Dimerization of free radicals

In another nonelectrolytic process, arylacetic acids are converted to vi c-diaryl compounds 2A1CR2COOH —> ArCR2CR2Ar by treatment with sodium persulfate (Na2S20g) and a catalytic amount of AgNOs." Both of these reactions involve dimerization of free radicals. In still another process, electron-deficient aromatic acyl chlorides are dimerized to biaryls (2 ArCOCl —> ArAr) by treatment with a disilane RsSiSiRs and a palladium catalyst." " ... 

Both mechanisms require an acceptor of protons and electrons which, as shown by preliminary data, may be molecular oxygen. Attempts to distinguish between the two mechanisms were based on the use of other oxidizing agents and kinetic studies U3). In the case of mechanism (b), and in the presence of an excess of oxygen, the bi-molecular reaction of dimerization of free radicals competes with the oxidation reaction. Hence, with an increase in the initial concentration of dimer, one should observe... 

In the intermediate complexe of free radical arylation, it is necessary to oxidize the reaction intermediate to avoid dimerization and disporportio-nation (190-193, 346) In this case isomer yield and reactivity will be highest with radical sources producing very oxidative radicals or in solvents playing the role of oxidants in the reaction. The results are summarized in Tables III-29 and III-30. 

A characteristic reaction of free radicals is the bimolecular self-reaction which, in many cases, proceeds at the diffusion-controlled limit or close to it, although the reversible coupling of free radicals in solution to yield diamagnetic dimers has been found to be a common feature of several classes of relatively stable organic radicals. Unfortunatly, only the rate constants for self-termination of (CH3)jCSO (6 x 10 M s at 173 K) and (CH3CH2)2NS0 (1.1 X 10 M s at 163K) have been measured up to date by kinetic ESR spectroscopy and consequently not many mechanistic conclusions can be reached. 

Reduction of nitrostyrene with aqueous TiCl3 gives a 3,4-diarypyrrole directly in moderate yield (Eq. 10.46).52 The reaction proceeds via dimerization of anion radicals of nitrostyrene and reduction of the nitro function in the dimer to imines. Reduction of dinitrile with diisobutylalu-minum hydride (DIBAL) gives a-free pyrroles (Eq. 10.47) 53 both reactions may proceed in a similar mechanism. These pyrroles are useful intermediates for functionalized porphyrins. 

Since glutathione is synthesized in cells in relatively huge amounts, it is seldom applied as pharmacological antioxidant. Furthermore, the mechanism of its antioxidant activity is not so simple as that of vitamins E and C. The major reason is that the GS radical formed during scavenging of free radicals by GSH does not disappear by dimerization but participates in the chain reaction, producing superoxide (Reactions (20)-(23)). Furthermore, it has recently been shown that contrary to previous findings the rate constant for the reaction of GSH with superoxide is relatively small (200-1000 lmol-1 s-1) [211,223],... 

Besides the mirror and addition reactions already discussed, gas phase radicals dimerize, disproportionate, transfer hydrogen, and polymerize olefins. Similar reactions in the liquid phase are an indication (but not proof) of free radical intermediates. 

Two additional systems were exploited in order to confirm the involvement of free-radical processes during vindoline oxidations. These were the enzyme peroxidase and photochemistry. Horseradish peroxidase (HRP) oxidized both vindoline and 16-O-acetylvindoline in the presence of hydrogen peroxide. Vindoline was converted to the enamine dimer 59 (78). During the reaction, the following sequence of redox reactions occurs ... 

In addition to the stabilization by suitable substituents and the absence of other termination reactions than recombination, it is the strength of the bond formed in the dimerization which is a necessary cofactor for the observation of free radicals by esr spectroscopy. The stability of nitroxides [4] or hydrazyls [5] (Forrester et al., 1968) derives not only from their merostabilized or captodative character but also from a weak N-N bond in the dimer. The same should be the case for captodative-substituted aminyls... 

A photochemical reaction in which the generation of free radicals results in dimerization of the starting mole-... 

Many reactive intermediates can decay via self-reactions, giving dimers or disproportionation products, as is the case of free radicals and carbenes. When these self-reactions are not the ones under study, it is desirable to keep the transient concentration low enough to minimize this type of interference. For example, for a radical that dimerizes with fet = 3 x 10 M s and a concentration c of lO M, its first half-life (ti/2 = 1/kc) would be 33 ps. Note that excited triplet states also undergo bimolecular decay by triplet-triplet... 

Much of the pioneering research on nitrosoalkane dimers is based on reactions involving the formation of free radicals. Most of the reactions are of little value from the preparative standpoint, either because a highly specialized apparatus (e.g., photolysis equipment, high-vacuum trains, even a Van de Graaff generator) is used or because complex mixtures of products are produced. However, this work is of such importance in the historical development of aliphatic nitroso chemistry that it merits a brief review here rather than relegation to Section 5. 

With resonance possibilities, the stability of free radicals increases 149 some can be kept indefinitely.150 Benzylic and allylic151 radicals for which canonical forms can be drawn similar to those shown for the corresponding cations (pp. 168, 169) and anions (p. 177) are more stable than simple alkyl radicals but still have only a transient existence under ordinary conditions. However, the triphenylmethyl and similar radicals152 are stable enough to exist in solution at room temperature, though in equilibrium with a dimeric form. The concen-... 

Ribonucleotide reductase is notable in that its reaction mechanism provides the best-characterized example of the involvement of free radicals in biochemical transformations, once thought to be rare in biological systems. The enzyme in E. coli and most eukaryotes is a dimer, with subunits designated R1 and R2 (Fig. 22-40). The R1 subunit contains two lands of regulatory sites, as described below. The two active sites of the enzyme are formed at the interface between the R1 and R2 subunits. At each active site, R1 contributes two sulfhydryl groups required for activity and R2 contributes a stable tyrosyl radical. The R2 subunit also has a binuclear iron (Fe3+) cofactor that helps generate and stabilize the tyrosyl radicals (Fig. 22-40). The tyrosyl radical is too far from the active site to interact directly with the site, but it generates another radical at the active site that functions in catalysis. 

Although there is little doubt that the electron transfer reaction (Reaction 2) is involved in the over-all reaction (21), the suggestion that quantitative yields of disulfide (13) arise from the dimerization of thiyl radicals is inconsistent with the observed behavior of other free radicals (24). It seems preferable to suggest that some kind of coordination occurs as a prerequisite to the transfer of electrons (12,15). In this case, metal-thiol complexes should be formed as intermediates in the oxidation, in which the metal acts not only as an electron acceptor but also to locate the resultant thiyl entities in close proximity, thereby favoring dimerization reactions and producing disulfide. The electrons gained by the metal may then be passed on to an oxygen molecule. The over-all reaction may be represented as... 

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