Cytochrome P-450 model reaction: effects of substitution on the rate of aromatic hydroxylation

The study of haemin-catalysed oxidation reactions was extended to substituted aromatic rings. Both electron-donating and electron-withdrawing substituents on aromatic rings act as para- and meta-directing agents in the presence of tetrakis(2,6-dichlorophenyl)porphyrin iron(III) chloride as catalyst and m-chloroperbenzoic acid as oxidant. A new kinetic method for measuring relative rates of epoxidation of alkenes and related compounds has been developed; while steric hindrance results in decreasing the rate of hydroxylation, electron-rich and electron-withdrawing substituents were found to increase the rate of hydroxylation. A linear relationship between the logarithm of the relative rate of hydroxylation and σ Hammet is obtained, although electron-donating and electron-withdrawing substituents fit separate lines. Addition of pyridine to haemin was shown to increase the yield of epoxidation but decrease the yield of aromatic hydroxylation.