Second-order kinetic isotope effects

SECOND-ORDER RATE COEFFICIENTS (Ar2) AND KINETIC ISOTOPE EFFECTS FOR REACTION... 

The reaction was second order in acid and first order in substrate, so both rearrangements and the disproportionation reaction proceed via the doubly-protonated hydrazobenzene intermediate formed in a rapid pre-equilibrium step. The nitrogen and carbon-13 kinetic isotope effects were measured to learn whether the slow step of each reaction was concerted or stepwise. The nitrogen and carbon-13 kinetic isotope effects were measured using whole-molecule isotope ratio mass spectrometry of the trifluoroacetyl derivatives of the amine products and by isotope ratio mass spectrometry on the nitrogen and carbon dioxide gases produced from the products. The carbon-12/carbon-14 isotope... 

In the remaining sections of this chapter we will discuss further examples of kinetic isotope effects. The first considers a system in which there is a competition between two mechanisms, Sn2 and E2 and returns to reaction 10.15. (By E2 we refer to a second order elimination reaction, see Fig. 10.6). In Equation 10.15 the hypochlorite... 

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 ... 

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. 

Oxidation of various alkylaromatics, including toluene, ethylbenzene, and cumene, by trans-[Ru (0)2(N202)] in MeCN also has large kinetic isotope effects k-alk-o = 16 for ethylbenzene), indicating C—bond cleavage in the transition state. The second-order rate constants for ethylbenzene and cumene are similar but are substantially higher than that for toluene. " Representative kinetic data for the oxidation of ethylbenzene, cumene, and toluene are collected in Table 10. 

A reaction described as Sn2, abbreviation for substitution, nucleophilic (bimolecular), is a one-step process, and no intermediate is formed. This reaction involves the so-called backside attack of a nucleophile Y on an electrophilic center RX, such that the reaction center the carbon or other atom attacked by the nucleophile) undergoes inversion of stereochemical configuration. In the transition-state nucleophile and exiphile (leaving group) reside at the reaction center. Aside from stereochemical issues, other evidence can be used to identify Sn2 reactions. First, because both nucleophile and substrate are involved in the rate-determining step, the reaction is second order overall rate = k[RX][Y]. Moreover, one can use kinetic isotope effects to distinguish SnI and Sn2 cases (See Kinetic Isotope Effects). 

The rate constant for the second order reaction was found to be at least two orders of magnitude greater than that for the corresponding Rh system. As with the corresponding Rh reaction, a modest kinetic isotope effect was observed when H-Mel was used, again consistent with an 5 2 mechanism for this step [33]. 

The reaction exhibited second-order kinetic isotope effects of h/ h = 1-32 for 115,... 

Second order reactions 458 Secondary kinetic isotope effect 592, 600 on fumarate hydratase 684 Secondary plots for kinetics of multisubstrate enzymes 465 Secondary structure 63... 

Hydration of several 1,2,3-triones including indane derivatives (70 Scheme 4) has been studied in dioxane-water mixtures.1053 Monohydration gives a 2,2-diol (71) forward rates and equilibrium constants have been measured over a wide range of solvent composition. Based on activation parameters, kinetic isotope effects, a Hammett treatment, and a second-order rate dependence on water, two water molecules are suggested to play distinct roles, one as nucleophile, the other as general acid-base, similar to dialdehydes.105b,c... 

The kinetics and the products of bromination of several substituted stilbenes with Bu4N+Br3 have been investigated in aprotic solvents at different temperatures and concentrations. Stilbenes bearing electron-withdrawing or moderately electron-donating substituents gave stereospecifically the anti addition products the reaction followed a second-order rate law and inverse kinetic isotope effect Ap/Ap = 0.85 ( 0.05) was... 

It had been established several decades ago that the reaction of 1-chloro-l-ni-troethane with sodium nitrite in aqueous-alcohol medium is second order overall and first order in each reactant (Hawthorne 1956). 1-Deutero-l-chloro-l-nitroethane reacts more slowly than its lighter isotopomer. This means that the kinetic isotopic effect is observed. The reaction proceeds only in moderately alkaline media in strongly alkaline media it does not take place. Only those geminal halo nitro compounds, which carry hydrogen in the geminal position, can undergo the conversion. Based on these facts, Hawthorne (1956) suggested the Sn2 substitution preceded by the isomerization of the initial substrate into the aci-nitro form ... 

Much effort has been devoted to the elucidation of the oxygenation mechanism (see reviews [8,9]). Extensive studies by Barton and coworkers led to the assumption that Gif chemistry was not a radical process. This assumption was based on two observations. First, in radical chemistry, the order of reactivity is C -H > Csec-H 3> Cprim-H, whereas in Gif systems, a significant preference for oxidation in the secondary position of the hydrocarbon was observed [10, 11] (Csec-H > C -H 3> Cprim-H). A second hint was the low kinetic isotope effect (about 2 for the ketone). Both findings were combined to the mechanism depicted in Scheme 3.2. 

Several reports deal with the action of heterocycle-chromate agents such as quinolin-ium dichromate on five-membered heteroaldehydes340 and quinolinium bromochromate on benzaldehydes,341,342 all in acetic acid solution. The latter studies show a second-order dependence on proton concentration, acceleration by electron-withdrawing para-substituents, and a substantial kinetic isotope effect for the deuterated aldehyde. 

A second-order dependence on both the reductant and acidity was observed in the oxidation of alcohols with butyltriphenylphosphonium dichromate study of MeCD2OH and Me2CDOH indicated the presence of a substantial kinetic isotope effect. The reaction was studied in 19 organic solvents and the rates were correlated with mul-tiparametric equations. The reaction is susceptible to both electronic and steric effects of the substituents. A mechanism involving the formation of a dichromate ester and an a-C-H cleavage has been proposed.4... 

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