Benzylic epoxides and arene oxides

A more complicated pH-rate profile is also observed for the hydrolysis reactions of benzo[a]pyrene diol epoxide epoxide 80, and is shown in Fig. 5.102 This profile shows Regions A-D that are similar to those for reaction of precocene I oxide 76 (Fig. 4), except that Region B reaches a full plateau that extends from pH 5 to 9 in water. The interpretation of this pH-rate profile is essentially the same as the interpretation of the profile for hydrolysis of precocene I oxide (Fig. 4). The pH-independent reaction of 80 in Region B (discussed in detail in Section Benzylic epoxides and arene oxides ) yields 60% tetrols in a stepwise mechanism involving a carbocation intermediate and 40% ketone from a completely separate pathway (Scheme 31). The negative inflection of the profile at pH 10-11.5 indicates that hydroxide ion reacts as a base with the intermediate carbocation to reform diol epoxide 80 and thus slow the reaction rate. There is a corresponding increase in the yield of ketone 107 at pH >11. 

General acid catalysis in the hydrolysis of 81 is quite facile. This reaction, as discussed in Section Benzylic epoxides and arene oxides and shown in Scheme 39, involves proton transfer to the epoxide oxygen concerted with epoxide C-O bond breaking to form a carbocation 83. For primary ammonium ions with pKa < 8, only the acid form of the amine is reactive, and carbocation formation is irreversible,... 

Hexamethylbenzene reacts with DMDO via three pathways (i) to an arene oxide, which rapidly rearranges to an oxepin tautomer that then is oxidized to a cw-diepoxide and then to a cis, cis,trans-triepoxide (ii) a methyl group migrates in the first epoxide to give a cyclohexadienone, which then reacts to give a frani -diepoxide (iii) C—H insertion to give the benzyl alcohol and then the corresponding benzoic acid. ... 

TABLE 3. ABSOLUTE CONFIGURATIONS AND SIGNS OF ROTATION ([a]D> FOR ENANTIOMERICALLY PURE, NON-K-REGION DERIVATIVES OF THE PAHS. The enantiomers shown for the arene oxides and dihydrodiols are either known or are expected to be those which predominate by the combined action of cytochrome P450c and epoxide hydrolase. The tetrahydrodiols result either by reduction of the dihydrodiols or by trans hydrolysis of the tetrahydroepoxides in which attack by water occurs at the benzylic oxirane carbon. ... 

The observations that the pH-independent reactions of deuterium-labeled 5-met-hoxyindene oxide and 6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2-oxide show significant primary kinetic deuterium isotope effects for the ketone-forming reactions, whereas the pH-independent reactions of deuterium-labeled naphthalene oxide and benzene oxide do not, are quite puzzling. Clearly, more work needs to be done to fully understand why transition-state structures for rearrangement of arene oxides to phenols differ from those for rearrangement of benzylic epoxides to ketones. 

A novel ring-opening reaction of oxirans, catalysed by copper and pyridine, generates c/s-diols under mild conditions. The bicyclic epoxides (186 = 1 or 2) yield (187 n = 1) (95%) and (187 = 2) (85%) in neutral, phosphate-buffered, solution. This type of reaction may have some relevance to the metabolic pathways for fused aromatic compounds, which are thought to proceed via arene oxides and diol epoxides. The catalyst system may be used to add OH", Cr, or MeO regiospecifically to the benzylic centre of indene oxide, with proton addition to the oxygen atom of oxiran. 

Figure 7.9 Another environmental carcinogen is benzo[a]pyrene (BaP). One site of metabolic attack is the terminal ring which is oxidized to form a 7,8-arene oxide. Epoxide hydrolase opens this to form a frans-7,8-dihydrodiol.The remaining C=C bond in the ring may also undergo oxidation to form an epoxide, with the oxidation directed to the same face as the allylic alcohol by coordination of the metabolizing enzyme. This epoxide is now on the opposite face as the benzylic hydroxyl group and is named BaP-frans-7,8-diol-anf/-9,10-epoxide.This is especially stable because it is adjacent to the sheltered bay region of the molecule. It can be opened by epoxide hydrolase to form a detoxified tetraol. Alternatively, DNA can open the epoxide to form a covalent adduct that is responsible for tumor initiation.

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