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Iron‐Promoted ortho ‐ and/or ipso ‐Hydroxylation of Benzoic Acids with H 2 O 2
Author(s) -
Makhlynets Olga V.,
Das Parthapratim,
Taktak Sonia,
Flook Margaret,
MasBallesté Rubén,
RybakAkimova Elena V.,
Que Lawrence
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901296
Subject(s) - chemistry , hydroxylation , decarboxylation , medicinal chemistry , heterolysis , substituent , carboxylate , stereochemistry , electrophile , benzoic acid , reactivity (psychology) , deprotonation , oxidative decarboxylation , organic chemistry , catalysis , medicine , ion , alternative medicine , pathology , enzyme
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 OO bond cleavage, producing a transient iron(V) oxidant.