Radical initiator inhibition

Uses. About 35% of the isophthahc acid is used to prepare unsaturated polyester resins. These are condensation products of isophthahc acid, an unsaturated dibasic acid, most likely maleic anhydride, and a glycol such as propylene glycol. The polymer is dissolved in an inhibited vinyl monomer, usually styrene with a quinone inhibitor. When this viscous hquid is treated with a catalyst, heat or free-radical initiation causes cross-linking and sohdification. A range of properties is possible depending on the reactants used and their ratios (97). 

The fact that these reactions are catalyzed by free-radical initiators and inhibited by galvinoxyl (a free-radical inhibitor) " indicates that free-radical mechanisms are involved. 

This problem was first approached in the work of Denisov [59] dealing with the autoxidation of hydrocarbon in the presence of an inhibitor, which was able to break chains in reactions with peroxyl radicals, while the radicals produced failed to contribute to chain propagation (see Chapter 5). The kinetics of inhibitor consumption and hydroperoxide accumulation were elucidated by a computer-aided numerical solution of a set of differential equations. In full agreement with the experiment, the induction period increased with the efficiency of the inhibitor characterized by the ratio of rate constants [59], An initiated inhibited reaction (vi = vi0 = const.) transforms into the autoinitiated chain reaction (vi = vio + k3[ROOH] > vi0) if the following condition is satisfied. 

Rodenas et al. [77] studied PMN-stimulated lipid peroxidation of arachidonic acid. As MDA formation was inhibited both with L-arginine (supposedly due to the formation of excess NO) and DTPA (an iron ion chelator), it was concluded that about 40% of peroxidation was initiated by hydroxyl radicals formed via the Fenton reaction and about 60% was mediated by peroxynitrite. However, it should be noted that the probability of hydroxyl radical-initiated lipid peroxidation is very small (see above). Phagocyte-mediated LDL oxidation is considered below. 

Thomas and Jackson [329] have shown that ebselen inhibited copper-initiated LDL oxidation in the presence of glutathione. Noguchi et al. [330] showed that the inhibitory effect of ebselen on copper-initiated LDL was also observed without glutathione, while in the case of radical-initiated LDL oxidation ebselen was inactive. However, it is possible that ebselen may inhibit both copper- and peroxyl radical-initiated LDL oxidation although in the latter case the inhibitory effect of ebselen depends on the size of peroxyl radical flux [331]. The inhibitory effect of ebselen on LDL oxidation also depends on its ability to reduce LDL hydroperoxides. 

In addition to initiation (Eq. (18)) and propagation (Eqs. (19) and (20)), termination steps are also possible (resulting in, for example, dimers of R ). Radical traps inhibit this type of oxidative addition [194]. 

Solomon (3, h, 5.) reported that various clays inhibited or retarded free radical reactions such as thermal and peroxide-initiated polymerization of methyl methacrylate and styrene, peroxide-initiated styrene-unsaturated polyester copolymerization, as well as sulfur vulcanization of styrene-butadiene copolymer rubber. The proposed mechanism for inhibition involved deactivation of free radicals by a one-electron transfer to octahedral aluminum sites on the clay, resulting in a conversion of the free radical, i.e. catalyst radical or chain radical, to a cation which is inactive in these radical initiated and/or propagated reactions. 

The detailed mechanism for these Co AlPO-18- and Mn ALPO-18-cata-lyzed oxidations are unknown, but as previously pointed out vide supra) and by analogy to other metal-mediated oxidations a free-radical chain auto-oxidation (a type IIaRH reaction) is anticipated [63], This speculation is supported by several experimental observations that include (1) an induction period for product formation in the oxidation of n-hexane in CoAlPO-36, (2) the reduction of the induction period by the addition of free-radical initiators, (3) the ability to inhibit the reaction with addition of free-radical scavengers, and (4) the direct observation of cyclohexyl hydroperoxide in the oxidation of cyclohexane [62],... 

Volume I. Liquid-Phase, Base-Catalyzed and Heteroatom Oxidations, Radical Initiation and Interactions, Inhibition... 

They do not react with R02 radicals. The inhibited oxidation rate is proportional to the oxygen pressure and inversely proportional to the nitroxide concentration, but it is independent of the substrate concentration—i.e., rate oc [02]/[nitroxide]. The nitroxides react slowly with hydrocarbons and hydroperoxides and therefore have little tendency to initiate oxidation. However, they are of disappointingly little practical value compared with more conventional chain-breaking antioxidants because they must compete with molecular oxygen for the R radicals, and the... 

The kinetics of the zinc diisopropyl dithiophosphate-in-hibited oxidation of cumene at 60°C. and Tetralin at 70°C. have been investigated. The results cannot be accounted for solely in terms of chain-breaking inhibition by a simple electrow-transfer mechanism. No complete explanation of the Tetralin kinetics has been found, but the cumene kinetics can be explained in terms of additional reactions involving radical-initiated oxidation of the zinc salt and a chain-transfer step. Proposed mechanisms by which zinc dialkyl dithiophosphates act as peroxide-decomposing antioxidants are discussed. 

The drug has a half-life of 6-8 hours. It is extensively metabolized in the liver, and stereoselective metabolism of its two isomers is observed. Since metabolism of ( R)-carvedilol is influenced by polymorphisms in CYP2D6 activity and by drugs that inhibit this enzyme s activity (such as quinidine and fluoxetine, see Chapter 4), drug interactions may occur. Carvedilol also appears to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis independently of adrenoceptor blockade. These effects may contribute to the clinical benefits of the drug in chronic heart failure (see Chapter 13). 

Oxidation of Tetramethylethylene. Tetramethylethylene, TME, was an excellent model olefin since it was rapidly and selectively oxidized in the presence of many transition metal complexes (12). Oxidation of TME in the presence of the group VIII metal complexes [MCI(CO)-(Ph3P)2] (M = Rh, Ir) at 50°C gave two major products 2,3-dimethyl-2,3-epoxybutane, I, and 2,3-dimethyl-3-hydroxy-l-butene, II (Reaction 5). Reaction mixtures were homogeneous with no observable deposits of insoluble materials. Little oxidation occurred under these conditions in the absence of the metal complexes, but low yields of I and II were obtained in the presence of a radical initiator (Table I). Reactions were severely inhibited by hydroquinone. The ruthenium (II) complex, [RuCl2(Ph3P)3]2, also promoted efficient oxidation of TME yielding I... 

Free-radical polymerization processes are used to produce virtually all commercial methaerylie polymers. Usually free-radical initiators tqv > such as a/o compounds or ieroxides are used to initiate the polymerisations. Photochemical and radiation-initiated polymerizations are also well known. At it constant temperature, the initial rate of the hulk or solution radical polymerization of methaerylie monomers is first-order with respect to monomer eoneentration. anil one-half order with respect to the initiator concentration. Methacrylate polymerizations are markedly inhibited by-oxygen therefore considerable care is taken to exclude air during the polymerization stages of manufacturing. 

A variation on the aryne mechanism for nucleophilic aromatic substitution (discussed above, Scheme 2.8) is the SrnI mechanism (see also Chapter 10). Product analysis, with or without radical initiation or radical inhibition, played a crucial role in establishing a radical anion mechanism [21]. The four isomeric bromo- and chloro-trimethylbenzenes (23-X and 25-X, Scheme 2.9) reacted with potassium amide in liquid ammonia, as expected for the benzyne mechanism, giving the same product ratio of 25-NH2/23-NH2 = 1.46. As the benzyne intermediate (24) is unsymmetrical, a 1 1 product ratio is not observed. 

Although the acetylene derivatives Co2(CO)6(C6H5C=CCOOH) and Co3(CO)9(H)(CH=CC6H5) were also found to initiate polymerization in the presence of CC14) Co2(CO)8 was found to be not only inactive, but actually to inhibit polymerization in the presence of conventional free radical initiators. The unusual behavior of dicobalt octacarbonyl may be related to its greater reactivity. The reaction with carbon tetrachloride has been studied by Dent et al. (22a) and Ercoli et al. (26a) who isolated a complex C1C [Co(CO)3]3. This could arise from a series of C—Cl cleavage reactions... 

It is thus apparent that hydrogen donors AH and hydroperoxide decomposers, such as PR"3, can act synergistically to inhibit radical initiated polymer chain oxidations. 

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