Highly Efficient, Combinatorial and Catalyst‐Free Approach for the Synthesis of 2‐Benzylidenehydrazono‐3‐phenyl‐4‐thiazolidinone‐5‐acetates in Ethanol

We have designed a sustainable, catalyst‐free, combinatorial protocol for the synthesis of highly functionalized thiazolidinone acetate derivatives via multicomponent reaction of aromatic aldehydes, N‐phenylhydrazinecarbothioamide and dimethoxyacetylenedicarboxylate in the ethanol. A consecutive one pot two step environmentally benign procedure has been developed for the synthesis of 2‐Benzylidenehydrazono‐3‐Phenyl‐4‐Thiazolidinone‐5‐Acetate derivatives by adopting regioselective thermal annulation with the operational simplicity with isolation of pure products without using chromatographic purification. One pot two step environmentally benign procedure has been developed for the synthesis of 2‐Benzylidenehydrazono‐3‐Phenyl‐4‐Thiazolidinone‐5‐Acetate derivatives by adopting regioselective thermal annulation with the operational simplicity with isolation of pure products without using chromatographic purification. The first step proceeds through condensation of aldehydes with N‐phenylhydrazinecarbothioamide yielding substituted thiosemicarbazones derivatives. Afterwards, thermal cyclization of substituted 2‐benzylidene‐N‐phenylhydrazinecarbothioamide with Dimethylacetylenedicarboxylate in ethanol gave (Z)‐methyl 2‐((Z)‐2‐((E)‐(2/3/4‐substituted‐benzylidene)hydrazono)‐4‐oxo‐3‐phenylthiazolidin‐5‐ylidene) acetate is formed.