title: Iron-promoted ortho- and/or ipso-hydroxylation of benzoic acids with H(2)O(2).
abstract: Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [Fe(II)(BPMEN)(CH(3)CN)(2)](ClO(4))(2) (1) and [Fe(II)(TPA)(CH(3)CN)(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 H(2)O(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.
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA 02155, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Makhlynets
authors.forename: Parthapratim
authors.initials: P
authors.lastname: Das
authors.forename: Sonia
authors.initials: S
authors.lastname: Taktak
authors.forename: Margaret
authors.initials: M
authors.lastname: Flook
authors.forename: Rubén
authors.initials: R
authors.lastname: Mas-Ballesté
authors.forename: Elena V
authors.initials: EV
authors.lastname: Rybak-Akimova
authors.forename: Lawrence
authors.initials: L
authors.lastname: Que
mesh_terms: D000631:Aminopyridines / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006900:Hydroxylation; D008024:Ligands; D008958:Models, Molecular; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000631:Aminopyridines; D001565:Benzoates; D005296:Ferrous Compounds; D008024:Ligands; D006861:Hydrogen Peroxide