Free radical clocks

Here we plan to devote further attention to reaction intermediates. The methods used to verify the intervention of an intermediate include trapping. That is, the intermediate can be diverted from its normal course by a substance deliberately added. A new product may be isolated as a result, which may aid in the identification of the intermediate. One can also apply competition kinetics to construct a scale of relative reactivity, wherein a particular intermediate reacts with a set of substrates. Certain calibration reactions, such as free radical clocks, can be used as well to provide absolute reactivities. 

A better-known example of a free radical clock is the 5-hexenyl radical. Timing is provided by the rearrangement reaction... 

The radical rearrangement reaction, serving as a timing device, has been called a free radical clock 2 It provides a means of evaluating the rate constant for reactions of this radical with other substrates. The example shows how the radical-chromium(II) rate constant can be determined. A number of other instances have been summarized.13... 

PRIMARY ALKYL RADICALS AND FREE-RADICAL CLOCK METHODOLOGY... 

The kinetic data for the reaction of primary alkyl radicals (RCH2 ) with a variety of silanes are numerous and were obtained by applying the free-radical clock methodology. The term free-radical clock or timing device is used to describe a unimolecular radical reaction in a competitive study [2-4]. Three types of unimolecular reactions are used as clocks for the determination of rate constants for this class of reactions. The neophyl radical rearrangement (Reaction 3.1) has been used for the majority of the kinetic data, but the ring expansion rearrangement (Reaction 3.2) and the cyclization of 5-hexenyl radical (Reaction 3.3) have also been employed. 

The free-radical clock methodology has been also applied to calibrate unim-olecular radical reactions based on the A h values of Table 3.2 and, when avail-... 

Free radical clocks are reactions with known rate constants such as the cyclization of 5-hexenyl radicals (equation 76) or the ring opening of cyclo-propylmethyl radicals 46 (equation 74). Competition reactions of these processes compared to other reactions permit the assignment of rate constants to... 

Another common scenario in competition kinetics utilizes unimolecular radical reactions as a clock against which other reactions can be timed. Among the most commonly used free radical clocks are the cyclization of 1 -hexenyl and other radicals with double or triple bonds in the chain,33 ring opening,34 and p-elimination from alkoxyl radicals.35... 

Xenon difluoride reacted with various carboxylic acids, and the type of transformation depends on the structure of the organic molecules35-39. The reaction with primary carboxylic acids involves free-radical intermediates. 6-Hexenoic acid was used as a free-radical clock device in which a A abs of 1.1 x 106 M-1s-1 at 25 °C was determined, while the alkyl radical was also spin-trapped to give an ESR signal37. The primary free radical was trapped by internal cyclization, and (fluoromethyl) cyclopentane in 25% yield was formed, while 6-fluoro-l-hexene could be formed from a radical or ionic intermediate, but 1-fluo-rocycloclohexane was not observed as a product (Scheme 42). 

The pioneering work on the calibration of intramolecular cy-clization of the 5-hexenyl radical by Ingold and co-workers provided the basis for the development of a large number of radical clocks." These are now used both for the calibration of rate constants for intermolecular radical reactions and as mechanistic probes to test for the intermediacy of radical intermediates in a variety of processes. Furthermore, the ready availability of bimolecular rate constants from competitive product studies using free radical clocks without the use of time-resolved experiments has greatly enhanced the synthetic utility of free radical chemistry. The same concept has recently been extended to radical ion chemistry. For example, rate constants for carbon—carbon bond cleavage reactions of a variety of radical cations and anions derived from substituted diarylethanes have been measured by direct time-resolved techniques. " ... 

In order to study the lifetimes of various radicals in new reactions, one requires several radical clocks with varying lifetimes. Incorporation of these clocks into the molecules under study is used both to show that radical intermediates do or do not exist, and if they do, their lifetimes relative to the clock. Several free radical clocks with their rate constants for rearrangement are shown in Table 8.7. Such a collection has been termed an horlogerie, after a French term for a small shop that sells clocks. Seven orders of magnitude can be spanned by choosing the correct clocks. 

Intramolecular rearrangements of free radicals are not nearly so common as those of carbo-cations. In fact, the most important rearrangements of free radicals are those associated with free radical "clocks", as discussed in Section 8.8.8 and listed in Table 8.7. Here we describe a few other rearrangements of radical. systems. 

The 1,2-vinyl shift shown in Eq. 11.72 proceeds via a familiar structure, the cyclopro-pylcarbinyl radical we introduced in the context of free radical clocks (Table 8.7). In this case, the two species involved, the allylcarbinyl and cyclopropylcarbinyl radicals, are both discrete chemical entities that have been thoroughly characterized by EPR spectroscopy (Eq. 11.74). The equilibrium very strongly favors the ring-opened form, making the clock reaction, the opening of cyclopropylcarbinyl, essentially irreversible. 

---