Catalyst-free synthesis of α-acyloxycarboxamides in aqueous media

Abstract

Organic syntheses in aqueous solutions are being developed because water is an environmentally friendly, inexpensive, non-toxic and non-flammable solvent. The common method for the synthesis of α-acyloxycarboxamides is the one-pot three-component condensation of a carboxylic acid, an aldehyde and an isocyanide, entitled the Passerini reaction. This reaction is usually performed in organic solvents such as dichloromethane or toluene. Herein we report a novel protocol for the synthesis of α-acyloxycarboxamides in aqueous solution under mild reaction conditions, for which one of the reactants, the carboxylic acid, is a micelle- or vesicle-forming compound. The reaction is carried out successfully with up to 93% yield in an aqueous solution without catalyst or surfactant addition. Our findings showed that the fatty acid used as a substrate accelerates the reaction due to its self-assembly properties. This environmentally benign protocol has several advantages such as high yields, mild reaction conditions and easy workup. Moreover, it allows to synthesize α-acyloxycarboxamides that are inaccessible under standard conditions.