Microwave assisted suzuki-miyaura and ullmann type homocoupling reactions of 2- and 3-halopyridines using a Pd(OAc)2/benzimidazolium salt and base catalyst system

Article abstract of DOI:10.3390/molecules18043712

A number of novel benzimidazole derivatives 1-4 were synthesized and the catalytic activity of these compounds in a catalytic system consisting of a benzimidazolium salt/Pd(OAc)₂/K₂CO₃ were investigated in the Suzuki-Miyaura and Ullmann type homocoupling reactions under microwave irradiation. We obtained both cross coupling and homocoupling products of pyridine and some side products such as dimethylaminopyridine and unsubstituted pyridine.

Full text of DOI:10.3390/molecules18043712

Molecules 2013, 18, 3712-3724; doi:10.3390/molecules18043712
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Microwave Assisted Suzuki-Miyaura and Ullmann Type
Homocoupling Reactions of 2- and 3-Halopyridines Using a
Pd(OAc)2/Benzimidazolium Salt and Base Catalyst System
Ülkü Yılmaz 1, Selma Deniz 2, Hasan Küçükbay 3,* and Nihat Şireci 4
1
Battalgazi Vocational School, İnönü University, Battalgazi, Malatya 44210, Turkey;
E-Mail: ulku.yilmaz@inonu.edu.tr
2
Department of Elementary Education, Faculty of Education, Hakkari University, Hakkari 30000,
Turkey; E-Mail: selmadeniz@hakkari.edu.tr
3
Department of Chemistry, Faculty of Science, İnönü University, Malatya 44280, Turkey
4
Department of Elementary Education, Faculty of Education, Adıyaman University,
Adıyaman 02040, Turkey; E-Mail: nsireci@adiyaman.edu.tr
* Author to whom correspondence should be addressed; E-Mail: hkucukbay@inonu.edu.tr;
Tel.: +90-422-377-3881; Fax: +90-422-341-0037.
Received: 1 March 2013; in revised form: 15 March 2013 / Accepted: 15 March 2013 /
Published: 25 March 2013
Abstract: A number of novel benzimidazole derivatives 1–4 were synthesized and the
catalytic activity of these compounds in a catalytic system consisting of a benzimidazolium
salt/Pd(OAc)2/K2CO3 were investigated in the Suzuki-Miyaura and Ullmann type
homocoupling reactions under microwave irradiation. We obtained both cross coupling and
homocoupling products of pyridine and some side products such as dimethylaminopyridine
and unsubstituted pyridine.
Keywords: Suzuki-Miyaura reaction; homocoupling; N-heterocyclic carbene; microwave;
pyridine derivatives
1. Introduction
Palladium-catalyzed cross-coupling reactions have emerged as a powerful method in organic
synthesis for the formation of carbon-carbon bonds [1]. Among them, the Suzuki-Miyaura reaction
plays an important role in modern synthetic chemistry [2]. Both symmetrical and unsymmetrical

Molecules 2013, 18
3713
biaryls can be prepared easily using this type of reactions. There are many reports on the Suzuki-
Miyaura cross-coupling reaction in the literature [3–5]. On the other hand, there are also noteworthy
reports on the Ullmann type homocoupling reaction of aryl halides using different catalysts other than
the traditional copper. Most of them involve stoichiometric amounts of transition metal salts such as
TiCl4, TiCl, Vo(OEt)Cl2, CoCl2, FeCl3, and Pd(OAc)2. Some of them also need very reactive phenyl
lithium or phenyl magnesium halide as a homocoupling partner [6–12]. In the coupling reactions, the
efficiency of the Pd-based catalyst is strongly dependent on the nature of the coordinated ligands,
solvent and reactivity of the aryl halides [13]. Bulky groups on the coupling partner also affect the
catalytic yield in the Suzuki-Miyaura cross-coupling reactions [14]. The phosphine-based ligands are
generally used as a ligand in this type of homocoupling reactions [15–24]. However tertiary phosphine
ligands usually require air-free handling to prevent ligand oxidation and their P-C bond is unstable at
elevated temperature, and as a consequence higher phosphine concentrations are required [25]. Since
the isolation of the first stable free carbene by Arduengo et al. in 1991, the chemistry of carbenes and
their transition metal-complexes have been very popular research subject in the organic and
organometallic chemistry. Due to strong σ-donor but poor π-acceptor abilities, low toxicity and their
stability to air and moisture, NHC ligands are considered alternatives to phosphine ligand in metal
complexes [26–32].
On the other hand, microwave irradiation has gained importance in organic synthesis due to an
increased life time of catalysts thorough the elimination of the wall effects, homogenous and short time
heating and energy saving [33]. We have also observed significant contributions of microwave heating
in Suzuki-Miyaura and Mizoroki-Heck cross coupling reactions using homoaromatic coupling
partners [34–39]. After these observations, we also focused on halopyridines as the heteroaromatic
coupling partner to obtain pyridine derivatives. As known, the pyridine motif is a ubiquitous building
block found in many biologically active compounds. For example, methoxatin displays antioxidant
properties, acodazole has antimicrobial and antineoplastic properties, whereas nifuroquine and
telithromycin are antibacterial agents that all contain substituted pyridine moieties [40]. Due to limited
information about cross coupling of arylboronic acid with aryl pyridines in the literature, we wish to
report on the base-palladium-NHC-catalyzed direct arylation at the 2 or 3 position of pyridines and
homocoupling of halopyridines and formation of some side products such as aminopyridine, biphenyl
and pyridine.
2. Results and Discussion
The preparation of 2- or 3-arylsubstituted pyridine derivatives is of great importance in the
synthesis of natural products, pharmaceutical and advanced functional compounds [41–46]. In recent
years, there was an increasing interest in the synthesis of bipyridine derivatives because they are used
in several areas such as an intermediate in chemical engineering and drug synthesis, inductor,
photosensitive reagent and among them 2,2'-bipyridine is also important metal catalyst ligand [47–51].
But most of the reported synthesis require a long reaction time and provide only moderate yields. To
our knowledge there is only one report of a catalytic synthesis of bipyridine under microwave
irradiation using a phosphine based ligand and there is no example of palladium NHC catalyzed direct

Molecules 2013, 18
3714
arylation using halopyridines and phenylboronic acid and homocoupling of the halopyridines under
microwave heating conditions [52].
In this work the synthesis of the benzimidazole salts (1–4, and I [53]) from 1-(4-bromobenzyl)-
benzimidazole [54] is shown in Scheme 1. Molecular structures of the new compounds 1–4 were
1
identified by H, 13C-NMR, IR spectroscopic methods and elemental analysis. The NCHN proton
signals for the benzimidazolium salts 1–4 were observed as singlets at δ = 10.23, 10.16, 9.77 and 9.88
ppm, respectively. The [13C{1H}], NCHN in benzimidazolium salts 1–4 were observed at δ = 143.5,
143.2, 142.9 and 142.7 ppm, respectively. These values are in good agreement with other recently
reported results [34–37]. IR data for the C=N band frequencies, υ(C=N), for benzimidazolium salts 1–4
were observed at 1,559, 1,559, 1,567 and 1,558 cm−1, respectively.
Scheme 1. Synthesis of new benzimidazolium salts.
Br
Br
N
RX
N
N
+
N
X
R
I. R:
X: Br
X: Cl
X: Br
X: Br
X: I
Br
Cl
1. R:
2. R:
Me
3. R:
4. R:
In the present work 2-bromopyridine was chosen as a model coupling partner for both the
Suzuki-Miyaura type C-C cross-coupling and the Ullmann type homocoupling reaction to determine
the best solvent for these reactions. The values of other parameters such as base, temperature and
catalyst loading true catalyst amount were based on our recently reported optimal parameters [35].
DMF/H2O (1:1) mixture was chosen as a best solvent for the both the Suzuki-Miyaura and the
Ullmann type coupling reactions.
2.1. The Suzuki-Miyaura Type Coupling Reaction
The Suzuki-Miyaura reaction is one of the most versatile and utilized reactions for the selective
construction of carbon-carbon bonds, in particular for the formation of biaryl and heterobiaryl
derivatives [2,55].

Molecules 2013, 18
3715
In this work, we aimed to determine efficiencies of benzimidazolium salts I and 1–4 in the coupling
reactions between 2- or 3-halopyridines and phenylboronic acid under optimized conditions. The
solvent effects were investigated using 2-bromopyridine and phenylboronic acid in terms of the main
product yield (Suzuki-Miyaura product) in EtOH/H2O (1:1) 57.6% (Table 1, entry 3), DMA/H2O (1:1)
63.4% (Table 1, entry 4), DMF/H2O (1:1) with a 70.0% (Table 1, entry 5). After these results,
DMF/H2O (1:1) mixture was chosen as a best solvent system for the coupling reaction. The catalytic
reactivity was also investigated in pure water as a green solvent, but the coupling product yield
decreased drastically to 2% (Table 1, entry 2). Furthermore, the yield of the Suzuki-Miyaura coupling
product was significantly decreased absence of the ligand in the catalytic system (Table 1, entry 1).
Finally, we found that the use of 1 mmol % Pd(OAc)2, 2 mmol % of I, 1–4 and 2 mmol of K2CO3 in
DMF/H2O (1.1) at 120 °C/300 W microwave heating given rise to the best conversation within 10 min.
Apart from the expected Suzuki-Miyaura cross coupling products, some side products such as
biphenyl, pyridine, 2,2'-bipyridine or 3,3'-bipyridine, and 2-dimethylaminopyridine were also obtained
varying amounts from the reaction mixtures. All of the results for the Suzuki-Miyaura type coupling
reactions with side products were given in Table 1. As can be expected, heteroaryl chloride was less
reactive than heteroaryl bromide, and the coupling yieldd of 2- or 3-chloropyridines with
phenylboronic acid (Table 1, entries 10–14, 20–24) were found to be lower than those of the
corresponding heteroaryl bromides (Table 1, entries 6–9, 15–19). It is noteworthy that the coupling
product yields of 3-halopyridines with phenylboronic acid were higher than with 2-halopyridines. This
is also expected result for the electrophilic reaction of the palladium catalyst with halopyridines due to
the fact their more active site for this reaction is the  (3) position (Table 1, entries 6–9 and 15–19; 10–14
and 20–24). In comparing the side products, we obtained very low levels of amination products from
2-halopyridines (Table 1, entries 1, 4–6, 8, 10 and 12). Contrary to the literature information [56,57],
we have not obtained any amination product for 3-halopyridines because the most active site for the
nucleophilic attack on pyridine is the 2-position. Similar amination of aryl(heteroaryl) halides with
amides using an expensive base such as KOtBu and a long reaction time, except without phenylboronic
acid, was reported in the literature recently [56,57].
We also obtained some bipyridine side product (Table 1, entries 1, 3–14, 18 and 22) almost with
similar reactivity of 2- or 3-halopyridines, but the yields are more than those of the amination. We
have also observed both biphenyl and bare pyridine as side products in reactions of both 2- and
3-halopyridines with phenylboronic acid (Table 1, last 2 columns). It is remarkable that the steric and
electronic properties of the benzimidazole ligands have an influence on the reactivity of arylboronic
acid with halopyridines for the Suzuki-Miyaura type cross-coupling reactions and also side product
yields. Among the benzimidazole ligands, compound 4 having only an ethyl group was found to be the
less reactive for the Suzuki-Miyaura type reactions (Table 1, entries 9, 14, 19 and 24). From the results
obtained, it can be concluded that, the substituted phenyl rings on both the nitrogen atoms of the
benzimidazole scaffold also play an important role for the catalytic conversion due to π-electron richness.

Molecules 2013, 18
Table 1. The Suzuki-Miyaura reactions of halopyridines and the side products.
3716
1 mmol % Pd(OAc)2,
2 mmol % I,1-4,
2 mmol K2CO3
z
z
z
Y
Y
Y
z
N
+
+
+
+
+
Y
N
mw, 120 oC, 10 min
DMF:H2O (1:1)
Y
z
X
B(OH)2
% Yields
z
z
z
Y
Y
Y
Entry X
Y
Z
Salt
N
Y
N
z
1 a
2 b
3 c
4 d
5 e
6
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
N
N
N
N
N
N
N
N
N
N
N
N
N
N
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
-
40.3
13.8
-
1.1
-
0.6
-
17.2
2
2
2
2
I
2.0
-
57.6
63.4
70.0
65.0
67.0
72.5
66.8
61.9
64.1
65.4
66.1
51.8
90.0
89.3
91.2
93.4
90.0
66.6
76.5
70.1
73.5
58.0
5.3
4.7
22.0
-
-
15.6
7.1
0.8
0.3
-
0.7
0.7
7.0
23.7 0.7
9.9
7
1
3
4
I
27.2
17.8
18.8
12.0
14.5
12.4
12.5
2.5
-
-
1.6
1.3
-
4.2
8
0.6
7.8
9
-
4.4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
0.4
3.1
9.1
5.4
4.4
6.8
2.8
2.1
2.9
1.9
2.4
2.5
6.7
2.0
1.8
4.8
12.6
6.1
1
2
3
4
I
-
0.2
-
12.8
9.0
-
4.3
Br CH
Br CH
Br CH
Br CH
Br CH
Cl CH
Cl CH
Cl CH
Cl CH
Cl CH
-
7.2
N
1
2
3
4
I
-
-
8.6
N
-
-
5.9
N
0.7
-
-
4.0
N
-
7.6
N
-
-
23.8
12.5
16.4
18.5
9.2
N
1
2
3
4
-
-
N
0.7
-
-
N
-
N
-
-
Reaction conditions: 1.0 mmol halopyridine, 1.2 mmol phenylboronic acid, 2 mmol K2CO3, 1 mmol %
Pd(OAc)2, 2 mmol % I or 1–4, DMF (3 mL)-H2O (3 mL). Temperature ramped to 120 °C 3 min. Yields are
a
b
based on aryl halide. Reactions were monitored by GC-MS. No salt (ligand); Solvent pure H2O;
c EtOH/H2O (1:1); d DMA/H2O (1:1); e DMF/H2O (1:1).
2.2. The Ullmann Type Homocoupling Reaction
Efficiencies of benzimidazolium salts in homocoupling reactions were examined using 2- or
3-halopyridines. Similar to the Suzuki-Miyaura cross-coupling reaction, we first tried different solvent
systems such as pure water (Table 2, entry 1), EtOH/H2O (1:1) (Table 2, entry 2) DMA/H2O (1:1)

Molecules 2013, 18
3717
(Table 2, entry 3) and DMF/H2O (1:1) (Table 2, entry 4) due to find the best one. Among the solvent
systems, DMF/H2O (1:1) was found the good solvent systems but the homocoupling yield was still
low. Hence, the reaction time was increased to 30 min. Running the reaction for 30 min at DMF/H2O
(1:1) mixture as a solvent we obtained reasonable homocoupling yield (Table 2, entry 5) and these
parameters; 1 mmol % Pd(OAc)2, 2 mmol % of benzimidazolium salts and 2 mmol K2CO3 in
DMF/H2O (1:1) at 120 °C/300 W microwave heating were chosen as an optimum reaction conditions.
All of the results obtained using the optimum parameters for the Ullmann type coupling reactions,
along with some side products, were given in Table 2.
Table 2. The Ullmann type homocoupling reactions of halopyridines and side products.
1 mmol % Pd(OAc)2,
z
z
2 mmol % I,1-4,
2 mmol K2CO3
Y
Y
z
N
2
+
+
Y
N
mw, 120 oC, 30 min
DMF:H2O (1:1)
Y
z
X
% Yields
z
z
Y
Entry
X
Y
Z
Salt
Y
Y
z
N
N
1 a
2 b
3 c
4 d
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
N
N
N
N
N
N
N
N
N
N
N
N
N
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
N
N
N
N
N
N
N
N
2
2
2
2
I
1
2
3
4
I
1
2
3
4
I
1
2
3
4
I
1.3
12.0
43.5
48.5
84.5
75.1
69.7
74.4
33.7
64.3
31.4
46.5
20.9
8.0
15.0
5.2
6.6
2.3
-
1.0
-
1.6
1.0
-
-
-
0.4
-
9.9
2.5
2.4
8.3
12.2
14.3
9.8
0.6
3.4
5.1
5.5
5.5
-
-
-
-
-
-
-
-
-
-
12.9
16.6
1.8
3.8
3.6
34.4
47.7
23.2
15.2
3.7
85.0
94.8
93.4
97.7
62.2
26.1
40.6
11.4
10.6
21.6
N
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
1
2
3
4
N
-
-
Reaction conditions: 2.0 mmol halopyridine, 2 mmol K2CO3, 1 mmol % Pd(OAc)2, 2 mmol % I or 1–4, DMF
(3 mL)- H2O (3 mL). Temperature ramped to 120 °C 3 min. Yields are based on aryl halide. Reactions were
a
b
c
monitored by GC-MS. Solvent pure H2O for 10 min; Solvent EtOH/H2O (1:1) for 10 min; DMA/H2O
(1:1) for 10 min; d DMF/H2O (1:1) and for 10 min.

Molecules 2013, 18
3718
It is noteworthy that 2- or 3-chloropyridines (Table 2, entries 10–14, 20–24) are less reactive than the
corresponding 2- or 3-bromopyridines (Table 2, entries 5–9, 15–19) in the Ullmann type homocoupling
reactions, like the Suzuki-Miyaura coupling reactions. One of the side products, 3-dimethylaminopyridine
was not observed in these reactions due to the less reactive site at the pyridine -position. On the other
hand, we obtained 2-dimethylaminopyridine as a side product in low yield (Table 2, entries 3–14). It is
also noteworthy that we obtained bare pyridine from the homocoupling reactions with very high yield,
particularly when using 3-bromopyridine as a homocoupling partner (Table 2, entries 15–19). Similar
to the Suzuki-Miyaura cross coupling reactions, benzimidazole salt 4 with an ethyl substituent, showed
the least activity in the homocoupling reactions, too (Table 2, entries 9, 14, 19 and 24).
The coupling products of halopyridines are given in the literature as a Suzuki-Miyaura type or the
Ullmann type coupling product only. In our work, we also determined some side products such as
dimethylaminopyridine, and pyridine in addition of the main coupling products. To the best of knowledge,
there is limited information about these types of products in the literature. Catalytic dimethylamino
group transfer from some amides to aryl halides using Ni(phen)Cl2, and NHC-Pd(II)-Im complexes has
been reported [56,57].
In conclusion, we prepared four new NHC precursor benzimidazolium salts containing substituted
benzyl and phenethyl or ethyl groups 1–4. The use of a palladium catalyst system including
benzimidazolium salts/base and solvent in the Suzuki-Miyaura and the Ullmann type coupling
reactions gives low to moderate yields under microwave-assisted conditions and relatively short
reaction times compared with those reported in the literature [41–51].
3. Experimental
3.1. General Procedures
All of using starting chemicals were supplied commercially by Merck, Fluka or Aldrich Chemical
Co. All catalytic activity experiments were carried out in a microwave oven system manufactured by
Milestone (Milestone Start S Microwave Labstation for Synthesis) under aerobic conditions. Both
1H-NMR (300.13 MHz) and 13C-NMR (75.47 MHz) spectra were determined using a Bruker DPX-300
high-performance digital FT-NMR spectrometer. FT-IR spectra were recorded on a Perkin-Elmer
spectrophotometer in the range 4,000–400 cm−1. Elemental analyses were performed by LECO CHNS-932
elemental analyzer. Melting points were recorded using an Electrothermal 9200 melting point apparatus,
and are uncorrected.
GC-MS analysis were performed on an Agilient 6890 N GC and 5973 Mass Selective Detector
system using by an HP-Innowax column of 60 m length, 0.25 mm diameter and 0.25 μm film thickness.
GC-MS parameters for the S-M and homocoupling reactions were as follows: initial temperature 60 °C;
initial time, 15 min; temperature ramp 1.30 °C/min; final temperature, 200 °C; ramp 2, 20 °C/min;
final temperature 230 °C; total run time 72 min; injector port temperature 250 °C; detector temperature
250 °C; injection volume, 1.0 μL; carrier gas, helium; mass range between m/z 50–550.
All coupling product yields are based on aryl halides and determined as follows: the percent of the
aryl halides were determined from the aryl halide chromatograms using the normalized peak areas
method taken at the optimized chromatographic conditions. After completion of the reaction, the %

Molecules 2013, 18
3719
coupling products were determined based on aryl halides. 1-(4-Bromobenzyl)benzimidazole [54] and
its salt numbered I [53] were prepared according to literature methods. The syntheses procedures of
new salts 1–4 are given below.
Synthesis of 1-(4-bromobenzyl)-3-(4-chlorobenzyl)benzimidazolium chloride (1). A mixture of 1-(4-
bromobenzyl)benzimidazole (2.00 g, 6.96 mmol) and 4-chlorobenzyl chloride (1.14 g, 7.08 mmol) in
DMF (5 mL) was refluxed for 4 h. After mixture was cooled solvent was removed under reduced
pressure. The precipitate was crystallized from EtOH/Et2O (1:1) (30 mL). The product was obtained as
white colored crystals. Yield: 2.28 g, 73%; mp 249–250 °C, IR, υ(C=N) = 1559 cm−1. Anal. found: C,
1
55.87; H, 3.48; N, 5.91%. Calcd for C21H17N2BrCl2 (448.18): C, 56.28; H, 3.82; N, 6.25%. H-NMR
(DMSO-d6) δ 5.83 (s, 2H, CH2C6H4Br), 5.84 (s, 2H, CH2C6H4Cl), 7.49-8.00 (m, 12H, Ar-H), 10.23
(s, 1H, NCHN). 13C-NMR (DMSO-d6) δ 49.8 (CH2C6H4Br and CH2C6H4Cl), 114.5, 122.6, 127.3, 129.5,
130.9, 131.2, 131.5, 132.4, 133.3, 133.8, 134.0 (Ar-C), 143.5 (NCHN). The compounds 2, 3, and 4
were similarly prepared from 1-(4-bromobenzyl)benzimidazole and the appropriate alkyl halides.
1-(4-Bromobenzyl)-3-(4-methylbenzyl)benzimidazolium bromide (2). Yield: 2.57 g, 78%; mp 255–256 °C,
IR, υ(C=N) = 1559 cm−1. Anal. found: C, 56.19; H, 4.34; N, 5.80%. Calcd for C22H20N2Br2 (472.21): C,
1
55.96; H, 4.27; N, 5.93%. H-NMR (DMSO-d6) δ 2.30 (s, 3H, CH2C6H4CH3); 5.77 (s, 2H,
CH2C6H4CH3), 5.82 (s, 2H, CH2C6H4Br), 7.23–8.01 (m, 12H, Ar-H), 10.16 (s, 1H, NCHN). 13C-NMR
(DMSO-d6) δ 21.2 (CH2C6H4CH3), 49.8 (CH2C6H4CH3), 50.4 (CH2C6H4Br), 114.5, 114.6, 122.6,
127.3, 128.8, 128.9, 130.0, 131.2, 131.3, 131.4, 131.5, 132.4, 133.8, 138.7 (Ar-C), 143.2 (NCHN).
1-(4-Bromobenzyl)-3-(2-phenylethyl)benzimidazolium bromide (3). Yield: 2.83 g, 86%; mp 144–145 °C,
IR, υ(C=N) = 1567 cm−1. Anal. found: C, 55.39; H, 4.44; N, 5.74%. Calcd for C22H20N2Br2 (472.21): C,
1
55.96; H, 4.27; N, 5.93%. H-NMR (DMSO-d6) δ 3.27 (t, J = 7.2 Hz, 2H, CH2CH2C6H5), 4.82 (t,
J = 7.2 Hz, 2H, CH2CH2C6H5), 5.72 (s, 2H, CH2C6H4Br), 7.17–8.13 (m, 13H, Ar-H), 9.77 (s, 1H, NCHN).
13C-NMR (DMSO-d6) δ 34.8 (CH2CH2C6H5), 48.4 (CH2CH2C6H5), 49.5 (CH2C6H4Br), 114.3, 114.5,
122.5, 127.2, 127.3, 127.4, 129.1, 129.3, 130.9, 131.1, 131.6, 132.3, 133.8, 137.3 (Ar-C), 142.9 (NCHN).
1-(4-Bromobenzyl)-3-ethylbenzimidazolium iodide (4). Yield: 2.07 g, 67%; mp 148–150 °C, IR, υ(C=N)
=
1558 cm−1. Anal. found: C, 44.03; H, 3.88; N, 6.04%. Calcd for C16H16N2BrI (443.12): C, 43.37; H,
1
3.64%; N, 6.32. H-NMR (DMSO-d6) δ 1.57 (t, J = 7.2 Hz, 3H, CH2CH3), 4.54 (q, J = 7.2 Hz, 2H,
CH2CH3), 5.76 (s, 2H, CH2C6H4Br), 7.48-8.13 (m, 8H, Ar-H), 9.88 (s, 1H, NCHN). 13C-NMR
(DMSO-d6) δ 14.5 (CH2CH3), 42.8 (CH2CH3), 49.7 (CH2C6H4Br), 114.3, 114.4, 122.5, 127.1, 127.2,
131.1, 131.3, 131.7, 132.3, 133.8 (Ar-C), 142.7 (NCHN).
3.2. General Procedure for the Suzuki-Miyaura and the Ullmann Type Homocoupling Reactions
3.2.1. The Suzuki-Miyaura Reaction
Pd(OAc)2 (1 mmol %), benzimidazole salt (I, 1–4) (2 mmol %), halopyridine (1 mmol), phenylboronic
acid (1.2 mmol), K2CO3 (2 mmol) and mixture of solvent, water (3 mL)-DMF (3mL) were added in
apparatus of microwave equipment in aerobic conditions. The mixture was heated at 120 °C, by
microwave irradiation (300 Watt) for 10 min. At the end of reaction, the mixture extracted by ethyl

Molecules 2013, 18
3720
acetate/n-hexane (1:5), filtered through 3 cm length column of silica gel. The solution was given to
GC-MS equipment. The yields were determined by GC-MS based on halopyridine using the
normalized peak areas method.
3.2.2. Ullmann Type Homocoupling Reaction
Pd(OAc)2 (1 mmol %), benzimidazole salt I, 1–4 (2 mmol %), halopyridine (2 mmol), K2CO3
(2 mmol) and mixture of solvent, water (3 mL)-DMF (3 mL) were added in apparatus of microwave
equipment in aerobic conditions. The mixture was heated at 120 °C, by microwave irradiation (300 Watt)
for 30 min. After competition of the reaction, work-ups similar to those of the Suzuki-Miyaura
reactions were followed to obtain the appropriate products.
4. Conclusions
In summary, we have synthesized several novel benzimidazolium salts through nucleophlic
substitution reactions. Catalytic studies were done using catalytic systems consisting of
Pd(OAc)2/benzimidazolium salt and K2CO3 for the Suzuki-Miyaura cross coupling and the Ullmann
type homocoupling reactions of 2- or 3-halopyridines. We also obtained some side products such as
dimethylaminopyridine dervivatives and pyridine with low yield in both the coupling reactions under
microwave irradiation.
Supplementary Materials
NMR spectra of the new compounds are available free of charge via the internet at
http://www.mdpi.com/1420-3049/18/4/3712/s1.
Acknowledgments
This work was financially supported by the İnönü University Research Fund (I.Ü. B.A.P. 2011/144
and İUBAP-2012/18).
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