Nitro-1,8-naphthyridines reduction

Catalytic hydrogenation (Pd/C) of 2-chloro-3-nitro-l,5-naphthyridine (125, R = Cl) in methanolic solution afforded 3-amino-l,5-naphthyridine (126, R = H, 74%) isolated in the form of its trihydrochloride (40MI1). Similar Pd/C hydrogenation of 2-ethoxy-3-nitro-l,5-naphthyridine (125, R = OEt) gave 3-amino-2-ethoxy-l,5-naphthyridine (126, R = OEt, 47%) (80RTC83). Reduction with tin(II) chloride in hydrochloric acid also leads to 126, (R = OEt, 73%) (63RTC997). 

Tin(II) chloride reduction of both 4-chloro-3-nitro-l,8-naphthyridine (129, R = Cl) (79PJC1665) and 3-nitro-l,8-naphthyridine (129, R = H) (76S691) gave in 30-35% yield 3-amino-l,8-naphthyridine (130, R = H) reduction of the 4-amino-3-nitro compound (129, R = NH2) yielded 3,4-diamino-l,8-naphthyridine (130, R = NH2,37%) (79PJC1665). 

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). 

Catalytic reduction of 3-nitro-7-phenyl-l,8-naphthyridin-2(lH)-one (136) with palladium on carbon in 2-ethoxyethanol gave the l,2-di(l,8-... 

Reduction of 8-nitro-5-(/3,/3,/3-trifluoroethoxy)-l,6-naphthyridine (141) afforded the corresponding 8-amino compound (142, 45%) (81JHC941). 

The reductive cyclization of ethyl (2-methoxy-5-nitro-4-pyridyl)pyruvates (187) with H2/Pd followed by treatment of the intermediates (188) with toluenesulfonyl chloride gave the 6-methoxy-l,7-naphthyridin-2-ones (189) (65JA3530, 73JOC1824). 

The one-pot Stille cross-coupling reaction of compound 256 produced all four isomeric thieno[3,2-c]naphthyridines (1994JHC11). The stepwise formation of the C(7)-C(7a) and C(4)-N(5) bonds of the thieno[3,2-c]pyridine system can be considered as a modification of the above-described approaches. For example, aldehyde 256 reacts with arene 265 to give 266 reduction of its nitro group is accompanied by cyclization to form thieno[3,2-c]isoquinoline A-oxide (267) (1990JHC1127). 

The halogenolysis of a nitro-1,5-naphthyridine (using phosphorus pentachloride) has been recorded in Section 3.1.2. The reduction of nitro-1,5-naphthyridines to... 

Most nitro-1,6-naphthyridines have been used for reduction to 1,6-naphthyridi-namines. A comprehensive review of all nitronaphthyridines appeared in 2000.1273 It includes information on those within the 1,6-series. The mass spectra of nitro derivatives in the 1,5-, 1,6-, and 1,8-naphthyridines have been reviewed.492... 

Note The only reported reaction of nitro-1,7-naphthyridines appears to be their reduction to the corresponding naphthyridinamines. 

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. 

Although nitro groups have a marked effect on the reactivity of other substituents on 1,8-naphthyridine,1273 the only reported reaction of the nitro group itself is reduction to an amino group, as illustrated by the following examples. 

The reaction sequence involves refluxing the appropriate 4-hydroxy-naphthyridine in concentrated nitric acid, followed by reduction of the nitro compound over Raney nickel at room temperature and... 

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]. 

---