Theoretical studies kinetic isotope effects

The use of reduced isotopic partition function ratios to study kinetic isotope effects was first undertaken by Bigeleisen this work was corrected and elaborated by Bigeleisen and Wolfsberg. References are cited at the end of this chapter. Application of the equations developed above to specific chemical reactions will be found in Chapter 10, where other theoretical approaches will also be presented. 

In a separate study, kinetic isotope effects were determined for the individual steps in methane loss from tungstanocene methyl hydride. These results were combined with theoretical studies that produced a complete picture for understanding isotope effects in terms of the contributing factors (zero point energy, mass moment of inertia, and excitation terms). The conclusion was that it is possible to observe either inverse or normal isotope effects, depending on the temperature at which the study is conducted. ... 

Most of the chemical reactions presented in this book have been studied in homogeneous solutions. This chapter presents a conceptual and theoretical framework for these processes. Some of the matters involve principles, such as diffusion-controlled rates and applications of TST to questions of solvent effects on reactivity. Others have practical components as well, especially those dealing with salt effects and kinetic isotope effects. 

More recent theoretical work has raised questions about these conclusions, how-ever. Particularly extensive calculational treatment of the rearrangement of 54 to vinyl chloride by several research groups failed to duplicate the predictions of an atypical kinetic isotope effect. These later studies indicate that tunneling effects should indeed be greater for H-shift than for the heavier D rearrangement. Consequently, the k /ko ratio should actually decrease at higher temperatures. The discrepancy in predicted results was eventually traced to an error in the earlier calculations. Nevertheless, it... 

Further evidence for the Aa11 mechanism was obtained from a solvent kinetic isotope study. The theoretical kinetic isotope effects for intermediates in the three reaction pathways as derived from fractionation factors are indicated in parentheses in Scheme 6.143,144 For the Aa11 mechanism (pathway (iii)) a solvent KIE (/ch2o A d2o) between 0.48 and 0.33 is predicted while both bimolecular processes (pathways (i) and (ii)) would have greater values of between 0.48 and 0.69. Acid-catalysed hydrolysis of ethylene oxide derivatives and acetals, which follow an A1 mechanism, display KIEs in the region of 0.5 or less while normal acid-catalysed ester hydrolyses (AAc2 mechanism) have values between 0.6 and 0.7.145,146... 

Table 3 collects the results obtained by different authors on the reaction of 0s04(NH3) with ethylene. Though the methods were not identical, the results are very similar, and in all cases there is a clear preference of the [3+2] over the [2+2] pathway. Additional confirmation was provided by a combined experimental and theoretical study using kinetic isotope effects (KIEs) to compare experiment and theory. Kinetic isotope effects were measured by a new NMR technique [25] and compared to values, which are available from calculated transition states. It showed that indeed only the [3+2] pathway is feasible [10]. 

The Truhlar group has reported an interesting theoretical study of H/D kinetic isotope effects for conversion of 2 phospho-D-glycerate to phosophoenolpyruvate catalyzed by the yeast enolase enzyme. The proton transfer step (first reaction step in Fig. 11.10) is the rate limiting step and was chosen for theoretical study. The KIE for proton/deuteron transfer is kn/kD = 3.3 at 300 K. 

Two sources of mechanistic information, new analytical and new theoretical methods, have surfaced in the past several years. The former class includes new methods in the study of kinetic isotope effects, in NMR spectroscopy, and in X-ray... 

The reactions of A-phenyl a-r-butyl nitrone (PEN) with maleimides, maleic anhydride, and diethyl maleate have been studied by EPR and two types of spin adduct detected. They arise from the reductive addition of PEN to the alkenes and the degradation product of DEN (2-methyl-2-nitropropane). The deuterium and muonium kinetic isotope effects for the addition of the hydrogen atom to a variety of alkenes have been determined experimentally and theoretically. ... 

These results, as well as rate studies " and kinetic isotope effects ", support a concerted, 5ptra-structured oxenoid-type transition state for the CH oxidations". The original oxygen-rebound mechanism has been discounted (see the computational work in Section I.D). Recently, however, the stepwise radical mechanism was revived in terms of the so-called molecule-induced homolysis , but such radical-type reactivity was severely criticized on the basis of experimental" and theoretical grounds. 

The decarboxylation of 3-carboxybenzisoxazole (225 R = H, NO2) gives CO2 and (226). This reaction has been studied using 13C and 15N kinetic isotope effects.201 The isotope effects were modelled theoretically at the semiempirical and ab initio levels, but comparison of experimental and theoretical results shows that die former cannot be successfidly predicted by theory at the level of calculation employed. The kinetics of decarboxylation and deamination of DL-leucine by acidic permanganate in die presence of silver ion in moderately concentrated sulfuric acid is a two-stage process.202 The... 

Today, the perepoxide intermediate proposed earlier by Sharp [35] seems to be the most popular mechanism that found support from results derived from kinetic isotope effects, stereochemical studies, trapping experiments [36-38], and theoretical calculations [39 43],... 

A new study has been reported of the hydrolysis of the p-tolyldiazonium cation using a combination of carbon kinetic isotope effects, theoretical calculations, and dynamics trajectories. Overall, the results are in best accord with a process at the boundary between. S N 1 and. S N2Ar mechanisms.1 There has been a kinetic study of the thermolysis of o-carboxybenzenediazonium fluoride to give o-fluorobenzoic acid in liquid hydrogen fluoride under pressure.2... 

Experimental and theoretical studies with 13C kinetic isotope effects have revealed that the C-C bond formation is the rate-determining step of the 1,6-cuprate additions to 2-en-4-ynoates.147 The reaction intermediates have been determined and the calculated activation barrier for the transition state was found to be in good agreement with the experimental value. 

The mechanism and kinetic aspects of the retro-ene reaction of the allyl n-propyl sulfide and its deuterated derivatives have been studied using four different types of DFT methods with eight different levels of the basis sets.7 The mechanistic studies revealed that the reaction proceeds through an asynchronous concerted mechanism. Theoretical calculations have indicated that the reaction displays a kinetic isotope effect of 2.86 at 550.65 K. 

The mechanism of cyclopropenations of alkynes with ethyl diazoacetate, catalysed by (AcO)4Rh2 and (DPTI)3Rh2(OAc), has been studied by a combination of kinetic isotope effects and theoretical calculations. With each catalyst, a significant normal 13C KIE was observed for the terminal acetylenic carbon, while a very small 13C KIE was detected at the internal acetylenic carbon. These isotope effects are consistent with the canonical variational transition structures for cyclopropenations with intact tetrabridged rhodium carbenoids but not with a 2 + 2-cycloaddition on a tribridged rhodium carbenoid structure.99... 

A study of kinetic isotope effects, theoretical calculations, and dynamic trajectories of the C(2)-C(6) (Schmittel)/ene cyclization of enyne-allenes has been reported.178 For (74), the isotope effect l=h/ l=d = 1-43 is consistent with a highly asynchronous... 

A concerted, spiro-structured, oxenoid-type transition state has been proposed for C-H oxidation by dioxiranes (Scheme 5). This mechanism is based mainly on the stereoselective retention of configuration at the oxidized C-H bond [20-22], but also kinetic studies [29], kinetic isotopic effects [24], and high-level computational work support the spiro-configured transition structure [30-32], The originally proposed oxygen-rebound mechanism [24, 33] was recently revived in the form of so-called molecule-induced homolysis [34, 35] however, such a radical-type process has been experimentally [36] and theoretically [30] rigorously discounted. 

Theoretical studies of the microsolvation effect on SN2 reactions have also been reported by our coworkers and ourselves (Gonzalez-Lafont et al. 1991 Truhlar et al. 1992 Tucker and Truhlar 1990 Zhao et al. 1991b, 1992). Two approaches were used for interfacing electronic structure calculations with variational transitional state theory (VST) and tunneling calculations. We analyzed both the detailed dynamics of microsolvation and also its macroscopic consequences (rate coefficient values and kinetic isotope effects and their temperature... 

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