Autoxidation initiation reactions

Two aspects of the autoxidation of (TMS SiH are of interest to synthetic chemists19 (i) for radical reactions having long chain length, traces of molecular oxygen can serve to initiate reactions, and therefore no additional radical initiator is needed, and (ii) the oxidized product does not interfere with radical reactions, and therefore the reagent can be used even if partially oxidized, taking into account the purity of the material. From GC analysis, the exact concentration of silane can be deduced. 

The addition of trace levels (> 10 M) of bis(bipyri-dine)cobalt(ll) to 02-saturated solutions of aldehydes in acetonitrile initiates their rapid autoxidation to carboxylic acids. The initial reaction rates appear to be first order in catalyst concentration, first order in substrate concentration, and first order in O2 concentration. However, within one hour the autoxidation process is almost independent of catalyst concentration. 

The initiation reaction is the hemolytic abstraction of hydrogen to form a carbon-centered alkyl radical in the presence of an initiator. Under normal oxygen pressure, the alkyl radical reacts rapidly with oxygen to form the peroxy radical, which in turn reacts with more unsaturated lipids to form hydroperoxides. The lipid-free radical thus formed can further react with oxygen to form a peroxy radical. Hence, the autoxidation is a free radical chain reaction. Because the rate of reaction between the alkyl radical and oxygen is fast, most of the free radicals are in the form of the peroxy radical. Consequently, the major termination takes place via the interaction between two peroxy radicals. 

The majority of compounds that are subject to autoxidation are unsaturated substances or highly condensed polymers, and the target of ROS is commonly the diene fimctionality—or double bonds. Autoxidation of unsaturated lipids is a good model to demonstrate this mechanism. The initial reaction between molecular oxygen and a polyunsaturated fatty acid (PUFA) occurs as RH -l- O2 —> ROOH, which involves the movement of a double bond as well as the insertion... 

During the inhibited self-initiated autoxidation of methyl linoleate by a-Toc in solution, Niki and coworkers made the interesting observation that a-Toc acts as an antioxidant at low concentrations, but high concentrations (up to 18.3 mM) actually increased hydroperoxide formation due to a pro-oxidant effect. The pro-oxidant effect of a-Toc was observed earlier by Cillard and coworkers in aqueous micellar systems and they found that the presence of co-antioxidants such as cysteine, BHT, hydroquinone or ascor-byl palmitate inverted the reaction into antioxidant activity, apparently by reduction of a-To" to a-Toc . Liu and coworkers ° found that a mixture of linoleic acid and linoleate hydroperoxides and a-Toc in SDS micelles exhibited oxygen uptake after the addition of a-Toc. The typical ESR spectrum of the a-To" radical was observed from the mixture. They attributed the rapid oxidation to decomposition of linoleate hydroperoxides, resulting in the formation of linoleate oxy radicals which initiated reactions on the lipid in the high concentration of the micellar micro-environment. Niki and coworkers reported pro-oxidant activity of a-Toc when it was added with metal ions, Fe3+25i Qj. jjj (jjg oxidation of phosphatidyl choline liposomes. a-Toc was found... 

Table 7-2 summarizes kinetic data for the reaction of O2 with esters, diketones, and carbon dioxide.35,37-39 Esters react with superoxide ion to form diacyl peroxides or the carboxylate and the alcohol. Initial reaction occurs via a reversible addition-elimination reaction at the carbonyl carbon (Scheme 7-9). This conclusion is supported by the products that are observed in the gas-phase reaction of O2 with phenyl acetate and phenyl benzoate, which has been studied by Fourier-transform mass spectrometry.40 in effect, there is a competition between loss of O2 and loss of the leaving group. Carbanions are poor leaving groups, so that simple ketones without acidic a-hydrogen atoms are unreactive. The KC(O)OO- radical should be a reactive intermediate for the initiation of the autoxidation of allylic hydrogens (see Chapter 5). 

A specific free radical can be produced from a precursor molecule either in an initiation step or a propagation step in which a reagent radical reacts with the precursor. Initiation requires either removal or addition of an electron or homolysis. Chemically this can be done in a number of ways, by using one-electron oxidants or reductants or by inducing homolysis in some way examples of these types of reactions include autoxidation [84-86], photochemical oxidation and reduction [87-90], and oxidation and reduction by metal ions and their complexes [91-93], In propagation reactions, the reagent radical might be the hydroxyl radical, the hydrated electron, or any other suitably reactive species that will interact with the precursor molecule in the desired manner. We will consider initiation reactions first. 

Prooxidant effects were observed at higher antioxidant concentrations and at higher temperatures. Reversal of the direction of the isotope effects observed under these conditions showed that initiation by direct reaction of the antioxidant with oxygen is an important initiation reaction. Peroxide decomposition is quite slow at 90 °C and begins to contribute significantly to initiation only at the start of a second stage of more rapid, but still retarded, autoxidation. We have suggested (4) that some oxidation product of polymer or antioxidant may induce hydroperoxide decomposition. 

Functional groups that stabilize radicals are expected to increase susceptibility to autoxidation. This is illustrated by two cases that have been relatively well studied. Aldehydes, in which abstraction of the formyl hydrogen is facile, are easily autoxidized. The autoxidation initially forms a peroxycarboxylic acid, but usually the corresponding carboxylic acid is isolated because the peroxy acid oxidizes additional aldehyde in a parallel heterolytic reaction. The final step is an example of the Baeyer-Villiger reaction, which is discussed in Section 12.5.2.1 of Part B. 

The hypothesis of a bimolecular initiation reaction for liquid phase autoxida-tions was extended beyond cyclohexanone as a reaction partner. Also other substances featuring abstractable H-atoms are able to assist in this radical formation process. The initiation barrier was found to be linearly dependent on the C-H bond strength, ranging from 30 kcal/mol for cyclohexane to 5 kcal/mol for methyl linoleate [14, 15]. Substrates that yield autoxidation products that lack weaker C-H bonds than the substrate (e.g., ethylbenzene) do not show an exponential rate increase as the chain initiation rate is not product enhanced [16]. 

An intrinsic problem during the investigation of lipid oxidative deterioration is the uncertainty about the rate of initiative reactions. One possible way of overcoming this problem is to introduce into the reaction mixture a compound that decomposes at a constant rate to free radicals (X ) capable of extracting a hydrogen atom from the fatty acid (RH) and consequently initiating the autoxidation process. 

The reactions were inhibited by hydroquinone which is consistent with a free radical initiated autoxidation. The reaction of tetramethylethylene was more rapid than was oxidation of less substituted olefins in the presence of the Rh(I) and Ir(I) complexes suggesting that initial coordinative interaction between the olefin and the metal center is not an important factor. 

Lewis bases and alkali metal aUtoxides have been used as additives to modify the initiation reaction with alkyllithium compounds. In the presence of THF, the... 

Autoxidation (Section 8.7) Autoxidation involves reaction of a CH bond, especially an allylic one, with oxygen under radical initiation conditions. The primary product is a hydroperoxide. The mechanism involves a radical chain process in which resonance-delocalized allylic radical intermediates react with molecular oxygen to give a peroxy radical that continues the radical chain. 

The conversion of dihydroartemisinic acid to artemisinin is believed to be a ntMienzymatic spontaneous photooxidation or autoxidation reaction. The mechanism of this complex transformation is shown to involve four steps first, initial reaction of the C11-C12 double bond of dihydroartemisinic acid with single molecular oxygen second is the Hock cleavage of the resulting tertiary allylic... 

Formation and reaction of radicals are closely linked. The general scheme of lipid autoxidation - initiation, propagation, and termination -provides an outline of typical radical reactions. 

Ozone is known to react with virtually all organic materials, the rate of reaction being considerably faster with certain unsaturated compounds than with saturated materials. In the latter case it is probable that ozone attack is associated with an autoxidation initiation process. In addition, certain reactions of ozone with organic materials may provide a source of singlet oxygen. It is however in unsaturated materials that ozone has the greatest effect and it is with this aspect that this section is concerned. 

The timehne of an autoxidation reaction is shown in Figure 3.34. At the beginning, the reaction is usually initiated by heat or radiation, so the initial reaction rate is low. This reaction stage is called the induction period. Hydroperoxides gradually accumulate in the system, which causes formation of other radicals, thus the initiating reaction rate increases with an increasing concentration... 

Antioxidants (see Section 11.2.2) are substances that can react with free radicals of the autoxidation chain, especially with peroxyl radicals (Figure 3.66). The reaction creates hydroperoxides or other non-radical Hpid products. The antioxidant is transformed to the form of a free radical, which, however, is fairly stable, so it is unable to continue in the autoxidation reaction. The role of the antioxidant thus lies in shortening the autoxidation chain and increasing the rate of termination reactions. During the reaction the antioxidant is consumed. When aU of the antioxidant has been consumed, the autoxidation reaction proceeds as if no antioxidant was present. Antioxidants therefore cannot completely stop the autoxidation reaction they just slow this reaction down, ideally to the initial reaction rate. 

With an adequate supply of oxygen, the hydrocarbon radicals (R ), formed in the initial phase of the autoxidation chain reaction, preferentially yield hydroperoxyl radicals (ROO ). When there is a limited supply of oxygen (with a low partial pressure of oxygen) and in the absence of antioxidants, hydrocarbon radicals react with each other and form lipid dimers (R R). In the presence of tocopherols, there is a competitive reaction of the hydrocarbon radicals with tocopheroxyl radicals that are stabilised by the formation of hydrocarbons (R H) and other stable products ... 

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