Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama Cross-Coupling Reaction Under Ligand Free Conditions

Article abstract of DOI:10.1007/s10562-018-2369-5

Abstract: In the current work, palladium nanoparticles (Pd NPs) were prepared from palladium acetate biogenically using the aqueous-ethanolic extract of black pepper (Piper nigrum) and characterized by various analytical techniques like XRD, FE-SEM, EDS, TEM, ATR-IR, UV–Vis spectroscopy, BET, TGA and ICP-OES analysis. The reduction of Pd(II)?to?Pd(0) is achieved by the action of various phytochemicals present in the black pepper extract like phenols, acids, pellitorine, ethyl piperonyl cyanoacetate, piperine and N-isobutyl-tetradeca-2,4-dienamide. The biosynthesized Pd NPs shown excellent catalytic activity in aryl halide cyanation and Hiyama cross-coupling reactions. Also, less toxic potassium hexacyanoferrate(II) trihydrate was used as cyanide source in aryl halide cyanation and Hiyama cross-coupling was performed under fluoride free condition. Both reactions proceeded well with Pd NPs under ligand free circumstances to give good to excellent yields. The Pd NPs were recovered after each reaction and recycled up to five times in aryl halide cyanation and ten times in Hiyama cross-coupling without considerable loss in the activity. Graphical Abstract: Green synthesis of palladium nanoparticles: applications in aryl halide cyanation and Hiyama cross-coupling reaction under ligand free conditions. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10562-018-2369-5

Catalysis Letters
https://doi.org/10.1007/s10562-018-2369-5
Green Synthesis of Palladium Nanoparticles: Applications in Aryl
Halide Cyanation and Hiyama Cross-Coupling Reaction Under Ligand
Free Conditions
Vishal Kandathil1 · Ramesh B. Dateer1 · B. S. Sasidhar2 · Shivaputra A. Patil3 · Siddappa A. Patil1
Received: 8 February 2018 / Accepted: 21 March 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
In the current work, palladium nanoparticles (Pd NPs) were prepared from palladium acetate biogenically using the aqueous-
ethanolic extract of black pepper (Piper nigrum) and characterized by various analytical techniques like XRD, FE-SEM,
EDS, TEM, ATR-IR, UV–Vis spectroscopy, BET, TGA and ICP-OES analysis. The reduction of Pd(II) to Pd(0) is achieved
by the action of various phytochemicals present in the black pepper extract like phenols, acids, pellitorine, ethyl piperonyl
cyanoacetate, piperine and N-isobutyl-tetradeca-2,4-dienamide. The biosynthesized Pd NPs shown excellent catalytic activity
in aryl halide cyanation and Hiyama cross-coupling reactions. Also, less toxic potassium hexacyanoferrate(II) trihydrate was
used as cyanide source in aryl halide cyanation and Hiyama cross-coupling was performed under fluoride free condition. Both
reactions proceeded well with Pd NPs under ligand free circumstances to give good to excellent yields. The Pd NPs were
recovered after each reaction and recycled up to five times in aryl halide cyanation and ten times in Hiyama cross-coupling
without considerable loss in the activity.
Graphical Abstract
Green synthesis of palladium nanoparticles: applications in aryl halide cyanation and Hiyama cross-coupling reaction under
ligand free conditions.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-018-2369-5) contains
supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
Vol.:(0123456789)
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V. Kandathil et al.
Keywords Biogenic synthesis · Piper nigrum · Palladium nanoparticles · Cyanation reaction · Hiyama cross-coupling ·
Recycle
comparatively less toxic cyanating reagents like phenyl
cyanates [32], acetone cyanohydrins [33] and benzyl thiocy-
anates [34] are often costly and dangerous. The use of potas-
sium hexacyanoferrate(II) trihydrate (K4Fe(CN)6·3H2O) as
a cyanide source in cyanation reactions by Beller and co-
workers [35, 36] drawn much attention due to its less toxic-
ity, inexpensiveness and environmental friendliness [37, 38].
In K4Fe(CN)6·3H2O, cyanide ions are bound strongly, slow-
ing down the release of CN− ions in the reaction medium
which in turn prevents the palladium catalyst from quick
deactivation caused by the palladium poisoning by CN− ions
[39]. There are reports wherein palladium acetate [40, 41],
palladium complex [42], palladium on carbon [43] are used
for catalyzing cyanation reaction with K4Fe(CN)6·3H2O.
The main drawback of these catalysts is the issue pertaining
with the recovery and recycling. Thus, development of pal-
ladium based catalysts which are highly active and heteroge-
neous in nature is still an area to be explored which can offer
an added advantage while considering the environmental as
well as economical aspect.
1 Introduction
Noble metal nanoparticles find a large potential applica-
tion in various fields of science because of their distinctive
optical properties [1, 2], electronic properties [3], catalytic
properties [4] and so on. In nanocatalysis field, the large sur-
face-to-volume ratios of these metal nanoparticles is the key
reason behind their activity along with the size and shape
[5]. Also, the physico-chemical properties of these nano-
particles can be fine-tuned by the design and manipulation
of the structure. Depending upon the shape and structure of
nanoparticles synthesized, their selectivity and reactivity can
be optimized [5].
Conventional methods for the synthesis of metal nanopar-
ticles include reduction of metal salts using chemicals like
sodium borohydride [6], sodium citrate [7], hydrazine [8]
etc. to their corresponding metal nanoparticles. Recently, the
biogenic synthesis of metal nanoparticles has gained a lot of
attention among the scientific community [9–16]. The bio-
genic synthesis employs different microorganisms or extract
from plant parts or any living organism for the reduction
process [17, 18]. The biogenic synthesis helps to avoid the
usage of aforementioned hazardous and toxic chemicals in
the metal nanoparticle synthesis thereby providing a green
and sustainable approach for metal nanoparticle synthesis
[9].
The use of organosilicon reagent as an organic nucleo-
phile is gaining much acceptance in C–C coupling reaction
as an alternative for Suzuki–Miyaura cross-coupling reaction
[44–47] due to the relatively less toxicity and inexpensive-
ness of organosilicon [48–51]. Thus Hiyama cross-coupling
reaction stands as an outstanding tool in the construction
of different C–C coupled products which has broad range
of application in numerous field including pharmaceuticals,
agrochemicals, polymers and natural products [48].
Among the spices available across the globe, Piper
nigrum (black pepper) is an important class with its unique
aroma and pungency and used in seasoning [19]. It is also
used as an ingredient in traditional medicines [20]. Black
pepper belongs to piperaceae family and is cultivated along
the tropical regions. The naturally occurring alkaloids, pip-
erine, along with some essential oils are responsible for the
flavor and pungency of black pepper [21, 22]. The piper-
ine content in black pepper varies with different piperaceae
family [22]. Pepper also contains a wide range of aroma-
contributing terpenes like germacrene, limonene, pinene,
alpha-phellandrene, and beta-caryophyllene [22]. All these
ingredients present in the black pepper makes it a very
important and valuable spice for different applications.
Aryl nitriles are an important class of molecules which
form fundamental structural units or building blocks in
various chemicals including agrochemicals, pharmaceuti-
cal ingredients and natural products as well [23–27]. The
synthesis of these aryl nitriles requires stoichiometric
amount of highly toxic cyanating reagents like copper cya-
nide [28], potassium cyanide [29], sodium cyanide [30], zinc
cyanide [23] or trimethylsilylcyanide [31]. Also, the use of
Herein, we report a convenient and efficient palla-
dium catalyzed cyanation of aryl halides using less toxic
K4Fe(CN)6·3H2O and fluoride free Hiyama cross-coupling
of aryl halides with trimethoxyphenylsilane using biogenic
synthesized palladium nanoparticles (Pd NPs) mediated by
black pepper extract. The major constituents of black pep-
per extract were confirmed by GC–MS analysis, ATR-IR
and UV–Vis analysis. The Pd NPs synthesized was char-
acterized by various analytical techniques like attenuated
total reflectance infrared spectroscopy (ATR-IR), UV–Vis
spectroscopy, inductively coupled plasma-optical emission
spectroscopy (ICP-OES), energy-dispersive X-ray spectros-
copy (EDS), field-emission scanning electron microscopy
(FESEM), transmission electron microscopy (TEM), X-ray
powder diffraction (XRD), thermogravimetric analysis
(TGA) and Brunauer–Emmett–Teller surface area analysis
(BET).
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Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
2.3 Preparation of Black Pepper Extract
2 Experimental
Dried black pepper seeds were rinsed with double distilled
water, air dried and powdered using a mechanical grinder.
From the powdered black pepper, 10.0 g was weighed
and transferred to a 250 mL Erlenmeyer flask containing
100 mL of 50% aqueous–ethanol. The mixture was heated
to 75–80 °C under magnetic stirring for 1 h. The obtained
mixture was centrifuged at 5000 rpm for 20 min to remove
the residue and then the supernatant liquid was filtered to get
clear extract. The prepared extract was stored in refrigerator
for further use.
2.1 Materials
Dried black pepper seeds were collected from the local area
of Kasaragod, Kerala, India. Unless otherwise stated, all
reactions were performed under aerobic conditions in oven-
dried glassware with magnetic stirring. Palladium acetate,
K4Fe(CN)6·3H2O, aryl halides, sodium carbonate, trimeth-
oxyphenylsilane, sodium hydroxide, sodium sulphate were
purchased from Sigma-Aldrich and Avra chemical com-
pany and were used without further purification. Heating
was accomplished by either a heating mantle or silicone oil
bath. Reactions were monitored by thin-layer chromatog-
raphy (TLC) performed on 0.25 mm Merck TLC silica gel
plates, using UV light as a visualizing agent. Purification of
reaction products was carried out by flash column chroma-
tography using silica gel 60 (230–400 mesh). Yields refer to
chromatographically pure material. Concentration in vacuo
refers to the removal of volatile solvent using a rotary evap-
orator attached to a dry diaphragm pump (10–15 mmHg),
followed by pumping to a constant weight with an oil pump
(<300 mTorr).
2.4 Biogenic Synthesis of Palladium Nanoparticles
To an aqueous solution of 50 mL 10 mM Pd(OAc)2 stir-
ring at 85 °C, 10 mL of black pepper extract was added
dropwise. Palladium nanoparticles (Pd0) were formed by the
reduction of palladium ions (Pd2+) over a time period of 2 h
which was monitored by UV–Vis spectrum of the reaction
mass. The gradual change in color of the solution from ini-
tial light brown to black over time indicated the conversion
of Pd2+ to Pd0. After the completion of reduction, the reac-
tion mass was cooled to room temperature and then Pd NPs
were collected from the reaction mass by centrifugation at
6000 rpm for 15 min followed by re-dispersion in double
distilled water. The wet Pd NPs were then dried at 60 °C
for 8 h.
2.2 Characterization
Attenuated total reflectance infrared spectra were
recorded with a Bruker Alpha Eco-ATR spectrometer.
Brunauer–Emmett–Teller surface areas were obtained by
physisorption of N2 using a Microtrac BELSORP MAX
instrument. The elemental palladium content in biogenic
synthesized palladium nanoparticles (Pd NPs) was deter-
mined by Perkin Elmer Optima 5300 DV inductively cou-
pled plasma optical emission spectrometer. Transmission
electron microscope images were obtained using Jeol/
JEM 2100 microscope. A JEOL JSM 7100F field-emis-
sion scanning electron microscope (FESEM), fitted with
energy dispersive X-ray spectroscopy, was used to observe
the morphology and elemental distributions of samples.
Thermogravimetric analysis was carried out using a Perkin
Elmer, Diamond TG/DTA with a heating rate of 10.0 °C/
min. X-ray powder diffraction patterns were obtained using
Rigaku X-ray diffraction Ultima-IV. 1H NMR spectra were
recorded at 400 MHz, and are reported relative to CDCl3
2.5 General Procedure for Cyanation of Aryl Halides
In a 25 mL round bottom flask containing 6 mL of DMF, aryl
halide (1 equiv), K4Fe(CN)6·3H2O (0.17 equiv), Na2CO3
(1.5 equiv) and Pd NPs (0.5 mol%) were added and stirred
magnetically at 120 °C for required time. The reaction mass
was cooled to room temperature after reaction completion
(as monitored by TLC), followed by the recovery of Pd
NPs by centrifugation at 6000 rpm for 15 min. The prod-
uct was then extracted using dichloromethane (2×20 mL)
and subjected to water wash (2×20 mL) followed by drying
of the organic layer over Na2SO4. The dried organic layer
was concentrated in vacuo, and the product was purified by
column chromatography using n-hexane and ethyl acetate
as eluents to afford the corresponding products in good to
excellent yields. All the aryl nitrile products were known
molecules and were confirmed by comparing the melting
1
(δ7.27). H NMR coupling constants (J) are reported in
Hertz (Hz) and multiplicities are indicated as follows: s
(singlet), d (doublet), t (triplet), and m (multiplet). Liquid
chromatography mass spectra (LC–MS) were recorded on
an Agilent technologies quadrupole LC-MS system. GC–MS
analysis was performed on a Shimadzu (Tokyo, Japan) Make
GC-MS-TQ8030 system.
1
point, H NMR and ATR-IR data with authentic samples
(see Supporting Information for details).
1 3

V. Kandathil et al.
phytochemicals present in the black pepper is responsible
for the reduction of Pd(II) to Pd(0).
2.6 General Procedure for Hiyama Cross‑Coupling
Reaction
The presence of various functional groups present in
the black pepper extract was confirmed by ATR-IR analy-
sis. The ATR-IR spectrum of the black pepper extract is
shown in Fig. 2a. The peaks at 3329, 3013, 2924, 2861,
1711, 1619, 1582, 1493, 1437, 1240, 1027 and 926 cm−1
are due to stretching and bending vibrations of functional
groups like –OH, –NH, aromatic and aliphatic –CH, –C=O
and –C=C. Thus the presence of functional groups which
play key role in the bioreduction of Pd(II) to Pd(0) were
identified by ATR-IR.
In a 25 mL round bottom flask containing 5 mL of ethylene
glycol, aryl halide (1 equiv), trimethoxyphenylsilane (1.5
equiv), NaOH (3 equiv) and Pd NPs (0.2 mol%) were taken
and stirred at 100 °C for required time. The reaction mass
was cooled to room temperature after reaction completion
(as monitored by TLC), followed by the recovery of Pd NPs
by centrifugation at 6000 rpm for 30 min. The product was
then extracted using dichloromethane (2×20 mL) and sub-
jected to water wash (1×20 mL) and brine wash (1×20 mL)
followed by drying of the organic layer over Na2SO4. The
dried organic layer was concentrated in vacuo, and the prod-
uct was purified by column chromatography using n-hexane
and ethyl acetate as eluents to afford the corresponding prod-
ucts in good to excellent yields. All the coupled products
were known molecules and were confirmed by comparing
the melting point, 1H NMR and LC-MS data with authentic
samples (see Supporting Information for details).
Further, the black pepper extract was subjected to
GC–MS analysis to find out the phytochemicals present and
their percentage so as to understand the role of different
phytochemicals in the reduction process. The GC–MS chro-
matogram of dichloromethane extract of the black pepper
showed the qualitative presence of the phenols, acids, pelli-
torine, ethyl piperonylcyanoacetate, piperine and N-isobutyl-
tetradeca-2,4-dienamide as the major components present in
it (Table 1) (see Supporting Information for GC–MS analy-
sis protocol).
2.7 Procedure for Recovery of Palladium
Nanoparticles
3.2 Biogenic Synthesis of Palladium Nanoparticle
After the reaction completion, the reaction mass was cooled
to room temperature and Pd NPs were recovered by centrifu-
gation at 6000 rpm for 15–30 min. The recovered Pd NPs
were then subjected to methanol wash (2×10 mL) and water
wash (2 × 10 mL). The Pd NPs collected were then dried
at 60 °C for 8 h. The dried Pd NPs were then used for next
round of reaction with no further purification.
In the present work, Pd NPs were synthesized from palla-
dium acetate using aqueous-ethanolic extract of black pep-
per. Even though the exact mechanism of the biosynthesis
of Pd NPs is not clear; we presumably consider that the
presence of phenols and acid compounds (Table 1) in the
extract are responsible for the bioreduction and stabilization
of Pd NPs. The plausible mechanistic pathway of Pd NPs
formation is shown in Scheme 1. This approach of reducing
3 Results and Discussion
3.1 Characterization of Black Pepper Extract
Initially, the black pepper extract was subjected to UV–Vis
analysis which is shown in Fig. 1. The presence of pip-
erine in the black pepper extract was confirmed by the
λmax observed at 341 nm in the UV–Vis spectrum of the
extract [52] (Fig. 1a). The absorption peaks in the range
of 240–320 nm in the UV–Vis spectrum is due to the π–π*
transition taking place in terpenoids and other phytochemi-
cals present [52]. Analysis of the extract after the reduction
of Pd(II)–Pd(0) shows the disappearance of the correspond-
ing peaks which were present in the fresh extract (Fig. 1c).
In order to confirm the active participation of piperine and
other phytochemicals present in the black pepper extract, a
blank reaction was also carried out wherein no palladium
acetate was used. The UV–Vis spectrum of extract from
blank reaction shows the presence of all the peaks as it was
in the fresh extract (Fig. 1b). Thus, it is confirmed that the
Fig. 1 UV–Vis spectra of (a) fresh extract, (b) extract after blank
reaction and (c) extract after reduction
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
The palladium acetate solution with light brown initial
color, changed to black upon stirring at 85 °C for 2 h, after
the dropwise addition of black pepper extract. Apart from
visual observation, the conversion of Pd(II) to Pd(0) was
also confirmed by UV–Visible analysis which is shown in
Fig. 3. The characteristic peak of Pd(II) can be seen in the
UV-spectrum of palladium acetate at 394 nm as shown in
Fig. 3a. After the conversion of Pd(II) to Pd(0), the peak at
394 nm was disappeared substantiating the completion of
reduction process (Fig. 3b).
3.3 Spectroscopic and Microscopic Characterization
of Palladium Nanoparticles
The biogenic synthesized Pd NPs were characterized using
UV–Vis spectroscopy, ATR-IR spectroscopy, BET, TEM,
FESEM, EDS, ICP-OES, XRD and TGA. As shown in
Fig. 3b, no peak is observed in the UV–Vis spectra for Pd
NPs. The disappearance of peak at 394 nm confirms the
conversion of Pd(II) to Pd(0).
Fig. 2 ATR-IR spectra of (a) fresh extract and (b) biogenic synthe-
sized Pd NPs
the metal ions to metal nanoparticles can circumvent the
usage of hazardous chemicals which are usually employed
for reduction process.
The ATR-IR spectrum of Pd NPs is given in Fig. 2b. The
peaks at 3383, 2935, 2863, 1605, 1403, 1252, 1081 and
1040 cm−1 which can be attributed to –OH, –NH, aromatic
Table 1 Secondary metabolites
identification using GC–MS
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V. Kandathil et al.
Scheme 1 Plausible mecha-
nistic pathway of Pd NPs
formation
OH
O
O
C
C
t
:
O
C O
E
H H
2O
O
+
2
0
C
O
O
0
P
d
P
d
+
+
P
d
O
C
O
C
85 °C 2h
,
H
O
Phytochemicals
stabilized Pd NPs
Phytochemicals
in black pepper extract
and aliphatic –CH, –C=O and –C=C stretching vibrations
of phytochemicals adsorbed on Pd NPs during the reduction
process. The phytochemicals thus not only act as reducing
agents but also as stabilizing agents for Pd NPs. Figure 4a,
b shows the ATR-IR spectra of Pd NPs after five recycles
from aryl halide cyanation reaction and Pd NPs after ten
recycles from Hiyama cross-coupling reaction respectively.
In Fig. 4a, the peaks corresponding to the adsorbed phyto-
chemicals were not recognized, which shows the possibility
of desorption of those phytochemicals from the surface of
Pd NPs which led to their agglomeration whereas Fig. 4b
showed peak signals similar to that of fresh Pd NPs with
slight shift.
BET analysis was carried out for checking the surface
area of synthesized Pd NPs as well as to understand the
porosity. Figure 5 shows the N2 adsorption–desorption iso-
therm for Pd NPs and it exhibited typical type-II isotherm
with small hysteresis loop. The BET surface area for Pd NPs
was found to be 15.52 m2 g−1.
Fig. 3 UV–Vis spectra of (a) Pd(OAc)2 and (b) biogenic synthesized
Pd NPs
The size and morphology of Pd NPs were analyzed using
TEM. Figure 6a shows the TEM image for biogenic synthe-
sized Pd NPs. The size of Pd NPs ranged from 2 to 7 nm
and exhibited spherical morphology. The TEM image for Pd
NPs after five recycles in cyanation reaction (Fig. 6b) and
TEM image of Pd NPs after ten recycle in Hiyama coupling
(Fig. 6c) shows that after reaction, Pd NPs agglomeration
has increased but morphology remained the same.
Further, FESEM study was also carried out to confirm
the spherical morphology of the Pd NPs which is shown in
Fig. 7a. From the FESEM images it is clear that the Pd NPs
possessed spherical morphology. Also, it is evident from the
FESEM images of five times recycled Pd NPs from cyana-
tion reaction (Fig. 7b) as well as ten times recycled Pd NPs
from Hiyama cross-coupling (Fig. 7c) that after recycling
the agglomeration has increased but it retained its spherical
morphology which is in good agreement with TEM analysis.
In order to confirm the presence of elements present along
with Pd NPs, EDS analysis was carried out which is given
in Fig. 8. The presence of palladium, carbon and oxygen was
confirmed by EDS and area mapping given in Fig. 9 shows
Fig. 4 ATR-IR spectra of (a) five times recycled Pd NPs from aryl
halide cyanation and (b) ten times recycled Pd NPs from Hiyama
cross-coupling
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
that all elements are distributed uniformly. The palladium
content was quantified by using ICP-OES analysis. The ICP-
OES analysis revealed a palladium content of 44.48% w/w
in the Pd NPs.
The powder X-ray diffraction study was carried out for
understanding the crystalline structure of prepared Pd NPs
(Fig. 10). Three peaks of palladium are found at 2θ=40.03°,
46.51° and 68.03° corresponding to lattice planes (111),
(200) and (220) respectively, which confirms the face cen-
tered cubic crystal structure for Pd NPs. The average particle
size of Pd NPs was found to be 5.38 nm, calculated using
Debye Scherrer equation, which is in good agreement with
TEM results.
Thermogravimetric analysis (TGA) was carried out to
identify the thermal stability of Pd NPs and presence of any
adsorbed phytochemicals on Pd NPs. TGA was performed
at a heating rate of 10 °C/min under a nitrogen atmosphere
between 40 and 750 °C (Fig. 11). An initial weight loss of
4–5% up to a temperature of 150 °C can be attributed to the
Fig. 5 Nitrogen adsorption–desorption curve for Pd NPs
Fig. 6 TEM images of a fresh Pd NPs, b five times recycled Pd NPs from aryl halide cyanation and c ten times recycled Pd NPs from Hiyama
cross-coupling
Fig. 7 FESEM images of a fresh Pd NPs, b five times recycled Pd NPs from aryl halide cyanation and c ten times recycled Pd NPs from Hiyama
cross-coupling
1 3

V. Kandathil et al.
Fig. 8 EDS spectrum of Pd NPs
removal of moisture adsorbed on Pd NPs. A sharp weight
loss of ~15% at a temperature range of 150–250 °C can be
due to the removal of volatile organic moiety and a total of
~30% weight loss up to a temperature of 750 °C confirms
the presence of adsorbed phytochemicals on Pd NPs.
gave better results over other bases and in the case of sol-
vent, DMF was found superior. A temperature of 120 °C,
a catalyst ratio of 0.5 mol% Pd and for a period of 7 h was
found optimal (Table 2, entry 7). With increased temperature
(Table 2, entry 12), catalyst loading (Table 2, entry 6) and
time period (Table 2, entry 9) there was no betterment in
yield and vice versa. Also, 0.17 equiv of K4Fe(CN)6·3H2O
was found to be best ratio of cyanide source. Increase in the
ratio of K4Fe(CN)6·3H2O (Table 2, entry 10) lead to low
conversion which may be due to the deactivating effect of
cyanide ions on Pd NPs [39]. Thus optimized conditions for
cyanation reaction of aryl halide (for 1 equiv) was identified
as 0.17 equiv of K4Fe(CN)6·3H2O, DMF solvent, 0.5 mol%
of Pd NPs, 1.5 equiv Na2CO3 base at 120 °C temperature for
required time period (Table 2, entry 7).
3.4 Application of the Pd NPs in Cyanation of Aryl
Halides
Following the characterization, catalytic activity of synthe-
sized Pd NPs was first assessed on cyanation of aryl halides.
K4Fe(CN)6·3H2O was chosen as the cyanide source in aryl
halide cyanation due to its low toxicity, ready availability
and cost effectiveness. The cyanation of 4-bromonitroben-
zene was chosen as the model reaction for optimizing the
reaction conditions. Evaluation of literature reports on aryl
halide cyanation made us to choose DMF as the solvent
initially. Then the reaction was carried out at different set
of conditions, as given in Table 2, to optimize the reaction
conditions. In the absence of base and palladium source,
the reaction did not proceed (Table 2, entry 1 and 2). Ini-
tially K2CO3 was employed as the base. But use of Na2CO3
A plausible mechanism for the catalytic cycle of aryl
halide cyanation with Pd NPs has been shown in Fig. 12.
Initially, aryl halide undergoes oxidative addition with Pd
NPs, followed by ligand exchange from the inner coordina-
tion sphere of K4[Fe(CN)6] to the Pd NPs and finally reduc-
tive elimination of aryl nitriles takes place from Pd NPs to
complete the catalytic cycle.
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
Fig. 9 EDS elemental mapping of Pd NPs
Fig. 10 XRD pattern of Pd NPs
Fig. 11 TGA curve of Pd NPs
The substrate scope in aryl halide cyanation reaction with
Pd NPs at optimized conditions was examined for various
aryl halides with electron withdrawing group as well as
electron donating groups which is given in Table 3. Aryl
halides with both electron withdrawing as well as electron
donating groups were tolerated well and gave good to excel-
lent yields by tuning the reaction time. Cyanation products
were isolated and purified by column chromatography. Both
aryl iodides and aryl bromides underwent cyanation reaction
satisfactorily and the yields were comparable. But conver-
sion of aryl chlorides to cyanated products was less when
compared to their iodide and bromide counterparts.
3.5 Recyclability of the Pd NPs in Cyanation of Aryl
Halides
The recovery and recyclability of Pd NPs were evaluated for
the cyanation of model reaction under optimized condition.
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V. Kandathil et al.
Table 2 Optimization of conditions for cyanation reaction of 4-bromonitrobenzene
.
K4FeCN6 3H2O, Pd NPs
Br
O2N
O2N
base, solvent
N
Entry
Base
Solvent
Temperature (°C)
Pd (mol %)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
–
DMF
DMF
DMF
DMF:H2O (1:1)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
ACN
EtOH
DMF
100
100
100
100
100
120
120
120
120
120
120
130
110
85
1
–
1
1
1
1
0.5
0.25
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
12
24
12
12
12
7
7
8
10
7
7
7
7
12
12
12
12
Trace
NR
60
35
72
85
85
60
85
70
75
85
78
60
Trace
40
K2CO3
K2CO3
K2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
NaOH
9
10b
11c
12
13
14
15
16
17
78
130
130
KOH
DMF
38
Bold value indicates the best reaction condition among the set of reactions performed
Reaction conditions: 4-bromonitrobenzene (1 equiv), K4Fe(CN)6·3H2O (0.17 equiv), base (1.5 equiv) and solvent (5 mL) in air
aIsolated yield after separation by column chromatography
bUsed 0.22 equiv of K4Fe(CN)6·3H2O
cUsed 0.14 equiv of K4Fe(CN)6·3H2O
The recyclability test was performed up to five cycles which
is depicted in Fig. 13. After each cycle, a decrease in yield
was observed. Up to three cycles a moderate decrease in
yield was observed followed by a drastic decrease in the
yield from fourth cycle onwards. The initial yield of 85%
reached up to 60% by the end of fifth recycle. After the fifth
recycle, Pd NPs were characterized by ATR-IR (Fig. 4a),
TEM (Fig. 6b) and FESEM (Fig. 7b) which showed that Pd
NPs are quite stable up to five recycles of cyanation reaction.
3.6 Application of the Pd NPs in Hiyama
Cross‑Coupling Reaction
In continuation to our investigation on catalytic activity of
biogenic synthesized Pd NPs, after cyanation reaction of aryl
Fig. 12 Plausible catalytic cycle for aryl halide cyanation catalyzed
by Pd NPs
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
Table 3 Cyanation reactions of different aryl halides with K4Fe(CN)6·3H2O catalyzed by Pd NPs
Entry
1
Aryl halide
Product
Time (h)
3
Yield (%)a
95
2
3
4
4
6
7
92
65
91
5
6
12
88
7
85
7
8
9
8
9
88
85
70
12
10
11
12
30
7
80
Reaction conditions: Aryl halide (1.0 equiv), K4Fe(CN)6·3H2O(0.17 equiv), Pd NPs (0.5 mol% Pd with respect to aryl halide), Na2CO3 (1.5
equiv) and DMF (5 mL) in air
aIsolated yield after separation by column chromatography; average of two runs
1 3

V. Kandathil et al.
any other source of anion is required for the enhancement of
the nucleophilicity of organosilicon compound by generation
of pentacoordinate aryl silicate which is more reactive than
corresponding tetracoordinated silane. Figure 14 depicts a
plausible mechanism for the catalytic cycle of Hiyama cross-
coupling using Pd NPs as catalyst. Sodium hydroxide is the
source for hydroxide ions here, which helps in the activation
of trimethoxyphenylsilane. The cycle starts with the oxida-
tive addition of aryl halide on Pd NPs. The pentavalent aryl
silicate anion then undergoes transmetallation followed by
reductive elimination to get the C–C coupled biaryls at the
end of the catalytic cycle.
The cross-coupling between 4-iodoanisole and trimeth-
oxyphenylsilane was chosen as the model reaction for opti-
mizing the reaction conditions. A series of reactions were
carried out under different set of conditions (Table 4) for
the optimization of Hiyama cross-coupling using Pd NPs.
Firstly, sodium hydroxide was selected as a base. Initial
study of Hiyama cross-coupling using DMF solvent at room
temperature did not produce any product (Table 4, entry 1).
Upon heating to 100 °C (Table 4, entry 2), 70% yield was
obtained which remained unchanged even when a 1:1 mix-
ture of DMF:water was used (Table 4, entry 3). A decrease
in the yield was observed when low boiling solvents like
ethanol and acetonitrile were used (Table 4, entry 4 and 5).
But use of ethylene glycol as a solvent increased the yield
within 2 h of time at 100 °C (Table 4, entry 7). Among
the bases used, sodium hydroxide was superior to potas-
sium hydroxide (Table 4, entry 6) and sodium carbonate
(Table 4, entry 14). The catalyst ratio was found to be opti-
mal at 0.2 mol% of Pd along with a temperature of 100 °C
and a reaction time of 2 h (Table 4, entry 8). An increase in
catalyst ratio (Table 4, entry 7), temperature (Table 4, entry
12) or time duration (Table 4, entry 9) had little effect on
yield where as a decrease in catalyst ratio (Table 4, entry
11) and time (Table 4, entry 13) resulted in lower yields.
Thus use of sodium hydroxide as a base, in ethylene glycol
solvent with 0.2 mol % of Pd catalyst and a temperature of
100 °C were found to be the optimum condition for Hiyama
cross-coupling using Pd NPs (Table 4, entry 8).
Fig. 13 Recycling efficiency of Pd NPs in aryl halide cyanation reac-
tion
Fig. 14 Plausible catalytic cycle for Hiyama cross-coupling catalyzed
by Pd NPs
With the availability of optimized condition of Hiyama
cross-coupling reaction, the substrate scope and limitation
were studied for different aryl halides with trimethoxyphe-
nylsilane which is shown in Table 5. The Hiyama cross-cou-
pling proceeded smoothly with outstanding functional group
tolerance to give good to excellent yields. Aryl halides with
halides we proceeded with fluoride-free Hiyama cross-cou-
pling reaction. Due to the small electronegativity difference
between C and Si, organosilicon compounds are weak nucle-
ophiles. Usually fluoride ion is employed for the activation
of organosilicon compounds. In the absence of fluoride ion,
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
Table 4 Optimization of reaction conditions for Hiyama cross-coupling between 4-iodoanisole and trimethoxyphenylsilane
O
Si
O
Pd NPs
O
I
O
+
O
base, solvent
Entry
Base
Solvent
Temperature (°C) Pd (mol %)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
Na2CO3
DMF
DMF
DMF:H2O(1:1)
EtOH
R.T
100
100
85
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.2
0.2
0.2
0.1
0.2
0.2
0.2
12
10
8
12
12
12
2
2
3
5
2
NR
70
70
50
20
55
97
97
97
82
88
97
92
ACN
85
DMF:H2O(1:1)
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol:H2O(1:1)
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
100
100
100
100
100
100
110
100
100
2
1
12
Trace
Bold values indicate the best reaction condition among the set of reactions performed
Reaction conditions: Aryl halide (1.0 equiv), trimethoxyphenylsilane (1.5 equiv), base (3 equiv) and solvent (5 mL) in air
aIsolated yield after separation by column chromatography
both electron donating group as well as electron withdraw-
ing group were able to produce the cross-coupled products
in quantitative yield even though the time duration varied.
Also, the difference in rate of the reaction among different
aryl iodides and aryl bromides with trimethoxyphenylsilane
were minimal. Reactions were clean with trace amount of
homocoupled byproducts and column purification of cou-
pled products gave pure biaryls in good to excellent yields.
resulted in steady decrease and reached up to 88% yield
after ten recycles. The ATR-IR (Fig. 4a), TEM (Fig. 6c)
and FESEM (Fig. 7c) analysis of ten times recycled Pd NPs
validate the permanence of biogenic synthesized Pd NPs in
Hiyama cross-coupling reaction.
3.8 Comparison of Catalytic Activity
The activity of biogenic synthesized Pd NPs catalytic sys-
tem was compared with other reported catalytic systems for
both aryl halide cyanation as well as Hiyama cross-coupling
which is shown in Tables 6 and 7 respectively. From Table 6,
it can be noticed that even though the yield reported by
other catalytic systems are high, our catalytic system has
the advantage of comparatively milder reaction conditions,
low catalyst loading and lesser reaction time along with the
advantage of recyclability and green method of synthesis.
In the case of Hiyama cross-coupling (Table 7), apart from
the aforesaid advantages, yield obtained with our catalytic
system is found superior.
3.7 Recyclability of the Pd NPs in Hiyama
Cross‑Coupling Reaction
The recovered Pd NPs after Hiyama cross-coupling were
reused for further round of reaction as shown in Fig. 15. The
recyclability study was carried out on the model reaction
under optimized conditions. The results show that Pd NPs
were active and was able to catalyze the reaction without
considerable loss of activity up to ten recycles. The decrease
in the yield after each run is minimal up to seven cycles
with a total decrease in 5% and further recycles of Pd NPs
1 3

V. Kandathil et al.
Table 5 Hiyama cross-coupling
of different aryl halides with
trimethoxyphenylsilane
catalyzed by Pd NPs
Entry
1
Aryl halide
Product
Time (h)
Yield (%)a
0.5
98
2
3
4
1
1
1
95
92
87
5
6
1
1
95
93
7
8
1
1
1
2
90
96
96
90
9
10
11
12
13
14
1
1
1
1
95
93
95
90
15
1
95
16
17
1
2
97
95
18
19
2
2
90
92
20
21
3
1
90
92
Reaction conditions: Aryl halide (1.0 equiv), trimethoxyphenylsilane (1.5 equiv), Pd
NPs (0.2 mol% Pd with respect to aryl halide), NaOH (3 equiv) and ethylene glycol
(5 mL) in air
aIsolated yield after separation by column chromatography; average of two runs
1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
4 Conclusion
In summary, aqueous-ethanolic extract of black pepper
was utilized for the reduction of Pd(II) to Pd(0) nanoparti-
cles which can be employed as a highly efficient and green
nanocatalyst in aryl halide cyanation as well as Hiyama
cross-coupling as demonstrated in the current work. The
prepared Pd NPs were characterized using various spec-
troscopic, microscopic, thermal and surface analyses. The
major emphasize of the present protocol is the application of
biogenic aspect in the reduction and stabilization of Pd NPs
thereby avoiding the usage of toxic and hazardous chemi-
cals. In addition, cyanation of aryl halides were carried out
using K4Fe(CN)6·3H2O as a cyanide source wherein the
toxic and dangerous cyanating reagents were omitted and
Hiyama cross-coupling was carried out without any fluoride
source. Yields obtained for both the organic transformations
were comparable with other reported catalytic system and in
some cases stood superior with the added benefit of green
method of synthesis, ligand free conditions and recyclability.
Fig. 15 Recycling efficiency of Pd NPs in Hiyama cross-coupling
reaction
Table 6 Comparison of results
Entry
Catalyst
Solvent
Tempera- Time (h)
ture (°C)
Yield (%)
References
for the Pd NPs catalyst with
other catalysts in cyanation of
4-bromonitrobenzene using
K4Fe(CN)6·3H2O as cyanide
source
r
r
1
Pd@CC1 /Pd@CC2
Pd-Zeolite
PdNCs/C@Fe3O4
Pd/C
Palladacycle-1
Pd/PPy
DMF
DMF
DMF
PEG4000-H2O
DMF
NMP
DMF
DMF
140
130
120
140
130
100
120
120
15
10
18
2
7
8
99
90
96
75
92
87
91
85
[53]
[54]
[55]
[43]
[56]
[57]
Present work
Present work
2a
3a
4b
5b
6
7a
8
Pd NPs
Pd NPs
7
7
Bold values indicate the present work among other reported literatures
aCyanation reaction of 4-bromobenzonitrile
bUnder microwave irradiation
Table 7 Comparison of
results for the Pd NPs
Entry
Catalyst
Solvent
Tempera-
ture (°C)
Time (h)
Yield (%)
References
catalyst with other catalysts
in Hiyama cross-coupling
between 4-bromoanisole and
trimethoxyphenylsilane
1
2
3
4
Pd NPs
H2O
H2O
H2O
THF
H2O-PEG2000
4.8% aq toluene
Ethylene glycol
Ethylene glycol
90
100
90
65
60
120
100
100
3
14
3
24
6
4.5
2
1
95
75
98
74
81
80
95
96
[58]
[59]
[60]
[61]
[62]
[63]
Present work
Present work
Pd-LHMS-3
Pd nanoparticle
Coreshell Ni-Pd
Pd(OAc)2
Pd/C
Pd NPs
Pd NPs
5
6a
7
8a
Bold values indicate the present work among other reported literatures
aHiyama cross-coupling between 4-bromonitrobenzene and trimethoxyphenylsilane
1 3

V. Kandathil et al.
30. Ushkov AV, Grushin VV (2011)
133(28):10999–11005
J
Am Chem Soc
Acknowledgements The authors thank Nano Mission, Ministry of
Science & Technology, Department of Science & Technology, Gov-
ernment of India, for financial support through the Grant SR/NM/
NS-20/2014. Authors also thank SAIF, CUSAT and SAIF, IITM for
the analytical support.
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1 3

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama…
Affiliations
Vishal Kandathil1 · Ramesh B. Dateer1 · B. S. Sasidhar2 · Shivaputra A. Patil3 · Siddappa A. Patil1
2
* Siddappa A. Patil
Organic Chemistry Section, National Institute
for Interdisciplinary Science and Technology (CSIR),
Trivandrum 695019, India
p.siddappa@jainuniversity.ac.in; patilsiddappa@gmail.com
1
Centre for Nano and Material Sciences, Jain University,
3
Pharmaceutical Sciences Department, College of Pharmacy,
Rosalind Franklin University of Medicine and Science,
North Chicago, IL 60064, USA
Jain Global Campus, Kanakapura, Ramanagaram,
Bangalore 562112, India
1 3