Alkyl radicals regeneration

Eor antioxidant activity, the reaction of aminyl radicals with peroxy radicals is very beneficial. The nitroxyl radicals formed in this reaction are extremely effective oxidation inhibitors. Nitroxides function by trapping chain-propagating alkyl radicals to give hydroxylamine ethers. These ethers, in turn, quench chain propagating peroxy radicals and in the process regenerate the original nitroxides. The cycHc nature of this process accounts for the superlative antioxidant activity of nitroxides (see Antioxidants). Thus, antioxidant activity improves with an increase in stabiUty of the aminyl and nitroxyl radicals. Consequendy, commercial DPA antioxidants are alkylated in the ortho and para positions to prevent undesirable coupling reactions. 

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

Since the peroxyl and alkyl radicals are regenerated, the cycle of propagation could continue indefinitely or until one or other of the substrates are consumed. However, experimentally the length of the propagation chain, which can be defined as the number of lipid molecules converted to lipid peroxide for each initiation event, is finite. This is largely because the cycle is not 100% efficient with peroxyl radicals being lost through radical-radical termination reactions (Reaction 2.4 in Scheme 2.1). 

The phenomena of nitroxyl radicals regeneration has been discovered in the study of the retarding effect of 2,2,6,6-tetramethyl-4-benzoyloxypiperidine-A-oxyl on PP initiated oxidation [51]. It has been shown that the limiting step of chain termination by the nitroxyl radical is the reaction with the alkyl macroradical of PP. The resulting compound AmOP is fairly reactive with respect to the peroxyl radical and nitroxyl radical is regenerated in this reaction. Thus, the cycle includes the following two reactions (mechanism I) [60-64] ... 

Consequently, in an inert atmosphere/= 2(1 + k(lls/krcc) > 2. When phenoxyl radicals react only with peroxyl radicals, /= 2 and there is no regeneration. At low dioxygen pressures, phenoxyl radicals react with both peroxyl and alkyl radicals / ranges between 2 and 2(1 +kdis/krec) and increases with decreasing p02- In addition to this, the product of phenol oxidation, quinone, becomes the efficient alkyl radical acceptor at low dioxygen pressure (see earlier). 

Allenylcobaloximes, e.g. 26, react with bromotrichloromethane, carbon tetrachloride, trichloroacetonitrile, methyl trichloroacetate and bromoform to afford functionalized terminal alkynes in synthetically useful yields (Scheme 11.10). The nature of the products formed in this transformation points to a y-specific attack of polyhaloethyl radicals to the allenyl group, with either a concerted or a stepwise formation of coba-loxime(II) 27 and the substituted alkyne [62, 63]. Cobalt(II) radical 27 abstracts a bromine atom (from BrCCl3) or a chlorine atom (e.g. from C13CCN), which leads to a regeneration of the chain-carrying radical. It is worth mentioning that the reverse reaction, i.e. the addition of alkyl radicals to stannylmethyl-substituted alkynes, has been applied in the synthesis of, e.g., allenyl-substituted thymidine derivatives [64],... 

In the propagation part, BuS- adds to the alkene to give an alkyl radical, which abstracts H- from BuSH to give the product and to regenerate the starting radical. 

This procedure has been used to prepare a variety of substituted a-bromohydrocinnamic acids 2 p-acetyl-a-bromohydro-cinnamic acid was prepared for the first time by this method. The method illustrates a typical application of the Meerwein reaction for the arylation of unsaturated substrates.3 In this reaction a catalytic amount of a copper(I) salt is used to reduce an aryl diazonium salt forming an aryl radical and a copper(II) halide. Addition of the aryl radical to an unsaturated substrate forms an alkyl radical that is reoxidized by the copper(II) halide present forming an alkyl halide and regenerating the copper(I) salt catalyst. In this preparation, the product, an a-bromo acid, is formed in an acidic reaction mixture and dehydro-halogenation does not occur. However, dehydrohalogenation... 

Reaction 8 may, therefore, be the major chain-propagating reaction of H02 between 250° and 400°C. The radicals produced will, of course, undergo the same fates as those produced in Reaction 4, regenerating (eventually) alkyl radicals. The main difference between the alkene-H02 addition route and the alkylperoxy radical isomerization route is that in the former case the hydroperoxyalkyl radicals formed are necessarily a-radicals—i.e., radicals in which the unpaired electron is borne by a carbon atom adjacent to that bearing the hydroperoxy group, such as... 

The hydroxyl radical will be the predominant entity which attacks the alkane to regenerate an alkyl radical (Reaction 10) under conditions where isomerization and decomposition are the usual fate of alkylperoxy radicals. The activation energy for attack on an alkane molecule by OH, although difficult to determine accurately (30), is low (I, 3) (1-2 kcal. per mole). This has an important consequence. The reaction will be unselective, being insensitive to C—H bond strength. Each and every alkyl radical derived from the alkane skeleton will therefore be formed. To describe the chain-propagation steps under conditions where isomerization is a frequent fate of alkylperoxy radicals it is necessary, then, to consider each and every alkylperoxy radical derived from the alkane and not just the tertiary radicals. 

Hydroperoxyalkylperoxy radicals will also be potential abstracters of hydrogen from C H2n + 2, giving a dihydroperoxide and regenerating an alkyl radical in a Reaction 11 analogous to Reaction 3. 

Large alkyl radicals are oxidized to alkylperoxy radicals which isomerize to hydroperoxyalkyl radicals the decomposition of these gives molecular products and hydroxyl radicals which attack alkanes unselec-tively to regenerate alkyl radicals. The alkene-H02 addition route is unimportant. 

This produces the major product HBr and a second radical which must undergo reaction to regenerate Br and form the other major product, CH3CHBrCH3, along with a similar reaction to produce the less substantial major product BrCH2CH2CH3. These must be produced by reaction of the two alkyl radicals produced in the two possible first steps of the propagation cycle. 

Radical reduction is followed by a rapid reaction of the 2-hydroxyphenoxyl radical with the boronate 46. In this manner, chain propagation is ensured by the regeneration of the initial alkyl radical and the formation of Meulenhoff s free acid 47 (Scheme 40). 

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