Immobilized Pd on magnetic nanoparticles bearing proline as a highly efficient and retrievable Suzuki-Miyaura catalyst in aqueous media

Article abstract of DOI:10.1039/c4dt02899f

A magnetically retrievable nanocatalyst was evaluated for a microwave assisted Suzuki-Miyaura reaction in aqueous media. Excellent yields and conversions were obtained with low Pd loadings (down to 0.01 mol% Pd). It was stable up to 6 months in water under aerobic conditions and efficiency remained unaltered even after 7 repeated cycles. This journal is

Full text of DOI:10.1039/c4dt02899f

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Immobilized Pd on magnetic nanoparticles bearing
proline as a highly efficient and retrievable
Suzuki–Miyaura catalyst in aqueous media†
Cite this: DOI: 10.1039/c4dt02899f
Received 21st September 2014,
Accepted 18th November 2014
E. Nehlig,a B. Waggeh,a N. Millot,b Y. Lalatonne,a L. Mottea and E. Guénin*a
DOI: 10.1039/c4dt02899f
www.rsc.org/dalton
A
magnetically retrievable nanocatalyst was evaluated for
a
their easy recovery.22–24 Hence, the simple use of an external
microwave assisted Suzuki–Miyaura reaction in aqueous media. magnet could afford the rapid recovery of the catalyst without
Excellent yields and conversions were obtained with low Pd load- the need of filtration or centrifugation.25 When preparing such
ings (down to 0.01 mol% Pd). It was stable up to 6 months in water a magnetically retrievable nanocatalyst for the Suzuki–Miyaura
under aerobic conditions and efficiency remained unaltered even reaction several strategies have been employed, one of which
after 7 repeated cycles.
consisted of binding Pd onto ligands attached to the surface of
the magnetic nanoparticles. Most of these ligands are phos-
phine derivatives26–30 or amine based complexes31–34 that are
mostly used as conventional ligands in homogeneous reac-
tions. More recently amino acids such as glycine35,36 or
proline37 were used as ligands in solution to catalyze C–C
coupling. This approach was also used to immobilize palla-
dium or copper on nanoparticle or solid silica surfaces and to
promote C–C coupling or oxidation reactions.38–40
Continuing our work on functionalising magnetic nanopar-
ticles with various derivatives for biomedical or catalysis
applications,41–43 we decided to study iron oxide nanoparticles
bearing a proline derivative at their surface to from Pd complex
and to evaluate this new nanocatalyst for the Suzuki–Miyaura
cross coupling in aqueous media under aerobic conditions.
Our nanocatalyst was obtained by a “grafting to” method-
ology. Several small molecules have been described to efficien-
tly coat and stabilize iron oxide nanoparticles. Among them
catechol functionalised molecules derived from mussel
adhesive proteins are highly popular coating agents.44–47 We,
therefore coupled proline to dopamine in a two-step protocol
to obtain a small bifunctional molecule bearing a catechol
ring (Cat-Pro). This molecule was then used to chelate the
surface of bare maghemite nanoparticles (Scheme 1).
Bare maghemite nanoparticles (γ-Fe2O3) of 10 nm mean
diameter were obtained using a previously described proto-
col.48,49 Coating was performed in water at basic pH by simply
mixing the Cat-Pro ligand and γ-Fe2O3 nanoparticles. The
excess of ligands was then removed by means of magnetic
separation. The presence of the Cat-Pro at the surface of the
nanoparticles was confirmed by the appearance of vibration
bands in Fourier transform infrared (FTIR) spectroscopy
characteristic of the catechol moiety (see ESI†). The number
of molecules bound to the surface was determined by two
Among the cross coupling reactions catalyzed by noble metals
and awarded by the 2010 Nobel prize, the Suzuki–Miyaura
reaction remains one of the most important reactions for
obtaining biaryl compounds owing to its high versatility.1 This
coupling of aryl halides (or tosylates and triflates) with stable
and readily available boronic acids has been used for the syn-
thesis of several pharmaceuticals, fungicides, light emitting
polymers or organic LED compounds.2–5 Most of these reac-
tions are performed in a homogeneous catalytic manner using
various Pd sources and ligands in organic solvents. Nowadays
one of the challenges is to be able to recover the catalyst due to
the Pd cost (mainly related to its low abundance) and environ-
mental toxicity. That is why an increasing effort was made to
develop heterogeneous Pd catalysts using a large variety of
solid supports (carbon, zeolites, clays, dendrimers, etc.).6–12
In addition the replacement of an environmentally harmful
organic solvent by an eco-friendly solvent2,13–17 such as
water or a mixture of water and alcohol is another area for
improvement.
In the last few decades more attention has been paid to the
use of nanomaterials as a support18–20 due to their high
surface/volume ratios putting them at the frontier between het-
erogeneous and homogeneous catalysis.21 In this field mag-
netic nanoparticles appear as an ultimate nano-support due to
aUniversité Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244),
UFR SMBH, 74 avenue M. Cachin, 93017 Bobigny Cedex, France.
E-mail: guenin@univ-paris13.fr
bLaboratoire Interdisciplinaire Carnot de Bourgogne (ICB),
UMR 6303 CNRS-Université de Bourgogne, BP 47870, F-21078 Dijon Cedex, France
†Electronic supplementary information (ESI) available: Experimental details,
literature examples of TOF values for similar “nanocatalyst” and spectra for
nanoparticle and chemicals characterization. See DOI: 10.1039/c4dt02899f
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γ-Fe2O3@Cat-Pro(Pd) nanoparticles are well dispersed and
have an unchanged diameter size of 10.5 0.2 nm. The mag-
netization curve at 300 K confirmed the superparamagnetic be-
havior of the iron oxide nanoparticle catalyst with a saturated
magnetization of 57 3 emu g−1 (Fig. 1) and the same mag-
netic behavior for the γ-Fe2O3@Cat-Pro with or without palla-
dium. The surface composition of the metal-supported
nanoparticles has been analyzed by X-ray photoelectron spec-
troscopy (XPS). Peaks corresponding to carbon, nitrogen, iron,
and palladium are clearly observed (see ESI†). The Pd 3d spec-
trum of the nanoparticles presented in Fig. 1 shows the peak
binding energies of 335.4 eV (Pd 3d5/2) and 340.2 eV (Pd 3d3/2),
which confirmed the presence of Pd(0). The most intensive
peaks were the Pd 3d5/2 and 3d3/2 peaks corresponding to the
PdN (or to Pd2+) in a complex with photoelectron energies of
337.4 and 342.6 eV.10,50,51 The average number of Pd per nano-
particle was deduced by electron dispersive X-ray (EDX) analy-
sis. 490 Pd atoms were found per nanoparticle indicating that
approximately one Pd is complexed by one ligand at the
surface.
To first evaluate our nanocatalyst a typical Suzuki–Miyaura
reaction was performed by coupling 4-tolylboronic acid
(0.22 mM) to 4-iodonitrobenzene (0.20 mM). Reactions were
performed either in water–ethanol (1/1) or in pure water, under
aerobic conditions. Microwave irradiation was used for heating
the reaction mixture to follow a green chemistry approach and
to precisely control reaction conditions (temperature, stirring,
and cooling). Test reactions performed by thermal heating
gave exactly the same results (data not shown). Two bases were
evaluated for these reactions (triethylamine and sodium car-
bonate). Both gave very similar results (data not shown). Con-
versions of starting materials in the desired cross-coupled
product are listed in Table 1.
Scheme 1 Grafting to methodology for γ-Fe2O3@Cat-Pro(Pd)
synthesis.
methodologies: thermogravimetric analysis and amine titra-
tion by the OPA (o-phthalaldehyde) method. Using both metho-
dologies 450 50 Cat-Pro were found at the γ-Fe2O3 surface
(corresponding to a 0.69 nm2 occupied surface per Cat-Pro
molecule). The immobilization of Pd onto the surface was
done by applying the conditions described by Allam et al.37 for
obtaining the palladium–proline complex. After Pd complexa-
tion, the as-obtained nanocatalysts are dispersed in water
(see ESI†). FTIR spectra show no major changes in the
γ-Fe2O3@Cat-Pro vibration bands, only a slight difference
in intensity of vibrations in the 1600–1400 cm−1 range could
be noticed (see ESI†). The transmission electron micro-
scopy (TEM) micrograph presented in Fig. 1 shows that
Two blank experiments (entries 1 and 2) were performed to
check that no traces of palladium were present on the glass-
ware or in the reactants to promote the reaction.52 Running
Table 1 Evaluation of Suzuki–Miyaura test reaction conditions
Conversiona
(isolated yield)
(%)
Pd quantity
(mol%)
Time
(min)
Temp
(°C)
Entry
Solvent
1
2
3
4
5
6
7
8
9
0
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O
H2O
H2O–EtOH
H2O–EtOH
30
30
30
30
30
30
30
30
15
30
80
80
80
80
80
80
80
100
80
80
Traces
Traces
100 (98)
100 (97)
100 (96)
95 (90)
80 (83)
100 (97)
96
0b
1
0.1
0.05
0.01
0.1
0.1
0.1
0.1c
10
100 (95)
a From 1H NMR. b Use of γ-Fe2O3@Pro-Cat without Pd. c After 7
consecutive runs.
Fig. 1 TEM image (A), size distribution (B), magnetization curve (C) and
XPS for γ-Fe2O3@Cat-Pro(Pd) (D).
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(Fig. 3). The EDX analysis showed that the Pd leaching was
relatively low as approximately 400 Pd were found per particle
indicating a Pd loss of less than 2.5% in each run. The slight
decrease in conversion observed could be explained by gradual
loss of the catalyst during washings between each run as a very
low amount of the catalyst was used (0.5 mg of the nanocata-
lyst for 0.1 mol% palladium).
One must note that our nanocatalyst is also extremely
stable. It was stored in aqueous solution, under aerobic con-
ditions at room temperature for more than 6 months after its
synthesis and was still active with the same efficiency in our
test reactions.
Fig. 2 Magnetic recovery of the γ-Fe2O3@Cat-Pro(Pd) nanocatalyst.
the reaction without the nanocatalyst (entry 1) or with a nano-
catalyst without Pd (entry 2) only traces of the product could
be found indicating that the catalysis is performed only in the
presence of the active nanocatalyst. Overall the catalyst system
is very efficient in a water–ethanol mixture for 30 min at 80 °C;
the loading of Pd can be decreased from 1 mol% down to
0.01 mol% with still high conversion of starting materials in
the desired cross-coupled products (entries 3–6). The solvent
can be substituted for pure water but with an increase in reac-
tion temperature to 100 °C (entries 7 and 8). Decrease of the
reaction time resulted in a decrease in conversion (entry 9).
The decrease of the temperature also impaired the conversion
(data not shown). In all the cases reactions were very clean and
no secondary products (dehalogenation or homocoupling)
were detectable. In fact only the cross coupling product was
The catalytic efficiency can be quantified for reaction con-
ditions using 0.1 mol% Pd and 0.01 mol% Pd. The turnover
frequency (TOF) values, determined on the basis of the yield of
formation of final product per hour, were 1940 and 18 000 mol
p-I-C6H4NO2 (mol Pd)−1 h−1. These results showed very high
efficiency of this nanocatalyst compared to that in the litera-
ture (see Table in ESI†). To the best of our knowledge, similar
approaches (where Pd is immobilized onto magnetic nanopar-
ticles) presented a TOF ranging from 5 to 500. The best TOF
value of 20 000 obtained so far was by using a resin encapsu-
lated Pd nanoparticle catalyst.53 Another data which are also
highly important in terms of environmental consideration are
that relatively small quantities of the nanocatalyst were used.
When catalysis was performed on 40 mg of 4-iodonitrobenzene
with 0.1 mol% Pd the total amount of nanoparticles was
0.5 mg (only 50 µg with 0.01 mol% Pd). In comparison most of
the nanocatalysts described in the literature were used in
ranges varying from 2 to 200 mg under comparable conditions.
Thus, the total amount of catalyst was drastically decreased in
our case.
1
found on H RMN spectra with a slight excess of boronic acid
remaining (see ESI† for spectra of the crude reaction mixture
after only extraction). The product was extracted by simply
adding diethyl ether to the reaction medium and when the
conversion was complete it was only purified by simple fil-
tration over silica to remove boronic acid. The nanocatalyst
was recovered by magnetic separation and washed several
times with water and ethanol, and could be reused straight-
away (Fig. 2).
The catalyst was subjected to successive reactions (up to 8
times). After 7 repeated cycles the catalyst’s efficiency was not
impaired (entry 10), only in the 8th cycle incomplete conver-
sion was observed (Fig. 3). Nanoparticles were collected after
the 8th run and were analyzed by TEM and EDX. The TEM
images showed that nanoparticles were unaltered by the treat-
ment and conserved their spherical shape with low aggregation
Finally, to probe the scope of our reaction, using our stan-
dard conditions (0.1 mol% catalyst, 80 °C, 30 min in water–
ethanol) we tried to evaluate several reactants (results are
listed in Table 2).
When studying the influence of the nature of the halide
(entries 1–3) as expected a drastic decrease in conversion was
observed when going from iodide and bromide to chloride. In
this latter case, an increase of the reaction time did not
improve the conversion and the homocoupling byproduct was
even detected when the reaction time was increased to two
hours. Using 4-iodonitrobenzene as a substrate we evaluated
several carbonyl functionalized phenylboronic acids (entries
4–8). These derivatives, possessing an electron withdrawing
group, were used as they represented less reactive boronic
acids with some presenting fragile functionalities. Conversions
were always complete for para substituted derivatives (entries
4, 7, and 8), it stayed complete for 3-acetylphenyl boronic acid
(entry 5) but no product formation was observed for 2-acetyl-
phenyl boronic acid probably due to steric hindrance (entry 6).
Finally two examples of heteroaromatic boronic acids and the
4-vinylphenylboronic acid were evaluated as reactants. For het-
eroaromatic boronic acids results were contrasted: good con-
version was obtained with the furan derivative (entry 9) but a
low conversion was obtained for thiofuran one (entry 10). In
Fig. 3 Recycling efficiency and the TEM image after the 8th run.
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and J. Perard (Université Paris 5) for specific optical rotation
measurements.
Table 2 Cross-coupling evaluation with various reactants
Notes and references
Conversion
Temp (isolated yield)
Time
(min) (°C)
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