Efficient photosensitized oxygenations in phase contact enhanced microreactors

Article abstract of DOI:10.1039/c1lc20071b

A transparent dual-channel microreactor with highly enhanced contact area-to-volume ratio was fabricated for efficient photosensitized oxygenations. The dual-channel microreactor shielded with polyvinylsilazane (PVSZ) consisting of an upper channel for liquid flow and a lower channel for O₂ flow, allows sufficient phase contact along the parallel channels through a gas permeable PDMS membrane for maintaining the O₂ saturated solution. Under full exposure of reactants to light, the reactions in high concentration are completed in minutes rather than hours that it takes to complete in a batch reactor. Moreover, the scale-up process using the microreactor revealed higher productivity than the batch reactor, which would be valuable for the practical applications in a broad range of gas-liquid chemical reactions.

Full text of DOI:10.1039/c1lc20071b

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PAPER
Efficient photosensitized oxygenations in phase contact enhanced
microreactors†
Chan Pil Park,‡ Ram Awatar Maurya,‡ Jang Han Lee and Dong-Pyo Kim*ab
a
a
ab
Received 26th January 2011, Accepted 21st March 2011
DOI: 10.1039/c1lc20071b
A transparent dual-channel microreactor with highly enhanced contact area-to-volume ratio was
fabricated for efficient photosensitized oxygenations. The dual-channel microreactor shielded with
polyvinylsilazane (PVSZ) consisting of an upper channel for liquid flow and a lower channel for O
flow, allows sufficient phase contact along the parallel channels through a gas permeable PDMS
2
2
membrane for maintaining the O saturated solution. Under full exposure of reactants to light, the
reactions in high concentration are completed in minutes rather than hours that it takes to complete in
a batch reactor. Moreover, the scale-up process using the microreactor revealed higher productivity
than the batch reactor, which would be valuable for the practical applications in a broad range of gas–
liquid chemical reactions.
Introduction
volume. With these advantages, the microchemical system could
34–36
be positioned as a powerful tool for the photoreactions.
Pioneering photosensitized oxygenations in microreactors
37–41
Photosensitized oxygenation conducted only with light and O2
gas is one of the most promising routes among green chemical
were recently reported by several groups.
The optical trans-
1,2
processes. Besides lab-scale applications in organic synthesis,
1
an activated singlet oxygen ( O
parency and short light path of the microreactors provided
a sufficient amount of light onto reaction species, unlike the
batch reactor. However, the insufficient gas transfer between the
gas and liquid binary phases in the single channel microreactor
lowered the reaction rate in the oxygenation. For this reason, the
reactions were often conducted in diluted reactant conditions
2
) has successfully been utilized in
the production of various fragrances, pharmaceuticals, and fine
3–7
chemicals with high selectivity.
In a typical batch system,
oxygen is bubbled through a liquid reactant under simultaneous
irradiation of light. This arrangement requires a prolonged
reaction time due to very low surface to volume ratio that results
in a poor supply of photons absorbed. Moreover, the short
(
less than 0.1 M), or under high pressure of supercritical condi-
tion (140 bar). Alternatively, pre-saturation of reactants solution
with O was also attempted to ensure better supply of O that is
1
lifetime of O in organic solvents (9.5 ms in CH OH and 77.1 ms
2
3
2
2
8,9
in CH CN) and long molecular diffusion distance in the system
3
continuously consumed during the reaction. However, it is still
unsatisfactory in that the conventional microreactors needed
reduce the reaction efficiency significantly.
Microfluidic systems have provided distinct advantages such
as very high surface area-to-volume ratio, short molecular
diffusion distance, simple feasibility study for scaling up, highly
prolonged reaction time with excess solvent wasted to dissolve O
2
into the liquid. These factors have made it difficult to achieve the
most important attempt in microchemical society, which is to
replace the typical batch system with a microchemical system for
the gas–liquid binary phase reactions. Therefore, it still demands
a new approach for making the intimate contact between the two
phases.
10–33
reduced waste, and precise control in reaction parameters.
Furthermore, the systems can provide high spatial illumination
homogeneity, excellent light penetration throughout the micron-
scale reactor and a very large illuminated surface area per unit
Herein we report a high-throughput microchemical approach
for photosensitized oxygenations in condensed solution, with
a microreactor specifically designed to ensure efficient supply of
a
National Creative Research Center of Applied Microfluidic Chemistry,
Chungnam National University, Daejeon, 305-764, South Korea. E-mail:
2
O into the liquid and full exposure of the reactants to light. The
dpkim@cnu.ar.kr; Fax: +82-42-823-6665
b
reactions are completed in minutes rather than hours that it
usually takes to complete in a typical batch reactor. Fig. 1
Graduate School of Analytical Science and Technology, Chungnam
National University, Daejeon, 305-764, South Korea
illustrates photosensitized oxygenation in
microreactor, which consists of an upper channel for liquid flow
and a lower channel for O flow. A gas permeable PDMS
a dual-channel
†
Electronic supplementary information (ESI) available: Experimental
details for the preparation of the microreactors and reaction procedure.
See DOI: 10.1039/c1lc20071b
2
‡
These authors contributed equally to this work.
membrane ensures separation between gas and liquid flows along
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Fig. 1 Schematic illustration of photosensitized oxygenation in a dual-
channel microreactor shielded with solvent resistant coating.
the parallel channels, and allows supply of O
channel to the upper channel that is sufficient for maintaining the
solution saturated with O , even though the reaction consumes
the dissolved O continuously.
2
from the lower
2
2
Fig. 2 (A) Schematic illustration for fabrication of a dual-channel
microreactor with PVSZ shielded upper channel. (B) Cross-sectional view
of dual microchannel with the PVSZ shielded upper channel. (C) The
Results and discussion
1
. Fabrication of a dual-channel microreactor with PVSZ
PVSZ shielded dual-channel microreactor filled with O
photosensitizer), and a-terpinene (reagent).
2
, methylene blue
shielded upper channel
(
It is well known that PDMS microfluidic channels fabricated by
the low-cost soft lithography technique suffer from solvent
4
2
swelling. Recently, we reported a poly(dimethylsiloxane)
PDMS) based dual-channel microreactor, in which two parallel
channels are divided by a gas permeable PDMS membrane and
the PVSZ cladding layer was solidified through a series of UV
and thermal curing steps. The PVSZ shielded, PDMS upper
liquid channel was bonded with a thin PDMS membrane and the
lower PDMS gas channel through a plasma treatment. Detailed
fabrication procedure and stability test against various organic
solvents are described in the ESI, Fig. 1S†. Eventually, the upper
channel surface shielded by the solvent resistant coating defi-
nitely promoted the solvent durability of the channel. The
bottom part of the upper channel, which is the upper surface of
the middle PDMS membrane layer, should not be coated with
(
43
as such, a continuous supply of gas was possible. The intimate
contact made possible between the gas and liquid phases led to
a significantly enhanced performance in the oxidative Heck
reactions with non-swelling solvent. However, the reported
PDMS microreactor could be used only for one day operation of
the photosensitized reaction due to the swelling problem.
Therefore, we needed to come up with a new fabrication tech-
nique for the microreactor that can be used for organic syntheses
without sacrificing the advantage of easy and cost-saving fabri-
ꢀ1
PVSZ layer to allow gas diffusion. Upon over 60 mL min of
continuous O injection flow through the PDMS membrane, the
2
44,45
cation that PDMS microfluidic devices offer.
We were
high enough internal pressure could be induced in the PDMS
network to prevent solvent diffusion at the upper solution
channel, resulting in no deformation under continuous running
(see ESI, Fig. 2S†). In addition, the PVSZ shielded PDMS
channel retained optical transparency as confirmed by UV-Vis
absorption spectrum (see ESI, Fig. 3S†).
motivated by our recent work on a monolithic type of solvent
resistant microfluidic device fabricated with polyvinylsilazane
(
PVSZ, KION VL-20ꢀ, Clarient, USA) in that the same
approach might lead to an improvement in the chemical stability
46
and solvent compatibility of the plain PDMS channel. We
shielded the inner surfaces of the upper channel among the two
channels that are in contact with the organic solvent, which
involves an inexpensive and simple method. Fig. 2A illustrates
the fabrication procedure for the microreactor with PVSZ
shielded channel, and Fig. 2B and C, respectively, show a cross-
sectional view of the dual-channel in the microreactor and the
image of the device filled with the reagent, blue photosensitizer,
In Fig. 3, we compared the reactor volumes and contact area-
to-volume ratios in the batch system, single layer channel system
(henceforth to be referred to as mono-channel), and the PVSZ
shielded dual-channel microreactor (henceforth to be referred to
as dual-channel). The measured volume of the upper liquid
channel in the dual-channel was 38.9 mL, and the calculated
contact area between the liquid channel and gas channel was
2
and gaseous O
2
for performing the photosensitized oxygenation.
1.98 cm . The contact area-to-volume ratio was significantly
ꢀ1
ꢀ1
The PVSZ polymer was first spin-coated onto a thick PDMS slab
with concave channel structure to obtain a cladding layer. Cross-
sectional images in Fig. 2B show a variable thickness, depending
on locations inside the channel, which ranges from 15 mm at the
top to 80 mm at the corner. The coated polymer on the PDMS
slab was gently wiped out with a glass slide to remove the excess
polymer except for the concave part of the surface. Subsequently,
enhanced to 50.9 cm , that is much larger than 14.9 cm of the
ꢀ1
mono-channel and 0.76 cm of the 50 mL batch system (see ESI,
Fig. 4S†). In addition, we prepared an alternative dual-channel
microreactor for the feasibility of scale-up (see ESI, Fig. 5S†),
which has the upper liquid channel with 285 mL volume and the
2
contact area of 12.2 cm , the calculated contact area-to-volume
ꢀ
1
ratio was 42.8 cm .
1
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The batch system with the lowest phase contact area-to-volume
ratio shows a very slow reaction rate even with the supply of the
solution pre-saturated with O . The mono-channel has an
2
inherent problem of controlling the heterogeneous gas and solu-
2
tion. Increasing the injection rate of O in the mono-channel also
caused the acceleration of solution droplets, thereby it resulted in
poor conversions with shorter retention times. However, the
injection rates and flow rates of the solution and O
separately controlled in the dual-channel, which forced rapid
diffusion of O into the solution through the membrane with the
2
could be
2
highest phase contact area-to-volume ratio. In the mono-channel
and batch system, poor supply of gaseous O into the organic
2
1
solution lowered the generation rate of O by activated photo-
Fig. 3 Comparative illustration of contacting modes between the gas
2
and liquid phases in the two types of microreactors and the batch system.
sensitizer with short lifetime. More importantly, high concentra-
tion results clearly show large differences in the throughput
(
entries 4–6). The dual-channel completed the reaction in exactly
2
. Photosensitized oxygenations in various reaction systems
the same time as for the low concentration case even though the
reactant concentration is increased by a factor of 3.5 (entry 4),
while the reaction time required for a similar yield is almost tripled
when the reactant concentration is increased by a factor of 3.5
from 0.1 M (entry 3) to 0.35 M when the batch is used (entry 6). A
comparison was made between the mono-channel and the dual-
channel in terms of the product obtainable in one day for the same
reactor volume of 38.9 mL. The dual-channels in entries 1 and 4
could generate 1.81 mmol and 6.34 mmol, respectively, while the
mono-channels in entries 2 and 5 only gave 0.35 mmol and 0.59
The first choice we made for the photosensitized oxygenation is
the reaction of (ꢀ)-citronellol which is an important synthetic
transformation industrially, and the reaction is used for the bulk
47
production of a fragrance, rose oxide. In the experiment we used
a 16 W white LED light source (FAWOO-Tech., Korea, LH16-
AFE39S-White) instead of classical halogen or filament lamps.
The LED lamp is small in size, efficient and ‘‘cold’’ such that it can
be kept in close contact with the microreactors without any
48
overheating hazard. Summarized in Table 1 are the results
50
obtained from 4 different types of reactors: two dual-channel
mmol. The results showed that the dual-channel can generate
more than 10 times the amount producible from the mono-
channel for the case of 0.35 M concentration, while it is more than
5 times in the case of lower reactant concentration of 0.1 M. In this
49
microreactors with solvent resistant coating, a mono-channel
microreactor for segmented flow reaction of O and the solution,
2
and a batch system with 20 mL solvent in 50 mL round bottom
flask. The reactions in the dual-channel conducted without pre-
comparison, the volume occupied by O
2
was not considered in the
in the 0.35 M
treated O bubbling are completed in 3 min (entry 1) while it took 3
2
calculation for the mono-channel. The volume of O
2
hours for the reactions to complete in the batch systems (entry 3).
solution was such that the reactor volume corresponding to the
liquid reactant was less than 20% of the original reactor volume,
while the liquid volume in the 0.1 M concentration was a little bit
51
Table 1 Photosensitized oxygenation of (ꢀ)-citronellol in 3 different
over 40% of the reactor volume. In order to test the feasibility for
scale-up, the reaction volume of the dual-channel microreactor
was increased to 285 mL (entry 7), which is 7.3 times higher than
the volume of the dual-channel microreactor in entries 1 and 4
with 38.9 mL reaction volume. Although the yield in entry 7 was
slightly decreased from the original dual-channel, the obtainable
a
types of microreactors, compared to the batch system
52
product from the 285 mLvolume was45.49 mmol in one day. The
productivity was 2.6 times that of the batch system which can
generate 17.6 mmol with 50 mL volume flask during the same time
53
c
b
(
entry 6). These results clearly demonstrate the superiority of the
Entry Reactor
Conc.
Time
Yield
Daily output
dual-channel over the mono-channel and batch system. The high-
throughput system in a solvent-saving manner would be a strong
incentive for practical applications of the dual-channel for
photochemical syntheses in gas–liquid binary phases.
1
2
3
4
5
6
7
Dual-channel 0.1 M
Mono-channel 0.1 M
Batch 0.1 M
Dual-channel 0.35 M 3 min
Mono-channel 0.35 M 31 min
3 min
15 min
180 min 92%
97%
95%
1.81 mmol
0.35 mmol
14.7 mmol
6.34 mmol
0.59 mmol
17.6 mmol
45.49 mmol
d
e
97%
94%
d
e
Batch
Dual-channel
0.35 M 510 min 89%
0.35 M 3 min 95%
f
3. The effect of reaction parameters in the dual-channel
a
(photosensitized oxygenation of a-terpinene into ascaridole)
Standard reaction conditions: 1 mol% methylene blue, 16 W LED lamp,
ꢁ
b
1
5
internal standard after NaBH
C. Yield and ratio were recorded with H NMR analysis using an
treatment of crude mixture.
To investigate the effect of reaction parameters in the dual-
channel (38.9 mL reaction volume), photosensitized oxygenation
of a-terpinene to ascaridole was carried out under various
4
c
d
Concentration of (ꢀ)-citronellol in reactors.
reaction of O and reagent solution pretreated with O
min. 20 mL solution (7 mmol scale) pretreated with O
Segmented flow
bubbling for 20
bubbling for
0 min in 50 mL round bottom flask. The dual-channel microreactor
2
2
e
2
reaction conditions:
O
2
flow rate, reaction temperature,
f
2
38–40,54
concentration of photosensitizer (Fig. 4).
The amount of
for feasible scale-up process with 285 mL reaction volume.
photosensitizer (PS) less than 1 mol% or the temperature higher
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Scheme 1 Photosensitized oxygenation of allylic alcohols.
dual-channel successfully retained the consistent reaction effi-
ciency with no degradation and no channel leaking problem.
Note that the dual-channel has a high illuminated surface to
2
volume ratio, and efficient O supply as well as highly trans-
parent solvent resistant coating. These factors led to the
completion of the reactions in a short retention time of only 122
seconds.
Conclusion
A phase contact enhanced microreactor most suitable for pho-
tosensitized oxygenation is presented that can compete with the
conventional batch reactor in practical applications. The dual-
channel, in which the surface of the liquid channel is shielded
from the ill effects of liquid reactants and solvents by a cured
Fig. 4 Photosensitized oxygenation of a-terpinene into ascaridole in the
dual-channel (0.35 M substrate, 38.9 mL reactor volume) and batch
system. The conversion was recorded by GC/MS analysis, yields were
2
PVSZ, allows efficient supply of O to the liquid and full expo-
1
sure to light. As a result, the reactions in high concentration are
completed in minutes rather than hours that it takes to complete
in a batch reactor, the dual-channel with only 285 mL volume can
provide 2.6 times productivity from the batch system with 50 mL
volume. As such, it would be invaluable not only for the pho-
tosensitized oxygenation but also for other gas–liquid organic
reactions.
measured by H NMR analysis. [a] Photosensitizer (methylene blue). [b]
Time required for reaction completion. [c] 7 mol scale in 50 mL round
bottom flask.
ꢁ
than 5 C resulted in unsatisfactory performance, the first due to
low efficiency in absorbing photons and the second due to
1
shortened lifetime of the O
9
tively. The optimized flow rate of O
2
at elevated temperature respec-
ꢀ1
2
was 105 mL min for
Acknowledgements
0
.35 M concentration with a reaction time of 3 min. N
2
used in
injection rates of 60 and
place of O
2
ꢀ
gave no oxygenation. O
1
2
This work was supported by the National Research Foundation
of Korea (NRF) grant funded by the Korea government (MEST)
8
5 mL min were found to slow down the reaction compared
ꢀ1
ꢀ1
2
with 105 mL min . O injection rate of over 105 mL min caused
(
20100000722).
bubble formation due to supply in excess of the solubility limit,
and the bubbles disturbed the liquid flow in the reaction system.
The batch system tested for comparison showed poor reaction
yield even after a prolonged reaction time as shown in the results
in Table 1. The trial of the condensed reaction with the
concentration in excess of 0.35 M was not successful due to the
low solubility of methylene blue in the concentration range.
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49 An acetonitrile solution (3 mL) of (ꢀ)-citronellol (3.5 mmol) was
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(concentration of (ꢀ)-citronellol ꢂ reactor volume ꢂ running time/
retention time ꢂ yield); entry 2 ¼ 0.1 mmol/1 mL ꢂ 38.9 mL ꢂ 24
ꢂ 60 min/15 min ꢂ 0.95; entry 4 ¼ 0.35 mmol/1 mL ꢂ 38.9 mL ꢂ
24 ꢂ 60 min/3 min ꢂ 0.97; entry 5 ¼ 0.35 mmol/1 mL ꢂ 38.9 mL ꢂ
24 ꢂ 60 min/31 min ꢂ 0.94.
51 Detailed calculation is described in the ESI, Fig. 6S†.
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retention time ꢂ yield).
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Lab Chip, 2011, 11, 1941–1945 | 1945