Microwave-assisted aqueous carbon-carbon cross-coupling reactions of aryl chlorides catalysed by reduced graphene oxide supported palladium nanoparticles

Article abstract of DOI:10.1039/d0gc00833h

The use of low cost and readily available aryl chlorides as starting reactants in palladium-catalyzed carbon-carbon cross-coupling reactions has drawn significant research attention. However, previously reported heterogeneous palladium catalysts suffered from poor reactivity and harsh conditions. Also, valuable industrial products were rarely obtained in these catalytic systems to date. Herein, a simple and green in situ assembly and reduction approach was developed for the fabrication of reduced graphene oxide supported palladium nanoparticles (Pd/rGO). Owing to the abundant surface functional groups, Pd NPs were uniformly dispersed on the sheets of rGO with an average size of around 2.0 nm. Interestingly, under microwave irradiation, Pd/rGO can efficiently promote Ullmann and Suzuki coupling reactions by using aryl chlorides as the reactants in aqueous media, which showed even better catalytic performances than a homogeneous catalytic system. Notably, this mild reaction system can be demonstrated in the gram-scale synthesis of 4′-methyl-2-biphenylcarbonitrile and 2-nitro-3′,4′,5′-trifluoro-1,1′-biphenyl, which are important pharmaceutical intermediates of sartans and fluxapyroxad, respectively. Based on material characterization and control experiments, this remarkable catalytic performance could be ascribed to its robust microwave absorption ability, efficient electron transfer and unique two-dimensional structure. Furthermore, it was easily recycled and used repetitively at least six times without significant loss of its activity.

Full text of DOI:10.1039/d0gc00833h

View Article Online
View Journal
Green
Chemistry
Cutting-edge research for a greener sustainable future
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Q. Zhang, Z. Mao,
K. Wang, N. T. S. Phan and F. Zhang, Green Chem., 2020, DOI: 10.1039/D0GC00833H.
Volume 20
Number
May 2018
Pages 1919-2160
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
9
7
Green
Chemistry
Cutting-edge research for a greener sustainable future
rsc.li/greenchem
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1463-9262
PAPER
Paul T. Anastas et al.
The Green ChemisTREE: 20 years after taking root with the 12
principles
rsc.li/greenchem

Page 1 of 11
Please Gd roe en no tC ha ed mj u iss tt r my argins
View Article Online
DOI: 10.1039/D0GC00833H
ARTICLE
Microwave-Assisted Aqueous Carbon-Carbon Cross-Coupling
Reactions of Aryl Chlorides Catalysed by Reduced Graphene Oxide
Supported Palladium Nanoparticles
Received 00th January 20xx,
Accepted 00th January 20xx
‡
a
‡a
a
*b
*a
DOI: 10.1039/x0xx00000x
Qingxiao Zhang , Zhan Mao , Kaixuan Wang , Nam Thanh Son Phan , and Fang Zhang
The use of low cost and readily available aryl chlorides as the starting reactants in the palladium-catalyzed carbon-carbon
cross-coupling reactions have drawn significant research focus. However, the previously reported heterogeneous
palladium catalysts suffered from poor reactivity and harsh condition. Also, the valuable industrial products were rarely
obtained in these catalytic systems until now. Herein, a simple and green in-situ assembly and reduction approach was
developed for the fabrication of reduce graphene oxide supported palladium nanoparticles (Pd/rGO). Owing to the
abundant surface functional groups, Pd NPs were uniformly dispersed on the sheets of rGO with an average size of around
2
.0 nm. Interestingly, under microwave irradiation, Pd/rGO can efficiently promote Ullmann and Suzuki coupling reactions
by using aryl chlorides as the reactants in aqueous media, which displayed even better catalytic performances than
homogenous catalytic system. Notably, this mild reaction system can be demonstrated in the gram-scale synthesis of 4’-
methyl-2-biphenylcarbonitrile and 2-nitro-3’,4’,5’-trifluoro-1,1’-biphenyl, which are important pharmaceutical
intermediates of Sartans and Fluxapyroxad, respectively. Based on material characterizations and the control experiments,
this remarkable catalytic performance could be ascribed to its robust microwave absorption capability, efficient electron
transfer and unique two-dimensional structure. Furthermore, it was easily recycled and used repetitively for at least six
times
without
the
significant
loss
of
its
activity.
economic and environmental requirements. Accordingly,
translating homogeneous catalysis to heterogeneous catalysis
Introduction
Cross-coupling reactions have become essential to industry
and academia for the formation of C−C and C−X bonds, even
for the construction of complex organic molecules . In this
area, palladium-catalyzed carbon-carbon bond formations
1
4-16
achieves considerable attention
. In recent years, various
palladium species including Pd salt, Pd organometallic complex
and Pd nanoparticles were immobilized on different solid
1
-3
1
7
18
19
20
supports such as metal oxide , zeolite , silica , polymer ,
carbon
1
6, 21
22
and metal-organic framework , generating a large
4
5,
6
7,
8
9
10
such as Ullmann , Suzuki , Negishi , Stille , Heck ,
amount of heterogeneous palladium catalysts. Among
different supports, carbon is believed as the excellent support
for the immobilization of palladium active sites owing to
chemical and thermal stability. To date, different allotropes of
carbon including carbon black, carbon nanotube, carbon fibre,
graphene, graphene oxide and C60 have been used as the
Sonogashira9
,
11
,
Tsuji-Trost reactions
12
are particularly
appealing in modern organic synthesis. Although these
reactions were discovered almost 50 years ago and now
represent mature technology, they are typically conducted in
homogeneous conditions by using inorganic palladium salts or
1
, 13
organic palladium complexes
. Accordingly, the expensive
2
3, 24
support to prepare carbon-supported Pd catalysts
. They
price of palladium, the high toxicity of palladium residues, the
use of organic toxic solvents and the tedious workup of the
reaction process are not able to satisfy the increasing
were able to promote several different carbon-carbon cross-
coupling reactions such as Suzuki-Miyaura, Mizoroki-Heck and
Sonogashira-Hagihara in organic solvents but also in aqueous
media. However, there is still a significant amount of
challenges to improve the scope of these reactions and make
reactions more practical. First, most of these reported
heterogeneous palladium catalysts displayed the inferior
reactivity compared with homogenous catalysts. They often
require the use of more reactive and expensive aryl iodides
a. The Education Ministry Key Lab of Resource Chemistry and Shanghai Key
Laboratory of Rare Earth Functional Materials, Shanghai Normal University, 100
Guilin Rd., Shanghai, 200234, China. E-mail: zhangfang@shnu.edu.cn.
b.
Faculty of Chemical Engineering, Ho Chi Minh City University of Technology, 268
Ly Thuong Kiet Street, District 10, Ho Chi Minh City, VN 84, Vietnam. E-mail:
ptsnam@hcmut.edu.vn
†
Electronic Supplementary Information (ESI) available: ICP results of different Pd-
rGO catalyst; Reaction optimization of Ullmann and Suzuki reactions; TEM image
of Pd/SiO ; Microwave absorption ability tests of different samples; TEM and XPS
25
and bromides as the reactants . But, for low cost and readily
available aryl chlorides, carbon-based Pd catalysts frequently
2
2
6
13
results of the reused Pd-rGO-60 catalyst. This material is available free of charge need very long reaction time , high catalyst dosage , harsh
via the Internet at http://pubs.acs.org. See DOI: 10.1039/x0xx00000x
These authors contributed equally to this work.
1
27, 28
reaction conditions or different additives
. Also, in many
‡
Please do not adjust margins

Please Gd roe en no tC ha ed mj u iss tt r my argins
Page 2 of 11
ARTICLE
Journal Name
o
cases, the valuable industrial products were rarely obtained in acid solution was slowly added and reacted for 2.0 h at 60 C
View Article Online
DOI: 10.1039/D0GC00833H
these previously reported catalytic systems until now. and subsequently 10 g hydrogen peroxide was added and
o
Moreover, the preparation of carbon-supported palladium stirred at 90 C for 1.0 h. After that, 1.0 L distilled water was
catalysts adopts the tedious procedures such as two-step added to continue the reaction for 1.0 h. Finally, the solid
2
9, 30
31
impregnation-reduction
or post-grafting approach .
sample was obtained by centrifugation and washed with a
Microwave-assisted organic synthesis provides an efficient tool 5.0% hydrochloric acid solution until the sulfate ion was
3
2
to accelerate carbon-carbon formation reactions . But, completely washed, and then it was continued to wash by
carbon-supported palladium particle catalysts are rarely deionized water to be near neutral. And then it was dried at
o
employed due to the potential arcing phenomena and hot 80 C for 8.0 h and ground into a powder to obtain the final
spots that formed by microwave irradiation. Recently, product.
Whittaker et al found that arcing is limited to large metal
particles, which supports nanometre-sized particles can ensure Synthesize of Pd nanoparticles/reduced graphene oxide (Pd/rGO).
3
3
safer reaction . Moreover, Vaccaro group revealed that hots
spots are usually observed with low boiling solvents such as
2
50 mg graphene oxide was dispersed into 100 mL sodium
hydroxide aqueous solution and then 200 mL 0.10 mol/L
sodium dodecyl sulfate solution was mixed. After ultrasonic for
1
h at a certain temperature. After washing by ethanol and
deionized water for three times and drying at 80 C for 12 h, a
series of solid sample was obtained. These samples were
denoted as Pd/rGO-30, Pd/rGO-60 and Pd/rGO-110, which
were corresponded to the temperature at which the catalyst
2 2
THF and CH Cl in the presence of heterogeneous metal
catalysts . Accordingly, Pd/C catalyst was widely used in the
microwave-assisted carbon-carbon cross-coupling reactions
3
4
.0 h, 100 mg palladium acetate was added and stirred for 4.0
such as Suzuki–Miyaura Coupling, Mizoroki–Heck and
o
Sonogashira5
, 6, 9-11
. Nevertheless, the small pore size of Pd/C
limited the reaction performance, especially for the reactants
with large molecular size. Moreover, although it shortened the
reaction time, the increase of reaction selectivity is still a
difficulty. In recent years, reduced graphene oxide (rGO)
represents an ideal support to form rGO-Pd nanoparticle
composite, which possesses unique properties favourable for
cross-coupling reactions due to large surface area, light weight,
excellent stability and efficient electron mobility
that the previously reported results revealed that rGO/metal
nanoparticles composites displayed the enhanced microwave
o
o
o
was prepared at 30 C, 60 C and 110 C, respectively.
Preparation of Pd nanoparticles/Silica (Pd/SiO
2
).
As a control sample, Pd/SiO was prepared by a similar
protocol with Pd/rGO, except instead of rGO support as SiO
support.
2
3
5-37
2
. Noted
3
6
Activity Test.
absorption ability compared with other traditional materials .
However, the combination of rGO supported Pd nanoparticles Ullmann reaction: In a typical run, 1.0 mmol chlorobenzene,
with microwave heat for chemical transformations is not fully 1.5 mmol sodium acetate, 0.50 mmol tetrabutylammonium
explored until now. In this work, we synthesized rGO bromide (TBAB), a certain amount of Pd/rGO, 1.0 mmol 1,3,5-
supported Pd nanoparticles composite by an in-situ assembly trimethylbenzene as the internal standard, 1.0 mL ethanol and
and reduction protocol. Owing to its unique two-dimensional 1.0 mL water were added into a 10 mL microwave reaction
structure and microwave absorption performance, it showed tube in Discover SP Microwave Synthesizer (CEM Discover SP)
excellent catalytic performance for Ullmann and Suzuki at a frequency of 2450 MHz with a maximum power of 300W.
reactions by using different aryl chlorides as the reactants in After the mixture was stirred under microwave irradiation at
o
the aqueous solvent under microwave heating. For important 100 C for 2.0 h, the solid catalyst was removed by filtration
pharmaceutical intermediates containing multiple substituents, and then 2.0 mL ethyl acetate was added to the clear solution
such as 4'-methyl-2-biphenylcarbonitrile and 2-nitro-3', 4', 5'- to extract the reaction products. The products were quantified
trifluoro-1, 1'-biphenyl, it also can obtain more than 90% yield using an Agilent 6410 Series Triple Quad LC/MS equipped with
in a gram-scale synthesis under the mild reaction conditions. UV detector and Agilent C18 column (20 cm*φ5 mm).
Moreover, it can be recycled for six times without significant
deactivation.
Suzuki reaction: 1.0 mmol chlorobenzene, 1.2 mmol
phenylboronic acid, 0.50 mmol TBAB, 3.0 mmol potassium
phosphate, 1.0 mmol 1, 3, 5-trimethylbenzene as internal
standard, 1.0 mL ethanol and 1.0 mL water with a certain
amount of Pd/rGO were added to a 10 mL microwave reaction
tube in Discover SP Microwave Synthesizer (CEM Discover SP)
at a frequency of 2450 MHz with a maximum power of 300W.
The reaction was stirred at 100°C for 3.0 hours to complete the
reaction. The products were quantified using a same method
with Ullmann reactions.
Experimental Section
Preparation of Graphene oxide.
Graphene oxide was synthesized by classical Hummers
method. In the ice water bath, 1.0 g natural graphite powder
and 1.0 g sodium nitrate were added into a 1.0 L three-necked
flask, and then 40 mL of concentrated sulfuric acid was slowly
introduced. After stirring for 2.0 h, 5.0 g potassium
permanganate was slowly added and the mixture was allowed
Recyclability test: To test the recoverability of the Pd/rGO
catalyst, the mixture was centrifuged after the completion of
o
to stir at 35 C for another 6.0 h. Then, 100 mL 5.0 % sulfuric
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 11
Please Gd roe en no tC ha ed mj u iss tt r my argins
Journal Name
ARTICLE
푍푖푛 ― 1
the reaction. To remove impurities which may be adsorbed by
the catalyst, it was washed for three times with distilled water
and ethanol, respectively. After drying at 80 C for 24 h, the
R(dB) = 20 log|푍푖푛 + 1
|
View Article(5
Online
)
DOI: 10.1039/D0GC00833H
o
mass of the recovered catalyst was weighed, and the loss due
to the washing and transfer of the catalyst was calculated. The
amounts of the corresponding reactants were used, and the
recycling reactions were carried out under the same
conditions. After each run of reactions, the content of Pd
leached off in each reaction was analysed by ICP analysis.
Results and discussion
Measurements and Characterization.
Fourier transform infrared (FTIR) spectra were obtained using
a Nicolet Magna Model 550 infrared spectrometer. X-ray
diffraction (XRD) patterns were acquired by a Rigaku D/Max-B
diffractometer with Cu Kα radiation. High-resolution
Transmission electron microscopy (TEM/HRTEM) images were
obtained by a JEOL-2100 transmission electron microscope. X-
ray photoelectron spectroscopy (XPS) analysis was performed
on a Perkin Elmer PHI 5000 ESCT System X-ray photoelectron
spectrometer. Inductively coupled plasma spectroscopy (ICP)
was analysed by Varian VISTA-MPX ICP-OES inductively
coupled plasma spectroscopy. The electromagnetic
parameters (complex permittivity and complex permeability)
were measured via a coaxial line method at the frequency
range of 1-18 GHz by an Agilent PNA-N5244A (E5071C)
network analyser and the calculations involving complex
numbers are performed by Fenghuo Technology Co., Ltd. via
Matlab.
Scheme 1. Schematic illustration of the preparation of Pd
nanoparticles/reduced graphene oxide (Pd/rGO).
As shown in Scheme 1, Pd/rGO samples were prepared by
an in-situ reduction approach using reduced graphene oxide as
the support and palladium acetate as the precursor,
respectively. We used sodium dodecyl sulfate to disperse rGO
Calculation method of microwave absorb ability.
The dielectric loss and magnetic loss properties of the GO, in the solution and after heating, it decomposed to 1-
Pd/rGO-60 and Pd/SiO
are respectively calculated by the dodecanol, which can reduce Pd(II) to Pd(0) by self-oxidizing to
equation (1) and equation (2). Calculation details of dielectric dodecanoic acid
loss tangent and magnetic loss are the data in Figure 4 (a) and content in the series of Pd/rGO samples was in the range of
2
3
8, 39
. ICP measurement showed that the Pd
Figure S2 (a). The equations are described as follows:
0.05 mmol/g to 0.89 mmol/g, confirming the existence of
palladium nanoparticles in these composites (Table S1).
휀″
tan 훿 =
(1)
(2)
푒
휀
′
휇″
tan 훿 =
푚
휇
′
In order to obtain the attenuation constant α, formula (3) can
be used.
2
훼 = 푐 휋푓·
″
푟
″
푟
′
′
푟
″
푟
″
푟
′
′
푟
2
′
″
푟
′′
′
푟
2
(
휇 휀 ― 휇 휀
)
+
(
휇 휀 ― 휇 휀
)
+
(
휇 휀 + 휇 휀
)
(3)
푟
푟
푟
푟
The microwave absorb ability of different samples can be
obtained by formula (4) and formula (5).
휇푟
휀푟
2휋
푍푖푛
=
tanh 푗( )
푓푑 휇푟휀푟]
(4)
[
푐
Figure 1. Powder X-ray diffraction (PXRD) patterns of Pd/rGO-30, Pd/rGO-60,
Pd/rGO-110 and GO (a); FT-IR spectra of GO and Pd/rGO-60 (b); Raman spectra
of GO and Pd/rGO-60 (c); XPS spectrum of Pd/rGO-60 (d).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please Gd roe en no tC ha ed mj u iss tt r my argins
Page 4 of 11
ARTICLE
Journal Name
Powder X-ray diffraction (PXRD) pattern revealed that GO
View Article Online
0,
sample only displayed a typical amorpDhOouI:s10p.1e0a3k9/D (Figure
a). The new diffraction peaks at 40.12° and 46.56° were
0GC00833H
4 41
1
found in a series of Pd/rGO samples. Comparing with the
standard patterns for pure Pd (JCPDS PDF #46-1043), the peak
at 40.12° was assigned to the (111) crystal plane of Pd NPs,
and the diffraction peak at 46.56° was considered to be the
4
2
peak of the (200) crystal plane of Pd NPs , confirming the
formation of Pd/rGO composites. Meanwhile, in the catalyst
synthesized at 110°C, the crystallinity of Pd NPs was
significantly higher than that of the catalyst synthesized at
3
0°C and 60°C, which was due to the increased particle size of
Pd NPs. FTIR spectrum of GO sample showed that it had a
-1
strong and broad absorption peak centred at 3421 cm , which
corresponded to the stretching vibration of the hydroxyl group
-1
(
-OH) on the sheet (Figure 1b). Also, the peak at 1732 cm was
the C=O stretching vibration at the carboxyl group, and the
-1
vibration absorption peaks at 1358, 1219, and 1049 cm were
4
3,
the stretching vibration of C-OH, C-O-C and C-O, respectively
.
4
4
After introducing palladium species on the GO, the C=O
stretching vibration peak in the representative Pd/rGO-60
sample was disappeared, and the intensity of the C-OH
vibration peak was weakened significantly, which indicated the
oxygen-containing group in the GO is partially removed. Thus,
Pd nanoparticles were probably bound to the sheets of rGO
through the coordination between Pd species and surface
oxygen-containing groups. Raman spectrum revealed that the
intensity ratio of G peak and D peak of Pd/rGO-60 (1.07) was
lower than that of graphene oxide (1.57), confirming the
increased regularity degree of carbon framework after our in-
4
5
situ palladium loading process (Figure 1c). This result further
demonstrated that oxygen-containing groups was partially
reduced in the preparation of Pd/rGO samples. Also, XPS
spectrum of Pd/rGO-60 confirmed that all the palladium
species existed as the zero metallic state, corresponding to the
binding energy (BE) of 341.1 and 335.8 eV in the Pd 3d3/2 and
4
2, 46
3
d5/2 levels
, respectively (Figure 1d). On basis of these
results, we can safely conclude that the successful
incorporation of the Pd metallic species on the rGO sheets.
Palladium particle size and distribution of different
Pd/rGO samples can be obtained by TEM images. As shown in
Figure 2, for all the samples, the apparent two-dimensional
morphology of rGO can be observed while the presence of Pd
nanoparticles on the basal plane of the materials was obvious.
o
o
In the low preparation temperature (30 C, 60 C),
homogeneously distributions of Pd nanoparticles with smaller
size of ca. 2.0 nm on the rGO were founded (Figure 2a-b). But,
o
in the high preparation temperature (110 C), the particle size
of Pd NPs of Pd/rGO-110 was around 11 nm and their
agglomerations were evident (Figure 2c). Also, for Pd/rGO-30,
the distribution of Pd NPs was sparse on the sheet due to the
low loading. Furthermore, HRTEM image of Pd/rGO-60
revealed that the lattice fringe width of Pd NPs was 0.224 nm,
Figure 2. TEM images and Pd nanoparticle size distributions of Pd/rGO-30 (a),
Pd/rGO-60 (b), and Pd/rGO-110 (c) and HRTEM image of Pd/rGO-60 (d).
4
7,
which corresponded to the Pd(111) crystal plane (Figure 2d)
4
8
12
.
On basis of the similar reported procedure , a plausible
growth mechanism of Pd/rGO was presented. The surface
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 11
Please Gd roe en no tC ha ed mj u iss tt r my argins
Journal Name
ARTICLE
hydroxyl groups can electrostatic absorb Pd(II) ions on the GO and selectivity (Table S2, Entry 1-3). The optimal reaction
View Article Online
o
DOI: 10.1039/D0GC00833H
basal planes. Then, the reduction process of Pd(II) to Pd(0) was temperature was 100 C. Meanwhile, we found that the
happened through the self-oxidation of the heating-generated mixture of CH COONa and KOH was the most effective base
3
1
-dodecanol to 1-dodecanonic acid.
among those tested (Table S2, Entry 4-9). After careful
investigation, Pd/rGO-60 allowed a high conversion (97.2%)
and selectivity (93.5%) by using CH COONa and KOH as the
3
Table 1. Catalytic performances of different Pd-based catalysts for Ullmann
coupling reaction. a
Cl
Pd Catalysts
Entry
Catalyst
Blank
Time (min)
60
Conversion (%)
Yield (%)
Trace
Trace
36.8
H O/MeOH
2
1
2
Trace
Trace
41.4
72.3
35.9
97.2
10.2
53.4
52.4
32.6
a
Reaction conditions: 1.0 mmol chlorobenzene, 0.50 mmol TBAB, 1.5 mmol
CH COONa, 2.5 mmol KOH, 2.0 mL solvent (Vwater:VMeOH=1/1), 0.50 mol% Pd
3
catalyst, 100 C (microwave heating); heating by oil bath; 150 C.
o
b
c
o
GO
60
3
Pd/rGO-30
Pd/rGO-60
Pd/rGO-110
Pd/rGO-60
Pd/rGO-60
Pd/rGO-60
60
4
60
69.5
5
60
33.3
6
120
120
120
120
120
93.5
7b
8c
9
5.4
Figure 3. (a) Reaction profiles with reaction time of Pd/rGO-60-catalyzed
Ullmann reaction under microwave heating or oil bath heating, (b) Reaction
profiles with reaction time of Ullmann reaction using Pd/rGO-60, Pd/SiO
Pd(OAc) catalyst under microwave heating, the solid point is the conversion rate
and the hollow point is the yield.
2
and
49.6
2
Pd(OAc)
2
49.2
In our initial investigation, homocoupling of
chlorobenzene (Ullmann-type reaction) was chosen as a model
reaction to explore the catalytic performances of our Pd/rGO
samples in aqueous solvent under microwave heating. As
shown in Table 1, all the Pd/rGO samples can promote
chlorobenzene to biphenyl with a 0.50 mol% catalyst dosage
Entry 3-5). The control experiments by without catalyst or
using rGO as the catalyst gave the negligible yields, confirming
the palladium catalytic nature of the reaction (Table 1, Entry 1-
). Under the same conditions, both Pd/rGO-30 and Pd/rGO-
10 exhibited the worse catalytic performances with the yields
of 36.8% and 33.3%, respectively (Table 1, Entry 3, 5).
Interestingly, Pd/rGO-60 displayed the good catalytic reactivity
and the selectivity, delivering the highest yield of 69.5% (Table
1
0
Pd/SiO
2
27.5
base, water/ethanol solvent and TBAB as the dispersant under
microwave radiation for 2.0 h (Table 1, Entry 6). Noted that
Pd/rGO-60 showed the negligible activity at 100 C for 2.0 h by
using oil bath heating (Table 1, Entry 7). Even at 150 C for 2.0
h, it only gave the conversion of 53.4% and the yield of 49.6%
Table 1, Entry 8). Furthermore, we found that homogeneous
catalyst Pd(OAc) also delivered the lower efficiency with the
yield of 49.2% for 2.0 h under microwave heating (Table 1,
Entry 9). By extending the reaction time to 20 h under oil bath
heating, it still exhibited the inferior catalytic performance
o
(
o
(
2
1
2
(
Table S2, Entry 10). The profiles of catalytic performances
1
, Entry 4). The poor catalytic efficiency of Pd/rGO-30 was
with the reaction time (Figure 3a) revealed that the conversion
of Pd/rGO-60 can reach 93.5% after 2.0 h under microwave
heating. In comparison, its catalytic activity by using oil bath
heating was only 5.4%. After 20 h, the reaction conversion in
the oil bath reached almost 100%. But the yield was only
probably attributed to the low loading of Pd NPs, which caused
the insufficient contact between the active site and the
reactant (Table S1). Also, the inferior catalytic performance of
Pd/rGO-110 was maybe ascribed to the large particle size of Pd
NPs (Figure 2c), which resulted in the decreased accessibility of
the active sites. Next, to explore the best utility of our Pd/rGO-
8
5.6%, which revealed microwave heating also enhanced the
reaction selectivity. Next, in order to compare the effect of the
microwave absorbing ability of different carriers on the
catalytic activity, we used the similar preparation method to
6
0 catalyst, we investigated the effect of various parameters
including temperature and type of base on the Pd/rGO-60
catalyzed Ullmann reactions (Table S2). Obviously, low
reaction temperature offered the lower reaction conversion
obtain Pd/SiO
2
catalyst as the control sample. TEM revealed
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please Gd roe en no tC ha ed mj u iss tt r my argins
Page 6 of 11
ARTICLE
Journal Name
2
catalyst was dissipate inside Pd/rGO-60 (Figure 4c). Pd/rGOV-ie6w0A'srticslecOrenleinne
that the particle size of Pd NPs in the Pd/SiO
similar as that of Pd/rGO-60 (Figure S1). However, the catalytic reflection loss graph (Figure 4d) furthDeOrI: s1h0.o10w3s9/Dth0GatC0i0t83h3aHs
activity of Pd/SiO
2
catalyst was much lower than Pd/rGO-60 efficient microwave absorption performance. The minimum
under the same reaction conditions, which demonstrated the reflection loss (RLmin) of Pd/rGO-60 is -51.8 dB (7.4 GHz) and
unique effect of rGO support.
the thickness of the absorber is 3.6 mm. On basis of these
results, we can safely conclude that Pd/rGO can effectively
absorb microwave radiation. Specially, the microwaves are
In order to study the correlations between the microwave
absorption property of the supports and their catalyst
performances, the relative complex permittivity and complex
permeability of different samples were measured using a
vector network analyser and the calculation method of
microwave absorb ability for different samples was shown in
Experimental Section. For the real part (energy storage
capacity, ε′) and imaginary part (energy consumption capacity,
ε″) of the complex dielectric constant, the complex dielectric
constant of Pd/rGO-60 was higher than that of Pd/SiO
2
catalyst
(Figure 4a), which was due to the highest electrical
conductivity of rGO. The complex permeability μ′ and μ′′ are
consistent for all samples (Figure S2a). The dielectric loss
tangent function and magnetic loss function were used to
evaluate the dielectric and magnetic losses of Pd/rGO-60 and
Figure 4. Frequency dependence of real part and imaginary part of permittivity
2
Pd/SiO . As show in Figure 4b, Pd/rGO-60 had the largest
(a), dielectric loss tangent (b), attenuation constant (c) of GO, Pd/rGO-60 and
dielectric loss ability, and all the samples had no difference in
magnetic loss (Figure S2b). The above phenomenon obviously
indicated that Pd/rGO-60 had the best microwave absorption
ability. Meanwhile, the attenuation constant was an important
parameter for microwave attenuation. Calculation results
showed that Pd/rGO-60 had the largest attenuation constant,
indicating that electromagnetic waves were more likely to
Pd/SiO samples, and reflection loss characteristic of Pd/rGO-60 with varying
the absorber thickness (d).
2
absorbed by rGO support and next rGO converted the energy
to the surface of Pd NPs, leading to the increased local high
temperature. This heating effect resulted in the enhanced
catalytic reactivity of the Pd/rGO-60 catalyst.
Table 2. Reaction scope of Pd/rGO-60 catalyzed Ullmann coupling reactions. a
Cl
Pd/rGO-60
R
R
H O/MeOH
2
R
Entry
Reactant
Conversion (%)
96.6
Yield (%)
93.0
TON c
186.0
190.0
177.0
82.4
TOF c
93.0
95.0
88.5
41.2
44.2
1
2
99.0
95.0
3
92.1
88.5
4
46.3
41.2
5b
92.4
88.3
176.6
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 11
Please Gd roe en no tC ha ed mj u iss tt r my argins
Journal Name
ARTICLE
a
3
Reaction conditions: 1.0 mmol aryl chlorides, 0.50 mmol TBAB, 1.5 mmol CH COONa, 2.5 mmol KOH, 2.0 mL solvent (Vwater:VMeOH=1/1), 0.50 mol% Pd catalyst,
00 C (microwave heating), 2.0 h; DMF as solvent, 4.0 h. c Turnover number: moles of product per mole of Pd. Turnover frequency: moles of product per mole of Pd
o
b
View Article Online
1
per
DOI: 10.1039/D0GC00833H
hour.
To verify the substrate universality of Pd/rGO-60, different the replacement of chlorobenzene by the ortho position with
aryl chlorides with various substituted groups were tested. As large steric hindrance, the good yield was also obtained by
shown in Table 2, under the same conditions, both electron- extending the reaction time to 4.0 h and changing ethanol to
withdrawing and electron-donating groups in the para- and DMF. These results confirmed that Pd/rGO-60 had the good
meta-position didn’t harm to the outcome of Pd/rGO-60. For substrate tolerance in Ullmann coupling reaction.
Table 3. Catalytic performances of Pd/rGO-60 catalyzed Suzuki cross-coupling reactions. a
Entry
Reactant
Conversion (%)
＞99
Yield (%)
94.8
91.2
94.2
68.8
90.4
59.6
78.5
70.2
88.3
TON c
189.6
182.4
188.4
137.6
180.4
119.2
157.0
140.4
176.6
TOF c
63.2
60.8
62.8
45.9
36.1
39.8
31.4
46.8
35.3
1
2
3
94.5
＞99
4
74.2
5b
6
95.2
64.2
7b
8
80.4
75.2
9b
92.4
a
o
Reaction conditions: aryl chloride (1.0 mmol), phenylboronic acid (1.2 mmol), TBAB (0.50 mmol), K
3
PO
4
(3.0 mmol), 0.50 mol% Pd/rGO-60, 100 C (microwave
heating), 2.0 mL (Vwater:VMeOH=1/1), 3.0 h; 5.0 h. c Turnover number: moles of product per mole of Pd. Turnover frequency: moles of product per mole of Pd per hour.
b
7
8.5% and 88.3% was obtained by extending reaction time to
Furthermore, we tested the reactivity of Pd/rGO-60 in the 5.0 h, respectively (Table 3, Entry 6-9).
Suzuki-Miyaura cross-coupling reaction, which is very popular
in the synthesis of pharmaceutical intermediates and fine
chemicals. By using chlorobenzene with phenylboronic acid as
the reactant, the excellent yield (94.8%) of biphenyl was
achieved. For substituted chlorobenzene, an electron-rich
group such as a methyl group, a hydroxyl group or a cyano
group in the para-position, the yields still can reach to at least
9
0% (Table 3, Entry 1-5). Even with the use of methoxy and 2-
chlorotoluene with a large steric hindrance, the good yield of
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please Gd roe en no tC ha ed mj u iss tt r my argins
Page 8 of 11
ARTICLE
Journal Name
To verify the reusability of Pd/rGO-60 catalyst, the
View Article Online
DOI: 10.1039/D0GC00833H
recyclability test was carried out in Ullmamn reaction by using
chlorobenzene as the reactant. As shown in Figure 6, it
displayed almost constant activity and selectivity even after
being used repetitively for 6 times. The hot filtration test was
performed to confirm the heterogeneity of the catalyst. After
On basis of these excellent results, we tried to use reacting for 1.0 h, Pd/rGO-60 was filtered and the reaction was
Pd/rGO-60 to catalyse the practical useful reactants. As shown allowed to proceed under the same reaction conditions. But,
in Figure 5, we selected 4'-methyl-2-biphenylcarbonitrile and we found that no coupling product of biphenyl was obtained
2
-nitro-3',4',5'-trifluoro-1,1'-biphenyl as the target product, even after allowing the reaction with for the longer reaction
which are the important intermediates of the drugs of Sartans time (6.0 h). Moreover, the liquid phase of the reaction
and Fluxapyroxad, respectively. After optimizing the reaction mixture was collected after each reaction to test if palladium
conditions (Table S3), Pd/rGO-60 can deliver 93.8% yield of 4'- was leaching from the solid catalyst during reaction. ICP-AES
methyl-2-biphenylcarbonitrile under microwave heating for analysis confirmed that an extremely low amount of Pd (less
3
.0 h. Compared with the catalytic activity of the previously than 1.0 ppm) was found in the filtrate. These results indicated
4
9
reported homogeneous catalysts including Pd
derived palladacycles , Pd(OAc)
heterogeneous catalysts such as PEG-PdL , Pd@NPad
Pd@PAN-Ad , the reaction conditions is quite mild and the catalyst (Figure S3) revealed that the zero-valence state of Pd
reaction time is shortest (Scheme 2). For more complicated 2- NPs didn’t changed after six cycles. TEM image (Figure S4) of
nitro-3', 4', 5'-trifluoro-1, 1'-biphenyl, the optimal reactivity the reused Pd/rGO-60 showed no significant change in the
was also obtained by carefully investigating the reaction two-dimensional morphology and only a small amount of
conditions, the final yield can reach to 89.7% (Table S4). To the palladium nanoparticles tended to agglomerate, which may
best of our knowledge, this is the first report of a explain the extremely slight decrease in reactivity of the
heterogeneous catalyzed system for this important substance.
2
(dba)
3
, oxime- that the current reaction was heterogeneous in nature, which
5
0
51
52
2
, Pd-KITPHOS-10
and was maybe attributed to the strong bonding between rGO and
5
3
54
2
,
Pd NPs. Furthermore, XPS spectrum of the reused Pd/rGO-60
5
5
Interestingly, even in the gram-scale synthesis, the yield of
8
5.1% can be obtained. These results fully demonstrated the
potential application of Pd/rGO-60 for the practical application
in the preparation of valuable molecules with complex
structures. Interestingly, even in the gram-scale synthesis, the
yield of 85.1% can be obtained. These results fully
demonstrated the potential application of Pd/rGO-60 for the
practical application in the fabrication of valuable molecules
with complex structures.
Scheme 2. Catalytic performance comparison of different catalytic system for
Suzuki reaction of 2-bromobenzonitrile and 4-tolueneboronic acid.
Figure 5. (a) Pd/rGO-60 catalyzed synthesis of the intermediate of Sartans by
Suzuki reaction of 2-bromobenzonitrile and 4-tolueneboronic acid; (b) Pd/rGO-
recycled Pd/rGO-60 catalyst after six repetitions.
6
0 catalyzed synthesis of the intermediate of Fluxapyroxad by Suzuki reaction
of 2-nitrochlorobenzene and 3,4,5-trifluorophenylboronic acid. Reaction
conditions were in Table S3 and Table S4.
Conclusions
In summary, palladium nanoparticles were introduced on the
sheets of reduced graphene oxide by a facile in-situ reduction
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 11
Please Gd roe en no tC ha ed mj u iss tt r my argins
Journal Name
ARTICLE
approach. The obtained Pd/rGO composite possessed the 15.
typical two-dimensional plane structure and uniformly
X. Li, L. Zhou, Y. Wei, A. M. El-Toni, F. ZhangVieawndArtDicl.eZOhnalinoe,
J. Am. Chem. Soc., 2015, 137, 5903D-O5I9: 0106..1039/D0GC00833H
L. He, K. Natte, J. Rabeah, C. Taeschler, H. Neumann, A.
Bruckner and M. Beller, Angew. Chem. Int. Ed., 2015, 54,
1
1
1
6.
7.
8.
dispersed Pd nanoparticles. With the assistance of microwave
heating, it can efficiently activate various aryl chlorides to the
desired biphenyl products with very high conversion and
selectivity as well as durability for aqueous Ullmann and Suzuki
cross-coupling reactions. Noted that it also realized the gram-
scale synthesis of key intermediates of important Sartans and
Fluxapyroxad medicines, showing a good potential in the
future industrial application. Further exploration of the
4
320-4324.
S. Zhang, C. R. Chang, Z. Q. Huang, J. Li, Z. Wu, Y. Ma, Z.
Zhang, Y. Wang and Y. Qu, J. Am. Chem. Soc., 2016, 138,
2
629-2637.
J. González-Rivera, I. R. Galindo-Esquivel, M. Onor, E.
Bramanti, I. Longo and C. Ferrari, Green Chem., 2014, 16,
1417-1425.
development of magnetite/rGO composite supported Pd 19.
nanoparticles with easy separation and enhanced
T. Kawasaki, Y. Araki, K. Hatase, K. Suzuki, A. Matsumoto,
T. Yokoi, Y. Kubota, T. Tatsumi and K. Soai, Chem.
Commun., 2015, 51, 8742-8744.
recyclability5
6, 57
is being pursued in our laboratory.
2
2
2
2
2
0.
1.
2.
3.
4.
H. Kaur, D. Shah and U. Pal, Catal. Commun., 2011, 12,
1
384-1388.
M. Cai, Q. Xu and Y. Huang, J. Mol. Catal. A: Chem., 2007,
71, 93-97.
Conflicts of interest
There are no conflicts to declare.
2
B. Yuan, Y. Pan, Y. Li, B. Yin and H. Jiang, Angew. Chem.
Int. Ed., 2010, 49, 4054-4058.
L. Yang, Y. Tang, S. Luo, C. Liu, H. Song and D. Yan,
ChemSusChem, 2014, 7, 2907-2913.
L. Yang, G. Yi, Y. Hou, H. Cheng, X. Luo, S. G. Pavlostathis,
S. Luo and A. Wang, Biosens Bioelectron, 2019, 141,
Acknowledgements
This work is supported by NSFC (21677098), Shanghai
government (19SG42, 19520710700 and 18230742500) and
the Program for Professor of Special Appointment (Eastern
Scholar) at Shanghai Institutions of Higher Learning
1
11444.
2
2
2
2
2
3
3
5.
6.
7.
8.
9.
0.
1.
Y. Li, X. Fan, J. Qi, J. Ji, S. Wang, G. Zhang and F. Zhang,
Nano Res., 2010, 3, 429-437.
(
TP2016034).
G. Li, H. Yang, W. Li and G. Zhang, Green Chem., 2011, 13,
2
939-2947.
B. Karimi and P. Fadavi Akhavan, Chem. Commun., 2011,
47, 7686-7688.
Notes and references
S. Jabeen, R. A. Khera, J. Iqbal and M. Asgher, J. Mol.
Struct., 2020, 1206, 127753.
Y. Du and R. Chen, Korean J. Chem. Eng., 2015, 32, 1759-
1
2
3
4
5
6
7
8
9
1
.
M. Gholinejad, Z. Naghshbandi and C. Nájera,
ChemCatChem, 2019, 11, 1792-1823.
X. Zhang, Z. Sun, B. Wang, Y. Tang, L. Nguyen, Y. Li and F.
F. Tao, J. Am. Chem. Soc., 2018, 140, 954-962.
A. Şengül and M. E. Hanhan, Appl. Organomet. Chem.,
018, 32, e4288.
X. Gong, J. Wu, Y. Meng, Y. Zhang, L.-W. Ye and C. Zhu,
Green Chem., 2019, 21, 995-999.
M. Niakan, Z. Asadi and M. Emami, Catal. Lett., 2020, 150,
04-418.
P. K. Prajapati, S. Saini and S. L. Jain, J. Mater. Chem. A,,
020, 8, 5246-5254.
M. Busch, M. D. Wodrich and C. Corminboeuf, ACS Catal.,
017, 7, 5643-5653.
C. Diner and M. G. Organ, Organometallics, 2018, 38, 66-
5.
M. J. Jin and D. H. Lee, Angew. Chem. Int. Ed., 2010, 49,
119-1122.
.
1
765.
J. S. K. Clark, M. J. Ferguson, R. McDonald and M.
Stradiotto, Angew. Chem. Int. Ed., 2019, 58, 6391-6395.
S. El Hankari, A. El Kadib, A. Finiels, A. Bouhaouss, J. J.
Moreau, C. M. Crudden, D. Brunel and P. Hesemann,
Chemistry, 2011, 17, 8984-8994.
.
2
.
.
3
3
2.
3.
G. W. Kabalka, R. M. Pagni, L. Wang, V. Namboodiri and C.
M. Hair, Green Chem., 2000, 2, 120-122.
H. J. Kitchen, S. R. Vallance, J. L. Kennedy, N. Tapia-Ruiz, L.
Carassiti, A. Harrison, A. G. Whittaker, T. D. Drysdale, S.
W. Kingman and D. H. Gregory, Chem. Rev., 2014, 114,
4
.
2
.
2
1
170-1206.
.
3
3
3
3
4.
5.
6.
7.
E. Petricci, C. Risi, F. Ferlin, D. Lanari and L. Vaccaro, Sci
Rep, 2018, 8, 10571.
7
.
S. Moussa, A. R. Siamaki, B. F. Gupton and M. S. El-Shall,
ACS Catal., 2011, 2, 145-154.
A. R. Siamaki, A. E. R. S. Khder, V. Abdelsayed, M. S. El-
Shall and B. F. Gupton, J. Catal., 2011, 279, 1-11.
S. K. Movahed, M. Dabiri and A. Bazgir, Appl. Catal. A:
Gen., 2014, 488, 265-274.
1
0.
A. Kamal, V. Srinivasulu, B. N. Seshadri, N. Markandeya, A.
Alarifi and N. Shankaraiah, Green Chem., 2012, 14, 2513-
2
522.
1
1
1
1.
2.
3.
K. Wang, L. Yang, W. Zhao, L. Cao, Z. Sun and F. Zhang,
Green Chem., 2017, 19, 1949-1957.
J. Liu, X. Huo, T. Li, Z. Yang, P. Xi, Z. Wang and B. Wang,
Chem. Eur. J. , 2014, 20, 11549-11555.
Y. Zhang, F. Han, M. Zhang, H. Zhang, Y. Li, R. Wang, Y.
Zeng and G. Liu, Chem. Res. Chinese U., 2019, DOI:
0.1007/s40242-019-9222-2.
3
3
8.
9.
J. Lu, Carbon, 2007, 45, 1599-1605.
W.-P. Wu, A. P. Periasamy, G.-L. Lin, Z.-Y. Shih and H.-T.
Chang, J. Mater. Chem. A,, 2015, 3, 9675-9681.
E. G. Mission, A. T. Quitain, M. Sasaki and T. Kida, Green
Chem., 2017, 19, 3831-3843.
A. Primo, A. Franconetti, M. Magureanu, N. B. Mandache,
C. Bucur, C. Rizescu, B. Cojocaru, V. I. Parvulescu and H.
Garcia, Green Chem., 2018, 20, 2611-2623.
4
4
0.
1.
1
1
4.
S. Song, X. Wang, S. Li, Z. Wang, Q. Zhu and H. Zhang,
Chem. Sci., 2015, 6, 6420-6424.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

Please Gd roe en no tC ha ed mj u iss tt r my argins
Page 10 of 11
ARTICLE
Journal Name
4
4
4
4
4
2.
3.
4.
5.
6.
N. Kaur, G. Kaur, A. Bhalla, J. S. Dhau and G. R. Chaudhary,
Green Chem., 2018, 20, 1506-1514.
C. Li, S. Liu, C. Shi, G. Liang, Z. Lu, R. Fu and D. Wu, Nat.
Commun., 2019, 10, 1363.
W. Xu, Z. Fu, G. Chen, Z. Wang, Y. Jian, Y. Zhang, G. Jiang,
D. Lu, J. Wu and Z. Liu, Nat. Commun., 2019, 10, 2684.
X. Jiao, Q. Hao, X. Xia, Z. Wu and W. Lei, Chem. Commun.,
View Article Online
DOI: 10.1039/D0GC00833H
2
019, 55, 2692-2695.
A. I. Ayad, C. B. Marin, E. Colaco, C. Lefevre, C. Methivier,
A. O. Driss, J. Landoulsi and E. Guenin, Green Chem., 2019,
2
1, 6646-6657.
4
4
4
5
5
5
5
5
5
5
5
7.
8.
9.
0.
1.
2.
3.
4.
5.
6.
7.
R. Nie, M. Miao, W. Du, J. Shi, Y. Liu and Z. Hou, Appl.
Catal. B-Environ., 2016, 180, 607-613.
X. Xu, J. Luo, L. Li, D. Zhang, Y. Wang and G. Li, Green
Chem., 2018, 20, 2038-2046.
Adam F. Littke, Chaoyang Dai and G. C. Fu, J. Am. Chem.
Soc., 2000, 122, 4020-4028.
L. Botella and C. Najera, Angew. Chem. Int. Ed., 2002, 41,
1
79-181.
H. Nowothnick, J. Blum and R. Schomacker, Angew. Chem.
Int. Ed., 2011, 50, 1918-1921.
S. Doherty, C. H. Smyth, J. G. Knight and S. A. Hashmi, Nat.
Protoc., 2012, 7, 1870-1883.
A. Corma, H. García and A. Leyva, J. Catal., 2006, 240, 87-
9
9.
L. Geng, Y. Li, Z. Qi, H. Fan, Z. Zhou, R. Chen, Y. Wang and
J. Huang, Catal. Commun., 2016, 82, 24-28.
H. Fan, Z. Qi, D. Sui, F. Mao, R. Chen and J. Huang, Chin. J.
Catal., 2017, 38, 589-596.
M. Tanhaei, A. Mahjoub and R. Nejat, Catal. Lett., 2018,
1
48, 1549-1561.
H. A. Elazab, S. Moussa, A. R. Siamaki, B. F. Gupton and M.
S. El-Shall, Catal. Lett., 2017, 147, 1510-1522.
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 11 of 11
Green Chemistry
View Article Online
DOI: 10.1039/D0GC00833H
Graphic Abstract
Microwave-assisted reduced graphene oxide supported palladium nanoparticles can
efficiently promote aqueous Ullmann and Suzuki coupling reactions of aryl chlorides