Novel regioselective preparation of 5-chloropyrazine-2-carbonitrile from pyrazine-2-carboxamide and coupling study of substituted phenylsulfanylpyrazine-2-carboxylic acid derivatives

A new method of 5-chloropyrazine-2-carbonitrile preparation in a regioselective fashion and the study of the coupling of the pyrazine ring with variously substituted benzenethiols are described. A radical-ionic mechanism of this coupling, carried out in the presence of a heterogeneous copper catalyst, has been proposed. The reactivity of the substituted chloropyrazines is correlated to the calculated values of electronic deficiency in positions C-(6) or C-(5) or C-(3) of the pyrazine ring. This nucleophilic substitution provided a series of substituted phenylsulfanylpyrazine-2-carboxylic acid derivatives. The synthetic approach, analytical and spectroscopic data of all compounds are presented.