Simple pyrimidines. Part XII. Synthesis and methylation of some 2-amino-5-phenylpyrimidines

Abstract

Syntheses of 2-amino-, 2-methylamino-, and 1,2-dihydro-2-imino-1-methyl- 5-phenylpyrimidines, and of their derivatives para-substituted by a methyl, chloro-, bromo-, fluoro-, methoxy-, dimethylamino-, nitro-, or amino-group, are described. The routes involve primary synthesis of appropriate 5-phenylpyrimidine-2-thiols followed by S-methylation, oxidation to the corresponding sulphones, and aminolysis. On methylation, the 2-aminopyrimidines produced give the imines, which undergo Dimroth rearrangement to the methylamino-isomers, also made directly by methylaminolysis of the sulphones. 2-Amino- and 2-methylamino-5-p-nitrophenylpyrimidine are better made by nitration of the corresponding phenylpyrimidines or by nitration of 2-methylsulphonyl-5-phenyl-pyrimidine followed by aminolysis. Reduction of the appropriate nitro-compounds gives 2-amino-5-p-amino-phenylpyrimidine and its 2-methylamino-homologue.

Linear relationships exist between the ionisation constants of these 2-amino-, imino-, and methylamino-pyrimidines and Berliner's σ values for para-substituted-phenyl substituents. The existence of a considerable interplanar angle in such molecules is inferred from the reduced transmission of substituent effects, illustrated not only by pK_a values but also by u.v. and ¹H n.m.r. spectra.