4- Nitropyridine-l-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. 

Azathianthrene (382) was prepared in good yield via the corresponding A-oxide 381, obtained by treating 3-chloro-4-nitropyridine-l-oxide (271) with... 

The catalytic effect of tetra-n-butylammonium fluoride in the homogeneous reduction of heterocyclic A-oxides and nitroarenes by hexamethyldisilane in tetra-hydrofuran can occur with EXPLOSIVE violence, but can be controlled by the slow addition of the disilane to the A-oxide (or nitroarene) and tetra-n-butylammonium fluoride to yield the parent heterocycle (>70%) (or azobenzene 84%). In a similar manner, azoxybenzene is converted into azobenzene (95%), and 4-nitropyridine-l-oxide, is reduced to azoxypyridine-l,l -dioxide (78%), with minor amounts of azopyridine-1, l -dioxide and azopyridine-1-oxide [5,6]. 

The visible n n absorption band is shifted hypsochromically by A1 = 53 nm on changing the medium from n-hexane to water. Based on the negative solvatochrom-ism of this aminyloxide radical, a spectroscopic solvent polarity scale, called the scale of Eewis acidity has been proposed [336]. Because of its pronounced negative sol-vatochromism, 4-nitropyridine-l-oxide has been recommended as an empirical indicator of the HBD acidity of solvents [330] cf. Section 7.4. The solvatochromic range of this A-oxide, measured in 48 different solvents, amounts to Av = +2840 cm (A1 = —31 nm) for the solvent change n-hexane water. 

The greater reactivity of pyridine-1-oxide towards nitration as compared to pyridine is noteworthy. It proceeds smoothly in nitrating acid, via the free base and the a-complex 77, yielding 4-nitropyridine-l-oxide 78 (see p 274). Other Sg reactions (sulfonation, halogenation) require drastic conditions. 

The A -oxide function is retained on treatment with nitric and sulfuric acids at somewhat lower temperatures. Thus Talik and Talik prepared 3-chloro-4-nitro-pyridine-1-oxide (84.5%) and 3-iodo-4-nitropyridine-l-oxide (56.4%) with this reagent at steam-bath temperature. 

Johnson investigated the reactivities of 2- and 4 alo- and 2- and 4-nitropyridine-l-oxides toward sodium methoxide and found that the energies of activation were lower for the nitropyridine-l-oxides than for the corresponding halo compounds. 

Talik studied the behavior of 3-chloro-4-nitropyridine-l-oxide with various reagents, and showed that sodium methoxide causes replacement of the nitro group, while amines, on the other hand, effect displacement of the halogen. 

Halo-4-nitropyridine-l-oxides react with two equivalents of sodium methoxide at room temperature to effect replacement of both halogen and nitro groups. One equivalent of sodium methoxide at that temperature, however, causes replacement of the nitro group alone to give 2-chloro-4-methoxypyridine--1-oxide in 84% yield. The use of two equivalents of the base in boiling methanol gives 2,4-dimethoxypyridine-l-oxide. 

Nitropyridine-l-oxide undergoes reduction with phenylhydrazine to give 4-hydroxylaminopyridine-l-oxide in nearly quantitative yield This product is very reactive it undergoes oxidation in aqueous ammonia to form 4,4 -azopyiidine-l,l -dioxide, and with potassium permanganate in acid solution to give 4-nitrosopyridine-l-oxide. 

Hydroxylaminopyridine-l-oxide (IX-7) was obtained from the reaction of hydroxylamine with 7-pyrone. Its structure was proved by hydrogenation to 4-aminopyridine and also by oxidation to 4-nitropyridine-l-oxide."... 

When 2-halo-4-nitropyridine-l-oxides are treated with hydrazine hydrate in ethanol, 4-amino-2-halopyridine-l-oxides result. " The reaction of 4-nitro-pyridine-1-oxide (IX-20, R = H) and of 4-nitro-2-picoline-l-oxide (IX-20, R = CHj) with phenylhydrazine gives 4-hydroxylaminopyridine-l-oxide (IX-21, R = H) and 4-hydroxylamino-2-picoline-l-oxide (DC-21, R= CH3), respectively, rather than the corresponding 4-amino derivatives "" "" (See also Chapter Vlll). 

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 history of the discovery of pyridine and of the development of its structure was outlined in Chapter 1, and its general character as an aromatic compound, as shown in its geometry and stability, was discussed in Chapter 2. The molecular dimensions of three important pyridine derivatives, 2-pyridonei , 2-pyridthionei, and nicotinic acid are indicated in the skeletons (1), (2), and (3). Data are available for pyridine hydrochloride , 1-hydroxypyridinium chloride, 4-nitropyridine l-oxide and /mwj-4,4 -azo-pyridine 1,1 -dioxide. ... 

Bromopyridine l-oxide248, 252, 254 give 4-nitro derivatives, in the second case with some deoxygenation2S2, 3j5-Dibromopyridine 1-oxide produces very high yields of 3,5-dibromo-4-nitropyridine l-oxide s. 

A few examples are known of the replacement by mercaptide groups of the nitro group from 4-nitropyridine l-oxide 07, 987, 994 and also of its replacement by a sulphonic acid group . ... 

---