A mild and eco-friendly, one-pot synthesis of 2-hydroxy-N-arylacetamides from 2-chloro-N-arylacetamides

Abstract

Abstract A mild and eco-friendly one-pot two-step procedure was developed for the synthesis of 2-hydroxy-N-arylacetamides from 2-chloro-N-arylacetamides. The procedure overcomes the cleavage of the amide linkage in 2-chloroacetamides which is usually observed under reflux condition with the hydroxide when the nucleophilic substitution of the halide is attempted. The reactions were performed by refluxing 2-chloro-N-arylacetamides with Cu(OAc)2 and DIPEA in ethanol medium to facilitate an acetate exchange with the halogen. Subsequently by the addition of ethanolic KOH solution to the same reaction flask the ester linkage was selectively cleaved in the presence of the amide taking advantage of the difference in electrophilicity. The procedure affords good yields of the desired products which are valuable intermediates for several biologically active molecules, in short reaction time with ease of isolation The experimental conditions employed are simple and offers the possibility of scale up to higher quantities.