Synthesis of 1,2,4-Triazoles via Oxidative Heterocyclization: Selective C–N Bond Over C–S Bond Formation

The
higher propensity of C–N over C–S bond forming
ability was demonstrated, through formal C–H functionalization
during the construction of 4,5-disubstituted 1,2,4-triazole-3-thiones
from arylidenearylthiosemicarbazides catalyzed by Cu­(II). However,
steric factors imparted by the o-disubstituted substrates
tend to change the reaction path giving thiodiazole as the major or
an exclusive product. Upon prolonging the reaction time, the in situ generated thiones are transformed to 4,5-disubstituted
1,2,4-triazoles via a desulfurization process. Two classes of heterocycles
viz. 4,5-disubstituted 1,2,4-triazole-3-thiones and 4,5-disubstituted
1,2,4-triazoles can be synthesized from arylidenearylthiosemicarbazides
by simply adjusting the reaction time. Desulfurization of 1,2,4-triazole-3-thiones
is assisted by thiophilic Cu to provide 1,2,4-triazoles with concomitant
formation of CuS and polynuclear sulfur anions as confirmed from scanning
electron microscope and energy dispersive X-ray spectroscopy measurements.
A one-pot synthesis of an antimicrobial compound has been successfully
achieved following this strategy.