Direct preparation of nitriles from carboxylic acids in continuous flow

J Org Chem. 2013 Oct 18;78(20):10567-71. doi: 10.1021/jo401945r. Epub 2013 Oct 8.

Abstract

A continuous-flow protocol for the preparation of organic nitriles from carboxylic acids has been developed. The method is based on the acid-nitrile exchange reaction with acetonitrile, used as the solvent, and takes place without any catalyst or additives under the high-temperature/high-pressure conditions employed. At 350 °C and 65 bar, where acetonitrile is in its supercritical state, the transformation of benzoic acid to benzonitrile requires 25 min. The protocol has been tested for a variety of nitriles, including aromatic and aliphatic substrates.