Substituent effects on radical stability

Radicals are particularly strongly stabilized when both an electron-attracting and an electron-donating substituent are present at the radical site. This has been called mero-slabilizalion or capto-dative stabilization, and results from mutual reinforcement of the two substituent effects. The bonding in capto-dative radicals can be represented by resonance or Linnett-type structures (see p. 8). 

A comparison of the rotational barriers in allylic radicals A to D provides evidence for the stabilizing effect of the capto-dative combination. 

The capto-dative effect has also been demonstrated by studying the bond dissociation process in a series of 1,5-dienes substituted at C(3) and C(4). 

Van Hoecke, A. Borghese, J. Penelle, R. Merenyi, and H. G. Viehe, Tetrahedron Lett., 27, 4569 

Generated by one-electron reduction of the corresponding pyridinium salt. Thermally stable to distillation and only moderately reactive toward oxygen. 

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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. 

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. 

F. G. Bordwell, J.-P. Cheng. Substituent Effects on the Stabilities of Phenoxyl Radicals and the Acidities of Phenoxyl Radical Cations. J. Am. Chem. Soc. 1991, 113, 1736-1746. 

Mechanistic Aspects of Cationic Copolymerizations The relative reactivities of monomers can be estimated from copolymerization reactivity ratios using the same reference active center. However, because the position of the equilibria between active and dormant species depends on solvent, temperature, activator, and structure of the active species, the reactivity ratios obtained from carbocationic copolymerizations are not very reproducible [280]. In general, it is much more difficult to randomly copolymerize a variety of monomers by an ionic mechanism than by a radical. This is because of the very strong substituent effects on the stability of carbanions and carbenium ions, and therefore on the reactivities of monomers substituents have little effect on the reactivities of relatively nonpolar propagating radicals and their corresponding monomers. The theoretical fundamentals of random carbocationic copolymerizations are discussed in detail and the available data are critically evaluated in Ref. 280. This review and additional references [281,282] indicate that only a few of the over 600 reactivity ratios reported are reliable. 

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. 

Table 11.1. Substituent Effects on the Stability of Allylic and Benzylic Radical from Calculation of Radical Stabilization Energy... 

Computational studies have compared substituent effects on the stability of ketenes, allenes, diazomethanes, diazirines, and cyclopropenes. Ketenes belong to the first generation of reactive intermediates along with carbocations, carbanions, radicals, and carbenes, and are intensively studied members of the cumulene family, with many useful synthetic applications. Ketenes were first recognized in 1905, when diphenylketene, a stable and isolable example, was obtained from the dehalogenation of the a-bromodiphenylacetyl bromide (Scheme 7.37). The most characteristic reaction of ketene is cycloaddition, as in the formation of p-laclams. 

Similarly, carboxylic acid and ester groups tend to direct chlorination to the / and v positions, because attack at the a position is electronically disfavored. The polar effect is attributed to the fact that the chlorine atom is an electrophilic species, and the relatively electron-poor carbon atom adjacent to an electron-withdrawing group is avoided. The effect of an electron-withdrawing substituent is to decrease the electron density at the potential radical site. Because the chlorine atom is highly reactive, the reaction would be expected to have a very early transition state, and this electrostatic effect predominates over the stabilizing substituent effect on the intermediate. The substituent effect dominates the kinetic selectivity of the reaction, and the relative stability of the radical intermediate has relatively little influence. 

The reaction rates and product yields of [2+2] cycloadditions are expectedly enhanced by electronic factors that favor radical formation. Olefins with geminal capto-dative substituents are especially efficient partners (equations 33 and 34) because of the synergistic effect of the electron acceptor (capto) with the electron donor (dative) substituents on radical stability [95]... 

One point of debate in defining the magnitude of the captodative effect has been the separation of substituent effects on the radical itself as compared to that on the closed shell reference system. This is, as stated before, a general problem for all definitions of radical stability based on isodesmic reactions such as Eq. 1 [7,74,76], but becomes particularly important in multiply substituted cases. This problem can be approached either through estimating the substituent effects for the closed shell parents separately [77,78], or through the use of isodesmic reactions such as Eq. 5, in which only open shell species are present ... 

Riichardt originally made the assumption that substituents do not exert a noticeable electronic effect on the ground state of the radical precursor. He attributed the full electronic substituent power to the radical. On the basis of this presumption, the BDEs in [24] and [25] were interpreted in terms of radical stability. The original value for the BDE in [24] (Zamkanei et al., 1983) was later slightly modified (Birkhofer et al., 1987). The BDEs were compared with those where only one cyano- or one methoxyl group was incorporated. From Table 9 (Birkhofer et al., 1989) it can be derived that phenyl, cyano-, and methoxy-groups exert an additive substituent effect on... 

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