Acid strength tautomers

In recent years the FEP method has fallen into disuse. However, as the studies outlined above show, in many cases the results obtained are in good agreement with experimental measurements. In these cases new information may be obtained, which may be difficult or even impossible to measure. Examples of this are the relative ratios of conformers in the histamine system, a detailed breakdown of the tautomers present in the guanine or cystine systems, or the acidity strengths of organic molecules such as ethane in water. In addition to this thermodynamic data, the simulations then also provide detailed information on the solvation of the species of interest. 

For example, addition of 2 equivalents of a nonnucleophilic base, 2,6-di-tert-butylpyridine, to the reaction system almost totally suppressed the reaction (Table 9). This proposes that acid catalyzed enolization is important for the a-Umpolung. In support of mechanism 1 the yields of the a-methoxylated products increased with decreasing oxidation strength of the oxidant (Table 10), since endergonic oxidation of the ketone 70 is slowed down (Fig. 2). On the other hand, in the presence of stronger aminium salts the ketone tautomer is oxidized which however does not lead to deprotonation in the benzylic position... 

Enols are generally more acidic (pA a ca 11-12) than their corresponding carbonyl tautomer (pATa ca 17-25). Exceptions to this arise when the carbonyl derivative is either destabilized relative to the enol component, or when the enol is exceptionally stable, as in the case of phenol [pATa (H20) = 9.95] vs. cyclohexa-2,4-dienone [pATa (H20) = —3 1]. Enol acidity can be controlled by O-H bond strength. In certain cases, the relative proportion of enol content can be determined by the relative strengths of the C=0 and C—H bonds in the carbonyl tautomer versus the C=C and O—H bonds in the enol. ... 

The individual ionization constants for pairs of tautomers and the constant for the equilibrium between them can be deduced from the experimentally determined ionization constants in another way. It will be seen (p. 156) that the effect of substituents on the basic strength of the pyridine nitrogen atom can be represented by the Hammett equation. Accordingly, the ionization constant for the NM form (T b) can be estimated from the Hammett substituent constant of the group — A H. Combined with the experimentally determined Ki this leads to estimates of the remaining quantities. In this way Jaffe 2 deduced that nicotinic and isonicotinic acids exist predominantly as zwitterions in aqueous solution. Similarly, Bryson s obtained the values pi B 5-0 and Kt = 0 78 for 3-hydroxypyridine (cf. Tables 5,10 and 5.12), Hammett correlations have been used in evaluating the tautomeric equilibria in a number of 2-arylsulphonamidopyridines . ... 

---