A comprehensive experimental, multivariate statistical, and DFT computational analysis of the catalytic oxidation of benzyl alcohols mediated by Mn(iii) and Fe(iii) metalloporphyrins

Abstract

The oxidation of p-substituted benzyl alcohols by metallated tetraphenylporphyrin catalysts [Mn^III(TPP)Cl] (1) and [Fe^III(TPP)Cl] (2) in the presence of the oxidizing agent (diacetoxyiodo)benzene (DAIB) was evaluated by means of an integrated approach considering the experimental results under the light of a three-level full factorial design (FFD) and density functional theory (DFT) analysis. Aiming to promote and maximize the formation of benzaldehyde and benzoic acid, the use of multivariate analysis allows us to study the interactivity and interplay between critical variables such as catalyst load (mol%) and time (minutes). On the one hand, benzaldehyde formation was optimized when 4.0 mol% of 1 catalyzed the reaction for 90 minutes or when 2.8 mol% of 2 catalyzed the reaction for 100 minutes. On the other hand, benzoic acid formation was favored when 5.0 mol% of 1 was used over 90 minutes or 4.8 mol% of 2 over 60 minutes. Several control tests were performed to verify the catalytic nature of the metalloporphyrins, including the use of butylated hydroxytoluene to confirm the presence of radical species involved in the catalytic process. The possible mechanisms as well as the electronic structures of the main reaction intermediates were assessed by means of DFT calculations and benchmarked against the experimental data and available literature. Catalysts 1 and 2 display subtle but distinct mechanistic pathways that explain the observed differences in chemical reactivity. Additionally, different linear free energy relationships associated with distinct spin densities of transition states were observed during the determinant step when p-substituted R-benzyl alcohol substrates containing R = OMe, H, Cl, NO₂ were considered.