Cyclization of isothiosemicarbazones. Part 7. Synthesis of N-alkenyl-1,2,4-triazoles with anti-Saytzeff orientation

Abstract

Aliphatic ketone 4-[2-cyano-2-(ethoxycarbonyl)vinyl]-3-methylisothiosemicarbazones (4) give N-alkenyl-1,2,4-triazoles (6) in moderate yields with elimination of ethyl cyanoacetate in hot acetic acid. When the carbonyl component is an unsymmetrical ketone, the reaction proceeds predominantly to afford the less substituted terminal alkenes, and little or no formation of the more substituted internal alkenes was observed, even though the internal alkene would be thermodynamically more favourable. Without an intervening isolation of the N(4)-(substituted vinyl) isothiosemicarbazones, these alkenes are obtained in much higher yields through a direct ‘cycloalkenylation’ of N(4)-unsubstituted isothiosemicarbazones (1) with ethyl β-ethoxy-α-nitroacrylate (3) along with a minor amount of 2(3)-(3-alkylthio-1,2,4-triazol-1-yl)alkan-2 (3)-yl acetates (7). The proposed mechanism involves preferential abstraction of a proton at the less crowded alpha-carbon of the potentially formed iminium ion.