Pyrimidines. 8. chlorination of 6‐methyluracil with phosphorus oxychloride in the presence of trialkyamines

Abstract The effect of the tertiary amines triethyl, tri‐ n ‐propyl, and tri‐ n ‐butylamines on the chlorination of 6‐methyluracil by phosphorus oxychloride was studied. A comparison with the reaction of preformed 2,4‐dichloro‐6‐methylpyrimidine and triethylamine in toluene was made. The reaction in phosphorus oxychloride in the presence of triethylamine afforded low yields of 2‐diethylamino derivative after short heating periods and high yields of the 2,4‐bis(diethylamino) derivative after 188 hours of boiling. Heating the preformed 2,4‐dichloro‐6‐methylpyrimidine in toluene in the presence of triethylamine yielded primarily the 2‐diethylaminopyrimidine along with a small amount of the 4‐diethylamino isomer. After 188 hours, the product mixture was composed of 87% 2‐diethylamino and 13% of 4‐diethylamino isomers. Although substituent orientation was essentially the same, the yields of products seem to have been influenced by the dielectric constants of the solvents. Tri‐ n ‐propylamine in phosphorus oxychloride yielded solely the dichloropyrimidine, even after 188 hours of boiling, and is recommended as the amine of choice in such chlorination reactions. Tri‐ n ‐butylamine was the same after 48 hours, but 4% of 4‐di‐ n ‐butylaminopyrimidine was found after 188 hours of heating.