Microfluidic hydrogenation reactions by using a channel-supported rhodium catalyst

Article abstract of DOI:10.1002/cctc.201301109

A glass-fabricated microfluidic device was used to screen a series of homogeneous alkene hydrogenation reactions by using Wilkinson's catalyst. Good to excellent conversions were achieved for a range of alkene substrates within short reaction times (<2 min) and low hydrogen pressures (<0.2 MPa). During the course of the screening procedure, a metallic Rh layer was found to build up on the channels of the microfluidic device. Further investigation of this layer revealed that it was a highly active catalyst for the hydrogenation of alkenes, enones, and alkynes. Furthermore, this Rh layer catalyzed the hydrogenation of toluene to methylcyclohexane. Chips away! A glass-fabricated microfluidic chip coated with a catalytically active layer of Rh effectively hydrogenates a range of alkenes at low hydrogen pressures (<0.2 MPa) and within short reaction times (2 min). Good to excellent conversions are achieved under these reaction conditions, including modest conversions of toluene into methylcyclohexane.

Full text of DOI:10.1002/cctc.201301109

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DOI: 10.1002/cctc.201301109
Microfluidic Hydrogenation Reactions by using a Channel-
Supported Rhodium Catalyst
[a]
Tom Haywood and Philip W. Miller*
A glass-fabricated microfluidic device was used to screen
a series of homogeneous alkene hydrogenation reactions by
using Wilkinson’s catalyst. Good to excellent conversions were
achieved for a range of alkene substrates within short reaction
times (<2 min) and low hydrogen pressures (<0.2 MPa).
During the course of the screening procedure, a metallic Rh
layer was found to build up on the channels of the microfluidic
device. Further investigation of this layer revealed that it was
a highly active catalyst for the hydrogenation of alkenes,
enones, and alkynes. Furthermore, this Rh layer catalyzed the
hydrogenation of toluene to methylcyclohexane.
chemical reactions that have been shown to impact chemical
yield and selectivity. Multiphase gas–liquid and gas–liquid–
solid reactions appear to be particularly suitable to the applica-
tion of microfluidic flow reactors, as the higher surface area to
volume ratios result in greater contact between the gas and
liquid phases than that observed in traditional glassware or re-
[9]
actors. Additionally, there are clear safety advantages if the
volumes of pressurized flammable or toxic gaseous reagents
are significantly reduced in volume; for typical microfluidic and
flow reactors this can range from 1 mL to 1 mL. There are now
many examples of multiphase flow reactors for performing
[10]
gas–liquid-phase reactions. In the area of catalytic hydroge-
nation commercial units, such as the H-cube reactor, typically
a heterogeneous catalyst loaded onto a solid support packed
For over a century, catalytic hydrogenation reactions have
been used for saturating double bonds and effecting function-
[11]
into the reaction channel is used. More recently, there has
been considerable interest in “tube-in-tube” reactors devel-
[
1]
al-group conversions. Hydrogenation processes are of enor-
mous industrial importance and are used on large scales in the
petrochemical, fine chemical, and food industries. Heterogene-
ous catalytic hydrogenation methods were established in the
[12]
oped by Ley et al. for safely performing gas–liquid-phase ho-
mogenous-catalyzed hydrogenation reactions up to pressures
of 2.5 MPa. The tube-in-tube reactor consists of a gas-permea-
ble but liquid-impermeable Teflon membrane tube that is
placed inside a larger stainless steel tube. By using a heated
[
2]
early 1900s, followed by advances in homogenous catalysis
[
3]
by using transition-metal catalysts in the 1960s. The discovery
of asymmetric transition-metal hydrogenation reactions soon
followed and paved the way for highly efficient syntheses of
[13]
tube-in-tube reactor, Leadbeater et al. demonstrated the ef-
fective hydrogenation of a number of alkene substrates by
using Wilkinson’s catalyst.
[
4]
single enantiomers. Today, catalytic hydrogenation research
continues at a pace with recent notable advances in the use of
An alternative strategy to using either homogeneous cata-
lysts or packed-bed heterogeneous catalysts involves support-
ing the catalyst directly on the channel walls of the microreac-
tor. This can provide advantages over homogeneous catalysis
for ease of catalyst separation and over-packed heterogeneous
catalysts systems in terms of flow stability, lower pressure re-
quirements, and reduced system blockages. There have been
a number of successful routes to generate channel-supported
[
5]
[6]
cheaper transition-metal catalysts, such as iron and cobalt,
[
7]
and also in the area of metal-free hydrogenations. Common
with all hydrogenation methods involving molecular hydrogen
is the need to ensure efficient mass transport of hydrogen gas
into the liquid phase. Owing to the poor solubility of molecular
hydrogen in common organic solvents, hydrogenation process-
es are typically performed at elevated pressures and tempera-
tures to enhance mass transport and reaction rates. Such ele-
vated temperatures and pressures have associated safety and
cost implications and require specialty high-pressure equip-
ment. One of the key drivers for the development of new cata-
lysts is to achieve efficient conversions at lower pressures and
temperatures, which would thus alleviate the need for forcing
high-temperature/pressure reaction conditions and their asso-
ciated safety and cost implications.
[
14]
catalysts including polymer coatings,
immobilization of
[15]
nanoparticles,
and direct deposition of metals onto the
[16]
channel surfaces. Herein, we report a chemical method for
coating a glass-fabricated microfluidic device with an active
rhodium catalyst and demonstrate its utility for the hydrogena-
tion of alkenes. Furthermore, initial investigations of the use of
this reactor for the hydrogenation of toluene are also de-
scribed.
In recent years, the development of microfluidics and micro/
meso flow reactors has impacted synthetic chemistry method-
Our reactor setup consisted of a glass microfluidic device
(Figure 1) that contained an inlet for hydrogen gas and an
inlet for the substrate/catalyst solution. The device contained
a long (5 m) reaction channel to provide a residence delay. The
exact design specifications of this device were previously re-
[
8]
ology. Such flow processes have given chemists a means of
more rigorously controlling the mixing and heating regimes of
[a] T. Haywood, Dr. P. W. Miller
[17]
ported by us. The catalytic hydrogenation reaction of sty-
Department of Chemistry
Imperial College London
South Kensington, London SW7 2AZ (UK)
E-mail: philip.miller@imperial.ac.uk
rene with the use of Wilkinson’s catalyst [RhCl(PPh ) ] was ini-
3
3
tially investigated as a model reaction. In a typical reaction,
a
solution of styrene (1 molar) and Wilkinson’s catalyst
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into the alkanes products. These results are in agreement with
previous studies with the use of Wilkinson’s catalyst, which is
known to hydrogenate terminal alkene groups; however, such
reactions are typically performed over much longer reaction
[3c]
times and at greater hydrogen pressures.
Good to excellent conversions were observed for the
double-bond saturation of a,b-unsaturated ketones (Table 1,
entries 4–9). For a double bond in a sterically hindered posi-
tion, the conversion was considerably lower, as seen for meth-
ylcyclohexenone (Table 1, entry 6), which has a methyl group
adjacent to the double bond. Alkyne bonds can also be hydro-
genated by using Wilkinson’s catalyst; however, under our re-
action conditions a low conversion (19%) was observed for the
internal alkyne diphenylacetylene (Table 1, entry 10). Poor con-
version (5%) was also seen for the sterically hindered alkene
phenylcyclohexene (Table 1, entry 11).
Figure 1. Glass-fabricated microfluidic device used in this study. Build-up of
catalytically active Rh deposit can be observed in the first 5–6 channels.
Inset: close-up of the gas–liquid inlet T-junction.
(0.5 mol%) in toluene was infused into the glass device along
with a stream of hydrogen. Under liquid flow rates of
À1
1
0 mLmin and a hydrogen flow rate of 2.0 sccm (0.2 MPa
inlet pressure), stable annular-type flow persisted. This flow
regime results in a high gas–liquid contact area within the mi-
crochannel, which thus assists the mass-transport processes.
Residence times of liquid regents under these flow conditions
were, however, relatively short (ꢀ2 min). Despite the short res-
idence times, conversions of styrene into ethylbenzene were
found to be quantitative (Table 1, entry 1). Under our flow con-
ditions, other substrates with terminal alkene groups (Table 1,
entries 2 and 3) showed similar near-quantitative conversions
During the course of these hydrogenation reactions, a black
material suspected to be a metallic Rh deposit was seen to ac-
cumulate at the gas–liquid T-junction of the microfluidic
device and along the first 4–5 reactor channels (Figure 1). Sub-
sequent hydrogenation reactions resulted in continued build-
up of this material to the point of almost complete occlusion
of the channel. Such channel blockages with the use of homo-
geneous transition-metal catalysts are a known prob-
lem and have been observed for a number of cata-
Table 1. Conversions of alkenes and enones into their corresponding saturated prod-
ucts.
lyzed reactions usually as a result of catalyst degrada-
tion into colloidal metallic particles. Recently, various
solutions have been proposed to overcome this
issue, including the use of high-frequency acoustics
[a]
Entry Substrate
Product
Conversion [%]
RhCl(PPh
3
)
3
Supported catalyst
and tuning solvents to ensure adequate solubili-
1
2
quant.
quant.
[13,18]
ty.
In our case, extensive and inconvenient clean-
ing procedures with the use of concentrated nitric
acid was required to remove this material between
reactions to regenerate a clean device.
98
quant.
3
4
88
93
quant.
quant.
Given that metallic rhodium is a well-known cata-
lyst, we also decided to investigate the catalytic activ-
ity of this coating for hydrogenation reactions. To our
surprise, the infusion of a styrene solution in toluene
5
6
7
quant.
39
quant.
quant.
98
(
1m) under similar reaction conditions (temperature,
pressure, and reaction time) in the absence of added
Wilkinson’s catalyst resulted in quantitative conver-
sion into ethylbenzene. In fact, this Rh coating
proved to be more catalytically active than the ho-
mogeneous-based Wilkinson’s catalyst for the majori-
ty of the reactions that were tested (Table 1). In con-
trol reactions under the same reaction conditions by
using polytetrafluoroethylene (PTFE) tubing of similar
dimensions (200 mmꢁ5 m), much lower conversions
of the model styrene hydrogenation were observed
95
8
9
69
90
10
<5
[
d]
10
19
5
quant.
(
<50%). During the course of these PTFE tube reac-
tions, Rh particulate material was observed to form,
but it passed quickly through the reactor and did not
deposit on the tubing walls. This may explain the
lower conversions of these tube reactions, as the cat-
alytically active material is not retained on the walls.
In comparable batch hydrogenation reactions with
the use of Wilkinson’s catalyst, no metallic Rh was
11
<1
[
[
b]
c]
1
1
2
3
0
0
7
18
[a] Percent conversion calculated by GC analysis (average of two runs). [b] Toluene
only. [c] 1 m toluene in decane. [d] 1,2-Diphenylethane/stilbene=69:31.
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observed to form; this indicates that microfluidic conditions
are required for this material to form, that is, efficient contact
of the gas and liquid phases is necessary. This suggests that
our initial hydrogenation reactions were not solely undergoing
a homogeneous catalytic process but also a heterogeneous-
catalyzed process. A heterogeneous catalyst was formed in situ
from the homogeneous Wilkinson’s catalyst as it passed
through the device and deposited on the channel walls.
In further experiments to better understand the robustness
of the Rh catalytic coating, a continuous flow of 1 m styrene in
toluene was infused into the device at a flow rate of
Figure 3. SEM image of the rhodium deposit from the microtube reactions
À1
10 mLmin over a 24 h period. Samples were taken for GC
(
20 mm scale bar).
analysis at two-hour time points to assess the styrene conver-
sion. In all cases, the GC traces showed no deterioration in the
conversion of styrene, with quantitative conversion over the
entire 24 h period. Additionally, there was no visible evidence
of catalyst degradation or flaking from the channel walls. This
indicated that the Rh catalytic coating was robust, strongly ad-
hered to the walls, and remained active for an extended
period of time. Closer visual inspection of the coated channels
indicated that the Rh layer was relatively uniform and thin
crochannel occurs at a fast rate and can be clearly observed to
form around the T-junction (Figure 1, inset) of the device once
the hydrogen comes into contact with the catalyst/substrate
solution. The first 4–5 channels of the device appear to be
evenly coated, after which there is a thin partial coating in the
next 1–2 channels. Assuming an even and thin coating of four
channels as an approximation, this would give a surface area
2
[1]
(Figure 2). By using optical microscopy, the Rh layer was esti-
of 2.0 cm on a device of this type.
Considering the activity of this Rh-supported catalyst for sty-
rene hydrogenation, it was decided to reinvestigate the sub-
strate scope again, this time without any added Wilkinson’s
catalyst. Results of this repeated screen are displayed in
Table 1 and show in most cases that the supported catalyst
outperforms the homogeneous Wilkinson’s catalyst in terms of
alkene conversion. One notable example is the improvement
in conversion of the sterically hindered alkene methylcyclohex-
enone (Table 1, entry 6), which showed an improvement in the
conversion from 39 to 100% by using the supported Rh
method. However, not all reactions showed improved conver-
sions for the supported catalyst; the enone substrates (Table 1,
entries 8 and 9) showed much lower conversions, which indi-
cates that a homogenous catalytic process is favored under
these particular microfluidic conditions. Conversion of the in-
ternal alkyne diphenylacetylene (Table 1, entry 10), in contrast,
showed quantitative conversion for the supported catalyst
system; however, the product distribution showed a 69:31
mixture of 1,2-diphenylethane/stilbene. The homogeneous
system gave much lower conversions, 19%, but showed exclu-
sive formation of 1,2-diphenylethane.
Figure 2. Magnified images (ꢁ20) of the microchannel with different levels
of rhodium deposits: a) no deposit, b) partially coated, c) fully coated.
mated to be 2–10 mm in depth. Although it was not possible
to easily remove the Rh layer from the enclosed glass device
without chemically dissolving it by using concentrated nitric
acid, the metallic Rh material could be generated by using
a PTFE microreactor, as mentioned above, and collected for
further analysis. Transmission electron microscopy (TEM) and
scanning electron microscopy (SEM) analysis of this Rh sample
first confirmed that metallic Rh was present and that the mor-
phology of the sample was not nanoparticulate in nature but
rather amorphous (Figure 3). Powder X-ray diffraction also con-
firmed that the sample was not crystalline. Although this did
not tell us the exact nature of the coating on the channel sur-
face, it did suggest that metallic Rh on the glass device did
not consist of nanoparticles. Attempts to prepare the Rh coat-
ing on the channel surface by using only a toluene solution of
Wilkinson’s catalyst and a flow of hydrogen were unsuccessful.
It was necessary to have an alkene, such as styrene, in the so-
lution to generate the coating. This suggests that an Rh–alkyl
intermediate, which is known to form after the initial insertion
of dihydrogen in the catalytic cycle, is the likely precursor to
the deposited metallic Rh catalyst following reduction to a sus-
Re-examination of the GC traces of these reactions also
showed noticeable conversions of toluene, used as the solvent,
into methylcyclohexane (MCH) for the supported Rh catalyst.
The conversion of aromatics into saturated hydrocarbon prod-
ucts is an important industrial process for synthetic precur-
[19]
sors and to reduce volatile organic compounds from diesel
[20]
combustion. The conversion of toluene into MCH and the re-
verse process to release hydrogen is currently attracting inter-
[21]
est for hydrogen-storage and hydrogen-release applications;
hence, routes to mildly and efficiently convert toluene into
MCH are currently of interest. Simply passing neat toluene
À1
through the Rh-coated device at a flow rate of 10 mLmin
with a flow of hydrogen (2 sccm, 0.2 MPa inlet pressure) at
0
pected Rh species. The formation of the Rh deposit on the mi-
1208C resulted in a 7% conversion of toluene into MCH
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(Table 1 entry 12). Although the conversion of toluene into
the H
2
gas line. Hydrogen flow was regulated by a Sierra Instru-
ments Micro-Trak mass flow meter. In a typical reaction procedure,
a toluene solution of the substrate (1m) and Wilkinson’s catalyst
MCH was relatively low, it was not surprising considering the
2
small surface area (ꢀ2 cm ) of the catalyst within the device,
(
1
0.5 mol%) was infused into the chip device at a flow rate of
0 mLmin . Hydrogen gas flow was maintained at 2.0 sccm (stan-
and the relatively large volume of toluene passing rapidly
through the device would result in saturation of the catalytic
sites. If a dilute solution of toluene (1 m in decane) was used,
conversion into MCH was found to increase markedly to 18%
À1
dard cubic centimeter per minute), which resulted in annular-type
flow through the device. Back pressure in the system for this par-
ticular chip device was 0.20 MPa under these flow conditions. The
device was heated to 1208C by using an aluminum heating block
placed on an IKA hotplate and regulated by using an electronic
contact thermometer. An aliquot (900 mL) was collected for each
sample, which was passed through a small pad of Celite prior to
GC analysis.
(Table 1 entry 13).
In conclusion the hydrogenation reaction of alkenes with
the use of Wilkinson’s catalyst can be rapidly and efficiently
performed by using a simple glass-fabricated microfluidic
device at low pressures and within short reaction times. A cat-
alytically active Rh layer formed during the course of these re-
actions that robustly adhered to the wall of the channel, which
made it possible to perform these reactions heterogeneously.
This supported catalyst showed high catalytic activity and was
able to effect the hydrogenation of toluene to MCH. Approxi-
mately 30 reactions were performed on the device, which
amounts to approximately 100 h of continuous reaction time,
without significant loss in activity. The exact nature of this sup-
ported Rh catalyst is under investigation, and we are currently
developing methods to give greater surface-area coverage of
the microchannel surface. At present, we can only achieve ap-
proximately 7% surface-area coverage of the supported cata-
lyst; hence, significant improvements in the conversion of tolu-
ene would be expected with increased catalyst surface area.
We are also investigating different flow regimes through the
device. The current method benefits from the large surface
areas generated from annular flow in the microchannel, but it
suffers from very short residence times that clearly impact the
conversion of more challenging substrates. By extending the
residence times with the use of a gas–liquid segmented flow
regime, it should be possible to achieve much improved
alkene conversions.
General procedure for Rh coating
The channel surface was coated in a layer of catalytically active
metallic Rh by simply passing a premixed toluene solution of sty-
rene (1m) and Wilkinson’s catalyst (0.5 mol%) through the device
À1
at a flow rate of 10 mL min , hydrogen flow of 2 sccm, and heating
to 1208C. Approximately 1 mL of solution was passed through the
device to generate an even coverage of the first 4–5 channels. At-
tempts to increase the surface coverage by infusing more catalyst/
substrate solution resulted in a deeper layer of the Rh deposit near
the gas–liquid inlets; this layer restricted flow, which resulted in an
undesirable increase in back pressure.
PTFE tube reactions
A 1/16 PEEK T-piece was connected to the liquid and gas inlet
lines, and a 5 m reaction coil of PTFE tubing (1/16 inch external di-
ameter, 0.2 mm internal diameter) was placed into an oil bath.
Identical liquid and gas flow rates to that described above were
employed. In a typical procedure, a premixed toluene solution of
styrene (1m) and Wilkinson’s catalyst (0.5 mol%) was infused into
the reactor. A black precipitate of metallic Rh was observed to
form over the course of the reaction. This passed through the reac-
tor without adhering to the tubing walls and was collected for
analysis by TEM.
Experimental Section
Heterogeneous reactions
General
An identical system to that of the homogeneous reaction system
described above was used. Liquid and gas flow rates were identical
in all cases. In a typical procedure, a toluene solution of the sub-
strate (1m) without any added catalyst was infused into the device
All preparations involving Wilkinson’s catalyst were performed
under an inert nitrogen atmosphere. Toluene was predried by
using a commercial drying column. All other starting materials
were of reagent grade, were purchased from Sigma–Aldrich, and
were used without further purification. GC analysis was performed
with a Hewlett-Packard 5890 Series II Gas Chromatograph.
À1
at a flow rate of 10 mLmin and under gas flow of 2.0 sccm. An ali-
quot (900 mL) was collected for each sample, which was analyzed
directly by GC. Reactions of toluene were performed either neat or
as a 1m solution in decane, as stated in Table 1.
Homogeneous hydrogenations
Acknowledgements
A detailed description of the microfluidic device was previously re-
[17]
ported by us. In short, the microfluidic device was fabricated by
Dolomite, Ltd., by using soda-lime glass substrates with the use of
wet chemical hydrogen fluoride etching and thermally bonded.
The reactor channels were 220 mm wide and 100 mm deep, and the
main reactor channel was 5 m in length. The total volume of the
device was 86 mL. External PTFE (1/16 inch external diameter,
We are grateful to Dr. Nick Brooks for the use of a high-quality
optical microscope. Dr. Mahmoud Ardakani and Mr. Richard
Sweeney are acknowledged for assistance with TEM, SEM, and
X-ray powder diffraction. P.W.M. is grateful to the Natural Science
Foundation of China (Grant No. 21350110212) for the award of
a Research Fellowship for International Young Scientists.
0
.25 mm internal diameter) tubing was connected to the microflui-
dic reactor by using a standard Dolomite edge connector. A Har-
vard apparatus pump 11 elite syringe pump was used to infuse the
substrate and catalyst solution. The second inlet was connected to
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Keywords: hydrogenation
microreactors · rhodium · supported catalysts
·
microfluidic
devices
·
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Received: December 29, 2013
Published online on March 12, 2014
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2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2014, 6, 1199 – 1203 1203