Product isotope effects

The complexities associated with these reactions were also evident during an intrazeolite product isotope effect study of 2,2,6,6-tetradeutero-l,4-dithiane97 (Fig. 29). The absence of an isotope effect during oxidation with m-chloroperbenzoic is consistent with the lack of C-H(D) abstraction on the reaction surface. The substantial isotope effect of 1.15 + 0.02 for the reaction of singlet oxygen is consistent with the... 

Fig. 29 A comparison of product isotope effects in MCPBA and singlet oxygen reactions in solution and zeolite media.

Powell, M.F. and Bruice, T.C. (1983). Effect of isotope scrambling and tunneling on the kinetic and product isotope effects for reduced nicotinamide adenine dinucleotide model hydride transfer reactions. J. Am. Chem. Soc. 105, 7139-7149... 

The inverse of 1 has also been called the product isotope effect and designated by the symbol r (Gold and Kessick, 1964b, 1965a, b). Using equation (51) and the symbol r in place of f1, equation (50) now takes the form... 

The difference between product isotope effects (r) and rate isotope effects ( / ) was independently recognized by Kreevoy and Kretchmer (1964) and by Gold and Kessick (1964). Equation (52) has been used for predicting the dependence of kn on n for the hydration of isobutene (Gold and Kessick, 1965a, b). 

These results can be handled in several ways, according to the point of view adopted. Following Gold and Kessick (1965b), one can combine the product isotope effect with the rate isotope effect ksjkD and solve equation (54) for a without, if necessary, any reference to rate measurements in H20-D20 mixtures. A suitable adaptation of equation (54) is... 

As a mechanistic tool in the investigation of acid- or base-catalysed reactions in aqueous solution, the measurements in isotopically mixed solvents are most useful for reactions where a certain amount is already known about the mechanism. In particular, the study of mixed solvents is also a good deal more informative whenever it is possible to measure product isotope effects in addition to rate isotope effects. In such cases (and A-Sb2 reactions spring to mind as a good example) solvent isotope effect studies can add considerably to the detailed picture of a transition state. The phenomena are as yet less suited to the ah initio assignment of reaction mechanism, such as the decision between weak nucleophilic participation of water in an acid-catalysed reaction and an A-l mechanism, when no information beyond the kn-n relation is available. For these reasons it is likely that mechanistic investigation by this method will increasingly be directed towards systems where both rate and product isotope effects are obtainable. 

Kinetic and product isotope effect discrepancies 95 Oxidations by inorganic oxidants and quinones 95 Substituent effects on rates and equilibria 98 Miscellaneous reactions of dihydropyridines 101 Secondary hydrogen isotope effects 102 Theoretical studies 103 References 105... 

Deductions about the structure of the transition state are based on the measured values of and 02 and hence the kinetic study involves the determination of values for 0t and 02 and this can be achieved in three ways. If the kinetic data are sufficiently precise values of 0] and 02 may be obtained by fitting eqn. (127) to the experimental values of kn/k0 in different mixtures of H20 and D20 [47, 212(b)]. An alternative method involves measurement of the value of from the fraction of deuterium found in the product (product isotope effect). This method is applicable providing the product of reaction, and all intermediates along the reaction pathway after the transition state, do not exchange the proton at position 1 with solvent. If this is the case the fraction of D found in the product will be the same as the fraction of D in the transition state at position 1. This value of 4>i when combined with the rate ratio in H20 and D20 (128) will give a value for 02 [42, 47b, 122, 212(b)]. Thirdly a value for... 

The analysis of isotope effects to give an exponent cq is useful when a Bronsted exponent cannot be obtained by measuring catalytic coefficients for a series of acids. In the hydration of isobutene, general catalysis is unobservable and the reaction is dominated by hydronium ion catalysis. A value of j ca. 0.9 was obtained [44] from eqn. (135) by measuring solvent and product isotope effects. This result is of the expected size, as discussed in Sect. 4.7. 

Scheme 2.32, R = H, half-life 40 s at 39 °C). Cyclization is rate determining and the reaction is not buffer catalyzed) [67]. (The lO -fold greater electrophilic reactivity of the alkyne means that the steric acceleration provided by the orthomethyl groups in 4.2 is not needed in 4.3.) The solvent deuterium isotope effect knio/ko20 on the proton transfer step (derived from the product isotope effect) is... 

A key line of evidence for a multistep mechanism, as opposed to the one-step hydride-transfer mechanism, had been derived from isotope effects measured in reduction of various substrates with monodeuterated analogs of NADH. One can compare the observed rate constants kHH and kno, which in the case of negligible secondary isotope effects should obey the relationship koH/kHM = (1 + kro/kyi])/2, allowing the calculation of the primary isotope effect kn/ku (if undeuterated, monodeuterated and dideuterated hydride donors are all used, both primary and secondary isotope effects can be obtained). In addition, for an oxidizing agent Acceptor one can determine the isotope ratio in the product Acceptor-H/Acceptor-D, called in these studies the product isotope effect Th/Td-... 

Powell, M. F. Beuice, T. C. 1982 J. Am. Chem. Soc. 104, 5834-5836 Reinvestigation of NADH analog reactions in acetonitrile Consequences of isotope scrambling on kinetic and product isotope effects. 

As expected, the product ratios were quite different in acetonitrile and acetonitrile-ris. For example, the major products were diphenylmethane and benzophenone and only a small amount of benzophenone azine when the reaction was carried out in acetonitrile whereas the percentage of benzophenone azine was ten times larger, i.e. almost equal to the diphenylmethane when the solvent was acetonitrile-hydrogen-deuterium kinetic isotope effect in acetonitrile-ris slows the hydrogen abstraction reaction which leads to diphenylmethane. These product isotope effects are only consistent with the mechanism shown in equation 28 and clearly demonstrate that the radical anion does not decompose by losing nitrogen to form the carbene radical anion when diazoalkanes are reduced. 

Kumar D, de Visser SP, Shaik S (2003) How does product isotope effect prove the operation of a two-state rebound mechanism in C-H hydroxylation by cytochrome P450 JAm Chem Soc 125 13024—13025... 

The discrepancy between kinetic and product isotope effects reported by Ohno et al. (1981e) and believed to provide a proof for the three-step electron-proton-electron transfer mechanism was recently claimed by Powell and Bruice (1983). They found that isotopes scramble between the reactant and product in the acridinium /acridane system, and attributed the discrepancy in kinetic isotope effects to this scrambling. It should be noted, however, that the scrambling is not a common phenomenon in the system so far studied. 

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