Pyridone–pyridol tautomerism in 2-hydroxypyridines with [5,6]-annelated rings and carbon atoms at positions [5] and [6] : 1,3-dihydro-5-hydroxyfuro[3,4-b]pyridine, 1,3-dihydro-5-hydroxythieno[3,4-b]pyridine, and 1,3-dihydro-5-hydroxythieno[3,4-b]pyridine S,S-dioxide

Abstract

U.v. spectra, in a range of solvents, i.r. spectra, and ionization constants in water have been determined for the title compounds (I) to (VI), their O- and N-methylated derivatives (VII) to (XII), counterparts that correspond to O- and S-ring fission products (XIII) to (XVI), and their methylated derivatives (XVII) to (XIX). All the the title compounds exist to an appreciable extent in the pyridol form in solution in dioxan. By a comparison of the cyclic sulphide with, on the one hand the cyclic sulphone, and on the other the cyclic ether, the effects of electron withdrawal and of ring strain have been assessed almost independently of one another. Replacement of the sulphide ring by the (smaller) ether ring (a) increases the ratio [pyridol]/[pyridone](K_T) in dioxan by a factor of 2·7, (b) lowers the base strength of the 2-methoxypyridine, (c) lowers the base strength of the 2-pyridone, but by a much smaller amount, (d) raises the acid strength of the 2-pyridone. Replacement of the sulphide by the sulphone ring (a) produces a 2·8-fold increase in K_T in dioxan, and (b), (c), and (d) reduces the base strengths and raises the acid strength, all by much greater amounts than in the above comparison. Analysis shows that no more than a third of the difference in K_T between the cyclic ether and the cyclic sulphide is attributable to greater electron withdrawal (inherent plus ring-strain-induced) by the oxygen ring; about two thirds of it is due to a Mills–Nixon–Brown type of ring strain in the pyridone (II), which is relieved by conversion into the pyridol (I) or by ionization. The effects of ‘ring closure’ of the di-(methyl ether) to the cyclic ether, e.g. of [(XIII), (XIV)] to the [(I), (II)], show clear evidence of ring strain in the latter, whereas the effects of ‘ring closure’ of the dimethylthio-compounds to the cyclic sulphides indicate only a small amount of ring strain in the last-named. All the 2-hydroxypyridines listed are in the pyridone form in the solid state.