Polyfluoroheterocyclic compounds. Part XVII. Preparation and nucleophilic substitution of tetrafluoropyrazine and the orientational effect of substituents in polysubstitution

Abstract

Chlorination of various pyrazine derivatives, preferably pyrazine-2,3-dicarboxylic acid, provides tetrachloropyrazine, which gives tetrafluoropyrazine when heated with potassium fluoride. A series of trifluoropyrazines has been obtained by reaction between tetrafluoropyrazine and nucleophiles in which the attacking atom is carbon, nitrogen, or oxygen. Trifluorohydroxypyrazine does not tautomerise appreciably to a pyrazinone. The structures of the difluoropyrazines resulting from a second nucleophilic substitution have been deduced by ¹⁹F n.m.r. spectroscopy, and substituent shielding parameters obtained from trifluoropyrazines give notably consistent values when applied to difluoropyrazines. Alkyl and chlorine substituents in a trifluoropyrazine direct nucleophilic attack to the para-, and alkoxy-substituents to the ortho-position. Tetrafluoropyrazine is also substituted in the presence of protic or Lewis acids; tetrabromopyrazine and a dibromodifluoropyrazine are obtained by use of aluminium bromide and hydrogen bromide. Various other halogeno-fluoropyrazines are obtained by incomplete fluorination of tetrachloropyrazine or from reaction of trifluorohydrazinopyrazine with metal halides.