Amination of heteroaryl chlorides: Palladium catalysis or SNAr in green solvents?

Abstract

The reaction of heteroaryl chlorides in the pyrimidine, pyrazine and quinazoline series with amines in water in the presence of KF results in a facile SNAr reaction and N-arylation. The reaction is less satisfactory with pyridines unless an additional electron-withdrawing group is present. The results showed that the transition-metal-free SNAr reaction not only compares favourably to palladium-catalysed coupling reactions but also operates under environmentally acceptable ("green") conditions in terms of the base and solvent. Substitutions go green: The reaction of heteroaryl chlorides with amines in water in the presence of KF results in a SNAr reaction and N-arylation as a viable green alternative to palladium-catalysed amination. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.