1.8- Naphthyridine 1-oxide, nitration

Several approaches to the synthesis of nitronaphthyridines and their derivatives are reported. Very common ones are those in which the construction of the nitronaphthyridine system was achieved by using nitro synthons (see Section II,A) or by nitration of the naphthyridine ring, although a successful nitration requires the presence of electron-donating substituents (see Section II,B). Furthermore, the oxidation of the amino group in aminonaphthyridines... 

Nitration, suggested to involve nitrosation/oxidation, occurs during diazotization of some substituted 2-amino-1,8-naphthyridine derivatives (15).41 The selectivity of this process was contrasted with that of the nitronium ion reaction. 

For 2,6-naphthyridine (184) and 2,7-naphthyridine (185), the C-1 o-adducts are both kinetically and thermodynamically stable (70JHC419 81JHC1349). At room temperature, 184 was aminated with potassium amide and potassium nitrate in liquid ammonia in 54% yield, but the yield was only 18% from low-temperature amination with potassium amide and potassium permanganate in liquid ammonia (Scheme 69). Similarly, permanganate oxidation afforded only 8% l-amino-2,7-naphthyridine (81JHC1349). 

---