Carbon-carbon bond formation via homocoupling reaction of substrates with a broad diversity in water using Pd(OAc)2 and agarose hydrogel as a bioorganic ligand, support and reductant

Article abstract of DOI:10.1016/j.molcata.2011.08.010

In this study, we have presented a new catalytic system in which Pd(OAc)₂ has been used as a pre-catalyst and agarose as a degradable bioorganic ligand, support and reductant for carbon-carbon bond formation via homocoupling reaction of different aryl halides, β-bromo styrene, phenylboronic acid and phenylacetylene as the substrates. The reactions proceeded smoothly with high yields at temperature <100 °C in water without using any organic co-solvent, phosphorus ligand or reducing agents. The catalyst is recyclable and has been recycled for four times with a tiny amount of leaching of Pd into the reaction media. The amount of leaching has been determined by ICP analysis.

Full text of DOI:10.1016/j.molcata.2011.08.010

Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Carbon–carbon bond formation via homocoupling reaction of substrates with a
broad diversity in water using Pd(OAc)2 and agarose hydrogel as a bioorganic
ligand, support and reductant
Habib Firouzabadi∗, Nasser Iranpoor∗, Faezeh Kazemi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 June 2011
Received in revised form 18 July 2011
Accepted 15 August 2011
Available online 22 August 2011
In this study, we have presented a new catalytic system in which Pd(OAc)2 has been used as a pre-
catalyst and agarose as a degradable bioorganic ligand, support and reductant for carbon–carbon bond
formation via homocoupling reaction of different aryl halides, ˇ-bromo styrene, phenylboronic acid and
phenylacetylene as the substrates. The reactions proceeded smoothly with high yields at temperature
<100 ◦C in water without using any organic co-solvent, phosphorus ligand or reducing agents. The catalyst
is recyclable and has been recycled for four times with a tiny amount of leaching of Pd into the reaction
media. The amount of leaching has been determined by ICP analysis.
Keywords:
Aryl halide
Homocoupling
Agarose hydrogel
Palladium
© 2011 Elsevier B.V. All rights reserved.
Water
1. Introduction
of aqueous solvent for this function has received less attention.
Since most of the phosphine ligands used for the reaction are
In recent years, palladium catalyzed reductive homocoupling
reaction of aryl halides has been of great interest for the syn-
thesis of agrochemicals and natural products [1–4]. This reaction
was first reported by Ullmann over a century ago [5]. Most of the
traditional methods suffer from both high temperatures >200 ◦C
and using stoichiometric amounts of copper salts [6]. As time goes
on, many procedures have been reported for avoiding the drastic
reaction conditions [7–9]. In recent years for this purpose, uti-
lizing other transition metals such as palladium [10–12], barium
[13], indium [14], zinc [15], gold [16] and nickel [17] have been
reported.
The increasing troubles of environmental pollution have
become a serious subject of concern among scientists [18–20].
Along this line, an endless activity in chemical communities has
been started in academia and industries. For this effort, over the
past few years, green media such as water, PEG and ionic liquids
[21,22] have been under much attention for the replacement of
organic solvents.
expensive, water-insoluble and toxic, we made a decision to inves-
tigate the possibility of employing a naturally occurring, non-toxic
and degradable bioorganic material to replace phosphine lig-
ands suitable for the reaction to be conducted in water. First,
we decided to investigate the capacity of agarose hydrogel for
this endeavour. Agarose is a polysaccharide, which is consisting
of 1,3-linked-d-galactopyranose and 1,4-linked-3,6-anhydro-␣-l-
galactopyranose. This basic agarobiose repeat unit forms long
chains with an average molecular mass of 120,000 Da (Fig. 1)
[24]. Agarose shows distinctive properties such as flexibility, non-
toxicity, freely soluble in hot water and forms a gel network that
contains double helices, which are formed by the presence of
water molecules bound inside the double helical cavity. Moreover,
agarose contains free hydroxyl groups on its backbone, which has
the potential for the reduction and chelation with transition metals.
Therefore, is able to reduce Pd(II) to Pd(0) species without using any
extra reducing agent. It also acts as a highly functionalized support
to catch up and stabilize the Pd(0) species formed in the mixture
by their ligation with agarose hydrogel. Furthermore, its low costs
also add to its many advantages, which make it a high potential
candidate for such an important venture.
Although, many methods are reported for palladium catalyzed
reductive homocoupling reaction of aryl halides [23], the use
In this article, we have presented a useful environmentally
friendly method for C–C bond formation via homocoupling reaction
of various aryl iodides, bromides and chlorides as well as heteroaryl
halides, ˇ-bromo styrene and phenylboranic acid using agarose
∗
Corresponding authors. Tel.: +98 711 228 4822; fax: +98 711 228 0926.
E-mail addresses: firouzabadi@chem.susc.ac.ir (H. Firouzabadi),
iranpoor@chem.susc.ac.ir (N. Iranpoor).
1381-1169/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2011.08.010

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
95
Evaporation of the solvent gave the desired pure product as a crys-
talline compound.
2.4. Highly green procedure for homocoupling reaction of
4-iodoanisole catalyzed by Pd-supported agarose hydrogel
catalyst in water
Fig. 1. Agarose structure unit.
In a flask containing water (4 mL), agarose (0.1 g) and Pd(OAc)2
(0.009, 4 mol%) were added and the resulting mixture was heated at
90◦ for 10 min. To the obtained black-grayish mass, 4-iodoanisole
(0.468 g, 2 mmol) and NaOH (1.2 g, 3 mmol) were added, while the
mixture was stirred at 90 ◦C under the air for 1.5 h. After completion
of the reaction (TLC), the resulting hot mixture was filtered quickly
through a thick cellulose paper under diminished pressure. The fil-
ter cake was washed with a portion of hot water (3 mL) and the
combined hot aqueous filtrates were allowed to cool down to room
temperature upon which the desired 4,4ꢀ-dimethoxybiphenyl was
precipitated as white crystals which after drying under vacuum the
desired product was isolated in 70–74% in a highly pure state.
hydrogel as an effective bioorganic ligand, support and reducing
agent for these reactions in water in the presence of Pd(OAc)2 as
the pre-catalyst.
Conjugated enzymes form building blocks of biologically active
compounds, natural products, electronic and optical materials
[25]. We have also presented that homocoupling of the terminal
acetylenic groups in the presence of this catalytic system. For this
purpose, the reaction of phenylacetylene as a model compound in
water in the presence of Pd(OAc)2 as the pre-catalyst and agarose
hydrogel has been presented.
However, in recent years, water-soluble palladium catalysts
have received significant attention from different sources due to
their potential environmental and economic benefits [26].
2.5. Homocoupling reaction of ˇ-bromo styrene catalyzed by
Pd-supported agarose hydrogel catalyst in water
2. Experimental
2.1. General
A mixture of agarose (0.05 g) and Pd(OAc)2 (0.0044 g, 2 mol%)
in a flask (5 mL) containing water (2 mL) was prepared and heated
at 90 ◦C with stirring for 5 min. To the resulting mixture, ˇ-bromo
styrene (185 g, 1 mmol) and NaOH (0.6 g, 1.5 mmol) were added
and stirred at 90 ◦C under the air for 12 h. The mixture was cooled
to room temperature and the resulting jelly mass was extracted
with diethyl ether (3 × 5 mL) and decanted. The ethereal solution
was evaporated to give the desired crude homocoupled product.
Purification of the crude was performed by silica gel column chro-
matography eluted with a mixture of n-hexane/ EtOAc. Evaporation
of the solvent gave the pure product in 80–85% yield.
All chemicals were purchased from Merck, Fluka or Acros Chem-
ical Companies and used without any further purification. NMR
spectra were recorded with a BrukerAvance DPX-250 Spectrom-
eter (1H NMR 250 MHz and 13C NMR 62.9 MHz) in CDCl3 with
TMS as the internal standard. UV–Vis spectra were recorded by
PerkinElmer, Lambda 25, UV/Vis spectrometer to visualize the con-
version of Pd(II) to Pd(0). Leaching of Pd into the mixture from
agarose hydrogel was measured by ICP analysis using Varian, Vista-
pro. All products are known compounds and their spectral data
along with their references are given in Section 2.
2.6. Homocoupling reaction of phenylboronic acid catalyzed by
Pd-supported agarose hydrogel catalyst in water
2.2. Homocoupling reaction of aryl halides (I, Br, Cl) catalyzed by
Pd-supported agarose hydrogel catalyst in water
Agarose (0.05 g) and Pd(OAc)2 (0.0044 g, 2 mol%) were dissolved
in water (2 mL) and heated at 90 ◦C for 5 min in a flask. To the result-
ing solution, phenylboronic acid (0.12 g, 1 mmol) and NaOH (0.6 g,
1.5 mmol) were added while being stirred at 90 ◦C under the air
atmosphere for 10 h. The mixture was cooled to room tempera-
ture in which a gelatinous mass was appeared. EtOAc or diethyl
ether (3 × 5 mL) were used to extract the desired product from the
hydrogel mass. Evaporation of the solvent gave the crude biphenyl
product. Purification of the product was performed by column chro-
matography on silica gel eluted with an appropriate mixture of light
petroleum ether/EtOAc to afford the pure biphenyl compound in
75–80% isolated yield.
Agarose (0.05 g) and Pd(OAc)2 (0.0044 g, 2 mol%)were dissolved
in water (2 mL). The resulting solution was heated for 5 min at 90 ◦C.
Then the aryl halide (1 mmol) and NaOH (0.6 g, 1.5 mmol) were
added to the vessel containing the catalyst. The mixture was stirred
for the specified time at 90 ◦C in the air (Table 3). After consumption
of the starting material (TLC or GC), the reaction mixture was cooled
to room temperature. A dark jelly like mass was appeared, which
was extracted with Et2O (2 × 3 mL). Evaporation of the solvent, gave
the desired biaryl in an almost pure state. Further purification, if
was necessary, was performed by silica gel column chromatogra-
phy using n-hexane/Et(OAc)2 as the eluent to give the pure product
in high to excellent yields (Table 2).
2.3. Large-scale homocoupling reaction of 4-iodoanisole
catalyzed by Pd-supported agarose hydrogel catalyst in water
2.7. Homocoupling reaction of phenylacetylene catalyzed by
Pd-supported agarose hydrogel catalyst in water
To a flask containing water (20 mL), agarose (0.5 g) and Pd(OAC)2
(0.022 g, 20 mol%) were added and the resulting mixture was
heated at 90 ◦C for 10 min. To the obtained dark black-grayish mass,
4-iodoanisole (2.34 g, 10 mmol) and NaOH (6 g, 15 mmol) were
added and the mixture was stirred at 90 ◦C for 2 h under the air.
After completion of the reaction (TLC), the mixture was extracted
with Et2O (3 × 10 mL) and the ethereal solution was evaporated to
give the desired biphenyl product in high purity>95% (GC). Further
purification was accomplished by silica gel column chromatog-
raphy eluted with an appropriate mixture of n-hexane/Et(OAc)2.
Phenylacetylene (0.102 g, 1 mmol) and NaOH (0.6 g, 1.5 mmol)
were added to a solution composed of a preheated (90 ◦C) mixture
of agarose (0.05 g), Pd(OAc)2 (0.0044 g, 2 mol%) and water (2 mL).
The resulting mixture was stirred at 90 ◦C under the air atmo-
sphere for 12 h. The mixture was cooled down to room temperature
to result a hydrogel mass. Extraction of the gel by diethylether
(2 × 10 mL) and evaporation of the solvent gave the desired crude
dienyne product, which was purified by column chromatography
on silica gel eluted with a mixture of n-hexane/EtOAc to give the
pure product in 75% isolated yield.

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H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
2.8. Recycling of the catalyst
To a flask (5 mL) containing agarose hydrogel (0.05 g), Pd(OAc)2
(0.0044 g, 2 mol%) and water (2 mL) while being stirred at 90 ◦C,
4-iodoanisole (1 mmol, 0.233 g) and NaOH (1.5 mmol, 0.6 g) were
added and steering was continued for 1.5 h at 90 ◦C. The resulting
mixture was cooled to room temperature upon which a gelati-
nous mass was formed. Addition of diethyl ether (5 × 10 mL) to
the jelly mass produced two distinct phases. The ethereal solution
was decanted and the dark gelatinous mass was reused for another
batch of the similar reaction. This process was repeated for four
repeated runs (Table 4).
Fig. 2. (A) Slight brownish colour homogenous solution of the mixture of agarose
hydrogel and Pd(OAc)2 in water. (B) Black homogenous solution of Pd(OAc)2in water
after heating in the presence of agarose hydrogel. (For interpretation of the refer-
ences to colour in this figure legend, the reader is referred to the web version of the
article.)
2.9. Spectral data
2a: White crystals, m.p. 71–72 ◦C (lit. 69–70 ◦C) [27], 1H NMR
(250 MHz, CDCl3): 7.64–7.32 (m, 10H), 13C NMR (62.5 MHz, CDCl3):
145.5, 130.3, 127.4, 127.2.
2b: White crystals m.p. 119–120.5 ◦C (lit. 118–120 ◦C) [28], 1H
NMR (250 MHz, CDCl3): 7.41–7.38 (m, 4H), 7.2–7.1 (m, 4H), 2.52 (s,
6H), 13C NMR (62.5 MHz, CDCl3): 139.2, 137, 129.5, 126.8, 21.0.
2d: White crystals m.p. 176–177 ◦C (lit. 178–179 ◦C) [29], 1H
NMR (250 MHz, CDCl3): 7.42–7.38 (m, 4H), 6.9–6.8 (m, 4H), 3.75 (s,
6H), 13C NMR (62.5 MHz, CDCl3): 159, 133.4, 127.7, 114.7, 55.83.
2i: White crystals m.p. 142–143 ◦C (lit. 142–145 ◦C) [28], 1H
NMR (250 MHz, CDCl3): 7.42–7.38 (m, 2H), 7.36–7.2 (m, 2H), 13C
NMR (62.5 MHz, CDCl3): 138.5, 133.7, 129.0, 128.2.
2h: White crystals m.p. 234–237 ◦C (lit. 236–240 ◦C) [30], 1H
NMR (250 MHz, CDCl3): 7.7–7.6 (m, 4H), 7.4–7.2 (m, 4H), 13C NMR
(62.5 MHz, CDCl3): 109.2, 120.2, 126.5, 133.4, 148.6.
Fig. 3. (A) UV–Vis spectra of Pd(II) before reduction with agarose hydrogel before
heating. (B) UV–Vis spectra for the formation of Pd(0)species after reduction with
agarose hydrogel after heating.
2c: Yellow solid, m.p. 237–239 ◦C (lit. 240 ◦C) [31], 1H NMR
(250 MHz, CDCl3): 7.85–7.82 (m, 4H), 7.45–7.43 (m, 4H), 13C NMR
(62.5 MHz, CDCl3): 152.5, 147.5, 125.7, 124.5.
solvents was investigated for the reaction of 4-iodoanisole (0.234 g,
1 mmol) as a model compound employing a variety of bases and sol-
vents in the presence of agarose (0.05 g) using Pd(OAc)2 (0.0044 g,
2 mol%) as the pre-catalyst. For this purpose, PEG, NMP, DMSO,
TBAB, PEG/H2O, DMSO/H2O, dioxane, toluene and H2O were exam-
ined as the solvents in the presence of NaOH, KOAc, DBU, K3PO4,
Pr3N and K2CO3 as bases (Table 1).
2j: Orange solid, m.p. 230–231 ◦C (lit. 232 ◦C) [32], 1H NMR
(250 MHz, CDCl3): 8.8 (s, 2H), 8.4–8.6 (m, 6H), 7.8–7.9 (m, 4H),
7.42–7.45 (m, 5H), 13C NMR (62.5 MHz, CDCl3): 150.4, 149.5, 136.8,
133.5, 123.3.
2k: White crystals m.p. 131–132 ◦C (lit. 131–133 ◦C) [33], 1H
NMR (250 MHz, CDCl3): 7.27 (s, 1H), 7.20–7.18 (m, 2H), 13C NMR
(62.5 MHz, CDCl3): 118.9, 118.2, 115.7, 93.3.
The results show that using NaOH at 90 ◦C in H2O (as indicated
in Table 1 in bold letters) was the most suitable condition for this
3i: White crystals m.p. 85–87 ◦C (lit. 86–87 ◦C) [34], 1H NMR
(250 MHz, CDCl3): 7.38–7.34 (m, 4H), 7.29–7.23 (m, 4H), 7.19–7.15
(M, 2H), 6.9–6.86 (d of d, J = 15.8 Hz, J = 2.7 Hz), 6.65–6.61 (d of d,
J = 15.8 Hz, J = 2.7), 13C NMR (62.5 MHz, CDCl3): 136.7, 133.8, 129.7,
128.5, 126.9, 126.1.
Table 1
Optimization studies for the homocoupling reaction of 4-iodoanisole (0.234 g,
1 mmol) with respect to different bases (1.5 mmol) and the solvents using Pd(OAc)2
(0.0044 g, 2 mol%) as a pre-catalyst in the presence of agarose hydrogel (0.05 g) in
5j: White crystals m.p. 84–85 ◦C (lit. 85–86 ◦C) [35], 1H NMR
(250 MHz, CDCl3): 7.5–7.45 (m, 4H), 7.32–7.2 (m, 6H), 13C NMR
(62.5 MHz, CDCl3): 133.6, 129.2, 128.5, 121.7, 80.7, 73.1.
different solvents
OMe
I
Pd(OAc)2, Agarose
.
MeO
Solvent, Base, 90 °C
MeO
3. Results and discussion
Entry
Base
Solvent
Temperature
(◦C)
Time (h)
Conversion %
(GC)
First of all, for preparation of the catalyst, agarose (0.05 g) and
Pd(OAc)2 (0.0044 g, 2 mol%) were dissolved in water (2 mL) to pro-
duce a homogenous solution in slight brownish colour (Fig. 2A). The
resulting solution was stirred for 5 min at 90 ◦C. In this operation,
the colour of the solution turned black (Fig. 2B). The resulting mix-
ture on cooling to room temperature produced a gelatinous mass in
the reaction vessel. Our preliminary investigations were focused on
the characterization of the resulting composite. UV–Vis spectrum
of the produced hydrogel reveals the disappearance of the peak at
420, which shows the reduction of Pd(II) to Pd(0) is occurred by
agarose hydrogel in the reaction mixture (Fig. 3) [36].
1
2
3
4
5
6
7
8
9
10
11
12
13
14
NaOH
NaOH
NaOH
NaOH
KOAC
NaOH
NaOH
KOAC
NaOH
DBU
H2O
PEG
NMP
DMSO
TABA
PEG/H2O
DMSO/H2O
Dioxane
Toluene
H2O
90
90
100
90
100
100
100
100
90
90
90
90
90
1.5
5
5
7
7
5
5
5
5
5
3
3
5
100
45
35
45
77
64
55
44
55
70
81
84
75
78
K3PO4
KOAC
Pr3N
H2O
H2O
H2O
H2O
Pd-catalyzed organic reactions are sensitive towards the nature
of the base and the solvent used for the reaction. Therefore, opti-
mization of the reaction condition with respect to bases and the
K2CO3
90
2

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
97
Table 2
Optimization condition with respect to the amounts of Pd(OAc)2 in the presence of agarose hydrogel (0.05 g) using NaOH (0.6 g, 1.5 mmol) and 4-iodoanisole (0.234 g, 1 mmol)
in water
Pd(OAC)2, Agarose
I
OMe
MeO
OMe
.
°
NaOH, Water, 90 C
Entry
Pd(OAc)2 (mol%)
Agarose (g)
Time (h)
Conversion % (GC)
1
2
3
4
5
6
7
8
1
2
5
10
1
2
None
None
None
None
0.05
0.05
0.05
0.05
48
48
48
48
0
0
0
0
48
70
100
100
100
1.5
1.5
1.25
5
10
homocoupling reaction producing the desired biphenyl compound
in a quantitative yield within 1.5 h (Table 1, entry 1).
a thick cellulose paper which adsorbs the Pd–agarose mass. The
resulting filter cake was washed with hot water. Combination of
the filtrates followed by cooling gave the pure white crystals of
4,4ꢀ-dimethoxybiphenyl in a high yield.
In order to show the more application of this catalytic sys-
tem in water, the homocoupling reaction of ˇ-bromo styrene and
phenylboronic acid under similar reaction conditions have been
also presented. The reactions were performed well as shown in
Schemes 1 and 2 and the desired coupled products were isolated
in 80–85% and 75–80%, respectively.
By applying this catalytic system, we have also investigated the
homocoupling reaction of phenylacetylene as a model compound
for the coupling of terminal acetylenes in water at 90 ◦C. The reac-
tion was performed well with a high isolated yield (75%) within
12 h as shown in Scheme 3.
In order to show that the catalyst acts heterogeneously in the
reaction mixture, we have used the hot filtration test [37]. For this
aim, we have studied the homocoupling reaction of iodobenzene
under the above mentioned optimized conditions. The hot reac-
tion mixture was filtered after 20% conversion of iodobenzene (GC)
In order to show the importance of using agarose hydrogel as
the ligand, reductant and support in the reaction, we studied the
reaction of 4-iodoanisole (0.234 g, 1 mmol) as a model compound
in the presence of NaOH (0.6 g, 1.5 mmol) using Pd(OAc)2 (0.022 g,
10 mol%) in water at 90 ◦C in the absence of agarose hydrogel. Under
these conditions, the reaction failed even after a long reaction time
(24 h).
For optimization of the reaction conditions with respect to the
amounts of Pd(OAc)2, we have studied the reaction of 4-iodoanisole
under the reaction conditions mentioned above by using 1, 2, 5 and
10 mol% of Pd(OAc)2. First, we tried to conduct the reaction in the
presence of 1 mol% of Pd(OAc)2 in the absence of agarose hydrogel.
The reaction was failed after 48 h reaction time (Table 2, entry 1).
Increasing the amounts of Pd(OAc)2 was not also successful for the
reaction to proceed (Table 2, entries 2–4). Surprisingly, addition of
agarose hydrogel to the reaction mixture put an excellent impact
on the reaction. The homocoupling reaction of 4-iodoanisole in the
presence of 1 mol% of Pd(OAc)2 and agarose hydrogel (0.05 g) pro-
ceeded within 48 h to give 70% (GC) of the product (Table 2, entry 5).
Increasing the amount of the catalyst to 2 mol% was accompanied
with a quantitative conversion 4-iodoanisole (GC) to the homocou-
pled product in 1.5 h (Table 2, entry 6). Increasing the amounts of
Pd(OAc)2 did not affect noticeably the yields and the rates of the
reaction. The results are summarized in Table 2.
Pd(OAc)2(0.02 mmol)
Agarose(0.05 g)
Br
NaOH (1.5 mmol), H2O (2 mL)
90 °C, 80-85%, 12 h
In order to indicate the general application and the merit of this
catalytic system for C–C bond formation, first we have applied it for
reductive homocoupling reaction of a wide variety of aryl halides
including the chlorides with success.
3 i
3
Scheme 1. Homocoupling reaction of ˇ-bromo styrene in the presence of agarose
Substrates with electron-donating or electron-withdrawing
functional groups afforded good yields of the desired products. The
nature of the halides substituted on the aromatic rings affects the
rates of the reaction and the sequence of the reactivity follows;
I > Br > Cl (Table 3). However, the reductive homocoupling of aryl
halides (I and Br) substituted with a nitro group was a rather diffi-
cult task and proceeded in longer reaction times. The reaction of an
aryl chloride substituted with nitro group under similar reaction
condition was failed completely (GC).
We have also scaled up the reaction of 4-iodoanisole (2.34 g,
10 mmol) in the presence of Pd(OAc)2 (0.044 g, 20 mol%), NaOH
(6 g, 15 mmol), agarose (0.5 g) at 90 ◦C. The reaction proceeded well
within 2 h producing the desired biphenyl compound in 75–78%
isolated yield.
hydrogel containing Pd(OAc)2 in water using NaOH as a base.
Pd(OAc)2(0.02mmol)
Agarose(0.05g)
B(OH)2
NaOH(1.5 mmol), H2O(2mL)
2 a
90 °C, 75-80%, 12 h
4
Scheme 2. Homocoupling reaction of phenylboranic acid by agarose hydrogel con-
taining Pd(OAc)2 in water using NaOH as base.
Pd(OAc)2(0.02 mmol)
Agarose(0.05g)
However, we have also shown that by using this catalytic sys-
tem, isolation of the pure product can be performed under highly
green process. For this purpose, the reaction of 4-iodoanisole
as a model compound was performed to completion under the
optimized reaction conditions as discussed in the preceeding para-
graphs. The hot reaction mixture was immediately filtered through
NaOH(1.5 mmol), H2O(2 mL)
90 °C, 12h, 75%
5 j
5
Scheme 3. Dimerization of phenylacetylene catalyzed by agarose hydrogel and
Pd(OAc)2 using NaOH in water.

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H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
Table 3
Homocoupling reaction of different aryl halides (I, Br, Cl) by Pd(OAc)2 in the presence of agarose hydrogel using NaOH in water
Pd(OAc)2 (0.02 mmol)
Agarose(0.05 g)
R
R
R
X
.
NaOH (1.5 mmol)
H2O (2 mL), 90 °C
2
Entry
1
Aryl halide
Product
Time (h)
1.5
Isolated yield (%)a
96
I
1a
2a
H3C
O2N
MeO
I
I
H3C
O2N
MeO
CH3
NO2
OMe
2
3
4
5
3
18
1.5
3
85
68
85
91
1b
1c
2b
2c
I
1d
2d
Br
2a
1e
H3C
O2N
Br
Br
H3C
O2N
NC
CH3
NO2
CN
6
7
6
18
3
87
62
89
91
56
91
83
80
86
1f
2b
2c
1g
NC
Cl
Br
8
1h
1i
2h
Br
Cl
Cl
9
4
2i
Br
10
11
12
13
16
2
N
N
N
1j
2j
Br
S
S
S
1k
2k
2a
Cl
24
24
24
1l
H3C
Cl 1m
H3C
NC
CH3
CN
2b
NC
Cl
1n
14
2h
a
Reaction conditions: substrate (1.0 mmol), agarose (0.05 g), NaOH (0.6 g, 1.5 mmol) and Pd(OAc)2 (0.0044 g, 0.02 mmol) at 90 ◦C.
to remove the Pd catalyst. Continuation of the reaction upon the
resulting filtrate under the same conditions showed 35% conversion
(GC) of iodobenzene after 4 h. This result shows that the amount
of leaching of the catalyst into the reaction mixture should be low
and confirms that the catalyst acts heterogeneously in the reaction.
Quantitative measurement of the amount of Pd leached into the
homocoupling reaction mixture of iodobenzene was determined
by ICP analysis to be <3.5% after completion of the reaction.
Recycling of the catalyst is an important process from differ-
ent aspects such as environmental concerns, costs of the catalyst
and its toxicity. However, Pd salts are expensive, some of them are
toxic, which makes the amounts of their leaching into the reaction
mixture a serious worry. Therefore, we studied the recycling of the
Pd-supported agarose hydrogel for the homocoupling reaction of 4-
iodoanisole. The reaction was allowed to proceed under optimized
conditions as described in the preceeding section. After comple-
tion of the reaction and cooling the mixture to room temperature, a
dark gelatinous mass was accumulated at the bottom of the reaction
vessel. Upon addition of diethyl ether to the resulting jelly accumu-
lation, two distinct phases were produced. The organic phase was
decanted and the amount of the leached Pd form the agarose hydro-
gel core into the decanted ethereal solution was measured by ICP
and atomic absorption analysis to be <3.5%. This amount of leach-
ing makes this catalytic system suitable for the reactions conducted

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 348 (2011) 94–99
99
Table 4
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I
OMe
MeO
OMe
.
NaOH, H2O
°
90 C
Run
Time (h)
Conversion % (GC)
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in water. The leaching amounts of Pd also show that the agarose
hydrogel has a high ability to entrap palladium in a good quantity
without remarkable amounts of discharge of the Pd species into the
reaction media. The resulting dark agarose hydrogel mass obtained
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In this study, a new protocol for carbon–carbon bond formation
via homocoupling reaction of using different aryl halides includ-
ing aryl chlorides in the presence of Pd(OAc)2 as the pre-catalyst
and agarose hydrogel as a reductant, support and bioorganic lig-
and in water at the temperatures <100 ◦C is discussed. Agarose is a
naturally occurring polysaccharide, which is cheap, soluble in hot
water, nontoxic and degradable in nature. All these make agarose
hydrogel an attractive and a highly green material for conducting
useful carbon–carbon bond formation using versatile substrates as
reported in this article. In addition to the homocoupling reactions of
aryl halides, important high yielding homocoupling reactions of ˇ-
bromo styrene, phenylboronic acid and phenylacetylene using this
catalytic system have been conducted in the presence of this cata-
lyst. The protocol has been also applied for a large-scale operation
in which a high yield of the product was obtained. This catalyst is
also a recyclable system. The leaching of Pd species into the reaction
mixture was found to be rather small amounts <3.5%.
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The authors are thankful to TWAS Chapter of Iran based at ISMO
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Appendix A. Supplementary data
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