Decarboxylation pyrazine dicarboxylic acid

The decarboxylation of pyrazine-2,3-dicarboxylic acids may be carried out by heating in vacuo or in glacial acetic acid at 130°-145°,211 or by heating in a solvent of high dielectric constant such as nitrobenzene.212 It is suggested that these solvents promote decarboxylation by zwitterion formation. 

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. 

Reference has already been made to the partial decarboxylation of pyrazinedicarboxylic acids.219 Both pyrazine itself,232 and 2,3-dimethylpyrazine,207 are conveniently prepared by decarboxylation of the appropriate dicarboxylic acids. The decarboxylation of pyrazine-2,3-dicarboxylic acid is carried out by heating in din-butyl phthalate and gives pyrazine in 90% yield. The 2,3-dicarboxylic acid forms an anhydride in the normal way. Pyrolysis of the anhydride at 800°/0.05 mm through a silica tube gives in 80% yield an approximately 1 1 mixture of maleonitrile and fumaronitrile (Scheme 19). 2,3-Dehydropyrazine is thought to be an intermediate in this reaction and a strong peak of m/e 78, corresponding to the dehydropyrazine ion, is observed in the mass spectrum of the anhydride.233... 

For a long time before the ring structure of pterins was known, compounds containing the pteridine ring were being prepared. In 1895, 2,4-dihydroxy-pteridine was prepared by oxidation of tolualloxazine and decarboxylation of the resulting 2,4-dihydroxypteridine-6,7-dicarboxylic acid, and the same compound was prepared in 1907 by the action of hypobromite on pyrazine-2,3-dicarboxamide. The condensation of 4,5-diaminopyrimidine and benziF to form 6,7-diphenylpteridine reported in 1906 was the first example of the most versatile general method of pteridine synthesis. 

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