A one-step base-free synthesis of N-arylamides via modified pivaloyl mixed anhydride mediated amide coupling

Org Biomol Chem. 2023 May 10;21(18):3825-3828. doi: 10.1039/d3ob00452j.

Abstract

Pivalic anhydride is shown to be an effective reagent for direct amidation of carboxylic acids with N-alkyl anilines. The only by-product of this reaction is nontoxic pivalic acid, which can be easily removed by aqueous workup. The reactions are conducted under mild conditions and found to be compatible with a range of carboxylic acids, including aromatic, heterocyclic, acrylic, and aliphatic carboxylic acids and amino acids generating the desired amides in short reaction times.