Regioselective synthesis and S-derivatization reactions of 4- and 6-trifluoromethyl-3-cyano-2(1H)-pyridinethiones

The regioselective synthesis of the title compounds was developed on the basis of condensation reactions of trifluoroacetylacetone and its methyl enacetal with cyanothioacetamide in the presence of bases. Thus, the condensation of trifluoroacetyl-acetone with cyanothioacetamide yields predominantly 4-trifluoromethyl-6-methyl-3-cyano-2(1H)-pyridinethiones, whereas the methyl enacetal of trifluoroacetylacetone gives exclusively the 6-trifluoromethyl-4-methyl isomer. S-Alkylation of the trifluoromethyl-pyridinethione salts can be achieved using methyl iodide or bromoacetophenone in DMF-water. Bromoacetophenone derivatives can be further transformed into 3-aminothieno-[2,3-b]pyridines in the presence of excess KOH.