Pyrimidines. Part II. Nucleophilic substitution reactions of ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate

Abstract

Treatment of ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate with dimethylamine, sodium phenoxide, sodium thiophenoxide, potassium fluoride, or the triethylamine salt of N-hydroxyphthalimide, yielded normal substitution products. However, when the chloropyrimidine was treated with sodium cyanide in dimethyl sulphoxide, or lithium cyanide in dimethylformamide, in attempts to prepare the 4-cyano-derivative, ethyl 2,4-bis-methylthiopyrimidine-5-carboxylate was obtained. Investigation of this reaction, and of the other products, suggested that the methylthio group in ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate is displaced by cyanide ion. 4-Chloro-2-methylthiopyrimidine reacts similarly to give 2,4-bismethylthiopyrimidine, indicating that this reaction may be a general one. The lability of the methylthio group in ethyl 4-chloro-2-methylthio-pyrimidine-5-carboxylate is also shown by the reaction with an excess of sodium methoxide to give methyl 2,4-di-methoxy pyrimidine-5-carboxylate. A number of other nucleophilic substitution products derived from ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate are described.