Revitalised Hofmann carbylamine synthesis made possible with flow chemistry

Abstract

Isocyanides are of relevance to several scientific fields; however, over the last 150 years only a limited number of synthetic strategies have been reported for preparing them. In a newly developed flow approach, a neglected method for preparing isocyanides, the Hofmann carbylamine reaction, has been revisited and revitalised. The approach developed afforded the preparation of a diverse library of isocyanides in good conversions while only requiring a 15 min residence time at 70 °C. In addition, the method is operationally easy to apply, and it affords several advantages over the more commonly employed strategy of preparing isocyanides which involves the conversion of amines to formamides followed by dehydration to an isocyanide.