Conformational Analysis of Steroids: Polymorphic Forms of 17β-Acetoxy-6β-bromo-4-androsten-3-one

X-ray crystal structure analysis of two polymorphic forms of 17β-acetoxy-6β-bromo-4-androsten-3-one provided three independent observations of the molecular conformation of this molecule. Polymorph I (mp 114-117 °C) was obtained by bromination of 17β-acetoxy-4-androsten-3-one with N-bromosuccimide and by acetylation of 6β-bromo-17β-hydroxy-4-androsten-3-one and consisted of conformers a and b in a 1:1 ratio. Polymorph II (mp 138-141 °C) was obtained by a treatment of polymorph I with chloroform-methanol (9:1) under epimerization condition and consists of one conformer only. Despite differences in solid IR spectra and dissimilarities in crystal packing environment, the three conformers are nearly identical in overall shape. The A rings of the three molecules have la-sofa conformations, and the B and C rings have chair conformations. The stacking of the 3-carbonyl groups in polymorph I contributes to denser packing and a shift in carbonyl frequency. The closest contact in the polymorph II involves the acetate carbonyl and is also reflected in a shift in spectra. The structure determinations demonstrate that while crystal packing has very little influence on overall molecular conformation, it does influence solid-state spectra.