Substituent effects on radicals

Table 12.4. Substituent Effects on Radical Stability from Measurements of Bond Dissociation Energies and Theoretical Calculations of Radical Stabilization Energies...

Isomerizations in which C—C bonds are cleaved homolytically have been chosen several times as probes for the study of substituent effects on radical stabilization. The nature of the intermediates—in some cases there may not even be intermediates but only biradical-like transition states—is often not known in detail. It may thus be uncertain whether the radicals include fully evolved radical centres, especially in the case of intramolecular isomerizations where biradicaloids might be involved. On this basis it is not expected that stabilization energies which derive from rate measurements for isomerizations will be identical to those obtained by other procedures. 

Table 1.2 illustrates an additional substituent effect on radical stability. Here the dissociation enthalpies of reactions that lead to (poly)alkylated radicals (alk)3-nHnC are listed ( alk stands for alkyl group). From these dissociation enthalpies it can be seen that alkyl substituents stabilize radicals. A primary radical is by 4 kcal/mol more stable, a secondary radical is by 7 kcal/mol more stable, and a tertiary radical is by 9 kcal/mol more stable than the methyl radical. 

The RSE is calculated here as the difference between the homolytic C-C bond dissociation energy in ethane (5) and a symmetric hydrocarbon 6 resulting from dimerization of the substituted radical 2. By definition the C-C bonds cleaved in this process are unpolarized and, baring some strongly repulsive steric effects in symmetric dimer 6, the complications in the interpretation of substituent effects are thus avoided. Since two substituted radicals are formed in the process, the reaction enthalpy for the process shown in Equation 5.5 contains the substituent effect on radical stability twice. The actual RSE value is therefore only half of the reaction enthalpy for reaction 5.5 as expressed in Equation 5.6. 

Radical stabilization energies for a wide variety of carbon-centered radicals have been calculated at G3(MP2)-RAD or better level. While the interpretation of these values as the result of substituent effects on radical stability is not without problems, the use of these values in rationalizing radical reactions is straight forward. This is not only true for reactions involving hydrogen atom transfer steps but also for other reactions involving typical elementary reactions such as the addition to alkene double bonds and thiocarbonyl compounds. 

A orking out the consequence of an important substituent effect on radical reactions the ci clopropyl group. 

The quantification of electronic substituent effects is made possible by linear free-energy relationships (e.g., the Hammett equation) [50,51] however, for radical reactions, this is considerably more cumbersome since such effects are orders of magnitude smaller than in their corresponding ionic counterparts [52], Thus, it should be evident that a number of criteria are important in choosing a suitable chemical model system for evaluating substituent effects on radical species [53], Some of the more significant ones are ... 

Many studies of substituent effects on radical stabilization involved C-C homolysis reactions leading to rather similar diradicals. Cis-trans isomerization of tetrasubstituted cyclopropanes 24 (Scheme 5) is found to occur fastest when the intermediate diradical 25 is stabilized by captodative substitution [25], with better donors yielding faster reactions. 

A good place to begin discussion of substituent effects on radicals is by considering the most common measure of radical stability. Radical stabilization is often defined by comparing C—H bond dissociation energies (BDE). For substituted methanes, the energy of the reaction should reflect any stabilizing features in the radical X-CHt... 

Substituent effects on radicals can be expressed as radical stabilization energies (RSE). Table 3.17 gives some RSEs determined by one such approach developed by Leroy, which can be defined as the difference between the observed enthalpy of atomization. H and the sum of standard bond energies. 

Where does this leave us in terms of understanding substituent effects on radicals The most general statement to be made is that the BDE, not the RSE, is the best indicator of reactivity of the C-H bond. This is evident in the relationship allyl benzyl < tert < sec < pri < methyl < ethenyl phenyl < ethynyl bonds to hydrogen. We also note that the statement all substituents weaken adjacent C-H bonds is generally true. The traditional RSE values, however, result from two substituent effects, those in the reactant and those in the radical, and ultimately depend on the definition of the inherent bond strength. The clearest guide to reactivity is the experimental BDE or its computational equivalent. We discuss the rates of hydrogen abstraction reactions in more detail in Topic 11.2. 

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