Highly active heterogeneous palladium nanoparticle catalysts for homogeneous electrophilic reactions in solution and the utilization of a continuous flow reactor

Article abstract of DOI:10.1021/ja108898t

A highly active heterogeneous Pd-nanoparticle catalyst for the intramolecular addition of phenols to alkynes was developed and employed in a continuous flow reaction system. Running the reaction in flow mode revealed reaction kinetics, such as the activat

Full text of DOI:10.1021/ja108898t

Published on Web 11/09/2010
Highly Active Heterogeneous Palladium Nanoparticle Catalysts for
Homogeneous Electrophilic Reactions in Solution and the Utilization of a
Continuous Flow Reactor
Wenyu Huang, Jack Hung-Chang Liu, Pinar Alayoglu, Yimin Li, Cole A. Witham, Chia-Kuang Tsung,
F. Dean Toste,* and Gabor A. Somorjai*
Department of Chemistry, UniVersity of California, Berkeley, California 94720, United States, and Chemical and
Materials Sciences DiVisions, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley,
California 94720, United States
Received October 2, 2010; E-mail: fdtoste@berkeley.edu; somorjai@berkeley.edu
Table 1. Heterogeneous and Homogeneous Pd Catalysts for the
Abstract: A highly active heterogeneous Pd-nanoparticle catalyst
for the intramolecular addition of phenols to alkynes was devel-
oped and employed in a continuous flow reaction system.
Running the reaction in flow mode revealed reaction kinetics, such
as the activation energy and catalyst deactivation, and provides
many potential practical advantages.
Hydroalkoxylation of 2-Phenylethynylphenol
loading,
mol %
temp,
°C
reaction
time, h
NMR
yield, %a
entry
catalyst
1b
2
Pd40/SBA-15
PdBr2
PdBr2
PdCl2
PdCl2
Pd(NCMe)2Cl2
Pd(NCMe)2Cl2
[(allyl)PdCl]2
Pd(PPh3)4
4
4
4
4
4
4
4
2
4
20
20
20
15
15
15
15
15
15
15
15
15
95
6
9
3
25
7
8
0
0
3c
4
One of the major research directions in the pharmaceutical and
fine chemical industries is to convert homogeneous catalytic
reactions to heterogeneous versions through immobilization of
homogeneous catalysts on polymer or inorganic supports.1,2 The
heterogenized catalysts offer the opportunity of easy catalyst
recycling which is particularly important for precious metal
catalysts. Additionally, these catalysts may be employed in continu-
ous flow processes, which provides many additional potential
advantages, such as improved product quality and yields, facile
automation, easy scale-up without substantial further optimization,
and improved safety.3-5 However, in most cases, homogeneous
catalysts cannot be simply replaced by a heterogeneous counterpart,
due to the well-known problem of lower activity and selectivity.6
Thus, new catalysis concepts for developing heterogeneous variants
of homogeneous catalysts, which avoid these issues, are of
paramount importance. Herein, we report the development of a
heterogeneous Pd-nanoparticle based catalyst that exhibits superior
catalytic activity for π-bond reaction and its application in a
continuous flow reactor.7
The Pd nanoparticles were synthesized by using a fourth
generation PAMAM dendrimer as the capping agent. The ratio
between the palladium salt, K2PdCl4, and PAMAM dendrimer
was 40:1, which resulted in 1 nm diameter nanoparticles.8 After
purification by dialysis, the 40 atom Pd nanoparticles (Pd40) were
supported on high surface area mesoporous silica, SBA-15.9 In
a recent report, we documented that SBA-15-supported Pt
nanoparticles can catalyze a range of π-bond activation reactions.
Prior to this report, they were only known to be catalyzed through
homogeneous processes.10 The analogous Pd40 nanoparticles
were found to be excellent in catalyzing these reactions, at
significantly faster rates.11 Strikingly, the supported catalyst Pd40/
SBA-15, using toluene as the solvent and PhICl2 as the oxidizer,
showed a much higher activity than all of the homogeneous
catalysts surveyed. For example, the hydroalkoxylation of
2-phenylethynylphenol reached completion within 15 h at 20 °C
(Table 1, entry 1). Under otherwise identical conditions, PdBr2,
known in the literature to catalyze this reaction at room
temperature,11 only gave 6% yield of 2-phenylbenzofuran after
20
5
100
100
100
100
100
6
7b
8
9
a Determined by using mesitylene as an internal standard. b PhICl2
(12 mol %) was added. c Dichloromethane was used as solvent.
15 h (entry 2-3). A homogeneous catalyt potentially related to
the present Pd40/SBA-15/PhICl2 system, PdCl2, only resulted in
3% of the desired product (entry 4). The diminished yields
associated with PdBr2 and PdCl2 were most likely due to their
minute solubility in toluene at room temperature. However,
increasing the reaction temperature to 100 °C only caused
a moderate improvement of the yield (entry 5). A few oth-
er Pd complexes were surveyed, including Pd(NCMe)2Cl2,
[(allyl)PdCl]2, and Pd(PPh3)4, but the product was not formed
to any significant extent (entries 6-9). Notably, the combination
of Pd(NCMe)2Cl2 and PhICl2 did not prove beneficial (entry 7).
The low conversion observed at 100 °C using homogeneous
catalysts was presumably the consequence of rapid catalyst
decomposition.
PtCl2, Rh(CO)2(acac), and cationic Ir hydride complexes are also
known as competent catalysts for this transformation, but they
typically require elevated temperatures to be efficient.13-15 For
example, with 5 mol % loading of PtCl2, 97% yield was achieved
within 1.5 h at 80 °C.15 Moreover, Zhang et al. reported that, with
a homogeneous Au catalytic system, (Ph3P)AuCl/AgOTf, a 95%
yield of benzo[b]furan could be obtained at room temperature in
0.5 h;16 however, the heterogeneous Pd40/SBA-15 catalysts reported
herein can be easily separated, recycled, and applied in a continuous
flow reactor.
Catalyst leaching is one of the major obstacles in heterogenizing
homogeneous catalytic reactions, in which case the reaction is
actually catalyzed by the leached active species presented in
solution. Therefore, having demonstrated the superior activity of
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C O M M U N I C A T I O N S
Figure 1. Pd40 nanoparticles supported on silica mesoporous pellet were
used as the catalyst for the hydroalkoxylation of 2-phenylethynylphenol.
The reaction reached 75% yield after 24 h. Reaction solution was then
removed from the reaction vessel under anaerobic conditions. A new solution
with starting material was recharged (indicated by the green dashed line).
In the removed solution, the reaction ceased (blue dots after green dashed
line), which indicates that no active homogeneous catalysts leached into
the solution. In the recharged solution, the reaction progressed (red triangles)
at almost the same rate as the first run.
Figure 2. Time on stream of product yield of the hydroalkoxylation of
2-phenylethynylphenol catalyzed by Pd40/SBA-15. In the presence of 5
mM PhICl2 in the reaction stream (a 50 mM solution of 2-phenylethy-
nylphenol in toluene), the catalyst was more stable and was deactivated
relatively slowly (red diamonds), compared to the case when only
reactant was flowed through the reactor (blue dots). The flow rate was
0.6 mL/h.
the Pd40/SBA-15 catalytic system, it was necessary to exclude the
possibility that the supported Pd40/SBA-15 exhibits its catalytic
function homogeneously by leached active Pd species. Pd40 nano-
particles were supported on pelletized mesoporous silica.10 The
pelletized catalyst does not form a fine suspension under the reaction
conditions; thus the solution phase of the reaction medium can be
easily and cleanly separated from the solid component without any
filtration, which involves exposure to air and may cause the
deactivation of the active catalyst.6 As shown in Figure 1, the
conversion stopped after the solution was removed from the reaction
vessel (blue dots after the green dashed line), indicating that Pd40/
SBA-15 did not leach out any homogeneous active species in
solution. Moreover, the reaction occurred at the same rate when
we added a fresh substrate solution to the reactor containing the
pellet catalyst (red triangles in Figure 1). Elemental analysis was
also conducted, which showed no evidence of Pd leaching (see
Supporting Information).
Since no leaching of catalytically active species was detected
from the Pd40/SBA-15 catalyst, this catalyst was applied in a
fixed bed plug flow reactor to catalyze the reaction in a
continuous flow mode (see Supporting Information), the purpose
of which being to avoid the necessity of separating the catalyst
from reaction medium. Furthermore, as long as a highly active
heterogeneous catalyst can achieve a full conversion of reactants
to products, any further purification of the product is obviated,
since the reaction stream coming out from the flow reactor will
only contain pure product. Since the heterogeneous Pd40/SBA-
15 catalyst is very active for the hydroalkoxylation reaction, it
would be possible to achieve 100% conversion of 2-phenyl-
ethynylphenol in a continuous flow reactor with reasonable
catalyst loading and acceptable reactant concentration and flow
rate. As shown by the blue dots in Figure 2, Pd40/SBA-15
pretreated with PhICl2 was initially able to convert 2-phenyl-
ethynylphenol to 2-phenylbenzofuran completely at room tem-
perature. However, the catalytic activity quickly deteriorated to
less than 5% conversion after 15 h. However, when the reaction
solution contained 5 mM of PhICl2, the activity was restored. A
complete conversion to 2-phenylbenzofuran was observed for
more than 10 h. Note that, in the latter case, the oxidation agent
constantly flowed through the catalyst bed.
Figure 3. Activation energy determination of hydroalkoxylation of
2-phenylethynylphenol catalyzed by Pd40/SBA-15 using a continuous flow
reactor.
agent is present in the reactant solution. If the oxidation agent is
introduced to the catalyst bed together with the reactant, the
deactivated catalysts can be reactivated in situ. However, after 10 h
of 100% conversion, the catalyst was eventually deactivated. The
deactivated catalysts can be nevertheless regenerated with H2
reduction at 100 °C followed by the PhICl2 oxidation at 20 °C,
which suggests that the oxidant alone is not sufficient to maintain
Pd40/SBA-15 in its active state at room temperature. Several factors,
such as the catalyst loading, concentration of the reactant and
oxidant, reaction temperature, flow rate, and catalyst support, are
considered to play major roles in the deactivation of the catalyst.
The mechanism of catalyst deactivation is currently under inves-
tigation. Nevertheless, the deactivation kinetics of catalyst under
steady reactant feeding conditions cannot be investigated in a batch
reactor because the concentrations of reactant and product keep
changing during a batch mode reaction. With the continuous supply
of the fresh reactant and removal of the product, catalyst deactiva-
tion induced by product poisoning could be diminished or elimi-
nated.17
Additionally, the continuous flow mode reaction can also be
a useful and convenient tool in probing other kinetic parameters
of a given reaction, such as the activation energy. Figure 3 shows
the activation energy of this reaction measured after the catalytic
turnover reached its steady state. In a flow reactor, the activity
of Pd40/SBA-15 at different reaction temperatures could be
conveniently measured, from which the apparent activation
The dependence of product yield on time shown by the flow
reactor indicates that the catalyst is deactivated faster if no oxidation
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C O M M U N I C A T I O N S
energy was determined to be 20.0 kcal/mol. Activation energy
is an important reaction parameter that can help to gain a deeper
understanding of reaction mechanisms. To measure the activation
energy in a batch mode, multiple reactions must be repeated at
different temperatures. As a result, any operational error in
these reactions will generate inaccuracy in the activation energy.
Using a flow reactor, all reaction parameters can be controlled
precisely and reproduced easily, while the only variable is
temperature.
Sciences and Engineering of the U.S. DOE under Contract No. DE-
AC02-05CH11231.
Supporting Information Available: Experimental procedures and
elemental analysis data. This material is available free of charge via
the Internet at http://pubs.acs.org.
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Catal. 2008, 350, 717–730.
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Acknowledgment. We acknowledge support from the Director,
Office of Science, Office of Basic Energy Sciences, Division of
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under Contract DE-AC03-76SF00098 and the Director, Office of
Science, Office of Basic Energy Sciences, Division of Materials
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