Synthesis, characterization and microwave-promoted catalytic activity of novel N-phenylbenzimidazolium salts in heck-mizoroki and suzuki-miyaura cross-coupling reactions under mild conditions

Article abstract of DOI:10.3390/molecules18032501

A number of novel benzimidazolium salts having aryl substituents such as N-phenyl, 4-chlorophenyl and various alkyl substituents were synthesized. Their microwave-assisted catalytic activities were evaluated in Heck-Mizoroki and Suzuki-Miyaura cross-coupling reactions using a catalytic system consisting of Pd(OAc)₂/K₂CO₃ in DMF/H₂O under mild reaction conditions with consistent high yields, except those of 2-bromopyridine.

Full text of DOI:10.3390/molecules18032501

Molecules 2013, 18, 2501-2517; doi:10.3390/molecules18032501
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis, Characterization and Microwave-Promoted Catalytic
Activity of Novel N-phenylbenzimidazolium Salts in
Heck-Mizoroki and Suzuki-Miyaura Cross-Coupling Reactions
under Mild Conditions
Ülkü Yılmaz 1, Hasan Küçükbay 2,*, Selma Deniz 3 and Nihat Şireci 4
1
Battalgazi Vocational School, İnönü University, Battalgazi, 44210 Malatya, Turkey;
E-Mail: ulku.yilmaz@inonu.edu.tr
2
Department of Chemistry, Faculty of Science, İnönü University, 44280 Malatya, Turkey
3
Department of Elementary Education, Faculty of Education, Hakkari University, 30000 Hakkari,
Turkey; E-Mail: selmadeniz@hakkari.edu.tr
4
Department of Elementary Education, Faculty of Education, Adıyaman University,
02040 Adıyaman, Turkey; E-Mail: nsireci@adiyaman.edu.tr
* Author to whom correspondence should be addressed; E-Mail: hasan.kucukbay@inonu.edu.tr;
Tel.: +90-422-377-3881; Fax: +90-422-341-0037.
Received: 25 December 2012; in revised form: 29 January 2013 / Accepted: 16 February 2013 /
Published: 25 February 2013
Abstract: A number of novel benzimidazolium salts having aryl substituents such as
N-phenyl, 4-chlorophenyl and various alkyl substituents were synthesized. Their
microwave-assisted catalytic activities were evaluated in Heck-Mizoroki and
Suzuki-Miyaura cross-coupling reactions using a catalytic system consisting of
Pd(OAc)2/K2CO3 in DMF/H2O under mild reaction conditions with consistent high yields,
except those of 2-bromopyridine.
Keywords: N-phenylbenzimidazoles; Suzuki-Miyaura reaction; Heck-Mizoroki reaction;
microwaves; NHC-precursor
1. Introduction
In recent years, palladium catalyzed the C–C bond forming reaction of aryl halides with
phenylboronic acid and styrene has been great interest for the synthesis of agrochemicals,

Molecules 2013, 18
2502
pharmaceuticals and advanced enantioselective synthesis of natural products [1,2]. These ingenious
carbon-carbon bond formation methods, the Heck-Mizoroki and Suzuki-Miyaura methods, also play
vital roles in the development of new generation organic materials with novel electronic, optical or
mechanical properties [3]. The Heck-Mizoroki and Suzuki-Miyaura reactions are most commonly used
as model reactions to evaluate and compare the catalytic activity of metal complexes, to highlight
ligand effects, and to understand the role of solvent and other additives [4–8]. Nevertheless, most
efficient Heck-Mizoroki and Suzuki-Miyaura reactions reported were carried out in organic solvents
with phosphine-based compounds as the ancillary ligand. In order to overcome the toxicity, air and/or
moisture-sensitivity of phosphine-based ligands, many efforts have been made to find out alternative
ligands [9–12]. In this context, N-heterocyclic carbenes (NHCs) are promising alternative ligands in
palladium-catalyzed cross-coupling reactions due to their strong σ-donor but poor π-acceptor abilities,
low toxicity, stability to air, moisture and heating. They are considered alternatives to phosphine
ligands in metal complexes. For this reason, the design and synthesis of novel and effective NHCs
have attracted a great deal of attention from both academia and industry [13–17]. Furthermore, ligand-
free palladium catalyzed C–C coupling reactions were also studied in water [18–22].
On the other hand, the application of microwave irradiation for promoting reactions has become a
versatile tool in organic synthesis. Rapid heating, reduced reaction times, and in many cases, increased
yields have made microwave assisted organic synthesis a commonly used tool, especially for
preparative medicinal chemistry. The shortened reaction times offered by microwave heating indicate
that additional benefits could be obtained from an energy-saving perspective by exploiting this
technology even further [23–25]. For this reason, microwave-promoted synthesis is an area of
increasing interest in both academic and industrial laboratories. The use of metal catalysts in
conjunction with microwaves may have significant advantages over traditional heating methods since
the inverted temperature gradient under microwave conditions may lead to an increased lifetime of
catalyst through the elimination of wall effects [26]. There are extensive studies about Heck-Mizoroki
and Suzuki-Miyaura type C–C cross-coupling reactions incorporating microwave irradiation using
various ligands other than the benzimidazole moiety [22,27–35].
During recent decades, many researchers have focused mainly on the development of milder
reaction conditions using new catalysts and reaction systems. In order to find a more efficient
palladium catalyst, we also synthesized a series of some new benzimidazole salts, containing alkyl or
heterocycle substituted alkyl and bis-benzimidazole salts as a NHC ligand and we tested the activity of
Pd-NHC based catalytic systems prepared in-situ for the Heck-Mizoroki and Suzuki-Miyaura
cross-coupling reactions under microwave heating conditions [36–40].
In continuation of this subject, herein we describe the synthesis of new benzimidazole salts 1–10
containing phenyl or 4-chlorophenyl on one nitrogen atom of the benzimidazole ring and an alkyl or
substituted alkyl on the other nitrogen atom. The compounds were fully characterized by elemental
13
1
analysis, IR, C-NMR, and H-NMR spectroscopy. We also report the microwave-assisted catalytic
activity of Pd(OAc)2/base/novel benzimidazoles catalytic system in Heck-Mizoroki and Suzuki-
Miyaura cross-coupling reactions.

Molecules 2013, 18
2503
2. Results and Discussion
1-Phenylbenzimidazole and 1-(4-chlorophenyl)benzimidazole were synthesized from N-phenyl-1,2-
diaminobenzene and N-(4-chlorophenyl)-1,2-diaminobenzene by reaction with formic acid in 4N HCl
according to the Phillips’ method, respectively [41,42].
Novel benzimidazolium salts, 1–10 were prepared in good yields of 70%–92% by treatment of
1-phenylbenzimidazole or 1-(4-chlorophenyl)benzimidazole with appropriate alkyl halides in refluxing
DMF. The synthesis of the benzimidazolium salts 1–10 is summarized in Scheme 1.
Scheme 1. Synthesis of N-arylbenzimidazole derivatives.
R : C2H5 , X: I
1.
2.
3.
4.
5.
R : NC-CH2CH2CH2 , X: CI
R X
N
R : CH=CH2OCH2CH2 , X: CI
R : CH2=CHCH2 , X: Br
Y
+
. X-
DMF
N
R
R : p-ClC6H4CH2 , X: CI
N
N
Cl
6.
7.
R : C2H5 , X: I
Y : H, Cl
R : NC-CH2CH2CH2 , X: CI
8. R : CH=CH2OCH2CH2 , X: CI
R X
N
+
N
R : CH2=CHCH2 , X: Br
9.
. X-
DMF
R : p-ClC H CH , X: CI
10.
R
6
4
2
The benzimidazolium salts are air and moisture-stable both in the solid state and in solution. The
1
new benzimidazole derivatives 1–10 were characterized by H-NMR, 13C {1H} NMR, IR and
elemental analysis techniques, which support the proposed structures. The value of δ[13C{1H}],
NCH2Ph in benzimidazolium salts 5 and 10 were both found to be 49.9 ppm. The benzylic protons
signals for the benzimidazolium salts 5 and 10 were found to be 5.89 and 5.92 ppm, respectively. The
value of δ[13C{1H}], NCHN in benzimidazolium salts is usually around 142 ± 4 [37]. For
benzimidazolium salts, 1–10 it was found to be 142.8, 143.6, 143.3, 143.3, 143.6, 142.9, 143.7, 143.5,
143.4 and 143.7 ppm, respectively. These values are in good agreement with the previously reported
results [10]. The NCHN proton signals for the benzimidazolium salts, 1–10 were observed as singlets
at 10.20, 10.74, 10.32, 10.28, 10.51, 10.18, 10.51, 10.30, 10.34 and 10.67 ppm, respectively. As
expected, the highest downfield shifts of the NCHN proton signals were observed among the
benzimidazolium salts which bear electron withdrawing chloride and cyanide substituents on the
nitrogen atom of the benzimidazole scaffold. Thus, the hydrogen atom on the 2-position of the
benzimidazolium salts behave as acids in the sense that they give up protons to suitably strong bases.
As a result of acidic proton of these type benzimidazolium salts, electron-rich olefins can be
synthesized easily, as shown in Scheme 2 [43–45]. The carbon-nitrogen band frequencies, ν(C=N) for
benzimidazole salts, 1–10 were observed at 1560, 1557, 1558, 1554 and 1558, 1559, 1557, 1557, 1552
and 1554 cm−1, respectively.

Molecules 2013, 18
Scheme 2. Electron-rich olefin synthesis through the acidic hydrogen atom removing on
2504
the 2-position of the benzimidazole.
R
N
R
R
THF
N
N
2
+
N
+
2 NaH
X
at inert
atmosphere
N
N
R'
R,R'= alkyl or aryl
R' R'
2.1. The Heck-Mizoroki Coupling Reaction
The Heck-Mizoroki coupling is one of the most studied C–C bond forming reactions between
alkenes and aromatic rings and is widely used by both academic and industrial laboratories. The
industrial applications of this reaction can be observed in the fine chemical field, such as in the
manufacture of pharmaceuticals and herbicides [46–48]. The catalytic yield of the Heck-Mizoroki
coupling reaction is dependent on a variety of parameters such as temperature, solvent, base and nature
of the catalyst and catalyst loading. For this reason, the optimum reaction parameters were investigated
before starting the series of coupling experiments.
In order to find the optimum reaction conditions for the Heck-Mizoroki coupling reaction, a series
of experiments was performed with 2-bromopyridine and styrene as model compounds. The test
reactions were performed using different bases such as K2CO3, Cs2CO3, Et3N and DBU
(1,8-diazabicyclo[5.4.0]undec-7-ene) and different solvents such as DMF/H2O, EtOH/H2O, DMA and
C2H4(OH)2/H2O for different times and temperatures. It was found that the Heck-Mizoroki coupling
reaction catalyzed by 1, Pb(OAc)2 and base catalyst system gave the highest yield when using
DMF/H2O mixture as a solvent and K2CO3 or Cs2CO3 as a base at 80 and 100 °C microwave heating
in 10 min. Very little improvement was observed for the catalytic yields upon increasing the
temperature from 80 °C to 100 °C. No considerable increase in catalytic reaction yields was observed
by prolonging the time from 10 to 20 min either. After these results, we chose K2CO3 as a base, being
cheaper than Cs2CO3, water/DMF as a solvent and 80 °C as reaction temperature for the lower energy
consumption than at 100 °C. We also tested the catalytic yields using a conventional heating system in
a preheated oil bath 5, 10 and 20 min at 60 °C and 80 °C, but the yields of the catalytic conversions
were either nil or very low (Table 1, entries 1–6). Control experiments showed that the yield of
Heck-Mizoroki coupling reaction were decreased in the absence of 1 in 10 min under microwave
heating (Table 1, entries 16, 17). Use of a higher amounts of benzimidazolium salt (4 mol %) did not
improve the catalytic yield (Table 1, entry 18). The coupling reaction did not occur in the absence of
Pd(OAc)2 after 10 min under microwave heating (Table 1, entry 19). The test experiments results for
optimization of the Heck-Mizoroki coupling reaction are given in Table 1. After optimization
experiments (Table 1), we found that use of the catalytic system consists of 1% mol Pd(OAc)2, 2% mol
of 1–10 and 2 mol K2CO3 in DMF/H2O (1:1) at 80 °C/300 W microwave heating led to the best
conversion within 10 min.

Molecules 2013, 18
Table 1. Test experiments for optimization of the Heck-Mizoroki coupling reactions.
2505
Pd(OAc)2 (1 mol %)
1 (2 mol %), heat
Br
N
+
N
Solvent mixture (1:1)
Base (2 equiv)
Thermal heating Microwave heating
Entry Ligand Base
Solvent
Time (min)
°C
60
60
60
80
80
80
Yield,% °C (300 W) Yield,%
1
2
1
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CsCO3
CsCO3
Et3N
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
EtOH/H2O
DMF/H2O
EtOH/H2O
DMF/H2O
EtOH/H2O
5
n.d.
n.d.
17
60
60
60
80
80
80
100
80
80
80
80
80
80
80
80
80
80
80
80
33
49
10
20
5
3
1
52
4
1
03
46
5
1
10
20
10
10
10
10
10
10
10
10
10
10
10
10
10
09
63
6
1
13
64
7
1
65
8
1
62
9
1
43
10
11
12
13
14
15
16
17
18
19
1
57
1
Et3N
52
1
DBU
59
1
DBU
54
1
K2CO3 C2H4(OH)2/H2O
51
1
K2CO3
K2CO3
DBU
DMA
32
no
no
1
DMF/H2O
EtOH/H2O
DMF/H2O
DMF/H2O
16
13
K2CO3
K2CO3
63 k
n.d. l
1
n.d.: not detected. Reaction conditions are same as indicated in the text. Yields are based on aryl bromide.
l
Reactions were monitored by GC-MS. 4 mol % of 1 k, without Pd(OAc)2 .
Using the above optimized reaction conditions, the coupling reactions of four different aryl halides
(bearing electron-donating, electron-withdrawing groups and 2-bromopyridine) and styrene were then
investigated. The results are shown in Table 2. Among the aryl halides, the catalytic yield of those
involving 2-bromopyridine were found to be moderate but the others gave high yields.
Table 2. The Heck-Mizoroki coupling reactions of aryl halides with styrene.
Pd(OAc)2 (1 mol %),
1-10 (2 mol %), mw (300 W)
R
R
X
+
z
DMF/H2O (1:1), 80 oC, 10 min
K2CO3 (2 equiv)
z
Entry
R
H
H
H
H
H
H
H
Z
N
N
N
N
N
N
X
Br
Br
Br
Br
Br
Br
I
Salt
Conversion a (%)
1
2
3
4
5
6
7
1
1
46 b
63 c
64 d
03 e
09 f
16 g
98
1
1
1
no
1
CH

Molecules 2013, 18
2506
Table 2. Cont.
Entry
8
R
H
Z
X
I
Salt
2
Conversion a (%)
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
98
97
9
H
I
3
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
44
45
H
I
4
96
H
I
5
96
H
I
6
93 91 i
90 i
89 i
87 i
88 i
99
H
I
7
H
I
8
H
I
9
H
I
10
1
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
H
I
I
2
98
I
3
98
I
4
98
I
5
97
I
6
95i
94 89 i
90 i
91 i
90i
99
I
7
I
8
I
9
I
10
1
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
2
99
3
98
4
95
5
96
6
94 i
96 92 i
90 i
87 i
86 i
62
7
8
9
10
2
H
N
3
62
H
N
4
60
H
N
5
61
H
N
6
59
H
N
7
58
H
N
8
56
H
N
9
57
H
N
10
58
a Conversions were determined by GC-MS based on the aryl halide. Reaction conditions: temperature ramped
to 80 C (3 min) and held for 5 b min, 10 c min and 20 d min. In preheated oil bath, 5 e min and 10 f min with
g
thermal heating at 80 C. Temperature ramped to 80 C (3 min) and held for 10 min without salt (1).
Isolated yields; i n.d., not detected.

Molecules 2013, 18
2507
The benzimidazolium salts bearing an electron releasing ethyl substituent (1 and 6) are generally
more effective than other salts examined. On the other hand, benzimidazole salts having a
4-chlorophenyl substituent on the nitrogen atom were generally slightly less reactive for the
Heck-Mizoroki reaction than the corresponding phenyl substituent. Of the four different aryl halides
used in the Heck-Mizoroki coupling with styrene, those with electron-withdrawing substituents
(4-bromoacetphenone) were found to give the highest yield (Table 2, entries 27–36). Furthermore, aryl
iodides, those with electron releasing methoxy substituents and without any substituent were also
found to give better yield than 2-bromopyridine.
2.2. The Suzuki-Miyaura Coupling Reaction
Biaryls represent the mostly common structural motif in a broad range of susbtances, from naturally
occurring potentially useful therapeutic agents to versatile building materials for light-emitting diodes,
liquid crystals and many organic compounds with novel electronic, optical properties [49,50].
In order to find the optimum reaction conditions for the Suzuki coupling reaction, a series of
experiments catalyzed couplings between 2-bromopyridine and phenylboronic acid as a model
compounds were performed using similar parameters as in the Heck-Mizoroki coupling reactions
described above. It was found that the Suzuki-Miyaura coupling reaction catalyzed by 1, Pb(OAc)2 and
base catalyst system gave the highest yield when using DMF/H2O mixture as a solvent and K2CO3 or
Cs2CO3 as a base at 80 °C microwave heating in 10 min. After these results, we chose K2CO3 as a
base, being cheaper than Cs2CO3, water/DMF as a solvent and 80 °C as reaction temperature for the
optimum reaction conditions. The conventional heating system in a preheated oil bath 5, 10 and 20 min
at 60 °C, 80 °C and 100 °C was not appropriate for these conversions (Table 3, entries 1–9). When
both microwave results and conventional preheated oil bath results were compared, we observed a
clear improvement in yield and reaction time with microwave heating. Control experiments showed
that the yield of Suzuki coupling reaction was decreased in the absence of 1 in 10 min under
microwave heating (Table 3, entry 18). No coupling reaction was observed in the absence of Pd(OAc)2
after 10 min under microwave heating (Table 3, entry 20). The test experiments results for
optimization of the Suzuki-Miyaura coupling reaction are given in Table 3.
After having established the optimized coupling reaction conditions (Table 3) the scope of the
reaction and efficiencies of the benzimidazolium salts were evaluated by investigating the coupling of
the phenylboronic acid with various aryl halides and a heteroaryl bromide. Under the optimized
conditions, reaction of p-bromoacetophenone, p-iodoanisole and iodobenzene with phenylboronic acid
gave almost identical high yields using a catalytic system consisting of 2 mol % benzimidazole salt 1–10,
1 mol % Pd(OAc)2 and 2 equiv. K2CO3 in DMF/H2O (1:1) at 80 °C under microwave irradiation (300 W)
within 10 min. On the other hand, 2-bromopyridine gave a moderate yield using the optimized
conditions. This is also good result considering the difficult synthesis of 2-arylpyridines using
expensive organometallic reagents such as phenyl lithium or phenyl magnesium halides under an inert
atmosphere. Of the four different aryl halides used in the Suzuki-Miyaura coupling with phenylboronic
acid, those with electron-withdrawing substituents were found to give the highest yield (Table 4,
entries 27–36).

Molecules 2013, 18
Table 3. Test experiments for optimization of the Suzuki-Miyaura coupling reactions.
2508
Pd(OAc)2 (1 mol %)
1 (2 mol %), heat
Br
B(OH)2
+
N
N
Solvent mixture (1:1)
Base (2 equiv)
Thermal heating Microwave
heating
Entry Ligand Base
Solvent
Time (min)
°C
60
Yield,% °C (300 W) Conver. a, %
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
no
1
1
1
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CsCO3
CsCO3
K2CO3
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
EtOH/H2O
H2O
5
0
4
60
60
60
80
80
80
100
100
100
80
80
80
80
80
80
80
80
10
10
10
10
10
47
53
10
20
5
60
3
60
9
55
4
80
6
67
5
10
20
5
80
11
13
7
75
6
80
76
7
100
100
100
67
8
10
20
10
10
10
10
10
10
10
10
10
10
10
10
10
11
14
76
9
77
10
11
12
13
14
15
16
17
18
19
20
21
22
75
66
39
K2CO3 C2H4(OH)2/H2O
56
K2CO3
DBU
DMA
47
DMF/H2O
EtOH/H2O
64
DBU
66
K2CO3 Glycerine/H2O
58
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
DMF/H2O
32
74 m
n.d. n
77 p
65 r
a
m
n
Conversions were determined by GC-MS based on the aryl halide. 4 mol % of 1 , without Pd(OAc)2
,
2 mol % of Pd(OAc)2 p, 0.5 mol % of Pd(OAc)2 .
r
Table 4. The Suzuki-Miyaura coupling reactions of aryl halides with phenylboronic acid.
Pd(OAc)2 (1 mol %),
1-10 (2 mol %), mw (300 W)
R
R
X
B(OH)2
+
DMF/H2O (1:1), 80 oC, 10 min
K2CO3 (2 equiv)
z
z
Entry
R
Z
N
X
Br
Br
Br
Br
Br
Br
I
Salt
1
Conversion a (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
67 b
75 c
76 d
06 e
11 f
32 g
98
N
1
N
1
N
1
N
1
N
no
1
CH
CH
I
2
98

Molecules 2013, 18
2509
Table 4. Cont.
Entry
R
H
Z
X
I
Salt
3
Conversion a (%)
9
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
97
97
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
44
45
H
I
4
H
I
5
96
H
I
6
97 95 i
94i
91i
90i
90i
99
H
I
7
H
I
8
H
I
9
H
I
10
1
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
H
I
I
2
99
I
3
97
I
4
98
I
5
98
I
6
97 95 i
95 i
94 i
94 i
93 i
99
I
7
I
8
I
9
I
10
1
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
2
99
3
99
4
99
5
98
6
98 96 i
96 i
95 i
95 i
95 i
72
7
8
9
10
2
H
N
3
69
H
N
4
70
H
N
5
63
H
N
6
70
H
N
7
67
H
N
8
68
H
N
9
70
H
N
10
70
a Conversions were determined by GC-MS based on the aryl halide. Reaction conditions: temperature ramped
to 80 C (3 min) and held for 5 b min, 10 c min and 20 d min. In preheated oil bath, 5 e min and 10 f min with thermal
heating at 80 C. Temperature ramped to 80 C (3 min) and held for 10 g min without salt (1). Isolated yields i.
The benzimidazole salts bearing an electron-withdrawing chloro substituent on the para-position of
the phenyl ring, 6–10, were found to be the less effective of the salts examined in the Suzuki-Miyaura
cross-coupling reactions (Table 4, entries 12–16, 22–26, 32–36 and 41–45). On the other hand,

Molecules 2013, 18
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benzimidazole salts 1 and 6 bearing an electron-donating ethyl group on the nitrogen atom are the most
effective for the catalytic activity in Suzuki coupling reactions. Similar catalytic results for the
Suzuki-Miyaura cross-coupling reactions have also been obtained using Pd(OAc)2 or PdCl2,
base and benzimidazole or imidazole catalytic systems bearing different electron-donating or
electron-withdrawing aryl, substituted aryl, alkyl and substituted alkyl groups on benzimidazole
or imidazole ligands [51–53].
A
comparison of our catalytic system consisting of
Pd(OAc)2/benzimidazolium salt/K2CO3 in DMF/H2O under microwave heating with similar catalytic
systems including NHC ligand [8,14,54–56], under conventional heating clearly indicates that
microwave heating improves in catalytic yields and reaction times.
3. Experimental
3.1. General Chemical Procedure
Starting materials and reagents used were of commercial grade and purchased from Aldrich or
Merck Chemical Co. Solvents were dried with standard methods and freshly distilled prior to use. All
catalytic activity experiments were carried out in a microwave oven manufactured by Milestone
(Milestone Start S Microwave Labstation for Synthesis, Sorisole, Italy) under aerobic conditions.
13
1H-NMR (300 MHz) and C-NMR (75 MHz) spectra were recorded using a Bruker DPX-300 high
performance digital FT NMR spectrometer (Billercia, MA, USA). Infrared spectra were recorded from
KBr pellets in the range 4000–400 cm−1 on a Perkin-Elmer FT-IR spectrophotometer. Elemental
analyses were performed with a LECO CHNS-932 elemental analyzer (St. Joseph, MI, USA). Melting
points were recorded using an electrothermal-9200 melting point apparatus, and are given uncorrected.
Synthesis of 3-ethyl-1-phenylbenzimidazolium iodide (1). To a solution of 1-phenylbenzimidazole
(1.35 g, 6.95 mmol) in dimethylformamide (5 mL) was added ethyl iodide (0.60 cm3, 6.95 mmol) and
the mixture was heated under reflux for 3 h. The mixture was then cooled and the solvent was removed
in vacuo. The residue was crystallized from EtOH/Et2O (1:1). Yield 1.90 g, 78%; m.p.: 203–204 °C;
υ
(N=C): 1560 cm−1. Anal. found: C, 51.32; H, 4.29; N, 7.94%. Calcd for C15H15N2I: C, 51.45; H, 4.32; N,
1
8.00%. H-NMR (300.13 MHz, DMSO-d6): δ 10.20 (s, 1H, NCHN), 8.24 (d, 1H, C6H4, J = 7.5 Hz),
7.86 (m, 3H, C6H4), 7.78–7.70 (m, 5H, C6H5), 4.63 (q, 2H, CH2CH3, J = 7.2 Hz), 1.64 (t, 3H, CH2CH3,
13
J = 7.2 Hz). C-NMR (75.47 MHz, DMSO-d6): δ 142.8 (NCHN), 133.7, 131.6, 131.5, 130.9, 130.8,
127.9, 127.4, 125.7, 114.5, 113.9 (C6H4 and C6H5), 42.9 (CH2CH3), 14.5 (CH2CH3).
Synthesis of 3-(3-cyanopropyl)-1-phenylbenzimidazolium chloride (2). This compound was similarly
was synthesized from 1-phenylbenzimidazole and 4-chloro-butyronitrile. Yield 1.54 g, 74%; m.p.:
101–102 °C; υ (N=C): 1557 cm−1. Anal. found: C, 68.44; H, 5.35; N, 14.06%. Calcd for C17H16N3Cl: C,
1
68.57; H, 5.42; N, 14.11%. H-NMR (300.13 MHz, DMSO-d6): δ 10.74 (s, 1H, NCHN), 8.35 (d, 1H,
C6H4, J = 8.1 Hz), 7.91–7.84 (m, 3H, C6H4), 7.79–7.68 (m, 5H, C6H5), 4.81 (t, 2H, CH2CH2CH2CN,
J = 6.6 Hz), 2.86 (t, 2H, CH2CH2CH2CN, J = 7.2 Hz), 2.40 (m, 2H, CH2CH2CH2CN). 13C-NMR
(75.47 MHz, DMSO-d6): δ 143.6 (NCHN), 133.7, 131.7, 131.4, 130.8, 127.9, 127.4, 125.6, 120.5, 114.6,
113.9 (C6H4 and C6H5), 46.3 (CH2CH2CH2CN), 34.3 (CH2CH2CH2CN), 25.0 (CH2CH2CH2CN), 14.3
(CH2CH2CH2CN).

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Synthesis of 3-(2-vinyloxy)ethyl-1-phenylbenzimidazolium chloride (3). Synthesized from 1-phenylbenz-
imidazole and 2-chloroethyl vinyl ether. Yield 1.66 g, 79%; m.p.: 112–113 °C; υ (N=C): 1558 cm−1.
Anal. found: C, 67.76; H, 5.64; N, 9.22%. Calcd for C17H17N2OCl: C, 67.88; H, 5.70; N, 9.31%.
1H-NMR (300.13 MHz, DMSO-d6): δ 10.32 (s, 1H, NCHN), 8.25 (d, 1H, C6H4, J = 7.8 Hz), 7.90–7.87
(m, 3H, C6H4), 7.80–7.70 (m, 5H, C6H5), 5.52 (t, 1H, CH2CH2OCH=CH2, J = 5.7 Hz), 4.69 (t, 2H,
CH2CH2OCH=CH2, J = 4.6 Hz), 3.92 (two d, 2H, CH2CH2OCH=CHH, J = 4.8 Hz and 15 Hz), 3.40 (t,
2H, CH2CH2OCH=CH2, J = 4.6 Hz). 13C-NMR (75.47 MHz, DMSO-d6): δ 143.3 (NCHN), 143.4,
133.7, 132.1, 131.5, 130.9, 130.8, 127.7, 127.2, 125.7 (C6H4 and C6H5), 114.9, 113.8 (CH=CH2), 59.2
(CH2CH2OCH=CH2), 50.4 (CH2CH2OCH=CH2).
Synthesis of 3-allyl-1-phenylbenzimidazolium bromide (4). Synthesized from 1-phenylbenzimidazole
and allyl bromide. Yield 1.87 g, 85%; m.p.: 171–172 °C; υ (N=C): 1554 cm−1. Anal. found: C, 60.91; H,
4.73; N, 8.73%. Calcd for C16H15N2Br: C, 60.97; H, 4.80; N, 8.89%. 1H-NMR (300.13 MHz, DMSO-d6):
δ 10.28 (s, 1H, NCHN), 8.40 (d, 1H, C6H4, J = 7.2 Hz), 7.96–7.85 (m, 3H, C6H4, 7.82–7.77 (m, 5H,
C6H5), 6.26–6.13 (m, 1H, CH2CH=CH2), 5.60 (dd, 1H, CH2CH=CHH, J = 15.9; 1.2 Hz), 5.46 (dd, 1H,
CH2CH=CHH, J = 9.0; 1.2 Hz), 5.30 (d, 2H, CH2CH=CH2, J = 6.0 Hz). 13C-NMR (75.47 MHz,
DMSO-d6): δ 143.3 (NCHN), 133.6, 131.7, 131.5, 131.2, 130.9, 130.8, 127.9, 127.4, 125.7, 121.4
(C6H4 and C6H5), 114.7, 114.1 (CH2CH=CH2), 49.7 (CH2CH=CH2).
Synthesis of 3-p-chlorobenzyl-1-phenylbenzimidazolium chloride (5). Synthesized from 1-phenylbenz-
imidazole and p-chlorobenzyl chloride. Yield 1.88 g, 76%; m.p.: 82–83 °C; υ (N=C): 1558 cm−1. Anal.
1
found: C, 67.45; H, 4.51; N, 7.73%. Calcd for C20H16N2Cl2: C, 67.62; H, 4.54; N, 7.89%. H-NMR
(300.13 MHz, DMSO-d6): δ 10.51 (s, 1H, NCHN), 8.06–8.03 (m, 1H, C6H4), 7.91–7.86 (m, 3H, C6H4),
13
7.76–7.73 (m, 5H, C6H5), 7.71 (d, 2H, C6H4, J = 8.4 Hz), 5.89 (s, 2H, CH2). C-NMR (75.47 MHz,
DMSO-d6): δ 143.6 (NCHN), 134.0, 133.6, 133.1, 131.8, 131.3, 131.0, 130.8, 129.4, 128.0, 127.6,
125.8, 114.6, 114.2 (C6H4 and C6H5), 49.9 (NCH2-).
Synthesis of 3-Ethyl-1-p-chlorophenylbenzimidazolium iodide (6). To a solution of 1-p-chlorophenylbenz-
imidazole (1.37g, 6.0 mmol) in dimethylformamide (5 mL) was added ethyl iodide (0.50 cm3, 6.0 mmol)
and the mixture was heated under reflux for 3 h. The mixture was then cooled and the solvent was removed
in vacuo. The residue was crystallized from EtOH/Et2O (1:1). Yield 1.98 g, 86%; m.p.: 216–217 °C;
υ (N=C): 1559 cm−1. Anal. found: C, 46.56; H, 3.63; N, 7.09%. Calcd for C15H14N2ICl: C, 46.84; H, 3.67; N,
1
7.28%. H-NMR (300.13 MHz, DMSO-d6): δ 10.18 (s, 1H, NCHN), 8.23 (d, 1H, C6H4, J = 6.3 Hz),
7.92–7.71 (m, 7H, C6H4 and C6H4Cl), 4.62 (q, 2H, CH2CH3, J = 7.3 Hz), 1.63 (t, 3H, CH2CH3, J = 7.3 Hz).
13C-NMR (75.47 MHz, DMSO-d6): δ 142.9 (NCHN), 133.5, 132.6, 131.6, 131.4, 130.8, 127.9, 127.7,
127.4, 114.5, 113.9 (C6H4 and C6H4Cl), 42.9 (CH2CH3), 14.4 (CH2CH3).
Synthesis of 3-(3-cyanopropyl)-1-p-chlorophenylbenzimidazolium chloride (7). Similarly synthesized
from 1-p-chlorophenylbenzimidazole and 4-chlorobutyronitrile. Yield 1.44 g, 72%; m.p.: 101–102 °C;
υ
(N=C): 1557 cm−1. Anal. found: C, 61.14; H, 4.43; N, 12.18%. Calcd for C17H15N3Cl2: C, 61.46; H,
1
4.55; N, 12.65%. H-NMR (300.13 MHz, DMSO-d6): δ 10.51 (s, 1H, NCHN), 8.27 (d, 1H, C6H4,
J = 8.1 Hz), 7.93–7.71 (m, 7H, C6H4 and C6H4Cl), 4.72 (t, 2H, CH2CH2CH2CN, J = 6.45 Hz), 2.81 (t,
2H, CH2CH2CH2CN, J = 7.2 Hz), 2.38 (m, 2H, CH2CH2CH2CN). 13C-NMR (75.47 MHz, DMSO-d6):

Molecules 2013, 18
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δ 143.7 (NCHN), 135.5, 132.5, 131.6, 131.5, 130.9, 127.9, 127.7, 120.4, 114.5, 113.9 (C6H4 and C6H4Cl),
46.3 (CH2CH2CH2CN), 34.4 (CH2CH2CH2CN), 24.9 (CH2CH2CH2CN), 14.3 (CH2CH2CH2CN).
Synthesis of 3-(2-vinyloxyethyl)-1-p-chlorophenylbenzimidazolium chloride (8). Synthesized from 1-p-
chlorophenylbenzimidazole and 2-chloroethyl vinyl ether. Yield 1.41 g, 70%; m.p.: 164–166 °C; υ
(N=C): 1557 cm−1. Anal. found: C, 60.26; H, 4.64; N, 8.08%. Calcd for C17H16N2OCl2: C, 60.91; H,
1
4.81; N, 8.36%. H-NMR (300.13 MHz, DMSO-d6): δ 10.30 (s, 1H, NCHN), 8.25 (d, 1H, C6H4,
J = 8.4 Hz), 7.94–7.70 (m, 7H, C6H4 and C6H4Cl), 5.54 (t, 1H, CH2CH2OCH=CH2, J = 6.0 Hz), 4.68
(t, 2H, CH2CH2OCH=CH2, J = 4.6 Hz), 3.92 (dd, 2H, CH2CH2OCH=CHH, J = 5.0 Hz), 3.40 (t,
CH2CH2CH2CN). 13C-NMR (75.47 MHz, DMSO-d6): δ 143.5 (NCHN), 133.5, 131.9, 131.6, 130.8,
127.8, 127.7, 127.3 (C6H4 and C6H4Cl), 114.8, 113.8 (CH=CH2), 59.1 (CH2CH2OCH=CH2), 50.5
(CH2CH2OCH=CH2).
Synthesis of 3-Allyl-1-p-chlorophenylbenzimidazolium Bromide (9). Synthesized from 1-p-chlorophenyl-
benzimidazole and allyl bromide. Yield 1.93 g, 92%; m.p.: 119–121 °C; υ (N=C): 1552 cm−1. Anal.
1
found: C, 54.23; H, 4.03; N, 7.83%. Calcd for C16H14N2BrCl: C, 54.96; H, 4.04; N, 8.01%. H-NMR
(300.13 MHz, DMSO-d6): δ 10.34 (s, 1H, NCHN), 8.14 (d, 1H, C6H4, J = 8.4 Hz), 7.94–7.70 (m, 7H,
C6H4 and C6H4Cl), 6.26–6.14 (m, 1H, CH2CH=CH2), 5.60 (d, 1H, CH=CHH, J = 17.1 Hz), 5.46 (d,
1H, CH2CH=CHH, J = 10.2Hz), 5.32 (d, 2H, CH2CH=CH2, J = 5.7 Hz). 13C-NMR (75.47 MHz,
DMSO-d6): δ 143.4 (NCHN), 135.5, 132.5, 131.7, 131.4, 131.1, 130.8, 127.9, 127.8, 127.4, 121.4 (C6H4
and C6H4Cl), 114.7, 114.0 (CH2CH=CH2), 49.7 (CH2CH=CH2).
Synthesis of 3-p-Chlorobenzyl-1-p-chlorophenylbenzimidazolium Chloride (10). Synthesized from 1-p-
chlorophenylbenzimidazole and p-chlorobenzyl chloride. Yield 2.01 g, 86%; m.p.: 209–210 °C; υ (N=C)
:
1554 cm−1. Anal. found: C, 61.05; H, 3.79; N, 7.02%. Calcd for C20H15N2Cl3: C, 61.64; H, 3.88; N,
7.19%. 1H-NMR (300.13 MHz, DMSO-d6): δ 10.67 (s, 1H, NCHN), 8.06–7.49 (m, 12H, C6H4, C6H4Cl
and CH2C6H4Cl), 5.92 (s, 2H, CH2). 13C-NMR (75.47 MHz, DMSO-d6): δ 143.7 (NCHN), 135.5,
134.0, 133.5, 133.1, 132.5, 131.8, 131.1, 130.7, 129.3, 128.0, 127.7, 127.5, 114.6, 114.1 (C6H4,
NC6H4Cl and NCH2C6H4Cl), 49.9 (NCH2).
3.2. General Procedure for the Heck-Mizoroki Reactions
Pd(OAc)2 (1 mmol %), benzimidazolium halides 1–10 (2 mmol %), the aryl halide (1 mmol),
styrene (1.2 mmol), K2CO3 (2 mmol), water (3 mL), and DMF (3 mL) were added to a microwave
apparatus and the mixture was heated at 80 °C (300 W) for 10 min. A ramp time of 3 min was used to
reach the temperature of 80 °C. At the end of reaction, the mixture was cooled; the product was
extracted with ethyl acetate/n-hexane (1:5) and filtered through a pad of silica gel with copious
washing. The percent conversion was determined by GC-MS based on aryl halide using the normalized
peak areas method. The Heck-Mizoroki coupling yields between styrene with phenyl iodide,
4-iodoanisole or 4-bromo-acetophenone were also determined as an isolated yield for the comparison
purposes with the GC based conversion (Table 2, entries 12–16, 22–26 and 32–36). The isolated yields
were determined as follow: at the end of the coupling reaction, the mixture was cooled to room
temperature; the contents of the reaction vessel were poured into a separatory funnel. Water (3 mL)

Molecules 2013, 18
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and ethyl acetate (5 mL) were added, and the coupling product was extracted and removed. After
further extraction of the aqueous phase with ethyl acetate (5 mL) and combining the extracts, the ethyl
acetate was removed in vacuo leaving the trans-stilbene or corresponding derivatives which was
characterized by comparison of NMR data with that in the literature.
3.3. General Procedure for the Suzuki Reactions
Pd(OAc)2 (1 mmol %), benzimidazolium halides 1–10 (2 mmol %), aryl halide (1 mmol),
phenylboronic acid (1.2 mmol), K2CO3 (2 mmol), water (3 mL), DMF (3 mL) were added to
microwave apparatus and the mixture was heated at 80 °C (300 W) for 10 min. A ramp time of 3 min
was used to reach the temperature of 80 °C. At the end of reaction, the mixture was cooled, the product
extracted with ethyl acetate/n-hexane (1:5), chromatographed on a silica gel column. The purity of
coupling products was checked by NMR and GC-MS, and yields are based on aryl halide. The
coupling products were confirmed by increasing the peaks on gas chromatograms and mass values
1
from MS spectrums. All coupling products were also isolated and characterized by H-NMR or MS
before the serial catalytic work up each time. The Suzuki coupling yields between phenylboronic acid
and phenyl iodide, 4-iodoanisole or 4-bromoacetophenone were also determined as an isolated yield
for comparison purposes with the GC based yields (Table 4 entries, 12–16, 22–26 and 32–36). The
isolated yields were determined as follows: at the end of the Suzuki coupling reaction, the mixture was
cooled to room temperature, the contents of the reaction vessel were poured into a separatory funnel.
Water (3 mL) and ethyl acetate (5 mL) were added, and the coupling product was extracted and
removed. After further extraction of the aqueous phase with ethyl acetate (5 mL) and combining the
extracts, the ethyl acetate was removed in vacuo leaving the coupling product which was characterized
by comparison of NMR data with that in the literature.
4. Conclusions
We have prepared ten non-symmetric 1,3-disubstituted benzimidazolium salts 1–10 bearing on the
nitrogen atoms of azolium ring phenyl, 4-chlorophenyl, 3-cyanopropyl, 2-vinyloxyethyl, allyl and
4-chlorobenzyl substituents. The catalytic activity of the novel benzimidazolium salts were evaluated
using catalytic systems consisting of Pd(OAc)2/benzimidazolium salt and K2CO3 for the Heck-
Mizoroki and Suzuki-Miyaura cross coupling reactions. The catalyst systems in the Heck-Mizoroki
and Suzuki-Miyaura reactions gave better yields under microwave-assisted moderate conditions after
very short reaction times compared to those given in the literature [52,57–59]. In addition, coupling of
2-pyridyl bromide with both styrene and phenylboronic acid afford the corresponding stilbene and
biaryl products in satisfactory yields after 10 min.
Acknowledgments
This work was financially supported by the İnönü University Research Fund (I.Ü. B.A.P. 2011/144).

Molecules 2013, 18
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Supplementary Materials
NMR spectra of the new compounds and some coupling products are available free of charge via
the internet at http://www.mdpi.com/1420-3049/18/3/2501/s1.
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Sample Availability: Samples of the all compounds are available from the authors.
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