Supporting Information
Membrane Reactor Immobilized with Palladium-Loaded Polymer
Nanogel for Continuous-Flow Suzuki Coupling Reaction
Hirokazu Seto,1 Tamami Yoneda,1 Takato Morii,1
Tatsuya Murakami,2 Yu Hoshino,1 and Yoshiko Miura1*
1
Department of Chemical Engineering, Graduate School of Engineering, Kyushu University,
744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
2
Center for Nano Materials and Technology, Japan Advanced Institute of Science and
Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
* Corresponding author
Tel: +81-92-802-2749
Fax: +81-92-802-2769
E-mail: miuray@chem-eng.kyushu-u.ac.jp
S1
Synthesis of poly(TMSMA-r-NAS)
Poly(TMSMA-r-NAS) was synthesized using a previously reported method.1
Poly(TMSMA-r-NAS) was obtained by copolymerization of 3-(trimethoxysilyl)propyl
methacrylate (TMSMA; Sigma Aldrich Co., USA) and N-acryloxysuccinimide (NAS;
Tokyo Chemical Industry Co., Ltd., Japan) (Figure S1). The TMSMA and NAS residues
act as the surface-reactive and amine-reactive parts, respectively. Polymerizing
inhibitor-free TMSMA (9 mmol) and NAS (9 mmol) were dissolved in anhydrous
dimethylformamide (DMF; 20 mL). The mixture was degassed using nitrogen gas. The
polymeric reaction was initiated by addition of 2,2'-azobisisobutyronitrile (0.2 mmol) at
70°C. After 20 h, the mixture solution was aerated to stop polymerization, and then
concentrated by evaporation. Completion of polymerization was determined by
hydrogen nuclear magnetic resonance (1H NMR) spectroscopy (JNM-ECP400, JEOL
Ltd., Tokyo, Japan) in deuterated dimethyl sulfoxide (DMSO-d6). The 1H NMR
spectrum (Figure S2) showed that the monomers were almost completely converted,
because of no vinyl-group peak appeared at 6 ppm. The ratio of TMSMA to NAS units
in the polymer was estimated from the integral values of the peaks for TMSMA (: 3.9
ppm, 2H per unit) and NAS (: 2.8 ppm, 4H per unit), and was 38:62. The resulting
poly(TMSMA-r-NAS) was used without purification.
Poly(TMSMA-r-NAS) was immobilized to form the NAS-activated surface for the
amine coupling reaction. The RCA-treated membranes were immersed in the
poly(TMSMA-r-NAS) solution (10 g L-1, DMF), and the membranes were incubated at
room temperature and 38°C for 1 h each. The membranes were then heated at 110°C for
5 min to form covalent bonds. After washing with DMF and water, the NAS-activated
membrane was obtained.
Figure S1 Synthesis of poly(TMSMA-r-NAS).
S2
Figure S2 1H NMR spectrum of poly(TMSMA-r-NAS) in DMSO-d6 at 400 MHz.
S3
Preparation of Pd(0) loaded in aminated membrane
Pd ions were directly adsorbed on the surface of a SiO2 membrane by amination, and
were reduced into Pd(0) (Figure S3). The amination was performed using
N-3-dimethylaminopropyl trimethoxysilane (DMAPTMS; Sigma Aldrich Co., USA).
The RCA-treated membranes were immersed in the DMAPTMS solution (5 g L-1,
DMF), and the membranes were incubated at room temperature and 38°C for 1 h each.
The membranes were then heated at 110°C for 5 min to form covalent bonds. After
washing with DMF and water, the aminated membrane was obtained. The aminated
membranes were immersed in the Pd solution (1.0 mmol L-1) for 24 h. The
concentration of Pd ions in the solution was determined by ultraviolet (UV) absorption
at 420 nm. The amount of Pd ions adsorbed on the aminated membrane was 7.9 mol
gM-1. The Pd ion-adsorbed membranes were washed with 1.0 mmol L-1 HCl, and
immersed into the NaBH4 solution (pH: 8, water) for reduction into Pd(0). After
washing with excess water, the Pd(0)-loaded membrane was obtained. The directly Pd
ion-adsorbed membrane was used for comparison with the membrane with Pd ions
adsorbed via NPs.
Figure S3 Preparation of Pd(0)-loaded membrane: (a) unmodified SiO2, (b) aminated,
(c) Pd ion-adsorbed, and (d) Pd(0)-loaded membranes. (i) 5 g L-1 DMAPTMS in DMF,
(ii) 1.0 mmol L-1 K2PdCl4 in 1.0 mmol L-1 HCl, and (iii) NaBH4 in water (pH 8).
S4
Properties of SiO2 membrane
A filter paper consisting of SiO2 was
used as a membrane matrix (Table S1).
The pressure loss of the SiO2 membrane
was low. The labeled pressure loss
corresponds to 80 mPa during permeation
of water at 1 mL h-1. A scanning electron
microscopy (SEM) image showed that the
SiO2 membrane had a fibrous structure
Table S1. Physical Properties of One Sheet
of SiO2 Membrane Used for Matrix.
(Figure S4). The specific surface area of
the SiO2 membrane was determined from the nitrogen adsorption-desorption isotherm at
-196oC (Tristar, Micromeritics Instrument Corporation, USA), and was calculated using
the Brunauer-Emmett-Teller equation. It was found that the specific surface area of the
SiO2 membrane was 4 m2 gM-1. The porosity of the SiO2 membrane was estimated from
the Kozeny-Carman equation:
2
∆P kμLS2 (1-ε)
=
u
ρ2 ε3
where P, u, k, , L, S, , and  are the pressure loss, permeation rate, Kozeny constant
(usually 5), viscosity, membrane thickness, specific surface area, membrane density,
and membrane porosity, respectively. The porosity of the SiO2 membrane was 83%. A
high porosity indicates that the throughput is so high that scale-up of reactor for
catalytic reaction can be achieved by stacking layers of filter paper.
Figure S4 SEM image of SiO2 membrane surface with fiber structure.
S5
Continuous-flow system for Suzuki coupling reaction using Pd(0)-loaded membranes.
The continuous-flow system was constructed to evaluate the catalytic activity and
storage stability of the Pd(0)-loaded membranes, as shown in Figure S5. Four
membrane sheets were joined using a connector, and the membrane reactor was placed
in an incubator at 60°C, with permeating water for conditioning. The reactant solution
was passed through the membrane reactor at various flow rates using a syringe pump
(Harvard Pump 11 Plus Single Syringe, Harvard Apparatus, USA). The effluent was
continuously collected, and the concentrations of the reactant and product in the effluent
were determined.
Figure S5 Continuous-flow reactor for Suzuki coupling reaction using Pd(0)-loaded
membranes.
S6
Preparation of Pd(0)-loaded NPs
Pd(0)-loaded NPs were prepared using a previously reported method.2
N-Isopropylacrylamide
(NIPAm),
N-3-dimethylaminopropyl
methacrylamide
(DMAPM), N-(3-aminopropyl) methacrylamide hydrochloride (APM), and
N,N’-methylenebisacrylamide (BIS) were dissolved in water (20 mL). The
NIPAm:DMAPM:APM:BIS molar ratios and total concentration of monomer were
adjusted to 80:10:5:5 and 312 mmol L-1, respectively. A surfactant,
cetyltrimethylammonium bromide (42 mol), was added to the monomer solution. The
solution was degassed under nitrogen for 30 min. The polymeric reaction was initiated
by the addition of 2,2'-azobis(2-amidinopropane) dihydrochloride (52 mol) at 70°C.
After 3 h, the mixture solution was aerated to stop polymerization. The resulting NPs
were dialyzed (molecular-weight cut off: 100,000) against water (which was changed
more than three times per day) for 3 days. The NP yield was determined from the
weight of NPs measured after freeze-drying a portion of the dialyzed solution, and was
estimated to be 91%. The 1H NMR spectrum of the NPs in deuterated methanol was
obtained (Figure S6), and the unit components of the NPs were estimated from the
integral values of the peaks for isopropyl in NIPAm (: 4.0 ppm, 1H per unit),
methylene in BIS (: 4.6 ppm, 2H per unit), and (meth)acrylamide main chains (:
0.3-3.0 ppm). The components of the amine units (DMAPM and APM) were calculated
by subtracting NIPAm and BIS from the total units. The ratios of NIPAm, amine, and
BIS units in the NPs were estimated to be 77:14:9, which was agreed to the feed ratio of
75:15:10. The theoretical amine density was 1190 mol (tertiary amine: 790 mol and
primary amine: 400 mol) per gram of NPs. The hydrodynamic diameter of the NPs in
Figure S6 1H NMR spectrum of NPs in deuterated methanol at 400 MHz.
S7
Figure S7 DLS profile of NPs in water (1 g L-1) at 60oC.
water was determined using dynamic light scattering (DLS; Zetasizer Nano ZS,
Malvern Instruments Ltd., UK) (Figure S7). The hydrodynamic diameter of the NPs
was found to be 383 nm at 60°C. The size distribution in the DLS profile was relatively
uniform (polydispersity index: 0.097). The NPs had high dispersion stability.
Pd solutions of various concentrations were prepared by dissolving potassium
tetrachloropalladate in 1.0 mmol L-1 HCl. The NPs were added to the Pd solution
(solid/liquid = 1.3 g L-1), and shaken at room temperature for 24 h. The mixture solution
was separated using ultrafiltration (Amicon Ultra, molecular-weight cut off: 10,000,
Millipore Co., USA). The concentration of Pd ions in the filtrate was determined by UV
absorption at 420 nm. The amount of Pd ions adsorbed on the NPs was calculated using
the following equation;
Amount of Pd ions adsorbed (mmol g-1 of NPs) =
[Pd ion]0 -[Pd ion]e
×v
WNP
where v and WNP are the solution volume and the NP weight, respectively. The
subscripts 0 and e denote the initial and equilibrium states, respectively. The adsorption
isotherm for Pd ions on the NPs is shown in Figure S8. The maximum adsorption
capacity of the NPs for Pd ions was calculated using Langmuir’s equation. The
maximum adsorption capacity was 495 mol per gram of NPs. Pd ions form anionic
complexes with chlorides in HCl. The Pd ions were adsorbed on the NPs via
electrostatic and coordination interactions.
S8
Figure S8 Adsorption isotherm for Pd ions on the NPs.
The NP with adsorbed Pd ion were dialyzed (molecular-weight cut off: 100,000)
against water. The Pd ions on the NPs were reduced to Pd(0) using NaBH4, until the
solution reached pH 8. The Pd(0)-loaded NPs were dialyzed against water. After
freeze-drying, the Pd(0)-loaded NPs were obtained as a grayish powder. The
Pd(0)-loaded NP solution (0.1 g L-1) was then added dropwise onto a Cu-microgrid
mesh (Okenshoji Co., Ltd., Japan). After drying the sample, the Pd(0) loaded on the
NPs was observed using transmission electron microscopy (TEM; TECNAI 20, Philips
FEI, Netherlands). In the TEM image (Figure S9), Pd(0) particles of average diameter 2
nm were observed in the NPs. It was estimated that the surface area of a Pd(0) particle
was 12.6 nm2. Pd(0) particles of similar size should be formed in the NPs on the
membrane. The Pd(0)-loaded NPs were used in a batch system for the Suzuki coupling
reaction, and their catalytic activities and stabilities were compared with those of
Pd(0)-loaded membrane in the continuous flow system.
Figure S9 TEM image of Pd(0) loaded in NP.
S9
SEM observations of unmodified SiO2, NAS-activated, NP-immobilized, and
Pd(0)-loaded membranes
The surfaces of the unmodified, NAS-activated, NP-immobilized, and Pd(0)-loaded
membranes were observed using field-emission scanning electron microscopy
(FE-SEM; Ultra55, Carl Zeiss NTS GmbH, Germany) with secondary electron (SE2)
and energy selective backscattered (EsB) detectors; the images are shown in Figure S10.
The FE-SEM images obtained using the SE2 detector showed that the fiber structures
were retained in all the membranes, suggesting that the pores of the membrane were not
fouled by the poly(TMSMA-r-NAS), NPs, and Pd(0) catalysts. The FE-SEM image
obtained using the EsB detector clearly indicates increasing numbers of atoms. The
parts, that are brighter than SiO2 fiber matrix, indicate Pd atoms. The Pd(0) catalysts
were finely observed on the Pd(0)-loaded membranes in the FE-SEM image obtained
using the EsB detector. The particle sizes of Pd(0) on the NP-immobilized and the
aminated membranes were different; the particles on the NP-immobilized membrane
were small, whereas those on the aminated membrane associated to form the aggregates
of ca. 1 m.
S10
Figure S10 SEM images of (a) unmodified, (b) NAS-activated, (c) NP-immobilized, (d)
Pd(0)-loaded (via NP-immobilized membrane), and (e) Pd(0)-loaded (via aminated
membrane) membranes. The left-hand and right-hand images were obtained using SE2
and EsB detectors, respectively.
S11
Suzuki coupling reaction using Pd(0)-loaded NPs in batch system
The Pd(0)-loaded NPs were used in the Suzuki coupling reaction between
phenylboronic acid and 4-iodebenzoic acid in the batch system. The reactant solution
was prepared by dissolving phenylboronic acid (50 mmol L-1), 4-iodebenzoic acid (55
mmol L-1, 1.1 equivalent), and Na2CO3 (55 mmol L-1, 1.1 equivalent) in water, and
heating at 60oC. The Pd(0)-loaded NPs were added to the reactant solution (10 mL). The
amount of Pd(0) catalyst added was 5.5 mol, which corresponded to 1 mol%. The
mixture solution was stirred at 60°C, and was arbitrarily collected. After removal of the
Pd(0) catalyst using a membrane filter, the concentrations of phenylboronic acid and
4-phenylbenzoic acid in the effluent were determined using a high performance liquid
chromatography system (LC-2000Plus, JASCO Co., Japan) with a reverse phase
column (Mightysil RP-18 GP 250-4.6, Kanto Chemical Co., Inc., Japan) and UV
detector. The mobile phase was a mixture solution of acetonitrile and water (50:50) with
0.1 v/v% trifluoroacetic acid. After completion of the catalytic reaction, the mixture
solution was centrifuged at 3,000 rpm at 90°C. The supernatant solution was removed,
the Pd(0)-loaded NPs were washed three times with water and methanol, and then the
NPs were lyophilized. The obtained Pd(0)-loaded NPs were reused for the Suzuki
coupling reaction. The Suzuki coupling reaction and washing were repeated six times.
The Pd(0)-loaded NPs used for the Suzuki coupling reaction were added dropwise onto
a Cu-microgrid mesh, and the Pd(0) loaded in the NPs was observed using TEM (Figure
S11). After the catalytic reaction, the size of the Pd(0) particles in the NPs increased
slightly (average diameter: ca. 5 nm). This increase is explained by Ostwald ripening,3
which is related to cluster growth. The catalytic activity of Pd(0) depends on the particle
size.4 This phenomenon might also occur in the NPs on the membrane. It is expected
that the use of stronger functional groups such as thiol, triphenylphosphine, and
quaternary amine groups will prevent intragel aggregation of Pd(0).
Figure S11 TEM image of Pd(0) loaded in NP after six cycles of Suzuki coupling
reaction.
S12
The time conversion curve for the Suzuki coupling reaction in the batch system with
recycled Pd(0)-loaded NPs is shown in Figure S12. All the reactants were converted
into 4-phenylbenzoic acid within 5 h for each cycle; especially 100% conversion was
reached at 2 h in first cycle. However, the time conversion showed sigmoidal behavior
with increasing cycle number. The Suzuki coupling reaction using Pd species
progresses sequentially via oxidative addition, transmetalation, and reductive
elimination steps.5,6 In general, the rate-determining step of the catalytic cycle depends
on the halogen in the aryl halide; oxidative addition and transmetalation are the
rate-determining steps using bromide and iodide, respectively.7 In this study, oxidative
addition was faster than transmetalation, because 4-iodebenzoic acid was used. When
oxidative addition step becomes slower, the time conversion curve changes to sigmoidal.
The sigmoidal behavior is attributed to inhibition of complex formation between Pd and
the aryl halide by NP aggregation during recovery and washing. The relative activity of
the Pd(0) catalyst was estimated from the conversion percentage into 4-phenylbenzoic
acid at 2 h. The relative activity of the Pd(0) catalyst in the continuous-flow system was
higher than that in the batch system. Catalyst recovery is unnecessary and the catalyst
stability is improved; these are great advantages for membrane reactors as
continuous-flow systems.
Figure S12 Changes in time conversion curves for Suzuki coupling reaction in batch
system with recycled Pd(0)-loaded NPs.
S13
Confirmation of presence of Pd(0) on membranes used six times and over 6 days
To confirm the presence of Pd, X-ray photoelectron spectroscopy (XPS; AXIS-ultra,
Shimadzu/Kratos, Japan) was performed on the Pd(0)-loaded membranes that had been
used six times or over 6 days. The XPS spectra were calibrated using the peak at 285.0
eV, corresponding to C-C. The Pd(3d) spectra are shown in Figure S13. In the spectra
of the Pd(0)-loaded membranes used in the storage and long-term stability
investigations, two peaks appeared at the same binding energies as those of the original
Pd(0)-loaded surface, shown in Figure 3.
The surfaces of the used membranes were observed using FE-SEM with SE2 and EsB
detectors; the images are shown in Figure S14. The brighter parts, i.e., Pd(0) catalysts,
were finely observed on both membranes in the FE-SEM image obtained using the EsB
detector. Pd remained on the membranes, even after the reactor was reused six times
and operated for 6 days. The SEM images also indicate that the morphologies of the
used membranes were similar to that of the original Pd(0)-loaded membrane, i.e., the
fibrous structures of the membrane were not broken. The Pd(0)-loaded membrane
reactor was industrial-strength and reusable.
Figure S13 Pd(3d) XPS spectra of Pd(0)-loaded membranes used for (a) storage
stability and (b) long-term stability tests in continuous-flow Suzuki coupling reaction .
S14
Figure S14 SEM images of Pd(0)-loaded membranes used for (a) storage stability and
(b) long-term stability tests in continuous-flow Suzuki coupling reaction. The left-hand
and right-hand images were obtained using SE2 and EsB detectors, respectively.
S15
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S16