Isotope exchange, rate, with carbanions

Kinetic Acidities in the Condensed Phase. For very weak acids, it is not always possible to establish proton-transfer equilibria in solution because the carbanions are too basic to be stable in the solvent system or the rate of establishing the equilibrium is too slow. In these cases, workers have turned to kinetic methods that rely on the assumption of a Brpnsted correlation between the rate of proton transfer and the acidity of the hydrocarbon. In other words, log k for isotope exchange is linearly related to the pK of the hydrocarbon (Eq. 13). The a value takes into account the fact that factors that stabilize a carbanion generally are only partially realized at the transition state for proton transfer (there is only partial charge development at that point) so the rate is less sensitive to structural effects than the pAT. As a result, a values are expected to be between zero and one. Once the correlation in Eq. 13 is established for species of known pK, the relationship can be used with kinetic data to extrapolate to values for species of unknown pAT. 

Two explanations were originally put forward to account for the asymmetry of sulphonyl carbanions. In the first [146] it was assumed that the carbanion is sp3 hybridized and pyramidal, for example, as shown in (XI) and (XII) and that the rate of pyramidal inversion was slower than the rate of protonation. This would explain why isotope exchange occurs more rapidly than loss of optical activity. An alternative explanation has been suggested in which the carbanion is assumed to be planar and sp2 hybridized. Overlap between the p-orbital with its pair of electrons and sulphur d-orbitals may be involved. A symmetric structure like (XIV) will not explain the results but an asymmetric structure (XIIII) in which asymmetry results from restricted rotation about the carbon—sulphur bond has been proposed [148]. Further, the kinetic results require that de-deuteration or protonation must occur preferentially from one side of... 

Now, in these elimination reactions, the reactivity of alkyl halides follows the same sequence as for substitution—and with element effects of just about the same size. Clearly, the rate of breaking the carbon halogen bond does affect the overall rate of reaction. On this evidence, if carbanions were formed, they carbanion formation has been ruled out by the absence of isotopic exchange. 

When the acidities of hydrocarbons are compared in terms of the relative stabilities of neutral and anionic forms, the appropriate data are equilibrium acidity measurements, which relate directly to the relative stability of the neutral and anionic species. For compounds with pA > 35, it is difficult to obtain equilibrium data. In such cases, it may be possible to compare the rates of deprotonation, i.e., the kinetic acidity. These comparisons can be made between different protons in the same compound or between two different compounds by following an isotopic exchange. In the presence of a deuterated solvent, the rate of incorporation of deuterium is a measure of the rate of carbanion formation. Tritium ( H)-NMR spectroscopy is also a sensitive method for direct measurement of kinetic acidity. ... 

The a-secondary IE of two deuteriums on the rate of base-catalyzed CD exchange of toluene, 3A ( PhC112D)/k(PhCD is 1.31, and the [3-secondary D IE on the rate of base-catalyzed a-C-D exchange of ethylbenzene, k(PhCHDCH3)//t(PhCHDCD3), is 1.11 0.03.58 Similarly, from the rates of base-catalyzed a-C-D exchange of tolucne-a,4-r/2, -a,2,4,6-c/4, and -a,2,3,4,5,6-d6 and with an assumption of linearity of IEs, the contributions of ortho, meta, and para deuteration lead to rate retardations of 2.4, 0.4, and 1.8%, respectively.59 These are all kinetic IEs, but to the extent that the transition state resembles closely the carbanion, or to the extent that the reverse reprotonation is encounter-controlled and independent of isotopic substitution, these kinetic IEs represent equilibrium IEs on acidity. The IEs were interpreted in terms of an electron-donating inductive effect of D relative to H. 

Deuterium exchange with the solvent does occur during the reaction, but at a rather slow rate. A symmetrical reaction intermediate must exist, since the rate of incorporation of tritium from the solvent into D-madelate as the substrate yields equimolar amounts of D-and L-product [50]. Thus the data are consistent with the formation of an a-carbanion intermediate with an enzymatic base group acting as the proton acceptor [50]. The proton transfer has to be rate-limiting, as indicated by the approximately 5-fold primary isotope effect for deuterium. In the enzyme-substrate complex, the epimerization occurs with a rate constant of the order of 10 s ... 

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