Novel heterogeneous catalyst systems based on Pd(0) nanoparticles onto amine functionalized silica-cellulose substrates [Pd(0)-EDA/SCs]: Synthesis, characterization and catalytic activity toward C-C and C-S coupling reactions in water under limiting basic conditions

Article abstract of DOI:10.1016/j.molcata.2015.07.005

Novel heterogeneous catalyst systems based on the immobilization of Pd(0) nanoparticles onto ethylene diamine functionalized silica-cellulose substrates [Pd(0)-EDA/SCs] are reported with a view to introduce new synthetic routes under base-free conditions. The base functionalized organic/inorganic hybrid provides specific basic sites for the reactions to occur under base-free or less basic conditions, and that too with excellent yields. Moreover, the basic nitrogen sites present on the substrate can effectively stabilize and enhance the activity of Pd(0) nanoparticles by preventing their agglomeration and controlling their size. All the catalysts were characterized by TGA and FTIR analysis and the most active catalyst, [Pd(0)-EDA/SC-2] was further characterized by SEM, TEM, HRTEM, EDX, CHN and XRD studies. Additionally, it is shown that the Pd(0)-EDA/SCs exhibits excellent activity under limiting basic conditions for the C-C and C-S coupling reactions employing water as the "Green solvent". Furthermore, the novel catalyst could be recovered in a facile manner from the reaction mixture and could be reused up to five times without significant loss of catalytic activity.

Full text of DOI:10.1016/j.molcata.2015.07.005

Accepted Manuscript
Title: Novel heterogeneous catalyst systems based on Pd(0)
nanoparticles onto amine functionalized silica-cellulose
substrates [Pd(0)-EDA/SCs]: Synthesis, characterization and
catalytic activity towards C-C and C-S coupling reactions in
water under limiting basic conditions
Author: Madhvi Bhardwaj Seema Sahi Hitesh Mahajan Satya
Paul James. H. Clark
PII:
S1381-1169(15)30012-1
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2015.07.005
MOLCAA 9555
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
20-1-2015
30-6-2015
1-7-2015
Please cite this article as: Madhvi Bhardwaj, Seema Sahi, Hitesh Mahajan, Satya Paul,
James.H.Clark, Novel heterogeneous catalyst systems based on Pd(0) nanoparticles
onto amine functionalized silica-cellulose substrates [Pd(0)-EDA/SCs]: Synthesis,
characterization and catalytic activity towards C-C and C-S coupling reactions in
water under limiting basic conditions, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2015.07.005
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1
Novel heterogeneous catalyst systems based on Pd(0)
nanoparticles onto amine functionalized silica-cellulose
substrates [Pd(0)-EDA/SCs]: Synthesis, characterization
and catalytic activity towards C-C and C-S coupling
reactions in water under limiting basic conditions
Madhvi Bhardwaj1, Seema Sahi1, Hitesh Mahajan1, Satya Paul*1 and James. H. Clark2
1Department of Chemistry, University of Jammu, Jammu Tawi-180006, India
2Green Chemistry Centre of Excellence, Department of Chemistry, University of York,
York, UK.
Graphical abstract

2
R
N
N
N
O
N
N
N
O
O
OH OH
Ph
Ph
Ph
+
O
R
O
R
R
H
or
H2O , 100 o
C
N
or
O
H
HN
NH
OH
OH
S
Br
X
Br
R
ArB(OH)2
+
Pd(0)-EDA/SC
+
H2N
NH2
+
R
K2CO3, TBAB,
MW, H2O, 100 o
K2CO3, H2O
100 o
C
C
Ar
S
R
R
• Base functionalized
• Recyclable
• Air and water stable
Highlights
 Synthesis and characterization of amine functionalized substrates [Pd(0)-EDA/SCs].
 Synergism of inorganic/organic properties to get silica/cellulose substrates.
 Base free or limiting base access to C-C and C-S couplings.
 Catalyst is recyclable up to five times with almost consistent activity.
Abstract
Novel heterogeneous catalyst systems based on the immobilization of Pd(0) nanoparticles
onto ethylene diamine functionalized silica-cellulose substrates [Pd(0)-EDA/SCs] are reported
with a view to introduce new synthetic routes under base-free conditions. The base
functionalized organic/inorganic hybrid provides specific basic sites for the reactions to occur
under base-free or less basic conditions, and that too with excellent yields. Moreover, the

3
basic nitrogen sites present on the substrate can effectively stabilize and enhance the activity
of Pd(0) nanoparticles by preventing their agglomeration and controlling their size. All the
catalysts were characterized by TGA and FTIR analysis and the most active catalyst, [Pd(0)-
EDA/SC-2] was further characterized by SEM, TEM, HRTEM, EDX, CHN and XRD studies.
Additionally, it is shown that the Pd(0)-EDA/SCs exhibits excellent activity under limiting
basic conditions for the C-C and C-S coupling reactions employing water as the “Green
solvent”. Furthermore, the novel catalyst could be recovered in a facile manner from the
reaction mixture and could be reused up to five times without significant loss of catalytic
activity.
Keywords
Heterogeneous catalysis; Pd (0) nanoparticles; base functionalization; C-C and C-S couplings;
Green solvent.
E-mail: paul7@rediffmail.com (S. Paul); james.clark@york.ac.uk (James H. Clark)
* Corresponding author

4
1. Introduction
From the standpoint of green chemistry, water is known to be a promising solvent and has
received considerable attention in the area of organic synthesis [1-5]. Further, reactions in
aqueous media offers key advantages such as rate enhancement and insolubility of the
final products, which facilitates their isolation by simple filtration.
Inspired by the need for green and sustainable chemistry, palladium catalyzed reactions in
aqueous media drew great interests of synthetic chemists [6-8]. Despite the remarkable
utility of Pd catalysts in organic synthesis, they suffer from one significant drawback
related to catalyst recovery and reuse, thus affecting the overall economics of the process.
Therefore, developing a facile and expedient approach by using heterogeneous catalysts
due to their easy handling, simple recovery and recycling is highly desirable [9]. Further,
the use of palladium nanoparticles (Pd NPs) in catalysis is crucial as they mimic metal
surface activation and catalysis at the nanoscale and thereby bring selectivity and
efficiency to heterogeneous catalysis [10]. Although there is now considerable literature
precedence for Pd catalysed transformations, the majority of the work has been carried out
in the presence of organic or inorganic bases. Only a handful of reports focus on the use of
base-free or less basic conditons for carrying out these transformations [11, 12]. The

5
commonly used inorganic bases (e.g. K3PO4, Cs2CO3) are poorly ionized in organic
solvents and therefore, impede the necessary deprotonation step. Further, the organic
bases are relatively expensive, hygroscopic and have to be stored and used under strictly
dry conditions. These disadvantages may hamper the utility of the inorganic and organic
bases in both Pd catalyzed reactions and other base-mediated organic transformations. To
overcome these disadvantages, there is a great need to develop such catalyst systems
which could efficiently limit the use of base in organic transformations. These days, base
functionalised supports have been efficiently employed in heterogeneous catalysis for
various organic synthesis [12-14].
The Pd catalyzed C-C bond formation via Suzuki-Miyaura reaction represents a viable
protocol for rapid access to biaryls which have a broad and diverse range of applications
from pharmaceuticals to material science [15]. Further, the synthesis of biologically
important bis(heterocyclyl)methanes via C-C bond formation is also an important
application of Pd NPs [16, 17]. Apart from C-C couplings, the formation of C-S bond for
the synthesis of thioethers is also of utmost importance and is a key step in the synthesis
of many organic molecules [18]. Majority of the developed protocols for the C-C and C-S
bond formations genarally requires 2 or more equivalents of base [17, 19, 20]. In addition
to this, the synthesis of thioethers involves the use of foul-smelling thiols, longer reaction
times and harsh reaction conditions [1]. Thus, devising new environment friendly Pd
catalysed strategies for the C-C and C-S bond formations avoiding the use of base or
reducing the amount of base is highly enviable.
Owing to the exhaustive applications of Pd mediated processes, we became interested to
explore new possibilities in catalyst design with more emphasis on base functionalised
catalytic systems. Initially, to search for the suitable support, it is found that silicas [21]
and activated carbons [22] are stable substrates for immobilization of Pd NPs, but in

6
recent years, several functionalised biopolymers such as cellulose has been efficiently
used as catalyst support because of its hydrophilicity, chirality, biodegradability and broad
chemical-modifying capacity [23]. The chemical modification of cellulose by
incorporating the ethylene-1,2-diamine moiety as a pendant chain covalently bonded to
the main polymeric framework provides more stability [24]. In order to further explore
the applications of both organic and inorganic substrates, herein, we investigate that when
the ethylene diamine functionalised cellulose is covalently bonded to silica, they can form
a very stable bond with a high degree of organofunctionalisation. Moreover, the basic
nitrogen sites present on the substrate increases the stability and activity of Pd NPs, and
can work quite effectively under base-free or requiring very little amount of base in an
aqueous media.
In this paper, we report the synthesis and characterization of novel heterogeneous catalyst
systems based on the immobilization of palladium(0) nanoparticles onto ethylene diamine
functionalized silica-cellulose substrates [Pd(0)-EDA/SCs] and explored their catalytic
activities for C-C and C-S bond forming reactions in aqueous media under base-free or
using very little amount of base.
2. Experimental
2.1 Reagents and instrumentation
1
The chemicals used were purchased from Aldrich Chemical Company or Merck. The H
and 13C NMR data were recorded in CDCl3 on Bruker Avance III (400 MHz and 100
MHz). The FTIR spectra were recorded on Perkin-Elmer FTIR spectrophotometer. SEM
images were recorded using FEG SEM JSM-7600F. Transmission Electron Micrographs
(TEM) were recorded on Philips CM-200. High Resolution Transmission Electron
Micrographs (HRTEM) were recorded on JEOL, JEM-2100F. X-ray diffratograms (XRD)

7
were recorded in 2 theta range of 10-80o on a Bruker AXSDB X-ray diffractometer using
Cu Kα radiations. EDX analysis was carried out using OXFORD X-MAX JSM-7600.
CHN analysis was recorded on ThermoFinnigan FLASH EA 1112 series. The amount of
metal in catalyst was determined by AAS analysis using GBC Avanta-M atomic
absorption spectrometer and thermal analysis was carried out on Linsesis STA PT-1000
make thermal analyzer. Microwave synthesizer used was manufactured by CEM
(DISCOVER SYSTEM).
2.2 Preparation of silica chloride
Firstly, activated silica (10 g) was charged to the three-neck flask (100 mL), equipped
with a dropping funnel containing thionyl chloride (40 mL) and a gas inlet tube for
conducting HCl over an absorbing solution of 10% NaOH. Thionyl chloride was added
drop-wise over a period of 15 min at room temperature followed by stirring for 10 h at
80 C. The untreated SOCl2 was removed by distillation and the resulting silica chloride
was vacuum dried at 90 oC to obtain as greyish white powder.
2.3 Preparation of ethylene diamine functionalized cellulose (EDACel)
o
Cellulose (10 g) previously activated at 80 C for 12 h was suspended in N,N-
dimethylformamide (200 mL), followed by the slow addition of thionyl chloride (35 mL)
o
at 80 C, under mechanical stirring. After the addition was complete, stirring was
continued for another 4 h. The cellulose chloride (CelCl) obtained was washed with
several aliquots of dilute ammonium hydroxide solution (0.5 mol/L NH4OH) and the
supernatant after each treatment was removed to bring the pH to neutral. To complete the
washing, the suspension was exhaustively treated with distilled water (3100 mL
approx.). The solid was then separated by filtration and dried in vacuum at room
temperature [24].

8
o
A mixture of CelCl (5 g) and ethylene-1,2-diamine (25 mL) was stirred at 116 C for 3 h.
The reaction mixture was filtered through a sintered glass crucible and the solid was dried
in vacuum at room temperature to afford EDACel as yellow powder.
2.4 Preparation of ethylene diamine functionalized silica-cellulose substrates (EDA/SCs)
A mixture of silica chloride and EDACel (8 g) was taken in three different ratios of 2:1,
1:1 and 1:2 respectively and magnetically stirred in CHCl3 (35 mL) using triethyl amine
o
(0.8 mL) at 60 C for 12 h. Then, the three mixtures were filtered and washed with
chloroform (3×10 mL) and water (3×10 mL) respectively, and dried under vacuum at
room temperature to get light to dark yellow powders.
2.5 Preparation of Pd nanoparticles onto ethylene diamine functionalized silica-cellulose
substrates [Pd(0)-EDA/SCs]
To a mixture of EDA/SCs (2.0 g) in H2O ( 12 mL), aqueous solution of PdCl2 (0.19 g,
1.10 mmol, 3 mL) was added, and the mixture was stirred at room temperature for 8 h.
Then, aqueous solution of NaBH4 (1.50 mmol, 5 mL) was added slowly during 5 h.
Finally, the mixture was filtered, and the residue was washed successively with H2O (3×5
mL) and CH3CN (3×5 mL), respectively, and dried under vacuum at room temperature to
give the dark polymeric Pd(0) nanoparticles (Scheme 1).

9
Scheme 1. General procedure for the synthesis of Pd(0) NPs onto ethylene diamine functionalized silica-
cellulose substrates [Pd(0)-EDA/SCs.
2.6 General procedure for the Pd(0)-EDA/SC-2 catalyzed Suzuki reaction
To a mixture of aryl halide (1 mmol), aryl/heteroaryl boronic acid (1.2 mmol), TBAB
(0.25 mmol), K2CO3 (0.25 mmol) and Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd), double
distilled water (5 mL) was added and the reaction mixture was stirred in a microwave
o
synthesizer at 100 C for an appropriate time (monitored by TLC) (Scheme 2). After
completion, the reaction mixture was cooled to room temperature and filtered. The
catalyst was washed with EtOAc (35 mL) followed by double distilled water (310 mL).
o
It was dried at 100 C for 1 h and could be used in subsequent reactions. The organic layer
was washed with water and dried over anhydrous Na2SO4. Finally, the product was

10
obtained after removal of the solvent under reduced pressure followed by crystallization
from a suitable solvent or passing through column of silica gel (EtOAc-pet. ether).
Br
Ar
Pd(0)-EDA/SC-2
+
ArB(OH)2
K2CO3, TBAB,
H2O, 100 oC
R
R
Scheme 2. Pd(0)-EDA/SC-2 catalyzed Suzuki coupling between arylhalides and boronic acids using water as
solvent under microwave irradiation.
2.7 General procedure for the Pd(0)-EDA/SC-2 catalyzed synthesis of
bis(heterocyclyl)methanes
To a mixture of C–H activated compound 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one,
dimedone or indole (2 mmol), aryl aldehyde (1 mmol) and Pd(0)-EDA/SC-2 (0.2 g, 2.5
mol% Pd), double distilled water (5 mL) was added and the reaction mixture was stirred at
o
100 C for an appropriate time (monitored by TLC) (Scheme 3). After completion, the
reaction mixture was cooled to room temperature and filtered. The product was extracted
o
with hot ethyl acetate (approx. 70 C, 3×10 mL) followed by washing with double
distilled water (3×50 mL). The organic layer was dried over anhydrous Na2SO4 and the
solvent was then removed under reduced pressure to get the crude product. Pure products
were obtained after crystallization or by passing through column of silica gel using
EtOAc-pet. ether as eluent. The catalyst was washed with EtOAc (35 mL) followed by
double distilled water (310 mL). It was dried at 100 oC for 1 h for subsequent use.

11
O
R
O
R
N
O
O
N
O
O
Ph
N
N
N
N
R
H
Pd(0)-EDA/SC-2
H2O, 100 oC
Pd(0)-EDA/SC-2
H2O, 100 oC
OH OH
OH
OH
Ph
Ph
1
2
N
H
Pd(0)-EDA/SC-2
H2O, 100 oC
R
HN
NH
3
Scheme 3. Pd(0)-EDA/SC-2 catalyzed synthesis of bis(heterocyclyl)methane derivatives in water at 100oC.
2.8 General procedure for the Pd(0)-EDA/SC-2 catalyzed thioetherification of aryl
halides
To a mixture of aryl halide (1 mmol), benzyl bromide (1.1 mmol), K2CO3 (0.50 mmol),
thiourea (1.2 mmol) and Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) in a round-bottom flask
(25 mL), water (5 mL) was added and the reaction mixture was stirred at 100 °C for an
appropriate time (Scheme 4). After completion of the reaction (monitored by TLC), the
reaction mixture was diluted with ethyl acetate and filtered. The organic layer was washed
with water (100 mL) and dried over anhydrus Na2SO4. Finally, the product was obtained
after removal of the solvent under reduced pressure followed by crystallization or column
chromatography on silica gel (EtOAc-pet. ether). The catalyst was washed with EtOAc
(35 mL), double distilled water (310 mL) respectively and dried under vaccum for 1 h
at 100 oC for further use.
X
S
S
Pd(0)-EDA/SC-2
Br
R
+
+
R
H2N
NH2
K2CO3, H2O
100 oC

12
Scheme 4. Pd(0)-EDA/SC-2 catalyzed one-pot thioetherification of arylhalides using thiourea as the source of
sulfur.
3. Results and Discussion
3.1 Characterization of Pd(0) nanoparticles onto ethylene diamine functionalized silica-
cellulose substrates [Pd(0)-EDA/SCs]
Synthesis of the Pd(0)-EDA/SCs was achieved in four steps as depicted in Scheme 1. In
this process, the silica chloride and 6-(2’-aminoethylamino)-6-deoxy-cellulose (EDACel)
were taken in three different ratios of 2:1, 1:1 and 1:2 to prepare different EDA/SCs.
Pd(0) NPs were then immobilized on EDA/SCs to get Pd(0)-EDA/SC-1 (prepared from
2:1 ratio of silica chloride and EDACel), Pd(0)-EDA/SC-2 (prepared from 1:1 ratio of
silica chloride and EDACel), and Pd(0)-EDA/SC-3 (prepared from 1:2 ratio of silica
chloride and EDACel), with a view to select the most active and selective heterogeneous
catalyst which could efficiently work under base-free or less basic conditions. Among
various catalysts screened, it was found that Pd(0)-EDA/SC-2 (prepared from 1:1 ratio of
silica chloride and EDACel) was found to be most active and selective. All the three
catalysts were characterised by Fourier Transform Infrared (FT-IR) spectroscopy and
Thermogravimetric Analysis (TGA). The most active heterogeneous catalyst, Pd(0)-
EDA/SC-2 was also characterised by Scanning Electron Microscopy (SEM), Transmission
Electron Microscopy (TEM), High Resolution Transmission Electron Microscopy
(HRTEM), Energy Dispersive X-ray analysis (EDX), Carbon, Hydrogen and Nitogen
analysis (CHN) and Powder X-ray Diffraction (XRD).
Fourier Transform Infrared analysis (FT-IR)

13
The FT-IR spectral analysis of Pd(0)-EDA/SCs was done to study the structure of
EDA/SC. All the three catalysts i.e., Pd(0)-EDA/SC-1, Pd(0)-EDA/SC-2 and Pd(0)-
EDA/SC-3 showed almost similar peaks in their corresponding FT-IR spectra due to the
presence of same functionalities in them. The FT-IR spectra of Pd(0)-EDA/SC-2 (Figure
S1, see ESI) showed bands in the range of 3700-3200 cm-1 due to the surface -OH and
-NH groups. The bands around 1105, 801 and 471cm-1 were presumably due to the
asymmetric stretching (νas), symmetric stretching (νs), and bending modes of Si–O–Si,
respectively. The broad peak centered at 3434 cm-1 was an envelope of streching
vibrations for O-H of the adsorbed water, silanol groups, and N–H of the amino groups
respectively. The characteristic bands around 2919 cm-1 and 1633 cm-1 were assigned to
the stretching vibrations of the C-H of CH2 groups and the bending vibrations of the
–NH of the NH2 groups respectively, both of which were associated with ethylene diamine
modified silica-cellulose substrate.
Thermogravimetric analysis (TGA)
The stability of the Pd(0)-EDA/SCs was determined by TGA. The major weight losses of
all the three catalysts are presented in Table 1. The difference between the thermal
stabilities of the three catalysts may be due to the different ratios of inorganic/organic
substates thus effecting the covalent bonding between the silica chloride and EDACel.
The TGA curve of Pd(0)-EDA/SC-2 (Fig. 1) showed no appreciable weight loss up to
o
o
241 C. The major weight loss from 241 to 300 C was due to the decomposition of
cellulose and chemisorbed material i.e. ethylene diamine groups from the Pd(0)-EDA/SC
substrate. Thus, the catalyst is stable up to 241 oC and it is safe to carry out the reaction at
100 °C under heterogeneous conditions.
Table 1. Characterization of ethylene diamine functionalized silica-cellulose
substrates [Pd(0)-EDA/SCs] by thermal analysis

14
Entry
Catalyst
TGA (oC)
Loss of organic functionality
1
2
3
Pd(0)-EDA/SC-1
Pd(0)-EDA/SC-2
Pd(0)-EDA/SC-3
230-300
241-300
210-290
Thermal analysis was carried out on Linsesis STA PT-1000 make thermal
o
analyzer with heating rate of 10 C/min.
Fig. 1 TGA curve of Pd(0)-EDA/SC-2.
Scanning Electron Microscopy (SEM)
Scanning Electron Micrographs (Fig. 2) of Pd(0)-EDA/SC-2 were recorded to understand
the morphological changes occur on the surface of EDA/SC. The SEM images showed
that the catalyst was a homogeneous powder and Pd nanoparticles were uniformely
distributed onto the surface of EDA/SC and most of the particles have quasi-spherical
shape.

15
Fig. 2 SEM images of Pd(0)-EDA/SC-2
Transmission Electron Microscopy (TEM)
The TEM was performed to observe the morphology and distribution of palladium
nanoparticles onto the surface of ethylene diamine functionalized silica-cellulose substrate
[Figure S2 (a and b), see ESI]. From the TEM image (a), it was inferred that
Pd(0)-EDA/SC-2 contained many small black spheres due to the presence of Pd(0)
nanoparticles. Further, in image (b), Pd(0)-EDA/SC-2 shows the formation of molecular
sieves which offers entrapment of metal particles inside the sieves of silica and cellulose, and
thereby showing the phenomenon of host-guest relationship.
High Resolution Transmission Electron Microscopy (HRTEM)
In order to determine the size of the Pd nanoparticles, high resolution TEM images of
Pd(0)-EDA/SC-2 were recorded Fig. 3. The histogram revealing the size distributions of
Pd nanoparticles is proposed according to the data, which is obtained from the HRTEM
image with an average size of 3.5 nm (Figure S3, see ESI).

16
Fig. 3 HRTEM images of Pd(0)-EDA/SC-2
Energy Dispersive X-ray (EDX) and Carbon Hydrogen Nitrogen (CHN) analysis
The elemental composition of Pd(0)-EDA/SC was determined by EDX analysis (Figure S4,
see ESI). The EDX spectrum reveals the presence of Pd on EDA/SC. It also showed the
presence of other elements like C, O, Si and Cl in EDA/SC. Moreover, the presence of
nitrogen was also determined by CHN analysis.
Atomic Absorbption spectroscopy (AAS)
In order to evaluate the content of Pd supported on EDA/SC-2, the catalyst was analyzed
using atomic absorption spectroscopy (AAS). The results indicated that the content of Pd
loaded onto EDA/SC was 6.67 wt%.
X-ray Powder Diffraction (XRD)
Unequivocal evidence of Pd(0) nanoparticles onto EDA-SC was provided by XRD data (Fig.
4). The XRD data of Pd(0)-EDA/SC-2 revealed its metallic nature. Three reflection patterns,
attributed to the planes (1 1 1), (2 0 0) and (2 2 0) are readily recognized from the XRD
pattern, which could be indexed to a face-centered cubic (fcc) palladium [25]. These
observations corresponds to the presence of Pd(0) nanoparticles onto the surface of EDA/SC.

17
Fig. 4 XRD spectrum of Pd(0)-EDA/SC-2.
3.2 Catalyst testing for C-C bond formation
Activity of Pd(0)-EDA/SCs was tested for Suzuki coupling, and synthesis of
bis(heterocyclyl)methanes via C-C bond formation. In order to optimize the reaction
conditions for Suzuki coupling, 4-bromoacetophenone and benzene boronic acid were
selected as test substrates and the reaction was carried out in water under microwave
irradiation. We, then began our experiment by carrying out the reaction with test substrates
using Pd(0)-EDA/SC-1, Pd(0)-EDA/SC-2 and Pd(0)-EDA/SC-3, with a view to find the best
catalytic system for the Suzuki coupling. The results are presented in Table 2, which
indicated that among the different catalysts screened, Pd(0)-EDA/SC-2 provided the best
results in terms of reaction time, yield and selectivity. As our developed catalyst system
[Pd(0)-EDA/SC-2] was base functionalised and since, our main motive was to carry out the Pd
catalysed transformations under base-free conditions, we then examined Suzuki coupling
under different conditions with respect to base and phase transfer catalyst, TBAB (Table 3).
Initially, we carried out the Suzuki coupling in case of test substrates using Pd(0)-EDA/SC-2
in the absence of base, unfortunately poor results were obtained (35% yield after 0.5 h, Table
3, entry 1). It is well known that the addition of base is necessary to carry out the Suzuki
coupling effectively, so K2CO3 was selected as the base, since it is mild, inexpensive and

18
easily available. We then carry out the test reaction in the presence of base (0.10 mmol to 0.50
mmol, Table 3, entries 2-4), but the reaction didn’t go to completion and the maximum yield
obtained was only 55%. Since water was used as solvent, we then carried out the reaction
using TBAB in order to increase the solubility of the reagents in water. Next, we carried the
Suzuki reaction in the presence of Pd(0)-EDA/SC-2 using different amounts of base and
TBAB (0.10 mmol to 0.50 mmol) (Table 3, entries 5-10). Without the presence of K2CO3,
47% of product was obtained using 0.25 mmol of TBAB (Table 3, entry 9). So, we further
tried the test reaction using 0.5 mmol of TBAB without using any base (Table 3, entry 10),
the results indicate that there is not much increase in yield as compared to 0.25 mmol of
TBAB. On the basis of the results, we conclude that 0.25 mmol each of K2CO3 and TBAB
were required to carry out the reaction with excellent yield (92%, Table 3, entry 7). With
these encouraging results, we had limited the amount of base in the presence of our base
functionalised catalyst, Pd(0)-EDA/SC-2 from 200 mol% [19] to 25 mol%. Although, there is
considerable literature precedence for Suzuki coupling, but till now, there is no report of
Suzuki coupling performed using such a low amount of base, which justifies the role of Pd(0)-
EDA/SC-2 as base functionalised catalyst system. Finally, to select the appropriate amount
of Pd(0)-EDA/SC-2, the test reaction was carried using different amounts of the catalyst i.e.
0.050 g (1 mol% Pd), 0.10 g (1.5 mol% Pd), 0.15 g (2.0 mol% Pd), 0.2 g (2.5 mol% Pd)
and 0.25 g (3 mol% Pd), and found that best results were obtained with 0.2 g (2.5 mol%).
The results are shown in Fig. 5. From the results, it is clearly depicted that the addition of sole
base in limited amount does not complete the reaction. However, with the addition of base
functionalised Pd(0)-EDA/SC-2 and that too in appropriate amount acts synergistically with
limited amount of base to complete the reaction with excellent yields. So, 0.2 g of catalyst
was selected for carrying out the Suzuki coupling. Thus, optimum conditions selected were:
aryl halide (1 mmol), aryl/heteroaryl boronic acid (1.2 mmol), K2CO3 (0.25 mmol) TBAB

19
(0.25 mmol) and Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% of Pd) using distilled water as solvent
under microwave irradiation (Table 4). The generality of the developed protocol was studied
by choosing different aryl halides substituted with both electron-donating and electron-
withdrawing groups, and good to excellent results were obtained (Table 4). Bromophenol and
bromoaniline which were considered as poor substrates for the Suzuki coupling, also undergo
reaction efficiently (Table 4, entries 6 and 7). Similar conditions were also successful for the
synthesis of polyaryls (Table 4, entries 8 and 9). Heteroarylboronic acids which generally
undergoes reaction slowly, also work efficiently using of Pd(0)-EDA/SC-2 in water (Table 4,
entry 12). To highlight the applicability of the developed catalytic system, Suzuki reaction
was also performed thermally under the same optimized reaction conditions and similar
results were obtained (Table 4, entries 2, 3, 5 and 12).
Table 2. Comparison of catalytic activities of ethylene diamine functionalized silica-cellulose substrates
[Pd(0)-EDA/SCs] for C-C and C-S coupling reactions
Catalyst
Pd(0)-EDA/SC-1
Pd(0)-EDA/SC-2
Time Yield
Pd(0)-EDA/SC-3
Entry
Reactions
Time
(h)
Yield
(%)d
Time
(h)
Yield
(%)d
(h)
(%)d
1.
2.
3.
Suzukia
0.50
2.0
7
89
88
83
0.5
2.5
8.5
90
86
82
0.25
92
Bis(heterocyclyl)
methanesb
1.5
6
90
88
Thioetherificationc
aReaction conditions: 4-bromoacetophenone (1 mmol), benzeneboronic acid (1.2 mmol), K2CO3 (0.25 mmol),
TBAB (0.25 mmol), Pd(0)-EDA/SCs (2.5 mol% Pd) and water (5 mL) at 100oC under microwave irradiation.
bReaction conditions: Benzaldehyde (1 mmol), 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (2 mmol), Pd(0)-
EDA/SCs ( 2.5 mol% Pd) and water (5 mL) at 100 oC.
cReaction conditions: 4-bromobenzaldehyde (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol), K2CO3
(0.5 mmol), Pd(0)-EDA/SCs ( 2.5 mol% Pd) and water (5 mL) at 100 oC
dIsolated yields.

20
Table 3. Optimization of base (K2CO3) for C-C and C-S couplings in the presence of ethylene diamine
functionalized silica-cellulose [Pd(0)-EDA/SC-2]
Entry
Reaction
Optimization
Time (h) Yield (%)e
Base
TBAB
(mmol)
(mmol)
1
2
3
4
5
6
7
-
-
0.5
0.5
0.5
0.5
0.5
0.5
35
40
50
55
45
75
92d
0.10
0.25
0.50
0.10
0.25
-
-
-
0.10
0.10
Suzukia
0.25
0.25
0.25
0.25
0.50
0.25
0.25
0.5
8
9
0.50
92d
-
-
47
10
0.5
52
11
12
13
14
0.10
0.25
0.50
-
-
-
-
-
1.0
1
91d
93d
93d
90d
Bis(heterocyclyl)methanesb
1
1.5
15
16
17
18
-
-
-
-
-
8
8
6
6
25
0.25
0.50
1.0
60
Thioethersc
88d
88d
aReaction conditions: 4-bromoacetophenone (1 mmol), benzeneboronic acid (1.2 mmol), K2CO3 ( x mmol),
o
TBAB (x mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 C under microwave
irradiation.
bReaction conditions: Benzaldehyde (1 mmol), 3-methyl-1-phenyl-1H- pyrazol-5(4H)-one (2 mmol), K2CO3 ( x
mmol), Pd(0)- EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100oC.
cReaction conditions: 4-bromobenzaldehyde (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol),
K2CO3, (x mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 oC.
dIsolated Yields
eColumn chromatography yields.

21
Table 4. Pd(0)-EDA/SC-2 catalyzed Suzuki coupling between arylhalides and boronic acids using water as
solvent under microwave irradiationa
Entry
Substrate
Product
Time (min)
Yield (%)b
1.
18
90
Br
Br
O
C
O
C
2.
3.
4.
15, 45c
15, 40c
17
92, 93c
90, 90c
90
H3C
H3C
NC
Br
NC
O
O
C
H
C
H
Br
Br
15, 40c
91, 92c
O
O
C
5.
Ph
C
Ph
6.
7.
8.
35
35
20
85d
82d
78
HO
Br
HO
H2N
Br
Br
H2N
Br
Br
9.
20
20
25
80
79
75
Cl
Cl
10.
11.
Br
H
H
N
N
Br

22
O
C
O
C
H3C
20, 60c
81, 83c
Br
H3C
12.
S
aReaction conditions: aryl halide (1 mmol), benzeneboronic acid/2-thiophene boronic acid (1.2 mmol), K2CO3
(0.25 mmol), TBAB (0.25 mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 oC under
microwave irradiation.
bIsolated yields.
cSame conditions as (a) but under thermal conditions.
dThe product was obtained after passing through column of silica gel and elution with EtOAc: pet ether (0.3-
9.7).
Fig. 5. Effect of catalyst loading. Reaction conditions: 4-bromoacetophenone (1 mmol), benzeneboronic acid
(1.2 mmol), K2CO3 (0.25 mmol), TBAB (0.25 mmol), catalyst (0.05 g to 0.25 g) and water (5 mL) at 100 oC
under microwave irradiation.
Our next endeavour was to extend the scope of Pd(0)-EDA/SC for the synthesis of
bis(heterocyclyl)methanes. The reaction was carried out by stirring a mixture of 3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one and benzaldehyde (test substrates) in the presence of Pd(0)-
o
EDA/SC-1, Pd(0)-EDA/SC-2 and Pd(0)-EDA/SC-3 in water at 100 C (Table 2). Again,
Pd(0)-EDA/SC-2 was found to be the best catalyst for the synthesis of
bis(heterocyclyl)methanes. Since our developed catalytic system, Pd(0)-EDA/SC-2 was base
functionalised, so the influence of external base on the catalytic performance of this system
was also investigated. The results are presented in Table 3, which indicated that with 0.25
mmol and 0.50 mmol of K2CO3 in water, the product was obtained in 93% yield after 1 h.

23
However, in the absence of K2CO3, the product was obtained in 90% yield in 1.5 h (Table 3,
entry 14). Although the reaction took a long time but we had significantly avoided the use of
K2CO3 in the presence of Pd(0)-EDA/SC-2 as base functionalised catalyst system. Again,
optimization with respect to the amount of catalyst was done and found that 0.2 g of Pd(0)-
EDA/SC-2 was sufficient to carry out the reaction efficiently in terms of reaction time and
yield. With these encouraging results, we turn to explore the generality of the developed
protocol using other C–H activated compounds such as dimedone and indole under the
optimized reaction conditions. The reaction of C–H activated compounds such as pyrazolone,
dimedone and indole was carried out with various aldehydes having both electron-releasing
and electron-withdrawing groups and excellent results were obtained (Table 5).
Table 5. Pd(0)-EDA/SC-2 catalyzed synthesis of bis(heterocyclyl)methane derivatives in water at 100oCa
Entry Substrate
Product
(1a-j)
Time/Yield
(h) (%)b
Product
(2a-j)
Time/Yield
(h) (%)b
Product
(3a-j)
Time/Yield
(h) (%)b
O
O
1
1.5/90
1.2/88
2/89
1/85
3/87
2/89
N
N
N
N
O
H
OH OH
Ph
Ph
NH
HN
OH
OH
1a
3a
2a
Br
Br
Br
Br
2
O
O
N
N
N
N
OH
O
H
NH
HN
OH
OH
OH
Ph
Ph
3b
1b
2b
Cl
Cl
Cl
Cl
3
1.2/85
1.2/88
2/86
O
O
N
N
N
N
OH
O
H
OH
OH
Ph
Ph
OH
NH
HN
1c
2c
3c

24
Cl
Cl
N
Cl
Cl
O
O
4
2/80
1.5/82
1/90
2.5/85
2/89
O
H
N
N
N
HN
NH
OH OH
OH
OH
Ph
Ph
3d
2d
1d
NO2
NO2
NO2
NO2
5
1.2/86
O
O
N
N
N
N
OH OH
O
H
NH
HN
OH
OH
Ph
Ph
3e
2e
1e
NO2
NO2
NO2
NO2
NH
O
O
6
7
2.5/79
1.2/85
1.2/90
2/92
2/86
O
N
N
N
H
N
HN
OH
OH
OH OH
Ph
Ph
3f
2f
1f
OMe
OMe
OMe
OMe
1.2 /90
O
O
N
N
N
N
OH
O
H
OH
OH
Ph
Ph
OH
NH
HN
1g
2g
3g
Me
Me
Me
Me
8
1.5/90
1.3/88
2/86
1.2/89
1.2/90
1.5/85
2.5/88
2.5/89
3/86
O
O
N
N
O
N
N
H
OH OH
HN
NH
Ph
OH
OH
Ph
3h
1h
2h
OH
OH
OH
OH
9
O
O
N
N
N
N
O
H
OH OH
Ph
OH
OH
Ph
NH
HN
1i
2i
3i
10
O
O
O
O
O
O
O
H
N
N
N
N
OH OH
HN
NH
OH
Ph
OH
Ph
3j
1j
2j
aReaction conditions: aryl aldehyde (1 mmol), 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one /dimedone/ indole
(2 mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 oC.
bIsolated Yields.

25
3.3 Catalyst testing for C-S bond formation
Fascinated by the impressive performance of Pd(0)-EDA/SC-2 in C-C couplings, its catalytic
activity was also tested for the thioetherification via C-S coupling reaction. The
thioetherification of 4-bromobenzaldehyde was carried out using benzyl bromide and thiourea
as sulphur source (test substrates ) in the presence of Pd(0)-EDA/SCs. Again, water was used
as a solvent. The screening of various catalysts allowed us to select Pd(0)-EDA/SC-2 as the
most effective catalyst for one-pot thioetherification of aryl halides with thiourea and benzyl
bromide in water at 100 °C (Table 2). Next, the reaction with test substrates was done in the
presence of Pd(0)-EDA/SC-2 without using base. But unfortunately, in the absence of base,
the yield of the product obtained was only 25% (Table 3, entry 15). So, we made a choice to
add the base (K2CO3), and further optimization was done to select the minimum amount of
base required for the complete conversion of reactants to products. The results are presented
in Table 3, which indicated that 0.5 mmole of K2CO3 showed the best performance,
furnishing the desired product in quantitative yield (Table 3, entry 17). Compared with
literature protocols [20], our catalyst Pd(0)-EDA/SC-2 successfully offers the
thioetherification reaction to get completed in less basic conditions which validates our
catalyst as base functionalised catalyst system. Using the optimized conditions and to evaluate
the scope of the developed method, the present reaction was further extended to a broader
range of substituted aryl halides (Table 6) and found that the reaction works well for both
electron-donating and electron-withdrawing groups. In order to select the optimum amount of
catalyst, reaction in case of test substrates was carried out with varying amounts of catalyst
and found that 0.2 g of Pd(0)-EDA/SC-2 gave the best results in terms of reaction time and
yield. In general, the reaction is clean, high yielding and leads to the synthesis of structurally
diverse thioethers in a more practical and convenient way.

26
Table 6. Pd(0)-EDA/SC-2 catalyzed thioetherification of different aryl halides using thiourea under aqueous
medium at 100 Ca.
Time (h)
Yield (%)b
Entry
Aryl halide
Product
1.
7.5
86
Br
S
6.0
7.0
7.0
6.0
7.0
8.5
8.0
6.0
88
87
88
88
86
81c
80c
85
S
2.
3.
4.
5.
6.
7.
NC
Br
NC
S
H3COC
H3COC
OHC
Cl
H3COC
S
Br
H3COC
S
Br
OHC
S
OHC
Cl
OHC
S
HO
Br
Br
HO
S
8.
9.
H2N
H2N
Br
S

27
H
10.
8.0
6.0
82
85
N
S
Br
N
H
11.
HOOC
Br
S
HOOC
aReaction conditions: aryl halide (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol), K2CO3, (0.50
mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 oC.
bIsolated yields.
cColumn chromatographic yields.
In order to demonstrate the role of Pd(0)-EDA/SC-2 as the base functionalised heterogeneous
catalyst, we performed the control experiments for the comparison of activity with other
catalysts. The experiments were done in case of Table 4, entry 2; Table 5, entry 1 (1a) and
Table 6, entry 5 and the results are summarised in Table 7. At first, the reactions were
performed without catalyst (Table 7, entry 1) and found that no reaction was observed in
each case. The reaction was also performed with PdCl2 (Table 7, entry 2) under
homogeneous catalysis using 0.25 eq. of K2CO3. The reactions occurred but with less
efficiency as compared to our base functionalized catalyst. Next, we employed various nano
Pd(0) based heterogeneous catalysts. Again, the catalysts were less effective than our catalyst
(Table 7, entries 3-5). These results clearly indicates that the base functionalization of Pd(0)-
EDA/SC-2 played a significant role in catalysing the C-C and C-S coupling reactions with
excellent yields.

28
Table 7. Control experiments for the comparison of activity of Pd(0)-EDA/SC-2 with other catalysts for the C-C
and C-S coupling reactions
Entry Reactions
Catalyst
Suzukia
Bis(heterocyclyl)methanesb
Thioetherificationc
Time (min) Yield (%)d
Time (h)
Yield (%)d
Time(h) Yield(%)d
1.
2.
3.
4.
5.
6.
No catalyst
15
15
15
15
15
15
NRe
60
1.5
1.5
1.5
1.5
1.5
1.5
traces
6
6
6
6
6
6
NRe
35
PdCl2
85
70
78
80
90f
Cellulose Pd(0)
Silica-Starch Pd(0)
Silica-cellulose Pd(0)
Pd(0)-EDA/SC-2
35
20
36
20
40
25
92f
88f
aReaction conditions: 4-bromoacetophenone (1 mmol), benzeneboronic acid (1.2 mmol), K2CO3 (0.25 mmol),
TBAB (0.25 mmol), catalyst (2.5 mol% Pd) and water (5 mL) at 100oC under microwave irradiation.
bReaction conditions: Benzaldehyde (1 mmol), 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (2 mmol), catalyst
(2.5 mol% Pd) and water (5 mL) at 100oC.
cReaction conditions: 4-bromobenzaldehyde (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol), K2CO3
(0.5 mmol), catalyst (2.5 mol% Pd) and water (5 mL) at 100 oC
dColumn chromatography yield.
eNR: No reaction.
fIsolated yield.
3.4 Recyclabilty and heterogeneity
Recyclability of Pd(0)-EDA/SC-2 was investigated in case of Table 4, entry 2; Table 5,
entry 1 (1a) and Table 6, entry 5. The catalyst was separated by filtration after
completion of the reaction and again used for subsequent reactions after adding fresh
substrates under similar conditions for five consecutive runs. The results are summarised
in Table 8. It was found that catalyst could be recycled upto five consecutive runs without
loss of significant activity. The thermogravimetric analysis and FTIR of the Pd(0)-
EDA/SC-2 after 5th run indicated negligible change in the structure of catalyst. The slight
loss of activity may be due to the microscopic changes on the surface of the catalyst.
Moreover, the AAS analysis of the used Pd(0)-EDA/SC-2 after 5th run showed 6.58 wt%.

29
of Pd content, which indicated that a very small amount of the Pd metal was removed
from the EDA/SC (fresh catalyst contains 6.67 wt% Pd). Recyclability in case of Table 6,
entry 5 also reveals that the catalyst successfully withstood the deactivation or poisoning
in the presence of sulphur. Moreover, there is enough data in the literature to support,
where palladium catalysts are able to withstand catalyst deactivation and form aryl-sulfur
bonds in high-yielding transformations [26].
In order to rule out the possibility of leaching of Pd(0) NPs from the surface of the
catalyst, we carried out the hot filtration test. The reaction in case of entry 2 (Table 4) has
been carried out in the presence of Pd(0)-EDA/SC-2, until the conversion was 45%
(7 min) and at that point, Pd(0)-EDA/SC-2 was filtered off at the reaction temperature.
The liquid phase was then transfered to another flask and allowed to react, but no further
significant conversion was observed. So, we conclude that there is no significant leaching
of Pd(0) NPs from the surface of the substate, thus pointing to a catalysis of
heterogeneous nature.
Table 8. Recyclability of Pd(0)-EDA/SC-2 for the C-C and C-S coupling reactionsa
Catalytic
runs
Suzuki
Bis(heterocyclyl)methanes
Thioetherification
Yield (%)b
Yield (%)b
Yield(%)b
1.
2.
3.
4.
5.
92
90
88
92
91
90
90
90
90
89
88
87
87
86
85
aReaction conditions [Suzuki coupling]: 4-bromoacetophenone (1 mmol), benzeneboronic acid (1.2 mmol),
K2CO3 (0.25 mmol), TBAB (0.25 mmol), Pd(0)-EDA/SC-2 (0.2 g, 2.5 mol% Pd) and water (5 mL) at 100 oC
for 15 minutes under microwave irradiation; [bis(heterocyclyl)methanes]: benzaldehyde (1 mmol), 3-methyl-1-