Suzuki Reaction of Aryl Bromides Using a Phosphine-Free Magnetic Nanoparticle-Supported Palladium Catalyst

Article abstract of DOI:10.1016/S1872-2067(10)60270-7

A palladium catalyst immobilized on superparaganetic nanoparticles was prepared with a palladium loading of 0.30 mmol/g. The catalyst was characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, thermogravimetric analysis, Fourier transform infrared, atomic absorption spectrophotometry, and nitrogen adsorption. The immobilized palladium catalyst was an efficient catalyst without added phosphine ligands for the Suzuki cross-coupling reaction of several aryl bromides with phenylboronic acid. The recovery of catalyst was simply by magnetic decantation in the presence of a magnet. The immobilized palladium catalyst can be reused many times without significant degradation in catalytic activity. No leaching of active palladium species into the reaction solution was detected.

Full text of DOI:10.1016/S1872-2067(10)60270-7

CHINESE JOURNAL OF CATALYSIS
Volume 32, Issue 11, 2011
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2011, 32: 1667–1676.
RESEARCH PAPER
Suzuki Reaction of Aryl Bromides Using a Phosphine-Free
Magnetic Nanoparticle-Supported Palladium Catalyst
Nghia T. BUI, Trung B. DANG, Ha V. LE, Nam T. S. PHAN*
Department of Chemical Engineering, HCMC University of Technology, VNU-HCM, 268 Ly Thuong Kiet, District 10, Ho Chi Minh City,
Viet Nam
Abstract: A palladium catalyst immobilized on superparaganetic nanoparticles was prepared with a palladium loading of 0.30 mmol/g. The
catalyst was characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, vibrating sample
magnetometry, thermogravimetric analysis, Fourier transform infrared, atomic absorption spectrophotometry, and nitrogen adsorption. The
immobilized palladium catalyst was an efficient catalyst without added phosphine ligands for the Suzuki cross-coupling reaction of several
aryl bromides with phenylboronic acid. The recovery of catalyst was simply by magnetic decantation in the presence of a magnet. The
immobilized palladium catalyst can be reused many times without significant degradation in catalytic activity. No leaching of active pal-
ladium species into the reaction solution was detected.
Key words: superparamagnetic nanoparticle; Suzuki reaction; palladium; aryl bromide
Biaryl units as molecular components in biologically active
molecules and functional polymers have attracted enormous
interest [1,2]. The Suzuki cross-coupling reaction is an in-
creasingly popular approach for the construction of unsym-
metrical biaryl compounds since the organoboranes used are
environmentally safer than other organometallic reagents [3].
Toxic and expensive homogeneous palladium phosphine
complexes, which are rarely recoverable [4], are used as the
catalysts for the Suzuki reaction [5–7]. The phosphines can be
more costly than even the palladium in some cases [8]. From
economic and environmental considerations, it is desirable to
use a solid catalyst that does not have the hazardous phosphine
additives as a green alternative to the conventional homoge-
neous processes for the Suzuki reaction [8,9]. Several
phosphine-free solid palladium catalysts have been investi-
gated for the Suzuki reaction, e.g., palladium species immobi-
lized on polymer [10–13], silica [14–21], zeolite [22–24],
hybrid organic-inorganic material [25,26], and palladium
nanoparticle-based catalysts [27–31].
When the size of the support is decreased to the nanometer
scale, the activity of the supported catalyst can be dramatically
improved compared to homogeneous catalysts immobilized on
conventional supports under conditions where internal pore
diffusion is rate limiting [32,34]. However, the facile separa-
tion and recycling of the nanoparticle materials from the reac-
tion media still remains a challenge [34]. The problem can be
solved by employing magnetic supports that allow the catalyst
to be easily separated from the liquid reaction media by a
magnet [35,36]. Magnetic nanoparticles have been utilized as
catalyst supports for several organic transformations [36,37]
such as olefin hydroformylation [38], alcohol hydrogenation
[39], olefin hydrogenation [40], asymmetric hydrogenation
[41,42], aldol reaction [43], Suzuki and Heck reactions [44–48],
Sonogashira and Carbonylative Sonogashira reactions
[44,49,50], Knoevenagel condensation [34], dehalogenation
[51], oxidation [52–54], ring-opening polymerization of
İ-caprolactone [55], ring-closing metathesis [56], cycloaddi-
tion reaction [57], and as supports for biocatalysts [58–61]. In
this paper, we report the Suzuki cross-coupling reaction of aryl
bromides with phenylboronic acid by a palladium catalyst
Nanoparticles have attracted significant interest as efficient
supports for homogeneous catalyst immobilization [32,33].
Received 30 May 2011. Accepted 20 July 2011.
*Corresponding author. Tel: +84-8-917416018; Fax: +84-8-38637504; E-mail: ptsnam@hcmut.edu.vn
This work was supported by the Ho Chi Minh City Department of Science and Technology, Viet Nam.
Copyright © 2011, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60270-7

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
without added phosphine ligands immobilized on superpara-
The superparamagnetic nanoparticles were synthesized and
functionalized with N-[3-(trimethoxysilyl)propyl]ethyl-
magnetic nanoparticles. The magnetic catalyst can be isolated
from the reaction mixture by simple magnetic decantation, and
can be reused without significant degradation in activity.
enediamine by a slight modification of a reported procedure
[34,62]. The nanoparticles (2.5 g) were dispersed in a mixture
of ethanol and water (400 ml, 1:1 by volume). Ammonium
hydroxide (40 ml, 25% v/v aqueous solution) was added, and
the mixture was stirred vigorously at 60 oC for 24 h under argon.
The nanoparticles were washed with copious amounts of de-
ionized water, ethanol, and n-hexane by magnetic decantation.
The resulting product was redispersed in a mixture of ethanol
and water (400 ml, 1:1 by volume), and sonicated for 30 min at
1 Experimental
1.1 Materials and instrumentation
Chemicals were purchased from Sigma-Aldrich, Fisher, and
Merck and used as received without further purification unless
otherwise noted. Distilled water was purged with nitrogen for 2
h prior to use. A Fischer Scientific FS60H ultrasonic bath was
used to sonicate samples. Fourier transform infrared (FT-IR)
spectra were obtained on a Bruker TENSOR37 instrument. The
samples were dispersed on potassium bromide pallets. Mag-
netic properties were measured with a PPMS 6000 vibrating
sample magnetometer (VSM) at 32 oC. Samples were sonicated
in dimethylformamide for 30 min before measurements were
taken. Scanning electron microscopy (SEM) studies were
conducted on a JSM 740 scanning electron microscope.
Transmission electron microscopy (TEM) studies were per-
formed using a JEOL JEM 1400 transmission electron micro-
scope at 100 kV. The samples were dispersed on holey carbon
grids for TEM observation. Nitrogen physisorption measure-
ments were conducted using a Quantachrome 2200e system.
room
temperature.
N-[3-(trimethoxysilyl)propyl]ethyl-
enediamine (2.8 g) was then added, and the solution was heated
at 60 oC with vigorous stirring for 36 h under argon. The final
product was washed with copious amounts of deionized water,
ethanol, and n-hexane by magnetic decantation, and dried
under vacuum at room temperature overnight to yield dia-
mino-functionalized magnetic nanoparticles (1.98 g).
1.3 Synthesis of palladium catalyst immobilized on
superparamagnetic nanoparticles
The diamino-functionalized magnetic nanoparticles (1.82 g)
were added to a round-bottom flask containing ethanol (99.5 %,
270 ml) and 2-acetyl pyridine (18 ml, 150 mmol) [63,64]. The
resulting mixture was sonicated for 30 min, and then heated
under reflux with rapid stirring for 36 h under argon. After that,
the reaction mixture was cooled to room temperature and the
solid was separated by magnetic decantation. The magnetic
solid was then redispersed in ethanol and hexane and sonicated
for 30 min at room temperature. The product was then sepa-
rated by magnetic decantation and dried under vacuum at room
temperature to yield the immobilized Schiff base (1.80 g). The
immobilized Schiff base (1.60 g) was added to the
round-bottom flask containing a solution of palladium acetate
(0.1815 g, 0.80 mmol) in acetone (280 ml). The mixture was
then stirred vigorously at room temperature for 36 h under
argon. The solid was separated by magnetic decantation, re-
dispersed in acetone, sonicated for 30 min at room temperature,
and then separated by magnetic decantation. The magnetic
catalyst was washed with copious amounts of acetone and
dried under vacuum at room temperature to yield the immobi-
lized palladium catalyst (1.50 g).
o
Samples were pretreated by heating under vacuum at 150 C
for 3 h. Elemental analysis with atomic absorption spectros-
copy (AAS) was performed on an AA-6800 Shimadzu in-
strument. X-ray diffraction (XRD) patterns were recorded
using a Cu KĮ radiation source on a D8 Advance Bruker pow-
der diffractometer.
A Netzsch Thermoanalyzer STA 409 was used for thermo-
gravimetric analysis (TGA) with a heating rate of 10 oC/min in
air. Gas chromatographic (GC) analyses were performed using
a Shimadzu GC 17-A chromatograph equipped with a flame
ionization detector (FID) and an DB-5 column (length = 30 m,
inner diameter = 0.25 mm, and film thickness = 0.25 ȝm). The
temperature program for the GC analysis was from 60 to 140
o
oC at 10 oC/min, held at 140 C for 1 min, heated from 140 to
300 oC at 50 oC/min and held at 300 oC for 3 min. The inlet and
o
detector temperatures were set at 300 C. n-Hexadecane was
used as an internal standard to calculate reaction conversions.
GC-MS analyses were performed using a Hewlett Packard
GC-MS 5972 instrument with a RTX-5MS column (length =
30 m, inner diameter = 0.25 mm, and film thickness = 0. 5 ȝm).
The temperature program for GC-MS analysis was from 60 to
1.4 Catalytic studies
Unless otherwise stated, a mixture of 4'-bromoacetophenone
(0.2149 g, 1.08 mmol), phenylboronic acid (0.1975 g, 1.62
mmol), K3PO4 (0.8628 g, 3.24 mmol), and n-hexadecane (0.12
ml) as the internal standard in dimethylformamide (5 ml) were
added to a round-bottom flask containing the required amount
of the immobilized palladium catalyst. The flask was heated at
the required temperature with magnetic stirring. Reaction
o
o
280 C at 10 oC/min and held at 280 C for 2 min. The inlet
temperature was set at 280 oC. MS spectra were compared with
the spectra in the NIST library.
1.2 Synthesis of amino-functionalized magnetic
nanoparticles

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
conversions were monitored by withdrawing aliquots (0.1 ml)
(a)
from the reaction mixture at different time intervals and
quenching with water (1 ml). The organic components were
extracted into diethylether (2 ml u 2), dried over Na2SO4, and
analyzed by GC with n-hexadecane as the reference. The
product identity was also further confirmed by GC-MS.
2 Results and discussion
100 nm
(b)
2.1 Catalyst synthesis and characterization
Superparamagnetic nanoparticles were synthesized by a
microemulsion method [34,65]. The elemental analysis (AAS)
of the particles showed the Co:Fe molar ratio of 1:2.08 corre-
sponding to the CoFe2O4 structure. The synthesis of CoxFe3-xO4
superparamagnetic nanoparticles with different Co:Fe ratios
was previously reported [66]. We recently prepared a palla-
dium catalyst immobilized on CoFe2O4 superparamagnetic
nanoparticles via silane and Schiff base chemistry using an
approach developed by Clark and coworkers [63,64] (catalyst
A, Scheme 1), which was used without added phosphine
ligands for the Sonogashira reaction [50]. The use of super-
paramagnetic nanoparticles as catalyst support offers advan-
tages in catalyst separation and recycling over similar sil-
ica-based catalysts. Interestingly, initial experimental results
showed that the catalytic activity was significantly improved
when the tether in the catalyst structure was extended by using
N-[3-(trimethoxysilyl)propyl]ethylenediamine instead of
3-(trimethoxysilyl)propylamine in the catalyst preparation
(catalyst B, Scheme 1). We therefore decided to use the latter
catalyst for further studies.
20 nm
Fig. 1. SEM (a) and TEM (b) micrographs of the functionalized super-
paramagnetic nanoparticles.
VSM analysis showed that the immobilized palladium catalyst
was superparamagnetic. The particle diameters were ap-
proximately 30–40 nm from SEM and TEM (Fig. 1) micro-
graphs of the particles. However, particle agglomeration was
clearly observed, and the primary particle size was likely to be
closer to 5–10 nm in diameter. Most oxide particles, regardless
of composition, aggregate on TEM grids, and thus, the TEM
images do not imply that the nanoparticles aggregate in solu-
tion [34].
The immobilized palladium catalyst was characterized using
a variety of different techniques as previously reported [50].
CH3
O
O Si
O
N
Catalyst A
N
Pd
CoFe2O4
AcO
OAc
O
N
CH
CH
CH
3O
3O Si
3O
NH2
CH3
OH
OH
N
H
OH
OH
OH
HO
HO
HO
O
O Si
O
NH2
N
H
Toluene
Ethanol
OAc
AcO
Pd
N
N
O
O Si
O
O
O Si
O
Pd(OAc)2
Acetone
N
N
N
H
N
H
CH3
CH3
Catalyst B
Scheme 1. Synthesis of the palladium catalyst immobilized on superparamagnetic nanoparticles (Catalyst B).

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
2.50
2.00
1.50
1.00
0.50
0.00
-0.50
100
98
(a)
0.15
0.10
DTA
0.05
0.00
96
94
92
DDTA
TG
-0.05
-0.10
-0.15
-0.20
-0.25
100 200 300 400 500 600 700 800 900
Temperature (oC)
30
40
50
2T/(o )
60
70
100
98
(b)
0.20
2
DTA
0.10
Fig. 2. XRD pattern of the immobilized palladium catalyst.
96
94
92
1
DDTA
TG
0.00
0
XRD patterns of the superparamagnetic nanoparticles were
consistent with those previously reported in the literature
[35,67,68] (Fig. 2). The BET surface areas were 150.44 m2/g
for the superparamagnetic nanoparticles, which was in good
agreement with the literature where BET surface areas ranged
from 120 m2/g to 200 m2/g [35,67].
-0.10
-0.20
-0.30
-0.40
-0.50
-1
-2
-3
90
88
86
84
100 200 300 400 500 600 700 800 900
Temperature (oC)
The significant features in the FT-IR spectra of the immobi-
lized palladium catalyst were the appearance of peaks near
1015 cm–1 for Si–O stretching. There were also peaks near
2900 cm–1 due to the –CH2 and aromatic C–H stretching vi-
brations, and the peak of the imine C=N stretching vibration
near 1600 cm–1 which was overlapped with the O–H deforma-
tion vibration (Fig. 3) [68,69].
100
98
0.15
(c)
1.50
DTA
0.10
96
94
92
0.05
1.00
0.50
0.00
-0.05
-0.10
-0.15
-0.20
-0.25
DDTA
TG
90
88
86
84
0.0
TGA results exhibited differences among the unfunctional-
ized nanoparticles, the immobilized Schiff base ligand, and the
immobilized palladium catalyst (Fig. 4). The TGA result
showed that a diamine loading of 0.50 mmol/g was achieved
for the diamine-functionalized nanoparticles. The elemental
analysis indicated a nitrogen loading of 1.04 mmol/g, corre-
sponding to 0.52 mmol/g of the diamine immobilized on the
superparamagnetic nanoparticles. The TGA analysis of the
immobilized Schiff base ligand showed a Schiff base loading
of 0.48 mmol/g. The AAS analysis of the immobilized palla-
dium catalyst exhibited a palladium loading of 0.30 mmol/g.
The metal loadings of several immobilized palladium catalysts
for cross-coupling reactions were previously reported to be in
the range of 0.1–0.5 mmol/g [8]. No meaningful data for the
-0.50
-1.00
100 200 300 400 500 600 700 800 900
Temperature (oC)
Fig. 4. TGA profiles of the unfunctionalized superparamagnetic
nanoparticles (a), immobilized Schiff base ligand (b), and immobilized
palladium catalyst (c).
palladium immobilization was obtained from the XRD and
FT-IR results due to the low loading of the metal. It was also
not possible to monitor changes on the surface of the particles
using electron microscopy techniques because the particles
were black. Therefore, proof that the palladium was immobi-
lized on the superparamagnetic nanoparticles came from the
AAS data of the catalyst, from leaching studies which showed
negligible activity of the reaction solution after the solid cata-
lyst was removed, and from the fact that the catalyst can be
recovered and reused several times without significant degra-
dation in catalytic activity.
70
65
60
55
50
45
2.2 Catalytic studies
3800 3200 2600 2000 1700 1400 1100 800 500
Wavenumber (cmꢀ1)
The immobilized palladium complex catalyst was initially
assessed for its activity in the Suzuki cross-coupling reaction
between 4'-bromoacetophenone and phenylboronic acid to
Fig. 3. FT-IR spectrum of the immobilized palladium catalyst.

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
100
Br
R
B(OH)2
[Pd]
+
80
60
40
20
0
R
K3PO4
R: COCH3, NO2, CN, F, H, CH3, OCH3
Scheme 2. Suzuki reaction of aryl bromides and phenylboronic acid
using the palladium catalyst immobilized on the superparamagnetic
nanoparticles.
110 oC
100 oC
90 oC
80 oC
form 4-acetylbiphenyl as the principal product (Scheme 2). As
dimethylformamide (DMF) is the solvent of choice for
cross-coupling reactions [8], it was decided to carry out the
0
20
40
60
80
100
120
Time (min)
o
Suzuki reaction in DMF at 100 C using 0.1 mol% of the im-
Fig. 6. Effect of temperature on reaction conversion.
mobilized palladium catalyst without added phosphine ligands.
As the presence of a base was necessary in the Suzuki catalytic
cycle [3,6,8], the effect of bases on the reaction conversion was
investigated by carrying out the reaction in the presence of
K3PO4, K2CO3, CH3COONa, and triethylamine. K2CO3 has
been effectively employed in several Suzuki cross-coupling
processes using homogeneous palladium phosphine complexes
as catalysts [3]. In our research, however, the immobilized
palladium catalyst in the presence of K2CO3 gave the Suzuki
reaction with a significant slower rate than with the reaction
using K3PO4. Triethylamine and CH3COONa were unsuitable
for the immobilized palladium catalyst in the Suzuki reaction.
It was previously reported that weaker bases gave better results
for less hindered arylboronic acids in several Suzuki reactions
[70]. Although phenylboronic acid is not sterically hindered,
the reaction using K3PO4 gave significantly better conversions
than the reactions using weaker bases, and a quantitative con-
version was achieved after 1 h (Fig. 5). Indeed, K3PO4 has been
found to be the base of choice for the Suzuki reaction in some
cases [12,47,71,72]. It was therefore decided to use K3PO4 for
the reaction in further experiments.
reactions and catalysts [3,5,6,73,74]. It was also reported that
the Suzuki reaction using phosphine-based catalysts can occur
at room temperature although a longer reaction time was re-
quired [75,76]. In our study, it was found that the Suzuki reac-
tion using the immobilized palladium catalyst proceeded ef-
o
fectively at 100 C with more than 99% conversion after 1 h.
Increasing the reaction temperature to higher than 100 oC was
unnecessary for the reaction, although the initial reaction rate
was slightly enhanced. As expected, decreasing the reaction
temperature from 100 oC to 90 or 80 oC resulted in a significant
drop in the conversion of 4'-bromoacetophenone. However, the
reaction still gave 95% and 71% conversions after 2 h at 90 and
o
80 C, respectively (Fig. 6). The most effective temperature
range for the Suzuki reaction using the immobilized palladium
catalyst in this research was in good agreement with the lit-
erature. No homo-coupling product was detected by GC
analysis. It was also observed that non-functionalized super-
paramagnetic nanoparticles exhibited no activity, indicating the
necessity of the catalyst.
The effect of catalyst concentration on the reaction conver-
sion was studied in the range of 0.01–0.5 mol% relative to
4'-bromoacetophenone. The reaction was carried out at 100 oC
using DMF as the solvent and K3PO4 as the base. A higher
catalyst concentration gave a higher reaction rate. More than
99% conversion was achieved for the reaction using 0.1 mol%
catalyst after 1 h. As expected, increasing the catalyst concen-
tration to 0.5 mol% led to an enhancement in reaction rate, with
a conversion of more than 99% after 40 min. A lower reaction
rate was observed at the catalyst concentration of 0.01 mol%,
although the reaction could still give a conversion of 94% after
2 h (Fig. 7). The catalyst concentrations used in this study were
therefore comparable to those of several previous reports,
where the palladium concentrations were varied from less than
0.1 mol% to more than 5 mol% for different catalysts and
substrates [3,5,6]. Indeed, some homogeneous palladium
complexes were effective for the Suzuki reaction at a catalyst
concentration as low as 0.0005 mol% [77]. However, Suzuki
reactions using solid catalysts require higher catalyst concen-
trations, normally in the range of 0.1–1 mol%.
To investigate the effect of temperature on the reaction
conversion, the reaction was carried out in DMF at a catalyst
concentration of 0.1 mol% in the presence of K3PO4 as the base.
The temperature range of 80–120 oC was previously employed
for several Suzuki cross-coupling processes with different
100
80
60
40
20
0
K3PO4
CH3COONa
K2CO3
Et3N
0
20
40
60
80
100
120
Time (min)
Fig. 5. Effect of different bases on reaction conversion.

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
100
100
80
60
40
20
0
(3)
(4)
80
(1)
(5)
60
(2)
40
(6)
0.01 mol%
0.1 mol%
0.5 mol%
20
0
(7)
0
20
40
60
80
100
120
0
20
40
60
80
100
120
Time (min)
Time (min)
Fig. 7. Effect of catalyst concentration on reaction conversion.
Fig. 9.
Effect of aryl bromide on reaction conversion. (1)
The reaction was then extended to the Suzuki reaction of
several aryl bromides containing the bromo group at different
positions, and with either electron-withdrawing or elec-
4'-Bromoacetophenone; (2) Bromobenzene; (3) 4-Bromonitrobenzene; (4)
4-Bromobenzonitrile; (5) 4-Bromoflorobenzene; (6) 4-Bromotoluene; (7)
4-Bromoanisole.
o
tron-donating groups. The reaction was carried out at 100 C
using 0.1 mol% catalyst in the presence of K3PO4 as the base.
Interestingly, it was found that the Suzuki reaction using the
reactive than 4'-bromoacetophenone. As expected, the Heck
reaction of 4'-chloroacetophenone proceeded with a signifi-
immobilized palladium catalyst gave
a selectivity for
cantly
slower
rate than was the
case with
4'-bromoacetophenone that was higher than those for the cor-
responding 3'- and 2'-isomers. The reaction of the 3'-isomer
gave 84% conversion after 2 h, while quantitative conversion
was achieved after 1 h for the 4'-isomer. Furthermore, there was
50% unreacted starting material in the case of the 2'-isomer,
which led us to believe that increased steric bulk at the
2-position inhibited substitution (Fig. 8) [78]. As expected, it
was observed that the presence of an electron-withdrawing
group on the benzene ring of the aryl bromide significantly
accelerated the Suzuki reaction, while the presence of an elec-
tron-donating group resulted in a significantly drop in reaction
rate. The reactivity of aryl bromides in the Suzuki reaction with
phenylboronic acid was in the order 4-bromonitrobenzene >
4'-bromoacetophenone, and a conversion of only 14% was
obtained after 6 h (Fig. 10). Chloroarenes were previously
reported to be inactive for several palladium-catalyzed
cross-coupling reactions [8]. The Suzuki reaction of
4'-bromoacetophenone was also carried using different sub-
stituted phenylboronic acids. It was found that the reactivity of
the phenylboronic acids with 4'-bromoacetophenone was in the
order 4-methoxyphenylboronic acid > phenylboronic acid >
4-fluorophenylboronic acid > 4-chlorophenylboronic acid (Fig.
11). However, the reaction could only proceed to 90% con-
version in these cases. It was previously reported that no sig-
nificant difference in reaction rate was observed for the Suzuki
reaction using different substituted phenylboronic acids
[44,76].
4-bromobenzonitrile
>
4'-bromoacetophenone
>
4-bromoflorobenzene > bromobenzene > 4-bromotoluene >
4-bromoanisole (Fig. 9).
As mentioned earlier, using a similar approach for palladium
immobilization on superparamagnetic nanoparticles, the cata-
lytic activity in the Suzuki reaction was significantly improved
It was also observed that 4'-iodoacetophenone was more
100
80
100
80
60
60
40
20
0
4'-Chloroacetophenone
4'-Bromoacetophenone
4'-Iodoacetophenone
40
2'-Bromoacetophenone
3'-Bromoacetophenone
4'-Bromoacetophenone
20
0
0
20
40
60
80
100
120
0
20
40
60
80
100
120
Time (min)
Time (min)
Fig. 8. Effect of bromine substitution position on reaction conversion.
Fig. 10. Effect of the halogen in arylhalide on reaction conversion.

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
of the palladium catalyst. It was previously reported that the
100
80
60
40
20
0
presence of an amine can increase the stability of the palladium
catalyst in the Suzuki and the Heck reactions [6,8]. The effect
of the nitrogen atom on the catalytic activity in the Suzuki
reaction using catalyst B still needs further investigation.
For a liquid-phase reaction using solid catalysts, an impor-
tant issue is the possibility that some active sites can get
leached [34]. After the catalyst was removed from the reaction
mixture by a small magnet, the solution was analyzed by
ICP-MS. The palladium concentration in the solution was
shown to be as low as 2 ppm. A minimal loss of palladium into
solution in the Suzuki and Heck reactions was previously
observed for the palladium catalyst immobilized on super-
paramagnetic nanoparticles [47]. A small amount of palladium
was previously detected in the solution of the Carbonylative
Sonogashira reaction with a superparamagnetic nanoparti-
cles-supported palladium catalyst [49]. However, it was also
reported that no palladium was detected in the reaction solution
for other superparamagnetic nanoparticles-supported palla-
dium catalysts [46,51]. In order to determine if leaching was a
problem for the Suzuki reaction using the immobilized palla-
dium catalyst, an experiment was performed to estimate the
contribution of leached active species to the total reaction
conversion. This was done by performing magnetic decanta-
tion during the course of the reaction to remove the solid
catalyst. A reaction conversion that continued increasing after
the solid catalyst was removed would indicate that the real
active species was leached palladium rather than the solid
catalyst. The reaction mixture that used 0.01 mol% fresh
catalyst at 100 oC was separated from the solid catalyst after 20
min reaction time by magnetic decantation. The reaction solu-
tion was then transferred to a new reactor vessel and stirred for
4-Methoxyphenylboronic acid
4-Fluorophenylboronic acid
Phenylboronic acid
4-Chlorophenylboronic acid
0
20
40
60
80
100
120
Time (min)
Fig. 11. Effect of substituted phenylboronic acids on reaction conver-
sions.
when the tether in the catalyst structure was extended. The
activity of the immobilized palladium catalyst obtained using
catalyst B was compared to that of the case when catalyst A
was used. The Suzuki reaction was carried out at 100 oC using
0.1 mol% palladium catalyst. It was found that the reaction of
4-bromonitrobenzene with phenylboronic acid using catalyst B
gave more than 99% conversion after 40 min, while 92%
conversion was obtained for the case of catalyst A. The dif-
ference in catalytic activity between these two catalysts was
also
observed
for
the
Suzuki
reactions
of
4'-bromoacetophenone, 4-bromotoluene, and 4-bromoanisole,
respectively, with phenylboronic acid (Fig. 12). This difference
indicated that although the catalytically active sites were the
same, the tether between the catalyst support and the active site
should also be taken into account. These results can be ration-
alized by that catalyst B possessed an active centre that is more
accessible to the reactants because of the more extended chain
tether as compared to the case of catalyst A [79]. Moreover,
there was a basic nitrogen atom on the tether chain of catalyst B,
and this nitrogen atom can have a positive effect on the stability
o
an additional 100 min at 100 C. Aliquots were sampled at
different time intervals and analyzed by GC. Within experi-
mental error, no further conversion was observed after the solid
catalyst was removed from the reaction mixture. This result
indicated that there was no contribution from leached palla-
dium, and that reaction was possible in the presence of the
immobilized palladium catalyst (Fig. 13). It was previously
proposed that the reaction using magnetic nanoparti-
cles-supported palladium catalysts proceeded on the catalyst
surface and dissolved palladium species did not catalyze the
reaction [51]. In other cases, it was reported that active palla-
dium species were dissolved from the solid catalyst during the
course of the reaction and partially or completely reprecipitated
onto the magnetic nanoparticles at the end of the reaction [49].
Further studies are needed to elucidate the real active species in
the Suzuki reaction using the immobilized palladium catalyst.
Another point of great concern for immobilized catalysts is
the ease of separation as well as the deactivation and reusability
of the catalyst. The catalyst should be recovered and reused
many times before it deactivates. At the same time, catalyst
recovery can also reduce environmental pollution caused by
(2)
(6)
100
80
60
40
20
0
Catalyst B
Catalyst A
(1)
(5)
(3)
(7)
(4)
(8)
0
20
40
60
Time (min)
80
100
120
Fig. 12. Comparison of catalyst A and catalyst B. (1) and (5)
4'-Bromoacetophenone; (2) and (6) 4-Bromonitrobenzene; (3) and (7)
4-Bromotoluene; (4) and (8) 4-Bromoanisole.

Nghia T. BUI et al. / Chinese Journal of Catalysis, 2011, 32: 1667–1676
100
80
(a)
100
80
60
40
20
0
60
40
0.01 mol%
Leaching test
20
0
1
2
3
4
5
6
Run
7
8
9
10 11
(b)
0
20
40
60
Time (min)
80
100
120
100
80
60
40
20
0
Fig. 13. Leaching test of the immobilized palladium catalyst.
the heavy metals used in the catalyst systems [8,9]. The im-
mobilized palladium catalyst was therefore investigated for
recoverability and reusability over eleven runs. After each run
1st run
2nd run
3rd run
4th run
o
using 0.1 mol% catalyst at 100 C for 2 h in the presence of
K3PO4, an external magnetic field was applied to the glass
reaction vessel containing the magnetic nanoparticles using a
small permanent magnet. The reaction solution was then easily
removed from the reaction vessel by decantation while the
magnet held the superparamagnetic nanoparticles inside the
vessel. The magnetic catalyst was washed with acetone, de-
ionized water, and then acetone to remove physisorbed re-
agents, dried under vacuum at room temperature overnight, and
reused in under identical conditions to the first run. It was
found that the immobilized palladium catalyst can be recovered
and reused several times without significant degradation in
catalytic activity. A conversion of 94% was still achieved in the
11th run (Fig. 14(a)). Kinetic studies indicated that the catalytic
activity of the immobilized palladium catalyst in the Suzuki
reaction decreased slightly after each use, although complete
reaction was still observed after 2 h (Fig. 14(b)). It was pre-
viously reported that no loss of activity was observed for sev-
eral reused immobilized palladium catalysts in the Suzuki
reaction, but no kinetic data was provided, and only the con-
versions at the end of the experiment were given [44,47]. Un-
fortunately, a stable activity cannot be proved by reporting only
similar reaction conversions at long times. Kinetic studies are
the true test of catalyst deactivation [34].
0
20
40
60
80
100
120
Time (min)
Fig. 14. Recycling studies of the immobilized palladium catalyst.
catalyst can be reused several times without significant deg-
radation in catalytic activity. The magnetic nanoparticles offer
advantages over conventional catalyst supports and should be
of interest to the chemical industry. Current research in our
laboratory is directed at the design and immobilization of
several catalysts on superparamagnetic nanoparticles for a
wide range of organic transformations.
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