Nitropyridines, synthesis

Kuduk, S.D. DiPardo, R.M. Bock, M.G. Tetrabutylammonium salt induced denitration of nitropyridines synthesis of fluoro-, hydroxy-, and methoxypyridines. Org Lett. 2005, 7 (4),577-579. 

The main reaction of this type has been the reductive cyclization of nitropyridine derivatives carrying an o-amino ester or o-aminocarbonyl substituent. These cyclize in situ via the o-diamino derivative to give pyridopyrazines of known constitution, either for establishment of structure of products obtained in the ambiguous Isay synthesis (see Section 2.15.15.6.1), or in the synthesis of aza analogues of biologically active molecules. 

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

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). ... 

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). 

A similar synthesis starting with l-(2-nitrobenzyl)pyrrol-2-aldehyde used ethanol-ethyl acetate as solvent (62). Indoles are prepared in excellent yield by hydrogenation of o-nitrobenzyl ketones over Pd-on-C (i). Azaindoles are correspondingly prepared from nitropyridines (97). 

In pyrrolopyridine synthesis reactions, nitropyridines are less reactive than the corresponding nitropyridone derivatives due to the decreased aromaticity of the pyridone ring. The pyridone is more attractive for nucleophilic attack in the reaction <2002H(58)301> (see Section 10.06.5.3). 

Having established that the end game of the proposed synthesis of cylindrospermopsin (1) from bromoketone 4 was viable, we turned our attention to the preparation of acetylene 5 from 4-methoxy-3-methylpyridine (7). 4-Methoxy-3-methylpyridine (7) was prepared by modifications of the literature procedure.17,18 3-Methyl-4-nitropyridine A-oxide (27),19 was treated with K2CO3 in methanol at 70 °C to displace the nitro group to... 

Table 8 Synthesis of nitropyridines using ammonium acetate ...

Recent reports of simple nitration methods using or its equivalents, led to the synthesis of nitropyridine... 

The synthesis of 5,7-dimethyl-l//-pyrrolo[2,3-c]pyridine (85) has been carried out starting with 4-chloro-2,6-dimethyl-3-nitropyridine (86) according to Scheme 35 <84H(22)1347>. 

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