Methylergometrine maleate from synchrotron powder diffraction data

organic compounds
Acta Crystallographica Section E
Specimen prepared at 101 kPa
Specimen prepared at 293 K
Particle morphology: needle, white
T = 293 K
Specimen shape: cylinder
40 1 1 mm
Structure Reports
Online
ISSN 1600-5368
Data collection
Methylergometrine maleate from
synchrotron powder diffraction data
BM01B, ESRF, Grenoble
Specimen mounting: 1.0 mm borosilicate glass capillary
Specimen mounted in transmission
mode
Jan Rohlı́ček,a Michal Hušák,a Bohumil Kratochvı́la and
Alexandr Jegorovb*
a
Institute of Chemical Technology Prague, Technická 5, 16628 Prague 6, Czech
Republic, and bTeva Czech Industries s.r.o., R&D, Branišovská 31, 370 05 České
Budějovice, Czech Republic
Correspondence e-mail: rohlicej@vscht.cz
Received 13 October 2009; accepted 23 November 2009
Key indicators: powder synchrotron study; T = 293 K; mean (C–C) = 0.004 Å;
R factor = 0.060; wR factor = 0.080; data-to-parameter ratio = 6.2.
Scan method: step
Absorption correction: none
2min = 0.5, 2max = 29.5
Increment in 2 = 0.003
Refinement
Rp = 0.060
Rwp = 0.080
Rexp = 0.021
RB = 0.088
S = 3.76
Wavelength of incident radiation:
0.6996 Å
Excluded region(s): none
Profile function: pseudo-Voigt
profile coefficients as parameterized in Thompson et al.
(1987), asymmetry correction
according to Finger et al. (1994)
617 reflections
100 parameters
96 restraints
H-atom parameters not refined
Preferred orientation correction:
March–Dollase (Dollase, 1986);
direction of preferred orientation
- 011, MD = 1.26
Table 1
The title compound {systematic name: 9,10-didehydro-N-[1(hydroxymethyl)propyl]-d-lysergamide maleate}, C20H26N3O2+C4H3O4, contains a large rigid ergolene group. This
group consists of an indole plane connected to a sixmembered carbon ring adopting an envelope conformation
and N-methyltetrahydropyridine where the methyl group is in
an equatorial position. In the crystal, intermolecular N—
H O, O—H N and O—H O hydrogen bonds form an
extensive three-dimensional hydrogen-bonding network,
which holds the cations and anions together.
Related literature
For background to ergometrine, see: Dudley & Moir (1935);
Kharasch & Legault (1935). Formethylergometrine, see Stoll
& Hofmann (1943). For crystal structure determinations of
ergometrine, see: Čejka et al. (1996); Hušák et al. (1998).
Hydrogen-bond geometry (Å, ).
D—H A
D—H
H A
D A
D—H A
O2s—H202 O4s
N13—H131 O3s
O23—H232 O19i
N20—H201 O1sii
N1—H11 O19iii
1.20
0.86
0.83
0.87
0.88
1.28
1.77
2.12
2.04
2.03
2.479
2.634
2.925
2.912
2.852
179
173
160
177
154
(5)
(4)
(8)
(5)
(4)
Symmetry codes: (i) x 1; y; z; (ii) x 12; y þ 32; z; (iii) x; y 12; z þ 12.
Data collection: ESRF SPEC package (Certified Scientific Software, 2003); cell refinement: GSAS (Larson & Von Dreele, 1994);
data reduction: CRYSFIRE (Shirley, 2000); program(s) used to solve
structure: FOX (Favre-Nicolin & Černý, 2002); program(s) used to
refine structure: GSAS; molecular graphics: Mercury (Macrae et al.,
2006) and PLATON (Spek, 2003); software used to prepare material
for publication: enCIFer (Allen et al., 2004).
This study was supported by the grant of the Czech Grant
Agency (GAČR 203/07/0040) and by the research programs
MSM6046137302 and NPV II 2B08021of the Ministry of
Education, Youth and Sports of the Czech Republic. We
acknowledge the European Synchrotron Radiation Facility for
provision of synchrotron radiation facilities and we thank
Denis Testemale for assistance in using beamline BM01B.
Supplementary data and figures for this paper are available from the
IUCr electronic archives (Reference: CV2630).
References
Experimental
Crystal data
C20H26N3O2+C4H3O4
Mr = 455.51
Orthorhombic, P21 21 21
a = 5.71027 (5) Å
b = 12.76978 (17) Å
o3252
Rohlı́ček et al.
c = 33.1455 (4) Å
V = 2416.93 (5) Å3
Z=4
Synchrotron radiation
= 0.6996 Å
Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J.
Appl. Cryst. 37, 335–338.
Čejka, J., Hušák, M., Kratochvı́l, B., Jegorov, A. & Cvak, L. (1996). Coll.
Czech. Chem. Commun. 61 1396–1404.
Certified Scientific Software (2003). SPEC. Certified Scientific Software,
Cambridge, MA, USA.
Dollase, W. A. (1986). J. Appl. Cryst. 19, 267–272.
Dudley, H. W. & Moir, C. (1935). Br. Med. J. 1, 520–523.
Favre-Nicolin, V. & Černý, R. (2002). J. Appl. Cryst. 35, 734–743.
doi:10.1107/S1600536809050351
Acta Cryst. (2009). E65, o3252–o3253
organic compounds
Finger, L. W., Cox, D. E. & Jephcoat, A. P. (1994). J. Appl. Cryst. 27, 892–900.
Hušák, M., Kratochvı́l, B. & Jegorov, A. (1998). Z. Kristallogr. 213, 195–196.
Kharasch, M. S. & Legault, R. R. (1935). Science, 81, 388.
Larson, A. C. & Von Dreele, R. B. (1994). GSAS. Report LAUR 86-748. Los
Alamos National Laboratory, New Mexico, USA.
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor,
R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.
Acta Cryst. (2009). E65, o3252–o3253
Shirley, R. (2000). CRYSFIRE User’s Manual. Guildford, England: The
Lattice Press.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.
Stoll, A. & Hofmann, A. (1943). Helv. Chim. Acta, 26, 944–965.
Thompson, P., Cox, D. E. & Hastings, J. B. (1987). J. Appl. Cryst. 20, 79–83.
Rohlı́ček et al.
C20H26N3O2+C4H3O4
o3253
supplementary materials
supplementary materials
Acta Cryst. (2009). E65, o3252-o3253
[ doi:10.1107/S1600536809050351 ]
Methylergometrine maleate from synchrotron powder diffraction data
J. Rohlícek, M. Husák, B. Kratochvíl and A. Jegorov
Comment
Methylergometrine is a semisynthetic ergot alkaloid derived from (+)-lysergic acid and (S)-(+)-2-amino-1-butanol (Stoll
& Hofmann, 1943). It is nearly isostructural with natural ergot alkaloid ergometrine maleate (Čejka et al., 1996). Previous
attempts to solve this structure by molecular modeling using ergometrine maleate as the starting model were successful, but
the result was not very precise (Čejka et al., 1996). Hence the crystal structure was not published. In this paper we report
crystal structure determination of the title compound (I) from synchrotron powder diffraction data.
The asymmetric unit of (I) contains a methylergometrinium cation and one molecule of maleate (Fig. 1). All bond lengths
and angles in (I) are comparable with reported structure of ergometrine maleate (Čejka et al., 1996). The molecule of
maleate is situated in the same position and the hydrogen bonding system is practically the same. Intermolecular N—H···O,
O—H···N and O—H···O hydrogen bonds (Table 1) form an extensive three-dimensional hydrogen-bonding network which
held cations and anions together.
Experimental
Crystallization of methylergometrine maleate from various solvents (alcohols, acetic acid esters, acetone, dioxane, dimethyl
sulphoxide) provided hair-like long needle crystals in all cases. One crystalline form with distinct powder patterns was found.
Refinement
The powder diffraction data measurement was done on BM01B beamline (Swiss-Norwegian Beamlines) at the ESRF, Grenoble. Before the measurement the diffractometer was calibrated by using LaB6 standard sample and the value of wavelength
was checked (0.6996 Å). The powder sample was placed in a 1 mm capillary. The measurement was done at room temperature. The capillary was rotating during the data collection. The diffractogram was measured from 0.515° to 29.49° 2θ with
0.0025° step scan and the sample was irradiated for 1 s per step. The data from all six detectors were finally binned.
The indexation confirmed unit-cell parameters and space group obtained from previous measurement (Čejka et al., 1996):
a =5.71 Å, b=12.77 Å, c =33.15 Å, Z = 4, V = 2 417 Å3, P212121. Molecule of ergometrine (Čejka et al., 1996) was used as a
starting model for structure solution. This model was transferred to the z-matrix and the missing methyl group was added in
the standard C—C distance (1.52 Å). This way changed z-matrix was loaded into the program FOX (Favre-Nicolin & Černý,
2002) and structure was solved by using parallel tempering algorithm. The structure solution result confirmed similarity with
ergometrine maleate, see Fig.2. Refinement of this result was carried out in GSAS (Larson & Von Dreele, 1994). Hydrogen
atoms were placed in their theoretical positions and structure was refined with bonds, angles and planar groups restraints
(N1—C10,C9/C10/C12/C16, C17/C18/O19/N20, C6s/C5s/O1s/O2s, C7s/C8s/O3s/O4s andC5s/C6s/C7s/C8s). All atomic
coordinates and Uiso parameters of non-hydrogen atoms were refined. Hydrogen atoms were not refined, it was necessary
to relocate H atoms into the correct positions after few cycles. Hydrogen atom H202 was manually placed between oxygen
sup-1
supplementary materials
atoms O2s and O4s. At the final stage of the refinement, only atomic coordinates of non-hydrogen atoms were refined to
the final agreement factors Rp = 0.0631 and Rwp = 0.0831. The diffraction profiles and differences between the measured
and calculated profiles are shown in Fig. 3.
Figures
Fig. 1. The molecular structure of methylergometrine maleate showing the atomic numbering.
Displacement spheres are drawn at the 30% probability level.
Fig. 2. Overlaid asymmetric parts of unit cells of methylergometrine maleate (blue) and ergometrine maleate (red)
Fig. 3. The final Rietveld plot showing the measured data (black thin-plus), calculated data
(red line) and difference curve (blue line). Calculated positions of the reflection are shown by
vertical bars.
9,10-didehydro-N-[1-(hydroxymethyl)propyl]-D-lysergamide maleate
Crystal data
C20H26N3O2+·C4H3O4−
F(000) = 960.0
Mr = 455.51
Dx = 1.246 Mg m−3
Orthorhombic, P212121
Synchrotron radiation, λ = 0.6996 Å
a = 5.71027 (5) Å
b = 12.76978 (17) Å
c = 33.1455 (4) Å
T = 293 K
Particle morphology: needle
white
V = 2416.93 (5) Å3
cylinder, 40 × 1 mm
Z=4
Specimen preparation: Prepared at 293 K and 101
kPa
Data collection
ID31
diffractometer
Scan method: step
Radiation source: X-Ray
2θmin = 0.52°, 2θmax = 29.49°, 2θstep = 0.0025°
sup-2
supplementary materials
Si(111)
DUMMY
Specimen mounting: 1.0 mm borosilicate glass capilDUMMY
lary
Data collection mode: transmission
Refinement
Least-squares matrix: full
Profile function: Pseudo-Voigt profile coefficients as
parameterized in Thompson et al. (1987), asymmetry
correction according to Finger et al. (1994)
Rp = 0.060
100 parameters
Rwp = 0.080
96 restraints
Rexp = 0.021
0 constraints
RBragg = 0.088
H-atom parameters not refined
R(F2) = 0.08232
Weighting scheme based on measured s.u.'s w = 1/
σ(Yobs)2
χ2 = 14.138
11591 data points
(Δ/σ)max = 0.03
Background function: Shifted Chebyschev
Preferred orientation correction: March–Dollase
(Dollase, 1986); direction of preferred orientation 011, MD = 1.26
Excluded region(s): no
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
N1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
N13
C14
C15
C16
C17
C18
O19
N20
C21
C22
O23
C24
x
y
z
Uiso*/Ueq
−0.2972 (5)
−0.1311 (5)
−0.0706 (4)
−0.2019 (3)
−0.3442 (4)
−0.4884 (4)
−0.4901 (4)
−0.3485 (4)
−0.2007 (3)
−0.0384 (3)
0.0703 (5)
0.1520 (3)
0.2572 (4)
0.4543 (6)
0.3333 (4)
−0.0506 (3)
0.1276 (3)
0.2054 (3)
0.3842 (5)
0.0695 (5)
0.0846 (6)
−0.1555 (8)
−0.2828 (7)
0.1859 (9)
0.6888 (3)
0.6344 (2)
0.6910 (2)
0.7843 (2)
0.7819 (3)
0.8647 (3)
0.9470 (3)
0.9500 (2)
0.86750 (18)
0.85683 (16)
0.66917 (18)
0.77235 (18)
0.7525 (2)
0.6780 (3)
0.8518 (2)
0.9178 (3)
0.9217 (2)
1.0353 (2)
1.0675 (3)
1.0956 (2)
1.2096 (2)
1.2575 (4)
1.2409 (7)
1.2439 (4)
0.29856 (7)
0.27627 (8)
0.24331 (7)
0.24509 (6)
0.27994 (6)
0.28782 (7)
0.26187 (8)
0.22692 (7)
0.21789 (6)
0.18355 (6)
0.20642 (8)
0.18765 (6)
0.14658 (7)
0.14769 (10)
0.12743 (7)
0.15108 (8)
0.11776 (6)
0.11406 (5)
0.13078 (10)
0.09146 (10)
0.08735 (7)
0.09008 (13)
0.12481 (15)
0.04775 (12)
0.07305*
0.04511*
0.03699*
0.03942*
0.05116*
0.04053*
0.03292*
0.02676*
0.04409*
0.05585*
0.01406*
0.02621*
0.02834*
0.04728*
0.0149*
0.01827*
0.05457*
0.01555*
0.03564*
0.0567*
0.12048*
0.13815*
0.18992*
0.16384*
sup-3
supplementary materials
C25
O1s
O2s
O3s
O4s
C5s
C6s
C7s
C8s
H21
H61
H71
H81
H111
H112
H121
H141
H142
H143
H151
H152
H161
H171
H211
H221
H222
H241
H242
H251
H252
H253
H601
H701
H11
H201
H131
H202
H232
0.254 (2)
0.1598 (8)
0.3200 (5)
−0.0518 (7)
0.2452 (6)
0.1379 (6)
−0.0894 (5)
−0.1334 (5)
0.0294 (5)
−0.0702
−0.5833
−0.5868
−0.3514
0.2034
−0.0222
0.273
0.5132
0.5746
0.4012
0.4358
0.4147
−0.1831
0.0579
0.1864
−0.1257
−0.2393
0.0678
0.3175
0.3132
0.118
0.3677
−0.223
−0.292
−0.3603
−0.0502
0.148
0.285
−0.3996
1.3598 (5)
0.5073 (3)
0.6095 (3)
0.6674 (3)
0.6788 (3)
0.56141 (17)
0.57248 (19)
0.61043 (19)
0.65414 (14)
0.5649
0.8631
1.0027
1.0068
0.6252
0.629
0.7969
0.6649
0.7014
0.6094
0.8844
0.8326
0.9588
0.8964
1.2337
1.3314
1.2362
1.2255
1.1955
1.3721
1.3943
1.3643
0.549
0.61
0.6651
1.0631
0.725
0.643
1.2015
0.0502 (2)
−0.05735 (10)
−0.01229 (11)
0.09751 (9)
0.05636 (10)
−0.02617 (8)
−0.00445 (9)
0.03209 (9)
0.06283 (8)
0.2836
0.3116
0.268
0.2101
0.2141
0.1881
0.2049
0.1216
0.165
0.1585
0.1458
0.1036
0.1491
0.0936
0.1082
0.0901
0.0685
0.0272
0.0415
0.0222
0.0536
0.068
−0.019
0.04
0.3211
0.0811
0.132
0.021
0.1235
0.24862*
0.05346*
0.09409*
0.05776*
0.06078*
0.06152*
0.0169*
0.05644*
0.01622*
0.0541*
0.0486*
0.0395*
0.0324*
0.0169*
0.0169*
0.0315*
0.0567*
0.0567*
0.0567*
0.0179*
0.0179*
0.0219*
0.0655*
0.1804*
0.2258*
0.2258*
0.1966*
0.1966*
0.4183*
0.4183*
0.4183*
0.0203*
0.0677*
0.0877*
0.068*
0.0411*
0.1129*
0.27*
Geometric parameters (Å, °)
N13—C14
N13—C15
N20—C18
N20—C21
C2—C3
C3—C4
C3—C11
C4—C5
sup-4
1.474 (4)
1.483 (4)
1.325 (4)
1.465 (4)
1.355 (4)
1.409 (3)
1.490 (4)
1.413 (3)
N13—H131
N20—H201
C2—H21
C6—H61
C7—H71
C8—H81
C11—H111
C11—H112
0.86
0.87
0.98
0.96
0.92
0.91
0.98
0.95
supplementary materials
C4—C9
C5—C6
C6—C7
C7—C8
C8—C9
C9—C10
C10—C12
C10—C16
C11—C12
C15—C17
C16—C17
C17—C18
C21—C22
C21—C24
C24—C25
O23—H232
N1—H11
1.393 (3)
1.365 (5)
1.358 (5)
1.413 (3)
1.383 (3)
1.474 (3)
1.538 (3)
1.330 (4)
1.530 (3)
1.510 (3)
1.503 (3)
1.522 (4)
1.504 (6)
1.500 (5)
1.532 (9)
0.84
0.88
C12—H121
C14—H141
C14—H142
C14—H143
C15—H151
C15—H152
C16—H161
C17—H171
C21—H211
C22—H221
C22—H222
C24—H241
C24—H242
C25—H251
C25—H252
C25—H253
0.95
0.94
0.94
0.99
0.94
0.95
0.92
0.95
0.95
0.96
0.90
0.99
0.99
1.00
0.90
0.88
C2—N1—C5
C12—N13—C14
C12—N13—C15
C14—N13—C15
C18—N20—C21
N1—C2—C3
C2—C3—C4
C2—C3—C11
C4—C3—C11
C3—C4—C5
C3—C4—C9
C5—C4—C9
N1—C5—C4
N1—C5—C6
C4—C5—C6
C5—C6—C7
C6—C7—C8
C7—C8—C9
C4—C9—C8
C4—C9—C10
C8—C9—C10
C9—C10—C12
C9—C10—C16
C12—C10—C16
C3—C11—C12
N13—C12—C10
N13—C12—C11
C10—C12—C11
N13—C15—C17
C10—C16—C17
C15—C17—C16
C15—C17—C18
109.2 (2)
112.9 (2)
111.0 (2)
109.8 (2)
126.6 (3)
109.7 (2)
106.4 (2)
134.4 (2)
118.7 (2)
108.8 (2)
127.96 (19)
123.3 (2)
106.0 (3)
134.9 (2)
119.1 (3)
118.8 (2)
122.4 (3)
120.4 (2)
115.97 (19)
115.61 (18)
128.4 (2)
116.18 (17)
122.53 (19)
121.28 (18)
109.71 (19)
108.63 (17)
110.09 (19)
115.12 (17)
111.62 (19)
125.4 (2)
110.6 (2)
110.70 (16)
C3—C2—H21
C5—C6—H61
C7—C6—H61
C6—C7—H71
C8—C7—H71
C7—C8—H81
C9—C8—H81
C3—C11—H111
C3—C11—H112
C12—C11—H111
C12—C11—H112
H111—C11—H112
N13—C12—H121
C10—C12—H121
C11—C12—H121
N13—C14—H141
N13—C14—H142
N13—C14—H143
H141—C14—H142
H141—C14—H143
H142—C14—H143
N13—C15—H151
N13—C15—H152
C17—C15—H151
C17—C15—H152
H151—C15—H152
C10—C16—H161
C17—C16—H161
C15—C17—H171
C16—C17—H171
C18—C17—H171
N20—C21—H211
126
119
122
117
120
121
119
108
109
111
112
107
108
110
105
111
112
110
111
106
106
106
106
111
111
110
116
119
108
109
112
107
sup-5
supplementary materials
C16—C17—C18
O19—C18—N20
O19—C18—C17
N20—C18—C17
N20—C21—C22
N20—C21—C24
C22—C21—C24
O23—C22—C21
C21—C24—C25
C22—O23—H232
C2—N1—H11
C5—N1—H11
C12—N13—H131
C14—N13—H131
C15—N13—H131
C18—N20—H201
C21—N20—H201
N1—C2—H21
106.8 (2)
123.1 (3)
121.6 (2)
115.37 (19)
110.2 (3)
113.2 (3)
106.6 (3)
117.9 (4)
109.5 (4)
118
124
127
107
108
109
114
119
124
C22—C21—H211
C24—C21—H211
O23—C22—H221
O23—C22—H222
C21—C22—H221
C21—C22—H222
H221—C22—H222
C21—C24—H241
C21—C24—H242
C25—C24—H241
C25—C24—H242
H241—C24—H242
C24—C25—H251
C24—C25—H252
C24—C25—H253
H251—C25—H252
H251—C25—H253
H252—C25—H253
112
108
104
110
104
108
113
106
107
116
115
103
101
105
107
109
111
121
Hydrogen-bond geometry (Å, °)
D—H···A
O2s—H202···O4s
N13—H131···O3s
D—H
1.20
0.86
H···A
1.28
1.77
D···A
2.479 (5)
2.634 (4)
D—H···A
179
173
O23—H232···O19i
0.83
2.12
2.925 (8)
160
ii
0.87
2.04
2.912 (5)
177
0.88
2.03
N1—H11···O19
Symmetry codes: (i) x−1, y, z; (ii) x−1/2, −y+3/2, −z; (iii) −x, y−1/2, −z+1/2.
2.852 (4)
154
N20—H201···O1s
iii
sup-6
supplementary materials
Fig. 1
sup-7
supplementary materials
Fig. 2
sup-8
supplementary materials
Fig. 3
sup-9