Fenton radical mechanism

The radical or nonradical chemistry of the Fenton-like systems, including the Fenton reaction and the Fe(III)—ROOH (or H2O2) system, is still hotly debated.1123,1130-1134 New information supporting a free-radical mechanism with carbon- and oxygen-centered radicals1135-1138 and new evidence for a nonradical process1139,1140 have been published. 

Hydroxylation of [Cu2(R—XYL—H)]2+ (10) by 02. As described in Section II.C.l, the complete kinetic analysis reveals an initial reversible binding of 02 by 10 to give [Cu2(H—XYL—H)(02)]2+ (11), followed by an irreversible hydroxylation reaction described by k2. The kinetics preclude that a Fenton-type mechanism (production of hydroxyl radical) is involved in the reaction (i.e., that an intermediate peroxo species is further attacked by LCu(I)). We note that [Cu2(H—XYL—H)]4+ (34) cleanly reacts with H202 to give product [Cu2(H—XYL—O—)(OH)]2+ (12), whereas reaction of [Cu2(H—XYL—H)]2+ (10) with hydrogen peroxide does not (unpublished observation). Addition of radical traps to solutions of 10 and 02 also does not affect the hydroxylation (unpublished observation), and all the evidence points to intramolecular hydroxylation by the peroxo-dicopper species 11. 

For phenol hydroxylation it is shown that Fe2+ and Fe3+ ion activity increases in the presence of other ions, among which the highest activity is displayed by salts and complexes of the following metals Co, Mn, Mo, Cu, Fe, etc. In aqueous solution Fenton s reagent oxidizes substrates according to the radical mechanism in which reactions with 0H radicals play the central role. In aprotic solvents oxidation with Fenton s reagent suggests the participation of different intermediates—complexes with iron ions, Fe=0, for example. 

Although Fenton did not observe hydroxyl radical-mediated reactions for mixtures of Fe3+ and hydrogen peroxide, more recent work has illustrated that such systems can produce hydroxyl radical. Haber and Weiss [5] originally proposed a free radical mechanism for the Fe3+-catalyzed decomposition of hydrogen peroxide. These reactions include [3] ... 

Shi and coworkers found that vinyl acetates 68 are viable acceptors in addition reactions of alkylarenes 67 catalyzed by 10 mol% FeCl2 in the presence of di-tert-butyl peroxide (Fig. 15) [124]. (S-Branched ketones 69 were isolated in 13-94% yield. The reaction proceeded with best yields when the vinyl acetate 68 was more electron deficient, but both donor- and acceptor-substituted 1-arylvinyl acetates underwent the addition reaction. These reactivity patterns and the observation of dibenzyls as side products support a radical mechanism, which starts with a Fenton process as described in Fig. 14. Hydrogen abstraction from 67 forms a benzylic radical, which stabilizes by addition to 68. SET oxidation of the resulting electron-rich a-acyloxy radical by the oxidized iron species leads to reduced iron catalyst and a carbocation, which stabilizes to 69 by acyl transfer to ferf-butanol. However, a second SET oxidation of the benzylic radical to a benzylic cation prior to addition followed by a polar addition to 68 cannot be excluded completely for the most electron-rich substrates. 

A Fenton-like mechanism was proposed to explain this product distribution. Hydroxyl radicals, formed by a reaction between the iron complex and H202, abstract protons from the substrate to form carbon radicals R- (equations 2-4) (38, 39). These are subsequently trapped by the diphenylselenide to give a phenylselenyl derivative (equation 4). Increasing the ratio of H202 to 11 switches the reactivity from stoichiometric to catalytic (Scheme 1). 

Photocatalytic activation of allyl and benzyl ethers results either in carbon-carbon coupling or oxygenation [148-151]. The photocatalyst used for these conversions can be generated in situ, by photolysis of a zinc dithiolene salt, by preformed catalysts, or by particles supported within surfactant vesicles. Radical intermediates formed by hydrogen abstraction by photogenerated hydroxyl or hy-droperoxyl radicals may also be important in the photoelectrochemically induced oxidation of hydrocarbons. In the Ti02-sensitized photooxidation of toluene to cresols, for example, a photo-Fenton (radical) type mechanism has been suggested [150]. ... 

The reactions of hydrogen peroxide were taken up by Haber and Weiss (3a,b), who studied certain aspects of the reaction between hydrogen peroxide and ferrous salts and also outlined the importance of the free radical mechanism in many other reactions of hydrogen peroxide. After the early work of Schonbein and the preparative work of Fenton the H2C>2-Fen-salt reaction was investigated by Manchot and Lehmann (4), who claimed to have obtained the following results ... 

Evans et al. (10) have shown that OH radicals produced by the Fenton reagent can initiate the polymerization of vinyl compounds and that the OH radicals, which in the first instance attack the double bond of the monomer, are built into the polymer chain. Stein and Weiss (45) have used the hydroxylation of benzene and of other simple aromatic compounds (e.g., benzoic acid and nitrobenzene) to detect these radicals. In the action of OH radicals on benzene in aqueous systems the formation of phenol and of diphenyl indicated a free radical mechanism of the following type ... 

The evidence for the free radical mechanisms of the reaction between ferrous and ferric ions and hydrogen peroxide is fully discussed in the article by J. H. Baxendale in this volume, and it is necessary here only to summarize and comment on those features especially relevant to hemoprotein reactions. This evidence is essentially indirect. Experiment shows very reactive intermediates to be present and extensive kinetic studies reveal competition reactions for these intermediates in that the overall order of the reaction is found to depend on the reactant concentrations. A free radical mechanism is adopted because it accounts for the chemical reactivity of the system in the oxidation of substrates (Fenton s reaction) and the initiation of the polymerization of vinyl compounds (Baxendale, Evans, and Park, 84) and it provides a set of reactions which largely account for the observed kinetics. The set of reactions which fit best the most recent experimental data is that proposed by Barb, Baxendale, George, and Hargrave (83) ... 

Formation of OH as the ultimate DNA damaging species in the Cr + H2O2 + DNA systems (by a Fenton-like mechanism Eq. 9 in Scheme 6, with n = A) has been proposed (65, 418 21, 426) on the basis of the following observations (1) formation of DMPO—OH adducts detected by EPR spectroscopy (418) (2) inhibition of DNA damage by commonly used radical scavengers, such as NaNs, mannitol, vitamin E, or melatonin (65, 418, 420-422) and... 

Baxendale (1950) explains the properties of the Fenton s reagent by a free radical mechanism ... 

Hydrogen peroxide may react directiy or after it has first ionized or dissociated into free radicals. Often, the reaction mechanism is extremely complex and may involve catalysis or be dependent on the environment. Enhancement of the relatively mild oxidizing action of hydrogen peroxide is accompHshed in the presence of certain metal catalysts (4). The redox system Fe(II)—Fe(III) is the most widely used catalyst, which, in combination with hydrogen peroxide, is known as Fenton s reagent (5). 

Much work has been done on the mechanism of the reaction with Fenton s reagent, and it is known that free aryl radicals (formed by a process such as HO- + ArH AR- + H2O) are not intermediates. The mechanism is essentially that outlined on page 898, with HO- as the attacking species, formed by... 

The reverse reaction (that is, the oxidation of a vinyl radical by Fe to the corresponding vinyl cation) may be involved in the reaction of the dimethyl ester of acetylenedicarboxyUc acid 261 with Fenton s reagent [Fe —H2O2, (217)] (216). When 261 was treated with Fe —H2O2 and the reaction mixture was extracted with ether, a small amount of furan 262 was isolated. A possible mechanism (216) for its formation may be addition of hydroxyl radical to the triple bond of 261, followed by addition of the intermediate vinyl radical to a second molecule of 261 and oxidation of the resulting radical with Fe to the corresponding vinyl cation, followed by cyclization to 262, as shown in Scheme XX. 

Reduction of vinyl radicals by to the corresponding anion also has been observed (216). When purified acetylene is bubbled through Fenton s reagent, acetaldehyde is formed as a product, presumably via the following mechanism ... 

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