Regeneration of alkyl radicals

The P-scission process with peroxy radicals that are highly resonance stabilized, such as with triphenyl methyl peroxyls may be observed even at a markedly lower temperature. The regeneration of alkyl radicals in a reaction system may however proceed through numerous fragmentation and transfer reactions which makes the correct determination of ceiling temperature of peroxy radicals backward decomposition more complicated. 

Chain reactions are usually studied in mixtures, where the situation is more complicated. In mixtures, processes such as electron capture (reaction 12), charge transfer (reaction 13) and energy transfer (reaction 14) might result in the preferential decomposition of the solute (SX) instead of the alkane solvent. However, even in that case, the transfer reactions 9-11 are replaced by reactions 19-21 so that the net effect Is reduction in the yield of hydrogen and the regeneration of alkyl radicals. 

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. 

Nitroxyl radicals are formed as intermediates in reactions of polymer stabilization by steri-cally hindered amines as light stabilizers (HALS) [30,34,39,59]. The very important peculiarity of nitroxyl radicals as antioxidants of polymer degradation is their ability to participate in cyclic mechanisms of chain termination. This mechanism involves alternation of reactions involving alkyl and peroxyl radicals with regeneration of nitroxyl radical [60 64],... 

The regeneration of nitroxyl radical from the product of the reaction of nitroxyl radical with the alkyl macroradical was proved in the following experiments [51]. The nitroxyl radical and initiator (dicumyl peroxide) were introduced in a PP powder and this sample was heated to T= 387 K in an argon atmosphere. The concentration of nitroxyl radical was monitored by the EPR technique. The nitroxyl radical was consumed in PP with the rate of free radical generation by the initiator (see Figure 19.3). Dioxygen was introduced in the reactor after the nitroxyl radical was consumed. The generation of peroxyl radicals induced the formation of nitroxyl radicals from the adduct of the nitroxyl radical with the PP macroradical. 

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],... 

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. 

Miura et al. built on Ryu s previous work to achieve four-component radical cascades leading to diketones (Scheme 63) [174]. This outstanding result relies on initial carbonylation of alkyl radicals to form acyl radicals, such as 196. The nucleophilicity of acyl radicals allowed them to react with electron-deficient olefins to form ct-cyano radicals (197), whose phihcity is now reversed. Thus, they were able to add onto stannyl enolates and led to ketyl radicals such as 198. Those latter radicals underwent / -elimination of trib-utylstannyl radicals. This key elimination regenerated the mediator for the initial dehalogenation. This very fine tuning of the radical reactivities is the key element that makes the whole process work. 

Under thermal conditions, hydroxylamine ethers can reversibly decompose (Reaction 15). The radicals formed disproportionate to eliminate olefins and yield hydroxylamine (Reaction 16). In the presence of sufficiently effective acceptors of alkyl radicals (e.g., oxygen), the reaction rate of peroxy radical formation is much higher than that of hydroxylamine formation. Thus, in the process of polymer photooxidation, nitroxyl radicals regenerate and can break multiple oxidative chains. 

The first step of the Hunsdiecker reaction is quite straightforward. The reaction between silver carboxylate 1 and bromine gives rise to insoluble silver bromide along with acyl hypobromite 3. The unstable acyl hypobromite 3 undergoes a homolytic cleavage of the O-Br bond to provide carboxyl radical 4. Carboxyl radical 4 then decomposes via radical decarboxylation to release carbon dioxide and alkyl radical 5, which subsequently reacts with another molecule of acyl hypobromite 3 to deliver alkyl bromide 2, along with regeneration of carboxyl radical 4. Because of the radical pathway, chirality is often lost for the chiral carbon atom immediately adjacent to the carboxylic acid. 

In continuance of studies on the radical ip.so-substitution of indolyl sulfones, Caddick has developed an alternative approach to fused [l,2-a]indoles based on the intramolecular cyclization of alkyl radicals <97TL6249>. Thus, treatment of 120 with sub-stoichiometric amounts of tosyl radical generates an alkyl radical which cyclizes to the indole ring leading to the fused ring derivatives 121 (n = 1,2) with regeneration of the catalyst. 

Photoreactions of aromatic ketones and quinones take place both in vacuum and in air. The subsequent reactions of alkyl radicals with oxygen significantly affect cross-linking since parent ketones are regenerated from ketyl radicals and simultaneously, hydrogen peroxyl radicals are formed. 

Scheme 9.17 Regeneration of nitroxyl radicals by the reaction of amino ethers with alkyl peroxyl or acyl peroxyl radicals.

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. 

In spirooxaziridines like (114), /3-scission proceeds with ring opening. Stoichiometric amounts of iron(II) salt in acidic solution lead to the dicarboxylic acid derivative (115). The radical undergoes some interesting reactions with added unsaturated compounds. For example, pyridine yields a mixture of 2- and 4-alkylation products in 80% yield. Catalytic amounts of iron(II) ion are sufficient here since the adduct of the radical with pyridine is oxidized by iron(III) ion to the final product (116), thus regenerating iron(II) ion (68TL5609). 

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). 

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