Preparation and acid-catalysed rearrangements of a steroidal 1,4-quinol

Abstract

Thallium perchlorate oxidation of 17β-acetoxy-1-hydroxy-4-methylestra-1,3,5(10)-triene (1) was used to prepare the steroidal quinol, 17β-acetoxy-4ξ-hydroxy-4-methylestra-2,5(10)-dien-1 -one (2), which could be isolated as a pair of diastereoisomers. Thallium nitrate in methanol yielded the corresponding 4-methoxy-quinol (3). Treatment of the quinol with HBr or HCl rearranged it to the 1,17β-diacetoxy-3-halogeno-4-methylestra-1,3,5(10)-trienes (4) and (5)(after acetylation) while HI expelled the 4-hydroxy-moiety and reduced it to 1,17βdiacetoxy-4-methylestra-1,3,5(10)-triene (6). Hydrogen fluoride failed to effect any reaction. Dienone-phenol type rearrangement, whereby the 4-methyl group migrated to C-3 affording 1,4,17β-tiacetoxy-3-methylestra-1,3,5(10)-triene (15), was accomplished with BF₃–ether and subsequent acetylation. Use of ZnCl₂–acetic anhydride was found, on the other hand, to bring about migration of the oxygen moiety and give 1,3,17β-triacetoxy-4-methylestra-1,3,5(10)-triene (12). Attempts to rearrange the 4-methoxy-quinol ether (3) by the above methods failed.