Novel 1,2,3-Thiadiazolyl Sulfines from the Reaction of N-Substituted Hydrazones with Thionyl Chloride

Article abstract of DOI:10.1021/jo00199a006

The reaction of 17β-acetoxy-5α-androstan-3-one (ethoxycarbonyl)hydrazone (5a) with neat SOCl2 at 65 deg C gave (1Z)-17β-acetoxy-5α-androst-2-eno<3,2-d><1,2,3>-thiadiazole-1-thione S-oxide (6) in 84percent yield.Under similar conditions the corresponding tosyl- and formylhydrazones afforded 17β-acetoxy-5α-androst-2-eno<3,2-d><1,2,3>thiadiazole (7) in 84percent and 85percent yields, respectively, while the acetylhydrazone gave a mixture of the two products.A single-crystal X-ray of 6 revealed a close (2.66 Angstroem) sulfine-O thiadiazole-S distance suggestive of a weakly attractive interaction.The ethoxycarbonyl hydrazones of a series of cyclohexanone derivatives were similarly reacted with SOCl2.Those substrates having γ-alkyl substituents afforded 1,2,3-thiadiazolyl sulfines in moderate to good yield.The 3,3,5,5-tetramethyl- and 2,5-methanocyclohexanone derivatives gave only the corresponding 1,2,3-thiadiazoles.When 5a was treated with 2 equiv of SOCl2 at -20 deg C, in addition to 6 and 7, the intermediates 17β-acetoxy-2'-(ethoxycarbonyl)-2',5'α-dihydro-5α-androstano<3,2-d><1,2,3>thiadiazole 1'-oxide (22) and 17β-acetoxy-2'-(ethoxycarbonyl)-2'H-5α-androst-1-eno<3,2-d><1,2,3>thiadiazole (23) were isolated.Based on the above and additional mechanistic studies, a mechanism for the formation of 6 and 7 from 5a is proposed.The general behavior of hydrazones with SOCl2 is rationalized in light of this mechanism.