Mercaptopyridines thiol-thione tautomerism

For the particular case of 2- and 4-mercaptopyridines and 2-mercaptopyrimidines and by means of absorption UV-VIS spectroscopy, Stoyanov and collaborators122 have shown that polar solvents shift the thiol/thione tautomerism towards the thione form, while in dilute solutions of nonpolar solvents the thiol form predominates. However, one of the most significant contributions of this work122 is the observation of self-association. It also favors the thione forms and is followed by quantitative transformation of the thiol form into the corresponding symmetrical disulfides (see Scheme 6). More importantly thione-disulfide process is reversible in water, which can be of some relevance in biological systems. 

TABLE 13. Ratio of concentrations of the tautomeric forms [thiol]/[thione] for mercaptopyridines and mercaptodiazines (AG gives the tree-energy differences between both tautomers, in kcal mol1)... 

Thiono-mercapto and amino-imino tautomerism of azines. In the same heterocyclic systems, the stability of thiols with respect to the corresponding thione form is considerably higher than hydroxy derivatives with respect to their oxo forms. In the gas phase 2- and 4-mercaptopyridine are the major tautomers, e.g., 191. 15N NMR spectroscopy is useful for estimating the tautomeric composition of mercaptopyridines in solution. 2-Mercaptopyr-idine in acetone or methanol and 4-mercaptopyridine 191 in methanol or acetone/DMSO were estimated to be ca. 95% in the thione form, e.g., 192. This solvent effect can be attributed to the polarity of the thione tautomers <2006AHC(91)1>. 

The systematic IR studies of the functional group and heteroatom effect on the position of the tautomeric equilibrium indicated that the stability of thiols (with respect to the corresponding thione forms) is considerably higher than the stability of the hydroxy forms (with respect to the oxo forms) in the same heterocyclic systems, so the mercapto tautomers of mercaptopyridines should be more favored in the equilibrium than their oxygen analogs (92JPC6250). 

Nitrogen chemical shifts in 14N NMR spectroscopy have been used to estimate the equilibrium compositions of a series of mercaptopyridines in solution. Thus, ca. 95% of the thione form was estimated for 2-mercaptopyridine in acetone and methanol and for 4-mercaptopyridine in methanol and acetone/DMSO (790MR379). 15N NMR shielding measurements provided the quantitatively reliable estimates of tautomeric equilibria for 3-methoxycarbonyl-2-mercaptopyridine and 3-mercaptopyridine. The equilibrium of 3-methoxycarbonyl-2-mercaptopyridine is shifted predominantly to the thione tautomer (95%), whereas 3-mercaptopyridine exists in the thiol form (at least 94%) (85MRC790). By 13C NMR spectroscopy, 3-nitropyridine-4-thiol exists in the thiol form (86H(24)1301). Another NMR criterion, used for estimation of the tautomeric equilibrium in mercaptopyridines, is based on 3/(ch) values for the CN-CH, C N = CH, and C = N-CFI structural elements (83OMR20). 

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