Benzylic epoxides benzo pyrene 7,8-diol 9,10-epoxide

Benzylic epoxides that undergo rate-limiting 1,2-hydrogen migration 280 Benzo[a]pyrene 7,8-diol 9,10-epoxides 281 Summary of pH-independent mechanisms 283... 

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. 

The first example of syn stereoselective expoxidation of arene dihydrodiols was reported in 1981.11 The trans-dihydrodiols 11 and 12, when treated with a 10-fold excess of MCPBA in tetrahydrofuran (THF) at room temperature, gave stereoselectively the syn-diol epoxides 13 and 14, respectively. This stereoselectivity has been ascribed to the operation of steric control by the axial benzylic hydroxy group the equatorial hydroxy group does not exert such control. The isomeric 9,10-epoxides of 7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene can be prepared by the same method.12... 

For benzo[a]pyrene benzylic carbocations (82 and 83)88,89 and 4-methoxyphenyl-stabilized carbocations (52a, 54b, 66b, 68b and 127),59,63,70,108 values of kaz/ks are in the range 25-600 M-1. It is reasonable to assume that these carbocations also react with azide ion at the diffusional limit of 1010M-1s-1. The rate constants for reaction of these carbocations with water (ks) are estimated to be (8 x 106) to (2 x 108)s, which correspond to energies of activation of 6.5-8.0kcalmol-1. Benzo[a]pyrene 7,8-diol 9,10-epoxides (80 and 81) and tetrahydronaphthalene epoxide each has two optimized conformations similar to structures 132 and 134, which are shown in Scheme 42. The carbocation formed from reaction of each of these... 

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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