Synthesis of isomeric 5-(phenylsulphonyl)pyrimidines

Abstract

The reaction of alkyl N-cyanoimidates (1a–d) with (phenylsulphonyl)acetonitrile (2) and sodium meth-oxide afforded intermediate salts (3a–d), which were characterized as their conjugate acids (10b,c). Acidic hydrolysis of salts (3a–d) yielded 3-[(aminocarbonyl)amino]propenenitriles (4a–d), which cyclized to pyrimidin-2-ones (5a–d) upon dissolution in 2M-sodium hydroxide. These, in turn, were methylated to pyrimidin-4-amines (6a,c,d). The isomeric pyrimidin-4-ones (8a–d) were prepared unambiguously from the imidates (1a–d) and 2-(phenylsulphonyl)acetamide (7) and were methylated to pyrimidin-2-amines (9a–d). Hydrogen chloride induced a selective cyclization of the dicarbonitriles (10b,c) to 2-chloro-(11) or 4-chloro-pyrimidine (12). Several representatives of pyrimidinamines (6) and (9) were obtained alternatively by selective cyclizations of the salts (3).