Cyclization of β‐Chlorovinyl Thiohydrazones into Pyridazines: A Mechanistic Study

Abstract

Extensive experimental and theoretical investigations on the isomerization and heterocyclizations of β‐chlorovinyl thiohydrazones derived from oxamic acid thiohydrazides and β‐chlorovinyl aldehydes were performed to elucidate the reaction mechanism of pyridazine formation. We showed that model β‐chlorovinyl thiohydrazone undergoes multiple isomerization reactions in solution induced by thione–thiol tautomerism and Z/E‐isomerization at the C=N bond. Mechanistic rationalization along with computational studies demonstrated that pyridazine is predominantly generated from the Z‐thiol isomers by 6π‐electrocyclization of the thiohydrazone‐derived 2,3‐diazatriene intermediate. The autocatalytic character of cyclization accelerated by the formation of acid was demonstrated by means of 1H NMR monitoring.