3- Nitropyridine, amination

Amine oxides, prepared to protect tertiary amines during methylation and to prevent their protonation in diazotized aminopyridines, can be cleaved by reduction (e.g., SO2/H2O, 1 h, 22°, 63% yield H2/Pd-C, AcOH, AC2O, 7 h, 91% yield Zn/HCl, 30% yield). Photolytic reduction of an aromatic amine oxide has been reported [i.e., 4-nitropyridine A-oxide, 300 nm, (MeO)3PO/CH2Cl2, 15 min, 85-95% yieldl. ... 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

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... 

N-Amination of amines by hydroxyl-amine-O-sulfonic add, 43, 1 p-Aminoacetanilide, oxidation to 4,4 -diaminoazobenzene, 40, 18 2-Amino-5-bromo-3-nitropyridine, 44,... 

The kinetics of the reactions of 2-fluoro-3-cyano-5-nitropyridine with various amine nucleophiles have also been studied211. These are complicated by the occurrence of base catalysis. 

Nitropyridine yields a mixture of 2-, 4- and 6-amino-3-nitropyridines by this method142. An amino group is introduced into the 2-position of l,n-dinitronaphthalenes (.n = 3-8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylarnino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145. 

In conclusion, the amination of 2-chloro-5-nitropyridine mainly occcurs according to the Sn(ANRORC) mechanism (about 75%) and to a smaller degree (about 25%) according to the Sn(AE) process. 

The reductive aminocarbonylation of nitrobenzenes and nitropyridines is catalyzed by SeCO, generated in situ from Se02 and CO, to form the corresponding isocyanates, which are trapped by amines to afford symmetrical and... 

Nitropyridines containing an adjacent bromomethyl substituent react with aromatic primary amines to give pyrazolo[3,4-c]- and -[4,3-6]pyridines. The intermediate secondary amines 98b undergo further reaction at elevated temperatures to afford arylamino derivatives 99 in good yield.108 A mechanism has been proposed for the analogous formation of pyrazolo[4,3-h]-pyridines (Section II,G,1).109... 

Most of the work with these compounds employs voltammetry. The isomeric nitropyridines (73) are reduced by either a reversible two-electron or an irreversible four-electron process (Scheme 22).111 The four-electron product, the hydroxylamine, can be further reduced to the amine. The (V-oxide of 4-(73) was reduced to the aminopyridine (74) in good yield (Scheme 23).112 At... 

As shown in the previous section, N-alkyl nitroanilines 23 are obtained in the reaction of pyridone 1 with ketones 22 in the presence of amines. In this case, amines are introduced as the dialkylamino substituents. On the contrary, different reactivity is observed when ammonia is used instead of amines. The TCRT reaction proceeds to afford 2,3-dialkyl-5-nitropyridines 24 upon treatment of pyridone 1 with ketones 22 in the presence of ammonia (Table 2) [42,43]. The C4 - C5 - C6 unit is derived from pyridone 1, the C2 - C3 unit is derived from ketone, and the ring nitrogen (Nl) is from ammonia, namely the new ring consists of three components. As electrophilic nitration of pyridines is quite difficult, the present TCRT will be an alternative method for preparation of nitropyridine derivatives. 

Amination of 3-nitropyridine with potassium permanganate in liquid ammonia, or an aliphatic amine, affords the 2-amino-pyridine 157 (Equation 83) <1999JPR75>. The nitropyridine 158 is aminated at C-6 with O-methylhy-droxylamine in the presence of ZnCl2 to give 159 in high yield (Equation 84) <1998CC1519>. 

The nitropyridines can be reduced to the corresponding aminopyridine and several new methods have been developed to achieve this transformation. 3-Nitropyridine is reduced in excellent yield by the mixed borohydride prepared from 1 equiv of ZrCU and 4 equiv of NaBFLi in THF under reflux <2000SL683>. 3-Nitropyridines may be reduced to the aminopyridine using sodium hydrosulfite in THF/H20 at room temperature <2005JME5104>. 2-Nitropyridine can be reduced to the amine in near quantitative yield by transfer hydrogenation in the presence of 10% Pd/C and recyclable polymer-supported formate, prepared from aminomethylpolystyrene resin and ammonium formate <2005SC223> (Equation 64). The resin is easily recovered by filtration and may be used up to 10 times. 

Diaminopyridine has been prepared by reduction of 2-amino-3-nitropyridine with iron and aqueous acidified ethanol,3 tin and hydrochloric acid,6 or stannous chloride and hydrochloric acid,6 by catalytic reduction of 3-amino-2-nitropyridine,nitro-pyridine,8 or 2-amino-5-bromo-3-nitropyridine 4 with sodium hydroxide solution and an aluminum nickel alloy, and by catalytic reduction of 2-amino-5-bromo-3-nitropyridine.4 Amination of... 

Site specificity was found to be considerably higher in oxidative amino-dehydrogenation reactions with derivatives of 3-nitropyridine. 2-R-3-nitropyridine (R = C1, OMe) when treated with liquid ammonia and permanganate gives a reasonable yield of 6-amino-2-R-3-nitropyridine (R = C1, OMe) 6-R-3-nitropyridine yields 2-amino-6-R-3-nitropyridine (R = C1, OMe) (Scheme 4) (91LAC875). The corresponding 4-amino compounds are only obtained in small amounts. A similar observation was made on the low temperature oxidative amination of 2-amino-5-R-3-nitropyridines (R = H, Cl, Br). 

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... 

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