Microwave - Assisted Direct Amidation of Thioesters: A Green Approach

Abstract

Direct amidation of thioesters represents a virtually nonclassical route in the synthesis of amides, frequently encountering limitations due to poor compatibility between thioester and amine structures as well as poor atomic efficiency. Herein, we describe a green, efficient and microwave-assisted protocol that not only facilitates high-yielding amide bond formation but also converts the sulfur-containing byproducts into valuable disulfides, significantly enhancing atom economy. Notably, the protocol has been successfully applied to the synthesis of difluoromethyl amides and β-mercaptoamides, highlighting its versatility in generating biologically relevant compounds. This work provides a novel and sustainable alternative to traditional amide synthesis methods, offering significant potential for applications in pharmaceutical and materials chemistry.