3- Nitro-1,8-naphthyridines, amination

In all 3-nitronaphthyridines with an unsubstituted C-2 position (84a, 84f, and 84j) no traces of the corresponding 2-amino-3-nitro-l,X-naphthyridines (X = 5, 6, and 8) were obtained. As already mentioned, in the aminations of 2-R-3-nitronaphthyridines where R is a chloro or ethoxy group, no amino-dechlorination or amino-deethoxylation was observed. 

The compounds 87a and 87b are aminated at position 4, yielding the 4-amino compound (88a, 40%) and the 2,4-diamino compound (88b, 11%) respectively the 2-ethoxy compound (87c), however, undergoes amination at position 4 as well at position 5, giving a mixture of the 4-amino compound (88c, 20%) and the 5-amino compound (89a, 14%).Tlie 2-chloro compound (87d) yields a highly complex reaction mixture from which the 5-amino compound (89b), the 2,4-diamino derivative (88b), and 2,5-diamino-l,8-naphthyridine (89c) could be isolated. l-Ethyl-3-nitro-l,8-naphthyridin-2(lH)-one (90a) and 3,6-dinitro-l-ethyl-l,8-naphthyridin-2(lH)-one (90b) were aminated exclusively in the 4-position to give compounds 91a (62%) and 91b (45%), respectively (93LA471). 

Treatment of ethyl 4-chloro-7-diethylamino-6-nitro-l,8-naphthyridine 3-carboxylate (104) with the amines RH [R = N(CH2)s NH(CH2)N(C2Hs)2] gives the corresponding 4-amino derivatives [105, R = N(CH2)s, 74% and 105, R = NH(CH2)N(C2Hs)2, 50%]. With diethylamine the 7-chloro-6-nitro derivative of nalidixic acid (i.e., 106) yields the 7-diethylamino compound 107 (62%) (79YZ155). 

Also, the observed highly regioselective course in the SnFI substitutions in 2-R-3-nitro-l, 8-naphthyridines (R = FI, OFI, Cl, NFI2, OEt) with the anion of chloromethyl phenyl sulfone was explained by MNDO quantum-chemical calculations showing that, like in the aminations, the interaction of FIOMO of the nucleophile with LUMO of the nitronaphthyridines controls the regioselectivity (91JFIC1075). 

Die selekdve Redukdon einer Nitro-Gruppe zum Amin gelingt beim 2-Chlor-3-nitro-1,8-naphthyridin mit Zinn(II)-chlorid in salzsaurer Losung1 ... 

Nitro functions attached to 5,6,7,8-tetrahydro[l,6]naphthyridines may easily be reduced to the corresponding amine employing hydrogen with palladium-on-carbon as the catalyst <2001SC787>. 

Studies have been made of the covalent amination of 3-nitro-l,X-naph-thyridines (X = 5,6, and 8).27 35 In contrast to the parent systems and their halogen and methyl derivatives, 3-nitronaphthyridines undergo covalent amination with weak nucleophilic liquid ammonia at — 45 C. The electrophilic character of the naphthyridine system is enhanced by the presence of the nitro group. 3-Nitro-l,8-naphthyridine (41a) undergoes addition at... 

Other work has been carried out concerning the amination of 3-nitro-1,5-naphthyridine (46a) with liquid ammonia containing potassium permanganate.27 The 4-amino-3-nitro- 1,5-naphthyridine (50) is obtained in 50% yield. Its precursor, the covalent rr-adduct (47a), has been detected by NMR spectroscopy (see Section II,B,3). 

Successful aminations were reported on treatment of a solution of 3-nitro-2-X-l,8-naphthyridines (41) with potassium permanganate, the 4-amino-3-nitro-2-X-l,8-naphthyridines (59) being obtained in 50-80% yields.35 The precursors of 59, i.e., [Pg.120]

Nitro-1,6-naphthyridine (11, R = H) gave 3-nitro-l,6-naphthyridin-4-amine (11, R = NH2) (KMn04, liq NH3, 55% no other details).514... 

Note These amino compounds have been made by primary synthesis (see Chapter 15), by aminolysis of halogeno-1,7-naphthyridines (see Section 17.2), by reduction of nitro-1,7-naphthyridines, (see Section 20.1), or by direct amination as illustrated in Section 16.1.3 and by further examples here. 

Nitro-l,8-naphthyridine (12, R = H) gave 3-nitro-l,8-naphthyridin-4-amine (13, R = H) (liquid ammonia then KMn04 45%) 1320 3,6-dinitro-... 

In a similar way, 3-nitro-l,8-naphthyridine gave 4-methylamino-3-nitro-l,8-naphthyridine (14, R = H) (neat MeNH2 KMn04 90%) 682 and 3-nitro-l,8-naphthyridin-2-amine gave 4-methylamino-3-nitro-l,8-naphthyridin-2-amine... 

Chloro-l, 5-naphthyridin-4( l//)-one 2-Chloro-3-nitro-1,5-naphthyridin-4-amine... 

Ethoxy-3-nitro-l,5-naphthyridin-4-amine 2-Ethoxy-3-nitro-l,5-naphthyridine... 

Chloro-8-nitro-1,6-naphthyridine 7-Chloro-3-phenyl-1,6-naphthyridin-2-amine... 

Ethoxy-1,6-naphthyridine 2-Ethoxy-3-nitro-l,6-naphthyridin-4-amine 2- Ethoxy-3-nitro- 1,6-naphthyridine Ethyl 5-amino-7-benzylseleno-8-cyano-2-methyl-1,6-naphthyridine-3-carboxylate Ethyl 6-amino-2-methyl-5-oxo-5,... 

Naphthyridin-2(177)-one 6-oxide 3-Nitro-l,6-naphthyridin-2-amine 3-Nitro-l,6-naphthyridin-4-amine... 

Anilino-5-methyl-l,8-naphthyridin-2-amine 2-Anilino-7-methyl-5-phenyl-l,8-naphthyridine 2-Anilino-1,8-naphthyridine 2-Anilino-3-nitro-1,8-naphthyridine 2-Azido-4-chloro-5,7-dimethyl-3-phenyl-l, 8-naphthyridine... 

Chloro-3-nitro-1,8-naphthyridin-4-amine 2-Chloro-3-nitro-1,8-naphthyridine... 

Chloro-3-nitro-7-piperidino-1,8-naphthyridine 2-Chloro-6-nitro-7-piperidino-1,8-naphthyridine 7-Chloro-3-phenyl-1,8-naphthyridin-2-amine 7-Chloro-4-phenyl-1,8-naphthyridin-2-amine 7-Chloro-5-phenyl-1,8-naphthyridin-2-amine 7-Chloro-6-phenyl-1,8-naphthyridin-2-amine 2-Chloro-3-phenyl-1,8-naphthyridine... 

Methylamino-1,8-naphthyridine-3-caibonitrile 2-Methylamino-1,8-naphthyridine-3-caiboxamide Methyl 2-amino-1,8-naphthyridine-3-carboxylate 4-Methylamino-3-nitro-1,8-naphthyridin-2-amine 2-Methylamino-3-nitro-1,8-naphthyridine 4-Methylamino-3-nitro-1,8-naphthyridine 2-[Pg.402]

---