Metal-Free Synthesis of Heteroaryl Amines or Their Hydrochlorides via an External-Base-Free and Solvent-Free C-N Coupling Protocol

Herein, a metal-free and solvent-free protocol was developed for the C-N coupling of heteroaryl halides and amines, which afforded numerous heteroaryl amines or their hydrochlorides without any external base. Further investigations elucidated that the basicity of amines and specific interactions derived from the X-ray crystallography analysis of 3j'center dot HCl played pivotal roles in the reactions. Moreover, this protocol was scalable to gram scales and applicable to drug molecules, which demonstrated its practical value for further applications.

Automated summary

A metal-free and solvent-free protocol was developed for the C-N coupling of heteroaryl halides and amines, yielding numerous heteroaryl amines or their hydrochlorides without the need for any external base. The basicity of amines and specific interactions derived from X-ray crystallography analysis played pivotal roles in the reactions. The protocol was scalable to gram scales and applicable to drug molecules, demonstrating its practical value for further applications.