4- Nitropyridine, methylamination

Amination of heterocyclic nitro compounds such as nitroquinolines, nitroisoquinolines, or nitropyridines can be carried out by means of a liquid ammonia-KMn04 system, which has been studied by Wozniak and coworkers (Eq. 9.44). Frontier molecular orbital calculation can predict the reactivity and regioselectivity of this amination.75 In a similar way, nitroquinolines are methylaminated with a liquid methylamine solution of KMn04.76... 

Methylamination of 2-amino-3-nitropyridine gives in good yield 2-amino-6-methylamino-3-nitropyridine, while methylamination of 6-amino-3-nitro-pyridine only gives (in a small yield) 6-amino-2-methylamino-3-nitropyr-idine (Scheme 7). The activating influence of the 3-nitro group on the C-6 para position explains this difference in reactivity. 

Chloro-3-nitropyridine undergoes SNH methylamination at C-6 as well as amino-dechlorination at C-2, 2,6-bis(methylamino)-3-nitropyridine being obtained (Scheme 7). 

H-NMR spectroscopy of a solution of 3-nitropyridine in liquid methylamine shows an upheld shift of 5.33 ppm for H-4, clearly showing... 

Rearrangement of the 2-ethoxycarbonylmcthyl-l,4,6-trimethylpyrimi-dinium salt with alcoholic aqueous methylamine gave the respective 2-mcthylaminopyridine-3-carboxylate (94MI2) (Scheme 39a). Similarly, in alkaline medium, even nonquaternized 2-methyl-5-nitropyrimidine gave 2-amino-5-nitropyridine (94MI2) (Scheme 39A). 

Chloropyridine-l-oxide when heated with 30% aqueous methylamine at 140° for 18 hours gives 4-methylaminopyridine-l-oxide. Several substituted 4-methylaminopyridines are similarly prepared. 2-Propylaminopyridine and 2-phenethylaminopyiidine are obtained by heating 2-bromopyridine with propylamine and phenethylamine, respectively. 2-Bromopyridine also reacts with 1-aminoindane to give 2-(l-indanylamino)pyridine. 2,6-Di-chloropyridine reacts with butylamine to give 2-butylamino-6-chloropyri-dine. 2-Benzylamino-3-nitropyridine and 2-(chlorobenzylamino)-3-nitro-pyridine are readily prepared from 2-chloro-3-nitropyridine with benzyl amine and p-chlorobenzyl amine, respectively. ... 

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