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 & PRIME;-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.

Automated summary

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. This approach is extended for the synthesis of 36 derivatives and 2 bioactive molecules using different substrates.