Isotope effects normal

Fig. 10. Isotope effect Normalized concentration mode for mixtures of protonated (C6H6) and deuterated (C6D6) benzene with cyclohexane (C6H12) at c 0.5. Also shown is the signal for pure dyed cyclohexane...

Deuterium isotope effect normal (Aih > kp) shows GA/BC, inverse solvent k(D20) > k(H20) shows SA/BC... 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

Predict whether normal or inverse isotope effects will be observed for each reaction below. Explain. Indicate any reactions in which you would expect > 2. The isotopically substituted hydrogens are marked with asterisks. 

Values of kH olki3. o tend to fall in the range 0.5 to 6. The direction of the effect, whether normal or inverse, can often be accounted for by combining a model of the transition state with vibrational frequencies, although quantitative calculation is not reliable. Because of the difficulty in applying rigorous theory to the solvent isotope effect, a phenomenological approach has been developed. We define <[), to be the ratio of D to H in site 1 of a reactant relative to the ratio of D to H in a solvent site. That is. 

It is apparent from equation (16) that if k x becomes much larger than k 2, the rate will depend upon k 2 and so a kinetic isotope effect will be observed. Now kL j will become large if there is steric hindrance to formation of the intermediate, and a number of examples are now known where an electrophile which normally gives no isotope effect, does so if formation of the intermediate is hindered. 

A small isotope effect has been observed in nitration of benzene by nitronium borofluoride in tetramethylene sulphone at 30 °C (kH/kD = 0.86) and this has been attributed to a secondary effect of the change in hybridisation from sp2 to sp3 of the ring carbon during the course of the reaction109. However, naphthalene gives an isotope effect of 1.15 under the same conditions, and anthracene a value of 2.6115. It does not seem at all clear why these relatively unhindered and normally more reactive molecules should give rise to an isotope effect when benzene does not. 

There is one further piece of kinetic evidence which throws light on an aspect of the benzidine rearrangement mechanism, and this is comparison of the rates of reaction of ring-deuterated substrates with the normal H compounds. If the final proton-loss from the benzene rings is in any way rate-determining then substitution of D for H would result in a primary isotope effect with kD < kH. This aspect has been examined in detail42 for two substrates, hydrazobenzene itself where second-order acid dependence is found and l,l -hydrazonaphthalene where the acid dependence is first-order. The results are given in Tables 2 and 3. 

One further approach, which has not properly been explored, is based upon the axiom of Harbottle s (29) that if an isotopic difference is found, there must have been little reaction subsequent to the initial hot stage. That is, these subsequent reactions are expected to be normal chemical reactions with essentially no isotopic preference, such that any such reaction would tend to wash out possible isotope effects. This problem is worth pursuing further, since some isotopic effects have been observed where subsequent exchange is to be expected. 

The effect of solvent upon k2 has been reported , and it was concluded that the activated complex is not sufficiently polar to be called ionic . The oxidations of toluene and triphenylmethane exhibit primary kinetic deuterium isotope effects of 2.4 and ca. 4 respectively. No isotopic mixing occurred during formation of the Etard complex from a mixture of normal and deuterated o-nitrotoluene . The chromyl chloride oxidation of a series of substituted diphenylmethanes revealed that electron-withdrawing substituents slow reaction while electronreleasing groups have the opposite effect, the values ofp andp being —2.28 + 0.08 and —2.20 + 0.07 respectively . ... 

These results do not prove that the ester is an essential intermediate in aqueous solution even though it is present, but the result with the hindred triterpene is convincing In this case the esterification step, which is normally fast, has become rate-determining and the disappearance of the isotope effect must mean that C-H cleavage occurs after the formation of the ester and not independently of it. The generality of this result is apparent from the stopped-flow investigation of isopropanol oxidation ... 

Interestingly, in a comparison of the CD3 and CHj carbenes, an unusual temperature dependence of the kinetic isotope effect was observed. In contrast to typical reactions, the ratio of rates of H versus D shift, k /ko, actually increased as temperature was raised. In fact, k was measured to be larger than k at 248 K. It was suggested that these results required a normal temperature dependence of the isotope effect for the classical component of the reaction, but an unusual diminished isotope effect for the QMT reaction. 

Product analysis by NMR indicated an isotope effect at 118°C of = 2.14, corrected for numbers of H versus D. On lowering the temperature to -12°C, however, it was found that the isotope effect increased to 3.25. Referring to earlier experimental results on the C-H shift in methylchlorocarbene, " the authors cited the normal temperature dependence of the isotope effect as evidence against tunneling in 64. In retrospect, however, as noted above, theoretical support for an atypical inverse temperature dependence in methylchlorocarbene has been refuted. Hence, the involvement of tunneling in 62/64 at ambient temperatures is still an open question. 

Kinetic isotope effects have not been observed for chlorination, and only rarely for bromination, i.e. the reactions normally follow pathway [2a] like nitration. In iodination, which only takes place with iodine itself on activated species, kinetic isotope effects are the rule. This presumably arises because the reaction is readily reversible (unlike other halogenations), loss of I occurring more often from the a complex (14) than loss of H, i.e. k, > k2 ... 

Figure 18 shows the spectrum of C3D6 in the CH deformation region. We would expect the normal isotope effect to shift C—D deformations about 400 cm-1, that is, completely out of this region. Thus, the observed bands are due to C—C vibrations. The band at 1473 cm-1 (with a shoulder at 1460 cm-1) can only correspond to the 1545 cm-1 band in C3H6. The... 

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