I. Mechanisms of Aryl Epoxide Hydrolysis II. Biphasic Peroxyacid Epoxidation
Creators: name: Zhao, Chumang
Publisher: name: Maryland Shared Open Access Repository
Year: 2008
Subjects: Epoxide
mechanism
transition state effect
substituent
carcinogent
biphasic
Chemistry, Organic (0490)
Chemistry, Physical (0494)
Chemistry, Analytical (0486)

description: Many environmental pollutants such as trichloroethene, styrene, benzo[a]pyrene, and cyclopenta[cd]pyrene are metabolized into epoxides in mammals. These epoxides are electron-deficient species, and they alkylate DNA. If DNA is not properly repaired, mutations leading to cancer may result. Therefore efforts to elucidate the mechanisms of epoxide reactions are very important. Epoxides are also important synthetic precursors of many organic compounds. A study of structure-reactivity relationships of epoxide reactions will lead to a better understanding of the mechanisms of epoxide reactions. 5-Methoxyacenaphthylene 1,2-oxide (47) was synthesized and its hydrolysis reactions were studied as a model for the hydrolysis reactions of cyclopenta[cd]pyrene 3,4-oxide (25). Acid-catalyzed hydrolysis of 47 yielded 62% of cis diol product, 37% of trans diol product, and &lt;1% of ketone. The pH-independent reaction of 47 yielded &gt;94% ketone. The cis and trans diols, treated with 0.1 M HClO4, underwent equilibration to form a mixture containing 81% of trans diol and 19% of cis diol. The fact that the less stable cis diol is the major product from acid-catalyzed hydrolysis of 47 is attributed to transition state effects. Favorable hydrogen bonding between the carbocation intermediate and attacking water molecule may lower the energy of the transition state leading to the less stable cis diol. 7-Methoxynaphthalene 1,2-oxide (61), 7-methoxy-1-deuterionaphthalene 1,2-oxide (61-1d) and 6-methoxynaphthalene 1,2-oxide (68) were synthesized, and their hydrolysis reactions to form phenols were studied. The kinetic deuterium isotope effect in the acid-catalyzed hydrolysis of 61 (kH(61)/ kH(61-1d) was found to be slightly inverse (0.96 ± 0.01). The kinetic deuterium isotope effect on pH-independent reaction of 61 was found to be normal (k0(61)/k0(61-1d) = 1.09 ± 0.01). The rate of the acid-catalyzed hydrolysis of 7-methoxy-substituted naphthalene oxide 61 was found to be only 20 times faster than that of the unsubstituted naphthalene 1,2-oxide (75). However, 61 is 1400 time more reactive than 75 in the pH-independent reaction. The fact that strong electron-donating methoxy group has a relatively small substituent effect on the acid-catalyzed hydrolysis of naphthalene oxide, but a fairly large substituent effect on its pH-independent reaction is rationalized by mechanisms involving an ""early"" transition state in the acid-catalyzed reaction and a ""late"" transition state in the pH-independent reaction.  In a third investigation, we studied the epoxidation of several olefins with MCPBA in basic biphasic conditions. We found that the epoxidation of cis-stilbene, cis-?-methylstyrene, cis-?-deuteriostyrene, cis-2-hexen-1-ol and cis-3-hexen-1-ol results in the formation of both cis and trans epoxides in varying ratios that depend on the conditions. Our results are consistent with two competing mechanisms for biphasic epoxidation, a concerted mechanism leading to only cis epoxide and a stepwise mechanism, involving an intermediate, leading to mostly trans epoxides.