Metal-free synthesis of 3-trifluoromethyl-1,2,4-triazoles via oxidative cyclization of trifluoroacetimidohydrazides with N,N-dimethylformamide as carbon synthons

Abstract

A metal-free approach for the synthesis of 3-trifluoromethyl-1,2,4-triazoles via I2-mediated oxidative cyclization of readily accessible trifluoroacetimidohydrazides with N,N-dimethylformamide (DMF) has been disclosed. In this transformation, the commonly used organic solvent DMF is applied as a C1 synthon and the methine unit of the 1,2,4-triazole products is independently from N-methyl and N-acyl of DMF. The application potential of the developed method has been demonstrated by the synthesis of the key skeleton of factor IXa inhibitors.

Keywords

• Metal-free
• Oxidative cyclization
• 3-Trifluoromethyl-1,2,4-triazole
• Trifluoroacetimidohydrazides
• N,N-Dimethylformamide
• Trifluoromethyl-substituted N-Heterocycles