Selective addition of amines to 5-trifluoromethyl-2,4-dichloropyrimidine induced by Lewis acids

A variety of 2,4-diamino-pyrimidine systems can be prepared from the corresponding 2,4-dichloro-pyrimidine by sequential addition of two amines, the first adding selectively to the 4-position. In contrast it was found that 2,4-dichloro-5-trifluoromethyl-pyrimidine yields a 1:1 mixture of the two possible isomers. Lewis acids were employed to increase the ratio of isomers to >10:1 in favor of the 2-addition product. Optimization of the effect of Lewis acid additives on this and other dichloropyrimidine systems will be discussed.