Tautomeric solvent effects

A theoretical, comparative study of the tautomerism of 56 five-membered heterocyclic rings announced in (76AHC(Sl)l) has appeared (81MI40402). The stabilities of the three forms for 5-pyrazolones, 5-pyrazolethiones and 5-aminopyrazoles have been calculated by a simple Hiickel o) iterative method. The relative energies and the substituent and solvent effects are in agreement with the experimental results. 

Among many examples of the solvent effects on chemical equilibria and reactions, the solvent effect on tautomerization has been one of the most extensively studied. Experi-... 

The second aspect is more fundamental. It is related to the very nature of chemistry (quantum chemistry is physics). Chemistry deals with fuzzy objects, like solvent or substituent effects, that are of paramount importance in tautomerism. These effects can be modeled using LFER (Linear Free Energy Relationships), like the famous Hammett and Taft equations, with considerable success. Quantum calculations apply to individual molecules and perturbations remain relatively difficult to consider (an exception is general solvation using an Onsager-type approach). However, preliminary attempts have been made to treat families of compounds in a variational way [81AQ(C)105]. 

There is an evolution with time the older calculations correspond to isolated molecules in the gas phase without any corrections, the more recent ones include solvent effects, with different approximations, and also some corrections, like ZPE (zero-point energy correction). The contributions of some authors to the understanding of tautomerism have been significant. Some of their contributions are collected in Table II. 

Thermochemical investigations of tautomeric equilibria solvent effects... 

Resonance energies and tautomerism of substituted aromatic heterocycles and their benzo derivatives Reaction-field-supermolecule approach to calculation of solvent effects... 

Solvent effects on tautomeric equiUbria in heterocycles, a 97MI4... 

In addition to the rather scattered data reported in the previous survey (76AHCSl,p. 510), a few new studies appeared on purine-6- and -2-thiones. Tire MO calculations of solvent effects (AMl-SMl and AM1-SM2) on the tautomerism of 6-thiopurine indicated that l//,9//-tautomer 7a is greatly stabilized in aqueous solution [94THE(309)137].Tlie same results were obtained experimentally from UV and and NMR studies (75JA3215, 75JA4627,75JA4636). 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

Adamo, C., and F. Lelj. 1994. Equilibrium solvent effects in the framework of density functional theory. Application to the study of the thermodynamics of some organic and inorganic tautomereic equilibria. Chem. Phys. Lett. 223, 54. 

G. Rastelli, L. Costanino, and A. Albasini, Solvent effects on the tautomerism of... 

The several theoretical and/or simulation methods developed for modelling the solvation phenomena can be applied to the treatment of solvent effects on chemical reactivity. A variety of systems - ranging from small molecules to very large ones, such as biomolecules [236-238], biological membranes [239] and polymers [240] -and problems - mechanism of organic reactions [25, 79, 223, 241-247], chemical reactions in supercritical fluids [216, 248-250], ultrafast spectroscopy [251-255], electrochemical processes [256, 257], proton transfer [74, 75, 231], electron transfer [76, 77, 104, 258-261], charge transfer reactions and complexes [262-264], molecular and ionic spectra and excited states [24, 265-268], solvent-induced polarizability [221, 269], reaction dynamics [28, 78, 270-276], isomerization [110, 277-279], tautomeric equilibrium [280-282], conformational changes [283], dissociation reactions [199, 200, 227], stability [284] - have been treated by these techniques. Some of these... 

For some compounds NMR data were collected to determine the equilibrium constants for the tautomerism between the azide form such as for 30 and the tetrazole derivative 31 (Scheme 3). Similar investigations were conducted for the compounds 28 and 29 and the solvent effects and substituent effects are discussed <1996JHC747>. 

The solvent effect on the azo-hydrazone equilibrium of 4-phenylazo-l-naphthol has been modelled using ab initio quantum-chemical calculations. The hydrazone form is more stable in water and in methylene chloride, whereas methanol and iso-octane stabilise the azo form, The calculated results were in good agreement with the experimental data in these solvents. Similar studies of l-phenylazo-2-naphthol and 2-phenylazo-l-naphthol provided confirmation. Substituent effects in the phenyl ring were rationalised in terms of the HOMO-LUMO orbital diagrams of both tautomeric forms [53]. 

Another focus of this chapter is the alkynol cycloisomerization mediated by Group 6 metal complexes. Experimental and theoretical studies showed that both exo- and endo- cycloisomerization are feasible. The cycloisomerization involves not only alkyne-to-vinylidene tautomerization but alo proton transfer steps. Therefore, the theoretical studies demonstrated that the solvent effect played a crucial role in determining the regioselectivity of cycloisomerization products. [2 + 2] cycloaddition of the metal vinylidene C=C bond in a ruthenium complex with the C=C bond of a vinyl group, together with the implication in metathesis reactions, was discussed. In addition, [2 + 2] cycloaddition of titanocene vinylidene with different unsaturated molecules was also briefly discussed. 

Even for a simple reaction, involving just one reactant species and one product species, such as a keto-enol tautomerism or a cis-trans isomerization, the above equation for a given solvent is complicated. StUl, in specific cases it is possible to unravel the solvent effects of cavity formation, for the solute species have different volumes, polarity/polarizability if the solute species differ in their dipole moments or polarizabilities, and solvent Lewis acidity and basicity if the solutes differ in their electron-pair and hydrogen-bond acceptance abilities. 

These results are, by analogy, in keeping with the hypothesis of tautomerization for in the series of benzene-azonaphthols there is a very similar solvent effect [2]. It there proved possible to demonstrate the tautomeric nature of the effect by synthesis of the N-methyl ether of the quinoid form and measurement of its spectrum. 

Isomer stabilities and activation energies have been calculated for keto-enol tautomerization of simple carbonyl compounds, MeC(R)=X (X = O R = H, Me) 129 both specific and bulk solvent effects have been analysed. Related isomerizations of acid derivatives (R = F, CN) and other related structures (R = H X = CF12, NH, S) are compared. 

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