Pyridine mediated palladium acetate-catalysed dehalogenation of biaryl halides in ionic liquid system

Article abstract of DOI:10.3184/174751912X13371621157105

The palladium acetate-catalysed dehalogenation of biaryl halides has been investigated in room temperature ionic liquids with pyridine acting as a co-solvent. The significant effect of pyridine in conjunction with Pd(OAc) ₂ in [bmim][PF₆] gave excellent results in the dehalogenation of biaryl iodines and bromides. The pyridine activated the C2-H of the imidazolium salt to be the source of hydrogen. The separation of desired product was easily performed by extraction with diethyl ether and the Pd(OAc)₂-[bmim][PF₆] system could be recycled five times with only a small decrease in activity. This procedure represents an environmentally friendly method for the preparation of biaryl compounds without the use of complex ligands.

Full text of DOI:10.3184/174751912X13371621157105

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 407
JULY, 407–410
Pyridine mediated palladium acetate-catalysed dehalogenation of biaryl
halides in ionic liquid system
Bingwei Xina*, Chunxiao Jiaa and Zhixun Qib
aKey Laboratory of Coordination Chemistry and Functional Materials in Universities of Shandong (Dezhou University), Dezhou 253023,
P. R. China
bChemical Engineering &Technology, Grade 2009, Class 1, Beijing University of ChemicalTechnology, Beijing 100029, P. R. China
The palladium acetate-catalysed dehalogenation of biaryl halides has been investigated in room temperature ionic
liquids with pyridine acting as a co-solvent. The significant effect of pyridine in conjunction with Pd(OAc)2 in
[bmim][PF6] gave excellent results in the dehalogenation of biaryl iodines and bromides. The pyridine activated the
C2-H of the imidazolium salt to be the source of hydrogen. The separation of desired product was easily performed
by extraction with diethyl ether and the Pd(OAc)2–[bmim][PF6] system could be recycled five times with only a
small decrease in activity. This procedure represents an environmentally friendly method for the preparation of
biaryl compounds without the use of complex ligands.
Keywords: dehalogenation, palladium acetate, ionic liquid, pyridine
Biaryls are important building blocks in the synthesis of natu-
ral products and functional materials.1–5 The development of
new methods for the preparation of biaryls continues to be the
subject of intense investigations. Good results have been
achieved by transition metal-catalysed transformations includ-
ing the Suzuki reaction, a modified Ullmann reaction, the
Stile reaction and the homocoupling of arylboronic acids.
In the past, the dehalogenation of biaryl halides has aroused
interest.6–8 The traditional methods for the dehalogenation
of biaryl carbon–halogen to carbon–hydrogen compounds
involved catalytic hydrogenation,9,10 soluble metal reduc-
tion,11,12 metal hydrides reduction13,14 and other methods.15,16
For example, Nolan and co-workers17 reported using Pd(dba)2
as the catalyst to dehalogenate both aryl chlorides and bro-
mides, employed SIMes.HCl ((2,4,6-trimethylphenyl)dihydroi
midazolium chloride) as the ligand. Although these methods
for dehalogenation are fast and complete, they used an organic
solvent and harsh conditions with complex ligands and other
strong reductants. Hazardous waste was generated by the
organic solvent. Other susceptible groups present in the
structure were also reduced.16
Room temperature ionic liquids (ILs), specially imidazo-
lium ions have been the subject of considerable current interest
as environmentally benign reaction media for organic synthe-
sis.18–20 Their advantages include wide liquid range, good ther-
mal and chemical stability, high ionic conductivity, negligible
vapour pressure, and the potential for recycling. These promis-
ing properties circumvent many of the problems associated
with volatile organic solvents. Furthermore, ionic liquids
facilitate the separation of the products with the retention of
the catalyst in the ionic phase due to their high compatibility
with transition metal catalysts and their immiscibility with
many organic solvents. Recently, ionic liquids have been
adopted as the reaction media for the recycling of catalysts
in a broad range of catalytic reactions. Palladium catalysed
reactions such as Heck,21,22 Suzuki,23–25 Stille,26 and Negishi27
have been reported in ionic liquids. We report our efforts to
develop the Pd(OAc)2/[bmim][PF6]/pyridine/base as a highly
active, air stable and recyclable catalytic system for the deha-
logenation reaction of biaryl iodides and bromides in a short
reaction time to give biaryls. The addition of pyridine to the
ionic liquid system was found to dramatically improve the
reactivity of the dehalogenation.
Results and discussion
To determine the standard conditions, we examined dehaloge-
nation of iodobiphenyl as a model reaction. Iodobiphenyl was
initially treated with 2.2 mol% of Pd(OAc)2 and 4 equiv. of
K2CO3 in 5 g [bmim][PF6] at 100 °C for 3 h in air to give
biphenyl. The separation of the products was easily performed
by extraction with ethyl ether. As shown in Fig. 1, almost no
reaction was observed in pure [bmim][PF6]. However, the
addition of pyridine to the [bmim][PF6] led to a clear increase
in the yield. Increasing the amount of pyridine enhanced, the
yield and an optimum yield (96%) was obtained when the
mass ratio of [bmim][PF6] to pyridine was 17:1. However,
further increasing the amount of pyridine was deleterious to
the reaction. This suggested that pyridine as a co-solvent would
dramatically improve the reactivity of the palladium-catalysed
dehalogenation reaction, and that the reactivity depended on
the ratio of the [bmim][PF6] and pyridine.
The effect of various bases was screened and the results are
presented in Table 1. The inorganic bases (NaOAc, KOAc,
Na3PO4, K3PO4, NaOH, KOH, KF, Na2CO3, K2CO3) and
organic base (Et3N) were examined in the dehalogenation reac-
tion. Na2CO3, K2CO3 and Et3N gave the desired product in high
yield (entries 8–10) and the best yield was obtained using
K2CO3 in 96% yield determined by gas chromatagraphy,
whereas NaOAc, KOAc, NaOH, KOH and KF were found to
be poor bases for the dehalogenation reaction (entries 1, 2 and
5–7). Moderate yields were afforded using Na3PO4 and K3PO4
Fig. 1 Effect of the addition of pyridine on dehalogenation
reaction in [bmim][PF6]. Reaction conditions: iodobiphenyl
(2 mmol), 2.2 mmol%Pd(OAc)2, base (8 mmol), at 100 °C for
3 h, [bmim][PF6] (5 g). Yields were determined by GC and are
the average of two runs.
* Correspondent. E-mail: bingweixin2@163.com

408 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 Effect of bases on the dehalogenation of iodobiphenyl
Table 2 Effect of solvent, temperature and the amount of the
in [bmim][PF6]a
catalyst on the dehalogenation reactiona
Entry
Base
Yield/%b
1
2
NaOAc
KOAc
Na3PO4
K3PO4
NaOH
KOH
42
48
67
72
49
50
46
87
96
83
Entry
Temp/°C
IL
Yield/%b
3
1
2
100
100
100
100
100
100
60
[PEG1mim][Cl]
[PEG1mim][BF4]
[PEG1mim][PF6]
[bmim][Cl]
[bmim][BF4]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
4
7
4
5
3
10
10
57
96
70
79
86
93
97
87c
70d
6
4
7
KF
5
8
Na2CO3
K2CO3
Et3N
6
9
7
10
8
70
a Reaction conditions: iodobiphenyl (2 mmol), 2.2 mmol%
Pd(OAc)2, base (8 mmol), pyridine (0.3 g), at 100 °C for 3 h,
[bmim][PF6] (5 g). b Yields were determined by GC and are the
average of two runs.
9
80
10
11
12
13
90
110
100
100
a Reaction conditions: iodobiphenyl (2 mmol), 2.2 mmol%
Pd(OAc)2, K2CO3 (8 mmol), pyridine (0.3 g), 3 h, IL (5 g).
b Yields were determined by GC and are average of two runs.
c 1.0 mmol% of Pd(OAc)2. d 0.5 mmol% of Pd(OAc)2.
as bases (entries 3 and 4). K2CO3 was therefore used as the
base in the following reactions.
Next, we employed iodobiphenyl to examine how the ionic
liquid, temperature, and the amount of Pd(OAc)2 affected the
dehalogenation reactions (Table 2). Ionic liquids containing
1-(2-hydroxyethyl)-3-methylimidazolium cation ([PEG1mim])
and dialkyl imidazolium cation ([bmim]) were studied. It was
found that PEG-ILs did not promote the reaction (entries 1–3).
However, ionic liquids consisting of 1,3-dialkylimidazolium
salts could improve the dehalogenation reaction. The countera-
nion influenced the reactivity of reaction strongly. When the
anion was Cl−, lower yield (10%) was observed under the
reaction conditions (entry 4). However, the hydrophobic 1-
butyl-3-methylimidazolium hexafluorophosphate [bmim][PF6]
significantly increased the reactivity to 96% (entry 6), while
the hydrophilic [bmim][BF4] had poor effect on the reactivity
(57%, entry 5). These results suggested that [bmim][PF6] was
superior to [bmim][BF4] and [bmim][Cl] as the media for the
dehalogenation reaction.
Reducing the temperature to 60 °C had a dramatic effect on
the dehalogenation reaction and the yield decreased to 70%
yield in the [bmim][PF6]-pyridine system (entry 7). Increasing
the temperature from 70 °C to 90 °C had a positive effect
on the reaction (entries 8–10). However, an increase of the
temperature to 110 °C hardly changed the yield (entry 11)
compared with 100 °C. Therefore, we employed a reaction
temperature of 100 °C (entry 6).
Pd(OAc)2 proved to be an excellent catalyst in the
[bmim][PF6]-pyridine system (Table 2). All the entries above-
described employed 2.2 mmol% of Pd(OAc)2. We attempted to
reduce the amount of catalyst but it was found that decreasing
the amount of Pd(OAc)2 from 1.0 mmol% to 0.5 mmol% had a
negative effect on the conversion (entries 12 and 13).
In an attempt to extend the scope of Pd(OAc)2/[bmim][PF6]/
pyridine/base system, several representative biaryl iodides
with different functional groups were tested, as shown in Table
3. As can be seen electron-rich iodobiphenyls showed an excel-
lent reactivity and furnished the products in high yield and in a
short reaction time (entries 2–4). This system was less efficient
in catalysing the dehalogenation of the electron-deficient iodo-
biphenyl (entries 7 and 8). 4-MeO-biphenyl was obtained in
97% yields from iodo-4-MeO-biphenyl-I, whereas 1-iodo-4-
nitrobiphenyl gave the nitrobiphenyl with a yield of only 57%.
A biaryl iodide with meta-substituent gave the corresponding
products in good yields (entry 4), showing that the steric
hindrance played little effect. Furthermore, reduction of
4-chloroiodobiphenyl gave exclusively 4-chlorobiphenyl in
87% yield, showing good chemoselectivity (entry 5).
Table 3 Dehalogenation of iodo biaryls in [bmim][PF6]a
Entry R
Product
Yield
/%b
M.p.
/°C
Lit. m.p.
/°C Ref.
1
2
3
H
96
97
94
68.8–68.9
88.3–89.1
46.7–47.0
69.029
86.0–90.030
44–4730
4-MeO
4-Me
4
2-Me
94 Yellow liquid
–2.031
5
6
7
4-Cl
4-Br
87
40
65
31.7–32.3
90.3–90.8
32.032
89.0–92.032
4-
MeCO
117.0–121 118.0–123.031
8
4-NO2
57
113.7–114.2
114.030
a Reaction conditions: biaryl iodide (2.0 mmol), 2.2 mmol%
Pd(OAc)2, K2CO3 (8 mmol), pyridine (0.3 g), [bmim][PF6] (5 g),
3 h, 100 °C. b Yields were determined by GC and are average of
two runs.
results encouraged us to investigate the possibility of deha-
logenation of biaryl bromides using the [bmim][PF6]–pyridine
system. We employed 4-bromobiphenyl as the substrate for the
debromination. A low conversion was obtained under the reac-
tion conditions described above. However, we found surpris-
ingly that prolonging the reaction time to 6 h and increasing
the reaction temperature to 120 °C ensured that the reaction
proceeded smoothly and afforded the desired products. As
shown in Table 4, 1-bromobiphenyl gave excellent yields with
89% (entry 1) and the electron-donating (entries 2–4) biaryl
bromides with electron-donating substituents were dehaloge-
nated cleanly to the corresponding products in good to excel-
lent yields. The electron-withdrawing biaryl bromides with
electron-withdrawing substituents gave low yields (entries 6–
9). The reduction of biaryl chlorides was also attempted under
similar conditions. However, there was only a trace reduction
product, while prolonging the reaction time and raising the
reaction temperature did not increase the yield.
However, 1-iodo-4-Br-biphenyl gave lower yield (only
40%) with a large amount of biphenyl being formed. These

JOURNAL OF CHEMICAL RESEARCH 2012 409
Table 4 Dehalogenation of bromobiaryl in [bmim][PF6]a
mass spectroscopy. Considering the possible source of the
hydrogen in this system, we suggest a plausible mechanism,
shown in Scheme 1. Palladium acetate is converted to the
active Pd0 species in ionic liquids,33–35 and the subsequent
oxidative addition of aryl halide onto palladium gives the
palladium complex of 1. It has been well documented that
deprotonation of C2 of imidazolium salts generates N-hetero-
cyclic carbene ligands (NHC) which form metal–carbene–
hydride complexes in situ during the course of catalysis. A
weak base is often necessary to deprotonate such salts under
the reaction conditions.36,37 Therefore, utilisation of pyridine as
the potential acceptor of H+ activates the C2–H of imidazolium
salt, and induce Pd to insert into the C2–H bond, promoting the
formation of (aryl)(NHC)palladium–H hydride intermediate
2.38 Following reductive elimination of 2 produces the hydro-
dehalogenation product,39 and X− is removed as the form
[bmim]X, which results in the regeneration of the palladium
catalyst, completing the catalytic cycle. [Bmim]X can undergo
counteranion exchange, recycling to [bmim][PF6] with the
generation of KX.
Entry
R
H
Product
Yield/%b
1
2
3
89
85
86
4-MeO
4-Me
4
2-Me
82
5
4-Cl
4-MeCO
4-NO2
4-CN
68
38
30
37
40
6
7
8c
9d
Conclusion
4-CF3
An efficient and recyclable catalytic biaryl dehalogenation
protocol has been developed using a palladium/[bmim][PF6]/
pyridine/base system. The use of pyridine in conjunction with
Pd(OAc)2 in mild conditions with [bmim][PF6] was found to
be the most effective for the dehalogenation of biaryl iodines
and bromides in short times. The use of an ionic liquid repre-
sents an environmentally friendly method for the preparation
of biaryl compounds, and results in the easy isolation of the
product as well as catalyst recycling.
a Reaction conditions: biaryl bromide (2.0 mmol), 2.2 mmol%
Pd(OAc)2, K2CO3 (8 mmol), pyridine (0.3 g), [bmim][PF6] (5 g),
6 h, 120 °C. b Yields were determined by GC and are average of
two runs. c M.p. of biphenyl-4-carbonitrile is 88.3–89.1 °C (litera-
ture m.p. 86.0–90.0 °C). d M.p. of 4-trifluoromethyl-biphenyl is
94.9–95.3 °C (literature m.p. 95.3 °C).
The reusability of the catalytic system was tested in the
dehalogenation reaction of iodobiphenyl under the optimum
reaction condition. Since [bmim][PF6] was insoluble in diethyl
ether, the products were easily isolated by simple extraction
with diethyl ether. The residue was washed with water several
times to remove the salt and byproducts generated in reaction,
which might retard the rate of the reaction.28 During this
process, [bmim][PF6] and Pd(OAc)2 were not affected because
they were immiscible with water. The remainder of the ionic
liquid and catalyst were recovered and reused with the
same substrates. It was found that the catalytic system could
be recycled five times with only a small decrease in activity
(Fig. 2).
Experimental
Starting materials and solvents were purchased from common
commercial sources and were used without additional purification.
1H NMR spectra were recorded at Bruker 400MHz Avance, using
TMS as internal standard. Mass spectroscopic data for the products of
dehalogenation reaction were collected on an Agilent 5975C MS-EI
instrument. Melting points were measured on X-4 melting-point
device.
Representative procedure for the dehalogenation reaction: A
mixture of biaryl halides (2 mmol), Pd(OAc)2 (5 mg, 2.2 mol%), base
(8 mmol), pyridine (0.3 g), IL (5 g) were stirred at a temperature of
100 °C for 3 hours. After the reaction the solution was cooled to room
temperature and the resulting solid was extracted with anhydrous
diethyl ether (4 × 15 mL). The combined diethyl ether phases were
concentrated. Further purification of the product was achieved by
To identify the mechanism of the reaction, we replaced the
pyridine by deuteriated pyridine as cosolvent in the dehaloge-
nation of iodobiphenyl. However, the product was identified as
still biphenyl rather than D-biphenyl by 1H NMR spectra and
Fig.2 RecyclingofPd(OAc)2/[bmim][PF6]/pyridine/basecatalytic
system. Reactionconditions:iodobiphenyl(2.0mmol), 2.2mmol%
Pd(OAc)2, K2CO3 (8 mmol), pyridine (0.3 g), [bmim][PF6] (5 g),
3 h, 100 °C.
Scheme 1 The plausible mechanism for the pyridine
mediated palladium acetate-catalysed dehalogenation of
biaryl halides in ionic liquid system.

410 JOURNAL OF CHEMICAL RESEARCH 2012
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Received 26 February 2012, accepted 16 April 2012
Paper 1201183 doi: 10.3184/174751912X13371621157105
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