Imidazolium supported palladium-chloroglycine complex: Recyclable catalyst for Suzuki-Miyaura coupling reactions

Article abstract of DOI:10.1016/j.tetlet.2013.10.111

1-Glycyl-3-methyl imidazolium chloride-palladium(II) complex [[Gmim]Cl-Pd(II)] was found to be a catalyst for the Suzuki-Miyaura reaction with excellent yields with high turnover number (6.5 × 10²-9.4 × 10²).

Full text of DOI:10.1016/j.tetlet.2013.10.111

Tetrahedron Letters 54 (2013) 7193–7197
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Tetrahedron Letters
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Imidazolium supported palladium–chloroglycine complex:
recyclable catalyst for Suzuki–Miyaura coupling reactions
a
a
b
Parasuraman Karthikeyan a, , Arumugam Vanitha , Pachaiappan Radhika , Kannan Suresh ,
⇑
Arunachalam Sugumaran b
a Department of Chemistry, Arunai College of Engineering, Tiruvannamalai 606 603, Tamilnadu, India
b Department of Mathematics, Government Arts College, Tiruvannamalai 606 603, Tamilnadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Glycyl-3-methyl imidazolium chloride–palladium(II) complex [[Gmim]Cl–Pd(II)] was found to be a
catalyst for the Suzuki–Miyaura reaction with excellent yields with high turnover number
(6.5 Â 102–9.4 Â 102).
Received 20 September 2013
Revised 23 October 2013
Accepted 24 October 2013
Available online 30 October 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Suzuki–Miyaura
Green chemistry
Catalyst
Development of recoverable and reusable catalysts for indus-
trial applications has become significant from ecological point of
view and has been well reviewed in the literature.1,10,11 In recent
years, metal complex ionic liquids have emerged as a set of green
solvent with unique properties such as tunable polarity, high ther-
mal stability, and immiscibility with a number of organic solvents,
negligible vapor pressure, and recyclability. Their non-volatile
character and thermal stability makes the metal complexes
potentially attractive alternatives to environmentally unfavorable
organic co-solvents. They are particularly promising as solvents
for the immobilization of transition metal catalysts, Lewis acids,
and enzymes.2 As a result of their green credential and potential
to enhance reaction rate and selectivities, ionic liquids are finding
growing use in organic synthesis.
The Suzuki–Miyaura reaction is an important task due to
valuable applications in both laboratory and industry. Moreover;
Suzuki cross-coupling reaction has emerged as one of the most
powerful, attractive, and widely utilized methods for the formation
of new carbon–carbon bonds. Additional advantages of the Suzuki–
Miyaura reaction include high tolerance toward functional groups
as substituent in substrates, mild reaction conditions, possibility of
performing the reaction in water, and in air.3
reactions at ambient temperature4 and Hou et al., reported the
effect of counterions and central cores of tripodal imidazolium
salts on palladium-catalyzed Suzuki–Miyaura cross-coupling reac-
tions.5a Furthermore, de Souza et al., have reported microwave as-
sisted Suzuki reaction in N-butyl pyridinium salts/water systems.5b
Wang et al., illustrated the use of palladium nanoparticles immobi-
lized by click ionic copolymers for Suzuki–Miyaura cross-coupling
reaction in water.6 Iranpoor et al., exemplified the palladium nano-
particles supported on silica diphenyl phosphinite (SDPP) as effi-
cient catalyst for Mizoroki–Heck and Suzuki–Miyaura coupling
reactions.7 Herein, we report a protocol based on palladium func-
tionalized 1-glycyl-3-methyl imidazolium chloride (Fig. 1), which
proved to be highly efficient at 25 °C for C–C bond formation.
However, recovery and leaching can occur in the extractive
work up resulting in the loss of catalyst from the reaction mixture
and requires additional effort to purify the extracted product. To
overcome such problems, novel palladium complex was devel-
oped8 by covalent linking of organo catalytic unit with an ionic
liquid moiety (often chloroglycine). This imparts low solubility of
O
H2
O
N
N
Cl
N
Cl
In the last 2 years, Wang et al., described silica supported
palladium–phosphine complex for Suzuki–Miyaura cross-coupling
Pd
N
N
N
H2
O
O
⇑
Corresponding author. Tel.: +91 9952754052.
E-mail address: pkarthikeyan99@gmail.com (P. Karthikeyan).
Figure 1. 1-Glycyl-3-methyl imidazolium chloride-palladium(II) complex
[[Gmim]Cl-Pd(II)].
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.10.111

7194
P. Karthikeyan et al. / Tetrahedron Letters 54 (2013) 7193–7197
Table 2
catalyst in the solvents used for extraction of the product on the
one hand and high solubility in the reaction medium on the other
hand.9 This strategy was applied to Suzuki reaction providing high
yields and good recyclability of the catalyst.10,11
The objectives of the present study are to: (i) develop an effi-
cient synthetic process for the facile conversion of Suzuki–Miyaura
reaction. (ii) The present method developed for the Suzuki–Miya-
ura reaction offers many advantages including high conversion,
short duration, and the involvement of non-toxic reagent.
The palladium complex catalyzed Suzuki–Miyaura reaction was
carried out using phenyl boronic acid and bromo benzene as a
model reaction to investigate different parameters, such as effects
of solvent and duration, diverse bases, different catalysts, and its
concentration. Initially, the influence of different bases on the
model reaction was studied and these results are summarized in
Table 1. It was observed that, organic bases showed maximum con-
version over the inorganic bases. Moreover, this reaction was
unsuccessful in the absence of base (Table 1, entry 1). There was
no product formation between phenyl boronic acid and bromo
benzene in the presence of pyridine and imidazole (Table 1, entries
2 and 3). Furthermore, Suzuki–Miyaura reaction was carried out
using K2CO3, KOH, NaOH, and Et3N; from the results the formation
of biphenyl increases from 40% to 94% (Table 1, entries 4–7). After
standardizing the best catalyst systems, we further optimized the
reaction conditions in the presence of Et3N.
The experimental results show that the decrease of reaction
time from 20 h to 1 h gave full conversion and 94% yield (Table 1,
entries 8–13). However, the yields dropped appreciably on
decreasing the time from 1 h to 0.25 h (Table 1, entries 14–16).
From these experimental results it was concluded that 1 mmol
Et3N is sufficient to complete the reaction in 1 h at 25 °C.
Subsequently, in order to find a suitable solvent for the reaction,
the coupling of bromo benzene and phenyl boronic acid was car-
ried out with different solvents and Et3N. According to publications
from Wang,4 Hou,5 Wang,6 and Iranpoor7 polar, aprotic solvents
tend to give the best results. Among the previous reports, catalysis
in the presence of 1-aminoethyl-3-methyl imidazolium bromide
Effect of the solvent on the Suzuki–Miyaura reactiona
Br
B(OH)2
[Gmim]Cl-Pd(II)
+
25°C/Base
[Aemim]Br
Entry
Solvent
Temp (°C)
Time (h)
Yieldb (%)
TONc
TOFc
1
2
3
4
5
6
7
8
9
Methanol
Ethanol
DCM
CHCl3
THF
CH3CN
DMF
[Aemim]Br
[Aemim]Br
[Aemim]Br
Water (5 mL)
50
65
35
50
50
60
130
25
20
35
90
24
24
24
24
24
24
24
1
Trace
Trace
Trace
Trace
Trace
51
67
94
90
95
—
—
—
—
—
—
—
—
—
—
510
670
940
900
950
430
21
27
940
900
950
17
1
1
24
10
11
43
a
Reaction condition: Bromo benzene (1 mmol), phenyl boronic acid (1.2 mmol),
solvent (5 mL), Et3N (1 mmol), solvent (1 mL), and [Gmim]Cl-Pd(II) (0.1 mol %)
stirring at different temperatures (see Table 2).
b
Yield determined by HPLC.
c
TON, turnover number; TOF, turnover frequency (mol product molÀ1 catalyst
hÀ1).
Table 3
Effect of various catalysts on Suzuki–Miyaura reactiona
Br
B(OH)2
[Gmim]Cl-Pd(II)
+
25°C/Base
[Aemim]Br
Entry
1
Catalyst
-Glycine
Time (h)
Yieldb (%)
TONc
—
TOFc
—
24
Trace
L
2
3
4
5
6
7
Chloroglycine [Cl-gly]
PdCl2/[Cemim]Br
PdCl2/[Aemim]Br
PdCl2/[Gmim]Cl
[Gmim]Cl-Pd(II)
[Gmim]Cl-Pd(II)
24
24
24
24
1
Trace
65
70
75
94
—
—
27
29
31
940
470
650
700
750
940
940
2
94
a
Reaction condition: Bromo benzene (1 mmol), phenyl boronic acid (1.2 mmol),
Table 1
triethylamine (1 mmol), [Aemim]Br (1 mL), and catalyst (0.1 mol %) stirring at
Effect of the base and time on Suzuki–Miyaura reactiona
25 °C.
b
Br
Yield determined by HPLC.
B(OH)2
[Gmim]Cl-Pd(II)
+
c
TON, turnover number; TOF, turnover frequency (mol product molÀ1 catalyst
hÀ1).
25°C/Base
[Aemim]Br
Entry
Base
Time (h)
Yieldb (%)
TONc
TOFc
[Aemim]Br was the most productive, as compared with the polar
and non-polar solvents (Table 2). This may be due to the easy coor-
dination of complex with organic co-solvents. It has also been re-
ported that water molecule sometimes is required to activate the
Pd(II) catalyst. In our case, carrying out the reaction in H2O
(5 mL) 90 °C gave a negative effect on the product yield in compar-
ison with [Aemim]Br. This lower yield could be due to decomposi-
tion of the complex under aqueous conditions.
Next, in order to optimize the conditions for this coupling reac-
tion of bromo benzene and phenyl boronic acid, the reaction was
executed in the presence of Et3N using different catalysts and the
results are given in Table 3. When the reaction was carried out
using various catalysts such as chloroglycine, PdCl2/1-carboxy
ethyl-3-methyl imidazolium bromide [Cemim]Br, PdCl2/[Ae-
mim]Br, and PdCl2/[Gmim]Cl with Et3N, it gave trace to 75% of
product respectively (Table 3, entries 1–5). When the same reac-
tion was conducted with [Gmim]Cl-Pd(II) as a catalyst it gave good
yield of the product in short duration (Table 3, entry 6). No further
increase in yield was observed on increasing the reaction time
(Table 3, entry 7).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
—
24
24
24
24
24
24
24
20
18
12
6
3
1
0.75
0.50
0.25
Trace
—
—
—
—
—
—
—
20
20
22
39
47
52
Imidazole
Py
—
KOH
K2CO3
NaOH
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
48
50
55
94
94
94
94
94
94
94
90
86
83
480
500
550
940
940
940
940
940
940
940
900
860
830
78
156
313
940
1200
1720
3320
a
Reaction condition: Bromo benzene (1 mmol), phenyl boronic acid (1.2 mmol),
different base (1 mmol), [Aemim]Br (1 mL), and [Gmim]Cl-Pd(II) (0.1 mol %) stirring
at 25 °C.
b
Yield determined by HPLC.
c
TON, turnover number; TOF, turnover frequency (mol product molÀ1 catalyst
hÀ1).

P. Karthikeyan et al. / Tetrahedron Letters 54 (2013) 7193–7197
7195
Table 4
Based on previous reports, increasing the quantity of the cata-
lyst improved the reaction yield and shortened reaction time. Ini-
tially, C-C formation was carried out in the absence of catalyst at
ambient temperature; it was found that no product was formed
even after 48 h (Table 4, entry 1). When the amount of the catalyst
was increased from 0.025 to 0.075 mol %, the yield increased from
58% to 79% (Table 4, entries 2–4). However using 0.1 mol % of
[Gmim]Cl-Pd(II), biphenyl was obtained with 94% in 1 h (Table 4,
entries 5–10). Almost similar yield was achieved by increasing
the catalyst amount from 0.1 to 0.15 mol % (Table 4, entry 11 and
12). Therefore, Suzuki–Miyaura reaction was carried out at the mo-
lar radio of bromo benzene, phenyl boronic acid, triethylamine,
[Aemim]Br, and [Gmim]Cl-Pd(II) 1:1.2:1:1 mL:0.1% mmol at ambi-
ent temperature.13
The substrate scope of the reaction of substituted aryl halides
with phenyl boronic acid is presented in Table 5. A wide range of
aromatic halides can be efficiently used in the Suzuki–Miyaura
reactions. Both electron-rich and electron-poor aryl halides could
be successfully converted to the desired products in (1–10 h) at
room temperature. On the other hand, the reaction of aryl chlo-
rides with phenyl boronic acid is usually very slow with moderate
yields.
Effect of the catalyst loading on Suzuki–Miyaura reactiona
Br
B(OH)2
[Gmim]Cl-Pd(II)
+
25°C/Base
[Aemim]Br
Time (h)
Entry
[Gmim]Cl-Pd(II) (mol %)
Yieldb (%)
TONc
TOFc
1
2
3
4
5
6
7
8
9
—
48
24
24
24
24
18
12
6
3
1
1
1
—
58
64
79
94
94
94
94
94
94
95
95
—
580
640
790
940
940
940
940
940
940
950
950
—
24
26
32
39
0.025
0.05
0.075
0.1
0.1
0.1
0.1
0.1
0.1
0.125
0.15
52
78
156
313
940
950
950
10
11
12
a
Reaction condition: Bromo benzene (1 mmol), phenyl boronic acid (1.2 mmol),
triethylamine (1 mmol), [Aemim]Br (1 mL), and catalyst (0.1 mol %) stirring at
25 °C.
b
Yield determined by HPLC.
c
TON, turnover number; TOF, turnover frequency (mol product molÀ1 catalyst
hÀ1).
Table 5
Suzuki–Miyaura reaction of different aryl halides with phenyl boronic acid in the presence of [Gmim]Cl-Pd(II)/[Aemim]Br and Et3N as basea
Entry
Aryl halides
Product
Time (h)
Yieldb (%)
TONc
940
TOFc
940
Br
1
1
94
5a
5b
Br
2
3
4
1.5
3
93
89
83
930
890
830
620
296
553
Br
5c
Br
Cl
1.5
Cl
5d
Br
NO2
5
2.5
90
900
360
O2N
5e
O
Br
6
7
1.5
2
92
90
920
900
613
450
O
Br
O
5f
O
5g
Br
O
8
2
92
920
460
O
5h
(continued on next page)

7196
P. Karthikeyan et al. / Tetrahedron Letters 54 (2013) 7193–7197
Table 5 (continued)
Entry
Aryl halides
Product
Time (h)
2
Yieldb (%)
90
TONc
900
TOFc
450
Cl
9
5i
5j
Cl
10
2
3
85
90
850
900
425
300
O
Cl
O
11
12
5k
5l
NO2
Cl
2.5
82
820
328
O2N
Br
Cl
13
14
3
5
69
65
690
650
230
130
5m
5n
5o
15
16
2
2
83
82
830
820
415
410
N
N
Br
N
Br
5p
N
Br
N
O
17
18
3.5
79
93
790
930
225
186
N
O
5q
5r
Br
5
N
N
N
N
N
N
19
20
7
7
90
92
900
920
128
131
Br
5s
5t
S
S
Br
Cl
N
O
21
22
10
10
80
85
800
850
80
85
N
O
5u
5v
Cl
N
N

P. Karthikeyan et al. / Tetrahedron Letters 54 (2013) 7193–7197
7197
Table 5 (continued)
Entry
Aryl halides
Product
Time (h)
10
Yieldb (%)
TONc
740
TOFc
N
N
N
N
Cl
Cl
23
24
74
74
76
5w
5x
10
76
760
N
N
All the compounds were characterized and compared to the literature.12
a
Reaction condition: Aryl halide (1 mmol), phenyl boronic acid (1.2 mmol), triethylamine (1 mmol), [Aemim]Br (1 mL), and [Gmim]Cl-Pd(II) (0.1 mol %) stirring at 25 °C.
Yield determined by HPLC.
b
c
TON, turnover number; TOF, turnover frequency (mol product molÀ1 catalyst hÀ1).
Srinivasan, K. V. Tetrahedron. Lett. 1815, 2003, 44; (e) Jarikote, D. V.; Siddiqui, S.
A.; Rajgopal, R.; Thomas, D.; Lahoti, R. J.; Srinivasan, V. Tetrahedron. Lett. 1835,
2003, 44.
Isolation of the heterogeneous catalyst was easily performed by
extraction or centrifugation. The isolated catalyst was washed with
diethyl ether and dried in air. The regenerated catalyst was used
for the reaction of bromo benzene with phenyl boronic acid for
eight runs to afford biphenyl with 94–86% isolated yields (Table 5).
The precise mechanism of the catalytic reaction needs to be
elucidated.
In summary, we have introduced [Gmim]Cl-Pd(II) as a catalyst
for Suzuki–Miyaura reaction with Et3N/[Aemim]Br in the absence
of an organic co-solvent. Aryl bromides reacted efficiently with
phenyl boronic acid at ambient temperature in the presence of
the catalyst. The [Gmim]Cl-Pd(II) is better than most of the re-
ported catalysts. The catalyst could be reused for 8 consecutive cy-
cles without any significant loss of its catalytic activity.
3. (a) Wu, X. F.; Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010,
49, 9047; (b) Wiedermann, J.; Mereiter, K.; Kirchner, K. J. Mol. Catal. A: Chem.
2006, 257, 67; (c) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871; (d) Hagiwara, H.; Ko, K. H.; Hoshi, T.;
Suzuki, T. Chem. Commun. 2007, 2838; (e) Yu, Y.; Hu, T.; Chen, X.; Xu, K.; Zhang,
J.; Huang, J. Chem. Commun. 2011, 3592; (f) Sau, S. C.; Santra, S.; Sen, T. K.;
Mandal, S. K.; Koley, D. Chem. Commun. 2012, 555; (g) Gyton, M. R.; Cole, M. L.;
Harper, J. B. Chem. Commun. 2011, 9200.
4. Chen, W.; Li, P.; Wang, L. Tetrahedron 2011, 67, 318.
5. Recent publication on Suzuki–Miyaura coupling reactions, see: (a) Zhong, R.;
Wang, Y. N.; Guo, X. Q.; Hou, X. F. J. Organomet. Chem. 2011, 696, 1703; (b)
Castro, K. L. S.; Lima, P. G.; Miranda, L. S. M.; de Souza, R. O. M. A. Tetrahedron
Lett. 2011, 52, 4168.
6. Zhang, D.; Zhou, C.; Wang, R. Catal. Commun. 2012, 22, 83.
7. Recent publication on Suzuki–Miyaura coupling reactions, see: (a) Firouzabadi,
H.; Iranpoor, N.; Gholinejad, M. J. Organomet. Chem. 2010, 695, 2093; (b)
Iranpoor, N.; Firouzabadi, H.; Motevalli, S.; Talebi, M. J. Organomet. Chem. 2012,
708–709, 118.
Acknowledgments
8. Redon, R.; Garcia-Pena, N. G.; Ugalde-Saldivar, V. M.; Garci, J. J. J. Mol. Catal. A:
Chem. 2009, 300, 132.
We gratefully acknowledge the Management of VIT University
and ACE-Campus for providing required facilities and SIF (VIT)
for providing the spectral data.
9. (a) Miao, W. S.; Chan, T. H. Adv. Synth. Catal. 2006, 348, 1711; (b) Lombardo, M.;
Pasi, F.; Easwar, S.; Trombini, C. Adv. Synth. Catal. 2007, 349, 2061; (c) Zhou, L.;
Wang, L. Chem. Lett. 2007, 36, 628; (d) Lombardo, M.; Pasi, F.; Easwar, S.;
Trombini, C. Synlett 2008, 2471; (e) Lombardo, M.; Easwar, S.; DeMarco, A.;
Pasi, F.; Trombini, C. Org. Biomol. Chem. 2008, 6, 4224.
Supplementary data
10. (a) Karthikeyan, P.; Muskawar, P. N.; Aswar, S. A.; Bhagat, P. R.; Sythana, S. K. J.
Mol. Catal. A: Chem. 2012, 358, 112; (b) Karthikeyan, P.; Muskawar, P. N.; Aswar,
S. A.; Bhagat, P. R.; Sythana, S. K. Appl. Organometal. Chem. 2012, 26, 562.
11. (a) Karthikeyan, P.; Aswar, S.A.; Muskawar, P.N.; Sythana, S.K.; Bhagat, P.R.;
Senthil Kumar, S.; Satvat, P.S. Arabian. J. Chem. doi: 10.1016/
j.arabjc.2011.11.007.; (b) Yang, S. D.; Wu, L. Y.; Yan, Z. Y.; Pan, Z. L.; Liang, Y.
M. J. Mol. Catal. A: Chem. 2007, 268, 107.
12. (a) Nishio, R.; Sugiura, M.; Kobayashi, S. Org. Lett. 2005, 7, 4831; (b) Zhang, L.;
Meng, T. H.; Wu, J. J. Org. Chem. 2007, 72, 9346; (c) Xu, L.; Li, B. J.; Wu, Z. H.; Lu,
X. Y.; Guan, B. T.; Wang, B. O.; Zhao, K. O.; Shi, Z. J. Org. Lett. 2010, 12, 884.
13. General experimental procedure for the Suzuki–Miyaura reaction: In a conical
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.10.
111. These data include MOL files and InChiKeys of the most
important compounds described in this article.
References and notes
flask (50 mL),
a mixture of aryl halide (1 mmol), phenyl boronic acid
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(1.2 mmol), triethylamine (1 mmol), [Aemim]Br (1 mL), and [Gmim]Cl-Pd(II)
(0.1 mol %, 5 mg) was added and stirred at 25 °C for a period as indicated in
Table
5 (The reaction was monitored by HPLC and TLC). The resulting
heterogeneous mixture was extracted with ethyl acetate or diethyl ether
(3 Â 5 mL). The organic phase was separated and dried over anhydrous Na2SO4
and evaporated. Evaporation of the solvent gave the crude product residue
which was further purified by flash chromatography using n-hexane/EtOAc
(9:1 v/v) to give the desired coupling product in 82–94% isolated yields.