On the Mechanism of the Oxidation of Toluenes in Artificial P450 Model Systems: Formation of Benzyl Alcohols, Benzaldehydes, and Phenols

Systems with pentafluoroiodosylbenzene (PFIB) and hemin (FeTPPCl8Cl) in dichloromethane were adopted to study the activities of the model system using toluenes as substrates for P450 enzymes. The oxidation products were mainly corresponding benzyl alcohols and benzaldehydes. Previously reported suspension systems were extended to homogeneous mixed solution systems of CH2Cl2/CH3OH/H2O to study the oxidation of benzyl alcohols to the corresponding benzaldehydes: the Hammett relation with (rho) = -0.86 against (sigma)+. As benzaldehydes were scarcely observed in natural P450 systems, the formation of benzaldehyde seemed characteristic only of the "open" model systems. In suspension systems, the product ratios between corresponding benzaldehydes and benzyl alcohols (ald/alc) were about 0.1-0.4, specific to the substituents and conditions applied. Curiously, the ratios (ald/alc) increased with the electronegativity of the substituents on the phenyl rings of the toluene derivatives. Time course experiments in suspension systems indicated that benzyl alcohols and benzaldehydes were formed not stepwise, but simultaneously from toluene. Separate experiments indicated that the reaction of benzyl alcohol to benzaldehyde was four-fold faster than that of toluene to benzyl alcohol. The rate was not enough to elucidate the amount of benzaldehyde. We suggest that the benzyl radical is formed by hydrogen abstraction and is attacked by the second oxidant, PFIB. Rebounding of the hydroxyl radical and the reaction with the oxidant were competitive depending on the conditions. Additionally, small amounts of phenols were formed from toluenes with electron-donating substituents. This was a minor reaction on which the aromatic hydroxylation occurred via epoxidation under the present conditions.