Palladium nanoparticles supported on agarose-catalyzed Heck-Matsuda and Suzuki-Miyaura coupling reactions using aryl diazonium salts

Article abstract of DOI:10.1002/aoc.2932

In this article, palladium nanoparticles supported on agarose were used as an efficient catalyst for Heck-Matsuda and Suzuki-Miyaura coupling reactions of structurally different aryldiazonium tetrafluoroborate substrates in aqueous media. Heck-Matsuda reactions proceeded at 40°C whereas Suzuki-Miyaura reactions were carried out at room temperature. Both reactions required low catalyst loading. The catalyst was also recycled for the model reaction for three runs.

Full text of DOI:10.1002/aoc.2932

Full Paper
Received: 10 September 2012
Accepted: 10 September 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2932
Palladium nanoparticles supported on agarose-
catalyzed Heck–Matsuda and Suzuki–Miyaura
coupling reactions using aryl diazonium salts
Mohammad Gholinejad*†
In this article, palladium nanoparticles supported on agarose were used as an efficient catalyst for Heck–Matsuda and Suzuki–
Miyaura coupling reactions of structurally different aryldiazonium tetrafluoroborate substrates in aqueous media. Heck–Matsuda
reactions proceeded at 40ꢀC whereas Suzuki-Miyaura reactions were carried out at room temperature. Both reactions required
low catalyst loading. The catalyst was also recycled for the model reaction for three runs. Copyright © 2012 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: agarose; palladium; aryl diazonium salts; Heck; Suzuki
by alginate/gellan-stabilized palladium nanoparticles[16] and the
Introduction
aluminium hydroxide-supported palladium nanoparticles[17] were
Palladium-catalyzed cross-coupling reactions are recognized as
essential tools for the generation of carbon–carbon or carbon–
heteroatom bonds for the preparation of fundamental precursors
used for the synthesis of pharmaceuticals, agrochemicals etc.[1,2]
Among vast number of reactions catalyzed by palladium, the
Heck–Mizoroki reaction, which occurs between aryl or vinyl
halides and olefins,[3] and the Suzuki–Miyaura reaction, which
takes place between aryl halides and arylboronic acids, could
be considered important reactions with very wide applications.
These important reactions have placed considerable impact upon
the preparation of aryl-olefin and biaryl compounds, which are
found in the building blocks of a wide range of pharmaceuticals
and natural products.[4–6]
In many palladium-catalyzed reactions leading to carbon–carbon
and carbon–heteroatom bond formation, use of phosphane ligands
is a common practice. However, many phosphane ligands are expen-
sive, poisonous and air sensitive, with poor thermal stability.[7]
Arenediazonium salts[8] are a potential alternative to aryl halides or
triflates, which are commonly used in Heck–Mizoroki and Suzuki–
Miyaura reactions. The diazonium salts show higher reactivity and
tolerance to many different reaction conditions. Moreover, they are
easily prepared from inexpensive anilines, which makes them
suitable surrogates for the aryl halides or triflates used in these cou-
pling reactions. Using aryl diazonium salts[9] in Heck,[10] Suzuki,[11]
Sonogashira[12] and Hiyama[13] reactions has attracted attention in
recent years. The reactions can be performed in the presence of
N-heterocyclic carbene ligands, palladacycle systems or under
ligand-free conditions.[9,14] A Pd/charcoal catalytic system has been
recently used as a heterogeneous catalyst in the Heck–Matsuda cou-
pling reaction of aryl diazonium salts.
reported in the literature.
Herein we report a new catalytic application of palladium
nanoparticles supported on agarose[18] for the Heck–Matsuda
and Suzuki–Miyaura coupling reactions using aryl diazonium salts
in aqueous media.
Experimental
General
Solvents and other reagents were used either as received from com-
mercial suppliers or, when necessary, purified. Using a Bruker Avance
1
III-400 instrument, H NMR spectra were recorded at 400 MHz and
13C NMR spectra at 100 MHz. NMR acquisitions were performed at
295 K and CDCl3 was used as solvent. Chemical shifts are reported
in ppm with solvent resonance as the internal standard (1H; CHCl3:
d 7.29 ppm and 13C, d 77.0 ppm). For scanning electron microscopy
(SEM) a Philips XL-30 FEG instrument, operating at 20 kV, was used.
Inductively coupled plasma (ICP) technique (Varian, Vista-pro) was
employed for determination of the amount of palladium nanoparti-
cles supported on agarose.
*
Correspondence to: Mohammad Gholinejad, Department of Chemistry, Institute
for Advanced Studies in Basic Sciences (IASBS), PO Box 45195-1159, GavaZang,
Zanjan, Iran. E-mail: gholinejad@iasbs.ac.ir
The high surface area-to-volume ratio of noble metal nanoparti-
cles makes them highly attractive tools for catalysis. Along this line,
palladium nanoparticles have been widely used as the catalysts in
different palladium-catalyzed coupling reactions.[15] Very recently,
the Suzuki-Miyaura cross-coupling of aryl diazonium salts catalyzed
†
This paper is dedicated to my mentor Professor Habib Firouzabadi on the
occasion of his 70th birthday.
Department of Chemistry, Institute for Advanced Studies in Basic Sciences
(IASBS), GavaZang, Zanjan, Iran
Appl. Organometal. Chem. 2013, 27, 19–22
Copyright © 2012 John Wiley & Sons, Ltd.

M. Gholinejad
Gram-Scale Preparation of Palladium Nanoparticles Supported
on Agarose Hydrogel
OH
O
OH
O
A solution of the agarose (1 g) in water (100 ml) was added with stir-
ring to an acidic solution (100 ml water with pH adjusted to 4 by HCl)
of Pd(OAc)2 (0.022 g, 1 mmol) at 80ꢀC. To the solution obtained, an
aqueous solution of citric acid (4 mmol in 20 ml H2O) was added
dropwise. The mixture was refluxed for 1 h then cooled to room
temperature to produce a gray-brown mass of hydrogel. Drying of
the resulting hydrogel mass under a flow of air overnight and under
vacuum for 24 h gave a black powder of agarose-supported palla-
dium nanoparticles of size 20–30 nm.
OH
n
O
O
H
O
OH
OH
Figure 1. Agarose molecule.
and Suzuki–Myiaura coupling reactions using aryl diazonium
tetrafluoroborate instead of aryl halides with low loading of
palladium catalyst at 25–40ꢀC in more friendly solvents.
The optimized conditions for Heck–Matsuda coupling reaction
were obtained using the reaction of 4-methoxyphenyl diazonium
tetrafluoroborate (1 mmol) with ethyl acrylate (1.5 mmol) in differ-
ent solvents such as toluene, methanol–water (1:1), acetonitrile,
methanol and water, in the presence or absence of Et3N using
0.25 g agarose supported palladium nanoparticles containing
0.0026 mmol Pd as determined by ICP analysis (Table 1).
As the results in Table 1 show, H2O is the most suitable solvent for
the reaction and the addition or elimination of Et3N does not indicate
any significant effect on the yield or progress of the reaction. The
resulting optimized conditions were then applied to the reactions
of various aryl diazonium tetrafluoroborates with styrene and ethyl
acrylate (Table 2).
General Procedure for Heck–Matsuda Coupling Reaction
Aryldiazonium tetrafluoroborate (1 mmol) and alkene (1.5 mmol)
were added to a flask containing Pd catalyst (0.025 g, 0.0026
mmol% Pd as determined by ICP analysis) and water (3 ml) at
40ꢀC. The resulting mixture was stirred in air for 5 h. The reaction
mixture was then cooled to room temperature and washed with
Et2O (3 Â 5 ml) to extract the desired product. Further purification
was performed using silica gel column chromatography eluted
with n-hexane–EtOAc to yield the desired aryl alkene products
in high yield (Table 2) (See supporting information for 1H and
13C NMR of the products).
General Procedure for Suzuki–Miyaura Coupling Reaction
The results shown in Table 2 indicate that the reaction of aryl
diazonium tetrafluoroborates bearing electron-donating as well
as electron-withdrawing groups proceeded well and in excellent
isolated yields.
Aryldiazonium tetrafluoroborate (1 mmol) and arylboranic acid
(1.5 mmol) were added to a flask containing Pd catalyst (0.025 g,
0.0026 mmol% Pd) and a mixture of water–methanol (1:1, 5 ml)
at room temperature. The mixture was stirred in air for 10 h
and extracted with Et2O (3 Â 5 ml). The ethereal solution was
evaporated and the resulting residue was purified by silica gel
column chromatography eluted with n-hexane–EtOAc to obtain
the pure biphenyl products in high yield (Table 4) (See support-
ing information for 1H and 13C NMR of the products).
In continuation of this study, we have also applied the catalyst to
the Suzuki–Miyaura coupling reaction, using aryl diazonium tetra-
fluoroborate. Initially, the effect of different solvents on the reaction
of 4-methoxyphenyl diazonium tetrafluoroborate (1 mmol) with
phenylboronic acid (1.5 mmol) as a model reaction at room temper-
ature was investigated. The reaction proceeded well in the mixture of
methanol–water (1:1, 5 ml) to give the desired biphenyl compound
in an excellent isolated yield. The results of this investigation are
shown in Table 3. The optimized conditions were then applied to
structurally different substrates, with excellent yields. The results
are presented in Table 4.
Typical Procedure for Recycling of the Catalyst for the Reaction
of 4-Methoxyphenyl Diazonium Tetrafluoroborate with
Ethyl Acrylate
After completion of the reaction, the resulting mixture was
cooled to room temperature, upon which a gelatinous mass
was formed. Product and organic substrates were extracted by
Et2O (3 Â 5 ml) and the obtained dark gelatinous residue was
reused for another batch of the similar reaction. The catalyst
was recycled for three runs, giving 90%, 87% and 87% isolated
yields respectively.
Table 1. Screening of different solvents for the reaction of 4-methoxy-
phenyl diazonium tetrafluoroborate with butyl acrylate in the presence
of the catalyst
O
Agarose supported
-
N2+BF4
O
nano Pd (0.0026 mmol)
CO2Et
+
solvent (3 mL), 3 h, 40 °
MeO
C
MeO
Results and Discussion
Agarose, as an eco-friendly degradable polysaccharide and abun-
dant in nature (Fig. 1), has the potential for use as a support and
ligand for the stabilization and entrapment of palladium nano-
particles generated in its presence.[18a,b] Along this line, in our
previous studies we demonstrated the use of agarose-supported
Pd nanoparticles as an effective catalyst for Suzuki–Miyaura,[18a]
Mizoriki–Heck and Sonogashira–Hagihara[18b] coupling reactions
under green conditions.
Entry
Solvent
Isolated yield (%)
1
2
3
4
5
6
Toluene
H2O
30
85
73
25
60
86a
MeOH-H2O
CH3CN
MeOH
H2O
In this study we present another important application of the
agarose-supported Pd nanoparticles for the Heck–Matsuda
aReaction in the presence of Et3N as a base.
wileyonlinelibrary.com/journal/aoc
Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 19–22

Heck and Suzuki reactions catalyzed by Pd nanoparticles on agarose
Table 2. Reaction of different diazonium tetrafluoroborates with styrene
and butyl acrylate in the presence of the catalyst in water
Agaros supported
-
nano Pd (0.0026 mmol)
H2O, 3 h, 40 °C
R2
R1 N2+BF4
R1
+
R2
Entry
R1
R2
Isolated yield (%)
1
2
Ph
Ph
Ph
81
83
80
86
85
85
84
90
80
84
COOEt
Ph
3
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-NO2C6H4
4-CNC6H4
4-CNC6H4
4
COOEt
Ph
5
6
COOEt
Ph
7
8
COOEt
Ph
9
19
COOEt
Figure 2. SEM picture of the catalyst after the third reaction cycle (scale
bar: 1 mm).
Table 3. The effect of different solvents on the reaction of 4-methox-
yphenyl diazonium tetrafluoroborate with phenylboronic acid in the
presence of the catalyst
In order to ascertain the major role of agarose-supported palla-
dium nanoparticles as a catalyst in the Heck–Matsuda reaction,
the reaction of 4-methoxyphenyl diazonium tetrafluoroborate
with ethyl acrylate was studied in the absence of the catalyst
and also in the presence of the same amount of unsupported
bulk Pd (0.0026 mmol) using Pd(OAc)2. In the absence of catalyst,
in the appropriate reaction time, the reaction did not proceed at
all. However, in the presence of bulk palladium as the catalyst the
reaction was performed with only 15% isolated yield.
Finally, recycling of catalyst was studied for the reaction of
4-methoxyphenyl diazonium tetrafluoroborate (5 mmol) with
ethyl acrylate (7.5 mmol) using 0.125 g of the catalyst. After com-
pletion of reaction, the reaction mixture was washed with ethyl
acetate (3 Â 10 ml) and decanted. The resulting mass was reused
for another batch with a similar reaction. This process was
repeated for three consecutive runs with 90%, 87% and 87%
isolated yield respectively. The SEM picture of the recovered
catalyst after the third run did not show any observable agglom-
eration of the nanoparticles of Pd catalyst (Fig. 2).
Agarose supported
nano Pd (0.0026 mmol)
-
N2+BF4
B(OH)2
+
solvent, 10 h, r.t
MeO
MeO
Entry
Solvent
Isolated yield
1
2
3
4
5
Toluene
H2O
15
60
90
20
72
MeOH–H2O
CH3CN
MeOH
Table 4. Reaction of structurally different diazonium tetrafluoroborates
with various aryl boronic acids in the presence of catalyst
Agarose supported
nano Pd (0.0026 mmol)
-
R1-N2+BF4
R1-R2
R2B(OH)2
+
MeOH-H2O (5 mL)
10 h, r.t
Conclusion
Heck-Matsuda and Suzuki-Miyaura coupling reactions of aryl
diazonium salts were studied using Pd nanoparticles supported on
agarose at 40ꢀC by the low loading of Pd nanoparticle supported
on agarose in neat water. In the presence of this catalyst, Suzuki–
Miyaura coupling reactions were performed at room temperature
in methanol–water mixture as a solvent. This air-stable catalyst
was recycled for three consecutive runs with preservation of the
catalytic activity in a Heck–Matsuda reaction. The SEM image of
the catalyst, after the third recycle, shows preservation of the
nanoparticles of Pd in the agarose network without noticeable
particle aggregation.
Entry
R1
R2
Isolated yield (%)
1
Ph
Ph
Ph
Ph
80
83
84
88
90
90
80
90
84
87
90
83
85
2
2-Me–C6H4
4-OMe–C6H4
4-OMe–C6H4
4-Me–C6H4
Ph
3
4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-CNC6H4
4-CNC6H4
5
6
7
4-Me–C6H4
4-OMe–C6H4
4-OMe–C6H4
Ph
8
9
10
11
12
13
Acknowledgments
2-Me–C6H4
Ph
The author acknowledge IASBS for financial support. The author
is also thankful to Professor Dr Babak Karimi for providing facili-
ties and chemicals used through this study.
4-Me–C6H4
Appl. Organometal. Chem. 2013, 27, 19–22
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

M. Gholinejad
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