Palladium nano-particles supported on agarose as efficient catalyst and bioorganic ligand for CC bond formation via solventless Mizoroki-Heck reaction and Sonogashira-Hagihara reaction in polyethylene glycol (PEG 400)

Article abstract of DOI:10.1016/j.molcata.2012.02.006

In this study, abundant naturally occurring agarose has been used as a support and ligand for palladium nanoparticles. In the presence of this catalytic system, Mizoroki-Heck and Sonogashira-Hagihara coupling reactions were performed successfully. The catalyst exhibits high activity in Mizoroki-Heck reaction under phosphane and solvent-free conditions for the reaction of iodo- and bromoarenes with butyl acrylate and styrene. This catalytic system also showed high catalytic activity for Sonogashira-Hagihara coupling reaction of various aryl halides (I, Br, Cl) under copper and ligand-free conditions in polyethylene glycol (PEG 400) as an ecofriendly and non-poisonous media. The catalyst can be separated from the reaction mixture and reused for the similar batches of the reaction. High efficiency of the catalyst along with its recycling ability and the rather low Pd-loading which are demonstrated in both Mizoroki-Heck and Sonogashira-Hagihara reactions are the merits of the presented catalyst system.

Full text of DOI:10.1016/j.molcata.2012.02.006

Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Palladium nano-particles supported on agarose as efficient catalyst and
bioorganic ligand for C C bond formation via solventless Mizoroki–Heck reaction
and Sonogashira–Hagihara reaction in polyethylene glycol (PEG 400)
a,∗
a,∗
a
a,b
Habib Firouzabadi , Nasser Iranpoor , Faezeh Kazemi , Mohammad Gholinejad
a
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P.O. Box 45195-1159, Gava Zang, Zanjan, Iran
b
a r t i c l e i n f o
a b s t r a c t
Article history:
In this study, abundant naturally occurring agarose has been used as a support and ligand for palladium
nanoparticles. In the presence of this catalytic system, Mizoroki–Heck and Sonogashira–Hagihara cou-
pling reactions were performed successfully. The catalyst exhibits high activity in Mizoroki–Heck reaction
under phosphane and solvent-free conditions for the reaction of iodo- and bromoarenes with butyl
acrylate and styrene. This catalytic system also showed high catalytic activity for Sonogashira–Hagihara
coupling reaction of various aryl halides (I, Br, Cl) under copper and ligand-free conditions in polyethy-
lene glycol (PEG 400) as an ecofriendly and non-poisonous media. The catalyst can be separated from the
reaction mixture and reused for the similar batches of the reaction. High efficiency of the catalyst along
with its recycling ability and the rather low Pd-loading which are demonstrated in both Mizoroki–Heck
and Sonogashira–Hagihara reactions are the merits of the presented catalyst system.
Received 3 December 2011
Received in revised form 29 January 2012
Accepted 6 February 2012
Available online 14 February 2012
Keywords:
Agarose
Mizoroki–Heck
Sonogashira–Hagihara
Nanoparticle
Palladium
© 2012 Published by Elsevier B.V.
Polyethylene glycol
Copper-free
1
. Introduction
Carbon carbon bond formation reactions have been under
[10], carbon nanofiber [11], clay [12], montmorillonite [13], silica
andmagneticmesoporoussilica [14], zeolite[15], metal oxides [16],
and silica-starch [17].
attention since the early attempts for introduction of protocols
regarding the transformation of easily available, cheap, simple and
small organic molecules to the more valuable complex molecules
In our recent reports, bioorganic polymers such as gelatin and
agarose as ecofriendly degradable materials and abundant in nature
have been used as the support and ligand for the reactions leading
to C C bond formation through a Pd-catalyzed reaction [18].
Agarose is a polysaccharide that is found extensively in nature
[19]. It is a linear polymer, made up of the repeating monomeric unit
of agarobiose. Agarobiose is a disaccharide made up of d-galactose
and 3,6-anhydro-l-galactopyranose as presented in Fig. 1. Prop-
erties of agarose, such as flexibility, non-toxicity, low cost, freely
soluble in hot water, carrying freely available hydroxy groups, make
this material an ideal candidate for numerous practices in different
areas of science [20]. It produces a gel network through its avail-
able hydroxy groups, which are formed by the presence of water
molecules bound inside the double helical cavity. Moreover, a mod-
erate reduction of Pd(II) to Pd(0) can occur on the backbone of
agarose molecules by the available free hydroxy groups. This slow-
rate reduction causes the formation of 10–30 nm of well distributed
nano particles of palladium on the surface of the agarose molecules
which are also stabilized by ligation with agarose hydroxy groups.
Palladium nanoparticles are employed in variety of catalytic
reactions including Mizoroki–Heck, Suzuki–Miyaura, Stille and
Sonogashira–Hagihara reactions. Using transition metal salts are
[
1–4]. Some of the most exciting protocols for this achievement
are the reactions catalyzed by palladium, an important topic which
has been recognized with the Nobel Prize for Chemistry 2010
[
5]. These reactions are commonly catalyzed by soluble palladium
phosphane complexes. However, the soluble palladium phosphane
complex catalysts suffer from problems associated with the separa-
tion, recovery, and instability at high temperatures. Moreover, most
of phosphane ligands are expensive, not easily available and toxic
which are associated with particular environmental and economic
concerns, especially when large-scale operations are of considera-
tion [6–8]. Palladium maintained on different supports may offer
solutions for some of the associated troubles as mentioned [9].
Consequently, much attention has been focused on improving the
reactions by synthesis and application of supports such as polymers
∗ Corresponding authors. Tel.: +98 711 2284822; fax: +98 711 2280926.
E-mail addresses: firouzabadi@chem.susc.ac.ir (H. Firouzabadi),
iranpoor@chem.susc.ac.ir (N. Iranpoor).
1
381-1169/$ – see front matter © 2012 Published by Elsevier B.V.
doi:10.1016/j.molcata.2012.02.006

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
155
OH
on Perkin-Elmer, Lambda 25, UV-Vis spectrometer which shows
the conversion of Pd(II) to Pd(0). Scanning electron micrographs
O
OH
(
SEM) were obtained (SEM, XL-30 FEG SEM, Philips, at 20 kV). X-
O
ray diffraction spectra of the catalyst were obtained by XRD, D8,
Advance, Bruker, axs. Inductively Coupled Plasma (ICP) technique
OH
O
O
H
O
(Varian, Vista-pro) was employed for the determination of the
OH
OH
amount of palladium nanoparticles supported on agarose.
n
2
.2. Gram-scale preparation of palladium nano-particles
Fig. 1. The structure of agarose monomeric unit (agarobiose) composed of d-
galactose and 3,6-anhydro-l-galactopyranose.
supported on agarose
◦
Agarose (1 g) was dissolved in water (100 mL) at 80 C. To this
solution, a solution of Pd(OAc)2 (100 mL, 1 mM) was added and
diluted with water (100 mL). To the resulting solution, a solution
of citric acid (20 mL, 4 mM) was added dropwise upon which a
grayish-brown color was developed. Refluxing of the obtained reac-
tion mixture was continued for 1 h. Upon cooling the resulting
mixture to room temperature, a grayish-brown mass of the agarose
hydrogel catalyst was formed which was dried by the flow of the air
over night and under vacuum for 24 h to produce the black powder
catalyst.
the most available and convenient way to deposit the metallic
nanoparticles onto supports by reduction [21–23,12,24,25].
Palladium-catalyzed Mizoroki–Heck coupling reaction is a pow-
erful and versatile method for arylation and vinylation of olefins
[
26–28]. Total synthesis of complex organic molecules has bene-
fited enormously from the Mizoroki–Heck reaction. In this reaction,
aryl, heteroaryl, alkenyl, and benzyl halides are coupled with
alkenes in the presence of palladium catalysts to give the cor-
responding substituted alkenes [3,29]. However, organic solvents
[
30], ionic liquids [31], and water [32] as the media have been
extensively used in these methods. On the other hand, similar
reactions conducted under solvent-free conditions received less
attention [33]. Solvent-free palladium catalyzed reactions are of
significant interest due to their potential of environmental and eco-
nomic benefits [34]. Very recently, we have reported a solvent-free
Mizoroki–Heck reaction in the presence of palladium nanoparticles
supported on aminopropyl-functionalized clay as an efficient cata-
lyst for the reaction of iodo- and bromoarenes with butyl acrylate
and styrene [35].
Also, in recent years, the Sonogashira–Hagihara reaction has
come into view as one of the most general, reliable, and effec-
tive methods for the synthesis of substituted alkynes [36]. The
Sonogashira–Hagihara protocol in which copper salts are used
as co-catalysts has contributed greatly to the straightforward
and facile construction of alkynyles. However, using copper salts
as co-catalysts sometimes lead to the homocoupling reaction
of terminal alkynes (Glaser-type reaction) upon exposure of
the copper–acetylide intermediate to the air or other oxidizing
agents [37–39]. Very recently, we have reported a copper-free
Sonogashira–Hagihara reaction for coupling of various aryl iodides,
bromides and chlorides and also ˇ-bromo styrene with phenyl
acetylene using Pd nanoparticles supported on gelatin [18a].
In our previous work [18b,c] we have demonstrated that agarose
can be used as an effective bioorganic ligand, support and reduc-
ing agent for generation and entrapment of the in situ generated
Pd(0) nanoparticles. This supported catalyst has been applied suc-
cessfully for Suzuki–Miyaura reaction in aqueous media [18a].
Moreover, Pd-supported agarose has been applied for C C bond
formation via homocoupling reactions in water by our research
group [18c].
2
.3. General procedure for the Mizoroki–Heck reaction of aryl
halides and styrene in the presences of Pd nano-particles
supported on agarose under solvent-free conditions
Et N (2 mmol, 0.27 mL) was added to a flask containing the
3
powder of agarose supported Pd nanoparticles [0.05 g, containing
5
aryl halide (1 mmol) and styrene (2 mmol, 0.22 mL) were added
and heated (for aryl iodides at 100 C and for aryl bromides at
−
5
5 × 10 g, 0.0052 mmol of Pd (ICP)]. To the resulting mixture,
◦
◦
1
20 C in an oil bath). After 1–16 h, the reactions were completed
(TLC and GC). The mixture was cooled to the room temperature
and extracted with Et O (3 mL × 5 mL). Evaporation of the ethe-
2
real solvent followed by chromatography on silica gel eluted with
n-hexane/EtOAc afforded the desired coupled products in 60–91%
yields (Table 2).
2.4. General procedure for the Mizoroki–Heck reaction of aryl
halides and butyl acrylate in the presences of Pd nanoparticles
supported on agarose in solvent-free conditions
Et3N (2 mmol, 0.27 mL) was added to a flask containing the
powder of agarose supported Pd nanoparticles [0.05 g, containing
55 × 10 g, 0.0052 mmol of Pd (ICP)]. The flask was placed in an
−
5
◦
◦
oil bath at 100 C for aryl iodides and at 120 C for aryl bromides
and stirred for 15 min. Then the aryl halide (1 mmol) and butyl
acrylate (2 mmol, 0.28 mL) were added to the mixture. Completion
of the reactions (1–24 h) was detected by TLC and GC. The result-
ing mixture was cooled to room temperature and extracted with
diethyl ether (3 mL × 5 mL). Evaporation of the ethereal solution fol-
lowed by chromatography on a short column of silica eluted with
n-hexane/EtOAc afforded the coupled products in 59–90% yield
(Table 3).
Now in this article, we report the use of agarose supported Pd
nanoparticles for Mizoroki–Heck reaction under solvent-free con-
ditions without using phosphorus ligands. We have also presented
the use of this catalyst for Sonogashira–Hagihara reaction under
ligand and amine-free conditions in polyethylene glycol (PEG 400)
as a green media.
2.5. Recycling of the catalyst in Mizoroki–Heck reaction
Recycling of the catalyst was performed upon the reaction of
iodobenzene with butyl acrylate under the condition discussed in
the preceeding sections. After completion of the reaction in the first
run, the mixture was washed with diethyl ether (3 mL × 5 mL) and
decanted. The resulting solid mass was reused for another batch of
the similar reaction. This process was repeated for four runs. As the
reaction was performed from the first run to the fifth, the required
time for the completion of the reaction was elongated from 1.5 to
2
. Experimental
2.1. General
NMR spectra were recorded on a Bruker Avance DPX-250 spec-
1
13
trometer ( H NMR 250 MHz and C NMR 62.9 MHz) in CDCl3
and TMS as the internal standard. UV-Vis spectra were recorded

1
56
H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
Fig. 2. (A) Pd(II) in the presence of agarose at room temperature before reduction and (B) UV-Vis spectra of Pd(0) supported on agarose generated by citric acid reduction.
5
h, which indicates that the activity of the catalyst was decreased
as the number of the runs was increased.
2.6. General procedure for Sonogashira–Hagihara reaction of aryl
halides catalyzed by palladium nanoparticles supported on
agarose in PEG 400
Aryl halide (1 mmol) and phenyl acetylene (1.5 mmol, 0.16 mL)
were added to a flask containing the powder of agarose supported
−5
Pd nanoparticles [0.05 g, containing 55 × 10 g, 0.0052 mmol of Pd
(
ICP)] and KOAc (1.5 mmol, 0.15 g) in PEG 400 (2 mL). The resulting
◦
mixture was stirred at 90 C in the air for the appropriate reac-
tion time. After completion of the reaction (TLC or GC), the reaction
mixture was cooled to room temperature and extracted with Et O
2
(
3 mL × 5 mL). The ethereal solution was evaporated to afford the
Fig. 3. SEM image of agarose supported Pd nanoparticles which shows the regular
dispersion of the palladium nano-particles on the surface of the agarose.
desired product in an almost pure state. Further purification, if it
was necessary, has been performed by using silica gel column chro-
matography eluted with n-hexane/EtOAc to give the pure biphenyl
products in high to excellent yields.
2 H, J = 5 Hz), 7.56 (d, 1 H, J = 16 Hz); 13C NMR (CDCl3, 62.9 MHz):
ı (ppm): 13.75, 19.20, 30.80, 55.35, 64.25, 114.28, 115.76, 129.67,
1
44.19, 161.30.
2
.7. Large-scale Sonogashira–Hagihara reaction catalyzed by
1
3c: H NMR (CDCl , 250 MHz): ı (ppm): 0.85 (t, 3 H, J = 2.5 Hz),
3
palladium nanoparticles supported on agarose in PEG 400
1
1
.32 (sex, 2 H), 1.57 (quint, 2 H), 2.30 (s, 3 H), 4.11 (t, 2H), 6.27 (dd,
ꢀ
H, J = 15.9 Hz, J = 4.8 Hz), 7.11 (m, 3 H), 7.41 (m, 1H), 7.84 (dd, 1 H,
1
-Bromo-4-nitrobenzene (5 mmol, 1 g) and phenyl acetylene
ꢀ
13
J = 13.7 Hz, J = 4.3 Hz); C NMR (CDCl , 62.9 MHz): ı (ppm): 13.76,
18.96, 19.74, 30.79, 64.36, 119.26, 126.31, 129.94, 130.75, 133.40,
1
3
(
7.5 mmol, 0.82 mL) were added to flask containing Pd-
a
−4
nanoparticles [0.5 g, containing 55 × 10 g, 0.0052 mmol of Pd
37.56, 142.20, 167.09.
(
ICP)] and KOAc (7.5 mmol, 0.74 g) in PEG 400 (10 mL). The mix-
1
◦
3d: H-NMR (CDCl3, 250 MHz) ı (ppm): 2.3 (s, 3H), 7.06–7.17
ture was stirred at 90 C for 3 h. After completion of the reaction
13
(m, 2H), 7.24–7.46 (m, 7H); C-NMR (62.9 MHz, CDCl ) ı (ppm):
3
(
TLC or GC), the reaction mixture was cooled to room temper-
ature and the mixture was extracted with Et O (5 mL × 10 mL).
2
After vaporation of the ethereal solution, an almost pure product
was obtained. Further purification was performed by silica gel col-
umn chromatography eluted with n-hexane/EtOAc to give the pure
biphenyl product in excellent yield.
2
.8. Selected 1H- and 13C-NMR spectra of the compounds
1
b: 1H NMR (CDCl , 250 MHz): ı (ppm): 7.13 (d, 2 H), 7.31 (m,
3
6
H), 7.52 (m, 4 H).
1
3
b: H NMR (CDCl , 250 MHz): ı (ppm): 2.32 (s, 3H), 6.89 (d, 1
3
13
H, J = 16.25), 7.06–7.29 (m, 7H), 7.40–7.52 (m, 3H); C NMR (CDCl3,
6
1
1
2.9 MHz): ı (ppm): 19.99, 124.95,125.44, 126.28, 126.61, 126.63,
27.28, 127.62, 127.66, 128.75, 130.08, 130.47, 135.86, 136.47,
37.75.
1
7
b: H NMR (CDCl , 250 MHz): ı (ppm): 6.98–7.57 (m, 9 H),
3
1
3
8
1
1
.14 (m, 2 H); C NMR (62.9 MHz, CDCl ) ı (ppm): 124.07, 124.95,
26.20, 126.93, 127.00, 128.08, 129.04, 129.93, 132.58, 133.25,
36.13, 143.82.
3
1
2
c: H NMR (CDCl , 250 MHz): ı (ppm): 0.89 (t, 3 H, J = 7.5 Hz),
3
1
.35 (sex, 2 H, J = 7.5 Hz), 1.61 (quint, 2 H, J = 5 Hz), 3.76 (s, 3 H), 4.13
Fig. 4. TEM image of the agarose supported Pd nanoparticles which shows the size
(
t, 2 H, J = 6.7), 6.24 (d, 1 H, J = 15 Hz), 6.83 (d, 1 H, J = 5 Hz), 7.40 (d,
distribution of the particles to be around 10–30 nm.

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
157
Table 1
Comparison of the conditions used for the reaction of iodobenzene with butyl acrylate in the presence of palladium nanoparticles supported on agarose in the presence of
◦
different bases and solvents at 100 C.
I
Agarose supported
nano catalyst
O
O
O
+
O
Base, 100 °C
solvent
.
Entry
Solvent
Base
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
NMP
DMF
Toluene
EtOH
H2O
None
None
None
None
None
None
None
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Pr3N
Morpholine
K2CO3
4
5
7
7
5
2
3
7
5
5
3
5
70
89
70
75
62
90
83
80
50
49
87
10
n
1
1
1
0
1
2
Cs2CO3
KOAc
NaOH
Table 2
Reaction of different aryl halides (I, Br) with styrene in the presence of agarose supported Pd nano catalyst in solvent-free conditions.
X
Agarose supported
nano catalyst
+
R
Et N, 100-120 °C
R
3
solvent free
R= Me, OMe, CN
COMe, NO , Cl
2
X= Cl, Br, I
.
◦
Isolated yield (%)a
90
−1
)
Entry
Ar-X
Product
Time (h)/temperature ( C)
TON/TOF (h
1
2
I
1b
2/100
173/86.5
MeO
I
2b
3b
2.5/100
4/100
90
84
173/69
161/40
I
3
Me
4
5
6
Br
1b
4b
5b
3/120
3/120
10/120
91
89
88
175/53
171/57
169/17
Br
NC
O
Br
Br
7
6b
10/120
72
138/14
8
9
O
2
N
Br
7b
8b
15/120
10/120
60
87
115/8
Cl
Br
167/17
Br
Br
1
0
1
9b
17/120
12/120
65
76
125/7
N
N
1
10b
146/12
N
aReactions were performed with ArX (1 mmol), styrene (2 mmol), Et3N (2 mmol) and catalyst (0.05 g containing 0.0052 mmol of Pd).

1
58
H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
Table 3
Reaction of different aryl halides (I, Br, Cl) with butyl acrylate in the presence of agarose supported Pd nano-catalyst under solvent-free conditions.
X
Agarose supported
nano catalyst
O
+
O
R
Et
3
N, 100-120 °C
solvent free
R
R= Me, OMe, CN
COMe, NO , Cl
2
X= Cl, Br, I
.
◦
Isolated yield (%)a
90
−1
)
Entry
Ar-X
Product
Time (h)/temperature ( C)
TON/TOF (h
1
2
I
1c
2c
1.5/100
173/115
MeO
I
2/100
3/100
89
80
171/85
154/51
I
3
3c
Me
4
5
Br
1c
4c
3/120
3/120
87
90
167/56
17358
Br
6
7
NC
O
Br
Br
5c
6c
8/120
88
69
160/21
13213
10/120
8
9
O
2
N
Br
7c
8c
10/120
7/120
59
95
113/11
182/26
Cl
N
Br
Br
1
0
9c
15/120
60
115/8
1
1
1
1
2
3
Cl
1c
4c
5c
24/120
24/120
24/120
65
57
61
125/5
110/5
117/5
H
C
Cl
Cl
3
NC
aReactions were performed with ArX (1 mmol), butyl acrylate (2 mmol), Et3N (2 mmol) and catalyst (0.05 g containing 0.0052 mmol of Pd).
2
1
1.52, 88.74, 89.58, 123.49, 128.08, 128.33, 128.46, 129.13, 131.56,
To the resulting solution, a solution of citric acid in water as a reduc-
ing agent was also added slowly and dropwise in order to reduce
Pd(II) to Pd(0) in the reaction mixture. On cooling the mixture to
room temperature, a grayish-brown hydrogel was appeared, which
after drying in the air and under vacuum at room temperature, a
black powder was obtained.
As discussed in our previously reported protocol [18b], the
resulting black powder has been characterized by UV-Vis spectrum
in which the complete conversion of Pd(II) to Pd(0) was confirmed
by the absence of the peak at 420 nm (Fig. 2). The XRD of the black
powder shows peaks at (1 1 1), (2 0 0), (2 2 0) and (3 1 1) crystallo-
graphic planes related to the formation of Pd(0).
32.51, 138.39.
1
5
d: H-NMR (CDCl , 250 MHz) ı (ppm): 3.75 (s, 3H), 6.80 (d, 2H,
3
13
J = 10 Hz), 7.18–7.46 (m, 7H); C-NMR (62.9 MHz, CDCl ) ı (ppm):
5
3
5.3, 89.2, 98.3, 113.9, 115.4, 123.6, 128.3, 128.8, 131.4, 133.0, 137.5.
1
7
d: H-NMR (250 MHz, CDCl ) ı (ppm): 7.13–7.25 (m, 3H),
3
1
3
7
1
.33–7.43 (m, 6H); C-NMR (62.9 MHz, CDCl ) ı (ppm): 88.2, 90.3,
3
21.8, 122.9, 128.4, 128.5, 128.7, 131.6, 132.8, 134.2.
3
. Results and discussion
The palladium nanoparticles supported on agarose were pre-
pared by dissolving agarose in hot water to produce a homogeneous
Scanning electron microscopy (SEM) of the composite shows
that the Pd particles are regularly deposited on the surface of
solution. To this solution, a solution of Pd(OAc) in water was added.
2

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
159
Table 4
Recycling of the catalyst for the reaction of iodobenzene with butyl acrylate in the presence of Et3N and 0.05 g of the catalyst at 100 C.
◦
I
Agarose supported
nano catalyst
O
+
O
Et N, 100 °C
3
R
solvent free
.
Run
Time (h)
Conversion%
1
2
3
4
5
1.5
1.5
2
3
5
100
100
100
100
100
agarose (Fig. 3). The TEM image indicates that the size of the pal-
ladium particles entrapped by agarose is in the range of 10–30 nm
and 1-bromo-4-nitrobenzene is rather unexpected, which is most
probably due to the less solubility of the above mentioned solid
substrates in this solvent free system (Table 2, Entries 6–8). Also,
3-bromopyridine and 5-bromopyrimidine were reacted efficiently
as hetero-aryl halides as illustrated in Table 2, Entries 10, 11.
In an additional series of experiments, we have also studied the
Mizoroki–Heck coupling reaction of aryl halides with butyl acry-
late. The similar protocol as has been described for styrene was also
employed for this purpose. The results of this study are presented
in Table 3.
(
Fig. 4).
The palladium content of the agarose composite was also
−
5
obtained by inductively coupled plasma (ICP) to be 55 × 10 g,
0
.0052 mmol of Pd per 0.05 g of the agarose support.
Application of the palladium nanoparticles supported on
agarose as a catalyst in Mizoroki–Heck reaction of aryl halides with
styrene and butyl acrylate under solvent and phosphane-free con-
ditions:
In order to optimize the reaction conditions, first we stud-
ied the effect of media upon the reaction. For this purpose, the
reaction of iodobenzene (1 mmol, 0.11 mL) with butyl acrylate
Afterwards, in order to investigate the recycling of the catalyst,
the reaction of iodobenzene with butyl acrylate employing 0.05 g
◦
of the catalyst in the presence of Et N at 100 C was tested. The first
3
(
2 mmol, 0.28 mL) in the presence of the agarose supported pal-
run reaction was carried out within 1.5 h. Similarly, the reaction for
the repeated runs were conducted after separation of the organic
compounds from the reaction mixture by extraction and the recov-
ered catalyst was recycled for 5 successive runs with a rather sharp
decrease in the catalytic activity from the 4th run (Table 4). The
leaching of the catalyst into the reaction mixture was also deter-
mined by ICP analysis for the first run of recycling to be <2% after
cooling the reaction mixture to room temperature.
ladium nanoparticles (0.05 g of the agarose composite contains
0
◦
.0052 mmol of Pd) in different solvents and bases at 100 C
(
Table 1). Comparison of the results shows that the reaction in the
absence of solvent proceeded much better than in solvents with
an excellent yield and in a much shorter reaction time. Among
the studied bases, Et N and KOAc were found to be more efficient
3
for this reaction (Table 1). Therefore, Et N was chosen as the most
3
suitable base under the optimized reaction conditions.
Application of the palladium nanoparticles supported on
agarose as a catalyst in Sonogashira–Hagihara reaction of aryl
halides with phenyl acetylene in polyethylene glycol (PEG 400):
As a part of our ongoing project on application of new cat-
alytic system in which Pd(OAc)2 has been used as a pre-catalyst
and agarose as a degradable bioorganic ligand, support and reduc-
tant, we decided to apply this system for Sonogashira–Hagihara
reaction of aryl iodides, bromides and chlorides with phenyl acety-
lene. Preliminary screening to compare different conditions in the
Sonogashira–Hagihara reaction were performed by using different
solvents and bases upon the reaction of 1-bromo-4-nitrobenzene
Under the optimized reaction conditions, 0.05 g of the cata-
−5
lyst (containing 55 × 10 g, 0.0052 mmol of Pd) and 2.0 mmol of
Et N, the desired products were obtained in excellent yields for
3
◦
a wide array of aryl iodides at 100 C and bromides with styrene
at 120 C (Table 2). The reaction of iodobenzene and 4-iodoanisole
◦
and 2-iodotoluene were performed smoothly within 2–4 h giving
the desired products in 84–90% isolated yields. The results are tab-
ulated in Table 2, Entries 1–3. This catalytic system was also applied
to different aryl iodides and also hetero aryl bromides. A com-
plete conversion was obtained for the reaction of bromobenzene
and 4-bromotoluene with styrene after 3 h (Table 2, Entries 5, 6).
For electron-deficient bromides, elongations of the reaction times
along with the decrease of the yields of the products were observed.
The low reactivity of 4-bromobenzonitrile, 4-bromoacetophenone,
◦
with phenyl acetylene as a benchmark at 90 C. For this aim,
two green solvents, water and polyethylene glycol (PEG 400)
were used in the presence of KOAc. As shown in Table 5, PEG
400 was a better solvent for this reaction. Therefore, the rest of
Table 5
Optimization studies for the Sonogashira–Hagihara reaction of 4-iodoanisole (0.234 g, 1 mmol) with phenyl acetylene (1.5 mmol) with respect to a few bases (1.5 mmol) and
◦
agarose supported Pd nanocatalyst at 90 C.
I
catalyst
+
Ph
R
Ph
base, solvent
0 °C
9
OMe
.
Entry
Base
Solvent
Time (h)
Conversion % (GC)
60
1
3
KOAc
KOAc
NaOAc
Morpholine
Cs2CO3
H2O
PEG
PEG 400
PEG 400
PEG 400
5
2
6
6
5
100
12
13
14
83
74
79

1
60
H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
Table 6
Reaction of different aryl halides (I, Br, Cl) with phenyl acetylene in the presence of agarose supported Pd nano catalyst in PEG 400.
Agarose supported
Pd nano catalyst
X
R + Ph
Ph
R
KOAc ( 2 mmol)
PEG (2 mL)
o
9
0 C
.
Isolated yield (%)a
95
TON/TOF (h
−1
)
Entry
1
Ar-X
Product
Time (h)
0.5
1d
182/365
2
3
4
2d
1d
3d
2
90
95
89
173/86
1.5
1.5
183/121
171/114
Br
5
6
NC
Br
4d
5d
5
5
90
88
173/35
169/34
7
8
6d
7d
7
7
80
90
154/22
173/25
Br
9
8d
8
93
179/22
N
1
0
1
Cl
1d
3d
14
14
70
69
135/10
133/9
1
NC
Cl
1
2
4d
14
75
144/10
aReactions were performed with ArX (1 mmol), phenyl acetylene (1.5 mmol), KOAc (2 mmol) and catalyst (0.05 g containing 0.0052 mmol of Pd) in PEG (400) (2 mL).
this study was performed in PEG 400. We also investigated the
effect of a few bases in this media upon the reaction. The results
given in Table 5 show that KOAc was a suitable base for the
reaction.
acetylene (7.5 mmol) under similar optimized reaction conditions.
The reaction proceeded well to produce the desired biphenyl
compound in 80% isolated yield
In order to get some information about the active catalytic
◦
As shown in Table 6, a range of aryl iodides, bromides and
chlorides reacted with phenyl acetylene to give the desired
products in high yields. As expected, the reaction of aryliodides
bearing electron donating groups went to completion in longer
reaction times (Table 6, Entry 2). The coupling reaction of phenyl
acetylene with both electron- releasing and electron withdraw-
ing aryl bromides afforded the desired products in high yields.
Heterocyclic bromides such as 3-bromopyridine led to the corre-
sponding bi-functionalized acetylene in a desirable yield (Table 6,
Entry 9). The catalytic system was also applied for the reaction
of aryl chlorides with phenyl acetylene. In these cases, the pro-
longed reaction times to 24 h were required to give the expected
products in good yields (Table 6, Entries 10–12). Moreover, we
have also applied this catalyst for a gram-scale reaction. For this
aim, 1-bromo-4-nitrobenzene (5 mmol) was reacted with phenyl
species at 90 C, we have performed poisoning test by using
poly(4-vinylpyridine) as poisoning additive [40]. For this purpose,
poly(4-vinylpyridine) with respect to the catalyst was used in the
ratio of 400: 1 for the reaction of 4-methoxyiodobenzene with
◦
phenyl acetylene at 90 C in PEG 400. Analysis of the reaction mix-
ture by GC showed the conversion to the desired product after 2 h
to be around 42–50% whereas, similar reaction in the absence of
poisoning additive was performed in 2 h with 90% isolated yield
(Table 6, Entry 2). Therefore, we may conclude that the catalyst acts
◦
as a heterogeneous–homogeneous catalyst at 90 C. The heteroge-
neous part of the catalyst is responsible for the above mentioned
conversion whereas, the homogeneous part of the catalyst per-
forms the rest of the reaction. However, by cooling the reaction
mixture to room temperature, absorption of the homogeneous Pd
species to the surface of agarose molecules can occur which after

H. Firouzabadi et al. / Journal of Molecular Catalysis A: Chemical 357 (2012) 154–161
161
separation of the agarose catalyst it can be used for another batch
of the reaction.
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In this study, we have applied agarose which is a non-
toxic, cheap, degradable natural product which can be used
for the entrapment and ligation with Pd(0) species for
Mizoroki–Heck reaction under phosphane and solvent-free
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The authors are thankful to Shiraz University Research Council
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helpful discussions and the Institute for Advanced Studies in Basic
Sciences (IASBS) for the support.
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Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2012.02.006.
[
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