Kinetic isotope effects variation with

The kinetics and mechanism of the aminolysis of phenyl-substituted phenyl phosphonyl chlorides (136) with anilines (135) were investigated in MeCN at 55.0 °C. Very sensitive variation of /Oy(5/Oy2>0) with the change of substituent on the nucleophile Sax) led to a large negative cross-interaction constant, pxY = Spy)/ Sox) = —1.31. The secondary kinetic isotope effects observed with deuteriated aniline nucleophiles were of the inverse type (/th/ d = 0.61-0.87), and small A// (1.6-9.7kcalmor ) and large negative A5 (—43 to —65 e.u.) values were... 

The kinetics of the decarboxylation of anthranilic acid have recently been examined. Earlier, an investigation of the decarboxylation of anthranilic acid in aqueous or acidic solution at 100 °C gave a C12 C13 value of 108.02 after 72 % reaction in 1.0 M sulphuric acid compared with 108.5 from complete decarboxylation, so that there is virtually no kinetic isotope effect for this compound646. First-order rate coefficients are given in Table 218 and from the variation of rate... 

Abstract Some of the successes and several of the inadequacies of transition state theory (TST) as applied to kinetic isotope effects are briefly discussed. Corrections for quantum mechanical tunneling are introduced. The bulk of the chapter, however, deals with the more sophisticated approach known as variational transition state theory (VTST). 

In the earliest work, Krouse and Thode (1962) found the Se isotope fractionation factor Sse(iv)-se(o) to bc 10%o ( l%o) with hydroxylamine (NH2OH) as the reductant. Rees and Thode (1966) obtained a larger value, 12.8%o, for reduction by ascorbic acid. Webster (1972) later obtained 10%o for NHjOH reduction. Rashid and Krouse (1985) completed a more detailed study, and found that the fractionation factor varied with time over the course of the experiments. They explained the variations observed among the experiments in all four studies using a model in which reduction consists of two steps. With the rate constant of the second step two orders of magnitude smaller than the first, and kinetic isotope effects of 4.8%o and 13.2%o for the hrst and second steps, respectively, all the data (Table 3) were fit. Thus, kinetic isotope effects of apparently simple abiotic reactions can depend on reaction conditions. 

Hammett relations, secondary kinetic isotope effects ", pressure studies and viscosity-independent rates ° have all pointed to a two-bond homolysis taking place via TS 3. The rates are, however, insensitive to change of the solvents = —1.18 in CDCI3, p+ = —1.17 in CCLt and p+ = —1.0 in C6H5CI at 80 °C). This may indicate that there is little solvent interaction taking place via 3. The variation of the activation parameters with the substituent can be solely dependent on the formation and cleavage of the bonds a and b in 3. 

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. 

In eqn. (54),feapp was considered to be a constant. In the determination of apparent activation energies and kinetic isotope effects, it is the variations in feapp as reflected in variations in vc with temperature or isotopic substitution while the concentrations are held constant that must be determined. The appropriate relationship becomes... 

Kinetic isotope effects (KIE) of silylene insertion reactions were determined in solution as well as in the gas phase. Steele and Weber39 found KIEs between 1.8 and 2.3 for the insertion of silylene 13 into various alcohols no significant variation of these values was observed with a change of solvent from cyclohexane to THF. These results are consistent with two mechanisms (Scheme 8), both of them proceeding via a nonlinear or triangular transition state. Mechanism B, which is favored over mechanism A by the authors, is in agreement with theoretical results, which, in general,... 

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... 

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... 

Fio. 1. Variation of the kinetic isotope effect with substituents of phenol in hydrogen atom abstraction bypolyvinyl acetate radicals. The straight line represents equation (25). Key Nos. 25-30 in Table 2. o Nos. 31 and 32 in Table 2. A No. 33 in Table 2. 

We have told you what sorts of starting materials and conditions favour El or E2 reactions, but we haven t told you how we know this. El and E2 differ in the order of their rate equations with respect to th.e base, so one way of finding out if a reaction is El or E 2 is to plot a graph of the variation of rate with base concentration. But this can be difficult with El reactions because the base (which need be only very weak) is usually the solvent. More detailed evidence for the differences between reaction mechanisms comes from studying the rates of elimination in substrates that differ only in that one or more of the protons have been replaced by deuterium atoms. These differences are known as kinetic isotope effects. 

Experimental data on primary and secondary kinetic isotope effects in the hydride-transfer step in liver alcohol dehydrogenase, LADH, were analyzed using canonical variational transition theory (CVT) for overbarrier dynamics and the optimized multidimentional path (OMT) for the nuclear tunneling (Alhambra et al., 2000 and references therein). This work demonstrates somewhat better agreement of theoretical values of primary and secondary Schaad- Swein exponents calculated by combining CVT/OMT methods with the experimental values instead of CVT and classical transition states (TST). 

H2/D2 exchange involves type (/) species, but their exact role is still under debate. A kinetic isotope effect operates such that HD is produced — 1.5 times faster from a 2H2 D2 mixture than from a H2 2D2 mixture. Naito et al favour an Eley-Rideal mechanism at 200 K involving a gas-phase molecule and a type (/) chemisorbed atom. Kokes et a/. initially favoured a similar mechanism involving a type Hi) chemisorbed molecule instead of one in the gas phase. However, in a later paper they show that type Hi) species are only important in allotropic ortho-para) conversion and that the exchange reaction involves a Bonhoeffer-Farkas mechanism, using type (/) adatoms, at all temperatures. Richard et al., on the basis of the variation of the first-order rate constant with pressure, deduced that the mechanism must involve atomic H on surface pair sites that most probably were adjacent ion pairs thus, a Rideal type of mechanism was favoured. 

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