Quantum chemical calculation of tautomeric equilibria

As is common in heterocyclic chemistry, many studies concern tautomeric equilibria. While quantum chemical calculations are straightforward for the question of the most stable isomer, experiments are sometimes very demanding. Therefore, quantum chemistry can easily provide answers that may require substantial experimental effort. Comparatively few studies concern the investigation of entire reaction paths. This is much more demanding than computing a limited number of tautomers, of course, but usually provides a very detailed picture of the reaction mechanism. In certain cases, it was only possible to judge the nature of a chemical reaction on the basis of quantum chemical calculations. 

There is an excellent correlation between the experimental microwave dipole moments of a variety of azoles and those calculated by the ab initio method at the 6-31G //6-31G level p,exp = 0.942p,ca, + 0.008 (86JPC5597). With this equation, the experimental values for 1H- and 2H-1,2,3-triazole are predicted as 4.35 D and 0.32 D, respectively (89JCO(10)426). Thus, quantum chemical calculations are a valuable aid in estimating tautomeric equilibria by dipole moment studies (90ZN(A)1328). 

As mentioned in the Introduction, tautomerism plays a major role in the chemistry of DNA and RNA bases. Colominas et al have made an extensive study of the tautomeric equilibria of guanine and cytosine (see Figure 5). The importance of protonation on the equilibria was also studied. To begin with all possible tautomers were considered. The least stable species were then screened out using increasingly accurate quantum chemical calculations with a SCRF solvent term. FEP calculations were then used for the most important equilibria. In the neutral cytosine molecule, four important tautomers are based on the amine form shown in Figure 5 as cytosine I. Another 2 tautomers are based on the imino form shown in the Figure 5 as cytosine II. In the gas phase, an admixture of forms is predicted, with the depicted cytosine I structure the most stable. In solution, all tautomers are destabilised with respect to this tautomer, which then dominates by about 20 kJ/mol. 

Also, recent developments in quantum theoretical calculations of NMR parameters have increased their reliability and usefulness, especially in studying the dynamic processes such as conformational equilibria and tautomerism of aniline derivatives. All the above-mentioned items will be included in the following discussion. However, owing to the huge amount of data about H NMR parameters, the main focus of this review is directed to 13C, 15N and 19F NMR spectral studies of aniline derivatives. Schiff bases are not included in this review although some of them show an amino-imino tautomerism and can thus be considered as anilines. One reason for this is that a search in Chemical Abstracts using key words schiff base and nmr produced more than 1000 hits. 

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