3β-Acetoxy-6-hydroxyiminocholestane

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.


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 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.  Carbon-bound H-atoms were placed in calculated positions (C-H 0.98 to 1.00 Å) and were included in the refinement in the riding model approximation, with U iso (H) set to 1.2 to 1.5U equiv (C). The oxygen-bound H atoms were located from a difference map and refined freely. In the absence of significant anomalous scattering effects, 5428 Friedel pairs were averaged in the final refinement. However, the absolute configuration was assigned on the basis of the known chirality of the 3β-acetoxy-5α-chloestan-6-one starting material. Two reflections, i.e. (0 0 1) and (0 0 2), were omitted from the final refinement owing to poor agreement. Fig. 1. The molecular structures of the two independent molecules comprising the asymmetric unit of (I) showing displacement ellipsoids at the 50% probability level. The molecules are connected into dimeric aggregates via pairs of O-H···N hydrogen bonds (dashed lines).

Fig. 2.
Overlay diagram the two independent molecules comprising the asymmetric unit of (I). The independent molecule having the N1 atom is shown in red. (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-  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.