Direct amidation of acids in a screw reactor for the continuous flow synthesis of amides

A simple and efficient solvent-free protocol for continuous flow synthesis of amides at room temperature is developed using easily available starting materials. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC.HCl) was used as the reagent for the formation of an amide bond without using any metal catalyst or additives. A jacketed screw reactor when operated over a residence time of 30 300 s helped achieve almost complete conversion. This approach is extended for the synthesis of 36 derivatives and 2 bioactive molecules using different substrates having different aliphatic mono and di-acids as well as aromatic acids, including aromatic hetero-acid compounds and phenyl hydrazine. The target amide was scaled up to 100 g with an average 90% yield.