On the reaction of 2-, 3- and 4-bromo(chloro)-1,8-naphthyridine with potassium amide in liquid ammonia

Evidence has been presented for the occurrence of 3,4-didehydro-1,8-naphthyridine in the reaction of 3-bromo(chloro)- and 4-bromo(chloro)-1,8-naphthyridine with potassium amide in liquid ammonia. The addition ratio of the amide ion (ammonia) to C(3) and C(4) in the didehydro bond was found to be 43/57, which is nearly identical with that found in 3,4-didehydroquinoline, 3,4-didehydro-1,7-naphthyridine and 3,4-didehydro-1,6-naphthyridine. It was calculated that 39% of the 4-amino compound, obtained from the 4-bromo-1,8-naphthyridine is formed by an SN(AE) process. In the reaction of 3-chloro-1,8-naphthyridine with potassium amide, besides the 3-amino and 4-amino compounds, 2-amino-3-ethynylpyridine and 3-ethynyl-2-(formylamino)pyridine were obtained, indicating a fission of the bond between C(2) and C(3). The last mentioned compound is also formed in the reaction of 4-chloro-1,8-naphthyridine. 1H-NMR spectroscopy has shown that 3-bromo(chloro)-1,8-naphthyridine forms with the amide ion a σ-adduct at C(2); this adduct formation preceded the formation of the didehydro compound. 2-Bromo(chloro)-1,8-naphthyridine gave exclusively 2-amino-1,8-naphthyridine. Conclusive evidence was obtained that part of the 2-amino compound was formed by a tele-substitution SN(AE)tele involving the 7-amino-2-chloro(bromo)-7,8-dihydro-1,8-naphthyridine (27% in the case of the 2-bromo compound, 8% in the case of the 2-chloro compound).