Some representative kinetic isotope effects

CHAPTER 4 STUDY AND DESCRIPTION OF ORGANIC REACTION MECHANISMS 

The description of the intermediates in a multistep reaction is a major objective of studies of reaction mechanisms when the nature of each intermediate in a reaction is fairly well understood, a great deal is known about the reaction mechanism. The amount of an intermediate present in a reacting system at any instant of time will depend on the rates of the steps by which it is formed and the rate of its subsequent reaction. A qualitative indication of the relationship between intermediate concentration and kinetics can be gained by considering a simple two-step mechanism  

In many reactions, the situation ki k2 holds in some cases, intermediates can actually be isolated. Any true intermediate isolated from an interrupted reaction, when resubjected to the reaction conditions, will give the expected reaction products. If both ki and /c2 are large, the reaction may proceed too rapidly to permit isolation of the intermediate. Kinetic and spectral studies in such cases should reveal, however, the existence of two distinct phases for the overall reaction first, formation of intermediate (I), with a rate constant ki second, its subsequent disappearance, characterized by rate constant 2- 

If the rate of formation of I only slightly exceeds its rate of disappearance, only a fraction of the reacting molecules will be present as I at any instant. It is sometimes possible to interrupt a reaction—for example, by lowering the temperature, or by removing a catalyst. If I is then fairly stable, isolation may be possible even though the amount is low. 

Sometimes, intermediates can be trapped A compound that is expected to react specifically with the intermediate is added to the reaction system. If trapping is efficient, the intermediate is then diverted from its normal course, and evidence for the existence of the intermediate can be obtained by establishing the identity of the trapped product. 

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Scheme 4.2. Some Representative Kinetic Isotope Effects...

While these four schemes by no means exhaust the possibilities, they represent a broad spectrum of mechanisms in terms of molecularity and polarity of the transition state. Some organolithium reactions, e.g., thermal decomposition, very probably proceed via radical formation. Furthermore, there is evidence that the coupling reaction with an alkyl halide may involve radicals (72), although these systems must be more extensively investigated. Reaction scheme iv) can probably be ruled out immediately it would require an inordinately high activation energy, would probably lead to a negligible lithium kinetic isotope effect, and would not account for stereospecificity in olefin polymerization 68, 73). It possibly becomes an important pathway, however, in the presence of more polar molecules such as ethers. 

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