Preparation and characterization of PEPPSI-palladium N-heterocyclic carbene complexes using benzimidazolium salts catalyzed Suzuki–Miyaura cross coupling reaction and their antitumor and antimicrobial activities

Article abstract of DOI:10.1080/00958972.2019.1572886

New palladium complexes were efficiently synthesized from the reaction of benzimidazolium salts 2a–e, potassium carbonate (K₂CO₃) and palladium chloride (PdCl₂) in pyridine (for 3a–e). The catalytic activity of these complexes in a catalytic system including palladium complexes and K₂CO₃ in DMF-H₂O was evaluated in Suzuki–Miyaura cross-coupling reactions of aryl bromides and chlorides with phenylboronic acid. Our novel complexes show excellent catalytic activities with high turnover numbers (TON) and high turnover frequencies (TOF) (e.g. for the Suzuki–Miyaura reaction: TON up to 370 and TOF up to 123.3 h^?1). Both benzimidazolium salts 2a–e and complexes 3 have been characterized using spectroscopic data and elemental analysis. The antimicrobial activity of the N-heterocyclic carbene palladium complexes 3a–e varies with the nature of the ligands. Also, the IC₅₀ values of both, complexes (3a–e) and benzimidazoles 2a–e, have been determined. In addition, the new palladium complexes were screened for their antitumor activity. Complexes 3e and 3d exhibited the highest antitumor effect with IC₅₀ values 6.85 μg/mL against MCF-7 and 10.75 μg/mL against T47D, respectively.

Full text of DOI:10.1080/00958972.2019.1572886

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: https://www.tandfonline.com/loi/gcoo20
Preparation and characterization of PEPPSI-
palladium N-heterocyclic carbene complexes
using benzimidazolium salts catalyzed by Suzuki-
Miyaura cross coupling reaction and their
bioactivities
L. Boubakri, K. Dridi, A. Sulaiman Al-Ayed, İ. Özdemir, S. Yasar & N. Hamdi
To cite this article: L. Boubakri, K. Dridi, A. Sulaiman Al-Ayed, İ. Özdemir, S. Yasar & N. Hamdi
(2019): Preparation and characterization of PEPPSI-palladium N-heterocyclic carbene complexes
using benzimidazolium salts catalyzed by Suzuki-Miyaura cross coupling reaction and their
bioactivities, Journal of Coordination Chemistry, DOI: 10.1080/00958972.2019.1572886
To link to this article: https://doi.org/10.1080/00958972.2019.1572886
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Preparation and characterization of PEPPSI-palladium N-heterocyclic
carbene complexes using benzimidazolium salts catalyzed by Suzuki-Miyaura
cross coupling reaction and their bioactivities
L. BOUBAKRI1, K. DRIDI2,3, A. SULAIMAN AL-AYED2, İ. ÖZDEMIR5, S. YASAR5 and N. HAMDI*1,2
1Research Laboratory of Environmental Sciences and Technologies (LR16ES09), Higher Institute of
Environmental Sciences and Technology, University of Carthage, Hammam-Lif, Tunisia
2Chemistry Department, College of Science and Arts, Qassim University, Al-Rass, Kingdom of Saudi Arabia
3Organic and Heterocyclic synthesis Laboratory, Chemistry Department, Faculty of Sciences,
Elmanar University, Tunis, Tunisia
4Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
5İnönü University, Faculty of Science and Art, Department of Chemistry, Malatya, Turkey
New palladium complexes were efficiently synthesized from the reaction of benzimidazolium
salts 2a-e, potassium carbonate (K2CO3) and palladium chloride (PdCl2) in pyridine (for 3a-e).
The catalytic activity of these complexes in a catalytic system including palladium complexes
and K2CO3 in DMF-H2O was evaluated in Suzuki-Miyaura cross-coupling reactions of aryl
bromides and chlorides with phenylboronic acid. Our novel complexes show excellent catalytic
activities with high turnover numbers (TON) and high turnover frequencies (TOF) (e.g., for the
Suzuki-Miyaura reaction: TON up to 370 and TOF up to 123.3 h-1). Both benzimidazolium salts
2a-e and complexes 3 have been characterized using spectroscopic data and elemental analysis.
The antimicrobial activity of the N-heterocyclic carbene palladium complexes 3a-e varies with
the nature of the ligands. Also, the IC50 values of both, complexes (3a-e) and benzimidazoles
2a-e, have been determined. In addition, the new palladium complexes were screened for their
antitumor activity. Complexes 3e and 3d exhibited the highest antitumor effect with IC50 values
6.85 μg/mL against MCF-7 and 10.75 μg/mL against T47D, respectively.
Keywords: Suzuki-Miyaura coupling; N-Heterocyclic carbene; Palladium(II) catalyst;
Antimicrobial activity; Antitumor activity
1. Introduction
For the formation of carbon-carbon (C-C) bonds in the midst of organic halides and organoboron
compounds, the palladium catalyzed Suzuki-Miyaura reaction is a very significant method [1, 2].
*Corresponding author. Email: naceur.hamdi@isste.rnu.tn
1

This reaction is harmonious with a broad range of functional groups, largely unaffected by the
presence of water, and can proceed stereo- and regioselectively. Other advantages include the
production of inorganic by-products that can be separated with ease from the reaction mixture,
hence rendering the process suitable for use in industrial purposes as well as in a small-scale
laboratory setting. For practical and economic reasons, the readily available aryl chlorides have
generally been used as the substrates of choice for this coupling reaction [3]. However, there
have been important endeavors in order to improve more reactive catalysts to facilitate the
conversion of challenging aryl chlorides [4-6]. For this purpose, many substances have been
investigated by various research groups, focusing especially on new catalyst structures and
ligand modifications such as bulky and electron-rich phosphines [7], palladacycles [8, 9], and
N-heterocyclic carbenes (NHCs), which provide highly reactive palladium-based carbon-carbon
coupling catalysts due to their unique electronic and steric properties [10].
The complexes of the NHC have been synthesized with almost every transition metal
[11-22]. Among these complexes, palladium-NHC complexes have come to the fore due to their
success in cross-coupling reactions [23-25]. Although excellent progress has been made in
mononuclear complexes [26-36], different type NHC-Pd complexes and their catalytic properties
started to attract attention and awaken curiosity [37-39]. The NHC-Pd catalyzed cross-coupling
reactions have increased in tendency over the past decade; palladium-catalyzed cross-coupling
reactions represent over 60% of the carbon-carbon bond formation reactions used in medicinal
chemistry [40-48].
The synthesis of biaryl compounds presents a unique challenge to chemists. In the
traditional reactions of organic chemistry, no methods exist for the efficient coupling of two
different aromatic groups in a single reaction. There are possible synthetic routes to make
biaryls, but the ability to complete such a transformation quickly and efficiently via catalyst
could be a potentially powerful tool for organic synthesis. Many developments utilizing homo-
coupling and cross-coupling reactions have been presented in the past few decades. A great
number of in situ generated NHC-Pd catalysts have been reported in Suzuki cross-coupling
reactions [26, 27]. Herrmann reported the first Pd-NHC catalyst used for Suzuki cross-coupling
reaction in 2002 [28]. Then, Pd-PEPPSI (pyridine-enhanced precatalyst preparation stabilization
and initiation) type Pd-NHC complexes have been extensively developed by Organ and co-
workers for the cross-coupling of challenging, aryl- and alkyl-electrophiles [29-36]. In particular,
2

our research group has achieved important improvements in Suzuki-Miyaura cross-coupling
reactions using PEPPSI complexes [49].
Herein, we report: (i) the synthesis of Pd-PEPPSI-NHC complexes 3a-e containing
benzimidazole (2a-e) moiety, which were obtained from the reaction of N-alkylbenzimidazole
with the addition of various alkyl halides, (ii) the structures of these compounds were
1
characterized by spectroscopic methods (FT-IR, H NMR, 13C NMR and elemental analysis),
(iii) the synthesized Pd-PEPPSI-NHC complexes 3a-e were tested in Suzuki-Miyaura cross-
coupling reactions of aryl bromides, and chlorides with phenylboronic acid; they exhibited
excellent catalytic activity. In addition, their antimicrobial and antitumor activities were studied
(scheme 1).
2. Results and discussion
The novel N,N-disubstituted 5,6-dimethylbenzimidazolium salts 2a-e were synthesized in good
yields of 89%-96% by reaction of N-substituted 5,6-dimethylbenzimidazoles (A), (B) and (C),
with appropriate substituted benzyl halides in DMF at 70 °C for two days. The synthesis of the
1,3-dialkyl-5,6-dimethylbenzimidazolium salts 2a-e is summarized in scheme 2.
1
13
The benzimidazolium salts 2a-e were identified by spectroscopic data (including H NMR,
C NMR and IR) and elemental analysis techniques.
The NCH N protons of benzimidazolium salts 2a-e appeared as singlets at 11.58, 11.17,
11.54, 11.63 and 11.57 ppm, respectively. The value of δ[13C{1H}] NCHN in benzimidazolium
salts 2a-e was 152.8, 142.9, 141.8, 163.0 and 141.6 ppm, respectively. The benzylic proton
signals H1’,1” appeared at 5.67 and 5.76 ppm, respectively.
The aromatic protons of 5,6-dimethylbenzimidazolium salts 2a were seen at δ between
6.94 and 7.37 ppm in the 1H NMR spectrum. The carbene carbon chemical shift value belonging
to 5,6-dimethylbenzimidazolium salts 2a was observed at 152.8 ppm in the 13C NMR spectra.
C1’,1” carbon was resonated at δ 51.8 and 51.4 ppm for 2a.
Benzimidazolium salts 2a-e were also characterized by FTIR spectroscopy in the range
4000-400 cm-1 to ensure their successful formation. In particular benzimidazolium salts 2a-e
exhibit a characteristic v(C=N) band at 1566, 1547, 1566, 1670 and 1559 cm-1, respectively.
3

M-NHC complexes can be synthesized by transmetallation from an Ag(I)-NHC salt [50]
or direct metalation from the benzimidazoles salts via reaction with a metal salt and a base. The
reaction of benzimidazolium salts 2a-e with PdCl2 in pyridine in the presence of K2CO3 afforded
yellow palladium(II)-NHC complexes 3a (96%), 3b (95%), 3c (98%), 3d (89%) and 3e (91%) in
good yields. Complexes 3a-e are air-stable solids and they are soluble in polar organic solvents
(scheme 3).
The carbon-nitrogen band frequencies ν(C=N) for complexes 3a-e were observed at 1613, 1597,
1614, 1612 and 1609 cm−1, respectively, implying the coordination of imine nitrogen with
palladium owing to the donation of electrons from nitrogen atom to the empty d-orbitals of the
1
metal in complexes 3a-e [51-53]. The H NMR spectra of complexes 3 and 4 further supported
the assigned structures.
The aromatic protons of complex 3b appeared between 6.86 and 8.90 ppm. No signal
corresponding to the iminium proton could be observed in the 1H NMR spectra of
complexes 3a-e, confirming the formation of the NHC-Pd bonds. The NCN resonance of
Pd-NHC complex 3b appeared at 162.1 ppm. Only few examples of Pd-carbene complexes
bearing benzimidazol-2-ylidene ligand for direct arylation of heteroaromatic compounds have
been reported so far [54].
3. The Suzuki-Miyaura cross coupling reactions
The catalytic activities of PEPPSI complexes 3a-e in Suzuki-Miyaura cross-coupling reaction
were examined. The reaction was made at 80 °C in DMF/H2O mixtures by using aryl bromides,
chlorides and phenylboronic acid and base K2CO3. The solvents were used without any further
purification in this coupling reaction.
In a typical catalytic experiment, the reactivity of 0.25 mol% loading of
PEPPSI complexes 3 (0.25 mol%) in the presence of 4-chloroacetophenone (0.5 mmol) with
phenylboronic acid (0.75 mmol) as a model reaction using the catalytic system (base
(1 mmol)/solvent (6 mL)) (K2CO3/DMF/H2O (1:1)). These reactions were carried out at 80 °C
with reaction time limited to 3 h.
The Suzuki-Miyaura cross-coupling catalyzed by unsymmetrical and symmetrical
palladium complexes 3 in the presence of the catalytic system: DMF/H2O and K2CO3 is
4

presented in table 1. From table 1, we can say that the aryl chlorides having a donor group
deactivate the formation of the corresponding complexes with respect to the oxidative addition
whereas the attracting groups have an inverse effect. The best yields have been obtained during
the coupling of activated aryl chlorides by attracting groups.
The results of the cross-coupling reactions of aryl bromides and chlorides with
phenylboronic acid are given in table 1. From these results, we can say that
4-chloroacetophenone, 4-chloroanisole and 4-chlorotoluene react with phenylboronic acid to
afford the corresponding compounds in moderate to goods yields (table 1, entries 1-15).
The synthesis of new heteroaryl in excellent yield in the presence of phenylboronic acid
with pyridinic substrates is given in table 2. These results reveal that pyridine-containing
palladium complexes 3a-e were found to be the most active catalysts for Suzuki reaction in
DMF/H2O (1:1). These results show that the synthesized compounds have catalytic activity.
Huang et al. also used aryl chlorides containing electron-rich, electron-poor and neutral groups
in their study, but they obtained lower yields than us even though they conducted their
experiments at higher temperature and longer period of reaction time [55]. All reactions afforded
the corresponding biaryl compounds in high yields and under optimized conditions with
excellent TON and TOF values (table 3).
The objective of this project was also to prepare carbene precursors that have sulfonate
groups to make them soluble in water. The N-heterocyclic carbene ligand precursor (4) has been
synthesized by adding sodium sulfonate bromide to a DMC solution of the 1-methyl-4,5-
dihydro-1H-imidazole. Compound 4 is a white solid, soluble in water and DMSO, and insoluble
in methanol and acetonitrile. Then the silver(I) complex (5) was prepared in water solution via
deprotonation of 4 with Ag2O (scheme 4).
The resonance of the NCHN proton of 4 in 1H NMR was at 10.72 ppm in DMSO-d6. The NCHN
carbon of 4 resonates in the 13C{1H} NMR spectra at 155.5 ppm. C2 carbon of silver(I)-NHC
complex 5 resonates as two doublets at 185.2 and 187.3 ppm. The obtained silver N-heterocyclic
carbene (Ag-NHC) complex 5 and the carbene precursor 4 will be interacted with [PtCl2(COD)],
[PtCl2(PR3)2]2 and [AuCl(PPH3)3] to afford new complexes; this work is under progress
(scheme 5).
5

4. Antimicrobial activity studies for synthesized complexes
The results of the antimicrobials activities of palladium complexes 3 activity [56] against three
used Gram-positive bacteria Micrococcus luteus LB 14110, Staphylococcus aureus ATCC 6538
and Listeria monocytogenes ATCC 19117 and Gram-negative bacteria Salmonella Typhimurium
ATCC 14028 and Pseudomonas aeruginosa ATCC 49189 are presented in table 4. In table 4 it is
shown that all complexes 3a-e exhibit antimicrobial activity against one or more strains and is
enhanced compared with the benzimidazoles 2.
The minimal inhibitory concentrations (MICs) of PEPPSI palladium(II) complexes 3a-e
were determined against Micrococcus luteus LB 14110, Listeria monocytogenes ATCC 19117
and Salmonella Typhimurium ATCC 14028. The obtained results are given in table 5.
Complex 3b showed potentially higher broad-spectrum activity compared to all the other
PEPPSI palladium(II) complexes.
5. Antitumor activity
The antitumor activity of synthesized PEPPSI palladium(II) complexes 3a-e was tested in vitro
against cancer human cell lines such as MDA-MB-231, MCF-7 and T47D. The results are
summarized in table 6. All synthesized compounds showed good antitumor activity against
MDA-MB-231, MCF-7 and T47D cell lines. The most active compounds are 3e and 3d against
MCF-7 and T47D.
6. Conclusion
New unsymmetrically and symmetrically substituted benzimidazolium protic salts, which consist
of inactive inorganic anion (Br-) and bioactive benzimidazolium cation, were synthesized in very
high yields from a benzimidazole and different alkyl halides.
Pd-PEPPSI-NHC complexes 3a-e were synthesized in good yields by the reaction of
N,N-disubstituted benzimidazolium salts 2a-e with PdCl2 in the presence of K2CO3 as base in
1
pyridine. The obtained compounds were identified by FT-IR, H NMR and 13C NMR
spectroscopies and elemental analysis. Among the tested complexes, the PEPSSI complexes 3a-e
containing NHC ligands exhibited excellent catalytic activity. The palladium PEPSSI complexes
3a-e presented enhanced antimicrobial activity compared with standard antibacterial. Some of
them can act as practical use as antimicrobial agents. In addition, the PEPPSI palladium(II)
6

complexes 3a-e showed good antitumor activity against MDA-MB-231, MCF-7 and T47D cell
lines.
7. Experimental
All reactions for the preparation of benzimidazolium salts and palladium-(NHC)-PEPPSI
complexes were carried out under air. PdCl2, pyridine and solvents were purchased from Sigma-
Aldrich and used as obtained. All solvents were purified and dried by the MBraun SPS 800
solvent purification system. Elemental analyses were performed by an Elementar Vario EL III
Carlo Erba 1108. The melting points of the complexes and NHC precursors were determined
using Stuart automatic melting point apparatus (SMP-40). IR spectra were recorded with a
Perkin Elmer Spectrum 100 GladiATR FT/ IR spectrophotometer. 1H and 13C NMR spectra were
recorded in CDCl3 or DMSO d6 solutions operating on a Bruker Avance III HD 400/300 MHz
1
NMR spectrometer and chemical shifts were reported relative to tetramethylsilane for H and
13C NMR spectra as standard. Column chromatography was performed using silica gel 60 (70–
230 mesh). Solvent ratio is given as v/v. The products were characterized by GC (gas
chromatography). Quantitative GC analyses were performed with a GC-2010 Plus gas
chromatograph (SHIMADZU). GC conditions: The GC analyses were performed on a GC
Agilent 7890B equipped with a HT 5 column (30 m, 0.25 mm i.d., 0.25 mm thickness).
Conditions: injector and detector = 250 °C, gas = nitrogen at 1.57 mL/min, temperature = 80 °C,
ramp of 5 °C/min up to 250 °C, and isotherm at 250 °C during 15 min. Calibration with
dodecane as internal standard.
N-substituted benzimidazoles A-C, benzimidazolium salts (2a-e) and PEPPSI complexes
(3a-e) were prepared according to the reported procedures [44]. Further experimental details and
the NMR spectra assignment are provided in the Supplementary Material.
Acknowledgements
The authors gratefully acknowledge Qassim University, represented by the Deanship of
Scientific Research, on the material support for this research under the number alrasscac2348-
alrasscac-2018-1-14-S during the academic year 1940/2019AD''.
7

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Graphical abstract
R1
R1
PdCl2
K2CO3
Cl
N
X
N
N
N
(X= Cl, Br)
Pd
N
pyridine
80°c
Cl
3(a-e)
2(a-e)
R2
a: R1 = 3,5-Dimethyl; R2 = 4-tertbutyl
R2
b:
R1 = 3,5-Dimethyl; R2 = 2,3,5,6-tetramethyl
c: R1 = 3,5-Dimethyl; R2 = 4-methyl
d: R1 = R2 = 4-tertbutyl
e:
R1 = R2 = 4-methyl
11

Table 1. The Suzuki-Miyaura cross coupling catalyzed by palladium complexes 3a-e.
K2CO3 (1 mmol)
HO
Pd.cat (0.25 mol%)
X
+
B
HO
DMF/H2O (1:1), 80°C
R
( 6 ml )
(0.75 mmol)
R
Under Argon
X = Cl, Br
(0.5 mmol)
Entry
1
Substrates
[Cat]
Time (h)
Conversions (%) a
3
3
95
94
95
89
96
15
19
11
10
8
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
2
O
3
3
Cl
4
3
5
3
6
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
3
7
8
O
Cl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
9
28
29
12
18
58
96
58
49
62
100
100
100
100
100
Cl
Cl
3
O
3
Br
Br
3
25
3
3e
26
27
28
29
30
31
32
33
34
35
6
6
6
6
6
6
6
6
6
6
100
100
100
100
100
100
100
100
100
100
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
O
Br
a Conversions were determined by GC
12

Table 2. The Suzuki Coupling Reaction of phenylboronic acid with 2,6-dibromopyridine by
catalyzed by palladium complexes 3.
N
X1
K2CO3(1 mmol),
Pd.cat (0.25 mol %)
X2
(0.5 mmol)
Br
N
N
+
+
HO
HO
6 ml DMF/H2O (1:1)
B
M
D
80°C, 6h
Under Argon
X1 = X2 = Br
Solvent
(0.75 mmol)
Entry
Substrate
[Cat] / (M/D) a ratio
Base
Conversions (%)b
1
2
3
4
5
0/100
0/100
0/100
0/100
0/100
3a
3b
3c
3d
3e
DMF/H2O
K2CO3
N
Br
Br
a (M/D): Monoarylated/Diarylated.
b Conversions were determined by GC.
13

Table 3. Suzuki Coupling Reactionsa.
O
O
HO
KOtbu
toluene
B
C
Cl
+
C
HO
80°C
3h
Entry
Substrate
Cat )mol%)
3a (0.2)
3b (0.5)
3c (0.5)
TOF b
123.3
53.3
TON c
370
Conversions (%) d
1
2
3
4
5
74
80
69
95
94
160
O
46
138
Cl
63.33
62.66
190
3d (0.2)
3e (0.5)
188
a
Reaction conditions: phenylboronic acid (0.75 mmol), parachloroacetophenone
(0.5 mmol), Pd.cat (0.2 or 0.5 mol %), base (1 mmol), 6 mL solvent (1:1), 80 °C. Under
argon.
b Turnover frequency in h-1 at 80 °C.
c Turnover number based on complexes 3.
d Conversions were determined.
14

Table 4. The zone of inhibition (in mm) exhibited by PEPPSI palladium(II) complexes 3a-e and
benzimidazoles salts 2a-e.
Inhibition zone (mm)
Compounds
LB14110
18±0.5
23±0.2
24±0.1
25±0.3
ATCC6538
ATCC19117
ATCC14028
ATCC49189
25±0.1
16±1.1
20±0.4
20±0.4
Complex 3a
Complex3b
Complex 3c
Complex 3d
17±0.5
16±1.5
24±0.4
25±0.3
15±0.3
19±0.5
25±0.3
24±0.3
15±0.3
16±0.3
30±0.1
26±0.2
30±0.5
17±0.5
21±0.2
22±0.1
20±0.3
25±0.5
14±0.5
13±1.1
15±0.5
14±0.3
13±0.3
14±0.5
16±0.3
18±0.4
15±1.5
17±0.5
14±0.3
13±0.3
23±0.5
18±0.4
21±0.4
22±0.3
28±0.1
21±0.5
31±0.2
23±0.1
22±0.3
21±0.3
23±0.2
27±0.2
Complex 3e
Salt 2a
Salt 2b
Salt 2c
Salt 2d
Salt 2e
15

Table 5. Determination of the Minimum Inhibitory Concentrations (MICs)
expressed in mg/mL of PEPPSI complexes 3a-e and benzimidazoles salts 2a–e.
MIC (mg/mL)
Compounds
LB14110
ATCC19117
ATCC14028
2.5
0.039
1.25
Complex 3a
Complex 3b
Complex 3c
Complex 3d
Complex 3e
Salt 2a
0.0192
0.0195
0.3125
0.039
0.078
1.25
1.25
2.5
2.5
2.5
0.3125
1.50
2.5
0.045
2.9
0.0202
0.0260
0.4123
0.052
0.095
2.50
2.25
3.1
Salt 2b
Salt 2c
3.6
2.9
Salt 2d
0.6125
0.039
2.9
Salt 2e
0.0195
0.625
Ampicillin
16

Table 6. Antitumor activity (IC50, in μg/mL)a of compounds 3a-e.
PEPPSI palladium(II)
complexes 3a-e
MDA-MB-231
MCF-7
T47D
19±1.30
21.30±0.85
9.45±2.75
15.75±1.45
8.85±1.20
18±2.0
22±1.30
3a
3b
3c
3d
3e
19.4±0.85
18.50±2.75
10.75±2.45
6.85±1.30
22.38±0.85
12.50±2.75
10.75±2.42
16.96±1.30
a The IC50 values represent an average of three independent experiments (mean ± SD).
17

R1
HO
HO
Y
X
B
Y
X = Cl, Br
Cl
Pd
Cl
N
N
N
R2
Scheme 1. Suzuki-Miyaura cross-coupling reactions of aryl bromides, and chlorides with
phenylboronic acid.
18

R1
R1
R1
H
N
R2
DMF
70°C
N
N
N
N
X
X
+
(X= Cl, Br)
X
EtOH, KOH
Reflux
N
A: R1 = 3,5-Dimethyl
B: R1 = 4-Methyl
2
C: R1 = 4-tert butyl
R2
N
Cl
N
N
N
N
Br
Br
N
2b
2a
2c
N
N
N
Br
Br
N
2e
2d
Scheme 2. General preparation and structural formulae of benzimidazolium salts 2a-e.
19

R1
R1
PdCl2
K2CO3
Cl
N
N
N
N
X
(X= Cl, Br)
Pd
N
pyridine
80°c
Cl
3(a-e)
2(a-e)
R2
a: R1 = 3,5-Dimethyl; R2 = 4-tertbutyl
R2
b:
R1 = 3,5-Dimethyl; R2 = 2,3,5,6-tetramethyl
c: R1 = 3,5-Dimethyl; R2 = 4-methyl
d: R1 = R2 = 4-tertbutyl
e:
R1 = R2 = 4-methyl
Scheme 3. General preparation of palladium complexes 3a-e.
20

SO Na
3
N
N
N
N
N
N
Ag2O
Br
DMC
Br
SO Na
AgBr
SO Na
3
AgOCOCH3
3
4
5
Scheme 4. Synthesis of silver(I) complex (5).
21

N
N
N
N
Ag2O
Br
SO Na
AgBr
SO Na
3
AgOCOCH3
3
4
5
MCl(PR3)3
M = Pt, Au
NaH
CH
3
N
+)
N
[PtCl2(COD)],
M
Free carbene
or
,[PtCl2(PR3)2]2
electron rich olefine
SO Na
3
6
[AuCl(PPH3)3]
7
Scheme 5. Synthesis of metal-carbene complexes.
22