Green and efficient procedure for Suzuki-Miyaura and Mizoroki-Heck coupling reactions using palladium catalyst supported on phosphine functionalized ZrO2 NPs (ZrO2@ECP-Pd) as a new reusable nanocatalyst

Article abstract of DOI:10.1246/bcsj.20160163

In this article, palladium supported on phosphine functionalized ZrO₂ NPs (ZrO₂@ECP-Pd) has been introduced as a novel and efficient nanocatalyst for Suzuki-Miyaura and Mizoroki-Heck reactions. This new catalyst was prepared from the reaction of Pd(OAc)₂ and PPh₂-functionalized ZrO₂ NPs, and then characterized using FT-IR, XRD, SEM, TEM, TGA and ICP techniques. The above experimental results showed that the synthesized catalyst existed as spheres with a mean size range of 10-40 nm. The prepared ZrO₂@ECP-Pd nanocatalyst was shown to be highly efficient in the Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions of a wide range of aryl halides including electron-rich and electron-poor aryl iodides/bromides, and heteroaryl iodides, affording the corresponding products in good to excellent yields in short reaction times. The notable feature of the present protocol is the use of water and [bmim]PF₆ as environmentally benign solvents, which eliminate the need of toxic solvent. In addition to the aforementioned favorable properties, the nanocatalyst can be recovered and reused for the subsequent reactions (at least six times) without any appreciable loss of efficiency.

Full text of DOI:10.1246/bcsj.20160163

Advance Publication Cover Page
Green and Efficient Procedure for Suzuki-Miyaura and Mizoroki-Heck Coupling
Reactions Using Palladium Catalyst Supported on Phosphine Functionalized
ZrO2 NPs (ZrO2@ECP-Pd) as a New Reusable Nanocatalyst
Monireh Zarghani and Batool Akhlaghinia*
Advance Publication on the web July 6, 2016 by J-STAGE
doi:10.1246/bcsj.20160163
© 2016 The Chemical Society of Japan

Green and efficient procedure for Suzuki-Miyaura and Mizoroki-Heck coupling
reactions using palladium catalyst supported on phosphine functionalized ZrO2 NPs
(ZrO2@ECP-Pd) as a new reusable nanocatalyst
Monireh Zarghani1 and Batool Akhlaghinia1*
1Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran
Email: akhlaghinia@um.ac.ir
Abstract
In this article, palladium supported on phosphine
In this term, nanoparticles have recently generated a new
research line which can be used as alternative surface for
supporting homogeneous catalysts. Because of their large
surface area, nanoparticles have higher catalyst loading
capacity and higher dispersion than many conventional support
matrixes, leading to dramatic enhancements in the catalytic
activity of the supported catalysts.23-28 To date, many
nanoparticles have been explored to be candidates for
immobilization of Pd complexes such as carbon nanotubes,29
nanoSiO2,30 graphene nanosheets (GNS),31-32 and Fe3O4
nanoparticles.33-34 In this area, zirconia nanoparticles (ZrO2
NPs) have received a great deal of attention because of their
superior chemical, thermal and mechanical properties in a wide
range of applications such as catalysts, oxygen sensors, fuel
cells, engine parts and thermal barrier coatings on metal
surfaces. Moreover, recent studies show that ZrO2 NPs have
emerged as promising supports for immobilization metal
nanoparticles. 35-38
In addition, during the past decades, a great deal of
attention has been paid to developing greener chemical
processes and synthetic methods. To date, the reported coupling
reactions were mostly carried out in organic solvents which are
a major cause of ecological contamination.39 In order to comply
with the idea of green chemistry, one approach is to utilize
water, which is non-toxic, cheap and inflammable instead of
toxic and expensive organic solvent.40 However, several
examples of palladium catalyzed coupling reactions in aqueous
media have been reported, but many substrates of these
reactions have poor solubility in water, and solubility is
generally considered as a prerequisite for reactivity. A way to
overcome this difficulty would be the use of ionic liquids (ILs),
which are known as ecofriendly, reusable and alternative
reaction media in organic synthesis. Among the various
solvents, ILs show several advantages which make them more
attractive and ecologically acceptable such as non-volatility,
wide liquid range, high thermal stability, low toxicity, good
solubility, reusability, and incombustibility. 41
functionalized ZrO2 NPs (ZrO2@ECP-Pd) has been introduced
as a novel and efficient nanocatalyst for Suzuki-Miyaura and
Mizoroki-Heck reactions. This new catalyst was prepared from
the reaction of Pd(OAc)2 and PPh2-functionalized ZrO2 NPs,
and then characterized using FT-IR, XRD, SEM, TEM, TGA
and ICP techniques. The above-experimental results showed
that the synthesized catalyst existed as spheres with a mean size
range of 10-40 nm. The prepared ZrO2@ECP-Pd nanocatalyst
was shown to be highly efficient in the Suzuki-Miyaura and
Mizoroki-Heck cross-coupling reactions of a wide range of aryl
halides including electron-rich and electron-poor aryl
iodides/bromides, and heteroaryl iodides, affording the
corresponding products in good to excellent yields in short
reaction times. The notable feature of the present protocol is
that use of water and [bmim]PF6 as environmentally benign
solvents, which eliminate the need of toxic solvent. In addition
to the aforementioned favorable properties, the nanocatalyst
can be recovered and reused for the subsequent reactions (at
least six times) without any appreciable loss of efficiency.
1. Introduction
Formation of carbon–carbon bond is one of the most
essential transformations in synthetic chemistry and industrial
processes.1-4 In this regard, many transition metals have been
recognized as powerful and versatile catalysts for this reaction.
5,6
In this among, palladium, which is one of the valuable
transition metal, is widely employed as an efficient catalyst for
the cross-coupling reactions such as the Mizoroki-Heck and
Suzuki-Miyaura reactions. Up to now, various palladium
catalytic systems have been developed for these couplings
including homogeneous and heterogeneous catalysts.7-10
Although, homogeneous palladium catalyst provides excellent
activity and selectivity but suffer from the problems such as
separating the catalyst from the reaction mixture, catalyst
recycling and the contamination of the ligand residue in the
final products.11 Considering these facts, there are numerous
efforts on the heterogenization of palladium complexes on
different supports, which is a promising way to solve some of
Based on this background, and in continuation of our
efforts in designing novel and efficient heterogeneous catalysts,
42-51
herein, we would like to report synthesis and
characterization of a novel palladium catalyst supported on
phosphine functionalized ZrO2 NPs and its application in the
Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions.
According to the urgent need for more environmentally
responsible chemistry, green solvents such as water and
the technical application problems associated with
12-20
homogeneous system.
The key features of the
heterogeneous Pd complex including easy separation and facile
recycling catalyst. However, one of the great drawbacks of such
catalysis is that the resulting immobilized catalysts often
display much lower catalytic efficiency than their
homogeneous counterparts. Therefore, in the last years many
different studies have been performed looking for obtaining
better catalytic activity for this type of catalyst. 21-22
1-butyl-3-methylimidazolium
hexafluorophosphate
([bmim]PF6) were employed instead of the most commonly
used toxic solvents in Suzuki-Miyaura and Mizoroki-Heck
reactions, respectively. Results showed that the new catalyst
can provide excellent reactivity in the coupling reactions under
environmentally friendly conditions (Scheme 1).
1

Scheme 1 Preparation steps of ZrO2@ECP-Pd nanocatalyst.
2. Experimental
citric acid (0.126 mol, 24.207 g) and ethylene glycol (0.126
mol, 7.045 mL) were added at room temperature. The resulting
solution was stirred at 80⁰C for 30 min and then refluxed for
12h until a white sol was obtained. In order to increase
polymerization between citric acid, ethylene glycol and
ZrOCl2.8H2O, the reaction mixture was cooled down and then
slowly heated at 80 ⁰C for 10 h in an open bath. After that the
sol became more viscous as a wet gel. Finally, the wet gel was
dried by direct heating on the hot plate at 120 ⁰C for 8 h to
afford brown powder. The brown powder was calcined at 750
⁰C for 4h at a rate of 4 ⁰C min to give ZrO2 NPs as a white
powder. 52
2.1 General. The purity determinations of the products
were accomplished by TLC on silica gel polygram STL G/UV
254 plates. The melting points of products were determined
with an Electrothermal Type 9100 melting point apparatus. The
FTIR spectra were recorded on pressed KBr pellets using
AVATAR 370 FT-IR spectrometer (Therma Nicolet
spectrometer, USA) at room temperature in the range between
4000 and 400 cm−1 with a resolution of 4 cm−1. The NMR
spectra were provided on Brucker Avance 300, 400 and 500
MHz instruments in DMSO-d6 and CDCl3. Mass spectra were
recorded with a CH7A Varianmat Bremem instrument at 70 eV
electron impact ionization, in m/z (rel %). TGA analysis was
performed using a Shimadzu Thermogavimetric Analyzer
(TG-50) in the temperature range of 25-800 ºC at a heating rate
of 10 ºC /min under air atmosphere. SEM images were
recorded using Leo 1450 VP (LEO, Germany) scanning
electron microscope operating at an acceleration voltage 20 kV,
resolution of about 2 nm. Transmission electron microscopy
(TEM) was performed with a Leo 912 AB microscope (Zeiss,
Germany) with an accelerating voltage of 120 kV. The crystal
structure of catalyst was analyzed by XRD using a D8
ADVANCE –Bruker diffractometer operated at 40 kV and 30
mA utilizing CuKα radiation (λ= 0.154 Aº). Inductively
coupled plasma (ICP) analysis was carried out with a Varian
VISTA-PRO, CCD (Australia). All yields refer to isolated
products after purification by thin layer chromatography. In
addition, all of the products were known compounds and they
2.3 Surface coating of ZrO2 NPs by epichrorohydrin
(ZrO2@EP NPs). ZrO2 NPs powder (2 g) was suspended to
o
pure epichrorohydrin (10 mL) at 60 C with vigorous stirring.
After 24 h the resulting suspension was cooled to room
temperature and centrifuged. The white precipitate was washed
with methanol (4×15) until removing additional amount of
epichlorohydrin. The epoxy modified ZrO2 NPs were then
dried at 100 oC under vacuum for 8 h. 42
2.4 Surface modification of ZrO2@Ep by cyanuric
acid (ZrO2@Ep-Cy NPs). Cyanuric acid (4 g, 0.031 mol) was
added portion by portion to a suspension of the synthetic
ZrO2@Ep NPs (1g) in DMF (20 mL). The mixture was stirred
o
at 120 C. After 12h the resulting ZrO2@Ep-Cy product was
collected by centrifuge, and washed with deionized water for
three times and dried under vacuum at 50 °C for 12h. 53
2.5 Synthesis of phosphine-functionalized ZrO2 NPs
(ZrO2@ECP NPs). To a magnetically stirred mixture of
ZrO2@Ep-Cy NPs (1 g), Et3N (3 mL) in dry toluene (20 mL), 5
mL of chlorodiphenylphosphine was added drop by drop at
room temperature. The above suspension was then stirred for
16 h at room temperature under the protection of N2
1
were characterized by H NMR, 13C NMR spectroscopy, and
mass spectrometry and comparison of their melting points with
known compounds (see supporting information).
2.2 Synthesis of ZrO2 NPs. To
ZrOCl2.8H2O (0.003 mol, 0.966 g) in 50 mL distilled water,
a solution of
2

atmosphere. The final product (phosphine-functionalized
ZrO2@ECP NPs), was separated by centrifuge and washed with
ethanol (5×10) to remove excess chlorodiphenylphosphine and
then dried at room temperature. 54
2.6 Synthesis of ZrO2@ECP-Pd nanocatalyst.
ZrO2@ECP-Pd was prepared by mixing the ZrO2@ECP NPs (1
g) and Pd(OAc)2 (0.34 mmol, 0.076 g) in ethanol (30 mL) and
refluxed in 100 mL flask with stirring. After 12 h the mixture
was cooled and the solid catalyst was separated by centrifuge
from the reaction medium. Then the collected precipitate
(ZrO2@ECP-Pd) was washed several times by ethanol before
being dried under vacuo at 50 ˚C overnight. The preparation
process was illustrated in Scheme 1.
2.7 Typical procedure for the Suzuki-Miyaura reaction.
In a typical procedure, iodobenzene (1.0 mmol, 0.203 g),
phenylboronic acid (1.2 mmol, 0.146 g), potassium carbonate
(1.5 mmol, 0.207 g), ZrO2@ECP-Pd nanocatalyst (0.31 mol %,
0.005 g), and water (3 mL) were allowed to react at 90 C.
Upon the completion of the reaction which monitored by TLC,
the reaction mixture was cooled to room temperature and the
catalyst was separated by centrifuge. The resulting solution was
extracted with ethyl acetate (3 × 10 mL). The organic layers
was combined, dried with sodium sulfate, and filtered. The
filtrate was concentrated by vacuum and purified by thin layer
chromatography using n-hexane/ethyl acetate (50/1) to afford
the pure product (0.150 g, % 98 yield).
Figure 1. FT-IR spectrum of (a) ZrO2 NPs (b) ZrO2@Ep NPs
(c) ZrO2@Ep-Cy NPs (d) ZrO2@ECP NPs (e) ZrO2@ECP-Pd
nanocatalyst (f) reused ZrO2@ECP-Pd nanocatalyst.
O group in ZrO2 NPs.36 In the case of the functionalized ZrO2
NPs by epichlorohydrin (Figure 1b), the characteristic
absorption bands at 2943 and 2877 cm−1 can be observed,
which corresponded to the stretching vibration of –CH2
groups.42 From the presence of these bands it can be inferred
that the ZrO2 NPs were modified by epoxy groups successfully.
From the FT-IR spectra presented in Figure 1c,
corresponding to the modification ZrO2 NPs with cyanuric acid,
the intensities of -OH stretching frequencies (3624-3251 cm−1)
were increased smoothly by reaction with cyanuric acid.
Successful functionalization of the ZrO2 NPs with cyanuric
acid was also evidenced by the absorption bands at 1730, 1610
and 1580 cm−1, attributed to the C=N vibration of cyanuric acid
ring.56 Surface treatment of these modified nanoparticles with
chlorodiphenylphosphine leads to the formation of
phosphinterminated zirconium nanostructures (Figure 1d). The
presence of phosphine ligand on the surface of ZrO2 NPs can
be seen by absorption band positioned at 1045 cm−1, which
corresponding to the P-O stretching bond. 57
2.8 Typical procedure for the Mizoroki-Heck reaction.
In a typical procedure, iodobenzene (1.0 mmol, 0.203 g),
methyl acrylate (1.2 mmol, 0.108 mL), potassium carbonate
(1.5 mmol, 0.207 g), ZrO2@ECP-Pd nanocatalyst (0.31 mol %,
0.005 g), and [bmim]PF6 (1g, 3.5 mmol) were allowed to react
at 100 C. Upon the completion of the reaction which
monitored by TLC, the reaction mixture was cooled to room
temperature and the catalyst was separated by centrifuge.
n-Hexane (5 ml) was added to the reaction mixture and
55
extraction was done for 15 minutes with vigorous stirring.
The organic layer was combined and concentrated under
reduced pressure to give the crude product. The final product
was purified by thin layer chromatography using
n-hexane/ethyl acetate (50/1) to afford the pure product (0.153
g, % 95 yield).
3. Results and Discussion
3.1 Characterization of catalyst. The palladium catalyst
supported on phosphine functionalized ZrO2 NPs as a new
reusable nanocatalyst was prepared via multiple steps as shown
in Scheme 1. The first step was to prepare ZrO2 NPs according
to the procedure presented in the literature.52 In the second step,
the obtained ZrO2 NPs were subsequently reacted with
epichlorohydrin. The modified ZrO2 NPs were then sequential
treated by cyanuric acid and chlorodiphenylphosphine to form
ZrO2@ECP. Finally, Pd particles were immobilized on the
ZrO2@ECP through the reaction of ZrO2@ECP with Pd(OAc)2
salt in ethanol under reflux condition. The synthesized
nanocatalyst was well characterized for its physicochemical
properties using analytical techniques such as Fourier transform
infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD),
scanning electron microscopy (SEM), transmission electron
microscopy (TEM), thermogravimetric analysis (TGA) and
inductively coupled plasma (ICP).
However, the FT-IR spectrum of the synthesized
nanocatalyst demonstrates that almost no change occurs after
immobilization of palladium on the ZrO2@ECP surface (Figure
1e), but it was clearly depicted in the XRD pattern of
ZrO2@ECP-Pd nanocatalyst. 58
Unambiguous evidence of palladium particles on
ZrO2@ECP is provided via X-ray powder diffraction analysis
(XRD). The XRD patterns are shown in Figure 2. According to
the reference JCPDS (card No. 37-1484 and 79-1771), mixture
phases of monoclinic and tetragonal were observed in the ZrO2
NPs and ZrO2@ECP-Pd structures.59 Moreover, as can be seen
from this figure, both standard patterns display the same
distinctive signals in the range 10° to 70° (2), indicating that
the crystalline structure of the ZrO2 NPs is essentially
maintained. The only difference between the patterns of ZrO2
NPs and ZrO2@ECP-Pd is two weak peaks appeared at 2θ =
40.1 and 46.5 which could be related to the palladium.60 The Pd
peaks of ZrO2@ECP-Pd nanoparticles agree well with the
standard Pd (cubic phase) XRD spectrum (card No. 05-0681).
According to the XRD pattern of ZrO2@ECP-Pd, the intensity
of the new peaks attesting the presence of Pd is weak which
The FT-IR spectrum of unmodified ZrO2 NPs (Figure 1a)
shows a broad band around 3450-3200 cm-1, indicative of the
presence of –OH groups on the nanoparticle surface. Also, as
shown in Figure1a, the strong absorption bands at 751 and 507
cm−1 have been assigned to the stretching vibrations of the Zr–
3

may be attributed to the good dispersion of Pd nanoparticles in
the catalysis matrix (see TEM images (Figure 3c and 3d)). So,
Pd nanoparticles cannot lead to the formation of regular crystal
lattice. The obtained result from XRD analysis revealed that Pd
particles have been successfully immobilized onto the surface
of the modified ZrO2 NPs and the peak positions of the
synthesized nanoparticles were unchanged.
To clarify the size and morphology of synthesized
nanocatalyst, we used scanning electron microscopy (SEM) as
well as transmission electron microscopy (TEM) techniques.
The SEM images of the surface of ZrO2@ECP-Pd nanocatalyst
are shown in Figure 3a and 3b. However size of the
ZrO2@ECP-Pd particles are not clearly defined in the SEM
images obtained in the present investigation. But it is evident
from these images that the synthesized nanocatalyst is
composed of similar spherical particles.38 In order to further
examine the morphological feature, TEM image was recorded
for the ZrO2@ECP-Pd nanocatalyst. The typical TEM
micrographs for the ZrO2@ECP-Pd nanocatalyst were shown
in Figure 3c and 3d. The particles with nearly spherical
morphology with size in the range of 10– 40 nm were
successfully prepared as shown in the figure. Moreover, the Pd
nanoparticles were found to be highly dispersed on the surface
of the ZrO2@ECP nanoparticles with the average diameter size
of ~5nm.
Figure 2. The XRD patterns of (a) ZrO2 NPs and (b)
ZrO2@ECP-Pd nanocatalyst.
The successful modified ZrO2 NPs by organic ligands
could also be confirmed by TGA analysis. As shown in Figure
4, the TGA thermogram of the ZrO2@ECP-Pd nanocatalyst
shows a weight loss of 5.45 % below 150 °C, which is due to
the loss of the adsorbed water in the sample. Another large
weight loss was observed in the temperature range of 150-650
⁰C (18.85 %), resulting from the decomposition of organic
functional groups grafted to the zirconium surface. Additionally,
the exact loading of Pd on the modified zirconium
nanoparticles was determined to be 0.62 × 10-3 mol/g based on
the inductively coupled plasma (ICP) analysis. The TGA
thermogram and ICP analysis also proved the successful
supporting of the Pd and organic ligands onto the catalyst
surface.
3.2 Catalytic performance of the ZrO2@ECP-Pd
nanocatalyst for the Suzuki-Miyaura reaction. To evaluate
the merit of application of this catalytic system in organic
synthesis, we applied it in the Suzuki-Miyaura and
Mizoroki-Heck cross-coupling reactions. The Suzuki-Miyaura
cross-coupling, the reaction between boronic acid derivatives
and aryl halides, is one of the most powerful and widely
preferred reactions for synthesis of biaryls. Substituted biaryl
compounds have considerable application for the synthesis of
biologically active substances such as pharmaceuticals and
herbicides.61-62 Now in this stage, the applicability of the
ZrO2@ECP-Pd as a novel nanocatalyst was evaluated in the
Suzuki-Miyaura cross-coupling reaction (Scheme 2).
Figure 3. (a and b) SEM images of ZrO2@ECP-Pd
nanocatalyst, (c and d) TEM images of ZrO2@ECP-Pd
nanocatalyst.
Scheme 2 Suzuki-Miyaura coupling reaction in the presence of
ZrO2@ECP-Pd nanocatalyst.
Figure 4. The TGA thermogram of ZrO2@ECP-Pd.
4

Table 1 The Suzuki-Miyaura reaction of iodobenzene with phenylboronic acide in the presence of ZrO2@ECP-Pd nanocatalyst under
different reaction conditions.
Entry
Catalyst
(mol%)
Molar ratios of
Iodobenzene / Base
Base
Temperature
Time
(min)
Isolated Yield (%)
98
(˚C)
1
0.31
1:2
K2CO3
100
15
2
3
4
5
6
7
8
9
10
11
0.15
0.31
0.31
0.31
0.31
0.31
0.31
0.31
0.31
0.31
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:1.5
1:1
K2CO3
K2CO3
K2CO3
Na2CO3
KHCO3
100
90
80
90
90
90
90
90
90
90
30
15
25
15
15
30
30
15
15
15
94
98
90
94
90
55
80
87
98
70
NaOAc
Et3N
Diisopropylethylamine
K2CO3
K2CO3
performance is excellent for a wide variety of aryl iodides,
and provided the corresponding products in high yields
(Table 2, entries 1-7). It is noteworthy that coupling reactions
of aryl iodides with electron-donating substituents proceeded
more slowly than coupling reactions of aryl iodides with
electron-withdrawing substituents (compare entries 2 and 3
with 4 and 5). In addition, 1-iodo-2-methyl-4-nitrobenzene
results the desired product in longer reaction time due to
steric effect and electron donation of –Me substitution at
ortho position (Table 2, entry 6). Heteroaryl iodide such as
2-iodothiophene was also good partner for this coupling
reaction (Table 2, entry 7). To investigate the role of
substituents on the phenylboronic acid, two reactions were
carried out using 3-nitrophenylboronic acid and gave desired
products in high yield after 20 and 30 min, respectively
(Table 2, entries 8 and 9). To expand the scope of this
methodology, a series of aryl bromides were employed to
react with phenylboronic acid under the optimized conditions
(Table 2, entries 10-16). Various functional groups including
4-Cl, 4-NO2, 4-CHO, 3-CHO, 4-CN, were well tolerated
under the standard conditions, and the desired products were
obtained in high yields. Also, when electron-rich aryl
bromide such as 1-bromo-4-methoxybenzene was explored,
the reaction proceeded more slowly with lower yield of the
product (Table 2, entry 16). Moreover, aryl chloride such as
chlorobenzene was chosen as the challenging substrate,
however, the catalytic system was less effective, even after
prolonged reaction time, which might be ascribed to the
strong strength of the C–Cl bond, whose bond dissociation
energy was 96 kcal/mol.
For initial assessment of the reaction, we examined the
Suzuki-Miyaura coupling reaction of the model substrate
iodobenzene with phenylboronic acid using ZrO2@ECP-Pd
nanocatalyst at 100 oC. Additionally, by considering the
principles of green chemistry, we tried to carry out this
reaction in water, which has economic and environmental
advantages. As it can be seen in Table 1, using of 0.31 mol%
(0.005 g catalyst contains 0.029 mg (0.0031 mmol) of Pd) of
ZrO2@ECP-Pd nanocatalyst in water afforded excellent yield
of product in short reaction time (15 min) (Table 1, entry 1).
The yield of the desired product did not exceed 94 %, when
the model reaction was performed using 0.15 mol % of
ZrO2@ECP-Pd nanocatalyst (Table 1, entry 2). Effect of
temperature on the activity of ZrO2@ECP-Pd nanocatalyst
was also studied. Lowering the temperature to 90 oC was
found to have no effect on the yield (98%) of cross-coupling
product (Table 1, entry 3). Further reducing the temperature
to 80 oC was accompanied by a considerable drop of yield by
90 % with longer reaction time (Table 1, entry 4). As it is
known, base plays crucial role for the yield of the
cross-coupling reaction, therefore, we examined the effect of
different organic and inorganic bases on the model reaction
(Table 1, entries 5-9). Slightly lower yields were obtained
with the other inorganic bases such as Na2CO3, KHCO3
(94 % and 93 %) (Table 1, entries 5 and 6). Meanwhile, for
the reaction in the presence of organic bases, the desired
product was obtained in low yield under other identical
reaction conditions (Table 1, entries 7, 8, 9). Thus, from the
bases screened, K2CO3 was found to be the best base giving
maximum yields of the desired product (Table 1, entry 3).
Finally, different molar ratios of iodobenzene / K2CO3 (1 :
1.5 and 1 : 1) (Table 1, entries 10, 11) were tried and it was
observed that decrease in molar ratio from 1 : 2 to 1 : 1.5 has
no significant effect on the yield as well as reaction time
(Table 1, entries 3, 10). But by reducing the molar ratio from
1 : 1.5 to 1 : 1, the yield of product decreased from 98 % to
70 % (Table 1, entry 11). According to the optimization
results and the essential goal of green chemistry, the best
result is obtained by using 1 : 1.5 molar ratio of iodobenzene
/ K2CO3 at 90 oC, in the presence of catalytic amount of
ZrO2@ECP-Pd nanocatalyst (0.31 mol %) and H2O as a
green solvent (Table 1, entry 10).
3.3 Catalytic performance of the ZrO2@ECP-Pd
nanocatalyst for the Mizoroki-Heck reaction. The
Mizoroki-Heck cross-coupling reaction, as
a powerful
synthetic tool for the formation of C-C bonds in organic
synthesis, has been shown to have widespread application in
the synthesis of natural products,63-64 agrochemicals,65 and
pharmaceuticals.66 This reaction usually involves the
interaction of an aromatic halide with an alkene, in the
presence of a palladium catalyst, to give an aryl alkene. So,
encouraged by the exciting results with the Suzuki-Miyaura
reactions, and to further evaluate the overall utility of the
current methodology, the ZrO2@ECP-Pd nanocatalyst was
applied to the Mizoroki-Heck reaction (Scheme 3).
Under these optimum conditions, we next explored the
generality and scope of the protocol using several substituted
aryl halides and phenylboronic acids. The results are
displayed in Table 2. As it is shown in Table 2, the catalytic
5

Table 2 Suzuki-Miyaura cross-coupling reactions of arylboronic acids and aryl halides catalyzed by ZrO2@ECP-Pd nanocatalyst.
Entry
1
2
3
4
5
6
7
8
R1
H
4-Cl
4-NO2
4-Me
R2
H
H
H
H
H
H
H
3-NO2
3-NO2
H
H
H
H
H
H
H
X
I
I
I
I
I
I
I
I
Product
3a
3b
3c
3d
3e
3f
3g
3h
3i
3a
3b
3c
Time (min)
Isolated Yield (%)
15
20
15
20
30
30
30
20
30
60
60
45
45
60
45
120
98
95
98
94
90
80
90
90
85
90
92
95
90
90
94
75
4-OMe
2-Me-4-NO2
2-Thiophene
H
4-OMe
H
9
I
10
11
12
13
14
15
16
Br
Br
Br
Br
Br
Br
Br
4-Cl
4-NO2
4-CHO
3-CHO
4-CN
3j
3k
3l
4-OMe
3e
catalyst did not improve the results to any great extent,
whereas, applying 0.15 mol% of catalyst led to lower
reaction yield (80%) (Table 3, entries 9 and 10). The overall
finding, based on the results given in Table 2, is that the
highest catalytic activity is achieved when the
Mizoroki-Heck reaction is carried out using 0.31 mol% of
ZrO2@ECP-Pd
nanocatalyst
in
[bmim]PF6
as
environmentally benign solvent at 100 oC (Table 2,entry 6).
With the optimum reaction conditions in hand, in the next
step, various substituted aryl halides and olefins were
examined to explore the scope and efficiency of this
approach. The representative results are summarized in Table
4. Generally, all of the coupling products were obtained in
good to excellent yields (70-98 %) during 20-180 min (Table
4, entries 1-20). In comparison, the coupling reactions of aryl
bromides result the desired products in longer reaction times
than the reactions of aryl iodides, due to the different
dissociation energies of the C–Br and C–I bonds (81 and 65
kcal mol −1, respectively)69 (Table 3, compare entries 1-5 with
7-11). It is worth to note that, when 2-iodothiophene was
used as coupling partner, 85% yield was obtained for
(E)-methyl 3-(thiophen-2-yl)acrylate (5f), although longer
reaction time (60 min) was required (Table 4, entry 6). This
catalytic system was also applicable to the cross-coupling of
n-butyl acrylate (Table 4, entries 12-20). Similarly, n-butyl
acrylate was found to be extremely reactive substrate
affording the relative product rapidly in the presence of
ZrO2@ECP-Pd nanocatalyst (Table 4, entries 12-17).
Meanwhile, with aryl bromides containing both electron
withdrawing and electron donating groups, the reactions
proceeded more slowly with lower yields of the desired
products (Table 4, entries 18-20).
Scheme 3 Mizoroki-Heck coupling reaction in the presence
of ZrO2@ECP-Pd nanocatalyst.
In order to find suitable conditions for the
Mizoroki-Heck reaction using the ZrO2@ECP-Pd
nanocatalyst, the reaction between iodobenzene and methyl
acrylate was used as
a model reaction and different
conditions were investigated (Table 3). According to Table 3,
when the model reaction was performed using 0.31 mol % of
ZrO2@ECP-Pd nanocatalyst in DMF at 90 oC, the desired
product was isolated in 90 % yield (Table 1, entry 1). In an
effort to perform coupling reaction in more eco-friendly
reaction media, various solvents such as CH3CN, H2O, EtOH
were screened and found that these solvents are not suitable
for the reaction (Table 3, entries 2- 4). Based on the literature,
it was established that ionic liquids are a candidate for using
as green solvents for Mizoroki-Heck reactions,55, 67-68 so, we
tested 1-butyl-3- methylimidazolium hexafluorophosphate
([bmim]PF6) as solvent for the reaction. The result showed
that the corresponding coupling product was obtained in
90 % yield, although longer reaction times were required
(Table 3, entry 5). For further improvement of the reaction
rate and yield, the coupling reaction was carried out using
higher temperature (100 oC). Pleasingly, this resulted in
excellent yield of the corresponding product within 30 min
(Table 1, entry 6). As illustrated in Table 3 (entries 7 and 8),
in the reactions employing K2CO3, and NaOAc as the bases,
the coupling reactions did not progress efficiently. In addition,
the amount of ZrO2@ECP-Pd nanocatalyst was optimized
using different amounts (0.40 mol% and 0.15 mol%) of the
catalyst. It was found that an increase in the amount of
Under the same reaction conditions, we examined
chlorobenzene for the Mizoroki-Heck reaction. It was
observed that the poor yield of product was obtained in
prolonged reaction time.
According to the results shown in Table 4, the
generality of this protocol using the synthesized catalytic
system is confirmed and good to excellent yields are obtained
in the presence of ZrO2@ECP-Pd nanocatalyst.
6

Table 3 The Mizoroki-Heck coupling reaction of iodobenzene with methyl acrylate in the presence of ZrO2@ECP-Pd nanocatalyst
under different reaction conditions.
Entry
1
2
3
4
5
6
7
8
Catalyst (mol %)
Solvent
DMF
CH3CN
H2O
EtOH
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
Base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
NaOAc
K2CO3
Et3N
Temperature (˚C)
Time (min)
30
Isolated Yield (%)
0.31
0.31
0.31
0.31
0.31
0.31
0.31
0.31
0.40
0.15
90
90
90
90
90
100
100
100
100
100
90
60
50
75
90
95
80
50
95
80
1(h)
3 (h)
1 (h)
1 (h)
30
1 (h)
1 (h)
30
9
10
Et3N
30
Table 4 The Mizoroki-Heck cross-coupling reactions of olefins and aryl halides catalyzed by ZrO2@ECP-Pd nanocatalyst.
Entry
R1
R2
X
Product
Time (min)
Isolated Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
H
4-Cl
4-NO2
4-Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Bun
Bun
Bun
Bun
Bun
Bun
Bun
Bun
Bun
I
I
I
I
I
5a
5b
5c
5d
5e
5f
5a
5c
5b
5g
5e
5h
5i
5j
5k
5l
5m
5h
5i
30
30
30
30
30
95
98
95
95
92
85
80
92
94
85
85
95
96
94
90
95
80
75
80
70
4-OMe
2-Thiophene
H
4-NO2
4-Cl
4-CN
4-OMe
H
4-NO2
4-Cl
4-OMe
4-Me
2-Thiophene
H
4-NO2
4-OMe
I
60
Br
Br
Br
Br
Br
I
I
I
I
I
180
180
180
180
180
30
30
30
45
40
I
120
180
180
180
Br
Br
Br
5k
use of Hg(0). The mercury poisoning test with Hg(0) is based
on the deactivation of colloidal metal via amalgam formation,
and, this test in general does not attack molecular metal
species. In our study we also found that ZrO2@ECP-Pd
nanocatalyst (0.31 mol %) maintains its activity in the Suzuki
coupling of iodobenzene with phenylboronic acid in the
presence of a large excess of Hg(0) (Hg/Pd, 300:1) under the
optimized reaction conditions, affording the corresponding
biphenyl in excellent conversion.70
3.4 Heterogeneity Tests
To determine whether the catalyst is actually
functioning in a heterogeneous manner, a hot-filtration test
was performed in the Suzuki-Miyaura coupling reaction of
iodobenzene with phenylboronic acid. After 30 % conversion
to product (5 min), the solid catalyst was separated from the
reaction mixture by filtration. The reaction was carried out
for a further 1h. No increase in the amount of product was
observed, as determined by thin layer chromatography. In a
separated test, a hot-filtration test was performed in the
Mizoroki-Heck coupling reaction of iodobenzene with
methyl acrylate. The same result was obtained from this
reaction. So, it can be concluded that no leaching of
palladium takes place during the reaction and that the catalyst
is purely heterogeneous in nature.
3.5 Recycling of the ZrO2@ECP-Pd nanocatalyst
As Pd salts are expensive and also some of them are
toxic, their leaching into the reaction mixture could be a
serious worry in viewpoint of green chemistry. In this regard,
catalyst immobilization is a good opportunity to obtain
materials that can be recovered and reused for several cycles
with low leaching. We therefore turned attention to this
feature of the present Pd nanocatalyst and examined the
In addition, one of the most common poisoning test to
distinguish heterogeneous vs. homogeneous catalysts is the
7

possibility of recycling of nanocatalyst in the reaction of
iodobenzene with phenylboronic acid under the optimized
reaction conditions (Figure 5). In a typical experiment, after
completion of the reaction, the coupled product was
repeatedly extracted from the reaction mixture with ethyl
acetate. The ZrO2@ECP-Pd nanocatalyst was recovered by
centrifuge, washed with water (10 mL) and ethyl acetate (3×5
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71
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Figure 5. The Suzuki-Miyaura reaction of iodobenzene with
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4. Conclusion
Suzuki-Miyaura and Mizoroki-Heck reactions using
palladium immobilized on phosphine functionalized ZrO2
NPs (ZrO2@ECP-Pd). As a novel heterogeneous catalyst,
ZrO2@ECP-Pd was prepared and characterized by FT-IR,
XRD, SEM, TEM, TGA and ICP techniques. It was found
that ZrO2@ECP-Pd nanocatalyst with spherical shape and
mean diameters of 10–40 nm was successfully synthesized.
Then synthesized nanocatalyst has been used as an efficient
catalyst for the Suzuki-Miyaura and Mizoroki-Heck reactions
of various aryl halide derivatives (aryl iodides/bromides)
under benign reaction conditions. Excellent yields of product,
short reaction times, elimination of dangerous and harmful
solvents, mild reaction conditions, simple workup procedures,
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and valuable features of this methodology.
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Acknowledgement
The authors gratefully acknowledge the partial support
of this study by Ferdowsi University of Mashhad Research
Council (Grant no. p/3/29760).
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9

Graphical Abstract
Green and efficient procedure for Suzuki-Miyaura and Mizoroki-Heck coupling reactions using palladium
catalyst supported on phosphine functionalized ZrO2 NPs (ZrO2@ECP-Pd) as a new reusable nanocatalyst
Monireh Zarghani and Batool Akhlaghinia *
New palladium catalyst supported on phosphine functionalized ZrO2 NPs (ZrO2@ECP-Pd) was synthesized and
characterized. ZrO2@ECP-Pd exhibited efficient catalytic activity in the Suzuki-Miyaura and Mizoroki-Heck coss-
coupling reactions under benign reaction conditions. Additionally, the synthesized nanocatalyst can be recovered and
reused for the subsequent reactions (at least six times) without any appreciable loss of efficiency.
Pd
Pd
Ar'-B(OH)
Ar-X
Ar-X
+
+
2
Ph2P
O
N
R
PPh2
N
O
ZrO2
Cat.
[bmim]PF6
O
Cat.
H2O
N
R
O
Pd
PPh2
Ar
Ar-Ar'
16 examples
75-98 %
20 examples
70-98 %
Cat.: ZrO2@ECP-Pd