Dual-channel microreactor for gas-liquid syntheses

Article abstract of DOI:10.1021/ja102666y

A microreactor consisting of two microfluidic channels that are separated by a thin membrane is devised for intimate contact between gas and liquid phases. Gas flowing in one microchannel can diffuse into the liquid flowing in the other microchannel through the thin membrane. An oxidative Heck reaction carried out in the dual-channel (DC) microreactor, in which gaseous oxygen plays a key role in the catalytic reaction, shows the significant improvement that can be made over the traditional batch reactor and the conventional segmental microreactor in terms of yield, selectivity, and reaction time. It also allows independent control of the flow of the gaseous reagent. The proposed DC microreactor should prove to be a powerful tool for fully exploring gas-liquid microchemistry.

Full text of DOI:10.1021/ja102666y

Published on Web 07/01/2010
Dual-Channel Microreactor for Gas-Liquid Syntheses
†
,†,‡
Chan Pil Park and Dong-Pyo Kim*
National CreatiVe Research Center of Applied Microfluidic Chemistry, and Graduate School of
Analytical Science and Technology, Chungnam National UniVersity, Daejeon, 305-764, South Korea
Received March 30, 2010; E-mail: dpkim@cnu.ac.kr
Abstract: A microreactor consisting of two microfluidic channels that are separated by a thin membrane
is devised for intimate contact between gas and liquid phases. Gas flowing in one microchannel can diffuse
into the liquid flowing in the other microchannel through the thin membrane. An oxidative Heck reaction
carried out in the dual-channel (DC) microreactor, in which gaseous oxygen plays a key role in the catalytic
reaction, shows the significant improvement that can be made over the traditional batch reactor and the
conventional segmental microreactor in terms of yield, selectivity, and reaction time. It also allows
independent control of the flow of the gaseous reagent. The proposed DC microreactor should prove to be
a powerful tool for fully exploring gas-liquid microchemistry.
Introduction
Microfluidic systems have opened up new concepts and
1
offered several attractive possibilities for organic chemists.
These systems have been applied in various standard organic
reactions, and new chemistry in microreactors has also been
reported. Such systems are advantageous in providing increased
surface-to-volume ratio, rapid mass- and heat-transfer, enhanced
process safety, and diminished waste. Moreover, the chemical
reactions in the confined microscale space can be completed in
a short time, and the result can be related to mass production.
The chemical reactions between gas and liquid phases have
traditionally been carried out in batch systems (Figure 1a). The
contact area between the two phases is quite small relative to
the reaction volume. This contact area per reaction volume
decreases with increasing reaction volume, and as a result the
reaction rate in a scaled-up reactor would be sharply decreased
due to the reduced contact area relative to the volume. The gas
diffusion into the liquid phase has generally been enhanced by
vigorous stirring, high pressure, supercritical conditions, or
additional means such as ultrasonic waves. The approach taken
in microdevices to enhance the contact between the two phases
Figure 1. Comparative illustration of various modes of contact area between
gas and liquid phases.
conceptual approach has not been attempted for microchemical
reactions that require intimate contact between two phases.
The porosity of poly(dimethylsiloxane) (PDMS) has been
used in microfluidic systems related to the fields of analytical
chemistry and biology, such as in the deoxygenation of
solutions, the sensing of gases, oxygenation, and devices for
3
cell culture. However, the PDMS materials were rarely tried
for organic reactions, and the oxygen permeability of PDMS
was not considered useful in organometallic chemistry. Herein,
(
(
2) For representative reports, see: (a) Wang, N.; Matsumoto, T.; Ueno,
M.; Miyamura, H.; Kobayashi, S. Angew. Chem., Int. Ed. 2009, 48,
4744–4746. (b) Miller, P. W.; Long, N. J.; de Mello, A. J.; Vilar, R.;
Audrain, H.; Bender, D.; Passchier, J.; Gee, A. Angew. Chem., Int.
Ed. 2007, 46, 2875–2878. (c) Rahman, M. T.; Fukuyama, T.; Kamata,
N.; Sato, M.; Ryu, I. Chem. Commun. 2006, 21, 2236–2238. (d)
Rebrov, E. V.; Klinger, E. A.; Berenguer-Murcia, A.; Sulman, E. M.;
Schouten, J. C. Org. Process Res. DeV. 2009, 13, 991–998.
was to utilize segmented flow of gas and solution in the
2
“
monochannel” (MC) reactor (Figure 1b). We visualized that
contact of gas-liquid phases in dual parallel microchannels is
a way of maximizing the contact area between the two phases
(
Figure 1c). Furthermore, exact control of gas flow into the
reaction system is very difficult in monochannel microreactors
but might be improved in dual parallel microchannels. This
3) The parallel contacting between gas and liquid was tried in the
chemical- and bio-engineering field. See: (a) Choudhary, V. R.;
Gaikwad, A. G.; Sansare, S. D. Angew. Chem., Int. Ed 2001, 40, 1776–
1779. (b) de Jong, J.; Verheijden, P. W.; Lammertink, R. G. H.;
Wessling, M. Anal. Chem. 2008, 80, 3190–3197. (c) Lemke, E. A.;
Gambin, Y.; Vandelinder, V.; Brustad, E. M.; Liu, H. W.; Schultz,
P. G.; Groisman, A.; Deniz, A. A. J. Am. Chem. Soc. 2009, 131,
13610–13612. (d) Timmer, B. H.; Olthuis, W.; Van den Berg, A. Lab
Chip 2004, 4, 252–255. (e) Ohira, S. I.; Toda, K. Lab Chip 2005, 5,
1374–1379. (f) Vollmer, A. P.; Probstein, R. F.; Gilbert, R.; Thorsen,
T. Lab Chip 2005, 5, 1059–1066. (g) Walker, G. M.; Ozers, M. S.;
Beebe, D. J. Biomed. MicrodeVices 2002, 4, 161–166. (h) Lam,
R. H. W.; Kim, M.-C.; Thorsen, T. Anal. Chem. 2009, 81, 5918–
5924. (i) Aota, A.; Nonaka, M.; Hibara, A.; Kitamori, T. Angew.
Chem., Int. Ed. 2007, 46, 878–880.
†
National Creative Research Center of Applied Microfluidic Chemistry.
Graduate School of Analytical Science and Technology.
‡
(
1) For reviews and books, see: (a) Yoshida, J. I.; Nagaki, A.; Yamada,
T. Chem.sEur. J. 2008, 14, 7450–7459. (b) Wiles, C.; Watts, P. Eur.
J. Org. Chem. 2008, 1655–1671. (c) Fukuyama, T.; Rahman, M. T.;
Sato, M.; Ryu, I. Synlett 2008, 151–163. (d) Ahmed-Omer, B.; Brandt,
J. C.; Wirth, T. Org. Biomol. Chem. 2007, 5, 733–740. (e) Mason,
B. P.; Price, K. E.; Steinbacher, J. L.; Bogdan, A. R.; McQuade, D. T.
Chem. ReV. 2007, 107, 2300–2318. (f) Microreactors in Organic
Synthesis; Wirth, T., Ed.; Wiley-VCH: Weinheim, 2008. (g) Handbook
of Micro Reactors; Hessel, V., Schouten, J. C., Renken, A., Wang,
Y., Yoshida, J. I., Eds.; Wiley-VCH: Weinheim, 2009.
1
0102 9 J. AM. CHEM. SOC. 2010, 132, 10102–10106
10.1021/ja102666y  2010 American Chemical Society

Microreactor for Gas-Liquid Syntheses
A R T I C L E S
5
designed to give a high contact area (Figures 3 and 4). The
solution channel is parallel with the gas channel for continuous
contact between the gas and the liquid through the thin
membrane, which facilitates permeation of the gas into the liquid
and prevents the flow from breaking into a segmented flow of
gas and liquid. Typically, the contact area between the dual
Figure 2. Segmented flow of gas bubbles and liquid slugs in the
monochannel microreactor (Inlet part).
2
channels was 3.6 cm for the identical channel volume of 30.6
µL, yielding a maximum contact area-to-volume ratio of 117.6
-
1
cm in the DC microreactor, which is almost an order of
we report a dual-channel microreactor in which a thin gas-
permeable membrane is sandwiched between two PDMS slabs,
the engraved microchannel in each of the slabs facing the other
microchannel across the thin PDMS membrane. The micro-
channel in one of the slabs is used for liquid flow, while the
other microchannel across the thin membrane is used for gas
flow. This arrangement of dual channels (DC) provides a
considerably higher contact area between gas and liquid than
the batch or MC microreactor. The three-layered PDMS
microreactor with dual-channel structure was readily prepared
by facile soft lithography and used for organic chemical
reactions without problematic swelling. In particular, the oxida-
tive Heck reaction was thoroughly explored using the dual-
channel microreactor. The results demonstrated that it is a highly
promising reaction system for achieving significantly improved
reaction yields and selectivities in a short time, due to sufficient
contact between dissolved Pd catalyst and oxygen gas for
generating the active Pd(II) species. To the best of our
knowledge, this membrane-assisted microfluidic system is
reported for gas-liquid organic chemical reactions for the first
time.
-
1
magnitude larger than the ratio of 13.3 cm for the MC
microreactor. In particular, it is worth noting that both microre-
actors have a much larger contact area to volume ratio than the
-
1
1/3
value of 3.20 cm for the cubic-shaped batch system [{a
×
1/3
1/3
1/3
1/3
a }/{a × a × a }, a (reaction volume) ) 30.6 µL] and
-
1
the value of 0.33 cm for the NMR tube (in a 0.6 mL reaction
6
volume). Therefore, it is anticipated that the relatively large
contact area between the two channels would facilitate rapid
gas diffusion from the gas channel to the solution channel
through the gas-permeable PDMS layer. A 45 µm thin PDMS
membrane layer was placed between the two PDMS micro-
channels (length, 120 cm; height, 85 µm; width, 300 µm). A
thinner PDMS membrane layer (20 µm) was also tested;
however, it gave poor results because the membrane deformed
due to the large pressure difference between the gas and liquid
channels.
2
. Oxidative Heck Reaction in Various Reaction Systems.
Palladium (Pd) catalysts frequently encountered in the traditional
batch reactions have widely been used for miniature chemical
systems with continuous flow. A heterogeneous Pd system with
nanoparticles immobilized on the microchannel inner surface
or supported on a block copolymer was shown to be highly
efficient in hydrogenation, Suzuki-Miyaura, Sonogashira, and
Results and Discussion
1
. Relative Contact Area between Gas and Liquid Phases
7
other reactions. Moreover, packed-bed systems, ionic liquid
in Various Reaction Systems. At first, we were interested in
the relative contact area between the two phases for the three
types of reaction systems shown in Figure 1. Typical monochan-
nel (MC) microreactors with discontinuous contact between
alternating gas bubbles and liquid slugs have a segmented flow
mode of gas-liquid contact, similar to that found in two
immiscible liquids in a capillary microreactor, which would yield
assisted systems, catalytic membrane reactors, and homogeneous
2c,4,8
catalytic systems have also been studied.
4
a larger contact area than a batch system (Figure 2).
In the MC microreactor (length, 120 cm; height, 85 µm;
width, 300 µm; inlet width, 100 µm), narrowed inlets were
designed to minimize the gap between the bubbles because the
contact area is proportional to the gap thickness (see Figure 2S
in the Supporting Information). Moreover, to maximize the
contact area, we regulated the feed rates of solution (DMF) and
gas (oxygen) and the outlet pressure. However, it was not
possible to get a gap narrower than 300 µm because the bubbles
easily combined or collapsed with the narrower gaps. Fine
control of a steady flow rate in a multiphase microfluidic system
is also difficult to achieve due to the presence of a combination
of the viscous solution and virtually nonviscous oxygen gas.
The volume of the MC microreactor was 30.6 µL (85 µm ×
Compared with the original Heck reaction (eq 1), the Pd-
catalyzed oxidative Heck reaction is recently receiving much
attention in synthetic chemistry for its ability to form C-C
(
(
5) The preparation procedure of the DC microreactor was described in
the Supporting Information (Figure 1S).
6) The contact area to volume ratio depends on the shape and volume of
the reactor. As the simulation for a reaction with narrow contacting
area between gas and liquid, a reaction in the NMR tube was tried
(
Table 2).
(
7) For representative reports on microreactors using immobilized Pd
catalysts, see: (a) Kobayashi, J.; Mori, Y.; Okamoto, K.; Akiyama,
R.; Ueno, M.; Kitamori, T.; Kobayashi, S. Science 2004, 304, 1305–
1
308. (b) Kirschning, A.; Solodenko, W.; Mennecke, K. Chem.sEur.
3
00 µm × 120 cm), and the calculated contact area between
J. 2006, 12, 5972–5990. (c) Baxendale, I. R.; Griffiths-Jones, C. M.;
Ley, S. V.; Tranmer, G. K. Chem.sEur. J. 2006, 12, 4407–4416. (d)
Kawanami, H.; Matsushima, K.; Sato, M.; Ikushima, Y. Angew. Chem.,
Int. Ed. 2007, 46, 5129–5132. (e) Mennecke, K.; Cecilia, R.; Glasnov,
T. N.; Gruhl, S.; Vogt, C.; Feldhoff, A.; Vargas, M. A. L.; Kappe,
C. O.; Kunz, U.; Kirschning, A. AdV. Synth. Catal. 2008, 350, 717–
730. (f) Shore, G.; Morin, S.; Organ, M. G. Angew. Chem., Int. Ed.
the gas bubble (1200 µm long) and liquid slug (300 µm) was
2
0
.408 cm (120 cm/1500 µm × 2 × 300 µm × 85 µm). The
maximum contact area-to-volume ratio in the MC microreactor
was 13.3 cm .
-1
On the other hand, the dual-channel (DC) microfluidic system
separated by a highly gas-permeable thin PDMS layer is
2
006, 45, 2761–2766.
(
8) (a) Uozumi, Y.; Yamada, Y. M. A.; Beppu, T.; Fukuyama, N.; Ueno,
M.; Kitamori, T. J. Am. Chem. Soc. 2006, 128, 15994–15995. (b)
Yamada, Y. M. A.; Watanabe, T.; Torii, K.; Uozumi, Y. Chem.
Commun. 2009, 5594–5596.
(
4) Ahmed-Omer, B.; Barrow, D. A.; Wirth, T. Tetrahedron Lett. 2009,
0, 3352–3355.
5
J. AM. CHEM. SOC. 9 VOL. 132, NO. 29, 2010 10103

A R T I C L E S
Park and Kim
Figure 3. Dual-channel microreactor. (a) Optical image with 45 µm PDMS membrane layer between two fabricated PDMS channels (length, 120 cm;
height, 85 µm; width, 300 µm). (b) The cross-section view of the corner of the dual-channel microreactor.
a
Table 1. Oxidative Heck Reactions in a DC Microreactor
entry
gas (injection rate)
heck
alcohol
Figure 4. Schematic of the dual-channel microchemical system.
1
2
3
4
5
6
7
O
O
O
O
O
N
2
2
2
2
2
2
(10 µL/min)
(20 µL/min)
(25 µL/min)
(30 µL/min)
(35 µL/min)
(30 µL/min)
25%
65%
74%
79%
78%
5%
1%
5%
7%
7%
6%
0%
1%
bonds between various aryl carbons and alkene carbons with
relatively mild reaction conditions and high reaction yields and
without the need for an additional base and expensive organic/
9
inorganic oxidants (eq 2). The push for environmentally
air (30 µL/min)
13%
friendly processes and highly efficient methods has created a
demand for the use of molecular oxygen as a terminal oxidant.
1
0
a
2
Standard reaction conditions: DMF, rt, 5 mol % of Pd(OAc) , 5 mol
%
of [2,2′]-bipyridinyl, 0.5 µL/min injection rate (reagents: 1.0 M
solution). The H NMR yields were recorded using an external capillary
standard.
On the other hand, the introduction of a gaseous reactant has
caused scale-up problems such as long reaction time and side
product formation. These problems are expected to be resolved
through the sufficient contact between dissolved Pd catalyst and
oxygen gas that is now made possible with the dual micro-
channels. It is noted that the oxygen is needed to regenerate
1
solvent (DMF), which was confirmed by a recent study showing
only negligible swelling with DMF. The reactions under dried
13
air and nitrogen gas were also tested, which led to a poor result
or stoichiometric reaction by palladium acetate. For comparison,
we also tried a coaxial microfluidic system developed by
Kobayashi and co-workers under fast gas flow and slow liquid
9
d,11
the active Pd(II) species.
The oxidative Heck reaction was carried out in the DC
microreactor (Figure 4). The two DMF solutions of reagent and
Pd(II) catalyst were injected into the top channel, and the
7a
flow. However, it was not appropriate for the oxidative Heck
injection rates were set at 0.5 µL/min (Table 1). The O
was supplied from the bottom inlet in a precisely controlled
manner by varying the flow rate. In the case of an O injection
rate of 40 µL/min, bubbles formed due to supersaturation of
the O in the solution channel, which in turn generated a
2
gas
reaction because a fast gas flow carried away the volatile alkenes
acrolein, ethyl acrylate) from the solution.
In the small-scale batch system 1 of the oxidative Heck
reaction (Table 2), the extended reaction period (reaction time
2 h) yielded a relatively low reaction selectivity, inevitably
generating a significant amount of aryl alcohol as a side product.
The H generated as an alternative byproduct caused the
decomposition of boronic acid and oxidation of some ligands,
hence excess addition of boronic acid was generally required
for the high reaction yields. Insufficient contact between the
dissolved Pd catalyst and oxygen gas further retarded the
conversion of Pd(0) species to active Pd(II), resulting in a much
delayed reaction, which in turn caused high production of side
products during the extended reaction time. However, both
systems of the MC microreactor and DC microreactor signifi-
cantly suppressed the formation of the aryl alcohol. In the MC
microreactor, total conversions in the range of 67-72% resulted
with 53-59% yields of Heck product and only 6-8% of aryl
alcohol in 30 min of reaction time.
14
(
2
2
1
discontinuous flow (the segmented flow) as in the MC microre-
actor. However, 10 and 20 µL/min injection rates gave low
reaction yields and caused liquid to leak from the solution
channel. Eventually, 30 µL/min was found to be suitable for
preventing supersaturation in the solution channel and leaking
of solution between channels. Furthermore, we found that an
injection rate over 30 µL/min did not increase the reaction yield
and selectivity any more as seen in Table 1. Under the reaction
conditions, neither a blackish tint due to a precipitated Pd(0)
2
O
2
1
2
deposit nor channel deforming was detected even for 2 days
of continuous running or repeated use. The lack of deformation
indicates the compatibility of the PDMS microchannel with the
(
9) (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400–3420. (b) Yoo,
K. S.; Yoon, C. H.; Jung, K. W. J. Am. Chem. Soc. 2006, 128, 16384–
16393. (c) Yoo, K. S.; Park, C. P.; Yoon, C. H.; Sakaguchi, S.; O’Neill,
J.; Jung, K. W. Org. Lett. 2007, 9, 3933–3935. (d) Gligorich, K. M.;
Sigman, M. S. Chem. Commun. 2009, 3854–3867.
(13) Lee, J. N.; Park, C.; Whitesides, G. M. Anal. Chem. 2003, 75, 6544–
6554. PDMS has a good transparency in UV-visible regions, chemical
inertness. A fabrication is easy and requires low cost, compared to
that for microfluidic materials (e.g., glass and silicon). For solvent
compatibility at elevated temperature (60 °C), see the Supporting
Information (Table 1S).
(
(
(
10) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. ReV. 2005, 105,
2
329–2363.
11) For the detailed reaction mechanism, see the Supporting Informa-
tion.
12) XPS spectra for the channel surface of the used DC microreactor show
that there is no significant deposition of Pd(0) species.
(14) In the Kobayashi device, gas over 20 equiv amount should be used to
conduct an efficient result.
1
0104 J. AM. CHEM. SOC. 9 VOL. 132, NO. 29, 2010

Microreactor for Gas-Liquid Syntheses
A R T I C L E S
Table 2. Comparative Synthetic Yields of Oxidative Heck Reactions in Two Types of PDMS Microreactors and Two Types of Batch Systems
a
batch 1 (A%:B%)
d
b
batch 2 (A%)
d
c
MC (A%:B%)
d
c
DC (A%:B%)
d
entry
Ar
R
e
e
e
e
f
1
2
3
phenyl-
phenyl-
4-bromo-phenyl-
-CO
-Ph
-CO
2
Et
Et
69:24
67:25
64:24
19 (20%)
17 (17%)
59:6 (72%)
53:8 (67%)
55:7 (69%)
82:8 (79%)
79:9 (76%)
79:8 (75%)
e
f
f
2
a
b
1
2 h reaction, 1.0 mmol of aryl boronic acid, 1.1 mmol of alkene, and 2 mL of DMF in a 10 mL flask. 3 days reaction, 0.3 mmol scale, and 0.6
c d
1
mL of DMF-d
Conversion. Isolation yield of Heck product A.
7
in an NMR tube. 30 min reaction in a microreactor. The H NMR yields were recorded using an external capillary standard.
e
f
Table 3. Oxidative Heck Reaction of Aryl Boronic Acids with
confirmed the reliable chemical performance of the DC mi-
croreactor. It is notable that all the reactions produced only (E)-
configuration Heck products. The product in entry 6 could be
further elaborated through a combination with a Suzuki or
Sonogashira reaction. It is noted here that the DC microreactor
enabled precise injection of required oxygen into the solution
phase of boronic acid and alkene. It is significant that the precise
control of a gaseous reagent makes it possible to complete a
multistep chemical process without unreacted gas remaining at
each of the successive steps.
Alkenes in the DC Microreactor
a
b
entry
Ar
R
NMR yield (Heck:alcohol)
Heck
1
2
3
4
5
6
phenyl-
2-naphthyl-
2-naphthyl-
2-naphthyl-
4-methoxyphenyl-
4-bromophenyl-
-CHO
-CHO
80%:8%
77%:10%
84%:6%
80%:10%
79%:7%
85%:7%
78%
75%
81%
78%
76%
82%
-CO
2
Et
-phenyl
-CO
-CO
2
2
Et
Et
a
Standard reaction conditions: DMF, rt, 5 mol % of Pd(OAc)
2
, 5 mol
Finally, it is plausible that this type of microreactor would
be extended to a wide range of gas-liquid reactions carried
out at mild temperatures and in polar solvents, including
carbonylation with Pd catalysts, gold-catalyzed reductions of
1
%
of [2,2′]-bipyridinyl, 30 min reaction in the microreactor. The
NMR yields were recorded using an external capillary standard.
Isolatied yield of Heck product.
H
b
1
5
16
nitro compounds, and Pd-catalyzed Saeguesa reactions.
The performance of the DC system was impressive. It should
be noted that the DC system improved significantly reaction
performance in all terms of yield and the reaction selectivity,
which produced yields of 76-85% for the Heck product with
about 10:1 selectivity. The highly effective contact between gas
and solution phases in the DC microreactor rapidly reactivated
Pd(0) species to accelerate the reaction. As a result, the reaction
time was reduced to 30 min, and the decomposition of phenyl
boronic acid to phenol was minimized (Table 2, entry 1). Similar
trends were also observed in the reactions with alternative
alkenes and boronic acids (entries 2 and 3). The usefulness of
the DC microreactor is more clear when the DC microreactor
is compared to a batch system with an extremely small contact
area between two phases and a low mixing efficiency in solution.
We tested the oxidative Heck reaction in an NMR tube (batch
Conclusions
A dual-channel (DC) microreactor has been prepared for
gas-liquid reactions in which intimate contact between gas and
liquid can significantly enhance reaction yield and selectivity.
The dual microchannel reactor that is 120 cm long has been
utilized to investigate an oxidative Heck reaction with gaseous
oxygen to fully derive the benefits attainable through efficient
gas-liquid contact. The DC microreactor has been shown to
deliver much improved reaction yield (72-82% isolation yield)
and selectivity (7.7:1-13.7:1) in much less reaction time (30
min), compared with a small-scale batch system where the
selectivity is 2.7:1-2.9:1 in 12 h of reaction time and with a
batch system with an extremely small contact area where the
yield (NMR yield) is 17-19% in 3 days of reaction. Although
the microreactor was fabricated with PDMS, it can be fabricated
), which has only 0.33 cm-1 contact area to volume ratio (in
2
0
.6 mL reaction volume). The reaction was still not completed
1
after 3 days. The H NMR yield of the Heck product was only
19% and 17%, and black precipitation of Pd(0) was significant.
1
7
The result simply demonstrates the extreme case that can be
encountered in the scaled-up reactor with highly limited contact
efficiency. The comparisons show that the membrane-assisted
DC microreactor is a powerful microfluidic device for gas-liquid
reactions.
with other materials that are more tolerant to solvents and
chemicals for wider applications. The microreactor should prove
to be a powerful tool for fully exploring reactions and syntheses
involving gaseous and liquid reagents.
3
. Various Oxidative Heck Reactions in a Dual-Channel
Microreactor. We further demonstrated the efficiency of the DC
microreactor with the C-C bond-forming reactions of a variety
of alkenes and boronic acids (Table 3). Phenyl boronic acid
effectively reacted with acryl aldehyde to produce cinnamal-
dehyde (entry 1). 2-Naphthyl boronic acid also reacted with
acrylic ester, styrene, and acrylaldehyde with even higher yields
and excellent selectivity. The oxidative Heck reactions with the
use of 4-methoxy- and 4-bromo-phenyl boronic acid further
(15) He, L.; Wang, L.; Sun, H.; Ni, J.; Cao, Y.; He, H.; Fan, K. Angew.
Chem., Int. Ed. 2009, 48, 9538–9541.
(
16) (a) Liu, J.; Zhu, J.; Jiang, H.; Wang, W.; Li, J. Chem. Asian J. 2009,
4
, 1712–1716. (b) Liu, J.; Zhu, J.; Jiang, H.; Wang, W.; Li, J. Chem.
Commun. 2010, 46, 415–417.
(17) We developed novel polymer microfluidic devices with high solvent
resistance: (a) Yoon, T. H.; Park, S. H.; Min, K. I.; Zhang, X.; Haswell,
S. J.; Kim, D.-P. Lap Chip 2008, 8, 1454–1459. (b) Kim, B.-Y.; Hong,
L.-Y.; Chung, Y.-M.; Kim, D.-P.; Lee, C.-S. AdV. Funct. Mater. 2009,
19, 3796–3803.
J. AM. CHEM. SOC. 9 VOL. 132, NO. 29, 2010 10105

A R T I C L E S
Park and Kim
Experimental Section
in the same manner as the reagent connections. The injection rates
of reagent and catalyst were set at 0.5 µL/min, and that of the gas
was set at 30 µL/min. The reaction result was collected in a vial
through a segment of PTFE tubing. Reaction yield and selectivity
were measured by the H NMR analysis using an external capillary
standard. The mixtures were purified through extraction with ethyl
acetate(EA)fromtheDMF/watersolutionandcolumnchromatography.
General Description of the Oxidative Heck Reaction Using
the MC Microreactor. In one syringe was loaded a 1 mL DMF-
d
7
solution of aryl boronic acid (1.0 mmol) and alkene (1.1 mmol),
and in another syringe was loaded a 1 mL DMF-d solution of the
Pd(II) complex prepared with 0.05 mmol of Pd(OAc) and 0.05
1
7
2
mmol of [2,2′]-bipyridinyl. Oxygen supply was placed in the third
inlet. The reaction streams were introduced to the three inlets of
the monochannel microreactor through a 25 cm segment of
polytetrafluoroethylene (PTFE) tubing. The injection rates of reagent
and catalyst varied from 0.2 to 0.5 µL/min, and that of the gas
varied from 20 to 200 µL/min. The reaction result was collected in
a vial through a segment of PTFE tubing. Reaction yield and
Acknowledgment. This work was supported by the National
Research Foundation of Korea (NRF) grant funded by the Korea
government (MEST) (20100000722).
Supporting Information Available: Experimental details for
the preparation of the microreactors and reaction procedure. The
solvent compatibility of PDMS at elevated temperature (60 °C).
The XPS spectra for a channel surface of the used DC
1
selectivity were measured by the H NMR analysis using an external
capillary standard.
General Description of the Oxidative Heck Reaction Using
the DC Microreactor. Three lines for reagent, catalyst, and oxygen
were prepared in the same manner as in the MC microreactor. The
streams of reagent and catalyst were introduced to the two top-
channel inlets through a 25 cm segment of PTFE tubing. The
oxygen gas stream was introduced to the inlet of the bottom channel
1
13
microreactor and H NMR and C NMR spectral data for
isolated Heck reaction products. This material is available free
of charge via the Internet at http://pubs.acs.org.
JA102666Y
1
0106 J. AM. CHEM. SOC. 9 VOL. 132, NO. 29, 2010