Synthesis and microwave-assisted catalytic activity of novel bis-benzimidazole salts bearing furfuryl and thenylmoieties in heck and suzuki cross-coupling reactions

Article abstract of DOI:10.1002/aoc.1633

A mixture of bis-benzimidazole salts (1-7), Pd(OAc)₂ and K ₂CO₃ in DMF - H₂O catalyzes, in high yield, the Suzuki and Heck cross-coupling reactions assisted by microwave irradiation in a short time. In particular, the yields of the Heck and Suzuki reactionswith aryl bromideswere found to be nearly quantative. The synthesized bis-benzimidazole salts (1-7) were identified by ¹H-¹³C NMR, IR spectroscopic methods and micro analysis. Copyright

Full text of DOI:10.1002/aoc.1633

Full Paper
Received: 26 November 2009
Revised: 13 January 2010
Accepted: 19 January 2010
Published online in Wiley Interscience: 24 February 2010
(www.interscience.com) DOI 10.1002/aoc.1633
Synthesis and microwave-assisted catalytic
activity of novel bis-benzimidazole salts
bearing furfuryl and thenyl moieties in Heck
and Suzuki cross-coupling reactions
a
b
a
a∗
¨
Ulku¨ Yılmaz , Nihat S¸ireci , Selma Deniz and Hasan Ku¨c¸u¨kbay
A mixture of bis-benzimidazole salts (1–7), Pd(OAc)2 and K2CO3 in DMF –H2O catalyzes, in high yield, the Suzuki and Heck
cross-coupling reactions assisted by microwave irradiation in a short time. In particular, the yields of the Heck and Suzuki
reactions with aryl bromides were found to be nearly quantative. The synthesized bis-benzimidazole salts (1–7) were identified
by 1H–13C NMR, IR spectroscopic methods and micro analysis. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
c
Keywords: bis-benzimidazole salt; carbene; palladium catalysis; coupling reaction; Heck coupling; Suzuki coupling; microwave
Introduction
Nowadays microwave heating has been used in various organic
reactions. Because of the formation of reactions faster than
conventional heating methods, microwave technique is used very
frequently. Carbon–carbon cross-coupling in Suzuki and Heck
reactions has also been carried out in short time in high yield,
incorporating microwave irradiation.[42–50]
Herein,wedescribethesynthesisofnewbis-benzimidazolesalts
(1–7) containing furfuryl and thenyl moieties. The compounds
were fully characterized by elemental analysis, IR, 13C-NMR and
1H-NMR spectroscopy. We also report on the microwave-assisted
catalytic activity of the Pd(OAc)2 –bis-benzimidazole catalytic
system in Heck and Suzuki cross-coupling reactions.
The palladium-catalyzed, Mizoroki–Heck cross-coupling reactions
of aryl halides with styrene and Suzuki–Miyaura cross-coupling
reactions of aryl halides with arylboranic acids are some of the
most valuable methods for the synthesis of stilbene and biaryl
derivatives developed over the past decades.[1–11] Biaryl and
stilbene moieties are high-value synthetic targets and can be
found as substructures in many pharmaceutically and biologically
active compounds.[12,13] A large number of synthetic methods
have been developed over the year for the selective construction
of carbon–carbon bonds, in particular for the formation of biaryl
and stilbene derivatives. The most widely used Mizoroki–Heck
and Suzuki–Miyaura coupling reactions allow the synthesis of a
range of useful stilbene and biaryl derivatives.
Experimental
Pd catalysts, containing phosphine and phosphinite ligands,
are very effective catalysts for Heck and Suzuki coupling
reactions.[14–16] However, inert reaction conditions must be
provided, for the nature of the ligands in these systems. The
catalysts, which incorporate N–Pd and S–Pd bonds, have been
used in cross-coupling reactions. The reactions have been realized
by good yields, especially for aryl bromides.[18–28] The ligand-free
systems consist of Pd(OAc)2, and base and solvents have also been
used as a catalyst system in Suzuki coupling reactions.[29–34]
However, the Pd(OAc)2 catalytic systems containing ligands
have been shown to have more effective catalytic activity than
ligand-free Pd(OAc)2 systems. For this reason, in situ prepared
N-heterocyclic carbenes (NHC) are widely used as ligands for
palladium complexes to accomplish carbon–carbon coupling
reactions in Suzuki and Heck reactions.
All preparations were carried out in an atmosphere of purified
argon using standard Schlenk techniques. Starting materials
and reagents used in reactions were supplied commercially
from Aldrich or Merck Chemical Co. Solvents were dried with
standard methods and freshly distilled prior to use. All catalytic
activity experiments were carried out in a microwave oven
system manufactured by Milestone (Milestone Start S Microwave
Labstation for Synthesis) under aerobic conditions. 1H-NMR
(300 MHz) and 13C-NMR (75 MHz) spectra were recorded using
a Bruker DPX-300 high performance digital FT NMR spectrometer.
Infrared spectra were recorded as KBr pellets in the range
∗
Correspondence to: Hasan Ku¨c¸u¨kbay, Department of Chemistry, Faculty of Arts
In particular, Pd(OAc)2 –benzimidazole or imidazole lig-
ands could be very effective catalytic systems in these
reactions.[35–38] Although there are extensive studies about
Pd(OAc)2 –benzimidazole or imidazole catalytic systems in Heck
and Suzuki cross-coupling reactions,[35–38] less attention has been
paid to the Pd(OAc)2 –bis-benzimidazole catalytic system in Heck
and Suzuki cross-coupling reactions.[39–41]
¨
and Science, Inonu¨ University, Malatya 44280, Turkey.
E-mail: hkucukbay@inonu.edu.tr
¨
a
Inonu¨ University, Faculty Science and Arts, Department of Chemistry, 44280
Malatya, Turkey
b
AdıyamanUniversity,FacultyScienceandArts,DepartmentofChemistry,02040
Adıyaman, Turkey
c
Appl. Organometal. Chem. 2010, 24, 414–420
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
2Cl-
2Cl-
N
+
N
N
+
N
N
+
N
N
+
N
Cl
2
N
N
N
N
2
Cl
S
O
2
I
1
S
S
O
O
R
R
R
2Cl-
2Cl-
N
+
N
N
+
N
N
+
N
N
+
N
N
N
N
N
Cl
2
2
Cl
S
O
O
O
3 R = H
II R = H
III R = Me
S
S
4 R = H
5 R = Me
O
S
N
N
N
+
N
N
+
N
-
Cl
Cl-
Cl
2
2
Cl
S
O
6
IV
N
N
7
N
+
N
-
Cl
N
+
N
Cl-
O
S
Scheme 1. Synthesis of bis-benzimidazole salts, 1–7.
4000–400 cm−1 on a Perkin-Elmer FT-IR spectrophotometer.
Elemental analyses were performed by LECO CHNS-932 elemental
analyzer. Melting points were recorded using an electrothermal-
9200 melting point apparatus, and are uncorrected.
1-Substitutebenzimidazoles (I–IV) used in this work as a
starting compounds were prepared according to the literature
procedures.[51,52]
CH2C4H3O), 4.78 (t, 4H, NCH2 bridge, 3J = 6.6 Hz), 2.73 (quin., 2H,
3
CH2 bridge, J = 6.6 Hz). 13C NMR (δ, DMSO-d6): 145.3 (NCHN),
144.6, 140.8, 111.9 and 111.0 (C4H3O), 130.7, 127.4, 127.3, 127.2,
113.5, and 112.6 (C6H4), 44.6 (NCH2-C4H3O), 43.3 (NCH2 bridge),
27.8 (CH2 bridge).
Similarly, 3,3ꢁ-dithenyl-1,1ꢁ-propylenedibenzimidazolium dich-
loride, 2 was synthesized from 1,1ꢁ-propylenedibenzimidazole
and thenyl chloride. Yield: 1.35 g, 81%, m.p. 177–178 ◦C. v(CN)
=
1560 cm−1. Anal. found: C, 59.69; H, 4.81; N, 10.29; S, 11.43. Calcd
for C27H26N4S2Cl2: C, 59.88; H, 4.84; N, 10.35; S, 11.84. 1H NMR (δ,
DMSO-d6): 10.66 (s, 2H, NCHN), 8.27, 7.58 and 7.05 (m, 6H, C4H3S),
8.15 and 7.65 (m, 8H, C6H4), 6.16 (s, 4H, CH2C4H3S), 4.85 (t, 4H,
NCH2 bridge, 3J = 6.6 Hz), 2.63 (quin, 2H, CH2 bridge, 3J = 6.6 Hz).
13C NMR (δ, DMSO-d6): 142.6 (NCHN), 135.6, 131.2, 114.1 and
113.9(C4H3S), 130.6, 129.6, 127.9, 127.3, 126.7 and 126.6 (C6H4),
44.5 (NCH2-C4H3S), 44.0(NCH2 bridge), 28.2 (CH2 bridge).
GC-MS Analysis
GC-MS spectra were recorded on an Agilient 6890 N GC and
5973 Mass Selective Detector using an HP-INNOWAX column of
60 m length, 0.25 mm diameter and 0.25 µm film thicknesses.
GC-MS parameters for both Suzuki and Heck coupling reactions
were as follows: initial◦temperature, 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 between
m/z 50 and 550.
Synthesis of 3,3ꢁ-difurfuryl-1,1ꢁ-butylenedibenzimidazolium
dichloride,3
In a similar fashion to that described in synthesis of compound 1,
heating under reflux of a mixture of 1,1ꢁ-butylenedibenzimidazole
(0.85 g, 2.93 mmol) and furfuryl chloride (0.86 g, 7.38 mmol) for
4 h and a similar work-up afforded in high yield (1.29 g, 84%)
Synthesis of 3,3ꢁ-difurfuryl-1,1ꢁ-propylenedibenzimidazolium
dichloride,1
A mixture of 1,1ꢁ-propylenedibenzimidazole (0.85 g, 3.08 mmol)
and furfuryl chloride (0.87 g, 7.46 mmol) in dimethylformamide
(5 ml) was refluxed for 4 h. Volatiles were removed in vacuo and
the residue was crystallized from dimethylformamide–ethanol
(1 : 3). Brown crystals of the title compound 1 (1.24 g, 79%) were
obtained, m.p. 184–185 ◦C; v(CN) = 1562 cm−1. Anal. found: C,
63.49; H, 5.11; N, 10.83. Calcd for C27H26N4O2Cl2: C, 63.66; H, 5.14;
N, 11.00. 1H NMR (δ, DMSO-d6): 10.40 (s, 2H, NCHN), 8.20, 6.82
and 6.50 (m, 6H, C4H3O), 8.15 and 7.70 (m, 8H, C6H4), 5.90 (s, 4H,
the white title compound 3, m.p. 154–155 ◦C; v(CN) = 1559 cm−1
.
Anal. found: C, 64.17; H, 5.32; N, 10.63. Calcd for C28H28N4O2Cl2: C,
64.25; H, 5.39; N, 10.70. 1H NMR (δ, DMSO-d6): 10.46 (s, 2H, NCHN),
8.17, 6.85 and 6.51 (m, 6H, C4H3O), 8.12 and 7.69 (m, 8H, C6H4),
5.95 (s, 4H, CH2C4H3O), 4.67(m, 4H, NCH2 bridge), 2.05 (m, 4H,
CH2 bridge). 13C NMR (δ, DMSO-d6): 145.7 (NCHN), 144.5, 140.9,
111.7 and 111.1 (C4H3O), 130.8, 130.2, 127.2, 126.9, 113.5 and 112.4
(C6H4), 46.6 (NCH2-C4H3O), 43.2 (NCH2 bridge), 23.9 (CH2 bridge).
c
Appl. Organometal. Chem. 2010, 24, 414–420
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

¨
U. Yılmaz et al.
Table 1. Test experiments for optimization of the Suzuki coupling reactions
Pd(OAc)2 (1 mol %)
LX (1 mol %), mw
Br
B(OH)2
H CCO
+
COCH3
3
Solvent mixture (1:1)
Base (2 mol %)
Thermal heating
◦C
Yield (%)
Microwave heating
Entry
LX (ligand)
Base
Solvent
Time (min)
◦C (W)
Yield (%)
1
2
2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CsCO3
CsCO3
Et3N
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
EtOH –H2O
DMF –H2O
EtOH –H2O
DMF –H2O
EtOH –H2O
Dioxane –H2O
DMF –H2O
EtOH –H2O
5
10
30
60
90
5
90
90
n.d.
8
60 (50)
60 (50)
43
52
57
61
2
3
2
90
43
55
63
n.d.
21
53
76
82
60 (50)
4
2
90
60 (50)
5
2
90
n.t.
6
2
145
145
145
145
145
90 (100)
90 (100)
90 (100)
90 (100)
n.t.
68
72
76
83
7
2
10
30
60
90
5
8
2
9
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
2
2
145(400)
145(400)
145(400)
145(400)
90(200)
90(300)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
99
99
99
99
69
69
99
96
91
89
95
93
86
02
04
2
10
30
60
5
2
2
2
2
5
2
5
2
5
2
5
2
Et3N
5
2
DBU
5
2
DBU
5
2
K2CO3
K2CO3
DBU
5
no
no
5
5
n.t., Not tested; n.d., not detected. Reaction conditions are same as indicated in the text. Yields are based on aryl bromide. Reactions were monitored
by GC-MS.
Similarly, 3,3ꢁ-dithenyl-1,1ꢁ-butylenedibenzimidazolium dichlo-
4H, CH2C4H3S), 5.30 (m, 1H, CH bridge), 4.61 (t, 2H, NCH2 bridge,
3J = 6.0 Hz), 2.20 (m, 2H, CH2 bridge), 2.04 (m, 2H, CH2 bridge),
1.46 (d, 3H, CH3, 3J = 4.8 Hz). 13C NMR (δ, DMSO-d6): 142,8 (NCHN),
140.9, 136.2, 114.5 and 113.4 (C4H3S), 131.5, 130.0, 128.5, 127.2,
126.1 and 114.8 (C6H4), 46.9 (NCH2 –C4H3S), 45.2 (NCH bridge),
36.6 (CH2 bridge), 34.4 (CH2 bridge), 31.3 (NCH2 bridge), 26.4 (CH3
bridge).
ride, 4 was synthesized from 1,1ꢁ-butylenedibenzimidazole and
thenyl chloride. Yield: 1.42 g, 87%, m.p. 142–143 ◦C; v(CN)
=
1556 cm−1. Anal. found: C, 60.38; H, 5.01; N, 9.82; S, 11.42. Calcd
for C28H28N4S2Cl2: C, 60.53; H, 5.08; N, 10.08; S, 11.54. 1H NMR (δ,
DMSO-d6): 10.58 (s, 2H, NCHN), 8.18, 7.51 and 7.03 (m, 6H, C4H3S),
8.13 and 7.58 (m, 8H, C6H4), 6.13 (s, 4H, CH2C4H3S), 4.68(m, 4H,
NCH2 bridge), 2.05 (m, 4H, CH2 bridge). 13C NMR (δ, DMSO-d6):
142,4 (NCHN), 135.8, 131.1, 114.0 and 113.9 (C4H3S), 130.6, 129.5,
127.9,127.3,126.6and114.1(C6H4),46.1(NCH2-C4H3S),44.5(NCH2
bridge), 23.3 (CH2 bridge).
Synthesis of 3,3ꢁ-difurfuryl-1,1ꢁ-trans-2-butenylenedibenzimidazo-
lium dichloride,6
In a similar fashion to that described in synthesis of com-
pound 1, heating under reflux of a mixture of 1,1ꢁ-trans-2-
butenylenedibenzimidazole (0.85 g, 2.95 mmol) and furfuryl chlo-
ride (0.87 g, 7.46 mmol) for 4 h and a similar work-up afforded
in high yield (1.26 g, 82%) the white title compound 6, m.p.
212–213 ◦C; v(CN) = 1553 cm−1. Anal. found: C, 64.45; H, 4.81; N,
10.44. Calcd for C28H26N4O2Cl2: C, 64.49; H, 5.03; N, 10.74. 1H NMR
(δ, DMSO-d6): 10.34 (s, 2H, NCHN), 8.14, 6.86 and 6.50 (m, 6H,
C4H3O), 8.05 and 7.64 (m, 8H, C6H4), 6.28 (s, 2H, CH CH bridge),
6.00 (s, 4H, CH2C4H3O), 5.33 (m, 4H, NCH2 bridge). 13C NMR (δ,
DMSO-d6): 147.5(NCHN), 144.8, 143.2, 114.3 and 111.8 (C4H3O),
131.5, 131.3, 129.3, 127.8, 127.2 and 125.6 (C6H4), 114.6 (CH CH),
48.2 (NCH2), 43.4 (CH2 –C4H3O).
Synthesisof3,3ꢁ-dithenyl-1,1ꢁ-(1-methylbutylene)dibenzimidazolium
dichloride,5
In a similar fashion to that described in synthesis of com-
pound 1, heating under reflux of
a
mixture of 1,1ꢁ-(1-
methylbutylene)dibenzimidazole (0.85 g, 2.79 mmol) and thenyl
chloride (1.0 g, 7.54 mmol) for 4 h and a similar work-up afforded
in moderate yield (1.10 g, 69%) the white title compound 5, m.p.
136–137 ◦C; v(CN) = 1550 cm−1. Anal. found: C, 61.03; H, 5.30; N,
9.76; S, 11.19. Calcd for C29H30N4S2Cl2: C, 61.15; H, 5.31; N, 9.84;
S, 11.26. 1H NMR (δ, DMSO-d6): 10.42 (s, 2H, NCHN) 8.18, 7.50
and 7.05 (m, 6H, CH2C4H3S), 8.16 and 7.60 (m, 8H, C6H4), 6.14 (s,
c
www.interscience.wiley.com/journal/aoc
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 414–420

Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
bridge). 13C NMR (δ, DMSO-d6): 142.5(NCHN), 135.6, 131.1, 114.3
and 113.9 (C4H3S), 130.6, 129.5, 128.8, 127.9, 127.3 and 126.7
(C6H4), 114.2(CH CH), 48.9 (NCH2), 43.4(CH2 –C4H3O).
Table 2. The Suzuki coupling reactions of aryl halides with phenyl-
boronic acid
Pd(OAc)2 (1 mol %)
1-7 (1 mol %), mw (400 W)
B(OH)2
X
+ R
R
General Procedure for the Suzuki Reactions
DMF/ H2O (1:1), 145 °C, 5 min
K2CO3 (2 equiv)
Pd(OAc)2 (1 mmol%), bis-benzimidazolium chlorides (1–7)
(1 mmol%), aryl halide (1 mmol%), phenylboronic acid
(1.2 mmol%), K2CO3 (2 mmol), water (3 ml) and DMF (3 ml) were
added to microwave apparatus and the mixture was heated at
145 ◦C (400 W) for 5 min. It was carried out over a ramp time of
4 min to reach to 145 ◦C temperature. At the end of reaction, the
mixture was cooled, the product extracted with ethyl acetate–n-
hexane (1 : 5), chromatographed on a silica gel column. The purity
of coupling products was checked by NMR and GC-MS, and yields
are based on aryl halide.
Entry
R
X
Salt
Yield (%)
1
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CH3
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
99
99
99
99
99
99
99
95
80
94
94
74
72
87
87
87
86
87
95
90
86
56
56
44
57
54
40
75
71
77
72
75
76
70
74
63
25
67
53
70
64
29
2
3
4
5
6
7
8
9
General Procedure for the Heck Reactions
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
Pd(OAc)2 (1 mmol%), bis-benzimidazolium chlorides (1–7)
(1 mmol%), aryl halide (1 mmol%), styrene (1.2 mmol%), K2CO3
(2 mmol), water (3 ml) and DMF (3 ml) were added to microwave
apparatus and the mixture was heated at 145 ◦C (400 W) for 5 min.
It was carried out over a ramp time of 4 min to reach to 145 ◦C
temperature. At the end of reaction, the mixture was cooled,
the product extracted with ethyl acetate–n-hexane (1 : 5) and
chromatographed on a silica gel column. The purity of coupling
products was checked by NMR and GC-MS, and yields are based
on aryl halide.
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
NH2
Results and Discussion
Bis-benzimidazolium chloride salts contain furyl and thienyl
heterocycles, 1–7, were prepared from by treatment of 1,1ꢁ-
alkylendibenzimidazoles with furfuryl or thenyl chloride in
refluxing DMF in good yields of 69–87%. The synthesis of the
bis-benzimidazoles 1–7 is summarized in Scheme 1. The bis-
benzimidazolium salts are air- and moisture-stable both in the
solid state and in solution. The structures of bis-benzimidazole
salts1–7wereidentifiedbyspectroscopicmethodsandelemental
1
analysis. The value of δ[13C{ H}], NCHN in benzimidazolium salts is
usuallyaround142 4.[51] Forbis-benzimidazoliumsalts1–7itwas
found to be 145.3, 142.6, 145.7, 142.4, 142.6, 145.7 and 142.5 ppm,
respectively. These values are good agreement with the previously
reported results.[41] In the 1H NMR spectrum of benzimidazolium
salts for NCHN, protons were observed as singlets at 10.40, 10.66,
10.46, 10.58, 10.42, 10.34 and, 10.53 ppm, respectively. These
chemical shift values are also typical for NCHN protons of bis-
benzimidazolium salts.[41]
NH2
NH2
NH2
NH2
NH2
NH2
The bis-benzimidazole derivatives, 1–7 showed IR absorption
at 1562, 1560, 1559, 1556, 1550, 1553 and 1558cm−1, respectively,
which are assigned to ν(C N). These values are slightly smaller
than the normal ν(C N) value because of the π-electron
delocalization on the imidazolium ring.
Yields are based on aryl halide. Reactions were monitored by GC-MS.
Similarly, 3,3ꢁ-dithenyl-1,1ꢁ-trans-2-butenylenedibenzimidazo-
lium dichloride,7, was synthesized from 1,1ꢁ-trans-2-but-
enylenedibenzimidazole and thenyl chloride. Yield: 1.41 g, 86%,
m.p. 201–202 ◦C; v(CN) = 1558 cm−1. Anal. found: C, 60.64; H, 4.63;
N, 10.09; S, 11.47. Calcd for C28H26N4S2Cl2: C, 60.75; H, 4.73; N,
10.12; S, 11.58. H NMR (δ, DMSO-d6): 10.53 (s, 2H, NCHN), 8.15,
7.51 and 7.05 (m, 6H, C4H3S), 8.06 and 7.66 (m, 8H, C6H4), 6.25
(s, 2H, CH CH bridge), 6.15 (s, 4H, CH2C4H3S), 5.30 (m, 4H, NCH2
The Suzuki and Heck Coupling Reactions
Recently, great deals of palladium catalytic systems have been
used in the Suzuki and Heck reactions. The catalytic activity
depends on many factors such as aryl halides, ligands, base,
solvent, time, temperature and nature of the catalyst. A lots of
good results have been obtained by means of a palladium catalyst
1
c
Appl. Organometal. Chem. 2010, 24, 414–420
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

¨
U. Yılmaz et al.
Table 3. Test experiments for optimization of the Heck coupling reactions
Pd(OAc)2 (1 mol %)
LX (1 mol %), mw
COCH3
+
Br
H3CCO
Solvent mixture (1:1)
Base (2 mol %)
Thermal heating
◦C
Yield (%)
Microwave heating
Entry
LX (ligand)
Base
Solvent
Time (min)
◦C (W)
Yield (%)
1
2
2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CsCO3
CsCO3
Et3N
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
DMF –H2O
EtOH –H2O
DMF –H2O
EtOH –H2O
DMF –H2O
EtOH –H2O
DMF –H2O
EtOH –H2O
5
5
90
145
145
145
145
145
n.d.
n.d.
21
60 (50)
90 (100)
90 (100)
90 (100)
90 (100)
n.t.
41
64
73
78
82
2
3
2
10
30
60
90
5
4
2
53
5
2
83
6
2
91
7
2
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
99
99
8
2
5
9
2
5
94
10
11
12
13
14
15
2
5
93
2
Et3N
5
89
2
DBU
5
95
2
DBU
5
93
no
no
K2CO3
DBU
5
n.d.
n.d.
5
n.t., not tested; n.d., not detected. Reaction conditions are same as indicated in the text. Yields are based on aryl bromide. Reactions were monitored
by GC-MS.
system consisting of Pd(OAc)2, bis-benzimidazole salt and base
under mild reaction conditions by conventional heating in DMF
–H2O (1 : 1).[39–41] However, these reactions requre a long time for
good results. Nowadays, palladium nanoparticles or palladium
nanoclusters are used as efficient green homogeneous and
heterogeneous carbon–carbon coupling precatalysts in Suzuki
and Heck reactions.[53,54] The coupling reactions of aryl iodide,
bromide and chlorides with phenylboranic acid and styrene have
been used in Suzuki and Heck reactions and surprisingly good
yields have been obtained in a short time using microwave
heating.[46,47]
After these results, we chose K2CO3 as a base, as it is less expen-
sive than Cs2CO3 and water–DMF as a solvent. Part of the solvent
mixture being water, a non-toxic, readily available, non-flammable
solvent, has clear advantages as a solvent for use in microwave-
mediated synthesis. Under the optimized conditions, reaction of
p-bromoacetophenone, p-chlorobenzaldehyde, p-chlorotoluene,
p-chloroanisol and p-chlorothioanisole with phenylboronic acid
gave almost as high a yield using a catalytic system consisting
of 1 mol% bis-benzimidazole salts (1–7), 1 mol% Pd(OAc)2 and 2
equivs K2CO3 in DMF-H2O (1 : 1) at 145 ◦C by microwave irradiation
(400 W) within only 5 min. The temperature of 145 ◦C was reached
over the ramp time of 4 min. We also tested the catalytic yields us-
ingconventionalheatingsysteminapreheatedoilbathat5, 10, 30,
60and90 minat90and145 ◦C.Weobservednearlythesameyields
only when the Suzuki reactions were carried out in a preheated
oil bath (145 ◦C) in 90 min instead of using microwave heating.
Importantly, no catalytic yield was obtained at either temperature
in 5 min. Control experiments showed that the coupling reaction
did not occur in the absence of 1–7 in 5 min. The results obtained
from optimum conditions for the Suzuki reactions are given in
Table 2. Of the six different aryl halides used in the Suzuki coupling
with phenylboronic acid, those with electron-withdrawing
substituents were found to give the highest yields (Table 2,
entries 1–14). The tetramethylene bridged bis-benzimidazolium
salt bearing a methyl substituent (5) is generally more effective
of the salts examined in Suzuki reactions. The furfuryl and thenyl
substituents on the N atom of the bis-benzimidazolium salts also
affect the catalytic activity. The more electron-donating effect of
S atoms than O atoms may be responsible for the better catalytic
activities of the bis-benzimidazolium salts in Suzuki coupling
reactions. It is important to note that the end of all these reactions
was clearly observed black particles in the reaction mixture, which
The Suzuki coupling reaction
In order to find the optimum reaction conditions for the
Suzuki coupling reaction, a series of experiments was performed
catalyzed by p-bromoacetophenone and phenylboronic acid as
model compounds. The test reactions were performed using
different bases such as Cs2CO3, K2CO3, Et3N and DBU (1,8-
diazabicyclo[5.4.0]undec-7-en)anddifferentsolventssuchasEtOH
–H2O,dioxaneandDMF –H2Oin5,10,30and60 minat60 ◦C/50 W,
90 ◦C/100 W, 90 ◦C/200 W, 100 ◦C/300 W and 145 ◦C/400 W. It
was found that the Suzuki coupling reaction catalyzed by bis-
benzimidazolium (1), Pd(OAc)2 and base catalyst system gave
the highest yield when using DMF –H2O mixture as a solvent
and Cs2CO3 or K2CO3 as a base at 145 ◦C/400 W microwave
heating in 5 min. No considerable increase in catalytic reaction
yield was observed by prolonging the time from 5 to 60 min.
We observed good effect for the catalytic yield of increasing the
temperature from 60 ◦C to 145 ◦C/400 W in 5 min. The results of
the optimization experiments for the Suzuki reactions are given in
Table 1.
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 414–420

Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
preparation of hydrocarbons, novel polymers, pharmaceuticals,
organic and fine chemistry, agrochemicals, dyes and new
enantioselective syntheses of natural products because of the
mild conditions required for the reaction.[53] In order to find the
optimum reaction conditions for the Heck coupling reaction,
a series of test experiments was performed with catalyzed
by p-bromoacetophenone and styrene as model compounds,
as mentioned in the Suzuki coupling reactions above. Similar
optimum parameters [1 mol% Pd(OAc)2, and 2 equivs K2CO3 in
DMF –H2O (1 : 1) at 145 ◦C/400 W by microwave irradiation in
5 min] were also used. The results of the optimization experiments
for the Heck reactions are given in Table 3.
Control experiments showed that the Heck coupling reaction
did not occur in the absence of 1–7 in 5 min. The results
obtained from optimum conditions for the Heck reactions are
given in Table 4. Under the optimized reaction conditions, six
different aryl halides bearing electron-donating and electron-
withdrawing groups reacted with styrene, affording the coupled
products in almost as high a yield. As expected, aryl chlorides with
electron-deficientsubstituentswerebeneficialfortheconversions.
The tetramethylene bridged bis-benzimidazolium salt bearing a
methyl substituent (5) is the most effective of the salts examined
in Heck reactions. It can be concluded that the furfuryl and
thenyl substituents on the N atom of the bis-benzimidazolium
salts generally effect the catalytic activity as mentioned in
Suzuki coupling reactions above. The end of the reaction, black
particles which probably derive from palladium nanoparticles, was
observed in the reaction mixture. As can be seen in Table 4, high
C–C coupling product (Table 4, entries 1–7) was observed from
reaction of aryl bromides with styrene as expected.
Table 4. The Heck coupling reactions of aryl halides with styrene
Pd(OAc)2 (1 mol %)
1-7 (1 mol %), mw (400 W)
R
X
+
R
DMF/ H2O (1:1), 145 °C,
5 min K2CO3 (2 equiv)
Entry
R
X
Salt
Yield (%)
1
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CH3
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
99
99
99
93
96
99
99
85
81
89
80
82
70
78
89
87
91
87
90
89
86
60
58
61
54
65
65
51
62
55
70
64
72
69
72
51
58
46
61
62
50
46
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
NH2
Conclusions
We prepared seven bis-benzimidazolium salts bearing furfuryl
and thenyl substituents (1–7) from bis-benzimidazole and furfuryl
chloride or thenyl chloride. The use of the palladium catalyst
system including bis-benzimidazole salts in the Suzuki coupling
and Heck reactions gives better yields under microwave-assisted
moderate conditions and very short reaction times compared with
those given in literature. Both the Suzuki and Heck reactions were
carried out by 400 W power microwave irradiation at 145 ◦C in only
5 min. It can be concluded that, both Suzuki and Heck coupling
reactions may accelerate by microwave irradiation even using aryl
chlorides particularly bearing electron-withdrawing substituents
in Suzuki and Heck coupling reactions, contrary to some literature
information.[15,40,53]
NH2
NH2
NH2
NH2
NH2
Acknowledgments
NH2
This work was financially supported by the Ino¨nu¨ University
Research Fund (I.U. B.A.P. 2008/59)
Yields are based on aryl halide. Reactions were monitored by GC-MS.
¨
probably derived from palladium nanoparticles. As can be seen in
Table 3, a high C–C coupling product was observed from reaction
of aryl bromides with phenylboronic acid as expected.
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Appl. Organometal. Chem. 2010, 24, 414–420
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