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

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.

Dataset for Modelling Reaction Mechanisms Using Density Functional Theory: Mechanism of ortho‐Hydroxylation by High‐Valent Iron‐Oxo Species

“…Iron catalyzed hydroxylations of organic compounds have been reported by several catalysts and studied by several experimentalists and theoreticians [3][4][5][6][7][8]. The Fe III -OOH, Fe IV =O, and Fe V =O species are reported to be involved in the hydroxylation of aromatic and aliphatic compounds [3,4]. At several instances, although the presence of Fe III -OOH species has been directly detected, high-valent iron-oxo species are invoked to explain the reactivity of many mononuclear heme/nonheme iron enzymes.…”

“…Particularly in the last decade the Fe IV =O species are very popular as they have been hypothesized as potential oxidants in several aliphatic/aromatic hydroxylation reactions [9][10][11][12][13]. Besides the Fe IV =O, the Fe V =O intermediates also captured attention very recently in the hydroxylation reactions [3,4] (Figure 2).…”

“…Of particular interest here is the recently reported ortho-hydroxylation of aromatic compounds by a putative iron(V)-oxo species [3,4]. In this dataset paper, we aim to list all the data which are collected over the years to underpin this reaction mechanism.…”

“…In this dataset paper, we aim to list all the data which are collected over the years to underpin this reaction mechanism. In our original study [17], we use [Fe II (TPA) (CH 3 CN) 2 ] 2+ (tpa = tris(2-pyridylmethyl)amine) complex (shown in Figure 1) which performs ortho-hydroxylation very selectively [3]. Experimentally the mechanism of this regiospecific reaction is probed by various sets of tools such as spectroscopy and 18 O labelling experiments [3].…”

“…In our original study [17], we use [Fe II (TPA) (CH 3 CN) 2 ] 2+ (tpa = tris(2-pyridylmethyl)amine) complex (shown in Figure 1) which performs ortho-hydroxylation very selectively [3]. Experimentally the mechanism of this regiospecific reaction is probed by various sets of tools such as spectroscopy and 18 O labelling experiments [3]. Since hydrogen peroxide is employed as the oxidant in this chemistry, the oxygen atom of the H 2 O 2 is found to be incorporated in the product.…”