Secondary isotope effects proton transfer

Isotope effect between the HH, HD, DH, and DD isotopomers was used as an important tool to determine the mechanism of the double-proton transfer. For concerted degenerate double-proton transfers in the absence of tunneling, the rule of the geometrical mean (RGM) should hold in good approximation, which states that /chh/ hd = /cdh/ dd-Tunneling may lead to a breakdown of this rule but the relation /chh > hd = dh > dd should remain valid. In the absence of secondary isotope effects the relation /chh HD = DH = 2 /cdd sliould liold for a stepwise pathway, even if tunneling is involved. 

The secondary isotope effects, (fcH/fcD)n, can be defined as all the kinetic isotope effects other than that associated with the transferring proton and is mathematically given by equation (16). They are also... 

In a hydronium ion catalyzed reaction with rate-determining proton transfer, we have to consider an additional secondary isotope effect referring to the two OH(OD) bonds of H30+(D30+) which are not broken. As the zero point energy per OH bond is higher for water than for hydronium ion [97, 98], the contribution of the secondary isotope effect to the experimental value of fcH/fcD must be smaller than 1 [99]. Accordingly, the range of expected values of fcH/fcn for rate-determining proton transfer from H30+ extends from ca. 0.8 to ca. 9. 

If secondary isotope effects are neglected, the ratio ky k can be estimated as 8.9 from the zero-point energies of the N-H and N-D bonds if we assume a linear transition state for proton transfer [28, 51 ]. and kjk y can then be used to estimate F = 0.63 [46]. At 263 K, a temperature at which both A j. and were measured, this gives k = 2.7 x 10 M s and p = 2.8 x 10" M s [46]. On this basis hydride protonation is ten times faster than metal protonation, thus the kinetic site of protonation of 3 is the hydride ligand [46]. 

Secondary isotope effects (15) and nmr evidence (16) clearly show that a C—O bond scission occurs during the acid hydrolysis of oxathiolanes. Proton-transfer rates for acidic alcohols are several orders of magnitude higher than those for the corresponding thiols (17). These species-specific interactions are in good agreement with the HSAB dictum. 

The interpretation of solvent isotope effects can be complicated by the large number of secondary isotope effects that can conceivably operate when it is the solvent molecule that is the site of isotopic substitution. The quantitative evaluation of solvent isotope effects is a very difficult problem. The relationship between the magnitude of the solvent isotope effect and the occurrence of equilibrium protonation as opposed to rate-limiting proton transfer is sufficiently general to be of significant value in mechanistic studies. As with nearly all mechanistic criteria, however, there are circumstances that permit exceptions, so corroborating evidence obtained from other types of studies is always desirable. 

Saunders, W. H., Jr. "Contribution of Tunneling to Secondary Isotope Effects in Proton-Transfer Reactions." /. Am. Chem. Soc., 106, 2223 (1984). 

The secondary isotope effect on proton transfer from the hydronium ion, (kH30+AD30+)ii. is the most frequent source of isotopic exponents of this kind. As shown in equation 7, removal of a proton from HjO converts the two non-reacting bonds of this species into O—H bonds of water the limiting value of this isotope effect may therefore be expressed in terms of /, the known D-H fractionation factor of the hydronium ion [/ = (D/H)h,d i i ,y(D/H),, ], as This leads to the relationship a, = [log(kH3oAkDjo0ii]/[log(P)]. This expression... 

A further method for obtaining Bronsted exponents is to compare kinetic and equilibrium acidities for proton transfers from the isotopic bases HjO and D2O [5, 76, 77]. This involves measurement of the secondary isotope effects in reactions of the type... 

The secondary Hke/T H KIE in the eliminations of 373, 374 and 375 presented above which are higher than this maximum possible secondary IE value, are taken as strongly implicating tunnelling. This conclusion has been supported also by intercomparison of secondary H/T and D/T isotope effects in E2 reactions of RNM3 1 Br at 50 °C. The secondary IE is depressed markedly when deuterium rather than proton is transferred, which also implicates tunnelling ... 

The ratio k r/k2 is the ratio of the rate of H versus T removal from the intermediate together with a small secondary effect which arises because for fe, and k2 different isotopes (tritium and hydrogen, respectively) remain attached to the carbon from which hydrogen and tritium are removed. The value of k j /k2 can be estimated and therefore the rate of proton transfer to the aromatic molecule (fej) can be calculated from the... 

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