Carbon-centered radicals stability

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

The last comprehensive review of reactions between carbon-centered radicals appeared in 1973.142 Rate constants for radical-radical reactions in the liquid phase have been tabulated by Griller.14 The area has also been reviewed by Alfassi114 and Moad and Solomon.145 Radical-radical reactions arc, in general, very exothermic and activation barriers are extremely small even for highly resonance-stabilized radicals. As a consequence, reaction rate constants often approach the diffusion-controlled limit (typically -109 M 1 s"1). 

Prior to the development of NMP, nitroxides were well known as inhibitors of polymerization (Section 5.3.1). They and various derivatives were (and still are) widely used in polymer stabilization. Both applications are based on the property of nitroxides to efficiently scavenge carbon-centered radicals by combining with them at near diffusion-controlled rates to form alkoxyamines. This property also saw nitroxides exploited as trapping agents to define initiation mechanisms (Section 3.5.2.4). 

The reaction with sulfides occurs efficiently only when the resulting carbon-centered radicals are further stabilized by a a-heteroatom. Indeed, (TMSfsSiH can induce the efficient radical chain monoreduction of 1,3-dithiolane, 1,3-dithiane, 1,3-oxathiolane, 1,3-oxathiolanone, and 1,3-thiazolidine derivatives. Three examples are outlined in Reaction (12). The reaction of benzothiazole sulfenamide with (TMS)3SiH, initiated by the decomposition of AIBN at 76 °C, is an efficient chain process producing the corresponding dialkylamine quantitatively. However, the mechanism of this chain reaction is complex as it is also an example of a degenerate-branched chain process. 

The reaction enthalpy and thus the RSE will be negative for all radicals, which are more stable than the methyl radical. Equation 1 describes nothing else but the difference in the bond dissociation energies (BDE) of CH3 - H and R - H, but avoids most of the technical complications involved in the determination of absolute BDEs. It can thus be expected that even moderately accurate theoretical methods give reasonable RSE values, while this is not so for the prediction of absolute BDEs. In principle, the isodesmic reaction described in Eq. 1 lends itself to all types of carbon-centered radicals. However, the error compensation responsible for the success of isodesmic equations becomes less effective with increasingly different electronic characteristics of the C - H bond in methane and the R - H bond. As a consequence the stability of a-radicals located at sp2 hybridized carbon atoms may best be described relative to the vinyl radical 3 and ethylene 4 ... 

Numerous reports published in recent years have focused on carbon-centered radicals derived from compounds with selected substitution patterns such as alkanes [40,43,47], halogenated alkanes [43,48,49,51-57], alkenes [19], benzene derivatives [43,47], ethers [51,58], aldehydes [48], amines [10,59], amino acids [23,60-67] etc. Particularly significant advances have been made in the theoretical treatment of radicals occurring in polymer chemistry and biological chemistry. The stabilization of radicals in all of these compounds is due to the interaction of the molecular orbital carrying the unpaired electron with energetically and spatially adjacent molecular orbitals, and four typical scenarios appear to cover all known cases [20]. 

The stabilization of carbon-centered radicals through alkyl groups is due to a closely similar orbital interaction as that shown for n systems (Scheme 2). 

Cyclization of nitro-stabilized radicals provides another method for the generation of cyclic nitronates (221). Oxidation of the aci-foim of nitroalkanes with ceric ammonium nitrate generates the ot-carbon centered radical, which in the presence of an alkene, leads to the homologation of the a-radical. In the case of a tethered alkene of appropriate length, radical addition leads to a cyclic nitronate (Scheme 2.20). 

A quantity called the radical stabilization energy (RSE) may be defined to relate the stabilities of substituted carbon radicals to the methyl radical. The effects of adjacent X , Z, and C substituents on the RSEs of carbon-centered radicals has been widely investigated [142,143]. The expectations based on simple orbital interaction theory as espoused above are widely supported by the experimental findings, except that when the the n donor or n acceptor ability of the group is weak and the inductive electron-withdrawing power is large, as in F3C and (Me N+CHj, the net effect is to destabilize the radical relative to the methyl radical [143]. The BDE of a C—H bond of a compound R—H is another measure of stability of the product radical, R. It is related to the RSE by... 

It was envisaged that the enones were produced following abstraction of H-1 (a process facilitated by the ability of sulfur atoms to stabilize radicals on bonded carbon centers), radical bromination, elimination of hydrogen bromide to give substituted glycals, allylic bromination at C-3, and loss of acetyl bromide. In the formation of compound 6, hydrogen abstraction from C-5 was deemed to compete with that from C-1, and to lead to substitution at the former site with the formation of a relatively stable product. 

Racemization of brinzolamide to the S isomer occurs under heat and light (pH independent) conditions (Fig. 113). This can occur via a radical mechanism from radical formation at the chiral center to form a resonance stabilized planar radical with hydrogen atom addition occurring on both sides of the planar carbon centered-radical to racemize the stereocenter (163). 

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