Water Soluble Benzimidazole Containing Ionic Palladium(II) Complex for Rapid Microwave-Assisted Suzuki Reaction of Aryl Chlorides

Article abstract of DOI:10.1002/aoc.4288

In this paper a water soluble benzimidazole – Pd complex used for Suzuki reaction under conventional heating and microwave heating. To increase the activity of complex, ionic group change with bulky TBA⁺ and Bmim⁺ groups. To determine whether the reaction is homogeneous or heterogeneous, Hg(0) poisoning tests, hot filtration tests and CS₂ poisoning tests were performed.

Full text of DOI:10.1002/aoc.4288

Received: 23 March 2017
DOI: 10.1002/aoc.4288
Revised: 26 December 2017
Accepted: 26 December 2017
F U L L P A P E R
Water Soluble Benzimidazole Containing Ionic
Palladium(II) Complex for Rapid Microwave‐Assisted
Suzuki Reaction of Aryl Chlorides
Abdurrahman Şengül | Murat Emre Hanhan
Bülent Ecevit University, Science and
In this paper a water soluble benzimidazole – Pd complex used for Suzuki
Letters Faculty, Chemistry Department,
67100 Zonguldak, Turkey
reaction under conventional heating and microwave heating. To increase the
activity of complex, ionic group change with bulky TBA+ and Bmim+ groups.
Correspondence
To determine whether the reaction is homogeneous or heterogeneous, Hg(0)
poisoning tests, hot filtration tests and CS2 poisoning tests were performed.
Murat Emre Hanhan, Bülent Ecevit
University, Science and Letters Faculty,
Chemistry Department, 67100 – Zonguldak,
Turkey.
KEYWORDS
Email: emrehanhan@beun.edu.tr
Benzimidazole, Green Chemistry, Microwave, Palladium Complex, Suzuki Reaction
Funding information
Bulent Ecevit University, Grant/Award
Numbers: BAP‐2012‐10‐03‐05, BAP‐2012‐
10‐03‐14, BAP‐2013‐72118496‐07 and
BAP‐2013‐72118496‐08
1 | INTRODUCTION
activate aryl chlorides several successful catalysts like
palladacycles,[3] palladium‐phosphine complexes[4] and
Palladium catalyzed Suzuki reaction is one of the most
important methods for the formation of new C–C bonds
and very powerful tool in organic synthesis. Due to
popularity of Suzuki reaction, Akira Suzuki won Nobel
Prize 2010.[1] Suzuki reaction can be performed with
using three distinctive steps. In the first step, an aryl
halide reacts with the palladium(0) through an oxidative
addition. After that a transmetallation reaction occurs
which yields palladium(II) complex and coupled products.
The last step includes reductive elimination of the prod-
ucts. Unfortunately, this very useful reaction has some lim-
itations. Reaction needs high loadings for Pd catalysts and
activity on aryl‐chlorides are very low. The high C–Cl bond
strength compared with C–Br and C–I bonds disfavors
oxidative addition step[2]. On the other hand, aryl chlorides
are more widely available and generally less expensive
than aryl bromides and aryl iodides. That's why research
on Suzuki reactions are focused on using aryl chlorides
as a substrate instead of aryl bromides and iodides. To
palladium‐carbene complexes[5] were used. Also our
recent study proved that bulky group protected ferrocene‐
diimine complexes with microwave irradiation can catalyze
aryl chlorides rapidly.[6]
Herein we report a convenient and environmentally
friendly method for Suzuki coupling reaction of
unreactive aryl chlorides with using water as a solvent
and microwave irradiation for heating. We replaced ionic
potassium with tetrabutylammonium bromide (TBA+)
and 1‐Butyl‐3‐methylimidazolium hexafluorophosphate
(Bmim+) to protect active Pd(0) species.[7] Water was
selected for the reaction media because aqueous reaction
conditions offer a safe, economic and environmentally
benign alternative in organic syntheses.[8] Microwave
irradiation serves several advantages including reduction
of reaction times and electricity costs.[9] As a result, modified
complex C managed to couple several aryl chlorides with
several boronic acids under MW irradiation with high
conversion approximately in 15 minutes.
Appl Organometal Chem. 2018;e4288.
wileyonlinelibrary.com/journal/aoc
Copyright © 2018 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4288

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ŞENGÜL AND HANHAN
2 | EXPERIMENTAL
2.1 | General
All reagents and solvents were obtained from commercial
sources and used without further purification. Melting
points were determined by BÜCHI Melting point B‐540
SCHEME 2 The molecular structure of the Pd complex
1
apparatus. H and 13C‐NMR spectra were recorded on a
Bruker Ultra Shield Plus, Ultra long time 400 MHz NMR
spectrometer. Elemental analysis data were performed
on a LECO CHNS analyzer (for C, H, N). FT‐IR spectra
were recorded on Perkin Elmer FT‐IR 100 spectrometer.
ESI MS spectra were obtained from the AB SCIEX 4000
Q TRAP. MALDI‐TOF mass spectra were obtained from
a Voyager DE matrix assisted laser desorption/ionization
time‐of‐flight spectrometer. Gas chromatographic analyses
were performed on an Agilent 6890 N instrument
equipped with a WCOT HP‐1 fused silica capillary column.
Microwave irritation were carried out with modified Bosch
Micro Combi commercial microwave oven (850 W).
C25H23Cl2K2N5O6PdS2·3H2O: C, 34.79; H, 3.39; N, 8.11;
found: C, 34.9; H, 3.1; N, 7.9. IR (ATR, ν/cm‐1): 3099 (aro-
matic C‐H), 2933 (aliphatic C‐H), 523 (C=N), 1485,1442
1
(C=C), 1160, 1031 (S=O). H‐NMR (dmso‐d6, δppm): 8.76
(2H, d, J = 7.35), 8.45 (1H, t, J = 7.48), 7.91 (2H, d, J =
7.17), 7.27 (2H, d, J = 7.41), 7.35 (4H, m), 4.74 (4H, m),
2.65 (4H, t, J = 7.17), 2.11 (4H, m). MALDI TOFF MS
m/z 773.9 [M]+.
2.4 | General Procedure for the Suzuki
Coupling Reaction
The aryl chloride (1.0 mmol), phenylboronic acid
(1.2 mmol), K2CO3 (5 mmol), C (0.02 mmol) and H2O
(10 ml) were added to a teflon capped Schlenk tube
(50 ml) and irradiated at 850 W for 10 min in a microwave
oven. After cooling to room temperature, the reaction
mixture was extracted with ethyl acetate – acetone
(5:1 v/v, 20 ml x 2). The organic phase was dried over
MgSO4. The solvent was removed by evaporation under
reduced pressure to afford the biaryls. The product was
purified by column chromatography on silica gel using
petroleum ether‐ethyl acetate (30:1 v/v) as the eluent to
give an analytically pure product.
2.2 | Synthesis of Potassium 2,6‐bis(1‐(3‐
propylsulfonate)benzimidazol‐2’‐yl)
pyridine, L
The ligand was synthesized by the reaction of 2,6‐bis(NH‐
benzimidazol‐2‐yl)pyridine [10] with 1,3‐propanesulfonate
in DMSO as reported by Po et al.[11] as illustrated in
Scheme 1.
The data obtained for the ligand are in good agree-
ment with the reported data. M.p. 265 °C. FT‐IR (ATR,
ν/cm‐1): 3020 (C‐Har), 2936 (C‐Hal), 1571 (C=N), 1437,
1418 (C=C), 1179, 1033 (S=O). 1H‐NMR (dmso‐d6, δppm):
8.32 (2H, d, J = 7.68), 8.21 (1H, m), 7.76 (4H, m), 7.31 (4H,
m), 4.90 (4H, t, J = 7.10), 2.26 (4H, t, J = 7.39), 2.0 (4H, m).
ESI‐MS (m/z): [M+K]+: 670.
2.5 | Optimization of Coupling Reaction
Because of its simplicity, coupling reaction between chlo-
robenzene (1.0 mmol) and phenylboronic acid (1.2 mmol)
with using C 0.1 mol %) as a catalyst was chosen as a
model reaction for the optimization. To compare the
advantage of microwave heating over conventional
heating and to understand the effect of ionic groups, a
series of experiments were established (Table 1). To
optimize the reaction time, K2CO3 was used as a base
which is very effective in related systems.[12] For
2.3 | Synthesis of Chloro‐2‐6‐bis(1‐(3‐
propylsulfonate)benzimidazol‐2’‐yl)
pyridinepalladium(II)chloride, [Pd(L)]Cl, C
The complex was obtained as yellow solid in 75% yield
by the reaction of L with K2PdCl4 in DMSO by the
similar procedure as reported for Pt(II) complex
(Scheme 2).[11] Elemental analysis calcd (%) for
SCHEME 1 Synthetic pathway of the ligand

ŞENGÜL AND HANHAN
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TABLE 1 Effect of Conventional Heating vs MW
chlorobenzene (1.0 mmol) using C (0.1 mol%) and nano-
particles (0.4 mol%) isolated from C as a catalyst under
the optimized conditions were carried out in the flask.
As a result the product biphenyl was obtained 72% yield
after 2 h even in the presence of excess Hg.
Yield*
Entry
Catalyst
80 °C
MW
1
Li2PdCl4
PdCl2
13
22
2
10
42
69
61
16
72
96
91
3
C
2.8 | Hot Filtration Test
4a
5b
C‐TBAB
C‐Bmim
Reactions with C were subjected to a hot filtration test.
Coupling reaction of phenylboronic acid (1.2 mmol) with
chlorobenzene (1.0 mmol) catalyzed with C (0.1 mol%)
under the optimized conditions was filtered hot through
G4 sintered glass crucible which contains 1.5 g celite until
the conversion reach 20% (monitored by GC). The conver-
sion was monitored in the filtrate with time, continued
and reached a maximum (71%) after 2 h.
Reaction Conditions: 1 mmol chlorobenzene, 1.2 mmol phenylboronic acid,
2 mmol of K2CO3, 0.1 mol% catalyst, 80 °C for conventional heating or
850 W microwave irradiation, 5 ml H2O. Reaction time = 2 h for conven-
a
tional heating, 15 min for microwave irradiation. 0.5 mmol TBAB added.
b 0.5 mmol Bmim added.
*GC yields.
base optimization, K2CO3, Na2CO3, Cs2CO3, K3PO4, and
NaOMe were tested (Table 2).
3 | RESULTS AND DISCUSSIONS
2.6 | PPh3 and CS2 Poisoning Test
3.1 | Characterization of the Ligand (L)
and the palladium(II) complex (C)
To the coupling reaction of chlorobenzene and
phenylboronic acid, C (0.1 mol %) was added as a catalyst
and PPh3 or CS2 (1 mol %) was added under optimized
conditions. The product biphenyl was obtained with 100
% conversion after 2 hours.
The synthesis of the ligand was previously reported and
fully characterized. The IR spectrum clearly indicates the
presence of sulfonate groups with the characteristic
stretching modes of S=O at 1179 and 1033 cm‐1, respec-
tively. In addition, the presence of the aromatic CH band
at 3020 cm‐1, and the corresponding aliphatic CH stretching
bands at 2936 and 2876 cm‐1 confirm the attachment of the
polysulfonate groups to the benzimidazole moieties. The
molecular structure was further confirmed by the ESI MS
in which the observed major peak at m/z 670 assigned to
the [M+K+H]+ for C25H23N5O6S2K3.. Furthermore, the
compound was also characterized by 1H‐NMR as shown in
Figure 1. The data are very identical to the reported data.[11]
As depicted in Figure 1, the protons belong to the benzimid-
azole rings appear as multiplets at 7.31 and 7.76 ppm,
respectively. The protons on the pyridine ring appear as a
doublet at 8.32 ppm, and as a multiplet at 8.21 ppm,
respectively. The protons belong to the propyl group appear
in the aliphatic regions as expected at 2.00 ppm as a
multiplet for the middle CH2, 2.26 ppm as a triplet for
CH2SO3 and 4.90 ppm as a triplet for CH2N, respectively
as shown in Figure 1. The integral value of total number
of 23 protons is confirmed the molecular structure.
2.7 | Mercury (Hg) Poisoning Test
The Hg poisoning test is very significant to understand
whether the reaction is homogeneous or heterogeneous.
Before the coupling reaction carried out, excess Hg (Hg:
Pd:400:1) was taken in the reaction flask. Thereafter the
coupling reactions of phenylboronic acid (1.2 mmol) with
TABLE 2 Optimization Results of Suzuki Coupling
Entry
Base
M.W (Watt)
Time(min)
Yield*
1
K2CO3
850
5
23
2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
K3PO4
NaOMe
850
850
850
600
360
850
850
850
850
10
15
20
15
15
15
15
15
15
58
72
74
51
NA
36
79
41
29
3
4
5
The Pd complex, C was fully characterized by elemen-
6
1
tal analysis. FTIR, H‐NMR and MALDI TOFF MS. The
7
infrared spectrum of the complex is very much akin to
that of the ligand. The characteristic stretching modes of
the S=O group are observed at 1031 and 1160 cm‐1,
respectively. The aromatic CH and aliphatic CH
stretching bands are observed at 3099 and 2933 cm‐1,
respectively. The molecular structure was clearly
8
9
10
Reaction conditions: aArylchloride (1.0 mmol), phenylboronic acid
(1.2 mmol), 0,1 mol% C‐K, 2 mmol base, H2O (5 ml).* GC yields.

4 of 6
ŞENGÜL AND HANHAN
FIGURE 1 1H‐NMR Spectrum of L
confirmed by the MALDI TOFF MS m/z 773.0 [M‐Cl]+ for
C25H23ClKN5O6PdS2 (calc.: 773.9). The 1H‐NMR spec-
trum of the complex (Figure 2) is very much similar to
that of the free ligand. The protons of the benzimidazole
rings slightly deshielding as appeared doublets at 7.27
and 7.91 ppm, and as a triplet at 7.35 ppm, respectively.
The pyridine protons also underwent deshielding as a
doublet at 8.76 ppm and as a triplet at 8.45 ppm in com-
parison to that of the free ligand. The propyl protons show
insignificant deshielding upon coordination to Pd(II) ion,
and they appear at 2.11, 2.65 and 4.74 ppm, respectively
with same pattern as the free ligand. The total number
suddenly when TBAB was added as an additive and the
conversion increased from 72 to 99% (Table 3, entry 1).
C‐TBA which the ion was TBA+, showed the highest
activity. Differences between the ions, K+ and TBA+ can
be explained by the stabilization effects of bulky groups.
Also, Bmim+ (C‐Bmim) showed the same stabilization
effect like TBA+ ion. Significantly C (with K+, TBA+
and Bmim+) was able to couple inactivated electron rich
aryl chlorides with various boronic acids in high yields
(Table 3, entry 2‐4). Also sterically hindered substrates
were tested. Suzuki reactions using sterically demanding
substrates are difficult and generally occur with the
formation of unwanted homocoupling products.[14] As
shown in Table 3 (entries 4‐7) sterically hindered biaryls
could be obtained in high yields. Also other functional
groups were tested and those groups underwent the
coupling reaction efficiently (Table 3, entries 8‐10).
It is very important to determine whether the reaction
is homogeneous or heterogeneous. Hg(0) poisoning test is
one of the well‐known test and easy to perform on C‐C
coupling reactions. Hg(0) amalgamates strongly bind to
Pd(0), Rh(0) and Ni(0) based complexes, thereby blocking
the access of the active site to the substrate. Thus, Pd(0)
species can possibly be poisoned by adding excess Hg(0)
to the reaction mixture during the reaction. If the catalytic
reaction stops after addition of Hg(0), the reaction
mechanism follows a heterogeneous pathway. It follows
homogeneous pathway if mercury does not suppress the
pathway.[15] In this work we performed the Hg poisoning
experiment in a coupling reaction between chlorobenzene
and phenylboronic acid (1 mol% C, 2 mmol K2CO3,
dioxan, 50 °C). Under these conditions 50% conversion
achieved after 30 min, and then Hg (400 equiv.) was
added. In all cases the reaction did not stop (86%
1
of 23 protons is identical to the H‐NMR integral value.
3.2 | Optimization Results
According to the base optimization results K2CO3 was
chosen as the reaction base whereas other alternatives
need more reaction times for high conversion or found
totally ineffective. The reaction time was optimized
15 min. for 850 W microwave irradiation and 2 h for con-
ventional heating at 80 °C where necessary. The optimum
concentration of catalyst C was found to be 0.1 mol%.
3.3 | Influence of the Complex on Suzuki
reaction
Table 3 summarizes the effect of catalyst on Suzuki reac-
tion. It is very clear from the results that, the sulfonate
group has a great effect on Suzuki coupling reaction. This
is because of the stabilization effect of big groups on active
Pd(0) nanoparticles. To prove its efficiency, TBAB was
added to the reaction media.[13] The catalytic activity of
C, which showed the moderate activity, increased

ŞENGÜL AND HANHAN
5 of 6
FIGURE 2 1H‐NMR Spectrum of C
TABLE 3 Suzuki cross‐ couplings between aryl halides and boronic acids using C as the catalyst
Yield %*
C‐K
Yield %*
Yield %*
Entry
Aryl Halide
Boronic Acid
Product
C‐TBAB
C‐Bmim
1
72
99
96
2
68
96
92
3
4
5
67
70
63
91
91
86
87
86
81
6
60
85
80
7
8
66
82
90
99
92
98
9
79
77
99
91
96
81
10
Conditions: 1.0 mmol arylchloride, 1.2 mmol eq. aryl boronic acid, 2 mmol K2CO3, 0.1% Complex, 850 W M.W. irradiation, 15 min, 5 ml H2O.
*GC yields.
conversion after 1 hour), indicating that monometallic
species are the true active species rather than Pd nanopar-
ticles or cluster particles. Hg(0) was not quenched the
reaction because these Pd(0) species were protected by
the ligand. Hg(0) poisoning experiments are not enough
to determine the process as being homogeneous or

6 of 6
ŞENGÜL AND HANHAN
[2] V. V. Grushin, H. Alper, Chem. Rev. 1994, 94, 1047.
heterogeneous. Therefore, we performed CS2 poisoning
and hot filtration experiments. To determine the number
of catalytically active metal atoms and provide evidence
as to the nature of the catalyst we used CS2 poisoning pro-
cedure.[16] CS2 poisoning experiments were performed
between chlorobenzene and phenylboronic acid using
the same conditions that were used in the Hg test. Under
these conditions, 50% conversion was achieved after
30 min. Different amounts of CS2 in dioxane were added
(0, 0.5, 1 or 1.5 equiv. of CS2) to different experiment sets
and reactions were screened by GC for 2 days. It was
found that 1.5 equiv. CS2 were necessary to completely
terminate the reaction, which also indicates that the cata-
lyst is of a molecular nature. Hot filtration experiments
were also performed.[17] Once a 50% conversion was
achieved by the coupling reaction between chlorobenzene
and phenylboronic acid, the reaction was filtered through
a sintered glass filter containing cellulose to remove the
metal particles. It was found that the filtrate was catalyti-
cally active (84% conversion) and no coupling product
was obtained using the Pd retained in the cellulose. These
results also support the activity of the presence of a solu-
ble catalyst (homogeneous catalyst).
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4 | CONCLUSION
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We have developed a new water soluble Pd catalyst con-
taining sulfonated imidazole ligand that showed excellent
Suzuki Coupling reactivity with aryl chlorides in water
under MW irradiation. Good to excellent yields of cross
coupling products were obtained when the ionic groups
exchanged with bulky TBA+ and Bmim+ ions. In addi-
tion, poisoning tests indicate that the homogeneous
molecular palladium species containing imidazole ligand
is responsible for the catalytic activity.
[14] A. F. Littke, C. Y. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122,
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ACKNOWLEDGEMENTS
[17] S. P. Andrews, A. F. Stepan, H. Tanaka, S. V. Ley, M. D. Smith,
Adv Synth Catal 2005, 347, 647.
This work was supported by Research Board of Bulent Ecevit
University (BAP‐ 2012‐10‐03‐14), (BAP‐ 2013‐72118496‐08),
(BAP‐ 2013‐72118496‐07), (BAP‐2012‐10‐03‐05).
SUPPORTING INFORMATION
Additional Supporting Information may be found online
in the supporting information tab for this article.
ORCID
Murat Emre Hanhan
http://orcid.org/0000-0003-2247-
1818
How to cite this article: Şengül A, Hanhan ME.
Water Soluble Benzimidazole Containing Ionic
Palladium(II) Complex for Rapid Microwave‐
Assisted Suzuki Reaction of Aryl Chlorides. Appl
Organometal Chem. 2018;e4288. https://doi.org/
10.1002/aoc.4288
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