16α,17α-Ep­oxy-17β-(1H-imidazol-1-yl)androst-4-en-3-one monohydrate

A G Anitha; R Hema; Ranju Bansal; Sridhar Thota; S Rizwana Begum

doi:10.1107/S1600536812029479

. 2012 Jul 7;68(Pt 8):o2345. doi: 10.1107/S1600536812029479

16α,17α-Epoxy-17β-(1H-imidazol-1-yl)androst-4-en-3-one monohydrate

A G Anitha ^a, R Hema ^a,^*, Ranju Bansal ^b, Sridhar Thota ^b, S Rizwana Begum ^a

PMCID: PMC3414280 PMID: 22904813

Abstract

In the title compound, C₂₂H₂₈N₂O₂·H₂O, rings B and C adopt chair conformations. Ring A adopts an envelope conformation, with the non-fused C atom adjacent to the fused C atom bearing a methyl group as the flap atom. Ring D also adopts an envelope conformation, with the fused C atom not bearing a methyl group as the flap atom. The water molecule links the molecules via O—H⋯O and O—H⋯N hydrogen bonds, forming zigzag chains which run parallel to the c axis. Weak C—H⋯O interactions also occur.

Related literature

For background information on steroid activity, see: Duax & Norton (1975 ▶). For conformational analysis, see: Altona et al. (1968 ▶); Cremer & Pople (1975 ▶). For details of the determination of the absolute configuration, see: Bansal et al. (2012 ▶).

Experimental

Crystal data

C₂₂H₂₈N₂O₂·H₂O
M _r = 370.48
Orthorhombic,
a = 9.7813 (2) Å
b = 13.5885 (3) Å
c = 14.2698 (3) Å
V = 1896.64 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004) ▶ T _min = 0.975, T _max = 0.983
10371 measured reflections
3331 independent reflections
2807 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.083
S = 1.06
3331 reflections
246 parameters
H-atom parameters constrained
Δρ_max = 0.12 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812029479/go2059sup1.cif

e-68-o2345-sup1.cif^{(24KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812029479/go2059Isup2.hkl

e-68-o2345-Isup2.hkl^{(94.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H31⋯N2	0.90	1.99	2.890 (3)	174
O3—H32⋯O1ⁱ	0.90	2.33	3.202 (3)	163
C20—H20⋯O3ⁱⁱ	0.93	2.43	3.208 (4)	142

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank Dr Babu Vargese, Regional Instrumentation Analytical Centre, IIT, Madras, India, for the data collection.

supplementary crystallographic information

Comment

It is well known that minor changes in the basic composition of steroids significantly alter their biological activities (Duax and Norton, 1975).

The structure determination of C₂₂H₂₈N₂O₂.H₂O , (I), was undertaken to investigate the conformation of the fused ring system. The puckering parameters in (I), ring-B: Q = 0.534 (2) Å, θ = 3.9 (2)°, ring-C: Q = 0.589 (2) Å, θ = 6.19 (19)°; (Cremer and Pople, 1975) show that rings B and C adopt chair confomation. The C4—C5-(Csp2-Csp2) distance of 1.336 (3) Å confirms the localization of a double bond at this position. Due to this double bond the environment of atom C5 is planar, and hence ring A is slightly distorted towards an envelope conformation with puckering parameters, Q = 0.435 (3) Å, θ = 56.4 (4)°, φ = 18.7 (4)°, with C1 being the flap. The five-membered ring-D exhibits an envelope conformation, with C14 being the flap, with pseudorotation parameter (P =14.7 (3)° and τ =38.7 (1)°), (Altona et al., 1968). The dihedral angle between the plane of imidazole moiety and the mean plane of rings A, B, C and D is 11.83 (9)°. The substitution of O2 between C17 and C16 does not affect the normal value of exocyclic angle of C16—C17—N1(121.8 (2)°). The water molecule links the molecules, via O3—H31···N2(within the asymmetric unit) and O3—H32···O1(3/2-x,2-y,-1/2+z hydrogen bonds, to form a zig-zag chains which run parallel to the c-axis. molecules. The molecular packing is also stabilized by weak C20—H20···O3( 1-x,-1/2+y,-1/2-z)) intermolecular interactions. Details of the determination of the absolute configuration can be found in (Bansal, et al. 2012).

Experimental

A mixture of imidazole(1 g, 2.75 mmol) and anhydrous potassium carbonate(1 g) was stirred and refluxed in ethyl methyl ketone(50) ml for one hour. 16α/β-bromo-4-androstene-3, 17-dione(0.4 g, 1.09 mmol) was added to the reaction mixture and further refluxed for 3 h with continous stirring. The completion of reaction was monitored by TLC. The slurry was cooled, filtered and excess of solvent was removed under reduced pressure to obtain an oily residue. Iced water was added to the oily residue and it was allowed to stand overnight. The solid obtained was filtered, washed with water, dried and crystallized from acetone and hexane to afford the title compound(0.25 g, 64.78%), mp 419–420K.