2-Nitro-3-hydroxypyridine

Alkylpyridines (picolines, and especially lutidines) can be nitrated much more readily, as Plazek [75] has shown. Introduction of the nitro group is greatly facilitated by the presence of the hydroxyl group in the pyridine ring. For example, 3-hydroxypyridine can be nitrated to 2-nitro-3-hydroxypyridine in good yield (Plazek and Rodewald [76]). It may be further nitrated to the dinitro derivative. From this, 3,5-dinitropyridine can be obtained (Plazek [77]). 

TABLE 13. Apparent stability constants of molecular complexes between 2-hydroxypyridine and some aromatic nitro derivatives in hen/enevA at 25 °C125. Reproduced by permission of societa chimica Italiana from Reference 125... 

The study of molecular complexation was then extended to other aromatic nitro derivatives125. Although, as was described before, one of the more frequent methods of studying the formation of molecular complexes is by UV-visible spectrophotometry, the author did not observe detectable differences in the UV-visible absorbance spectra between the 2-hydroxypyridine-l-fluoro-2,4-dinitrobenzene (FDNB) mixtures and the sum of their separate components. The author observed that the signals of the 1II NMR spectra of FDNB in apolar solvents were shifted downward by the addition of 2-hydroxypyridine from solutions where [2-hydroxypyridine] [FDNB] he calculated the apparent stability constants, which are shown in Table 13. 

Hydroxypyridines undergo a variety of other electrophilic substitution reactions. Sulfonation of 2-pyridone with 10% oleum at 180° gave the 5-sulfonic acid.69 110 A-Methyl-2-pyridone is similarly sulfonated with chlorosulfonic acid. The action of fuming sulfuric acid gave a mixture of the 5-sulfonic acid and the 3,5-disulfonie acid. A nitro group at C-5 is said not to hinder the reaction, sulfonation at the... 

Azine approach. The parent cation and substituted derivatives are available by acid-catalyzed cyclization of 2-/3-oxoalkylthiopyridines (401) using an acid such as sulfuric, phosphoric or PPA. Chloro or nitro substituents in the pyridine ring do not seriously interfere (66JHC27). The cyclization of 3-hydroxypyridine analogues (402) is also at the nitrogen to yield the thiazole derivatives. The cyclization, however, is sensitive to the peri interaction between 3- and 5-substituents. In 3,5-dimethyl derivatives (403 R2 = R3 = Me) the steric repulsion is apparent by the unusually low field signals for the methyl protons <81H(15)1349>. 

Nitration of 2-substituted-3-hydroxypyridine N-oxides (9.94) gave —50% yield of 4-nitro derivatives, as also did 2,6-dimethyl-3-hydroxypyr-idine N-oxide (70BAU2440). 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

Note Bathochromic shifts and ti in alkaline solution are not exclusive to phenols, but also occur in hydroxypyridines [2806] and ketones capable of forming enols pyridone [909] and benzoxazolinone [2402], in benzodiazepinones [2604] and also in nitro-compounds (metronidazole [916], nifurprazine [917], nitrofural [918], nitrofurantoin [919]). 

Catalytic hydrogenation of a 2-nitro-a Oxocarboxylic ester with a large amount of platinum oxide present reduces both nitro and oxo groups a 3-hydroxypyridin-2-one ring is formed. A smaller proportion of catalyst tends to favour the formation of a five-membered ring. 

The gas-phase equilibrium between 2-hydroxypyridine and 2-pyridone favours the hydroxy-form, but in the equilibrium between 2-hydroxypyridine iV-oxide and N-hydroxy-2-pyridone, the major tautomer is the hydroxy-pyridone. Bicyclic adducts between 2-pyridones and dimethyl acetylene-dicarboxylate, unobtainable at atmospheric pressure, have been obtained at 10—15 kbar. A novel route to iV-hydroxy-2-pyridone involves the trimethyl-silylation of 2-pyridone followed by oxidation of the resulting 2-(trimethyl-silyloxy)pyridine with the DMF complex of molybdenum pentoxide. p-Nitro-phenols (45) and nitro-acetamides (46) are formed from the reaction of 3,5-dinitro-2-pyridones (43) with the sodium salts of /3-keto-esters (44) (Scheme 20). ... 

Another example of an approach to pyridoxol began with the cycloaddition of 4-methyloxazole 5 with the sulfonyl-alkene 43 (Fig. 3.14)." The bridged cycloadduct 44 was formed with the expected regiochemistry, directed by the electron-withdrawing sulfonyl group. Elimination of methanesulhnic acid then provided hydroxypyridine 45, a precursor of pyridoxol. In a related synthesis reaction of the nitro-olehn 46 with 5 afforded the pyridoxol precursor 47 in low yield. 

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