C-N cross-coupling reaction catalysed by efficient and reusable CuO/SiO2 nanoparticles under ligand-free conditions

Article abstract of DOI:10.1002/aoc.3203

Nanometric copper oxide supported on silica has been found to be a highly efficient and reusable catalyst for the C-N cross-coupling reaction of amines with aryl halides under ligand-free conditions. Various arylamines with different substituted groups can be synthesized in moderate to good yields. The catalyst can be recycled at least five times without obvious loss in catalytic activity.

Full text of DOI:10.1002/aoc.3203

Full Paper
Received: 14 July 2014
Revised: 5 August 2014
Accepted: 7 August 2014
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3203
C–N cross-coupling reaction catalysed by
efficient and reusable CuO/SiO2 nanoparticles
under ligand-free conditions
Abdol R. Hajipoura*, Fatemeh Dordahana, Fatemeh Rafieeb
and Mohammad Mahdavic
Nanometric copper oxide supported on silica has been found to be a highly efficient and reusable catalyst for the C–N cross-
coupling reaction of amines with aryl halides under ligand-free conditions. Various arylamines with different substituted groups
can be synthesized in moderate to good yields. The catalyst can be recycled at least five times without obvious loss in catalytic
activity. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: nano-heterogeneous catalysis; reusability; C–N cross-coupling; arylamines
it is worth mentioning that the development of several highly effec-
tive classes of catalysts for the cross-coupling of aryl chlorides with
Introduction
low catalyst loadings, excellent yields and reasonable scope re-
Due to the significance of N-arylamines and N-arylheterocycles
in biologically important natural products, pharmaceuticals
mains a challenge.[16,17]
and polymers and considering their applications in materials
research, their synthesis is an active area in organic
Results and Discussion
synthesis.[1] Therefore, there has been great attention given
to their preparation. Until now, Pd- and Cu-catalysed cross-
coupling reactions have been the most efficient ones in the
construction of aromatic C–N bonds both in industrial and ac-
ademic settings.[2–6] Copper catalysts have proven to be not
only cheaper and more readily available but also superior in
terms of efficiency and functional group tolerance.[7]
In continuation of our recent investigations on the synthesis
and applications of various catalysts in cross-coupling
reactions,[18–25] in this study, we report that CuO nanoparticles
supported on silica (CuO NPs/SiO2) catalyse C–N cross-
coupling of amines with various aryl halides with good yields.
The reactions are effective at 120 °C in DMSO in the presence
of KOH under atmospheric conditions (Scheme 1).
The CuO NPs/SiO2 catalyst was prepared as follows. First, copper
sulfate (1.2 g) was dissolved in the minimum amount of distilled
water. Then, ammonia solution (1ml, 25% w/w) was added to the
solution in order to make the tetra ammine copper(II) complex
[Cu(NH3)4]SO4. Then sodium silicate (Na2SiO3) solution (15 g, 45wt
%) was dissolved in water (10 ml) and the tetra ammine copper(II)
complex was added dropwise to it. By mixing the reaction mixture,
Nanomaterials with high surface areas as well as reactive mor-
phologies have been widely investigated. Recently, using nanocrys-
talline metal oxides as catalysts in organic synthesis has attracted
much attention. Nanomaterial-catalysed reactions are generally
characterized by easy product purification, efficient recycling of
the catalyst and minimizing metal traces in the products.[8–13]
In almost all methods, ligands or well-defined catalysts/reagents
are required. This fact contributes to an increase in the costs and, as
a consequence, limits the applications. Hence, finding new recycla-
ble catalytic systems for synthesizing such highly useful organic
compounds especially under ligand-free conditions is desirable.
During the past few years, there have been significant efforts in
the area of heterogeneous catalysis for various organic transforma-
tions. In general, heterogeneous catalysts have higher surface area
and lower coordinating sites, which contribute to their higher cata-
lytic activity. High atom efficiency, easy product purification and re-
usability of the catalyst are some of the other advantages of
heterogeneous catalysts.[14,15]
*
Correspondence to: Abdol R. Hajipour, Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan University of Technology, Isfahan 84156, IR
Iran. E-mail: haji@cc.iut.ac.ir
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan
University of Technology, Isfahan 84156, IR, Iran
b Department of Chemistry, Faculty of Science, Alzahra University, Vanak, Tehran,
IR, Iran
Generally, aryl chlorides are less expensive and more abundant
than their bromide and iodide counterparts. They are less reactive
and of much greater interest for industrial applications. However,
c
Catalysis Research Laboratory, Department of Chemistry, Isfahan University,
Isfahan 81746-73441, IR, Iran
Appl. Organometal. Chem. (2014)
Copyright © 2014 John Wiley & Sons, Ltd.

A. R. Hajipour et al.
Scheme 1. C–N cross-coupling reaction using CuO NPs/SiO2.
a uniform and homogeneous solution was produced. Then this so-
lution was dried in an oven at 150 °C to give a porous and spongy
material. After washing the sediment, sodium sulfate was washed
up and the remnant included a solid with CuO nanoparticles sup-
ported on amorphous silica. Copper oxide particles which are insol-
uble in water were distributed on the silica support. Then the blue
solid obtained was crushed into a fine powder. Atomic adsorption
spectroscopy was used to determine the amount of copper oxide
supported on the silica bed. In this analysis, it was found that
0.000055 mol of copper was supported on 1 g of catalyst.
The X-ray diffraction (XRD) pattern of CuO NPs/SiO2 is
shown in Fig. 1. All diffraction peaks are indexed to the corre-
sponding planes of CuO. The intense peak at 36.4° in the XRD
spectrum corresponds to the (111) plane, which is the crystal
plane of CuO. The diffraction of SiO2 is only seen at around
2θ = 21.7° with a broad and diffuse diffraction peak, which is
related to amorphous silica of the catalyst. After reduction,
the peaks of copper oxides disappear and the peaks of metal-
lic copper appear.
Figure 3. TEM image of CuO nanoparticles supported on silica.
Table 1. C–N cross-coupling of N-methyl-N-benzylamine with
bromobenzene in various solvents and basesa
In order to obtain detailed information about the microstructure
and morphology of the catalyst, scanning electron microscopy
(SEM; Fig. 2) and transmission electron microscopy (TEM; Fig. 3)
Entry
Solvent
Base
Temperature
(°C)
Conversion
(%)b
1
DMF
KOH
120
120
120
80
20
10
100
—
60
—
40
30
0
2
NMPc
DMSO
CH3CN
Dioxane
H2O
KOH
3
KOH
4
KOH
5
KOH
100
80
6
KOH
7
DMSO
DMSO
DMSO
DMSO
DMSO
NaCO3
NaHCO3
NaOAC
K2CO3
NaOH
120
120
120
120
120
8
9
10
11
70
60
aReaction conditions: N-methyl-N-benzylamine (1.2 mmol), bromobenzene
(1 mmol), base (2 mmol), CuO NPs/SiO2 (1.1 mmol%, 0.1 g) and solvent
(2 ml), 30 min.
Figure 1. XRD pattern of CuO nanoparticles.
bGC yield.
cN-methyl-2-pyrrolidone.
Table 2. C–N cross-coupling of N-methyl-N-benzylamine with
bromobenzene using various amounts of catalysta
Entry
CuO NPs/SiO2
(mmol%)
Time (min)
Conversion (%)b
1
2
3
4
5
0.11
0.22
0.33
0.55
1.1
60
60
25
10
10
85
100
100
100
100
aReaction conditions: N-methyl-N-benzylamine (1.2 mmol), bromobenzene
(1 mmol), KOH (2 mmol), and DMSO (2 ml), 120 °C.
bGC yield.
Figure 2. SEM image of CuO nanoparticles supported on silica.
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Appl. Organometal. Chem. (2014)

C–N cross-coupling reaction catalysed by CuO NPs/SiO2
Table 3. C–N cross-coupling reaction of various aryl halidesa
Entry
X
R1
R2
R3
Time (min)
Yield (%)b
1
I
H
CH3
CH3
CH3
Ph
CH2Ph
CH2Ph
CH2Ph
Ph
30
90
12
60
180
50
42
70
30
15
35
40
55
90
60
55
10
45
7
76
56
75
68
52
74
72
68
92
89
72
75
94
68
73
78
88
64
79
68
71
63
82
75
76
90
95
86
84
76
96
73
88
74
83
90
84
94
87
81
84
92
68
2
I
4-OMe
3
I
4-NO2
4
I
H
5
I
4-OMe
Ph
Ph
6
I
4-NO2
Ph
Ph
7
I
H
Morpholine
Morpholine
Morpholine
Indole
8
I
4-OMe
9
I
4-NO2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
I
H
I
H
Cyclohexyl
Cyclohexyl
I
H
CH3
Et
Cyclohexyl
I
H
Et
Et
I
H
H
I
H
Piperidine
Pyrrolidine
I
H
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
CH3
CH3
CH3
CH3
Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
Ph
4-OMe
4-NO2
4-CN
H
12
30
120
30
45
25
60
25
8
4-OMe
4-NO2
4-CN
H
Ph
Ph
Ph
Ph
Ph
Ph
Morpholine
Morpholine
Morpholine
Indole
4-OMe
4-NO2
H
H
Cyclohexyl
Cyclohexyl
Cyclohexyl
Et
25
25
40
60
12
10
35
35
30
30
12
30
35
50
75
H
CH3
Et
H
H
H
Et
H
CH3
CH3
Ph
Ph
CH2Ph
CH2Ph
Ph
4-NO2
H
4-NO2
H
Ph
Morpholine
Morpholine
Indole
4-NO2
H
H
Cyclohexyl
Cyclohexyl
H
CH3
Et
Cyclohexyl
H
Et
Et
H
H
aReaction conditions: aryl halide (1mmol), amine (1.2mmol), KOH (2mmol), DMSO (2ml), CuO NPs/SiO2 (0.55mmol%), oil bath (120 °C).
bIsolated yield.
observations were carried out. The results show the spherical mor-
phology of CuO nanoparticles. Careful observation of these images
indicates that particle surfaces are not smooth but some small
round structures are formed on the surface. The morphology of
CuO NPs/SiO2 shows that copper species in the catalyst have
spherical shapes and are distributed uniformly over the SiO2 sup-
port. Copper particles exhibit a narrow size distribution of
20–40nm with an average diameter of 30 nm.
The efficiency of this catalytic system was examined in the C–N
coupling reaction by optimizing the reaction conditions for the
Appl. Organometal. Chem. (2014)
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A. R. Hajipour et al.
Scheme 2. Proposed mechanism for the catalysed C–N cross-coupling reaction.
cross-coupling of bromobenzene with N-methyl-N-benzylamine as
a model reaction.
Table 4. Recycling of CuO NPs/SiO2
Run
1
2
3
4
5
To study the effect of the solvent on the yield of this reaction, the
model reaction was carried out in various solvents using 0.1g
(0.011mmol Cu) of CuO NPs/SiO2 as the catalyst. As evident from
Table 1, the highest yields and the shortest reaction times are re-
lated to the reactions in which DMSO is used as the solvent at
120 °C. We also investigated this coupling reaction using different
types of bases. Among the bases we selected, KOH shows the best
result.
Time (min)
Yield (%)
10
88
10
85
12
85
15
81
15
80
recovered through simple filtration, washing with distilled water
and acetone, and then drying in vacuo. The recovered catalyst
was used directly in the next cycle. The recycling results are
listed in Table 4. These results show that the catalyst is still highly
efficient after at least five cycles.
The loading of catalyst was also optimized by employing various
amounts of catalyst. The results are shown in Table 2. An amount of
0.05 g of CuO NPs/SiO2 catalyst gives the best result.
The optimized reaction conditions were applied to the C–N cross-
coupling reactions of various aryl halides with different secondary
amines (Table 3). The substituent effects of the aryl iodides prove
to be less significant than those of the aryl bromides, and the reac-
tivity of aryl bromides with electron-withdrawing substituent is
higher than that of aryl bromides with electron-donating substitu-
ent. Because of the inexpensiveness and availability of aryl chlo-
rides, they are the best substrates for coupling reactions in
comparison with their bromide or iodide counterparts. This catalytic
system can be used for the C–N cross-coupling reaction of even less
reactive aryl chloride derivatives with longer reaction times.
Dialkylamines, secondary arylamines, N-heterocyclic compounds
and primary arylamines including N-methyl-N-benzylamine, diphe-
nylamine, morpholine, indole, dicyclohexylamine and N-
methylcyclohexanamine can be coupled with various aryl halides
in excellent yields and in reasonable reaction times.
Conclusions
We report the synthesis of CuO NPs/SiO2 that was used as an ef-
ficient catalyst for the C–N cross-coupling reaction of amines
with aryl halides under ligand-free conditions. The scope of the
reaction using this catalytic chemistry is broad: various aryl, alkyl
and N-heterocyclic amines react with aryl halides. Of particular
importance is the reaction with aryl chlorides due to their low
cost. Furthermore, the CuO NPs/SiO2 catalyst can be recovered
and recycled through simple filtration of the reaction solution
and can be reused for at least five consecutive trials without a
decrease in its activity.
A general catalytic cycle for the C–N cross-coupling reaction
using CuO NPs/SiO2 as the catalyst is presented in Scheme 2. The
reaction may occur via oxidative addition and then reductive elim-
ination providing the C–N cross-coupled product followed by re-
moval of hydrogen halide with base.[10]
As CuO NPs/SiO2 is a heterogeneous catalyst, the recyclability
of the catalyst in this coupling reaction was examined. The cou-
pling of N-methyl-N-benzylamine with bromobenzene was cho-
sen as a model reaction. After each cycle, the catalyst was
Experimental
General
1H NMR spectra were recorded at 400 MHz in CDCl3 solutions at
room temperature (tetramethylsilane was used as an internal
standard) with a Bruker Avance 500 instrument (Rheinstetten, Ger-
many) and Varian 400 NMR. FT-IR spectra were recorded with a
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Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2014)

C–N cross-coupling reaction catalysed by CuO NPs/SiO2
spectrophotometer (Jasco-680, Japan). Spectra of solids were ob-
tained using KBr pellets. Vibrational transition frequencies are re-
ported in wavenumber (cmÀ1). We used GC (BEIFIN 3420 gas
chromatograph equipped with a Varian CP SIL 5CB column: 30 m,
0.32 mm, 0.25 μm) for examination of reaction completion and
yields. Powder XRD patterns were obtained using an X’PERT MPD,
with Cu Kα radiation (40 kV, 30mA). TEM images were obtained
using a Philips CM10 microscope. The Cu content in the catalyst
was measured using atomic absorption spectroscopy (PerkinElmer
2380 spectrophotometer). All chemical materials were purchased
from Merck and Aldrich and were used as received.
Acknowledgements
We gratefully acknowledge the funding support received for this
project from the Isfahan University of Technology (IUT), IR Iran
and Isfahan Science & Technology Town (ISTT), IR Iran. Further fi-
nancial support from the Center of Excellence in Sensor and Green
Chemistry Research (IUT) is gratefully acknowledged. We also grate-
fully acknowledge the partial financial support received from the
Research Council of Alzahra University.
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General Procedure for the Recyclability of Catalyst
The coupling of N-methyl-N-benzylamine (1.2 mmol) with
bromobenzene (1 mmol) was chosen as a model reaction
for the investigation of the recyclability of the catalyst
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(2 mmol) as base at 120 °C. After completion of the C–N
cross-coupling, the reaction mixture was treated with water
(30 ml) and ethyl acetate (30 ml). The CuO NPs/SiO2 catalyst
was recovered through simple filtration, washing with dis-
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Supporting Information
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web-site.
Appl. Organometal. Chem. (2014)
Copyright © 2014 John Wiley & Sons, Ltd.
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