Studies on pyrazines. Part 25. Lewis acid-promoted deoxidative thiation of pyrazine N-oxides: new protocol for the synthesis of 3-substituted pyrazinethiols

Abstract

Reaction of 3-substituted pyrazine 1-oxides with p-methoxytoluene-α-thiol in the presence of diethylcarbamoyl chloride in refluxing acetonitrile gave the corresponding 3-substituted 2-(methoxybenzylthio)pyrazines. Based on these yields, the ease of substitution is remarkably affected by nucleophilicity of the N-oxide oxygen. Addition of zinc bromide to the reaction mixture increased the yields of thiation products of 3-methyl-, 3-phenyl-, 3-(N-butylcarbamoyl)-, 3-methoxycarbonyl- and the parent pyrazine 1-oxides, but their regioselectivities were rather low. The Lewis acid-mediated reaction of 3-methoxypyrazine 1-oxide gave a different major product, the 2,6-isomer. Conversion of the sulfides to pyrazinethiols was accomplished by mercuriation and successive reduction. This debenzylation was also found to be dependent on the electron density in the pyrazine ring.