Direct Amide Formation Avoiding Poor Atom Economy Reagents

Abstract

In 2005, the American Chemical Society, Green Chemistry Institute, Pharmaceutical Roundtable, which consisted of several prominent pharmaceutical companies, was formed in order to encourage and implement green chemical principles into the global pharmaceutical and chemical industry. The Roundtable highlighted the amide formation reaction as a key process that invariably involved poor atom economy reagents. It was, therefore, highlighted as a key challenge to synthetic chemists to develop greener direct amide formation reactions, starting from carboxylic acids and amines, without the use of stoichiometric and high molecular weight reagents. This chapter presents a survey of recent developments that address these issues. It examines the current state-of-the-art in direct amide formation, mainly involving boronic and boric acid-based systems, being perhaps most developed, though also examining other catalytic solutions, including triazine-based reagents, titanium(IV)-based reagents and antimony-based reagents. It ends with a discussion of heterogeneous catalysts and microwave-assisted amide synthesis.