Palladium(II)-N-heterocyclic carbene-catalyzed direct C2- or C5-arylation of thiazoles with aryl bromides

Article abstract of DOI:10.1016/j.tet.2018.03.026

Herein we report, a series of new benzimidazolium chlorides as N-heterocyclic carbene (NHC) ligand and their corresponding palladium(II)-NHC complexes with the general formula [PdCl₂(NHC)₂] were synthesized. All new compounds were characterized by ¹H NMR, ¹³C NMR, IR spectroscopy and elemental analysis techniques. The catalytic activity of palladium(II)-NHC complexes was investigated in the direct C2- or C5-arylation of thiazoles with aryl bromides in presence of palladium(II)-NHC at 150 °C for 1 h. These complexes exhibited the good catalytic performance for the direct arylation of thiazoles. The arylation of thiazoles regioselectively produced C2- or C5-arylated thiazoles in moderate to high yields.

Full text of DOI:10.1016/j.tet.2018.03.026

Accepted Manuscript
Palladium(II)-N-heterocyclic carbene-catalyzed direct C2- or C5-arylation of thiazoles
with aryl bromides
Murat Kaloğlu, İsmail Özdemir
PII:
S0040-4020(18)30269-2
10.1016/j.tet.2018.03.026
TET 29366
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 February 2018
Revised Date: 9 March 2018
Accepted Date: 10 March 2018
Please cite this article as: Kaloğlu M, Özdemir İ, Palladium(II)-N-heterocyclic carbene-catalyzed direct
C2- or C5-arylation of thiazoles with aryl bromides, Tetrahedron (2018), doi: 10.1016/j.tet.2018.03.026.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Palladium(II)-N-heterocyclic carbene-
catalyzed direct C2- or C5-arylation of
thiazoles with aryl bromides
Murat Kaloğlua,b and İsmail Özdemir
aİnönü University, Faculty of Science and Arts, Department of Chemistry, 44280 Malatya, Turkey
bİnönü University, Catalysis Research and Application Center, 44280 Malatya, Turkey

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Palladium(II)-N-heterocyclic carbene-catalyzed direct C2- or C5-arylation of
thiazoles with aryl bromides
Murat Kaloğlua,b and İsmail Özdemira,b,
aİnönü University, Faculty of Science and Arts, Department of Chemistry, 44280 Malatya, Turkey
bİnönü University, Catalysis Research and Application Center, 44280 Malatya, Turkey
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Herein we report, a series of new benzimidazolium chlorides as N-heterocyclic carbene (NHC)
ligand and their corresponding palladium(II)-NHC complexes with the general formula
[PdCl2(NHC)2] were synthesized. All new compounds were characterized by 1H NMR, 13C
NMR, IR spectroscopy and elemental analysis techniques. The catalytic activity of
palladium(II)-NHC complexes was investigated in the direct C2- or C5-arylation of thiazoles
with aryl bromides in presence of palladium(II)-NHC at 150 °C for 1 h. These complexes
exhibited the good catalytic performance for the direct arylation of thiazoles. The arylation of
thiazoles regioselectively produced C2- or C5-arylated thiazoles in moderate to high yields.
Available online
Keywords:
N-Heterocyclic carbene
Benzimidazolium halide
Palladium
2009 Elsevier Ltd. All rights reserved
.
Thiazole
Direct arylation
———
Corresponding author. Tel. and fax: +90-422-341-0212; e-mail: ismail.ozdemir@inonu.edu.tr

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
The direct arylation of thiazoles generally gives the C2- and
C5-arylated products with high regioselectivity. The C2-position
of thiazole is electron poor and acidic (pKa ~ 29.5) due to the
proximity of the two heteroatoms, and the C5-position is the most
electron-rich as a consequence of the resonance. The C4-position
of thiazole is neither electron-rich nor electron poor and as such
will only react under forcing conditions when the C2- and C5-
positions are blocked30-32 (Scheme 1).
Heteroaryls attached with aryl or heteroaryl groups represent
privileged structural motifs that are utilized in both natural and
synthetic compounds, as well as in bioactive compounds and
pharmaceuticals.1-5 Due to their essentiality, heteroaryl motifs
have attracted synthetic chemists for more than a century, and
numerous protocols have since been developed for the
construction of (hetero)aryl-(hetero)aryl bonds by employing
transition-metal catalysts.6-16 Among them, the Suzuki-Miyaura,17
Negishi18 and Kumada19 reactions are so successful that they
have already become routine practices in synthetic laboratories.
However these methods have still some fundamental drawbacks,
as they required an additional synthetic operations for access to
organometallic substrates, and produce a stoichiometric amount
of metal waste from the arene-activating groups upon completion
of the cross-coupling reaction.20 Therefore, environmentally
benign and atom economical strategies for heteroaryls synthesis,
in terms of overall minimization of the formation of by-products
and the simplification of overall synthesis processes, are
required. The transition-metal-catalyzed direct arylation of
aromatic C-H bonds is an ideal alternative. In the direct C-H
bond activation, one of the preactivated reaction partners is
replaced by a simple C-H containing compound, which is not
only just of academic interest but also attractive for industrial
applications, since only one preactivated reaction partner is
needed.21
Scheme 1. Generalized palladium-catalyzed direct C5-arylation
of C2-position blocked thiazole with aryl halides.
The palladium-catalyzed direct arylation of an azole ring was
first accomplished in 1989 by Ohta et al.33 The impressive foray
into the direct arylation of thiazole, oxazole and imidazole
yielded astounding results, both in terms of conversion and
selectivity. Taking thiazole and oxazole in dimethylacetamide,
together with tetrakistriphenylphosphino palladium(II) and
potassium acetate, a heterocyclic chloride could be coupled at the
C5-position of the azole ring in yields of up to 83%. Since these
exciting results, the palladium-catalyzed direct arylation of
various heteroaromatics with aryl halides has proved to be a
powerful method for the synthesis of a wide variety of arylated
heterocycles.34 In this connection, recently we have also reported
direct arylation of different heteroaromatic compounds with aryl
halides catalyzed by palladium(II) complexes containing N-
heterocyclic carbene (NHC) ligands.35 The strong σ-donating but
poor π-accepting ability of NHC ligands lead to the formation of
many stable palladium complexes. Due to activity, stability and
selectivity of palladium(II)-NHC complexes, they have been
widely used as highly reactive and rather selective catalysts for
numerous direct arylation reactions. But, only a few examples of
palladium(II)-NHC-catalyzed direct arylation of thiazoles were
found in the literature to date.36 For this reason, we synthesized a
series of new benzimidazolium chlorides as NHC ligands, (1a-f),
and their corresponding palladium(II)-NHC complexes, (2a-f),
with the general formula [PdCl2(NHC)2], in this study. All new
compounds were characterized by 1H NMR, 13C NMR, IR
spectroscopy and elemental analysis techniques. Next,
palladium(II)-NHC complexes were tested as catalyst in the
direct C2-arylation of 4,5-dimethylthiazole and C5-arylation of
2-n-propylthiazole with aryl bromides in moderate to high yields.
Thiazoles have vast application, being prominent components
of biologically active natural products,22 as well as
pharmaceuticals,23 agrochemicals,24 and novel optical materials.25
As selected examples, Meloxicam is a non-steroidal anti-
inflammatory compound used to treat arthritis, dysmenorrhea and
fever,26 and Cefotaxime is a third generation cephalosporin
antibiotic with broad spectrum activity against both gram positive
and gram negative bacteria.27 Also, Thiamin (Vitamin B1) is a
vital vitamin for neural function and the metabolism of
carbohydrate,22 Ethaboxam is a fungicide used to treat mould and
blight,24 and Thiamethoxam is a neonicitinoid insecticide used as
seed treatments28 (Figure 1). Considering the importance of
thiazoles in pharmaceutical and agrochemical industry, it is clear
that, how popular these substrates are for the direct arylation
studies.29
2. Results and discussion
2.1. Synthesis of benzimidazolium chlorides
The benzimidazolium chlorides 1a-f were synthesized by the
reaction of N-(3-methoxybenzyl)benzimidazole with different
alkyl chlorides in anhydrous dimethylformamide (DMF) at 80 oC
for 36 h. All compounds were isolated as air- and moisture-stable
crystalline solids in high yields (65-93%). The structures of the
1a-f were determined by their characteristic spectroscopic data
Figure 1. Examples of biologically active thiazole derivatives.

3
and elemental analyses. In the 13C NMR spectra of 1a-f, the
characteristic peak of the imino carbon, (NCHN), resonance were
NMR values are similar to those found for other
ACCEPTED MANUSCRIPT
benzimidazolium salts in the literature.35d,e The formation of the
1a-f were also evident through their IR spectra, which showed
peaks v(C=N) at between 1557-1563 cm-1 for the -C=N- bond
vibration of 1a-f. The benzimidazolium chlorides were prepared
according to general reaction pathway depicted in Scheme 2.
1
detected as typical singlets at between 142.9-144.1 ppm. The H
NMR spectra of the 1a-f further supported the assigned
structures, the resonances for C(2)-H were observed as sharp
singlets at between 11.42-12.10 ppm (see SI, pp. S1-S12). The
Scheme 2. Synthesis of benzimidazolium chlorides (1a-f).
suggests the formation of the palladium complexes. The
characteristic peak of the Pd-Ccarbene resonance for all
palladium(II)-NHC complexes were detected at between 181.7-
182.4 ppm, however, NMR studies showed that all palladium(II)-
NHC complexes except 2d were a mixture of cis/trans isomers in
an approximate 40:60 ratio (see SI, pp. S13-S24). The results of
the elemental analysis were in good agreement with the
theoretical values. Palladium(II)-NHC complexes exhibit a
characteristic v(NCN) band typically at between 1402-1408 cm-1.
The spectroscopic data are similar to those found for other
palladium(II)-NHC complexes in the literature.35b,c The 2a-f
complexes were prepared according to general reaction pathway
depicted in Scheme 3. The analytical data are in good agreement
with the compositions proposed for all the new compounds we
prepared, and are summarized in the Table 1.
2.2. Synthesis of palladium(II)-NHC complexes
The palladium(II)-NHC complexes 2a-f were synthesized by
the reaction of benzimidazolium chlorides, (1a-f), with Pd(OAc)2
in degassed dimethyl sulfoxide (DMSO) at 100 C for 24 h. All
o
palladium(II)-NHC complexes were obtained as light yellow
solids in 40-59% yields. The air- and moisture-stable
palladium(II)-NHC complexes were soluble in organic solvents
such as acetone, dichloromethane, chloroform, DMF, ethanol and
acetonitrile. The structures of the 2a-f complexes were also
determined by their characteristic spectroscopic data and
1
elemental analyses. In the H NMR and 13C NMR spectra of the
all palladium(II)-NHC complexes, loss of the benzimidazolium
proton (NCHN) and benzimidazolium C2-carbon (NCHN) signal

4
Tetrahedron
ACCEPTED MANUSCRIPT
Scheme 3. Synthesis of palladium(II)-NHC complexes (2a-f).
Table 1. Physical and spectroscopic properties of new compounds.
Isolated yield
(%)
M.p.
(oC)
v(CN)
H(2) 1H NMR
(ppm)
C(2) 13C NMR
(ppm)a
Compound
Molecular formula
(cm-1)
1a
1b
1c
1d
1e
1f
C22H20Cl2N2O
65
79
85
75
93
82
52
53
59
59
40
45
126-127
102-103
131-132
190-191
195-196
141-142
201-203
148-150
150-152
296-298
263-265
198-200
1558
1560
1557
1557
1558
1563
1408
1403
1406
1406
1402
1408
12.10
144.1
143.6
C19H23ClN2O
11.86
C22H21ClN2O
11.85
143.7
C23H23ClN2O2
12.09
142.9
C26H29ClN2O
11.42
143.9
C25H27ClN2O2
11.78
143.5
2a
2b
2c
2d
2e
2f
C44H38Cl4N4O2Pd
C38H44Cl2N4O2Pd
C44H40Cl2N4O2Pd
C46H44Cl2N4O4Pd
C52H56Cl2N4O2Pd
C50H52Cl2N4O4Pd
-
-
-
-
-
-
182.3 and 182.5
181.7 and 181.8
182.3 and 182.4
181.9
182.2 and 182.3
181.7 and 181.8
aAs previously reported by several groups,37 NMR data showed that all palladium(II)-NHC complexes except 2d were cis/trans mixtures.
5-membered heterocycles.38 We focused on the direct arylation at
the C5-position of 2-n-propylthiazole. The coupling reactions
were regioselective, and in almost all cases, only the C5-arylated
products were formed. The results of varying the other reaction
conditions, including catalyst loading, chlorinated acetophenone,
reaction time and reaction temperature are given in Table 2. The
chemical characterizations of the products were made by NMR.
The conversions were based on the aryl halide by GC and GC-
MS.
2.3. Direct arylation of thiazole derivatives
To determine the optimal catalytic conditions, we selected the
complex 2a as the model catalyst, and the 2-n-propylthiazole as
the model heteroaromatic substrate with a blocked C2-position.
We used the 4-bromoacetophenone or 4-chloroacetophenone as
the model coupling partner. Also, we selected DMAc as the
solvent, and KOAc as the base, because the DMAc/KOAc
combination has been commonly used for the direct arylation of

5
Table 2. Influence of the reaction conditions for palladium(II)-NHC-catalyzed direct C5-arylation of 2-n-propylthiazole with 4-
ACCEPTED MANUSCRIPT
chloroacetophenone and 4-bromoacetophenonea
Entry
2a (mol-%)
X
Time (h)
Temperature (oC)
Conversion(Yield)b,c (%)
1
2
No
2
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
2
2
150
150
150
120
90
-
100(91)
100(91)
78(64)
67(53)
94(85)
64(47)
57(36)
-
3
1
2
4
1
2
5
1
2
6
1
1
150
150
150
150
150
150
150
150
150
7
1
0,5
1
8
0.5
1
9
1
10
11
12
13
14
1
2
-
1
4
4(<2)
12(<5)
22(10)
25(15)
1
8
1
16
20
1
aConditions: 2-n-propylthiazole (2.0 mmol), aryl halide (1.0 mmol), KOAc (2.0 mmol), DMAc (2 mL), 150 °C.
bConversions were calculated with respect to aryl halide from the results of GC and GC-MS spectrometry.
cIsolated yields were shown in parentheses.
The arylation of 2-n-propylthiazole with 4-bromo-
acetophenone was first carried out at 150 C for 2 h without the
entries 9 and 10). Although the reaction time was gradually
increased from 4 h to 20 h, no significant increase in the
conversion rate was observed (4-25%) (Table 2, entries 11-14).
Therefore, no direct arylation of aryl chloride compounds with
thiazole derivatives has been performed.
o
addition of palladium complex in order to examine the effect of
catalyst on the reaction. As attempt, no products were formed
without the addition of palladium complex (Table 2, entry 1). In
the presence of 2 mol% of 2a as the catalyst, KOAc as the base,
DMAc as the solvent and 4-bromoacetophenone as the coupling
partner at 150 °C for 2 h, the C5-arylated product was obtained
full conversion with 91% isolated yield (Table 2, entry 2). An
decrease of the catalyst loading from 2 mol% to 1 mol% when
the reaction was performed at similar conditions had no
significant effect on the reaction, because of the full conversion
were obtained (Table 2, entry 3). Decreasing the reaction
Under the determined optimal conditions, KOAc as the base
in DMAc at 150 °C for 1 h, the palladium(II)-NHC complexes
2a-f (1 mol%) were further examined in the direct C5-arylation
of 2-n-propylthiazole with a blocked C2-position and the direct
C2-arylation of 4,5-dimethylthiazole with a blocked C4- and C5-
positions with five aryl bromides, namely, bromobenzene, 4-
bromotoluene, 4-bromoanisole, 4-bromobenzaldehyde and 4-
bromoacetophenone (Table 3 and Table 4). Initially, we
performed the palladium-catalyzed direct arylation of 2-n-
propylthiazole with aryl bromides. Regioselective arylation on
only the C5-position of 2-n-propylthiazole was observed using
different aryl bromides, because the hydrogen at the C5-position
of 2-n-propylthiazole is more reactive than that of C4-position.
When the reaction of 2-n-propylthiazole with bromobenzene, 4-
bromotoluene, 4-bromoanisole, 4-bromobenzaldehyde and 4-
bromoacetophenone using complexes 2a-f as catalysts was
investigated, conversions at between 67-93%, 64-92%, 66-85%,
82-97% and 76-94% were observed, respectively (Table 3). The
reaction of 2-n-propylthiazole with bromobenzene generated the
5-phenyl-2-n-propylthiazole in 93% conversion in the presence
of 2a and 2f (Table 3, entries 1 and 6). The reaction of 2-n-
propylthiazole with 4-bromotoluene gave the expected product in
80% isolated yield in the presence of 2a (Table 3, entry 7). The
reaction of the electron-rich 4-bromoanisole with 2-n-
propylthiazole gave the 5-(4-methoxyphenyl)-2-n-propylthiazole
in 85% conversion and 73% isolated yield in the presence of 1
o
temperature from 150 °C to 120 C or 90 °C had a detrimental
effect on the conversion (Table 2, entries 4 and 5). When the
reaction time was reduced from 2 h to 1 h no noticeable effect on
the conversion (94%) was observed (Table 2, entry 6), but when
the reaction time was reduced to 0.5 h, the conversion dropped to
64% (Table 2, entry 7). Reducing the catalyst loading from 1
mol% to 0.5 mol% at 150 oC for 1 h decreased the isolated yield
(36%) (Table 2, entry 8). Finally, the best conditions leading to
94% conversion with 85% isolated yield of 4-
bromoacetophenone with high selectivity in favor of the C5-
arylated product were obtained, when the reaction was carried
out in DMAc/KOAc combination in the presence of 1 mol% 2a
o
catalyst at 150 C for 1 h (Table 2, entry 6). The conditions are
commonly used for the direct arylation of 5-membered
heterocycles. For this reason, the conditions are also consistent
with
the
literature.36,38
When
the
less
reactive
4-chloroacetophenone was used as substrate in the presence of 1
mol% of 2a catalyst at similar conditions, no conversion was
observed after lower reaction time such as 1 or 2 h (Table 2,

6
Tetrahedron
ACCEPTED MANUSCRIPT
mol% of palladium complex 2f (Table 3, entry 18). 4-
the 2-(4-methylphenyl)-4,5-dimethylthiazole in 90% conversion
Bromoanisole was also successfully coupled with 2-n-
propylthiazole in the presence of 2a to give desired product in
68% isolated yield (Table 3, entry 13). 2-n-Propylthiazole also
reacts with 4-bromobenzaldehyde to give in 97% conversion and
80% isolated yield with 2f (Table 3, entry 24). High yields of 5-
(4-acetylphenyl)-2-n-propylthiazole were obtained for the
coupling with 4-bromoacetophenone using catalyst 2a (Table 3,
entry 25).
and 74% isolated yield in the presence of 2a (Table 4, entry 7).
Moderate yields of 2-(4-methoxyphenyl)-4,5-dimethylthiazole
were obtained for the coupling with 4-bromoanisole using
catalysts 2a-f (Table 4, entries 13-18) with little variance
between the complexes. 4-Bromobenzaldehyde and 4-
bromoacetophenone gave moderate to high yields of C2-arylation
products in the presence of 1 mol% 2a-f (Table 4, entries 19-30).
Generally, the reactivity of 4,5-dimethylthiazole was similar to 2-
n-propylthiazole, and the conversions for substrates containing
electron-withdrawing groups were higher than those for
substituents containing electron-donating groups.
Finally, the scope of the direct arylation reaction was
extended to 4,5-dimethylthiazole. Regioselective arylation on
only the C2-position of 4,5-dimethylthiazole was observed.
Because the C4- and C5-positions of 4,5-dimethylthiazole is
blocked with methyl group, only the C2-position was arylated.
When the reaction of 4,5-dimethylthiazole with bromobenzene,
4-bromotoluene, 4-bromoanisole, 4-bromobenzaldehyde and 4-
bromoacetophenone using complexes 2a-f as catalysts was also
investigated, conversions at between 71-97%, 74-90%, 59-87%,
76-91% and 80-93% were observed, respectively (Table 4).
Bromobenzene gave to high isolated yields of C2-arylation
products in the presence of 1 mol% 2f (Table 4, entry 6). The
reaction of 4,5-dimethylthiazole with 4-bromotoluene generated
The palladium-catalyzed direct arylation of thiazoles with
aryl bromides has also been previously described by various
groups.36,39 In the previous works, similar substrates have been
employed with higher catalyst loading (2-5 mol%),36b,39a-d and
higher reaction time has been chosen (4-48 h)36a,c,39 for arylation
of thiazoles with aryl bromides. But, in the present work the
catalyst loading was reduced to 1 mol%, and the reaction time
was shortened to 1 h. Moreover, in the present study satisfactory
results were obtained as compared to previous results.36,39
Table 3. Pd-NHC-catalyzed direct C5-arylation of 2-n-propylthiazole by using aryl bromidesa
Entry
Aryl bromide
Catalyst
Product
Conversion(Yield)b,c (%)
1
2
2a
2b
2c
2d
2e
2f
93(83)
73(61)
67(54)
89(75)
84(70)
93(80)
92(80)
75(62)
82(68)
64(50)
85(70)
90(77)
81(68)
66(54)
71(58)
76(63)
68(57)
85(73)
85(70)
82(70)
89(74)
90(76)
92(79)
97(80)
3
4
5
6
7
2a
2b
2c
2d
2e
2f
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2a
2b
2c
2d
2e
2f
MeO
S
N
2a
2b
2c
2d
2e
2f

7
25
26
27
28
29
30
2a
94(85)
76(62)
84(70)
79(66)
89(74)
92(78)
ACCEPTED MANUSCRIPT
2b
2c
2d
2e
2f
aConditions: Pd-NHC 2a-f (0.01 mmol), 2-n-propylthiazole (2.0 mmol), aryl bromide (1.0 mmol), KOAc (2.0 mmol), DMAc (2 mL), 150 °C, 1 h.
bConversions were calculated with respect to aryl bromide from the results of GC spectrometry.
cIsolated yields were shown in parentheses.
Table 4. Pd-NHC-catalyzed direct C2-arylation of 4,5-dimethylthiazole by using aryl bromidesa
Entry
Aryl bromide
Catalyst
Product
Conversion(Yield)b,c (%)
1
2a
2b
2c
2d
2e
2f
90(76)
78(65)
71(57)
83(70)
93(80)
97(84)
90(74)
81(67)
88(75)
74(60)
86(73)
84(70)
83(68)
59(45)
68(53)
75(60)
68(55)
87(73)
90(76)
76(63)
89(74)
79(66)
91(76)
79(66)
93(80)
80(65)
85(66)
81(61)
89(76)
90(75)
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
9
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
2a
2b
2c
2d
2e
2f
2a
2b
2c
2d
2e
2f
2a
2b
2c
2d
2e
2f
aConditions: Pd-NHC 2a-f (0.01 mmol), 4,5-dimethylthiazole (2.0 mmol), aryl bromide (1.0 mmol), KOAc (2.0 mmol), DMAc (2 mL), 150 °C, 1 h.
bConversions were calculated with respect to aryl bromide from the results of GC spectrometry.
cIsolated yields were shown in parentheses.
3. Conclusion
In summary, six new benzimidazolium halides and their
corresponding palladium(II)-NHC complexes were successfully
synthesized and characterized by NMR and IR spectroscopy, and
microanalysis techniques. The catalytic activities of the new
palladium(II)-NHC complexes were investigated in the direct C2-
or C5-arylation of thiazole derivatives. In all cases, except in a
few cases with complex 2a, high conversions of the aryl
bromides were observed. Only a minor effect of the NHC ligand
on the palladium complex was observed for the coupling of aryl
bromide with thiazole derivatives. Surprisingly, similar
conversions were obtained for the coupling of each aryl
bromides. We can say that there is no significant difference
between these complexes on the catalytic activity of direct
arylation of thiazole derivatives by aryl bromides. The only
significant difference between 2a-f complexes indicates that
electronic effects are also playing some role in these processes.
The performances and stabilities of these processes may be
attributed to the ability of the possibility of flexible substituents

8
Tetrahedron
ACCEPTED MANUSCRIPT
on 2a-f complexes, which would rotate away from the axial site
from ethanol/diethyl ether mixture (1:2, v/v) at room temperature
of the palladium center. Also, Glorius has recently reported that
the possibility of in situ generated of palladium nanoparticle
when used less bulky substituents, and this process would be
rapid occurred.40 Finally, when compared to previous reports,36,39
satisfactory results were obtained with aryl bromides in presence
of low catalyst loading in this study. This low catalyst loading
procedure is economically and environmentally attractive. Also,
the only byproducts are AcOH/KBr instead of metallic salts with
classical coupling procedures such as Suzuki, Stille, or Negishi
reactions. Moreover, no preparation of an organometallic
derivative is required, reducing the number of steps and
consequently the amount of waste to prepare these compounds. It
has to be emphasized that this procedure is environmentally more
attractive than these classical coupling procedures.
and, completely dried under vacuum. All benzimidazolium
chlorides (1a-f) were isolated as air- and moisture-stable white
solids and were isolated in 65-93% yields.
4.2.1. 1-(3-Methoxybenzyl)-3-(4-chlorobenzyl)benzimidazolium
Chloride (1a)
1
o
(1.10 g, yield 65%) H NMR (300 MHz, CDCl3, 25 C): δ =
3.72 (s, 3H, CH2C6H4(OCH3)-3); 5.74 (s, 2H, CH2C6H4(Cl)-4);
5.86 (s, 2H, CH2C6H4(OCH3)-3); 6.76-7.53 (m, 12H, arom. CHs,
NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H4(Cl)-4); 12.10 (s, 1H,
NCHN) ppm. 13C NMR (75 MHz, CDCl3, 25 oC): δ = 50.7
(CH2C6H4(Cl)-4);
51.6
(CH2C6H4(OCH3)-3);
55.6
(CH2C6H4(OCH3)-3); 113.7, 113.8, 114.9, 120.2, 127.1, 129.5,
129.9, 130.4, 131.2, 131.3, 131.4, 134.0, 135.2, 160.3 (arom. Cs,
NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H4(Cl)-4); 144.1
(NCHN) ppm. Elemental analysis calcd (%) for C22H20Cl2N2O
(Mr = 399.30): C 66.17, H 5.05, N 7.02; found (%): C 66.19, H
5.08, N 7.05.
4. Experimental
4.1. General methods
All manipulations were carried out under argon using
standard Schlenk line techniques. Chemicals and solvents were
purchased from Sigma-Aldrich Co. (Poole, Dorset, UK). The
solvents used were purified by distillation over the drying agents
indicated and were transferred under argon. DMAc analytical
grade (99%) was not distilled before use. KOAc (99%) was
employed. Elemental analyses were performed by İnönü
University Scientific and Technological Research Center
(Malatya, Turkey). Melting points were measures in open
capillary tubes with an Electrothermal-9200 melting points
apparatus. IR spectra were recorded on ATR unit in the range of
400-4000 cm-1 with Perkin Elmer Spectrum 100
4.2.2. 1-(3-Methoxybenzyl)-3-(n-butyl)benzimidazolium Chloride
(1b)
1
o
(1.10 g, yield 79%) H NMR (500 MHz, CDCl3, 25 C): δ =
3
3
0.97 (t, J = 7.4 Hz, 3H, CH2CH2CH2CH3); 1.45 (hext, J = 7.4
Hz, 2H, CH2CH2CH2CH3); 2.04 (pent, 3J = 7.4 Hz, 2H,
CH2CH2CH2CH3); 3.77 (s, 3H, CH2C6H4(OCH3)-3); 4.61 (t, J =
3
7.5 Hz, 2H, CH2CH2CH2CH3); 5.88 (s, 2H, CH2C6H4(OCH3)-3);
6.82-7.70 (m, 8H, arom. CHs, NC6H4N and CH2C6H4(OCH3)-3);
11.86 (s, 1H, NCHN) ppm. 13C NMR (125 MHz, CDCl3, 25 oC):
δ = 13.5 (CH2CH2CH2CH3); 19.8 (CH2CH2CH2CH3); 31.3
(CH2CH2CH2CH3);
47.6
(CH2CH2CH2CH3);
51.3
1
Spectrofotometer. H NMR and 13C NMR spectra were recorded
(CH2C6H4(OCH3)-3); 55.6 (CH2C6H4(OCH3)-3); 113.0, 113.8,
113.9, 114.7, 120.4, 127.0, 127.1, 130.3, 131.2, 131.4, 134.4,
160.2 (arom. Cs, NC6H4N and CH2C6H4(OCH3)-3); 143.6
(NCHN) ppm. Elemental analysis calcd (%) for C19H23ClN2O
(Mr = 330.90): C 68.97, H 7.01, N 8.47; found (%): C 68.96, H
7.03, N 8.49.
using Bruker Avance AMX and Bruker Avance III spectrometer
operating at 300, 400 and 500 MHz (1H NMR) and at 75, 100 and
125 MHz (13C NMR) in CDCl3. The NMR studies were carried
out in high-quality 5 mm NMR tubes. The chemical shifts (δ) are
reported in ppm relative to CDCl3. Coupling constants (J values)
are given in hertz. NMR multiplicities are abbreviated as follows:
s = singlet, d = doublet, t = triplet, pent = pentet, hext = hextet, m
= multiplet. 1H NMR spectra are referenced to residual protiated
solvents (δ = 7.26 ppm for CDCl3), 13C chemical shifts are
reported relative to deuteriated solvents (δ = 77.16 ppm for
CDCl3). All catalytic reactions were monitored on an Agilent
6890N GC and Schimadzu 2010 Plus GC-MS system by GC-FID
with an HP-5 column of 30 m length, 0.32 mm diameter, and
0.25 ꢀm film thickness.
4.2.3. 1-(3-Methoxybenzyl)-3-(benzyl)benzimidazolium Chloride
(1c)
1
o
(1.30 g, yield 85%) H NMR (500 MHz, CDCl3, 25 C): δ =
3.76 (s, 3H, CH2C6H4(OCH3)-3); 5.87 (s, 2H, CH2C6H5); 5.90 (s,
2H, CH2C6H4(OCH3)-3); 6.81-7.60 (m, 13H, arom. CHs,
NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H5); 11.85 (s, 1H,
o
NCHN) ppm. 13C NMR (125 MHz, CDCl3, 25 C): δ = 51.6
(CH2C6H5); 51.7 (CH2C6H4(OCH3)-3); 55.6 (CH2C6H4(OCH3)-
3); 113.7, 113.8, 113.9, 114.7, 114.8, 120.3, 127.0, 127.1, 127.9,
128.3, 129.2, 129.4, 130.4, 131.3, 131.4, 132.8, 134.2, 160.2
(arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H5); 143.7
(NCHN) ppm. Elemental analysis calcd (%) for C22H21ClN2O
(Mr = 364.90): C 72.42, H 5.80, N 7.68; found (%): C 72.45, H
5.83, N 7.70.
4.2. General procedure for the preparation of benzimidazolium
chloride (1a-f)
N-(3-Methoxybenzyl)benzimidazole (1.0 g; 4.2 mmol) was
dissolved in degassed DMF (3 mL) and alkyl chloride (4.2
mmol) was added at room temperature. The reaction mixture was
stirred at 80 °C for 36 h under argon. After completion of the
reaction, the solvent was removed by vacuum and diethyl ether
(15 mL) was added to obtain a white crystalline solid, which was
filtered off. The solid was washed with diethyl ether (3×10 mL)
and dried under vacuum. The crude product was recrystallized
4.2.4. 1-(3-Methoxybenzyl)-3-(4-methoxybenzyl)benzimidazolium
Chloride (1d)

9
1
o
(1.20 g, yield 75%) H NMR (300 MHz, CDCl3, 25 C): δ =
3.69 (s, 3H, CH2C6H4(OCH3)-4); 3.73 (s, 3H, CH2C6H4(OCH3)-
3); 5.73 (s, 2H, CH2C6H4(OCH3)-4); 5.76 (s, 2H,
CH2C6H4(OCH3)-3); 6.78-7.54 (m, 12H, arom. CHs, NC6H4N,
CH2C6H4(OCH3)-3 and CH2C6H4(OCH3)-4); 12.09 (s, 1H,
NCHN) ppm. 13C NMR (75 MHz, CDCl3, 25 oC): δ = 50.2
Pd(OAc)2 (0.50 mmol) in degassed DMSO (3 mL) was heated
ACCEPTED MANUSCRIPT
with vigorous stirring at 100 oC for 24 h. Volatiles were removed
in vacuo, and the residue was washed with n-pentane (2×5 mL).
The crude product was dissolved with CH2Cl2 then filtered
through a pad of celite and silica gel to remove the unreacted
Pd(OAc)2 and benzimidazolium chloride. Next, the crude
complex was crystallized from dichloromethane/diethyl ether
mixture (1:2, v/v) at room temperature and, completely dried
under vacuum. All palladium complexes were isolated as air- and
moisture-stable yellow solids and were isolated in 40-59% yields.
(CH2C6H4(OCH3)-4);
50.5
(CH2C6H4(OCH3)-3);
54.3
(CH2C6H4(OCH3)-4); 54.6 (CH2C6H4(OCH3)-3); 112.7, 112.8,
113.7, 119.3, 123.7, 126.0, 126.1, 129.0, 129.4, 130.2, 130.4,
133.1, 159.2, 159.3 (arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and
CH2C6H4(OCH3)-4); 142.9 (NCHN) ppm. Elemental analysis
calcd (%) for C23H23ClN2O2 (Mr = 394.90): C 69.95, H 5.87, N
7.09; found (%): C 69.97, H 5.88, N 7.11.
4.3.1. cis/trans-Dichloro-bis[1-(3-methoxybenzyl)-3-(4-chloro-
benzyl)benzimidazol-2-ylidene]palladium(II) (2a)
(0.234 g, yield 52%) 1H NMR (400 MHz, CDCl3, 25 oC): δ =
3.69 and 3.70 (s, 6H, CH2C6H4(OCH3)-3); 5.26 and 5.29 (s, 4H,
CH2C6H4(Cl)-4); 6.20 and 6.23 (s, 4H, CH2C6H4(OCH3)-3); 6.80-
7.59 (m, 24H, arom. CHs, NC6H4N, CH2C6H4(OCH3)-3 and
4.2.5.
1-(3-Methoxybenzyl)-3-(2,3,5,6-tetramethylbenzyl)benz-
imidazolium Chloride (1e)
1
o
(1.64 g, yield 93%) H NMR (300 MHz, CDCl3, 25 C): δ =
2.18 and 2.19 (s, 12H, CH2C6H(CH3)4-2,3,5,6); 3.72 (s, 3H,
CH2C6H4(OCH3)-3); 5.83 (s, 2H, CH2C6H(CH3)4-2,3,5,6); 5.84
(s, 2H, CH2C6H4(OCH3)-3); 6.76-7.51 (m, 9H, arom. CHs,
NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H(CH3)4-2,3,5,6); 11.42
o
CH2C6H4(Cl)-4) ppm. 13C NMR (100 MHz, CDCl3, 25 C): δ =
52.7 and 52.8 (CH2C6H4(Cl)-4); 52.9 and 53.0 (CH2C6H4(OCH3)-
3); 55.6 and 55.7 (CH2C6H4(OCH3)-3); 111.3, 111.4, 112.5,
112.6, 114.5, 114.7, 120.2, 120.3, 123.0, 127.8, 127.9, 128.7,
128.8, 129.5, 134.8, 135.4, 135.5, 137.0, 137.1, 160.0, 160.1
(arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H4(Cl)-4);
182.3 and 182.5 (Pd-Ccarbene) ppm. Elemental analysis calcd (%)
for C44H38Cl4N4O2Pd (Mr = 903.00): C 58.52, H 4.24, N 6.20;
found (%): C 58.54, H 4.26, N 6.22.
(s, 1H, NCHN) ppm. 13C NMR (75 MHz, CDCl3, 25 C): δ =
o
16.2 and 20.6 (CH2C6H(CH3)4-2,3,5,6); 47.9 (CH2C6H(CH3)4-
2,3,5,6); 51.5 (CH2C6H4(OCH3)-3); 55.6 (CH2C6H4(OCH3)-3);
113.6, 113.8, 114.7, 120.1, 127.0, 127.6, 130.3, 131.6, 133.4,
133.6, 134.1, 134.5, 135.0, 135.1, 160.2 (arom. Cs, NC6H4N,
CH2C6H4(OCH3)-3 and CH2C6H(CH3)4-2,3,5,6); 143.9 (NCHN)
ppm. Elemental analysis calcd (%) for C26H29ClN2O (Mr =
421.00): C 74.18, H 6.94, N 6.65; found (%): C 74.20, H 6.95, N
6.67.
4.3.2.
cis/trans-Dichloro-bis[1-(3-methoxybenzyl)-3-(n-butyl)
benzimidazol-2-ylidene]palladium(II) (2b)
(0.203 g, yield 53%) 1H NMR (300 MHz, CDCl3, 25 oC): δ =
3
0.72 and 1.01 (t, J = 7.4 Hz, 6H, CH2CH2CH2CH3); 1.22 and
4.2.6. 1-(3-Methoxybenzyl)-3-(4-phenoxybutyl)benzimidazolium
Chloride (1f)
3
1.53 (hext, J = 7.6 Hz, 4H, CH2CH2CH2CH3); 2.06 and 2.21
3
(pent, J = 7.6 Hz, 4H, CH2CH2CH2CH3); 3.56 and 3.68 (s, 6H,
1
o
(1.46 g, yield 82%) H NMR (500 MHz, CDCl3, 25 C): δ =
1.97 (pent, 3J = 5.8 Hz, 2H, CH2CH2CH2CH2OC6H5); 2.32 (pent,
3J = 7.3 Hz, 2H, CH2CH2CH2CH2OC6H5); 3.78 (s, 3H,
CH2C6H4(OCH3)-3); 4.68 and 4.79 (t, 3J = 7.8 Hz, 4H,
CH2CH2CH2CH3); 5.90 and 6.07 (s, 4H, CH2C6H4(OCH3)-3);
6.65-7.32 (m, 16H, arom. CHs, NC6H4N and CH2C6H4(OCH3)-3)
o
CH2C6H4(OCH3)-3); 4.04 (t, 3J
CH2CH2CH2CH2OC6H5); 4.75 (t, 3J
=
5.8 Hz, 2H,
7.3 Hz, 2H,
ppm. 13C NMR (75 MHz, CDCl3, 25 C): δ = 13.7 and 14.0
=
(CH2CH2CH2CH3); 20.4 and 20.7 (CH2CH2CH2CH3); 31.8 and
31.9 (CH2CH2CH2CH3); 48.3 and 48.4 (CH2CH2CH2CH3); 52.8
and 53.2 (CH2C6H4(OCH3)-3); 55.6 and 55.8 (CH2C6H4(OCH3)-
3); 110.3, 110.4, 111.4, 111.5, 112.5, 112.6, 114.4, 114.8, 120.2,
122.8, 122.9, 129.4, 129.7, 134.3, 134.6, 134.9, 135.0, 137.1,
137.2, 160.0, 160.3 (arom. Cs, NC6H4N and CH2C6H4(OCH3)-3);
181.7 and 181.8 (Pd-Ccarbene) ppm. Elemental analysis calcd (%)
for C38H44Cl2N4O2Pd (Mr = 766.10): C 59.57, H 5.79, N 7.31;
found (%): C 59.59, H 5.80, N 7.33.
CH2CH2CH2CH2OC6H5); 5.84 (s, 2H, CH2C6H4(OCH3)-3); 6.82-
7.71 (m, 13H, arom. CHs, NC6H4N, CH2C6H4(OCH3)-3 and
CH2CH2CH2CH2OC6H5); 11.78 (s, 1H, NCHN) ppm. 13C NMR
o
(125 MHz, CDCl3, 25 C): δ = 26.1 (CH2CH2CH2CH2OC6H5);
26.4 (CH2CH2CH2CH2OC6H5); 47.4 (CH2CH2CH2CH2OC6H5);
51.3 (CH2C6H4(OCH3)-3); 55.6 (CH2C6H4(OCH3)-3); 66.7
(CH2CH2CH2CH2OC6H5); 113.1, 113.8, 114.4, 114.8, 120.4,
120.8, 127.2, 129.5, 130.4, 131.2, 131.5, 134.3, 158.5, 160.2
(arom.
Cs,
NC6H4N,
CH2C6H4(OCH3)-3
and
4.3.3. cis/trans-Dichloro-bis[1-(3-methoxybenzyl)-3-(benzyl)benz
imidazol-2-ylidene]palladium(II) (2c)
CH2CH2CH2CH2OC6H5); 143.5 (NCHN) ppm. Elemental
analysis calcd (%) for C25H27ClN2O2 (Mr = 422.90): C 70.99, H
6.43, N 6.62; found (%): C 71.02, H 6.44, N 6.63.
(0.246 g, yield 59%) 1H NMR (400 MHz, CDCl3, 25 oC): δ =
3.61 and 3.62 (s, 6H, CH2C6H4(OCH3)-3); 5.92 and 5.94 (s, 4H,
CH2C6H5); 5.95 and 5.97 (s, 4H, CH2C6H4(OCH3)-3); 6.71-7.39
(m, 26H, arom. CHs, NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H5)
4.3. General procedure for the preparation of palladium(II)-
NHC complexes (2a-f)
o
All benzimidazolium chlorides were converted, with
moderated yields, into the palladium(II)-NHC complexes (2a-f).
A suspension of the benzimidazolium chloride (1.0 mmol) and
ppm. 13C NMR (100 MHz, CDCl3, 25 C): δ = 52.7 and 52.8
(CH2C6H5); 52.9 and 53.0 (CH2C6H4(OCH3)-3); 55.6 and 55.7
(CH2C6H4(OCH3)-3); 111.3, 111.4, 114.5, 114.7, 120.2, 120.3,

10
Tetrahedron
ACCEPTED MANUSCRIPT
127.8, 127.9, 128.6, 128.7, 134.8, 135.5, 137.0, 137.1, 160.0,
55.5 and 55.7 (CH2C6H4(OCH3)-3); 67.1 and 67.3
160.1 (arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and CH2C6H5);
182.3 and 182.4 (Pd-Ccarbene) ppm. Elemental analysis calcd (%)
for C44H40Cl2N4O2Pd (Mr = 834.10): C 63.36, H 4.83, N 6.72;
found (%): C 63.38, H 4.85, N 6.75.
(CH2CH2CH2CH2OC6H5); 110.4, 110.5, 111.3, 111.4, 112.3,
112.4, 114.4, 114.5, 114.6, 114.7, 119.9, 120.0, 120.6, 120.7,
123.1, 123.2, 129.4, 129.5, 129.6, 129.7, 134.1, 134.3, 134.6,
134.7, 137.3, 158.9, 160.0, 160.1, 160.3 (arom. Cs, NC6H4N,
CH2C6H4(OCH3)-3 and CH2CH2CH2CH2OC6H5); 181.7 and
181.8 (Pd-Ccarbene) ppm. Elemental analysis calcd (%) for
C50H52Cl2N4O4Pd (Mr = 950.30): C 63.19, H 5.52, N 5.90; found
(%): C 63.34, H 5.58, N 5.97.
4.3.4.
Dichloro-bis[1-(3-methoxybenzyl)-3-(4-methoxybenzyl)
benzimidazol-2-ylidene]palladium(II) (2d)
(0.263 g, yield 59%) 1H NMR (400 MHz, CDCl3, 25 oC): δ =
3.61 (s, 6H, CH2C6H4(OCH3)-4); 3.66 (s, 6H, CH2C6H4(OCH3)-
3); 5.96 (s, 4H, CH2C6H4(OCH3)-4); 5.99 (s, 4H,
CH2C6H4(OCH3)-3); 6.69-7.40 (m, 24H, arom. CHs, NC6H4N,
CH2C6H4(OCH3)-3 and CH2C6H4(OCH3)-4) ppm. 13C NMR (100
MHz, CDCl3, 25 oC): δ = 51.8 (CH2C6H4(OCH3)-4); 52.4
4.4. General procedure for the direct arylation of thiazole
derivatives
An oven dried 10 mL Schlenk tube was charged with
palladium(II)-NHC complex (0.01 mmol), thiazole derivative, (2-
n-propylthiazole or 4,5-dimethylthiazole), (2.0 mmol), aryl
bromide derivative, (bromobenzene, 4-bromotoluene, 4-
bromoanisole, 4-bromobenzaldehyde or 4-bromoacetophenone),
(1.0 mmol), KOAc (2.0 mmol), and DMAc (2 mL) under argon.
The Schlenk tube was placed in a preheated oil bath at 150 °C,
and the reaction mixture was stirred for 1 h. Completion of the
reaction, the solvent was removed under vacuum and the residue
was charged directly onto a micro silica gel column. The
products were eluted by using n-pentane/diethyl ether mixture
(4:1, v/v). The chemical characterizations of the products were
made by NMR. The conversions were based on the aryl halide by
GC and GC-MS.
(CH2C6H4(OCH3)-3);
55.2
(CH2C6H4(OCH3)-4);
55.6
(CH2C6H4(OCH3)-3); 111.3, 112.4, 114.0, 114.1, 114.5, 114.7,
120.1, 123.0, 127.7, 129.0, 129.1, 129.5, 134.5, 137.3, 159.2,
160.1 (arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and
CH2C6H4(OCH3)-4); 181.9 (Pd-Ccarbene) ppm. Elemental analysis
calcd (%) for C46H44Cl2N4O4Pd (Mr = 894.20): C 61.79, H 4.96,
N 6.27; found (%): C 61.81, H 4.98, N 6.29.
4.3.5.
cis/trans-Dichloro-bis[1-(3-methoxybenzyl)-3-(2,3,5,6-
tetramethylbenzyl)benzimidazol-2-ylidene]palladium(II) (2e)
(0.189 g, yield 40%) 1H NMR (400 MHz, CDCl3, 25 oC): δ =
2.23, 2.24, 2.27 and 2.34 (s, 24H, CH2C6H(CH3)4-2,3,5,6); 3.66
and 3.68 (s, 6H, CH2C6H4(OCH3)-3); 6.09 and 6.20 (s, 4H,
CH2C6H(CH3)4-2,3,5,6); 6.23 and 6.34 (s, 4H, CH2C6H4(OCH3)-
3); 6.72-7.32 (m, 18H, arom. CHs, NC6H4N, CH2C6H4(OCH3)-3
and CH2C6H(CH3)4-2,3,5,6) ppm. 13C NMR (100 MHz, CDCl3,
Acknowledgements
This work was financially supported by the Technological
and Scientific Research Council of Turkey TÜBİTAK-
BOSPHORUS (109T605) and the İnönü University Research
Fund (İ.Ü. B.A.P. 2015/41).
o
25 C): δ = 16.5, 16.7, 20.5 and 20.6 (CH2C6H(CH3)4-2,3,5,6);
50.7 and 50.8 (CH2C6H(CH3)4-2,3,5,6); 52.2 and 52.3
(CH2C6H4(OCH3)-3); 55.4 and 55.5 (CH2C6H4(OCH3)-3); 111.0,
111.1, 111.8, 111.9, 112.3, 112.6, 114.4, 114.5, 119.9, 120.2,
122.4, 122.5, 122.9, 123.1, 129.4, 129.6, 131.0, 131.1, 132.2,
132.3, 134.2, 134.3, 134.6, 134.7, 134.8, 134.9, 137.3, 137.4,
160.0, 160.1 (arom. Cs, NC6H4N, CH2C6H4(OCH3)-3 and
CH2C6H(CH3)4-2,3,5,6); 182.2 and 182.3 (Pd-Ccarbene) ppm.
Elemental analysis calcd (%) for C52H56Cl2N4O2Pd (Mr =
946.40): C 66.00, H 5.96, N 5.92; found (%): C 66.01, H 5.98, N
5.94.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
https://
References
1.
2.
Pozharskii, A. F.; Soldatenkov, A. T.; Katritzky, A. R., (Eds.); In
Heterocycles in Life and Society: An Introduction to Heterocyclic
Chemistry, Biochemistry and Applications; John Wiley & Sons, Ltd.:
West Sussex, United Kingdom, 2011; 2nd ed.
Eicher, T.; Hauptmann, S.; Speicher, A., (Eds.); In The Chemistry of
Heterocycles: Structures, Reactions, Synthesis, and Applications;
Wiley-VCH: Weinheim, Germany, 2013; 3nd, Completely Revised
and Enlarged ed.
Ellis, G. P.; Taylor, E. C., Ed.; In Chemistry of Heterocyclic
Compounds: Synthesis of Fused Heterocycles; John Wiley & Sons,
Ltd.: West Sussex, United Kingdom, 2008; Vol. 47.
Nylund, K.; Johansson, P., (Eds.); In Heterocyclic Compounds:
Synthesis, Properties and Applications; Nova Science Publishers, Inc.:
New York, 2010.
4.3.6. cis/trans-Dichloro-bis[1-(3-methoxybenzyl)-3-(4-phenoxy-
butyl)benzimidazol-2-ylidene]palladium(II) (2f)
(0.213 g, yield 45%) 1H NMR (400 MHz, CDCl3, 25 oC): δ =
3
1.65 and 1.95 (pent, J = 6.0 Hz, 4H, CH2CH2CH2CH2OC6H5);
2.29 and 2.46 (pent, J = 7.0 Hz, 4H, CH2CH2CH2CH2OC6H5);
3.36 and 3.63 (s, 6H, CH2C6H4(OCH3)-3); 3.69 and 3.94 (t, J =
5.8 Hz, 4H, CH2CH2CH2CH2OC6H5); 4.80 and 4.90 (t, J = 7.0
3
3.
4.
3
3
Hz, 4H, CH2CH2CH2CH2OC6H5); 5.93 and 6.10 (s, 4H,
CH2C6H4(OCH3)-3); 6.70-7.34 (m, 26H, arom. CHs, NC6H4N,
CH2C6H4(OCH3)-3 and CH2CH2CH2CH2OC6H5) ppm. 13C NMR
5.
6.
Ackermann, L., Ed.; In Modern Arylation Methods; Wiley-VCH
Verlag GmbH & Co. KGAa: Weinheim, Germany, 2009.
Beller, M.; Bolm, C., (Eds.); In Transition Metals for Organic
Synthesis: Building Blocks and Fine Chemicals; Wiley-VCH Verlag
GmbH: Weinheim, Germany, 2004; 2nd Revised and Enlarged ed.
(100 MHz, CDCl3, 25 oC):
(CH2CH2CH2CH2OC6H5);
(CH2CH2CH2CH2OC6H5);
δ
=
26.8 and 27.0
27.1
47.9
and
and
27.2
48.0
(CH2CH2CH2CH2OC6H5); 52.3 and 52.5 (CH2C6H4(OCH3)-3);

11
7.
de Meijere, A.; Diederich, F., (Eds.); In Metal-Catalyzed Cross-
31. Belen'kii LI, Gromova GP, Cheskis MA, Gol'dfarb YL. Chemica
Scripta 1985; 25:295-300.
ACCEPTED MANUSCRIPT
Coupling Reactions; 2nd, Completely Revised and Enlarged Edition,
Wiley-VCH Verlag GmbH & Co. Weinheim: Germany, 2014; Vol. 1.
Alberico D, Scott ME, Lautens M. Chem. Rev. 2007; 107:174-238.
Lebrasseur N, Larrosa I. J. Am. Chem. Soc. 2008; 130:2926-2927.
32. Begtrup M, Hansen LBL. Acta Chem. Scandinavica, 1992; 46:372-
383.
33. Aoyagi Y, Inoue A, Koizumi I, Hashimoto R, Tokunaga K, Gohma K,
Komatsu J, Sekine K, Miyafuji A, Kunoh J, Honma R, Akita Y, Ohta
A. Heterocycles 1992; 33:257-272.
34. (a) Roger J, Poźgan F, Doucet H. J. Org. Chem. 2009; 74:1179-1186;
(b) Campeau LC, Stuart DR, Fagnou K. Aldrichimica Acta, 2007;
40:35-41; (c) Seregin I. V, Gevorgyan V. Chem. Soc. Rev. 2007; 36:
1173-1193; (d) Turner GL, Morris JA, Greaney MF. Angew. Chem.
Int. Ed. 2007; 46:7996-8000; (e) Li BJ, Yang SD, Shi ZJ. Synlett,
2008; 7:949-957; (f) Sun CL, Li BJ, Shi ZJ. Chem. Commun. 2010;
46:677-685; (g) Xi P, Yang F, Qin S, Zhao D, Lan J, Gao G, Hu C,
You J. J. Am. Chem. Soc. 2010; 132:1822-1824.
8.
9.
10. Bellina F, Rossi R. Tetrahedron, 2009; 65:10269-10310.
11. Ackermann L, Vincente R, Kapdi AR. Angew. Chem. Int. Ed. 2009;
48:9792-9826.
12. Yang N, Dong L, Su Z, Hu C. RSC Adv. 2013; 3:20772-20781.
13. Fischmeister C, Doucet H. Green Chem. 2011: 13;741-753.
14. Idris I, Tannoux T, Derridj F, Dorcet V, Boixel J, Guerchais V, Soule
JF, Doucet H, Mater J. Chem. C. 2018; Accepted Article,
DOI: 10.1039/C7TC05395A.
15. Patra T, Nandi S, Sahoo SK, Maiti D. Chem. Commun. 2016;
52:1432-1435.
16. Vásquez-Céspedes S, Chepiga KM, Möller N, Schäfer AH, Glorius F.
ACS Catal. 2016; 6:5954-5961.
35. (a) Gürbüz N, Özdemir İ, Çetinkaya B. Tetrahedron Lett. 2005;
46:2273-2277; (b) Arslan H, Özdemir İ, Vanderveer D, Demir S,
Çetinkaya B. J. Coord. Chem. 2009; 62:2591-2599; (c) Özdemir İ,
Gürbüz N, Kaloğlu N, Doğan Ö, Kaloğlu M, Bruneau C, Doucet H.
Beilstein J. Org. Chem. 2013; 9:303-312; (d) Kaloğlu M, Özdemir İ,
Dorcet V, Bruneau C, Doucet H. Eur. J. Inorg. Chem. 2017; 10:1382-
1391; (e) Kaloğlu N, Kaloğlu M, Tahir MN, Arıcı C, Bruneau C,
Doucet H, Dixneuf PH, Çetinkaya B, Özdemir İ. J. Organomet. Chem.
2017; Accepted Article, DOI: 10.1016/j.jorganchem.2017.10.019; (f)
Yiğit B, Gürbüz N, Yiğit M, Dağdeviren Z, Özdemir İ. Inorg. Chim.
Acta 2017; 465:44-49.
36. (a) Özdemir İ, Gök Y, Özeroğlu Ö, Kaloğlu M, Doucet H, Bruneau C.
Eur. J. Inorg. Chem. 2010; 12:1798-1805; (b) Yiğit B, Yiğit M,
Dağdeviren Z, Özdemir İ. Transit. Met. Chem. 2016; 41:751-757; (c)
Hu LQ, Deng RL, Li YF, Zeng CJ, Shen DS, Liu FS. Organometallics,
2018; 37:214-226.
17. (a) Miyaura N, Yamada K, Suzuki A. Tetrahedron Lett. 1979;
20:3437-3440; (b) Miyaura N, Suzuki A. Chem. Rev. 1995; 95:2457-
2483; (c) Zhang C, Huang J, Trudell ML, Nolan SP. J. Org. Chem.
1999; 64:3804-3805; (d) Lei P, Meng G, Ling Y, Szostak J. An, M. J.
Org. Chem. 2017; 82:6638-6646.
18. (a) Negishi E. Acc. Chem. Res. 1982; 15:340-348; (b) Hadei N,
Kantchev E. A. B, Brien C. J. O, Organ M. G. Org. Lett. 2005; 7:3805-
3807; (c) Negishi E. Bull. Chem. Soc. Jpn. 2007; 80:233-257.
19. Kumada M. Pure Appl. Chem. 1980; 52:669-679.
20. (a) Trost BM. Acc. Chem. Res. 2002; 35:695-705; (b) Vasapollo G,
Mele G, Maffei A, Sole R. D. Appl. Organomet. Chem. 2003; 17:835-
839; (c) Bayardon J, Holz J, Schäffner B, Andrushko V, Verevkin S,
Preetz A, Börner A. Angew. Chem. Int. Ed. 2007; 46:5971-5974; (d)
Berman AM, Lewis JC, Bergman RG, Ellman JA. J. Am. Chem. Soc.
2008; 130:14926-14927; (e) Colby D. A, Bergman R. G, Ellman JA.
Chem. Rev. 2010; 110:624-655.
37. (a) Herrmann WA, Elison M, Fischer J, Kocher C, Artus GR. Angew.
Chem., Int. Ed. 1995; 34:2371-2374; (b) Baker MV, Brown DH,
Simpson PV, Skelton BW, White AH. Eur. J. Inorg. Chem. 2009;
13:1977-1988; (c) Zhou X, Jordan R. F. Organometallics, 2011;
30:4632-4642.
21. (a) Gorelsky S, Lapointe D, Fagnou K. J. Org. Chem. 2012; 77:658-
668; (b) Ma W, Ackermann L. Chem. Eur. J. 2013; 19:13925-13928;
(c) Figg TM, Wasa M, Yu JQ, Musaev DG. J. Am. Chem. Soc. 2013;
135:14206-14214.
22. (a) Jin Z. Nat. Prod. Rep. 2003; 20:584-605; (b) Jin Z. Nat. Prod. Rep.
2006; 23:464-496.
38. (a) Roy D, Mom S, Beauperin M, Doucet H, Hierso JC. Angew.
Chem. Int. Ed. 2010; 49:6650-6654; (b) Jin R, Yuan K, Chatelain E,
Soule, H. Doucet JF. Adv. Synth. Catal. 2014; 356:3831-3841.
39. (a) Yokooji A, Okazawa T, Satoh T, Miura M, Nomura M.
Tetrahedron, 2003; 59:5685-5689; (b) Roger J, Gottumukkala AL,
Doucet H. ChemCatChem, 2010; 2:20-40; (c) Campeau LC, Bertrand-
Laperle M, Leclerc JP, Villemure E, Gorelsky S, Fagnou K, J. Am.
Chem. Soc. 2008; 130:3276-3277; (d) Tamba S, Okubo Y, Tanaka S,
Monguchi D, Mori A. J. Org. Chem. 2010; 75:6998-7001; (e) Luo BT,
Liu H, Lin ZJ, Jiang J, Shen DS, Liu RZ, Ke Z, Liu FS.
Organometallics, 2015, 34:4881-4894; (f) Ouyang JS, Li YF, Shen DS,
Ke Z, Liu FS. Dalton Trans. 2016; 45:14919-14927; (g) Chen FM,
Huang FD, Yao XY, Li T, Liu FS. Org. Chem. Front. 2017; 4:2336-
2342; (h) Chen FM, Lu DD, Hu LQ, Huang J, Liu FS. Org. Biomol.
Chem. 2017; 15:5731-5736.
23. Jin Z. Nat. Prod. Rep. 2005; 22:196-229.
24. Grayson I. Spec. Chem. Mag. 2001; 21:10-12.
25. Mori A, Sekiguchi A, Masui K, Shimada T, Horie M, Osakada K,
Kawamoto M, Ikeda T. J. Am. Chem. Soc. 2003; 125:1700-1701.
26. Struengmann A, Freudensprung B, Klokkers K. US Patent 6284269
B1, 1999.
27. Sahoo PK, Sundaravadivelan S. WO. Patent 2011042775 A1. 2011.
28. Bristow JT. WO. Patent 2015180585 A1. 2015.
29. (a) Stuart DR, Fagnou K. Science 2007; 316:1172-1175; (b) Alberico
D, Scott ME, Lautens M. Chem. Rev. 2007; 107:174-238; (c) Satoh T,
Miura M. Chem. Lett. 2007; 36:200-205.
30. Shen K, Fu Y, Li JN, Liu L, Guo QX. Tetrahedron 2007; 63:1568-
1576.
40. Ernst JB, Schwermann C, Yokota G, Tada M, Muratsugu S, Doltsinis
NL, Glorius F. J. Am. Chem. Soc. 2017; 139:9144-9147.

ACCEPTED MANUSCRIPT
• A series of new benzimidazolium chlorides (1a-f) and their corresponding palladium(II)-NHC
complexes (2a-f) with general formula [PdCl2(NHC)2] were synthesized, (NHC = N-heterocyclic
carbene).
• The obtained palladium(II)-NHC complexes were characterized by NMR (1H and 13C), IR
spectroscopy and microanalysis techniques.
• These palladium(II)-NHC complexes were used as efficient catalysts in the direct C2- or C5-
arylation of thiazoles with aryl bromides.