Labeling and Kinetic Isotope Effects

In the general field of reaction kinetics isotopic techniques are of considerable value for determining fine details in the mechanism of chemical reactions. Such isotopic studies in mercury-photosensitized reactions may be divided into three distinct categories the investigation of the kinetic isotope effects in the primary energy-transfer interactions, isotopic labeling and kinetic isotope effect in processes other than the primary one, and monoisotopic photoexcitation. 

Because the elimination can occur in either branch of the nonane, isotope effects can be calculated from the product ratios. These deuterium labelling and kinetic isotope effect studies have enabled the authors to determine the rate-determining step of the reaction and to understand the gas-phase decomposition of the metastable ion complex. 

Ammonia borane acts as a metal-free reductant for ketones and aldehydes in methanol solution, via the MeOH BHj complex.In THF, borate esters are the only organic products, with dissociation of ammonia from ammonia borane being rate determining. H-, B-, and C-NMR studies, deuterium labelling, and kinetic isotope effects are... 

Triphenyltris-(tetrahydrofuran)chromium(m) (4) reacts with but-2-yne to give 1,2,3,4-tetramethylnaphthalene (5). From deuterium labelling and kinetic isotope effects, and from the isolation of intermediates, it proved possible to propose the mechanism shown in Scheme 1. The sequence is insertion, then cyclization of the styrylchromium intermediate to a benz-chromole, followed by reaction with a second molecule of but-2-yne. ... 

A number of methods including product analysis, isotopic labelling, kinetics and kinetic isotope effects, and stereochemical studies have been used to show the presence of sulfenes. The case for the existence of sulfenes has been summarized before1,3 and, except for the next section (IV.A.l), which is necessarily complex, the present account will note, as briefly as possible, the evidence for each method of sulfene formation, the reasons for concluding that sulfenes are present and the extent to which non-sulfene reactions also appear with this method. 

Dissociation and dimerization of C-nitroso componnds was studied by Vancik et al. under different solvent-free conditions, inclnding mechanochemical [69], Reaction rates and kinetic isotope effects were obtained from experiments carried out with labeled C-nitroso compound (p-bromonitrosobenzene) as shown for homodimers 376 and 377 (Scheme 3.104). Heterodimers 380 and 381 were prepared by mixing equimolar amounts of p-Cl, P-NO2 p-l nitrosobenzene derivatives, and isotope labeled... 

The oxidation of benzylic alcohols was quantitative within hours and selective to the corresponding benzaldehydes, but the oxidation of allylic alcohols was less selective. The oxidation of aliphatic alcohols was slower but selective. In mechanistic studies considering oxidation of benzylic alcohols, similar to the oxidation of alkylarenes, a polyoxometalate-sulfoxide complex appears to be the active oxidant. Further isotope-labeling experiments, kinetic isotope effects, and especially Hammett plots showed that oxidation occurs by oxygen transfer from the activated sulfoxide and elimination of water from the alcohol. However, the exact nature of the reaction pathway is dependent on the identity of substituents on the phenyl ring. 

Experiments carried out with labeled substrate 1 provided a set of primary (deuterium label placed at C3 position), secondary (deuterium label placed at C4 position) and leaving group (labeled F) kinetic isotope effects (KlEs). These data were determined for a set of bases with different strengths (formate, acetate and imidazole) in Me0H/H20 as solvent and are collected in Table 37.1. 

A disadvantage of this technique is that isotopic labeling can cause unwanted perturbations to the competition between pathways through kinetic isotope effects. Whereas the Born-Oppenheimer potential energy surfaces are not affected by isotopic substitution, rotational and vibrational levels become more closely spaced with substitution of heavier isotopes. Consequently, the rate of reaction in competing pathways will be modified somewhat compared to the unlabeled reaction. This effect scales approximately as the square root of the ratio of the isotopic masses, and will be most pronounced for deuterium or... 

The kinetic parameters are E = 6.3 kcal.mole" and AS = —38.4 eu, and at 25 °C the reaction exhibits a primary kinetic isotope effect of 6.6. When 0-labelled MnO was employed, no labelled oxygen appeared in the benzophenone. The mechanism involves abstraction of hydrogen, either as a hydride ion or a hydrogen atom, from the anion of the alcohol... 

A kinetic isotope effect 160/180 of 2% in the spontaneous hydrolysis of the 2,4-dinitrophenyl phosphate dianion, whose ester oxygen is labeled, suggests a P/O bond cleavage in the transition state of the reaction, and thus also constitutes compelling evidence for formation of the metaphosphate 66,67). The hydrolysis behavior of some phosphoro-thioates (110) is entirely analogous 68). 

The authors have also synthesized134 fatty acids labelled with deuterium and carbon-11 in order to investigate if kinetic isotope effects related to fatty acid metabolism can be observed in vivo by pet133,135-137. In vitro, the large kinetic deuterium isotope effects are observed in the oxidation of deuteriated aliphatic carboxylic acids with alkaline permanganate and manganate135-139. 

Labelling experiments provided the evidence that the Fe1- and Co1-mediated losses of H2 and 2H2 from tetralin are extremely specific. Both reactions follow a clear syn- 1,2-elimination involving C(i)/C(2) and C(3)/C(4), respectively. In the course of the multistep reaction the metal ions do not move from one side of the rr-surface to the other. The kinetic isotope effect associated with the loss of the first H2 molecule, k( 2)/k(Y)2) = 3.4 0.2, is larger than the KIE, WFLj/ATHD) = 1.5 0.2, for the elimination of the second H2 molecule. A mechanism of interaction of the metal ion with the hydrocarbon n-surface, ending with arene-M+ complex 246 formation in the final step of the reaction, outlined in equation 100, has been proposed241 to rationalize the tandem MS studies of the unimolecular single and double dehydrogenation by Fe+ and Co+ complexes of tetraline and its isotopomers 247-251. 

The crystal structure of an isopropylamine complex of Ru of this type has been reported [78]. Surprisingly, a negligible kinetic isotope effect (kRuHOH/kRUDOD= 1.05 0.14) was found when D labels on both the OH and RuH sites were used,... 

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