Kinetic isotope effects of deuterium

Kinetic isotope effects of deuterium ( h/ d) n the dehydration of 2-propanol on various catalysts at 300°C [123]... 

Warshel, a., Bromberg, A., Oxidation of 4a,4b-Dihydrophenanthrenes. III. A Theoretical Study of the Large Kinetic Isotope Effects of Deuterium in the Initiation Step of the Thermal Reaction With Oxygen, J. Chem. Phys. 1970, 52, 1262. 

Dilsopinocampheylborane derivatives continue to be attractive as reagents for enantloselective processes. Studies on the secondary kinetic isotope effect of deuterium on enantioselective hydroborations with (+)(Ipc)2BH have provided significant experimental evidence which provides a test for any detailed explanation of the process. The reagent has been used in a systematic study with representative heterocycles bearing an endocycllc double bond in order to establish the asymmetric induction achieved. It turns out that the reaction provides a simple and efficient method of synthesising heterocyclic boronates... 

The lighter the element, the larger is the ratio of the heavy and the light isotope masses. Thus, the ratio of deuterium and hydrogen masses is 2/1, and that of sulfur-34 and sulfur-32 is 34/32 = 1.0625. This is why the primary kinetic isotope effect of deuterium is relatively high compared to that of sul-fur-34. Consequently, the lowering of the zero-point energies is... 

It is clear from the results that there is no kinetic isotope effect when deuterium is substituted for hydrogen in various positions in hydrazobenzene and 1,1 -hydrazonaphthalene. This means that the final removal of hydrogen ions from the aromatic rings (which is assisted either by the solvent or anionic base) in a positively charged intermediate or in a concerted process, is not rate-determining (cf. most electrophilic aromatic substitution reactions47). The product distribution... 

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

The first term was found to correspond to the rate of enolisation (measured by an NMR study of hydrogen-deuterium exchange at the methylene group). The second term predominates at [Cu(II)] > 10 M and is characterised by a primary kinetic isotope effect of 7.4 (25 °C) and a p value of 1.24. Addition of 2,2 -bipridyl (bipy) caused an increase in 2 up to a bipy Cu(II) ratio of 1 1 but at ratios greater than this 2 fell gradually until the enolisation term dominated. The oxidation of a-methoxyacetophenone is much slower but gives a similar rate... 

Based on C-H versus C-D zero point vibrational differences, the authors estimated maximum classical kinetic isotope effects of 17, 53, and 260 for h/ d at -30, -100, and -150°C, respectively. In contrast, ratios of 80,1400, and 13,000 were measured experimentally at those temperatures. Based on the temperature dependence of the atom transfers, the difference in activation energies for H- versus D-abstraction was found to be significantly greater than the theoretical difference of 1.3kcal/mol. These results clearly reflected the smaller tunneling probability of the heavier deuterium atom. 

Three mechanisms have been proposed for this reaction (Scheme 21). The reaction is first order in each of the reactants. In another study, Reutov and coworkers159 found a large primary hydrogen-deuterium kinetic isotope effect of 3.8 for the reaction of tri-(para-methylphenyl)methyl carbocation with tetrabutyltin. This isotope effect clearly demonstrates that the hydride ion is transferred in the slow step of the reaction. This means that the first step must be rate-determining if the reaction proceeds by either of the stepwise mechanisms in Scheme 21. The primary hydrogen-deuterium kinetic isotope effect is, of course, consistent with the concerted mechanism shown in Scheme 21. 

The primary hydrogen-deuterium kinetic isotope effect for the reaction was 3.7 and the secondary alpha-deuterium kinetic isotope effect was found to be 1.1. It is worth noting that the primary hydrogen-deuterium kinetic isotope effect of 3.7 is in excellent agreement... 

Song and Beak found intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects of 1.1 0.2 and 1.2 0.1, respectively, for the tin tetrachloride catalysed ene reaction. Since significant intramolecular and intermolecular primary deuterium kinetic isotope effects of between two and three have been found for other concerted ene addition reactions161, the tin-catalysed reaction must proceed by the stepwise pathway with the k rate determining step (equation 107). 

This method gave a primary hydrogen-deuterium kinetic isotope effect of 1.3 for the reaction between the aryl radical and tributyltin hydride. This isotope effect is smaller than the isotope effect of 1.9 which San Filippo and coworkers reported for the reaction between the less reactive alkyl radicals and tributyltin hydride163 (vide infra). The smaller isotope effect of 1.3 in the aryl radical reaction is reasonable, because an earlier transition state with less hydrogen transfer, and therefore a smaller isotope effect164, should be observed for the reaction with the more reactive aryl radicals. 

Other primary hydrogen-deuterium kinetic isotope effects have been measured for radical reactions with tributyltin hydride. For example, Carlsson and Ingold167 found primary hydrogen-deuterium kinetic isotope effects of 2.7 and 2.8, respectively, for the... 

The third equation in Equation 11.47 represents a kinetic isotope effect of the first isotopomer pair measured in the presence of the second (which IE has perturbed the commitment). In order to make the changes in apparent commitment (cf/H2k3) sufficiently pronounced, deuterium is usually selected as the second isotope (H2). The first, (HI), on the other hand, is usually a heavy-atom (e.g. 13C, lsO, etc.). Most frequently this approach has been used for carbon kinetic isotope effects in which case Equation 11.47 becomes ... 

Alhambra and co-workers adopted a QM/MM strategy to better understand quantum mechanical effects, and particularly the influence of tunneling, on the observed primary kinetic isotope effect of 3.3 in this system (that is, the reaction proceeds 3.3 times more slowly when the hydrogen isotope at C-2 is deuterium instead of protium). In order to carry out their analysis they combined fully classical MD trajectories with QM/MM modeling and analysis using variational transition-state theory. Kinetic isotope effects (KIEs), tunneling, and variational transition state theory are discussed in detail in Chapter 15 - we will not explore these topics in any particular depth in this case study, but will focus primarily on the QM/MM protocol. 

Direct evidence about the first step of activation of butane was obtained on a V-P oxide catalyst in the butane oxidation to maleic anhydride based on deuterium kinetic isotope effect (34). It was found that when a butane molecule was labeled with deuterium at the second and third carbon, a deuterium kinetic isotope effect of 2 was observed. No kinetic isotope effect was observed, however, if the deuterium label was at the first or fourth carbon. By comparing the observed and theoretical kinetic isotope effects, it was concluded that the first step of butane activation on this catalyst was the cleavage of a secondary C—H bond, and this step was the rate-limiting step. 

Fomarini and colleagues gave also experimental evidence that in the reaction of trime-thylsilicenium ion with arenes, cr-complexes such as 54 are produced29-31. The kinetic isotope effect of the gas phase deprotonation reaction and specific deuterium labeling... 

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