CuCl heterogenized on metformine-modified multi walled carbon nanotubes as a recyclable nanocatalyst for Ullmann-type C-O and C-N coupling reactions

Article abstract of DOI:10.1039/c7nj03240d

Herein, a novel MWCNTs-Met/CuCl nanocatalyst synthesis method by metformine covalent grafting on the surface of carbon nanotubes and subsequent coordination with a CuCl catalyst is described. The nanocatalyst formation was analyzed by FTIR, energy dispersive spectroscopy (EDS), Raman spectroscopy and ICP analysis. The nanocatalyst morphology was examined by transmission and scanning electron microscopies (TEM and SEM). Moreover, in the N-arylation of anilines and indole, the nanocatalyst (MWCNTs-Met/CuCl) could be successfully used by formation of intermolecular C(aryl)-N bonds of the relevant aryl halides (Ar-I, Ar-Br, Ar-Cl) with amines by coupling reactions of Ullmann-type. The O-arylation of substituted phenols is also promoted by this heterogeneous copper catalyst with different aryl iodides and bromides. Additionally, without any considerable loss in activity, the novel catalyst was recovered and recycled several times.

Full text of DOI:10.1039/c7nj03240d

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January 2016 Pages 1–846
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PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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CuCl heterogenized on metformine-modified multi walled carbon
nanotubes as recyclable nanocatalyst for Ullmann-type C-O and C-N
coupling reactions
a
Marym Akhavan, Saba Hemmati, Malak Hekmati Hojat Veisi
b
a
*,b
a
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences
Branch, Islamic Azad University, (IAUPS), Tehran, Iran
b
Department of Chemistry, Payame Noor University, Tehran, Iran
E-mail: hojatveisi@yahoo.com
Abstract. Herein the novel MWCNTs-Met/CuCl nanocatalyst synthesis by metformine
covalent grafting on surface of carbon nanotubes and subsequent coordination with CuCl
catalyst is described. The nanocatalyst formation was analyzed by FTIR, energy dispersive
spectroscopy (EDS), Raman spectroscopy and ICP analysis. The nanocatalyst morphology
was explained by transmission and scanning electron microscopes (TEM and SEM).
Moreover, in the N-arylation of anilines and indole, the nanocatalyst (MWCNTs-Met/CuCl)
could be successfully used through formation of intermolecular C(aryl)-N bond from the
relevant aryl halides (Ar–I, Ar–Br, Ar–Cl) with amines by coupling reactions of Ullmann-
type. The O-Arylation of substituted phenols is also promoted by this heterogeneous copper
catalyst with different aryl iodides and bromides. Additionally, without any considerable loss
in activity, the novel catalyst was recovered and recycled several times.
Keywords: Carbon nanotubes, Metformine, CuCl, Nanocatalyst, Ullmann
2. Introduction
Carbon nanotubes such as single-walled (SWCNT) and multi-walled (MWCNT) nanotubes
4
have attracted significant interests because of their considerable mechanical, electrical
-6
6-7
1-3
properties, and thermal conductivity. Moreover, their large surface area and excellent
mechanical and chemical stability make them a potentially and ideal useful selection for
9
7,8
12
10,11
various applications in electronics, optics, polymer composites, catalysis,
and many
others. In this study, the metal deposition on carbon nanotubes (also known as
decoration”) has provided more reliable utilities for these materials in an extensive
applications range from solar cells, hydrogen storage, sensor devices, energy storage, and
13
“
14,15
catalysis. Therefore, cross coupling reactions is one of the potential areas in which carbon
nanotubes as an influential solid support may be used.
16-20
The aryl-oxygen and aryl-nitrogen bonds formation via cross-coupling reactions show
powerful methods for the different compounds preparation that are of biochemical,
2
1-23
biological, pharmaceutical and materials interest.
synthesized by coupling with organometallic reagents or via N-H nucleophilic aromatic
Conventionally, these compounds were
substitution including π-electron-rich nitrogen heterocycles with electron-deficient aryl
24
halides, limiting its scope. They were also obtained by the classical Ullmann-type coupling
with aryl halides, mainly suffering from limitations like high reaction temperatures (often 150
°C or as high as 200 °C), the application of copper reagents stoichiometric amounts,
copper(I) salts insolubility in organic solvents, the substituted aryl halide sensitivity to the
harsh reaction conditions, moderate yields, and poor substrate generality.
1

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25
Because of the copper economic attractiveness and by applying some particular ligands
26,27
3
0,31,
32,33
like N,N- and N,O-bidentate compounds, many CuI-catalyzed C-S,
C-N,
C-C
28,29
and C-O,
carbon-heteroatom, and their uses.
been disclosed, include amino acids, diamines, diimines, 1,10-phenanthroline,
bond forming reactions caused a resurgence of interest in coupling reactions of
34,35
For these coupling reactions, effective ligands have
36
37
38
39
41
40
42
phosphine ligands,
aminoarenethiolate,
2-aminopyrimidine-4,6-diol,
pyrrolidinylmethylimidazole, 8-hydroxyquinoline. glyoxal bis(phenylhydrazone), β-keto
(S)-
44
43
45
4
6
48
47
esters,
aminoethyl)amine.
BINAM-Cu(II)
2,2,6,6-tetramethylheptane-3,5-dione,
and
tris-(2-
49
Regarding copper-catalyzed oxidation chemistry, currently CuI/metformine complex has
been reported as an effective and novel catalyst for C-O and C-N cross-coupling reactions by
50
Ullmann-type coupling. Therefore, considering our previous studies on C-N, C-C, and C-O
5
1
coupling reactions,
functionalized multi walled carbon nanotubes anchored CuCl (MWCNTs-Met/CuCl)
Scheme 1) and through Ullmann-type coupling reactions, their application as heterogeneous
an efficient approach was designed for preparing the metformine-
(
catalyst in the formation of C(aryl)-N/O bond from relevant aryl halides with phenols or
amines (Scheme 2).
2
2
. Experimental
.1. Materials and apparatus
All the reagents were purchased from Aldrich and Merck and were used without any
purification. The pure MWCNTs without functional groups were purchased from
Petrol Co. (Tehran, Iran). Fourier transform infrared (FT-IR) spectra were recorded
with a Perkin Elmer 65 spectrometer in the range of 400-4000 cm-1. The structure and
the morphology of the samples were characterized using a digital scanning electron
microscope (SEM) (Model KYKY-EM3200, KYKY, China) and a Hitachi HT-7100
(
100 kV) transmission electron microscope (TEM).
2.2. Covalent grafting of metformine to MWCNTs
Pristine MWCNTs were refluxed under stirring in the mixture of 1:3 (v/v) HNO
3
2 4
and H SO
at 70 ºC for 30 h, which was followed by centrifugation and repeated washings with DI
water. The carboxylated MWCNTs (MWCNTs-COOH) thus obtained were dried at 60 ºC for
1 day under reduced pressure and reacted with excess of SOCl at room temperature for 24 h.
2
The acylated MWCNTs (MWCNTs-COCl) were separated by centrifugation, subsequently
washed with anhydrous THF to remove excess of SOCl , and dried in vacuum at 50 ºC for 12
2
h. The final product was then subjected to functionalization with metformine. Free
metformine (metformine-to-MWCNTs weight ratio was 5:1) were mixed with 1 mL solution
3
of DMF and Et N and then stirred for 1 hour. The obtained acyl chloride MWCNTs in 20 mL
DMF were then added to the suspension. The reaction mixture was kept at 120 °C for 3 days.
2 2
The solid was then separated by filtration and washed with CH Cl and deionized water for
several times and dried in vacuum.
2.3. Preparation of MWCNTs-Met/CuCl nanocatalyst
The MWCNTs-Met (1 g) were dispersed in 100 mL DI water by sonication for 10 min and an
aqueous solution of CuCl (50 mL, 1.0 mmol) was added to dispersion of MWCNTs-Met. The
mixture was stirred for 24 h in room temperature to complete attainment of coordination.
Thus yielded MWCNTs-Met/CuCl nanocatalyst was subjected to centrifugation, washed with
2

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DI water and dried in vacuum at 40 ºC for 12 h. Elemental analysis of the MWCNTs-
Met/CuCl using ICP-AES gave a 0.65 mmol/g loading of copper. The overall synthesis of
MWCNTs-Met/CuCl nanocatalyst is schematically demonstrated in Scheme 1.
2.4. N-Arylation of amines in the presence of MWCNTs-Met/CuCl
In a 25 mL balloon, the catalyst (20 mg catalyst = 0.013 mmol Cu), aryl halides (1 mmol),
DMF (3 mL), indole/aniline (1 mmol), and Et N (2 mmol) were added. The mixture was then
3
stirred for the desired time at 80 ºC. The reaction was monitored by thin layer
chromatography (TLC). After completion of reaction, the reaction mixture was cooled to
room temperature and the catalyst was recovered by centrifuge and washed with ethyl acetate
and ethanol. The combined organic layer was dried over anhydrous sodium sulfate and
evaporated in a rotary evaporator under reduced pressure. The resultant material was purified
by preparatory TLC with silica gel to afford the desired product.
2.5. O-Arylation of phenols in the presence of MWCNTs-Met/CuCl
In a 25 mL balloon, the catalyst (20 mg catalyst = 0.013 mmol Cu), aryl halides (1.1 mmol),
DMF (3 mL), phenol (1 mmol), and K CO (2 mmol) were added. The mixture was then
2
3
stirred for the desired time at 80 ºC. The reaction was monitored by thin layer
chromatography (TLC). After completion of reaction, the reaction mixture was cooled to
room temperature and the catalyst was recovered by centrifuge and washed with ethyl acetate
and ethanol. The combined organic layer was dried over anhydrous sodium sulfate and
evaporated in a rotary evaporator under reduced pressure. The resultant material was purified
by preparatory TLC with silica gel to afford the desired product.
3. Results and discussion
From cheap and commercially accessible materials, the metformine-functionalized Multi-
Walled Carbon Nanotubes (MWCNTs-Met) was synthesized conveniently by acylated
carbon nanotubes reaction with metformine. Then, CuCl were coordinated onto the
2
MWCNTs-metformine surface. The Cu loading in the prepared material was measured as
0.65 mmol/g by inductively coupled plasma (ICP) analysis. The MWCNTs-Met/CuCl
fabrication pathways can be observed in Scheme 1.
3

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O
OH
OH
HNO3
H SO
2
4
SOCl2
O
O
Cl
Cl
O
Metformine Et N, DMF
3
O
NH NH
CH3
N
N
H
N
H
CH
3
H
N
CH
3
H
N
N
CH3
NH NH
O
Cl
CuCl
Cu
O
HN
NH
CH3
N
N
H
N
H
CH
3
H
N
CH
3
H
N
N
CH3
HN
NH
O
Cu
Cl
Scheme 1. Schematic diagram of MWCNTs-Met/CuCl fabrication.
The modified carbon nanotubes surface structure was approved by fourier transform infrared
FTIR) spectroscopy. Figure 1 indicates the FT-IR spectra achieved for (a) MWCNTs, (b)
MWCNTs-COOH, (c) MWCNTs-Met and (d) MWCNTs-Met/CuCl. As can be observed in
(
-1
the curve b, the band at 1705 cm is relevant to carboxylic acid group carbonyl stretch. In
-1
addition, broad peak presence in 2400-3450 cm implies to OH group, meaning that the
MWCNTs oxidation have induced functional groups like hydroxyl and carboxyl on the nano
particles surface. Curve c indicates the MWCNTs-Met spectrum and the absorption band at
-1
1637 cm was assigned to the amide groups (-CONH-) carbonyl stretching. Moreover, the
band in the 1671 cm spectral region can be attributed to the attached metformine imine
-1
-
1
(C=NH) bond. Moreover, the prominent IR bands at 3436 and 3184 cm were ascribed to the
NH stretching vibrations. These results showed that the metformine has been bonded to the
SWCNTs surface via amidation reaction. In curve c, the signals observed at 1671 and 1637
52,53
-
1
cm for the metal-ligand co-ordination
may lead to a shift to lower frequencies (1671 to
656 cm ) for these two peaks. By comparing curve d, this shift can be seen. These peaks at
-1
1
curves c and d showed the metformin successful attachment organic ligands and Cu ions
subsequent coordination within the hybride material.
1
+
4

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Fig. 1. FTIR spectra of (a) MWCNTs, (b) MWCNTs-COOH, (c) MWCNTs-Met and (d)
MWCNTs-Met/CuCl.
54
Another approach for functionalization reaction evaluation is Raman spectroscopy. Figure 2
indicates the samples Raman spectra. Two main peaks in the Raman spectra could be shown
-1
in the samples at 1338 and 1596 cm known as D and G bonds, respectively. D band is
3
corresponding to MWCNTs disordered carbon atoms related to sp hybridized and G band
2
indicates the carbon atoms sp -hybridized in the graphene sheets. Area ratio of the D to G
bands (I
/I ratio was increased for MWCNTs-Met/CuCl
MWCNTs to MWCNTs-Met/CuCl conversion. In the amorphous carbon absence, the I
increase is relevant to carbon containing sp increase hybridized and implies to a successful
functionalization reaction.
D
/I
G
) can be applied to evaluate the defects amount in structures of nanoparticles.
I
D
G
2
D G
(I /I =1.27) approving the successful
D
3
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Fig. 2. Raman spectra of the (a) MWCNTs, and (b) MWCNTs-Met/CuCl.
Moreover, analysis of field emission scanning electron microscopy (FE-SEM) of
MWCNTs-Met/CuCl (Fig. 3a) approved the successful multi-walled carbon nanotubes
functionalization. It can be seen that in the MWCNTs-Met/CuCl , the CNTs surface coated,
2
so evidently an indication of desired groups which are attached to MWCNTs. This was also
observed by EDS analysis (Fig. 3c), showing well explained peaks of C, N, O, S, Cu and Cl,
thereby approving the successful CuCl anchoring on the surface of metformine-MWCNTs.
Figure 3b reveals MWCNTs-Met/CuCl nanocomposite transmission electron microscopy
(TEM) image. The TEM approves that the CNTs are successfully decorated with Met-CuCl
groups.
Fig. 3. (a) FESEM, (b) TEM, and (c) EDS analysis of the MWCNTs-Met/CuCl.
The obtained MWCNTs-Met/CuCl heterogeneous nanocatalyst was subsequently evaluated,
by Ullmann cross coupling reaction, in the formation of C-N and C-O bond reaction of aryl
halides with phenols and amines (Scheme 2).
6

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Cl
Ar-OH
or
Cu
O
HN
NH
R -NH-R
1
2
CH3
N
N
H
N
H
CH
3
Ar
X
H
N
CH
3
H
N
N
CH3
Ar-O Ar
or
HN
NH
O
Cu
Cl
R -N-R
1
2
Ar
Scheme 2. MWCNTs-Met/CuCl catalyzed N/O-arylation reactions.
In order to characterize optimal settings, the substrate of designated model was the reaction
between bromobenzene and indole (Table 1). Various parameters, such as selection of
solvent, base, reaction temperature and catalyst loading, were examined to achieve at the
optimal combination.
a
Table 1. Optimization of reaction condition for the N-arylation of indole with bromobenzene.
+
Ar-Br
N
H
N
Ar
b
Entry catalyst (g) Base
Solvent t (h)
8
Yield (%)
70
80
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
0.01
0.01
0.01
0.01
0.01
0.01
0.02
0.03
0.02
-
0.02
0.02
0.02
0.02
0.02
0.02
Et
Et
Et
Et
3
3
3
3
N
N
N
N
EtOH
DMF
Toluene
c
6
5
70
25
40
70
H
2
O
CH Cl2
8
6
Et N
3
2
Et
Et
Et
-
3
3
3
N
N
N
CH
3
CN
6
c
DMF
DMF
DMF
DMF
DMF
DMF
DMF
3
3
24
24
3
96
96
c
c
Trace
c
0
1
2
3
4
5
6
Et
K CO3
3
N
0
75
c
2
c
Na
KOH
NaHCO3 DMF
Et
Et
2
CO
3
3
65
80
65
65
c
3
c
3
d
3
N
N
DMF
DMF
12
12
e
50
3
a
Reaction conditions: indole (1.0 mmol), bromobenzene (1.0 mmol), catalyst, base (2.0 mmol), solvent (3.0
mL), reflux.
b
Isolated yield.
80 ºC.
c
d
50 ºC.
e
2
5 ºC.
Firstly, the solvents which include H
analyzed under reflux conditions with 2 equiv, of Et
2
O, toluene, DMF, CH
3 2 2
CN, EtOH and CH Cl , were
3
N and 0.01 g of the MWCNTs-
Met/CuCl (Table 1). The solvent nature significantly affected the reaction results (entries 1-6,
Table 1). DMF (entry 2, 80%) considerably produced the greatest yield. Then, the bases
7

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(
3 2 3 2 3 3 3
KOH, Et N, Na CO , K CO and NaHCO ) were analyzed. Et N was the best one, resulting
in the highest yields (entries 7, 11-14, Table 1). A minimal yield was obtained without a base
inclusion (entry 9, Table 1) and the temperature of reaction was seen to have a high
performance on this transformation (entries 7, 15, Table 1). By reducing reaction
temperatures to 25 °C, in yield there was a loss (entry 15, Table 1). Moreover, as the added
catalyst proportion was rose from 0.01g to 0.02g, the excellent yield was obtained (entry 7,
96%). When 0.02g of catalyst was applied, however, the resulting yield and time of the
reaction were equal to those of just 0.02g of catalyst (entries 7, 8, Table 1). It is crucial to
consider that indole N-arylation would not happen without the MWCNTs-Met/CuCl catalyst
3
inclusion (entry 10, Table 1). The optimally chosen conditions were Et N as the base, DMF
as the solvent, and 0.02g of the MWCNTs-Met/CuCl as catalyst and under aerobic conditions
were refluxed in the following tests (entry 7, Table 1).
The catalyst was subsequently applied to other reactions under the optimized conditions using
a wider range of aniline/indole and aryl halides. Mainly, the coupling reaction among amines
and aryl iodides/bromides was clean and high yielding (entries 1, 2, 4, 5, 7, 8, 10-13, 15, 16
Table 2). However, lower yield was achieved when to chlorides the leaving group was altered
(entries 3, 6, 9, 14, Table 2). These results ascertained the reactivity arrangement: R-I>R-
Br>R-Cl.
a
Table 2. MWCNTs-Met/CuCl catalyzed coupling of aryl halides and amines.
NHAr
NH2
+
Ar-X
N
N
H
Ar
b
Time (h) Yield (%) Ref
c
Entry Aryl halides
amines
Indole
Indole
Indole
Indole
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
Ph-I
Ph-Br
1
96
96
65
96
96
55
96
88
60
96
90
96
96
65
88
75
55
55
55
55
55
55
56
56
56
57
57
57
57
56
56
56
3
12
2
4
12
1
Ph-Cl
4-MeO-C
4-MeO-C
6
6
H
H
4
-I
-Br
4
Indole
Indole
4-MeO-C H -Cl
6
4
Ph-I
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
Ph-Br
Ph-Cl
4-Cl-C
4-Cl-C
2
12
1.5
3
2
3
0
1
2
3
4
5
6
6
6
H
H
4
-I
-Br
4
4-Me-C H -I
4-Me-C
4-Me-C
6
6
6
4
4
4
H
H
-Br
-Cl
12
2
5
4-NO
4-NO
2
-C
-C
6
H
H
4
-I
-Br
2
6
4
a
Reactions were carried out under aerobic conditions in 3 mL of DMF, 1.0 mmol aryl halides, 1.0 mmol amines
and 2.0 mmol Et N in the presence of MWCNTs-Met/CuCl (20 mg) and 80 ºC.
3
b
Isolated yield.
Known product
c
To more examine this protocol scope, it was decided to study this Ullmann-type C-O
coupling reaction (Scheme 2). Firstly, the reaction conditions systematic screening was
carried out by a model reaction between iodobenzene and phenol (Table 3).
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a
Table 3. Optimization of reaction condition for the O-arylation of phenol with iodobenzene.
OAr
OH
+
Ar-I
b
Entry catalyst (g) Base
Solvent
EtOH
DMF
t (h)
12
12
12
10
12
12
8
Yield (%)
65
70
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
0.01
0.01
0.01
0.01
0.01
0.01
0.02
0.03
0.02
-
0.02
0.02
0.02
0.02
0.02
0.02
K
2
CO
3
c
K CO3
2
K
2
K
2
CO
CO
3
Toluene
THF
CH Cl2
60
45
40
70
3
K CO3
2
2
K
2
K
2
CO
CO
3
3
CH CN
c
3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
96
96
c
K CO3
2
8
c
-
24
24
8
8
8
Trace
c
0
1
2
3
4
5
6
K
2
CO
N
3
0
90
c
Et
Na
KOH
Cs CO
3
c
2
CO
3
60
80
c
c
2
3
8
12
12
70
48
35
d
K
K
2
CO
CO
3
e
2
3
a
Reaction conditions: phenol (1.0 mmol), iodobenzene (1.1 mmol), catalyst, base (2.0 mmol), solvent (3.0 mL),
reflux.
b
Isolated yield.
80 ºC.
c
d
50 ºC.
e
2
5 ºC.
2 3
Table 3 reveals that when 20 mg of (MWCNTs-Met/CuCl), 2 mmol of K CO , and DMF
at 80 °C were applied (Table 3, entry 7), the best result (96% yield) was achieved. After the
conditions optimization on the model reaction, a range of various aryl halides with phenol
were screened to examine this protocol scope. As can be seen in Table 4, the desired products
in good to excellent yields were obtained. The relative reactivities of the halogen-substituted
substrates toward attack by the phenol were also investigated and the following order was
ascertained: R-I, R-Br or R-Cl, with a bond reactivity order of: C-I > C-Br > C-Cl (entries 1-
3, Table 4). On the other hand, the reaction was very sensitive to the steric effects of the aryl
iodides (entries 10, and 11). As can be seen from Table 4, most of the tested substituted iodo-
and bromo-benzenes, including those bearing electron-donating and electron-withdrawing
groups reacted under these conditions to afford the corresponding diaryl ethers in good to
excellent yields.
a
Table 4. Catalytic O-arylation of phenol with aryl halides by MWCNTs-Met/CuCl
OAr
OH
+
Ar-X
b
b
Entry Aryl halide
Product
Diphenylether
Time (h) Yield(%)
Ref
58
58
58
59
58
59
59
60
60
1
2
3
4
5
6
7
8
9
C
C
6
H
H
5
I
Br
8
96
90
25
96
92
95
90
85
75
6
5
Diphenylether
Diphenylether
12
24
10
10
10
12
14
15
C H Cl
6
5
p-NCC
p-NCC
p-CH C H I
p-CH
p-CH
6
H
H
4
I
Br
4-Phenoxybenzonitrile
4-Phenoxybenzonitrile
4-Methyl-diphenylether
4-Methyl-diphenylether
4-Methoxy-diphenylether
4-Methoxy-diphenylether
6
4
3
3
3
6
4
C
6
H
4
Br
6 4
OC H I
p-CH OC H Br
4
3
6
9

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DOI: 10.1039/C7NJ03240D
1
1
0
1
o-CH
3
OC
6
H
4
I
o-CH OC H Br
2-Methoxy-diphenylether
2-Methoxy-diphenylether
16
20
64
55
58
58
3
6
4
a
Reaction conditions: phenol (1 mmol), aryl halide (1.1 mmol), K CO (2.0 mmol), DMF (3.0 mL),
3
2
MWCNTs-Met/CuCl (20 mg) and 80 ºC.
Known product
b
A mechanism of the MWCNTs-Met/CuCl-catalyzed Ullmann-type C-N coupling reaction
61
was proposed (Scheme 3). The complex A can react with aryl halide with oxidative addition
to provide intermediate B, following reductive elimination to generate the 1-aryl-indole
product; complex A is released to accomplish the catalytic cycle.
Cu+1
O
HN
NH
CH3
CH3
N
N
H
N
H
H
N
CH3
H
N
N
CH3
Reductive
elimination
N
HN
NH
Cu+1
O
A
Ar
Oxidative
addition
ArX
X
Ar
N
Ar
Cu+3
Cu+3
O
HN
NH
O
HN
NH
CH3
CH3
CH3
CH3
N
N
N
H
N
H
N
H
N
H
H
N
CH3
H
N
CH3
H
H
N
N
N
N
CH3
CH3
HN
NH
HN
NH
B
O
O
C
Cu+1
Cu+1
N
H
Base
Scheme 3. The probable mechanism of MWCNTs-Met/CuCl-catalyzed Ullmann-type C-N
coupling reaction.
The reusability of heterogeneous catalysts is very important, especially for commercial
applications. Therefore, the recycling performance of MWCNTs-Met/CuCl was investigated
in the reaction of iodobenzene and indole under the optimized reaction conditions. After the
completion of the reaction, the reaction mixture was cooled to room temperature, EtOAc was
added and the catalyst separated from the reaction mixture by centrifuge, washed with water
and ethanol, and reused in a next reaction. The data listed in Fig. 4 shows that catalyst could
be reused 7 times without significant loss of its catalytic activity. The high stability and
excellent reusability of the catalyst should result from the chelating action of metformine
groups on CuCl and the mesoporous structure of the MWCNTs support.
1
0

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Fig. 4. The recycling of the MWCNTs-Met/CuCl.
In this research, we also report amounts of copper leaching in the synthesis of N-phenyl-
indole (Table 1) by checking the copper loading amount before and after recycling of the
catalyst by ICP-AES technique. It can be should that the amount of copper in fresh catalyst
-1
and the recycled catalyst after 7 times recycling is 0.65 and 0.48 mmolg , respectively, which
indicated that copper leaching of this catalyst is very low. In order to perform hot filtration
test, two reactions for the synthesis of N-phenyl-indole has been investigated under optimized
reaction conditions (Table 1). In the first reaction, we found the yield of product in half time
of the reaction that it was 65%. Simultaneously in second reaction, the same reaction was
repeated, but in the half time of the reaction, the catalyst was separated from the reaction
mixture by filtration process and allowed to react further under identical reaction conditions.
Noteworthy, the yield of reaction in this stage was 67% that confirmed the leaching of copper
hasn’t been occurred.
Also, CuCl existence in the MWCNTs-Met nanostructure was re-confirmed by XPS analysis
through studying binding energy range of 930 to 955 eV. The analysis resolved Cu 2p
spectrum into two spin-orbit pairs with 932.2 eV and 952.1 eV binding energies, respectively.
The peak binding energy values of 932.2 eV (Cu 2p3/2) and 952.1 eV (Cu 2p1/2) regard to
+1
cupper ions (Cu ) on the surface of modified CNTs [62]. The Cu 2p photoelectron
transitions of the MWCNTs-Met/CuCl catalyst was observed at 933.2 eV. The differences of
Cu 2p binding energy between MWCNTs-Met/CuCl and CuCl are 0.6 eV. This chemical
shift of the binding energy of Cu element is induced by the coordination bonding when Cu (I)
is immobilized on MWCNTs-Met structures [63]. Thus copper ions have been successfully
immobilized on the MWCNTs-Met support.
Fig. 5. XPS spectrum of the MWCNTs-Met/CuCl in Cu 2p region for a) fresh and b) reused
catalyst after 3 runs.
1
1

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Finally, to assess the present protocol with respect to other reported methods for the N-
arylation of indole, our procedure was compared with some of the reported catalysts. From
Table 5, it can be seen that present catalyst exhibited higher conversions and yields compared
to the other reported catalysts.
Table 5
Comparison of the activity of different catalysts in the N-arylation of indoles.
Substrate
Catalyst
Reaction conditions
DMSO, KO-t-Bu, 120 C, 24 h.
Yield (%) Ref.
º
1
1
1
2
0 mol% CuI/
0 mol% Bezotriazole
0 mol% CuI/
87
94
90
[64]
º
, 130 C, 12 h.
DMF, CsCO
3
[65]
0 mol% Metformine
º
, toluene, 110 C, 24 h.
Indole
+
MCM-41-2N-CuI
(4.0 mol %)
K
3
2
PO
4
[66]
º
, CTAB, 110 C, 10 81
4-CH
3
OC
6
H
4
I
Polystyrene-supported
copper(II)
H
O, K
2
CO
3
[67]
h.
º
O, 90 C, 10 h
10 mol% CuI/
K
3
PO
4
, betain, H
2
81
96
[68]
20 mol% 2,2´-bipyridine
º
N, 80 C, 2 h.
MWCNTs-Met/CuCl
0.13 mol%)
DMF, Et
3
This study
(
4. Conclusion
In this study, metformine was successfully bonded on the surface of MWCNTs to subsequent
coordination by CuCl as a novel nanocatalyst. The synthesized catalyst was confirmed by
2
FT-IR, TEM, FESEM, ICP, Raman and EDS techniques. The results indicated that the
stability of the catalyst was much improved and MWCNTs-Met/CuCl was an efficient and
recyclable catalyst for C-N and C-O bond formations by Ullmann cross-coupling reactions.
The catalyst showed good stability and could be reused 7 times without significant loss of its
catalytic activity.
Acknowledgments. We are thankful to Payame Noor University and Pharmaceutical
Sciences Branch, (IAUPS), Tehran for partial support of this work.
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DOI: 10.1039/C7NJ03240D
Graphical Abstract
CuCl heterogenized on metformine-modified multi walled carbon
nanotubes as recyclable nanocatalyst for Ullmann-type C-O and C-N
coupling reactions
*
Marym Akhavan, Saba Hemmati, Malak Hekmati, Hojat Veisi
Cl
Ar-OH
or
Cu
O
HN
NH
R -NH-R
1
2
CH3
N
N
H
N
H
CH
3
Ar
X
H
N
CH
3
H
N
N
CH3
Ar-O Ar
or
HN
NH
O
Cu
Cl
R -N-R
1
2
Ar
1
5