Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones.

The in situ-generated thiocarbonyl S-methanides (thiocarbonyl ylides), derived from cycloaliphatic thioketones, are efficiently trapped by enolizable 1-substitued 5-mercapto-1H-tetrazoles and formation of the corresponding N-H or S-H insertion products, i.e., thioaminals or dithioacetals, respectively, was observed. In some instances, both products were formed side by side and could be separated by chromatography. Two novel, sterically overcrowded bis-spiro(cyclopentyl) and bis-spiro(cyclohexyl)-substituted thiocarbonyl S-methanides were thermally generated from the corresponding 1,3,4-thiadiazolines and their reactivity towards 5-mercapto-1H-tetrazoles was compared with well-known analogues derived from adamantanethione and 2,2,4,4-tetramethyl-3-thioxocyclobutanone. Some of the isolated thioaminals were observed to undergo thermal isomerization in CDCl₃ solution yielding the corresponding dithioacetals. Structural analysis of the isolated products of S-H and N-H insertion was carried out based on spectroscopic data (¹H and ¹³C NMR) and the structures of two representatives were established by using the X-ray single crystal diffraction analysis method. Biological activity (cytotoxicity) of some selected products derived from 5-mercapto-1H-tetrazoles was also examined.