Viral-templated palladium nanocatalysts for Suzuki coupling reaction

Article abstract of DOI:10.1039/c0jm03145c

We demonstrate and thoroughly examine tobacco mosaic virus (TMV)-templated palladium (Pd) nanocatalysts for the ligand-free Suzuki coupling reaction under mild conditions. The surface-assembled TMV templates allow for facile catalyst synthesis under mild aqueous conditions that leads to high Pd surface loading and stability. Further, the chip-based format enables simple catalyst separation and reuse as well as facile product recovery. Reaction condition studies demonstrated that the solvent ratio played an important role in the selectivity of the Suzuki reaction, and that a higher water/acetonitrile ratio significantly facilitated the cross-coupling pathway. We envision that our viral template-based bottom-up assembly approach can be readily extended to other biotemplates, metal catalysts and organic reaction systems. The Royal Society of Chemistry.

Full text of DOI:10.1039/c0jm03145c

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PAPER
Viral-templated palladium nanocatalysts for Suzuki coupling reaction†
a
a
b
Cuixian Yang, Amy K. Manocchi, Byeongdu Lee and Hyunmin Yi
a
*
Received 19th September 2010, Accepted 21st September 2010
DOI: 10.1039/c0jm03145c
We demonstrate and thoroughly examine tobacco mosaic virus (TMV)-templated palladium (Pd)
nanocatalysts for the ligand-free Suzuki coupling reaction under mild conditions. The surface-
assembled TMV templates allow for facile catalyst synthesis under mild aqueous conditions that leads
to high Pd surface loading and stability. Further, the chip-based format enables simple catalyst
separation and reuse as well as facile product recovery. Reaction condition studies demonstrated that
the solvent ratio played an important role in the selectivity of the Suzuki reaction, and that a higher
water/acetonitrile ratio significantly facilitated the cross-coupling pathway. We envision that our viral
template-based bottom-up assembly approach can be readily extended to other biotemplates, metal
catalysts and organic reaction systems.
Introduction
Palladium (Pd) is the most versatile and widely applied catalytic
metal for a variety of organic reactions including hydrogena-
tion,1 oxidation,2 and C–C coupling reactions.3 For industrial
applications, heterogeneous catalysts are the first option due to
their inherent advantages of simple separation, stability, and
better handling compared to homogeneous catalysts. However,
heterogeneous catalysts also face several hurdles, such as harsh
preparation conditions, difficulty in uniform metal particle
dispersion on supports, uncontrollable particle size distribution,
and the unclear influences from the supports on reactivity.
Biological supramolecules have recently gained significant
attention as alternative template materials for well-dispersed
metal nanoparticle formation, largely via electroless deposition.4–10
Particularly, tobacco mosaic virus (TMV) has been extensively
enlisted for a range of metals in various applications due to
the well-defined structure and dimension, along with high
stability (a wide range of pH, temperature, and resistance to
organic solvents).11 Importantly, the ability to confer precisely
spaced functionalities through genetic modification12–14 leads to
enhanced and readily controllable metal nanoparticle forma-
tion,7–9,15 increased stability,16 and tunable high density surface
assembly.17 Despite a few recent studies on the catalytic applica-
tions of viral-templated nanoparticles,5,6,18–20 there has been no
endeavor to harness catalytic activities of such attractive materials
aDepartment of Chemical and Biological Engineering, Tufts University,
Medford, MA, 02155, United States. E-mail: hyunmin.yi@tufts.edu
bX-ray Science Division, Argonne National Laboratory, Argonne, IL,
60439, United States
Fig. 1 Pd-TMV nanocatalyst catalyzed Suzuki reaction. (a) Scheme of
† Electronic supplementary information (ESI) available: Solvent ratio
effect for 4-methoxyphenylboronic acid; X-ray Photoelectron
Spectroscopy (XPS) results; Inductively Coupled Plasma Optical
Emission Spectrometry (ICP-OES) analysis; chip removal study results.
See DOI: 10.1039/c0jm03145c
Suzuki cross- and homo-coupling reactions catalyzed by nanostructure
Pd-TMV complex. (b) Diagram of TMV templated Pd catalyst and
simple reaction setup. (c) AFM images of TMV assembled gold chip
(i) and Pd formation on assembled TMV (ii).
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for organic synthesis reactions of value-added chemicals and
small molecule drugs in order to exploit the unique advantages
that these potent nanotubular templates offer.
biphenyl (4-MB) (98%), and sodium carbonate (Na2CO3) were
purchases from Alfa Aesar (Ward Hill, MA) and used without
further purification. Phenylboronic acid (PBA) (>95%), bromo-
benzene (99%), biphenyl (BP) (99.5%), Sodium tetra-
The Pd-catalyzed Suzuki-Miyaura reaction3 represents one of
the most important routes to synthesize biaryl compounds
through the cross-coupling of aryl halides with aryl boronic acids,
as shown in the general scheme of Fig. 1(a). These reactions are
typically carried out with phosphine-based or phosphine-free
homogeneous Pd catalysts21–23 in organic solvents. In the past few
years, a number of ligand-free heterogeneous Pd catalysts on
various supports have emerged.24–26 While offering simpler
catalyst recovery, these ligand-free heterogeneous systems face
a number of complications including the need to employ
surfactants in aqueous solution27,28 or microwave29 to assist phase
transfer. Despite the improved conversion and yield, such addi-
tives also present obstacles, such as product contamination, more
arduous downstream purification, and increased cost.
chloropalladate
(Na2PdCl4)
(99.998%)
and
sodium
hypophosphite (NaPH2O2) (>98%) were purchased from Sigma-
Aldrich (St. Louis, MO).
Synthesis of TMV-templated Pd catalysts
The Pd-TMV catalyst chips were prepared as previously
described19 with minor modifications. Briefly, clean gold chips
(0.7 cm ꢀ 2 cm) were immersed in TMV1cys solution (200 mg/ml)
for surface assembly that yielded highly dense and consistent
surface loading. These TMV-assembled chips were then exposed
to 5 mM Na2PdCl4 precursor solution containing 15 mM
NaPH2O2 reducer for 20 min, which provided reproducible
formation of about 13 nm Pd nanoparticles along the TMV
tubes.16 These Pd-TMV chips were then thoroughly rinsed with
deionized water, dried, and stored for the reaction studies.
In this paper, we demonstrate and thoroughly examine catal-
ysis of Suzuki coupling reactions by nanostructured Pd nano-
particles templated on TMV, as shown in Fig. 1(b). Specifically,
genetically modified TMV templates were assembled on clean
gold-coated chip surfaces as shown in the tapping mode atomic
force microscopy image of Fig. 1(c)-(i), resulting in dense
coverage of TMV that is stable under extensive rinsing processes.9
These TMV-assembled chips are then exposed to Pd precursor
solution to form nanoparticles via electroless deposition9,19 as
shown in Fig. 1(c)-(ii), resulting in highly dense coverage of Pd
nanoparticles formed on TMV templates (Pd-TMV) with well-
controlled particle size.9 These Pd-TMV complexes have shown
high chemical stability under acidic environment for catalytic
dichromate reduction19 as well as enhanced thermal stability than
Pd particles without TMV templates.16 These chips (i.e. Pd-TMV
chips) were then simply immersed in the reaction mixtures, con-
taining the reactants in various ratios of acetonitrile/water
mixtures, in well-sealed vials to carry out the Suzuki reactions,
and the catalytic reactivity was then analyzed by High-Perfor-
mance Liquid Chromatography (HPLC). The results show high
selectivity and facile product separation with high water content
and complete conversion under mild conditions. Additionally,
these catalysts exhibit consistent stability throughout reaction
and sample analysis using Atomic Force Microscopy (AFM) and
Grazing Incidence Small Angle X-ray Scattering (GISAXS), as
well as simple catalyst recovery and reusability rising from
surface-assembled chip format. Combined these results demon-
strate the facile fabrication of nanostructured viral-metal cata-
lytic systems for ligand-free Suzuki coupling reactions. We believe
that our viral-templated bottom-up assembly approach can be
readily applied to a wide range of organic synthesis reactions and
other noble metal or alloy catalysts where facile catalyst recovery,
product separation, and mild reaction conditions are desired.
Suzuki reaction studies
The Suzuki reactions between iodoanisole (IA) and phenyl-
boronic acid (PBA) were catalyzed by as-prepared Pd-TMV
chips. For this, various amounts of IA, PBA and Na2CO3 were
dissolved in 5 ml acetonitrile/water (CH3CN/H2O) solvent. After
the reaction mixture was heated to 50 ꢁC, one Pd-TMV chip was
added to start the reaction with stirring at 600 rpm for 24 h.
To study the solvent effect, 0.05 mmol IA (10 mM), 0.05 mmol
PBA (10 mM) and 0.15 mmol Na2CO3 (30 mM) were dissolved in
5 ml CH3CN/H2O mixture with different volume ratio of 3 : 1,
3 : 2, 1 : 1 and 2 : 3. For the reactant ratio study, concentration
ratios of IA : PBA : Na2CO3 (mM : mM : mM) were varied as
10 : 10 : 30, 10 : 15 : 30, 10 : 20 : 30, 10 : 30 : 30, 10 : 20 : 40, and
10 : 30 : 60 all in a CH3CN/H2O (2 : 3) mixture. Reusability
studies of Pd-TMV chips were carried out by taking the chips out
of the completed reaction mixture, rinsing with deionized water,
drying, and then immersing in a fresh reaction mixture for three
more reaction cycles without further treatments or activation
steps. Suzuki reactions between phenylboronic acid and other
aryl halides, including bromoanisole, chloroanisole, iodophenol,
iodobenzene, bromobenzene, were carried out under various
reaction conditions, as described in Table 1.
High-performance liquid chromatography (HPLC) analysis
The reactants and products in the Suzuki reaction mixture were
analyzed by HPLC (Waters LC module 1 plus, Milford, MA)
equipped with a UV detector at 254 nm. A reversed-phase Nova-
Pak C18 column (Waters, 4.6 ꢀ 150 mm, 4 mm) was used with an
acetonitrile/water (60 : 40, v/v) mixture as the eluent at a flow
rate of 1 ml/min.
Experimental
Calibration curves, for determining the concentration of all
reactants and products, were constructed by plotting the peak
area versus the concentration of all standard compounds. The
solutions were diluted 4 or 8 times to be within the range of
calibration curves. The product yields at each time point were
calculated based on the original concentration of the aryl halides.
For example, the 4-MB yield was calculated by eqn (1).
Materials
ꢀ
Gold-coated silicon wafers with 1000 A thicknesses of Au layer
were purchased from Platypus Technologies (Madison, WI).
Iodoanisole (IA) (>98%), bromoanisole (99%), chloroanisole
(99%), iodophenol (>98%), iodobenzene (>98%), 4-methoxy-
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½methoybiphenylꢂ
t
Yield; % ¼
ꢀ 100%
(1)
½iodoanisoleꢂ
0
Catalyst characterization
(1) Atomic force microscopy (AFM). AFM images of Pd-
TMV chips before and after Suzuki reactions were acquired
using a Dimension 3100 series Scanning Probe Microscope
(SPM) (Veeco, Woodbury, NY) in tapping mode with TAP-Al-
50 AFM tips (Budget Sensors, Sofia, Bulgaria) and analyzed by
NanoScope software.30
(2) Grazing incidence small angle X-ray scattering (GISAXS).
GISAXS measurements were conducted at the Advanced Photon
Source (Argonne National Lab, Argonne, IL) BESSRC/XOR 12
ID-C beamline as previously described.9,19 As shown in Fig. 3(a),
the X-ray beam, with energy of 8 keV, was irradiated on the
sample at an incident angle (ai) of 0.1ꢁ and the scattered X-rays
were collected on a CCD detector (Rayonix, Mar165).
The scattering pattern was analyzed in terms of the scattering
vector qxy for all GISAXS measurements.31 For a single spherical
Pd nanoparticle, the scattered intensity P(qxy) can be related to
particle radius R, volume n and density r, as given in eqn (2).31
Fig. 2 The effect of solvent ratio on reaction selectivity and surface
characterization by AFM. Reaction conditions: iodoanisole 10 mM,
phenylboronic acid 10 mM, sodium carbonate 30 mM, 5 ml CH3CN/H2O
mixture, temperature 50 ꢁC. (a) The effect of solvent CH3CN/H2O
volume ratio on reaction selectivity. (b) Products precipitation at room
temperature (c) AFM images of Pd-TMV chip after reaction in CH3CN/
H2O mixed solvent with volume ratio of 3 : 2 (i) and 2 : 3 (ii).
ꢀ
ꢁ
2
ꢀ
ꢁ
9 sinðqxyRÞ ꢃ qRcosðqxyRÞ
qxyR
P qxy ¼ r2v2
(2)
ꢀ
ꢁ
6
and scattering intensity I(qxy) of various particles with size
distribution, n(R), described by eqn (3).32
addition, higher or lower water content, beyond the range shown
in Fig. 2(a), did not provide adequate solubility of Na2CO3 or
Ð
I(qxy) ¼ n(R)P(qxy)dR
(3)
ꢁ
iodoanisole at 50 C. Meanwhile, Suzuki reaction of iodoanisol
with another boronic acid compound, 4-methoxyphenylboronic
acid, was also examined to confirm this selectivity (ESI 1†), and
exhibited similar selectivity toward the cross-coupling pathway
in higher water content as shown in Table S1†. This further
confirms that this effect is not limited to phenylboronic acid, and
appears to be general. Furthermore, the homo-coupling reaction
between phenylboronic acid in the absence of iodoanisole yielded
similar selectivity (i.e. suppression of homo-coupling product
yield with high water content), as shown in Table S2 (ESI 1†).
There have been limited number of studies with contradictory
conclusions on the effect of water on the selectivity of Suzuki
reaction.25,34 The results shown in Fig. 2(a) demonstrate that
a CH3CN/H2O mixture with the appropriate ratio is crucial in
directing cross- vs. homo-coupling pathways, leading to efficient
selectivity control. In-depth studies on the mechanism of this
striking effect of water content on the selectivity are currently
under way.
The size distribution, n(R), was calculated with Irena data
fitting software, where the scattering curves were fit using the
Maximum Entropy Method.33
Results and discussion
Effect of solvent ratio on reaction selectivity
We first examine the effect of the solvent ratio between aceto-
nitrile and water (CH3CN/H2O) on the selectivity of the Suzuki
coupling reaction catalyzed by Pd-TMV chips, as shown in
Fig. 2. For this, we prepared Pd-TMV chips, as shown in the
schematic diagram of Fig. 1(b), then carried out reactions with
10 mM phenylboronic acid, 10 mM iodoanisole, 30 mM sodium
ꢁ
carbonate at 50 C in well-sealed vials, and analyzed the reac-
tants and products via HPLC.
First, Fig. 2(a) shows that the CH3CN/H2O ratio is critical to
the competition of cross-coupling against the homo-coupling
pathway. Specifically, higher water content (i.e. CH3CN/H2O ¼
2 : 3) is beneficial for the production of cross-coupling product 4-
methoxybiphenyl (4-MB), and suppresses the production of
homo-coupling product biphenyl (BP). When the CH3CN/H2O
ratio was changed from 3 : 1 to 2 : 3, the yield of 4-MB increased
from 23.3% to 66.9%, while the yield of BP decreased from 20.1%
to 14.4% under the reaction conditions studied. This trend clearly
shows that water facilitates the cross-coupling pathway while
providing mild reaction conditions with less organic solvent. In
Importantly, no catalytic conversion was observed for several
negative controls (e.g. no chip, gold chip and TMV-assembled
gold chip) examined under the same reaction conditions (0%
conversion for all). This clear difference in conversion demon-
strates the catalytic activity of TMV-templated palladium
nanoparticles in the Suzuki coupling reaction.
Next, the photograph of Fig. 2(b) shows that both 4-MB and
BP products were precipitated as white flocculates while cooling
the reaction mixture to room temperature due to their relatively
low solubility in CH3CN/H2O (2 : 3) mixture. The products can
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thus be separated by centrifuge or sedimentation upon comple-
tion of the reaction, highlighting an additional advantage of the
high water content condition enlisted here. Importantly, this
result illustrates the facile and robust nature of our chip-based
catalyst format that enables the simple separation of both cata-
lysts and products upon reactions without additional steps such
as centrifugation or filtration, as compared to homogeneous Pd
catalysts.21,23
Next, to qualitatively evaluate the surface morphology and
stability of Pd-TMV chip under the conditions employed, the
chips were simply taken out of the reaction mixture and analyzed
by AFM, as shown in Fig. 2(c). Compared to the AFM image of
the Pd-TMV chip before the catalytic reaction (Fig. 1(c)-(ii)),
chips after the reaction in various CH3CN/H2O ratios (Fig. 2(c))
show no apparent changes in the Pd loading density or particle
size. This preliminary examination indicates that the surface-
assembled Pd-TMV complexes were stable under the range of
reaction conditions studied. Combined, the results in Fig. 2 show
clear reactivity and selectivity, stability of the nanostructured Pd-
TMV catalyst chips, along with facile catalysts and products
separation for the Suzuki coupling reaction.
Surface characterization by GISAXS
As shown in Fig. 3, we next employed grazing incidence small
angle X-ray scattering (GISAXS) to further examine the stability
of Pd-TMV chips in the Suzuki reaction. First, the schematic
diagram of Fig. 3(a) shows a typical GISAXS setup where the
incident X-ray strikes the surface of the Pd-TMV chip and the
scattered rays are recorded at low angles (less than 2ꢁ) on a 2D
CCD detector.31 Fig. 3(b) shows scattering images of various
samples as a function of the scattering angles 2q in the horizontal
direction and af in the vertical direction. First, the TMV1cys-
assembled gold chip (i) shows strong scattering in the out-of-
plane direction (at 2q ¼ 0), characteristic of the rod shaped
TMV.35 Second, the Pd-TMV chips before (ii) and after (iii and
iv) reactions all show nearly identical isotropic scattering, rising
from abundant spherical Pd particles. This result clearly indi-
cates that most Pd particles and Pd-TMV complexes were well-
preserved after completion of the Suzuki reactions under
different solvent ratios (CH3CN/H2O ¼ 2 : 3 and 3 : 2) at 50 ꢁC.
Next, a Guinier analysis9,31,32 was employed to further examine
the average Pd particle diameters. For this, scattering curves
were first created by making a horizontal line-cut of intensity
(shown by the red line in Fig. 3(b)-(ii)) and plotting intensity vs.
the scattering vector, qxy. The table in Fig. 3(c) shows that the
average Pd particle diameter did not change significantly under
all the reaction conditions examined, with slight variations rising
from different Pd-TMV chips for the ex-situ GISAXS analysis.
Finally, normalized particle volume distributions of Pd-TMV
chips before and after reactions under different reaction condi-
tions were examined by simulating size distributions from the
scattering curves using Irena software. The Irena software
utilizes the Maximum Entropy Method (MEM) with a 15% error
allowance to simulate particle size distributions.33 As shown in
Fig. 3(d), the average Pd particle size remained nearly identical
upon completion of the reactions in all three solvent ratios
examined, which further confirms the results in Fig. 3(c) acquired
from Guinier analysis and the preliminary observation via AFM
Fig. 3 Pd particle size distribution of Pd-TMV catalyst examined by
GISAXS. (a) Schematic diagram of GISAXS. (b) Scattering patterns of
TMV-gold chip (i), Pd-TMV chip before reaction (ii), Pd-TMV after
reaction in CH3CN/H2O solvent with ratio of 2 : 3 (iii) and 3 : 2 (iv). (c)
Summary of average Pd particle size on Pd-TMV chip before and after
reaction. (d) Pd particle size distribution of Pd-TMV chips before and
after reactions. Y-axis represents normalized number density of Pd
nanoparticles n(R).
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shown in Fig. 2(c). While the particle size distribution for all
three samples appears to broaden upon reaction, we note that the
ex-situ GISAXS measurements without direct comparison to the
same pre-reaction chips may not provide reliable means to
examine the change in particle size distribution. The reaction
mechanism of the Suzuki reaction is generally considered to
occur by a small number of molecular Pd species that leach out
into the bulk solution, which then re-deposit rapidly onto
supports.36 Our consistent particle size retention results in Fig. 3
show no apparent disappearance of the original particles or
increase of larger size particles (through Ostwald ripening) that
may lead to different size distributions and larger average
particle sizes. Given the potential of GISAXS for the statistically
meaningful in situ examination of dynamic yet subtle changes at
nanoscale,16,37,38 further in situ GISAXS studies are currently
under way to gain deeper understanding.
Fig. 4 Concentration of reactants and products vs. reaction time
Reaction condition: iodoanisole 10 mM, phenylboronic acid 15 mM,
sodium carbonate 30 mM, 5 ml CH3CN/H2O mixture solvent with ratio
of 2 : 3, temperature 50 ꢁC.
Meanwhile, in-depth X-ray Photoelectron Spectroscopy
(XPS) analysis revealed further information on the elemental
composition and chemical states of the Pd-TMV chips before
and after reactions as shown in Fig. S1 (ESI 2†). Briefly, the
spectra show full coverage of Pd nanoparticles on the TMV-
assembled chips, either before or after reaction, confirming the
AFM-based observations made in Fig. 1 and 2. The relative
metallic Pd content over the overall Pd species, Pd/(Pd + PdO),
were determined to be 60.9 ꢄ 2.7%. Importantly, only minimal
change in chemical states upon reactions was observed, as shown
in Fig. S1.†
In summary, the GISAXS-based in-depth analysis (Fig. 3) and
XPS surface characterization (Fig. S1†) clearly demonstrate the
dimensional, structural and chemical stability of Pd-TMV chips
for Suzuki reaction, and further corroborate the enhanced
thermostability16 of Pd-TMV complexes under the catalytic
reaction conditions employed in this study.
Batch reaction profile
Fig. 4ꢁshows the reactants conversion and products yield curves
at 50 C. For this, Suzuki reaction of 10 mM iodoanisole with
15 mM phenylboronic acid was carried out in the presence of Pd-
TMV chips in 5 ml CH3CN/H2O (2 : 3) mixture for 24 h. Samples
were taken at certain intervals and analyzed with HPLC as
described above.
Fig. 5 Effect of reactants ratios on product yields. Reactions were
carried out with Pd-TMV chips at solvent ratio of CH3CN/H2O ¼ 2 : 3
and temperature 50 ꢁC.
The concentration of both reactants (iodoanisole and phe-
nylboronic acid) decreased rapidly in the first 2 h, and then
decreased slowly until the end of the reaction. Meanwhile, the
target product 4-MB started forming rapidly in the first 0.5 h and
kept increasing steadily until the 4th hour. After 5 h, the 4-MB
concentration reached the maximum value of 8.2 mM and didn’t
change significantly until the end of the reaction. A similar trend
was observed for the formation of BP. The curves show that the
majority of both products (4-MB and BP) were formed within
the first 5 h, which is sufficient for near-complete conversion of
IA at 50 ꢁC. In addition, the reaction time didn’t affect the
reaction selectivity. Meanwhile, further in-depth Inductively
Coupled Plasma Optical Emission Spectrometry (ICP-OES)
experiments (ESI 3†) revealed the total Pd amount per chip to be
8.3 mg, which leads to the Pd catalyst ratio of 0.15 mol% based on
iodoanisole (0.05 mmol per batch). Furthermore, the ‘‘apparent’’
reaction rate within the first 5 h was determined to be 0.0165 mol/
(min$g) based on this amount of Pd employed for each batch
reaction (ESI 3†).
Meanwhile, Suzuki reactions at lower reaction temperatures
(25 and 40 ꢁC) were also examined and yielded much slower
reaction rates (data not shown). Therefore, a moderately high
temperature clearly facilitated the Pd-TMV catalyzed Suzuki
reaction.
Effect of reactant ratio on the reaction conversion
To further investigate the effect of reactant ratio (iodoanisole
(IA):phenylboronic acid (PBA):base) on the product yields, we
carried out Suzuki reactions with different reactant concentra-
tions in CH3CN/H2O (2 : 3) mixture, as shown in Fig. 5.
We first studied the influence of PBA amount on the product
yields by keeping IA and base concentration constant (Entries 1–
4). In Entry 1, equivalent amount of two reactants IA and PBA
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(both 10 mM) resulted in only 68.6% yield of 4-MB. When PBA
concentration was increased from 10 mM to 20 mM from Entry 1
to 3, both 4-methoxybiphenyl (4-MB) and biphenyl (BP) yields
increased simultaneously. Entry 3 shows that two-fold higher
concentration of PSB than IA leads to 100% yield of 4-MB and
29.6% of BP. Meanwhile, further addition of PBA up to 30 mM
(Entry 4) didn’t have a significant influence on either reaction
conversion or selectivity. The mass balance analysis based on
HPLC quantification indicated that all BP was formed from the
homo-coupling of PBA. These results indicate that more PBA
content than IA is needed to complete the cross-coupling
reaction, since a certain amount of PBA follows the homo-
coupling pathway catalyzed by Pd39,40 or Au41 as previously
reported.
fourth batches did not show a further decrease in activity, as
shown in the fourth reuse of catalysts: the yield of 4-MB was
maintained at 91.4%. These results are consistent with our
previous findings in the dichromate reduction reaction,19,20 and
clearly demonstrate the stability and reusability of Pd-TMV
catalysts for the Suzuki reaction under the conditions studied.
More importantly, the surface-assembled TMV-templated
format enables the significantly simpler recovery and repeated
use of the catalysts (i.e. mechanical removal of the chip from the
reaction mixture) with minimal loss of catalytic activity without
arduous separation and/or regeneration procedures.
In the meantime, preliminary reaction mechanism was studied
through chip removal experiments along with ICP-OES analysis
(ESI 4†). The results suggest that the Suzuki reactions may be
catalyzed largely by trace amounts of Pd species (1–90 ppb) in the
reaction solution under the conditions employed in our study.
The Pd nanoparticles formed on TMVs in this study can thus be
considered as a reservoir, or ‘‘pre-catalysts’’ of the catalytically
active Pd species in the reaction solution.36,43,44 In addition, the
simplicity of this chip removal experiment (i.e. mechanical
removal of the entire chip from the reaction solution) further
supports the advantage of our surface-assembled catalyst format
toward facile mechanistic studies. Further in situ SAXS studies to
understand the molecular mechanisms are currently underway.
Next, the effect of base (Na2CO3) amount was investigated
(Entries 5 and 6). Compared to Entry 3, 33% higher base
concentration (Entry 5) yielded similar final product amounts. A
two-fold higher base amount (Entry 6, 60 mM) yielded 8% more
byproduct (BP) than Entry 4, showing relatively lower reaction
selectivity. It is well known that base could activate phenyl-
boronic acid in the Suzuki coupling reaction;42 the results shown
here indicate that excess base may lead to more homo-coupling
byproducts while certain amount of base is required to complete
the cross-coupling reaction. Overall, the results in Fig. 5
demonstrate that proper reactant ratio plays an important role
on both reaction conversion and selectivity.
Catalytic Suzuki reaction of other aryl halides with
phenylboronic acid
Reusability of Pd-TMV catalysts
Finally, we further examined the conversion and selectivity of the
Pd-TMV catalyzed Suzuki reaction for a range of aryl halides as
summarized in Table 1. Entries 1 and 2 show that Pd-TMV
catalysts are active for the cross-coupling of PBA with bro-
moanisole, but not chloroanisole. This result is consistent with
previous reports, where the relative cross-coupling reactivity
decreased in the order of I > Br [ C1.3,36 Next, Entries 3–6 show
the Suzuki reaction of 4-iodophenol with PBA, where the solvent
ratio also played a significant role on the reactivity. Higher water
content (Entry 3 vs. 4) produced more of the cross-coupling
product 4-phenylphenol (80%) and less biphenyl (14%), which is
consistent with the trend shown in Fig. 2 for iodoanisole.
Contrary to other reports,24 iodophenol is only slightly soluble in
water, thus no product was observed in aqueous solution (Entry
6). Meanwhile, the commonly used dimethylacetamide (DMA)/
water (1 : 1) mixture25,34 (Entry 5) did not yield significant
conversion for this catalytic reaction. Next, Suzuki reactions
using benzene halides were also studied (Entries 7 and 8). The
reaction with iodobenzene (Entry 7) led to 133.7% yield (vs.
initial iodobenzene) of biphenyl, most likely from both the cross-
coupling (between iodobenzene and PBA) and the homo-
coupling reactions (between two moles of PBA). The reaction
with bromobenzene in Entry 8 showed a much lower conversion,
as expected from the lower reactivity of bromides.
As shown in Fig. 6, we further conducted recycle reaction studies
to examine the reusability of our Pd-TMV catalysts based on the
clear stability shown via GISAXS in Fig. 3 and XPS in Fig. S1†.
For this, Pd-TMV chips were thoroughly rinsed with deionized
water and applied to three more batch reaction cycles without
any regeneration treatments. The reactions were carried out in
the optimized conditions as described above, with 10 mM IA,
20 mM PBA and 30 mM base in CH3CN/H2O (2 : 3) solvent at
50 ꢁC for 24 h. The results in Fig. 6 show a small decrease in the
catalytic activity of Pd-TMV chip in the second cycle: the yield of
4-MB decreased from 100% (first run) to 91.7% (second run) and
BP decreased from 29.6% to 28.8%. However, the third and
Considering the unoptimized reaction conditions for each
reactant case shown in Table 1, higher product yields could be
expected upon further examination of parameters (e.g. solvent
ratio, base addition amount, reactants ratio). Overall, these
studies show that our TMV-templated Pd catalysts are active
with several different reactants examined, further confirming the
general catalytic activity for Suzuki coupling reactions.
Fig. 6 Recycling test of Pd-TMV chip catalyzed Suzuki reaction of
iodoanisole with phenylboronic acid.
192 | J. Mater. Chem., 2011, 21, 187–194
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Table 1 Pd-TMV chip catalyzed Suzuki reaction of aryl halides with phenylboronic acid
Concentration (mM) ArX:
C6H5B(OH)2: Base
Entry ArX
Solventa
Base
Yield of Ar-C6H5, % Yield of C6H5-C6H5, %
1
2
3
4
5
6
7
8
4-BrC6H4OCH3 CH3CN:H2O ¼ 2 : 3 Na2CO3 10 : 30 : 60
4-ClC6H4OCH3 CH3CN:H2O ¼ 2 : 3 Na2CO3 10 : 30 : 60
30.8
0
29.9
10.9
14.0
30.5
0
4-IC6H4OH
4-IC6H4OH
4-IC6H4OH
4-IC6H4OH
IC6H5
CH3CN:H2O ¼ 1 : 3 Na2CO3 10 : 20 : 30
CH3CN:H2O ¼ 2 : 3 Na2CO3 10 : 20 : 30
80.0b
68.4b
0
0
/
DMA:H2O ¼ 1 : 1
K2CO3
K2CO3
10 : 10 : 30
10 : 10 : 30
H2O
0
CH3CN:H2O ¼ 1 : 1 Na2CO3 10 : 20 : 30
133.7c
53.0
BrC6H5
CH3CN:H2O ¼ 1 : 1 Na2CO3 10 : 20 : 30
/
a
c
b
Solvent ratios are all based on volume ratio. The yield of Ar-C6H5 is calculated from the conversion of IC6H4OH on a basis of mass balance.
Byproduct from homo-coupling of C6H5B(OH)2 is the same as cross-coupling product, so the yield of biphenyl based on iodobenzene is higher
than 100%.
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In this paper, we demonstrated and thoroughly examined, for the
first time, the catalytic activity of TMV-templated Pd nano-
particles for the Suzuki coupling reaction toward value-added
chemical synthesis. The surface-assembled chip based format
allowed for simple catalyst and product separation as well as
simple catalysts recycling for several reaction batches. Over 90%
of the initial catalytic activity was retained for four reaction
cycles. In depth reaction condition studies indicated that the
solvent ratio played an important role in the selectivity of the
Suzuki reaction, and that a higher water content is beneficial for
the cross-coupling pathway. Importantly, these results suggest
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Acknowledgements
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We gratefully acknowledge financial support by the Stanley
Charm Fellowship (C.Y.). Partial funding for this work was also
provided by the Wittich Family Fund for Sustainable Energy
and by the National Science Foundation under Grant No.
CBET-0941538 and DMR-1006613. GISAXS work at Argonne
National Laboratory was supported by the US Department of
Energy, BES-Chemical Sciences and BES-Scientific User Facili-
ties under Contract DE-AC-02-06CH11357 with UChicago
Argonne, LLC, operator of Argonne National Laboratory. We
thank Jessica Englehart and Yonggang Wang from Department
of Civil and Environmental Engineering of Tufts University for
the help in ICP examination.
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