Magnetically induced Suzuki and Sonogashira reaction performed using recyclable, palladium-functionalized magnetite nanoparticles

Article abstract of DOI:10.1016/j.jorganchem.2019.120905

A magnetically reusable, ligand-free palladium functionalized Fe₃O₄ catalyst system was successfully prepared. To overcome current problems such as the recyclability of the nanoparticle and the control and safety of the reaction, full advantage of the magnetite support was used. The palladium functionalized magnetite nanoparticle was removed by precipitation using a permanent magnet, while local heating, around the catalytic site, was induced using an external magnetic field. It was found that it was possible to perform the Suzuki reaction resulting in good to excellent conversions under air, with a magnetic field strength of 210 G and a frequency of 160 kHz. Despite the good results for the Suzuki reaction, it was not possible to perform the Sonogashira reaction magnetically due to an insufficient heat generation around the catalytic site. Further, the reusable catalyst system was recycled and reused for five times, resulting in a separable and straightforward catalyst system with the advantage of having full control of the reaction.

Full text of DOI:10.1016/j.jorganchem.2019.120905

Journal of Organometallic Chemistry 899 (2019) 120905
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Magnetically induced Suzuki and Sonogashira reaction performed
using recyclable, palladium-functionalized magnetite nanoparticles
Amaury De Cattelle a, Arne Billen b, Ward Brullot b, Thierry Verbiest b,
,
*
Guy Koeckelberghs a
a Laboratory for Polymer Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Heverlee, Belgium
b Laboratory for Molecular Electronics and Photonics, Department of Chemistry, KU Leuven, Celestijnenlaan 200D, B-3001, Heverlee, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
A magnetically reusable, ligand-free palladium functionalized Fe3O4 catalyst system was successfully
prepared. To overcome current problems such as the recyclability of the nanoparticle and the control and
safety of the reaction, full advantage of the magnetite support was used. The palladium functionalized
magnetite nanoparticle was removed by precipitation using a permanent magnet, while local heating,
around the catalytic site, was induced using an external magnetic field. It was found that it was possible
to perform the Suzuki reaction resulting in good to excellent conversions under air, with a magnetic field
strength of 210 G and a frequency of 160 kHz. Despite the good results for the Suzuki reaction, it was not
possible to perform the Sonogashira reaction magnetically due to an insufficient heat generation around
the catalytic site. Further, the reusable catalyst system was recycled and reused for five times, resulting in
a separable and straightforward catalyst system with the advantage of having full control of the reaction.
© 2019 Elsevier B.V. All rights reserved.
Received 1 August 2019
Received in revised form
14 August 2019
Accepted 17 August 2019
Available online 19 August 2019
Keywords:
Magnetic heating
Immobilized catalyst
Magnetically separable
Suzuki reaction
Sonogashira reaction
1. Introduction
recoverable catalysts, but despite the many applications and
various examples of such catalysts, a lot of improvement is still
Cross-coupling reactions are powerful and versatile tools in
modern organic synthesis for the formation of mainly carbon-
carbon bonds. More specifically, palladium-catalyzed cross-
coupling reactions have become of great importance over the last
decades [1e3]. The importance was recognized by awarding the
2010 Chemistry Nobel Prize for “palladium-catalyzed cross cou-
plings in organic synthesis” [4,5]. Over the past decades, significant
progress has been achieved using a variety of homogeneous cata-
lysts. Generally, homogeneous palladium catalysts are popular for
their high selectivity, activity, and resistance towards poisons, but
are difficult to recover and reuse. To overcome the fact that such
catalysts cannot be used in large-scale synthesis for environmental
and economic concerns, the application of reusable heterogeneous
catalysts has attracted much attention due to the increasing mo-
mentum for the development of environmental friendly reactions.
In this context, a lot of efforts have been made to synthesize
possible. The most important examples are Pd nanoparticles [6e8]
and Pd immobilized on silica nanoparticles [9e12], carbon nano-
tubes [13,14], polymers [15e19], dendrimers [20e23] and graphene
[24,25]. Furthermore, Pd has also been immobilized on metal ox-
ides [26e28] and metal oxide nanoparticles [29e32]. Improvement
of such heterogeneous catalysts has also been performed using
halloysite nanotubes [33,34]. This system does not only show a high
catalytic activity, but also exhibited excellent recyclability and low
Pd leaching. One of the most used metal oxide nanoparticles are
magnetite nanoparticles. By performing reactions with Pd func-
tionalized magnetite nanoparticles and using its super-
paramagnetic property, it is easy to recover the catalyst by a
magnet. This is in contrast with other nanoparticles, like silica or
polymer nanoparticles, which can only be recovered by precipita-
tion. A lot of the Pd functionalized magnetite nanoparticles make
use of a difficult and time-consuming ligand synthesis [35e38]. To
obtain an as easy as possible catalyst preparation, no ligands will be
used. Palladium functionalized magnetite nanoparticles were used
in previous work for the performance of Suzuki- and Sonogashira-
reactions. From this study it was concluded that the Suzuki reaction
reached a conversion of 67% after 4 h at 60 ꢀC, while the Sonoga-
shira reaction was completed after 3 h at 100 ꢀC. Nonetheless, many
Abbreviations: PEG, Poly(Ethylene Glycol); ICP-AES, Inductively Coupled Plasma
Atomic Emission Spectroscopy.
* Corresponding author. Department of Chemistry, Celestijnenlaan 200f - box
2404, 3001, Heverlee, Belgium.
E-mail address: guy.koeckelberghs@kuleuven.be (G. Koeckelberghs).
https://doi.org/10.1016/j.jorganchem.2019.120905
0022-328X/© 2019 Elsevier B.V. All rights reserved.

2
A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
of these reported processes with heterogeneous catalysts require
relatively elevated reaction temperatures resulting in the disad-
vantage of having poor control of the reaction. This disadvantage
can be solved by making use of a local heating procedure, which can
be achieved using magnetic induced heating. Magnetic induced
heating can be achieved by applying an AC magnetic field onto a
reaction mixture containing a Pd functionalized magnetite catalyst
system. The local temperature at the catalytic site can be straight-
forwardly adjusted by changing the magnetic field. This allows full
control of the reaction rate, which is an asset for production
regulation, but also leads to a valuable safety feature as it prevents
runaway reactions. In the case of magnetic local heating, runaway
reactions can be stopped by simply switching off the magnetic field.
The local temperature at the catalytic site will then drop rapidly
below the required catalytic temperature aided by efficient cooling
by the much colder reaction medium. In this way, full advantage is
obtained using the superparamagnetic property of the Fe3O4
nanoparticles, at which the nanoparticle not only induce an easy
way to recover the catalyst but also implements a heating pro-
cedure which is not only efficient but also provides a higher control
and safety of the reaction. To study this effect, a ligand-free Pd
functionalized magnetite nanoparticle will be implemented in the
Suzuki- and the Sonogashira-reaction using magnetic induced
heating, performed at relative low temperatures. As a reference a
thermal reaction will be performed at the temperature obtained in
the magnetic reactor. This comparison leads to the proof of prin-
ciple of the magnetic induced reaction and by this result in a safe
and excellent controlled reaction together with the advantage to
recuperate the valuable Pd catalyst and make this protocol a valid
candidate towards the goal of green chemistry. It should be
mentioned that such study has never been performed using a low
cost reusable catalyst resulting in an alternative heating method
using an AC magnetic field. Not only will the reactions be per-
formed using an easily reusable catalyst combined with an alter-
native heating source, they will also be executed under air in order
to facilitate these reactions.
to a tarred vial. The nanoparticles are isolated by the influence of a
magnetic field and subsequently washed three times with 1,4-
dioxane. The nanoparticles are dried under reduced pressure and
the yield is determined gravimetrically. Thereafter dioxane is added
to obtain a stock dispersion of nanoparticles. For more detailed
information: see Supplementary Information.
2.3. General procedure for the Suzuki-Miyaura couplings
To a 8 mL glass vial, the aryl halide (0.180 mmol), the boronic
acid-compound (0.270 mmol), K2CO3 (0.360 mmol, 52.5 mg) and
1,3,5-trimethoxybenzene (0.180 mmol, 30.3 mg) are added.
A
dispersion of Fe3O4/PEG/Pd nanoparticles is made in EtOH
(0.500 mL, 0.200 mg/mL) and this is added to the glass vial. After
the addition of 0.500 mL H2O, the reaction mixture is stirred for
4 h at 210 G with a frequency of 160 kHz. After stirring, the nano-
particles are isolated from the mixture with a magnet and the
conversion, in respect to the desired end-product, is determined by
1H NMR of the crude reaction mixture. 1,3,5-trimethoxybenzene is
used as internal standard. For more detailed information: see
Supplementary Information.
3. Results and discussion
3.1. Catalyst preparation
To produce the catalyst system, two types of nanoparticles are
synthesized, one with a higher affinity for aprotic solvents, and one
with a higher affinity for protic solvents. The affinity of the nano-
particle for the solvent can easily be changed by the use of different
stabilizers. Nanoparticles stabilized with a poly(ethylene glycol)
(PEG) chain have a higher affinity for protic solvents compared to
the oleic acid stabilized nanoparticles. It is known that Suzuki
cross-coupling reactions perform better in the presence of water
and require protic conditions [39], while Sonogashira cross-
coupling reactions are performed in aprotic solvents. Therefore,
poly(ethylene glycol) (PEG) stabilized nanoparticles will be used in
the Suzuki reaction and oleic acid stabilized nanoparticles will be
used in the Sonogashira reaction. The magnetite nanoparticle sta-
bilized with oleic acid are synthesized using the method of Chen
et al. [40] The PEG-silane stabilized magnetite nanoparticles are
also synthesized using a procedure found in literature resulting in
monodisperse and water-soluble nanoparticles [41]. Both type of
nanoparticles are characterized using Transmission Electron Mi-
croscopy (TEM) (Fig. 1). As depicted in Fig. 1 the PEG stabilized
magnetite nanoparticles as well as the oleic acid stabilized have a
size of approximately 20 nm and show a relative low size distri-
bution. Statistical analysis of the oleic acid stabilized nanoparticles
are included in Fig. S1 and result in a mean size of 19.1 1.7 nm. In
addition, to prove the presence of the stabilizer on the nanoparticle,
FT-IR spectra were recorded of the oleic acid and PEG stabilized
2. Experimental
2.1. Experimental information
All reagents were purchased from TCI, Sigma-Aldrich, J&K Sci-
entific and Acros Organics and used without further purification. 1H
NMR spectra were recorded on a Bruker Avance 300 MHz spec-
trometer. Infrared spectra were recorded on a Bruker Alpha FT-IR-
spectrometer equipped with a Platinum ATR single reflection dia-
mond ATR module. The ultrasonication bath used for the func-
tionalization of the magnetite nanoparticle was a Bransonic Model
5510 sonicator with a capacity of 10 L. The UV chamber used in the
siloxane functionalization is equipped with 3 LEDs (365 nm) with
an output power of 200 mW. For the TEM images, an 80 kV Zeiss
EM-900 electron microscope was used in combination with 300
mesh Formvar coated copper grids from Ted Pella. For the induc-
tively coupled plasma - atomic emission spectroscopy (ICP-AES)
measurements, a Varian 720 ES was used with a A Varian patented
vistachip CCD detector. For the magnetically induced reaction, an
in-house built magnetic setup was used.
2.2. Pd functionalization of nanoparticles
Oleic acid stabilized Fe3O4 nanoparticles or poly(ethylene gly-
col) (PEG)-silane stabilized Fe3O4 nanoparticles in 1,4-dioxane are
brought into a 100 mL flask. Its weight in palladium acetate is
added accordingly, and the reaction mixture is brought under argon
atmosphere. After stirring for four days, the mixture is transferred
Fig. 1. TEM image of oleic acid (left) and PEG (right) functionalized iron oxide
nanoparticles.

A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
3
nanoparticles together with the corresponding stabilizer (Fig. 2 and
Fig. 3). From Figs. 2 and 3 there can be derived that the stabilizer,
which are respectively oleic acid and PEG, are attached onto the
magnetite nanoparticle. The functionalization of these nano-
particles with Pd is done using the same procedure for all types of
nanoparticles (Scheme 1). Therefore, Pd(OAc)2 is stirred together
with the nanoparticles in 1,4-dioxane for 4 days under argon at-
mosphere. Note that our approach does not use any reducing re-
agents or surface modification employing the reducing nature and
coordinating ability of the Fe3O4 support [39]. The amount of Pd
present on the different types of catalyst systems is determined
using inductively coupled plasma - atomic emission spectroscopy
(ICP-AES), (Table 1) resulting in 0.080 mg Pd/mg Fe3O4/PEG/Pd
nanoparticles and 0.014 mg Pd/mg Fe3O4/oleic acid/Pd nano-
particles. It should be mentioned that the amount of Pd varies with
the type of nanoparticle used. The fact that the amount of Pd on a
PEG stabilized nanoparticle is higher compared to the oleic acid
stabilized nanoparticle can be explained by the difference in the
stabilizer. The Pd, originating from Pd2þ, will be easier inserted
Scheme 1. Functionalization of the different types of nanoparticles with Pd.
Table 1
ICP-AES results of Pd functionalized nanoparticles.
Nanoparticles
Amount of Pd
(mg Pd/mg NPs)
Amount of Pd
(10ꢁ4 mmol Pd
/mg NPs)
Fe3O4/PEG/Pd
Fe3O4/oleic acid/Pd
0.080
0.014
7.5
1.3
inside the PEG stabilizer and by this making more direct contact
with the magnetite nanoparticle due to the higher polarity of the
PEG stabilizer. This in contrast with the oleic acid stabilizer which
explains the difference in Pd amount present on the nanoparticle.
3.2. Suzuki cross-coupling reactions
The reaction of 4-bromophenol with phenyl boronic acid is used
for initial studies as a model reaction and is carried out in the
presence of K2CO3, which is a base resulting in a high conversion
and is applied in many Suzuki reactions (Scheme 2) [42e46].
The reason for the choice of 4-bromophenol as substrate is
because in the previous study there has been concluded that, due to
the presence of K2CO3, 4-bromophenol is deprotonated resulting in
a phenolate. This phenolate has a high affinity for the magnetite
nanoparticle, resulting in a higher conversion compared to a similar
electron-donating group like methoxy (4-bromoanisole). Due to
this effect, it is possible that a large difference can be depicted
between the magnetically induced reaction and the corresponding
thermal reaction. Because, when the hypothesis is correct, the
substrate will not only be closer to the catalyst but also closer to the
heating source, resulting in an even higher conversion for the
magnetically induced reaction compared to the corresponding
thermal reaction, which is performed at the same temperature as
measured inside the reaction vial during the magnetic reaction. The
solvent chosen for this reaction was an EtOH/H2O (1:1) mixture,
which according to Vienot et al. result in optimal conditions [39].
The presence of water in the reaction mixture is the reason for the
use of PEG-stabilized Pd-functionalized magnetite nanoparticles
(Fe3O4/PEG/Pd).
Fig. 2. FT-IR spectrum of Fe3O4 nanoparticles functionalized with oleic acid (Fe3O4/
oleic acid NPs) (black) and oleic acid (red). (For interpretation of the references to
colour in this figure legend, the reader is referred to the Web version of this article.)
First, the proof of principle is given using the magnetically
induced model reaction together with the thermal reaction, per-
formed at the same temperature as that of the bulk during the
magnetically induced reaction in function of time (Fig. 4).
As is depicted in Fig. 4, the magnetically induced reaction tends
to stop after 4 h, and a difference of 44% of conversion is displayed
between the magnetic induced and the corresponding thermal
contribution. The thermal contribution is obtained performing a
reaction under the same conditions as the magnetic reaction, but
using the temperature measured inside the reaction vial of the
magnetically induced reaction, which was 32 ꢀC, but without the
Fig. 3. FT-IR spectrum of Fe3O4 nanoparticles functionalized with PEG-silane (Fe3O4/
PEG NPs) (black) and PEG-silane (red). (For interpretation of the references to colour in
this figure legend, the reader is referred to the Web version of this article.)
Scheme 2. Model reaction used for investigation of the magnetic induced Suzuki
reaction.

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A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
Fig. 6. Effect of the amount of Fe3O4/PEG/Pd on the magnetic induced Suzuki cross-
coupling. 4-Bromophenol (0.18 mmol), phenylboronic acid (0.27 mmol), K2CO3
(0.36 mmol), Fe3O4/PEG/Pd, EtOH/H2O (1:1) (1.0 mL), under air. Applied frequency:
160 kHz, applied magnetic field: 210 G. The reaction was monitored by 1H NMR. 1H
NMR conversions were determined using 1,3,5-trimethoxybenzene as an internal
standard.
Fig. 4. Conversion in function of time for the magnetic induced Suzuki reaction (black)
and the thermal contribution (red). 4-Bromophenol (0.18 mmol), phenylboronic acid
(0.27 mmol), K2CO3 (0.36 mmol), Fe3O4/PEG/Pd (0.2 mg), EtOH/H2O (1:1) (1.0 mL),
under air. Applied frequency: 160 kHz, applied magnetic field: 210 G (black). Reaction
temperature: 32 ꢀC (red). The reaction was monitored by 1H NMR. 1H NMR conversions
were determined using 1,3,5-trimethoxybenzene as an internal standard. (For inter-
pretation of the references to colour in this figure legend, the reader is referred to the
Web version of this article.)
presence of an external magnetic field. This means that the use of
an external magnetic field resulted in an increase of approximately
7 ꢀC inside the reaction vial. To obtain stronger evidence of this
principle, the magnetic induced and the corresponding thermal
reaction is performed in triple and error bars are added resulting in
an average difference of 49% of conversion (Fig. 5).
As the Suzuki reaction is largely affected by the amount of
catalyst, the reaction conditions are optimized using the model
reaction (Fig. 6). Since no conventional heat is used during the
magnetically induced reaction, not the influence of the tempera-
ture will be examined but the influence of the magnetic field and
the applied frequency (Fig. 7).
As evident from Fig. 6, a catalyst loading of 0.1 mg of Fe3O4/PEG/
Pd nanoparticles in 1 mL is optimal and will be used in future re-
actions. It is depicted that there is only a small influence of catalyst
loading using magnetically induced heating with a magnetic field
Fig. 7. Influence of the magnetic field strength and frequency on the magnetic Suzuki
reaction (black) and the thermal contribution (red). 4-Bromophenol (0.18 mmol),
phenylboronic acid (0.27 mmol), K2CO3 (0.36 mmol), Fe3O4/PEG/Pd (0.1 mg), EtOH/H2O
(1:1) (1.0 mL), under air. The reaction was monitored by 1H NMR. 1H NMR conversions
were determined using 1,3,5-trimethoxybenzene as an internal standard. (For inter-
pretation of the references to colour in this figure legend, the reader is referred to the
Web version of this article.)
of 210 G and a frequency of 160 kHz. Although a drop in conversion
is observed when a catalyst loading is applied lower than 0.05 mg
of nanoparticles in 1 mL and it should also be mentioned that a
catalyst loading of 0.05 mg of nanoparticles in 1 mL results in a
conversion decrease of 10% compared to 0.1 mg of nanoparticles.
Therefore, using an amount of 0.1 mg of Fe3O4/PEG/Pd nano-
particles, a Pd amount is present of only 0.42 10ꢁ3 mol% in the re-
action mixture.
In Fig. 7 the influence is given of the magnetic field strength and
the frequency of the magnetic field on the reaction yield. The
contribution of the thermal effect is also depicted. It can be
concluded that by increasing the strength and/or the frequency of
the magnetic field an increase in reaction yield is observed. Despite
Fig. 5. Proof-of-principle of the magnetic induced Suzuki reaction and the thermal
contribution.

A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
5
this increase, a higher contribution of the thermal effect is noticed
results are summarized in Table 2.
when either one or both parameters are increased. This can be due
to two factors. Firstly, by increasing the strength of the frequency or
the magnetic field, the coil will heat up by a few degrees, which has
a direct result in a higher temperature inside the reaction vial.
Secondly, it can also increase the temperature generated by the
nanoparticle, resulting in a higher temperature of the reaction
medium due to the thermal convection of the heat generated at the
nanoparticle to the reaction mixture. The optimal conditions
resulting in a high conversion with a low contribution of the
thermal effect are obtained using a magnetic field strength of 210 G
with a frequency of 160 kHz. To examine the magnetically induced
Suzuki reaction, these conditions are used, resulting in a high dif-
ference between the magnetically induced reaction and the ther-
mal contribution.
With the optimized conditions in hand, the magnetically
induced reaction performance of Fe3O4/PEG/Pd for various sub-
strates is investigated. All the reactions were carried out at 210G
and 160 kHz under air using K2CO3 as the base and EtOH/H2O (1:1)
as the reaction medium, with a catalyst loading of 0.1 mg of
nanoparticles, resulting in a Pd amount of 0.42 10ꢁ3 mol%. The
The cross-coupling reactions of aryl halides with phenyl boronic
acids afforded mostly the desired biaryls. The only exceptions are
the chlorinated substrates and the highly sterically hindered 2-
bromotoluene (Table 2; Entry 5, 6 and 8). It should be mentioned
that not all substrates result in an as efficient reaction as the re-
action using 4-bromophenol. By introducing more steric hindrance
on the aryl bromide the yield decreases (Table 2; Entry 3, 7 and 8).
This was also noticed for the use of an electron-donating methoxy-
or amine group (Table 2; Entry 9 and 11). Very interesting results
are shown when a comparison is made between entry 4 and 9
(Table 2). All two are strong electron donating groups but there is a
large difference in conversion between these groups. Actually, by
the presence of the base, the phenol is deprotonated to the phen-
oxide and is even more electron donating, which should result in an
even lower conversion. The reason for this opposite result is
twofold. Firstly, this phenoxide has a high affinity for magnetite
nanoparticles. Due to the interaction of the phenoxide with the
nanoparticle, the substituent becomes a less electron donating
group compared to a “pure” alkoxide-species. Second and most
importantly, due to the high affinity of the phenoxide for the
Table 2
The scope of Suzuki cross-coupling reactions with different substituents.
Entry
1
Reactant 1
Reactant 2
Magnetic conversionb
21%
Thermal conversionb
0%
2
72%
24%
3
4
5
6
7
15%
74%
0%
0%
24%
0%
0%
0%
0%
5%
8
0%
0%
9
1%
1%
10
11
12
13
14
87%
8%
8%
0%
42%
69%
5%
13%
24%
0%
aReaction conditions: reactant 1 (0.18 mmol), reactant 2 (0.27 mmol).
K2CO3 (0.36 mmol), Fe3O4/PEG/Pd (0.1 mg), EtOH/H2O (1:1).
(1.0 mL), magnetic field strength: 210 G, frequency: 160 kHz, 4 h, under air.
b1H NMR conversions were determined using 1,3,5-trimethoxybenzene as an internal standard.

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A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
nanoparticles, the binding brings the substrate in closer proximity
to the catalytic system and to the heating source resulting in a
higher yield compared to 4-bromoanisole for which no deproto-
nation can occur. Because the substrate is not only closer to the
catalyst system, but also closer to the heating source, an even
higher conversion is obtained for the magnetic heating compared
to the thermal contribution. The electronic nature of substituents of
aryl boronic acid was also investigated. The results show that aryl
boronic acids bearing either electron-donating groups or electron-
withdrawing groups can provide the corresponding product
(Table 2; Entry 13 and 14). The use of an electron-donating sub-
stituent results in a higher yield compared to an electron-
withdrawing group on the aryl boronic acid species. This results
in an opposite effect compared to the aryl halide.
magnetic induction and thermal heating (Fig. 9). Therefore, the
model reaction (Scheme 2) is used under the same optimized
conditions, but with a reaction time of 2 h. The reason for the use of
this reaction time is due to the fact that at this time the reaction still
tends to continue and does not reach its maximal reachable con-
version. For the thermal reactions the same conditions are used as
for the magnetic induced reaction, but with the presence of con-
ventional thermal heating and in absence of an external magnetic
field. From Fig. 9 there can be depicted that a temperature of
around 60 ꢀC is reached at the catalytic site.
3.3. Sonogashira cross-coupling reaction
A
second cross-coupling reaction investigated with the
Recycling of the heterogeneous catalyst system is important
from both the economic and environmental points of view. The
reusability of the Fe3O4/PEG/Pd nanoparticles is examined using
the optimized model reaction at 210 G and 160 kHz with a reaction
time of 4 h. The results are illustrated in Fig. 8. The catalyst was used
for five runs, in which each run the conditions are kept identical.
After each run, the catalyst was separated by an external magnet,
and the resulting supernatant can be decanted. This minimizes the
loss of catalyst during separation. The catalyst system is then sub-
sequently washed 3 times with 2 mL ethanol and 1 time with water.
After being dried, the catalyst system could be reused directly
without further purification. As shown in Fig. 8 the catalyst can be
reused at least 5 times, although with a linear loss in activity over
the various cycles. At the 5th reaction, a conversion of only 27% was
obtained. It should be mentioned that the amount of nanoparticles
after each recuperation was taken into account. This means that the
amount of starting reagents and solvents are adapted to the amount
of nanoparticles present after the recuperation step. Due to this
procedure, the loss in conversion cannot be the cause of the loss of
Fe3O4/PEG/Pd nanoparticles during the recuperation step, but can
only be due to a change in the composition of the Fe3O4/PEG/Pd
nanoparticles. This means that the loss in activity is the result of Pd
leaching of the catalyst system, which is confirmed using ICP-AES
measurements after each run (Supplementary Information
Table S1).
palladium-functionalized Fe3O4 catalyst is the Sonogashira reac-
tion. In previous work a method was developed using a Cu-free and
aerobic reaction, resulting in a reaction time of only 3 h possible for
a wide range of substrates (Scheme 3).
Therefore, the same conditions are used for the examination of
the Sonogashira reaction performed with a magnetic field as the
same Pd functionalized oleic acid stabilized Fe3O4 catalyst is used.
As already mentioned, the magnetic reactor has an adaptable fre-
quency of the magnetic field. Also, each frequency has a certain
magnetic field strength range. To determine whether the reaction
has a possibility to succeed, a maximum magnetic field was used at
different frequencies, thus generating maximum heat around the
nanoparticle. Accordingly, the same reaction, using 1-(tert-butyl)-
4-iodobenzene and phenylacetylene in air, with KOAc as a base and
DMSO‑d6 as solvent, is attempted for various frequencies, each time
at the maximal magnetic field strength obtainable with the mag-
netic reactor. These results are shown in Table 3.
The results of the reactions with altering the frequency and
magnetic field show that the catalysis by magnetic heating is not
accomplished. The reaction with a frequency of 107 kHz at the
highest magnetic field gives no conversion. A frequency of 160 kHz
with a magnetic field of 210 G are the optimal conditions for our
nanoparticles, as this gave the best results in the Suzuki reaction,
but the reaction at this frequency gives no adequate results. Also, no
conversion to the end-product is detected in the reactions con-
ducted at a frequency of 240 kHz and 350 kHz at maximum
To get a better insight of the temperature at the catalytic site, a
comparison is made between the conversion obtained using
Fig. 9. Comparison between the conversion using magnetic induction (black) and
thermal heating (red). 4-Bromophenol (0.18 mmol), phenylboronic acid (0.27 mmol),
K2CO3 (0.36 mmol), Fe3O4/PEG/Pd (0.1 mg), EtOH/H2O (1:1) (1.0 mL), under air. The
reaction was monitored by 1H NMR. 1H NMR conversions were determined using 1,3,5-
trimethoxybenzene as an internal standard. (For interpretation of the references to
colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 8. The reusability of the Fe3O4/PEG/Pd nanoparticles for the Suzuki reaction using
the model reaction with adapting the amount of substrates to the amount of nano-
particles recycled after each cycle.

A. De Cattelle et al. / Journal of Organometallic Chemistry 899 (2019) 120905
7
frequency of 160 kHz and that a temperature of around 60 ꢀC was
reached at the catalytic site. Although, it should be mentioned that
not all substrates give rise to high conversions. Only substrates
having an affinity for a magnetite nanoparticle result in high con-
version. Despite the results obtained for the Suzuki reaction, it can
be concluded that no magnetically induced reaction is possible for
the Sonogashira reaction, which can be explained by the fact that
Sonogashira reactions are only possible at high temperatures using
our catalyst system.
Scheme 3. Model reaction used for investigation of the magnetic induced Sonogashira
reaction.
Table 3
Magnetic induced Sonogashira reaction with different magnetic field strength and
frequency.
Frequency (kHz)
Magnetic field (G)
Conversionb
Acknowledgments
350
230
160
106
170
210
210
260
0%
0%
0%
0%
The authors are grateful to the Onderzoeksfonds KU Leuven/
Research Fund KU Leuven and the Special Research Fund (BOF) of
the Flemish community as a C3 project for financial support. AB
acknowledges financial support from the Agency for Innovation
and Technology in Flanders (IWT).
aKOAc (0.27 mmol), Fe3O4/oleic acid/Pd (2.0 mg), DMSO‑d6 (1.0 mL), 4 h, 1-(tert-
butyl)-4-iodobenzene (0.18 mmol), phenylacetylene (1.8 mmol).
b1H NMR conversions were determined using 1,3,5-trimethoxybenzene as an in-
ternal standard.
Appendix A. Supplementary data
magnetic field. Although all possible frequencies attainable with
the magnetic reactor are investigated, no reaction is achieved with
local heating by magnetic induction.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jorganchem.2019.120905.
Knowing that there is indeed an effect of the substrate in the
Suzuki cross-coupling reaction, 4-iodophenol is used as substrate
to examine the possibility for the magnetic induced Sonogashira
reaction (Scheme 4). Therefore, 4-iodophenol and phenylacetylene
are used, with KOAc as a base and DMSO‑d6 as reaction medium.
Although no positive results are obtained for the Sonogashira re-
action and resulted in a conversion of 0%.
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