Synthesis of highly functionalized thiazolo[3,2-a]pyridine derivatives via a five-component cascade reaction based on nitroketene N,S-acetal

Abstract

A highly efficient and straightforward synthesis of N-fused heterocyclic compounds including 5-amino-7-(aryl)-8-nitro-N'-(1-(aryl)ethylidene)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide derivatives is successfully achieved via a five-component cascade reaction utilizing cyanoacetohydrazide, various acetophenones, aromatic aldehydes, 1,1-bis(methylthio)-2-nitroethylene and cysteamine hydrochloride in ethanol at reflux conditions. The new approach involves domino N,S-acetal formation, Knoevenagel condensation, Michael reaction, imine–enamine tautomerization and N-cyclization sequences. The prominent advantages of this protocol include: facility of operation, available and economical starting materials, no need for toxic solvents, high yields and tolerance of a wide variety of functional groups.