Safe use of a toxic compound: Heterogeneous OsO4 catalysis in a nanobrush polymer microreactor

Article abstract of DOI:10.1002/anie.201301124

Putting osmium in its place: The immobilization of hazardous OsO ₄ on polymer nanobrushes in a microreactor is a safe, effective, and green concept. The method allows reactions to be performed in a time- and chemical-saving manner, with little environmental impact, as compared to spill-over bulk processes. Copyright

Full text of DOI:10.1002/anie.201301124

Angewandte
Chemie
DOI: 10.1002/anie.201301124
Microreactors
Safe Use of a Toxic Compound: Heterogeneous OsO4 Catalysis in
a Nanobrush Polymer Microreactor**
K. C. Basavaraju, Siddharth Sharma, Ram Awatar Maurya, and Dong-Pyo Kim*
Some catalysts are toxic and volatile, this volatility allows
permeation of the toxin throughout its environment, and yet
these catalysts are, in many cases, essential for organic
synthesis. Therefore, in recent years, much attention has
been given to immobilization and reuse of these catalysts,
mostly on solid supports in bulk reaction systems.
Osmium tetroxide (OsO4) is such a catalyst. It is an
excellent catalyst for dihydroxylation and oxidative cleavage
of olefins, but it is highly toxic, hazardous, expensive, and
volatile in nature. To overcome these issues, many researchers
have developed different strategies for its immobilization or
encapsulation on polymers and inorganic substrates.[1] How-
ever, all of these supported catalyst systems need a high
loading of osmium to achieve good conversions in reasonable
reaction times compared to homogeneous reactions. Despite
various attempts to recycle the catalyst, the recovery and
reuse of osmium is still a very difficult task, as leaching of
osmium is inevitable in a bulk reaction system under
mechanical agitation for good mixing.[1l,n]
These difficulties suggest the use of microfluidic systems,
which have already been shown to offer various advantages
over traditional large-scale batch chemistry.[2] In particular,
the microreactor is a suitable system for the synthesis and use
of potentially hazardous compounds, as only very small
amounts of compounds/reagents are handled. Therefore, the
robust immobilization of toxic catalysts on microreactor
channel is a promising strategy to increase safety and reaction
efficiency, while reducing environmental impact.[3]
catalyst for complete utilization. Immobilization of OsO4
onto nanobrush-like poly(4-vinylpyridine) (P4VP) on the
inner wall of the microreactor is more convenient and
efficient than a packed-bed microreactor, because there are
few problems with blocking/clogging or pressure drop in
a continuous flow system.[4] The silicone rubber PDMS has
been the most widely used for manufacturing microfluidic
devices, owing to its simplicity, low cost, and easy fabrication
(only requiring a photomask and photoresist) versus other
complicated techniques. However, plain PDMS is not suitable
for organic reactions, as it swells in organic solvents.[5]
Therefore, the surface of the PDMS channel was modified
using a photo/thermal-curable preceramic polyvinylsilazane
(PVSZ) polymer to form a protective coating layer, as
reported from our own work.[6] The PVSZ-coated PDMS is
not only resistant to organic solvents, but also allows attach-
ment of a nanobrush-like P4VP polymer layer to the PVSZ
wall by a “grafting-to” approach.
For the attachment, a method was developed to covalently
bond the P4VP nanobrush layer to the inner wall of the
PVSZ-modified PDMS microchannel. The P4VP polymer
chains contain tertiary nitrogen atoms in the para position of
a repeating pyridine unit that can be used for the immobi-
lization of OsO4.[1k] Scheme 1 shows dihydroxylation and
Herein, we present the concept behind and the fabrication
of a microreactor that allows the safe use of OsO4 without
leaching or spill problems of this toxic catalyst, and yet
permits its use at the molecular level in a durable and reusable
manner. The microreactor is
a poly(dimethysiloxane)
(PDMS) microchannel reactor, the modified wall surface of
which is covered with a nanobrush polymer coating that is in
turn used to immobilize the costly and highly toxic OsO4
Scheme 1. Continuous flow dihydroxylation and oxidative cleavage of
olefins in the PVSZ/PDMS-based microreactor with immobilized OsO4
catalyst on P4VP polymer nanobrushes.
[*] Dr. K. C. Basavaraju, Dr. S. Sharma, Prof. Dr. D.-P. Kim
National Centre of Applied Microfluidic Chemistry, Dept. of Chem.
Eng., POSTECH (Pohang Univ. of Sci. & Tech.)
Pohang, 790-784(South Korea)
oxidative cleavage reactions (See the Supporting Information
for details) that take place inside the microchannel, the
surface of which is covered with OsO4 immobilized on P4VP
nanobrushes, which is attached to the microchannel wall. In
this approach, the mono-hydroxyl-terminated P4VP polymer
with a molecular weight around 52 kDa (Mn) and a narrow
polydispersity was initially synthesized by a radical polymer-
ization technique mediated by hydroxytetramethylpiperidine
(HO-TEMPO; Figures S2 and S3). The monohydroxy-termi-
nated P4VP was then converted into NCO-terminated P4VP
by treatment with excess hexamethylene diisocyanate at
E-mail: dpkim@postech.ac.kr
Homepage: http://camc.postech.ac.kr/
Dr. R. A. Maurya
Division of Natural Product Chemistry, CSIR-Indian Institute of
Chemical Technology, Hyderabad-500007(India)
[**] This work was supported by National Research Foundation of Korea
(NRF) grant funded by the Korean government (MEST) (2008-
0061983).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201301124.
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PDMS channel was very stable, with no degradation during
modification in organic solvent at elevated temperature
(Figure S5). To estimate the thickness of the nanostructure
on the channel wall, a PVSZ-coated layer on a silicon wafer
was grafted by keeping the wafer in P4VP-NCO polymer
solution for 1 h at 608C; AFM analysis then confirmed that
the thickness is around 85 nm (Figure S6). It is significant that
the thickness of the nanobrush layer is close to the theoretical
value calculated based on the degree of polymerization. (L =
ca. N2/3, where L and N are the thickness and the degree of
polymerization of the polymer chains, respectively).[8] The
surface morphology was also investigated by AFM at differ-
ent scales (Figure S7), and it is clear that the P4VP layer fully
covered the PVSZ coated surface with a dense globular
structure, with a size distribution that is ca. 30–50 nm wide
and ca. 2–10 nm high. The observed morphology resembles
the characteristic nature of polymer brushes obtained through
the grafting-to approach.[9]
Figure 1. OsO4 immobilization on P4VP nanobrush anchored micro-
reactor; A) Cross-sectional SEM images of P4VP–NCO coated micro-
channel, B) Optical image of the fabricated microreactor with immobi-
lized OsO4. Microchannel dimension: 90 cm long, 500 mm wide, ca.
85 mm high.
To immobilize OsO4 catalyst on the nanobrush P4VP
polymer, the microreactor was connected to a syringe pump
through PTFE tubing with airtight joints to prevent leakage
or exposure to the toxic OsO4 catalyst. An OsO4 solution
(0.1 wt.%) in water was infused continuously through the
channel at 100 mLminÀ1 at room temperature for 40 min. The
amount of immobilized OsO4 inside the microreactor could
be quantified by an in-house method using ICP-MS instru-
ments (Table S1). Figure 2 shows that about 50 mg of OsO4 in
elevated temperature. The free NCO stretching peak at
2260 cmÀ1 and N H stretching peak from the urethane group
À
at 3420 cmÀ1 were confirmed by FTIR analysis (Figure S3B).
Figure 1 illustrates the immobilization of OsO4 and
stabilization in a microreactor (Figure S1). Two identical
PDMS channels were fabricated that are 500 mm wide and 40–
45 mm high. The concave surface was treated with plasma and
then spin-coated with PVSZ. The two PVSZ-coated channels
were carefully aligned, and consolidated by UV irradiation
for 30 min followed by thermal curing at 1508C in open
atmosphere for 2 h with a controlled heating and cooling rate.
Open exposure to a humid atmosphere during the curing step
À
À
À
caused partial hydrolysis of the Si H and Si NH Si bonds of
À
the PVSZ polymer into silanol (Si OH) groups.
Further modification of the microchannel surface was
conducted through the grafting-to approach, which takes
advantage of the dual functionalities on the channel wall and
the linear P4VP polymer nanobrushes. The single-end-
functionalized P4VP-NCO polymer (0.5 wt.%) was dissolved
in anhydrous chloroform and continuously passed through the
channel for 1 h at a rate of 100 mLminÀ1 using a syringe pump
at 608C. The NCO group of the polymer was very reactive
towards the silanol group of the PVSZ surface and formed
urethane bridges to covalently bond the P4VP chain to the
chemically stable microreactor channel wall.
À
À
P4VP-NCO can also react with the remaining NH
functional groups of partially hydrolyzed PVSZ, which
provides an alternative reaction route.[7] FTIR analysis
confirmed that the NCO stretching peak at 2260 cmÀ1
Figure 2. Amount of immobilized OsO4 as a function of flow time in
different microreactors with identical channel dimensions (90 cm long,
500 mm wide, ca. 85 mm high) when OsO4 (0.1 wt.%) solution was
infused with a flow rate of 100 mLminÀ1
.
À
disappeared and the N H stretching peak from the urethane
group at 3420 cmÀ1 remained, which is an indication of
a bridge between the P4VP polymer and the PVSZ surface
(Figure S4C). The channel was further washed with chloro-
form to remove any unreacted P4VP and then the nanobrush-
decorated microreactor was dried under vacuum. It is
believed that the nanobrushes were covalently bound by
total was immobilized inside the microreactor channel (90 cm
long, 500 mm wide, ca. 85 mm high), which had been coated
with a P4VP nanobrush layer with a molecular weight of
52 kDagmolÀ1, in 40 min of flow time.
À
coupling between NCO at the chain end of the linear brush
The microchannel loaded with OsO4–P4VP showed
a yellowish tint and the catalytic activity almost vanished
after 1 day, even in a closed environment. This is presumably
À
À
À
P4VP polymers and the OH/ NH functionalized PVSZ
layer on the substrate. The protective PVSZ layer on the
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Table 1: Dihydroxylation of olefins in the OsO4–P4VP nanobrush micro-
due to the instability of OsO4. Therefore, further treatment
was conducted to enhance the stability of the immobilized
catalyst by continuously feeding THF as a reducing agent
through the channel after loading the OsO4, and the yellow
color turned to dark blue, indicating the formation of an oxo-
osmium(VI) pyridine complex. Hermann and co-workers
reported that THF as a reducing agent lowered the oxidation
state of osmium to the osmium(VI) oxide complex. They
found that the structure was more stable in open atmosphere
than OsO4 and that identical catalytic activity to OsO4 was
maintained in the presence of oxidizing agents.[10]
Furthermore, the distribution of osmium metal inside the
channel was determined by observing the horizontally cut
OsO4-P4VP nanobrush microchannel using a high resolution
SEM. Both EDX (energy dispersive X-ray spectroscopy) Os
mapping and EDX spectra confirmed the uniform distribu-
tion of osmium throughout the channel surface (Figure 3; see
also Figure S8).
reactor[a]
Entry Substrate
Product
Conversion[b]
(Yield)[c] [%]
1
2
3
4
5
99 (92)
98 (93)
98 (94)
99 (95)
99 (94)
[a] All reactions were performed at room temperature for 10 min using one
microreactor for each product with identical reactor dimensions (l=90 cm,
w=500 mm, h=ca. 85 mm, volume=ca. 40 mL), acetone/water (10:1) as
solvent, olefin (10 mmol), and NMO (1 equiv). [b] Conversions were
determined by GCMS using anisole as an internal standard. The average of
three independent runs in the same microreactor is given in the table.
[c] Yield of isolated product.
Figure 3. Horizontal cross-sectional SEM image of the OsO4–P4VP
nanobrush microchannel and the corresponding EDX mapping of Os
metal (see also Figure S4 for EDX spectra).
was also confirmed by running the same experiment and
observing no significant change in the results after the reactor
had been stored for three months after fabrication. Oxidative
cleavage reactions were performed in a THF/water mixture in
the presence of NaIO4 as an oxidant. As shown in Table 2,
these reactions, with an average productivity of around
With the osmium oxide bonded nanobrush microreactor
prepared, the catalytic performance and the efficiency of the
microreactor were investigated in two reactions:
dihydroxylation and oxidative cleavage of olefins.
Table 2: Oxidative cleavage of olefins in the OsO4–P4VP nanobrush microreactor.[a]
Both of these reactions are quite important in both
academia and industry for the production of active
intermediates that are required for the syntheses of
natural products, pharmaceuticals, and fine chem-
icals.
Entry Substrate
Product
Conversion[b]
(Yield)[c] [%]
1
2
99 (91)
99 (92)
For dihydroxylation reactions, N-methylmorpho-
line N-oxide (NMO) was used as a co-oxidant in an
acetone/water mixture (10:1).[1m] A 72 cm long
microchannel was fabricated for this study, including
an 18 cm long serpentine mixing zone. For the
dihydroxylation, biomass-based aliphatic and aro-
matic olefins were selected. As shown in Table 1, the
reactions reached 99% conversion in 10 min. Only
0.002 mol% of OsO4 was needed in the microfluidic
reactor to catalyze the reaction of 10 mmol of olefins
with excellent conversion (based on 50 mg of OsO4),
this is 50 times more efficient than bulk reaction
systems.[1m,n] Furthermore, the productivity of
around 1.0 mmolhÀ1 remained the same, even when
the microreactor was continuously used for 10 h
under identical conditions, thus indicating good
3
4
98 (94)
99 (93)
99 (A: 75)
(B: 67)
5
[a] All reactions were performed at room temperature for 7 min using one
microreactor for each product with identical reactor dimensions (l=90 cm,
w=500 mm, h=ca. 85 mm, volume=ca. 40 mL), THF/water (2:1) as solvent, olefin
(10 mmol), and NaIO4 (2 equiv). [b] Conversions were determined by GCMS using
anisole as an internal standard. The average of three independent runs in the same
durability. Reusability of the reactor and the catalyst microreactor is given in the table. [c] Yield of isolated product.
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1.3 mmolhÀ1, were faster than the dihydroxylation reactions,
reaching more than 98% conversion within 7 min of reaction
time. The reaction times were optimized for both dihydrox-
ylation and oxidative cleavage by periodically checking the
conversions at different residence times. The height of the
microchannel for this P4VP nanobrush system was varied
with the width fixed at 500 mm. It was found that a height of
less than 100 mm is desirable for better performance, this is
presumably due to better access of the reactants to the
catalyst under flow conditions. The osmium content in the
reaction mixtures was analyzed by ICP-MS to check for
leaching during these reactions, and was found to be in the
range of 30–50 PPB level in both reactions.
The superiority of the present microfluidic polymeric
nanobrush strategy over other supported systems can be
explained by the excellent solubility and wettability of the
nanobrushes in the reaction medium. Thus, the reagents
readily diffuse and reach all of the catalytic units on the
nanobrush, which is not so readily accomplished in an
insoluble-solid-supported catalytic system. The dihydroxyla-
tion and oxidative cleavage results clearly demonstrate that
a tiny amount of OsO4 anchored to the P4VP nanobrush layer
is sufficient for excellent reaction efficiency, presumably
owing to a uniform distribution of catalyst at the molecular
level without aggregation and to complete utilization of
loaded catalyst dispersed on the nanobrush. The results also
revealed the durability and reusability of the microreactor
without spillage of hazardous catalyst, which has not yet been
demonstrated with any solid-supported bulk-reaction sys-
tems.
In conclusion, we have devised a nanobrush microreactor
for use in heterogeneous catalytic processes, in particular ones
involving toxic, volatile, or expensive catalysts, using a simple
microfluidic platform in the PVSZ-PDMS microreactor. The
method of immobilization of hazardous OsO4 on the nano-
brush P4VP layer was shown to be a safe, efficient, and green
process, with little environmental impact, and allowed
reactions to be conducted in a time- and chemical-saving
manner, as compared to spill-over bulk processes. The
concept and method can be easily extended to other hazard-
ous-metal-catalyst systems in glass- or metal- based micro-
reactors after appropriate surface modifications for high
throughput screening and upscale production.
Keywords: dihydroxylation · immobilization · microreactors ·
osmium · oxidation
.
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Experimental Section
Monohydroxyl-terminated P4VP was synthesized by standard
Schlenk techniques, and further functionalized with NCO groups.
The same NCO-P4VP nanobrush polymer was used for all micro-
reactor fabrication. To perform the dihydroxylation and oxidative
cleavage reactions, the OsO4–P4VP nanobrush microreactor was
connected to a programmable syringe pump through PTFE tubing
with an internal diameter of 500 mm. All of the reactions were carried
out at room temperature.
Received: February 7, 2013
Revised: March 7, 2013
Published online: && &&, &&&&
4
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Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Microreactors
K. C. Basavaraju, S. Sharma,
R. A. Maurya, D.-P. Kim*
&&&& — &&&&
Safe Use of a Toxic Compound:
Heterogeneous OsO4 Catalysis in
a Nanobrush Polymer Microreactor
Putting osmium in its place: The immo-
bilization of hazardous OsO4 on polymer
nanobrushes in a microreactor is a safe,
effective, and green concept. The method
allows reactions to be performed in
a time- and chemical-saving manner, with
little environmental impact, as compared
to spill-over bulk processes.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!