Tautomers rates

Kinetic data for the reaction of [U02] + with thenoyltrifluoroacetone are consistent with a scheme involving attack by only the enol tautomer rate constants for protonated and deprotonated forms are > 1 x 10 and > 3 x 10 1 mol s , respectively. The reactions of molybdate and tungstate with a series of catechol derivatives have been studied by the stopped-flow method in all cases a rather complex picture was observed. 

Compounds of types (286) and (287) are in tautomeric equilibria with 4- or 5-hydroxyazoles. However, the non-aromatic form is sometimes by far the most stable. Thus oxazolinone derivatives of type (287) have been obtained as optically active forms they undergo racemization at measurable rates with nucleophiles (77AHC(21)175). Reactions of these derivatives are considered under the aromatic tautomer. 

In a neutral azole, the apparent rate of formation of an A-substituted derivative depends on the rate of reaction of a given tautomer and on the tautomeric equilibrium constant. For example, with a 3(5)-substituted pyrazole such as (199), which exists as a mixture of two tautomers (199a) and (199b) in equilibrium, the product composition [(200)]/[(201)] is a function of the rate constants Ha and fcs, as well as of the composition of the tautomeric mixture (Scheme 16) <76AHC(Si)l). 

Annular tautomerism does not occur in isothiazoles or benzisothiazoles. Substituent tautomers can sometimes be distinguished by chemical methods, but it is important that reaction mechanisms and the relative rates of interconversion of tautomeric starting materials or isomeric reaction products are carefully investigated. Physical methods only will be considered in this section, and references to original publications can be found in a comprehensive review (76AHC(S1)1). 

Interconversion between two tautomeric structures can occur via discrete cationic or anionic intermediates (scheme 24, where T is an anion capable of reacting with a proton at a minimum of two distinct sites). Alternatively, interconversion can occur by simultaneous loss and gain of different protons (scheme 25, w here T has the same definition as in scheme 24). These mechanisms are well established for acyclic compounds, but they have been much less thoroughly investigated for heteroaromatic systems. The rate of interconversion of two tautomers is greatest when both of the alternative atoms to which the mobile proton can be attached arc hetero atoms, and isolation of the separate isomers is usually impossible in this case. If one of the alternative atoms involved in the tautomerization is carbon, the rate of interconversion is somewhat slower, but still fast. When both of the atoms in question are carbon, however, interconversion is... 

Methods of the first type have been used for both qualitative and quantitative investigation. An important limitation is that the rates of interconversion of the tautomeric forms must be small as compared with those of the test reaction (s). The method is further complicated since the test reactions are sometimes complex and it is difficult to be certain that only one tautomer is reacting. An even more fundamental objection is that much chemical evidence is based on incorrect reaction mechanisms. Thus, the formation of condensation products (30) with aldehydes has repeatedly been quoted as evidence for structures of type 31 and against type 32,. whereas if 31 does react with an aldehyde it must either first tautomerize to 32 or ionize to 33. 

Although not a heteroaromatic compound, the case of citrinin studied by Destro and Luz ([97JPC(A)5097] and references therein) is so significant that it deserves mention here. Citrinin exists in the crystal as a mixture of the p-quinone 5a and o-quinone 5b tautomers (Scheme 3). The equilibrium ii temperature dependent and by using CPMAS NMR (Section VI,F) and, more remarkably. X-ray crystallography, the authors were able to determine the AH and AS values (the rate is extremely fast on the NMR time scale, >10 s ). 

Tile data on H- and C-cliemical shifts, H-relaxation rates, and protonation for 2-arylimidazo[l,2- ]imidazoles (107) and their methyl derivatives 108 and 109 indicate that 107 exists predominantly as the 1/7 tautomer 107a in CDCI3 and as the IH tautomer 107b in DMSO-dg or CD3OD-D2O (91MRC1147). An X-ray crystallographic study has demonstrated the IH tautomer 107a in the lattice. 

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. 

Tautomers are defined as isomers which are readily interconvertible. It is clear that the distinction between tautomerism and ordinary isomerism is very vague indeed, and that it depends on the interpretation of the adverb readily. It is customary to designate as tautomers those isomers whose half-lives (with respect to interconversion) are under ordinary circumstances less than the times required for laboratory operations to be carried out (some minutes or hours), so that the separation of the isomers from the equilibrium mixtures is difficult. The distinction between tautomers and ordinary isomers has no molecular significance whatever, since it is dependent on the accidental ordinary rate of human activity. 

Seminal studies on the dynamics of proton transfer in the triplet manifold have been performed on HBO [109]. It was found that in the triplet states of HBO, the proton transfer between the enol and keto tautomers is reversible because the two (enol and keto) triplet states are accidentally isoenergetic. In addition, the rate constant is as slow as milliseconds at 100 K. The results of much slower proton transfer dynamics in the triplet manifold are consistent with the earlier summarization of ESIPT molecules. Based on the steady-state absorption and emission spectroscopy, the changes of pKa between the ground and excited states, and hence the thermodynamics of ESIPT, can be deduced by a Forster cycle [65]. Accordingly, compared to the pKa in the ground state, the decrease of pKa in the... 

Quinolizine exists as a mixture of up to three species, namely the 2H-, 4H- and 9a/7-tautomers (17 and 18, respectively). This tautomeric equilibrium has been extensively studied in the case of tetramethyl quinolizine-1,2,3,4-tetracarboxylate, where, as previously mentioned, the 4/7-tautomer 17 has been shown to be thermodynamically more stable than the 9/7-species 18 through ab initio Hartree-Fock calculations. An interesting feature of these compounds is that the rate of the interconversion of the 9a//-tautomer 18 into the more stable 4//-cornpound 17 depends on the position of substituents in ring B <2003JST651>. 

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