Pyridone–pyridol tautomerism in 2-hydroxypyridines with [5,6]-annelated rings and oxygen at the [6]-position: 2,3-dihydro-6-hydroxy-4-methylfuro[2,3-b]pyridine and 3,4-dihydro-7-hydroxy-5-methylpyrano-[2,3-b]pyridine

Abstract

U.v. spectra in a range of solvents, i.r. and 1H n.m.r. spectra, and ionization constants in water have been determined for the title compounds (I) to (IV) and their O- and N-methylated derivatives (V) to (VIII). Replacement of the annelated five-membered ring by a six-membered one (a) reduces the ratio [pyridol]/[pyridone](KT) by a factor of ca. 15–30; (b) raises the base strength of the 2-methoxypyridine; (c) scarcely changes the base strength of the 2-pyridone; (d) lowers the acid strength of the 2-pyridone. The greater part of the ring-size effect on the tautomeric equilibrium is attributable to a Mills–Nixon–Brown type of ring strain, which is present in the five-membered ring in (II) but absent from the six-membered one in (IV); this strain is relieved by conversion into the pyridol (I), and by ionization; in part the ring-size effect is due to electron-withdrawal by the (strained) five-membered ring. In cation formation by the 2-pyridone (II) this electron-withdrawal and relief of ring strain oppose and almost cancel one another. 2-Hydroxy-6-methoxypyridine is intermediate between [(I). (II)] and [(III). (IV)] in both tautomeric equilibrium constants and ionization constants, but when allowance is made for the effect that a 4- and 5-alkyl group is expected to have in the first-named compound it is found that the properties of the pyrano-compound are quite similar to those of the ‘open-chain’ counterpart, whereas those of the furocompound are normally different. In the solid state all three above compounds exist in the pyridone form. Differences in zwitterionic character between the furopyridones and the pyranopyridones are shown not to be significant.In an Appendix attention is drawn to the relatively large errors in KT values derived by some common pK–KT relations.