4- pyridine 1-oxides tautomerism

Pyridinethiones acylation, 2, 357 alkylation, 2, 357 aromaticity, 2, 148 protonation, 2, 357 tautomerism, 2, 356 Pyridine-2-thiones aromaticity, 2, 156 basicity, 2, 157 oxidation, 2, 357 N-oxide, sodium salt biocide, 1, 399 synthesis, 2, 360... 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

Vasudevan, D. Dorley, P.J. Zhuang, X. (2001) Adsorption of hydroxy pyridines and quinolines at the metal oxide-water interface Role of tautomeric equilibrium. Environ. Sci. 

The reliability of semi-empirical methods (AMI, PM3, and MNDO) for the treatment of tautomeric equilibria has been tested for a series of five-membered nitrogen heterocycles, including 1,2,3-triazole and benzotriazole. The known tendency of MNDO to overestimate the stability of heterocycles with two or more adjacent pyridine-like lone pairs is also present in AMI and to a somewhat lesser extent in PM3. Tautomers with a different number of adjacent pyridine-like nitrogens cannot be adequately treated by these semi-empirical methods. Both AMI and PM3 represent major improvements over MNDO in the case of lactam-lactim tautomerism. The stability of N-oxides as compared to N-hydroxy tautomers is overestimated by PM3 method. All three methods give reliable ionization potentials and dipole moments (90ZN(A)1328). 

Hydroxy pyridine 1-oxides are also tautomeric the 4-isomer exists in about equal amounts of forms (783) and (784). 4-Hydroxy-pyrones and -pyridones exhibit a different type of tautomerism the a-one (e.g. 785) structure is favored relative to the y-one structure. (3-Hydroxy-4-pyrones such as kojic acid (786) show phenolic properties (CHEC 3.28, Scheme 30). a- and 3-Hydroxy cations (e.g. 787) are the conjugate acids of pyridones and pyrones and are considered in the next section. 

Generally, the structures of the 1,2,3,5-thiatriazoles (114) and (113 X = S) are inferred from the mode of synthesis. The structure of l,2,3,5-thiatriazoIo[5,4-a]pyridine 3-oxide (117) has been discussed in more detail. 2-Hydrazinopyridine is formed upon hydrolysis and the IR spectrum exhibits an NH stretching vibration at 3280 cm-1. This suggests the interesting possibility of tautomeric and zwitterionic structures (Scheme 8). Methylation with diazomethane gives the 1-methyl derivative which apparently is best formulated as the zwitterionic A4-thiatriazoline (118). UV spectroscopic properties of (117) (Amax 235, 290 and 342) and (118) (Amax 235, 290 and 345 nm) reveal a close structural similarity (63CB2519). A comparative NMR spectroscopic study of (117) and the A3-l,2,3,5-thiatriazo-line (119 R1 = H, R2 = Me) supports the description of (117) as a pyridinium salt (Scheme 9) (70CB1918). 

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