Functionalization of 2-Methyl- and 2,7-Dimethyl-1,8-naphthyridine

Article abstract of DOI:10.1021/jo00296a051

A new synthesis of 2,7-dimethyl-1,8-naphthyridine (dmnap) from 2-methyl-1,8-naphthyridine (mnap) upon treatment with 3 equiv of methyllithium is described.Oxidation of dmnap with 8 equiv of N-chlorosuccinimide gave (98percent) 2,7-bis(trichloromethyl)-1,8-naphthyridine (2), while oxidation with 4 equiv gave (97percent) 2,7-bis(dichloromethyl)-1,8-naphthyridine (1).Hydrolysis of 2 phosphoric acid followed by esterification gave the corresponding diester 3 in 80percent overall yield.Reduction of 3 with NaBH(OMe)3 afforded (55percent) diol 4.Similar functionalization of mnap afforded 2-(trichloromethyl)-1,8-naphthyridine (6) in 85-94percent yield along with 6-chloro-2-(trichloromethyl)-1,8-naphthyridine (7).Methanolysis of 6 gave (78percent) 2-(methoxycarbonyl)-1,8-naphthyridine (8), which upon reduction with NaBH(OMe)3 afforded (59percent) the alcohol 9.Treatment of 6 with KOH caused a displacement of the trichloromethyl moiety, generating 1,8-naphthyridin-2-one (10) as the sole product.Similarly, 2 gave 7-(trichloromethyl)-1,8-naphthyridin-2-one (11) under mild conditions or 7-(ethoxycarbonyl)-1,8-naphthyridin-2-one (12) when refluxed.