Physical Methods Used to Study Tautomerism

In general, physical methods have been used to study tautomerism more successfully than chemical methods, and, of the physical methods, those involving measurements of basicities and ultraviolet spectra are the most important, followed by those involving measurement of infrared and proton resonance spectra. An attempt is made here to delineate the scope and to indicate the advantages and disadvantages of the various methods. A short review by Mason of the application of spectroscopic methods appeared in 1955. Recently a set of reviews on the applications of physical methods to heterocyclic chemistry has appeared, which treats incidentally the determination of tautomeric structure. 

The determination of pi a values is probably the most generally useful method for the investigation of tautomerism. This method was first employed in the heterocyclic field in the early 1950 s by Tucker and Irvin and by Angyal and Angyal. There are two empirical dissociation constants, and K2, for the conjugate acid (HXH+) of a tautomeric compound. Constants Kt and K2 are, in effect, a summation of the true dissociation constants Ka, Kb, Kc, and Kd of the individual tautomeric forms (see scheme 43, where XH and HX are tautomers) and the tautomeric constant, Kt] these constants are related by the following equations  

Albert, in Physical Methods in Heterocyclic Chemistry (A. R. Katritzky, ed.), Chapter 1. Academic Press, New York, 1962. 

Replacement of a hydrogen atom by an alkyl group such as a methyl group Usually has no effect, or only a very small effect, on the ionization constant thus, the ionization constant of HXMe+ is approximately equal to Ku and that of MeXH to Ka. Therefore, 

It follows that Kt can be theoretically calculated from Kt and the ionization constant of either of the alkylated derivatives. In practice, however, this can only be done if there is an appreciable difference between the constant for the alkylated derivative and the value of Kt. Mason has argued that it is better to use the ionization constants of both alkylated forms in the equation Kt = X MeXH )/ for in this case the errors introduced by assuming that — Ka, etc., may well partially cancel. However, methyl groups can be base-weakening as well as base-strengthening the data shown in Table I indicate that the base-weakening inductive 

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II. Chemical Methods Used to Study Tautomerism. m. Physical Methods Used to Study Tautomerism. ... 

Proton resonance spectroscopy has been used to study the tautomerism of 4-hydroxypyridine and its 1-oxide, with results in agreement with those obtained by other physical methods discussed here. Resonance spectroscopy also indicated that the cations of 4-hydroxypyridine, 1-methyl-4-pyridone and 4-methoxypyridine are of the type (32), that of 4-hydroxy-pyridine 1-oxide as (33), and that 2-pyridone cation is protonated on... 

Tautomerism can be studied by various chemical and physical techniques, In principle, it is possible to obtain significant results from chemical evidence, but in practice this is very difficult, and physical methods are much more useful. Chemical methods are discussed first and emphasis is placed on the dangers inherent in their application. It... 

The experimental evidence for the existence of the corresponding tautomeric forms in solutions has been based on the study of their chemical reactivity and, to a lesser extent, on the study of tautomeric systems by means of physical methods. Not even an approximate quantitative evaluation can be presented by chemical experiments because of the different reaction rates of the individual tautomers at best, they can be used as negative evidence, viz., the absence of a certain tautomeric form in the reaction mixture can be assumed under the conditions used. The physico-chemical methods, due to low sensitivity, also did not give a satisfactory picture of the ratio of the corresponding tautomers.50... 

Within the last decade, ab initio and hybrid quantum-chemical methods were in considerable use in tetrazole chemistry, and the level of calculations significantly improved with extended basis sets used for quite complex polyatomic molecules. During this time, theoretical methods were exploited in the study of several fundamental properties of the terazole ring, such as aromaticity and capability to be involved in various kinds of tautomerism, including the effects of substituents and media on these parameters. It was demonstrated that many physical and physicochemical characteristics of tetrazoles could be successfully estimated by these methods not only for the gas phase but also for the condensed state (solvents, crystals). 

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