Ullmann coupling of aryl iodides catalyzed by gold nanoparticles stabilized on nanocrystalline magnesium oxide

Article abstract of DOI:10.1039/c3cy20826e

Gold nanoparticles stabilized on nanocrystalline magnesium oxide is shown to be an efficient heterogeneous catalytic system for the synthesis of symmetrical biaryls via homocoupling of aryl iodides.

Full text of DOI:10.1039/c3cy20826e

Catalysis
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Ullmann coupling of aryl iodides catalyzed by gold
nanoparticles stabilized on nanocrystalline
magnesium oxide
Cite this: Catal. Sci. Technol., 2013,
3, 1147
Keya Layek, H. Maheswaran* and M. Lakshmi Kantam
Received 30th November 2012,
Accepted 9th January 2013
Gold nanoparticles stabilized on nanocrystalline magnesium oxide is shown to be an efficient
heterogeneous catalytic system for the synthesis of symmetrical biaryls via homocoupling of aryl
iodides.
DOI: 10.1039/c3cy20826e
www.rsc.org/catalysis
Introduction
Aryl–aryl bond formation reactions are one of the most important
reactions in organic synthesis as they give rise to many naturally
occurring biologically and pharmaceutically active products.1
Though this area has been mainly dominated by transition
metal based catalysts like iron,2 copper,3 nickel,4 rhodium5 and
palladium,6 gold nanoparticles have surprisingly shown excellent
catalytic activity as well as selectivity for carbon–carbon bond
formation reactions like homocoupling of phenylboronic acid,7
Suzuki Miyaura coupling,8 as well as Sonogashira reactions.9
Other than these reactions, the Ullmann coupling of aryl halides
to yield symmetrical biaryls is a very important carbon–carbon
bond forming reaction for organic synthesis.10 Traditionally
this reaction is catalyzed with an excess of copper at elevated
temperatures of about 200 1C.11 Although several new methodologies
for the synthesis of biaryls have been developed, the century old
Ullmann reaction still remains important because of its efficiency
and simplicity.12
Scheme 1 Ullmann coupling of aryl iodides catalyzed by the NAP-Mg-Au(0)
catalyst.
show NAP-Mg-Au(0) as an active heterogeneous catalyst for the
Ullmann coupling of aryl iodides (see Scheme 1). This work
forms the focus of this paper.
Results and discussion
Nanocrystalline magnesium oxide commercially available as
NAP-MgO (NanoActivet Magnesium Oxide Plus) was selected
as a support for heterogenizing gold nanoparticles. NAP-MgO is
a superior support compared to other supports because of
certain unique physical and chemical features associated with
it.17 For example, the Lewis acidic (Mg2+) and Lewis basic (O2ꢀ
)
Literature reports involving homocoupling of aryl iodides
catalyzed by nano-gold are very scarce and to date, only a couple of
reports exist. For example, gold nanoparticles supported on periodic
mesoporous silica has been demonstrated to be catalytically active
for the Ullmann homocoupling of aryl iodides.13 Another example is
that of Ullmann homocoupling catalyzed by gold nanoparticles in
water and ionic liquid, which has been reported very recently.14 In
our previous works we have successfully synthesized, characterized
and employed gold nanoparticles stabilized on nanocrystalline
magnesium oxide, NAP-Mg-Au(0), for the one pot synthesis of
propargylamines15 as well as for the reduction of nitroarenes.16
In an endeavor to further explore the catalytic efficiency of this
catalyst for carbon–carbon bond forming reactions, we herein
sites along with other cationic and anionic vacancies enable it
to possess a high concentration of reactive surface ions that
may play a role in stabilizing the reaction intermediates during
the course of the reaction. Also the high surface area of NAP-
MgO enhances the catalytic activity of the support.
First, reaction was carried out between HAuCl4 and NAP-
MgO to obtain NAP-Mg-Au(III) species, which was subsequently
reduced by excess of sodium borohydride to yield gold nano-
particles that are deposited on the surface of NAP-MgO as in the
NAP-Mg-Au(0) catalyst. The transmission electron microscopy
(TEM) image of the NAP-Mg-Au(0) catalyst shows a homogeneous
distribution of gold nanoparticles on the MgO support with an
average particle diameter of 5–7 nm (see Fig. 1).
To determine the optimum loading of gold in the NAP-
Mg-Au(0) catalyst required for the homocoupling reaction as
well as to determine the most appropriate solvent and base, a
Inorganic and Physical Chemistry Division, Indian Institute of Chemical
Technology, Hyderabad-500607, India. E-mail: maheswaran@iict.res.in
c
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Table 2 Ullmann coupling of various aryl iodides catalyzed by NAP-Mg-Au(0)a
Entry Substrate
1
Product
Yieldb (%)
92
2
3
5
78
90
88
5
6
75
52
Fig. 1 TEM image of the NAP-Mg-Au(0) catalyst.
Table 1 Optimization of reaction conditions for the Ullmann homocoupling of
aryl iodides catalyzed by the NAP-Mg-Au(0) catalysta
Mol% of Au in
NAP-Mg-Au(0) catalyst
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
0.75
0.75
0.75
0.75
0.75
0.75
1
1
1
—
1
DMF
Toluene
H2O
K3PO4
K3PO4
K3PO4
K2CO3
K2CO3
Na2CO3
K2CO3
K3PO4
Nil
70
55
Traces
50
73
65
78
73
No reaction
No reaction
68
63
7
45
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
8c
Traces
a
Reaction conditions: aryl iodide (1 mmol), NAP-Mg-Au(0) (1 mol%
Au), K2CO3 (2 equiv.), DMF (3 mL) stirred at 140 1C for 48 hours.
9
b
c
10c
11d
12e
K2CO3
K2CO3
K2CO3
Isolated yields. Reaction time 72 hours.
1
demonstrates that the unique features that are associated with
the NAP-MgO support enhance the catalytic activity of the gold
nanoparticles heterogenized onto it.
Having optimized reaction conditions in hand, we now evaluated
the catalytic activity of our NAP-Mg-Au(0) catalytic system for the
homocoupling of various aryl iodides. As can be seen from Table 2,
a
Reaction conditions: 4-iodoanisole (1 mmol), base (2 mmol), solvent
(3 mL) and catalyst (with the given mol% of Au) was stirred at reflux
b
c
temperature (140 1C for DMF) for 48 hours. Isolated yields. 100 mg
of NAP-MgO was used as the catalyst. meso-CeO2-Au(0) was used as
the catalyst. meso-HAP-Au(0) was used as the catalyst.
d
e
series of reactions were carried out by employing 4-iodoanisole iodobenzene afforded an excellent yield of the biaryl product
as the model substrate (see Table 1). All the reactions were (Table 2, entry 1). 4-Iodoanisole and 4-iodotoluene also afforded
carried out at the reflux temperature of the solvent (140 1C for decent yields of the product under our optimized experimental
DMF) and were monitored for 48 hours duration. Among the conditions (Table 2, entries 2 and 3). 1-Chloro, 4-iodobenzene
various solvents and bases that were subjected to screening, exclusively yielded 4,40-dichlorobiphenyl (Table 2, entry 4). 3-Iodo-
DMF was the solvent of choice, whereas K2CO3 proved to be the toluene gave good yields for the corresponding biaryl product under
most efficient base. The NAP-Mg-Au(0) catalyst with 1 mol% of these conditions (Table 2, entry 5). Interestingly, ortho-substituted
Au was found to be the optimum loading required for the substrates viz. 2-iodotoluene and 2-iodoanisole afforded relatively
homocoupling of 4-iodoanisole. No reaction occurred in the poor yields of the corresponding coupled product (Table 2, entries 6
absence of either base or gold nanoparticles. This proves that and 7). This demonstrates that our NAP-Mg-Au(0) catalytic system is
the presence of both gold nanoparticles and base is essential sensitive to steric effects. When bromobenzene was employed as the
for the reaction. It is to be noted here that though NAP-MgO is substrate under our optimized experimental conditions no product
highly basic in nature, yet the basicity of the NAP-Mg-Au(0) formation was observed. Even on prolonging the duration of
catalyst is much less compared to that of 2 mmol of K2CO3, reaction only traces of biphenyl were observed (Table 2, entry 8)
hence the requirement of base is essential for the reaction. with the bromobenzene substrate. This clearly demonstrates that
Other supported gold catalysts like meso-CeO2-Au(0) and meso- the present catalytic system is unsuitable for the homocoupling of
HAP-Au(0) were also catalytically active for this reaction though aryl bromides.
the yields were lower when compared to the NAP-Mg-Au(0)
The recyclability of the NAP-Mg-Au(0) catalyst was also
catalyst under similar experimental conditions. This further examined by the Ullmann coupling of 4-iodoanisole used as a
c
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Table 3 Recyclability studies on the Ullmann homocoupling of 4-iodoanisole
proposed that DMF, containing water as impurity, reduces the
cationic gold back to metallic gold, thereby regenerating the
active catalytic surface. DMF gets oxidized to carbamic acid
which then further decomposes to dimethylamine and CO2 at
high reaction temperature.18 Notably, the introduction of DMF
based half reaction ensures smooth release of iodide ions as
hydroiodic acid (HI) in the mechanistic cycle.
using NAP-Mg-Au(0) catalysta
Reaction cycle
1st
78
2nd
73
3rd
70
4th
66
Yieldb (%)
a
4-Iodoanisole (1 mmol), NAP-Mg-Au(0) (fresh catalyst containing
1 mol% Au), K2CO3 (2 equiv.), DMF (3 mL) stirred at 140 1C for 48 hours.
b
Isolated yield after column chromatography.
Conclusion
model substrate and it was observed that the yield of the
product gradually dropped with each reaction cycle (see
Table 3). To verify whether any leaching occurs, the gold
content in the used NAP-Mg-Au(0) catalyst (after three reaction
cycles) was analyzed by ICP-OES and it revealed the loss of
about 9.5% of the initial amount of gold that was originally
present in the fresh catalyst. This may be the underlying cause
for the gradual drop in the yield of the product with each cycle.
That the leached gold was not active for the coupling reaction
was also verified by performing a heterogeneity test. For this
study, two batches of reactions were carried out simultaneously.
For the first batch, the solid catalyst was separated from the
reaction mixture after 20 hours. The yield of the product
obtained was about 40%. At this point, the catalyst was also
separated from the second batch and the filtrate was allowed to
stir for another 28 hours. There was no improvement in the yield
of the product in the latter case as deduced both by TLC and
column chromatographic studies. As seen in Table 2, with
4-iodoanisole, we have obtained 78% yield for the biaryl product
when the reaction was allowed to continue for 48 h. This result
demonstrates that the leached gold is not active for the reaction,
and the reaction truly followed a heterogeneous pathway.
We have shown that the gold nanoparticles stabilized on
a nanocrystalline magnesium oxide support is an efficient
heterogeneous catalytic system for the Ullmann homocoupling
of aryl iodides. The catalytic system requires low reaction
temperatures as compared to traditional copper based catalysts,
and the catalyst can be separated by simple centrifugation and
reused for further reaction cycles.
Experimental section
General
NAP-MgO (commercial name: NanoActivet Magnesium Oxide
Plus) was purchased from NanoScale Corporation (Manhattan,
USA). All chemicals were purchased from commercial sources,
and were used as received. All solvents used for experiments
were dried using standard procedures (except water), and
distilled prior to use. The particle size and external morphology
of NAP-Mg-Au(0) were observed by a Transmission Electron
Microscope (JEOL JEM-2100 in ISSP, Univ. Tokyo) operating
at 200 kV. Energy dispersive X-ray (EDX) spectroscopy was
performed on a Hitachi SEM S-520, EDX-Oxford Link ISIS-300
instrument. An inductively coupled plasma optical emission
spectrometer (ICP-OES, Intrepid II XDL, Thermo Jarrel Ash) was
used for determining the gold content in the used catalyst.
1H and 13C Nuclear Magnetic Resonance (NMR) spectra
were recorded on an Avance 300 (300 MHz for 1H-NMR and
13C-NMR) spectrometer in CDCl3 solvent using TMS as an
internal standard. ACME SILICA GEL was used for column
chromatography purposes using ethyl acetate/hexane as eluting
agents, and thin layer chromatography was performed on
Merck precoated silica-gel 60-F254 plates.
Probable reaction mechanism
A probable reaction mechanism is proposed for the Ullmann
coupling of aryl iodides catalyzed by gold nanoparticles stabilized
on nanocrystalline magnesium oxide14 (Scheme 2). First, aryl
iodide molecules get adsorbed onto the surface of gold nano-
particles. Release of the biaryl product and iodide ions takes place
with the oxidation of the catalytic gold species. It is to be noted
that DMF, which acts as a solvent in this case, is well known to be a
good reducing agent for both silver and gold salts.18 Therefore, it is
Synthesis of the NAP-Mg-Au(0) catalyst
The NAP-Mg-Au(0) catalyst was synthesized according to a
procedure reported earlier.16 Commercial NAP-MgO was calcined
at 450 1C for four hours in air. This NAP-MgO support (3.5 g) was
treated with chloroauric acid solution (1 g, 2.54 mmol; dissolved in
100 mL of double distilled water), and stirred at 25 1C for 12 h
under a nitrogen atmosphere to give NAP-Mg-Au(III) species. To this
reaction mixture, excess of sodium borohydride (3.5 g, 92.5 mmol)
was slowly added and the contents were allowed to stir under a
nitrogen atmosphere for another 12 h. The solid catalyst was then
filtered through a G-3 sintered glass funnel, washed thoroughly
with double distilled water and then with acetone. It was then oven
dried at 70 1C to obtain NAP-Mg-Au(0) as a dark purple coloured
Scheme 2 Proposed reaction mechanism for the Ullmann coupling of aryl
iodides catalyzed by the NAP-Mg-Au(0) catalyst.
c
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Representative procedure for the Ullmann homocoupling of
4-iodoanisole using NAP-Mg-Au(0) catalyst
1 mmol of 4-iodoanisole, 2 mmol of K2CO3, 150 mg of the NAP-Mg-
Au(0) catalyst (1 mol% of Au) and 3 mL of the DMF solvent were
taken in a sealed pressure tube and heated at 140 1C for 48 hours.
The contents were then allowed to cool to room temperature and
the reaction mixture was centrifuged to separate the catalyst. The
solid residue was first washed with distilled water and then with
acetone to remove any traces of organic material. It was then dried
in air at room temperature and used as it is for further reactions.
The filtrate containing the reaction mixture was diluted with ethyl
acetate (10 mL) and extracted multiple times with water to remove
DMF. It was then washed with brine solution (10 mL), and dried
over anhydrous Na2SO4. Then the solvent was evaporated under
reduced pressure to yield the crude product, which was then
purified by column chromatography using silica gel and hexane/
ethyl acetate as an eluent to afford the pure 4,40-dimethoxybiphenyl
7 H. Tsunoyama, H. Sakurai, N. Ichikuni, Y. Negishi and
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1
product. Spectral data: H-NMR (300 MHz, CDCl3, TMS): d = 3.24
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(s, 6H), 6.93–6.96 (d, J = 8.876 Hz, 4H), 7.45–7.48 (d, J = 8.876 Hz,
4H); 13C-NMR (300 MHz, CDCl3, TMS): 55.682, 114.505, 128.062,
133.794, 159.015.
12 J. Hassan, M. Sevignon, C. Gozzi, E. Schulz and M. Lemaire,
Chem. Rev., 2002, 102, 1359.
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Acknowledgements
K.L. thanks the Council of Scientific & Industrial Research for
the award of a fellowship.
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