Glyoxal with 2,3-diaminopyridine

Diaminopyridine has been condensed with glyoxal, benzil, - diacetyl,and the pyridils 4. ° Ethyl oxalate yields the 2,3-dioxo compound. The conditions employed for these condensations can be critical. Thus glyoxal in neutral solution yields an unidentified, insoluble, infusible solid, whereas in the presence of acetic acid the reaction readily provides the parent heterocycle.The preferred method makes use of glyoxal sodium bisulfite. Many symmetrical dicarbonyl compounds have been condensed with a variety of 2,3-diaminopyridines substituted in the pyridine ring by bromo, ° chloro, methyl, " or combinations of these substituents. ... 

The condensation of 3,4-diaminopyridine with glyoxal hydrate in alcohol gives a 50% yield of the parent heterocycle m.p. 97°. This method is more convenient than the use of the bisulfite compound in aqueous acetic acid, which provides only a low yield of the required compound. Benzil and diacetyl and l,4-dibromobutane-2,3-dione provide the expected 2,3-disubstituted products 4 in good yields. Dimethyl oxalate reacts with 3,4-diaminopyridine in refluxing M hydrochloric acid to give the open-chain compound 5." This may be cyclized to the dioxo compound 6 by heating at 230°. 

Pyrido[3,4-b]pyrazines substituted in the pyridine ring are available from the reactions of suitably substituted 3,4-diaminopyridines and the appropriate dicarbonyl compounds. No problems are encountered with diamines substituted with halogen or hydroxy groups. Similarly the pyridones 7 provide the oxo compounds 8 and 9. In contrast, 3,4-diamino-5-nitropyridine did not react with glyoxal, and only a low yield of 2,3-dimethyl-8-nitropyrido[3,4-b]pyrazine could be obtained using diacetyl. ... 

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