Ternary deep eutectic solvent-mediated direct amidation of carboxylic acids.

A ternary deep eutectic solvent (DES) has been developed as a multifunctional platform for the direct amidation of carboxylic acids. Composed of choline chloride, urea and imidazole in a 1 : 2 : 1 molar ratio, the DES serves as the reaction medium, while imidazole is proposed to act as a recoverable acyl-transfer mediator. A broad range of primary amides were obtained under organic-solvent-free reaction conditions, with straightforward product isolation and no chromatographic purification. On a 100 g scale, product yields remained above 90% over seven consecutive runs. This combination of simple operation, mediator recovery and preparative-scale recycling provides a lower-waste alternative to conventional coupling-reagent-based amidation.