Side chain oxidation rings

Tocotrienols differ from tocopherols by the presence of three isolated double bonds in the branched alkyl side chain. Oxidation of tocopherol leads to ring opening and the formation of tocoquinones that show an intense red color. This species is a significant contributor to color quaUty problems in oils that have been abused. Tocopherols function as natural antioxidants (qv). An important factor in their activity is their slow reaction rate with oxygen relative to combination with other free radicals (11). 

The mechanism of side-chain oxidation is complex and involves reaction of C-J-l bonds at the position next to the aromatic ring to form intermediate ben-zylic radicals, tert- Butyl benzene has no benzylic hydrogens, however, and is therefore inert. 

The oxidation of benzene to phenol and 1,4-dihydroxybenzene (Figure 2.11a) (Hyman et al. 1985), both side chain and ring oxidation of ethyl benzene, and ring-hydroxylation of halogenated benzenes and nitrobenzene (Keener and Arp 1994). 

FIGURE 8.3 Aerobic degradation of toluene by (a) side-chain oxidation, (b) dioxygenation of the ring, and (c) monooxygenation. (From Neilson, A.H. and Allard, A.-S. The Handbook of Environmental Chemistry, Springer, 1998. With permission.)... 

Lonza, for example, has commercialized processes for highly chemo- and regioselective microbial ring hydroxylation and side-chain oxidation of heteroaromatics (see Fig. 2.32 for examples) (Kiener, 1995, 1999). The pharmaceutical intermediate 5-methylpyrazine-2-carboxylic acid, for example, is manufactured by microbial oxidation of 2,5-dimethylpyrazine. Many conversions of the type shown in Fig. 2.32 would not be possible by conventional chemical means. 

Ni et al. [143] investigated the profile of the major metabolites of primaquine produced by in vitro liver microsomal metabolism, with silica gel thin-layer and high performance liquid chromatography analysis. Results indicated that the liver microsomal metabolism could simultaneously produce both 5-hydroxyprimaquine (quinoline ring oxidation product) and carboxyprimaquine (side-chain oxidative deamination product). However, the quantitative comparative study of microsomal metabolism showed that the production of 5-hydroxyprimaquine was far much higher than that of carboxyprimaquine. 

When the alkyl substituent contains secondary C-H bonds, both ring and side chain oxidation at the secondary C-H bond occur. Thus, ethylbenzene gives... 

This reaction does not occur readily spontaneously but is catalyzed by an ATP-dependent magnesium protoporphyrin chelatase.419 422 Subsequently, the carboxyethyl side chain on ring C undergoes meth-ylation (Fig. 24-23, step b) and (3 oxidation (step c). 

Other aromatic molecules also suffer oxygenation on irradiated semiconductor powders. For example, both ring and side chain oxidation products can be observed when toluene is allowed to contact excited Ti02> eq. 91 (289) ... 

A marked difference in hepatic activity of aldehyde oxidase between rats and monkeys was found to be responsible for the reported marked species difference in the metabolism of Zaleplon in vivo. In the postmito-chondrial fractions, S-9s, from liver homogenates of these animals, zaleplon was transformed in the presence of NADPH into the side chain oxidation product, N-desethyl-zaleplon, and the aromatic ring oxidation product, 5-oxo-zaleplon. In the rat S-9, N-desethyl-zaleplon and 5-oxo-zaleplon were a major and a very minor metabolites, respectively. 

Two-electron redox phenomena are rare for Cu, and therefore Cu is not a suitable catalyst for epoxidations, for example. However, Cu is useful for free radical reactions such as deep oxidation of organic molecules in waste streams and ring or side chain oxidation of aromatic compounds. 

Cationic clays have also been used as supports for Cu. Cu-doped alumina-pillared montmorillonites have been employed in the oxidation of toluene and of xylenes with H2C>2. The pillaring and the Cu exchange are performed under acidic conditions at pH 2 and 3.5, respectively. It is unclear whether the Cu2+ remains fully associated with the clay in the presence of H2O2, which is itself acidic. Moreover, the reactions are unselective mixtures of ring-hydroxylated and side chain-oxidized products are obtained (180). 

With branched catechols carrying nucleophilic groups in the side chains, the ring closure reaction occurs. Typical examples are the peroxidase oxidation of dopa and dopamine, which produce a series of compounds such as dopachrome and dopami-nechrome, respectively, which further evolve to compounds related to melanin pigments [46] (Fig. 6.3c). 

Attack other than on the amino group apparently does represent a competitive reaction course when the substituents on the aromatic ring are less electronegative than the nitro group. This is demonstrated by the strong coloration and tar formation observed when N,IV-dimethyl-aniline and p-chloro-N,A7-dimethylaniline are ozonized and by the fact that more ozone is consumed by these compounds than can be accounted for by side chain oxidation (Table III, Experiments 1 and 2). 

The selection of one preferred route for dark secondary reactions from photogenerated cation radicals can also be seen in the products derived from 1-methylnaphthalene. Although ring cleavage is observed on irradiated Ti02 suspensions, side-chain oxidation of the corresponding radical cation takes place in homogeneous solution (Eq. 6) [61]. 

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