Synthesis of 2,3-dihydro-6-methyl-2-thiopyrimidin-4(1 H)-one (6-methylthiouracil) derivatives and their reactions

Abstract

The synthesis and characterization of 2,3-dihydro-6-methyl-2- thioxopyrimidin-(1H)-one (I) and some of its derivatives has been performed in our lab. Ring-closing cyclization, as a result of the condensation of ethyl-3-oxobutanoate with thiourea in KOH in an ethanol medium produced 2,3-dihydro-6-methy -2-thioxopyrimidin-(1H)-one (I). The reaction of compound (I) with 2- chloroacetic acid in an alkaline KOH solution produced the carboxylate derivative, 2-(2,6-dihydro-4-methyl-6-oxopyrimidin-2-yl-thio) ethanoic acid (II). The reaction of the resulted derivative of carboxylate (II) with the salt of copper sulphate, produced a new copper salt (III). A substitution reaction between synthesized compound (I) and 2-chloroethanol in an aqueous solution of KOH, created 2-(2-hydroxyethylthio)-6-methylpyrimidin-4(3H) -one (IV). The reaction of compound (I) with 2-(chloromethyl)oxirane in the presence of an aqueous solution of KOH, resulted yielded 2-(3-chloro-2-hydroxy- propylthio)-6-methylpyrimidin-4(3H)-one (V). Sodium mercaptide compound (VI), was produced by the reaction of (I) with NaOH and then the sodium salt of 2,3-dihydro-6-methyl-2-thioxopyrimidin-(1H)-one (VI) was reacted with 2-(chloromethyl)oxirane to result in 2-((oxiran-2-yl) methyl-thio)-6-methyl- pyrimidin-4(3H)-one (VII). Different acylation reagents (acetyl chloride, benzoyl chloride) were reacted with compound (I), in dimethylformamide, acylation happens on sulfur and furnished S-acylified derivatives of (VIII-IX). All the synthesized and obtained products were confirmed by IR, 1H, and 13C NMR and elemental analysis. © 2013 Mohammad Barmaki et al.