Aquasoluble iron(III)-arylhydrazone-β-diketone complexes: Structure and catalytic activity for the peroxidative oxidation of C5-C 8 cycloalkanes

Article abstract of DOI:10.1016/j.jinorgbio.2012.05.008

The aquasoluble Fe^III complexes [Fe(H₂O) ₃(L¹)] 4H₂O (3) and [Fe(H₂O) ₃(L²)] 3H₂O (4), bearing the basic forms of 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl) -2-hydroxy-benzenesulfonic acid (H₃L¹, 1) and 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzenesulfonic acid (H₃L², 2), were synthesized and fully characterized including by X-ray crystal structural analysis. In the channels of the water-soluble 3D networks of 3 and 4, the uncoordinated water molecules are held by oxygen atoms of the carbonyl and sulfonyl groups, and by the water ligands. The Fe^III coordination environment resembles that in the active sites of some mononuclear non-heme iron-containing enzymes. The complexes show a high catalytic activity for the peroxidative oxidation (with aqueous H ₂O₂) of C₅-C₈ cycloalkanes to the corresponding alcohols and ketones under mild conditions. The effects of various factors, such as amounts of oxidant, catalyst and HNO₃ additive, were investigated allowing to reach overall yields of ca. 25% and turnover numbers (TONs) up to 290. The catalytic reactions proceed via both oxygen- and carbon-radicals as shown by radical trap experiments.

Full text of DOI:10.1016/j.jinorgbio.2012.05.008

Journal of Inorganic Biochemistry 115 (2012) 72–77
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Journal of Inorganic Biochemistry
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Aquasoluble iron(III)-arylhydrazone-β-diketone complexes: Structure and catalytic
activity for the peroxidative oxidation of C5–C8 cycloalkanes
Maximilian N. Kopylovich a, Tatiana C.O. Mac Leod a, Matti Haukka b, Gunel I. Amanullayeva c,
Kamran T. Mahmudov a,d, Armando J.L. Pombeiro a,
⁎
a
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Technical University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
Department of Chemistry, University of Eastern Finland, P.O. Box 111, FIN-80101, Joensuu, Finland
Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, Hojaly Ave. 30, 1025 Baku, Azerbaijan
Baku State University, Department of Chemistry, Z. Xalilov Str. 23, Az 1148 Baku, Azerbaijan
b
c
d
a r t i c l e i n f o
a b s t r a c t
The aquasoluble FeIII complexes [Fe(H2O)3(L1)]∙4H2O (3) and [Fe(H2O)3(L2)]∙3H2O (4), bearing the basic
forms of 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxy-benzenesulfonic
acid (H3L1, 1) and 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzenesulfonic acid
(H3L2, 2), were synthesized and fully characterized including by X-ray crystal structural analysis. In the chan-
nels of the water-soluble 3D networks of 3 and 4, the uncoordinated water molecules are held by oxygen
atoms of the carbonyl and sulfonyl groups, and by the water ligands. The FeIII coordination environment re-
sembles that in the active sites of some mononuclear non-heme iron-containing enzymes. The complexes
show a high catalytic activity for the peroxidative oxidation (with aqueous H2O2) of C5–C8 cycloalkanes to
the corresponding alcohols and ketones under mild conditions. The effects of various factors, such as amounts
of oxidant, catalyst and HNO3 additive, were investigated allowing to reach overall yields of ca. 25% and turn-
over numbers (TONs) up to 290. The catalytic reactions proceed via both oxygen- and carbon-radicals as
shown by radical trap experiments.
Article history:
Received 20 February 2012
Received in revised form 21 May 2012
Accepted 21 May 2012
Available online 28 May 2012
Keywords:
Arylhydrazones of β-diketones
Mimicking of active sites of iron-containing
oxidases
X-ray structure
Oxidation of C5–C8 cycloalkanes
© 2012 Elsevier Inc. All rights reserved.
1. Introduction
to prepare model for such enzymes still constitutes a significant chal-
lenge. Good solubility in water, the common solvent in biological pro-
Mononuclear non-heme iron-containing enzymes are essential for
many biological processes, namely involving substrate oxidation, hy-
droxylation, halogenation, desaturation and ring-closure [1–8]. The
reactivity of such enzymes via Fenton-type chemistry [9] provides
the conversion of superoxide anion and hydrogen peroxide to hy-
droxyl radical [10], reactions essential to initiate lipid peroxidation
[11] or to prevent tissue damage [12,13].
Within the large versatility of mononuclear non-heme iron-
containing enzymes, in a number of cases their metal centers can dis-
play a main structural motif with iron bound by two histidines and a
carboxylic acid side chains of a protein, showing an O,N,O-coordina-
tion environment. The other coordination sites can be vacant in the
resting state (e.g., with labile water molecule ligands) and participate
in the oxidation or hydroxylation upon interaction with substrate, ox-
ygen and/or a cofactor (e.g., ketoglutarate) [1,2,5].
cesses, is an important feature of the model to be achieved and
usually the preparation of water-soluble complexes involves the use
of a ligand with a hydrophilic functionality which can be created by
attaching a water-solubilizing group, such as sulfonato [15].
Arylhydrazones of β-diketones (AHBD) (Scheme 1, for those of the
present study) are compounds which can be easily prepared from rela-
tively cheap starting materials (aromatic amines and beta-diketones)
by the easy and well-studied two-step Japp–Klingemann procedure
[16,17]. The utilization of an aromatic amine with a sulfo-substituent al-
lows the easy introduction of the water-solubilizing functionality. Fur-
ther, AHBD compounds contain a O,N,O donor site of high flexibility,
which can chelate a number of metal–ions, thus leading to CuII
[18–24], ZnII [25–28], NiII [19,29], NaI [30], KI [24,29], PbII [25], CdII
[26] complexes. The preparative procedures for these complexes are
usually rather straightforward giving high yields of the final products.
It was demonstrated [31] that, in solution, FeIII also interacts with
AHBD but, before the current work, FeIII–AHBD complexes in solid
phase had not yet been isolated and structurally characterized.
A high number of complexes have been prepared to model active
sites of mononuclear non-heme iron-containing enzymes [1,8,14], but
the syntheses of most of them appear to be rather complicated, expen-
sive and time-consuming. Hence, the design of a simple, cheap and easy
Peroxidative oxidation of alkanes, in particular cyclohexane, is a
widely used model to check and compare the activity of the complexes
when biomimicking active sites of various oxygenases [32–34]. More-
over, alkane functionalization stands as a challenge for the establishment
⁎
Corresponding author. Tel.: +351 218419237; fax: +351 21 846 4455.
E-mail address: pombeiro@ist.utl.pt (A.J.L. Pombeiro).
0162-0134/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.jinorgbio.2012.05.008

M.N. Kopylovich et al. / Journal of Inorganic Biochemistry 115 (2012) 72–77
73
Scheme 1. Arylhydrazones of β-diketones (AHBD) of this work.
of hydrocarbon feedstocks, and new methodologies for C\H bond oxida-
tion can result in synthetic strategies toward more complex and valuable
organic products [35–40]. Several CuII–AHBD complexes have been suc-
cessfully applied as catalysts for a few oxidation reactions, in particular
the peroxidative oxidation of cyclohexane and benzylalcohol [18,21],
but FeIII–AHBD compounds have not yet been reported as catalysts for
the cycloalkane oxidation.
Thus, we focused this work on the following aims: (i) to prepare, by an
easy and convenient way, new water-soluble iron(III)–AHBD complexes
with a O,N,O-chelating environment and potentially unsaturated by bear-
ing labile ligands (water molecules); (ii) to demonstrate the viability of
the synthesized complexes to mimic oxygenases, in particular alkane per-
oxidase [1,3,4,6–8,40]. To reach these aims, 5-chloro-3-(2-(4,4-dimethyl-
2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxybenzenesulfonic acid
(H3L1, 1) and 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-
5-nitrobenzenesulfonic acid (H3L2, 2) (Scheme 1) were chosen as ligand
sources to prepare the FeIII complexes, and the peroxidative oxidation of
C5–C8 cycloalkanes was applied as a model reaction.
ethanol. The solution was cooled in an ice bath to ca. 273 K, and a suspen-
sion of 3-amino-5-chloro-2-hydroxybenzenesulfonic acid diazonium (see
above) was added in three portions under vigorous stirring for 1 h.
H3L1 (1). Yield, 75% (based on 5,5-dimethylcyclohexane-1,3-dione),
yellow powder, soluble in water, methanol, ethanol, and insoluble in chlo-
roform. Anal. Calcd for C14H15ClN2O6S (Mr=374.8): C, 44.86; H, 4.03; N,
7.47. Found: C, 44.65; H, 3.98; N, 7.36%. IR, cm−1: 3504 ν(OH), 3385
ν(NH), 1647 ν(C_O), 1597 ν(C_N). 1H NMR (300.13 MHz, DMSO-d6)
δ: 1.03 CH3, 4.03 CH2, 7.23–7.58 (2H, C6H2), 11.30 (s, 1H, Ar\OH),
14.95 (s, 1H, NH). 13C{1H} NMR (75.468 MHz, DMSO-d6) δ: 30.0 (2CH3),
30.3 (Cipso), 51.7 (CH2), 52.0 (CH2), 115.6 and 123.0 (2Ar\H), 123.6
(Ar\Cl), 130.8 (Ar\NH\N), 131.3 (Ar\SO3H), 132.8 (C_N), 141.8
(Ar\OH), 192.8 (C_O), 197.7 (C_O).
2.3. Syntheses of FeIII complexes
1 mmol of 1 (or 2) was dissolved in 15 mL water (pH 2), then 1 mmol
of FeCl3∙2.5H2O was added. The mixture was stirred at room temperature
for 5 min and left for slow evaporation; the greenish-black crystals of the
product started to form after ca. 4 d at room temperature; they were then
filtered off and dried in air.
2. Experimental
2.1. Materials and instrumentation
[Fe(H2O)3(L1)]∙4H2O (3). Yield, 52% (based on Fe). Calcd. for
The 1H and 13C NMR spectra were recorded at room temperature on
a Bruker Avance II+300 (UltraShield™ Magnet) spectrometer operating
at 300.130 and 75.468 MHz for proton and carbon-13, respectively. The
chemical shifts are reported in ppm using tetramethylsilane as the inter-
nal reference. The infrared spectra (4000–400 cm−1) were recorded on
a BIO-RAD FTS 3000MX instrument in KBr pellets. Carbon, hydrogen, and
nitrogen elemental analyses were carried out by the Microanalytical Ser-
vice of the Instituto Superior Técnico. Chromatographic analyses were
undertaken by using a Fisons Instruments GC 8000 series gas chromato-
graph with a DB-624 (J&W) capillary column (flame ionization detector)
and the Jasco–Borwin v.1.50 software. The internal standard method
was used to quantify the organic products.
C
14H26ClFeN2O13S (Mr=553.72): C 30.37, H 4.73, N 5.06. Found C
30.79, H 4.56, N 4.87. IR (KBr), cm−1: 3319 and 3074 (s, br) ν(OH),
1655 (s) ν(C_O) and δ(OH), 1554 (s) ν(C_N).
[Fe(H2O)3(L2)]∙3H2O (4). Yield, 45% (based on Fe). Calcd. for
C
11H20FeN3O14S (Mr=506.20): C 26.10, H 3.98, N 8.30. Found C
25.90, H 4.00, N 8.06. IR (KBr), cm−1: 3431 and 3089 (s, br) ν(OH),
1664 (s) ν(C_O), 1629 (s) ν(C_O) and δ(OH), 1591 (s) ν(C_N).
2.4. X-ray measurements
The crystals of 3 and 4 were immersed in cryo-oil, mounted in a Nylon
loop, and measured at the temperature of 100 K. The X-ray diffraction
data were collected on a Bruker Smart Apex II [42] (3) Bruker Kappa
Apex II Duo (4) diffractometer using Mo Kα radiation (λ=0.710 73 Å).
The APEX2 program package was used for cell refinements and data re-
ductions. The structures were solved by direct methods using the
SHELXS-97 program with the WinGX graphical user interface [43–45]. A
semi-empirical multi-scan absorption correction based on equivalent re-
flections (SADABS) [46] was applied to all data. Structural refinements
were carried out using SHELXL-97 [44]. The H2O hydrogen atoms were lo-
cated from the different Fourier map but constrained to ride on their par-
ent atom with Uiso =1.5 Ueq (parent atom). Other hydrogen atoms were
positioned geometrically and constrained to ride on their parent atoms
with Uiso =1.2–1.5 Ueq (parent atom). The crystallographic details are
summarized in Table S1. CCDC 851668 and 851669 contain the supple-
mentary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2.2. Synthesis of 1
The synthesis and characterization of 2 were reported earlier [20];
the previously unknown arylhydrazone 1 was synthesized by a mod-
ified [41] Japp–Klingemann reaction between the aromatic diazonium
salt of 3-amino-5-chloro-2-hydroxybenzenesulfonic acid and 5,5-
dimethylcyclohexane-1,3-dione in water–ethanol solution containing
sodium hydroxide.
Diazotization: 3-amino-5-chloro-2-hydroxybenzenesulfonic acid (2.
24 g, 10 mmol) was dissolved in 50 mL water, and 0.40 g (10 mmol) of
NaOH was added. The solution was cooled in an ice bath to 273 K and
0.69 g (10 mmol) of NaNO2 was added; 5.00 mL HCl was then added in
0.5 mL portions for 1 h. The temperature of the mixture should not ex-
ceed 278 K.
Azocoupling: NaOH (0.40 g, 10 mmol) was added to a solution of
1.40 g (10 mmol) of 5,5-dimethylcyclohexane-1,3-dione with 50 mL of

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M.N. Kopylovich et al. / Journal of Inorganic Biochemistry 115 (2012) 72–77
Scheme 2. Schematic representations of complexes 3 and 4.
14.95 which is assigned [18] to the proton of the protonated nitrogen
2.5. Oxidation of C5–C8 cycloalkanes
atom adjacent to the aryl unit (=N–NH–hydrazone form, Scheme 1).
The IR spectrum of the isolated compound discloses ν(OH) and ν(NH)
vibrations at 3504 and 3385 cm−1, respectively, while ν(C_O) and
The reaction mixtures were prepared as follows: to 0.1–10.0 μmol
of the complex 3 or 4 contained in the reaction flask were added 4 mL
of MeCN, 0–400 μmol of HNO3, 1.00 mmol of cycloalkane and
2.5–12.5 mmol of H2O2 solution (30% in H2O), in this order. The reac-
tion mixture was stirred for 6 h at room temperature (ca. 298 K) and
air atmospheric pressure, then 90 μL of cycloheptanone (as internal
standard) and 5.0 mL of diethyl ether (to extract the substrate and
the products from the reaction mixture) and 1.0 g of PPh3 (to reduce
the cycloalkanyl hydroperoxide, if formed, to cycloalkanol) [47,48]
were added. The resulting mixture was stirred for 15 min, and then
a sample taken from the organic phase was analyzed by GC using a
FISONS Instruments GC 8000 series gas chromatograph with a DB
WAX fused silica capillary column (P/N 123-7032) and the Jasco–
Borwin v.1.50 software. Blank experiments were performed and con-
firmed that no cycloalkane oxidation products (or only traces, below
0.3%) were obtained in the absence of the metal catalyst. In the experi-
ments with radical traps, the carbon radical trap CBrCl3 or TEMPO was
used in a stoichiometric amount relative to the substrate (cycloalkane),
and the oxygen radical trap Ph2NH was added in a stoichiometric
amount relative to H2O2.
ν(C_N) are observed at 1647 and 1597 cm−1
, correspondingly,
supporting the existence of the H-bonded hydrazone structure in the
solid state.
Slow evaporation of an aqueous solution (pH 2) of 1 or 2 and FeIII chlo-
ride hydrate furnishes greenish-black crystals of the monomeric complex
[Fe(H2O)3(L1)]∙4H2O (3) or [Fe(H2O)3(L2)]∙3H2O (4) (Scheme 2, Fig. 1).
Elemental analyses support the formulation, while IR spectra reveal
3074 and 3319 (s, br) ν(OH), 1655 (s) ν(C_O) and δ(OH), 1554 (s)
ν(C_N) for 3 and 3089 and 3431 (s, br) ν(OH), 1664 (s) ν(C_O), 1629
(s) ν(C_O) and δ(OH), 1591 (s) ν(C_N) cm−1 for 4.
The molecular structures of complexes
3 and 4 have been
established by single-crystal X-ray diffraction (Table S1 with the crystal
data and structure refinement details) which discloses the coordination
of the deprotonated basic (L1)3− and (L2)3− species, respectively
(Scheme 2, Fig. 1). In spite of the variation of the β-diketone fragment
(pentane-2,4-dione in 3 or 5,5-dimethylcyclohexane-1,3-dione in 4)
and of the substituent of the aromatic part (NO2 in 3 or Cl in 4), both
structures are quite similar, the positive charges of the FeIII ions being
compensated by negative charges of N1, O4, O1 (sulfo group oxygen)
in 3 and N1, O6, O1 in 4. The iron atoms in 3 and 4 are 6-coordinated,
the Fe\O bond lengths range from 1.9247(9) to 2.0691(10)Å in 3 and
from 1.958(4) to 2.029(4)Å in 4, whereas the Fe(1)\N(1) distance is
2.0998(10)Å in 3 and 2.092(4)Å in 4 (Table S2 with selected bond
lengths and angles). The coordination environment of the iron is best
described as a distorted octahedron (4+2); one part of (L1)3−
(N1O4O6O8) in 3 and (L2)3− (N1O5O6O7) in 4, and the water mole-
cules (O7O9) in 3 and (O8O9) in 4, the latter being coordinated at
axial positions. The iron atom belongs to two fused five- and six-
membered metallacycles, Fe1–N1–C5–C6–O4 and Fe1–N1–N2–C7–
3. Results and discussion
3.1. Synthesis and characterization of 1–4
Compound H3L1 (1) (Scheme 1) was prepared by a modified (see
Experimental section) known [39] aqueous diazotization of 3-amino-5-
chloro-2-hydroxybenzenesulfonic acid with subsequent coupling with
5,5-dimethylcyclohexane-1,3-dione, while the preparation and charac-
terization of H3L2 (2) have been reported earlier [20]. The 1H-NMR spec-
trum of 1 in DMSO-d6 solution at room temperature shows a signal at δ
(b)
(a)
Fig. 1. Thermal ellipsoid plots, drawn at the 50% probability level, of the complexes 3 (a) and 4 (b).

M.N. Kopylovich et al. / Journal of Inorganic Biochemistry 115 (2012) 72–77
75
Scheme 3. Oxidation of cyclohexane using 3 or 4 as a catalyst precursor.
C14–O6 in 3, and Fe1–N1–C6–C1–O6 and Fe1–N1–N2–C7–C10–O5 in 4.
3.2. Catalytic activity of complexes 3 and 4
Coordinated water molecules are anti to each other and involved in two
hydrogen bonds with the non-coordinated water molecules. The aver-
age H2O⋯O distances of the hydrogen bonds in 3 and 4 fall within the
2.5879(14)–3.6224(13)Å and 2.592(6)–3.058(7)Å ranges, respectively
(Table S3), consistent with formation of a strong hydrogen bonding
[49,50]. Thus, 3 and 4 show 3D networks with channels, in which
water molecules interconnect with carbonyl and sulfonyl oxygen
atoms of the ligands and other water molecules. In accord with the ge-
ometry of the complexes, the channels incorporating the coordinated
water have a nearly quadratic cross-section, whereas those containing
the hydrate water molecules have an elongated profile. Moreover, the
building blocks of [Fe(H2O)3(L1)] in 3 and [Fe(H2O)3(L2)] in 4 are asso-
ciated in layers separated by water molecules. In the structures of 3 and
4, the neighboring iron units are positioned in relative proximity to each
other (Fe⋯Fe separation of 5.612 and 5.447 Å, respectively) as a result of
their linkage via strong H-bonds (Table S3). In the latter case, the pack-
ing structure is determined by the coordination behavior of the water
molecules, leading to O\H⋯O bonded molecular zigzag strands which
are further associated by the edge-to-face aromatic interactions.
In general, the coordination (O5NFe) environment of the FeIII cen-
ter in 3 and 4 resembles that in the active site of, e.g., the peroxidase
Desulfovibrio vulgaris [10], among others mononuclear non-heme iron
enzymes [1,3,4,6–8]. As has been mentioned, the enzymes share a
common structural motif in which two histidines and one carboxylate
occupy a trigonal face of the metal coordination sphere [2]. This facial
triad is proposed to anchor the FeIII center in the active site, leaving
the remaining coordination sites available for binding exogenous
ligands such as cofactor, substrate, and/or H2O2 [6]. Such an arrange-
ment allows the enzyme to juxtapose reactants to facilitate catalysis.
In addition, it has been suggested that ligating anionic exogenous li-
gands may prime the iron center for binding and activating O2 or
H2O2, presumably by altering the redox potential of the metal center
[3]. Thus, we applied the synthesized FeIII–AHBD complexes as model
catalysts for the peroxidative oxidation of cycloalkanes with H2O2.
To prove the viability of the FeIII complexes 3 and 4 as peroxidase
models, their catalytic activity in the oxidation of cyclohexane, a
model reaction to test and compare activities of oxidase bio-
mimicking complexes, was tested. In accord, 3 and 4 exhibit good cat-
alytic activities in the oxidation of that alkane to a cyclohexanol and
cyclohexanone mixture, by aqueous hydrogen peroxide in acidic me-
dium at room temperature (Scheme 3, n=1), with a total yield of ca.
25% and turnover number (TON) values up to 290 mol of products per
mole of catalyst, for a single batch (Table S4). Both 3 and 4 catalyst
precursors display a high selectivity toward cyclohexanone (the
main final product) and cyclohexanol, as no other products of the ox-
idation of cyclohexane were detected. The obtained maximum yields
are higher than those reported for mono-, di-, tetra- and polynuclear
CuII–AHBD species under similar conditions (Table S5) [18,21].
A positive effect is observed upon addition of nitric acid as an ad-
ditive. In the absence of acid, the oxidation proceeds with overall
yields not higher than 7%. The addition of the acid promoter (up to
a HNO3: catalyst molar ratio of 10:1) leads to a remarkable yield
growth for both 3 and 4 (up to 25%, Fig. 2). A high promoting effect
of that acid on the oxidation of alkanes (and other substrates), cata-
lyzed by various iron, copper or vanadium complexes [40,51–60],
has previously been recognized [36–39,47,48]. The role of HNO3 is
conceivably associated with (i) the activation of the metal center by
further unsaturation upon protonation of the anionic basic ligand,
(ii) the enhancement of oxidative properties of metal complexes,
(iii) the stabilization of oxidant and promotion of peroxo (or hydro-
peroxo)-complexes formation [32].
The effect of the H2O2 amount on the overall yield is depicted in
Fig. 3. The increase of the n(H2O2)/n(catalyst) molar ratio up to 750
(which corresponds to the H2O2:substrate molar ratio of 7.5:1.0)
leads to an enhancement of the yield up to 23% or 25%, for 3 or 4, re-
spectively. However, further increase of the oxidant amount results in
a significant yield drop, eventually due to the increase of the water
content in the reaction mixture, resulting in lowering of alkane solu-
bility, and/or to overoxidation reactions at higher H2O2 amounts.
Fig. 2. Effect of nitric acid-to-catalyst molar ratio on the total (cyclohexanol and cyclo-
hexanone) yield, in the peroxidative oxidation of cyclohexane. Reaction conditions:
CH3CN (4 mL), C6H12 (1 mmol), H2O2 (7.5 mmol), catalyst (10 μmol), nitric acid addi-
tive (0–400 μmol), 25 °C, 6 h.
Fig. 3. Effect of the oxidant-to-catalyst molar ratio on the total (cyclohexanol and cy-
clohexanone) yield, in the peroxidative oxidation of cyclohexane. Reaction conditions:
CH3CN (4 mL), C6H12 (1 mmol), H2O2 (2.5–12.5 mmol), catalyst (10 μmol), acid addi-
tive (100 μmol), 25 °C, 6 h.

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M.N. Kopylovich et al. / Journal of Inorganic Biochemistry 115 (2012) 72–77
(a)
(b)
Fig. 4. Effects of the amounts of catalysts 3 and 4 on the total (cyclohexanone and cyclohexanol) yield (a) and TON (b), in the peroxidative oxidation of cyclohexane. Reaction con-
ditions: CH3CN (4 mL), C6H12 (1 mmol), H2O2 (7.5 mmol), n(HNO3)/n(cat)=10, 25 °C, 6 h.
The catalyst amount also plays a significant role and its increase
leads to a yield enhancement (Fig. 4(a)), e.g., from 2.9% to 25% for the
respective amounts of 0.1 and 10 μmol of catalyst 4 (corresponding to
catalyst-to-substrate molar ratios of 1·10−4 and 1·10−3, respective-
ly). On the other hand, a decrease of the catalyst amount below the typ-
ical value of 10 μmol results in enhancements of the overall TON
(Fig. 4(b)), e.g., from 25 up to 290 for catalyst 4, the maximum TON
corresponding to the catalyst amount of 0.1 μmol (substrate/catalyst
molar ratio of 10,000).
catalyze the oxidation of cycloalkanes (Table 1) to the corresponding
alcohols and ketones. The maximum total yields of products are
achieved in the oxidation of C5H10 (17%), C6H12 (25%), C7H14 (17%)
and C8H16 (13%). In the case of cyclooctane a lower yield is observed
(Table 1, entries 7 and 8), probably due to substantial sterical hin-
drance. In all cases, catalyst 4 shows a slightly higher activity over
the complex 3.
4. Conclusions
The cyclohexane oxidation appears to proceed mainly by mecha-
nisms that involve both carbon-centered and oxygen-centered radi-
cals (the former upon homolysis of an alkane C\H bond), since
very pronounced decreases in product yields occur when the reac-
tions are carried out in the presence of either a carbon-radical trap
such as CBrCl3 or TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl) or
an oxygen-radical trap such as Ph2NH. In fact, the use of CBrCl3 almost
completely suppresses the formation of cyclohexanol and cyclohexa-
none (Table S4, entries 29 and 32) when used in excess relative to the
alkane, whereas the presence of TEMPO leads to 77–84% suppression
of activity (Table S4, entries 30 and 33) for a stoichiometric amount in
relation to the alkane. The use of Ph2NH (stoichiometric amount rel-
ative to H2O2) leads to a lowering of the activity of ca. 86–92%
(Table S1, entries 31 and 34). Thus, the pronounced yield drops veri-
fied for cyclohexane oxidations when containing free radical scaven-
gers corroborate the involvement of radical pathways that can
compete with metal-based oxidations catalyzed by other FeIII com-
plexes with N,O\ or O,O\ ligands [18,32–34].
In this work, an easy and straightforward synthesis of new
aquasoluble FeIII complexes bearing sulfonate-functionalized AHBD
ligands was performed by simple reaction of an iron salt with the
corresponding AHBD in water (pH 2) and under air at room temper-
ature. To our knowledge, they are the first FeIII–AHBD complexes to
be structurally characterized. Moreover, they display catalytic activity
(overall yields of alcohols and ketones up to 25% with TONs up to
290) in the peroxidative oxidation of C5–C8 cycloalkanes, thus exten-
ding for the first time the application of FeIII–AHBD complexes to this
type of catalytic reactions. These proceed via both oxygen- and
carbon-radicals as shown by experiments with radical traps.
These FeIII catalysts (or catalyst precursors) are more active for
such a peroxidative oxidation than the other known AHBD complexes
with different metals, and the study deserves to be extended to the
syntheses of FeIII complexes with other aquasoluble AHBD ligands
and their expected applications as oxidation catalysts for various
types of substrates, mimicking the functions of iron-oxidases.
Tables listing crystallographic data, atomic coordinates, bond lengths
and bond angles, anisotropic displacement parameters, hydrogen
The oxidation of other C5–C8 cycloalkanes was also tested with
previously optimized reaction parameters. Both compounds 3 and 4
Table 1
Peroxidative oxidation of cycloalkanes (C5–C8) to the corresponding alcohols and ketones.a
Entry
Cycloalkane
Catalyst
Yield of products (%)b
Alcohol
Ketone
Totalc
1
2
3
4
7.4
6.5
8.1
10.2
15.5
16.7
3
4
3
4
11.3
10.8
12.3
14.6
23.6
25.4
5
6
3
4
7.9
7.6
9.0
9.5
16.9
17.1
7
8
3
4
6.1
5.4
6.7
7.9
12.8
13.3
a
Reaction conditions: catalyst (10 μmol), cycloalkane (1 mmol), H2O2 (7.5 mmol), n(HNO3)/n(cat)=10 in acetonitrile (4 mL), 25 °C, 6 h.
Moles of product/100 mol of cycloalkane.
Yield of products.
b
c

M.N. Kopylovich et al. / Journal of Inorganic Biochemistry 115 (2012) 72–77
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drogen bonds and some catalytic results can be found on line at http://
dx.doi.org/10.1016/j.jinorgbio.2012.05.008.
Acknowledgments
This work has been partially supported by the Foundation for Sci-
ence and Technology (FCT), Portugal, and its PTDC/QUI-QUI/102150/
2008 and PEst-OE/QUI/UI0100/2011 projects, and “Science 2007”
program. The authors acknowledge the Portuguese NMR Network
for providing access to the NMR facility. G. I. A. expresses gratitude
to the Science Development Foundation of Azerbaijan.
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