1.1 Peroxidation

The reactions of dioxygen with organic materials are arguably among the most important of all chemical reactions. The oxidation of carbon-based nutrients is the basis of life energy and the combustion of hydrocarbon minerals is the primary source of domestic and industrial energy. Directed oxidation of primary oil-based hydrocarbons is currently the method of choice for the manufacture of intermediates in the chemical industry; a large number of the primary intermediates for the polymer and fine organic chemicals industries are based upon products derived from hydrocarbons by oxidation. Very often, as in the manufacture of phenol from isopropyl benzene, oxidation occurs (see Scheme 1.1) by the classical radical chain reaction first proposed by Bolland, Bateman and co-workers [1,2] and which is common to all peroxidation reactions [3,4]. In the case of cumene and other highly peroxidisable hydrocarbons, the mild oxidation conditions allow the intermediate hydroperoxide to be isolated.

In general, the more reactive is the substrate to autoxidation, the higher is the yield of hydroperoxide. However, when the desired product is not the hydroperoxide itself but one of its decomposition products, the oxidation is carried out under conditions where the intermediate hydroperoxide undergoes thermolysis to give a stable end-product. Thus, in the oxidation of cyclohexane to adipic acid or of ρ-xylene to ρ-toluic acid, the intermediate hydroperoxides are not isolated (see Scheme 1.2).

A common feature of many industrial autoxidation processes is the use of transition metal ions, frequently cobalt carboxylates, which in small amount catalyse the radical breakdown of the intermediate hydroperoxide by reactions (1) and (2), thus reducing the activation energy of this process and increasing the rate of the overall reaction:

+M2→RO·+−OH+M3+ (1)

+M3+→ROO·+H++M2+ (2)

Catalysis by low concentrations of transition metal ions is a common feature of all oxidation processes and is particularly important in biological systems due to the ubiquitous presence of iron in both complexed and ionic form.

Many peroxidation processes are autoinhibiting; that is the rates of oxygen absorption and hydroperoxide formation become slower as the reaction proceeds. In the case of iso-propyl benzene, it was discovered empirically that the addition of a small amount of a base markedly increased the yield of hydroperoxide [5]. It was suggested by Roberston and Waters [6] that the autoinhibition of alkyl aromatic oxidation was due to the formation of a small amount of phenol by the acid catalysed process shown in Scheme 1.1. Phenol is a weak antioxidant which functions by reducing the intermediate alkylperoxyl:

(3)

and is thus a retarder of the radical chain reaction which leads to the accumulation of hydroperoxide. The phenoxyl radical is relatively stable and readily undergoes dimerisation to dimers and trimers (reaction 3(b)) which are themselves weak chain-breaking antioxidants [7]. However, it is unlikely that reaction 3(a) is primarily responsible for autoinhibition, because phenols without ortho tertiary alkyl groups are not efficient antioxidants since they undergo chain transfer with oxidisable substrates like cumene (reaction 3(c)). It is much more likely that acid catalysed decomposition of cumene hydroperoxide is the main cause of inhibition in Scheme 1.1. This is a general antioxidant mechanism which will be discussed in more detail in Chapter 4, but it should be noted that, following the pioneering work of Oberright et al on the mechanisms of sulphur antioxidants in petroleum hydrocarbons [8], measurement of the ratio between the ionic decomposition products of cumene hydroperoxide (phenol + acetone) and the homolytic decomposition products (a-cumyl alcohol + a-methylstyrene + acetophenone) is frequently used as a diagnostic technique to identify and quantify the significance of peroxidolytic antioxidants in peroxide initiated peroxidations [9–16]. Autoinhibition is very general in peroxidation since low molecular weight carboxylic acids are widely formed by breakdown of hydroperoxides. Most important of these are formic acid (see Scheme 1.1) which has pKa = 3.8 and malonic acid (pKa = 1.9). Even benzoic acid (pKa = 4.2) and acetic acid (pKa = 4.8) are sufficiently acidic to provide a mild antioxidant effect, although benzoic acid and to a lesser extent other carboxylic acids can also induce radical decomposition of hydroperoxides at higher concentrations [17]:

(4)

In industrial practice, alkali is added continuously to autooxidising cumene in order to maintain the pH at 7.0 [18] and thus inhibit the acid catalysed decomposition of the hydroperoxide.

Many industrial chemicals undergo peroxidation under ambient conditions, particularly in the presence of light. The explosion danger of peroxidised diethyl ether during distillation is well known and warnings about their removal before distillation is an essential part of the safety advice given to chemistry students. Similar problems are encountered with other dialkyl ethers. For example, tetrahydrofuran is widely used in polymer characterisation (e.g. in size exclusion chromatography) and unless hydroperoxides are removed before using this solvent, their thermal degradation products may confuse the outcome of the analysis.

1.2 Effect of Substrate Structure on Peroxidation Rate

For most carbon-based substrates at ambient oxygen pressures, the reaction of an alkyl radical with dioxygen, reaction (5), occurs with zero activation energy. Consequently, the rate-controlling step in the radical chain oxidation process is the rate of reaction of alkylperoxyl with the substrate. Two alternative reactions have to be considered.

·+O2→ROO· (5)

· + RH→ROOH + R· (6a)

· + C=C→ROOC−C· (R′·) (6b)

The first, reaction 6(a), is the rate of hydrogen abstraction of the most labile hydrogen atom in the substrate and the second, reaction 6(b) is the addition of alkylperoxyl to a reactive double bond. Both reactions may occur together if the activation energies are similar. For example, allyl benzene and indene copolymerise with ground state oxygen to give a low molar mass copolymer of oxygen and olefin [19]. This is illustrated for indene in Scheme 1.3 [20]. where it can be seen that hydroperoxide formation constitutes a chain-transfer process. 1,2-substituted double bonds do not normally participate in reaction 6(b) but olefins conjugated, either with carbonyl groups, with other olefinic double bonds or with aromatic rings may copolymerise with oxygen [19].

The driving force for both 6(a) and 6(b) is the stability of the radical produced. Many polyunsaturated allylic and benzylic compounds form delocalised radicals and autoxidise slowly at ambient temperature even in the absence of light. However, polar factors are also involved in the transition state since alkylperoxyl is electrophilic and it was elegantly shown by Russell many years ago that the relative oxidisabilities of the para substituted alkyl benzenes obey the Hammett relationship [21]. This is shown for substituted toluenes in Table 1.1. In general, substrates containing alkyl are activated to oxidation, whereas those containing halogens, nitryl, nitro and carboxyl groups are deactivated [21].