Hydroxypyridines 1-oxides

Molecular orbital calculations have been used to estimate equilibrium constants, although up to the present these attempts have not met with much success. Using calculations of this type, 2- and 4-hydroxypyridine 1-oxide were predicted to be more stable than 1-hydroxypyrid-2- and -4-one by ca. 20 kcal/mole, which corresponds to a ratio of ca. 10 between the forms. It was later shown experimentally that, at least in the series of 4-substituted compounds, there is very little energy difference between the forms and that the ratio between them is about unity. Molecular orbital calculations for... 

Hoffman and Gronowitz - have applied this technique with marked success to the study of hydroxy-, amino-, and mercapto-thiophenes. Similarly, it has been shown that pyrid-4-one exists predominantly as such and that 4-hydroxypyridine 1-oxide is in equilibrium with comparable amounts of l-hydroxypyrid-4-one. - The method has also been used to investigate the structure of ions (see Section II,C, of article II by Katritzky and Lagowski). 

The pKa values of 4-hydroxypyridine 1-oxide (51 52) and the methylated derivatives of both tautomeric forms indicate that the parent compound exists as a mixture containing comparable amounts of both forms in aqueous solution. Nuclear magnetic resonance spectra support this conclusion, but the ultraviolet spectra of the tautomeric compound and both alkylated derivatives are too similar to give information concerning the structural nature of the former. ... 

Hydroxypyridine 1-oxide is insoluble in chloroform and other suitable solvents, and, although the solid-state infrared spectrum indicates that strong intermolecular hydrogen bonding occurs, no additional structural conclusions could be reached. Jaffe has attempted to deduce the structure of 4-hydroxypyridine 1-oxide using the Hammett equation and molecular orbital calculations. This tautomeric compound reacts with diazomethane to give both the 1- and 4-methoxy derivatives, " and the relation of its structure to other chemical reactions has been discussed by Hayashi. ... 

Fixed derivatives of the two tautomeric forms of 2-hydroxypyridine 1-oxide do not give cations of similar structure which precludes the use of pKa measurements to elucidate its structure (cf. preceding... 

Hydroxypyridine 1-oxide is methylated at the 3-hydroxyl group165,167 just as is 3-hydroxypyridine. On the other hand, 3-hydroxy-l-amino-4-methyl-5-phenylpyridinium chloride (88) gives... 

According to UV spectroscopic studies, 3-hydroxypyridine 1-oxide exists in ethanol, and aqueous acidic and alkaline media in forms 142a, 142b, and 142c, respectively. No bipolar form 142d has been detected (74KG92). The relative stabilities of tautomers of... 

Gardner and Katritzky (200) prepared and characterized about 24 amirfo- and hydroxypyridine oxides, and showed that 2-hydroxypyridine 1-oxide exists as the strongly hydrogen-bonded l-hydroxypyrid-2-one. Weiss and Harvey (201) described the water-soluble monovalent 6-coordinated silicon chloride salt, soluble in water and alcohol. The tetrachloroferrate (III)... 

Her examined the pH-tltration behavior of silicic acid in the presence of 2-hydroxypyridine 1-oxide by titrating 16 mA/ (1000 ppm SiO ) silicic acid silica from pH 10.5 to 3.0 in the presence and absence of a 43 mA/ concentration of the N-oxide. At no point did the titration curves differ, indicating that no complex had formed. In another experiment, a solution of Si(OH) containing 100 ppm as SiOj was mixed with a 200-fold excess of the above -oxidc at pH 6.15 and aged for a few hours. Tests with molybdic acid showed that the reaction rate with silica monomer was the same as a control, indicating either that no complex was formed at this pH or that it dissociated very rapidly. However, the rate of dissolution of monomer from colloidal silica particles at pH 1.4 was apparently doubled in the presence of a 20 mA/ concentration of the yV-oxide, indicating some type of interaction at low pH. -... 

Hydroxypyridine 1-oxide 2-(2-Hydroxyphenyl)pyridine Phenyl(2-pyridyl)methanol 2-(l-Hydroxyethyl)pyridine... 

By the use of ionization constants it has been concluded that 2- and 4-aminopyridine 1-oxide exist predominantly as such in aqueous solution, whilst 4-hydroxypyridine 1-oxide is in equilibrium with a comparable amount of l-hydroxypyrid-4-one. Application of the method to the pyridine 1-oxides is more complicated than in the pyridine series, and it fails with 2-hydroxypyridine 1-oxide . ... 

II 4-Amino- and 4-hydroxypyridines 1-oxides and isoquinoline 2-oxide were omitted. 

Phosphorus halides can deoxygenate pyridine 1-oxides (p. 387). Consequently, when a 4-hydroxypyridine 1-oxide is treated with phosphoryl chloride, deoxygenation and substitution can give the 4-chloropyridine . The experimental conditions are important with phosphoryl chloride at 60°, 3-chloro-4-hydroxypyridine 1-oxide gives 3,4-dichloropyridine 1-oxide, but at 90-100° 3,4-dichloropyridine results. ... 

Ethoxy-, -chloro- and -phenoxy-pyridine 1-oxides give 2-hydroxypyridine 1-oxide, the oxide function surviving in these cases" . An unusual example is that of 2-carboxy-5-methoxycarbonylpyridine 1-oxide. With benzoyl chloride in dioxan this gives 6-hydroxynicotinic acid. However, with acetic anhydride or acetyl chloride, methyl 4-acetoxynicotinate results . 

A number of 2-alkoxypyridine 1-oxides have been converted into 2-hydroxypyridine 1-oxides by treatment with hydrochloric acid, 256, 524-5. The reactions go easily 2-benzyloxypyridine 1-oxide dissolves in 20 per cent hydrochloric acid with the rapid separation of benzyl chloride a. This may well be a case of nucleophilic attack upon the alkyl group. 4-Benzyloxy-pyridine 1-oxide is also easily converted into 4-hydroxypyridine 1-oxide... 

Table 6J4, Some Hydroxypyridines and Hydroxypyridine 1-Oxides (cf. Tables 6.1, 6.2, 6.8 and 6.13)...

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