organic papers
Acta Cryst.(2005). E61, o3245–o3248 doi:10.1107/S1600536805028357 Ravikumar and Sridhar C
21H26O2N3S+0.5C4H2O42
o3245
Acta Crystallographica Section EStructure Reports
Online
ISSN 1600-5368
Quetiapine hemifumarate
Krishnan Ravikumar* and Balasubramanian Sridhar
Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Correspondence e-mail: ravikumar_iict@yahoo.co.in
Key indicators
Single-crystal X-ray study
T= 273 K
Mean(C–C) = 0.003 A˚
Rfactor = 0.055
wRfactor = 0.136
Data-to-parameter ratio = 18.2
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
#2005 International Union of Crystallography Printed in Great Britain – all rights reserved
Quetiapine hemifumarate (systematic name: 1-[2-(2-hydroxy- ethoxy)ethyl]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-ium hemifumarate), C21H26O2N3S
+
0.5C4H2O4 2
, a new dibenzothiazepine antipsychotic, has international approvals for the treatment of schizophrenia. In the tricyclic framework, the central thiazepine ring has a boat conformation and the dihedral angle between the planar benzene rings is 108.6 (1). The protonated piperazine ring exhibits a chair conformation with its ethoxyethanol side chain oriented equatorially. The fumarate anion possesses a centre of symmetry. The quetiapinium and fumarate ions are connected by O— H O and N—H O hydrogen bonds.
Comment
Quetiapine, marketed by AstraZeneca under the brand name Seroquel, is a new atypical antipsychotic licensed for the treatment of schizophrenia (Lieberman, 1996). The Seroquel formulation is a fumarate salt. Quetiapine is a dibenzo-thiazepine derivative with a chemical structure reminiscent of that of other antipsychotics,e.g.clozapine and olanzapine. It is a dopamine, specifically D1 and D2 dopamine, inhibitor. Compared with conventional antipsychotics, such as chlor-promazine and haloperidol, quetiapine and other atypical antipsychotics provide superior efficacy or fewer side effects, particularly extrapyramidal symptoms (EPS) (Peuskens & Link, 1997; Arvanitis & Miller, 1997). Quetiapine has a well tolerated side-effect profile and in long-term open-label extension studies is found to be popular with patients, with high levels of patient acceptability and satisfaction (Casey, 1996).
Our interest in the crystal structure of (I) is in continuation of our ongoing programmes on the structural elucidation of drug molecules and in gaining further insight into structure– activity relationships.
The asymmetric unit of (I) consists of one singly charged quetiapine cation and one-half of a doubly charged fumarate
anion; the latter is completed by inversion symmetry (Fig. 1). Bond lengths and angles in quetiapine do not differ signifi-cantly from the expected values (Table 1). The C—S bond lengths are essentially equal. The protonation site of the cation is established as N3. The N—C bonds at N3 are lengthened [mean value 1.494 (2) A˚ compared to 1.430 (2) A˚ for N2], as would be expected for a protonated system. Consequently, N3 shows quaternary character and bears a positive charge in a tetrahedral configuration, with bond angles ranging from 110.7 (1) to 114.5 (1). The positive
charge of two cations is balanced by the negative charge of the fumarate anion, which is connected to each cation via N— H O and O—H O hydrogen bonding (Table 2).
The conformation of the central thiazepine ring in the (6,7,6)-tricyclic ring system can be described as a boat, with the atoms common to the benzene rings (C1, C2, C9 and C4) as the basal plane, the S atom as the bow and the N1 C3 bridge as the stern [puckering parameters (Cremer & Pople, 1975) areq2= 1.009 (2),q3= 0.291 (2) A˚ ,QT= 1.051 (1),’1= 50.6 (1),’
2=107.4 (3)and= 73.9 (1)]. The bow angle is 130.5 (1) and the stern angle is 138.5 (1). This enables the dibenzothiazepine ring skeleton to form a flattened V-shaped conformation. A similar conformation is observed in the crystal structures of the related antipsychotic agents amox-apine, clozamox-apine, loxamox-apine, loxapine succinate monohydrate, clothiapine-modified, clothiapine, olanzapine, olanzipinium nicotinate, oxyprothepine, and metitepine maleate. Least-squares plane calculations through the aromatic rings flanking the thiazepine ring show that benzene ringBis more nearly planar [(/)2 = 23.7] than benzene ring A [(/)2 = 438.9]. The dihedral angle () between these benzene rings is 108.6 (1) and falls in the range 104–127.2 observed for
related antipsychotic agents (Table 3). Incidentally, molecular modelling of quetiapine using HYPERCHEM (Hypercube, 1995) predicts this angle to be 145 (Lien et al., 1996). A
superimposed fit of related antipsychotic drugs with the central thiazepine ring atoms of (I) shows significant structural similarity (Fig. 2).
A piperazine ring attached to the tricyclic system and its orientation with respect to the tricyclic system is essential for activity (Chakrabartiet al., 1982). The piperazine ring is in a normal chair conformation. The thiazepine nucleus can be viewed as being in an equatorial orientation to the piperazine ring. Interestingly, in related antipsychotics, the corresponding torsion angles are observed as similar. The ethoxyethanol side chain at the cationic N-atom site of the piperazine ring occupies an equatorial orientation and is in a folded confor-mation. The torsion angles about C19, O1, C20 and C21 indicate that these atoms do not have fully extended bonds, suggesting possible accommodation of the receptor site of dopamine. However, the solid-state conformation need not reflect the conformational preference at the receptor (or in solution).
It has been shown that these drugs are capable of competing with dopamine in synaptosinal preparations (Seeman et al., 1975; Burt et al., 1975). The relationship of the protonated piperazine ring system to the aromatic ring system may be
important for neuroleptic activity (Horn & Snyder, 1971). Further parameters have been compiled in Table 3. These data show a remarkable similarity in the disposition of the mol-ecular fragments for the analysed compounds and may be useful for postulating receptor interactions towards structure– activity relationship.
organic papers
o3246
Ravikumar and Sridhar C [image:2.610.336.537.73.340.2]21H26O2N3S+0.5C4H2O42 Acta Cryst.(2005). E61, o3245–o3248 Figure 1
A view of the title compound in the crystal structure, including the symmetry-generated half of the fumarate anion. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radii and the hydrogen bond as a dashed line. Unlabelled atoms are generated by the symmetry code (x, 1y, 1z).
Figure 2
[image:2.610.313.566.418.610.2]The molecular topography of this class of drugs studied by X-ray crystallography features some important structural and conformational determinants: (a) two benzene rings (AandB) linked by a seven-membered ring are drawn towards each other to form a semi-rigid V-shaped conformation; (b) the central seven-membered ring consisting of one or two heteroatoms, similar or dissimilar, exists in a boat conforma-tion; (c) the conformation of the piperazine ring is in a chair form.
The packing (Fig. 3) shows the hydrogen bond which binds the quetiapine cationic species to the anionic fumarate. The protonated distal atom N3 of the piperazine ring and O2 of the ethoxyethanol side chain hydrogen bonds to the fumarate dianion through atom O4.
Experimental
To obtain crystals suitable for X-ray studies, quetiapine fumarate (procured from Ind-Swift Laboratories Ltd, Punjab, India) was dissolved in a methanol–water solution (95:5) and the solution was allowed to evaporate slowly.
Crystal data
C21H26O2N3S+0.5C4H2O42
Mr= 441.54 Monoclinic,P21=c a= 11.9479 (8) A˚
b= 13.2197 (9) A˚
c= 13.9479 (9) A˚ = 92.327 (1) V= 2201.2 (3) A˚3
Z= 4
Dx= 1.332 Mg m
3
MoKradiation Cell parameters from 5025
reflections = 2.3–27.6
= 0.18 mm1
T= 273 (2) K Block, colourless 0.220.130.08 mm
Data collection
Bruker SMART APEX CCD area-detector diffractometer !scans
24936 measured reflections 5179 independent reflections 4655 reflections withI> 2(I)
Rint= 0.024
max= 28.0 h=15!15
k=17!17
l=18!18
Refinement
Refinement onF2 R[F2> 2(F2)] = 0.055 wR(F2) = 0.136
S= 1.12 5179 reflections 285 parameters
H atoms treated by a mixture of independent and constrained refinement
w= 1/[2
(Fo2) + (0.0578P)2
+ 0.9667P]
whereP= (Fo2+ 2Fc2)/3
(/)max< 0.001 max= 0.33 e A˚
3
min=0.25 e A˚ 3
Table 1
Selected geometric parameters (A˚ ,). S1—C1 1.7710 (18) S1—C9 1.773 (2) N2—C3 1.374 (2) N2—C17 1.457 (2)
N2—C14 1.460 (2) N3—C15 1.493 (2) N3—C16 1.493 (2) N3—C18 1.496 (2)
C15—N3—C16 110.65 (12) C15—N3—C18 109.41 (12) C16—N3—C18 113.33 (13)
N3—C15—C14 110.80 (13) N3—C18—C19 114.46 (15)
C9—S1—C1—C10 118.05 (16) C20—O1—C19—C18 69.2 (2)
[image:3.610.313.565.110.149.2]N3—C18—C19—O1 72.8 (2) C19—O1—C20—C21 152.51 (17)
Table 2
Hydrogen-bond geometry (A˚ ,).
D—H A D—H H A D A D—H A
O2—H2 O4 0.82 1.96 2.747 (2) 162 N3—H1N O4i
0.90 (2) 1.71 (2) 2.606 (2) 176 (2)
Symmetry code: (i)x;y1 2;zþ
[image:3.610.314.565.226.438.2]3 2.
Table 3
Selected conformational parameters (A˚ and ) derived from crystal
structures of antipsychotic compounds.
Reference d1 d2 d3 d4
1 6.005 7.727 4.763 6.980 108.6 2 6.148 7.694 4.603 6.699 119.5 3 5.965 7.718 4.603 6.903 115.0 4 6.196 7.737 4.615 6.729 113.7 5 6.130 7.773 4.624 6.865 121.5 6 5.977 7.749 4.698 6.886 105.3 7 6.098 7.730 4.697 6.699 105.0 8 5.881 7.783 4.639 6.967 127.2 9 5.926 7.759 4.550 6.974 119.9 10 6.025 7.765 4.786 6.512 104.0 11 6.618 7.683 5.107 7.219 123.1
References: (1) quetiapine fumarate (this work); (2) amoxapine (Cosulich & Lovell, 1977); (3) clozapine (Fillers & Hawkinson, 1982a); (4) loxapine (Cosulich & Lovell, 1977); (5) loxapine succinate monohydrate (Fillers & Hawkinson, 1982b); (6) clothiapine-modified (Dupontet al., 1992); (7) clothiapine (Sbit et al., 1987); (8) olanzapine (Wawrzycka-Gorczycaet al., 2004); (9) olanzipinium niconitate (Ravikumaret al., 2005); (10) oxyprothepine (Koch & Evrard, 1974); (11) metitepine maleate (Blatonet al., 1995).
The H atom on N3 was located in a difference density map and refined freely. All other H atoms were positioned geometrically and treated as riding, with C—H distances in the range 0.93–0.98 A˚ and withUiso(H) = 1.2Ueq(CH).
Data collection:SMART(Bruker, 2001); cell refinement:SAINT
(Bruker, 2001); data reduction:SAINT; program(s) used to solve structure:SHELXS97(Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
SHELXTL/PC (Sheldrick, 1990) and MERCURY (Bruno et al., 2002); software used to prepare material for publication:
SHELXL97.
The authors thank Dr J. S. Yadav, Director of IICT, for his kind encouragement and support.
References
Arvanitis, L. A. & Miller, B. G. (1997).Biol. Psychiatr.42, 233–246. Blaton, N. M., Peeters, O. M. & De Ranter, C. J. (1995).Acta Cryst.C51, 777–
780.
Bruker (2001).SAINT(Version 6.28a) andSMART(Version 5.625). Bruker AXS Inc., Madison, Wisconsin, USA.
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Bruno, I. J., Cole, J. C., Edgington, P. R., Kessler, M., Macrae, C. F., McCabe, P., Pearson, J. & Taylor, R. (2002).Acta Cryst.B58, 389–397.
Burt, D. R., Enna, S. J., Creese, I. & Snyder. (1975).Proc. Natl Acad. Sci. USA,
72, 4655–4659.
Casey, D. E. (1996).J. Clin. Psychiatry,57, 40–45.
Chakrabarti, J. K., Hotten, T. M., Morgan, S. E., Pullar, I. A., Rackham, D. M., Risius, F. C., Wedley, S., Chaney, M. O. & Jones, N. D. (1982).J. Med. Chem. 25, 1133–1140.
Cosulich, D. B. & Lovell, F. M. (1977).Acta Cryst.B33, 1147–1154. Cremer, D. & Pople, J. A. (1975).J. Am. Chem. Soc.97, 1354–1358. Dupont, L., Dideberg, O., Liegeois, J. F. & Delarge, J. (1992).Acta Cryst.C48,
1851–1853.
Fillers, J. P. & Hawkinson, S. W. (1982a).Acta Cryst.B38, 1750–1753. Fillers, J. P. & Hawkinson, S. W. (1982b).Acta Cryst.B38, 3041–3045. Horn, A. S. & Snyder, S. H. (1971).Proc. Natl Acad. Sci. USA,68, 2325–2328. Hypercube (1995).HYPERCHEM. Release 4.5. Hypercube Inc., 419 Phillip
Street, Waterloo, Ontario, Canada N2L 3X2.
Koch, M. H. J. & Evrard, G. (1974).Acta Cryst.B30, 2925–2928. Lieberman, J. A. (1996).J. Clin. Psychiatr.57, 68–71.
Lien, E. J., Das, A. & Lien, L. I. (1996).Chin. Pharm. J.48, 387–396. Peuskens, J. & Link, C. G. (1997).Acta Psychiatr. Scand.96, 265–273. Ravikumar, K., Swamy, G. Y. S. K., Sridhar, B. & Roopa, S. (2005).Acta Cryst.
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Sbit, M., Dupont, L., Dideberg, O., Lie´geois, J. F. & Delarge, J. (1987).Acta Cryst.C43, 720–722.
Seeman, P., Chau-Wong, M., Tedesco, J. & Wong, K. (1975).Proc. Natl Acad. Sci. USA,72, 4376–4380.
Sheldrick, G. M. (1990).SHELXTL/PC User’s Manual. Bruker AXS Inc., Madison, Wisconsin, USA.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Go¨ttingen, Germany.
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organic papers
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Ravikumar and Sridhar C [image:4.610.55.286.70.253.2]21H26O2N3S+0.5C4H2O42 Acta Cryst.(2005). E61, o3245–o3248 Figure 3
supporting information
sup-1
Acta Cryst. (2005). E61, o3245–o3248
supporting information
Acta Cryst. (2005). E61, o3245–o3248 [doi:10.1107/S1600536805028357]
Quetiapine hemifumarate
Krishnan Ravikumar and Balasubramanian Sridhar
S1. Comment
Quetiapine, marketed by AstraZeneca under the brand name Seroquel, is a new atypical antipsychotic licensed for the
treatment of schizophrenia (Lieberman, 1996). The Seroquel formulation is a fumarate salt. Quetiapine is a novel
dibenzothiazepine derivative with its chemical structure reminiscent of that of other antipsychotics, e.g. clozapine and
olanzapine. It is a dopamine, specifically D1 and D2 dopamine, inhibitor. Compared to conventional antipsychotics, such
as chlorpromazine and haloperidol, quetiapine and other atypical antipsychotics provide superior efficacy or, less side
effects, particularly extrapyramidal symptoms (EPS) (Peuskens & Link, 1997; Arvanitis & Miller, 1997). Quetiapine has
a well tolerated side effect profile and in long term open label extension studies is found to be popular with patients with
high levels of patient acceptability and satisfaction (Casey, 1996). Our interest in the crystal structure of (I) is in
continuation of our on-going programmes on the structural elucidation of drug molecules and to gain further insight into
structure–activity relationships.
The asymmetric unit of (I) consists of one singly charged quetiapine cation and one-half of a doubly charged fumarate
anion; the latter is completed by inversion symmetry (Fig. 1). Bond lengths and angles in quetiapine do not differ
significantly from the expected values (Table 1). The C—S bonds are symmetrical. The protonation site of the cation is
established as N3. The N—C bonds at N3 are lengthened [mean value 1.494 (2) Å compared to 1.430 (2) Å for N2], as
would be expected for a protonated system. Consequently, N3 shows quaternary character and bears a positive charge in
a tetrahedral configuration, with bond angles ranging from 110.7 (1) to 114.5 (1)°. The positive charge of the cation is
balanced by the negative charge of the fumarate anion which is connected to the cation via N—H···O and O—H···O
hydrogen bonding (Table 2).
The conformation of the central thiazepine ring in the (6,7,6)-tricyclic ring system can be described as a boat, with the
atoms common to the benzene rings (C1, C2, C9 and C4) as the basal plane, the S atom as the bow and the N1═ C3
bridge as the stern [puckering parameters (Cremer & Pople, 1975) are q2 = 1.009 (2), q3 = 0.291 (2) Å, QT = 1.051 (1),
φ1 = 50.6 (1)°, φ2 = −107.4 (3)° and θ = 73.9 (1)°]. The bow angle is 130.5 (1)° and the stern angle is 138.5 (1)°. This
facilitates the dibenzothiazepine ring skeleton to form a flattened V-shaped conformation. A similar conformation is
observed in the crystal structures of the related antipsychotic agents amoxapine, clozapine, loxapine, loxapine succinate
monohydrate, clothiapine-modified, clothiapine, olanzapine, olanzipinium nicotinate, oxyprothepine, and metitepine
maleate. Least-squares plane calculations through the aromatic rings flanking the thiazepine ring show that benzene ring
B is more planar [Σ(Δ/σ)2 = 23.7] than benzene ring A [Σ(Δ/σ)2 = 438.9]. The dihedral angle (χ) between the aromatic
rings flanking the thiazepine ring planes is 108.6 (1)° and falls in the range 104–127.2° observed for related antipsychotic
agents (Table 3). Incidentally, molecular modeling of quetiapine using HYPERCHEM (Hypercube, 1995) predicts this
angle to be 145° (Lien et al., 1996). A superimposed fit of related antipsychotic drugs with the central thiazepine ring
supporting information
sup-2
Acta Cryst. (2005). E61, o3245–o3248
A piperazine ring attached to the tricyclic system and its orientation with respect to the tricyclic system is essential for
activity (Chakrabarti et al., 1982). The piperazine ring is in a normal chair conformation. The thiazepine nucleus can be
viewed as being in equatorial orientation to the piperazine ring. Interestingly, in related antipsychotics, the corresponding
torsion angles are observed as similar (Table 3). The ethoxyethanol side chain at the cationic N-atom site of the
piperazine ring occupies an equatorial orientation and is in a folded conformation. The torsion angles about C19, O1, C20
and C21 indicate that these atoms do not have fully extended bonds, suggesting possible accommodative aspects of the
receptor site of dopamine. However, the solid-state conformation need not reflect the conformational preference at the
receptor (or in solution).
It has been shown that these drugs are capable of competing with dopamine in synaptosinal preparations (Seeman et al.,
1975; Burt et al., 1975). The relationship of the protonated piperazine ring system to the aromatic ring system may be
important for neuroleptic activity (Horn & Snyder, 1971). Some more parameters were compiled in Table 3. These data
show a remarkable similarity in the disposition of the molecular fragments for the analyzed compounds and may be
useful for postulating receptor interactions towards structure–activity relationship.
The molecular topography of this class of drugs studied by X-ray crystallography features some important structural
and conformational determinants (Fig. 3): (a) two benzene rings (A and B) linked by a seven-membered ring are drawn
towards each other to form a semi-rigid V-shaped conformation; (b) the central seven-membered ring consisting of one or
two heteroatoms, similar or dissimilar, exists in a boat conformation; (c) the conformation of the piperazine ring is in a
chair form.
The unit-cell packing (Fig. 2) shows the hydrogen bond which binds the quetiapine cationic species to the anionic
fumarate. The protonated distal atom N3 of the piperazine ring and O2 of the ethoxyethanol side chain hydrogen bonds to
the half fumarate dianion through atom O4.
S2. Experimental
To obtain crystals suitable for X-ray studies, quetiapine fumarate (procured from Ind-Swift Laboratories Ltd, Punjab,
India) was dissolved in a methanol–water solution (95:5) and the solution was allowed to evaporate slowly.
S3. Refinement
The H atom on N3 was located in a difference density map and refined freely. All other H atoms were positioned
supporting information
sup-3
[image:7.610.137.476.72.518.2]Acta Cryst. (2005). E61, o3245–o3248
Figure 1
A view of the title compound in the crystal structure, including the symmetry-generated half of the fumarate anion.
Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radii and
supporting information
sup-4
[image:8.610.129.484.71.336.2]Acta Cryst. (2005). E61, o3245–o3248
Figure 2
The superposition of the title compound (I) (red) with clozapine (magenta), amoxapine (green) and olanzapine (orange),
revealing the structural similarities. Substituents at the piperazine ring and H atoms have been omitted for clarity.
Figure 3
Part of unit cell, showing the fumarate bridge between the quetiapinium molecules, through O—H···O and N—H···O
[image:8.610.120.494.396.676.2]supporting information
sup-5
Acta Cryst. (2005). E61, o3245–o3248
1-[2-(2-hydroxyethoxy)ethyl]-4-(dibenzo[b,f][1,4]thiazepin-11- yl)piperazinium hemifumarate
Crystal data
C21H26O2N3S+·0.5C4H2O42−
Mr = 441.54
Monoclinic, P21/c Hall symbol: -P 2ybc
a = 11.9479 (8) Å
b = 13.2197 (9) Å
c = 13.9479 (9) Å
β = 92.327 (1)°
V = 2201.2 (3) Å3
Z = 4
F(000) = 936
Dx = 1.332 Mg m−3
Mo Kα radiation, λ = 0.71073 Å Cell parameters from 5025 reflections
θ = 2.3–27.6°
µ = 0.18 mm−1
T = 273 K Needle, colorless 0.22 × 0.13 × 0.08 mm
Data collection
CCD Area Detector diffractometer
Radiation source: fine-focus sealed tube Graphite monochromator
ω scans
24936 measured reflections 5179 independent reflections
4655 reflections with I > 2σ(I)
Rint = 0.024
θmax = 28.0°, θmin = 1.7°
h = −15→15
k = −17→17
l = −18→18
Refinement
Refinement on F2 Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.055
wR(F2) = 0.136
S = 1.12 5179 reflections 285 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
H atoms treated by a mixture of independent and constrained refinement
w = 1/[σ2(F
o2) + (0.0578P)2 + 0.9667P] where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001 Δρmax = 0.33 e Å−3 Δρmin = −0.25 e Å−3
Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
S1 0.67917 (5) 0.23918 (4) 1.21306 (4) 0.04982 (16)
O1 0.02234 (11) 0.41896 (10) 0.83165 (9) 0.0455 (3)
O2 −0.16062 (13) 0.56205 (15) 0.78615 (12) 0.0703 (5)
H2 −0.1591 0.5660 0.7275 0.106*
N1 0.46811 (12) 0.36975 (12) 1.16361 (10) 0.0372 (3)
H1N 0.2176 (16) 0.2380 (16) 0.8787 (14) 0.037 (5)*
N2 0.41724 (11) 0.31784 (12) 1.01269 (10) 0.0371 (3)
supporting information
sup-6
Acta Cryst. (2005). E61, o3245–o3248
C1 0.70266 (14) 0.29197 (14) 1.09893 (12) 0.0378 (4)
C2 0.61584 (14) 0.34007 (12) 1.04670 (11) 0.0333 (3)
C3 0.49932 (13) 0.34088 (12) 1.08108 (11) 0.0320 (3)
C4 0.54110 (14) 0.40333 (14) 1.23794 (11) 0.0364 (4)
C5 0.50722 (18) 0.48747 (16) 1.28965 (13) 0.0496 (5)
H5 0.4427 0.5221 1.2696 0.060*
C6 0.5678 (2) 0.52017 (19) 1.37005 (15) 0.0619 (6)
H6 0.5441 0.5767 1.4033 0.074*
C7 0.6632 (2) 0.4697 (2) 1.40139 (15) 0.0637 (6)
H7 0.7037 0.4918 1.4558 0.076*
C8 0.69821 (18) 0.38651 (18) 1.35184 (14) 0.0538 (5)
H8 0.7631 0.3528 1.3726 0.065*
C9 0.63751 (15) 0.35192 (14) 1.27059 (12) 0.0401 (4)
C10 0.80920 (16) 0.28831 (17) 1.06292 (16) 0.0509 (5)
H10 0.8661 0.2537 1.0965 0.061*
C11 0.83106 (17) 0.33554 (19) 0.97797 (16) 0.0573 (6)
H11 0.9024 0.3319 0.9538 0.069*
C12 0.74784 (19) 0.38824 (16) 0.92836 (14) 0.0526 (5)
H12 0.7638 0.4228 0.8725 0.063*
C13 0.64046 (16) 0.38960 (14) 0.96192 (12) 0.0413 (4)
H13 0.5841 0.4240 0.9275 0.050*
C14 0.43095 (14) 0.24429 (13) 0.93601 (12) 0.0360 (4)
H14A 0.4021 0.1791 0.9553 0.043*
H14B 0.5099 0.2365 0.9240 0.043*
C15 0.36893 (14) 0.27925 (13) 0.84560 (11) 0.0348 (4)
H15A 0.4026 0.3412 0.8230 0.042*
H15B 0.3752 0.2283 0.7960 0.042*
C16 0.23632 (14) 0.36913 (14) 0.94511 (12) 0.0366 (4)
H16A 0.1577 0.3764 0.9585 0.044*
H16B 0.2647 0.4351 0.9276 0.044*
C17 0.29978 (14) 0.33152 (15) 1.03376 (12) 0.0387 (4)
H17A 0.2933 0.3800 1.0854 0.046*
H17B 0.2684 0.2678 1.0541 0.046*
C18 0.18940 (15) 0.33216 (15) 0.77255 (12) 0.0406 (4)
H18A 0.2076 0.2861 0.7213 0.049*
H18B 0.2178 0.3984 0.7561 0.049*
C19 0.06342 (16) 0.33834 (15) 0.77731 (15) 0.0468 (4)
H19A 0.0317 0.3438 0.7124 0.056*
H19B 0.0367 0.2755 0.8040 0.056*
C20 0.03659 (17) 0.51652 (16) 0.79182 (15) 0.0496 (5)
H20A 0.0323 0.5128 0.7223 0.060*
H20B 0.1093 0.5436 0.8118 0.060*
C21 −0.0544 (2) 0.58319 (17) 0.82660 (18) 0.0617 (6)
H21A −0.0569 0.5765 0.8957 0.074*
H21B −0.0359 0.6530 0.8126 0.074*
O3 −0.06674 (14) 0.68278 (12) 0.48024 (13) 0.0689 (5)
O4 −0.16634 (12) 0.62037 (11) 0.59699 (10) 0.0521 (4)
supporting information
sup-7
Acta Cryst. (2005). E61, o3245–o3248
C23 −0.04473 (16) 0.50922 (15) 0.52307 (13) 0.0438 (4)
H23 −0.0802 0.4553 0.5521 0.053*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
S1 0.0578 (3) 0.0458 (3) 0.0453 (3) 0.0060 (2) −0.0041 (2) 0.0118 (2)
O1 0.0474 (7) 0.0426 (7) 0.0466 (7) 0.0092 (6) 0.0048 (6) 0.0041 (6)
O2 0.0576 (10) 0.0902 (13) 0.0641 (10) 0.0193 (9) 0.0135 (8) 0.0275 (9)
N1 0.0348 (7) 0.0478 (8) 0.0290 (7) −0.0036 (6) 0.0001 (5) −0.0012 (6)
N2 0.0308 (7) 0.0495 (8) 0.0308 (7) 0.0036 (6) 0.0003 (5) −0.0089 (6)
N3 0.0314 (7) 0.0335 (7) 0.0272 (6) −0.0012 (5) 0.0023 (5) −0.0032 (5)
C1 0.0356 (9) 0.0396 (9) 0.0382 (9) −0.0016 (7) 0.0005 (7) −0.0014 (7)
C2 0.0344 (8) 0.0349 (8) 0.0307 (8) −0.0047 (6) 0.0023 (6) −0.0010 (6)
C3 0.0333 (8) 0.0323 (8) 0.0304 (8) −0.0007 (6) 0.0000 (6) 0.0030 (6)
C4 0.0390 (9) 0.0440 (9) 0.0263 (7) −0.0092 (7) 0.0019 (6) 0.0032 (7)
C5 0.0565 (12) 0.0544 (12) 0.0378 (9) −0.0013 (9) 0.0001 (8) −0.0054 (8)
C6 0.0779 (16) 0.0630 (14) 0.0445 (11) −0.0100 (12) −0.0015 (11) −0.0162 (10)
C7 0.0713 (15) 0.0776 (16) 0.0408 (11) −0.0226 (12) −0.0141 (10) −0.0078 (11)
C8 0.0492 (11) 0.0708 (14) 0.0404 (10) −0.0120 (10) −0.0108 (8) 0.0101 (10)
C9 0.0427 (9) 0.0457 (10) 0.0318 (8) −0.0085 (8) 0.0004 (7) 0.0071 (7)
C10 0.0359 (10) 0.0600 (12) 0.0567 (12) 0.0011 (8) −0.0010 (8) −0.0134 (10)
C11 0.0388 (10) 0.0746 (15) 0.0595 (13) −0.0142 (10) 0.0152 (9) −0.0212 (11)
C12 0.0643 (13) 0.0554 (12) 0.0394 (10) −0.0255 (10) 0.0183 (9) −0.0103 (9)
C13 0.0502 (10) 0.0416 (9) 0.0324 (8) −0.0091 (8) 0.0031 (7) −0.0007 (7)
C14 0.0336 (8) 0.0391 (9) 0.0351 (8) 0.0035 (7) 0.0003 (6) −0.0071 (7)
C15 0.0344 (8) 0.0400 (9) 0.0304 (8) 0.0018 (7) 0.0067 (6) −0.0062 (6)
C16 0.0337 (8) 0.0434 (9) 0.0326 (8) 0.0040 (7) 0.0016 (6) −0.0111 (7)
C17 0.0313 (8) 0.0566 (11) 0.0283 (8) 0.0014 (7) 0.0027 (6) −0.0085 (7)
C18 0.0469 (10) 0.0469 (10) 0.0279 (8) 0.0076 (8) −0.0007 (7) −0.0031 (7)
C19 0.0440 (10) 0.0445 (10) 0.0510 (11) 0.0038 (8) −0.0088 (8) −0.0051 (8)
C20 0.0491 (11) 0.0499 (11) 0.0498 (11) 0.0003 (9) 0.0017 (9) 0.0053 (9)
C21 0.0732 (16) 0.0485 (12) 0.0634 (14) 0.0170 (11) 0.0034 (11) 0.0054 (10)
O3 0.0691 (10) 0.0533 (9) 0.0867 (12) 0.0146 (8) 0.0316 (9) 0.0097 (8)
O4 0.0599 (9) 0.0479 (8) 0.0492 (8) 0.0172 (6) 0.0107 (7) 0.0016 (6)
C22 0.0396 (9) 0.0405 (9) 0.0454 (10) 0.0077 (7) −0.0031 (8) −0.0050 (8)
C23 0.0449 (10) 0.0424 (10) 0.0441 (10) 0.0056 (8) −0.0006 (8) −0.0028 (8)
Geometric parameters (Å, º)
S1—C1 1.7710 (18) C11—C12 1.377 (3)
S1—C9 1.773 (2) C11—H11 0.9300
O1—C19 1.408 (2) C12—C13 1.384 (3)
O1—C20 1.417 (2) C12—H12 0.9300
O2—C21 1.396 (3) C13—H13 0.9300
O2—H2 0.8200 C14—C15 1.509 (2)
N1—C3 1.282 (2) C14—H14A 0.9700
supporting information
sup-8
Acta Cryst. (2005). E61, o3245–o3248
N2—C3 1.374 (2) C15—H15A 0.9700
N2—C17 1.457 (2) C15—H15B 0.9700
N2—C14 1.460 (2) C16—C17 1.508 (2)
N3—C15 1.493 (2) C16—H16A 0.9700
N3—C16 1.493 (2) C16—H16B 0.9700
N3—C18 1.496 (2) C17—H17A 0.9700
N3—H1N 0.90 (2) C17—H17B 0.9700
C1—C10 1.388 (3) C18—C19 1.511 (3)
C1—C2 1.396 (2) C18—H18A 0.9700
C2—C13 1.393 (2) C18—H18B 0.9700
C2—C3 1.491 (2) C19—H19A 0.9700
C4—C5 1.395 (3) C19—H19B 0.9700
C4—C9 1.398 (3) C20—C21 1.496 (3)
C5—C6 1.379 (3) C20—H20A 0.9700
C5—H5 0.9300 C20—H20B 0.9700
C6—C7 1.376 (4) C21—H21A 0.9700
C6—H6 0.9300 C21—H21B 0.9700
C7—C8 1.373 (3) O3—C22 1.225 (2)
C7—H7 0.9300 O4—C22 1.272 (2)
C8—C9 1.397 (3) C22—C23 1.509 (3)
C8—H8 0.9300 C23—C23i 1.293 (4)
C10—C11 1.374 (3) C23—H23 0.9300
C10—H10 0.9300
C1—S1—C9 97.66 (8) N2—C14—H14A 109.7
C19—O1—C20 115.34 (15) C15—C14—H14A 109.7
C21—O2—H2 109.5 N2—C14—H14B 109.7
C3—N1—C4 124.35 (15) C15—C14—H14B 109.7
C3—N2—C17 119.91 (13) H14A—C14—H14B 108.2
C3—N2—C14 123.93 (14) N3—C15—C14 110.80 (13)
C17—N2—C14 111.61 (13) N3—C15—H15A 109.5
C15—N3—C16 110.65 (12) C14—C15—H15A 109.5
C15—N3—C18 109.41 (12) N3—C15—H15B 109.5
C16—N3—C18 113.33 (13) C14—C15—H15B 109.5
C15—N3—H1N 107.7 (13) H15A—C15—H15B 108.1
C16—N3—H1N 108.8 (12) N3—C16—C17 110.86 (14)
C18—N3—H1N 106.7 (13) N3—C16—H16A 109.5
C10—C1—C2 119.99 (17) C17—C16—H16A 109.5
C10—C1—S1 119.51 (15) N3—C16—H16B 109.5
C2—C1—S1 120.46 (13) C17—C16—H16B 109.5
C13—C2—C1 118.60 (16) H16A—C16—H16B 108.1
C13—C2—C3 120.11 (15) N2—C17—C16 109.38 (13)
C1—C2—C3 121.28 (14) N2—C17—H17A 109.8
N1—C3—N2 117.63 (14) C16—C17—H17A 109.8
N1—C3—C2 126.89 (15) N2—C17—H17B 109.8
N2—C3—C2 115.12 (13) C16—C17—H17B 109.8
C5—C4—C9 118.16 (16) H17A—C17—H17B 108.2
supporting information
sup-9
Acta Cryst. (2005). E61, o3245–o3248
C9—C4—N1 124.58 (17) N3—C18—H18A 108.6
C6—C5—C4 121.1 (2) C19—C18—H18A 108.6
C6—C5—H5 119.4 N3—C18—H18B 108.6
C4—C5—H5 119.4 C19—C18—H18B 108.6
C7—C6—C5 120.5 (2) H18A—C18—H18B 107.6
C7—C6—H6 119.8 O1—C19—C18 115.73 (16)
C5—C6—H6 119.8 O1—C19—H19A 108.3
C8—C7—C6 119.56 (19) C18—C19—H19A 108.3
C8—C7—H7 120.2 O1—C19—H19B 108.3
C6—C7—H7 120.2 C18—C19—H19B 108.3
C7—C8—C9 120.8 (2) H19A—C19—H19B 107.4
C7—C8—H8 119.6 O1—C20—C21 107.97 (17)
C9—C8—H8 119.6 O1—C20—H20A 110.1
C8—C9—C4 119.92 (19) C21—C20—H20A 110.1
C8—C9—S1 119.74 (16) O1—C20—H20B 110.1
C4—C9—S1 120.26 (13) C21—C20—H20B 110.1
C11—C10—C1 120.4 (2) H20A—C20—H20B 108.4
C11—C10—H10 119.8 O2—C21—C20 114.3 (2)
C1—C10—H10 119.8 O2—C21—H21A 108.7
C10—C11—C12 120.30 (18) C20—C21—H21A 108.7
C10—C11—H11 119.8 O2—C21—H21B 108.7
C12—C11—H11 119.8 C20—C21—H21B 108.7
C11—C12—C13 119.80 (19) H21A—C21—H21B 107.6
C11—C12—H12 120.1 O3—C22—O4 125.06 (17)
C13—C12—H12 120.1 O3—C22—C23 120.94 (17)
C12—C13—C2 120.78 (19) O4—C22—C23 114.00 (17)
C12—C13—H13 119.6 C23i—C23—C22 123.6 (2)
C2—C13—H13 119.6 C23i—C23—H23 118.2
N2—C14—C15 110.03 (13) C22—C23—H23 118.2
C9—S1—C1—C10 118.05 (16) N1—C4—C9—S1 3.5 (2)
C9—S1—C1—C2 −59.75 (16) C1—S1—C9—C8 −120.59 (16)
C10—C1—C2—C13 −4.3 (3) C1—S1—C9—C4 62.67 (15)
S1—C1—C2—C13 173.48 (13) C2—C1—C10—C11 2.8 (3)
C10—C1—C2—C3 176.95 (17) S1—C1—C10—C11 −175.02 (16)
S1—C1—C2—C3 −5.3 (2) C1—C10—C11—C12 0.9 (3)
C4—N1—C3—N2 −174.76 (16) C10—C11—C12—C13 −3.1 (3)
C4—N1—C3—C2 −2.1 (3) C11—C12—C13—C2 1.5 (3)
C17—N2—C3—N1 3.1 (2) C1—C2—C13—C12 2.2 (3)
C14—N2—C3—N1 −150.93 (16) C3—C2—C13—C12 −179.03 (16)
C17—N2—C3—C2 −170.47 (15) C3—N2—C14—C15 −144.34 (16)
C14—N2—C3—C2 35.5 (2) C17—N2—C14—C15 59.76 (19)
C13—C2—C3—N1 −125.31 (19) C16—N3—C15—C14 54.35 (18)
C1—C2—C3—N1 53.4 (2) C18—N3—C15—C14 179.91 (14)
C13—C2—C3—N2 47.6 (2) N2—C14—C15—N3 −56.15 (18)
C1—C2—C3—N2 −133.72 (17) C15—N3—C16—C17 −55.19 (18)
C3—N1—C4—C5 138.06 (18) C18—N3—C16—C17 −178.52 (14)
supporting information
sup-10
Acta Cryst. (2005). E61, o3245–o3248
C9—C4—C5—C6 0.9 (3) C14—N2—C17—C16 −60.21 (19)
N1—C4—C5—C6 173.51 (19) N3—C16—C17—N2 57.50 (19)
C4—C5—C6—C7 −0.4 (3) C15—N3—C18—C19 171.36 (15)
C5—C6—C7—C8 0.2 (4) C16—N3—C18—C19 −64.6 (2)
C6—C7—C8—C9 −0.6 (3) C20—O1—C19—C18 69.2 (2)
C7—C8—C9—C4 1.2 (3) N3—C18—C19—O1 72.8 (2)
C7—C8—C9—S1 −175.56 (17) C19—O1—C20—C21 152.51 (17)
C5—C4—C9—C8 −1.3 (3) O1—C20—C21—O2 −71.7 (2)
N1—C4—C9—C8 −173.27 (16) O3—C22—C23—C23i 15.3 (4)
C5—C4—C9—S1 175.44 (14) O4—C22—C23—C23i −165.0 (2)
Symmetry code: (i) −x, −y+1, −z+1.
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
O2—H2···O4 0.82 1.96 2.747 (2) 162
N3—H1N···O4ii 0.90 (2) 1.71 (2) 2.606 (2) 175.8 (19)
