Transition metals hydroperoxides

However, because of the high temperature nature of this class of peroxides (10-h half-life temperatures of 133—172°C) and their extreme sensitivities to radical-induced decompositions and transition-metal activation, hydroperoxides have very limited utiUty as thermal initiators. The oxygen—hydrogen bond in hydroperoxides is weak (368-377 kJ/mol (88.0-90.1 kcal/mol) BDE) andis susceptible to attack by higher energy radicals ... 

Hydroperoxides are more widely used as initiators in low temperature appHcations (at or below room temperature) where transition-metal (M) salts are employed as activators. The activation reaction involves electron-transfer (redox) mechanisms ... 

Eithei oxidation state of a transition metal (Fe, Mn, V, Cu, Co, etc) can activate decomposition of the hydiopeioxide. Thus a small amount of tiansition-metal ion can decompose a laige amount of hydiopeioxide. Trace transition-metal contamination of hydroperoxides is known to cause violent decompositions. Because of this fact, transition-metal promoters should never be premixed with the hydroperoxide. Trace contamination of hydroperoxides (and ketone peroxides) with transition metals or their salts must be avoided. 

This reaction is one example of several possible radical transition-metal ion interactions. The significance of this and similar reactions is that radicals are destroyed and are no longer available for initiation of useful radical reactions. Consequentiy, the optimum use levels of transition metals are very low. Although the hydroperoxide decomposes quickly when excess transition metal is employed, the efficiency of radical generation is poor. 

Ketone Peroxides. These materials are mixtures of compounds with hydroperoxy groups and are composed primarily of the two stmctures shown in Table 2. Ketone peroxides are marketed as solutions in inert solvents such as dimethyl phthalate. They are primarily employed in room-temperature-initiated curing of unsaturated polyester resin compositions (usually containing styrene monomer) using transition-metal promoters such as cobalt naphthenate. Ketone peroxides contain the hydroperoxy (—OOH) group and thus are susceptible to the same ha2ards as hydroperoxides. 

The most important process to produce 1-naphthalenol was developed by Union Carbide and subsequently sold to Rhc ne-Poulenc. It is the oxidation of tetralin, l,2,3,4-tetrahydronaphthalene/719-64-2] in the presence of a transition-metal catalyst, presumably to l-tetralol—1-tetralone by way of the 1-hydroperoxide, and dehydrogenation of the intermediate ie, l-tetralol to 1-tetralone and aromatization of 1-tetralone to 1-naphthalenol, using a noble-metal catalyst (58). 1-Naphthol production in the Western world is around 15 x 10 t/yr, with the United States as the largest producer (52). 

Another method of manufacture involves the oxidation of 2-isopropylnaphthalene ia the presence of a few percent of 2-isopropylnaphthalene hydroperoxide/i)ti< 2-22-(y as the initiator, some alkaU, and perhaps a transition-metal catalyst, with oxygen or air at ca 90—100°C, to ca 20—40% conversion to the hydroperoxide the oxidation product is cleaved, using a small amount of ca 50 wt % sulfuric acid as the catalyst at ca 60°C to give 2-naphthalenol and acetone in high yield (70). The yields of both 2-naphthalenol and acetone from the hydroperoxide are 90% or better. 

With most transition metals, eg, Cu, Co, and Mn, both valence states react with hydroperoxides via one electron transfer (eqs. 11 andl2). Thus, a small amount of transition-metal ion can decompose a large amount of hydroperoxide and, consequendy, inadvertent contamination of hydroperoxides with traces of transition-metal impurities should be avoided. 

The reactions of alkyl hydroperoxides with ferrous ion (eq. 11) generate alkoxy radicals. These free-radical initiator systems are used industrially for the emulsion polymerization and copolymerization of vinyl monomers, eg, butadiene—styrene. The use of hydroperoxides in the presence of transition-metal ions to synthesize a large variety of products has been reviewed (48,51). 

Alkyl hydroperoxides are among the most thermally stable organic peroxides. However, hydroperoxides are sensitive to chain decomposition reactions initiated by radicals and/or transition-metal ions. Such decompositions, if not controlled, can be auto accelerating and sometimes can lead to violent decompositions when neat hydroperoxides or concentrated solutions of hydroperoxides are involved. 

Transition-metal ions also interact with hydroperoxide-generated radicals by converting them into ions, eg ... 

The radicals are destroyed and are not available to take part in the desired radical reactions, eg, polymerizations. Thus, transition-metal ion concentrations of metal—hydroperoxide initiating systems are optimized to maximize radical generation. 

As with other hydroperoxides, hydroxyaLkyl hydroperoxides are decomposed by transition-metal ions in an electron-transfer process. This is tme even for those hydroxyaLkyl hydroperoxides that only exist in equiUbrium. For example, those hydroperoxides from cycHc ketones (R, R = alkylene) form an oxygen-centered radical initially which then undergoes ring-opening -scission forming an intermediate carboxyalkyl radical (124) ... 

Metal-Catalyzed Oxidation. Trace quantities of transition metal ions catalyze the decomposition of hydroperoxides to radical species and greatiy accelerate the rate of oxidation. Most effective are those metal ions that undergo one-electron transfer reactions, eg, copper, iron, cobalt, and manganese ions (9). The metal catalyst is an active hydroperoxide decomposer in both its higher and its lower oxidation states. In the overall reaction, two molecules of hydroperoxide decompose to peroxy and alkoxy radicals (eq. 5). 

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Oxidation catalysts are either metals that chemisorb oxygen readily, such as platinum or silver, or transition metal oxides that are able to give and take oxygen by reason of their having several possible oxidation states. Ethylene oxide is formed with silver, ammonia is oxidized with platinum, and silver or copper in the form of metal screens catalyze the oxidation of methanol to formaldehyde. Cobalt catalysis is used in the following oxidations butane to acetic acid and to butyl-hydroperoxide, cyclohexane to cyclohexylperoxide, acetaldehyde to acetic acid and toluene to benzoic acid. PdCh-CuCb is used for many liquid-phase oxidations and V9O5 combinations for many vapor-phase oxidations. 

Alkyl hydroperoxides give alkoxy radicals and the hydroxyl radical. r-Butyl hydroperoxide is often used as a radical source. Detailed studies on the mechanism of the decomposition indicate that it is a more complicated process than simple unimolecular decomposition. The alkyl hydroperoxides are also sometimes used in conjunction with a transition-metal salt. Under these conditions, an alkoxy radical is produced, but the hydroxyl portion appears as hydroxide ion as the result of one-electron reduction by the metal ion. ... 

Deprotonation of H2O2 yields OOH , and hydroperoxides of the alkali metals are known in solution. Liquid ammonia can also effect deprotonation and NH4OOH is a white solid, mp 25° infrared spectroscopy shows the presence of NH4+ and OOH ions in the solid phase but the melt appears to contain only the H-bonded species NH3 and H202. " Double deprotonation yields the peroxide ion 02 , and this is a standard route to transition metal peroxides. 

There are several available terminal oxidants for the transition metal-catalyzed epoxidation of olefins (Table 6.1). Typical oxidants compatible with most metal-based epoxidation systems are various alkyl hydroperoxides, hypochlorite, or iodo-sylbenzene. A problem associated with these oxidants is their low active oxygen content (Table 6.1), while there are further drawbacks with these oxidants from the point of view of the nature of the waste produced. Thus, from an environmental and economical perspective, molecular oxygen should be the preferred oxidant, because of its high active oxygen content and since no waste (or only water) is formed as a byproduct. One of the major limitations of the use of molecular oxygen as terminal oxidant for the formation of epoxides, however, is the poor product selectivity obtained in these processes [6]. Aerobic oxidations are often difficult to control and can sometimes result in combustion or in substrate overoxidation. In... 

The phenomenon that early transition metals in combination with alkyl hydroperoxides could participate in olefin epoxidation was discovered in the early 1970s [30, 31]. While m-CPBA was known to oxidize more reactive isolated olefins, it was discovered that allylic alcohols were oxidized to the corresponding epoxides at the same rate or even faster than a simple double bond when Vv or MoVI catalysts were employed in the reaction [Eq. (2)] [30]. 

Hydroperoxides react with transition metals in lower oxidation states (TiJ, Fe", Cu+, etc.) and a variety of other oxidants to give an alkoxy radical and hydroxide anion (Scheme 3.38)46 224,22"... 

Common components of many redox systems are a peroxide and a transition metal ion or complex. The redox reactions of peroxides are covered in the sections on those compounds. Discussion on specific redox systems can be found in sections on diacyl peroxides (3,3.2.1.5), hydroperoxides (3,3.2.5) persulfate (3.3.2.6.1) and hydrogen peroxide (3.3.2.6,2). 

Colona and coworkers oxidized a variety of alkyl aryl and heterocyclic sulfides to the sulfoxides using t-butyl hydroperoxide and a catalytic amount of a complex (97) derived from a transition metal and the imines of L-amino acids. Of the metals (M = TiO, Mo02, VO, Cu, Co, Fe), titanium gave the highest e.e. (21%), but molybdenum was the most efficient catalyst. The sulfoxides were accompanied by considerable sulfone125. 

Anions of hydroperoxides may be used to successfully obtain sulphones by the oxidation of sulphoxides in non-aqueous media, without the use of transition metal catalysts. This is in contrast to oxidations with peracids where aqueous media are invariably used. Thus, dimethyl sulphoxide was oxidized by the anion of cumene hydroperoxide in ethanol or benzene solution at room temperature in 90% yield66. The yield is very much dependent on the base used and decreases along the series ... 

Variable valence transition metal ions, such as Co VCo and Mn /Mn are able to catalyze hydrocarbon autoxidations by increasing the rate of chain initiation. Thus, redox reactions of the metal ions with alkyl hydroperoxides produce chain initiating alkoxy and alkylperoxy radicals (Fig. 6). Interestingly, aromatic percarboxylic acids, which are key intermediates in the oxidation of methylaromatics, were shown by Jones (ref. 10) to oxidize Mn and Co, to the corresponding p-oxodimer of Mn or Co , via a heterolytic mechanism (Fig. 6). 

Organic hydroperoxides have also been used for the oxidation of sulphoxides to sulphones. The reaction in neutral solution occurs at a reasonable rate in the presence of transition metal ion catalysts such as vanadium, molybdenum and titanium - , but does not occur in aqueous media . The usual reaction conditions involve dissolution of the sulphoxide in alcohols, ethers or benzene followed by dropwise addition of the hydroperoxide at temperatures of 50-80 °C. By this method dimethyl sulphoxide and methyl phenyl sulphoxide have been oxidized to the corresponding sulphone in greater than 90% yields . A similar method for the oxidation of sulphoxides has been patented . Unsaturated sulphoxides are oxidized to the sulphone without affecting the carbon-carbon double bonds. A further patent has also been obtained for the reaction of dimethyl sulphoxide with an organic hydroperoxide as shown in equation (19). 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

Interactions between Lipid Hydroperoxides and Transition Metals... 

In this reaction scheme, the steady-state concentration of peroxyl radicals will be a direa function of the concentration of the transition metal and lipid peroxide content of the LDL particle, and will increase as the reaction proceeds. Scheme 2.2 is a diagrammatic representation of the redox interactions between copper, lipid hydroperoxides and lipid in the presence of a chain-breaking antioxidant. For the sake of clarity, the reaction involving the regeneration of the oxidized form of copper (Reaction 2.9) has been omitted. The first step is the independent decomposition of the Upid hydroperoxide to form the peroxyl radical. This may be terminated by reaction with an antioxidant, AH, but the lipid peroxide formed will contribute to the peroxide pool. It is evident from this scheme that the efficacy of a chain-breaking antioxidant in this scheme will be highly dependent on the initial size of the peroxide pool. In the section describing the copper-dependent oxidation of LDL (Section 2.6.1), the implications of this idea will be pursued further. 

An example of an experiment in which LDL has been treated with 15-lipoxygenase and the oxidation monitored by the formation of conjugated diene is shown in Fig. 2.2. In the absence of transition metal, a rapid increase in absorbance occurs, with no lag phase, which ceases after a period of about 90 min under these conditions. If copper is added to promote LDL oxidation at this point, LDL treated with lipoxygenase oxidizes at a faster rate with a short lag phase when compared to the control. During this procedure there is only a minimal loss of a-tocopherol and so we may ascribe the shortened lag phase to the increase in lipid peroxides brought about by lipoxygenase treatment. A similar result was found when LDL was supplemented with preformed fatty acid hydroperoxides (O Leary eta/., 1992). 

In summary, in our view the principal fectors that contribute to the oxidizability of LDL assessed by the addition of a transition metal such as copper ate (1) the lipid hydroperoxide content of the LDL particle and (2) the a-tocopherol content. Other chain-breaking antioxidants such as ubiquinol and the carotenoids are present only at low concentrations in most individuals, and are unlikely to make a significant contribution. 

The accumulation of hydroperoxides and their subsequent decomposition to alkoxyl and peroxyl radicals can accelerate the chain reaction of polyunsaturated fatty-acid p>eroxidation leading to oxidative damage to cells and membranes as well as lipoproteins. It is well-recognized that transition metals or haem proteins, through their... 

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