Pyrazinecarboxylic acids decarboxylation

Most pyrazines are thermally stable, but pyrazinecarboxylic acids undergo decarboxylation at high temperature above 200 °C. This reaction is practically utilized for the synthesis of alkyl- or arylpyrazines, pyrazinones, and pyrazinamines from the corresponding pyrazinecarboxylic acids (Section 8.03.7.1). 

A useful reaction involving substitution of carbon functionalities is decarboxylation of pyrazinecarboxylic acids. This conversion is readily achieved by heating directly or in high-boiling solvent, or distillation over copper compounds. Fusion under reduced pressure has been occasionally effective for the transformation <2002JOC556>. 

Pyrazinecarboxylic acid has been obtained by selenious acid oxidation in pyridine of methylpyrazine or aqueous permanganate oxidation of ethylpyrazine, in yields of 64 and 48%, respectively.171,218 It has also been obtained in 70% yield by partial decarboxylation of pyrazine-2,3-dicarboxylic acid on heating in vacuo at 210°.219 Aqueous permanganate oxidation of 2,5-distyrylpyrazine gives the 2,5-dicarboxylic acid.220 Pyrazine-2,5-dicarboxylic acid has also been prepared in 45% yield by direct carboxylation of pyrazine with carbon dioxide at 50 atm pressure at 250° for 3 hours in the presence of a potassium carbonate and calcium fluoride catalyst.221 Pyrazine-tricarboxylic acid (57), obtainable in only very poor yields by oxidation of 2,5-dimethyl-3-ethylpyrazine, is prepared in 87% yield by alkaline permanganate oxidation of 2-(D-arabo)tetrahydroxybutyl-quinoxaline (56).222 Decarboxylation of the tricarboxylic acid by... 

The pyrazinecarboxylic acids have properties similar to the pyridinecarboxylic acids and aromatic carboxylic acids in general. The pKa of pyrazine-2-carboxylic acid is 2.92 it is thus considerably stronger than pyridine-2-carboxylic acid (pff0 5.52), and comparable in acidic strength to pyridazine-3-carboxylic acid (pKa 3.0). The pKa values of pyrazine-2,3-dicarboxylic acid are 0.9 and 3.57.231 Pyrazinecarboxylic acids form colored salts with Fe11 ions and they are readily esterified and decarboxylated. 

Like pyrazinecarboxylic acids, alkylpyrazinecarboxylic acids are decarboxylated on heating to elevated temperatures. For example, 23-dicarboxypyrazine and 2,3-dicarboxy-5,6-dimethylpyrazine are decarboxylated in acetic acid at 180 to pyrazine and 23-dimethylpyrazine, respectively, but on distillation under vacuum they give 2-carboxypyrazine and 5-carboxy-2,3-dimethylpyrazine, respectively (397). 

Pyrazinecarboxylic acids undergo decarboxylation at high temperatures above 200°C. By this procedure, alkyl- or arylpyrazines <78JOC3367>, pyrazinones <78JHC665>, and aminopyrazines <80JHC143> are effectively prepared from the corresponding carboxylic acids. 

Electrophilic substitutions accompanied decarboxylation are induced by an electron-donating ort/jo-amino group (Equation (2)). Replacement of the carboxylic acid in 3-amino-5,6-dichloro-pyrazinecarboxylic acid (42 X = Cl) by a nitro group is accomplished by treatment with nitric acid in sulfuric acid, producing compound (43 X = N02) <83JHC1089>. Decarboxylative iodination of... 

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