Continuous amination of aryl/heteroaryl halides using aqueous ammonia in a Teflon AF-2400 tube-in-tube micro-flow reactor

Abstract

The annual production of primary (hetero)arylamines has exceeded 6 million tons and has been extensively employed in the pharmaceutical, agrochemical, and materials industries. Catalyst-free and protecting group-free nucleophilic amination using ammonia represents a green and atom-economical method. However, due to the innate reactivity, chemical compatibility issue and the safety hazardous properties of ammonia gas, such transformation is still underused. By implementing a gas-permeable Teflon AF-2400 tube-in-tube system, diffusion of NH₃ from aqueous ammonia to a reaction mixture for amination can be achieved in a continuous flow fashion. In this communication, we herein report the use of aqueous ammonia as the NH₃ source in the amination of heteroaryl chorides to generate primary heteroaryl amines, providing a protocol that is green, economical and safe.