Self-condensation of a- Primary Amino Carbonyl Compounds

SELF-CONDENSATION OF a -(PRIMARY AMINO) CARBONYL COMPOUNDS 

The most general method for the synthesis of 2,5-disubstituted and 23.5,6-tetrasubstituted pyrazines (3) depends on the self-condensation of a-(primary amino) carbonyl compounds (1) to form dihydropyrazines, for example, (2), which are subsequently oxidized to the pyrazines as shown in the transformation of (1) to (3). 

Oxidation of the dihydropyrazines to pyrazines occurs easily with mild oxidizing agents such as air hydrogen peroxide cupric, ferric, or mercuric ions or with bromine water, bromine in acetic acid, or aqueous nitric acid. The a-(primary amino) carbonyl compounds required for the synthesis of pyrazines may be prepared by a large variety of synthetic methods. The products are usually stable as their salts, for example, hydrochlorides, but the free bases show a strong tendency to undergo self-condensation to the pyrazine and for this reason the amino carbonyl compounds are rarely isolated. 

In the following survey, the literature preparations of some pyrazines (and also dihydro derivatives) from preformed a-amino carbonyl compounds (irrespective 

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Self-condensation of a-(Primary Amino) Carbonyl Compounds... 

Self-condensation of a-(Primary Amino) Carbonyl Compounds M. 1 2-Dicarbony I Compounds with a -Amino Acids... 

Dihydropyrazines may be prepared by the self-condensation of o -(primary amino)carbonyl compounds and some of these syntheses have been described in Sections II.lA (169, 172, 178, 186, 190), Il.lJ (294-298), and II.IL (306). The conversion of a-amino acids through piperazine-2,5-diones (2,5-dihydroxy-3,6-dihydropyrazines) to pyrazines has been described in Section II.IN (93, 95, 101, 282, 312-314a) and Section II.6 (314, 314a) and ring transformations to 2,5-dihydropyrazines in Section II.9 (302, 505a, cf. 1541). 3-Phenylazirine dimerizes on standing to 2,5-diphenyl-3,6-dihydropyrazine (1577). 

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