Radical clock method

The kinetic data for these reactions are numerous, as shown in Table VI. Most of values were obtained by radical clock methods. The ring expansion of radical 7 has been employed as the clock in a study that provided much of the data in Table VI.74 Cyclizations of 5-hexenyl-type radicals also have been used as clocks,75-77 and other competition reactions have been used.78 Hydrogen atom abstraction from n-Bu3GeH by primary alkyl radicals containing a trimethylsilyl group in the a-, >8-, or y-position were obtained by the indirect method in competition with alkyl radical recombi-... 

Using the D values of the dialkylanilines at 298K and Equation 13.13, the time required for 1-phenylethyl and 1-naphthoxy radicals to move to the locations amenable to combine at the 2- and 4-positions of 1-naphthoxy, ca. 3.1 and 5.0 A, respectively, correspond to ca. 2.4-24 and 6.3-63 ns in unstretched PEG and ca. 24—240 and 63-630 ns in unstretched PE46, depending on the specific diffusion coefficient employed. The times required for formation of the keto intermediates of 2-AN and 4-AN from lb by the radical clock method described above are ca. 3 and 14 ns, respectively, in unstretched or sttetched PEG and ca. 2-3 and 26-33 ns, respectively, in unstretched LDPE. In stretched LDPE, where translocation increases... 

The rate of the ring-opening reaction of 5, " and other substrates have been determined using an indirect method for the calibration of fast radical reactions, applicable for radicals with lifetimes as short as 1 ps/ This radical clock method is based on the use of Barton s use of pyridine-2-thione-Al-oxycarbonyl esters as radical precursors and radical trapping by the highly reactive thiophenol and benzeneselenol/ A number of radical clock substrates are known/ Other radical clock processes include racemization of radicals with chiral conformations, one-carbon ring expansion in cyclopentanones, norcarane and sprro[2,5]octane, a-and p-thujone radical rearrangements, and cyclopropylcarbinyl radicals or... 

This brief overview was intended to introduce the concepts of the radical clock method with a relatively limited number of examples. Extensive tables of radical kinetics exist, and many reactions can be used as clocks. In regard to the kinetic values available, however, one should appreciate that determinations of radical kinetics tend to involve a series of increasingly precise and accurate approximations. For that reason, more recently determined rate constants usually were selected for this overview. When using radical clocks, one is well advised to search a reference in the forward direction for improved kinetic values, especially those involving recalibrations of absolute rate constants. 

It was shown by Ortiz de Montellano et al. that bicyclo[2.1.0]pentane was oxidized by rat liver microsomes to a 7 1 mixture of e <7o-2-hydroxy-bicyclo[2.1.0]pentane and 3-cyclopenten-l-ol, consistent with a radical ring-opening reaction. Applications of the radical-clock method by Ingold and by Newcomb began to measure the lifetime of the suspected radical cage intermediate. The rate constant for the rearrangement of bicyclo[2.1.0]pent-2-yl radical to 3-cyclopenten-... 

Strength) [24, 25]. There is a smaller rate difference between Cp/Cp with the more reactive 5-hexenyl radical radical clock methods have shown that the rate constant for H" transfer decreases by a factor of two from Cp(CO)3MoH to Cp (CO)3MoH at 298 K [30]. The considerable primary secondary tertiary selectivity of Cp (CO)3MoH in these radical clock studies (26 7 1) arises from steric interactions with the radical substituents [30]. 

Newcomb has measured the rate of H transfer to carbon-centered radicals from the water and methanol complexes of Cp2TiCl [34]. The rate constant (IkH) for HAT to the radical below (determined by the radical clock method. Scheme 1.3) in THF at room temperature is 1.0 x 10 M s . 

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 major source of error in any indirect method is inaccuracy of the basis rate constants. Errors can result from determinations of rate constants by a sequence of several indirect studies or by an unanticipated solvent effect on the kinetics of a basis reaction. An error can also result in calibration of a radical clock if the requisite assumption that the clock radical will react with a rate constant equal to that of a simple model radical is not correct. Nevertheless, indirect methods in general, and radical clock studies in particular, have been the workhorse of radical kinetic determinations. 

LFP-Clock Method. In this method, rate constants for the radical clock reactions are measured directly by LFP, and the clocks are used in conventional competition kinetic studies for the determination of second-order rate constants. The advantages are that the clock can be calibrated with good accuracy and precision in the solvent of interest, and light-absorbing reagents can be studied in the competition reactions. The method is especially useful when limited kinetic information is available for a class of radicals. 

Table VIII contains rate constants for reactions of tin hydrides with carbon-centered radicals. A striking feature of Table VIII in comparison to other tables in this work is the high percentage of reactions for which Arrhenius parameters were determined by direct LFP or the LFP-clock method. These results are expected to be among the most accurate listed in this work. Scores of radical clocks have been studied with Bu3SnH, but the objectives of those studies were to determine rate constants for the clocks using tin hydride trapping as the calibrated basis reaction.

The rate constants for reaction of Bu3SnH with the primary a-alkoxy radical 24 and the secondary ce-alkoxy radical 29 are in reasonably good agreement. However, one would not expect the primary radical to react less rapidly than the secondary radical. The kinetic ESR method used to calibrate 24 involved a competition method wherein the cyclization reactions competed with diffusion-controlled radical termination reactions, and diffusional rate constants were determined to obtain the absolute rate constants for the clock reactions.88 The LFP calibrations of radical clocks... 

Cyclizations of amidyl radicals have been studied both synthetically and kinetically. A detailed study on the rates of a variety of amidyl radical reactions was determined by both LFP and indirect competition methods (Table l) In addition, the rate constants for reactions with BusSnH and PhSH were also reported (thus giving a range of simple amidyl radical clocks). The results obtained will be useful in synthetic sequenceplanning involving amidyl radicals. 

The kinetic data reported in this chapter have been determined either by direct measurements, using for example kinetic EPR spectroscopy and laser flash photolysis techniques or by competitive kinetics like the radical clock methodology (see below). The method for each given rate constant will be indicated as well as the solvent used. An extensive compilation of the kinetics of reaction of Group 14 hydrides (RsSiH, RsGeH and RsSnH) with radicals is available [1]. 

The concept of this method is illustrated in Scheme 3.1, where the clock reaction (U R ) is the unimolecular radical rearrangement with a known rate constant ( r)- The rate constant for the H atom abstraction from RsSiH by a primary alkyl radical U can be obtained, provided that conditions are found in which the unrearranged radical U is partitioned between the two reaction channels, i.e., the reaction with RsSiH and the rearrangement to R. At the end of the reaction, the yields of unrearranged (UH) and rearranged (RH) products can be determined by GC or NMR analysis. Under pseudo-first-order conditions of silane concentration, the following relation holds UH/RH = (A H/A r)[R3SiH]. A number of reviews describe the radical clock approach in detail [3,4]. 

The reaction of azide ions with carbocations is the basis of the azide clock method for estimating carbocation lifetimes in hydroxylic solvents (lifetime = 1 lkiy where lq, is the first-order rate constant for attack of water on the carbocation) this is analogous to the radical clock technique discussed in Chapter 10. In the present case, a rate-product correlation is assumed for the very rapid competing product-forming steps of SN1 reactions (Scheme 2.24). Because the slow step of an SN1 reaction is formation of a carbocation, typical kinetic data do not provide information about this step. Furthermore, the rate constant for the reaction of azide ion with a carbocation (kaz) is assumed to be diffusion controlled (ca. 5 x 109 M 1 s 1). The rate constant for attack by water can then be obtained from the mole ratio of azide product/solvolysis product, and the molar concentrations of azide (Equation 2.18, equivalent to Equation 2.14) [48]. The reliability of the estimated lifetimes was later... 

The mechanism of insertion of 2-alkylphenylnitrenes into a 1,5-related CH bond was studied by three methods 80 determination of isotope effects, stereochemistry, and radical clock. During the formation of indolines, a kn/kD of 12.6-14.7 was observed coupled with complete loss of stereochemical integrity at the CH carbon. When the CH insertion carbon bore a cyclopropane group, ring-opening products were observed. These observations suggest a mainly radical H-atom abstraction mechanism. The sensitivity of the isotope effects to solvent was taken to imply a small concerted nitrene insertion contribution. 

There has been considerable debate as to what degree Cl, like Br, radicals might play a role in Arctic springtime tropospheric chemistry. To obtain information on this, Jobson et al. (1994) collected daily air samples at Alert (82.5° N, 62.3° W) from January 21 to April 19, and on an ice floe 150 km north of Alert during April 2-15, 1992. They derived information on the concentrations of OH, Cl, and Br from the different decay rates of a suite of non-methane hydrocarbons the so-called hydrocarbon clock method. Besides some removal of alkanes by reaction with OH during ODEs, additional alkane losses, consistent with removal by reaction with Cl, were measured. 

The term radical clock is used to describe a unimolecular radical reaction that is kinetically calibrated and, thus, can be applied in a competition study to time a particular radical reaction of interest [1], Such kinetic information is necessary for mechanistic studies where a radical might be formed as a transient. It is also important for synthetic applications because most radical-based methods involve chain reactions that commonly have several competing reaction steps with absolute kinetic values available, one can calculate the concentrations of reagents necessary for a high-yield synthetic conversion. Because lifetimes of simple radicals are usually in the microsecond range, direct kinetic measurements require sophisticated instrumentation. Radical clocks provide an inexpensive alternative for kinetic studies because the rate constants for the competing reactions are determined from the product mixtures present at the end of the reaction, usually with common organic laboratory instruments. 

This chapter contains a brief description of the background and methods of radical clock studies and examples of clocks. A wide range of calibrated clock reactions exists for many types of radicals, and the examples are only representative. 

The most convenient radical clock studies are based on radical chain reactions because these processes usually have high conversions with small amounts of initiation. Two general types of radical chain processes have been extensively employed in clock studies, the tin hydride method and the PTOC-thiol method. 

If one of the reactions in a radical chain sequence is too slow to compete effectively with radical-radical reactions, the chain will collapse. Slow reactions of simple silanes such as Et3SiH with alkyl radicals precludes their use in the tin hydride method. Although quite reactive with alkyl radicals, thiols and selenols fail in the tin hydride method because the thiyl and selenyl radicals do not react rapidly with organic halide precursors. Nonetheless, it is possible to use thiols and selenols in tin hydride sequences when a Group 14 hydride is used as a sacrificial reducing agent. The thiyl or selenyl radical reacts with the silane or stannane rapidly, and the silicon- or tin-centered radical thus formed reacts rapidly with the organic halide [8], In practice, benzeneselenol in catalytic amounts has been used in radical clock studies where BusSnH served as the sacrificial reductant [9]. 

The evolution of kinetic scales has been highly dependent on radical clock and, more generally, indirect competition kinetic studies [6], These types of studies provide ratios of rate constants as discussed above. One can build an extensive series of relative rate constants for unimolecular clocks and bimolecular reactions, and the relative rate constants often are determined with very good to excellent precision. At some point, however, absolute rate constants are necessary to provide real values for the entire kinetic scale. These absolute kinetic values are the major source of error in the kinetics, but the absolute values are becoming more precise and, one certainly hopes, more accurate as increasingly refined techniques are introduced and multiple methods are applied in studies of specific reactions. 

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