Insights into the formation and isomerization of the benzene metabolite muconaldehyde and related molecules: comparison of computational and experimental studies of simple, benzo-annelated, and bridged 2,3-epoxyoxepins.

2,8-Dioxabicyclo[5.1.0]octa-3,5-diene ("2,3-epoxyoxepin") has been postulated as an intermediate in ring-opening metabolism of benzene. Density functional theory (B3LYP/6-31G*) is employed to study the activation and reaction energies for ring-opening isomerization of 2,3-epoxyoxepin, its 4,5-benzo derivative, and its 3,6-hexamethylene derivative. The results are compared with published experimental data. The markedly different fates of these three molecules suggest a means for testing the postulated metabolic pathway.