3β-Acet­oxy-6-hy­droxy­imino­cholestane

Kamal Aziz Ketuly; A Hamid A Hadi; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536811007306

. 2011 Mar 5;67(Pt 4):o773–o774. doi: 10.1107/S1600536811007306

3β-Acetoxy-6-hydroxyiminocholestane

Kamal Aziz Ketuly ^a,^‡, A Hamid A Hadi ^a, Seik Weng Ng ^a, Edward R T Tiekink ^a,^*

PMCID: PMC3100065 PMID: 21754066

Abstract

Two independent molecules comprise the asymmetric unit of the title cholestane derivative, C₂₉H₄₉NO₃ {systematic name: (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-6-hydroxyimino-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate}. The major differences between the molecules relate to the relative orientations of the terminal acetyl [C—C—O—C torsion angles = −158.8 (3) and −81.7 (3)°] and alkyl groups [C—C—C—C = 168.9 (3) and 65.8 (4)°]. In the crystal, the independent molecules associate via pairs of O—H⋯N hydrogen bonds, forming dimeric aggregates. Supramolecular layers in the ab plane are mediated by C—H⋯O interactions.

Related literature

For background to this study and further details of the synthetic procedures, see: Ketuly & Hadi (2010 ▶). For previous syntheses, see: Anagnostopoulos & Fieser (1954 ▶); Petersen (1963 ▶); Choucair et al. (2004 ▶). For related structures, see: Ketuly et al. (1997 ▶, 2010 ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₉H₄₉NO₃
M _r = 459.69
Monoclinic,
a = 11.3934 (13) Å
b = 9.6588 (11) Å
c = 25.018 (3) Å
β = 93.466 (2)°
V = 2748.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 100 K
0.35 × 0.30 × 0.03 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.757, T _max = 0.862
26531 measured reflections
6690 independent reflections
4553 reflections with I > 2σ(I)
R _int = 0.086

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.114
S = 0.99
6690 reflections
615 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.23 e Å⁻³
Absolute structure: nd
Flack parameter: ?
Rogers parameter: ?

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶), DIAMOND (Brandenburg, 2006 ▶) and Qmol (Gans & Shalloway, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks general, I. DOI: 10.1107/S1600536811007306/hb5806sup1.cif

e-67-0o773-sup1.cif^{(44.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811007306/hb5806Isup2.hkl

e-67-0o773-Isup2.hkl^{(327.4KB, 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
O1—H1⋯N2	0.98 (4)	1.88 (4)	2.809 (3)	157 (4)
O4—H4⋯N1	0.95 (4)	1.82 (4)	2.733 (3)	160 (3)
C9—H9c⋯O6ⁱ	0.98	2.58	3.404 (4)	142
C37—H37c⋯O3ⁱⁱ	0.98	2.40	3.373 (4)	169

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

Acknowledgments

The authors thank the University of Malaya for support and greatly appreciate UMRG grant No. RG035/10BIO.

supplementary crystallographic information

Comment

The title compound, 3β-Acetoxy-6 N-hydroxyiminocholestane, (I), is a known species and has been utilized as an intermediate for the preparation of 6-ketocholestanol acetate, which it readily affords upon reduction with zinc and acetic acid followed by acid hydrolysis (Anagnostopoulos & Fieser, 1954; Petersen, 1963). Interest in hydroxyimino-steroids stems from a broad investigation into the correlation of structure with biological activity of modified steroid hormones (Choucair et al., 2004). In continuation of systematic structural analyses of related steroidal compounds (Ketuly et al., 1997; Ketuly et al., 2010), the X-ray crystallographic analysis of (I) was conducted.

Two independent molecules comprise the asymmetric unit of (I), Fig. 1. These are linked into dimeric aggregates via O—H···N hydrogen bonds, Table 1. From the overlay diagram, Fig. 3, it is evident that the molecules differ in the relative orientations of the terminal acetyl and alkyl substituents. For the former, the different conformation is manifested in the values of the C3—C4—O2—C8 and C30—C31—O5—C36 torsion angles of -158.8 (3) and -81.7 (3) °, respectively. For the alkyl chains, the differences are seen in the C22—C24—C25—C26 and C51—C53—C54—C55 torsion angles of 168.9 (3) and 65.8 (4) °, respectively. Each of the six-membered rings adopts a chair conformation or close to a chair conformation, and each of the five-membered rings has a twisted conformation, about the C14—C15 and C42—C43 bonds, respectively (Cremer & Pople, 1975).

The most notable feature of the crystal packing other than the aforementioned O—H···N hydrogen bonds is the presence of C—H···O interactions, Table 1. These lead to the formation of supramolecular layers in the ab plane, Fig. 3.

Experimental

Hydroxylamine hydrochloride (13.5 mg) was dissolved in dried and purified pyridine (2 ml) and 3β-acetoxy-5α-chloestan-6-one (10 mg) added. The solution mixture was heated at 353 K for 4 h. The solvent was dried under vacuum, yielding crude crystals. Recrystallization from methanol and water (10:1, v/v) yielded compound (I): yield 9.1 mg, 88%, M.pt. 474–475 K. Lit. M.pt. 475–476 K (Petersen, 1963). Compound (I) was also isolated as an intermediate byproduct during the reduction of 3β-acetoxy-6-nitrocholest-5-ene to 3β-acetoxy-6-oxo-cholestanol. Thus, 3β-acetoxy-6-nitrocholest-5-ene (5 g, 10.6 mmol) was dissolved in glacial acetic acid (100 ml) and stirred with a Hershbury stirrer and diluted with water (5 ml). Zinc dust (10 g) was added in small portions over a period of 0.5 h. The suspension was then heated under reflux for 4.5 h. The solution was filtered and washed with acetic acid (2 x 6.5 ml). The filtrate was diluted with water (100 ml), cooled in an ice-bath and the organic layer was extracted with ether. The yellow viscous product was crystallized from methanol, dried (4.41 g) and recrystallized four times from methanol with a few drops of ether, yielding 3β-acetoxy-6-oxo-cholestanol (3.12 g), M.pt. 402–404 K. Lit. 409 K (Choucair et al., 2004). The combined mother liquors were dried and four times recrystallized from methanol and water (10:1, v/v), yielding colourless plates of (I), (0.24 g), M.pt. 474–475 K. The purification and vacuum sublimation methods employed in the study follow literature precedents (Ketuly & Hadi, 2010).