Efficient C-C cross-coupling reactions by (isatin)-Schiff base functionalized magnetic nanoparticle-supported Cu(II) acetate as a magnetically recoverable catalyst

Article abstract of DOI:10.3906/kim-1506-32

Copper catalysts were simply fabricated through surface modification of superparamagnetic iron nanoparticles with indoline-2,3-dione(isatin)-Schiff-base and interaction with Cu from low-cost commercially available starting materials. Catalysts were characterized using atomic absorption spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, vibrating sample magnetometry, UV/Vis spectroscopy, scanning electron microscopy, and transmission electron microscopy. These catalysts showed high efficiency for phosphine-free Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions with good diversity and generality. The catalysts could be easily recovered and reused several times without a significant loss in their catalytic activity and stability.

Full text of DOI:10.3906/kim-1506-32

Turk J Chem
Turkish Journal of Chemistry
(2015) 39: 1232 – 1246
¨
http://journals.tubitak.gov.tr/chem/
˙
c
⃝ TUBITAK
doi:10.3906/kim-1506-32
Research Article
Efficient C–C cross-coupling reactions by (isatin)-Schiff base functionalized
magnetic nanoparticle-supported Cu(II) acetate as a magnetically recoverable
catalyst
Seyedeh Simin MIRI1, Mehdi KHOOBI2,3, Fatemeh ASHOURI4, Farnaz JAFARPOUR1,
Parviz RASHIDI RANJBAR1, Abbas SHAFIEE2,∗
1School of Chemistry, College of Science, University of Tehran, Tehran, Iran
2Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, Iran
3Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran, Iran
4Department of Applied Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch,
Islamic Azad University, Tehran, Iran
Received: 14.06.2015
•
Accepted/Published Online: 07.09.2015
•
Printed: 25.12.2015
Abstract: Copper catalysts were simply fabricated through surface modification of superparamagnetic iron nanopar-
ticles with indoline-2,3-dione(isatin)-Schiff-base and interaction with Cu from low-cost commercially available starting
materials. Catalysts were characterized using atomic absorption spectrophotometry, Fourier transform infrared spec-
troscopy, X-ray diffraction, thermogravimetric analysis, vibrating sample magnetometry, UV/Vis spectroscopy, scanning
electron microscopy, and transmission electron microscopy. These catalysts showed high efficiency for phosphine-free
Mizoroki–Heck and Suzuki–Miyaura cross-coupling reactions with good diversity and generality. The catalysts could be
easily recovered and reused several times without a significant loss in their catalytic activity and stability.
Key words: Copper, coupling, magnetic nanoparticles, catalyst, Schiff base
1. Introduction
C–C bond formation is one of the most commonly employed chemical transformations generally used in both
academic1 and industrial chemistry.2 Mizoroki–Heck and Suzuki–Miyaura cross-coupling reactions are the most
widely used methods for extensive production of key intermediates during preparation of natural,3 nonnatural,4
and bioactive compounds.5,6 Although homogeneous palladium complexes as conventional catalysts in cross-
coupling reactions have shown high reaction rates, suitable turnover numbers, and sometimes perfect selectivity
and yield, these types of catalysts suffer from the problem of recycling of the catalyst as well as instability
during reaction at high temperatures.7,8 Recoverability and reusability of the catalyst are a challenge from
environmental and economic points of view, especially when precious metal catalysts are used. In this regard,
magnetic nanoparticles (MNPs) can particularly meet this challenge due to their ability to easily separate
from liquid reaction media by an external magnetic field. Among various MNPs, magnetite (Fe3 O4) has
attracted considerable interest and has applications in various fields due to its large surface-to-volume ratio,
biocompatibility, nontoxicity, ease of synthesis, and surface functionalization.9,10
∗Correspondence: shafieea@tums.ac.ir
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MIRI et al./Turk J Chem
In addition, the type of ligand in transition metal cross-coupling is one of the pivotal factors determining
catalytic performance. Conventionally, homogeneous palladium/phosphine complexes were used in Mizoroki–
Heck and Suzuki–Miyaura reactions. However, limiting aspects of palladium catalysts like high cost and toxicity
have limited their immense applications on industrial scales.11 In recent years, copper catalytic systems have
been attracting more attention because of their low costs, biocompatibility, and increased catalytic ability in
comparison with palladium and other frequently used systems for catalyzing cross-coupling reactions.12−14
Since ligands can influence the selectivity and reactivity of transformations, careful choice of ligand is
required for functionalization of catalyst supports.15−21 Among the various applied ligands, nitrogen-containing
ligands and especially Schiff bases as potent organic ligands in coordination chemistry play an important role
in tuning the electronic properties of metal ions in complexes.22
Since isatin-based Schiff base ligands have shown variable denticities toward several metal ions,23,24
we were encouraged to fabricate a new magnetic copper Schiff base complex via surface modification of
superparamagnetic iron nanoparticles with an indoline-2,3-dione (isatin)-Schiff base and subsequent ligand
coordination with Cu (Scheme).
Scheme. The consecutive steps for preparing copper catalyst.
2. Results and discussion
2.1. Catalyst preparation and characterization
The sequential steps for stabilizing Cu(II) ions by indoline-2,3-dione (isatin)-Schiff base containing MNPs is
shown in the Scheme. Condensation reaction of Fe3 O4 @SiO2 –NH2 with isatin (Isa) was used to produce
a suitable interaction capacity of N–O Schiff base and metal species. An inductive coupled plasma-atomic
emission spectrometry (ICP) analyzer was used to determine the content of Cu and revealed the presence of
0.17 mmol/g. Fourier transform infrared (FT-IR) analysis was used to confirm the modification of the magnetite
1233

MIRI et al./Turk J Chem
surface with functional groups and also metal anchoring on the nanocomposite. The FT-IR spectra of Fe3 O4 ,
Fe3 O4 @SiO2 –NH2 , Fe3 O4 @SiO2 –Isa, and Fe3 O4 @SiO2 –Isa Cu(II) are shown in Figure 1. The absorption
band at 584–633 cm−1 in the MNPs is attributed to the stretching vibration of Fe–O, and the peak at 3415
cm−1 is assigned to the stretching vibrations of Fe–OH groups on the surface of the MNPs. The strong broad
band at 1000–1100 cm−1 corresponds to the stretching vibration of the Si–O–Si group and confirmed the silica
coating on the surface of Fe3 O4 . The bands at 2940 and 1446 cm−1 could be ascribed to the stretching
vibrations of C–H and C–N bonds, respectively (Figure 1, line b). After condensation of isatin with amine
groups of Fe3 O4 @SiO2 –NH2 , more peaks appeared at 1714 and 1621 cm−1 , which are due to the stretching
vibration of carbonyl and C=N bands, respectively. The FT-IR spectrum of the Cu(II) catalyst shows a red
shift in the carbonyl bond at a lower frequency (1708 cm−1) in comparison with the band for Fe3 O4 @SiO2 –Isa.
The stretching bands correspond to the carbonyl and C=N bonds of complexes show a red shift compared with
the Schiff base (Fe3 O4 @SiO2 –Isa) and appear at a lower frequency (Figure 1, line c in comparison with line
d). This could be attributed to the coordination of the carbonyl and C=N bands with copper ions.25,26
Figure 1. FT-IR spectra of (a) Fe3 O4 , (b) Fe3 O4 @SiO2 –NH2 , (c) Fe3 O4 @SiO2 –Isa, and (d) Fe3 O4 @SiO2 –Isa
Cu(II).
The thermogravimetric analysis (TGA) curves of Fe3 O4 , Fe3 O4 @SiO2 –Isa, and copper catalyst are
shown in Figure 2. Weight loss observed during heating from 50 to 200 ◦ C could be ascribed to the loss
of physisorbed water and other solvents on the particles during nanocatalyst procurement (Figure 2, line a).
Thermal decomposition of the immobilized Schiff base and corresponding complexes revealed the continuous
weight loss of organic moiety absorbed on the particle surface in the temperature range of 200–600 ◦ C. As
illustrated in Figure 2 (line b), the amount of Schiff base ligand loading on the surface of the MNPs is
approximately 8%. As a result, the nanocatalyst is stable up to at least 200 ◦ C.
The X-ray powder diffraction (XRD) patterns of naked Fe3 O4 and catalyst are shown in Figure 3. The
XRD results showed that diffraction peaks at 2θ of 30.09◦ , 35.7◦ , 43.3◦ , 53.85◦ , 57.31◦ , and 62.97◦ correlated
to diffraction of (220), (311), (400), (422), (511), and (440) of the Fe3 O4 nanoparticles were found in all samples.
Therefore, the multiple steps of catalyst preparation did not change the crystal structure of the Fe3 O4 cores.
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MIRI et al./Turk J Chem
The new peaks at 2θ = 40.33◦ , 59.57◦ , and 66.19◦ corresponding to the (111), (202), and (311) planes of
Cu+2 indicated the existence of Cu+2 in the catalyst.27 The broad peak that appeared at 2θ = 21–25◦ in
both catalysts is related to the amorphous silica shell on the surface of the MNPs28 The average crystallite
sizes of MNPs were estimated as 13.5 nm using the Scherrer equation.
Figure 2. TGA curves of (a) Fe3 O4 , (b) Fe3 O4 @SiO2 –Isa, and (c) Fe3 O4 @SiO2 –Isa Cu(II) catalyst.
Diffuse reflectance spectroscopy (DRS) was used for corroboration of oxidation states of Cu species in the
structure. The spectrum of Fe3 O4 @SiO2 –Isa Cu(II) shows higher absorption at ∼700–800 nm compared to
Fe3 O4 @SiO2 –Isa, which can be assigned to the Cu(II) d–d transition intensity in the presence of Fe3 O4 @SiO2 –
Isa Cu(II) (Figure 4).29−32 The Fe3 O4 @SiO2 –Isa Cu(II) and Fe3 O4 @SiO2 –Isa indicated a peak at 220 nm,
which can be attributed to the existence of the magnetic core.
10
9
8
7
a
6
5
b
4
3
2
1
0
200
400
600
800
1000
1200
1400 1600
Wavelength (nm)
Figure 3.
XRD pattern of (a) Fe3 O4 and (b)
Figure 4. DRS pattern of Fe3 O4 @SiO2 –Isa Cu(II) cat-
Fe3 O4 @SiO2 –Isa Cu(II) catalyst.
alyst (a) and Fe3 O4 @SiO2 –Isa (b).
The magnetic feature of Fe3 O4 MNPs and Fe3 O4 @SiO2 –Isa was measured with a VSM (vibrating
sample magnetometry) instrument (Figure 5, lines a and b, respectively). Base on the hysteresis loop, magnetic
1235

MIRI et al./Turk J Chem
saturation of Fe3 O4 MNPs and Fe3 O4 @SiO2 –Isa is 46.5 and 37.5 emu g−1 , respectively. The decrease in
mass saturation magnetization of Fe3 O4 @SiO2 –Isa could be ascribed to the nonmagnetic silica and organic
moieties. Although the σs values of the Fe3 O4 @SiO2 –Isa are decreased, the superparamagnetic properties
of nanoparticles have been still been preserved and the absence of remanence magnetization and coercivity
confirm this. The catalyst could be efficiently isolated magnetically from the solution and reused for several
runs (Figure 5).
Figure 5. VSM curve of Fe3 O4 MNPs (a) and Fe3 O4 @SiO2 –Isa (b); reaction mixture (c) and isolation of catalyst by
external magnet (d).
The SEM and TEM images of the catalysts are presented in Figures 6a–6c. According to these images,
most of particles have a narrow size distribution (the inset histogram of Figure 6c) with quasi-spherical shape.
The mean diameter of the nanoparticles was about 12 nm. These results are consistent with the average
crystallite sizes estimated from XRD by using Scherrer’s equation. Energy dispersive X-ray spectroscopy (EDS)
spectra were also used to determine the elemental composition of catalysts. EDS spectra of Fe3 O4 @SiO2 –Isa
Cu(II) clearly demonstrate the presence of Cu, Fe, and Si as well as other elements attributed to the organic
moiety. The presence of these signals confirms the successful preparation of catalyst and copper loading (Figure
6d).
2.2. Catalytic activity of catalysts in Mizoroki–Heck coupling reaction
The catalytic activity of the as-prepared Cu catalysts was investigated in Mizoroki–Heck coupling reactions. As
a model reaction, the coupling of iodobenzene and methyl acrylate was screened in order to find the optimized
conditions (Table 1). A careful view into the C–C cross-coupling reaction process indicates that the reaction
conditions have affected the yield of the Mizoroki–Heck reaction.33,34 The influence of different experimental
parameters, such as reaction time and amount of catalyst and base, were also optimized in the model reaction.
Among them, the best condition was obtained in the presence of Et3 N as base and DMF as solvent (Table 1,
entry 8). Using Cs2 CO3 as a strong base caused a decrease in the yield of the desirable stilbene due to the
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MIRI et al./Turk J Chem
formation of homocoupling products (Table 1, entry 4).35 The results showed that 1,4-dioxane and MNPs are
also effective (Table 1, entries 10 and 14). The same results were also obtained when the amount of the catalyst
was decreased to 0.33 mol% and temperature was decreased to 80 ◦ C (Table 1, entry 18). It was noted that,
as expected, temperature had a noteworthy effect on the effectiveness of the present catalytic system.
Figure 6. SEM images of Fe3 O4 (a) and Fe3 O4 @SiO2 –Isa Cu(II) (b); TEM image and particle size distribution
histogram of Fe3 O4 @SiO2 –Isa Cu(II) catalyst (particle size: 12 nm) (c); and EDS of Fe3 O4 @SiO2 –Isa Cu(II) catalyst
(d).
Because good yield of the product was acquired at 100 ◦ C, a variety of iodobenzenes and alkenes
including either aromatic or aliphatic alkenes with electron-donating or electron-withdrawing substitution were
1237

MIRI et al./Turk J Chem
investigated under the optimized reaction conditions (100 ◦ C). It was observed that the system for the coupling
reaction of aryl halides with alkenes can be adopted for the catalytic active and regioselective coupling (Table 2).
Table 1. Optimization of reaction condition for Heck coupling reaction of methylacrylate with iodobenzene in the
presence of Fe3 O4 @SiO2 –Isa Cu(II) catalyst.a
I
O
O
O
O
Entry Base
1
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Conversion (%)b
91
50
30
Trace
-
-
98
Na2CO3
2
3
4
5
6
7
8
KH2PO4
Na2HPO4
Cs2CO3
NaOAc
DABCO
K2CO3
NEt3
100
-
9
(CH3)3COK DMF
10
11
12
13
14
15
16
c17
d18
e19
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NMP
DMF
PEG
EtOH
1,4-Dioxane
Mesitylene
Ethylene glycol Trace
DMF
DMF
DMF
100
100
80
80
100
Trace
100
90
100
a Reaction conditions: iodobenzene (1.0 mmol), methylacrylate (1.1 mmol), base (2.0 mmol), solvent (5.0 mL), 120 ◦ C,
12 h, copper catalyst (0.82 %mol); b Checked by GC analysis; c Copper catalyst (0.33 %mol), 100 ◦ C; d Copper catalyst
e
(0.33 %mol), 80 ◦ C; 100 ◦ C, 8 h.
2.3. Catalytic activity of the copper catalyst in Suzuki–Miyaura coupling reaction
The efficiency of the Fe3 O4 @SiO2 –Isa Cu(II) catalyst in Mizoroki–Heck coupling reaction led us to study the
potential of this catalyst in the Suzuki–Miyaura cross-coupling reactions of aryl halides and arylboronic acids.
In order to optimize the reaction condition, coupling of 4-iodotoluene and 4-methoxyphenylboronic acid was
selected as the model reaction. Influence of different bases and solvents as well as the amount of the catalyst,
temperature, and time of the reaction were also investigated. The results showed that the model reaction can
be promoted in NMP and DMF with high yield (Table 3, entries 1 and 2). Due to the importance of green
solvent application in organic reactions, we examined the performance of ethanol as a green solvent in the
model reaction. Fortunately, excellent yield was obtained in the presence of K2 CO3 as the base in ethanol
solvent (Table 3, entry 3). However, addition of water slightly declined the yield of the reaction in comparison
with ethanol. The effects of different bases such as NEt3 , DABCO (1,4-diazabicyclo[2.2.2]octane), KH2 PO4 ,
1238

MIRI et al./Turk J Chem
Table 2. The copper catalyzed Mizoroki–Heck coupling reactions of various aryl iodides with terminal alkenes.a
I
R2
R2
R1
R1
Entry
1
Aryl iodide
Product
Time (h)
12
Conversionb (%)
90
Selectivityb (%)
86
I
I
Me
Me
2
3
4
5
12
15
12
15
96
65
97
90
75
90
95
I
OMe
MeO
I
Me
Me
I
OMe
78
91
e
OM
I
CF3
F3C
6
7
8
8
8
8
100
50
I
I
100
100
O
O
O
O
O
O
100
I
(CH2)3CH3
O
O(n-Bu)
9
8
76
100
90
72
55
80
90
90
90
70
O
O
I
10
11
12
13
8
N
C
NC
I
(CH2)9CH3
O
O
8
O(n-dedecyl)
O
Br
O
O
O
O
8
Me
Br
12
Me
Me
a Reaction conditions: the reactions were done in the present of copper catalyst (0.33 mol%) in the coupling reaction of
aryl iodide (1.0 mmol), alkene (1.1 mmol), and NEt3 (2.0 mmol) in DMF (5.0 mL) at 100 ◦ C in a sealed tube; b GC
conversion.
1239

MIRI et al./Turk J Chem
(CH3)3 COK, and Na2 CO3 were also studied. The best result was obtained by 0.33 mol% copper catalyst in
the presence of K2 CO3 in ethanol at 70 ◦ C for 5h (Table 3, entry 11). Changing the amount of catalyst and
temperature did not show meaningful improvement in the yield of the reaction.
Table 3. Optimization of effective factors in Suzuki–Miyaura cross-coupling reaction catalyzed by immobilized copper
complex.a
B(OH)2
I
Cu comple x
Me
OMe
MeO
Me
Entry Solvent
Base
Time (h) Conversionb (%)
1
2
3
4
5
6
7
8
DMF
NMP
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
K2CO3
K2CO3
K2CO3
KH2PO4
12
12
12
12
92
90
94
Trace
75
90
Trace
75
55
(CH3)3COK 12
Na2CO3
NEt3
DABCO
12
12
12
12
5
9
10
11
EtOH:H2O (1:1) K2CO3
EtOH
EtOH
K2CO3
K2CO3
94
94c
5
a Reaction conditions: 4-iodotoluene (1.0 mmol), 4-methoxyphenylboronic acid (1.2 mmol), base (2.0 mmol), solvent (5
mL), Fe3 O4 @SiO2 –Isa Cu(II) catalyst (0.82 mol%), 70 ◦ C in a sealed tube; b Determined by GC; c Copper catalyst
0.33 mol%.
The couplings between various aryl halides and arylboronic acids were investigated. As indicated in Table
4, good to excellent yields were obtained for various substrates. The reaction progressed reasonably well with
bromobenzene to afford the stilbene in good yield (70%) (Table 4, entry 2). Thus, the Fe3 O4 @SiO2 –Isa Cu(II)
catalyst is efficient for Suzuki–Miyaura cross-coupling reaction.
To evaluate the efficiency and stability of the catalysts during several runs, our study was concentrated on
the recyclability and reusability of these catalysts. After each catalytic run, catalysts were easily recovered by
a magnetic field, washed repeatedly with aqueous methanol, and dried under a vacuum at 50 ◦ C to be checked
in the next run. Leaching tests after each catalytic run in iodobenzene and methylacrylate coupling as a model
reaction under optimized conditions revealed that the amount of Cu leached from the heterogeneous catalyst
was negligible (less than 0.2 ppm) as determined by ICP-AES of the clear filtrate. This result shows that there
is no contribution from homogeneous catalysis of active Cu species leaching into the reaction solution.
A hot filtration test was also conducted to confirm that the reaction was indeed catalyzed by Cu
heterogeneous catalyst instead of free Cu. After the first catalytic reaction, the catalyst was simply separated
from the reaction mixture by an external magnet. The fresh reagents were then added to the filtrated solution.
The resulting mixture was stirred at 100 ◦ C. The conversion was negligible after adequate time (8 h). These
results confirmed that the coupling reaction could only proceed in the presence of the solid catalyst, and there
was no contribution from leached Cu species in the liquid phase.
Efforts were directed toward the study of recycling of such catalytic systems using the Mizoroki–Heck
reaction of iodobenzene with methyl acrylate. The supported catalysts were recovered by a magnetic field
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MIRI et al./Turk J Chem
Table 4. The Suzuki–Miyaura cross-coupling reactions of aryl halides with phenylboronic acids in the present of
Fe3 O4 @SiO2 –Isa Cu(II) catalyst.a
(HO)2B
Cu complex
X
+
R1
R2
R1
R2
X:Br, I
R2
R1
Aryl halide Product
Br
Conversionb (%)
OMe
1
2
3
4-Me
4-OMe
35
70
99
MeO
H
H
4-OMe
4-OMe
Br
MeO
I
4
4-Me
3-NO2
I
91
NO2
5
6
4-OMe
2-Me
4-OMe
4-OMe
I
I
MeO
OMe 99
94
MeO
F3C
7
2-CF3
4-OMe
I
85
MeO
8
9
2-Me
4-OMe
H
Br
I
40
92
MeO
MeO
4-OMe
OMe
10
2-OMe
H
I
85
MeO
11
12
2-OMe
4-Me
4-OMe
4-OMe
I
I
99
94
MeO
MeO
a Reaction conditions: aryl halide (1.0 mmol), phenyl borinic acid (1.2 mmol), K2 CO3 (2.0 mmol), Cu catalyst (0.33
mol%), EtOH (5 mL), 70 ◦ C, 5 h; b Determined by GC.
1241

MIRI et al./Turk J Chem
for the next reaction, washed with aqueous methanol, and dried under vacuum at 50 ◦ C to reactivate the
catalysts for the next run. The model reaction under the optimized conditions mentioned above was run for
five consecutive cycles repeating the regeneration process of two catalysts. There was a drop in the yield of
the reaction catalyzed by copper catalyst after the fourth cycle, which could be attributed to the leaching of
copper ions (Figure 7). ICP analysis result showed 6% deterioration of copper content at the fifth cycle. Lower
stability of copper catalyst for Suzuki–Miyaura reaction may be attributed to the metal leaching due to the
effect of protic solvent and high temperature of the reaction media.36
Mizoroki - Heck reaction Suzuki - Miyaura reaction
100
90
80
70
60
50
40
30
20
10
0
1
2
3
Run
4
5
Figure 7. Recovery of Fe3 O4 @SiO2 –Isa Cu(II) catalyst in Heck and Suzuki coupling reactions.
Considering published reports in this field, it has been revealed that some heterogeneous copper-catalyzed
cross-coupling reactions suffer from elevated temperature to obtain desirable results (Table 5, entries 2–4),12,37,38
low yield under the optimum conditions,39 or costly and difficult procedures40,41 for catalyst preparation (Table
5, entry 5, and Table 6, entry 2). In this study, not only was an efficient hybrid magnetic copper catalyst
conveniently prepared for the C–C cross-coupling reactions with a low level of the catalyst, but it also gave the
desired products in moderate to excellent yields without using bimetallic systems (Table 5, entry 6, and Table
6, entries 4–6).42−44
Table 5. Comparison of catalytic activity of various heterogeneous catalysts in the Mizoroki–Heck cross-coupling
reactions.
I
R2
R2
R1
R1
Temperature Yield (%)/
Entry R1
R2
Ph
Catalyst
Fe3O4@SiO2–Isa Cu(II)
Ref.
(◦C)
100
130
150
150
130
Time (h)
90a/8
70/24
40/48
70/48
99/40
91/18
1
2
4
3
5
6
H
H
H
This work
COOBu Copper bronze
Ph
12
37
38
40
42
Si-NH2-Cu(OAc)2
Cu/Al2O3
OMe Ph
H
H
COOBu Cu/PrePAN fiber mats
Ph
Pd/Cu (4:1) bimetallic NPs 100
aConversion.
1242

MIRI et al./Turk J Chem
In summary, we have presented a simple procedure for preparing a magnetically recoverable copper
catalyst with high efficiency for Mizoroki–Heck and Suzuki–Miyaura cross-coupling reactions with low price
for industrial applications. The catalyst showed good diversity and generality in both reactions. This method
requires remarkably small amounts of catalyst without any activator or any toxic ligand. The superparamagnetic
nature of the catalyst provides its easy isolation and reuse. In addition, high activity and selectivity, easy
separation of catalysts, and good performance in the recycling reaction are the valuable advantages of this
Fe3 O4 @SiO2 –Isa Cu(II) catalyst.
Table 6. Comparison of the catalytic activity of various heterogeneous catalysts in the Suzuki–Miyaura cross-coupling
reaction.
B(OH)2
Temperature (◦C) Yield (%) Ref.
I
Entry Catalyst
1
2
3
Fe3O4@SiO2–Isa Cu(II)
Cu nanocolloid
70
110
92a
62
This work
39
41
3D
tba)2](solvent)}
MOF{[Cu(4- 25
88
n
4
5
Cu-Pd bimetallic cata- 78
> 99
43
43
˚
lysts supported on 4A
molecular sieve
Cu, monometallic cata- 78
62a
˚
lysts supported on 4A
molecular sieve
Pd-Cu/C
6
78
97.5
44
aConversion.
3. Experimental
3-Aminopropyltriethoxysilane (APTES), tetraethyl orthosilicate (TEOS), isatin (Isa), and other chemicals and
solvents were purchased from Merck and used as received without further purification. Deionized water was
used throughout the experiments. All solvents were of analytical grade. TEM images were carried out using a
Philips EM208 at 100 kV. Metal existence, phase purity, and crystallinity of the sample were characterized by
XRD using a Philips X’Pert MPD with Cu Kα radiation. The UV-DRS of samples was recorded with a PE
Lambda 20 spectrometer. FT-IR spectra were obtained using a Bruker Equinox 55 spectrophotometer. ICP
was conducted on a Vista-MPX (Varian) for content determination of copper on supports. Conversion % was
determined by GC on a Shimadzu model GC-14A instrument. TGA results were obtained by TA Q50 V6.3.
SEM images were carried out on a Hitachi S-4160. EDS data were recorded on a VEGA3 XMU. Magnetic
properties of modified MNPs were studied by VSM (Meghnatis Kavir Kashan Co., Kashan, Iran).
3.1. Catalyst preparation
Preparation of Fe3 O4 nanoparticles: Fe3 O4 MNPs were prepared via the chemical coprecipitation method.45
An aqueous solution (100 mL) of FeCl2 .4H2 O (1.0 g, 5.0 mmol) and FeCl3 .6H2 O (2.6 g, 9.6 mmol) was mixed
under nitrogen atmosphere with vigorous stirring, and then NH4 OH (10 mL of 25 wt%, excess) was added
dropwise to the solution. The solution was heated to 70 ◦ C and kept at this temperature for 2 h. The resultant
black dispersion was cooled and separated from the solution with a permanent magnet and washed several times
1243

MIRI et al./Turk J Chem
with deionized water and ethanol until the pH value held at 7. The precipitate was dried in a vacuum oven at
80 ◦ C for 24 h.
Preparation of Fe3 O4 @SiO2 nanoparticles: Fe3 O4 MNPs (0.7 g) were dispersed in a mixture of ethanol
(40 mL) and deionized water (10 mL). To this dispersion, TEOS (0.3 mL) and NH4 OH (0.6 mL) were added
and the mixture was stirred vigorously at room temperature for 12 h. Silica-coated MNPs were magnetically
isolated by a permanent magnet, repeatedly washed with ethanol and deionized water, and finally dried in a
vacuum at 50 ◦ C for 24 h.46
General procedure for preparation of amine functionalized MNPs (Fe3 O4 @SiO2 –NH2) : presynthesized
Fe3 O4 @SiO2 MNPs (1.0 g) were well dispersed in anhydrous toluene and then an excess amount of 3-
aminopropyltriethoxysilane (0.7 mL, 0.66 g) was added dropwise to this dispersion. The mixture was refluxed
for 24 h under argon protection. The resulting amine functionalized MNPs were magnetically separated by
external magnet, washed with methanol and acetone several times, and dried in a vacuum oven at 50 ◦ C
overnight.47
Preparation of isatin functionalized MNPs (Fe3 O4 @SiO2 –Isa): the appropriate Schiff base was prepared
by condensation reaction of Fe3 O4 @SiO2 –NH2 with isatin. The solution of isatin (10 mmol) in ethanol (25
mL) was added dropwise to the dispersed Fe3 O4 @SiO2 –NH2 nanoparticles (1.0 g) in ethanol (25 mL). The
resulting mixture was refluxed under argon atmosphere for 24 h. The product was collected by an external
magnet and carefully washed with ethanol. Subsequently, it was treated by Soxhlet extraction with ethanol for
24 h to remove unreacted substrates and byproducts and finally dried at 50 ◦ C overnight in a vacuum oven.
Preparation of copper loading on Fe3 O4 @SiO2 –Isa MNPs (Fe3 O4 @SiO2 –Isa Cu(II)): the immobilized
Schiff base (300 mg) and copper acetate (0.6 mmol) were dispersed in acetonitrile (80 mL) under sonication for
30 min. The mixture was stirred vigorously for 24 h under argon at room temperature. The magnetic catalyst
was washed with acetone, ethanol, and water several times and dried under a vacuum at room temperature to
yield the immobilized copper Schiff base complex.
3.2. General procedure for Heck coupling reaction
A mixture of aryl iodide (1.0 mmol), methyl acrylate (1.1 mmol), triethylamine (2.0 mmol), and an adequate
amount of copper catalyst (0.33 mol%) was taken in a round-bottom flask and stirred in DMF (5.0 mL) at
100 ◦ C, and the progress of the reaction was monitored by GC.48 At the end of the reaction, the mixture was
cooled to room temperature and the catalyst was isolated by magnetic decantation. The recovered catalyst
was thoroughly rinsed with ethyl acetate and distilled water, dried at room temperature, and used without
any pretreatment for the next runs. The recyclability of the catalyst was screened in the reaction between
iodobenzene and methyl acrylate according to the above procedure.
3.3. General procedure for Suzuki coupling reaction
The mixture of aryl iodide (1.0 mmol), phenyl boronic acid (1.1 mmol), potassium carbonate (2.0 mmol), and
copper catalyst (0.33 mol%) was taken in a round-bottom flask and stirred in ethanol (5.0 mL) under reflux
conditions (70 ◦ C), and the progress of the reaction was monitored by GC.49 At the end of the reaction, the
mixture was cooled to room temperature and the solid catalyst was isolated by magnetic decantation. The
recyclability of the catalyst was screened in the reaction between iodoanisole and phenylboronic acid according
to the same method described above.
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MIRI et al./Turk J Chem
Acknowledgment
This work was supported by grants from the Research Council of Tehran University of Medical Science.
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