Elusive Active Intermediates and Reaction Mechanisms of ortho -/ ipso -Hydroxylation of Benzoic Acid by Hydrogen Peroxide Mediated by Bioinspired Iron(II) Catalysts.

Aromatic hydroxylation of benzoic acids (BzOH) to salicylates and phenolates is fundamentally interesting in industrial chemistry. However, key mechanistic uncertainties and dichotomies remain after decades of effort. Herein, the elusive mechanism of the competitive ortho -/ ipso -hydroxylation of BzOH by H 2 O 2 mediated by a nonheme iron(II) catalyst was comprehensively investigated using density functional theory calculations. Results revealed that the long-postulated Fe V (O)(anti-BzO) oxidant is an Fe IV (O)(anti-BzO • ) species 2 ( anti - and syn - are defined by the orientation of the carboxyl oxygen of BzO to the oxo), which rules out the noted two-oxidant mechanism proposed previously. We propose a new mechanism in which, following the formation of an Fe V (O)( syn -BzO) species ( 3 ) and its electromer Fe IV (O)( syn -BzO • ) ( 3' ), 3 / 3' either converts to salicylate and phenolate via intramolecular self-hydroxylation (route A) or acts as an oxidant to oxygenate another BzOH to generate the same products (route B). In route A, the rotation of the BzO group along the C-O bond forms 2 , in which the BzO group is orientated by π-π stacking interactions. An electrophilic ipso -addition forms a phenolate by concomitant decarboxylation or an ortho -attack forms a cationic complex, which readily undergoes an NIH shift and a BzOH-assisted proton shift to form a salicylate. In route B, 3 oxidizes an additional BzOH molecule directed by hydrogen bonding and π-π stacking interactions. In both routes, selectivity is determined by the chemical property of the BzO ring. These mechanistic findings provide a clear mechanistic scenario and enrich the knowledge of hydroxylation of aromatic acids.