Collect. Czech. Chem. Commun. 1980, 45, 539-547

On the synthesis of 4- and 5-pyrimidinyl-diphenyl-(1-imidazolyl)methanes and their antifungal activity

Zdeněk Buděšínský, Josef Vavřina, Leon Langšádl and Jiří Holubek

Research Institute for Pharmacy and Biochemistry, 130 00 Prague 3


On reaction of phenylmagnesium bromide with ethyl ester of 5-chloro-2-methyl-, 5-chloro-2-methylthio-, 5-bromo-2-methylthio-4-pyrimidinecarboxylic acid and 2,4-dimethyl-5-pyrimidinecarboxylic acid (IIa, IIb, IIc, V) corresponding 4-pyrimidinyl- or 5-pyrimidinyl-diphenylmethanols (IIIa, IIIb, IIIc, VI) were obtained. On reaction of thionyl-bis-imidazole with these methanols (4- or 5-pyrimidinyl)-diphenyl-(1-imidazolyl)-methanes IVa, IVb, IVc and VII were prepared. Phenylmagnesium bromide reacted with ethyl 4-methyl-2-methylthio-5-pyrimidinecarboxylate (VIII) under formation of dihydro derivative IX. We were unable to prepare Grignard's reagent from 5-bromo-2-methylthiopyrimidine and magnesium; it reacted with ethylmagnesium bromide under formation of dihydro derivative I. 5-Chloro-2-methylthio-4-pyrimidinecarboxylic acid when heated with NaOH in dimethyl sulfoxide gave 5-hydroxy-2-methylsulfinyl-4-pyrimidinecarboxylic acid. Compounds IVb and IVc prevented the growth of Candida albicans in vitro at almost the same concentrations as clotrimazole.