2-Amino-3-nitropyridines, formation

All these amination reactions show exclusive SNH substitution. There is hardly any indication for the formation of 3-nitropyridines, in which the chloro or methoxy group was replaced by an amino group, even when these leaving groups are present at the reactive a-position of the pyridine ring. It seems to be a characteristic feature of the oxidative amination... 

Nitration of pyridines via rearrangement of nitramines has been studied. 4-Amino-3-bromopyridine forms, with nitric acid, the nitramine 9.67 in 85% yield 9.67 rearranges in sulfuric acid to 4-amino-3-bromo-5-nitro-pyridine (9.68) in 97% yield (62RC967). The rearrangement of 2-nitrami-no-4-nitropyridine (9.69) to 2-amino-3,4-dinitropyridine is accompanied by the formation of 4-nitro-2-pyridone (64T81), subsequently shown to arise via nitrosation (79T2895). 

Nitro compounds are easily reduced, catalytically or chemically, to amino compounds. Incomplete reduction can lead to a hydroxylamino derivative or to binuclear azo, azoxy, and hydrazo compouds, e.g., 789 790, 791. Examples include reduction of 3-nitropyridines using aqueous sodium hydrosulfite at room temperature <2005JME5104> and of 2-nitropyridine by transfer hydrogenation in the presence of 10% Pd/G and recyclable polymer-supported formate, prepared from aminomethylpolystyrene resin and ammonium formate <2005SC223>. A nitro group can be reduced in the presence of an A-oxidc group, e.g., 784 782. 

Halo-4-nitropyridines and their A -oxides react at the C-nitro group when treated with bases or alkoxides to give XII-357 or MI-358 (X = Cl, Br, I). However, 3-fluoro-4-nitropyTidine and its 1-oxide form 4-nitro-3-pyridinols and 4-nitro-3-alkoxypyridines, respectivelyThe 3-alkoxy-4-nitropyridine-l-oxides have been converted to 3,4-dialkoxypyridine-l-oxides. Because of this marked reactivity of the 3-fluoro substituent, these studies have been extended to 3-fluoro-5-methyl-4-nitropyridine-l-oxide, 3-fluoro-2-methyl-4-nitropyri-dine-l-oxide, and 2,6-dimethyl-3-fluoro-4-nitropyridine-l-oxide. Several of these fluoronitropyridines have been extensively studied as potential reagents for formation of amino acid derivatives. 2-Fluoro-3,5-dinitropyridine, a typical example, is hydrolyzed by hot water and reacts with hot alcohols to form 2-alkoxy-3,5-dinitropyridines and reacts with amino acids and their derivatives to give well-defined products. The reactions of a number of fluoronitropyridines and their N-oxides have been summarized by Talik and Talik and the relative reactivities toward simple nucleophiles have been observed, as shown on p. 689. 

The directing and activating power of the amino group shows clearly in 2-dimethylaminopyridine, where nitramine formation is impossible. Nitration in mixed acids gives about 90 per cent of 2-dimethylamino-5- and 10 per cent of 2-dimethylamino-3-nitropyridine. 3,5-Dinitration is readily... 

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