An efficient polymer-supported copper(II) catalyst for the N-arylation reaction of N(H)-heterocycles with aryl halides as well as arylboronic acids

Article abstract of DOI:10.1007/s11243-011-9489-8

Immobilization of copper onto polystyrene provided a polymer-supported copper(II) catalyst, which was effective in cross-coupling reactions between N-containing substrates and arylboronic acids using methanol as a solvent in air under base-free conditions

Full text of DOI:10.1007/s11243-011-9489-8

Transition Met Chem (2011) 36:447–458
DOI 10.1007/s11243-011-9489-8
An efficient polymer-supported copper(II) catalyst
for the N-arylation reaction of N(H)-heterocycles
with aryl halides as well as arylboronic acids
Manirul Islam
Kazi Tuhina
•
Sanchita Mondal
Noor Salam Sumantra Paul
•
•
Paramita Mondal
•
•
Anupam Singha Roy
Manir Mobarok
•
•
Dildar Hossain
•
Received: 3 January 2011 / Accepted: 23 March 2011 / Published online: 7 April 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Immobilization of copper onto polystyrene
provided a polymer-supported copper(II) catalyst, which
was effective in cross-coupling reactions between N-con-
taining substrates and arylboronic acids using methanol as
a solvent in air under base-free conditions. This catalyst
was also effective in N-arylation of imidazole with aryl
halides in DMSO using K CO as a base under nitrogen
formation of the aryl-nitrogen bond. However, the standard
practice for carrying out such reactions involves nucleo-
philic aromatic substitution [6] and traditional Ullmann
reactions [7] as well as the coupling of imidazoles with
aryllead, arylbismuth, arylborane, and arylsilane reagents
[8]. These reactions have been carried out at high tem-
peratures and many functional groups are not tolerated, and
therefore their use is greatly limited [9]. In addition, these
reactions often require the use of stoichiometric amounts of
copper reagents, which, on scaleup, leads to problems of
waste disposal [10]. To overcome these drawbacks, several
Pd-catalyzed C–N bond formation methods have been
developed, which, together with sterically hindered phos-
phine ligands, allow many coupling reactions of aryl
halides with N-containing compounds to proceed under
relatively mild conditions and at low temperature [11].
However, industrial use of these methods is problematic in
many cases due to their air and moisture sensitivity, as well
as the higher costs of Pd catalysts and the ligands [12].
However, copper-mediated couplings are still the reaction
of choice for large- and industrial-scale formation of C–N
bonds. Chan and Lam established an efficient approach
2
3
atmosphere. The catalyst was characterized by physico-
chemical and spectroscopic techniques. The product
N-arylimidazoles and N-arylbenzimidazoles were isolated
in good to excellent yields. This copper catalyst was air
stable and could be recycled with minimal loss of activity.
Introduction
Recently, copper-catalyzed Ullmann-type C(aryl)–N bond
formation under mild conditions has become a focus of
research to include a wide range of subsrates [1–3]. The
synthesis of N-arylimidazoles and N-arylbenzimidazoles
has attracted significant interest because of the frequent
occurrence of these structural units in biologically active
inhibitors [4]. N-arylimidazoles and N-arylbenzimidazoles
are prevalent in compounds that are of biological, phar-
maceutical, and material interest [5]. The most straight-
forward route to N-arylimidazoles involves the direct
to N-arylimidazoles via Cu(OAc) - mediated coupling of
2
imidazoles with readily available arylboronic acids [13].
Xie and coworkers have shown the simple copper salt-
catalyzed coupling of imidazoles with arylboronic acids in
protic solvent without any base [14]. Recently, Buchwald
used diimine as ligand for effective copper-mediated cross-
coupling reactions under mild conditions [15]. Very
recently, Buchwald et al. and others have reported a cop-
per-based protocol for the formation of N-aryl bonds
M. Islam (&) Á S. Mondal Á P. Mondal Á
A. S. Roy Á N. Salam Á S. Paul Á D. Hossain Á M. Mobarok
Department of Chemistry, University of Kalyani, Kalyani,
Nadia, West Bengal 741235, India
e-mail: manir65@rediffmail.com
[
16–18]. Immobilization of the soluble catalysts onto an
insoluble matrix using a simplified protocol will allow easy
separation and recyclability of the catalyst with minimal
amount of product. In this direction, we have already
K. Tuhina
Department of Chemistry, B. S. College, S-24 PGS, Canning,
West Bengal, India
123

4
48
Transition Met Chem (2011) 36:447–458
reported reusable palladium catalysts for C–C cross-
coupling reaction [19, 20]. Homogeneous catalysts have
some disadvantages, such as they may easily be destroyed
during the course of the reaction and they cannot be easily
recovered after the reaction for reuse. These disadvantages
can be overcomed by anchoring the metal on a polymer
chemical analysis, SEM, EDAX, IR, TGA-DTA, and
UV–Vis spectral data. Table 1 provides the data of elemental
analysis of different functionalized polymers and the cop-
per(II) catalyst. Copper content in the catalyst determined by
AAS suggests 1.98 wt% Cu in the catalyst. The morphology
of the copper catalyst was studied using scanning electron
microscopy. The micrographs of the polymer-supported
Schiff base ligand and the catalyst obtained from the scan-
ning electron microscope are presented in Fig. 1a and b,
respectively. The morphological change in the polymer-
supported Schiff base ligand and the immobilized copper
catalyst is quite evident from these images, suggesting the
loading of copper metal on the surface of the polymer matrix.
Energy dispersive spectroscopy analysis of X-rays (EDAX)
data for the polymer-supported Schiff base ligand and the
catalyst is given in Fig. 2a and b, respectively. The EDX data
also inform the attachment of copper metal on the surface of
the polymer matrix.
[
21]. There are many examples of heterogeneous catalysts
for C–N coupling reactions, and they are prepared by dif-
ferent approaches like encapsulation or immobilization of a
catalytically active metal complex on solid supports [22].
In this present work, N-arylation reactions of imidazole
and benzimidazole with various arylboronic acids were
carried out in methanol with polymer-supported copper(II)
catalyst, without the need of any organic cosolvent, base,
or additives such as phase-transfer catalysts. This catalyst
was also effective in N-arylation reactions of imidazole
with various aryl halides using K CO in DMSO medium.
2
3
The experimental results reveal that the anchoring of the
complex on a solid support not only exhibits improved
catalyst activity, stability and selectivity of the product but
also enables easy recovery and reuse of the catalyst.
The IR data of the various functionalized polystyrenes
and the corresponding metal complex are presented in
Table 2. The presence of the Schiff base moiety in the
-
1
ligand is indicated by the absorption band at 1,639 cm
due to C=N-stretching vibration of azomethine group. This
-
on complexation with Cu shifted to 1,614 cm , while the
1
Results and discussion
-
1
bands at 1,583 and 1,453 cm have been assigned to the
aromatic skeletal vibration [23, 24]. The lowering in fre-
quency of C=N is indicative of the formation of the metal–
Preparation of catalysts
-
1
The synthesis of the polymer-anchored Cu(II) Schiff base
catalyst is shown in Scheme 1.
ligand bonding. The absorption signal at 1,594 cm can
be assigned to the stretching frequency of C=N (m C=N) of
pyridine in the Schiff base ligand which on complexation
-
1
Characterization of the polymer-anchored Cu(II) Schiff
base catalyst
with Cu shifted to 1,600 cm [25]. In the metal complex,
-
a medium or weak band is observed at 545 cm which can
1
be attributed to the metal with pyridine nitrogen mode [26]
-
and a band at 462 cm can be attributed to the metal with
1
Due to insolubilities of the polymer-supported Cu(II) cat-
alyst in all common organic solvents, its structural inves-
tigation was limited to the physicochemical properties,
azomethine nitrogen mode [27]. In this catalyst, a medium
-
1
intensity band observed at 1,318 cm
suggests the
monodentate coordination of the acetate groups [28].
Monodentate acetate usually shows two bands at 1,630 and
-1
Ac
2
O/ HOAc
SnCl
HOAc
2
/ HCl
p
NO
P
NH
3
Cl
1,310 cm due to antisymmetric and symmetric stretch-
P
2
HNO
3
0
,
(
1a) 50 C 6h
(3a)
NaOH
ing, respectively [29]. Since the absorption of the Schiff
(
2a)
base moiety (m C=N) also appeared in this region, the band
MeOH
-
1
at 1,630 cm could not be located. The acetate oxygen
involved in the complexation with copper in copper cata-
lyst which is clearly evident from the presence of a new
OHC
N
P
N
CH
P
NH
2
Reflux/ Toluene
N
(
5a)
(
4a)
Cu(OAc)
2
/
HOAc
-1
medium intensity band at 430 cm assignable to m Cu–O
in the IR spectra [29].
Reflux
The electronic spectrum of the polymer-supported
Cu(II) Schiff base catalyst was recorded in diffuse reflec-
tance mode as a MgCO /BaSO disk due to its solubility
HC
N
P
N
3
4
AcO
limitations in common organic solvents. In Fig. 3, the
electronic spectrum for the copper catalyst is shown. The
spectrum exhibits five bands at ca. 218, 265, 295, 322, and
380 nm. The first two peaks in the UV region can be
6 4 2
P-[(C H N=CHPy)Cu(OAc) ]
Scheme 1 Synthesis of the polymer-anchored copper(II) Schiff base
catalyst. P polystyrene framework
1
23

Transition Met Chem (2011) 36:447–458
449
Table 1 Chemical analysis of different compounds
Compound
Color
Cl %
C %
H %
N %
Cu %
(
(
(
(
(
1a)
2a)
3a)
4a)
5a)
Colorless
Light yellow
Yellow
–
92.50
74.10
72.01
84.12
83.23
67.80
7.60
5.69
6.72
7.34
6.28
5.46
–
–
–
–
–
–
6.01
5.81
6.72
9.07
6.62
13.25
–
Pale yellow
Brown
a
P-[(C
H
6 4
N=CHPy)Cu(OAc)
2
]
Deep brown
–
1.98 (1.97)
P polystyrene framework
a
Used catalyst
ligand-to-metal charge transfer [31]. The expected d–d
bands are not observed in the polymer-supported copper
catalyst. Possibly poor loading of the complex on the
polymer matrix has prevented the observation of the d–d
band, which are a low energy and eventually less intense
band [32].
Thermal stability of the catalyst was investigated using
TGA-DTA at a heating rate of 10 °C/min in air over a
temperature range of 30–600 °C. The catalyst is stable up
to 300 °C, and above this temperature, it decomposed.
Thermogravimetric study suggests that the polymer-sup-
ported copper(II) catalyst degrades at a slightly higher
temperature.
Catalytic activity
The N-arylation reaction is a convenient method for the
C–N bond formation between N–H heterocycles with aryl
halides and arylboronic acids. To test the applicability of
the polymer-anchored copper(II) catalyst, we examined the
N-arylation reaction between N–H heterocycles with vari-
ous aryl halides and arylboronic acids.
N-arylation reaction of imidazole with aryl halides
using polymer-supported copper(II) Schiff base catalyst
To optimize the conditions for the N-arylation reaction, we
have chosen the reaction between iodobenzene and imid-
azole as a model reaction (Scheme 2) and various catalysts,
solvents, and bases were screened. In an effort to evolve a
better catalytic system, various catalysts were screened for
N-arylation of imidazole and iodobenzene in DMSO using
K CO at 120 °C. The results are summarized in Table 3.
2
3
Fig. 1 FE SEM image of polymer-supported Schiff base ligand (1a)
and polymer-supported copper(II) Schiff base catalyst (1b)
Homogeneous copper catalyst, CuI, CuCl , and Cu(OAc) ,
2
2
gave very low yield (entries 2–4). As can be seen from
Table 3, polymer-supported copper catalysts were superior.
Among polymer-supported copper(II) catalysts, polymer-
supported copper(II) Schiff base catalyst from copper(II)
acetate was found to be the most effective one (entry 7).
assigned to intraligand p–p* transitions. The two bands at
295 nm and 322 nm arise due to n–p* [30] and p–p* [26]
transitions of pyridine. The peak at 380 nm may be due to
123

4
50
Transition Met Chem (2011) 36:447–458
Fig. 2 EDAX data of polymer-
supported Schiff base ligand
(
2a) and polymer-supported
copper(II) Schiff base catalyst
2b)
(
-
Table 2 IR spectral data (cm ) of the compounds
1
a
b
c
d
Compound dNH mNH
2
3
Cl
mNO
2
mC=N
mC=N
mCu–N
mCu–N
mCu–O
(
(
(
(
2a)
3a)
4a)
5a)
1,520(s)
,350(s)
1,520(w)
,350(w)
1,520(w)
,350(w)
1,520(w)
,350(w)
1,520(w)
,350(w)
1
2,550
1
1,625
1
1,639
1,614
1,594
1,600
1
P-[(C
H
6 4
N=CHPy)Cu(OAc)
2
]
462
545
430
1
P Polystyrene, s strong, w weak
a
Azomethine group
b
Pyridine moiety
c
Azomethine nitrogen
d
Nitrogen in the pyridine moiety
The comparison of heterogeneous Schiff base copper cat-
alyst and corresponding homogeneous Schiff base copper
catalyst in the N-arylation reaction was carried out under
the same reaction conditions. The results (entries 7, 8)
clearly show that the polymer-supported copper(II) Schiff
base catalyst was more active than its homogeneous
1
23

Transition Met Chem (2011) 36:447–458
451
Table 4 N-arylation reaction using copper catalyst at various bases
and solvents
2
65 295
3
22
1.2
1.0
0.8
0.6
0.4
0.2
I
3
80
N
2
18
N
copper catalyst
N
N
H
a
Entry Base
Solvent Temperature (°C) Time (h) Yield (%)
1
2
3
.
.
.
K
K
2
CO
PO
3
DMSO 120
DMSO 120
DMSO 120
DMSO 120
14
18
12
18
20
20
20
20
18
93
78
45
47
90
89
90
67
62
3
4
3
Et N
4.
2 3
Cs CO
5
6
.
K
K
2
CO
CO
3
DMF
NMP
ACN
THF
140
130
100
100
100
2
3
3
3
3
2
00
300
400
500
600
700
800
7.
2
K CO
Wave length (nm)
8
9
.
.
K
K
2
CO
CO
2
DME
Fig. 3 DRS-UV–Visible absorption spectra of polymer-supported
Cu(II) catalyst
Reaction conditions: Polymer-supported copper(II) catalyst (0.05 g,
0
2
a
.0156 mmol), 1 mmol of iodobenzene, 1.2 mmol of imidazole,
mmol base, solvent (10 mL), N atm
Yield determined by GC and GCMS analysis
I
2
N
N
copper catalyst
N
DMSO , K CO3
2
N
0
removed easily from the reaction mixture by a simple fil-
tration, and it is more easily handled. Several bases were
screened using the polymer-supported copper(II) catalyst
for the N-arylation of imidazole with iodobenzene in
DMSO solvent at 120 °C, and the results are summarized
in Table 4. It was observed that K CO gave the best result
,
14 h
20 C
1
H
Scheme 2 N-arylation of imidazole with iodobenzene using poly-
mer-supported copper(II) catalyst
Table 3 Effect of copper source on the coupling of imidazole with
iodobenzene
2
3
I
(Table 4, entry 1). K PO was also found to be fairly active
3 4
N
(entry 2). But the organic bases like Et N and Cs CO were
3 2 3
N
DMSO , K2CO3
almost inactive (entries 3, 4). Next, to check the solvent
effects in the N-arylation of imidazole with iodobenzene,
several solvents were screened and results are summarized
in Table 4. It was observed that the polar solvents like
DMSO, DMF, NMP, and acetonitrile were effective
N
0
1
20 C, 14 h
N
H
R1
a
Yield (%)
Entry Copper source
1
2
3
4
5
6
7
8
.
.
.
.
.
.
.
.
None
No reaction
(
Table 4, entries 1, 5–7). THF and dimethoxyethane
DME) were less effective (entries 8, 9). Consequently,
CuI (0.05 g)
30
56
64
(
CuCl
2
(0.05 g)
(0.05 g)
DMSO was used as a solvent for the rest of the studies.
With optimized conditions now in hand, we explored the
scope of this process with respect to aryl iodide structure,
and the results are summarized in Table 5. To our delight,
the N-arylation of imidazole is smoothly performed with
the extensive pool of aryl iodides to afford the corre-
sponding products in good to excellent yields. It was
observed that iodoarenes with electron-withdrawing groups
Cu(OAc)
2
b
Polymer-supported copper(I) catalyst (0.05 g) 72
c
Polymer-supported copper(II) catalyst (0.05 g) 79
d
Polymer-supported copper(II) catalyst (0.05 g) 93
d
Homogeneous copper(II) catalyst (0.05 g)
83
Reaction conditions: Polymer-supported copper(II) catalyst (0.05 g,
0
2
a
.0156 mmol), 1 mmol of iodobenzene, 1.2 mmol of imidazole,
mmol K CO atm
, DMSO (10 mL), 120 °C, N
2
3
2
(
Table 5, entries 4, 5) reacted at a faster rate than iodo-
arenes with electron-donating groups (Table 5, entries
, 3). Sterically hindered 2-iodotoluene took longer dura-
Yield determined by GC and GCMS analysis
b
c
d
Catalyst prepared from CuI
2
Catalyst prepared from CuCl
2
tion to afford a good yield (Table 5, entry 6). Extension of
this arylation process with aryl bromides yielded interest-
ing results: The use of bromobenzene in place of iodo-
benzene afforded lower conversion with 74% yield (entry
7) with longer reaction time and longer reaction tempera-
ture. Bromobenzene with an electron-donating group
Catalyst prepared from Cu(OAc)
2
analogue copper(II) Schiff base analogue. Additionally, the
supported catalyst is expected to have several advantages
over the homogenous one. The immobilized catalyst can be
123

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52
Transition Met Chem (2011) 36:447–458
Table 5 N-Arylation of imidazoles with different aryl halides
X
polymer supported
copper(II) catalyst
N
N
N
DMSO, K2CO3, 120 0C
N
H
R1
R1
X=I, Br; R
1
2
= H, Me, OMe, COMe, NO .
a
Entry Aryl halides
Products
Time (h)
Isolated Yield (%)
I
N
N
1
.
14
92
(
A)
H
I
2
.
N
15
83
N
Me(B)
Me
I
3
4
5
.
.
.
N
18
10
12
82
93
92
N
OMe (C)
COMe (D)
NO2 (E)
OMe
I
N
N
COMe
I
N
N
NO
2
I
Me
6
.
N
20
24
62
74
Me
N
(
F)
c
Br
7
.
.
.
N
N
(
A)
H
c
Br
8
9
N
24
18
37
88
N
Me(B)
Me
Br
c
N
N
NO2 (E)
NO
2
Reaction conditions: Polymer supported copper(II) catalyst (0.05 g, 0.0156 mmol), 1 mmol of aryl halide, 1.2 mmol of imidazole, 2 mmol
K
a
2
CO
3
, DMSO (10 mL), 120 °C, N
2
atm
Isolated yield after column chromatography
Yield after consecutive cycles
b
c
Reaction teamparature = 150 °C
1
23

Transition Met Chem (2011) 36:447–458
453
gave lower yield (entry 8), whereas bromobenzene with an
electron-withdrawing group gave excellent yield of product
and temperature (40 °C) parameters were kept constant
for further arylation reaction of substituted phenylboronic
acid with N(H)-heterocycles using this copper(II) catalyst
under base-free conditions. Our method was successfully
amenable to a wide range of arylboronic acids, allowing
preparation of N-arylimidazoles and N-arylbenzimidazoles
in high yield, and the results are shown in Table 7. It was
observed that arylboronic acids with electron-donating
groups reacted at a faster rate and afforded better yields than
arylboronic acids with electron-withdrawing groups (entries
2–6). Similar observations were made when benzimidazole
was used in place of imidazole to obtain the corresponding
N-arylbenzimidazoles but the reactions took longer time
compared with the reactions of imidazole (entries 9–11). o-
and p-substituted arylboronic acids were equally effective
for the coupling with imidazole (entries 2, 7).
(
entry 9).
N-arylation reaction of N(H)-heterocycles
with arylboronic acids using polymer-supported
copper(II) Schiff base catalyst
N-arylation of N(H)-heterocycles with arylboronic acids is
complementary to the N-arylation with aryl halides as it
requires very mild conditions and less time but uses expen-
sive arylboronic acids (Scheme 3). N-arylation reaction
of imidazole with phenylboronic acid using the polymer-
supported copper(II) catalyst was carried out in absence of
any base. Table 6 illustrates the effect of solvent in the N-
arylation reaction of imidazole with phenyl boronic acid
using copper(II) catalyst. Methanol (MeOH), Acetonitrile
We compared the activity of the copper catalyst in the
N-arylation reaction with other reported copper catalysts
[33–35] (Table 8). From Table 8, it can be seen that the
activity of the copper catalyst is more than the other
reported systems.
(
ACN), dimethylformamide (DMF), toluene, and dimeth-
ylsulfoxide (DMSO) were used as a solvent without any
base. It was observed that MeOH was effective providing
higher yield than the other solvents. The solvent (MeOH)
N
N
Heterogeneity tests
N
N
,
12 h
H
B(OH)2
To determine whether the catalyst was actually functioning
in a heterogeneous manner, a hot-filtration test [36] was
performed in the N-arylation reaction of imidazole with
phenyl boronic acid. The solid catalyst was filtered out
after the reaction had proceeded for 6 h and the yield
determined by GC and GCMS analysis was 72%, and the
liquid phase of the reaction mixture was collected at the
reaction temperature. Atomic absorption spectrometric
analysis of the liquid phase of the reaction mixtures col-
lected by filtration confirmed that Cu was absent from the
reaction mixture. The obtained filtrate was stirred under the
reaction conditions. After 12 h, the yield was determined to
be still 72%. This result indicated that the catalytic reaction
was caused by the solid catalyst. Cu was also not detected
in the liquid phase of the reaction mixture after the com-
pletion of the reaction. It is noteworthy that the MeOH
remains completely colorless on addition of copper(II)
catalyst. These results also suggested that the Cu was not
being leached out from the catalyst during the N-arylation
reactions.
copper(II) catalyst
N
N
,
40 0
C
N
methanol
N
H
,
20 h
Scheme 3 N-arylation of imidazole and benzimidazole with phenyl-
boronic acid using polymer-supported copper(II) catalyst
Table 6 Effect of solvent on the coupling of imidazole with phen-
ylboronic acid
B(OH)2
N
N
,
air
N
N
polymer supported
copper(II) catalyst
H
a
Yield (%)
Entry
Solvent
Temperature
Time
1.
2.
3.
4.
5.
MeOH
ACN
40 °C
70 °C
120 °C
115 °C
100 °C
12 h
12 h
16 h
16 h
20 h
96
87
79
75
67
DMF
DMSO
Toluene
Catalyst recycling
The best advantage of the heterogeneous catalysis was
the possibility of recovering and reusing the catalyst during
the reaction. The capability of recycling of the catalyst was
confirmed after five consecutive N-arylation reactions of
Reaction conditions: Polymer-supported copper(II) catalyst (0.05 g,
.0156 mmol), phenylboronic acid (0.0182 g, 1.5 mmol), imidazole
0
(
0.082 g, 1.2 mmol), solvent (10 mL), air
a
Yield determined by GC and GCMS analysis
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54
Transition Met Chem (2011) 36:447–458
Table 7 N-Arylation of
imidazole/benzimidazole with
various arylboronic acids
B(OH)
2
N
N
N
N
H
polymer supported
copper(II) catalyst
R
1
R1
B(OH)
2
methanol , 40
air
°
C
N
N
N
N
H
R
2
R
2
R
1
= H, Me, OMe, F, CF
= H, Me, OMe.
3 2
, NO .
R
2
a
Entry
N(H)-
arylboronic
acid
Products
Time
Isolated Yield (%)
heterocycles
Imidazole
1
2
3
.
.
.
B(OH)2
N
N
12
95
N
(
A)
H
Imidazole
Imidazole
B(OH)2
14
14
93
92
N
Me (B)
Me
B(OH)2
N
N
OMe (C)
OMe
4
.
.
Imidazole
Imidazole
B(OH)2
N
18
18
85
74
N
F (G)
F
5
B(OH)2
N
N
NO2
NO2
(H)
6
.
.
Imidazole
Imidazole
B(OH)2
N
18
16
71
88
N
CF3 (I)
CF3
7
B(OH)2
Me
N
Me
N
(
F)
8.
Imidazole
B(OH)2
N
18
79
N
OMe
OMe
OMe
OMe
(
J)
9
.
Benzimidazole
Benzimidazole
B(OH)2
N
20
20
91
85
N
H
(K)
10.
B(OH)2
N
N
Me
Reaction conditions: polymer
supported copper(II) catalyst
Me
(
0.05 g, 0.0156 mmol),
(
L)
1
1
.5 mmol of arylboronic acid,
.2 mmol of imidazole/
11.
Benzimidazole
B(OH)2
OMe
N
20
86
N
benzimidazole, MeOH (10 mL),
4
OMe
0 °C, air
Isolated yield after column
chromatography
a
1
23

Transition Met Chem (2011) 36:447–458
455
Table 8 Comparison of activity of different copper catalysts in the N-arylation reaction
Reaction
Catalyst
Reaction conditions
Yield (%)
Reference
N-Arylation (imidazole ? iodobenzene)
P-[(C
Cu
Nano-CuO
P-[(C
6
H
4
N=CHPy)Cu(OAc)
2
]
]
DMSO, 120 °C, 14 h
DMSO, 110 °C, 24 h
DMSO, 110 °C, 24 h
MeOH, 40 °C, 12 h
MeOH, 5 h, rt.
92
90
91
95
88
94
This study
2
O
38
a
39
N-Arylation (imidazole ? phenylboronic acid)
H
6 4
N=CHPy)Cu(OAc)
2
This study
b
PANI-Cu
c
CuFAP
40
21
MeOH, 80 °C, 1.5 h
a
CuO nanoparticles
b
Polyaniline-supported copper catalyst
c
Copper-exchanged fluorapatite
after reusing several times showed no change in its IR and
UV–vis spectra.
R1
R2
1
00
8
6
4
2
0
0
0
0
0
Conclusion
In summary, this paper describes a simple method for the
preparation of N-arylated imidazoles and benzimidazoles.
The catalytic system adopted is simple and cheap, starting
from commercially available compounds and employing
only a catalytic amount (0.05 g, 0.0156 mmol) of the
Cu(II) Schiff base catalyst. We have developed a hetero-
geneous polymer-supported copper-catalyzed N-arylation
of imidazoles and benzimidazoles under base-free condi-
tion with various arylboronic acids. This catalyst was also
effective in N-arylation of imidazole with various aryl
halides. Moreover, the catalyst can easily be separated by
simple filtration and reused for several cycles with con-
sistent activity.
1
2
3
4
5
No of cycles
Fig. 4 Recycling activity of the Cu(II) catalyst toward the N-aryla-
tion reaction. Reaction condition: R1 ? Polymer-supported cop-
per(II) catalyst (0.05 g, 0.0156 mmol), 1 mmol of iodobenzene,
1
1
0
.2 mmol of imidazole, 2 mmol K
4 h, N atm. R2 ? polymer-supported copper(II) catalyst (0.05 g,
.0156 mmol), 1.5 mmol of phenylboronic acid, 1.2 mmol of imid-
2
CO
3
, DMSO (10 mL), 120 °C,
2
Experimental
azole, MeOH (10 mL), 40 °C, 12 h, air
Surface morphology and particle size of the samples were
analyzed using a scanning electron microscope (SEM)
(ZEISS EVO40, England) equipped with EDX facility.
Thermogravimetric analysis (TGA) of the immobilized
catalyst was determined using a Mettler Toledo TGA/
SDTA 851. The FTIR spectra were recorded on a Perkin-
Elmer FTIR 783 spectrophotometer using KBr pellets.
Diffuse reflectance UV–Vis spectra were taken using a
Shimadzu UV-2401PC doubled beam spectrophotometer
having an integrating sphere attachment for solid samples.
A Perkin-Elmer 2400C elemental analyzer was used to
collect microanalytical data (C, H and N). Copper content
in the catalyst was determined using a Varian AA240
atomic absorption spectrophotometer (AAS). Analytical
grade reagents and freshly distilled solvents were used
throughout. All reagents and substrates were purchased
imidazole with phenylboronic acid in MeOH medium and
imidazole with iodobenzene in DMSO medium. After the
first run, the catalyst was separated by filtration, washed,
dried under vacuum, and then subjected to the second run
under the optimized reaction conditions. The catalytic run
was repeated with further addition of substrates in appro-
priate amounts under optimum reaction conditions, and the
nature and yield of the final products were comparable with
that of the original one. The results summarized in Fig. 4
demonstrate that there was almost no change in catalytic
activity even after the fifth recycle. Metal content of the
recycled catalyst remained unaltered, indicating no leach-
ing of the metal from the polymer support (Table 1). The
nature of the recovered catalyst has been followed by IR
and UV–Vis spectra. The results indicated that the catalyst
123

4
56
Transition Met Chem (2011) 36:447–458
from Merck. Liquid substrates were predistilled and dried
by appropriate molecular sieve, and solid substrates were
recrystallized before use. Distillation, purification of the
solvents and substrates were done by standard procedures.
Macroporous polystyrene beads cross-linked with 2%
divinylbenzene and 2-pyridinecarboxaldehyde were pur-
chased from Aldrich Chemical Company, USA. Copper
salts were purchased from Merck and used without further
purification.
flask. Copper acetate (0.05 g) in acetic acid (5 mL) was
added to the above suspension with constant stirring and
then refluxed on an oil bath for 24 h. After cooling the
reaction mixture to room temperature, the separated deep
brown color solid was filtered out, washed thoroughly with
methanol and dried under vacuum.
Preparation of homogeneous copper(II) Schiff base
complex
Preparation of p-nitro-polystyrene (2a)
The corresponding Schiff base ligand was prepared
according to the published protocol [38]. The copper
complex was prepared by mixing equal volumes (50 mL)
A suspension of macroporous polystyrene beads (1a)
(
(
5.0 g) in a mixture of acetic anhydride (20 mL), nitric acid
of methanol solution of CuCl (0.170 g, 1.0 mmol) with
2
*70%, 2 mL), and glacial acetic acid (4 mL) was stirred
Schiff base ligand (0.182 g, 1.0 mmol). The mixtures
were refluxed at about 75 °C for 2–3 h on a water bath.
On cooling immediately, precipitate which settled out
was filtered off, washed several times with a minimum
of methanol, and dried under vacuum over anhydrous
CaCl2.
for 30 min at 5 °C followed by 5 h at 50 °C [37]. The
corresponding p-nitro polystyrene (2a) was washed suc-
cessively with acetic acid, water, and methanol and finally
dried under vacuum.
Preparation of p-amino-polystyrene (4a)
General procedure for the N-arylation of imidazole
with iodobenzene catalyzed by homogeneous
copper(II) Schiff base catalyst
A mixture of acetic acid (20 mL), stannous chloride
(
5.0 g), concentrated hydrochloric acid (6 mL), and
p-nitropolystyrene (2) (5.0 g) was stirred for 72 h at room
temperature to reduce the nitro-compound to the corre-
sponding aminehydrochloride (3a) [37]. The residue was
washed several times with hydrochloric acid (12 M) and
glacial acetic acid (1:4) mixture and then with methanol.
The product on repeated treatment with dilute alcoholic
NaOH (5%) produced the corresponding free amine (4).
This was washed with alcohol and dried under vacuum.
In a 100 mL RB flask, homogeneous copper catalyst
(0.0156 mmol), iodobenzene (1 mmol), imidazole
(1.2 mmol), K CO (2 mmol), and DMSO (10 mL) were
2
3
stirred under nitrogen atmosphere at 120 °C. After the
completion of the reaction, the filtrate was extracted with
ethyl acetate (3 9 20 mL) and the combined organic layers
were dried with anhydrous Na SO . The filtrate was con-
2
4
centrated by vacuum, then the reaction mixture was iden-
tified by GC–MS and quantified by GC analysis.
Preparation of the polymer-supported Schiff base
ligand (5a), P-[C H N=CHPy]
6
4
General procedure for the N-arylation of imidazole
with aryl halides catalyzed by heterogeneous copper(II)
Schiff base catalyst
A suspension of macroporous amino polystyrene (4a)
2.0 g) in toluene (25 mL) was taken in a 100 mL round
(
bottom flask and stirred for 30 min. 2-Pyridinecarboxal-
dehyde (5 mL) was added dropwise to the reaction mix-
ture. The suspension changed its color from pale yellow
to yellowish brown. The reaction mixture was refluxed
for 48 h at 120 °C. After cooling it to room temperature,
the brown polymer-anchored Schiff base ligand (5a) was
filtered out, washed thoroughly with methanol, and dried
under vacuum.
In an oven dried 100 mL RB flask, copper catalyst (0.05 g,
0.0156 mmol), aryl halide (1 mmol), imidazole (1.2 mmol),
K CO (2 mmol), and DMSO (10 mL) were stirred under
2
3
nitrogen atmosphere at 120 °C. The reaction mixtures were
collected at different time intervals and identified by GC–MS
and quantified by GC analysis. After the completion of the
reaction, the catalyst was filtered off, washed with water
followed by acetone, and oven dried. The filtrate was
extracted with ethyl acetate (3 9 20 mL), and the combined
organic layers were dried with anhydrous Na SO . The fil-
Preparation of the polymer-supported copper(II) Schiff
base catalyst, P-[(C H N=CHPy)Cu(OAc) ]
6
4
2
2
4
trate was concentrated by vacuum, and the resulting residue
was purified by column chromatography on silica gel to
provide the desired product.
Polymer-supported Schiff base ligand (5a) (2.0 g) was
added to acetic acid (20 mL) placed in a round bottom
1
23

Transition Met Chem (2011) 36:447–458
457
General procedure for the N-arylation of N(H)-
heterocycles with arylboronic acids catalyzed
by heterogeneous copper(II) Schiff base catalyst
NMR (100 MHz, CDCl ) d: 196.4, 140.7, 135.7, 135.4,
131.0,130.3, 120.6, 117.7, 26.5.
1
1-(4-Nitrophenyl)-1H-imidazole (E) [39]. H NMR
3
(
400 MHz, CDCl ) d: 8.39 (d, 2H), 7.99 (bs, 1H), 7.58
3
1
(d, 2H), 7.38 (bs, 1H), 7.28 (bs, 1H); C NMR (100 MHz,
3
In a 100 mL RB flask, copper(II) catalyst (0.05 g,
0
.0156 mmol), aryl boronic acid (1.5 mmol), N(H)-hetero-
CDCl ) d: 146.3, 141.9, 135.4, 131.7, 125.7, 121.0, 117.6.
3
1
1-o-Tolyl-1H-imidazole (F) [39]. H NMR (400 MHz,
cycles (1.2 mmol), and MeOH (10 mL) were stirred under
open air, at 40 °C. To study the progress of the reaction, the
reaction mixtures were collected at different time intervals
and quantified by GC analysis. After the completion of the
reaction, the catalyst was filtered off, washed with water
followed by acetone, and oven dried. Then, it was extracted
with ethyl acetate (3 9 20 mL), and the combined organic
layers were dried with anhydrous Na SO . The filtrate was
CDCl ) d: 7.64 (br s, 1H), 7.40–7.17 (m, 5H), 7.03 (br s,
3
1
3
1H), 2.19 (s, 3H). C NMR (100 MHz, CDCl ) d: 137.4,
3
136.5, 133.8, 131.2, 129.2,128.7, 126.8, 126.4, 120.4, 17.5.
1
1-(4-Fluorophenyl)-1H-imidazole (G) [21]. H NMR
(400 MHz, CDCl ) d: 7.77 (br s, 1H), 7.33–7.37 (m, 2H),
3
1
3
7.15–7.20 (m, 4H); C NMR (100 MHz, CDCl ) d: 163.2,
3
2
4
162, 133.6, 130.1, 123.0 (2C), 118.0, 116.4 (2C).
1
1-(3-nitrophenyl)-1H-imidazole (H) [39]. H NMR
concentrated by vacuum, and the resulting residue was
purified by column chromatography on silica gel to provide
the desired product.
(400 MHz, CDCl ) d: 8.366 (s, 1H), 8.25–8.01 (m, 2H),
3
7.92 (d, 1H, J = 9.4 Hz), 7.75 (t, J = 8.6 1H), 7.51 (br s,
1H), 7.16 (br s, 1 H).
1
1-(4-Trifluoromethylphenyl)-1H-imidazole (I) [21]. H
Characterization of the products
NMR (400 MHz, CDCl ) d: 7.83 (br s, 1H), 7.67 (d, 2H,
3
Melting points were recorded on a melting point apparatus.
1 13
All H and C NMR spectra were recorded at 400 and
J = 8.91 Hz), 7.47 (d, 2H, J = 8.91 Hz), 7.22 (br s, 1H),
7.14(br s, 1H).
1
1
00 MHz, respectively. The characterizations of the prod-
1-(3,4-dimethoxyphenyl)-1H-imidazole (J) [21].
NMR (400 MHz, CDCl ) d: 7.78 (s, 1H), 7.13 (br s, 1H),
H
1
ucts were carried out by H NMR spectroscopy using
3
Bruker DPX-400 in CDCl with TMS as internal standard.
3
7.10 (br s, 1H), 6.86 (br s, 2H), 6.85 (br s, 1H), 3.92 (s, 6H).
1
1-phenyl-1H-benzimidazole(K)[21]. H NMR(400 MHz,
Chemical shifts are given as d value with reference to
tetramethylsilane (TMS) as the internal standard. The
reaction products were quantified (GC data) using a
Varian 3400 gas chromatograph equipped with a 30-m
CP-SIL8CB capillary column and a flame ionization
detector and identified (GC–MS) by Trace DSQ II GC–MS
CDCl ) d: 8.07 (s, 1H), 7.82–7.85 (m, 1H), 7.44–7.61 (m,
3
1
3
6H), 7.5–7.3 (m, 2H); C NMR (100 MHz, CDCl ) d: 142,
3
142.4, 136.7, 133.6, 130, 127.7, 126, 123.8, 122.7 (2C),
120.3, 110.3.
1
1-(4-Methylphenyl)-1H-benzimidazole (L) [21].
NMR (400 MHz, CDCl ) d: 8.01 (br s, 1H), 7.77–7.85 (m,
H
1
equipped with a 60-m TR-50MS capillary column. H and
1
C NMR data of all the products are given below:
3
3
1H), 7.40–7.47 (m, 1H), 7.20 –7.33 (m, 6H), 2.40 (s, 3H);
1
3
Spectroscopic data are as follows:
1
-Phenyl-1H-imidazole (A) [39]. H NMR (400 MHz,
C NMR (100 MHz, CDCl ) d: 144, 142, 137, 135 (2C),
3
1
130.4, 124, 123.8, 122.8 (2C),120.2, 110.1(2C), 21.
1
CDCl ) d = 7.82 (s, 1H), 7.54–7.42 (m, 2H), 7.41–7.40
1-(4-Methoxyphenyl)-1H-benzimidazole (M) [21].
NMR (400 MHz, CDCl ) d: 8.06 (br s, 1H), 7.85–7.88 (m,
H
3
1
3
m, 3H), 7.27 (bs, 1H), 7.24 (bs, 1H); C NMR (100 MHz,
(
3
CDCl ) d = 136.4, 134.5, 130.5, 129.0, 126.9, 121.1,
1H), 7.45–7.47 (m, 1H), 7.40 (d, 2H, J = 9.0 Hz),
3
1
18.2.
-(4-Methylphenyl)-1H-imidazole (B) [39]. H NMR
400 MHz, CDCl ) d = 7.78 (s, 1H), 7.22 (m, 4H), 7.17
7.30–7.33 (m, 2H), 7.05 (d, 2H, J = 9.0 Hz), 3.90 (s, 3H).
1
1
Acknowledgments We thank the Department of chemistry,
University of Calcutta, for providing us the instrumental support. We
gratefully acknowledge DST, New Delhi, for award of grant under its
FIST program to the Department of Chemistry, University of Kalyani.
SMI acknowledges the following agencies for funding: DST, CSIR,
and UGC, New Delhi, India.
(
(
3
1
3
bs, 1H), 7.13 (bs, 1H), 2.42 (s, 3H); C NMR (100 MHz,
CDCl ) 137.2, 135.7, 134.4, 130.1, 130.3, 121.6, 118.0,
3
2
0.90.
-(4-Methoxyphenyl)-1H-imidazole (C) [40]. H NMR
400 MHz, CDCl ) d = 7.70 (s, 1H), 7.25 (d, 2H,
1
1
(
3
J = 9.0 Hz), 7.15 (bs, 1H), 7.13 (bs, 1H), 6.97 (d, 2H,
References
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J = 9.0 Hz), 3.81 (s, 3H); C NMR (100 MHz, CDCl3)
d = 158.8, 135.6, 131.2, 130.6, 120 (2C), 118.4, 114.7
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