Palladium-benzimidazolium salt catalyst systems for Suzuki coupling: development of a practical and highly active palladium catalyst system for coupling of aromatic halides with arylboronic acids

Article abstract of DOI:10.1016/j.tet.2005.06.060

Palladium-benzimidazolium salt catalyst systems have been studied for the Suzuki coupling. A different substitutent effect has been uncovered with respect to nitrogen substituents in the benzimidazolium salts from the palladium-imidazolium salt analogs. A practical and highly active palladium catalyst system, PdCl₂/N,N′-dibenzylbenzimidazolium chloride 2, has been identified for the Suzuki coupling of aromatic halides with arylboronic acids. The coupling of a wide array of aromatic halides with arylboronic acids with the PdCl₂-2 catalyst system gave good to excellent yields. The effective palladium loading could be as low as 0.0001 mol% and 0.01-0.1 mol% for iodide and bromide substrates, respectively. The coupling of unactivated aromatic chlorides with arylboronic acids also gave good results using Cs₂CO₃ as base with a 2 mol% palladium loading. The electronic factors from aromatic halides exert a significant influence on the Suzuki coupling catalyzed by the PdCl₂-2 system while the electronic effect from the arylboronic counterparts is negligible. The aromatic halides with modest steric hindrance could also couple smoothly with phenylboronic acids using the PdCl₂-2 catalyst system.

Full text of DOI:10.1016/j.tet.2005.06.060

Tetrahedron 61 (2005) 9783–9790
Palladium–benzimidazolium salt catalyst systems for Suzuki
coupling: development of a practical and highly active palladium
catalyst system for coupling of aromatic halides with
arylboronic acids
*
Wen Huang, Jianping Guo, Yuanjing Xiao, Miaofen Zhu, Gang Zou and Jie Tang
Department of Chemistry, East China Normal University, 3663 North Zhongshan Rd. Shanghai 200062, China
Received 4 February 2005; revised 2 May 2005; accepted 10 June 2005
Available online 14 July 2005
Abstract—Palladium–benzimidazolium salt catalyst systems have been studied for the Suzuki coupling. A different substitutent effect has
been uncovered with respect to nitrogen substituents in the benzimidazolium salts from the palladium–imidazolium salt analogs. A practical
and highly active palladium catalyst system, PdCl2/N,N0-dibenzylbenzimidazolium chloride 2, has been identified for the Suzuki coupling of
aromatic halides with arylboronic acids. The coupling of a wide array of aromatic halides with arylboronic acids with the PdCl2–2 catalyst
system gave good to excellent yields. The effective palladium loading could be as low as 0.0001 mol% and 0.01–0.1 mol% for iodide and
bromide substrates, respectively. The coupling of unactivated aromatic chlorides with arylboronic acids also gave good results using Cs2CO3
as base with a 2 mol% palladium loading. The electronic factors from aromatic halides exert a significant influence on the Suzuki coupling
catalyzed by the PdCl2–2 system while the electronic effect from the arylboronic counterparts is negligible. The aromatic halides with modest
steric hindrance could also couple smoothly with phenylboronic acids using the PdCl2–2 catalyst system.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
stability of free benzimidazolylidenes than imidazolylidenes
few attention has been paid to the nucleophilic N-hetero-
cyclic carbenes derived from benzimidazole5 although
fundamental thermodynamic studies have shown that
benzimidazolylidenes behave intermediately between
imidazolylidenes and their saturated analogs, imidazolinyl-
idenes.6 The first NHC, derived from benzimidazole, N,N0-
bis(2,2-dimethylpropyl)benzimidazolylidene, was isolated
in 1998 by reduction of thione.7 Direct deprotonation of
N,N0-bis-alkylsubstituted benzimidazolium salts with a less
sterically demanding substituent yields an enetetramine
instead of a free carbene.8 However, it has recently been
shown that NHC-transition metal complexes containing
benzimidazolylidene ligands could be generated from the
corresponding benzimidazolium salts as well as enetetra-
mines under mild conditions.9 That means, similar to
imidazolium salts, a combination of benzimidazolium salts
with metal precursors would finally lead to the correspond-
ing NHC–metal complexes under proper conditions.
The imidazolium-based nucleophilic N-heterocyclic car-
benes (NHC), imidazolylidenes, have recently emerged as a
versatile class of ligands in transition metal chemistry.1
With their stronger donor electronic property, thus high
dissociation energies of the corresponding metal–carbon
bonds,2 the transition metal complexes of imidazolylidenes
appeared to be extraordinarily stable toward heat, air and
moisture, showing potential in practical organic synthesis.
These advantages of imidazolylidene ligands make them
ideal alternatives to tertiary phosphines used in a variety of
transition-metal based homogeneous catalysts. Through
formation of catalytic species in situ, use of a combination
of imidazolium salts with metal precursors has proven to be
not only practical but also more efficient in some cases than
the isolated NHC–metal complexes of imidazolylidenes.3 A
variety of highly active catalyst systems have recently been
developed by combination of proper imidazolium salts with
palladium precursors.3,4 However, possibly due to the lower
The Suzuki coupling, where organoboronic acids are
employed as neuclophilic partners to couple with electro-
philes such as arylhalides, is one of the most important
protocols in organic synthesis, permitting the construction
of a wide variety of organic compounds ranging from
Keywords: Palladium; Suzuki coupling; Benzimidazolium; Arylboronic
acid; Aromatic halide.
*
Corresponding author. Tel.: C86 21 62232764; fax: C86 21 62232100;
e-mail: gzou@chem.ecnu.edu.cn
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.060

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W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
artificial materials to natural products.10 Compared with the
other nucleophilic partners in the cross-coupling with
organic halides, such as organomagnesium, organotin, and
organozinc, organoboron compounds possess many attrac-
tive features, such as air- and water-stability, non-toxicity
and excellent compatibility with a variety of functional
groups. The palladium–imidazolium salt systems have
proved to be one of the most successful catalysts for the
Suzuki coupling. Substituents on nitrogen atoms of
imidazolium significantly influence the catalytic activities
of the corresponding palladium–imidazolium salt systems in
the Suzuki coupling. As mentioned above, little is known
about the catalyst systems based on benzimidazolium salts
in the Suzuki coupling. We report here the development of
a highly active palladium–benzimidazolium catalyst system
employing the simplest palladium source PdCl2 and the
readily accessible N,N0-dibenzylbenzimidazolium chloride
for Suzuki coupling of aromatic halides, including
chlorides.
Unfortunately, both resulted in complicated mixtures, from
which only trace amount of the desired product, N,N0-
diphenyl-1,2-diaminobenzene, was isolated. The prep-
aration of N,N0-diphenyl-1,2-diaminobenzene was finally
achieved by a slightly modified amino acid-promoted
Ullmann coupling in 30% yield.13 A similar cyclization to
that for 4 with orthoformate in the presence of HCl(con.)
provided N,N0-diphenylbenzimidazolium chloride 5 in 90%
yield.
Scheme 2. Reagents and conditions: (i) 2.5 equiv Ph2CHCl, 30% NaOH
(aq), Bu4NCBrK (1.5% equiv), 55 8C. (ii) iodobenzene (5.0 equiv) CuI
(0.20 equiv), L-proline (0.40 equiv), K2CO3 (4.1 equiv), DMSO, N2, 80 8C,
18 h. (iii) HC(OEt)3, HCl (con. aq), HCO2H, N2, 80 8C, 2 h.
2.2. Suzuki coupling of arylboronic acids with aromatic
halides
2. Results and discussion
2.2.1. Establishing catalyst system. With these benzimi-
dazolium derivatives in hand, we started to investigate the
performance of the palladium–benzimidazolium catalyst
systems in the Suzuki coupling. Cross-coupling of
4-bromoacetophone with phenylboronic acid was selected
as the model reaction considering the ease of monitoring the
reaction progress. Although there are a couple of
parameters, such as base, temperature and solvent to be
scanned to optimize the reaction conditions, thanks to the
extensive research on NHC–palladium catalysts in recent
years, we have readily set the starting point: 0.01%Pd
loading, 2–3 equiv K2CO3 in DMF–H2O at 110 8C.
Although palladium sources have showed effects on the
performance of the corresponding palladium catalyst
systems,3 it is possibly the most practical and economical
to use palladium chloride. Thus palladium chloride PdCl2
was chosen as the palladium source in our palladium–
benzimidazolium catalyst systems. The reaction 4-bromo-
acetophone with phenylboronic acid catalyzed by the
palladium–benzimidazolium 1–5 catalyst systems gave the
cross-coupling product in good to excellent yields while no
reaction occurred in the absence of a benzimidazolium salt
under the otherwise identical conditions (Table 1, entries
1–6). On the effects of N,N0-substituents of benzimidazo-
lium on the performance of the catalyst systems, benzimi-
dazolium salts displayed a trend in contrast to the reported
imidazolium analogs. Aromatic or bulky substituents on the
N atoms of imidazolium normally increase the catalytic
activity of the corresponding systems.4d However, the
palladium–benzimidazolium catalyst system based on 5,
the N,N0-diphenylbenzimidazolium salt, displayed lower
catalytic activity in the model reaction than those based on
alkyl substituted ones, such as butyl 1, benzyl 2 and
benzhydryl 4. Bis-ethoxycarbonylmethyl imidazolium 3
also showed a lower activity although the imidazolium with
coordinative side arms was reported to display higher
activities than the corresponding simple alkyl analogs in
palladium-catalyzed C–C bond forming reactions.14 The
systems of dibenzylbenzimidazolium 2 and dibenzhydryl
imidazolium 4 displayed higher activities than that of 1 and
2.1. Synthesis of benzimidazolium salts
N,N0-Dialkylbenzimidazolium salts with primary alkyl
groups could be readily prepared from benzimidazoles by
consecutive alkylations with alkylhalides. N,N0-Dibutyl-
benzimidazolium bromide 1, N,N0-dibenzylbenzimidazolium
chloride 2 and N,N0-bis-ethoxycarbonylmethylbenzimidazo-
lium bromide 3 were obtained following this procedure in
good yields (Scheme 1).
Scheme 1. Reagents and conditions: (i) 1.2 equiv RX, 30% NaOH(aq),
Bu4NCBrK (1.5% equiv), 55 8C. (ii) 2.0 equiv RX, toluene, reflux.
According to the systematic work from Nolan group that
aryl or bulky alkyl substituents on nitrogen atoms were
crucial to the high performance of the corresponding
palladium–imidazolium salt systems.4 Thus, we wonder if
the palladium–benzimidazolium systems show a similar
trend. However, synthesis of N,N0-dibenzhydrylbenzimida-
zolium chloride 4 with the same procedure suffered from
poor yields under various conditions although the first
alkylation of benzimidazole with benzhydryl chloride
proceeded smoothly. Benzimidazolium salts with aromatic
substituents on N atoms are not accessible with a simple
alkylation procedure from benzimidazole. Thus, alternative
procedures were used to obtain 4 and N,N0-diphenylbenzi-
midazolium chloride 5 (Scheme 2). Benzimidazolium 4 was
prepared by alkylation of 1,2-diaminobenzene with benz-
hydryl chloride followed by cyclization of the resulting
N,N0-dibenzhydryl 1,2-diaminobenzene with orthoformate
in the presence of HCl (aq). Introduction of phenyl group to
the amino groups of 1,2-diaminobenzene was first tried
using palladium-catalyzed procedures with iodobenzene11
and copper-promoted arylation12 with phenylboronic acid.

W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
9785
Table 1. Cross-coupling of 4-bromoacetophone with phenylboronic acid catalyzed by palladium–benzimidazolium catalyst systems
Entry
Ligand
R
Pd loading (%)
Pd/L
Solvent (vol%)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
/
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3
CH3
CH3
CH3
CH3
0.01
0.01
0.01
0.01
0.01
0.01
0.001
0.01
0.1
0.1
0.1
0.1
0.1
0.01
0.01
0.01
0.01
0.01
0.01
/
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–5%H2O
DMF–25%H2O
DMF
3
3
1
12
1
Trace
91
94
85
96
1
2
3
4
5
2
2
1
2
3
4
5
2
2
2
2
2
2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/1
1/5
1/2
1/2
1/2
1/2
3
94
12
12
3
2
12
4
6
5
1
8
12b,c
20b,c
86
9
10
11
12
13
14
15
16
17
18
19
87
73
83
CH3
71c
93
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
CH3CO
90
82
3
3
3
12b,c
20b,c
25b,c
Dioxane–5%H2O
Tol–10%H2O
a Isolated yield.
b Conversion determined by GC.
c Aromatic halides recovered.
3 with butyl and ethoxycarbonylmethyl groups, respect-
ively. These results clearly indicated a sharp difference
between the imidazolium and benzimidazolium catalyst
systems. The trend displayed in the model reaction was
unmistakably confirmed by the coupling of 4-bromotoluene
with phenylboronic acid although the reaction required a
higher loading of palladium (Table 1, entries 8–13). Indeed,
the loading of palladium showed a significant effect on the
performance of the catalyst systems. When the loading of
PdCl2 was decreased to 0.001 mol% from 0.01 mol%, the
coupling of 4-bromoacetophone with phenylboronic acid
became rather sluggish (Table 1, entry 7). N,N0-Dibenzyl-
benzimidazolium salt 2 was chosen for further optimization
of the reaction conditions considering its easy accessibility.
The palladium–ligand ratio did not show significant impact
on the model reaction (Table 1, entries 3, 14 and 15). The
2:1 ratio of benzimidazolium salt to palladium gave slightly
better results than 1:1 ones. But an excess amount of
benzimidazolium salt looked like not necessary for the
stabilization of the active catalytic species. DMF proved to
be the choice of solvent (Table 1, entries 3, 18 and 19). The
presence of some amount (5–10% v/v) of water as co-
solvent was crucial to the success of the coupling albeit
larger amount of water depressed the reaction (Table 1,
entries 2, 16 and 17).
employing 1–5 as supporting ligands looked like to abide by
a general rule for phosphine–palladium systems, that is
electronic-rich ligands perform better for substrates resistant
to oxidative-addition, for example, chlorides, while steri-
cally demanding ligands would show higher activities in
coupling reactions if the reductive-elimination is the rate-
determining step.15 For example, the comparative elec-
tronic-rich N,N0-dialkylbenzimidazolium salts 1, 2 and 4
displayed better performances than 3 and 5 with ethoxy-
carbonylmethyl and phenyl groups, respectively (Table 1,
entries 2–6 and 9–13). Within the sub-sort of N,N0-
dialkylbenzimidazolium salts 1, 2 and 4, the catalytic
activities to the activated substrate, 4-bromoacetophone,
slightly increased with the increase of the bulk of alkyl
groups, implying that the reductive-elimination could be a
slow step. However, these are in contrast to those reported
for the imidazolium catalyst systems, in which electronic-
rich N,N0-dialkylimidazoliums showed lower activities,
especially for the substrates resistant to oxidative addition,
than the comparative electronic-poor N-aryl analogs in
Suzuki coupling.4d Obviously, further investigations
employing benzimidazoliums with various electron proper-
ties are needed to shed light on the issue.
The generally accepted catalytic cycle for the Suzuki
coupling reaction involves an oxidative-addition of the
arylhalide to a coordinatively unsaturated palladium
LnPd(0), transmetalation between organoboronic acid and
the palladium intermediate LnPd(Ar)(X) assisted by base
and a reductive-elimination producing the coupling product
and regeneration of LnPd(0) (Scheme 3).10
In the model reactions with 4-bromoacetophone or
4-bromotoluene, the behavior of these catalyst systems
Scheme 3. A general catalytic cycle for Suzuki coupling.

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W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
Table 2. Suzuki coupling of arylboronic acids with aromatic halides catalyzed by the palladium–benzimidazolium catalyst system
Entry
1
Ar–X
R
H
Pd loading (%)
0.01
Base
T (8C)
Time (h)
1
Yield (%)a
93 (100)b
3 equiv K2CO3
110
2
H
H
H
H
H
H
0.0001
0.0001
0.1
3 equiv K2CO3
3 equiv K2CO3
3 equiv K2CO3
3 equiv K2CO3
3 equiv K2CO3
3 equiv K2CO3
110
110
110
110
110
110
1
/ (91)b
94 (100)b
93 (100)b
76
3
2
4
2
5
0.1
12
2
6
0.1
92
7c
0.1
8
90
8
H
H
H
0.1
0.5
3
3 equiv K2CO3
3 equiv K2CO3
3 equiv K2CO3
110
110
110
12
12
6
16
44
94
9
10d
11
12
13
H
H
H
0.5
2
3 equiv Ba(OH)2
3 equiv Ba(OH)2
3 equiv Cs2CO3
140
140
140
12
6
70
82
2
6
88 (100)b
14d
15d
16d
17d
H
2
2
2
2
3 equiv Cs2CO3
3 equiv Cs2CO3
3 equiv Cs2CO3
3 equiv Cs2CO3
140
140
140
140
12
12
12
12
64
70
77
69
p-CH3CO
p-CH3O
H
a Isolated yield and the products were identified by comparison data with those reported in literature, see Section 4 for details.
b Conversion determined by GC.
c 2.5 equiv phenylboronic acid was used and diarylation product was isolated.
d Xylenes (2 mL) were added to maintain a reflux and prevent the chlorides from evaporating.

W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
9787
2.3. Coupling of arylboronic acids with aromatic halides
of Ba(OH)2, the yield of cross-coupling product reached
88% under the otherwise identical conditions (Table 2, entry
13). Using the PdCl2–2–Cs2CO3 catalyst system, the cross-
coupling of unactivated aromatic chlorides, such as
chlorobenzene and 4-chlorotoluene, with arylboronic acids
also gave the biaryl products in good yields (Table 2, entries
14–16). In contrast to the electronic effect from aromatic
halides, the electronic factor from arylboronic acids showed
a negligible influence on the coupling. Sterically hindered
2-chlorotoluene was equally reactive producing the cross-
coupling product in 70% yield (Table 2, entry 17).
The Suzuki coupling catalyzed by the PdCl2–2–K2CO3
system was explored in details (Table 2). At the loading of
PdCl2 as low as 0.0001 mol%, the coupling of iodobenzene
with phenylboronic acid still proceeded smoothly, indicat-
ing the system are highly active for aromatic iodides. The
conversion of iodobenzene reached to 91% in 1 h
determined by GC, showing TOF up to 9.1!105 mol/
mol h. We next focused on the Suzuki reactions of usually
less reactive electrophiles, aromatic bromides and chlorides
using the PdCl2–2–K2CO3 catalyst system. However, at the
low loading of palladium (0.001 mol%) for iodobenzene,
bromobenzene remained almost untouched under the
otherwise identical conditions. When 0.1 mol% palladium
loading was used bromobenzene could be smoothly
converted and gave biphenyl in 93% isolated yield. The
electronic factor from aromatic halides exerted a significant
influence on the coupling. The reactions of unactivated
(electron-neutral) arylbromides employing the PdCl2–2–
K2CO3 catalyst system proceeded in good yields while
deactivated (electron-rich) arylbromides with electron-
donating groups, such as MeO, reacted slowly and the yield
decreased to 76% (Table 2, entry 5). In contrast, activated
(electron-poor) arylbromides with electron-withdrawing
groups, such as CH3CO and NO2, reacted fast and provided
cross-coupling product in high yields (Table 1, entry 3 and
Table 2, entry 6). For an aromatic bromide with modest
steric hindrance, 2,5-dibromoxylene, the coupling still went
well, giving diarylation product, in 90% yield (Table 2,
entry 7). Even, the sterically demanding di-ortho-sub-
stituted-2-bromomesitylene also reacted well providing the
cross-coupling product in 94% yield with an increased
loading of palladium (3 mol%) (Table 2, entry 10).
3. Conclusion
In summary, five representative benzimidazolium salts have
been studied in constructing palladium catalyst systems for
the Suzuki coupling, from which a practical and highly
active palladium catalyst system has been developed from
the simplest palladium source PdCl2 and readily available
N,N0-dibenzylbenzimidazolium chloride 2 for the Suzuki
coupling of aromatic halides with arylboronic acids. A
different substitutent effect has been uncovered with respect
to nitrogen substituents of benzimidazolium salts from the
imidazolium salt analogs. The PdCl2–2 catalyst system has
proven to be highly efficient for the coupling of a wide array
of aromatic halides including chlorides with arylboronic
acids. The effective palladium loading could be as low as
0.0001 mol% and 0.01–0.1 mol% for iodide and bromide
substrates, respectively. The coupling of aromatic chlorides
with arylboronic acids also gave good results using the
PdCl2–2 catalyst system with 2 mol% palladium loading
and Cs2CO3 as the base. Electron-deficient aromatic halides
reacted faster and gave higher yields than the electron-rich
ones, indicating electronic factor from aromatic halides
exerted a significant influence on the Suzuki coupling
catalyzed by the palladium–benzimidazolium system while
the electronic effect from the arylboronic counterparts is
almost negligible. The obvious advantages of the PdCl2–2
system lie in its ready availability and yet high catalytic
activity. These results suggest that the N-heterocyclic
carbenes from benzimidazolium salts are promising ligands
for the homogenous transition metal catalysts. Further
modification of the benzimidazolium salts and applications
in transition metal catalyzed organic transformations are in
progress in our laboratory.
The usually unreactive aromatic chlorides were further
explored as the coupling partner using the PdCl2–2–K2CO3
catalyst system. The low reactivity of aromatic chlorides has
been attributed to their resistance to the oxidative addition to
Pd(0) species because of a large Csp2–Cl bond dissociation
energy.16 Due to the low cost of aromatic chlorides and the
challenge to activate the Csp2–Cl bond, it has attracted much
attention from both the industry and academic communities
to couple aromatic chlorides with arylboronic acids.15,16
Electron-rich phosphine ligands, such as tri(tert-butyl-
phosphine), and N,N0-diarylsubstituted imidazolium–
palladium systems have been reported to be suitable for
the Suzuki coupling of aromatic chlorides. Using the PdCl2–
2–K2CO3 catalyst system, which worked well for the
coupling of aromatic bromides, only trace amount of the
activated chloride, 4-chloroacetophone, was converted. A
stronger base Ba(OH)2, a higher loading of palladium
(0.5 mol%) and higher reaction temperature (130–140 8C)
were required for the reaction to proceed to completion
(Table 2, entries 11 and 12). The yields of the cross-
coupling increased from 70 to 82% with the increase of the
loading of PdCl2 from 0.5 to 2 mol%. However, palladium
black was observed on the wall of the reaction vessel with
2 mol% palladium loading, indicating the true catalytic
species should be less than 2 mol% and ratio of palladium to
benzimidazolium should be lower than 1:2. Further
increasing the loading of palladium did not increase the
yield of the cross-coupling. When Cs2CO3 was used instead
4. Experimental
4.1. General
All reactions and manipulations were performed in air
unless otherwise indicated. All the commercially available
chemicals, reagents and solvents, were used as received
with an exception of iodobenzene that was distilled prior to
1
use. H and 13C NMR spectra were recorded on a Bruker
500 spectrometer using the residue of deuterated solvents as
the internal standard. GC and Mass analyses were
performed using a Hewlett Packard Model HP 6890 Series
with HP-5 column. Elemental analysis was performed at the
Center of Analysis and Structure Determination of ECNU.

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W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
4.2. Synthesis of benzimidazolium salts
HC(OEt)3, 0.50 mL HCl(con. aq) and two drops of HCO2H.
The resulting mixture was stirred under nitrogen at 80 8C for
2 h. A white fine powder formed was collected by filtration.
Recrystallization of the residue from EtOH gave N,N0-
dibenzhydrylbenzimidazolium chloride 4, 2.39 g (86%),
4.2.1. N,N0-Dibutylbenzimidazolium bromide 1. To a
50 mL flask charged with benzimidazole (1.18 g, 10 mmol)
was added 10 mL 30% NaOH(aq) and 1.5% equiv Bu4-
NCBrK (TBAB) (50 mg, 0.15 mmol) followed by 1.2 equiv
1-bromobutane (1.3 mL, 12 mmol) at room temperature.
The mixture was stirred at 55 8C for 3 h before being poured
into 50 mL water and extracted with toluene (20 mL!3).
The toluene extracts was dried with Na2SO4, filtrated and
added to a solution of 1-bromobutane (2.3 mL, 20 mmol) in
a 100 mL flask. The mixture was refluxe0d for 6 h and slowly
cooled to room temperature giving N,N -dibutylbenzimida-
zolium bromide 1 as a white powder, which was further
purified by recrystallization from CH2Cl2 to give 1 as
colorless crystals 1.9 g (61%, two steps), mp: 140–142 8C.
1H NMR (CDCl3, 25 8C), d, ppm: 11.33 (1H, s, H2), 7.77–
7.80 (2H, m, H4, H7), 7.67–7.70 (m, 2H, H5, H6), 4.67 (4H,
t, JZ7.0 Hz, CH2), 2.24 (2H, s, H2O), 2.05–2.10 (4H, m,
CH2), 1.45–1.52 (4H, m, CH2), 0.98–1.01 (6H, t, JZ7 Hz,
CH3). 13C NMR (CDCl3, 25 8C), d, ppm: 142.5, 131.3,
127.2, 113.2, 47.5, 31.4, 19.8, 13.6. Anal. Calcd for
C15H25N2OBr (1.H2O): C, 54.71; H, 7.65; N, 8.51. Found:
C, 54.86; H, 7.55; N, 8.28.
1
mp: 245–247 8C. H NMR (DMSO, 25 8C), d, ppm: 9.15
(1H, s, H2), 7.56–7.60 (6H, m, overlapping), 7.41–7.50
(20H, m, overlapping). 13C NMR (CD3OD, 25 8C), d, ppm:
142.1, 136.9, 133.7, 130.7, 130.7, 129.5, 128.6, 116.3, 67.6.
Anal. Calcd for C33H27N2Cl: C, 81.38; H, 5.59; N, 5.75.
Found: C, 80.88; H, 5.63; N, 5.58.
4.2.5. N,N0-Diphenylbenzimidazolium chloride 5. To a
100 mL flask charged with 1,2-diaminobenzene (1.08 g,
10 mmol) in 30 mL DMSO was added 0.2 equiv CuI
(0.39 g, 2.0 mmol), 0.4 equiv L-proline (0.46 g, 4.0 mmol),
5 equiv iodobenzene (5.6 mL, 50 mmol) and 4.1 equiv
K2CO3 (5.7 g, 41 mmol) under nitrogen at room tempera-
ture. The mixture was stirred at 80 8C for 18 h before being
cooled and poured into 50 mL water and extracted with
ethyl acetate (30 mL!3). The extracts were dried with
Na2SO4 and solvents were removed under reduced pressure.
The residue was purified by flash chromatography through a
short pad of silica gel (eluent: ethyl acetate/petroleum
etherZ1:50 v/v). N,N0-Diphenyl-1,2-diaminobenzene was
obtained as a slight yellow powder containing about 2–3%
isomers (0.78 g, 30%). To the powder in 50 mL flask was
added 20 mL HC(OEt)3, 0.30 mL HCl(con.) and two drops
of HCO2H. The resulting mixture was stirred under nitrogen
at 80 8C for 2 h. After removal of solvents, the slight yellow
residue was purified by recrystallization from EtOH to
provide slight yellow microcrystals 0.83 g (90%), mp: 241–
243 8C (dehydrolyze 127–131 8C). 1H NMR (CDCl3,
25 8C), d, ppm: 11.19 (1H, s, H2), 8.10 (4H, d, JZ7.0 Hz,
Ph), 7.79–7.81 (2H, m, H4, H7), 7.62–7.72 (6H, m, Ph),
7.29–7.35 (2, m, H5, H6). 13C NMR (CDCl3), d, ppm:
141.9, 132.8, 131.6, 131.1, 130.7, 128.3, 125.5, 114.1. Anal.
Calcd for C19H17N2ClO (5$H2O): C, 70.26; H, 5.28; N,
8.62. Found: C, 69.80; H, 5.05; N, 8.46.
4.2.2. N,N0-Dibenzylbenzimidazolium chloride 2. A
similar procedure to that for the preparation of 1 was
adopted employing benzimidazole (5.9 g, 50 mmol) to
provide 2 as colorless microcrystals 10.2 g (61%), mp:
210–212 8C. 1H NMR (DMSO, 25 8C), d, ppm: 10.36 (1H, s,
H2), 7.98–8.01 (2H, m, H4, H7), 7.63–7.65 (m, 2H, H5,
H6), 7.56 (4H, d, JZ7.2 Hz, Ph), 7.35–7.45 (6H, m, Ph),
5.84 (4H, s, CH2Ph). 13C NMR (DMSO, 25 8C), d, ppm:
142.8, 133.9, 130.9, 128.8, 128.5, 128.2, 126.6, 113.9, 49.8.
Anal. Calcd for C21H21N2OCl (2$H2O): C, 71.48; H, 6.00;
N, 7.94. Found: C, 71.24; H, 5.87; N, 7.68.
4.2.3. N,N0-Bis-ethoxycarbonylmethyl benzimidazolium
bromide 3. A similar procedure to that for the preparation
of 1 was adopted employing benzimidazole (1.18 g,
10 mmol) to provide 3 as colorless microcrystals 3.2 g
(86%), mp: 157–159 8C. 1H NMR (DMSO, 25 8C), d, ppm:
9.80 (1H, s, H2), 8.08–8.10 (2H, m, H4, H7), 7.71–7.73 (2H,
m, H5, H6), 5.70 (4H, s, CH2CO2Et), 4.23 (4H, q, JZ
7.2 Hz, CH2), 1.26 (6H, t, JZ7.2 Hz, CH3). 13C NMR
(DMSO, 25 8C), d, ppm: 166.4, 144.3, 131.0, 126.9, 113.9,
62.0, 47.7, 13.9. Anal. Calcd for C21H21N2OCl (3$H2O): C,
46.29; H, 5.44; N, 7.20. Found: C, 46.08; H, 5.23; N, 6.88.
4.3. General procedure for Suzuki coupling of aromatic
halides with arylboronic acids
Under an atmosphere of nitrogen to a 25 mL Schlenk flask
charged with 1.0 mmol arylhalide, 1.1–1.2 mmol aryl-
boronic acid and a base (3 equiv) in DMF (10 mL)–H2O
(0.5 mL) were added stock solutions of PdCl2 and
benzimidazolium salts in DMF, respectively. The flask
was placed and stirred in an oil bath at the temperature as
required. The progress of the reactions was monitored by
TLC or GC. After be cooled to room temperature, the
mixture was poured into water and extracted with ether.
Removal of solvents gave the crude products, which were
purified either by flash chromatography or by
recrystallization.
4.2.4. N,N0-Dibenzhydrylbenzimidazolium chloride 4. To
a 100 mL flask charged with 1,2-diaminobenzene (1.08 g,
10 mmol) was added 20 mL 30% NaOH(aq) and
1.5% equiv Bu4NCBrK (TBAB) (50 mg, 0.15 mmol)
followed by 2.5 equiv benzhydryl chloride (5.0 g,
25 mmol) at room temperature. The mixture was stirred at
55 8C for 8 h before being poured into 50 mL water and
extracted with ether (20 mL!3). The ether extracts were
dried over Na2SO4 and concentrated. The resulting residue
was purified by flash chromatography through a short pad of
silica gel (eluent: ethyl acetate/petroleum etherZ1:50 v/v).
Spectroscopically pure N,N0-dibenzhydryl-1,2-diamino-
benzene was obtained as a yellow powder (2.5 g, 57%).
To the yellow powder in 100 mL flask was added 50 mL
4.4. Data for biaryls
4.4.1. 4-Acetylbiphenyl. Mp: 121–123 8C (lit.17 120–
121 8C). H NMR (CDCl3, 500 MHz, 25 8C), d, ppm: 8.00
1
(2H, d, JZ8.3 Hz), 7.69 (2H, d, JZ8.3 Hz), 7.63 (2H, dd,
J1Z7.2 Hz, J2Z1.1 Hz), 7.46 (2H, t, JZ7.5 Hz), 7.39 (1H,

W. Huang et al. / Tetrahedron 61 (2005) 9783–9790
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intensity) 196 (99%, MC), 181 (100%).
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4.4.2. 4-Methylbiphenyl. Mp: 48–50 8C (lit.18 44–46 8C,
49–50 8C). H NMR (CDCl3, 500 MHz, 25 8C), d, ppm:
7.58 (2H, dd, J1Z8.0 Hz, J2Z1.0 Hz), 7.50 (2H, d, JZ
7.5 Hz), 7.38–7.44 (2H, m), 7.29–7.33 (1H, m), 7.24 (2H, d,
JZ8.0 Hz), 2.38 (s, 3H, CH3). EI-MS: m/z (relative
intensity) 168 (100%, MC).
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(CDCl3, 500 MHz, 25 8C), d, ppm: 7.60 (4H, dd, J1Z
7.5 Hz, J2Z1.0 Hz), 7.42–7.46 (4H, m), 7.32–7.36 (2H, m).
EI-MS: m/z (relative intensity) 154 (100%, MC).
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103 8C, 114–114.5 8C). 1H NMR (CDCl3, 500 MHz, 25 8C),
d, ppm: 8.29 (2H, d, JZ8.5 Hz), 7.93 (2H, d, JZ8.5 Hz),
7.62 (2H, d, JZ7.5 Hz), 7.49 (2H, t, JZ7.5 Hz), 7.44 (1H, t,
JZ7.5 Hz). EI-MS: m/z (relative intensity) 199 (99%, MC),
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182 8C (lit.20 180 8C). H NMR (CDCl3, 500 MHz, 25 8C),
d, ppm: 7.38–7.44 (4H, m), 7.31–7.36 (6H, m), 7.15 (2H, s),
2.27 (6H, s, CH3). EI-MS: m/z (relative intensity) 258
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1H NMR (CDCl3, 500 MHz, 25 8C), d, ppm: 7.35–7.50 (2H,
m), 7.30–7.35 (1H, m), 7.15 (2H, d, JZ7.5 Hz), 6.95 (2H,
s), 2.33 (3H, s), 2.00 (6H, s). EI-MS: m/z (relative intensity):
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7.26–7.33 (3H, m), 7.20–7.25 (4H, m), 2.25 (3H, s, CH3).
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Acknowledgements
We thank National Natural Science Foundation of China
(20402006), Shanghai Rising-star program (02QA14016)
and Shanghai Education Commission for financial support.
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