Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

Article abstract of DOI:10.1039/c6gc03377f

Chitosan (CS) is a porous, self-standing, nanofibrillar microsphere that can be used as a metal carrier. Amino groups on CS enable to modulate cobalt coordination using a safe organic ligand (methyl salicylate). This catalyst efficiently promotes Heck cross-coupling of a large library of functional substrates under mild and sustainable conditions (polyethylene glycol as solvent at 80 °C in a short time (1 h)). The cobalt complex was also used as a heterogeneous, efficient, inexpensive, and green catalyst for Sonogashira cross-coupling reactions. The reactions of various aryl halides and phenylacetylene provided the corresponding products in moderate to good yields. More importantly, this phosphine, copper, and palladium-free catalyst was stable under the reaction conditions and could be easily reused using an external magnet for at least five successive runs without a discernible decrease in its catalytic activity.

Full text of DOI:10.1039/c6gc03377f

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Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co
nanoparticles immobilized on magnetic chitosan as reusable
catalyst
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Abdol R. Hajipoura,b* Fatemeh Rezaeia and Zahra Khorsandia
www.rsc.org/
The chitosan (CS) is a porous self-standing nanofibrillar microspheres which can be used as a metal carrier. Amino-groups
on CS enable to modulation of cobalt coordination using safe organic ligand (methyl salicylate). This catalyst efficiently
promote Heck cross-coupling of
a large library of functional substrates under mild and sustainable conditions
(polyethylene glycol as solvent at 80 °C in short time (1 h)). The cobalt complex was also used as a heterogonous efficient,
inexpensive and green catalyst for Sonogashira cross-coupling reactions. The reactions of various aryl halides and
phenylacetylene provided the corresponding products with moderate to good yields. More importantly, this phosphine,
copper and palladium-free catalyst is stable under the reaction conditions and can be reused easily by an external magnet
for at least five successive runs without discernible decrease in its catalytic activity.
mesoporous silicas represent some advantages while their
porous system is instable in aqueous and basic conditions,
Introduction
The carbon−carbon bond forming reacꢀon is one of the most
important reaction in organic synthesis and in the
pharmaceutical, agrochemical, and fine chemical industries.1-3
So, improvement of efficient methodologies for generating
carbon−carbon bonds received considerable aꢁenꢀon.4-8
However, performance of convenient, safe, green and
necessary for cross coupling catalysis.24-25 In this regards uses
of environment-friendly polymer supports are very promising
due to low cost and less toxicity.26 Chitosan, a byproduct of the
fishing industry, is a linear polysaccharide which known as
important family of bioresources with enormous potential
functionalization properties due to the presence of free amino
and alcoholic groups.27
inexpensive approaches have proved to be
challenging problem.
a serious
Currently, magnetic nanoparticles (MNPs) supports provides a
very useful separation approach with an external magnet.
Meanwhile, various metal complex immobilized on MNPs have
been developed the more stable, efficient and user-friendly
catalysts in a number of C–C coupling reactions.28 To date
there are only a few examples of metal-chitosan anchored to
MNPs with the catalytic behaviour in the organic
transformations.29
Considering to economical and environmental factors,
encourage to our previous work on cobalt-catalyzed C–C-
coupling reactions30-32 and on successfully prepared of an
environmentally friendly and heterogeneous palladium-based
catalyst supported on chitosan and their good performance in
cross-coupling reaction,33 we designed and prepared cobalt
tagged on MNPs-chitosan functionalized with methyl salicylate
Over the past decade there has been an increased focus on
cross coupling reactions using novel transition-metal
catalysts.9 The high cost and toxicity of palladium complexes10
has stimulated the search for alternative affordable transition
metal catalysts, including nickel,11 copper,12 iron13 and cobalt14-
16 to the more sustainable metal-free cross-coupling catalysis.17
Unfortunately, these approach in homogeneous catalysis and
appalling harsh reaction conditions appears to be promising;
so, using novel catalyst which can overcome to these
limitations is required.
Indeed, a large library of inorganic and organic supports have
been already applied including charcoal, inorganic silica,
alumina and synthetic polystyrene. For instance, carbon
nanotubes exhibits unique features;18-22 but, it have been
found as a serious health hazard material through assessment
on its toxicity and environmental health risks.23 As well as
(Co-MS@MNPs/CS) as
a new highly stable catalyst and
investigated its application in Heck and Sonogashira reactions.
The Sonogashira reaction is one of the most valid metal-
catalyzed carbon–carbon cross-coupling reactions of aryl
halides with terminal acetylene.34-42
The original catalytic system for Sonogashira couplings contain
the use of palladium catalyst and a co-catalyst of copper (I)
salt.34 Many different synthetic methods based on copper free
palladium catalysts have been reported for this reaction.42 But
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the use of effective palladium-free systems is much more
interesting in view of modern organic synthesis, due to the
high cost and toxicity of palladium. Recent attention has been
concerned with employing copper-only catalytic systems in
Sonogashira coupling reactions. To overcome some
disadvantages of this more economical catalytic systems, such
as unrecoverable or complicated recovery and instability of the
copper(I) salt, using other types of metal complexes
immobilizing on solid supports such as cobalt would be logical
and interesting. In continuation of our recent studies on the
development of green catalytic systems for Sonogashira cross-
coupling reactions.44-46 Herein, we report the new palladium
and copper free catalytic system using cobalt complex. To the
best of our knowledge, Sonogashira reactions employing
heterogonous cobalt complexes were not reported previously.
Cobalt-catalyzed couplings are of interest in organic synthesis,
because cobalt is readily available, non-toxic, low-cost, stable
and exhibits powerful catalytic activities.47-49
For the Heck reactions, in spite of rarity of using cobalt catalyst
in this reaction, a few reports which refer to the application of
cobalt catalysts in this coupling reaction are available.50-53 For
example, in 2009, Qi et al. reported Heck reaction using cobalt
nanoparticles during long reaction time at extremely high
temperature (150 °C).50 Application of uniform Co−B
amorphous alloy nanoparticles as catalyst in C–C coupling
reaction was also described by Zhu and his co-workers in 2012
(at 120 °C using DMF/water as solvent and during 12–24 h).51
These reported cobalt catalysts have various advantages such
as good mechanical and excellent chemical stabilities and
better economic and ecological properties compared to
palladium catalysts. In contrast, they exhibited lower activity in
Mizoroki–Heck reaction in an expanded range of aryl halides,
in spite of spending high temperature and long reaction time.
Therefore, to overcome these problems, more convenient
approaches using a cobalt catalyst are required.
In the present Letter, we wish to report a new green and
inexpensive strategy for Mizoroki–Heck and Sonogashira
coupling reaction. Therefore, the cobalt was supported on
magnetic chitosan applying methyl salicylate as a green and
safe ligand for the first time. Using our catalytic system, the
reaction conditions can be improved and it accelerated the
Heck reaction without using palladium and phosphine.
Moreover, it is an effective catalyst for palladium and copper
(I) free Sonogashira cross-coupling reactions.
Scheme 1. Synthesis of the catalyst
The synthesis of CS-supported Pd(II) has been reported in the
literature, as well as CS-imine derivatives used in C–C coupling
reactions.54-55 Studies on the structure of CS supported ligand-
free Pd(II) have been also reported56 However, as we know,
only a few reports refer to the application of such complexes
in coupling reactions,57 Opportunely, this is the first report of
application of magnetic CS-supported Co catalyst in Heck and
Sonogashira coupling reactions without any co-catalyst and
additives.
Our catalytic system in comparison with previous unrecyclable
palladium-free catalysts,58-60 not only is low cost, but also are
readily prepared in few steps from available starting materials
and can remove easily from the reaction media due to its
ferromagnetic nature. This is very important because the
remaining metal-based catalyst in the product can be unsafe;
especially in the cases that the end product is directly related
to human life such as in pharmaceutical synthesis.
Furthermore, the nan size characteristic catalysts provides a
large accessible surface area for better interaction with
reactants in the media with applying small amount of the
catalysts in short times.
In the FT-IR spectrum of chitosan (Fig. 1(a)), the characteristic
absorption bands appeared at 1641 cm-1 ascribe to N-H
bending vibration. The presence of a strong band at 565 cm-1
was related to the Fe-O band in MNPs and MNPs/CS. The 1383
cm-1 band is related to the C-O stretching of primary alcoholic
group of chitosan in MNPs/CS and the peak around 3422 cm-1
ascribe to O-H and N-H groups vibrations. (Fig.1 (b) and (c)). In
comparison of the spectrum of chitosan composite with those
of MNPs/CS, the 1641 cm-1 peak of N-H bending vibration
shifted to 1615 cm-1. In final catalyst, the absorption bands
which appear in the spectrum at 1657 cm-1 and 754 cm-1
correspond to C=O group and aromatic C-H angular out- of-
plan deformation, respectively. (Fig.1 (d)).61
Results and discussion
A novel synthetic method was used for the preparation of a
Co-MS@MNPs/CS complex in the form of a recyclable solid
catalyst (Scheme 1). The NH2 functional group in CS was
reacted with methyl salicylate, yielding salicylic-functionalized
chitosan via an amide bond formation. Then, the resulting
salicylic acid-functionalized chitosan was treated with cobalt
salt to form the complex as shown in Scheme 1. These
processes were monitored by FT-IR, thermogravimetric
analysis (TGA) and elemental analysis.
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Table 1. Thermogravimetric analysis (TGA) and elemental analysis (EA)
results
Sample
Organic
[Wt. %]
Organic
[mmolg-1
MNPs]
0
EA (wt%)
Total
C
H
-
N
-
MNPs
MNPs/CS
MS@MNPs/CS
aChitosan; bChitosan+ methyl salicylate
0
-
0
61a
70b
3.84a
2.629 0.473 0.438 3.54
1.996 0.227 0.166 2.39
2.45b
The XRD spectrum (Fig. 3) provided more evidence for the
presence of cobalt and iron in the catalyst. As presented in Fig.
3, 8 characteristic diffraction peaks 2θ = 30.1°, 35.5°, 43.1°,
47.2°, 53.5°, 57.0°, 62.6° and 75.1° can be clearly considered
for Fe3O4 nanoparticles, which are related to the cubic phase
of Fe3O4. According to Fig. 3, characteristic diffraction peaks
2θ= 33.1°, 38.0°, 58.6° and 62.1° confirms the crystalline
nature of the cobalt species, which are related to the cubic
phase of cobalt nanoparticles.
Figure 1. FT-IR spectra: (a)MNPs; (b)MNPs/CS (c) MS@MNPs/CS;
(d)Co-MS@MNPs/CS
The amount of organic moieties in the magnetic chitosan-
functionalized methyl salicylate cobalt complex Co-
MS@MNPs/CS was determined by TGA and elemental analysis.
The total amount of organic moieties on MS@MNPs/CS was
about 2.3 mmolg-1. The weight loss of MNPs/CS between 30–
800 ºC as a function of temperature was determined using
TGA, which is an irreversible process because of thermal
decomposition. The TGA plots of MNPs/CS and Co-
MS@MNPs/CS (Figure 2) depict
a
two-step thermal
decomposition. The first step of weight loss in the cases
corresponds to the removal of physically adsorbed water,
whereas, the main weight loss in the second step is due to the
removal of organic moieties on the surface. The TGA results
are summarized in Table 1. The observed total weight losses
for MNPs, MNPs/CS and MS@MNPs/CS are 0 %, 61 % and 70
%, respectively. A good agreement was observed between
elemental analysis and TGA data (Table 1).
After preparation and characterization of MNPs/CS-MS, the
cobalt were immobilized onto this ligand. As shown in Scheme
1, the cobalt immobilized on magnetic chitosan-functionalized
with methyl salicylate (Co-MS@MNPs/CS) was prepared by
addition of cobalt chloride in ethanol at 80ºC in the presence
of MNPs/CS-MS.
Figure 3. XRD pattern: (a)MNPs/CS and (b)Co-MS@MNPs/CS
The morphology of the surfaces of Co-MS@MNPs/CS were
studied by field emission scanning electron microscopy (FE-
SEM) (Figure 4). The energy dispersive X-ray (EDX) results,
obtained from SEM analysis for the Co-MS@MNPs/CS clearly
show the presence of cobalt nanoparticles in catalyst.
Further characterization of catalyst was performed by
transmission electron microscopy (TEM). The TEM images
showed well-defined spherical Co particles dispersed in
MNPs/CS (Figure 5). The size distribution of Co nanoparticles
was about 13.5 nm, indicating that cobalt nanoparticles did
not aggregate upon immobilization on MNPs/CS. All these
observations indicate that the magnetic chitosan
functionalized with methyl salicylate polymer is a good host
and ligand for cobalt nanoparticles.
The cobalt content of the catalyst, measured by ICP, showed a
value 2.17 mmolg-1.
The magnetization curves of catalyst was shown in Figure 6,
the magnetization value for Fe3O4 is equal to 69.4 emu/g and
for catalyst is equal to 21.1 emu/g. This investigation proved
the paramagnetic behaviour of catalyst which is found
significantly lower than the bulk magnetite due to the coating
of magnetic nanoparticles with chitosan.
Figure 2. TGA thermogram: (a)MNPs; (b)Cs (c)MNPs/CS (d)
MS@MNPs/CS
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Figure 6. Room temperature magnetization curves of catalyst
Table 2. Optimization of reaction conditions on Heck reaction of
iodobenzene with methyl acrylate in the presence of catalysta
Figure 4. (a) FE-SEM images and (b) SEM-EDX spectra of catalyst
Entry Cat
(mg/mol%Co)
Base
Solvent
Temp.
(ºC)
100
100
100
100
100
100
100
100
100
80
Yieldb
(%)
81
89
67
82
81
85
79
91
-
89
43
-
88
77
-
1
2
3
4
5
6
7
8
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
10/2.2
5/1.1
K2CO3
K2CO3
K2CO3
K2CO3
Li2CO3
DMF
DMSO
NMP
PEG
PEG
NaHCO3 PEG
KOH
K3PO4
-
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
PEG
PEG
PEG
PEG
PEG
PEG
PEG
PEG
PEG
9
10
11
12
13
14
15
50
r.t.
80
80
2/0.5
-
80
aThe reaction was carried out with iodobenzene (1.0 mmol), methyl
acrylate (1.1 mmol), base (4 eq.) solvent (3.0 mL) for 1 h.
bGC yield
Encouraged by our initial studies, we then examined the
generality and versatility of this supported cobalt-catalyzed
Mizoroki–Heck cross-coupling of aryl halides with olefins. As
can be seen in Table 3, under the optimized conditions, a
diversity of aryl iodides, bromides and chloride containing
electron-donating and electron-withdrawing substituents
reacted efficiently with methyl acrylate and styrene under air
atmosphere at relatively mild conditions of 80 ºC to afford the
desired cross-coupling products in high yields (Table 4, entries
1–14). The experimental results showed that the electronic
properties of the substituents on the aromatic rings of the
starting materials had no significant effect on the reaction,
however, aryl iodides were found to be more reactive than aryl
bromides.32 Among aryl halides, aryl chlorides are ideal
substrates for coupling reactions due to they are inexpensive
and widely available comparison to their bromide or iodide
counterparts. The first step in catalytic coupling reactions
(oxidative addition) disfavour in aryl chlorides substrates
because of high strength of C-Cl bond. The most reported
methods required high loadings palladium catalyst and harsh
conditions; anyway they show little or no activity with aryl
Figure 5. (a) TEM images and (b) particle size distribution for catalyst
To test the catalytic activity of the Co-MS@MNPs/CS, it was
applied in the Mizoroki-Heck and Sonogashira reaction.
Initially, the Heck cross-coupling of iodobenzene with methyl
acrylate in the presence of catalyst was chosen as a model for
the optimization of reaction parameters such as the base and
solvent types, temperature and catalyst loading. The results
are summarized in Table 2. The model reaction was first
performed in the presence of different bases such as K2CO3,
Li2CO3, KOH, NaHSO4 and K3PO4; amongst them K3PO4 was
found to be the most effective base. Then, the same reaction
was carried out in different solvents. Among the solvents
examined, PEG was proved to be the best reaction medium.
The effects of the amount of catalyst were also explored; the
best result was obtained using 5 mg of catalyst. Therefore, it
was concluded that the optimum reaction conditions involved
iodobenzene (1 mmol), methyl acrylate (1.1 mmol), K3PO4 (4
mmol) and Co-MS@MNPs/CS (5 mg) in PEG (3 mL) at 80 ºC
(Table 2, entry 13).
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chloride substrates. In order to further explore the efficiency
and applicability of this method, the cross-coupling of aryl
chlorides with olefins was also checked under the same
conditions. Aryl chlorides proceeded smoothly in the presence
of the same catalyst amount as used for aryl iodides and
bromides. It is important to note that reported cobalt catalytic
system, used in Heck reaction, was totally inactive for aryl
chlorides.31,32,51 Herein, we report good results in Heck
coupling of less reactive aryl chloride derivatives with olefins in
presented cobalt catalyst for the first time.
Table
4
.
Optimization of reaction conditions on Sonogashira
reaction of iodobenzene with phenyl acetylene in the presence of
catalysta
Entry Solvent
base
NaHCO3
Li2CO3
K3PO4
KOH
-
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
Cat (mg) Temp. (ºC) Yieldb(%)
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMSO
DMSO
EtOH
10
10
10
10
10
10
10
10
10
10
10
-
140
140
140
140
140
140
140
140
120
100
80
51
56
68
72
-
-
PEG
DMF
11
69
39
16
-
It is noteworthy that, based on NMR spectra, in all Heck
olefination reactions, the trans-product was obtained with
100% selectivity.
9
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
10
11
12
13
14
15
Table 3. Scope of Mizoroki–Heck cross coupling reactiona
140
140
140
140
-
5
10
20
31
72
74
X
W
MNPs@Cs-MS-Co
W
K3PO4, PEG, 80( C)
aThe reaction was carried out with iodobenzene (1.0 mmol), phenyl
acetylene (1.1 mmol), base (4 eq.) solvent (3.0 mL) for 10 h.
bGC yield
R
R
Entry
X
R
Olefin
Yieldb (%)
1
2
3
4
5
6
7
8
I
I
I
H
MA
MA
MA
MA
MA
MA
MA
MA
MA
MA
MA
MA
88
92
90
81
87
79
73
67
41
53
71
65
45
75
79
71
69
71
63
49
35
15
22
57
41
30
Using the optimized reaction conditions,
a variety of
4-OMe
3-Me
H
4-OMe
4-NO2
2-Me
2-Cl
4-CHO
2-NO2
H
4-CN
3-NO2
H
4-OMe
3-Me
H
4-OMe
4-NO2
2-Me
2-Cl
4-CHO
2-NO2
H
4-CN
3-NO2
structurally divergent aryl iodides, bromides and chlorides was
used in the reaction with phenyl acetylene to generate the
desired coupling products in (Table 5).
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
I
Table 5. Sonogashira cross-coupling of various aryl halides in the
presence of catalysta
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
MNPs@Cs-MS-Co
X
R
KOH, DMSO, 140( C)
R
R"
R"
MA
Entry
1
2
3
4
5
6
7
8
R
R”
H
H
H
H
H
H
H
H
H
H
H
H
H
H
X
Time(h)
10
10
10
10
12
12
12
12
12
12
12
24
24
24
12
12
Yieldb (%)
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
H
I
I
I
I
72
69
80
78
56
45
58
61
53
52
55
-
-
-
57
43
66
61
I
I
I
4-OMe
4-NO2
4-COCH3
H
4-OMe
4-COCH3
4-NO2
4-Cl
4-COH
2-NO2
H
4-NO2
4-NH2
4-COCH3
4-OMe
4-COCH3
4-OMe
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Br
Br
Br
Br
9
10
11
12
13
14
15
16
17
18
aThe reaction was carried out with aryl halide (1.0 mmol), alkene
(1.1 mmol), K3PO4 (4.0 equiv.) in 3.0 mL PEG, 5 mg of catalyst (1.1
mol % of Co) at 80 ºC for 1 h.
4-Me
4-Me
2-NO2
2-NO2
bIsolated yield
12
12
aThe reaction was carried out with aryl halide (1.0 mmol), phenyl
acetylene (1.1 mmol), KOH (4.0 equiv.) in 3.0 mL DMSO , 10 mg of
catalyst (2.2 mol % of Co) at 140 ºC .
Encouraged by the obtained results in the Heck cross-
coupling, we then investigated the potential of our Co-
MS@MNPs/CS catalyst in the Sonogashira reaction. In order
to obtain the optimum experimental conditions, the reaction
of phenyl acetylene with iodobenzene was considered as a
model reaction in the presence of our catalyst.
The effects of the reaction conditions such as the type of base
and solvent, temperature and catalyst amount was tested and
a summary of the optimization experiments is provided in
Table 4. As can be seen, the best result was obtained using
iodobenzene (1 mmol), phenyl acetylene (1.1 mmol), KOH (1.5
mmol) and 10 mg of Co-MS@MNPs/CS (1.1 mol% Co) in DMSO
at 140 ºC (Table 4, entry 14).
bIsolated yield
The corresponding alkyne products were obtained in moderate
to good yields. The electronic and steric effects on the yields
was examined in this reaction system. This catalyst was
compatible with a wide range of functional groups such as
nitro, methoxy and carbonyl on the aryl halides. Aryl halides
substituted with electron-withdrawing groups in comparison
with electron-donating substituents gave better conversions.
As can be seen in Table 5, aryl iodides were converted to the
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corresponding Sonogashira products in good yields. The small amount (less than 1%) of cobalt metal was removed
reactivity of aryl bromides was lower than that of aryl iodides from the catalyst.
and they required longer times giving lower yields. Aryl
chlorides were inactive in this reaction system.45
Table 6. Recyclability in the Mizoroki–Heck reaction
Run
1
Yielda,b
88
Yielda,c
The Co-MS@MNPs/CS display high activities which may be
related to good dispersion and small size of cobalt
nanoparticles and good synergistic effects of cobalt
nanoparticles with ligand which grafted on MNPs-Cs.
53
50
46
-
2
88
3
86
4
85
According to previous studies;62-63 dendritic and highly
branched polymers are spherical three-dimensional
5
83
-
aIsolated yield
macromolecules. Due to their structure and multiple internal bcatalyst (Co-MS@MNPs/CS)
and external functional groups, these can selectively act as
cCo@MNPs/CS
suitable hosts for a wide range of ions and molecules and the
immobilization of nanoparticle-based catalytic systems on
these solid supports makes the catalyst recyclable and
reusable, and minimizes the leaching of the particles. To
investigate the effect of ligand (MS), the efficiency and
reusability of Co@MNPs/CS in Heck cross-coupling reaction
was investigated and compared with our catalyst Co-
MS@MNPs/CS. The results which given in Table 7 confirmed
the good and effective role of ligand (MS) in our catalyst.
Nevertheless, reusability of Co@MNPs/CS in the Mizoroki–
Heck reaction was also studied and it was reused three times
without significant loss of activity, the results was given in
Table 6
Figure 8. TEM of recovered catalyst.
Leaching of metal ions is a serious problem for supported
metal catalysts, and prevents catalyst separation and recycling.
To explore the leaching of the catalyst, two similar control
experiments were performed. To this end, the reaction
between iodobenzene and methyl acrylate was carried out
simultaneously in two different vessels under the exactly same
conditions. In each case, the reaction progress was monitored
using GC, after 30 min the catalyst were separated from one of
these vessels using magnetic bar, while the other was
remained unchanged. Thereafter, both of the reactions were
continued under the same conditions. After another 30 min,
both the reactions was stopped and their completion was
again examined using GC. The results showed that the
reactions in the absence of the catalyst were not proceeded
any more, while the reaction in other vessel was improved. In
fact, the leaching phenomenon does not present here. This
result suggested that this novel catalyst was heterogeneous in
nature perhaps because of the specific nature of designed
catalyst.
Moreover, the catalyst recycling is an important property from
economic, environmental and industrial points of view.
Therefore, the catalyst reusability was checked in the
Mizoroki–Heck reaction of iodobenzene (1.0 mmol) and
methyl acrylate (1.1 mmol). At the end of each reaction, the
catalyst was separated, using an external magnetic field,
washed with ethanol and acetone and reused. As reported in
figure 2, the catalyst was reused five times without significant
loss of activity. The yield for the fifth run is 84 % for the
heterogeneous catalyst. The TEM images of recovered catalyst
was also investigated. As shown in Fig. 8. TEM micrographs
indicate that the nano-sized particles have been well
distributed in the recovered catalyst; although some
aggregations are observed. Therefore, it can be realized that
the nano-sized particles in catalyst was preserved after use in
the reaction media. Additionally, ICP of catalyst was carried
out after five reuses and the results showed that only a very
Nevertheless it should be noted that, to the best of our
knowledge, this phosphine and palladium-free catalyst is one
the rare demonstration of the combination of cobalt and
organic ligands supported onto magnetic chitosan to generate
a high efficient and recyclable catalyst which can be used more
than five time without any considerable loss of its catalytic
activity. In addition, this is efficient catalytic system which
result the Mizoroki–Heck cross-coupling reactions in
significantly faster reaction times, lower temperatures and
greener media (moderate temperature and safe metal and
32-33
green media) in comparison with current methods.51-53,
The present catalytic method was compared with some
procedures published for the Mizoroki–Heck reaction of
iodobenzene and methyl acrylate in the literature, and the
results are shown in Table 7. Evidently, the reaction conditions
are mild, but the most important benefits of this study are
contributed to the advantages of heterogeneous catalysis such
as easy separation, efficient recycling, minimization of metal
contamination and low cost.
Experimental
General procedure for the catalyst preparation
The magnetic nanoparticles (MNPs) were prepared according
to the literature.64 based on precipitation of magnetite
nanoparticles from the mixture of iron (III) chloride and iron(II)
sulfate by ammonia (25% solution in water). Subsequent, in a
round-bottom flask equipped with mechanical stirrer and
condenser a mixture of magnetic nanoparticles and sodium
sulfate (20%, W V) was added to a soluꢀon of chitosan (1%,
W V) in aceꢀc acid (2%, W V) on sꢀrring.
6 | J. Name., 2012, 00, 1-3
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Table 7. Comparison of catalytic activities of our catalyst with literature examples for Heck reaction between iodobenzene and methyl acrylate
Entry
Catalystref
Nano Co50
Co/Al2O3
Reaction conditions
Time (h)
Yield (%)
78
56
85
98
85
87
53
88
1
2
3
4
5
6
7
7
Co (2 mol%) in NMP at 130 ºC
Co (10 mol%) in NMP at 150 ºC
Co (2 mol%) in NMP at 140 ºC
Co (5 mol %) in water/DMF (5/5) at 130 ºC
Co (3.5 mol %) in PEG at 80 ºC
Co (5 mol %) in toluene at 100 ºC
Co (1.1 mol %) in PEG at 80 ºC
Co (1.1 mol %) in PEG at 80 ºC
14
24
16
12
5
3
1
1
53
Nano Co52
Co-B51
Co–NHC@MWCNTs32
Co-IL@MWCNTs33
Co@MNPs/CS
Present catalyst
It was continued for 1h to obtain the aqueous suspension of
MNPs/CS. After this time, the magnetic nanoparticles were
separated from the reaction mixture by an external permanent
magnet, washed with ethanol and methanol several times and
dried under vacuum at 70 ºC. For the preparation of supported
methyl salicylate ligands, a solution of ethanol suspension of
MNPs/CS (1.5 g/10 mL) was added to methyl salicylate (6.5
mmol) and the mixture was stirred at 60 ºC for 24h. The final
Co-MS@MNPs/CS was obtained as a brown solid by addition
of CoCl2.6H2O (4.2 mmol) solved in 10 mL ethanol to dispersed
mixture of MNPs/CS-MS (1.01 g) in ethanol (5 mL) and stirred
at 60 ºC for 18 h. The resulting complex was collected by an
external permanent magnet and washed with ethanol (3 × 10
mL) to remove the unreacted materials and finally dried under
air (89 % yield based on the amount Co in the catalyst
determined by ICP).
To summarize, this work highlights the multifaceted
advantages of CS as a sustainable material for textural
engineering of macroporous supports, while chemical
modification of its amino groups with safe and green organic
compounds such as methyl salicylate allows the tuning of the
metal-support interaction. Mild and sustainable reaction
conditions (palladium and copper-free, polyethylene glycol as
solvent, 80 °C) enables Heck cross coupling catalysis to be
performed in good yields with low metal contamination, easy
and good recyclability. This straightforward and sustainable
chemistry affords useful and eco-efficient catalysts bearing
many useful properties: their green and easy conditions to
produce catalyst (without using toxic agents and solvent) and
good efficiency in Heck and Sonogashira coupling reaction. In
generally, this work presents the first example of the
application of functionalization of magnetic chitosan with
methyl salicylate to prepare the stable heterogonous cobalt
complex. The requirement energy and time for the Heck
reaction extremely minimized in this method compared to
previously report cobalt-catalyzed Heck cross-coupling
reactions as an inevitable trend in development of green
chemistry. Moreover, it is the first report of applying cobalt
catalyst in Sonogashira reaction.
General procedure for the Heck reaction
In a round-bottom flask equipped with a mechanical stirring, a
mixture of K3PO4 (4 eq), olefin (1.1 mmol) and aryl halide (1
mmol) in solvent (3 mL) were added 5 mg of catalyst (1.1 mol%
of Co) and equipped with a condenser for refluxing. The above
mixture was heated at 80 ºC in an oil bath. The reaction’s
progress was monitored by TLC (hexane/EtOAc, 80:20) and gas
chromatography (GC). After completion of the reaction the
mixture was diluted with dichloromethane and water. The
organic layer was washed with brine, dried over anhydrous
MgSO4, and concentrated under reduced pressure. The residue
was purified by column chromatography. The products were
characterized by comparing their physical pmroperties m.p.,
IR, 1H, 13C NMR spectra with those found in the literature.65-69
Acknowledgements
We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT), IR
Iran, Further financial support from the Centre of Excellence in
Sensor and Green Chemistry Research (IUT) is gratefully
acknowledged.
General procedure for Sonogashira reaction
In a round- bottomed flask equipped with a mechanical
stirring, phenyl acetylene (1.2 mmol), aryl halide (1.0 mmol),
catalyst (10mg) and KOH (2eq) in DMSO (3 mL) were stirred
under air atmosphere at 140 ºC. The progress of the reaction
was monitored using TLC and GC. After completion of the
reaction the mixture was diluted with dichloromethane and
water. The organic layer was washed with brine, dried over
anhydrous MgSO4, and concentrated under reduced pressure.
The product was isolated by column chromatography to afford
the corresponding products in yield of 55-80%. The products
were characterized by comparing their physical properties
m.p., IR, 1H, 13C NMR spectra with those found in the
literature.
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