Iron-Promoted ortho- and/or ipso-Hydroxylation of Benzoic Acids with H2O2

Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [Fe-II(BPMEN)-(CH3CN2)](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 H2O2 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-hhydroxylation/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 I 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.