6- Methoxy-2-pyridone, tautomerism

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

The jump-relaxation technique has also been used to study the influence of temperature on the position and on the dynamics of the tautomeric equilibrium of 6-methoxy-2(liY)-pyridone in neutral water, which was shown to be an essentially a pH-independent process. The equilibrium and activation parameters obtained indicate that the interconversion mechanism is ionic rather than concerted and involves the anionic form of the substrate in a cyclic transition state, in which at least two solvent molecules would temporarily ensure a hydrogen bond connection between the sites which undergo tautomerism (83JCS(P2)979). 

The substituent effect on the tautomeric equilibrium in solution has been studied using experimental pKa values and UV spectra (in water at 20 °C) of several 4(177)-pyridones and their N- and O-fixed derivatives. It was concluded that most of the factors affecting the tautomerism of 4(l/7)-pyridones are due to the electronic effect, including steric effect, of the substituents in the 2-position. Thus, the proportion of the hydroxy form increases on introduction of an electron-withdrawing group into the 2-position. For example, 5-methoxy-4(l/7)-pyridones with a methyl, hydroxymethyl, and methoxymethyl groups in the 2-position exist essentially in the pyridone form however, 2-methoxycarbonyl-substituted derivative exists as a mixture of hydroxy and oxo form in water (77BCJ710). The effect of substituents in the 3-position... 

Nondegenerate double proton migrations between a solute molecule and the molecules of the solvent (water) may determine the mechanism of intermolecular proton transfers that give rise to a new tautomeric form. Thus, using the relaxation method of temperature jump, it was found [97] that the tauto-merization of 6-methoxy-2-pyridone proceeds as a nondissociative concerted process of bifunctional interaction with one molecule of water ... 

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