Ligand-free Mizoroki–heck reaction using reusable modified graphene oxide-supported Pd(0) nanoparticles

Article abstract of DOI:10.1002/aoc.4067

Palladium nanoparticles supported on graphene oxide surfaces modified with metformin was found to be an effective and recyclable nanocatalyst in Mizoroki–Heck coupling reactions under aerobic conditions without requiring any phosphine or ligand coordinati

Full text of DOI:10.1002/aoc.4067

Received: 28 June 2017
DOI: 10.1002/aoc.4067
Revised: 7 August 2017
Accepted: 8 August 2017
F U L L P A P E R
Ligand‐free Mizoroki–heck reaction using reusable
modified graphene oxide‐supported Pd(0) nanoparticles
Hojat Veisi1
| Najibeh Mirzaee2
1 Department of Chemistry, Payame Noor
University, Tehran, Iran
2 Department of Pharmaceutical
Chemistry, Pharmaceutical Sciences
Branch, Islamic Azad University, Tehran,
Iran
Palladium nanoparticles supported on graphene oxide surfaces modified with
metformin was found to be an effective and recyclable nanocatalyst in
Mizoroki–Heck coupling reactions under aerobic conditions without requiring
any phosphine or ligand coordination. Excellent product yields were achieved
with a wide variety of substrates and the catalyst could be recycled seven times
without any noticeable loss of its catalytic activity.
Correspondence
Hojat Veisi, Department of Chemistry,
Payame Noor University, Tehran, Iran.
Email: hojatveisi@yahoo.com
KEYWORDS
graphene oxide, heck, metformin, nanocatalyst, palladium
1 | INTRODUCTION
active and stable catalytic systems for the Heck reaction.
In this respect, carbon nanomaterials,[13] silica,[14]
One of the important cross‐coupling reactions is the
Mizoroki–Heck reaction. In general, cross‐coupling
reactions are known as powerful synthesis approaches
that enable formation of carbon–carbon bonds. This
means that they can provide arylation, alkylation or
vinylation of various alkenes through reaction with aryl,
vinyl, benzyl or allyl halides in the presence of an
appropriate base. Catalysis of these reactions is usually
undertaken using homogeneous palladium complexes,
in which Pd is coordinated to phosphine ligands to make
the complexes water soluble. However, such homoge-
neous catalytic systems are not recoverable and need
coordinated unstable and toxic ligands.[1–10] The ligands
aim to activate and stabilize Pd against agglomeration
and Pd black formation, in many homogeneous catalysts.
Alternatively, heterogeneous Pd nanocatalysts should be
developed, which can exhibit high activity, stability and
recyclability, simultaneously. Recyclability is a consider-
able objective of nanomaterial research that would
significantly impact chemical and pharmaceutical
industries in the future.
hydroxyapatite,[15] magnetic NPs,[16] molecular sieves,[17]
metal–organic frameworks[18] and polymers[19,20] have
been used to stabilize NPs.
One of the catalyst supports that should be evaluated
for Pd stabilization and immobilization is graphene oxide
(GO), which can be produced by oxidation of graphene.
GO is one of the most large‐scale cost‐effective products
of chemically modified graphene.[21,22] Moreover, it is
superior to other carbon‐based supports, e.g. carbon
nanotubes and porous carbon, due to its higher surface‐
to‐weight ratio, accessible surface area and controllability
of its chemical composition.[23,24] These advantageous GO
characteristics make it a more convenient catalyst support
since surface chemistry of catalyst supports can play an
important role in tuning catalytic activity and preventing
leaching of supported metallic NPs. Furthermore,
application of GO‐supported Pd catalysts for the Heck
reaction is motivated by their improved catalytic activities
in oxygen reduction and Suzuki–Miyaura cross‐coupling
reactions.[25,26] Recently, we reported the preparation of
Pd NPs that were incorporated into a metformin/GO
nanocomposite (Pd/Met/GO) and Pd/Met/GO was found
to be a novel recoverable heterogeneous catalyst in
Suzuki–Miyaura reactions.[27] In the work reported
herein, the catalytic activity of Pd/Met/GO was
investigated in Mizoroki–Heck reactions.
The reason that this study has applied Pd to the Heck
reaction is that Pd nanoparticles (NPs) have demonstrated
high catalytic activity for this reaction.[11,12] Also,
immobilization of Pd NPs on various solid supports has
been studied by several researches for the preparation of
Appl Organometal Chem. 2017;e4067.
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https://doi.org/10.1002/aoc.4067

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VEISI AND MIRZAEE
and stirred at 100 °C for 24 h. The obtained Met/GO
was separated by filtration and washed successively with
acetone and water. Met/GO was dried in vacuum at 40 °C.
For the preparation of Pd(II)/Met/GO and Pd(0)/Met/
GO,[27] 50 mg of Met/GO was dispersed in 100 ml water.
After the solution was sonicated for 15 min, 5 mg of PdCl2
was added and the mixture was sonicated for 10 min.
Then the solution was stirred overnight. After filtration,
the solid was washed successively with water and acetone.
The obtained Pd(II)/Met/GO was dried in vacuum at
40 °C. The reduction of Pd(II)/Met/GO using hydrazine
hydrate was performed as follows: 30 mg of Pd(II)/Met/
GO was dispersed in 50 ml of water, and then 90 μl of
hydrazine hydrate (80%) was added. The pH of the
mixture was adjusted to 10 with 25% ammonium
hydroxide and the reaction was carried out at 95 °C for
2 h. The final product, Pd(0)/Met/GO, was washed with
water and dried in vacuum at 50 °C. The concentration
of Pd in Pd/Met/GO was 4.2 wt% (0.39 mmol g−1), which
was determined using inductively coupled plasma atomic
emission spectrometry (ICP‐AES).
2 | EXPERIMENTAL
2.1 | Preparation of GO
GO nanosheets were prepared from natural graphite
powder using a modified Hummers method.[28]
2.2 | Synthesis of Pd(II)/met/GO and
Pd(0)/met/GO
Met/GO was synthesized by the condensation reaction of
GO and Met. Briefly, 50 mg of GO was dispersed in 50 ml
of dimethylformamide (DMF). After ultrasonication for
1 h, the GO solution was cooled to 0 °C and then 6 mmol
of EDC and 6 mmol of NHS were added. The mixture was
stirred for 2 h at 0 °C. Then 10 mmol od Met was added
2.3 | General procedure for Mizoroki–
heck reactions
A mixture of aryl halide (1 mmol), olefin (1.2 mmol),
triethylamine (2 mmol), DMF (3 ml) and Pd/Met/GO
(10 mg, 0.1 mol%) was added into a round‐bottomed flask
and stirred at 110 °C in atmosphere for 1–12 h. After
completion of the reaction, the reaction mixture was
cooled to room temperature and the catalyst was recov-
ered by centrifugation and washed with ethanol, and then
dried under vacuum for reuse. The residual mixture was
extracted with EtOAc (3 × 20 ml), and the combined
organic layer was dried over MgSO4. The solvent was
FIGURE 2 Size distribution of Pd NPs from TEM imaging of Pd/
FIGURE 1 (a) FESEM and (b) TEM images of Pd/met/GO
met/GO

VEISI AND MIRZAEE
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FESEM image of Pd/Met/GO with large quantities of Pd
NPs distributed on Met/GO surfaces. According to TEM
analysis (Figure 1b), Pd is dispersed well on the surface
of Met/GO. More importantly, the morphology results
indicate that Met has a significant role in promoting the
dispersibility of Pd/Met/GO and preventing aggregation
of Pd NPs. Figure 2 shows the size distribution of the Pd
NPs and reveals that their average size is about 14.23 nm.
To evaluate the catalytic activity of the synthesized
Pd/Met/GO nanocomposite in heterogeneous catalysis,
the Heck coupling reaction was considered (Scheme 1).
As the first step of exploring the performance of the cata-
lyst in Heck reactions, the conditions of coupling reaction
between bromobenzene and styrene were optimized as a
model reaction through choosing various amounts of cat-
alyst and applying various solvents and bases (Table 1).
Among the examined bases, Et3N displayed the
highest level of effectiveness and the other bases were
substantially less effective. In addition, evaluation of the
effect of solvent on the Heck coupling reaction indicated
that DMF is the best solvent choice (Table 1, entry 9).
After optimizing and identifying the most reliable set
of conditions (Table 1, entry 9), the scope and generality
of the developed protocol were investigated with respect
to aryl halide structures and olefins using 0.1 mol% Pd/
Met/GO, in the presence of 2 eq. of Et3N in DMF at
110 °C. The obtained results are summarized in Table 2.
SCHEME 1 Pd/met/GO as heterogeneous catalyst in heck
coupling reactions
evaporated and the crude products were purified by
column chromatography (hexane–acetone, 6:1).
3 | RESULTS AND DISCUSSION
The main objective of our ongoing research programme is
the development of new synthetic methodologies.[29]
Therefore, the title catalyst was fabricated,[27] and its
surface morphology was investigated using field‐emission
scanning electron microscopy (FESEM) and transmission
electron microscopy (TEM). Figure 1(a) presents a
TABLE 1 Optimization of conditions for heck reaction of bromobenzene with styrenea
Entry
Solvent
Pd (mol%)
Base
Time (h)
Yield (%)b
1
EtOH–H2O
0.1
K2CO3
6
50
2
Toluene
EtOH
MeOH
CH2Cl2
H2O
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.05
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
6
8
8
8
12
6
3
3
3
3
3
3
6
70
3
35
4
35
5
Trace
45
6
7
CH3CN
DMF
60
8
80
9
DMF
96
10
11
12
13
14
DMF
NaOAc
KOH
72
DMF
65
DMF
NaOH
Et3N
60
DMF
96
DMF
Et3N
75
aReaction conditions: bromobenzene (1 mmol), styrene (1.2 mmol), Pd/Met/GO, solvent (3 ml), reflux.
bIsolated yield.

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VEISI AND MIRZAEE
TABLE 2 Scope of heck–Mizoroki reaction
M.p. (°C)
Time
(h)
Yield
(%)b
Entry
R1
R2
X
Found
Reported
1
Ph
H
I
1
96
96
75
96
96
96
85
96
95
75
96
90
90
85
122–124
121–123[30]
2
Ph
H
Br
Cl
I
3
122–124
122–124
134–136
134–136
37–39
142–145
118–120
118–120
118–120
—
121–123[30]
121–123[30]
135–137[30]
135–137[30]
38–40[31]
142–145[32]
117–119[32]
117–119[32]
117–119[32]
3
Ph
H
24
1
4
Ph
4‐OMe
4‐OMe
4‐Cl
4‐COCH3
4‐CH3
4‐CH3
4‐CH3
H
5
Ph
Br
I
5
6
Ph
2
7
Ph
Br
I
8
8
Ph
1
9
Ph
Br
Cl
I
3
10
11
12
13
14
Ph
24
1
CO2Bu
CO2Bu
CO2Me
CO2Me
H
Br
I
2
—
H
1
—
H
Br
2
—
aReaction conditions: bromobenzene (1 mmol), olefin (1.2 mmol), Pd/Met/GO (10 mg, 0.1 mol%), Et3N (2 mmol), DMF (3 ml).
bIsolated yield.
Phenyl iodide, phenyl bromide and phenyl chloride can
react efficiently with styrene, under optimized conditions
(Table 2, entries 1–3). Both electron‐withdrawing and
electron‐releasing functional groups on styrene can give
the corresponding trans‐stilbene products in good yields
(Table 2, entries 4–10). Olefins, such as methyl acrylate
and or butyl acrylate, were very well tolerated under
the optimum conditions (Table 2, entries 10–14).
Recyclability of a heterogeneous catalyst is essential
for its large‐scale application. Therefore, it was
imperative to recycle and reuse Pd/Met/GO, in the
reaction between bromobenzene and styrene under
optimal conditions. With this purpose, when the reaction
was completed, the reaction mixture was cooled to room
temperature. Then, EtOAc was added to the reaction
mixture and the catalyst was separated through centrifu-
gation. The separated catalyst particles were then rinsed
with water and ethanol and reused in further catalytic
runs. The data for catalytic activity of the reused catalyst
(Figure 3) indicate that the catalyst can be recycled seven
times without any significant loss of its activity. The
observed high level of catalytic activity can be attributed
to the strong interaction between Pd NPs and the active
sites of Met.
between bromobenzene and styrene under the optimum
conditions. After 60 min of reaction progress, 54% product
yield was achieved, and then Pd/Met/GO was separated
by centrifuging the reaction mixture. After separating
the catalyst, the reaction was continued for another hour.
However, no increase in yield of the target product was
observed. This observation verified the heterogeneity of
the catalyst. The amount of Pd leached into the reaction
solution was determined using ICP‐AES. The Pd content
of Pd/Met/GO (after seven cycles) was determined to be
0.38 mmol g−1, which means the Pd content had
To determine heterogeneity of Pd/Met/GO, the hot
filtration test was carried out with the Heck reaction
FIGURE 3 Recycling of Pd/met/GO for heck coupling reaction

VEISI AND MIRZAEE
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convenient separation from a reaction mixture by
centrifugation; and (c) reusability for several reaction
cycles with no significant loss of activity. The presence
of Met stabilizes of the catalyst particles. The favourable
results presented suggest new perspectives for
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141.
We are grateful to Payame Noor University and
Pharmaceutical Sciences Branch (IAUPS), Tehran, for
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How to cite this article: Veisi H, Mirzaee N.
Ligand‐free Mizoroki–heck reaction using reusable
modified graphene oxide‐supported Pd(0)
nanoparticles. Appl Organometal Chem. 2017;
e4067. https://doi.org/10.1002/aoc.4067
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