Ring transformations and <i>tele</i>‐aminations in the reaction of 2‐halogeno‐ and 8‐halogeno‐1,7‐naphthyridines by potassium amide in liquid ammonia

Abstract

Abstract 2‐X‐1,7‐Naphthyridines (X = Br, Cl) give a variety of products on treatment with potassium amide, namely 2‐amino‐1,7‐naphthyridine [formed by an S N (AE) process], 4‐amino‐ and 8‐amino‐1,7‐naphthyridine (obtained by a tele ‐amination[5 N (AE) t ]) and a ring transformed product, 2‐methyl‐4‐amino‐1,3,7‐triazanaphthalene. By 1 H‐NMR spectroscopy of a solution of 2‐chloro‐1,7‐naphthyridine and its 8‐deutero‐ and 6,8‐dideutero derivatives in KNH 2 /NH 3 good evidence has been obtained that at −40° 2‐chloro‐1,7‐naphthyridine is completely converted into a mixture of three 1 : 1 adducts formed by addition of the amide ion at C(8), C(6) and C(4). 8‐X‐1,7‐Naphthyridines (X = Cl, Br) give as sole reaction products 8‐amino‐1,7‐naphthyridine [5 N (AE)] and 2‐amino‐1,7‐naphthyridine [5 N (AE) t ]. By 1 H‐NMR spectroscopy strong evidence has been obtained that in 8‐X‐1,7‐naphthyridines the adduct formation occurs exclusively at C(2). The mechanism of the tele ‐amination is discussed.