A highly active and magnetically retrievable nanoferrite-DOPA-copper catalyst for the coupling of thiophenols with aryl halides

Article abstract of DOI:10.1039/c2cc17283f

Diaryl sulfides were synthesized using a magnetically recoverable heterogeneous Cu catalyst via one-pot multi component reaction using MW irradiation; the use of isopropanol as a benign reaction medium, easy recovery of the catalyst using an external magnet, efficient recycling, and the high stability of the catalyst render the protocol economic and sustainable. This journal is The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc17283f

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COMMUNICATION
A highly active and magnetically retrievable nanoferrite–DOPA–copper
catalyst for the coupling of thiophenols with aryl halidesw
R. B. Nasir Baig and Rajender S. Varma*
Received 22nd November 2011, Accepted 13th January 2012
DOI: 10.1039/c2cc17283f
Diaryl sulfides were synthesized using a magnetically recoverable
heterogeneous Cu catalyst via one-pot multi component reaction
using MW irradiation; the use of isopropanol as a benign reaction
medium, easy recovery of the catalyst using an external magnet,
efficient recycling, and the high stability of the catalyst render the
protocol economic and sustainable.
Scheme 1 Cross-coupling of aryl halides and thiols.
Carbon–sulfur cross-coupling reaction plays a significant role
in organic synthesis and constitutes a key step in the synthesis
of many molecules that are of biological and material interest.1
Organosulfur compounds are used in diverse fields with
various applications, such as treatment of diabetes, cancer,
inflammation, Alzheimer’s disease, and HIV.2–4 Traditionally,
couplings were achieved under drastic reaction conditions such
as high reaction temperatures with the use of toxic and high
boiling polar solvents like quinoline, HMPA N,N-dimethylace-
tamide or DMF. Alternatively, sulfides can be prepared by the
reduction of aryl sulfones or aryl sulfoxides using strong
reducing agents such as LiAlH4 and DIBAL-H.5 Organosulfur
chemistry has been a beneficiary of the progress in transition
metal catalysis but C–S cross-coupling reactions are under-
explored as compared to C–N or C–O bond formation due to the
deactivation of the metal catalyst by organosulfur compounds.6
Palladium catalyzed C–S cross-coupling reactions, using
Pd(PPh3)4 as catalyst,7 require an additional ligand along with
precious Pd and an inert atmosphere.8 On the other hand, Co
and Ni catalysts are associated with toxicity.9,10 Thus, develop-
ment of alternative, inexpensive, ligand-free, air and moisture
insensitive and recyclable catalysts for this useful reaction is highly
desirable in the context of environmental and industrial concerns.
Metal catalysts anchored on a heterogeneous support have
received tremendous attention recently.11 The primary advantages
of metal catalysts, as opposed to homogeneous catalysts, are
the ease of separation of product, reusability of catalyst,
improved efficiency due to stable active site and better steric
control of the reaction intermediate.12 Recently, functionalized
magnetic nanoparticles have emerged as viable alternatives to
Scheme 2 Synthesis of nano-Fe3O4–DOPA–Cu catalyst (nano-
FeDOPACu).
conventional materials, as robust, readily available, high-surface-
area heterogeneous catalyst supports.13 They offer an additional
advantage of being magnetically separable, thereby eliminating
the requirement of catalyst filtration after completion of the
reaction. Engaged in the development of greener and sustainable
pathways for organic transformations,14 nano-catalysis,15 and
nanomaterials,16 herein, we report on the utility of a nano-
ferrite-supported, magnetically recyclable, and inexpensive Cu
catalyst in C–S coupling reaction (Scheme 1).
The first step entails the synthesis and functionalization of
magnetic nanoparticles (Scheme 2). The catalyst was prepared
by sonicating nano-ferrites with dopamine hydrochloride
(DOPA) in water for 2 h, followed by addition of CuCl2 at a
basic pH. The material with Cu nanoparticles on the DOPA
functionalized nano-ferrites was separated using an external
magnet, washed with water followed by methanol and dried
under vacuum at 60 1C for 8 hours.
Sustainable Technology Division, National Risk Management
Research Laboratory, U. S. Environmental Protection Agency, MS 443,
Cincinnati, Ohio 45268, USA. E-mail: varma.rajender@.epa.gov;
Fax: +1 513-569-7677; Tel: +1 513-487-2701
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2cc17283f
Catalyst characterization by X-ray diffraction (XRD)
(Fig. 1b and d) and transmission electron microscopy (TEM)
(Fig. 1a and c) confirmed the formation of single-phase Fe3O4
c
2582 Chem. Commun., 2012, 48, 2582–2584
This journal is The Royal Society of Chemistry 2012

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Table 2 Synthesis of diaryl sulfides
Entry
Substrate
Thiophenols
Product
Times
Yielda
Fig. 1 (a) TEM of nano-FeDOPA, (b) XRD of nano-FeDOPA,
(c) TEM of nano-FeDOPACu, (d) XRD of nano-FeDOPACu.
nanoparticles, with spherical morphology and a size range of
10–25 nm. FT-IR confirms the anchoring of DOPA on ferrite
surfaces.15c The signals of Cu metal were not detected in XRD,
indicating that the Cu species is highly dispersed on ferrites.
The weight percentage of copper was found to be 0.82% by
inductively coupled plasma-atomic emission spectroscopy
(ICP-AES) analysis.
Experiments were performed to identify the appropriate
catalyst for the coupling of thiophenols (1.2 equiv.) with
4-bromonitrobenzene (1.0 equiv.). First, the reaction was
explored using nano-a-Fe3O4 and nano-a-Fe3O4–dopamine
(nano-FeDOPA) in DMF at reflux temperature using Cs2CO3
as a base, but no product formation occurred.
a
Reaction conditions: 1.2 mmol of thiophenol, 1.0 mmol of aryl
halide, 100 mg of nano-FeDOPACu catalyst, MW, 120 1C, power
100 Watts.
The catalyst was modified using CuCl2 with particle size of
10–25 nm, termed nano-a-Fe3O4–dopamine copper (nano-
FeDOPACu) (Scheme 2). The coupling of thiophenols with
1-bromo-4-nitrobenzene using this catalyst afforded a selective
formation of corresponding sulfides in 70% yield (Table 1). In
the context of optimization of solvent and base, the reaction in
water did not proceed, and that in DMF, THF and CH3CN
gave coupled products in moderate yield (ESIw, Table S1). The
use of K2CO3 or Cs2CO3 did not significantly affect the
outcome of the reaction. The observation that rapid formation
of the corresponding disulfide takes place, which precluded the
availability of free thiol for coupling after a certain reaction
time, prompted us to search for a reductive environment for
the reaction. Isopropanol appeared to be the logical choice. The
reaction in a THF : iPrOH (1: 1) mixture at reflux temperature
for 24 h showed a significant improvement but did not proceed
to completion. To reduce reaction time the reaction was next
conducted under microwave (MW) irradiation conditions at
120 1C for 25 min, which afforded the corresponding coupled
product in quantitative yield (ESIw, Table S1, entry 14). The
cross-coupling of a wide variety of commercially available aryl
iodides and aryl bromides with thiophenols occurred neatly
and the corresponding diaryl sulfides were obtained in good to
excellent yields (Table 2). Electron withdrawing and donating
substituents on aryl halides did not show significant effect on
the yield or the reaction time. Interestingly, as in the case of
thiophenols, para-chlorothiophenol did not undergo self-coupling
and gave the desired cross-coupled products (Table 2, entries 2, 4,
7, 9 and 11). The reaction of 4-nitrothiophenol, however,
proceeded sluggishly and required 45 min for completion
(Table 2, entry 5).
For practical applications of heterogeneous systems, the lifetime
of the catalyst and its level of reusability are significant factors. To
clarify this issue, the reaction of 1-bromo-4-nitrobenzene with
thiophenols using the recycled nano-FeDOPACu catalyst was
examined. After completion of the first reaction, the catalyst was
recovered magnetically, washed with methanol, and dried at 60 1C
for 30 min. A new reaction was then performed with fresh
reactants, under the same conditions. The nano-ferrite-
supported Cu catalyst could be reused at least three times
without any change in activity (ESIw, Table S2).
Table 1 C–S coupling of 1-bromo-4-nitro-benzene: screening of
catalysts
Metal leaching, as measured by ICP-AES analysis of the catalyst
before and after the three reactions, showed Cu concentration to be
0.82% before the reaction and 0.81% after the reaction.
Entry
Catalyst
Time
Yield
1
2
3
Fe3O4
nano-FeDOPA
nano-FeDOPACu
24 h
24 h
24 h
0%
0%
70%
The TEM image of the catalyst taken after the third cycle of
the reaction does not show significant change in the morphology
c
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Chem. Commun., 2012, 48, 2582–2584 2583

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and the size of the catalyst nanoparticles (10–25 nm) (ESIw,
Fig. S1), which indicates the retention of the catalytic activity
after recycling. No Cu metal was detected in the reaction
solvent after completion of the reaction which confirms the
fact that dopamine provides enough binding sites on the surface
of Fe3O4 nanoparticles and serves as a pseudo-ligand by
coordinating with Cu thus minimizing deterioration, preventing
metal leaching, and enabling efficient catalyst recycling.
In conclusion, an efficient, sustainable, and green procedure
for C–S coupling of aryl halides with thiophenols has been
developed using a magnetically separable and easily recyclable
heterogeneous Cu catalyst in isopropanol under microwave
irradiation conditions. Easy magnetic separation of the catalyst
eliminates the requirement of catalyst filtration after completion
of the reaction, which is an additional greener attribute of
this reaction. This unprecedented C–S coupling reaction in
isopropanol proceeds efficiently and uses a magnetically retrie-
vable heterogeneous catalyst with low copper loading (0.82%).
Nasir Baig R B is supported by the Postgraduate Research
Program at the National Risk Management Research Labora-
tory administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the
U.S. Department of Energy and the U.S. Environmental
Protection Agency.
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