Fast metal-free CO2-mediated N-aryl amide synthesis from nitroarenes under continuous flow conditions

Abstract

Improving access to functionalized N-aryl amides efficiently remains a key challenge in organic synthesis, particularly when starting from nitroaromatic compounds. Direct amidation of nitroarenes has emerged as an attractive alternative to multistep synthetic sequences; however, existing methods often require long reaction times, transition metals, and harsh and inert conditions, and exhibit limited functional group tolerance. Herein, we describe a fast, metal-free, and scalable flow protocol for the synthesis of functionalized N-aryl amides directly from nitroarenes. This protocol integrates an electrochemical reduction of nitroarene with a CO₂-mediated amidation of carboxylic acids, enabling the synthesis of twenty amides in yields of up to 89% while containing valuable yet reducible functional groups, in a semi-telescoped fashion.