Epoxidation of aromatic rings

Epoxides of aromatic rings (arene oxides) rearrange to phenols and are substrates for glutathione-S-epoxide transferase to give glutathione conjugates, the precursors of mercapturic acids (Boyland and Williams 1965). 

Direct epoxidations of aromatic rings are very difficult to achieve by chemical methods because of the high stability of the double bonds within such systems due to their aromatic character. For the same reason the formed epoxides are usually very unstable, undergoing a number of reactions and rearrangements. Therefore, only few thoroughly investigated examples of epoxidations at aromatic rings have been described ... 

Arene(tricarbonyl)chromium complexes, 19 Nickel boride, 197 to trans-alkenes Chromium(II) sulfate, 84 of anhydrides to lactones Tetrachlorotris[bis(l,4-diphenyl-phosphine)butane]diruthenium, 288 of aromatic rings Palladium catalysts, 230 Raney nickel, 265 Sodium borohydride-1,3-Dicyano-benzene, 279 of aryl halides to arenes Palladium on carbon, 230 of benzyl ethers to alcohols Palladium catalysts, 230 of carboxylic acids to aldehydes Vilsmeier reagent, 341 of epoxides to alcohols Samarium(II) iodide, 270 Sodium hydride-Sodium /-amyloxide-Nickel(II) chloride, 281 Sodium hydride-Sodium /-amyloxide-Zinc chloride, 281 of esters to alcohols Sodium borohydride, 278 of imines and related compounds Arene(tricarbonyl)chromium complexes, 19... 

Zirconium(IV) isopropoxide, 352 Reductive alkylation of aromatic rings Birch reduction, 32 (S)-Prolinol, 261 of carbonyl groups Trityl perchlorate, 339 of other substrates Lithium-Ammonia, 158 Reductive cleavage (see also Reduction of epoxides)... 

The active oxygen species of cytochromes P-450 is reactive enough to transfer its oxygen atom to most organic compounds. However, the most frequently encountered reactions are (1) the hydroxylation of C—H bonds, (2) the epoxidation of double bonds, (3) the hydroxylation of aromatic rings, and (4) the transfer of an oxygen atom to compounds containing an N, S, or P heteroatom. 

Cytochromes P-450 also catalyze the hydroxylation of aromatic rings. In most cases, these reactions involve the intermediate formation of arene oxides derived from the epoxidation of a double bond of the aromatic compound and an isomerization of these very reactive epoxides into the corresponding phenols. 

Sodium hypochlorite is used for the epoxidation of double bonds [659, 691] for the oxidation of primary alcohols to aldehydes [692], of secondary alcohols to ketones [693], and of primary amines to carbonyl compounds [692] for the conversion of benzylic halides into acids or ketones [690] for the oxidation of aromatic rings to quinones [694] and of sulfides to sulfones [695] and, especially, for the degradation of methyl ketones to carboxylic acids with one less carbon atom [655, 696, 697, 695, 699] and of a-amino acids to aldehydes with one less carbon [700]. Sodium hypochlorite is also used for the reoxidation of low-valence ruthenium compounds to ruthenium tetroxide in oxidations by ruthenium trichloride [701]. 

S. Banfi, M. Cavazzini, G. Pozzi, S. V. Barkanova, O. L. Kaliya, Kinetic studies on the interactions of manganese-porph)Tins with peracetic acid. Part 1. Epoxidation of alkenes and hydroxylation of aromatic rings, J. Chem. Soc. Perkin Trans. 2(4) (2000) 871. 

In sum, considerable evidence is now available for the oxidation of aromatic rings not only via the conventional epoxidation pathway, but also by mechanisms that do not involve formation of an epoxide as an intermediate. The non-epoxide mechanisms involve addition of the ferryl oxygen... 

SCHEME 13 CYP-catalyzed epoxidation of aromatic and heteroaromatic rings. 

The formation of epoxides in the P450-cat-alyzed oxidation of aromatic rings has been directly demonstrated, for example in the oxidation of benzene [203], or can be irrferred from isolation of subsequently formed trawx-dihydrodiol or glutathione conjugates, of which there are many examples, e.g., phenanthrene [204]. However, epoxide metabolites are not mandatory intermediates in the oxidation of aromatic rings. One example is provided by hydroxylations, often meta to a halide substituent, in which the hydrogen on the hydroxylated carbon is quantitatively... 

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