2- Chloro-4 -pyridone , tautomerism

Different tautomeric species (e.g., 6-chloro-2-pyridone/6-chloro-2-hydroxypyridine). 

The concentration dependence of FTIR and UV spectra of 2-hydroxypyridine and its 6-chloro analog was measured in chloroform and CCI4 in order to elucidate their tautomeric equilibrium and determine the association constants (96MI1). For unsubstituted 2-hydroxypyridine, the hydroxy monomer or dimer was not detected in both solvents, and the equilibrium existed exclusively between oxo monomer and dimer. In contrast, for 6-chloro-2-pyridone both monomeric hydroxy (about 72%) and oxo (about 28%) forms were observed in chloroform. Increase in the substrate concentration led to decrease in the content of the monomeric species in favor of relevant dimers. In CC14, 6-chloro-2-hydroxypyridine was found to exist mainly in hydroxy monomer hydroxy dimer equilibrium. 

Temperature-jump experiments were performed with aqueous solutions of 2-chloro-4(l/7)-pyridone and 2,6-di(methoxycarbonyl)-4(17/)-pyridone (chelidamic acid dimethyl ester). It was suggested that when the tautomeric functional group is remote, tautomeric interconversion occurs through intermediate ionization and dissociation followed by ion recombination (77JA4438). 

Nitro derivatives of a variety of heteroaromatic compounds enter the VNS reactions with alkyl hydroperoxide anions to produce the expected hydroxylation products [41, 137-139]. For instance, the VNS hydroxylation of 2-chloro-5-nitropyridine with ferf-butylhydroperoxide was shown to give 2-chloro-5-nitro-6-hydroxypytidine that exists in its tautomeric form of pyridone [41] (Scheme 44). It should be stressed that the SNAr of chlorine located in the highly activated position 2 was not competing with the VNS. 

Tautomeric equilibrium constants Kf = [pyridone]/[pyridinol] have been measured for a number of 2-pyridones (Table XII-8). The constant Kf has been estimated by a Hiickel approximation for 2- and 4-pyridone. The Kf values obtained from ultraviolet spectra and those obtained from acidity constants are in poor agreement for 6-chloro-4-substituted-2-pyridones (XII477 R = CH3, CeHs) and 6-chloro-3,4-polymethylene-2-pyridones (XII-478 n = 3,4) in water. For example, in XII477 where R = CH3, values of 6% and 44%respec-tively of pyridinol tautomer (XII477b) are obtained from ultraviolet data and from acidity constants. However, values obtained from ultraviolet studies appear to be more reliable. ... 

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