Tautomers, interaction

An estimation of the absolute value of the tautomeric constant (a b in solution [i.e., an estimation of A aJb] by means of quantum-mechanical calculations is impossible due to practical considerations a quantum-mechanical estimation of the A a)b value would require calculations of the potential surfaces for the tautomers interacting with all solvent molecules in the first two solvation shells at least. 

An estimate of the relative change of the stabilities of tautomers caused by solvent prevents a less complicated problem. In practice it is necessary to calculate the interaction energies between tautomers and solvent and to compare the values of these energies. In calculations of this type it is usually assumed that the environment does not change the geometries of the tautomers and that the energy of the tautomer interacting with the solvent is estimated either classically or quantum mechanically. 

It is also well known that the keto-enol equilibrium is modified fundamentally in aqueous solution due to the specific interaction of solvent molecules with the substrates through hydrogen bonds Calculated results summarized in Figure 39a indicate that the keto-enol equilibrium is markedly modified in the bimolecular neutral systems in which each tautomer interacts with one water molecule. In particular, the energy barrier for hydrogen transfer from oxygen to carbon is reduced appreciably, in going from... 

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

Is the second step of the overall reaction for R=Me (N-methylphthalimide + hydrazine —> phthalimide hydrazide + methylamine) exothermic or endothermic Will higher temperatures accelerate or inhibit the reaction Is the structure drawn above for phthalimide hydrazide its lowest-energy form or are either the imine or diimine tautomers preferred Compare energies for the hydrazide and imine and diimine tautomers. Examine the geometry of phthalimide hydrazide and any low energy tautomer, and draw the Lewis structure(s) that best describes it. Can your Lewis structures account for the energy differences Examine electrostatic potential maps for all three molecules. Which molecule(s) are stablized by favorable electrostatic interactions Which are destabilized Can this help explain the energy differences Elaborate. 

The reaction is carried out in both acidic and basic media. Thus, for example, the interaction of 4-diethylaminobut-3-en-2-one with thiocarbamide is performed at 75°C for 30 h (EtOK, EtOH) to result in 54% yield of the major product. The existence of two tautomers 274 and 275 was proved for 2-mercapto-4-methylpyrimidine (Y = S) by IR and H NMR spectroscopy (76ZOR2063). 

Thomsont Click Organic Interactive to learn to interconvert enol and carbonyl tautomers. 

The photolysis of 2 -azido-2,4,4, 6-tetramethylbiphenyl (47) in diethylamine gives 10% of a mixture of A,iY-dicthyl-4-methyl-7-mesityl-3//-azcpin-2-amine (48) and the isomeric 3H-azepine 49, together with the unexpected 4//-azepine SO as the major product." Formation of the 4//-azepine is attributed to severe steric interactions in all conformers of the 3H-tautomers. 

Katsumura, Kitaura and their coworkers [74] found and discussed the high reactivity of vinylic vs allylic hydrogen in the photosensitized reactions of twisted 1,3-dienes in terms of the interaction in the perepoxide structure. Yoshioka and coworkers [75] investigated the effects of solvent polarity on the product distribution in the reaction of singlet oxygen with enolic tautomers of 1,3-diketones and discussed the role of the perepoxide intermediate or the perepoxide-Uke transition state to explain their results. A recent review of the ene reactions of was based on the significant intervention of the perepoxide structure [76], which can be taken as a quasi-intermediate. 

Shukla MK, Leszczynski J (2002) Interaction of water molecules with cytosine tautomers An excited-state quantum chemical investigation. J Phys Chem A 106 11338... 

To the best of our knowledge the sensitivity of FEP calculations to this overestimation of electrostatic interaction has received little attention. Cox et al24 did use scaled 6-31G charges in their successful treatment of the 1,2,3-and 1,2,4-triazole tautomer equilibria, but no comparison was made with unsealed charges. This factor could however be of crucial importance in calculation of tautomeric equilibria, where fine differences are important. 

In 5 (6) -substituted benzofuroxans, there are a number of reasons for the preference for a tautomer at equilibrium. Nevertheless, the presence of an electron-withdrawing group in 5(6)-substituted benzofuroxans frequently favors the 6- tautomer over the 5- tautomer. In 4(7)-substituted benzofuroxans the steric interactions between the substituent and the N+-CT moiety play important roles, and thus the 4-isomer is frequently favored at equilibrium. 

In conjunction with the present review we have carried out AM1-SM4 calculations in solvent -hexadecane (e = 2.06) for the benzotriazole equilibrium. We find that 35 is better solvated than 34 by 0.9 kcal/mol, with all of the differential solvation being found in the AG pterm. Not surprisingly, PM3-SM4 results are very similar. This seems to be out of step with the data from CDCb, the most nonpolar solvent for which experimental results are available. It is not clear, however, whether this difference is attributable to (i) the smaller dielectric constant of -hexadecane compared to CDCb (for CHCb e = 4.8 at 293 K [240]), (ii) specific interactions between weakly acidic chloroform and the basic benzotriazole tautomers, (iii) inadequacies in the semiempirical electronic structure, (iv) inadequacies in the SM4 model, or (v) some combination of any or all of the above. When SM5 models are available for CHCI3 and DMSO, it will be interesting to revisit this system. 

Figure 4. Scheme of lipophilicity profile of zwitterionic compounds. The line drawn represents the case where the neutral tautomer predominates or the zwitterion is rather hydrophobic, resulting in a bell-shaped profile. The dashed line represents the case where the zwitterion predominates and intramolecular interactions are not possible, resulting in a U-shaped profile. Adapted with permission from [133] Pagliara, A. et al. (1997). Lipophilicity profiles of ampholytes , Chem. Rev., 97, 3385-3400 copyright (1997) American Chemical Society... 

Particularly interesting examples are also the lipophilicity profiles of ampholytes. Depending on the ratio between the neutral tautomer and the zwitterionic tautomer, the log Dow versus pH profile may be bell-shaped or U-shaped [133] (Figure 4). For zwitterions, the shape of the lipophilicity profile depends upon the structure and conformation of the molecule. If the charged groups are situated in proximity and can interact with each other, the zwitterion might be more hydrophobic than the anionic and the cationic species, resulting in a bell-shaped lipophilicity profile. If, however, intramolecular interactions are not possible for steric reasons, the lipophilicity profile is U-shaped [133],... 

In 2-hydroxyfuran (Scheme 12), tautomerism always involves loss of aromatic stabilization, but the energy loss is far less here. Moreover, favorable interaction in the carbonyl tautomers offsets part of this loss, and the higher bond energy of the carbonyl group means that the carbonyl form is favored for... 

The MS of some nitro derivatives of imidazole-4(5)-carboxaldehyde have been studied100. Based on the compounds 15-17, several new features caused by the interaction between the nitro group and adjacent substitutents were disclosed. It should be noted that for the compounds 16 and 17, there is a rapid equilibrium between the two possible tautomers resulting in equivalence of the 4 and 5 positions. 

Fig. 5.5 Putative interactions of the cocrystallized selective Cox2 ligand SC-558 with its active site, assuming a neutral sulfonamide group - the state used to assign pharmacophore feature flags by the used software. Dotted lines stand for hydrogen bonds, the other residues being responsible for hydrophobic contacts. From a physicochemical point of view, an ionized SO2 NH involved in a salt bridge with Arg 513 and hydrogen bonding to the other tautomer of His 90 would make more sense.

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