3-Nitropyridine

Here again the question of reactive species in the acidic medium remains open. It must be noted that bromination of 2-amino-5-methyl-pyridine (pK = 7) and 2-amino-5-nitropyridine (pJC = 2.8) in N sulfuric acid takes place on the free base (443). 

Derivatives such as 3-fluoro-4-nitropyridine [13505-01 -6] (396) or the 1-oxide [769-54-0] (397) have been used to characteri2e amino acids and peptides. 5-Eluoro-3-pyridinemethanol [22620-32-2] has been patented as an antihpolytic agent (398). A promising antidepressant, l-(3-fluoro-2-pyridyl)pipera2ine hydrochloride [85386-84-1] is based on 2-chloro-3-fluoropyridine [17282-04-1] (399). 

Pyridine oxide [694-59-7] is converted to 4-nitropyridine oxide in 80—90% yield on heating with concentrated sulfuric acid and filming nitric acid at 100°C (38). 

Much of the reactivity shown by the ring atoms and substituents of pyrimidine is akin to that of the corresponding parts of 1,3-dinitrobenzene and 3-nitropyridine. This arises from the quantitatively similar electron-withdrawing effects of doubly-bound ring nitrogen atoms and of nitro groups in reducing sharply the aromaticity of the cyclic system. 

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... 

Monochloroacetamides are cleaved (by assisted removal ) by reagents that contain two nucleophilic groups (e.g., o-phenylenediamine, thiourea, 1-piperi-dinethiocarboxamide, 3-nitropyridine-2-thione, 2-aminothiophenol ) ... 

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. ... 

Chloro-3-nitropyridine [5470-18-8] M 158.5, m 100-103°, 101-102°, 103-104° (sublimes), pK -2.6. Forms needles from H2O. Purified by continuous sublimation over a period of 2 weeks at 50-60°/0.1mm [Barlin J Chem Soc 2150 1964]. The N-oxide has m 99-100°(from CH2Cl2-Et20). [Taylor and Driscoll J Org Chem 25 1716 I960-, Ochiai and Kaneko Chem Pharm Bull Jpn 8 28 I960.]... 

METHYL-4-NITROPYRIDINE-1-OXIDE (3-Picoline, 4-nitro-, 1-oxide)... 

Methyl-4-nitropyridine-l-oxide has been prepared by the nitration of 3-methylpyridine-l-oxide hydrochloride with a mixture of concentrated sulfuric acid and potassium nitrate. The I)reparation of this compound has been mentioned briefly by Talikowa, but no experimental details have been given. 

Fluorodenitration with potassium fluoride has been applied to mtropyndines and nitrothiazoles 2 Nitropyridine can be converted to 2 fluoropyridme in 55-60% yield [107] (equation 34)... 

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). ... 

A few studies on solvolyses by alcohols and by water are available. The hydrolyses studied include displacement of alkylamino groups from acridine antimalarials and of halogen from other systems. In all cases, these reactions appeared to be first-order in the heterocyclic substrate. By a detailed examination of the acid hydrolysis of 2-halogeno-5-nitropyridine, Reinheimer et al. have shown that the reaction rate varies as the fourth power of the activity of water, providing direct evidence that the only reactive nucleophile is neutral water, as expected. 

The good correlation found between the reactivities of 2-chloro-3-cyano-5-nitropyridine and the polar effects of the substituents on the aniline reagent has enabled Chapman and his co-workers to illustrate the steric requirements of the reagent by including in their studies... 

The relative effects of methanol and ethanol as solvents in the reaction of 2-chloro-5-nitropyridine with aniline can be deduced from recent data by Chapman et and are reported in Table V. These... 

---