2-Hydroxy-6-methoxy-pyridines 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... 

Next, the substituent effect on the tautomeric preference should be considered. For example, ortho-derivatives of pyridine with substituents which have an acidic proton may participate in prototropic tautomerism (Scheme 12 2002A(11)198). Stabihty of the particular tautomeric form depends on an additional substituent and intermolecular H-bonding (Scheme 13). Moreover, tautomeric preferences can be changed by a solvent. For 6-X substituted 2-hydroxypyridines, the tautomeric equihbrium is stron y affected by substituents which can change the Tt-electron structure of fragments involved in the prototropy. For example, it was found that 2-hydroxy-6-chloro-and 2-hydroxy-6-methoxy-pyridines exist mainly in the aromatic form a... 

Methylation of 6-chloro-4-hydroxy-3-methylisothiazolo[5,4-6]pyridine (200) with ethereal diazomethane for 13 h gave the 4-methoxy derivative (201) (93%) <90JCS(P1)1477>. None of the 7-methyl derivative was observed in the reaction, indicating that compound (200) exists almost exclusively as the 4-hydroxy tautomer and that the tautomeric 6-chloro-3-methylisothiazolo[5,4-6]pyridin-4-one (202) does not contribute significantly to the equilibrium. 

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