Studies on naphthyridines. An unexpected product in Hantzsch pyridine synthesis

Besides the expected pyridinedicarboxylate (4), triethyl 2,7,8a-trimethyl-1,4,4a,5,8,8a-hexahydro-1,8-naphthyridine-3,4a,6-tricarboxylate (6) was also isolated in the Hantzsch pyridine synthesis starting from ethyl acetoacetate and hexamethylenetetramine in acetic acid. The 1,8-naphthyridine (6) was probably formed in the [4 + 2]cycloaddition of heterodiene (5) and the 1,4-dihydropyridinedicarboxylate (3). The observed regioselectivity was explained in terms of simple Hückel molecular orbital calculations. Diethyl 2,6-dimethylpyridine-3,5-dicarboxylate (4) gave ethyl 2-methyl-5-oxo-5,6-dihydro-1,6-naphthyridine-3-carboxylate (9) in high yield in a one-step reaction with 1,3,5-triazine in the presence of ethanolic sodium ethoxide, or in a two-step procedure with DMF diethyl acetal followed by ring closure with ammonia.