Ligand-free Pd catalyzed cross-coupling reactions in an aqueous hydrotropic medium

Article abstract of DOI:10.1039/c5gc02314a

A simple, efficient and ligand-free protocol for the Suzuki-Miyaura reaction and base-free Heck-Matsuda reactions under mild reaction conditions have been developed over palladium supported on activated carbon (Pd/C) in an aqueous hydrotropic solution. The catalyst Pd/C was fully characterized by TG-DTA, SEM, EDS, XRD, XPS, BET and ICP-AES analyses. This green methodology represents a cost-effective and operationally convenient method for the synthesis of a variety of biaryls, prochiral ketones, and acrylates under the conditions that are tolerant for a broad range of functional groups with good to excellent yields. The developed Pd/C-aqueous hydrotrope combined catalytic system is well suited for the 3R approach (reducible, robust, and recyclable) for different cross-coupling reactions without an appreciable loss of its activity.

Full text of DOI:10.1039/c5gc02314a

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Page 1 of 25
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Ligand-free Pd Catalyzed Cross-coupling Reactions in Aqueous Hydrotropic Medium
a
a
b
a
Sanjay N. Jadhav , Arjun S. Kumbhar , Chadrashekhar V. Rode , Rajashri S. Salunkhe *
a
Department of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India
b
CSIR-National Chemical Laboratory, Pune-411008, M. S. India
Eꢀmail: rss234@rediffmail.com
∗Corresponding Author Tel. +91 231 260 9240; fax: +91 231 269 2333.
Abstract
A simple, efficient and ligandꢀfree protocol for the SuzukiꢀMiyaura reaction and baseꢀ
free HeckꢀMatsuda reactions under mild reaction conditions has been developed over
palladium supported on activated carbon (Pd/C) in aqueous hydrotropic solution. The catalyst
Pd/C was fully characterized by TGꢀDTA, SEM, EDS, XRD, XPS, BET and ICPꢀAES
analysis. This green methodology represents a costꢀeffective and operationally convenient
method for synthesis of a variety of biaryls, prochiral ketones, and acrylates under conditions
that are tolerant for a broad range of functional groups with good to excellent yields. The
developed Pd/Cꢀaqueous hydrotrope combined catalytic system is well suitable for 3R
approach (reducible, robust, and recyclable) for different crossꢀcoupling reactions without
appreciable loss of its activity.
Keywords: Palladium, Crossꢀcouplings, Pd/C, Hydrotropes, Aqueous, Prochiral Ketones,
Acrylates.
Introduction
Biphenyls and acrylates constitute a class of key structural motifs present in numerous
biologically important compounds, e. g. Biphenylindanone A, Nifedipine, Losartan HIVꢀ1
1
Protease and Taxol as they are present as subunits in many marketed drugs. They also
2
constitute the basis for a number of natural molecules with different biological activities.
These compounds are also useful for the construction of structurally important compounds,
such
as
triphenylaminoꢀ1,8ꢀnaphthalimides,
poly(9,9ꢀdihexyl)ꢀfluorene
and
3
Benzothiadiazole− cyclopentadithiophene (BTZꢀCDT), which are widely used in solar cells
4
and electroluminescent materials. There has been considerable interest in designing and
5
synthesizing compounds containing such motifs by using transition metal catalysts. The
number of palladium catalyzed CꢀC crossꢀcoupling reactions were explored including
6
7
8
9
10
11
SuzukiꢀMiyaura, Stille, Negishi, Hiyama, Songashira, MizorokiꢀHeck and Heckꢀ
1

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12
Matsuda. Out of these, SuzukiꢀMiyaura and HeckꢀMatsuda crossꢀcoupling reactions are
13
reliable and powerful methods to form CꢀC bond for the synthesis of biaryls, prochiral
14
15
ketones, and acrylates.
Recently, ligandless approach for the carbonꢀcarbon bond forming crossꢀcoupling
16
reaction has attracted an increasing attention as it renders the process more cost effective
17
and also avoids the contamination of ligands and metal in the final product. Such a
18
ligandless catalysis is achieved by Pd(0) species in the form of Pd nanoparticles. Although
the ligandless Pd catalyzed reactions are frequently performed with reasonably faster rates in
water, but many a times complete conversion of the substrate is not possible, due to the active
19
Pd(0) species undergo quick agglomeration under these conditions. This drawback of
ligandless coupling may be overcome by dispersing catalytic material in in an aqueous
2
0
21
hydrotropic medium as it possesses surfactant like properties. In addition, hydrotropism
22
which is similar to miceller catalysis has a great advantage of increasing the potential of
water as a solvent for organic synthesis. This enables the replacement of toxic, expensive,
flammable and volatile organic solvents by easily available water which is highly desirable,
from economic as well as environmental points of view. Hydrotropism gives a very simple
protocol for solubilizing several types of organic functionalities at room temperature in
absence of coꢀsolvent and without modification in commercial catalyst design. Recently, we
23
reported the use of hydrotropes for synthesis of many heterocyclic compounds,
demonstrating that hydrotrope can serve as an excellent reaction medium.
Supported Pd catalysts were developed for CꢀC coupling reactions primarily with the
24
objective of easy separation of precious Pd metal from reaction mixture. For this purpose,
activated carbon with high specific surface area and large pore size playshas been extensively
25ꢀ26
used.
Activated carbon supported Pd catalysts have been widely applied for the oxidation
27
28
28
29
of organic compounds, chemical syntheses, hydrogen storage, electrocatalysis and
3
0
selective hydrogenation. In addition Pd/C has also emerged as one of the promising
31
heterogeneous catalyst for CꢀC bond forming reactions.
Herein we report the realization of utility of Pd/Cꢀaqueous hydrotrope mediated
ligandꢀfree SuzukiꢀMiyaura and baseꢀfree HeckꢀMatsuda cross coupling reactions at ambient
temperature.
Results and Discussion
Characterization
Activated carbon supported Pd catalyst used for various SuzukiꢀMiyaura and Heckꢀ
Matsuda cross coupling reactions was thoroughly characterized by different techniques like
2

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TGꢀDTA, SEM, EDS, XRD, XPS and BET. TGꢀDTA analysis (Fig. 1) shows that the
catalyst was stable up to 550 °C. The loss in weight at temperatures below 200 °C was caused
by the evaporation of physically adsorbed water molecules in the catalyst. The significant
decrease in the weight up to 76.45 % observed in the range of 500ꢀ568 °C was mainly due to
32
the decomposition of organics to form CO
2
.
The stable weight fraction obtained after
complete combustion showed that the 9.23 wt % loading of Pd on the carbon.
Fig. 1 TGꢀDTA spectra of Pd/C catalyst
Powder Xꢀray diffraction (XRD) analysis of fresh and recycled Pd/C catalysts is
shown in Fig. 2. The XRD diffraction pattern of the recycled Pd/C was also identical with a
fresh Pd/C catalyst. The reflection of peaks at 2θ= 40.11, 46.66, 68.12, 82.09 and 86.61°,
corresponded to the (111), (200), (220), (311) and (222) planes of cubic lattice structure of Pd
metallic phase (JCPDS 46ꢀ1043). The reflection peak observed at 2θ=26.62° (JCPDS 25ꢀ
0284) was assigned to the (002) plane of the carbon. A broad peak at 2θ = 35° was likely to
be due to the oxide phase, PdO·H O (JCPDS 09ꢀ0254). XRD pattern of recycled Pd/C did
2
not show any additional peaks indicating that the Pd metal retained onto the surface of the
3
2a, 33
carbon.
3

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rd
Fig. 2 XRD of Pd/C catalyst (a) fresh and (b) used (after 3 cycle) samples
SEM micrograph (Fig. 3a) of Pd/C clearly revealed the distinct morphology as small
white discrete particulates of Pd dispersed on the carbon material. The EDS spectrum (Fig.
3b) of the Pd/C taken at random points on the surface indicated composition as C, O and Pd
in the weight % ratio of 83.79, 7.92 and 8.28, respectively.
Fig. 3 SEM and EDS parameters of Pd/C catalyst
4

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XPS analysis of the fresh Pd/C catalyst (Fig. 4a) and recovered Pd/C catalyst after
third recycle (Fig. 4b) provided useful information about the chemical state of the Pd. Lower
binding energy doublet was assigned to metallic Pd whereas higher binding energy one could
3
4
be related to PdO. The peaks due to Pd(0) were much stronger than those of Pd(II) in both
the samples, suggesting that majority of the catalyst existed in a metallic Pd state and also
that the Pd/C catalyst was highly stable for subsequent recycle runs.
rd
Fig. 4 XPS analysis of (a) fresh Pd/C catalyst, (b) used (after 3 cycle) Pd/C catalyst
BET surface area measurement of the fresh and reused Pd/C catalyst showed that
2
ꢀ1
2 ꢀ1
there was slight decrease in surface area from 1247.72 m g to 1152.32 m g which was in
accordance to the corresponding decrease in pore diameter of the reused catalyst (13.78 nm),
as compared to that of the fresh sample (17.96 nm).
Suzuki-Miyaura cross-coupling reaction of aryl halides, arenediazonium salts, and acyl
chlorides with boronic acids
SuzukiꢀMiyaura coupling of 4ꢀbromobenzophenone with phenylboronic acid was
studied over Pd/C in presence of K
2
CO
3
as a base at room temperature (Scheme 1).
O
O
B(OH)2
+
Hydrotropic solution
Pd/C, base, r. t.
Br
Scheme 1 SuzukiꢀMiyaura crossꢀcoupling reaction under ligandꢀfree condition
The preliminary studies on screening and effect of concentration of hydrotropes
showed that the nature of hydrotrope and its concentration had a significant effect on the
5

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yield and time of reaction. As shown in Fig. 5, a control experiment in water without any
hydrotrope gave only 20 % yield in 12h. While the reaction performed in presence of a
hydrotrope, 60 % sodium xylene sulphonate (NaXS) solution instead of only water, the yield
was remarkably improved to 93 % in just 2h. Among the several hydrotropes screened in this
work, sodium xylene sulphonate (NaXS) exhibited the highest yield of 93 %.
Fig. 5 Screening and optimization of various hydrotropes and its concentrations for Suzuki–
Miyaura crossꢀcoupling reaction.
In order to understand the role of a hydroptrope, another control experiment was
carried out using a surfactant because hydrotrope, similar to the surfactant also contains
amphiphilic head and hydrophilic tail. However, Pd/C catalyst in presence of a surfactant
(SDS), gave only 10 % yield in 12h. The hydrophobic tail of a hydrotrope is smaller which
21ꢀ22
forms aggregates instead of micelles in case of a surfactant
hence hydrotrope is believed
to stabilize the active palladium species in water. In the presence of a hydrotrope, the
substrate forms an emulsion in water and the powdered catalytic material is well dispersed in
this emulsion, increasing the activity of catalyst. All the further studies were then carried in
presence of a hydrotrope, NaXS.
Effect of reaction time on the yield of the final product was studied by carrying out
the model reaction in a time range of 15 to 150 minutes. Fig. 6 shows that the percentage
yield of the final product linearly increased with increase in reaction time from 15 to 120 min
and after that it remained constant at ~ 93 %.
6

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Fig. 6 Optimization of effect of reaction time on yield of desired product
Fig. 7 shows the results of screening of various organic and inorganic bases. The
reaction did not proceed in the absence of a base and it was revealed that K
2 3
CO showed the
best efficiency giving the maximum yield of 93 % in 2h.
Fig. 7 Screening of bases for Suzuki–Miyaura crossꢀcoupling reaction
The influence of catalyst concentration is very important as it not only affects the cost
of process but also hinders the activity of catalyst due to Pd agglomeration beyond a certain
35
concentration. Optimization of catalyst loading showed that 2 mol % Pd was found to be the
most effective with a maximum yield (93%) of the desired coupling product within 2h (Table
7

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1
, entry 6). The lower catalyst loading (0.25ꢀ1.5 mol %) furnishes lower conversion (50ꢀ
5%).
8
a
Table 1 Optimization of catalyst loading for Suzuki–Miyaura crossꢀcoupling reaction .
b
Entry
Pd/C (mol %) Time (h) Yield (%)
1
2
3
0.25
0.50
0.75
12
10
8
50
55
65
4
5
6
7
1
1.5
2
4
3.5
2
70
85
93
93
3
2
a
Reaction conditions: 4ꢀbromobenzophenone (1 mmol),
2 3
phenylboronic acid (1 mmol), Pd/C (mol %), K CO (2.0
b
mmol), 60 % NaXS solution (5.0 mL), at RT. Isolated yields
after column chromatography.
Having established the optimized reaction conditions, the scope and generality of the
reaction was then explored by using a series of aryl halides and aryl boronic acids. As shown
in Table 2, the substrates with different substituents on the benzene ring of aryl halides
afforded the desired products in excellent yield. Even the sterically hindered trisubstituted
mesitylene (Table 2, entry 19) was obtained (60 % 12h) by our catalystꢀhydrotrope mediated
SuzukiꢀMiyaura coupling reaction. However in case of 4ꢀchlorobenzene and 4ꢀ
chlorobenzophenone, yields obtained were in a range of 20ꢀ25% (Table 2, entries 21 and 22).
Table 2 The SuzukiꢀMiyaura Crossꢀcoupling reaction of various aryl halides with boronic
a
acids .
b
Sr. No.
1
Aryl Halides
Boronic Acids
Product
Time (h) Yield (%)
O
B(OH)2
O
2
93
Br
Br
O
O
2
3.5
90
(
2
HO) B
8

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O
O
3
4
(
HO)
2
B
F
3
85
Br
F
O
O
2
(HO) B
4
88
88
Br
O
O
O
O
5
6
1.5
(
(
HO)
2
B
Br
Br
HO)
2
B
3
.5
85
94
O
O
H
7
8
2
(
(
HO)
2
B
B
Br
Br
H
O
HO)
2
H
O
H
3
90
92
9
1.5
F
Br
(HO)
2
B
B
F
10
(
HO)
2
Br
N
Br
N
3
.5
89
93
92
91
90
93
11
12
13
14
15
16
1.5
2
O
O
2
2
N
N
Br
(HO)
2
B
2
O N
Br
(HO)
2
B
2
O N
3.5
4
MeO
Br
Br
(HO)
(HO)
2
B
B
MeO
H
2
N
2
2
H N
2
NC
NC
Br
Br
(HO)
2
B
NC
(HO) B
2
5
.
86
NC
9

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Br
17
(
HO)
2
B
7
2
80
90
60
1
8
9
Br
(HO)
2
2
B
B
1
12
(
HO)
Br
2
0
12
12
45
25
Br
(HO)
(HO)
2
B
2
1
2
Cl
2
2
B
B
O
O
2
(
HO)
1
2
20
Cl
a
2 3
Reaction conditions: aryl halides (1 mmol), arylboronic acids (1 mmol), Pd/C (2 mol %), K CO (2.0 mmol),
b
6
0 % NaXS solution (5.0 mL), at RT. Isolated yields after column chromatography.
Encouraged by the success of coupling aryl halides with boronic acids for making
biphenyls, we then attempted to couple arenediazonium salts with aryl boronic acids.
Though, considerable efforts have been exerted on the coupling of aryl halides under
36
Suzuki−Miyaura coupling reactions conditions, two major drawbacks associated with aryl
37
halides are their insolubility in water and competing homocoupling reaction. This can be
overcome by using diazonium salts due to their high solubility in water. These can be easily
3
8
and efficiently prepared from organoamine compounds by diazotization in water.
The optimized reaction conditions were the same for the cross coupling of 4ꢀ
nitroarendiazonium tertafluoroborate salt with phenylboronic acid as those used for aryl
halide substrates (Table 3, entry 1). Here also inorganic base K CO was more effective than
2
3
organic bases (Table 3, entries 3 and 4) and the reaction did not proceed in the absence of a
base (Table 3, entry 5). The reaction in aqueous medium at room gave a poor yield of the 4ꢀ
c
nitrobiphenyl (Table 3, entry 6 ).
1
0

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a
Table 3 Screening of nature of bases for the Suzuki–Miyaura reaction
B(OH)2
O N
2
6
0 % NaXS solution
Pd/C, base, r. t.
+
O N
2
+
ꢀ
N BF
2
4
b
Entry
Base
CO
NaOAc
Et
Time (h)
Yield (%)
1
2
3
4
5
K
2
3
1
90
85
86
80
15
20
1.5
2
3
N
Pyridine
free
1.5
12
12
c
6
2 3
K CO
a
Reaction conditions: 4ꢀnitroꢀdiazonium salt (1 mmol),
arylboronic acid (1 mmol), Pd/C (2 mol %), base (2.0 mmol), 60
b
%
NaXS solution (5 mL) at RT. Isolated yields after column
c
chromatography. Reaction carried out in water.
To explore the scope and generality of the catalytic system, a variety of
arenediazonium salts and aryl boronic acids were reacted under the optimized protocol and
the results are shown in Table 4. Both activated and deactivated arenediazonium salts showed
a maximum conversion in a range of 85ꢀ94 %. More importantly, it is interesting to that the
chemoselectivity could be achieved in these coupling reactions using halogenꢀbased
arenediazonium salt with the olefin (Table 4, entry 4).
Table 4 Results on SuzukiꢀMiyaura Crossꢀcoupling of various arenediazonium salts with
a
boronic acids
b
Sr. No.
1
Aryl Halides
Boronic Acids
Product
Time (h)
1
Yield (%)
88
B(OH)
2
N
2
+BF -
4
2
3
1.5
1.5
85
94
(
2
HO) B
N
N
2
2
+BF -
4
(
2
HO) B
+BF -
4
1
1

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Cl
4
5
6
7
2.5
1
86
90
87
93
(
(
HO)
HO)
2
2
B
B
Cl
N
2 4
+BF
-
O
O
O
2
N
N
N
2
O N
+BF
+BF
+BF
-
N
2
2
2
4
4
4
2
2
3.5
(
HO)
2
B
2
O N
-
-
N
N
1.5
(
(
HO)
HO)
2
B
B
2
O N
MeO
MeO
MeO
8
9
2.5
2
88
89
92
2
MeO
N
N
N
2
2
2
+BF -
4
(
HO)
2
B
MeO
+BF -
4
10
3
(
HO)
2
B
+BF -
4
MeO
a
Reaction conditions: arenediazonium salts (1 mmol), arylboronic acids (1 mmol), Pd/C (2 mol %), K CO (2.0
2
3
b
mmol), 60% NaXS solution (5 mL) at RT. Isolated yields after column chromatography.
3
9
Diarylketones exist as a common structural motif in natural products as well
40
biological and pharmaceutically important compounds. The wellꢀknown method for
4
1
synthesis of such compounds is the FriedelꢀCrafts acylation having several inherent
limitations. Recently, Pd catalyzed crossꢀcoupling reactions of various electrophilic acid
derivatives of carboxylic acids such as acid chlorides, acid esters, acid anhydrides and
42
dimethyl dicarbonates with organoboranes have been reported. These are also prepared by
the crossꢀcoupling reaction of aryl halides involving carbonylation with carbon monoxide in
43
the presence of organometallic reagents. Both these reactions have emerged as new
catalytic tools for the synthesis of such important compounds. Herein, we report a much
simpler synthesis of prochiral ketones under mild conditions without using CO, by Pd
catalyzed ligandꢀfree, SuzukiꢀMiyaura crossꢀcoupling reactions of acid chlorides with
organoboranes in water.
A model reaction of 4ꢀnitrobenzoyl chloride (1 mmol) and phenylboronic acid (1
mmol) was studied under different reaction conditions and the results are shown in Table 5.
2 3
Among the various bases screened, K CO showed the excellent activity with 88 % yield at
60 °C (Table 5, entry 8). It was observed that with increasing temperature from 25 to 60 °C,
1
2

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the product yield significantly increased from 10 to 88% as well as the reaction time
decreased significantly from 12 to 2 (Table 5, entries 5ꢀ8). When water used as the solvent
the conversion was as low as 15% even after 12 h and at 60 °C (Table 5, entry 10).
Table 5 Optimization of reaction conditions for SuzukiꢀMiyaura crossꢀcoupling of
a
acid chlorides
O
B(OH)2
O
Cl
60 % NaXS solution
+
Pd/C, base, temperature
O N
2
O N
2
b
Entry
Base
Temperature (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
NaOAc
60
60
60
60
25
40
50
60
70
60
2.5
3.5
3.5
12
12
6
85
82
78
15
10
70
80
88
89
15
Et N
3
pyridine
base free
K
2
CO
CO
CO
CO
CO
3
3
3
3
3
3
K
2
K
2
3.5
2
K
2
K
2
2
c
10
K CO
2
12
a
Reaction conditions: 4ꢀnitrobenzoyl chloride (1 mmol), phenylboronic acid (1
b
mmol), Pd/C (2 mol %), base (2 mmol), 60 % NaXS solution (5 mL). Isolated
c
yields after column chromatography. Reaction is carried out in water.
The generality and scope of this approach was proved by the successful coupling of
2 3
various benzoyl chloride with aryl boronic acid substrates, using K CO as a base at 60 °C
and the results are summarized in Table 6. A wide range of prochiral ketones were obtained
with excellent yields.
Table 6 The SuzukiꢀMiyaura Crossꢀcoupling reaction of various acyl chlorides with boronic
a
acids
b
Sr. No.
1
Aryl Halides
Boronic Acids
Product
Time (h) Yield (%)
O
B(OH)
2
O
1.5
85
Cl
1
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O
O
O
O
2
3
2
90
(
2
HO) B
Cl
2.5
84
88
85
82
(
2
HO) B
Cl
O
O
4
5
6
2
3
4
Cl
Cl
Cl
(
2
HO) B
O
O
2
2
2
N
N
N
NO
2
O
O
O
O
2
(HO) B
NO
2
(
(
HO)
HO)
2
B
B
O
O
NO
2
O
O
O
7
8
4
5
85
84
2
Cl
Cl
O
O
(
HO)
2
B
O
O
O
O
O
9
3.5
4.5
88
87
(
2
HO) B
Cl
10
O
(
2
HO) B
Cl
a
2 3
Reaction conditions: acyl chlorides (1 mmol), arylboronic acids (1 mmol), Pd/C (2 mol %), K CO (2 mmol), 60
b
%
NaXS solution (5 mL) at 60 °C. Isolated yields after column chromatography.
Ligand and base free Heck-Matsuda cross-coupling reaction of arenediazonium salts
We also extended the applicability of Pd/C combined with hydrotrope catalytic
system for the HeckꢀMatsuda crossꢀcoupling reaction involving arenediazonium
38,44
tetrafluoroborate salts as excellent aryl electrophilic component.
The major advantage of
the arenediazonium salt is that it undergoes easy oxidative addition during the mechanistic
cycle to generate active cationic arylꢀPd (II) intermediate which increases the rate of the
4
5
reaction.
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2 3 3
Initially, we screened various bases such as K CO , NaOAc, Et N and pyridine for the
model reaction of 4ꢀnitrodiazonium tetrafluoroborate with methyl acrylate in 60 % NaXS at
room temperature. To our surprise, an excellent yield (93%) of the product was obtained
under baseꢀfree condition in a comparatively very less reaction time of only 1 h (Table 7,
entry 5). However, in water medium, (in absence of a hydrotrope) very low conversion of
only 25% was observed (Table 7, entry 6).
a
Table 7 Effect of bases for HeckꢀMatsuda crossꢀcoupling reaction
O N
60 % NaXS solution
2
O N
2
+
COOMe
Pd/C, base/ base free, r. t.
+
ꢀ
N BF
2
4
COOMe
b
Entry
Base
Time (h)
Yield (%)
1
2
3
4
5
K CO
5
6
65
68
40
60
93
25
2
3
NaOAc
Et
3
N
4
Pyridine
base free
base free
8
1
c
6
12
a
Reaction conditions: 4ꢀnitroꢀarenediazonium salt (1 mmol),
methyl acrylate (1 mmol), Pd/C (2 mol %), base (2 mmol), 60
b
%
NaXS solution (5 mL), at RT. Isolated yields after column
c
chromatography. Reaction is carried out in water.
The synthesis of a variety of substituted acrylates could be successfully accomplished
by reacting a range of olefins and arenediazonium salts. As can be seen from Table 8, various
substrates with electronꢀrich or electronꢀpoor functional groups could react smoothly with
olefins to give the desired arylate products in good to excellent yields. It was found that the
ratio of E/Z isomers was dramatically affected by the nature of substituent present on
1
arenediazonium salt. Eꢀ and Zꢀisomers were confirmed by J coupling values of H NMR
spectra. The compounds containing electron withdrawing groups showed > 90 % Eꢀisomers,
but 4ꢀchloroarenediazonium salt gave 100 % Eꢀisomer formation (Table 8, entries 3, 8, and
13) while electron donating groups gave predominantly Zꢀisomers to the extent of 80ꢀ85%.
Unfortunately, 4ꢀmethylarenediazonium salt gave 53:47 (E/Z) isomer ratio (Table 8, entry 4).
Methyl acrylate reacted with different arenediazonium salts to give the corresponding product
in 84ꢀ93 % yields. More bulky butyl acrylate showed a good activity to give 81ꢀ90 % yield
with various diazonium salts. Different stilbene derivatives obtained were in comparatively
lower yields of 58ꢀ80 % due to their steric hindrance (Table 8, entries 11ꢀ14).
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Table 8 Results on HeckꢀMatsuda Crossꢀcoupling of various arenediazonium salts with
a
olefins
b
Sr. No.
Aryl Halides
Boronic Acids
COOMe
Product
Time (h) Yield (%)
(
E/Z ratio)
O
2
N
O N
2
1
2
3
1
1
93
+BF
-
COOMe
N
2
4
(92:08)
90
COOMe
COOMe
N
2
+BF -
4
(100:00)
91
Cl
Cl
COOMe
2
COOMe
+BF
N
2 4
-
(100:00)
4
5
6
7
8
9
COOMe
COOMe
COOBu
COOBu
COOBu
2.5
1
88
(53:47)
90
COOMe
COOMe
N2+BF4-
MeO
MeO
N
2
+BF -
4
(100:00)
90
O
2
N
O N
2
1.5
1
N
2
+BF
4
-
COOBu
COOBu
(95:05)
89
N
2
+BF -
4
(100:00)
91
Cl
Cl
3
COOBu
COOBu
+BF -
N
2 4
(100:00)
COOBu
COOBu
3
92
N2+BF4-
(55:45)
MeO
MeO
10
11
12
N
2 4
+BF -
COOBu
1.5
6
90
(
(
(
82:18)
O
2
N
O N
2
+BF
-
N
2
4
65
81:19)
N
2
+BF -
4
6
80
91:09)
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Cl
Cl
13
14
15
+BF -
N
2 4
6
58
(96:04)
MeO
MeO
N
2
+BF -
4
6
6
62
94:06)
67
(
N2+BF -
(65:35)
4
a
Reaction conditions: arenediazonium salts (1 mmol), olefins (1 mmol), Pd/C (2 mol %), 60 % NaXS solution
b
(
5 mL), at RT. Isolated yields after column chromatography.
Heterogeneity of Pd/C catalyst
It is obligatory to study the catalyst stability in terms of leaching of Pd from the solid
46
support. The leaching of Pd from the carbon was inveterate by carrying out an analysis of
the desired product mixture of model reaction with The ICP–AES analysis of the reaction
crude of SuzukiꢀMiyaura crossꢀcoupling reaction, after separating the catalyst by filtration,
showed that palladium metal was not leached out (< detection limit of 1ppm) as reported by
47
48
Felpin et al and Sajiki et al. This result strongly supports that the Pd/C is characteristic
heterogeneous in nature.
Possible mechanism
A generalized possible mechanism of CꢀC bond formation reactions in presence of an
hydrotrope is shown in Fig. 8. The low solubility of organic reactants in water can often be
overcome by using hydrotropes though amphiphilic in character, have hydrophobic chains
and thus differ from classical surfactants; yet they display substantial ability to
solubilize, nonꢀpolar compounds in water. In an aqueous medium, the water molecules
hydrate the amphiphilic head groups of the hydrotrope decreasing the electrostatic interaction
23
between these groups. This makes the head groups to move apart creating the driving
force for two hydrophobic chains to interact and facilitate aryl halide to bind with Pd/C in the
oxidative addition step forming a Pd(II) intermediate complex. In the next step RꢀPdꢀX
(
II)
undergoes transmetalation reaction with carbon nucleophile to form RꢀPd ꢀR’ in presence of
a base. The resultant complex undergoes reductive elimination to form coupling product with
6a
the regeneration of Pd (0) which participates in the next catalytic cycle.
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Fig. 8 Plausible mechanism of the CꢀC bond forming reactions in the presence of an
Hydrotrope
Very importantly, the product precipitates on dilution with water from hydrotropic
solution, which leads to the product formation in a crystalline form with an improved purity,
and the mother liquor can be used to concentrate the hydrotrope for recycling.
Separation of catalyst
For any catalytic process, recovery and reꢀutilization of the catalyst is a very
important aspect for sustainability for possible application on an industrial scale. The
recyclability of Pd/C catalyst in the present work was investigated as follows. After the fresh
catalytic cycle, the catalyst was recovered by simple filtration and was washed with water,
DCM, and acetone and dried under vacuum. The recovered Pd/C catalyst was then used for
next catalytic cycle (Fig. 9).
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8

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Fig. 9 Procedure for recyclability of Pd/C catalyst
The recycling results of Pd/C for model reactions of SuzukiꢀMiyaura and Heckꢀ
Matsuda crossꢀcoupling were summarized in Fig. 10. The catalyst was recycled three times
with no appreciable change in product yield at same reaction time of model reaction. These
results revealed that the catalyst is stable and can be renewed for frequent use.
Fig. 10 Recyclability study of Pd/C
Conclusion
In this work, we developed a very simple route for the synthesis of diversely
functionalized biphenyls, acrylates and prochiral ketones by ligandꢀfree SuzukiꢀMiyaura and
baseꢀfree HeckꢀMatsuda crossꢀcoupling reactions using Pd/C catalyst combined with
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hydrotrope in an aqueous medium under atmospheric conditions. Initially, we used Suzukiꢀ
Miyaura crossꢀcoupling reaction as model reaction for screening of various reaction
conditions and then optimized reaction conditions are extended for the synthesis of biaryls (at
room temperature), prochiral ketones (at 60 °C) and acrylates (at room temperature). This
experimental method offers promising green development in terms of reaction time, wide
scope of applicability, mild reaction conditions, good to excellent yields of desired product
and operational simplicity. To best of our knowledge use hydrotrope as inexpensive, easily
available, green reaction medium and Pd/C as reusable catalyst for CꢀC bond forming
reaction. Further study is continued in our laboratory to investigate the mechanistic pathway
of hydrotrope mediated CꢀC coupling reactions.
ꢀ
Acknowledgement
One of the authors Dr. Sanjay N. Jadhav grateful to the University Grants Commission, New
Delhi, India, for the award of SAPꢀBSR fellowship.
Notes and references
ꢀ
ꢀ
Corresponding author
Department of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India.
ꢀ
ꢀ
Eꢀmail: rss234@rediffmail.com. Tel. +91 231 260 9240; fax: +91 231 269 2333.
1
13
Supporting information. H and C NMR spectra of our compounds.
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Ligand-free Pd Catalyzed Cross-coupling Reactions in Aqueous Hydrotropic Medium
a
a
b
a
Sanjay N. Jadhav , Arjun S. Kumbhar , Chadrashekhar V. Rode , Rajashri S. Salunkhe *
a
Department of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India
b
CSIR-National Chemical Laboratory, Pune-411008, M. S. India
E-mail: rss234@rediffmail.com
∗Corresponding Author Tel. +91 231 260 9240; fax: +91 231 269 2333.
Graphical Abstract