Substituted 2-amino-4-nitropyridines

The product is 2-amino-5-nitropyridine because substitution occurs preferentially at the sterically less hindered position para to NH,. The conditions are milder than those for nitration of pyridine, because NH is activating. 

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... 

A variety of 3-substituted 8-nitro-[l,2,4]triazolo[4,3-a]pyridines (70JHC1019) have been prepared via a number of the aforementioned ring closure methods with 2-hydrazino-3-nitropyridine. These products readily undergo rearrangement to the isomeric [1,5-fl] series as described elsewhere in this chapter. Reduction of the 8-nitro substituent of several of these derivatives resulted in the corresponding 8-amino products that offer the potential starting point for other 3,8-disubstituted systems of this type. 

Vicarious nucleophilic substitution (3.3.3) permits the introduction of amino groups para (or ortho if para blocked) to nitro groups by reaction with methoxyamine or 1-amino-l,2,4-triazole. In contrast, VNS substitution of 3-nitropyridine with benzyl chloroacetate proceeds at C-4. °... 

As in benzene chemistry, electron-releasing amino groups facilitate electrophilic substitution, so that, for example, 2-aminopyridine undergoes 5-bromination in acetic acid even at room temperature this product can then be nitrated, at room temperature, forming 2-amino-5-bromo-3-nitropyridine. Bromina-tion of all three amino-pyridines is best achieved with iV-bromosuccinimide at room temperature, products being 2-amino-5-bromo-, 3-amino-2-bromo- and 4-amino-3-bromopyridines. Similarly, chlorination of 3-amino-pyridines affords 3-amino-2-chloro-pyridines. Nitration of amino-pyridines in acid solution is also relatively easy, with selective attack of 2- and 4-isomers at P-positions. A mechanistic study of dialkylamino-pyridines showed nitration to involve attack on the salts. ... 

As in benzene chemistry, electron-releasing groups facilitate electrophilic substitution, so that, for example, 2-aminopyridine undergoes 5-bromination in acetic acid even at room temperature this product can then can be nitrated, at room temperature, forming 2-amino-5-bromo-3-nitropyridine. Chlorination of 3-ami-... 

If 2- and 4-aminopyridines are diazotized in dilute mineral acids, diazonium salts are formed however, the diazonium ions are not stable and they hydrolyze rapidly to the corresponding pyridones. " For example, the diazotization of 2-amino-4-nitropyridine in sulfuric acid yields 85% of 4-nitro-2-pyridone. Diazonium salts of 2-substituted-4-aminopyridines with electron-withdrawing substituents such as COOH, CONH2 and CN are particularly unstable. ... 

Catalytic reductions of substituted pyridinecarboxylic acids continue to play an important role in some syntheses of pyridoxol. Thus 4-carbethoxy-6-chloro-5-cyano-2-methyl-3-nitropyridine (X-132) is reduced over Raney Nickel in water to 3-amino-5-aminomethyl-4-carboxy-2-methylpyridine-4,5-lactam (X-133). - ... 

The reaction of 5-nitropyrimidine with amidines to afford 2-substituted 5-nitropyrimidines and 2-amino-5-nitropyridines and a new synthesis of 2-nitroimidazoles have been reported. ... 

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