Microwave-Mediated, Catalyst-Free Synthesis of 1,2,4-Triazolo[1,5-<i>a</i>]pyridines from Enaminonitriles

Abstract

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

Keywords

• enaminonitrile
• 1,2,4-triazolo[1,5-<i>a</i>]pyridine
• microwave irradiation
• tandem reaction
• acyl hydrazide