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Synthesis and microwave-assisted catalytic activity of novel bis-benzimidazole salts bearing furfuryl and thenyl moieties in Heck and Suzuki cross-coupling reactions.

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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
Ülkü Yılmaza , Nihat Şirecib , Selma Deniza and Hasan Küçükbaya∗
A mixture of bis-benzimidazole salts (1–7), Pd(OAc)2 and K2 CO3 in DMF –H2 O 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
c 2010 John Wiley & Sons, Ltd.
by 1 H– 13 C NMR, IR spectroscopic methods and micro analysis. Copyright Keywords: bis-benzimidazole salt; carbene; palladium catalysis; coupling reaction; Heck coupling; Suzuki coupling; microwave
Introduction
414
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.
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.
In particular, Pd(OAc)2 –benzimidazole or imidazole ligands 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]
Appl. Organometal. Chem. 2010, 24, 414–420
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, we describe the synthesis of new bis-benzimidazole salts
(1–7) containing furfuryl and thenyl moieties. The compounds
were fully characterized by elemental analysis, IR, 13 C-NMR and
1 H-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.
Experimental
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. 1 H-NMR
(300 MHz) and 13 C-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 Küçükbay, Department of Chemistry, Faculty of Arts
and Science, Inönü University, Malatya 44280, Turkey.
E-mail: hkucukbay@inonu.edu.tr
a Inönü University, Faculty Science and Arts, Department of Chemistry, 44280
Malatya, Turkey
b Adıyaman University, Faculty Science and Arts, Department of Chemistry, 02040
Adıyaman, Turkey
c 2010 John Wiley & Sons, Ltd.
Copyright Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
N
+
N
2Cl-
N
+
N
2
Cl
O
N
N
1
O
I
Cl
2
N
N
+
N
S
N
2
R
N 2Cl N
+
+
N
N
S
R
R
-
2
O
Cl
O
3R=H
N
+
N
S
O
O
2Cl-
N
N
N
N
N 2Cl N
+
+
N
N
Cl
2
S
II R = H
III R = Me
S
S
4R=H
5 R = Me
O
S
Cl-
N
+
N
N
N
2
O
6
N
+
N
S
N
Cl-
N
+
N
Cl-
Cl
2
Cl
IV
7
N
+
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 electrothermal9200 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]
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 3,3 -difurfuryl-1,1 -propylenedibenzimidazolium
dichloride,1
Appl. Organometal. Chem. 2010, 24, 414–420
Synthesis of 3,3 -difurfuryl-1,1 -butylenedibenzimidazolium
dichloride,3
In a similar fashion to that described in synthesis of compound 1,
heating under reflux of a mixture of 1,1 -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%)
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 C28 H28 N4 O2 Cl2 : C,
64.25; H, 5.39; N, 10.70. 1 H NMR (δ, DMSO-d6 ): 10.46 (s, 2H, NCHN),
8.17, 6.85 and 6.51 (m, 6H, C4 H3 O), 8.12 and 7.69 (m, 8H, C6 H4 ),
5.95 (s, 4H, CH2 C4 H3 O), 4.67(m, 4H, NCH2 bridge), 2.05 (m, 4H,
CH2 bridge). 13 C NMR (δ, DMSO-d6 ): 145.7 (NCHN), 144.5, 140.9,
111.7 and 111.1 (C4 H3 O), 130.8, 130.2, 127.2, 126.9, 113.5 and 112.4
(C6 H4 ), 46.6 (NCH2 -C4 H3 O), 43.2 (NCH2 bridge), 23.9 (CH2 bridge).
c 2010 John Wiley & Sons, Ltd.
Copyright www.interscience.wiley.com/journal/aoc
415
A mixture of 1,1 -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 C27 H26 N4 O2 Cl2 : C, 63.66; H, 5.14;
N, 11.00. 1 H NMR (δ, DMSO-d6 ): 10.40 (s, 2H, NCHN), 8.20, 6.82
and 6.50 (m, 6H, C4 H3 O), 8.15 and 7.70 (m, 8H, C6 H4 ), 5.90 (s, 4H,
CH2 C4 H3 O), 4.78 (t, 4H, NCH2 bridge, 3 J = 6.6 Hz), 2.73 (quin., 2H,
CH2 bridge, 3 J = 6.6 Hz). 13 C NMR (δ, DMSO-d6 ): 145.3 (NCHN),
144.6, 140.8, 111.9 and 111.0 (C4 H3 O), 130.7, 127.4, 127.3, 127.2,
113.5, and 112.6 (C6 H4 ), 44.6 (NCH2 -C4 H3 O), 43.3 (NCH2 bridge),
27.8 (CH2 bridge).
Similarly, 3,3 -dithenyl-1,1 -propylenedibenzimidazolium dichloride, 2 was synthesized from 1,1 -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 C27 H26 N4 S2 Cl2 : C, 59.88; H, 4.84; N, 10.35; S, 11.84. 1 H NMR (δ,
DMSO-d6 ): 10.66 (s, 2H, NCHN), 8.27, 7.58 and 7.05 (m, 6H, C4 H3 S),
8.15 and 7.65 (m, 8H, C6 H4 ), 6.16 (s, 4H, CH2 C4 H3 S), 4.85 (t, 4H,
NCH2 bridge, 3 J = 6.6 Hz), 2.63 (quin, 2H, CH2 bridge, 3 J = 6.6 Hz).
13
C NMR (δ, DMSO-d6 ): 142.6 (NCHN), 135.6, 131.2, 114.1 and
113.9(C4 H3 S), 130.6, 129.6, 127.9, 127.3, 126.7 and 126.6 (C6 H4 ),
44.5 (NCH2 -C4 H3 S), 44.0(NCH2 bridge), 28.2 (CH2 bridge).
Ü. Yılmaz et al.
Table 1. Test experiments for optimization of the Suzuki coupling reactions
Br
B(OH)2 + H3CCO
Pd(OAc)2 (1 mol %)
LX (1 mol %), mw
COCH3
Solvent mixture (1:1)
Base (2 mol %)
Thermal heating
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
LX (ligand)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
no
no
Base
Solvent
Time (min)
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
CsCO3
CsCO3
Et3 N
Et3 N
DBU
DBU
K2 CO3
K2 CO3
DBU
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
EtOH –H2 O
DMF –H2 O
EtOH –H2 O
DMF –H2 O
EtOH –H2 O
Dioxane –H2 O
DMF –H2 O
EtOH –H2 O
5
10
30
60
90
5
10
30
60
90
5
10
30
60
5
5
5
5
5
5
5
5
5
5
5
◦
C
Yield (%)
90
90
90
90
90
145
145
145
145
145
n.d.
8
43
55
63
n.d.
21
53
76
82
Microwave heating
◦
C (W)
Yield (%)
60 (50)
60 (50)
60 (50)
60 (50)
n.t.
90 (100)
90 (100)
90 (100)
90 (100)
n.t.
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)
43
52
57
61
68
72
76
83
99
99
99
99
69
69
99
96
91
89
95
93
86
02
04
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, 3,3 -dithenyl-1,1 -butylenedibenzimidazolium dichloride, 4 was synthesized from 1,1 -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 C28 H28 N4 S2 Cl2 : C, 60.53; H, 5.08; N, 10.08; S, 11.54. 1 H NMR (δ,
DMSO-d6 ): 10.58 (s, 2H, NCHN), 8.18, 7.51 and 7.03 (m, 6H, C4 H3 S),
8.13 and 7.58 (m, 8H, C6 H4 ), 6.13 (s, 4H, CH2 C4 H3 S), 4.68(m, 4H,
NCH2 bridge), 2.05 (m, 4H, CH2 bridge). 13 C NMR (δ, DMSO-d6 ):
142,4 (NCHN), 135.8, 131.1, 114.0 and 113.9 (C4 H3 S), 130.6, 129.5,
127.9, 127.3, 126.6 and 114.1 (C6H4 ), 46.1 (NCH2 -C4 H3 S), 44.5 (NCH2
bridge), 23.3 (CH2 bridge).
Synthesis of 3,3 -dithenyl-1,1 -(1-methylbutylene)dibenzimidazolium
dichloride,5
416
In a similar fashion to that described in synthesis of compound 1, heating under reflux of a mixture of 1,1 -(1methylbutylene)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 C29 H30 N4 S2 Cl2 : C, 61.15; H, 5.31; N, 9.84;
S, 11.26. 1 H NMR (δ, DMSO-d6 ): 10.42 (s, 2H, NCHN) 8.18, 7.50
and 7.05 (m, 6H, CH2 C4 H3 S), 8.16 and 7.60 (m, 8H, C6 H4 ), 6.14 (s,
www.interscience.wiley.com/journal/aoc
4H, CH2 C4 H3 S), 5.30 (m, 1H, CH bridge), 4.61 (t, 2H, NCH2 bridge,
3 J = 6.0 Hz), 2.20 (m, 2H, CH bridge), 2.04 (m, 2H, CH bridge),
2
2
1.46 (d, 3H, CH3 , 3 J = 4.8 Hz). 13 C NMR (δ, DMSO-d6 ): 142,8 (NCHN),
140.9, 136.2, 114.5 and 113.4 (C4 H3 S), 131.5, 130.0, 128.5, 127.2,
126.1 and 114.8 (C6 H4 ), 46.9 (NCH2 –C4 H3 S), 45.2 (NCH bridge),
36.6 (CH2 bridge), 34.4 (CH2 bridge), 31.3 (NCH2 bridge), 26.4 (CH3
bridge).
Synthesis of 3,3 -difurfuryl-1,1 -trans-2-butenylenedibenzimidazolium dichloride,6
In a similar fashion to that described in synthesis of compound 1, heating under reflux of a mixture of 1,1 -trans-2butenylenedibenzimidazole (0.85 g, 2.95 mmol) and furfuryl chloride (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 C28 H26 N4 O2 Cl2 : C, 64.49; H, 5.03; N, 10.74. 1 H NMR
(δ, DMSO-d6 ): 10.34 (s, 2H, NCHN), 8.14, 6.86 and 6.50 (m, 6H,
C4 H3 O), 8.05 and 7.64 (m, 8H, C6 H4 ), 6.28 (s, 2H, CH CH bridge),
6.00 (s, 4H, CH2 C4 H3 O), 5.33 (m, 4H, NCH2 bridge). 13 C NMR (δ,
DMSO-d6 ): 147.5(NCHN), 144.8, 143.2, 114.3 and 111.8 (C4 H3 O),
131.5, 131.3, 129.3, 127.8, 127.2 and 125.6 (C6 H4 ), 114.6 (CH CH),
48.2 (NCH2 ), 43.4 (CH2 –C4 H3 O).
c 2010 John Wiley & Sons, Ltd.
Copyright Appl. Organometal. Chem. 2010, 24, 414–420
Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
Table 2. The Suzuki coupling reactions of aryl halides with phenylboronic acid
B(OH)2 + R
X
bridge). 13 C NMR (δ, DMSO-d6 ): 142.5(NCHN), 135.6, 131.1, 114.3
and 113.9 (C4 H3 S), 130.6, 129.5, 128.8, 127.9, 127.3 and 126.7
(C6 H4 ), 114.2(CH CH), 48.9 (NCH2 ), 43.4(CH2 –C4 H3 O).
Pd(OAc)2 (1 mol %)
1-7 (1 mol %), mw (400 W)
R
DMF/ H2O (1:1), 145 °C, 5 min
K2CO3 (2 equiv)
Entry
R
X
Salt
Yield (%)
1
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
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CH3
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
NH2
NH2
NH2
NH2
NH2
NH2
NH2
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
Yields are based on aryl halide. Reactions were monitored by GC-MS.
Appl. Organometal. Chem. 2010, 24, 414–420
Pd(OAc)2 (1 mmol%), bis-benzimidazolium chlorides (1–7)
(1 mmol%), aryl halide (1 mmol%), phenylboronic acid
(1.2 mmol%), K2 CO3 (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–nhexane (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.
General Procedure for the Heck Reactions
Pd(OAc)2 (1 mmol%), bis-benzimidazolium chlorides (1–7)
(1 mmol%), aryl halide (1 mmol%), styrene (1.2 mmol%), K2 CO3
(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.
Results and Discussion
Bis-benzimidazolium chloride salts contain furyl and thienyl
heterocycles, 1–7, were prepared from by treatment of 1,1 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 bisbenzimidazolium salts are air- and moisture-stable both in the
solid state and in solution. The structures of bis-benzimidazole
salts 1–7 were identified by spectroscopic methods and elemental
analysis. The value of δ[13 C{1 H}], NCHN in benzimidazolium salts is
usually around 142±4.[51] For bis-benzimidazolium salts 1–7 it was
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 1 H 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 bisbenzimidazolium salts.[41]
The bis-benzimidazole derivatives, 1–7 showed IR absorption
at 1562, 1560, 1559, 1556, 1550, 1553 and 1558 cm−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.
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
c 2010 John Wiley & Sons, Ltd.
Copyright www.interscience.wiley.com/journal/aoc
417
Similarly, 3,3 -dithenyl-1,1 -trans-2-butenylenedibenzimidazolium dichloride,7, was synthesized from 1,1 -trans-2-butenylenedibenzimidazole 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 C28 H26 N4 S2 Cl2 : C, 60.75; H, 4.73; N,
10.12; S, 11.58. 1 H NMR (δ, DMSO-d6 ): 10.53 (s, 2H, NCHN), 8.15,
7.51 and 7.05 (m, 6H, C4 H3 S), 8.06 and 7.66 (m, 8H, C6 H4 ), 6.25
(s, 2H, CH CH bridge), 6.15 (s, 4H, CH2 C4 H3 S), 5.30 (m, 4H, NCH2
General Procedure for the Suzuki Reactions
Ü. Yılmaz et al.
Table 3. Test experiments for optimization of the Heck coupling reactions
Pd(OAc)2 (1 mol %)
LX (1 mol %), mw
+ H CCO
3
COCH3
Br
Solvent mixture (1:1)
Base (2 mol %)
Thermal heating
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
LX (ligand)
2
2
2
2
2
2
2
2
2
2
2
2
2
no
no
Base
Solvent
Time (min)
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
K2 CO3
CsCO3
CsCO3
Et3 N
Et3 N
DBU
DBU
K2 CO3
DBU
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
DMF –H2 O
EtOH –H2 O
DMF –H2 O
EtOH –H2 O
DMF –H2 O
EtOH –H2 O
DMF –H2 O
EtOH –H2 O
5
5
10
30
60
90
5
5
5
5
5
5
5
5
5
◦
C
Yield (%)
90
145
145
145
145
145
n.d.
n.d.
21
53
83
91
Microwave heating
◦
C (W)
60 (50)
90 (100)
90 (100)
90 (100)
90 (100)
n.t.
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
145(400)
Yield (%)
41
64
73
78
82
99
99
94
93
89
95
93
n.d.
n.d.
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
–H2 O (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]
The Suzuki coupling reaction
418
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 Cs2 CO3 , K2 CO3 , Et3 N and DBU (1,8diazabicyclo[5.4.0]undec-7-en) and different solvents such as EtOH
–H2 O, dioxane and DMF –H2 O in 5, 10, 30 and 60 min at 60 ◦ 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 bisbenzimidazolium (1), Pd(OAc)2 and base catalyst system gave
the highest yield when using DMF –H2 O mixture as a solvent
and Cs2 CO3 or K2 CO3 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.
www.interscience.wiley.com/journal/aoc
After these results, we chose K2 CO3 as a base, as it is less expensive than Cs2 CO3 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 microwavemediated 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 K2 CO3 in DMF-H2 O (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 using conventional heating system in a preheated oil bath at 5, 10, 30,
60 and 90 min at 90 and 145 ◦ C. We observed nearly the same yields
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
c 2010 John Wiley & Sons, Ltd.
Copyright Appl. Organometal. Chem. 2010, 24, 414–420
Novel bis-benzimidazole salts bearing furfuryl and thenyl moieties
Table 4. The Heck coupling reactions of aryl halides with styrene
X
+ R
Pd(OAc)2 (1 mol %)
1-7 (1 mol %), mw (400 W)
R
DMF/ H2O (1:1), 145 °C,
5 min K2CO3 (2 equiv)
Entry
1
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
R
X
Salt
Yield (%)
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CH3
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
SCH3
NH2
NH2
NH2
NH2
NH2
NH2
NH2
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
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.
The Heck coupling reaction
Appl. Organometal. Chem. 2010, 24, 414–420
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]
Acknowledgments
This work was financially supported by the Inönü University
Research Fund (I.Ü. B.A.P. 2008/59)
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420
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