Journal of heterocyclic chemistry. 24:1243-1247.




Ring-chlorination of 6-trifluoromethyluracil in phosphorus oxychloride in the presence of triethyl, tri-npropyl, and tri-n-butylamines was studied with respect to by-product formation. Comparisons were made with the results obtained by treating the preformed chlorinated pyrimidine with triethyl amine in boiling toluene. Amination of chloropyrimidines by tertiary amines takes place by a Hofmann type reaction with substituent orientation generally in the 2 position of the ring. Yields of products depended on the base and reaction time. The rate of substitution in the 2 position is significantly enhanced by the presence of the trifluoromethyl group in the 6 position as compared with a methyl group. Heating preformed chloropyrimidines with tertiary amines in toluene, offers a satisfactory approach for the preparation of 2-N,N-disubstituted aminopyrimidines. For the formation of ring-chlorinated pyrimidines in phosphorus oxychloride with a minimum of by-products, tri-n-propylamine, after a short reflux period is most useful

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