Iron‐Promoted ortho‐ and/or ipso‐Hydroxylation of Benzoic Acids with H2O2 |
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Authors: | Olga V. Makhlynets Parthapratim Das Sonia Taktak Dr. Margaret Flook Rubén Mas‐Ballesté Dr. Elena V. Rybak‐Akimova Prof. Dr. Lawrence Que Jr. Prof. Dr. |
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Affiliation: | 1. Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA 02155 (USA), Fax: (+1)?617‐627‐3443;2. Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 (USA), Fax: (+1)?612‐624‐7029 |
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Abstract: | Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [FeII(BPMEN)(CH3CN)2](ClO4)2 ( 1 ) and [FeII(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‐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 FeIV?O species as potential reaction intermediates, but strongly indicate the involvement of an FeIII? OOH intermediate that undergoes intramolecular acid‐promoted heterolytic O? O bond cleavage, producing a transient iron(V) oxidant. |
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Keywords: | aromatic hydroxylation hydrogen peroxide iron oxidation regioselective hydroxylation |
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