
accelerate the coagulation of the light yellow 3-nitrophthalhydrazide and set the tube in an ice bath for
a few minutes.
o
O
C—O-
+NH3
+ 2H 2 0
+NH;
1
E. H. Huntress, L. N. Stanley and A. S. Parker, J. Chem.
Educ, 11, 142-145 (1934).
187
C—NH
C—NH
N0 2 ||
O
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
188
As soon as the 3-nitrophthalhydrazide has settled
well, pour off the supernatant solution and shake the
residual yellow powder with another 40-ml. portion of
water. Warm the mixture, if necessary, to increase the
rate of sedimentation, and, after chilling in ice, decant
the clear upper solution from the 3-nitrophthalhydrazide which remains in the bottom of the tube.
Reduction of 3-Nitrophthalhydrazide to 3-Aminophthalhydrazide. The nitro compound is now contained
in the test tube along with a little water. Add to the
contents of the tube 5 ml. of a 10 per cent solution of
sodium hydroxide. To the red solution thus obtained
add 3 g. of sodium hydrosulfite as a reducing agent and
heat the contents of the tube to boiling.
Maintain a temperature at or near the boiling point
for 3-4 minutes. The red color of the solution quickly
gives way to the yellow color of the 3-aminophthalhydrazide, some of which usually precipitates almost immediately. The quantity of this precipitated amino comO
C—NH
+ Na2S204 + 2H20 •
C—NH
+ 2NaHS04
pound increases when the contents of the tube are
cooled and acidified with glacial acetic acid (about 2
ml. of the acid will be required).
Collect the 3-aminophthalhydrazide ("Luminol") on
a small Buchner funnel and wash it twice with 25-ml.
portions of water. Remove the filter paper with the
"Luminol," and place both the paper and moist product
on a watch glass. Use part of the moist "Luminol" for
PartTI and place the watch glass (or Petri dish) containing the remainder in an oven to dry. The recorded
melting point of 3-aminophthalhydrazide is about 310°.
II. CHEMILUMINESCENCE
Prepare the following solutions:
A. Dissolve a quantity of the moist "Luminol" estimated to contain 0.1 g. of the dry material in 10 ml. of
10 per cent sodium hydroxide solution and dilute the
solution to 1 liter.
B. Dissolve 0.5 g. of potassium ferricyanide
[K3Fe(CN)6] in 75-100 ml. of water, add 15 ml. of
ordinary 3 per cent hydrogen peroxide solution, and
dilute the solution to 1 liter.
Take these solutions to a room that can be darkened
where you have at hand a reagent bottle of hydrochloric
acid and one of sodium hydroxide solution. Place a
6-inch funnel in the mouth of a large flask (3-5 liters),
turn off the lights, and mix solutions A and B by pouring them through the funnel into the large flask. The
chemiluminescence appears as soon as the solutions are
mixed. The light emitted will illuminate the room so
that you can now easily locate your bottles of reagents.
Add to the mixed solutions in the large flask a little
sodium hydroxide and note that the chemiluminescence
is intensified. Then acidify a portion of the luminescent
solution with hydrochloric acid and note that the emission of light ceases and that it reappears if the solution
is again quickly made alkaline.
EXPERIMENT 80
Heterocyclic Compounds
Phenylmethylpyrazolone, Furfural, and Pyridine
(1)
CH 3 —C-
-CH 2
CH 3 —C-
I
c=o
I
O
H
H^N
-HjO
\
H
HO—C-
H
-C—OH
/
\
/
\
OH HO
/
:
c=o
I. PREPARATION OF PHENYLMETHYLPYRAZOLONE
20-80
80-120
N
I
CeHs
Phenylmethylpyrazolone
HC-
-CH
HC
H
C—C=0
H
An Aldopentose
0-20
C=0
/
-3H2o
H
H
H
N
\
N—rH OQH,
Phenylhydrazone of
ethyl acetoacetate
I
(2)
-CsH.OH
CeH5
N—H
-CH 2
CH 3 —C-
I
c=o
N
OQH6
\
-CH 2
In a large test tube (25 x 200 mm.) mix 6.5 g. (6.5
ml., 0.05 mole) of ethyl acetoacetate with 5.4 g. (5 ml.,
0.05 mole) of phenylhydrazine. Note that a little heat
is evolved and that the original clear solution soon becomes turbid owing to the separation of droplets of
water in the formation of the phenylhydrazone of ethyl
acetoacetate. Fit the tube with a cork stopper through
which is inserted a piece of glass tubing about 18 inches
long.
Heat the tube in a bath of molten paraffin wax (see
Figure 31, page 139) for 1 hour at a temperature of
135°-145°.
\
O
/
Furfural
warm 10 per cent solution of hydrochloric acid. Cool
the solution and make it basic by addition of ammonium
hydroxide solution. Result? How do you account for
the amphoteric nature of phenylmethylpyrazolone?
II. PROPERTIES OF FURFURAL
Introduction. The commercially important aldehyde,
furfural, is obtained by heating oat hulls, crushed corn
cobs, and other materials containing pentosans with
sodium chloride and 10 per cent sulfuric acid solution
in water. Note the similarity of the molecular structures
of furfural and benzaldehyde, particularly the lack of an
alpha hydrogen atom in each of the molecular formulas.
The following short experiments serve to show the simi[During this period in the preparation of phenylmethyl- lar properties of these two aldehydes.
pyrazolone, go on to Parts II and III.]
Procedure. Redistill 10 ml. of commercial furfural
When the heating period has been completed, pour for use in the following tests.
(a) Action of Tollens' Solution. Warm a few drops
the contents of the tube into a small beaker, cool the
beaker in cold water and stir the material with 30-40 of furfural with 5 ml. of Tollens' solution. Does any
ml. of ether. As soon as crystals form, chill the beaker reduction take place? Equation.
(b) Reaction with Ammonia. Place approximately
in ice and collect the product on the Buchner funnel.
Recrystallize the phenylmethylpyrazolone from alcohol 1 ml. of furfural in a test tube and add 5 ml. of concentrated ammonium hydroxide solution. Close the mouth
or hot water. Yield 6-8 g. M.p. 127°.
Test the solubility of phenylmethylpyrazolone in 5 of the test tube with a stopper, shake the tube thoroughly
per cent sodium hydroxide solution by warming 0.2 g. and let it stand for a few minutes. The reaction is simof the compound with a few ml. of the alkaline solution. ilar to that which takes place between benzaldehyde and
Cool the solution and acidify it with acetic acid. Result. ammonia. Equation.
(c) Auto-oxidation and Reduction. Shake 1 ml. of
Test the solubility of phenylmethylpyrazolone in a
189
20-60
UNITIZED EXPERIMENTS IN ORGANIC CHEMISTRY
190
furfural in a test tube with 5 ml. of a 20 per cent solution of sodium hydroxide. What are the crystals which
separate? What other product is produced? Equation.
Does benzaldehyde give a similar reaction?
III.
PROPERTIES OF PYRIDINE
(a) Action on Litmus Paper. Shake a few drops of
pyridine with 5-10 ml. of water and test the solution
with litmus paper. Write an equation for the reaction of
pyridine and water.
(b) Reaction with Ferric Chloride Solution. To the
solution of pyridine prepared above add a few ml. of
ferric chloride solution. What is the brown gelatinous
precipitate? Equation.
(c) Addition of Methyl Iodide. Add 1 ml. of pyridine to 1 ml. of methyl iodide. Result. Write the equation to show the formation of the methylpyridinium
iodide (a quaternary ammonium salt).
EXPERIMENT 81
Preparation of Quinoline by the Skraup Synthesis
HO—CH2
\
1^1
V \
f^il
^ \
NH 2
HC-OH
H2C—OH
( ^ V >
Sx^N^
N02
Introduction, In the conversion of a molecule of aniline into a molecule of quinoline three additional carbon atoms must be supplied by a reactant, other than
the aniline, and an oxidizing agent must ordinarily be
used to effect ring closure. In the Skraup synthesis,
glycerol, which presumably is converted into acrolein
by the sulfuric acid used, supplies the needed three
carbon atoms and nitrobenzene serves as the oxidizing
agent. The aniline produced by reduction of the nitrobenzene is likewise converted to quinoline.
Procedure. In a 500-ml. flask mix 6 g. of powdered
ferrous sulfate, 10 ml. of nitrobenzene, and 18.6 g. (18
ml., 0.2 mole) of aniline. Then add in small portions,
and with constant shaking of the flask, 25 ml. of concentrated sulfuric acid. The reaction between the aniline and sulfuric acid is so highly exothermic that it
may be necessary to cool the flask somewhat, although,
for convenience in mixing, the temperature of the mixture should remain high enough to maintain the contents of the flask in afluidcondition. Finally, again with
constant shaking of the flask, add 50 g. (40 ml.) of
glycerol.""
Clamp the flask securely to a ring stand and support
it by means of a wire gauze resting on a ring. Fit a
reflux condenser to the flask and heat the flask gently
by waving a small, semiluminous flame of the Bunsen
burner beneath it. Agitate the flask as much as possible and continue heating the flask cautiously until
an exothermic reaction begins. The burner is then removed and the reaction allowed to proceed spontaneously. Be prepared to cool the flask in a bath of ice and
water if the rate of boiling should become excessively
rapid. When the automatic reaction has subsided, heat
the contents of the flask to boiling for 40 minutes.
Removal of Excess Nitrobenzene. Cool the flask
somewhat, add 200 ml. of water, and pour the liquid
into a larger flask for steam distillation. The collection
of about 100 ml. of distillate, requiring about 10 min-
utes, will serve to remove any nitrobenzene that was not
utilized in the reaction. This distillate is discarded.
Conversion of Excess Aniline to Phenol. Cool the
contents of the steam-distillation flask to 25°-30° and
add a solution of sodium nitrite until a drop of the
solution on starch-potassium iodide paper shows that
an excess of sodium nitrite is present. (Note: Nitrous
acid liberates iodine from potassium iodide; iodine and
starch give a blue coloration.) Ordinarily about 5 g. of
sodium nitrite is sufficient.
Warm the flask to 50° for the evolution of nitrogen
from the diazonium salt and then, with constant shaking and cooling of the flask, make the contents alkaline
by the slow addition of a cold solution of 40 g. of sodium hydroxide in 100 ml. of water. If a test drop of
the well-shaken liquid is not alkaline to litmus, more
sodium hydroxide must be added.
Isolation of the Quinoline. Subject the contents of the
flask to steam distillation and collect 400-450 ml. of
distillate. This will require about 40 minutes. Pour the
distillate into a 500-ml. separatory funnel and remove
the lower layer (10-12 ml.) of quinoline. Then extract
the water suspension twice with 15-ml. portions of carbon tetrachloride, combine the extract with thefirstportion of quinoline, and dry the combined material over a
little solid sodium hydroxide. Decant the liquid from the
drying agent and distill it. The carbon tetrachloride
boils at 77° and the quinoline at 237°. Quinoline is a
pale yellow liquid with a disagreeable odor. Yield 1012 g.
QUESTIONS
1. What compound will be produced by the Skraup
process if the aniline used is replaced (a) by p-anisidine,
(b) by o-bromoaniline?
2. How may nicotinic acid be obtained from quinoline?
191
Special Reagents
Tollens' Reagent. Thirty grams of silver nitrate are
dissolved in 500 ml. of water and a solution of ammonium hydroxide is added until the precipitate of silver
oxide which first forms is barely redissolved. Dilute the
solution to a liter. The solution may be used in this
form. If greater sensitivity is desired a portion of the
solution should be mixed immediately before use with
an equal volume of a 5 per cent solution of sodium
hydroxide. Upon standing or heating, this mixture deposits a black precipitate which is explosive.
Fehling's Solution. Dissolve 34.64 g. of pure copper
sulfate (CuS0 4 • 5H 2 0) in 350-400 ml. of distilled
water and dilute the solution to 500 ml. Label this solution Fehling's Solution I.
Prepare* another solution containing 173 g. of Rochelle salt and 65 g. of sodium hydroxide in about 350
ml. of water and dilute the solution to a volume of 500
ml. Put this in a bottle labeled Fehling's Solution II.
Use equal volumes of I and II in making a test. One
ml. of the mixed solutions will oxidize 0.005 g. of glucose.
Benedict's Qualitative Reagent. Prepare solution A
by dissolving 173 g. of sodium citrate and 100 g. of
anhydrous sodium carbonate in about 600 ml. of water
and dilute the solution to 850 ml. Prepare solution B
by dissolving 17.3 g. of crystalline copper sulfate
(CuS04 • 5H 2 0) in 100 ml. of water and diluting the
solution to 150 ml. Add solution B to solution A and
mix well for the preparation of Benedict's solution.
Schiffs Reagent. Dissolve 1 g. of fuchsine (rosaniline) in 350-400 ml. of warm water. Cool the solution
and pass sulfur dioxide through it until the solution is
colorless or only a pale yellow. Dilute to 1000 ml. Keep
the solution in amber-colored bottles.
MoliscKs Solution. Ten grams of a-naphthol are dissolved in 100 ml. of ethyl alcohol or chloroform.
Iodine in Potassium Iodide. Dissolve 5 g. of iodine
in 200 ml. of water containing 10 g. of potassium iodide.
This solution may be used in this concentration for making iodoform tests. When used for the detection of
starch, a portion of the solution should be diluted to
10-25 times its original volume.
Potassium Mercuric Iodide. Dissolve 14 g. of mercuric chloride and 50 g. of potassium iodide in 1 liter of
water.
Millon's Reagent. Ten grams of mercury are dissolved in 20 ml. of hot concentrated nitric acid and the
resulting solution is diluted with 30 ml. of water.
Ammoniacal Cuprous Chloride. Ten grams of cuprous chloride are dissolved in 100 ml. of concentrated
ammonium hydroxide and the solution diluted to 500
ml. If solid cuprous chloride is not at hand it may be
prepared as described in Experiment 59. The precipitate of cuprous chloride there formed is removed by
filtration and dissolved in ammonium hydroxide.
Lucas' Reagent. Dissolve 136 g. of anhydrous zinc
chloride in 105 g. of concentrated hydrochloric acid,
with cooling.
2,4-Dinitrophenylhydrazine Reagent. Three grams of
2,4-dinitrophenylhydrazine are dissolved in 15 ml. of
concentrated sulfuric acid, and this solution is then
added, with stirring, to a solution of 20 ml. of water in
70 ml. of 95 per cent ethanol. The mixture is stirred
thoroughly and filtered. The filtrate is used as the test
reagent.
Periodic Acid Reagent. Dissolve 0.5 g. of paraperiodic
acid (H 5 I0 6 ) in 100 ml. of distilled water.
192
Index
;e numbers followed by t refer to a ta
Abderhalden drying pistol, 22
Acetals, 124
Acetamide, 19, 87
hydrolysis of, 91
preparation of, 91
properties of, 91
p-Acetaminobenzenesulf onamide, 149
p-Acetaminobenzenesulfonyl chloride,
149
Acetanilide, It, 9t, 136, 140, 149
nitration of, 142
preparation of, 136, 140
recrystallization of, 23
sulfonation of, 149
use in preparation of sulfanilamide,
149
Acetate test, for alcohols, 57
Acetic acid, 18t
decarboxylation of, 44
glacial, 89
Acetic anhydride, apparatus for distillation of, 90
hydrolysis of, 91
preparation of, 90
properties, 91
use in preparation of acetophenone,
163
Acetobromoamide, 93
Acetone, It, 18t, 73t
Acetone 2,4-dinitropheny lhy drazone,
preparation of, 73
Acetone phenylhydrazone, preparation
of, 73
Acetone semicarbazone, preparation
of, 73
Acetonitrile, preparation of, 95
properties of, 95
Acetophenone, 73t, 163
preparation of, by a Friedel and
Crafts reaction, 163
Acetoxime, preparation of, 73
Acetylation, of aniline, 136
Acetyl chloride, 90
apparatus for preparation of, 88
hydrolysis of, 89
preparation of, 88
properties of, 89
use in preparation of acetophenone,
163
Acetylene, acidity of, 54
alkylation of, 54
oxidation of, 54
preparation of, 54
properties of, 54
Acetylsalicylic acid (aspirin), preparation of, 178
Acid anhydrides, 90
Acid chlorides, preparation of, 88
Acid splitting, of ^-ketoesters, 104
Acidity, of acetylene, 54
of alcohols, 56
of ethyl acetoacetate, 100
of ethyl malonate, 100
Acids, use in extraction, 27
Active hydrogen, test for, 46
Active methylene group, 100, 104
Acylating agents, 90
Addition reactions, of bromine to
acetylene, 54
of bromine to amylene, 53
of bromine to ethylene, 50
of sodium bisulfite to aldehydes and
ketones, 70
of water to amylene, 52
Adipic acid, 9t, 19
preparation of, 106
pyrolysis of barium salt, 67
Adsorption chromatography, use of
activated carbon in, 35
use of alumina in, 35
use of calcium carbonate in, 35
use of calcium phosphate in, 35
use of Fuller's earth in, 35
use of inulin in, 35
use of magnesia in, 35
use of slaked lime in, 35
use of starch in, 35
use of sucrose in, 35
use of Super-Cel in, 35
use of talc in, 35
Air condenser, use of glass tube as, 83
L( + ) -Alanine, 113
Albumin, coagulation of, 111
Alcohols, acetate test for, 57
acidity of, 56
chemistry of, 56
dehydration of, 56
dehydrogenation of, 69
oxidation of, 56, 69
preparation of derivatives of, 180
relative ease of dehydration, 49
rule to predict major olefin in dehydration, 52
salicylate test for, 57
use of alumina in dehydration of,
49
Aldehyde resins, 70
Aldehydes, derivatives of, 72
oxidation of, 70
preparation from primary alcohols,
69
tests for, 69, 70, 179
193
Alkalies, use in extraction, 27, 28
Alkylacetic acids, preparation of, 104
Alkylation, of acetylene, 54
Alkyl halides, properties of, 62
Alkyl halides, reactivity of, 59
Alkyl iodides, preparation of, 59
Alumina, use in adsorption chromatography, 35
use in dehydration of alcohols, 49
use in preparation of ether, 64
Aluminum carbide, hydrolysis of, to
produce methane, 45
Amides, preparation of, 90, 95
test for, 179
Amino acids, 111, 113
action of nitrous acid on, 114
buffer action of, 114
Aminoazobenzene, 135, 154
by rearrangement of diazoaminobenzene, 153
preparation of, 153
p-Aminobenzenesulfonamide, 149
Aminodimethylbenzenes, 136
3-Aminophthalhydrazide, preparation
of, 187
Ammoniacal cuprous chloride, preparation of, 192
Ammonium hydrosulfide, use of in
preparation of m-nitroaniline, 143
tt-Amyl alcohol, acetate test for, 57
5-Amyl alcohol, dehydration of, 52
/-Amyl alcohol, dehydration of, 52
Amyl alcohols, dehydration of, 52
H-Amyl iodide, 60
Amylene, hydration of, 52
Amylene bromide, preparation, 53
Amylenes, preparation, 52
Analysis, principles as applied to organic chemistry, 41
Anhydrous aluminum chloride, as a
catalyst in preparation of acetophenone, 163
use in preparation of benzophenone,
165
Aniline, It, 134, 136, 138t, 141
acetylation of, 136
basic character of, 136
action on indicators, 136
ferric chloride test, 136
formation of aniline acid sulfate,
136
formation of aniline hydrochloride, 136
benzene solution of, 134
derivatives of, 136
194
Aniline (cont.)
diazotization of, 155
isocyanide test for, 136
melting point of derivatives of, 138t
preparation of, 134
reaction with acetic anhydride, 91
reaction with acetyl chloride, 89
reaction with oxidizing agents, 136
solid derivatives of, 136
use in the preparation of quinoline,
191
Aniline acid sulfate, 140
formation of, 136
use in preparation of phenol, 155
Aniline hydrochloride, 136, 153
o-Anisidine, 138t
melting points of derivatives of,
138t
Anthracene, 22, 128
oxidation to anthraquinone, 172
Anthranilic acid, 9t
Anthraquinone, preparation of, 172
Anti-freeze compounds, 96
Apparatus, for the calibration of a
thermometer, 2
for decarboxylation of an acid, 127
for distillation of acetic anhydride,
90
for distillation of ether, 64
for nitrosation of methyl ethyl ketone, 75
for preparation of acetyl chloride,
88
for preparation of bromobenzene,
129
for preparation of rt-butyraldehyde,
70
for preparation of ethane, 46
for preparation of ether, 64
for preparation of ethyl iodide, 60
for preparation of methane, 44
for preparation of methylamine, 93
for synthesis of ethylene and ethylene bromide, 49
L( + )-Arginine, 113
Aromatic amino compounds, 136
Aromatic hydrocarbons, properties of,
127, 128
Aromatic nitro compounds, 132, 133
solid, 132
L( —)-Aspartic acid, 113
Aspirin, preparation of, 178
properties of, 178
Associated liquids, 19
Azeotropes, 87
Azeotropic mixtures, 16
Azo dyes, 182
Azobenzene, 147, 148
preparation of, 147
Baeyer test, 54
Baeyer's test for unsaturation, 51
INDEX
Basicity of aniline, 136
Beckmann rearrangement, 167
of a ketoxime, 167
Beilstein, F. K., biographical footnote,
41
Beilstein test, 41
Benedict's qualitative reagent, preparation of, 192
Benzaldehyde, 73t, 162
atmospheric oxidation of, 162
auto-oxidation and reduction of
(Cannizzaro reaction), 162
condensation with acetone, 162
properties of, 162
reaction with ammonia, 162
reaction with phenylhydrazine, 162
reaction with sodium bisulfite, 162
reducing action of, 162
solubility of, 162
use in preparation of benzoin, 169
use in preparation of cinnamic acid,
171
Benzamide, 9t
Benzanilide, 9t, 136
preparation of, by Schotten-Baumann method, 136
Benzene, It, 18t, 141
flammability of, 127
nitration of, 128, 132
permanganate test for, 127
properties of, 127
reaction with bromine, 127
as a solvent, 127
sulfonation of, 127
use as an extracting solvent, 25
use in preparation of benzophenone,
165
use in preparation of bromobenzene,
129
use in preparation of iodobenzene,
131
use in preparation of nitrobenzene,
132
Benzenediazonium chloride, 151
coupling with aniline, 153
Benzenediazonium salts, hydrolysis of,
155
Benzidine, 147
as a reagent for free chlorine, 148
precipitation of, 148
preparation of, 148
Benzidine hydrochloride, 147, 148
Benzidine sulfate, 148
Benzil, preparation of, 169
Benzilic acid, preparation of, 169, 170
Benzoic acid, It, 9t, 22
Benzoic acid, extraction with sodium
hydroxide solution, 28, 29
preparation by Grignard method, 80
preparation from benzyl chloride,
174
use in preparation of benzene, 127
Benzoin, 9t
preparation of, 169
Benzophenone, 165
preparation by a Friedel and Crafts
reaction, 165
use in preparation of benzophenone
oxime, 167
use in preparation of triphenylcarbinol, 168
Benzophenone dichloride, 165
Benzophenone oxime, preparation of,
167
rearrangement of, to benzanilide,
167
p-Benzoquinone, preparation of, 172
Benzyl chloride, preparation of benzoic acid from, 174
Biacetyl, 75
Biphenyl, It
by-product in preparation of triphenylcarbinol, 168
Biuret, 115
Biuret test, 112
Bleaching powder, 77
Blue print paper, 109
Boiling chips, 11
Boiling points, correction for pressure
changes, 1
effects of hydrogen bonding on, 96
Boric acid, reaction with 1,2-diols, 96
Bromination, of kerosene, 48
Bromine, use in preparation of bromobenzene, 129
/7-Bromoacetanilide, 141
hydrolysis of, 141
preparation of, 141
p-Bromoaniline, 138t, 141
melting point of derivatives of, 138t
preparation of, 141
Bromobenzene, It
apparatus for preparation and collection of, 129
distillation of, 32, 34
preparation of, 129
use in preparation of triphenylcarbinol, 168
/7-Bromophenol, melting point of derivatives of, 161t
Brown sugar, decolorization, 23
(-)-Brucine, 118
Bubble plate column, 14
Buffer action, of amino acids, 114
Bumping, 11
Butanal, see w-butyraldehyde
/-Butyl alcohol, extraction with chloroform, 28
n-Butyl bromide, reaction with ethyl
sodiomalonate, 103
/-Butyl chloride, Grignard reagent derived from, 80
preparation of, 60
reaction with sodium cyanide, 80
INDEX
H-Butyl iodide, 60
j-Buiyl iodide, 60
w-Butylmalonic acid, 104
w-Butyraldehyde, 73t
apparatus for preparation of, 70
preparation of, 69
Calcium carbide, use in preparation of
acetylene, 54
Calcium carbonate, use in adsorption
chromatography, 35
Calcium chloride, use as drying agent,
31
Calcium hydride, use as drying agent,
30
Calcium oxide, use as drying agent, 30
Calcium phosphate, use in adsorption
chromatography, 35
Calcium sulfate, use as drying agent,
30, 31
Calibration of a thermometer, apparatus for, 2
Camphor, purification by sublimation,
9
vapor-pressure-temperature diagram, 8
Cane sugar, oxidation of, 98
preparation of oxalic acid from, 98
Canned heat, 57
Cannizzaro reaction, 162
Caproamide, 19
«-Caproanilide, 106
Caproic acid, 19
rc-Caproic acid, preparation of, 104,
106
Carbanilide, 136
Carbohydrates, 111
chemical properties of, 122
optical properties of, 119
Carbon, activated, use in adsorption
chromatography, 35
Carbon monoxide, generation from
formic acid, 83
Carbon tetrachloride, 18t
use as an extracting solvent, 25
use in preparation of benzophenone,
165
Carborundum stones, 1 If
Carboxylic acids, methods of preparation, 80
preparation of, 95
Carotenes, isolation from leaf pigments, 39
Cellulose, 124
use in partition chromatography, 38
Celulose acetate, 125
Cellulose nitrate, 125
Cellulose xanthate, 125
Chemiluminescence, 187, 188
Chlorine, "available," 78
o-Chloroaniline, 136, 138t
melting points of derivatives of,
138t
p-Chloroaniline, 138t
melting points of derivatives of, 138t
Chlorobenzene, It, 151
by the Sandmeyer reaction, 151
o-Chlorobenzoic acid, 9t
Chloroform, 18t, 136
preparation of, 77
properties of, 78
reduction of to methane, 45
use as an extracting solvent, 25
o-Chlorophenol, melting points of derivatives of, 161t
p-Chlorophenol, melting points of derivatives of, 16 It
Chlorophyll-a isolation from leaf pigments, 39
Chlorophyll-b, isolation from leaf pigments, 39
Chlorosulfonic acid, use in preparation
of sulfanilamide, 149
Chromatography, adsorbents, 35
adsorption, 35
adsorbability of organic compounds, 37
apparatus, 36
of colorless compounds, 37
packing of columns, 37
uses of, 37
definitions of terms, 35
ion exchange, 38
paper, 38, 113
partition, 38
solvents, 35
Cinnamaldehyde, 73t
Cinnamic acid, preparation of, 171
frarc.y-Cinnamic acid, 9t
Citric acid, properties of, 109
Claisen condensation, 100
Cloth, dyeing of, 182
Collodion, 125
Copper carbonate, use in preparation
of cuprous chloride solution, 151
Copper cyanurate, 115
Copper salts, quantitative determination of, 76
Copper turnings, use in preparation of
chlorobenzene, 151
Cotton, 125
dyeing of, 183
Coupling, 182
Cream of tartar, 109
m-Cresol, melting points of derivatives
of, 161t
o-Cresol, melting points of derivatives
of, 161t
p- melting points of derivatives of, 16It
p-Cresol, 157
Crotonaldehyde, 73t
Crystallization, 18
collection of crystals, 21
drying of crystals, 22
195
relation between rate and size of
crystals, 20
selection of solvent, 22
washing of crystals, 21
Crystal Violet, dyeing with, 183
extraction, 28
use in dyeing, 182
Cumene, 128
Cuprous acetylide, formation of, 54
Cuprous chloride, 151
from copper carbonate, 151
from copper sulfate, 151
from cupric chloride, 151
Cuprous chloride, ammoniacal, preparation of, 192
Cyanuric acid, 115
Cyclohexanone, 73t, 106
oxidation of, 106
Cyclopentanone, preparation of, 67
L(-)-Cystine, 113
Darco, use in decolorization, 20
Decarboxylation, 67
of acetic acid, 44
of malonic acids, 104
partial, 67
of salicylic acid, 178
Decarboxylation of an acid, apparatus
for, 127
Decolorization, of brown sugar, 23
of solutions, 20
use of Darco in, 20
use of Norit in, 20
use of Nuchar in, 20
Dehydration, of alcohols, 56
of amyl alcohols, 52
of ethyl alcohol, 49
of glycerol, 97
partial, of ethyl alcohol, 64
Dehydrogenation, of alcohols, 69
Dehydrohalogenation, preparation of
acetylenes by, 54
Desiccator, vacuum, 22
Dextrin, 124
N,AT-Diacetylbenzidine, It
Dialkylacetic acids, preparation of,
104
Dialysis, 125
Diazoaminobenzene, 153
preparation of, 153
rearrangement to aminoazobenzene,
153
Diazotization, 151, 153, 155, 182
of aniline, 155
p-Dibromobenzene, 130
p-Dichlorobenzene, 28, 29
2,4-Dichlorophenol, melting points of
derivatives of, 1611
Dichromate test, for aniline, 136
Diethyl adipate, preparation of, 108
Diethyl ketone, 73t
Diethyl phthalate, 100
196
ra-Dihydroxybenzene, 186
Di-isopropyl ether, use as an extracting solvent, 25
Dimethylaniline, 144
Dimethylformamide, 18t
Dimethylglyoxal, 75
Dimethylglyoxime, preparation of, 75
properties of, 76
Dinitrobenzene, 132
ra-Dinitrobenzene, 132, 143
preparation of, 132
reduction of, 143
3,5-Dinitrobenzoic acid, It
2,4-Dinitrochlorobenzene, 157
2,4-Dinitrophenol, 159
ether of, 158
2,4-Dinitrophenylhydrazine, 73
2,4-Dinitrophenylhydrazine
reagent,
preparation of, 192
2,4-Dinitrophenylhydrazones, 72
1,2-Diols, oxidation of, 96
properties of, 96
Dioxane, effect on Grignard reagents,
80
Diphenylamine, It
Diphenylcarbinol, 168
Diphenyldichloromethane (benzophenone dichloride), 165
Diphenyl ether, 157
Diphenylthiourea, 136, 145
Diphenylurea, 136, 161
Direct dyeing, 182
Distillation, fractional, 12, 14
simple, 11
Distillation apparatus, 11
for use in vacuum distillation, 102
Distillation assembly, for preparation
of formic acid from glycerol
monoxalate, 84
Distillation column, simple packed
column, 14
Bubble plate, 14
Vigreux, 14
Young, 14
Distribution coefficient, 25
Drierite, 30, 31
Dry ice, 81
Drying, by hydrate formation, 30
importance of, 29
mechanical means of, 29
use of adsorbing agents, 31
Drying agents, 29
chemical, 29
Drying reactions, nonreversible, 30
Dyeing, 182
Dyes, preparation of, 182
Egg albumin, preparation of solution
of, 111
Elements, qualitative tests for, 41
Emulsions, 26
Enol form, of ethyl acetoacetate, 104
INDEX
Enols, ferric chloride test for, 105
Enzyme action, 123, 125
Erlenmeyer flask, use in crystallization,
20
Esterification, azeotropic, 108
of salicylic acid, 178
use of acid chlorides, 89
Esters, formation of, 96
hydrolysis of, 86
preparation of, 90
Ethane, apparatus for preparation of,
46
preparation of, 46
Ethanol, absolute, 100, 101
binary azeotropes of, 108
Ether, 18t
absolute, preparation of, 45, 46
apparatus for distillation of, 64
apparatus for preparation of, 64
preparation of, 64
properties of, 65
role in formation of Grignard reagent, 80
use as an extracting solvent, 25
Ethers, peroxides of, 64
Ethyl acetate, 18t
binary azeotrope with ethanol, 108
preparation of, 86
use in the preparation of ethyl acetoacetate, 100
Ethyl acetoacetate, acidity of, 100
preparation of, 100, 102
reactions of, 104
use in the preparation of phenylmethylpyrazolone, 189
Ethyl alcohol, 18t
distinguishing tests for, 57
dehydration of, 49
partial dehydration of, 64
reaction with acetic anhydride, 91
Ethylaniline, 138t
melting points of derivatives of, 138t
Ethylbenzene, 128
Ethyl bromide, preparation of, 62
Ethyl /z-butylmalonate, 100, 103
Ethylene, apparatus for synthesis of,
49
oxidation of, 51
preparation of, 49
properties of, 51
Ethylene bromide, apparatus for synthesis of, 49
preparation of, 49
regeneration of ethylene from, 51
Ethylene glycol, oxidation of, 96
properties of, 96
Ethylene glycol diacetate, 96
Ethylene glycol dibenzoate, 96
Ethyl ether, preparation of, 64
Ethyl iodide, apparatus for preparation of, 60
preparation of, 59
Ethylmagnesium bromide, preparation
of, 46
Ethyl malonate, acidity of, 100
alkylation of, 100, 103
Ethyl nitrite, preparation of, 75
Ethyl nitrite generator, 75
Eutectic composition, 5
Eutectic point, 4, 5
Eutectic temperature, 4, 5
Eveready, 96
Extraction, 25
Extraction apparatus, continuous
methods, 27
Fats, 86, 111
Fehling's solution, 69, 70, 109
preparation of, 192
reaction with benzoin, 169
Ferric bromide, 129
as a catalyst in preparation of bromobenzene, 129
Ferric chloride test, for aniline, 136
for an a-hydroxyacid, 109
for enols, 105
for phenol, 155
Filter aids, 20
Filtration, 20
Fischer esterification, 86
Fluorescein, preparation of, 185, 186
separation from methylene blue by
chromatography, 38
Fluted filter paper, use in filtration,
20, 21
Formaldehyde, 162
alkaline solution of, 152
reaction with ammonia, 70
use in preparation of toluene, 152
Formaldehyde color reaction, 112
Formalin, 152
use in preparation of toluene, 152
Formic acid, apparatus for distillation
of, 84
oxidation of, 83
preparation from methanol, 83
properties of, 83
Fractional distillation, 12, 14
Friedel and Crafts reaction, for preparation of acetophenone, 163
for preparation of benzophenone,
165
D(—) -Fructose, reaction with phenylhydrazine, 122
source of, 119
Fuller's earth, use in adsorption chromatography, 35
Funnel heater, use in filtration of hot
solutions, 20, 21
Furfural, 73t
properties of, 189
Gay-Lussac, 98
Gelatine, hydrolysis of, 111, 113
INDEX
Hydrogen bonds, 18f, 19
Glacial acetic acid, 89
Gliadin, isolation from wheat flour, Hydrogen bromide, evolution of in
preparation of bromobenzene,
111
129
Glucose, 119
Hydrogen halides, reactivity of, 59
mutarotation of, 119
Hydrolysis, of acetamide, 91
D ( + ) -Glucose, 124
of acetic anhydride, 91
acetylation of, 120
action of periodic acid on, 97
of acetyl chloride, 89
oxidation of, 122
of esters, 86
reaction with phenylhydrazine, 122
of gelatine, 111, 113
source of, 119
of /?-ketoesters, 104
a-D( + )-Glucose pentaacetate, 120
of nitriles, 95
/?-D(+)-Glucose pentaacetate, prepaof p-nitroacetanilide, 142
ration of, 120
of 5-octyl hydrogen phthalate, 120
D( + )-Glucose phenylosazone, prepaof sodium formate, 83
ration of, 122
of starch, 124, 125
L( + )-Glutamic acid, 113
of sucrose, 119, 123
Glycerol, 19, 84, 86
of urea, 115
dehydration of, 97
Hydroquinone, reducing power of,
properties of, 96
156
source of, 87
use in preparation of /?-benzoquiuse in preparation of quinoline, 191
none, 172
Glyceryl esters, 86
Hydroxy acids, aromatic, 178
Glycine, 113
a-Hydroxy acids, 109
Glycols, preparation of derivatives of, Hydroxylamine, 73
180
Hydroxylamine hydrochloride, use in
Grignard reagent, 46, 80
preparation of
benzophenone
role of ether in formation of, 80
oxime, 167
use in preparation of benzoic acid, L( — )-Hydroxyproline, 113
80
Hyflo filter aid, 20
use in preparation of ethane, 46
use in preparation of triphenylcarbi- Ignition test, 41
nol, 168
Indigo-A, 183
Grignard reagents, effect of addition Inulin, use in adsorption chromatograof dioxane, 80
phy, 35
reaction with oxygen, 80
Iodine, use in preparation of iodobenreaction with water, 80
zene, 131
Grignard, V., 46
Iodine test, 124
Guaiacol, melting points of derivatives Iodobenzene, preparation of, 131
of, 161t
Iodobenzene-dichloride, 131
Iodoform test, 77, 78
Haloform reaction, 77
Isocyanide reaction, 94
preparation of benzoic acid by Isocyanide test, for aniline, 136
means of, 174
Isopropyl iodide, 60
Halogens, detection of in organic
compounds, 141
Kerosene, properties of, 48
Helianthin, preparation of, 182
Ketones, derivatives of, 72
rc-Heptaldehyde, 73t
preparation of, 90
2-Heptanone, 73t
preparation from carboxylic acids,
Heterocyclic compounds, 189
67
Hinsburg reaction, 136
preparation from secondary alcoHirsch funnel, 20, 21
hols, 69
Hofmann hypobromite reaction, 93
test for, 179
HTH, 77
Ketone splitting, of /?-ketoesters, 104
Hydrazobenzene, 147
/3-Ketoesters, acid splitting, 104
preparation of, 147
hydrolysis of, 104
rearrangement of, 147, 148
ketone splitting, 104
Hydrobromic acid, 129
preparation of, 100
utilization of, 130
Keto form, of ethyl acetoacetate, 104
Hydrogen bonding, 69
Ketoximes, Beckmann rearrangement
of alcohols, 56
of, 167
of 1,2-diols, 96
Kjeldahl flask, 6
197
Lactic acid, properties of, 109
Lactose, 122
Law of mass action, 86
Lead formate, 84
Lead tetraacetate, action on 1,2-diols,
96
L(—) -Leucine, 113
Leuco dyes, 183
Ligroin, 18t
use in preparation of aminoazobenzene, 153
Lime, slaked, use in adsorption chromatography, 35
Lucas, H., 59
Lucas' reagent, preparation of, 192
Lucas test, 59
Luminol, preparation of, 187, 188
L( + ) -Lysine, 113
Magnesia, use in adsorption chromatography, 35
Magnesium methoxide, 147
Magnesium sulfate, use as drying
agent, 30, 31
Malachite Green, carbinol base of, 184
dyeing with, 183
leuco base of, 184
preparation of, 184
Malonic acids, decarboxylation of, 104
Maltose, 122, 124
Maximum boiling mixture, 14
Melting point, definition, 4
effect of impurity on, 5
mixed, 7
Melting point baths, 6
Melting point tubes, 6
Mercuric chloride, reaction with formic acid, 83
Mesitylene, 128
Methane, apparatus for preparation
of, 44
preparation of, 44, 45
reactions of, 44, 45
Methanol, oxidation of, 83
use in preparation of formic acid,
83
Methyl alcohol, 18t
distinguishing tests for, 57
Methylamine, apparatus for preparation of, 93
preparation of, 93
properties of, 94
Methylammonium chloride, 94
Methylaniline, 138t
melting points of derivatives of,
138t
2-Methyl-2-butene, preparation of, 52
Methylene blue, separation from other
dyes by chromatography, 39
Methylene chloride, use as an extracting solvent, 25
198
Methyl ethyl ketone, 73t
apparatus for nitrosation of, 75
nitrosation of, 75
Methyl iodide, 60
addition to pyridine, 190
Methyl orange, preparation of, 182
separation from other dyes by chromatography, 39
Methyl oxalate, 98
Methyl salicylate, preparation of, 178
use in preparation of salicylic acid,
178
Methyl Violet, use in dyeing, 182
Millon's reagent, preparation of, 192
Millon's test, 112
Minimum boiling mixture, 15
Mixed melting point, 7
Molecular sieves, use as drying agent,
31
Molisch's solution, preparation of, 192
Mordant, 183
Mutarotation, of glucose, 119
Naphthalene, 128
reactions of, 128
Naphthalene picrate, 128
/?-Naphthol, 28, 29
Ninhydrin, 113
Ninhydrin reaction, 114
Nitrating acid, 132
Nitration, of acetanilide, 142
of benzene, 128, 132
of naphthalene, 128
Nitriles, hydrolysis of, 95
preparation of, 95
reduction of, 95
test for, 179
Nitroacetanilide, hydrolysis of, 142
preparation of, 142
Nitroanilines, 136
m-Nitroaniline, preparation of, 143
p-Nitroaniline, preparation of, 142
Nitrobenzene, It, 18t, 132, 141
action of alkali on, 132
preparation of, 132, 133
reduction of, 147
reduction to aniline, 134
/7-Nitrobenzoic acid, It
preparation of, 176
Nitro compounds, test for, 180
Nitroethane, 132
action of alkali on, 132
Nitrogen, detection of in organic compounds, 41
a-Nitronaphthalene, 128
o-Nitrophenol, preparation of, 159
p-Nitrophenol, preparation of, 159
melting points of derivatives of,
161t
Nitrophenols, acidity of, 159
INDEX
3-Nitrophthalhydrazide, reduction to
"Luminol," 188
3-Nitrophthalic anhydride, use in
preparation of "Luminol," 187
3-Nitrosalicylic acid, 9t
Nitrosation, of methyl ethyl ketone,
75
p-Nitrosodimethylaniline, 143
preparation of, 144
/7-Nitrosodimethylaniline hydrochloride, 144
p-Nitrotoluene, oxidation to p-nitrobenzoic acid, 176
Norit, use in decolorization, 20
Normal boiling point, 12
Nuchar, use in decolorization, 20
Nylon, 67, 106
2-Octanol, optically active, preparation of, 120
D,L-2-Octanol, resolution of, 118, 120
2-Octanone, 73t
D,L-5-Octyl hydrogen phthalate, 117
Oil of Wintergreen, use in preparation
of salicyclic acid, 178
Oils, 86
ortho-Oxalic acid, 98
Orthophosphorous acid, 88
Oxalic acid, 83
preparation of, 96, 98
properties of, 98
Oxalic acid dihydrate, 98
Oxamide, preparation of, 98, 99
Oxanthranol, preparation of, 172
Oxidation, of acetylene, 54
of alcohols, 56, 69
of aldehydes, 70
of cane sugar, 98
of cyclohexanone, 106
of 1,2-diols, 96
of ethylene, 51
of ethylene glycol, 96
of formic acid, 83
of D( + )-glucose, 122
of methanol, 83
of a methylene group adjacent to a
carbonyl group, 75
Oximes, 72
Oxonium salts, 56
Paper chromatography, 38, 113
Para-periodic acid, 96
Parchment paper, 124
Partial pressure, 13
2-Pentene, preparation of, 52
Perchloron, 77
Periodic acid, action on 1,2-diols, 96
Periodic acid reagent, preparation of,
192
Perkin reaction, use in preparation of
cinnamic acid, 171
Permanganate test, for benzene,
127
for olefins, 51
Peroxides, of ethers, 64
test for, 65
Petroleum ether, 18t
use as an extracting solvent, 25
Phenacetin, 9t
Phenanthrene, 128
o-Phenetidine, melting points of derivatives of, 138t
p-Phenetidine, melting points of derivatives of, 138t
Phenetole (phenyl ethyl ether), preparation of, 157
by the Williamson method, 157
Phenol, acidity of, 159
melting points of derivatives of,
161t
preparation of, 155
properties of, 155
reaction with bromine water, 156
reaction with ferric chloride, 155
reducing power of, 156
solid derivatives of, 157
solubility in alkali, 155
solubility in water, 155
use in preparation of nitrophenols,
159
Phenolic compounds, benzoyl derivatives of, 157
bromine derivatives of, 157
ethers of 2,4-dinitrophenol, 158
identification of, 161
melting points of derivatives of,
161t
solid derivatives of, 157, 158
substituted ester of carbamic acid,
158
Phenolphthalein, preparation of, 185
L(-)-Phenylalanine, 113
Phenyl benzoate, production of, 157
by the Schotten-Baumann reaction,
157
Phenyl 2,4-dinitrophenyl ether, 158
ra-Phenylenediamine, 143
Phenyl ethyl ether (phenetole), 157
Phenylhydrazine, 73
Phenylhydrazone, of ethyl acetoacetate, 189
Phenylhydrazones, 72
Phenyl isocyanate, 161
Phenyl isocyanide, 136
Phenyl isothiocyanate, preparation of,
145
use in identification of amines, 136,
146
Phenylmagnesium bromide, 80
preparation of, 168
Phenylmethylpyrazolone, preparation
of, 189
Phenyl 4-nitrophenyl ether, 157
INDEX
Phosphoric anhydride, use as drying
agent, 30
Phosphorus oxychloride, 88
Phosphorus pentachloride, 88
use in preparation of benzophenone
oxime, 167
Phosphorus tribromide, generation of,
59
Phosphorus trichloride, 88
Phosphorus triiodide, generation of,
59
Phthalic anhydride, 9t, 118
use in preparation of phenolphthalein, 185
Picric acid, 159
Pimelic acid, 67
Polysaccharides, 124
Potassium benzilate, preparation of,
169
Potassium bromate, use in preparation
of p-benzoquinone, 172
Potassium carbonate, use as drying
agent, 31
Potassium cyanate, 115
Potassium cyanide, as a catalyst in the
benzoin condensation, 169
Potassium hydroxide, use as drying
agent, 31
Potassium mercuric iodide, preparation of, 192
Potassium tetroxalate, 98
Prestone, 96
Primary amines, identification of, 143
L(-)-Proline, 113
/i-Propyl alcohol, 19
w-Propyl iodide, 60
Proteins, 111
action of formaldehyde on, 112
precipitation by anions, 112
precipitation by cations, 111
Prussian blue, 41
Pyridine, 118
binary azeotrope with water, 108
properties of, 190
Pyrogallol, reducing power of, 156
Pyrolysis, of sodium acetate, 45
of sodium formate, 98
Qualitative organic analysis, 179
Qualitative tests for elements, 41
Quinhydrone, preparation of, 172
Quinoline, preparation of, 191
Skraup synthesis of, 191
Quinones, 172
Rt values, 113
Racemates, resolution of, 117
Raoult's law, 13
Rearrangements, Hofmann, 93
Reduction, of nitriles, 95
Reflux assembly, 90
Reflux ratio, 15
Resolution, of D,L-.s-octyl hydrogen
phthalate, 118
Resorcinol, 22
reducing power of, 156
use in preparation of fluorescein,
186
Rochelle salt, 109
Salicylaldehyde, 73t
Salicylate test, for alcohols, 57
Salicylic acid, It, 9t, 57, 178
decarboxylation of, 178
esterification of, 178
preparation of, 178
properties of, 178
Salting-out effect, 26, 28, 65
Sandmeyer reaction, 151
for preparation of chlorobenzene,
151
Saponification, 86
Sawdust, preparation of oxalic acid
from, 98
Scheele, 98
SchifFs reagent, 69, 70
preparation of, 192
Schotten-Baumann reaction, 136, 157
Schweitzer's reagent, 124
Secondary amines, identification of,
143
Seeding, as aid in crystallization, 20
Semicarbazide, 73
Semicarbazones, 72
Separation of a mixture, 141
Separatory funnel, 26
Silica gel, use as drying agent, 31
use in partition chromatography, 38
Silk, dyeing of, 182
Silver acetylide, formation of, 54
Skraup synthesis, of quinoline, 191
Soap, preparation of, 87
Sodio derivative, of ethyl acetoacetate,
100
of ethyl malonate, 100
Sodium, use as drying agent, 30
Sodium acetate, 90
pyrolysis of to produce methane, 44
Sodium alkoxides, 96
Sodium benzoate, 22
decarboxylation of, 127
use in preparation of benzene, 127
Sodium bisulfite, addition compounds
with aldehydes and ketones, 70
Sodium ethyl phthalate, 100
Sodium formate, hydrolysis of, 83
pyrolysis of, 98
Sodium fusion, 42
Sodium hydroxide, use in preparation
of benzene, 127
Sodium nitrite, use in diazotization of
aniline, 151
use in preparation of phenol, 155
Sodium phenoxide, 157
199
Sodium phthalate, 100
Sodium sulfate, use as drying agent,
31
"Solid alcohol," 57
Solution, boiling point, 12
Solvent pairs, use in crystallization, 19
Solvents, effect of polarity in chromatography, 36
relation between structure and solvent action, 18
Soxhlet extractor, 27
Special reagents, preparation of, 192
Starch, 124
hydrolysis of, 124, 125
use in adsorption chromatography,
35
Steam distillation, 32
apparatus, 33
applications of, 32
behavior of a mixture of benzene
and xylene, 34
principle of, 32
separation of p-dichlorobenzene and
salicylic acid, 34
Steam generator, 33
Steam trap, 33
Stearic acid, 22
Stem correction, 3n, 7
Strychnos nux vomica, 118
Suberic acid, distribution coefficient,
25
Sublimation, 7
Substitution reaction, 129
Succinic acid, It
Sucrose, 122
hydrolysis of, 119, 123
preparation of oxalic acid from, 98
use in adsorption chromatography,
35
Sulfanilamide, preparation of, 149
Sulfanilic acid, 139, 140
isolation of, 140
preparation of, 139
Sulfonation, of benzene, 127
of naphthalene, 128
Sulfonyl chloride, 149
Sulfur, detection of in organic compounds, 41
Super-Cel, hyflo, use in adsorption
chromatography, 35
Super-Cel filter aid, 20
Talc, use in adsorption chromatography, 35
Tallow, 86
Tannic acid, properties of, 178
Tartar emetic, 109
Tartaric acid, properties of, 109
Tautomerism, of /?-ketoesters, 104
Temperature—composition diagram,
5, 13
200
Tertiary amines, 143, 144
identification of, 144
Thermometer, calibration of, 1
Thiele apparatus, 6
Thiocarbanilide, 136, 145, 146
preparation of, 145
Thionyl chloride, 88
Titration, 84
o-Tolidine, 148
Tollens' reagent, 69, 70
preparation of, 192
reaction with formic acid, 83
Toluene, 128, 151, 152
binary azeotrope with ethanol, 108
preparation by the deamination of
p-toluidine, 151, 152
ternary azeotrope with ethanol and
water, 108
use of formalin in preparation of,
152
/7-Toluenediazonium chloride, reduction of with alkaline formaldehyde solution, 152
m-Toluidine, melting points of derivatives of, 138t
o-Toluidine, melting points of derivatives of, 138t
p-Toluidine, deamination of, 152
diazotization of, 152
melting points of derivatives of,
138t
Toluidines, 136
INDEX
s-/j-Tolylurea, It
Trap, for absorption of hydrogen
chloride, 88
Trialkylammonium nitrite, 144
2,4,6-Tribromophenol, 157
Trichloroacetone, 77
Triketohydrindene hydrate, 113
Trimethylacetaldehyde, 162
Trimethylacetic acid, 80
Trimethylacetonitrile, 80
2,4,6-Trinitrophenol (picric acid), 159
Triphenylcarbinol, preparation of, 168
Triphenylguanidine, isolation of, 145,
146
Triphenylguanidine hydrochloride,
145, 146
L(-)-Tyrosine, 113
Ullmann process, 157
Unknowns, identification of aldehydes
and ketones, 72
melting points of derivatives of aldehydes and ketones, 73
systematic procedure for identification of, 72, 179
Unsaturation, Baeyer's test for, 51
Urea, 9t
hydrolysis of, 115
preparation of, 115
properties of, 115
Urea nitrate, 115
Urea resin, 116
Vacuum distillation, 16, 102
Vapor pressure, 12
Vapor pressure diagram, 12
Vapor pressure-temperature diagram,
4
Vat dyes, 183
Victoria blue B, separation from
methyl orange by chromatography, 39
Vigreux column, 14
Viscose, 125
Viscosity, effect of hydrogen bonding
on, 96
Water, tests for presence of in alcohol,
57
Williamson reaction, Ullmann variation, 157
Wohler's synthesis of urea, 115
Wool, dyeing of, 182
Xanthophylls, isolation from leaf pigments, 39
Xanthoproteic reaction, 112
Xylene, 128
Xylidines, 136
Young column, 14
Zerewitinoff determination, 46
Zerex, 96
Zinc-copper couple, 45
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