Efficient and green catalytic system incorporating new benzimidazolium salts for the Sonogashira cross-coupling reaction

Article abstract of DOI:10.1002/aoc.3897

A number of novel benzimidazole salts were synthesized and their structures were determined using ¹H NMR, ¹³C NMR and infrared spectroscopic techniques and elemental analysis. A catalyst system consisting of Pd(OAc)₂ and copper nanoparticles in the presence of Cs₂CO₃ and incorporating the novel benzimidazole salts in poly(ethylene glycol) solvent significantly improved the yields of Sonogashira reactions between aryl halides and phenylacetylene under microwave irradiation in 10?min.

Full text of DOI:10.1002/aoc.3897

Received: 19 January 2017
DOI: 10.1002/aoc.3897
Revised: 15 April 2017
Accepted: 28 April 2017
F U L L PA P E R
Efficient and green catalytic system incorporating new
benzimidazolium salts for the Sonogashira cross‐coupling reaction
Kemal Yavuz | Hasan Küçükbay
Faculty of Arts and Sciences, Department of
Chemistry, İnönü University, 44280 Malatya,
Turkey
A number of novel benzimidazole salts were synthesized and their structures were
1
determined using H NMR, 13C NMR and infrared spectroscopic techniques and
elemental analysis. A catalyst system consisting of Pd(OAc)2 and copper nanoparti-
cles in the presence of Cs2CO3 and incorporating the novel benzimidazole salts in
poly(ethylene glycol) solvent significantly improved the yields of Sonogashira reac-
tions between aryl halides and phenylacetylene under microwave irradiation in
10 min.
Correspondence
Hasan Küçükbay, İnönü University, Faculty
of Arts and Sciences, Department of
Chemistry, 44280 Malatya, Turkey.
Email: hasan.kucukbay@inonu.edu.tr
KEYWORDS
benzimidazole salts, copper nanoparticles, cross‐coupling, homocoupling, microwave, Sonogashira reaction
1 | INTRODUCTION
electricity costs, and the use of metal catalysis in conjunction
with microwave heating provides significant advantages.[22,23]
The first cross‐coupling reaction with terminal alkynes and
aryl or vinyl halides in the presence of a palladium and copper
iodide catalyst was reported in 1975 by Sonogashira and co‐
workers.[1] Since then, this protocol has been popularized as
the Sonogashira cross‐coupling reaction. Today, the
Sonogashira coupling reaction is known as a powerful method
for the synthesis of novel alkynes derived from terminal acet-
ylenes and aryl or vinyl halides.[2–11] Although palladium–
phosphine complexes and copper‐based catalysts have been
mostly used in the Sonogashira reaction, the addition of
copper(I) salts as co‐catalysts has some drawbacks such as
Glaser‐type homocoupling and phosphine‐based ligands caus-
ing environmental pollution.[2] In order to prevent these
unwanted effects, many researchers have also tried copper‐free
and metal‐free Sonogashira reaction protocols.[4,12–19] Many
of these methods involve long reaction times and low reaction
yields. After the isolation of stable N‐heterocyclic carbenes by
Arduengo and co‐workers in 1991, a new window was opened
for scientists who worked on metal‐mediated catalytic synthe-
ses due to the ease of synthesis of N‐heterocyclic carbene
ligands which have better σ‐donor ability, lower toxicity and
better thermal stability than phosphine‐based ligands.[20,21]
Microwave irradiation accelerates chemical reactions and
increases reaction yields and decreases reaction times and
In our previous studies, we used several in situ prepared pal-
ladium–N‐heterocyclic carbenes derived from benzimidazole
for the Suzuki, Heck and Buchwald–Hartwig reactions under
microwave irradiation conditions and obtained promising cat-
alytic results.[24–30]
The use of a metal catalyst as nanoparticles generally
accelerates the catalytic conversion and the use of nanoparti-
cles in cross‐coupling reactions has attracted a great deal of
interest because of their effectiveness. Therefore, several
studies have been reported relating to the use of palladium
nanoparticles in cross‐coupling reactions.[31–34] However, as
far as we know, there has been only one report of the use of
copper nanoparticles as a co‐catalyst in the Sonogashira
cross‐coupling reaction which was also reported by us.[26]
Palladium‐catalysed reactions are important in synthetic
organic chemistry.[35–38] In this context, both homogenous
and heterogeneous catalyst systems incorporating palladium
have been used. Comparing these systems, homogeneous
systems seem to be more active due to their acting at the
molecular scale whereas heterogeneous systems are active
only on the catalytic surface. Immobilization is a method to
improve catalytic activity and recyclability of homogeneous
catalysts using an appropriate supporting system such as
polymers, resins etc.[39–42] However, it has been reported that
Appl Organometal Chem. 2017;e3897.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 8
https://doi.org/10.1002/aoc.3897

2 of 8
YAVUZ AND KÜÇÜKBAY
palladium immobilization is generally complicated and
involves multiple steps with undesirable palladium black for-
mation and relatively long reaction times.[40,41]
2.2 | Optimization of Sonogashira reactions
In order to determine the optimum reaction conditions for the
Sonogashira coupling reaction we chose to study the cou-
pling of iodobenzene with phenylacetylene as model com-
pounds. The test reactions were performed in the presence
of 0.05 or 1 mol% of Pd(OAc)2 and 1 or 0.05 mol% of CuI
or 2 or 4 mol% of CuNPc as co‐catalyst using different bases
such as KOH, K2CO3 and Cs2CO3 in various solvents such as
DMF, EtOH, DME, C2H4(OH)2, glycerol and PEG300 for 5,
10 and 20 min at 60, 80, 100 and 120 °C under microwave
irradiation. Solvents can play an important role in organic
synthesis. In this context, PEG has been used as a solvent,
phase‐transfer catalyst and to enhance the recyclability of cat-
alysts.[43–45] Optimization data are shown in Table 1. It was
found that the Sonogashira coupling reaction catalysed by
1, 1 mol% of Pd(OAc)2, 4 mol% of CuNPc as co‐catalyst
and base catalyst system gave the highest yield when using
PEG as a solvent and Cs2CO3 as a base at 100 °C with micro-
wave heating in 10 min (Table 1, entry 19). Having established
the optimal reaction conditions, the recycling of the catalyst
was investigated. The catalyst can be recycled at least three
times without significant loss of activity (Table 1, entry 19).
Neither prolonging the reaction time from 10 to 20 min nor
enhancing the reaction temperature from 100 to 120 °C
affected significantly the coupling product yields. Experi-
ments showed that the yields of Sonogashira coupling reaction
were decreased in the absence of 1 in 10 min under optimized
conditions (Table 1, entry 21). We also explored whether the
reaction can be effected using conventional heating system
in a preheated oil bath for 10 min under optimized reaction
conditions. However, we did not detect desired coupling prod-
uct under the optimal reaction conditions using conventional
heating (Table 1, entry 23).
In our previous work, we investigated the catalytic
activity of N‐phthalimidoethyl and 4‐substituted benzyl‐
bearing benzimidazolium salts in the Sonogashira cross‐
coupling reaction. With the hope of obtaining the most
efficient catalyst for Sonogashira cross‐coupling reactions,
the work presented here focused on a catalyst system con-
taining a series of novel benzimidazole compounds (hav-
ing 2‐oxo‐2‐phenylethyl, alkyl, substituted alkyl and
benzyl), Pd(OAc)2, copper nanoparticles (CuNPc) and
CsCO3 for reaction in poly(ethylene glycol) (PEG) under
microwave irradiation.
2 | RESULTS AND DISCUSSION
2.1 | Synthesis and characterization of new
Benzimidazole salts
Benzimidazole salts are good source for in situ formation of
palladium–N‐heterocyclic carbene complexes from Pd(OAc)2
in the presence of an appropriate base. Substituents in benz-
imidazole salts incorporated in the catalytic system also play
a role in catalytic activity, and electron‐donating substituents
slightly enhance catalytic activity whereas electron‐withdraw-
ing substituents slightly decrease it. In this context, new benz-
imidazole salts were prepared in good yields by treating
appropriate alkyl halide with 1‐benzyl‐1H‐benzo[d]imidazole
(I) or 2‐(1H–benzo[d]imidazol‐1‐yl)‐1‐phenylethanone (II) or
1‐phenethyl‐1H‐benzo[d]imidazole (III). All benzimidazole
salts were smoothly crystallized from an EtOH–Et2O mixture.
The structures of benzimidazole complexes 1–10 were eluci-
dated using 1H NMR, 13C NMR and infrared (IR) spectromet-
ric analyses. All spectral data were in agreement with the
proposed structures. IR spectra of compounds show strong
2.3 | Sonogashira coupling reaction of Aryl
halides with Phenylacatylene
ν
(C═O) and ν(C═N) bands at 1682–1703 and 1560–1595 cm−1
,
respectively. The IR spectrum of 4 shows a ν(C&‐N) band at
2200 cm−1. The characteristic CH resonances for the proton
at the 2‐position of benzimidazole salts 1–10 were observed
between 9.71 and 10.29 ppm. As expected, salt formation
shifts the 1H NMR signals of the benzimidazolium salts down-
field from those of the naked benzimidazole (Δδ ≈ 0.63 to
2.21 ppm) for the proton at the 2‐position of benzimidazole
ring. The carbon resonances for the carbon at the 2‐position
of benzimidazole salts 1–10 were observed between 142.3
and 144.9 ppm. Salt formation shifts the 13C NMR signals
of the benzimidazolium salts downfield from those of the
naked benzimidazole (Δδ ≈ 0.8 to 3.4 ppm) for the carbon
at the 2‐position of the benzimidazole salt. All other ali-
phatic and aromatic protons and carbons were observed at
expected regions.
After having established the optimized coupling reaction
conditions (Table 1).we investigated the reaction using a vari-
ety of aryl halides having electron‐neutral, electron‐rich and
electron‐poor
bromobenzene,
properties,
chlorobenzene,
such
as
iodobenzene,
4‐iodotoluene,
4‐
bromonitrobenene, 4‐iodoanisole, 4‐bromobenzaldehyde
and 4‐bromoacetophenone, with phenylacetylene as substrate
under the optimized conditions. The results are given in
Table 2. Regardless of aryl halide reactivity, both aryl iodides
and aryl bromides coupled smoothly with phenylacetylene to
form the desired corresponding products in good to excellent
yields (Table 2, entries 1–20 and 32–81). Among the aryl
halides, phenyl iodide and aryl bromides bearing electron‐
withdrawing substituent such as nitro, formyl and acetyl gave
excellent Sonogashira‐type coupling yields (Table 2, entries

YAVUZ AND KÜÇÜKBAY
3 of 8
TABLE 1 Optimization of Sonogashira coupling reactions under microwave irradiationa
Co‐catalyst
Entry
1
Salt
Base
CuI (mol%)
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.05
—
CuNPc (mol%)
Solvent
DMF
Time (min)
Temperature (°C)
Yield (%)
1
1
KOH
—
—
—
—
—
—
—
—
—
10
20
10
10
10
20
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
60
60
38
2
KOH
DMF
43
3
1
KOH
DMF
100
120
100
100
60
51
4
1
KOH
DMF
57
5
1
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMF
60
6
1
DMF
63
7
1
DMF
45
8
1
DMF
80
50
9
1
DMF
100
120
120
100
120
100
100
100
100
100
100
100
100
100
100
59
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1
—
—
DMF
60
1
DMF
53
1
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.04
0.04
0.04
0.04
0.04
DMF
71
1
—
—
—
—
—
—
—
—
DMF
73
1
EtOH
43
1
DME
35
1
Ethylene glycol
Glycerol
PEG300
PEG300
PEG300
PEG300
PEG300
PEG300
61
1
52
1
90
100, 97b, 92c
74d
1
1
None
1
—
—
—
59e
92
n.d.f
1
10
aYields are based on aryl iodide. Reactions were monitored by GC–MS.
bSecond run.
cThird run.
d0.5% Pd(OAc)2 was used.
eSalt was not used.
fOn preheated oil bath, for 10 min with thermal heating at 100 °C; n.d., not detected.
1–10, 42–51, 62–71 and 72–81). On the other hand, a strong
electron‐donating methoxy group and weak electron‐donat-
ing methyl group on the aryl iodide gave a moderate or good
yield using the optimized conditions (Table, 2, entries 52–61
and 32–41). It is noteworthy that only aryl chloride gave low
Sonogashira cross‐coupling yields and Glaser‐type
homocoupling products under optimized reaction conditions
(Table 2, entries 21–31). We investigated the reactivity of
chlorobenzene with phenylacetylene in the Sonogashira cou-
pling reaction with extending the reaction time from 10 to
20 min. The extended reaction time slightly decreased the
Sonogashira coupling yield but increased the homocoupling
yield (Table 2, entry 22). We did not detect any Glaser‐type
homocoupling product from the other aryl bromides or
iodides having electron‐neutral, electron‐poor or electron‐
rich substituents. Whereas significant differences were not
observed among the substituents at position 3 of the benz-
imidazole ring incorporated in the catalytic system, the more
electron‐donating substituents led to desired Sonogashira‐
type coupling and slightly improved the catalytic yields.
Comparing the catalytic activities of benzimidazolium salts
incorporated in the catalytic system in our previous work[24]
and the present work, benzimidazolium salts having 2‐oxo‐
2‐phenylethyl substituent showed slightly better catalytic
activity than benzimidazolium salts bearing N‐
phthalimidoethyl substituent. Aryl chlorides were also

4 of 8
YAVUZ AND KÜÇÜKBAY
TABLE 2 Sonogashira coupling reactions of aryl halides with phenylacetylene
Entry
1
X
I
R
H
Salt
1
Yield A (%)
Yield B (%)
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
42
Entry
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
X
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
R
BimHX
Yield A (%)
95 (90)a
Yield B (%)
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
90
95
NO2
1
2
2
I
H
2
NO2
92
3
I
H
3
97
NO2
3
96 (91)a
92
4
I
H
4
98
NO2
4
5
I
H
5
95
NO2
5
91
6
I
H
6
94
NO2
6
91
7
I
H
7
96
NO2
7
90
8
I
H
8
98
NO2
8
93
9
I
H
9
100 (94)a
98 (92)a
80
NO2
9
90
10
11
12
13
14
15
16
17
18
19
20
21
22b
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
I
H
10
1
NO2
10
1
90
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
I
H
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
CHO
88
H
2
80
I
2
81
H
3
80
I
3
82
H
4
86
I
4
76
H
5
83
I
5
83
H
6
82
I
6
90
H
7
83
I
7
86
H
8
84
I
8
84
H
9
85
I
9
89
H
10
1
82
I
10
1
82
H
50
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
85
H
1
47
44
CHO
2
92
H
2
52
40
CHO
3
92
H
3
47
43
CHO
4
91
H
4
35
45
CHO
5
93
H
5
37
49
CHO
6
92
H
6
47
50
CHO
7
90
H
7
39
45
CHO
8
92
96 (92)a
H
8
56
44
CHO
9
H
9
56
26
CHO
10
1
90
H
10
1
64
35
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
91
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
92
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
2
90
I
2
89
3
91
I
3
86
4
93
I
4
85
5
93
I
5
82
6
91
I
6
90
7
88
94 (90)a
I
7
87
8
I
8
87
9
92
I
9
94
10
92
I
10
80
aIsolated yield.
bTemperature ramped to 100 °C (3 min) and held for 20 min.

YAVUZ AND KÜÇÜKBAY
5 of 8
SCHEME 1 Synthesis of the
benzimidazole derivatives
investigated in the present work and it is noteworthy that,
besides the Sonogashira cross‐coupling products, Glaser‐type
homocoupling products were also obtained.
INNOWAX column of 60 m in length, 0.25 mm in diameter
and 0.25 μm film thicknesses. GC–MS parameters for
Sonogashira coupling reactions were as follows: initial tem-
perature, 60 °C; initial time, 5 min; temperature ramp 1,
30 °C min−1; final temperature, 200 °C; ramp 2, 20 °C
min−1; final temperature, 250 °C; run time, 30.17 min;
injector port temperature, 250 °C; detector temperature,
250 °C; injection volume, 1.0 μl; carrier gas, helium; mass
range, m/z between 50 and 550.
3 | CONCLUSIONS
We have developed an efficient, simple and environmentally
benign catalytic system incorporating novel benzimidazole
salts for the Sonogashira cross‐coupling reaction. The
Sonogashira coupling yields were found to be excellent for aryl
iodide bearing electron‐neutral and electron‐withdrawing
substituents at position 4 of the phenyl ring. Aryl bromide
bearing only electron‐withdrawing substituents at position 4
of the phenyl ring gave excellent yields. Aryl chloride gave
both Sonogashira cross‐coupling and Glaser‐type homo-
coupling products, each in yields of approximately 50%.
Furthermore, the catalyst system consisting of Pd(OAc)2,
CuNPc, benzimidazole salts and Cs2CO3 in PEG300 can be
recycled at least three times without loss of activity in short
reaction time (10 min) without any palladium black formation.
4.3 | Synthesis of Benzimidazolium salts
1‐Benzyl‐1H‐benzo[d]imidazole (I),[46] 2‐(1H–benzo[d]
imidazol‐1‐yl)‐1‐phenylethanone (II)[47,48] and 1‐phenethyl‐
1H‐benzo[d]imidazole (III)[49] used in this work as starting
compounds were prepared by treating benzimidazole with
(chloromethyl)benzene, 2‐bromo‐1‐phenylethanone and (2‐
bromoethyl)benzene, respectively, according to a modified
literature procedure (Scheme 1). Compounds 1[46,48] and
10[50] have been reported in the literature but their synthesis
methods need multi‐step reactions and long reaction times.
Thus, these compounds were prepared using a new one‐step,
easy synthetic method according to our previous studies
(Scheme 1).[51]
4 | EXPERIMENTAL
4.1 | Materials and methods
4.4 | General method for synthesis of
compounds 1–10
Starting materials and reagents used in reactions were sup-
plied commercially by Aldrich or Merck. All catalytic activ-
ity experiments were carried out in a microwave oven
system manufactured by Milestone (Milestone Starts S
Microwave Labstation for Synthesis) under aerobic condi-
tions. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra
were recorded using a Bruker DPX‐300 high‐performance
digital FT NMR spectrometer. Elemental analyses were per-
formed with a LECO CHNS‐932 elemental analyser. IR spec-
tra were recorded with ATR equipment in the range 650–
4000 cm−1 using a PerkinElmer Spectrum One FTIR spectro-
photometer. Melting points were recorded using an Electro-
thermal‐9200 melting point apparatus and are uncorrected.
A mixture of 1 eq. of 1‐substituted benzimidazole deriva-
tives (I, II or III) and 1.1 eq. of appropriate alkyl halide
was subjected to microwave irradiation (300 W, 100 °C) in
DMF (10 ml) for 20 min. After completion of the reaction,
all volatiles were removed under reduced pressure and the
obtained crude product was crystallized from ethanol–
diethyl ether (1:2).
4.4.1 | 3‐Methyl‐1‐(2‐oxo‐2‐phenylethyl)‐1H–
benzo[d]imidazol‐3‐ium iodide (1)
Yield 0.53 g (cream crystals), 66%; m.p. 164–166 °C. IR
(νmax, cm−1): 1566 (C═N), 1682 (C═O). Anal. Found (%):
C 51.39, H 3.84, N 7.66. Calcd for C16H15IN2O (378.2)
(%): C 50.81, H 4.00, N 7.41. 1H NMR (DMSO‐d6, δ,
ppm): 9.71 (s, 1H, NCHN), 7.66–8.17 (m, 9H, Ar‐H), 6.48
4.2 | GC–MS analysis
GC–MS spectra were recorded using an Agilient 6890 N GC
and 5973 mass selective detector using with an HP‐

6 of 8
YAVUZ AND KÜÇÜKBAY
(s, 2H, CH2COPh), 4.22 (s, 3H, CH3). 13C NMR (DMSO‐d6,
δ, ppm): 191.8 (CH2COPh), 144.1 (NCHN), 135.1, 134.2,
132.3, 132.0, 129.6, 129.0, 127.2, 127.0, 114.3, 114.2 (Ar‐
C), 53.8 (CH2COPh), 34.2 (CH3).
4.4.5 | 1‐Benzyl‐3‐(2‐oxo‐2‐phenylethyl)
benzimidazolium bromide (5)[35,37]
Yield 1.78 g (white crystals), 90%; m.p. 170–171 °C. IR
(νmax, cm−1): 1562 (C═N), 1695 (C═O). Anal. Found (%):
C 80.72, H 5.86, N 8.62. Calcd for C22H19BrN2O
1
(327.1))%): C 80.71, H 5.85, N 8.56. H NMR (DMSO‐d6,
4.4.2 | 3‐Ethyl‐1‐(2‐oxo‐2‐phenylethyl)‐1H–
benzo[d]imidazol‐3‐ium iodide (2)
δ, ppm): 9.86 (s, 1H, NCHN), 7.40–8.15 (m, 14H, Ar‐H),
6.45 (s, 2H, CH2COPh), 5.92 (s, 2H, CH2Ph). 13C NMR
(DMSO‐d6, δ, ppm): 191.7 (CH2COPh), 144.0 (NCHN),
135.1, 134.4, 134.3, 134.2, 132.6, 131.0, 129.6, 129.5,
129.3, 128.9, 128.8, 127.4, 127.3, 114.6, 114.4 (Ar‐C),
53.8 (CH2COPh), 50.45 (CH2Ph).
Yield 0.51 g (cream crystals), 52%; m.p. 94–95 °C. IR (νmax
,
cm−1): 1570 (C═N), 1699 (C═O). Anal. Found (%): C
51.80, H 4.17, N 6.90. Calcd for C17H17IN2O (392.2) (%): C
1
52.06, H 4.37, N 7.14. H NMR (DMSO‐d6, δ, ppm): 9.77
(s, 1H, NCHN), 8.09–8.18 (Ar‐H, 4H), 7.80 (Ar‐H, 1H),
7.68–7.75 (Ar‐H, 4H), 6.43 (s, 2H, CH2COPh), 4.66 (q, 4H,
CH2CH3, J = 3.6 Hz), 1.59 (t, 3H, CH3, J = 3.6 Hz). 13C
NMR (DMSO‐d6, δ, ppm): 191.7 (CH2COPh), 143.4
(NCHN), 135.1, 134.2, 132.5, 131.0, 129.6, 128.9, 127.3,
127.0, 114.5, 114.2 (Ar‐C), 53.7 (CH2COPh), 42.8 (CH2),
14.7 (CH3).
4.4.6 | 3‐(4‐Bromobenzyl)‐1‐(2‐oxo‐2‐
phenylethyl)‐1H–benzo[d]imidazol‐3‐ium
bromide (6)
Yield 1.5 g (cream crystals), 88.2%; m.p. 245–246 °C. IR
(νmax, cm−1): 1567 (C═N), 1696 (C═O). Anal. Found (%):
C 54.65, H 3.76, N 5.87. Calcd for C22H18Br2N2O (484.0)
(%): C 54.35, H 3.73, N 5.76. 1H NMR (DMSO‐d6, δ,
ppm): 9.84 (s, 1H, NCHN), 8.04–8.15 (m, 4H, Ar‐H),
7.51–7.83 (m, 9H, Ar‐H), 6.44 (s, 2H, CH2COC6H5), 5.91
(s, 2H, CH2C6H4Br). 13C NMR (DMSO‐d6, δ, ppm): 191.2
(CH2COC6H5), 143.6 (NCHN), 134.5, 133.7, 133.2, 132.1,
132.0, 130.6, 130.4, 129.0, 128.4, 126.9, 126.8, 122.2,
114.1, 113.8, (Ar‐C), 53.3 (CH2COC6H5), 49.3
(CH2C6H4Br).
4.4.3 | 1‐Isopropyl‐3‐(2‐oxo‐2‐phenylethyl)
benzimidazolium iodide (3)
Yield 0.70 g (cream crystals), 76.9%; m.p. 182–183 °C. IR
(νmax, cm−1): 1595 (C═N), 1685 (C═O). Anal. Found (%):
C 53.49, H 4.82, N 6.99. Calcd for C18H19IN2O (406.1)
(%): C 53.22, H 4.71, N 6.90. 1H NMR (DMSO‐d6, δ,
ppm): 9.77 (s, 1H, NCHN), 8.05–8.21 (m, 4H, Ar‐H),
7.66–7.81 (m, 6H, Ar‐H), 6.35 (s, 2H, CH2COPh), 5.16 (m,
1H, CH(CH3)2), 1.67 (d, 6H, CH(CH3)2, J = 6.6 Hz). 13C
NMR (DMSO‐d6, δ, ppm): 191.7 (CH2COPh), 142.3
(NCHN), 135.28, 134.2, 132.7, 130.6, 129.6, 128.9, 127.3,
127.0, 114.5, 114.4 (Ar‐C), 53.5 (CH2COPh), 51.3
CH(CH3)2), 22.0 (CH(CH3)2).
4.4.7 | 3‐(4‐Chlorobenzyl)‐1‐(2‐oxo‐2‐
phenylethyl)‐1H–benzo[d]imidazol‐3‐ium bro-
mide (7)
Yield 1.3 g (white crystals), 87.2%; m.p. 216–217 °C. IR
(νmax, cm−1): 1567 (C═N), 1696 (C═O). Anal. Found (%):
C 59.30, H 4.17, N 6.63. Calcd for C22H18BrClN2O (440.0)
(%): C 59.82, H 4.11, N 6.34. 1H NMR (DMSO‐d6, δ,
ppm): 10.29 (s, 1H, NCHN), 8.17–8.23 (m, 4H, Ar‐H),
7.46–7.76 (m, 9H, Ar‐H), 6.72 (s, 2H, CH2COC6H5), 6.11
(s, 2H, CH2C6H4Cl). 13C NMR (DMSO‐d6, δ, ppm): 191.8
(CH2COC6H5), 144.1 (NCHN), 144.0, 135.0, 134.2, 134.0,
133.4, 132.6, 131.0, 130.9, 129.5, 129.0, 127.3, 127.2,
114.8, 114.5 (Ar‐C), 54.3 (CH2COC6H5), 49.7
(CH2C6H4Cl).
4.4.4 | 3‐(Cyanomethyl)‐1‐(2‐oxo‐2‐
phenylethyl)‐1H–benzo[d]imidazol‐3‐ium bro-
mide (4)
Yield 0.75 g (cream crystals), 71%; m.p. 199–200 °C. IR
(νmax, cm−1): 1566 (C═N), 1689 (C═O), 2200 (C&‐N).
Anal. Found (%): C 56.98, H 3.95, N 11.76. Calcd for
C17H14BrN3O (355.0) (%): C 57.32, H 3.96, N 11.80.
1H NMR (DMSO‐d6, δ, ppm): 9.93 (s, 1H, NCHN),
8.15–8.22 (m, 4H, Ar‐H), 7.67–7.84 (m, 5H, Ar‐H), 6.55
(s, 2H,CH2COPh), 6.11 (s, 2H, CH2CN). 13C NMR
(DMSO‐d6, δ, ppm): 191.5 (CH2COPh), 144.9 (NCHN),
144.8, 135.1, 134.2, 132.3, 130.5, 129.5, 129.0, 127.8,
115.0, 114.8 (Ar‐C), 113.9 (CH2CN), 54.2 (CH2COPh),
35.9 (CH2CN).
4.4.8 | 1‐(2‐Oxo‐2‐phenylethyl)‐3‐phenethyl‐
1H‐benzo[d]imidazol‐3‐ium bromide (8)
Yield 0.8 g (cream crystals), 84.2%; m.p. 157–158 °C. IR
(νmax, cm−1): 1563 (C═N), 1695 (C═O). Anal. Found (%):
C 65.75, H 5.03, N 6.86. Calcd for C23H21BrN2O (420.1)
(%): C 65.57, H 5.02, N 6.63. 1H NMR (DMSO‐d6, δ,

YAVUZ AND KÜÇÜKBAY
7 of 8
ppm): 9.72 (s, 1H, NCHN), 8.05–8.15 (4H, Ar‐H), 7.65–7.83
(6H, Ar‐H), 7.23–7.30 (m, 4H, Ar‐H), 6.43 (s, 2H,
CH2COPh), 4.90 (t, 2H, CH2CH2Ph, J = 7.2 Hz), 3.29 (t,
2H, CH2CH2Ph, J = 7.2 Hz). 13C NMR (DMSO‐d6, δ,
ppm): 191.6 (CH2COPh), 143.7 (NCHN), 137.3, 135.1,
134.2, 132.3, 131.2, 129.5, 129.4, 129.0, 128.9, 127.4,
127.2, 127.0, 114.4, 114.3 (Ar‐C), 53.7 (CH2COPh), 48.4
(CH2CH2Ph), 35.2 (CH2CH2Ph).
products was determined by GC–MS using the normalizing
peak areas method. Some coupling yields were also deter-
mined through isolated coupling products.
4.6 | General procedure for recycling of
catalyst for Sonogashira reaction
After completing the first catalytic cycle, a mixture of ethyl
acetate–n‐hexane (1:5) (10 ml) was added to the reaction
mixture and coupling product was extracted into the organic
phase. Insoluble palladium–N‐heterocyclic carbene complex
formed in situ from Pd(OAc)2, benzimidazolium salt and
CuNPc was recovered by decantation of the reaction mixture
and transferred to a microwave tube with PEG. After
reloading the coupling partners and Cs2CO3 (1 mmol%) the
reaction was repeated following the general Sonogashira
reaction procedure described above.
4.4.9 | 1‐(2‐Oxo‐2‐phenylethyl)‐3‐(3‐
phenylpropyl)‐1H–benzo[d]imidazol‐3‐ium
bromide (9)
Yield 0.56 g (cream crystals), 54.5%; m.p. 156–157 °C. IR
(νmax, cm−1): 1564 (C═N), 1703 (C═O). Anal. Found (%):
C 65.56, H 5.27, N 6.87. Calcd for C24H23BrN2O (434.1)
(%): C 66.21, H 5.32, N 6.43. 1H NMR (DMSO‐d6, δ,
ppm): 9.81 (s,1H, NCHN), 8.09–8.17 (m, 4H, Ar‐H), 7.67–
7.81(m, 5H, Ar‐H), 7.20–7.30 (m, 5H, Ar‐H), 6.43 (s, 2H,
CH2COPh), 4.68 (t, 2H, NCH2CH2CH2Ph, J = 3.4 Hz),
2.72 (t, 2H, CH2CH2CH2Ph, J = 3.9 Hz), 2.28 (q, 2H,
CH2CH2CH2Ph, J = 3.8 Hz). 13C NMR (DMSO‐d6, δ,
ppm): 191.8 (CH2COPh), 143.9 (NCHN), 140.9, 135.1,
134.2, 132.5, 131.2, 129.6, 128.9, 128.8, 128.7, 127.3,
127.1, 126.6, 114.5, 114.2 (Ar‐C), 53.6 (CH2COPh), 47.1
ACKNOWLEDGEMENT
We thank İnönü University Research Fund (BAPB‐2012/
193) for financial support of this study.
REFERENCES
[1] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975,
16, 4467.
(CH2CH2CH2Ph),
32.2
(CH2CH2CH2Ph),
30.6
(CH2CH2CH2Ph).
[2] R. Chinchilla, C. Nájera, Chem. Rev. 2007, 107, 874.
[3] R. Chinchilla, C. Najera, Chem. Soc. Rev. 2011, 40, 5084.
[4] M. Bakherad, Appl. Organomet. Chem. 2013, 3, 125.
[5] H. Doucet, J. C. Hierso, Angew. Chem. Int. Ed. 2007, 46, 834.
[6] K. Sonogashira, J. Org. Chem. 2002, 653, 46.
4.4.10 | 1,3‐Bis(2‐oxo‐2‐phenylethyl)‐1H–
benzo[d]imidazol‐3‐ium bromide (10)[39]
Yield 2.9 g (cream crystals), 61.5%; m.p. 219–220 °C. IR
(νmax, cm−1): 1563 (C═N), 1690 (C═O). Anal. Found (%):
C 63.34, H 4.46, N 6.69. Calcd for C23H19BrN2O2 (434.1)
(%): C 63.46, H 4.40, N 6.44. 1H NMR (DMSO‐d6, δ,
ppm): 9.76 (s, 1H, NCHN), 8.15–8.18 (m, 6H, Ar‐H),
7.80–7.82 (m, 2H, Ar‐H), 7.68–7.72 (m, 6H, Ar‐H), 6.60 (s,
4H, CH2COPh). 13C NMR (DMSO‐d6, δ, ppm): 191.7
(CH2COPh), 144.9 (NCHN), 135.0, 134.3, 132.1, 129.5,
128.9, 127.3, 114.5 (Ar‐C), 54.1 (CH2COPh).
[7] L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133.
[8] A. M. Thomas, A. Sujatha, G. Anilkumar, RSC Adv. 2014, 4,
21688.
[9] M. Schilz, H. Plenio, J. Org. Chem. 2012, 77, 2798.
[10] C. Kieffer, P. Verhaeghe, N. Primas, C. Castera‐Ducros, A. Gellis,
R. Rosas, S. Rault, P. Rathelot, P. Vanelle, Tetrahedron 2013, 69,
2987.
[11] G. Altenhoff, S. Würtz, F. Glorius, Tetrahedron Lett. 2006, 47,
2925.
4.5 | General procedure for Sonogashira
reactions
[12] M. Bakherad, A. Keivanloo, A. Hadi, M. Siavoshi, Org. Chem.
2014, 3, 1189.
Pd(OAc)2 (1 mmol%), CuNPc (4 mol%), benzimidazolium
halides 1–10 (2 mmol%), aryl halide (1 mmol),
phenylacetylene (1 mmol), Cs2CO3 (2 mmol) and PEG300
(6 ml) were added to the microwave apparatus and the mix-
ture was heated at 100 °C (300 W) for 10 min after a ramp
time of 3 min to reach to 100 °C. At the end of the reaction,
the mixture was cooled and the product extracted with ethyl
acetate–n‐hexane (1:5) and filtered through a pad of silica
gel with copious washing. The purity and yield of coupling
[13] E. Buxaderas, D. A. Alonso, C. Nájera, Eur. J. Org. Chem. 2013,
5864.
[14] A. Dewan, M. Sarmah, U. Bora, A. Thakur, Tetrahedron Lett.
2016, 57, 3760.
[15] Y. He, C. Cai, J. Org. Chem. 2011, 696, 2689.
[16] M. Hellal, G. D. Cuny, Tetrahedron Lett. 2011, 52, 5508.
[17] K. Heuzé, D. Méry, D. Gauss, J.‐C. Blais, D. Astruc, Chem. – Eur.
J. 2004, 10, 3936.

8 of 8
YAVUZ AND KÜÇÜKBAY
[18] A. R. Hajipour, H. Rahimi, F. Rafiee, Appl. Organomet. Chem.
2012, 26, 727.
[40] M. J. García‐Muñoz, F. Foubelo, M. Yus, J. Org. Chem. 2016, 81,
10214.
[19] A. R. Hajipour, F. Rezaei, Z. Khorsandi, Green Chem. 2017, 19,
[41] Q. Cui, H. Zhao, G. S. Luo, J. H. Xu, Ind. Eng. Chem. Res. 2017,
56, 143.
1353.
[20] A. J. Arduengo, M. Kline, R. L. Harlow, J. Am. Chem. Soc. 1991,
113, 361.
[42] D. Shah, H. Kaur, J. Mol. Catal. A 2016, 424, 171.
[43] V. N. Mikhaylov, V. N. Sorokoumov, K. A. Korvinson, A. S.
[21] M. Eckhardt, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 13642.
[22] C. O. Kappe, Angew. Chem. Int. Ed. 2004, 43, 6250.
Novikov, I. A. Balova, Organometallics 2016, 35, 1684.
[44] S. Thogiti, S. P. Parvathaneni, S. Keesara, J. Org. Chem. 2016,
822, 165.
[23] M. Larhed, C. Moberg, A. Hallberg, Acc. Chem. Res. 2002, 35,
717.
[45] M. Kidwai, N. K. Mishra, S. Bhardwaj, A. Jahan, A. Kumar, S.
Mozumdar, ChemCatChem 2010, 2, 1312.
[24] H. Küçükbay, N. Şireci, Ü. Yılmaz, S. Deniz, M. Akkurt, Z. Baktir,
O. Büyükgüngör, Turk. J. Chem. 2012, 36, 201.
[46] J. Chen, S. K. Spear, J. G. Huddleston, R. D. Rogers, Green Chem.
2005, 7, 64.
[25] H. Küçükbay, N. Şireci, Ü. Yılmaz, M. Akkurt, Ş. P. Yalçin, M. N.
Tahir, H. Ott, Appl. Organomet. Chem. 2011, 25, 255.
[47] A. Kumar, A. Saxena, M. Dewan, A. De, S. Mozumdar, Tetrahe-
dron Lett. 2011, 52, 4835.
[26] H. Küçükbay, Ü. Yılmaz, K. Yavuz, N. Buğday, Turk. J. Chem.
2015, 39, 1265.
[48] B. Wang, J. Hu, X. Zhang, Y. Hu, H. Hu, J. Heterocycl. Chem.
2000, 37, 1533.
[27] Ü. Yılmaz, H. Küçükbay, S. Deniz, N. Şireci, Molecules 2013, 18,
2501.
[49] M. Abdel‐Megid, M. H. Elnagdi, A. M. Negm, J. Heterocycl.
Chem. 2002, 39, 105.
[28] Ü. Yılmaz, S. Deniz, H. Küçükbay, N. Şireci, Molecules 2013, 18,
3712.
[50] E. Georgescu, A. Nicolescu, F. Georgescu, F. Teodorescu, S.
Shova, A. T. Marinoiu, F. Dumitrascu, C. Deleanu, Tetrahedron
2016, 72, 2507.
[29] Ü. Yilmaz, N. Şireci, S. Deniz, H. Küçükbay, Appl. Organomet.
Chem. 2010, 24, 414.
[51] H. Küçükbay, R. Durmaz, E. Orhan, S. Gunal, Farmaco 2003, 58,
[30] Ü. Yılmaz, H. Küçükbay, N. Şireci, M. Akkurt, S. Günal, R.
Durmaz, M. N. Tahir, Appl. Organomet. Chem. 2011, 25, 366.
431.
[52] I. I. Popov, A. A. Konstantinchenko, Khim. Geterotsikl. Soedin.
1996, 10, 1352.
[31] W. Xu, Y. Sun, M. Guo, W. Zhang, Z. Gao, Chinese J. Org. Chem
2013, 33, 820.
[53] S. Öztürk, M. Akkurt, H. Kücükbay, N. Okuyucu, H. K. Fun, Acta
Crystallogr. E 2003, 59, o1014.
[32] Ö. Metin, F. Durap, M. Aydemir, S. Özkar, J. Mol. Catal. A 2011,
337, 39.
[33] D. Astruc, Inorg. Chem. 2007, 46, 1884.
[34] A. Monopoli, V. Calò, F. Ciminale, P. Cotugno, C. Angelici, N.
SUPPORTING INFORMATION
Cioffi, A. Nacci, J. Org. Chem. 2010, 75, 3908.
Additional Supporting Information may be found online in
the supporting information tab for this article.
[35] A. R. Hajipour, Z. Shirdashtzade, G. Azizi, Appl. Organomet.
Chem. 2014, 28, 696.
[36] A. R. Hajipour, Z. Tavangar‐Rizi, Appl. Organomet. Chem. 2017,
https://doi.org/10.1002/aoc.3701.
How to cite this article: Yavuz K, Küçükbay H.
Efficient and green catalytic system incorporating new
benzimidazolium salts for the Sonogashira cross‐
coupling reaction. Appl Organometal Chem. 2017;
e3897. https://doi.org/10.1002/aoc.3897
[37] L. A. Aronica, G. Albano, L. Giannotti, E. Meucci, Eur. J. Org.
Chem. 2017, 955.
[38] J. W. Chen, H. F. Xiang, L. Yang, X. G. Zhou, RSC Adv. 2017, 7,
7753.
[39] C. Najera, ChemCatChem 2016, 8, 1865.