Isotope effects, kinetic limits regarding

These reactions proceed through symmetrical transition states [H H H] and with rate constants kn,HH and kH,DH, respectively. The ratio of rate constants, kH,HH/kH,DH> defines a primary hydrogen kinetic isotope effect. More precisely it should be regarded as a primary deuterium kinetic isotope effect because for hydrogen there is also the possibility of a tritium isotope effect. The term primary indicates that bonds at the site of isotopic substitution the isotopic atom are being made or broken in the course of reaction. Within the limits of TST such isotope effects are typically in the range of 4 to 8 (i.e. 4 < kH,HH/kH,DH < 8). 

With thermal systems either in the gas phase or in solution, it is in ter -molecular isotope effects which are more commonly studied. Intramolecular isotope effects involve distinguishing and measuring two, or more, chemically identical but isotopically different products produced in the same reaction vessel from the same reactant. The situation is different in mass spectrometry. Intramolecular isotope effects are conveniently studied, because the chemically identical products are naturally separated according to their masses. Intermolecular isotope effects on ion abundances are also easily measured, but, as regards kinetics and mechanism of reaction, their value is limited. Whereas an intramolecular isotope effect (on ion abundances) reflects kinetic isotope effects, an intermolecular isotope effect (on ion abundances) reflects kinetic isotope effects, isotope effects on the internal energy distribution, P(E), and other factors as well and the effects cannot be easily separated (vide infra). 

Isotopes play a multifaceted role in mechanistic chemistry. Isotopic labelling at specific sites of a reagent is often used to support or exclude a hypothetical reaction mechanism based on the location of the isotopic label in the products. Kinetic isotope effects, that is, changes in rate constants that are induced by isotopic substitution, may be seen in time-resolved experiments or may express themselves as changes in product quantum yields. They hold important information regarding the nature of the rate-determining step that limits the overall rate in a sequence of reactions. 

This principal reaction mechanism is widely believed to apply to most S Ar reactions irrespective of the electrophilic reagent. There are however a number of experimental observations that indicate exceptions to this mechanism. There are examples of thermodynamically controlled Friedel-Crafts reactions, when using reaction conditions like polyphosphoric acid and elevated temperatures [27,28]. In iodination and some cases of Friedel-Crafts acylation, the last step of the reaction, the proton abstraction, has been shown to have a substantial kinetic isotope effect, which indicates that this step is at least partially rate limiting [29-31]. There are also still open questions regarding the exact nature of the reaction intermediates, and we will focus on these issues in the remaining part of the chapter. 

A study has been reported regarding the ruthenium-catalysed reaction of benza-mides with alkynes, which yields ort/io-alkenylated derivatives. Here, the mechanism is likely to involve rate-limiting metalation, followed by alkyne insertion to form intermediates such as (63) which on protonolysis yield the alkenylated products. An allylic carbon-carbon double bond has also been used as a coordination site in palladium-catalysed alkenylation reactions, as shown in Scheme 3. Here measurement of kinetic isotope effects suggests that coordination of the palladium with the allylic double bond occurs before palladation to give (64). Insertion of the alkene into the carbon-palladium bond gives (65) and -hydride elimination " leads to the product... 

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