Amination of heteroaryl chlorides: palladium catalysis or SN Ar 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 SN Ar 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 SN Ar 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.