Rate of Tautomeric Change

It is well accepted that tautomerism relates to the equilibrium between two or more different tautomers e.g., it corresponds to determining if the structure of a compound is, for instance, a pyridone or an hydroxypyridine. The kinetic aspects are often neglected and when the tautomeric equilibrium constant, Kt, is equal to 1 (e.g., for imidazole), the problem may seem 

In Section VI,G, which deals with NMR dynamic studies, the results concerning rate constants in solution and in the solid state are discussed. In the gas phase, no activation barriers have been reported but the fact that tau- 

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The reactivity of ketones towards iodine and the relative rates of tautomeric change. J. Chem. Soc., 97, 2048-2054. 

In contrast, in cyclic amidines free rotation does not occur, and conformational changes of the ring system cannot lead to intramolecular hydrogen bonding. Only intermolecular proton transfer is possible. Confirming this interpretation is the observation that in cyclic amidines a concentration dependence is observed on the rates of tautomerism, whereas in acyclic systems the proton transfer is independent of concentration. 

The effect of the substrate concentration on the rate of the tautomeric equilibrium also depends on substitution. Thus, for compounds 56 with r or = H, the equilibrium rate is faster in concentrated solutions, while a change in concentration has a little effect for the 2,2-disubstituted derivatives. Tautomers 56a and 56b (Ar = Ph, r = R = Me) could be obtained in the pure tautomeric forms and do not equilibrate in the solid state. 

Rice, Fryling, and Weselowski (J. Amer. Chem. Soc., 1924, 46, 2405) make all reaction rates proportional to the concentration of what they call residual molecules, which have to be formed endothermically from one of the reactants. The proportion of these increases with temperature and accounts for the increase in reaction rate. Something of this kind may be true in special cases, for example, in the formation of HBr the residual molecule would be the bromine atom. But this resolution into atoms is only the limiting case of ordinary activation, and it is difficult indeed to see what the residual molecule could be, or what tautomeric change could occur in the simple decomposition of hydrogen iodide or nitrous oxide. 

MelMider points out that unless hydrogen is firmly attached by a covalent bond Mid cmi change its position (as in tautomerism), heavy isotopes react more slowly. The influence of heavy water on the rate of neutralization of a pseudo-acid such as nitroethMie, as observed by Wynne-Jones [89], may be cited as an example. According to him the rate of the reaction involving deuterium loss was about ten times lower than when the proton was lost. 

Since the publication of the exchange results , there is no substantial objection to the proposition that moderately slow phosphite reactions involve the tautomeric structure. Silver and Luz have presented evidence which appears to establish tautomeric change as kinetically significant but only with acid concentrations greater than 1 M. The rate equation for the iodine oxidation, viz. 

Of particular interest is the scope that this system offers for quantita tive calculation of relative rates of photoreaction." Valence tautomerization reactions of the kind under consideration are probably very fast, the rates being of the order of the rates of electronic excitation. As a result, the intemuclear distance between various atoms in the reactant would undergo very little change during the process. It is reasonable to assume that bicyclobutane would result only from a transoid conforma tion of excited butadiene, and that cyclobutene would be formed from the cisoid conformation only. This assumption is based on the known rates of rotation around single bonds which are of the order of 10 sec. The reactions should be represented as two equilibria ... 

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