Cyclization of isothiosemicarbazones. Part 8. Formation and structure of gem-bis(3-alkylthio-1H-1,2,4-triazol-1-yl)alkanes and related compounds

Abstract

Symmetrical gem-bis(3-alkylthio-1H-1,2,4-triazol-1-yl)alkanes (6) are directly obtained by the reaction of aliphatic ketone isothiosemicarbazones (1) with ethyl ethoxymethylenenitroacetate (2) as a methine donor in aqueous formic acid. Aldehyde isothiosemicarbazones indirectly give both symmetrical and unsymmetrical terminal gem-bis(triazolyl)alkanes, after conversion into the 4-[2,2-bis(ethoxycarbonyl)vinyl]-3-alkylisothiosemicarbazones (5) and exposure to aqueous acidic media, with the former being the major product. Electronic and steric factors in the starting isothiosemicarbazones exert a marked influence on the yield of bis(triazolyl)alkanes. Two unsymmetrical bis(azole)s are obtained through these reactions, one in which the two triazole rings are linked together by the different nitrogens, and the other, which carries a different substituent on each sulphur in two azole rings, the latter being obtained through the cross-reaction between differently substituted isothiosemicarbazones. The gem-bis(azole) formation may involve nucleophilic attack of 4-(substituted vinyl)isothiosemicarbazone (4) or (5) on an intermedially formed iminium cation (14) as the key step, followed by intramolecular cyclization of the resulting oxonium ion.