2-Amino-6-nitro-l,8-naphthyridine

Tlie condensation of nitromalonic aldehyde (26) with 2,6-diaminopyridine (27) in the presence of phosphoric acid, affording 2-amino-6-nitro-l,8-naphthyridine (28,37%) (77TL2087), is another example of a successful application of a nitro aliphatic compound in the synthesis of nitronaphthy-ridines. 

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. 

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). 

Aryl-l,2-dihydro-3-nitro[l,8]naphthyridines have been obtained by the 6jt-thermal electrocyclization of l-(2-arylide-neamino-3-pyridyl)-2-nitroethylenes, obtained in situ from aromatic aldehydes and l-(2-amino-3-pyridyl)-2-nitroethylene in xylene <2002SC747>. 2-Chlorotetrahydro[l,8]naphthyridines have also been obtained from 2,6-dichloropyridines using a free radical xanthate-mediated cyclization <20040L3671>. 

A low-temperature nitration of 2-amino-l,8-naphthyridine (59a) and 2-amino-l,5-naphthyridine (59b) yielded the 2-nitramino-l,8-naphthyridine (60a, 65%) (98MI3) and 2-nitramino-l,5-naphthyridine (60b, 70%) (63RTC988) respectively. Attempts to rearrange (60a) and (60b) to 2-amino-3- (or 6-) nitro-l,8-(or -1,5-) naphthyridines failed. 

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). 

Taking into account the high reactivity of the ehloro atoms in 2-ehloro-3-nitro- (99a, 99d, and 99f), 7-ehloro-3-nitro- (99e and 99g), 2,7-diehloro-3-nitro- (99c), and 2-ehloro-3,6-dinitro-l,8-naphthyridines (99b), a great variety of 2- (or 7-) substituted amino produets [99, = NHCH3, N(CH3)Ph,... 

Ami no-3-nitro-1,8-naphthyridin-2(l //)-one 7-Ami no-6-nitro-1,8-naphthyridin-2(l //)-one 7-Ami no-6-nitro-1,8-naphthyridin-4(l //)-one 7-Ami no-6-nitro-4-oxo-l,4-dihydro-l, 8-naphthyridine-3-carboxylic acid 4-Amino-3-nitro-l-phenyl-l,8-naphthyridin-2(l//)-one... 

For the same reasons as discussed for the 3-nitro-l,8-naphthyridines, addition at C-4 is strongly promoted. If position 4 is occupied, no addition takes place 4-amino-3-nitro-l,6- and -1,5-naphthyridine do not undergo addition at C-2 when subjected to treatment with liquid ammonia. It is interesting that 46a does not undergo covalent hydration in neutral nor in acidic medium. ... 

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