Supported palladium nanoparticles: A general sustainable catalyst for microwave enhanced carbon-carbon coupling reactions

Article abstract of DOI:10.1016/j.molcata.2016.08.032

Synergism between nanocatalysts and microwave heating has emerged as a tool for sustainable organic synthesis. In the present investigation scope of palladium nanoparticle for ligand free carbon-carbon coupling reactions namely Suzuki, Hiyama, Heck and Sonogashira under microwave heating is investigated. Palladium nanoparticles of less than 10?nm dimension were impregnated onto a commercially available, non-functional, microporous polystyrene resin and were characterized by UV–vis spectroscopy, HRTEM attached with EDX, powder X-ray Diffraction (XRD) and ICP-AES. Highly pure coupled products in various reactions were obtained in 6–35?min using microwave heating in closed vials using benign mixed low boiling solvents, which otherwise require 4–30?h of inert atmosphere under conventional heating. Reaction parameters such as temperature, time and concentration of catalyst were optimized and catalyst was successfully recycled five to six times without any noticeable leaching or decrease in performance. Post reaction TEM analysis showed that size of the nanoparticles was still in the range of 3–10?nm. The catalyst was successfully used to synthesize asymmetric terphenyls in a single pot by sequential addition of aryl boronic acids.

Full text of DOI:10.1016/j.molcata.2016.08.032

Accepted Manuscript
Title: Supported palladium nanoparticles: A general
sustainable catalyst for microwave enhanced carbon–carbon
coupling reactions
Author: Dipen Shah Harjinder Kaur
PII:
S1381-1169(16)30367-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.08.032
MOLCAA 10019
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Journal of Molecular Catalysis A: Chemical
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26-5-2016
6-8-2016
30-8-2016
Please cite this article as: Dipen Shah, Harjinder Kaur, Supported palladium
nanoparticles: general sustainable catalyst for microwave enhanced
A
carbon–carbon coupling reactions, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2016.08.032
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Supported palladium nanoparticles: A general sustainable catalyst for
microwave enhanced carbon-carbon coupling reactions
Dipen Shah, Harjinder Kaur*
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, India
E- mail: hk_ss_in@yahoo.com, Fax: +91 79 26308545; Tel: +91 79 26300969
1

GRAPHICAL ABSTRACT
Highlights of the work


Palladium nanoparticle catalyzed Suzuki, Hiyama, Heck and Sonogashira reactions.
Synergism between microwave and recyclable palladium nanoparticles on inert
support



Reaction time 6 to 35 min with catalyst quantity less than 0.1 %.
A versatile recyclable catalyst with general applicability
The catalyst can be used for facile synthesis of asymmetric terphenyls.
2

Abstract
Synergism between nanocatalysts and microwave heating has emerged as a
tool for sustainable organic synthesis. In the present investigation scope of palladium
nanoparticle for ligand free carbon-carbon coupling reactions namely Suzuki, Hiyama, Heck
and Sonogashira under microwave heating is investigated. Palladium nanoparticles of less
than 10 nm dimension were impregnated onto a commercially available, non-functional,
microporous polystyrene resin and were characterized by UV-Vis spectroscopy, HRTEM
attached with EDX, powder X-ray Diffraction (XRD) and ICP-AES. Highly pure coupled
products in various reactions were obtained in 6 to 35 min using microwave heating in closed
vials using benign mixed low boiling solvents, which otherwise require 4 to 30 h of inert
atmosphere under conventional heating. Reaction parameters such as temperature, time and
concentration of catalyst were optimized and catalyst was successfully recycled five to six
times without any noticeable leaching or decrease in performance. Post reaction TEM
analysis showed that size of the nanoparticles was still in the range of 3 to 10 nm. The
catalyst was successfully used to synthesize asymmetric terphenyls in a single pot by
sequential addition of aryl boronic acids.
Keywords: Supported Palladium nanoparticles, Heck reaction, Sonogashira reaction,
Microwave heating, Terphenyl, Recycling
3

1
. Introduction
Today, palladium is widely accepted as one of the most versatile and
beneficial metal used in a variety of catalytic applications ranging from organic synthesis to
fuel cells, oil refining etc. In chemistry, this silvery-white precious metal as catalyst was first
reported in Wacker process developed for the oxidation of ethylene to acetaldehyde in 1959.
Study of nucleophilic allylation and its mechanistic studies performed by Tsuji et al. started
the modern era in organo-palladium chemistry [1]. Since then, several palladium catalyzed
organic transformations were developed. Especially noteworthy are those involving carbon-
carbon bond formation such as Suzuki, Hiyama, Heck, Kumada, Negishi, Stille, Sonogashira
etc. which changed the way in which organic synthesis is conceptualized. These highly
important reactions were carried out in high boiling organic solvents and required phosphine
ligands which were expensive and toxic. Moreover, separation of palladium metal ions
especially from pharmaceuticals is a cumbersome necessity. Eventually, efforts for greening
of reaction protocols for these reactions became important which led to synthesis of water
soluble ligands on one hand and polymer supported ligand or palladium catalysts on the other
hand [2].
In the last two decades which saw intense research in the field of metal
nanoparticle synthesis, palladium catalyzed carbon-carbon reactions have witnessed a
complete revolution. PdNPs catalyzed C-C coupling reaction and its mechanistic issues were
first reported by Beller et al. in 1996. They prepared Pd colloids stabilized by tetra-
octylammonium bromide following the Bonne-man procedure and used it to study Heck
arylation [3]. Reetz et al. also reported independently in 1996 the preparation of
nanostructured PdNPs of sizes 8-10 nm on propylene carbonate which were highly stable
under the Heck reaction conditions (140-155°C) [4]. A lot of research in the field of PdNPs
catalyzed C-C coupling reactions followed which resulted in ligandless reactions in water at
4

temperatures ranging from RT to moderate. To facilitate separation of nanoparticles,
supporting them on insoluble supports is very attractive but supports can decrease the
accessibility of the catalytic sites. As nanoparticles are extremely structure-sensitive, their
catalytic activity not only depends upon their size and shape but also on their support [5]. A
support that can stabilize nanoparticles, without hindering catalytic sites is highly desirous.
Challenge also lies in the facile synthesis and uniform or narrow distribution of sizes of
nanoparticles on supports that allow facile movement of materials in the reaction medium.
Therefore, innumerable and extremely varied approaches to synthesize supported
nanoparticles have been pursued [6]. Supporting nanoparticles on supports can further
enhance the sustainability of catalyst by facilitating recovery and reuse.
Microwave induced heating in closed vessels for organic synthesis has
emerged as one of the most efficient ways of carrying organic synthesis. Combining
microwave heating with Pd nanoparticle catalysis has led to ligand-free carbon-carbon
coupling reactions with unprecedented reaction rates using catalyst in such miniscule
amounts called homeopathic doses, thus, enhancing the sustainability of these procedures.
We have earlier reported palladium nanoparticles supported on nonfunctional inert
commercial polystyrene resin Amberlite XAD-4 for microwave enhanced Suzuki and
Hiyama coupling reactions. Herein, we first report some more developments in the catalytic
activity of resin-PdNPs in different C-C coupling reactions and then discuss the general
advantages in terms of time and yield for reactions carried under microwave heating over
those carried out under conventional heating. All the reaction parameters were studied and
reaction conditions optimized for the best Turnover numbers (TON) and Turnover
frequencies (TOF) in benign organic solvents. Further, the reusability of the resin was
checked and post reaction TEM analysis was carried out to check the stability of
nanoparticles.
5

2
. Materials and instruments
All chemicals used were of analytical grade or of the highest purity available.
All glassware was thoroughly cleaned with freshly prepared 3:1 HCl/HNO (aqua regia) and
3
rinsed thoroughly with Millipore-Q water. Styrene, phenyl boronic acid,
phenyltrimethoxysilane, methyl acrylate, phenyl acetylene, Iodobenzene, 4-iodoanisole, 4-
iodoacetophenone, 4-iodonitrobenzene, 4-iodotoulene, bromobenzene, 4-bromoanisole, 4-
bromoacetophenone,
chloronitrobenzene were purchased from Aldrich. All aryl halides standards were of 98–99%
purity. Dichloromethane (DCM), diethyl ether (Et O), Na CO and K CO were purchased
4-bromonitrobenzene
4-bromotoulene,
chlorobenzene,
4-
2
2
3
2
3
from Finar chemicals. The resin supported palladium nanoparticles were synthesized by a
method developed in our lab [7] and further characterized by TEM-EDX.
High resolution Transmission electron microscopy (HR-TEM-EDX) pictures were
taken using a JEOL, JEM 2100 instrument with EDX analyzer facility. The swollen resin
beads were milled and a drop of alcoholic suspension was placed onto a 200 mesh carbon
coated copper grid. It was then dried to evaporate the solvent and used for microscopy.
Inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements was
carried out on a HJY Ultima-2 instrument: power 1000 W, nebulizer flow 1.29, nebulizer
pressure 2.96, wave length 340.458 nm. GC–MS measurements were carried on Perkin Elmer
USA Auto system XL. The GC-MS programs applied throughout the analysis was as follows:
the column temperature was 40 ºC at the beginning of the program and it was heated with a
rate of 5 ºC/min up to 250 ºC. UV-Visible absorption spectra were acquired on a Jasco V-570
UV-Vis spectrophotometer. 1H NMR spectra were recorded on a Bruker Advance II 400
NMR spectrometer. Reactions were carried out in CEM Microwave synthesizer
(benchemate), in closed vessels with external cooling under aerobic conditions.
6

2
.1
Protocol for sequential synthesis of asymmetric terphenyl
Into a 10 mL vial 4-iodo bromobenzene (1.0 mmol) phenylboronic acid (1.0 mmol)
sodium carbonate (2.0 mmol), 200 mg resin-PdNPs (Pat dried between the folds of filter
paper), 1.5 mL ethanol, 1.0 mL water was taken and heated at 140 ºC at 100 watt in a CEM
benchmate microwave reactor. After 10 minutes 1.0 mmol of substituted phenylboronic acid
was added and reaction mixture heated for another 10 min under same conditions. The
reaction was quenched by filtering the hot solution into 10 mL of cold water. The resulting
solution was extracted with Et O (2×5 mL). The combined ether extract was dried over
2
anhydrous MgSO4 and crude isolated after removing the solvent. The product was
recrystallized from appropriate solvent.
2
.2
Protocol for Mizoroki-Heck cross-coupling reaction using Resin_PdNPs
Into a 10 mL vial, aryl halide (1.0 mmol), alkenes (1.5 mmol), base (2.0 mmol),
ethanol (3.0 mL), water (1.0 mL) and resin - PdNPs catalyst (300 mg) were taken and heated
in a CEM microwave (120 w, 120 ºC) for different intervals of time (Scheme 5.1). The
reaction was quenched by pouring the reaction mixture in 10 mL cold water. The resulting
solution was extracted with Et O. The combined ether extract was dried over anhydrous
2
MgSO
4
and the solvent removed using a rotaevaporator. The crude products thus isolated
1
were recrystallized from appropriate solvents and analyzed by H NMR.
The effect of various parameters such as base, solvent, temperature, catalyst
concentration, time and recyclability was studied taking coupling of iodobenzene and styrene
as the standard reaction
2
.3
Protocol for Sonogashira cross-coupling reaction using Resin_PdNPs
Into a 10 mL vial, aryl halide (1.0 mmol), phenylacetylene (1.2 mmol), K
2
CO
3
(3.0 mmol), ethanol (3.0 mL), water (1.0 mL) and resin-PdNPs catalyst (300 mg) were taken
º
and heated in a CEM microwave (150 w, 90 C) for different intervals of time (Scheme 6.1).
7

The reaction was quenched in 10 mL cold water. The resulting solution was extracted with
Et O. The combined ether extract dried over anhydrous MgSO and solvent removed using a
2
4
rotaevaporator. The crude product thus isolated was recrystallized from appropriate solvents.
The effect of various parameters was studied taking coupling of iodobenzene
and phenylacetylene as the standard reaction
3
. Result and Discussion
Amberlite XAD-4 resin is a microporous material with high surface area,
durability and chemical stability towards acids, bases and oxidizing agents. This makes it an
ideal solid support for the immobilization of the metal nanoparticles [8-9]. The resin is
thermally stable under microwave conditions and due to its inert nature there is no
interference with reaction conditions. The resin was impregnated with nanoparticles by a
protocol mentioned before. Diffusion of precursor ion takes place into the polymer matrix
which is passive as no chelating or ion exchange groups are present. Sajiki et al. [10] were of
the opinion that some complexation occurs with electron rich benzene ring. But we observed
that absorption of metal precursor was not complete even after equilibrating the resin with 1
molar solution for 24 h. So, these interactions must be very weak. After excess of precursor
solution was filtered off, palladium ions were reduced by passing cold sodium borohydride
solution quickly (Fig. 1). Microporous resins such as XAD-4 has two types of porosities:
micropores which are permanent and nanopores that develop only after swelling with solvent.
Size of nanopores is dependent on the degree of cross linking and the nature of solvent used
for swelling. Hanson and co-workers [11] showed that if low concentration of metal
precursor is used small nanoparticles are formed in the nanopores. The size of nanopores can
control the growth of metal particles which resulted in very small distribution in the size of
PdNPs. Micropores present in the resin facilitate movement of material through the resin that
8

enhances contact with catalytic sites. This makes these microporous polymer resins highly
suitable for supporting nanoparticles for solution phase reactions. After impregnation with
PdNPs colorless resin beads turn brown. HRTEM images (Fig. 2) revealed that palladium
nanoparticles were uniformly embedded in the matrix of resin with narrow distribution of
particles size (3-10 nm in diameter) and d-lattice spacing as measured from HR-TEM was
0
.2118 nm which is close to d-spacing of the (1 1 1) planes of fcc Pd crystal [12]. The UV-
Visible spectroscopy was also used to check the reduction of Pd(OAc) . UV-visible spectrum
Fig. 3) of Pd(OAc) showed a peak at 400 nm which indicated the existence of Pd(II). This
2
(
2
peak disappeared completely after passing sodium borohydride indicating complete reduction
of Pd (II) to Pd(0). Resin was incinerated in a furnace and the amount of palladium in the
residue was determined by ICP-AES after preparing its solution [8]. It was found to be
0
.00235 mmol /g (0.249 mg /g) of the resin for resin-PdNPs. It is noteworthy to mention here
that this technique can be used to recover precious palladium from the catalyst once it
becomes inactive. Though, it is possible to load higher concentration of metal, we kept it low
for two reasons: one to prevent overheating of the catalyst during microwave heating and
two, over loading can hinder mass transfer through the resin matrix.
3
.1 Catalytic activity of Resin_PdNPs
The synergism between nano-catalysts and microwave heating is leading to
highly efficient protocols in terms of both turn over number and turn over frequency. Also,
the ability to heat low boiling solvents above their boiling points in microwave assisted
closed vessel reactions have diminished the need for high boiling organic solvents to conduct
reactions at high temperatures. Judicious choice of mixed solvents can further enhance
general applicability of the protocols. It also minimized the need for usage of surfactants such
as TBAB leading to truly green protocols.
9

3
.1.1 Catalytic activity of Resin_PdNPs for Suzuki and Hiyama reactions
We have already demonstrated the huge potential of microwave heating to
carry out Hiyama and Suzuki reactions using Resin_PdNPs [for details see references 7-8].
Excellent results were obtained in both the cases using less reactive bromo derivatives. We
further used these protocols to synthesize terphenyl a chemical used industrially as heat
storage and transfer agents. Terphenyl can be easily synthesized by using either Suzuki or
Hiyama coupling of di-iodo or 4-bromo iodobenzene with appropriate reagent. When 4-
bromo iodobenzene was reacted with equivalent amount of phenylboronic acid or
phenyltrimethoxysilane, major isolated coupled product was 4-bromobiphenyl. However,
when two moles of phenylboronic acid or phenyltrimethoxysilane were used terphenyl was
isolated in high yield (Fig. 4). We used this selectivity to synthesize asymmetric terphenyls in
one pot by sequential addition of different boronic acids. The products were identified by
their NMR data (See supplementary data).
3
.1.2 Catalytic activity of Resin_PdNPs for Mizoroki-Heck reactions
Heck Reaction” refers to the C-C coupling reaction between aryl halides or
“
vinyl halides and activated alkenes catalyzed by palladium in the presence of a base. It was
first discovered by Mizoroki [13] and further developed by Richard F. Heck [14] in the early
1
970’s. Soluble Pd complexes with phosphine ligands were used to be general catalysts for
Heck Reaction [15-16] as active sites are more accessible. However, separation and recycling
of the homogeneous catalysts is extremely difficult and in consideration of economic, as well
as environmental issues, heterogenization of catalyst was an obvious necessity. Thus,
palladium complexes or nanoparticles were immobilized on various supports such as silica
[
17-21], alumina [22], zeolite [23], organic polymers [24, 25], carbon nanotube [26],
grapheme [27, 28] and biological materials [29] to create heterogeneous catalysts. Although
1
0

many of them were reported to be effective for Heck reactions, very few catalysts showed
high stability of Pd species and successful recyclability. Mehnert et al. reported that Pd
nanoparticles supported on mesoporous silica showed good yield for Heck reaction of aryl
bromides, but recycling of this catalyst was hampered by significant agglomeration of PdNPs
[
30]. Dams et al. published Pd-exchanged zeolites with obvious formation of Pd cluster.
Structural damage to the support were reported after use in Heck reaction as catalyst [31].
Köhler et al. synthesized Pd/C catalysts for Heck reaction and showed that the average Pd
crystallite size significantly increased after reactions [32]. Therefore, heterogeneous catalysts
with excellent catalytic activity and recyclability, which is the key factor for the practical
applications, are still limited and remain a challenge.
In the present study resin-PdNPs were used to study Mizoroki-Heck reaction
and the effect of solvent, catalyst quantity, time, nature of base, etc. were studied and reaction
conditions optimized for the coupling between iodobenzene and styrene. Optimization of the
conditions is summarized in Table 1. The solvents play an important role in this reaction.
Literature showed that many organic solvent such as DMSO, DMF, toluene, dioxane etc.
have been used. Under microwave heating the choice of solvent is even more important as
they not only provide a medium for reaction but also affect the rate at which microwaves are
absorbed. So, polar solvents such as alcohols, DMF and DMSO are more efficient compared
to nonpolar solvents like toluene and dioxane. Based on our earlier studies we carried out the
reactions at a temperature of 120 ºC using ethanol/ water mixture in a closed vessel protocol.
A mixture of ethanol water was tried in different proportions and best resulted were obtained
when EtOH: H
reaction took place in its absence. Both nature and quantity of base are reported to have a
great effect on the yield of the Mizoroki-Heck reaction [33-35]. Many bases such as Na CO ,
2
O in 3:1 ratio was used. The presence of base was essential for reaction as no
2
3
1
1

Et
3
N, NaHCO
3
and CH
3
COONa were tried and among them Na
2
CO was found to be the
3
most effective (Table 1).
The catalytic activity of the nanoparticle systems was investigated by varying
the amount of catalyst while keeping the other parameters constant. It was observed that 300
mg resin (≈ 0.0007 mmol of Pd, 0.07 mol % with respect to aryl halide) was sufficient for
-1
completing the reaction. Using the obtained results, we calculated the, TON and TOF (h )
values which were found to be 1,430 and 7,150 respectively. To study the effect of time the
reaction mixture was analyzed at different intervals of time. The reactions were quenched by
filtering the hot solutions in water after appropriate time. The product extracted into ether and
was analyzed by GC-MS (Fig. 5). The analysis of the ether extract showed a peak for
unreacted iodobenzene at retention time of 10.40 min whereas the peak for stilbene appeared
at retention time of 16.60 min. Total conversation of iodobenzene was obtained after 12 min
as the peak for iodo benzene disappeared completely at this point. It was also observed that
trans-stilbene was produced exclusively. No homocoupling product was observed
After optimizing the reaction conditions, we checked the versatility of
protocol by coupling various aryl halides with styrene or methyl acrylate (Table 2). The
course of the reaction was monitored periodically by analyzing reaction mixture by means of
TLC (or GC if necessary). Characterization of the products was performed by their melting
points and comparison of their NMR spectra with the reported data. The results demonstrate
that aryl iodides with either electron withdrawing or electron donating substituents react with
olefins rapidly and generate the coupled products with excellent yields in EtOH/water
mixture at 120 ºC. A wide range of substituents, which included –CH
3
, -OCH
3
, -NO , and –
2
COCH , were compatible with this procedure. The chemo-selectivity for the reaction was
3
1
2

totally in the favour of trans cross-coupled product. We also tried reaction with aryl bromide
(
entry 6-10) and found that under the present set of conditions reaction with bromobenzene
entry 6), did not proceed to completion. However, on increasing the reaction time from 12 to
(
2
0 min, we could isolate the products in high yields. We successfully carried out reaction
with less active chlorobenzene (entry 11) with good yield by increasing the reaction time to
0 min. This difference in reactivity of various aryl halides can be attributed to the
3
differences in the strengths of C-I bond, C-Br bond and C-Cl bond. We also applied this
protocol to coupling of methyl acrylate (12-14) and iodobenzene using sodium acetate as
base. The product isolated in all the reactions were of high purity as no stabilizers, surfactants
or ligands were used in the nanoparticle synthesis or in the reaction mixture.
A comparison of the present protocol with others reported in the literature
under microwave heating was carried out and the results are reported in Table 3. It can be
seen that the present catalyst exhibited equally high conversions and yields without using any
surfactant or ligand. Reactions were completed in short time compared to others. Moreover
the Resin-PdNPs were easily separated and recycled many times.
3
.1.3
Catalytic activity of resin supported PdNPs for Sonogashira reaction
Sonogashira cross-coupling, a palladium-copper catalyzed reaction of aryl
2
halides and terminal acetylenes, is another important and widely used reaction for sp–sp C -
C bond formation. It provides an efficient route for the synthesis of diaryl-substituted
acetylenes [36], an important intermediate for the synthesis of natural products [37],
pharmaceutical agents [38], dendrimers and conjugated polymers [39–41] etc. The reaction is
generally conducted in organic soivents in the presence of amine base, copper(I) iodide as a
co-catalyst and like other palladium catalyzed reactions, it showed a wide tolerance to
functional groups. Both homogeneous palladium catalyst such as Pd (PPh
3
)
2
Cl
2
or Pd(PPh ) ,
3
4
1
3

and heterogeneous palladium catalysts which are supported on charcoal, zeolites and
magnesium oxide [42–47], etc. has been reported. Cu(I) which is used as activator in these
reactions, also promotes Glaser-type homocoupling reactions of terminal alkynes to diynes
in the presence of oxygen. These undesirable by-products reduce yield and are also difficult
to separate from the target products [48-50]. Hence, considerable effort is devoted to
developing copper-free Sonogashira cross-coupling reactions under mild conditions. These
reactions are reported in a variety of solvents using a variety of supports [51, 52]. Thathagar
et al. used Cu and Pd mixed metal clusters in DMF for this reaction [53, 54]. Gao et al. used
palladium nanowires for efficient coupling reaction in isopropanol at 75 ºC [55]. We studied
the effect of solvent, catalyst quantity, time, nature of base etc. on coupling between
iodobenzene and phenylacetylene and the results are tabulated in Table 4.. It was observed
that in the absence of base reaction does not proceed. Previous researchers have found that
the reaction rate depends on the nature of the base also. In our lab we tried Et
CO and CH COONa and obtained best results with K CO3. Though, in conventional
methods protic polar solvents such as DMF and CH CN are common [56], we were
3
N, Na
2
CO ,
3
K
2
3
3
2
3
successful in conducting the reactions at 90 ºC using 3:1 ethanol/water mixture in a closed
vessel protocol. The catalytic activity of the nanoparticle system was investigated by varying
the amount of catalyst while keeping the other parameters constant. It was observed that 300
mg resin (≈ 0.0007 mmol of Pd, 0.07 mol % with respect to aryl halide) was sufficient for
-1
completing the reaction. Using the obtained result, TON and TOF (h ) were calculated and
the values were found to be 1,430 and 3,489 respectively. The kinetic of reaction was studied
by taking GC-MS of the reaction mixture at different intervals of time and results are
presented in Fig. 6. Total conversion of iodobenzene was obtained in 25 min. GC-MS
analysis of the ether extract showed that diphenylacetylene was the sole product. The mass
spectrum of the peak at retention time = 10.098 min was identified as diphenylacetylene from
1
4

its molecular peak in the highest mass region at m/z 178. The other prominent peaks were
found at m/z 176, 152, 126, 76 and 61.
After optimizing the reaction conditions, we performed the Sonogashira
reaction of various aryl iodide and bromide with phenylacetylene and results are shown in
Table 4. Trend similar to those observed in Heck reaction were observed here also. A total of
twelve reactions were tried and 25 to 35 minutes of microwave heating was sufficient to
complete the reactions. Reaction of chlorobenzene (entry 12) with phenyl acetylene was very
slow and only 50% yield was obtained even after 45 min of microwave heating.
Very few examples of microwave enhanced Sonogashira reaction catalyzed by
PdNPs are reported in literature. A comparison of the protocol with other reported methods
under microwave heating is shown in Table 5.
3
.2 Recycling of the catalyst after Heck and Sonogashira Reactions
Easy catalyst separation and recycling in successive batch operations can
greatly increase efficiency of any reaction protocol. In this study we found that Resin-PdNPs
were highly recyclable. At the completion of the reaction, the catalyst was recovered by
simple filtration. The resin beads were collected and washed with hot alcohol/water to
remove the product sorbed onto the resin and reused. The recovered catalyst was employed in
the next run after further addition of substrates in appropriate amount and results are reported
in Fig. 7. To check the agglomeration of particles during the reaction TEM images of the
resin beads were taken after sixth cycle and the results were compared with those of freshly
synthesized catalyst and the results are shown in Fig. 8. It was observed that most of the
particles were still in the size range of 3 to 10 only.
1
5

Additionally, leaching of the catalyst was probed by hot filteration test. The
reactions were stopped after some time and the resin beads were filtered off while the
solution was still hot. The filterate was further heated and the reaction mixture analyzed by
GC–MS after various intervals of time. The results are shown in Fig. 9. It was observed that
the reaction stopped after the resin was filtered off. Which indicated that there were no
soluble active species in the reaction mixture. Further, the reaction mixture was extracted
with ether and aqueous layer was analyzed for palladium by ICP-AES. Total palladium
concentration was found to be 65±10 ppb in case of Heck reaction and 45±10 ppb in case of
Sonogashira reaction. Thus leaching of palladium was negligible.
3
.3 Efficiency of microwave heating
Microwave heating is not only very efficient but also green. Thus, using
microwave heating, the reactions can be performed at a faster pace with higher yield as
compared to conventional heating [59]. In majority of the reactions, power of microwave was
maintained between 120 to 150 W and appropriate temperature was maintained by external
cooling. The temperature and potency profile for the Sonogashira reaction under microwave
irradiation is shown in Fig. 10.
We have earlier reported Suzuki [7] and Hiyama [8] coupling reactions under
microwave heating using resin-PdNPs. Presently, we carried out the standard reactions for
all the four coupling reactions under conventional heating also (see supplementary
information for protocols) and compared reaction time and yield with those obtained under
microwave heating as shown in Fig. 11 (see ref. 7 and 8 for Suzuki and Hiyama reaction
conditions). As expected the reaction times were greatly reduced under microwave heating
(6-35 min) as compared to conventional heating (4-30 h). Isolated yields of products under
conventional heating were only 65 to 85% in contrast to 88 to 95% isolated under microwave
heating. It is also noteworthy that under microwave heating continuous purging of inert gas
through the reaction mixture was not required. No side products were observed and in most
cases the products were purified by simple crystallization. The simplicity of protocol and
1
6

efficiency of catalyst coupled with its recyclability can lead to truly sustainable and green
protocols for C-C coupling reactions.
4
. Conclusions
Cross-linked polystyrene resins are ideal for supporting palladium nanoparticles for
microwave heating that can tremendously reduce the reaction times for C-C coupling
reactions such as Suzuki, Hiyama, Heck and Sonogashira. The catalyst was successfully used
to synthesize asymmetric terphenyls a useful industrial commodity. The choice of non-
functional resin probably increased the accessibility of reaction sites as there were no
strongly coordinating groups on the surface of the nanoparticles and less than 0.1 % of
palladium was sufficient to carry out any of the C-C coupling reactions. The presence of
permanent pores and hydrophobic nature or the resin creates a favorable mass transfer of the
materials (generally non polar in C-C couplings) inside the resin matrix which allows the
reactants to come in contact with the catalyst leading to high reaction rates (TOFs of the
order of >103) for bromo derivatives. In comparison to direct usage of palladium salts as
catalyst [60], converting them to well dispersed nanoparticles on a support is advantageous as
the amount of catalyst required is much less. Besides the ease of separation of catalyst, its
reuse and recovery of metal from the used catalyst are other useful benefits. Thus, synergism
between microwaves and palladium nanoparticles can lead to truly green and sustainable
protocols for C-C coupling reactions in general.
Acknowledgments
Authors are grateful to Nanomission DST Project and UGC, New Delhi for the financial
support to carry out this work and to SICART Vallabh Vidyanagar, Gujarat for GC-MS,
CSMCRI Bhavnagar for TEM-EDX analysis PRL Ahmedabad for ICP-AES results, SAIF
Panjab University for NMR.
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Figure 1. Sorption reduction method for nanoparticle synthesis
2
2

Figure 2. HRTEM image and ED patterns of Resin_PdNPs
2
3

Figure 3. UV–visible spectrum for the resin supported PdNPs
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4

Figure 4. Synthesis of asymmetric terphenyls
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Figure 5. Time course of Heck reaction between iodobenzene and styrene
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6

Figure 6. Time course of Sonogashira reaction between iodobenzene and phenylacetylene
2
7

Figure 7. Recycling of the catalyst for the standard Mizoroki-Heck and Sonogashira reaction
2
8

Figure 8. TEM image of freshly prepared Resin_PdNPs [A], and after sixth recycle of Heck
reaction [B]
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