Study of methylation reactions of 2-phenylquinazoline-4-tion with “soft” and “hard” methylation agents and determination of its biological activity

Abstract

Alkylation reactions of 2-phenylquinazoline-4-thion with methylation agents “soft” (methyl iodide) and “hard” (dimethyl sulfate, methyltozylate) were studied. It was found that the reaction proceeds with the formation of alkyl products at the N3 - and S4 - reaction centers, depending on the methylation agent, solvent and temperature. This indicated the ambivalent nature of the 2-phenylquinazoline-4-tion anion. Prolongation of the reaction time leaded to the formation of a second isomeric product (VII). A slight increase in phenyl N3-product (VII) yield was noted when dimethyl sulfate and methylfolate were used as methylation agents. In non-polar proton-free solvent DMF and dipolar proton-free solvent acetonitrile, only N-methyl product (VII) was formed because of the reaction. An increase in the polarity of the solvent and the “hardness” of the methylation agent leads to an increase in the yield of N3 products.