Multicomponent Domino Reaction for Concise Access to 2-Amino-Substituted 1,3,4 Oxadiazoles via Smiles Rearrangement.

Abstract

A multicomponent domino reaction has been developed for the preparation of N-substituted 2-amino-1,3,4-oxadiazoles directly from various hydrazides (32 examples). The formation of 2-amino-1,3,4-oxadiazole involves the Smiles rearrangement of thiazolidinone, which results in the formation of carbodiimide intermediate that concomitantly undergoes amide-imidic acid tautomerism followed by cyclization. The protocol developed has wide applicability and provides the desired 2-amino-1,3,4-oxadiazole in excellent yields. The GSD studies of NMR spectra of aliphatic substrates (4di, 4dh) revealed the formation of three products, whereas, in the case of allylic and benzylic substrates, thiazolidinones were obtained as the sole products. Furthermore, to elucidate the plausible mechanism, DFT studies were performed affirming carbodiimide as the crucial intermediate for the interconversion of thiazolidinone to oxadiazole.