Cyclization of 2-Dicyanomethylene-1,2-dihydropyridine-3-carbonitriles with Hydrogen Halides: A Re-examination on the Regioselectivity

Abstract

The cyclization of the title compounds (Sac) with HCI and HBr has been re-examined.In all cases 5-amino-7-halo-substituted 1.6naphthyridines (Ila-c and 12a-c) were formed independently of the thermal level and the hydrogen halide employed.The structures of lla-c and 12ac were unequivocally established by reaction with hydrazine which afforded the corresponding pyrazolol3.4-h][l,6]naphthyridines(14a-c).The structure of the methoxy derivatives (15a,c and 16a,c) was assigned by two-d~mensional nmr studies.During the past years the research of our group has been mainly focused on the cyclization of 1,5dinitriles in the presence of anhydrous hydrogen halldes as a method for the construction of fused heterocyclic rings.lAs a part of this study we have developed a method for the synthesis of 1,2,3,4tetrahydro-l,6-naphthyndines starting from a$-unsaturated e ~t e r s .~ Thus, the treatment of the obtained pyridones (1) with malononitrile (2) yielded the corresponding substitution products (3) which undelwent cyclization in acid medium (HCI or HBr in dioxanelbenzene) to afford the 7-amino-5-halo-8cyano-l.2,3,4-tetrahydro-l,6-naphthyridin-2-ones (4) (X = CI, Br)