Nitropyridines

Much of the reactivity shown by the ring atoms and substituents of pyrimidine is akin to that of the corresponding parts of 1,3-dinitrobenzene and 3-nitropyridine. This arises from the quantitatively similar electron-withdrawing effects of doubly-bound ring nitrogen atoms and of nitro groups in reducing sharply the aromaticity of the cyclic system. 

Oxadiazolo[3,4-c]pyridine, 3(l)-oxo-synthesis from 4-azido-3-nitropyridines, 6, 730... 

Monochloroacetamides are cleaved (by assisted removal ) by reagents that contain two nucleophilic groups (e.g., o-phenylenediamine, thiourea, 1-piperi-dinethiocarboxamide, 3-nitropyridine-2-thione, 2-aminothiophenol ) ... 

Chloro-3-nitropyridine [5470-18-8] M 158.5, m 100-103°, 101-102°, 103-104° (sublimes), pK -2.6. Forms needles from H2O. Purified by continuous sublimation over a period of 2 weeks at 50-60°/0.1mm [Barlin J Chem Soc 2150 1964]. The N-oxide has m 99-100°(from CH2Cl2-Et20). [Taylor and Driscoll J Org Chem 25 1716 I960-, Ochiai and Kaneko Chem Pharm Bull Jpn 8 28 I960.]... 

A further stepwise synthesis of this type, in which 2-bromomethyl-3-nitropyridine (105) was the starting material, is the only method so far reported which directly produces pyrido[3,2-d]pyrimidines without nuclear oxygen substituents (106). ... 

Halopyridines undergo self-quaternization on standing while the less reactive 2-halo isomers do not. However, more is involved here than the relative reactivity at the ring-positions. The reaction rate will depend on the relative riucleophilicity of the attack-ing pyridine-nitrogens (4-chloropyridine is more basic) and on the much lower steric hindrance at the 4-position. Related to this self-quatemization are the reactions of pyridine and picolines as nucleophiles with 4-chloro- and 2-chloro-3-nitropyridines. The 4-isomer (289) is. again the more reactive by 10-30-fold (Table VII, p. 276). 

Tile same methodology as mentioned for the preparation of (9) was applied for the synthesis of 8-nitro-l,6-naphthyridines. Heating diethyl N- 3-nitropyridin-4-yl)aminomethylenemalonate (12) in diphenyl ether yields ethyl 8-nitro-l,6-naphthyridin-4(lH)-one 3-carboxylate (13) (63JCS4237, 30%) and acid treatment of 4-( y, y-diethoxypropylamino)-5-nitro-2-(/3,/3 -trifluoroethoxy)-pyridine (14) gives in a similar way 8-nitro-5-(/3, /3-triflu-oroethoxy)-l,2-dihydro-l,6-naphthyridine (15, 76%). Subsequent oxidation with chloranil, acid hydrolysis, and methylation with methyl iodide gives 8-nitro-6-methyl-l,6-naphthyridin-5(6H)-one (16,63%) (81JHC941). 

The reaction of 4-methoxy-3-nitropyridines 129 with guanidine under similar conditions results in 3-aminopyrido[3,4-e]-l,2,4-triazine 1-oxides 130 (76MI). 

Treatment of 2-amino-3-hydroxypyridine (185) with 2-chloro-3-nitropyridine (193) easily provided intermediate 194. Attempts to cyclize 194 with potassium hydroxide in aqueous ethanolic solutions failed, probably due to strong H-bonding. Similarly as with phenoxazines, the cyclization smoothly proceeded in DMSO to give low yield (31%) of 1,9-diazaphenoxazine (195) (Scheme 30) (74CC878, 76JHC107, 77H391). 

Reaction of disodium salt of pyridine-2,3-dithiol (385) with l-chloro-2-nitrobenzene provided in 45% yield the corresponding aza analog 386 (82JHC1441). Similar treatment with 2-chloro-3-nitropyridine (193) provided... 

Direct aminadon of 3-nitropyridines v/ith methoxyamine in the presence of zinc chloride under basic conthdons proceeds to give 3-amino amino-3-nitropyridines fEq 9 51 ... 

Reaction of nitroketene animals with enaminoketones provides a route for the derivatives of 2-amino-3-nitropyridines (Eq. 10.87).147... 

Compound 248 treated with (EtOhP in refluxing xylene provides an 89% yield of 19 (Equation 37) <2005AGE7089>. Similarly, [l,2,3]triazolo[4,5- /]pyridazine 249 provided a 68% yield of the corresponding mesomeric betaine 250 (Equation 38). However, reductive cyclizations of the analogous 3-(2-nitrophenyl)-377-[l,2,3]triazolo[4,5-//Jpyrimidine, 3-(3-nitropyridin-2-yl)-3//-[l,2,3]triazolo[4,5-. 

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