Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using Recyclable Palladium/Amide-Silica Catalyst

Article abstract of DOI:10.1007/s10562-016-1796-4

Abstract: Silica-immobilized benzamide palladium complex was prepared and characterized. The complex exhibits excellent catalytic activity and stability for Suzuki–Miyaura cross-coupling reaction under mild aqueous reaction condition. Various aryl bromide

Full text of DOI:10.1007/s10562-016-1796-4

Catal Lett
DOI 10.1007/s10562-016-1796-4
Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using
Recyclable Palladium/Amide-Silica Catalyst
Manoj Mondal1 Anindita Dewan2 Tahshina Begum1 Pradip K. Gogoi1
•
•
•
•
Ashim Jyoti Thakur2 Utpal Bora2
•
Received: 1 May 2016 / Accepted: 14 June 2016
Ó Springer Science+Business Media New York 2016
Abstract Silica-immobilized benzamide palladium complex
was prepared and characterized. The complex exhibits excel-
lent catalytic activity and stability for Suzuki–Miyaura cross-
coupling reaction under mild aqueous reaction condition.
Various aryl bromides were coupled with arylboronic acids in
i-PrOH/H2O, under open air at room temperature, in the
presence of 0.22 mol% of the catalyst to afford corresponding
cross-coupled products in high yields. Furthermore, the novel
heterogeneous catalyst can be conveniently recovered by
simple filtration and reused several times without significant
loss in activity.
Keywords Silica-immobilized Á Heterogeneous catalyst Á
Suzuki–Miyaura cross-coupling Á Biaryls Á Aqueous
solvent Á Room temperature
1 Introduction
The palladium-catalyzed Suzuki–Miyaura cross-coupling reac-
tion is one of the important, powerful and frequently employed
protocols in organic synthesis for the construction of carbon–
carbon bond [1–7]. This reaction has been widely used to syn-
thesize molecules possessing significant biological or physical
properties [8–12], and can be extended to large scale synthesis.
Graphical Abstract
AcO
OAc
Pd
O
O
O
Si
N
O
SiO2
H
Cl, Br
(HO)2B
+
X
X
Ph
X
R2
R1
R1
X
R2
i-PrOH/H2O, K2CO3, rt, 1-6.5 h
X= C, N
R1= H, NO2, OMe, CHO, Ac
Aqueous medium
R2= H, Cl, OMe, Me, CN
Room temperature
Cheap and Recyclable Catalyst
Short reaction time
In the last three decades numerous homogeneous pal-
ladium catalysts ligated with phosphines [13–15], NHC
[16–19], imidazole [20], imine [21], oxime [22], oxazo-
line [23], triazole [24], amino acid [25], amine [26, 27],
Schiff-base [28–30], oxime-ether [31], hydrazone [32],
etc. have been employed in this cross-coupling method,
due to their high reactivity and high turnover numbers.
Moreover, many unique ligandfree protocols were also
developed in recent years for this transformation [33–40].
& Manoj Mondal
manojjmondal@gmail.com
& Utpal Bora
utbora@yahoo.co.in
1
Department of Chemistry, Dibrugarh University, Dibrugarh,
Assam 786004, India
2
Department of Chemical Sciences, Tezpur University,
Tezpur, Assam 784028, India
123

M. Mondal et al.
However, the use of homogeneous catalysis has some
inherent disadvantage, as the expensive metal catalysts
are not easily reusable, hard to separate from reaction
mixture (a frequent industrial concern) and often con-
taminates the final products, especially the pharmaceuti-
cals, and poses a serious issue for large-scale synthesis.
To overcome these issues, heterogeneous catalysis seems
promising and advantageous over homogenous catalysts,
owing to easy recovery of the highly stable solid catalyst
from the reaction mixture with minimum contamination
of products, and many of the heterogeneous systems are
recyclable and retain their reactivity even after several
catalytic cycles.
2 Results and Discussion
2.1 Synthesis and Characterization of the Catalyst
The palladium complex was synthesized in three steps, fol-
lowing a previously reported procedure, summarized in
Scheme 1 [53, 54]. The first step involves the modification of
silica surface by the reaction of solid silica gel (60–120
mesh) and APTES in dry toluene under N2 atmosphere at
refluxing temperature. In the second step, the condensation
of APTES@SiO2 and benzoyl chloride in diethyl-ether at
reflux condition produces the corresponding benzamide
complex, benzamide@SiO2, which was light yellow colored
solid after purification. Finally, the benzamide@SiO2 pre-
cursor was used for the synthesis of Pd–benzamide@SiO2
complex by treatment with Pd(OAc)2 in acetone at room
temperature for 24 h.
Palladium can be immobilized on several solid supports
such as organic polymers, clays, oxides, activated carbon,
zeolites etc. [41–49]. However, the most common hetero-
geneous supports are based on silica, because of their easy
availability, high stability and porosity, which allows easy
binding of organic groups on the surface [41–49]. The
presence of highly active silanol-sites in the silica-surface
promotes effective anchoring of organic ligands, followed
by the immobilization of the metal on the support.
Numerous efficient silica-supported palladium catalyst have
been synthesized and used in Suzuki–Miyaura reaction
[50–52]. But they still suffer from the problem concerning
the use of volatile organic solvent system, elevated reaction
temperature, high metal loading and poor recyclability
[50–52]. Hence, there is a strong need to develop recyclable
heterogeneous catalyst which can perform efficiently under
mild aqueous condition with diverse range of substrates.
In continuation of our studies in developing novel sup-
ported heterogeneous catalysts, herein we report an effi-
cient, easily accessible and widely applicable silica
immobilized benzamide palladium complex and its appli-
cation in Suzuki–Miyaura cross-coupling reaction.
Due to insolubility of the Pd–benzamide@SiO2 complex
in most of the organic solvents, its structural investigations
were limited to its physicochemical properties, such as FT-
IR, BET surface area measurements, SEM, SEM–EDX,
EDS-mapping and ICP-AES analysis.
2.2 FT-IR, XRD, SEM–EDX, ICP-AES and EDS
Mapping Analysis
The FT-IR spectra of SiO2, APTES@SiO2, benza-
mide@SiO2 and Pd–benzamide@SiO2 are presented in
Fig. 1. The FT-IR spectra of the silica samples shows
absorption bands at 1642 cm-1 for mO–H bending vibrations
of the adsorbed water. The absorption peaks at
1080–1140 cm-1 are due to the stretching vibrations of the
Si–O–Si groups. Except in Fig. 1(i), the peak for mN–H in
the region 1500–1600 cm-1 appears in all samples (Fig. 1).
This indicates the attachments of APTES onto the silica
Scheme 1 Preparation of the silica-supported Pd–benzamide@SiO2
123

Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using Recyclable Palladium/Amide–Silica…
matrix. The bands observed at 1680 cm-1 in (iii) shifts to
1670 cm-1 in (iv), which could be attributed to the mC=O
stretching frequency, and 540 cm-1 in (iv) indicates the
mPd–N stretching frequency [55]. The presence of a
less intense band at 1440 cm-1 may be assigned to ms
(CH3CO2-) group of palladium acetate [56].
The silica immobilized Pd catalyst was examined by
powder X-ray diffraction (XRD) study (Fig. 2). It is
observed that the distinct Pd nano-particles peaks are not
observed in the XRD diffractogram, probably due to the
very low concentration of palladium particles within the
complex or due to amorphous nature of the silica matrix.
The major peak at 2h values *20° to 25° indicates the
presence of silica in a high concentration. The presence of
PdNPs could be inferred from the 2h values observed at
Fig. 2 XRD pattern of the Silica supported Pd catalyst
39°, 46° and 66° which corresponds to (111), (200) and
(220) plane (JCPDS card No. 001-1310 and 001-12010).
Similarly, the 2h values observed of 33°, 44° and 61°
corresponds to (101), (102) and (113) planes of PdO
(JCPDS card No. 043-1024 and 002-1432).
of palladium complex with the anchored benzamide ligand
at various sites. The palladium content of the supported
catalyst was determined by ICP-AES, which suggests
2.2 wt% or 0.022 mol% palladium loading in the immo-
bilized complex.
The SEM–EDX analyses of the silica gel before and
after palladium immobilization are shown in Fig. 3a and b.
The results shows the palladium content along with the
silica and oxygen proportions, which indicate the formation
The change in surface morphology of free silica and the
supported Pd-catalyst are clearly visible from the SEM
images (Fig. 4a, b).
To further confirm the components of the Pd–benza-
mide@SiO2 we record the elemental mapping by energy
dispersive X-ray absorption spectroscopy (EDS). Figure 5
shows a uniform distribution of active palladium sites
throughout the matrix.
2.3 N2 Adsorption–Desorption Isotherm
The N2 adsorption–desorption isotherms analysis, mea-
sured at 77 K, of the silica based samples are shown in
Fig. 6, and the respective textural parameters, such as the
specific surface area (ABET), pore volume (Vp) and pore
radius are presented in Table 1. The isotherms of all the
samples exhibited typical type IV patterns according to the
IUPAC definition of porosity [57], featuring mesoporous
material with uniform pore size distribution.
The specific surface area (ABET) obtained by the BET
method for free SiO2 was 422.7 m2 g-1 which upon
functionalization with APTES and subsequent benzoyl
chloride treatment decreased to 333.2 and 314.5 m2g-1
respectively. A further decrease in ABET for Pd–benza-
mide@SiO2 (247.1 m2 g-1
)
compared to benza-
mide@SiO2 confirms the successful immobilization of
palladium onto silica surface. In a similar manner, a
gradual decrease in pore volume (Vp) from SiO2
(0.448 cm3 g-1) to Pd–benzamide@SiO2 (0.279 cm3 g-1
)
was observed, to further ascertain the immobilization of
palladium onto silica. N2-isotherm indicates an increase in
Fig. 1 FT-IR spectra of i SiO2, ii APTES@SiO2, iii benza-
mide@SiO2 and iv Pd–benzamide@SiO2
123

M. Mondal et al.
Fig. 3 SEM–EDX spectra of a SiO2 (Figure copyright the Royal Society of Chemistry and reproduced with permission) and b Pd–
benzamide@SiO2
Fig. 4 SEM image of a SiO2 (Figure copyright the Royal Society of Chemistry and reproduced with permission) and b Pd–benzamide@SiO2
pore radius in the case of Pd–benzamide@SiO2 (3.05 nm)
than the parent SiO2 (2.05 nm). Thus, the BET surface
area, pore volume and pore radius suggest the successful
anchoring of the palladium-organic moieties on the surface
of SiO2.
aqueous/organic co-solvent was used, high yields of
87–99 % were obtained within lower reaction time
(Table 2, entries 9–11). The advantage of the aqueous co-
solvent may be attributed to the good solubility of the
inorganic base and boronic acid substrates. Finally, we
found that the i-PrOH/H2O (1:1) combination is the best
solvent system for the present benzamide-Pd-based
Suzuki–Miyaura coupling.
2.4 Pd–Benzamide@SiO2 Catalyzed Suzuki–
Miyaura Reaction
Further investigations were carried out to test the
influence of different bases on Suzuki reaction in i-PrOH/
H2O (1:1) at room temperature. The inorganic bases like
K2CO3, Na2CO3, Cs2CO3, Na3PO4.12H2O, NaOH and
KOH were investigated (Table 3, entries 1–6).
2.4.1 Catalyst Screening and Base-Solvent Optimization
To investigate the catalytic efficiency of the silica-APTES
immobilized benzamide based palladium catalyst, in the
Suzuki–Miyaura reaction, the coupling between
4-bromonitrobenzene and phenylboronic acid was chosen
as the prototype reaction. Initially, single solvent such as
EtOH, i-PrOH, PEG400, THF, CH3CN, DMF, toluene and
H2O were studied. It may be noted that, the use of single
solvent gave moderate to excellent yields at the room
temperature (Table 2, entries 1–8). However, when
As shown in Table 3, K2CO3 was the best base for the
reaction with very short reaction time (3.5 h) (Table 3,
entry 1). The use of Na3PO4Á12H2O provides good yield
although within extended reaction time (Table 3, entry 4).
We studied the effect of alkali metal hydroxides under
present reaction conditions. Both NaOH and KOH have
provided comparably identical amount (78 and 81 %) of
123

Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using Recyclable Palladium/Amide–Silica…
Fig. 5 a SEM image; EDS
mapping of elements: b Pd, c Si,
d oxygen and e Pd ? Si ? O
tested for the cross-coupling reaction. As illustrated in
Table 3, 10 mg of catalyst showed very high efficiency
(Table 3, entry 1), whereas, with lower amount of catalyst
poor yield was obtained (Table 3, entry 10). Thus, we
selected K2CO3 as the base, i-PrOH/H2O in ratio of 1:1,
and 10 mg (0.22 mol% Pd) of catalyst as the optimal
conditions for the reaction.
2.4.2 Substrate Screening
Encouragedbytheexcellentefficiencyofthereactionsystem,
we applied the optimized condition for the Suzuki–Miyaura
cross-coupling of structurally diverse aryl and hetero-aryl
bromide with arylboronic acids. As shown in Table 4, the
reaction tolerates a wide range of functional groups in both
coupling partners. The coupling between aromatic bromides
and arylboronic acids, bearing both electron-donating and
electron-withdrawing groups, proceeded readily to afford the
corresponding products in 92–100 % yields. We next tried to
examine the activity of chloride containing substrates
Fig. 6 N2-adsorption–desorption isotherm of the prepared samples
isolated product (Table 3, entries 5 and 6). However, with
organic base (NEt3) negligible conversion was noticed
(Table 3, entry 7). Different catalyst loadings were also
123

M. Mondal et al.
Pore radiusb (nm)
Table 1 Surface area and pore size distribution of the silica based samples
Entry
Materials
Surface areaa (ABET) (m2 g-1
)
Pore volume (Vp) (cm3 g-1
)
1
2
3
4
a
SiO2
422.7
332.2
314.5
247.1
0.448
0.413
0.394
0.279
2.05
2.21
2.33
3.05
APTES@SiO2
Benzamide@SiO2
Pd–benzamide@SiO2
b
BET method used in N2 sorption, Adsorption average pore radius (by BET method)
Table 2 Optimization of the Pd–benzamide@SiO2 catalyzed Suzuki–Miyaura reaction
Entry
Solvent (4 mL)
Time (h)
Yield (%)a
1
Ethanol
5.5
5
97
99
63
93
91
51
62
55
95
87
99
2
i-PrOH
3
PEG400
8
4
THF
6
5
MeCN
7
6
DMF
8
7
Toluene
8
8
H2O
8
9
Ethanol/H2O (1:1)
PEG400/H2O (1:1)
i-PrOH/H2O (1:1)
4.5
6.5
3.5
10
11
Reaction conditions: 4-bromonitrobenzene (0.5 mmol), phenylboronic acid (0.55 mmol), Pd–benzamide@SiO2 (10 mg, 0.22 mol% Pd), solvent
a
(4 mL), K2CO3 (1 mmol), ca. 28 °C, in air, Isolated yield
2.4.4 Role of Pd–Benzamide@SiO2 in the Suzuki–Miyaura
Reaction
towards this Suzukireaction. However, lower conversion was
obtained with chloroarenes after prolonged reaction time at
80 °C (Table 4, entries 16–17).
Most of the solid supported catalysts are known to follow
heterogeneous pathway, however, in certain condition they
were found to serve as precatalyst which liberates highly
active soluble palladium species or nanoparticles into the
reaction [58, 59]. Thus, to evaluate the actual role of the
silica catalyst, we have performed various control experi-
ments that are often used to distinguish homogenous and
heterogeneous catalysis [55, 60, 61].
2.4.3 Scale-Up Synthesis
The Suzuki coupling reactions have wide applications in
many chemical industries due to the easy accessibility and
broad functionality of organoboron derivatives. Thus, we
have explored the scale-up scope to prepare in grams scale
instead in milligrams of biaryl derivatives.
In the filtration test, we pretreated 10 mg (0.22 mol%
Pd) of Pd–benzamide@SiO2 with K2CO3 in i-PrOH/H2O
(1:1) for 2 h and then passed the reaction mixture through a
filter paper. The filtrate was subjected to a fresh run of
cross-coupling by charging with required amount of
4-bromonitrobenzene and phenylboronic acid at room
temperature. However, no significant progress (3 % by
GC–MS analysis) in the reaction was observed upon
With the optimized reaction conditions we next inves-
tigated the performance of the reaction upon gram scale.
The reaction with excess 4-bromonitrobenzene (5 mmol),
phenylboronic acid (5.5 mmol), K2CO3 (10 mmol), Pd–
benzamide@SiO2 (100 mg, 2.2 mol% Pd) and i-PrOH/
H2O (25 mL) was performed at room temperature for 4 h.
Finally, we were able to isolate 0.9895 grams (99.4 %) of
4-nitrobiphenyl.
123

Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using Recyclable Palladium/Amide–Silica…
Table 3 Screening of bases for the synthesis of biphenyl
i
Entry
Base
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
10
K2CO3
Na2CO3
Cs2CO3
Na3PO4.12 H2O
NaOH
3.5
4
99
91
5.5
5
95
96
8
78
KOH
8
81
Et3N
24
24
3.5
6
trace
no reaction
99b
–
K2CO3
K2CO3
72c
Reaction conditions: 4-bromonitrobenzene (0.5 mmol), phenylboronic acid (0.55 mmol), Pd–benzamide@SiO2 (10 mg, 0.22 mol% Pd), i-PrOH/
a
b
c
H2O (4 mL), base (1 mmol), ca. 28 °C, in air, Isolated yield, Pd–benzamide@SiO2 (20 mg), Pd–benzamide@SiO2 (5 mg)
Table 4 Suzuki–Miyaura reaction of aryl halides with a variety of arylboronic acids
-
i
Entry
X
R1
R2
Time (h)
Yield (%)a
1
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
NO2
NO2
NO2
OCH3
OCH3
OCH3
H
H
3.5
4
99
96
94
98
94
92
100
97
95
96
96
97
2
4-Cl
3
4-OCH3
H
6
4
2.5
3.5
4.5
1
5
4-Cl
6
4-OCH3
H
7
8
H
4-OCH3
4-OCH3
H
2.5
3.5
4.5
4
9
CHO
CHO
COCH3
10
11
12
Cl
4-OCH3
6.5
13
Br
5
95
14
15
16
17
Br
Br
Cl
Cl
OCH3
OCH3
CH3
3-CN
2-CH3
H
5
96
3
94
12
12
43b
41b
OCH3
H
Reaction conditions: aryl bromide (0.5 mmol), arylboronic acid (0.55 mmol), Pd–benzamide@SiO2 (10 mg, 0.22 mol% Pd), i-PrOH/H2O
a
b
(4 mL), K2CO3 (1 mmol), ca. 28 °C in air unless otherwise noted, Isolated yield, at 80 °C
123

M. Mondal et al.
benzamide@SiO2 catalyst again with the reaction of
4-bromonitrobenzene with phenylboronic acid as the model
reaction. After the first run, the catalyst was centrifuged and
recovered from the reaction mixture by centrifugation and
filtration, washed thoroughly with i-PrOH/H2O followed by
EtOAc, dried and reused for another runs. It was observed
that the catalyst could be reused consistently up to six con-
secutive cycles without any significant decrease in activity
(Fig. 7; 1st cycle: 99 % vs 6th cycle: 95 %). Determination
of palladium content by ICP-AES analysis shows a very
negligible decrease (\6 %) in the Pd content on the solid
catalyst after sixth cycle. Although, no significant leaching
of palladium occurs during the catalysis, the slight decrease
in the yield of the reaction may be due to the deactivation of
the catalyst after successive cycles. The results of catalyst
leaching and reusability test strongly suggest that the Pd–
benzamide@SiO2 catalyzed Suzuki–Miyaura reaction pro-
ceeds via heterogeneous mechanism.
Fig. 7 Recycling of the catalyst for the Suzuki–Miyaura reaction
stirring the reaction mixture for 6 h. The leached palladium
in the filtrate was analyzed by inductively coupled plasma
atomic emission spectrometry (ICP-AES), and determined
to be 0.16 ppm.
To confirm the catalytic nature of the Pd–benza-
mide@SiO2, we have performed the metal poisoning test
using mercury (Hg(0)). The ability of Hg(0) to poison Pd,
Rh and Ni-based heterogeneous catalysts, by amalgamating
with the metal or adsorbing on the metal surface, has been
known for more than 90 years [62, 63] and is a commonly
used test [64–71]. The Hg(0)-poisoning experiment is
performed by adding excess Hg(0) to the reaction solution
during the course of the reaction. The suppression of
catalysis by Hg(0) is an evidence for the presence of Pd(0)
in heterogeneous catalyst, however, if the catalyst retains
its activity, the presence of palladium in high oxidation
state can be assumed. For the mercury poisoning test, we
have performed a coupling reaction using 4-bromoni-
trobenzene and phenylboronic acid. After 1 h of reaction
(37 % conversions vide GC–MS) excess Hg(0) (molar ratio
to [Pd] * 600) was added to the reaction solution and the
mixture was stirred at room temperature. After stirring for
another 2.5 h no further increase in the yield was observed
(indicated by GC–MS). This suggests the presence of
palladium in zero oxidation state during the reaction.
However, these data do not exclude the process of ‘‘release
and re-depositing’’ back of the soluble palladium particles
on the insoluble support during the reaction [72–74].
3 Conclusions
In summary, we have successfully prepared a silica
immobilized benzamide palladium complex which was
used as heterogeneous catalyst for the room temperature
Suzuki–Miyaura cross-coupling reaction in aqueous sol-
vent. The supported catalyst has showed excellent catalytic
activities for the reaction affording a wide range of
biphenyls in high yields. Moreover, the solid catalyst could
be recovered easily by simple filtration and reused up to six
times without significant loss in activity. The excellent
catalytic activity as well as the recyclability made this
catalyst an effective alternative to the existing systems.
4 Experimental Sections
4.1 Instrumentation and Chemicals
All chemicals were reagent grade and used as received
without further purification. Silica gel (60–120 mesh) was
purchased from Merck, India. 3-Aminopropyltriethoxysi-
lane (APTES) was purchased from Sigma Aldrich.
Pd(OAc)2 was purchased from Spectrochem Pvt. Ltd.
Infrared spectra (4000–250 cm-1) were recorded in KBr on
a Shimadzu Prestige-21 FT-IR spectrophotometer. The
surface area of the silica samples were determined by BET
surface area analysis using liquid nitrogen at -78 °C on
BET, Quantachrome Instrument, BOYNTON BEACH, FL
33426. The specific surface area of the silica samples were
calculated according to the BET equation. 1H spectra were
recorded in CDCl3 operating at 400 on a JEOL, JNM ECS
NMR spectrometer, and chemical shifts were calculated
2.4.5 Recycling of Pd–Benzamide@SiO2 in Suzuki–
Miyaura Reaction
We have demonstrated the generality and scope of the pre-
sent catalytic system by investigating the Suzuki–Miyaura
reactions. All these reactions proceeded smoothly to produce
the desired products with excellent yields. For practical and
industrial applications, the lifetime of the heterogeneous
catalyst and its level of reusability are important features.
Therefore, we explored the reusability of the Pd–
123

Suzuki–Miyaura Cross-Coupling in Aqueous Medium Using Recyclable Palladium/Amide–Silica…
relative to TMS. All reaction products were known com-
1
pounds and were identified by H and confirmed by com-
mixture was stirred at room temperature for 24 h. The
gradual change in the color of the supported material from
light yellow to brown indicates the palladium uptake by
benzamide@SiO2. The resulting solid was filtered off and
washed with acetone in Soxhlet and then dried in oven. The
catalyst was denoted as Pd–benzamide@SiO2.
paring with those reported in the literature. The following
abbreviations are used for the description of signals:
s (singlet), d (doublet), t (triplet), m (multiplet). Coupling
constants (J) were measured in Hz. GC–MS was performed
on an Agilent Technologies GC system 7820A coupled
with a mass detector 5975 and SHRXI-5MS column (15 m
length, 0.25 mm inner diameter, 0.25 micron film thick-
ness). SEM analyses were carried out using JEOL, JSM
Model 6390 LV scanning electron microscope, operating at
an accelerating voltage of 15 kV. Elemental mapping and
EDX spectra were performed in the same instrument
attached to the scanning electron microscope. Palladium
content of the catalyst and its possible leaching during
catalysis was determined using inductively coupled
plasma-atomic emission spectrometry (ICP-AES) on a
Thermo Electron IRIS Intrepid II XSP DUO. Progress of
the reactions was monitored by TLC using aluminum-
coated Merck silica gel 60 F254 plates under UV light.
5.4 General Information About Catalytic
Experiments
Cross-coupling reactions were carried out under aerobic
conditions at room temperature (ca. 28 °C). Progress of the
reactions was monitored by thin layer chromatography.
The reaction products were purified by column chromato-
graphic using silica gel (60–120 mesh). The isolated
products were confirmed by comparing the 1H spectral data
with literature data.
5.5 Standard Procedure for Suzuki–Miyaura
Reaction
5 Preparation of Catalyst
A 50 ml round-bottom flask was charged with a mixture
of aryl halide (0.5 mmol), arylboronic acid (0.55 mmol),
K2CO3 (1 mmol), catalyst (10 mg, 0.22 mol% Pd) and i-
PrOH/H2O (4 mL). The mixture was stirred at room
temperature for the indicated time. After completion, the
reaction mixture was subjected to centrifugation followed
by filtration and the residual solid was washed with the
same solvent (3 9 5 mL). The resultant filtrate was
diluted with brine (10 mL) and extracted with diethyl
ether (3 9 mL), dried over anhydrous Na2SO4, and
evaporated under reduced pressure. The crude residue
was subjected to silica gel column chromatography (ethyl
acetate–hexane, 0.5: 9.5) to obtain the desired products.
For recycling experiments, the residue catalyst was
recovered from the reaction mixture by centrifugation and
filtration and washed thoroughly with i-PrOH/H2O fol-
lowed by EtOAc. After drying for overnight at 100 °C
overnight in an oven, the residual catalyst was subjected to
subsequent run of the cross-coupling by charging with the
required amount of substrates (aryl halide, arylboronic
acid), K2CO3 and solvent, without further addition of
catalyst.
5.1 Synthesis of APTES Functionalized Silica Gel:
APTES@SiO2
The silica gel (60–120 mesh) was dehydrated by heating at
100 °C for 2 h prior to use. 2.5 g of silica gel was added to
dry toluene (30 mL) and refluxed with 1 mmol
(221.35 mg) of APTES for 6 h under nitrogen atmosphere.
After reaction, the solids were filtered and washed
repeatedly through Soxhlet extraction with dry toluene.
The residue was dried overnight in oven at 100 °C and the
resulting material is denoted as APTES@SiO2.
5.2 Synthesis of Benzamide Functionalized Silica
Gel
In a suspension of 1.25 g of APTES@SiO2 in 30 mL
diethyl ether 2 mmol (281.2 mg) of benzoyl chloride was
added and the resulting mixture was refluxed for 6 h. The
resulting yellow colored solid was separated by filtration
and washed repeatedly through Soxhlet extraction with
ethanol and acetone. The final benzamide grafted silica was
dried in oven at 100 °C for overnight and denoted as
benzamide@SiO2.
5.6 Analytical Data of the Prepared Biaryl
Derivatives
5.3 Immobilization of Pd(OAc)2
onto Benzamide@SiO2
1
4-Nitrobiphenyl (Table 4, entry 1) [75]. Yellow solid, H
NMR (CDCl3, 400 MHz, ppm) d: 8.31–8.28 (m, 2H),
7.75–7.73 (m, 2H), 7.62–7.61 (m, 2H), 7.50–7.48 (m, 3H);
GC–MS m/z: 199.1 (M?, 100).
1.0 g of benzamide@SiO2 was added to the solution con-
taining 50 mg of Pd(OAc)2 in acetone (20 mL) and the
123

M. Mondal et al.
4-Chloro-40-nitro-biphenyl (Table 4, entry 2) [75].
White solid, 1H NMR (CDCl3, 400 MHz, ppm) d:
8.30–8.29 (m, 2H), 7.71–7.70 (m, 2H), 7.57–7.56 (m, 2H),
7.48–7.46 (m, 2H); GC–MS m/z: 233.10 (M?, 100).
4-Methoxy-40-nitro biphenyl (Table 4, entry 3) [75].
Yellow solid, 1H NMR (CDCl3, 400 MHz, ppm) d:
8.28–8.27 (m, 2H), 7.67–7.65 (m, 2H), 7.58–7.55 (m, 2H),
7.02–7.01 (m, 2H), 3.87 (s, 3H); GC–MS m/z: 229.3 (M?,
100).
7.52–7.50 (m, 3H), 7.03–6.97 (m, 2H), 3.86 (s, 3H); GC–
MS m/z: 209.1 (M?, 100).
40-Methoxy-2-methyl-1,10-biphenyl (Table 4, entry 15)
1
[75]. White solid, H NMR (CDCl3, 400 MHz, ppm) d:
7.25–7.22 (m, 6H), 7.0–6.95 (s, 2H), 3.85 (s, 3H), 2.28 (s,
3H); GC–MS m/z: 198.3 (M?, 100).
4-Methylbiphenyl (Table 4, entry 16) [75]: White solid,
Yield: 98 %, 1H NMR (CDCl3, 400 MHz, ppm) d: 7.73 (d,
J = 8.0 Hz, 2H), 7.59–7.56 (m, 2H), 7.49 (t, J = 7.6 Hz,
2H), 7.44–7.39 (m, 1H), 7.34–7.31 (m, 2H), 2.39 (s, 3H);
GC–MS m/z: 168.10 (M?, 100).
4-Methoxybiphenyl (Table 4, entry 4 & 8) [75]. White
1
solid, H NMR (CDCl3, 400 MHz, ppm) d: 7.53–7.51 (m,
4H), 7.42–7.39 (m, 2H), 7.32–7.22 (m, 1H), 6.98–6.95 (m,
2H), 3.81 (s, 3H); GC–MS m/z: 184.1 (M?, 100).
4-Chloro-40-methoxybiphenyl (Table 4, entry 5) [75]
White solid, 1H NMR (CDCl3, 400 MHz, ppm) d:
7.48–7.46 (m, 4H), 7.11–7.09 (m, 2H), 6.96–6.95 (m, 2H),
3.85 (s, 3H); GC–MS m/z: 218.4 (M?, 100).
4-Methoxybiphenyl (Table 4, entry 17) [75]. White
1
solid, H NMR (CDCl3, 400 MHz, ppm) d: 7.52–7.51 (m,
4H), 7.44–7.41 (m, 2H), 7.31–7.24 (m, 1H), 6.99–6.95 (m,
2H), 3.85 (s, 3H); GC–MS m/z: 184.2 (M?, 100).
Acknowledgments Dr. A. Dewan acknowledges UGC-New Delhi
for Dr. D. S. Kothari Postdoctoral fellowship. Dr. M. Mondal and T.
Begum are thankful to UGC, New Delhi for financial assistance in the
form of UGC-BSR (RFSMS) Fellowship. SAIF (STIC), Cochin is
acknowledged for ICP-AES analytical service.
4, 40-Dimethoxybiphenyl (Table 4, entry 6) [75].
Colourless solid, 1H NMR (CDCl3, 400 MHz, ppm) d:
7.48–7.46 (m, 4H), 6.96–6.94 (m, 4H), 3.84 (s, 6H); GC–
MS m/z: 214.10 (M?, 100).
1
1,10-Biphenyl (Table 4, entry 7) [75]. White solid, H
References
NMR (CDCl3, 400 MHz, ppm) d: 7.63–7.59 (m, 4H),
7.47–7.41 (m, 4H), 7.35–7.32 (m, 2H); GC–MS m/z:
154.10 (M?, 100).
40-Methoxy-[1,10-biphenyl]-4-carbaldehyde (Table 4,
1
entry 9) [75]. White solid, H NMR (CDCl3, 400 MHz,
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100).
[1,10-Biphenyl]-4-carbaldehyde (Table 4, entry 10) [75].
White solid, 1H NMR (CDCl3, 400 MHz, ppm) d: 10.05 (s,
1H), 7.95 (d, J = 8.28 Hz, 2H), 7.75 (d, J = 8.28 Hz, 2H),
7.63 (d, J = 7.36 Hz, 2H) 7.47 (d, J = 7.36 Hz, 2H),
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1-(40-Chloro-[1,10-biphenyl]-4-yl)ethanone
(Table 4,
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entry 11) [75]. White solid, H NMR (CDCl3, 400 MHz,
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5-(4-Methoxyphenyl)pyrimidine (Table 4, entry 12) [75].
Yellow solid, 1H NMR (CDCl3, 400 MHz, ppm) d: 9.16 (s,
1H), 8.92 (s, 2H), 7.53 (d, J = 8.72 Hz, 2H), 7.05 (d,
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1
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7.80–7.78 (m, 1H), 6.91–6.89 (m, 1H), 4.01 (s, 3H); GC–
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40-Methoxy-[1,10-biphenyl]-3-carbonitrile
(Table 4,
1
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