4- Amino-3-nitro-1 -naphthyridines, formation

Subjecting 8-chloro-5-iiitro-l,7-iiaphthyridiiie (97) to reduction with tin(II) chloride leads, besides loss of the chloro atom and reduction of the nitro group, i.e., formation of 5-amino-l,7-naphthyridine (131, 22%), to the formation of small amounts of 5-amino-6,8-dichloro- (132, 1.5%) and 5-amino-6-(or 8-)chloro-l,7-naphthyridine (133, 2.5%) (88PJC305). 

It was reported that the Niementowski synthesis of 4-hydroxy-3-nitro-7-phenyl-l,8-naphthyridin-2(lH)-one (25) from ethyl 2-amino-6-phenylni-cotinate (23) and ethyl nitroacetate (24) in the presence of sodium was unsuccessful, producing only traces of (25), while condensation of ethyl 2-amino-6-phenylnicotinate (23) with the less reactive ethyl acetate resulted in the formation of 4-hydroxy-7-phenyl-l,8-naphthyridin-2(lH)-one in good yield [66JCS(C)315], It seems that the more reactive nitroacetate tends to precipitate rapidly from the reaction mixture as its sodio derivative, which explains the low yield of (25). 

Amino-l,8-naphthyridin-7(8H)-one (61a) and their 3-nitro and 6-nitro derivatives (61b) and (61c) respectively can be nitrated successfully. The nitro substituent enters preferentially at position 6, i.e., formation of 62a from 61a when position 6 is already occupied by a nitro group, the second nitro group is introduced at position 3, i.e., formation of 62b from 61c (69GCI823). It has been mentioned that diazotation of 61 (R=Ph) with sodium nitrite/sulfuric acid also gives the 3-nitro derivative [97JHC1501]. This reaction proceeds via nitrozation, in which the NO+ is the attacking electrophile. 

A similar reaction is found in the formation of 5-amino-l-cyano-2,4-dimethyl-3.106-dihydrobenzo[c][2,7]naphthyridine by reduction of 3,5-dicyano-2,6-dimethyl-4-(2-nitro-phenyl)-l,4-dihydropyridine [87] and tetrahydroquino[2,l-c]benzodiazepines from 2-cyano-l-(2-nitrobenzyl)-l,2,3,4-tetrahydroquinoline [88], When the hydroxylamino group has a choice between a nitrile or an ester group, as in 3-ethoxycarbonyl-5-cyano-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine, it condenses with the nitrile in acidic solution and with the ester in basic media [89]. 

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