N-cyano-N-phenyl-p-toluenesulfonamide as electrophilic nitrile source for the synthesis of oxadiazoles

Abstract

A streamlined protocol for the synthesis of amino-1,3,4-oxadiazole heterocycles using NCTS (N-cyano-N-phenyl-p-toluenesulfonamide) as a less toxic and easy-to-handle electrophilic nitrile source, in combination with hydrazides, has been developed. This novel methodology enables the synthesis of amino-1,3,4-oxadiazole derivatives bearing both electron-donating and electron-withdrawing substituents in fewer steps, with improved operational simplicity and yields ranging from 42 % to 70 %. Although several methodologies for the synthesis of amino-1,3,4-oxadiazoles have been reported, our approach offers significant advantages in terms of efficiency, safety, and environmental impact.