Mild alkane C-H and O-H oxidations catalysed by mixed-N,S copper, iron and vanadium systems

Article abstract of DOI:10.1016/j.apcata.2011.05.035

Reactions of 1,6-bis(2′-pyridyl)-2,5-dithiahexane (Py ₂S₂) with different sources of Cu(II), Fe(II) and V(III) afford the corresponding novel complexes [CuCl(Py₂S₂)]Cl (1), [CuCl(Py₂S₂)](CuCl₂) (1′), [Cu(OTf)₂(Py₂S₂)] (2), [Cu(Py₂S ₂)(H₂O)₂](OTf)₂ (2′), [FeCl₂(Py₂S₂)] (3), [Fe(Py₂S ₂)(CH₃CN)₂][SbF₆]₂ (4) and [VCl₂(Py₂S₂)]Cl (5), bearing Py ₂S₂ as a tetradentate ligand. All the compounds were characterised by IR, ESI-MS, elemental analyses and, in the cases of 1′, 2′ and 4, the molecular structures were also elucidated by single X-ray crystal diffraction analysis. Complexes 1-5 were evaluated as catalysts or catalyst precursors for the mild peroxidative oxidation of cyclohexane in acetonitrile typically at 25 °C and in the solvent-free oxidation of primary and secondary alcohols under microwave (MW) irradiation. The influences of the type and amount of acid promoter, amounts of oxidant and catalyst, time and temperature, on the product yields and TONs, are investigated. The iron(II) complexes 3 and 4 are the most active catalysts in the oxidation of cyclohexane with H₂O₂ in a slightly acidic medium, leading to maximum overall yields (based on the alkane) of 38 and 28%, and turnover numbers (TON) up to 950 and 1450, respectively. Additionally, the Cu and Fe complexes (1-4) proved to be useful catalysts in various MW-assisted alcohol oxidations at 80 °C with t-BuOOH. The oxidation of 1-phenylethanol catalysed by the Fe complex 3 in the presence of pyrazine-2-carboxylic acid (co-catalyst) is very fast, giving the acetophenone product (TOF = 4470 h^-1) in good yield (75%) just after 5 min of reaction time.

Full text of DOI:10.1016/j.apcata.2011.05.035

Applied Catalysis A: General 402 (2011) 110–120
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Mild alkane C–H and O–H oxidations catalysed by mixed-N,S copper, iron and
vanadium systems
Ricardo R. Fernandesa, Jamal Lasria, M. Fátima C. Guedes da Silvaa,b, José A.L. da Silvaa,
João J.R. Fraústo da Silvaa, Armando J.L. Pombeiroa,∗
a Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
b Universidade Lusófona de Humanidades e Tecnologias, ULHT Lisbon, Av. do Campo Grande, 376, 1749-024 Lisbon, Portugal
a r t i c l e i n f o
a b s t r a c t
Reactions of 1,6-bis(2ꢀ-pyridyl)-2,5-dithiahexane (Py2S2) with different sources of Cu(II), Fe(II)
and V(III) afford the corresponding novel complexes [CuCl(Py2S2)]Cl (1), [CuCl(Py2S2)](CuCl2) (1ꢀ),
[Cu(OTf)2(Py2S2)] (2), [Cu(Py2S2)(H2O)2](OTf)2 (2ꢀ), [FeCl2(Py2S2)] (3), [Fe(Py2S2)(CH3CN)2][SbF6]2 (4)
and [VCl2(Py2S2)]Cl (5), bearing Py2S2 as a tetradentate ligand. All the compounds were characterised by
IR, ESI–MS, elemental analyses and, in the cases of 1ꢀ, 2ꢀ and 4, the molecular structures were also eluci-
dated by single X-ray crystal diffraction analysis. Complexes 1–5 were evaluated as catalysts or catalyst
precursors for the mild peroxidative oxidation of cyclohexane in acetonitrile typically at 25 ◦C and in the
solvent-free oxidation of primary and secondary alcohols under microwave (MW) irradiation. The influ-
ences of the type and amount of acid promoter, amounts of oxidant and catalyst, time and temperature,
on the product yields and TONs, are investigated.
Article history:
Received 8 April 2011
Received in revised form 13 May 2011
Accepted 26 May 2011
Available online 2 June 2011
Keywords:
N,S-ligands
Peroxidative oxidations
Acid additives
C–H bond activation
O–H bond activation
The iron(II) complexes 3 and 4 are the most active catalysts in the oxidation of cyclohexane with H2O2
in a slightly acidic medium, leading to maximum overall yields (based on the alkane) of 38 and 28%, and
turnover numbers (TON) up to 950 and 1450, respectively.
Additionally, the Cu and Fe complexes (1–4) proved to be useful catalysts in various MW-assisted
alcohol oxidations at 80 ◦C with t-BuOOH. The oxidation of 1-phenylethanol catalysed by the Fe complex
3 in the presence of pyrazine-2-carboxylic acid (co-catalyst) is very fast, giving the acetophenone product
(TOF = 4470 h−1) in good yield (75%) just after 5 min of reaction time.
© 2011 Elsevier B.V. All rights reserved.
1. Introduction
The utilisation of peroxides as surrogates of dioxygen has
been extensively investigated for the oxidation of various organic
Recent endeavours to find efficient metal-catalysed oxidative
transformations of ubiquitous C–H and O–H bonds are fuelled by
the possible direct conversion of largely available alkanes and other
constituents of natural gas and petroleum, and possible oxygenated
derivatives, to more valuable functionalised products for chemi-
cal industry [1–3]. Thus, the development of a selective, chemical-,
energy- and atom-efficient oxidation process is a key problem to
be tackled.
In the biological systems, the activation of O2 or H2O2 occurs in
the active site of certain iron-, copper- and vanadium-containing
metallobiomolecules that regulate the incorporation of oxygen into
natural substrates, allowing for example the natural detoxification
of certain xenobiotics [4–8].
substrates [8,9], including amines, sulfides, alkanes, alkenes or alco-
hols. To date a truly efficient and selective oxidation system has
not yet been found and the vast majority of the reported examples
show either active, but unselective reactivity patterns, or selective,
but often much less active, systems [9,10].
The catalyst models [9–12] for these types of reactions are
often based on metal (e.g. Fe, Cu or V) complexes with polyden-
tate pyridine-type ligands [13–18], polyamino alcohols [19–21],
tris(pyrazolyl)borates and tris(pyrazolyl)methanes [22–24] or
macrocyclic amino derived ligands [25]. Despite the fact that sulfur
is a naturally occurring donor in the active centre of many metal-
loenzymes, oxidation catalysts based on all-S or mixed-N,S ligands
have been little explored [9,12] if compared to their N- and O-
analogues in view of the concerns arising from their tendency to
form sulfoxides or disulfides upon oxidation [4–8,26,27].
We have just reported an efficient {FeN2S2} catalytic centre that
can catalyse at room temperature the oxidation of cycloalkanes
to cyclic alcohols and ketones, and of benzene to phenol, in the
presence of certain heteroaromatic acids or nitric acid [28].
∗
Corresponding author. Tel.: +351 218419237; fax: +351 218464455.
E-mail address: pombeiro@ist.utl.pt (A.J.L. Pombeiro).
0926-860X/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2011.05.035

R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
111
Additionaly, Britvosek and co-workers recently reported the
use of a series of tetradentate pyridine- and pyrazine-type ligands
containing in the backbone unit either nitrogen, oxygen or sulfur
donor atoms. In that work, it was found that the formed iron com-
plexes bearing S-ligands, including the linear tetradentate ligand
1,6-bis(2ꢀ-pyridyl)-2,5-dithiahexane (Py2S2), were inactive in the
oxidation of cyclohexane under the few experimental conditions
tested [29].
Herein, we report the structural and catalytic properties of vari-
ous novel Cu(II), Fe(II) and V(III) complexes, bearing this N,S-ligand
(Py2S2), which we find to behave, in acidic medium, as catalyst pre-
cursors for the peroxidative oxidations of cyclohexane and alcohols
(primary and secondary ones), focusing on the optimisation of the
experimental conditions by varying in a systematic way different
reaction parameters, such as the type of acid additives, the acid-to-
catalyst and the oxidant-to-catalyst molar ratios and the amount
of metal catalyst. Furthermore, the influence of microwave irra-
diation in the solvent-free oxidation by t-BuOOH of primary and
secondary alcohols is reported and compared with conventional
thermal experiments.
2967 (w), 2360 (w), 1605 (m), 1439 (m), 1257 (vs), 1240 (s), 1165
(s), 1032 (vs), 777 (s), 642 (vs), 518 (m) cm−1
.
2.2.4. [Cu(Py2S2)(H2O)2](OTf)2 (2ꢀ)
X-ray quality single crystals of 2ꢀ were obtained by slow diethyl
ether diffusion over a concentrated solution of 2 in CH2Cl2.
2.2.5. [FeCl2(Py2S2)]·0.5H2O (3·0.5H2O)
A suspension of FeCl2·4H2O (431 mg, 2.17 mmol) in CH3CN
(5 mL) was combined with Py2S2 (600 mg, 2.17 mmol) and stirred
for 5 h under a dinitrogen atmosphere. The resulting yellow powder
was filtered off, washed with Et2O and dried in vacuo to yield 3 as
a yellow solid (787 mg, 88%). ESI–MS (positive mode, CH2Cl2): m/z
+
+
367 {[FeCl(Py2S2)]} , 277 {[Py2S2 + H]} . C14H16Cl2FeN2S2·0.5H2O
(M = 412.18 g mol−1): calcd. C 40.80, H 4.16, N 6.80, S 15.56; found
C 40.74, H 3.76, N 6.77, S 15.51. IR (KBr) (selected bands): 3429 (m),
3040 (w), 1599 (m), 1479 (s), 1435 (s), 1385 (m), 1161 (m), 1056
(s), 1014 (vs), 886 (s), 773 (vs), 715 (vs), 637 (m) cm−1
2.2.6. [Fe(Py2S2)(CH3CN)2][SbF6]2 (4)
Ag[SbF6] (200 mg, 0.58 mmol) was weighted under dinitrogen
and then added to a vigorously stirred yellow suspension of 3
(120 mg, 0.29 mmol) in CH3CN (8 mL) contained in a Schlenk tube
which was wrapped with aluminum foil to protect the sensitive
silver salts from light. After stirring for 20 h the purple solution
was filtered several times through Celite and all the solvent was
evaporated under an intense dinitrogen stream to furnish a pur-
ple powder of complex 4 in quantitative yield. Slow Et2O diffusion
over a concentrated solution of 4 in CH3CN afforded cubic sin-
gle crystals after ca. 24 h. ESI–MS (positive mode, CH3CN): m/z
2. Experimental
2.1. General methods
Unless stated otherwise, all reactions and operations were car-
ried out at room temperature under dinitrogen, by using standard
Schlenk techniques. Solvents were dried and distilled before use
and reagents were obtained from commercial sources (Aldrich)
and used as received. 1,6-Bis(2ꢀ-pyridyl)-2,5-dithiahexane (Py2S2)
was obtained by reacting 2-(chloromethyl)pyridine hydrochloride
with 1,2-ethanedithiol in basic NaOH methanolic media, following
a published method [30]. The vanadium complex [VCl2(Py2S2)]Cl
(5) was prepared according to the general procedure previously
described [31] for the related [VX2(Py2S2)]X (X = Br, I).
+
+
2+
567 {[Fe(Py2S2)][SbF6]} , 277 {[Py2S2 + H]} , 166 {[Fe(Py2S2)]}
.
C
18H22F12FeN4S2Sb2 (M = 885.87 g mol−1): calcd. C 24.40, H 2.50, N
6.32, S 7.24; found C 24.04, H 2.34, N 5.64, S 7.71. IR (KBr) (selected
bands): 3447 (w), 3258 (w), 3197 (w), 2254 (m), 1627 (vs), 1530
(vs), 1466 (s), 1434 (s), 1396 (m), 1256 (m), 1172 (m), 1015 (m),
925 (m), 680 (m) cm−1
.
2.2.7. [VCl2(Py2S2)]Cl (5)
2.2. Catalyst preparation
This compound was prepared according to the general proce-
dure previously described [31] for [VX2(Py2S2)]X (X = Br, I).
2.2.1. [CuCl(Py2S2)]Cl·0.6 H2O (1·0.6 H2O)
To a light yellow solution of Py2S2 (100 mg, 0.36 mmol) in
MeOH (10 mL) was added CuCl2 (48 mg, 0.36 mmol). The result-
ing green solution was stirred in air for 5 h and upon the addition
of Et2O a green precipitate appeared. This precipitate was fil-
tered off, washed thoroughly with Et2O and dried in vacuo to
afford 1 as a dark green powder (132 mg, 87%). ESI–MS (positive
2.3. Characterisation techniques
C, H and N elemental analyses were carried out by the Microan-
alytical Service of the Instituto Superior Técnico. Infrared spectra
(4000–400 cm−1) were recorded on a Bio-Rad FTS 3000MX instru-
ment in KBr pellets and the wavenumbers are in cm−1. Electrospray
mass spectra were performed with an ion-trap instrument (Varian
500-MS LC Ion Trap Mass Spectrometer) equipped with an electro-
spray (ESI) ion source. For electrospray ionisation, the drying gas
and flow rate were optimised for each sample with 35 psi nebu-
liser pressure. Scanning was performed from m/z = 50 to 1500. The
compounds were observed in the positive mode (capillary volt-
age = 80–105 V).
+
mode, MeOH): m/z 374 {[CuCl(Py2S2)]} . C14H16Cl2CuN2S2·0.6 H2O
(M = 421.68 g mol−1): calcd. C 39.88, H 4.11, N 6.64, S 15.21; found
C 39.39, H 3.81, N 6.41, S 15.29. IR (KBr) (selected bands): 3470 (w),
2939 (w), 2900 (w), 1600 (s), 1564 (m), 1482 (m), 1434 (m), 1260
(m), 1025 (m), 931 (m), 772 (vs), 706 (m) cm−1
.
2.2.2. [CuIICl(Py2S2)](CuICl2) (1ꢀ)
Dark green single crystals of 1ꢀ were formed by slow diffusion
X-ray quality single crystals of 1ꢀ, 2ꢀ and 4 were obtained as
indicated above. They were mounted in an inert oil within the
cold N2 stream of the diffractometer. Intensity data were collected
using a Bruker AXS-KAPPA APEX II diffractometer with graphite
of Et2O in an equimolar acetonitrile mixture of CuCl2 and Py2S2.
2.2.3. [Cu(OTf)2(Py2S2)] (2)
˚
Cu(OTf)2 (130 mg, 0.36 mmol) was added to a light yellow
solution of Py2S2 (100 mg, 0.36 mmol) in THF (10 mL). The result-
ing greenish blue mixture was stirred in air for 3 h. The formed
precipitate was separated by filtration, washed with Et2O and
dried in vacuo (175 mg, 76%). ESI–MS (positive mode, CH3CN): m/z
monochromated Mo-K␣ radiation (ꢀ = 0.71073 A). Data were col-
lected at 150 K using omega scans of 0.5◦ per frame and a full
sphere of data was obtained. Cell parameters were retrieved using
Bruker SMART software and refined using Bruker SAINT [32] on
all the observed reflections. Absorption corrections were applied
using SADABS [32]. The structures were solved by direct methods
by using the SHELXS-97 package [33]. Calculations were per-
formed using the WinGX System-Version 1.80.03 [34]. All hydrogen
+
+
488 {[Cu(OTf)(Py2S2)]} , 339 {[Cu(Py2S2)]} . C16H16CuF6N2O6S4
(M = 638.11 g mol−1): calcd. C 30.12, H 2.53, N 4.39, S 20.10; found
C 30.07, H 2.51, N 4.18, S 20.03. IR (KBr) (selected bands): 3479 (w),

112
R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
Table 1
Crystallographic data and structure refinement details for complexes 1ꢀ, 2ꢀ and 4.
Data
1ꢀ
2ꢀ
4
Empirical formula
Mr/g mol−1
C14H16ClCuN2S2, Cl2Cu
509.84
C14H20CuN2O2S2, 2(CF3O3S)
674.12
C18H22FeN4S2, 2(F6Sb)
885.87
crystal system
space group
Triclinic
Monoclinic
C2/c (No. 15)
21.7145(8)
8.3387(3)
13.5446(6)
90
92.678(2)
90
2449.85(17)
4
Triclinic
P-1 (No. 2)
8.1471(9)
10.1037(11)
12.8616(14)
68.283(6)
84.602(7)
67.918(7)
910.17(17)
2
P-1 (No. 2)
12.297(2)
13.773(2)
18.119(3)
87.527(11)
87.716(12)
69.762(11)
2875.6(8)
4
˚
a/A
˚
b/A
˚
c/A
␣/◦
␤/◦
␥/◦
3
˚
V (A )
Z
Dc/g cm−3
1.860
3.003
0.0449
1.828
1.325
0.0281
2.046
2.603
0.0973
ꢁ(Mo K␣)/mm−1
Rint
No. of collected reflns
No. of unique reflns
Final R1a, wR2b (I ≥ 2 ␴)
GOF on F2
8428
3289
0.0412, 0.0832
1.015
13096
3053
0.0270, 0.0785
1.169
27670
10469
0.1027, 0.2561
1.057
a
R1 = ꢂ||Fo| − |Fc||/ꢂ|Fo|.
wR2 = [
ꢀ
ꢀ
[w(Fo2 − Fc2)2]/
[w(Fo2)2]]1/2
.
b
atoms were inserted in calculated positions. Least square refine-
ments with anisotropic thermal motion parameters for all the
non-hydrogen atoms and isotropic for the remaining atoms were
employed. Table 1 contains the crystallographic parameters for the
described crystals. CCDC 819150–819152 contains the supplemen-
tary 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.
2.4.2. Peroxidative oxidation of alcohols with aqueous t-BuOOH
2.4.2.1. Conventional method. Oxidation reactions were carried out
in air using a 25 mL round-bottom flask equipped with a reflux con-
denser. Under typical conditions, the catalyst 1–4 (10 ␮mol) was
placed to the flask, followed by the addition of the alcohol (5 mmol),
pyrazine-2-carboxylic acid (Hpca) (50 ␮mol) and an aqueous solu-
tion of t-BuOOH (70%) (10 mmol). In all cases, the reaction solutions
were vigorously stirred for 30 min using magnetic bars. The desired
reaction temperature (typically 80 ◦C) was maintained using an oil
bath.
2.4. Catalytic tests
2.4.2.2. Microwave-assisted method. Typical oxidation reactions of
alcohols were carried out in a sealed Pyrex tube under focused
microwave irradiation as follows: alcohol substrate (5 mmol), cat-
alyst 1–4 (10 ␮mol) and Hpca (50 ␮mol) were introduced into
the reactor. Thereafter, an aqueous solution of t-BuOOH (70%)
(10–15 mmol) was added and finally the cylindrical Pyrex reactor
was placed in the microwave reactor. The system was left under
stirring and irradiation (10 W) for 5–240 min at 80−120 ◦C tem-
perature range.
The batch catalytic studies in acetonitrile were performed in a
Stem Omni Reactio Station with capacity for 10 reactors (50 mL)
with no additional concerns to remove air or moisture prior the
reactions. The catalytic investigations under microwave irradiation
(10 W) were performed in a focused microwave CEM Discover reac-
tor (10 mL, 13 mm diameter), fitted with a rotational system and
an IR detector of temperature. The catalytic reactions were anal-
ysed by GC (gas chromatography) using a Fisons Instruments model
8160 gas chromatograph equipped with a DB-WAX (column length:
30 m; internal diameter: 0.32 mm; film: 0.25 ␮m) capillary column
(helium as a carrier gas) with a FID detector.
2.4.2.3. Extraction and GC analysis for alcohol oxidations. The reac-
tion mixtures were allowed to cool to room temperature and upon
product extraction with 5 mL of CH3CN, the internal standard 2-
octanone (150 ␮L) (in the case of the oxidation of linear alcohols),
cyclopentanone (150 ␮L) (in the case of cyclohexanol oxidation) or
benzaldehyde (300 ␮L) (in the case of 1-phenylethanol oxidation),
was added and the system centrifuged. Then, diethyl ether (10 mL)
was added for dilution and, after mixing, a sample for GC analysis
was taken from the organic phase.
Blank tests indicate that only traces of acetophenone are gen-
erated from 1-phenylethanol in the absence of the copper or iron
catalyst in the conventional method, while under MW-irradiation
the formation of acetophenone does not exceed 6% in a metal-free
system.
2.4.1. Peroxidative oxidation of cyclohexane with aqueous H2O2
in acetonitrile
Typical cyclohexane oxidation reactions were carried out in
50 mL screwtop glass reactors (Stem Omni Reactio Station) in air
as follows: catalyst 1–5 (0.1–10 ␮mol), cyclohexane (1–5 mmol),
CH3CN (3 mL) and acid additive (10–1000 ␮mol). The reactors were
placed on the reaction station and stirred vigorously at a controlled
temperature of 25 ◦C. An aqueous solution of hydrogen peroxide
(30%) (1–20 mmol) was then added and the reaction mixture stirred
for 6 h. The product analysis was performed as follows: 90 ␮L of
internal standard (cycloheptanone) and 10 mL of diethyl ether (to
extract the substrate and the organic products from the reaction
mixture) were added. To the obtained mixture was added an excess
of triphenylphosphine before GC analysis, in order to reduce the
formed cyclohexyl hydroperoxide to the corresponding alcohol,
and hydrogen peroxide to water, following a method developed by
Shul’pin [35,36]. After stirring the final reaction mixture for 10 min
a sample was taken from the organic phase and then analysed
by GC.
3. Results and discussion
3.1. Syntheses and spectroscopic characterisation of complexes
1–5
The mixed N,S-compound 1,6-bis(2ꢀ-pyridyl)-2,5-dithiahexane
(Py2S2), bearing two thioether functions, reacted at room temper-

R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
113
Scheme 1. Syntheses of copper(II) (1,2), iron(II) (3,4) and vanadium(III) (5) complexes.
ature with different Cu(II), Fe(II) and V(III) metal sources i.e., CuCl2,
Cu(OTf)2 (OTf = OSO2CF3), FeCl2 or [VCl3(THF)3], respectively, to
originate the corresponding chloro complexes [CuCl(Py2S2)]Cl 1,
[FeCl2(Py2S2)] 3 and [VCl2(Py2S2)]Cl 5 (Scheme 1, reactions a, e
and d), and the triflate complex [Cu(OTf)2(Py2S2)] 2 (Scheme 1,
reaction b). The reactions with the Cu(II) salts were in acetoni-
trile and in air, while those with Fe(II) and V(III) were undertaken
under N2, in CH3CN or THF, respectively. The di-acetonitrile iron
complex [Fe(Py2S2)(CH3CN)2][SbF6]2 4 was prepared by treating a
CH3CN solution of 3 with two equivalents of silver hexafluoroanti-
monate (Ag[SbF6]) under a dinitrogen atmosphere for 20 h at room
temperature (Scheme 1, reaction f).
Both Cu and Fe complexes 1–4 were obtained as air-stable
solids, whereas the V complex 5 is very sensitive to O2 and
moisture, converting likely into high-valent oxo-vanadium deriva-
tives [31]. All the complexes have been fully characterised by
IR, ESI+–MS and elemental analyses, and, in the case of 4, also
by X-ray structural diffraction analysis (Fig. 1c). Crystallisation
attempts of 1 and 2 afforded also [CuIICl(Py2S2)](CuICl2) 1ꢀ and
[Cu(Py2S2)(H2O)2](OTf)2 2ꢀ, respectively, which have been char-
acterised only by X-ray analyses (Fig. 1a and 1b). Compound 1ꢀ
possesses a CuICl2 counter-ion, which was conceivably formed
−
upon CuII reduction by the “soft” dithioether Py2S2 ligand [37,38].
In the case of the aqua derivative 2ꢀ, the two water ligands (from
the moisture present in the crystallisation solvent) displaced the
weakly coordinating triflate (OTf−) anions. The ESI+–MS spectra
of the complexes reveal typically the [MX(Py2S2)]+ peak with the
expected isotopic patterns.
3.2. X-ray crystal structures of complexes 1ꢀ, 2ꢀ and 4
The molecular structures of [CuIICl(Py2S2)](CuICl2) (1ꢀ),
[Cu(Py2S2)(H2O)2](OTf)2 (2ꢀ) and [Fe(Py2S2)(CH3CN)2][SbF6]2 (4)
were determined by X-ray crystallography and are shown in Fig. 1,
while the selected distances and angles are listed in Tables 2 and 3.
In complex 1ꢀ the copper ion exhibits a five-coordinate distorted
trigonal bipyramidal conformation, but the metal centres in 2ꢀ and
4 display six-coordinate octahedral geometries, with the chelat-
ing ligand adopting a cis-␣ configuration. The bond lengths of all
three compounds lie in expected characteristic ranges [17,29]. A
Fig. 1. ORTEP diagrams of (a) [CuCl(Py2S2)]+ (cation of 1ꢀ), (b) [Cu(Py2S2)(H2O)2]2+ (dication of 2ꢀ) and (c) [Fe(Py2S2)(CH3CN)2]2+ (dication of 4) showing the atom labelling
scheme. The hydrogen atoms and counter ions were omitted for clarity.

114
R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
Table 2
◦
ꢀ
˚
Selected bond lengths (A) and angles ( ) for complexes [CuCl(Py2S2)](CuCl2) (1 ) and
[Cu(Py2S2)(H2O)2](OTf)2 (2ꢀ).
Complex 1ꢀ
Cu1–S1
Cu1–S2
Cu1–Cl1
2.4317(12)
2.4363(13)
2.2733(13)
Cu1–N1
Cu1–N2
1.996(4)
1.995(4)
Cl1–Cu1–S1
Cl1–Cu1–S2
S1–Cu1–S2
S1–Cu1–N1
S1–Cu1–N2
S2–Cu1–N1
Complex 2ꢀ
Cu1–S1
128.59(5)
140.18(5)
91.21(4)
84.74(10)
91.15(10)
91.48(11)
S2–Cu1–N2
Cl1–Cu1–N1
Cl1–Cu1–N2
N1–Cu1–N2
84.27(12)
93.06(11)
92.89(11)
174.03(15)
2.5073(6)
Cu1–O10
2.1543(15)
Cu1–N1
2.0091(15)
S1–Cu1–S1i
87.02(2)
177.49(5)
91.08(5)
90.87(9)
172.05(8)
S1–Cu1–N1
83.66(4)
90.57(4)
83.66(4)
98.00(6)
87.60(5)
98.00(6)
S1–Cu1–O10
S1i–Cu1–O10
O10–Cu1–O10i
N1–Cu1–N1i
S1–Cu1–N1i
S1i–Cu1–N1i
O10–Cu1–N1
O10i–Cu1–N1
O10i–Cu1–N1i
Scheme 2. Oxidation of cyclohexane with H2O2 catalysed by Cu (1,2), Fe(3,4) or V
(5) compounds.
Although it was reported [29] that the related iron complex
[Fe(OTf)2(Py2S2)] was inactive in the oxidation of cyclohexane with
H2O2 in acetonitrile, in that study it was not investigated the possi-
ble effect of additives and only a few experimental conditions were
tested.
Symmetry code to generate equivalent atoms: (i) 1 − x, y, 3/2 − z.
relevant difference in the structures of these complex cations con-
cerns the –S–CH2–pyridyl moiety which, for 1ꢀ, is almost plane
(Cpyridyl–Cpyridyl–C–S torsion angle of av. 172.56◦), while for the
other cations it is markedly twisted. Indeed, for 2ꢀ this torsion angle
is of 142.78◦ and for 4, which presents two independent complex
units in the asymmetric unit, that parameter assumes the average
values of 145.64◦ for the Fe1 containing cation, and 151.79◦ for the
Fe2 one. Additionally, the angles between the planes of the two
pyridyl rings are also quite different, taking values of 84.86◦ (1ꢀ),
67.17◦ (2ꢀ) or 53.73◦ and 56.77◦ (4, Fe1 and Fe2 cations, respec-
tively).
In the current work, under our conditions, the catalytic activ-
ity of 1–5 was disclosed. At the initial stage of our study, we
screened all the complexes 1–5 in the presence of various acid
additives and with the purpose to find the most active system
(complex/acid) in the oxidation, with H2O2 at 25 ◦C, of cyclohexane
(CyH) to cyclohexyl hydroperoxide (CyOOH), cyclohexanol (CyOH)
and cyclohexanone (Cyꢀ = O) (Scheme 2). Under our typical condi-
tions, i.e. 10 ␮mol catalyst, 200 ␮mol of acid additive, 5 mmol CyH,
7 mmol H2O2 (25 ◦C, 6 h), the primary product of the cyclohexane
oxidation is CyOOH, as revealed by the quite different amounts
of cyclohexanol and cyclohexanone in the GC analyses before and
after quenching the reaction with an excess of triphenylphosphine
(PPh3), which quantitatively reduces CyOOH to CyOH, following a
method developed by Shul’pin [35,36]. Thus, all catalytic runs were
analysed after the addition of PPh3 for accurate determination of
the final oxygenated products, i.e. CyOH and Cyꢀ = O.
3.3. Catalytic results
The catalytic study focused on the use of cyclohexane and vari-
ous alcohols, mainly 1-phenylethanol, as model substrates for the
investigation of the catalytic properties of the Cu(II) (1,2), Fe(II)
(3,4) and V(III) (5) complexes bearing the bis-pyridyl dithioether
ligand, under mild oxidations using hydrogen peroxide (H2O2) and
tert-butyl hydroperoxide (t-BuOOH) as oxidants.
3.3.1. Effect of different acid additives
The dramatic role of certain additives, in particular acids, on
the activity in oxidation catalysis of various transition metal com-
plexes, e.g. of Cu, Fe and V, is well known [20,21,35,36,39–42].
Vanadium centres combined with different heteroaromatic [41],
sulfuric and oxalic [42] acids as co-catalysts can be very active
in peroxidative oxidations of cyclic, linear and branched satu-
rated hydrocarbons. In several bioinspired Fe-catalysed oxidations
of alkanes, alkenes and other organic molecules, the addition of
acetic acid (typically 50–100 equivalents relatively to the Fe cata-
lyst) resulted in significant improvements of activity and selectivity
[15,18,43–45].
Table 3
◦
˚
Selected bond lengths (A) and angles ( ) for the two independent molecules of
[Fe(Py2S2)(CH3CN)2][SbF6]2 (4).
I
II
Fe1–S11
Fe1–S12
Fe1–N31
Fe1–N51
Fe1–N11
Fe1–N12
2.249(6)
2.249(5)
1.999(14)
1.952(16)
1.954(18)
1.940(16)
Fe2–S21
Fe2–S22
Fe2–N41
Fe2–N61
Fe2–N21
Fe2–N22
2.244(5)
2.245(6)
2.017(17)
1.973(15)
1.944(17)
1.937(17)
S11–Fe1–S12
S11–Fe1–N31
S11–Fe1–N51
S11–Fe1–N11
S11–Fe1–N12
S12–Fe1–N31
S12–Fe1–N51
S12–Fe1–N11
S12–Fe1–N12
N11–Fe1–N12
N11–Fe1–N31
N11–Fe1–N51
N12–Fe1–N31
N12–Fe1–N51
N31–Fe1–N51
90.9(2)
89.7(5)
85.4(5)
178.3(5)
90.2(5)
85.0(5)
89.1(6)
90.6(5)
178.8(5)
88.3(7)
89.7(7)
95.4(7)
94.6(7)
91.4(7)
172.3(7)
S21–Fe2–S22
S21–Fe2–N41
S21–Fe2–N61
S21–Fe2–N21
S21–Fe2–N22
S22–Fe2–N41
S22–Fe2–N61
S22–Fe2–N21
S22–Fe2–N22
N21–Fe2–N22
N21–Fe2–N41
N21–Fe2–N61
N22–Fe2–N41
N22–Fe2–N61
N41–Fe2–N61
89.9(2)
84.2(5)
89.8(5)
178.4(6)
91.8(5)
93.4(4)
84.3(4)
89.8(5)
178.3(6)
88.6(7)
94.3(7)
91.7(8)
87.2(6)
95.2(6)
173.6(7)
Recently, we have also reported an {FeN2S2} catalytic system
that exhibited a good activity in the oxidation of cycloalkanes and
benzene in the presence of certain heteroaromatic acids or nitric
acid [28].
Hence, the catalytic oxidations of cyclohexane by complexes 1–5
were examined in the presence of different acid additives, such as
pyrazine-2-carboxylic acid (Hpca), nitric acid (HNO3), hydrochloric
acid (HCl), triflic acid (HOTf), acetic acid (AcOH) and trifluoracetic
acid (TFA) (Table 4).
In the absence of acid, the overall yields (CyOH and Cyꢀ = O)
(after treatment with PPh3) are practically equal (4–5%) for the
reactions catalysed by complexes 2, 3 and 5, what contrasts with

R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
115
Table 4
Effect of different acids on the oxidation of cyclohexane catalysed by 1–5.a
Entry
Acid
n(acid)/n(catalyst)
Overall yieldb,c (%)
1
2
3
4
5
1
2
3
4
5
6
7
8
9
–
0
5
20
40
9.8(1.8d)
0.2
6.2
5.7
3.0
7.1
6.3
7.9
11.8
7.3
4.3
0.5
4.4
6.9
5.1
14.5
3.8
6.2
5.2
5.0
4.8
1.3
4.0
Hpca
HNO3
13.8(12.9e)(13.5f)
17.1
16.7
14.6
9.3
4.5
1.8
22.9
1.0
11.3
11.0(12.7g)
7.2
18.0(4.2d)
16.5
10.6
6.6
1.0
9.8
12.6
8.5
7.4
7.5
100
HCl
20
40
20
20
20
HOTf
AcOH
TFA
13.9
3.3
4.8
5.7
10
20.2(22.1g)
a
Reaction conditions (unless stated otherwise): CH3CN (3 mL), cyclohexane (5 mmol), catalyst (10 ␮mol), H2O2 (7 mmol), reaction time (6 h), temperature (25 ◦C).
Molar yield (%) based on cyclohexane, i.e. number of moles of product per 100 moles of substrate, determined by GC after treatment with PPh3; molar yields (%) based
b
on H2O2, if required, can be estimated as TON × 100 × n(catalyst)/n(H2O2).
c
Cyclohexanol and cyclohexanone (after treatment with PPh3).
Reaction carried out in the presence of diphenylamine (DPA) (5 mmol).
Controlled addition of H2O2 during 15 min.
d
e
f
Controlled addition of H2O2 during 5 h.
g
Reaction carried out at 40 ◦C.
Table 5
Effect of the acid promoter-to-catalyst molar ratio on the oxidation of cyclohexane catalysed by 3.a
Entry
Acid
n(acid)/n(catalyst)
Yieldb (%)
CyOH
TONd
Cyꢀ = O
Overallc
1
2
3
4
5
6
0
1
5
10
20
40
2.3
6.5
17.0
17.1
2.5
0.2
1.7
1.5
4.8
6.7
18.7
18.6
24.0
33.5
93.5
93.0
90.0
82.5
HNO3
14.6(4.0e)
14.8
3.4(10.8e)
1.7
18.0(14.8e)
16.5
7
8
1
5
5.8
12.9
0.4
0.9
6.2
13.8
31.0
69.0
9
10
11
10
20
40
15.8
1.3
17.1
85.5
101.0
91.5
TFA
18.6(4.5e)
17.0
1.6(10.6e)
1.3
20.2(15.1e)
18.3
a
Reaction conditions: CH3CN (3 mL), cyclohexane (5 mmol), catalyst (10 ␮mol), acid additive (0–400 ␮mol), H2O2 (7 mmol), reaction time (6 h), temperature (25 ◦C).
Molar yield (%) based on cyclohexane, i.e. number of moles of product per 100 moles of substrate, determined by GC after treatment with PPh3.
Cyclohexanol and cyclohexanone (after treatment with PPh3).
Turnover number (moles of product per mol of metal catalyst).
GC analysis carried out before the addition of PPh3.
b
c
d
e
the very weak activity of 4 (ca. 1%) and a moderate activity of 1
The influence of the H2O2 addition rate to 3/Hpca (Table 4, entry
2) was also investigated, but the yields obtained for the single and
controlled 15 min and 5 h additions are comparable (ca. 13–14%).
This suggests that no major decomposition of the peroxide to H2O
and O2 occurs in the beginning of the reaction and that the rate of
addition does not alter considerably the reaction efficiency.
Based on these results, we selected the best catalytic systems, i.e.
the iron 3/TFA and 4/HOTf, and attempted the optimisation of the
acid and oxidant amounts, and the obtained results are summarised
in Tables 5 and 6, and Figs. 2 and 3 (see also in Supplementary data
– Tables S1 and S2).
(ca. 10%, TON = 49). The addition of the heteroaromatic acid Hpca
has a divergent effect on the various catalytic systems. The oxida-
tions catalysed by the Cu complexes 1 and 2 are inhibited by Hpca,
while a marked yield growth is observed for the Fe 3 and 4, and V 5
catalysed reactions, in accord with previous reports [21,25,46–50]
of the co-catalytic effect of Hpca and other acids for different sys-
tems. In general, we observe that the addition of acid to the Cu
systems 1 and 2 does not influence significantly the overall yield,
except for enhanced catalytic activity of the system 2/HCl (ca. 15%
yield).
The vanadium catalyst 5 showed its maximum activity in the
presence of Hpca and for the higher tested amounts of HNO3, ca.
11% and 13%, respectively.
3.3.2. Effect of acid amount and time
Since the amounts of the oxygenated products are expected
[19–21,28,43–45] to depend on the quantity of the acid promoter,
in search for the optimal conditions we varied the acid promoter-
to-catalyst molar ratio in the oxidations catalysed by 3 and 4.
Tables 5 and 6 show the variation of the CyOH and Cyꢀ = O yields
under various acidic conditions and in Fig. 2 is depicted the depen-
dence of the overall yield as a function of the acid amount.
The oxidation of cyclohexane by the system 3/HNO3 has the
maximum overall yield and TON (ca. 19% and 94, respectively)
(Table 5, entry 3) for the considerably low amount of 50 ␮mol
of HNO3 (acid-to-catalyst molar ratio = 5) and remains practically
A positive effect was displayed by both iron complexes 3 and
4 in the presence of any acid additive, except for high acid-to-
catalyst molar ratios and for AcOH (inhibition effect). Among all the
catalyst/acid systems surveyed, the iron 3/TFA and 4/HOTf combi-
nations exhibited the highest activities, 20% (TON = 101) and 23%
(TON = 115) yields, respectively.
Performing the reactions at 40 ◦C for the systems 3/TFA (Fe) and
5/Hpca (V) lead only to a slight enhancement of activity from ca.
20 to 22% and from ca. 11 to 13%, respectively (Table 4, entries 2
and 10).

116
R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
Fig. 2. Overall yields in the Fe-catalysed oxidation of cyclohexane by (a) 3 and (b) 4 as function of the amounts of nitric (᭹, circles), trifluoroacetic (ꢀ, squares) and triflic (ꢁ,
diamonds) acid promoters. Reaction conditions: CH3CN (3 mL), CyH (5 mmol), H2O2 (7 mmol), catalyst (10 ␮mol), acid additive (0–400 ␮mol), 25 ◦C, 6 h.
constant (19–17%) for higher acid-to-catalyst molar ratios (Table 5,
entries 4–6). In the presence of TFA a higher acid-to-catalyst molar
ratio of 20 is required to reach the maximum activity (overall yield
of 20% and TON of 101) (Table 5, entry 10). Furthermore, the sharp
differences observed in the GC analyses, concerning the yields of
CyOH and Cyꢀ = O, before and after the treatment of the reaction
mixture with triphenylphosphine (PPh3) (Table 5, entries 5 and 10),
hints at the formation of cyclohexyl hydroperoxide (CyOOH) as the
major product of these oxidations. The appreciable deviation of the
overall yields, before and after the addition of PPh3, results from the
likely decomposition of CyOOH under the GC conditions into other
products (e.g. adipic acid) [51] rather than only CyOH and Cyꢀ = O
[35,36].
entry 10), which dropped to less than half for a 2-fold increase of the
triflic acid content. The yields of Cyꢀ = O remain in the 2–3% range
for acid amounts of 50–200 ␮mol (which correspond to acid-to-
catalyst ratios of 5–20), but, for higher HNO3 amounts, a ca. 2-fold
increase of Cyꢀ = O content is observed (4.6%, Table 6, entry 6), and
for both systems (4/HNO3 and 4/HOTf) an overall yield drop is then
observed. The cyclohexane oxidations catalysed by 4/HOTf were
also performed for different reaction times of 1, 3, 6, 12 and 24 h
(Table 6, entries 10–14). The CyOH yield remains invariant after 6 h
(ca. 20%), whereas only a slight increase is observed for the Cyꢀ = O
yield upon prolonged reaction times (12 and 24 h) (Table 6, entries
13 and 14), thus resulting in a hardly noticeable enhancement of
the overall yield.
In the case of the di-acetonitrile complex 4, we found that nitric
acid (HNO3) and triflic acid (HOTf) are the most favourable acids
and their relative amounts were optimised (ca. 10 and 20 acid-to-
catalyst molar ratios, respectively) as summarised in Table 6 and
depicted in Fig. 2b.
The oxidation catalysed by 4 proceeds more efficiently in the
presence of the very strong acid HOTf, but is more sensitive to the
variation of the acid relative amount. For a HOTf/4 molar ratio of 20
the very good overall yield of 23% (TON = 115) was attained (Table 6,
3.3.3. Effect of oxidant amount
The influence of the H2O2 concentration in the product dis-
tribution for the cyclohexane oxidation is shown in Fig. 3 and
Table S1 (Supplementary data). It should be pointed out that
these experiments were carried out using only 1 mmol of CyH and
10 ␮mol of Fe catalysts 3 or 4 (i.e. 1.0 mol%) and that the maximum
overall yields of ca. 38% and 28%, respectively, were achieved for
a peroxide-to-catalyst molar ratio of 500 (which corresponds to
Fig. 3. Dependence of the CyOH (ꢁ, diamonds), Cyꢀ = O (᭹, circles) and overall (ꢀ, rectangles) yields on the oxidant-to-catalyst molar ratio in the oxidation of cyclohexane
catalysed by (a) 3 and (b) 4. Reaction conditions: CH3CN (3 mL), CyH (1 mmol), H2O2 (0–20 mmol), catalyst (10 ␮mol), acid additive (200 ␮mol), 25 ◦C, 6 h.

R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
117
Table 6
The maximum yields and turnover values reported with these
systems based on mononuclear Fe 3 and 4 complexes are among
the best ones reported so far in the oxidation of cyclohexane under
mild conditions (25 ◦C) and are comparable to those obtained with
a few polynuclear iron and copper species [19,20,52,53].
Effect of the acid promoter-to-catalyst molar ratio on the oxidation of cyclohexane
catalysed by 4.a
Entry
Acid
n(acid)/n(catalyst)
Yieldb (%)
CyOH
TONd
Cyꢀ = O
Overallc
1
2
3
4
5
6
0
1
5
10
20
40
0.8
1.6
10.1
14.3
14.5
10.0
0.5
0.4
2.4
2.6
2.2
4.6
1.3
2.0
12.5
16.9
16.7
14.6
6.5
10.0
62.5
84.5
83.5
73.0
3.3.5. Microwave-assisted solvent-free peroxidative oxidation of
alcohols
HNO3
The catalytic performance of the Cu(II) and Fe(II) complexes was
also surveyed in the oxidation of different alcohols. The studies
were based on a recent procedure reported by some of us [54,55],
by using a very low power of microwave irradiation to accelerate
the solvent-free oxidation of primary and secondary alcohols with
aqueous t-BuOOH in the presence of the catalysts 1–4 and using
Hpca as additive. Various alcohols were tested as substrates, includ-
ing 1-phenylethanol and various C6 alcohols (linear and cyclic),
and, as expected, the yields are much higher than those achieved
for cyclohexane oxidation, in view of the higher reactivity of the
O–H bonds. The ketones are the only oxidation products obtained
from these MW-assisted transformations and the high selectivities
observed (typically > 98%) were confirmed by mass balances.
The copper(II) complexes 1 and 2 catalyse poorly the perox-
idative oxidation of 1-phenylethanol under MW at 80 ◦C, leading,
respectively, to 29 and 13% yields of acetophenone after 30 min
(Table 7, entries 2 and 4). Once again, Hpca demonstrated an
inhibitory effect on the Cu-catalysed reactions and, in particular
for the oxidation of 1-phenylethanol, a significant yield drop from
ca. 29% to 3% was observed for the 1/Hpca system (Table 7, entries
2 and 3). In contrast, the efficiency of the iron-catalysed oxidations
is dramatically improved by Hpca and 76% yield of acetophenone
is obtained after 30 min at 80 ◦C. The reaction is very fast; in fact
after 5 min the maximum yield is nearly reached (75%, Table 7,
entry 11). Moreover, the reaction strongly depends on the tem-
perature and at 120 ◦C the maximum yield of 80% was attained
after 15 min (Table 7, entry 8). Using lower catalyst loadings (i.e.
1 ␮mol, which corresponds to a substrate-to-catalyst molar ratio
of 5000), the maximum TON of 835 and TOF of 8580 h−1 (Table 7,
entries 10 and 12), corresponding to yields of 17 and 14%, were
achieved for the short reaction times of 15 and 5 min. The oxidation
of 1-phenylethanol by 3/Hpca under conventional thermal heating
(80 ◦C) is much less efficient furnishing the acetophenone prod-
uct in 26% yield after 30 min (compare Table 7, entries 6 and 13).
Somehow unexpectedly, the di-acetonitrile Fe complex 4 exhibited
a much lower activity than the related dichloro-complex 3, leading
to the acetophenone yield of only 22%.
7
8
9
1
5
1.2
6.8
15.7
6.9
15.5
20.3
20.7
20.3
7.5
0.4
1.8
2.5
1.3
2.1
2.6
3.4
4.1
2.0
1.6
8.6
18.2
8.2
17.6
22.9
24.1
24.4
9.5
8.0
43.0
91.0
41.0
88.0
115
121
122
47.5
10
20
20
20
20
20
40
10e
11f
12
13g
14h
15
HOTf
a
Reaction conditions (unless stated otherwise): CH3CN (3 mL), cyclohexane
(5 mmol), catalyst (10 ␮mol), acid additive (0–400 ␮mol), H2O2 (7 mmol), reaction
time (6 h), temperature (25 ◦C).
Molar yield (%) based on cyclohexane, i.e. number of moles of product per 100
moles of substrate, determined by GC after treatment with PPh3.
b
c
Cyclohexanol and cyclohexanone (after treatment with PPh3).
Turnover number (moles of product per mol of metal catalyst).
Reaction time: 1 h.
Reaction time: 3 h.
Reaction time: 12 h.
Reaction time: 24 h.
d
e
f
g
h
the H2O2-to-substrate molar ratio of 5:1). Further increasing the
H2O2 amount results in a lower activity, conceivably associated
to overoxidation reactions and diminished alkane solubility due
to the higher water content of the reaction medium. Both iron(II)
systems 3/TFA and 4/HOTf show a similar behaviour (Fig. 3a and b,
respectively) in relation to the H2O2 amount. Despite the labile ace-
tonitrile ligands in complex 4, the chloride system 3/TFA displays
a significantly higher activity.
3.3.4. Effect of catalyst amount
The effect of the catalyst amount on the overall yield and TON
was also investigated and is illustrated in Fig. 4 and Table S2 (Sup-
plementary data). In the case of the 3/Hpca system, the maximum
TON of 950 (corresponding to 9.5% of overall product yield)
was achieved at 25 ◦C for a substrate-to-catalyst molar ratio of
10,000, while for 4/HOTf even higher TONs of 1450 and 1190
(corresponding to 3 and 12% of overall yields) were obtained for
substrate-to-catalyst molar ratios of 50,000 and 10,000 (Fig. 4 and
Table S2).
The activity of the 3/Hpca system in the oxidation of other alco-
hols is rather modest since only moderated yields were obtained
in the oxidation of cyclohexanol (36%, Table 7, entry 15), 1-hexanol
(16%, Table 7, entry 18), 2-hexanol (28%, Table 7, entry 16) and 3-
hexanol (32%, Table 7, entry 17) for the extended reaction time of
240 min at 80 ◦C.
As mentioned above, the addition of pyrazine-2-carboxylic acid
(Hpca) has an opposing effect on the Cu and Fe systems, since it acts
as strong inhibitor for both cyclohexane and 1-phenylethanol Cu-
catalysed oxidation reactions (compare entries 1 and 2 in Table 4
and entries 2 and 3 in Table 7) and as a potent co-catalyst in the
case of Fe-catalysed oxidations, e.g., ca. 15-fold yield boosts were
observed in the oxidation of 1-phenyethanol upon addition of Hpca
(compare entries 5 and 6 in Table 7).
The active catalytic species in our reaction mixtures could not
be discovered, but by reacting Hpca with the Cu and Fe complexes
we attempted to shed light into the type of complexes formed.
Hence, we studied the reactivity of the chloro-complexes of Cu
1 and Fe 3 with Hpca (2 equivalents) and attempted to use the
formed species as catalysts for comparison with the corresponding
1/Hpca and 3/Hpca systems. The reaction of copper(II) 1 with Hpca
Fig. 4. Effect of the amount of catalysts precursors 3 (black bars) and 4 (grey bars)
on the turnover number (TON) in the catalytic oxidation of cyclohexane. Reaction
conditions: CH3CN (3 mL), CyH (5 mmol), H2O2 (7 mmol), catalyst (0–10 ␮mol), cat-
alyst/acid additive molar ratio (1/20), 25 ◦C, 6 h.

118
R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
Table 7
Solvent-free and MW-assisted oxidation of different alcohols with t-BuOOH catalysed by 1–4.a
e
Entry
Substrate
Catalyst
Time (min)
Product
Yieldb,c (%)
TONd
TOF (h −1
)
1
–
1
1
2
3
3
3
30
30
30
30
30
30
30
6.5
29.3
2.6
12.7
4.9
–
147
13.0
63.5
24.5
382
16.0
–
293
26.0
127
49.0
763
32.0
2f
3
4f
5f
6
76.3
3.2
7g
3
8h
9
3
3
3
3
3
3
4
15
15
15
5
5
30
30
80.1
75.4
16.7
74.5
14.3
26.3
22.4
401
377
835
373
715
132
112
1602
1508
3340
4470
8580
263
10i
11
12i
13j
14
224
15
16
17
3
3
3
240
240
240
35.9
28.3
31.7
180
142
159
44.9
35.4
39.6
18k
3
3
240
240
15.9
16.7
79.5
83.5
19.9
20.9
19k,l
a
Reaction conditions (unless stated otherwise): substrate (5 mmol), catalyst 1–4 (10 ␮mol), Hpca (50 ␮mol), t-BuOOH (10 mmol, aq. 70%), reaction time (30 min), MW
irradiation (10 W power), temperature (80 ◦C).
b
Molar yield (%) based on substrate, i.e. number of moles of product per 100 moles of substrate, determined by GC.
In all reactions, selectivity was >98%.
Turnover number (moles of product per moles of metal catalyst).
Turnover frequency (TON per hour).
c
d
e
f
Reaction carried out in the absence of Hpca.
g
Reaction carried out in the presence of diphenylamine (DPA) (5 mmol).
h
Reaction performed at 120 ◦C.
i
Catalyst loading of 1 ␮mol and 5 ␮mol of Hpca.
j
Reaction carried out under conventional thermal heating at 80 ◦C during 30 min.
k
Traces of hexanal were detected (<1%).
t-BuOOH amount of 15 mmol.
l
in MeOH afforded after 2 h a light blue insoluble precipitate, which
was isolated by filtration and thoroughly washed with methanol
and diethyl ether. The elemental analysis of this compound reveals
a very low percentage of sulfur (<2%) and is consistent with the
tentative formulation of [Cu(pca)2] (with methanol) as the main
product. In accord, the ESI+–MS and IR spectra show peaks at
m/z 340, assigned to [Cu(pca)2(MeOH)]+, and 1637 cm−1 [␯(CO)],
respectively. These observations support the replacement of the
ligated Py2S2 by two chelating pca− ligands.
In the case of the iron(II) 3 complex, although we failed to
isolate a pure compound, the equimolar reaction with Hpca in
MeOH resulted in a dark red solution and its ESI+–MS spectrum
shows a fragment at m/z 455 that tentatively can be attributed to
[Fe(Py2S2)(pca)]+.
age the nature of the oxidizing species and the type of mechanism
for some of the above metal catalyst/acid additive systems.
The addition of an acid additive is beneficial for both Fe- and
V-catalysed oxidation reactions and does not affect significantly
the product yields obtained with the Cu systems. The acid pro-
moter is believed to accelerate these reactions by improving the
oxidation properties of the complexes, by creating unsaturation of
metal centres and allowing the formation of tentative M-OOH per-
oxo intermediates that by homolysis produce the active hydroxyl
and peroxyl radicals, likely to attack the organic substrate (H-
abstraction) [21,35,49,50,56]. Thus, the formation of cyclohexyl
hydroperoxide (CyOOH) as the major product in the oxidation
of cyclohexane and the pronounced yield drops verified for both
cyclohexane (Table 4, entries 1 and 3) and 1-phenylethanol (Table 7,
entry 7) oxidations when containing free radical scavengers (such
as diphenylamine) corroborate the hypothesis involvement of rad-
ical pathways that can compete with more selective metal-based
oxidants commonly involved in related Fe bis-pyridyl type systems
[12–18,43–45].
The above pale blue solid obtained from the reaction of 1 with
Hpca was tested as catalyst for the MW assisted oxidation of 1-
phenylethanol with t-BuOOH and, as expected, a very low yield
(2%) was obtained, thus confirming the very low activity of copper
centres bearing pyrazine-2-carboxylate (pca−) ligands.
The acid promoter structure has a relevant effect on the inves-
tigated oxidations and the obtained results suggest a possible
influence of the ionisation degree of the acid co-catalyst on the cat-
alytic activity for related acids [57–59]. Indeed, the performances
of the iron systems 3/TFA and 4/TFA are far superior to those of
3.3.6. Type of mechanism and role of acid additives
Albeit a detailed mechanistic study on the oxidation pathways
for both alkane and alcohol oxidations was not within the objectives
of this work, we conducted some experiments in the way to envis-

R.R. Fernandes et al. / Applied Catalysis A: General 402 (2011) 110–120
119
3/AcOH and 4/AcOH, which use acetic acid as additive instead of the
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4. Conclusion
In the present work, we evaluated a series of copper(II), iron(II)
and vanadium(III) complexes bearing a N2S2-type ligand as catalyst
precursors for the oxidation of cyclohexane and various alcohols
under mild conditions, using H2O2 and t-BuOOH as oxidants. It
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effects on the Cu- or Fe-/V-based systems and that minor modifica-
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From all the catalysts screened, the iron-based systems 3/TFA
and 4/HOTf are the most promising ones and their activities are
comparable to state-of-the-art systems for both cyclohexane and
1-phenyethanol oxidations, thus demonstrating that S-containing
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the harsh oxidizing conditions. To this regard, it should be under-
lined the importance not only of the catalyst precursor structure
but also of the reaction conditions to develop an efficient catalytic
system, since in an previous study an analogous iron triflate com-
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with H2O2 [29].
Very good yields are achieved for both cyclohexane (maximum
yield of ca. 38% and TON up to 1450) and 1-phenylethanol (maxi-
mum yield of ca. 80% and TOF up to 8580) oxidations.
The 1-phenylethanol oxidation with t-BuOOH occurs very
rapidly under microwave (MW) irradiation and, just after 5 min,
ca. 75% of all substrate is converted to acetophenone.
The experimental results evidence the extensive involvement of
radical species, namely HO•, R• and ROO•, as confirmed by the large
formation of CyOOH in the cyclohexane oxidation reaction and by
the pronounced yield drop when diphenylamine (radical trapping
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This work has been partially supported by the Fundac¸ ão para
a Ciência e a Tecnologia (FCT), Portugal, and its PPCDT program
(FEDER funded). J. L. expresses gratitude to the FCT and the Insti-
tuto Superior Técnico (IST) for his research contracts (CIÊNCIA
2007 program). R.R.F. expresses gratitude to FCT for a fellowship
(grant SFRH/BD/31150/2006). The authors gratefully acknowledge
the Portuguese NMR Network (IST-UTL Centre) for providing access
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.apcata.2011.05.035.
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