Ullmann homocoupling of aryl iodides catalyzed by gold nanoparticles stabilized on magnetic mesoporous silica

Article abstract of DOI:10.1007/s13738-017-1050-z

Abstract: We demonstrated a convenient new procedure of the Ullmann homocoupling reaction for the synthesis of symmetrical biaryls via homocoupling of aryl iodides over a recyclable gold catalyst comprising Au nanoparticles supported on functional magnetic mesoporous silica (α-Fe₂O₃)-MCM-41-HS-Au. The catalyst was easily separated by an external magnet, and the recovered catalyst was reused in six successive reaction cycles without any significant loss of activity. So, using this catalyst is affordable. Also, the reaction time is much shorter than a few previously reported work. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-017-1050-z

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1050-z
ORIGINAL PAPER
Ullmann homocoupling of aryl iodides catalyzed by gold
nanoparticles stabilized on magnetic mesoporous silica
Shahnaz Rostamizadeh1 · Hamid Estiri1 · Mohammad Azad1
Received: 19 June 2016 / Accepted: 2 January 2017
© Iranian Chemical Society 2017
Abstract We demonstrated a convenient new procedure
of the Ullmann homocoupling reaction for the synthesis
of symmetrical biaryls via homocoupling of aryl iodides
over a recyclable gold catalyst comprising Au nanoparti-
cles supported on functional magnetic mesoporous silica
(α-Fe2O3)-MCM-41-HS-Au. The catalyst was easily separated
by an external magnet, and the recovered catalyst was reused
in six successive reaction cycles without any significant loss of
activity. So, using this catalyst is affordable. Also, the reaction
time is much shorter than a few previously reported work.
Graphical Abstract
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1050-z) contains supplementary
material, which is available to authorized users.
* Shahnaz Rostamizadeh
rostamizadeh@kntu.ac.ir
1
Department of Chemistry, K. N. Toosi University
of Technology, P. O. Box 15875-4416, Tehran, Iran
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J IRAN CHEM SOC
Keywords Ullmann homocoupling reaction · Symmetrical
biaryls · Magnetic nanocatalyst · Gold nanoparticles
Introduction
Biaryls are important building blocks of numerous agro-
chemicals, pharmaceuticals, natural products, conducting
materials and asymmetric catalysts [1]. Due to their wide-
spread applications, the development of straightforward
and environmentally friendly methods for the preparation
of biaryls has attracted a lot of attention [2]. These meth-
ods have been mainly dominated by transition metal-based
catalysts such as copper [3, 4], nickel [5], rhodium [6] and
palladium [7]. The original and most widely used route
to biaryls is the Ullmann reaction in the copper-mediated
homocoupling of aryl halides [8]. The need to avoid the
harsh conditions typically required for Ullmann couplings
(neat, >200 °C) has motivated the search for milder condi-
tions [9].
Fig. 1 TEM image of (α-Fe2O3)-MCM-41-HS-Au
(a-Fe2O3)-MCM-41-HS-Au
K3PO4, DMF, 140 0C, 6h
R
I
R
R
Although several new methods for the synthesis of biar-
yls have been developed, the old Ullmann reaction still
remains important because of its efficiency and simplicity
[2].
Scheme 1 Ullmann coupling of aryl iodides catalyzed by (α-Fe2O3)-
MCM-41-HS-Au catalyst
The interest in gold nanoparticles as catalyst can be
quantitatively ascertained by the exponential growth in the
number of publications in the past decade [10–12]. These
Au nanoparticle catalysts are mainly employed for reac-
tions including oxidation [13–15], chemoselective reduc-
tion of nitroarenes [16] and wide varieties of commercially
important synthetic protocols [17, 18] reactions. It has
also been recently shown that Au nanoparticles are active
and selective catalysts for carrying out the homocoupling
of boronicacids [19], and Suzuki–Miyaura cross-coupling
of aryl halides [20], as well as Sonogashira reactions [21].
Although, the literature reports involving homocoupling of
aryl iodides catalyzed by nano-gold are very scarce, some
of them are reviewed in Ref. [22–24].
Clearly there are few reports on Ullmann homocou-
pling reaction using Au nanoparticles as catalyst. Accord-
ing to these reports, the catalyst was separated by filtration
method which not only takes longer process time, but also
wastes some of the catalyst. Therefore, the improvement
in a magnetic catalytic system involving Au nanoparticles
with superior recoverability and easy separation would be
beneficial.
properties of the catalysts have led to a significant decrease
in reaction time compared to previous reports.
Due to the inherent properties of magnetic nanoparticles
such as biocompatibility, easy renewability and recovery by
magnetic separation, thermal stability against degradation,
large surface area and higher loading of active sites, these
magnetic particles have emerged as a useful group of het-
erogeneous catalysts. Lately, many excellent studies about
magnetic composite nanocatalysts have been reported
[25–29].
We have recently reported the results obtained for the
water medium and solvent-free alkyne hydration reaction
using Au anchored to magnetic mesoporous silica cata-
lyst (α-Fe2O3)-MCM-41-HS-Au [25]. In order to demon-
strate the applicability of our catalyst in other important
organic transformations, we herein report the Ullmann
homocoupling of aryl iodide to yield symmetrical biaryls
(Scheme 1).
Experimental
Uniform distribution of Au nanoparticles, besides the
mesoporosity with 2–3 nm in pore diameters and large sur-
face area of MCM-41-HS matrix caused the higher loading
of finer Au nanoparticles, which is quite useful for catalytic
activity in Ullmann homocoupling reaction (Fig. 1). These
Chemicals and instruments
The reagents and solvents used in this work were obtained
from Fluka or Merck and used without further purification.
Melting points were recorded on a Buchi B-540 apparatus.
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J IRAN CHEM SOC
Table 1 Optimization of reaction conditions for the Ullmann homo-
coupling of aryl iodides catalyzed by the (α-Fe2O3)-MCM-41-HS-Au
catalyst
IR spectra were recorded on an ABB Bomem Model FTLA
1
200–100 instrument. H and 13CNMR spectra were meas-
ured on a Bruker DMX-400 spectrometer, at 400 and
100.6 MHz, using TMS as an internal standard. Chemical
shifts (δ) were reported relative to TMS, and coupling con-
stants (J) were reported in hertz (Hz). The pore structure
of the prepared catalyst was verified by the nitrogen sorp-
tion isotherm ([5.0.0.3] Belsorp, BEL Japan, Inc.). X-ray
powder diffraction (XRD) was carried out on a Philips
X’Pert diffractometer with CoKα radiation. The structure
and morphology of the products which were characterized
by transmission electron microscope (TEM) was recorded
on a Philips CM-10 instrument on an accelerating voltage
of 100 kV, and scanning electron microscopy (SEM) analy-
ses were performed by VEGA II TESCAN electron micro-
scope (Czech Republic) operating at an accelerating volt-
age of 15 kV. The chemical compositions of the samples
were evaluated by scanning electron microscopy (SEM,
SAMX) equipped with an energy-dispersive X-ray (EDX).
Entry
Catalyst (mg)
Solvent
Base
Yielda (%)
1
30
30
30
30
40
40
40
50
0
DMSO
Toluene
H2O
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
KOH
70
2
55
3
Trace
4
DMF
DMF
DMF
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
80
5
65
6
87
7
75
8
87
9
No reaction
10b
11
12
13
40
40
40
40
68
52
Et3 N
–
78
No reaction
Reaction conditions: 4-iodoacetophenone (1 mmol), base (2 mmol),
solvent (5 mL) and catalyst (mg) were stirred at reflux temperature
(140 °C for DMF) for 6 h
Representative procedure for the Ullmann
homocoupling of 4‑iodoacetophenone using
(α‑Fe2O3)‑MCM‑41‑HS‑Au catalyst
a
Isolated yields
b
The reaction was carried out at 100 °C
1 mmol of 4-iodoacetophenone, 2 mmol of K3PO4, 40 mg
(α-Fe2O3)-MCM-41-HS-Au (containing 0.012 mmol Au)
and 5 mL of the DMF solvent were taken in a sealed pres-
sure tube and heated at 140 °C for 6 h. The contents were
then allowed to cool to room temperature, and the catalyst
was separated by an external magnet. 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 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 solu-
tion (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 passing through
a column of silica gel, eluting with 10% EtOAC in hexane
to afford the pure 4, 4′-diacetyl biphenyl product.
Table 2 Alkyne hydration reaction catalyzed by various catalysts
Entry
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
7
No catalyst
24
24
24
24
24
24
6
Trace
Trace
Trace
Trace
Trace
Trace
87
AuCl3
MCM-41
Fe3O4
(α-Fe2O3)-MCM-41
(α-Fe2O3)-MCM-41-HS
(α-Fe2O3)-MCM-41-HS-Au
Reaction condition: 4-iodoacetophenone (1 mmol), 40 mg catalyst
(containing 0.012 mmol Au), K3PO4 (2 equiv.) and DMF (5 mL)
stirred at 140 °C
To determine the optimum loading of gold on the
(α-Fe2O3)-MCM-41-HS-Au catalyst required for the
homocoupling reaction as well as to determine the most
appropriate solvent and base, a series of reactions were car-
ried out by employing 4-iodoacetophenone as the model
substrate (Table 1). All the reactions were carried out at
the reflux temperature of the solvent (140 °C for DMF)
and were monitored for 6-h duration. Among the various
solvents such as H2O, DMSO, Toluene and DMF that were
Results and discussion
The prepared catalyst [(α-Fe2O3)-MCM-41-HS-Au] was
characterized with IR, XRD, TEM, SEM, EDX and nitro-
gen physisorption measurements (see Figures S1–S6, Sup-
porting Information).
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J IRAN CHEM SOC
Table 3 Ullmann coupling of various aryl iodides catalyzed by (α-Fe2O3)-MCM-41-HS-Au
Entry
Substrate
Product
Yieldb (%)
90
I
1
2
Me
Br
I
86
88
I
Br
Br
3
4
5
MeO
I
MeO
OMe
O
80
87
I
O
O
NC
I
NC
CN
6
82
7c
Trace
Br
Reaction condition: aryl iodide (1 mmol), 40 mg catalyst (containing 0.012 mmol Au), K3PO4 (2 equiv.) and DMF (5 mL) stirred at 140 °C for
6 h
a
Isolated yields
b
50 mg catalyst (containing 0.015 mmol Au), 150 °C, 24 h
subjected to screening, DMF was the solvent of choice.
Different bases such as K2CO3, Na2CO3, K3PO4, KOH and
Et3N were examined in the reaction. Among just mentioned
bases, K3PO4 showed the highest influence for homocou-
pling of 4-iodoacetophenone to afford the corresponding
biaryl in 87% yield in DMF as solvent at 140 °C (Table 1,
entry 6). According to the experiments results, no reaction
occurred in the absence of either base or gold nanoparti-
cles. A total of 40 mg of the (α-Fe2O3)-MCM-41-HS-Au
catalyst with 0.012 mmol Au loading was found to be
the optimum loading required for the homocoupling of
4-iodoacetophenone (Table 1, entry 6). These prove that the
presence of both gold nanoparticles and base is essential
for the reaction.
Furthermore, in order to show the unique catalytic
behavior of (α-Fe2O3)-MCM-41-HS-Au and to show the
role of Au in this catalyst, this reaction was performed in
the presence of catalytic amounts of AuCl3, Fe3O4, MCM-
41, (α-Fe2O3)-MCM-41 and (α-Fe2O3)-MCM-41-HS as
catalyst in a longer reaction time, 24 h (Table 2). No sig-
nificant reaction conversion was observed. Thus, the pres-
ence of gold nanoparticles in the (α-Fe2O3)-MCM-41-
HS-Au catalyst is essential for this organic transformation
(Table 2, entry 7). This table also shows that the homogene-
ous catalyst AuCl3 did not show any activity for the Ull-
mann homocoupling reaction (entry 2).
The gold-catalyzed homocoupling protocol that we
have developed is applicable to various substituted
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J IRAN CHEM SOC
prior to the next run. During the recycling experiments
with fresh reactants, under the same reaction conditions,
no considerable change in the reactivity of the catalyst was
observed for at least six successive runs which clearly show
the stability of the catalyst for these conditions in the Ull-
mann homocoupling reaction (Fig. 2).
a
90
85
80
75
70
65
In order to show the merit of this study, we compared
the obtained results with the results reported of Au cata-
lysts. For this purpose, the reaction of iodobenzene homo-
coupling was chosen as model reactions, and comparison
was carried out on the basis of reaction conditions, reaction
time and percentage yields obtained (Table 4). It is worth
mentioning that this method is a greener than catalysts
entry 1–3, and the recovery of catalyst is easier than them.
A probable reaction mechanism is proposed for the
Ullmann homocoupling of aryl iodides catalyzed by gold
nanoparticles (Scheme 2). After diffusion of the reactant to
the channels of the magnetic catalyst, aryl iodide molecules
get adsorbed onto the surface of catalyst involved gold
nanoparticles. Release of the biaryl product and iodide ions
takes place with the oxidation of the catalytic gold species.
According to previous research, our solvent DMF is a
good reducing agent for both silver and gold salts [28].
Therefore, it is proposed that DMF, containing water as
impurity, reduces the Au+ back to Au (0). DMF gets oxi-
dized to carbamic acid which then further decomposes to
dimethyl amine and CO2 at high reaction temperature [24,
30].
60
1
2
3
4
5
6
Run
b
Fig. 2 a Recyclability of the catalyst (α-Fe2O3)-MCM-41-HS-Au for
the Ullmann homocoupling reaction. b The catalyst in a typical reac-
tion mixture in the absence and the presence of a magnetic field
iodobenzenes, as is evident from Table 3. The homocou-
pling reaction of various aryl iodides including electron-
rich and electron-deficient substrates proceeded smoothly
using as low as 40 mg (α-Fe2O3)-MCM-41-HS-Au (con-
taining 0.012 mmol Au) to give the desired products in
good to excellent yields (Table 3, entries 1–6). In this work
we showed that this method is not applicable for the Ull-
mann homocoupling of aryl bromides even upon increasing
the reaction temperature to 150 °C and using 50 mg cata-
lyst after 24 h (Table 3, entry 7).
The catalytic activity and reusability of this mag-
netic nanocatalyst were also examined for the Ullmann
homocoupling of 4-iodoacetophenone (1 mmol), K3PO4
(2 mmol) and DMF (5 mmol) for 6 h at 140 °C. Upon
completion of the reaction, the mixture was diluted with
EtOAc, and the catalyst was easily separated and recovered
by an external magnet. Then it was washed with distilled
water and acetone and finally dried at 100 °C for 30 min
Conclusion
In summary, Ullmann homocoupling of aryl iodides was
performed successfully to prepare symmetrical biaryls
using (α-Fe2O3)-MCM-41-HS-Au as the catalyst. Due
to rare reports of Ullmann homocoupling catalyzed by
gold nanoparticles, this report is of great importance.
In order to improve catalyst recovery, gold nanoparti-
cles are loaded on the (α-Fe2O3)-MCM-41-HS magnetic
mesoporous matrix. The catalyst can be easily separated
with an external magnet and used in subsequent runs
without significant decrease in activity even after six runs.
The shorter reaction time, high selectivity, no observation
Table 4 Comparison of
Entry
Catalyst
Reaction conditions
Time (h)/Yield (%) [Lit.]
biphenyl formation by
(α-Fe2O3)-MCM-41-HS-Au
catalyst with the literature
reported methods
1
2
3
4
Au@PMO
NMP, K3PO4, 100 °C
16/95 [23]
6/90 [22]
48/92 [24]
6/90a
Au (0) nanoparticles
NAO-Mg–Au (0)
Glucose, TBAOH, water, 90 °C
DMF, K2CO3, 140 °C
(α-Fe2O3)-MCM-41-SH-Au
DMF; K3PO4, 140 °C
a
Present study
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J IRAN CHEM SOC
Scheme 2 Plausible reaction
mechanism of Ullmann homo-
coupling reaction
Me2NH+CO2
2
I
Me2NCOOH+2H+
Au (0)
HCONMe2+H2O
I
Au (0)
+
Au
I
2I-
Au (0)
I
I
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Acknowledgements We gratefully acknowledge the partial support
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