Iron-promoted ortho-And/or ipso-hydroxylation of benzoic acids with H ₂O₂

Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [Fe^II(BPMEN)-(CH₃CN) ₂](ClO₄)₂ (1) and [Fe^II(TPA)- (CH₃CN)₂](OTf)₂ (2), where BPMEN=N, N'-dimethyl-N, N'-bis(2-pyridylmethyl)-1,2-ethylenediamine, TPA=tris-(2- pyridylmethyl)amine. Two cis-sites, which are occupied by labile acetonitrile molecules in 1 and 2, are available for coordination of H₂O ₂ and substituted benzoic acids. The hydroxylation of the aromatic ring occurs exclusively in the vicinity of the anchoring carboxylate functional group: ortho-hydroxylation affords salicylates, whereas ipso-hydroxylation with concomitant decarboxylation yields phenolates. The outcome of the substituent directed hydroxylation depends on the electronic properties and the position of substituents in the molecules of substrates:3-substituted benzoic acids are preferentially ortho-hydroxylated, whereas 2-and, to a lesser extent, 4-substituted substrates tend to undergo ipso-hydroxylation/decarboxylation. These two pathways are not mutually exclusive and likely proceed via a common intermediate. Electron-withdrawing substituents on the aromatic ring of the carboxylic acids disfavor hydroxylation, indicating an electrophilic nature for the active oxidant. Complexes 1 and 2 exhibit similar reactivity patterns, but 1 generates a more powerful oxidant than 2. Spectroscopic and labeling studies exclude acylperoxoiron(III) and Fe^IV=O species as potential reaction intermediates, but strongly indicate the involvement of an Fe^III-OOH intermediate that undergoes intramolecular acid-promoted heterolytic O-O bond cleavage, producing a transient iron(V) oxidant.