Green Solvents for the Formation of Amide Linkage

Amide bond is among the most commonly performed transformation within the pharmaceutical industry and the wider chemical industry. Current methods towards its installation in organic compounds frequently relies on the use of large amounts of organic solvents, mainly N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and dichloromethane (DCM), which have been associated with important environmental and health concerns over the last decades. This fact led the academic research and industries to address significant efforts in the development of synthetic routes with the aim to avoid, reduce or replace the use of hazardous solvents. The present review fits into this framework and discusses the latest insights in solvent lessening and replacement strategies, focusing on the use of biobased and neoteric solvents, such as ionic liquids and deep eutectic solvents (ILs and DESs, respectively), as well as reaction media that proved to be greener alternatives for amide bond synthesis.