Continuous Flow Pickering Emulsion Catalysis in Droplet Microfluidics Studied with In Situ Raman Microscopy

Article abstract of DOI:10.1002/chem.202002479

Pickering emulsions (PEs), emulsions stabilized by solid particles, have shown to be a versatile tool for biphasic catalysis. Here, we report a droplet microfluidic approach for flow PE (FPE) catalysis, further expanding the possibilities for PE catalysis

Full text of DOI:10.1002/chem.202002479

Accepted Article
Accepted Article
Title: Continuous Flow Pickering Emulsion Catalysis in Droplet
Microfluidics Studied with In-situ Raman Microscopy
Authors: Carolien M. Vis, Anne-Eva Nieuwelink, Bert M. Weckhuysen,
and Pieter Bruijnincx
This manuscript has been accepted after peer review and appears as an
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To be cited as: Chem. Eur. J. 10.1002/chem.202002479
Link to VoR: https://doi.org/10.1002/chem.202002479
01/2020

10.1002/chem.202002479
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Continuous Flow Pickering Emulsion Catalysis in Droplet Microfluidics
Studied with In-situ Raman Microscopy
Carolien M. Vis*[a], Anne-Eva Nieuwelink*[a], Bert M. Weckhuysen#[a], Pieter C.A. Bruijnincx#[a,b]
[a]
[b]
*
C. M. Vis, A.-E. Nieuwelink, prof. dr. ir. B. M. Weckhuysen, prof. dr. P. C. A. Bruijnincx
Inorganic Chemistry and Catalysis
Debye Institute for Nanomaterials Science, Utrecht University
Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
E-mail: b.m.weckhuysen@uu.nl
prof. dr. P. C. A. Bruijnincx
Organic Chemistry and Catalysis
Debye Institute for Nanomaterials Science, Utrecht University
Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
E-mail: p.c.a.bruijnincx@uu.nl
These authors contributed equally to this work
Supporting information for this article is given via a link at the end of the document.
Abstract: Pickering emulsions (PEs), emulsions stabilized by solid
particles, have shown to be a versatile tool for biphasic catalysis. Here
we report a droplet microfluidic approach for flow PE (FPE) catalysis,
further expanding the possibilities for PE catalysis beyond standard
batch PE reactions. This microreactor allowed the inline analysis of
the catalytic process with in-situ Raman spectroscopy, as
demonstrated for the acid-catalyzed deacetalization of benzaldehyde
dimethyl acetal to form benzaldehyde. Furthermore, the use of the
FPE system showed a nine fold improvement in yield compared to the
simple biphasic flow system (FBS), highlighting the advantage of
emulsification. Finally, FPE allowed an antagonistic set of reactions,
the deacetalization-Knoevenagel condensation, which proved less
efficient in FBS due to rapid acid-base quenching. The droplet
microfluidic system thus is a versatile new extension of PE catalysis.
vigorous stirring and as a result show broad droplet size
distributions, making it difficult to measure kinetics, for example.
Furthermore, the opacity and intimate phase mixing in batch PE
make in-situ investigations impossible, with analysis necessitating
sampling, de-emulsification and further work-up.
To deal with these analytical complexities and to make a more
industrially relevant reaction system, continuous flow (w/o) PEs
were developed by Yang et al. as liquid equivalent of a packed
bed reactor.[17] In this system, the flow is determined by gravity
and droplet size, which is not trivial to control with the PE being
prepared by vigorous stirring. Analysis of reaction products was
done ex-situ by collection of the oil phase at the end of the reactor,
leaving litttle room for changing parameters or measuring kinetics
during reaction. While reaction kinetics could possibly be
measured spectroscopically at different column heights, this is
generally impossible to measure in a PE using spectroscopy due
to scattering at the solid particles and droplet surface. The use of
a continuous flow droplet microreactor could overcome this
challenge. In addition, droplet microfluidics provide a way to gain
control over the droplet size, e.g. to create a more homogeneous
system.[18]
Biphasic catalysis has shown to be a great tool for efficient
chemical transformations, e.g. enabling facile product
separation[1,2], and extraction of reactive species to reduce side
product formation.[3] A major drawback of classical biphasic
systems, however, is the low interfacial area between the two
phases. Increasing the interfacial area, and thus reactivity and
extraction[4,5], of a biphasic system can be accomplished by
adding emulsifying agents, such as surfactants or amphiphilic
solid particles. Emulsions stabilized by the latter are called
Pickering emulsions (PEs). With the particles adsorbed onto the
liquid-liquid interface, water-in-oil (w/o) or oil-in-water (o/w)
emulsions are formed, depending on the solid’s affinity for one of
the two phases.[6,7] While with surfactant-stabilized emulsions,
surfactants recovery and phase separation is difficult, with PEs
this can be easily done. PEs can therefore be considered
reversible reaction media. Such de-emulsification can be
achieved by centrifugation or, when responsive particles are used,
changing the pH[8] or applying a magnetic field[9].
The rapidly growing microfluidics field uses small channel
systems in the micrometer range that allow increased
temperature control, homogeneity of the droplets and enhanced
mixing due to convectional flow in- and outside the droplets.
Droplets in a microchannel are more stable compared to bulk
biphasic systems and can exist without the use of surfactants due
to regular spacing, but surfactants still improve stability and
prevent droplet coalescence when two droplets do collide. Solids
have been used less as stabilizing agents in microfluidics and
most reported examples focus solely on stability[19–21] or
applicability for the food and biomedical industry[22,23]. One of the
difficulties in preparing in-flow PEs is the lack of shear, causing
particle adsorption at the interface to be very slow requiring
sufficient time to fully cover the droplets with particles before they
encounter each other.[24]
Previous research has mainly focused on the formation and
stability of PEs[10–12] to replace surfactant-stabilized emulsions for
pharmaceutical and cosmetic applications.[13] More recently, the
use of batch PEs as reaction media for catalysis[14–16] has drawn
attention, an approach that comes with considerable potential but
also with experimental challenges. Batch PEs are prepared by
Here, we developed, as outlined in Figure 1, a tube-in-tube co-
flow microreactor for the production of droplets to prepare FPEs.
1
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The use of hydrophobic FEP outer tubing with hydrophilic fused
silica inner tubing led to the formation of w/o droplets, as
schematically shown in the SI (Figure S1). The chemically
resistant and optically transparent polymer tubing allows for
observation of the formation and stability of droplets over the
whole tubing, enabling in-situ Raman spectroscopy. By
measuring spectra at different positions in the flow channel, the
reaction mixture can be monitored at various reaction times for
kinetic profiling of reactants and products. The reaction time can
be easily controlled by changing the total flow rate or the tube
length. Furthermore, the advantage of automatic phase
separation after the tubing’s outlet[13] simplifies post-analysis of
both phases.
formation increased the viscosity of the continuous phase, it did
not change the droplet size significantly. The spherical droplets
were of similar size to the inner diameter of the FEP tubing.
However, without solid stabilization droplet coalescence was
observed during reaction, possibly due to product formation
changing the viscosity. In contrast, the droplets remained stable
in the PE system and no coalescence was observed.
The FPE system was uniformly heated by coiling the tubing
around a cylindrical heating device. The temperature accuracy of
the heating device was tested with luminescence thermometry as
described earlier[25,26], using Yb-Er doped NaYF4 particles. The
temperature inside the tubing showed a maximum deviation of
2.2 °C from the temperature setpoint (SI). The flow rates of the
continuous organic and dispersed aqueous phase were set at 20
µL/min and 5 µL/min respectively, leading to a 25 mol% catalyst
ratio with respect to the substrate.
This microreactor was used to demonstrate the advantage of
Pickering stabilized droplets over non-stabilized droplets for
biphasic flow catalysis, using the acid-base catalyzed
deacetalization-Knoevenagel condensation of benzaldehyde
dimethyl acetal as probe reaction. We previously showed PEs to
positively influence this reaction in batch.[15] In this microreactor,
the progress of the acid-catalyzed deacetalization reaction, could
be followed with in-situ Raman spectroscopy, at various
temperatures with both stabilized and non-stabilized droplets.
Secondly, a positive effect of Pickering stabilization of a
microfluidic flow system is shown for the deacetalization-
Knoevenagel tandem reaction, now using ex-situ GC analysis.
The acid-catalyzed deacetalization of the acetal to benzaldehyde
was probed inside the tubing with a 532 nm in-situ Raman laser;
a full spectrum with assignments of the most important peaks is
given in the SI (Figure S2); the silica in the FPE did not influence
the Raman measurements. The spectra were taken at different
positions in the tubing, each loop equating to approximately 2 min
of reaction time (Figure 2a). The first measurement at loop 0,
almost directly after droplet formation, corresponds to 5 s of
reaction. The Raman spectra as function of position in the tubing
and temperature are shown in Figure 2b. In the Raman spectra at
60 and 90 °C, a shoulder originating from benzaldehyde can be
observed at the 460 cm-1 peak, growing in concomitantly with the
peak at 1700 cm-1.[27]
Droplets were created using an acidic, aqueous phase and 4-
propylguaiacol (PG) as oil phase. The w/o droplets formed with a
homogeneous size distribution, with and without the addition of
solid stabilizing particles. Although addition of silica for PE
Figure 1. Droplet microfluidic approach for in-flow PE catalysis with 4-propylguaiacol as continuous phase (CP) and water as dispersed phase (DP). Top inset: The
deacetalization reaction can be monitored in-situ using Raman spectroscopy, bottom inset: scheme of the deacetalization-Knoevenagel reaction inside the tubing,
bottom left inset: particles on droplet surface.
2
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that time. At 90 °C, the reaction was too fast to measure any
differences between the FBS and FPE. A control experiment, with
only silica and no HCl, showed no significant benzaldehyde
formation, indicating that the higher droplet stability and therefore
higher interfacial area in the PE are causing the enhanced
reactivity.
The simple microreactor thus enabled a facile real-time analysis
of the deacetalization of benzaldehyde dimethyl acetal in FBS and
FPEs, again demonstrating the advantage of using PEs for
biphasic catalysis. The use of in-situ Raman spectroscopy
eliminates the need for the work-up procedures normally used for
batch BS and PEs, offering new analytical opportunities for PE
catalysis characterization, e.g. access to more accurate kinetic
profiles.
The FPE also proved beneficial for antagonistic tandem catalysis
in flow, in this case by coupling deacetalization to an additional
Knoevenagel condensation. Addition of a base catalyst (2-(1-
ethylpropyl)piperidine) and malononitrile as second substrate to
the mixture used before, resulted in a slight increase of the
viscosity of the organic phase. To retain stable droplets, the flow
rates were adjusted to 10 μL/min for both the organic as the
aqueous phase, resulting in a total reaction time of 34 min. The
reaction was executed at 90 °C, as the Knoevenagel
condensation is much slower than the deacetalization, with 20
mol% acid and 10 mol% base and analyzed ex-situ by GC, as
strong malononitrile fluorescence unfortunately precluded in-situ
Raman spectroscopy in this particular case. In the FBS,
benzaldehyde dimethyl acetal conversion was only 34%, yielding
10% and 17% of the intermediate benzaldehyde and the final
product benzylidene malononitrile, respectively (Figure 4). The
low conversion and yields were attributed to rapid acid-base
quenching in the FBS. The use of an FPE system considerably
improved the reaction, giving full conversion of benzaldehyde
dimethyl acetal under identical conditions, with 69%
benzaldehyde and 25% of final product. The acid-base quenching
was slower in this system, attributed to the physical boundary
present at the interface between the two phases. The yield of final
product is limited in this case by the available short reaction time,
dictated by the number of loops that could be coiled around the
heating device. Residence time of the reactants in the
microchannel can, however, in principle be extended by simply
extending the tube length.
Figure 2. a) Schematic drawing of the measurement positions, b) CCl4 peak
(460 cm-1) and benzaldehyde peak (1700 cm-1) in the Raman spectra at different
positions in the tubing at room temperature (1, 2), 60 °C (3, 4) and 90 °C (5, 6)
without silica (1, 3, 5) and with 2 wt% silica (2, 4, 6) in the continuous phase
monitoring the deacetalization reaction.
The kinetic profiles of benzaldehyde formation at all temperatures
and with and without silica are shown in Figure 3. At room
temperature without any silica present, the reaction proceeds
slowly, yielding only 10% of benzaldehyde after 22 min. Full
conversion was reached after ~18 min at a reaction temperature
of 60 °C, and after 2 min at 90 °C. Addition of silica had a clear
positive effect on the reaction at room temperature and at 60 °C.
At room temperature, silica addition resulted in a jump in activity,
increasing the yield from 10% in the normal flow biphasic system
(FBS) to 90% in the PE after 22 min. At 60 °C full conversion was
reached within 2 min, whereas the FBS gave only 10% yield at
Figure 3. Concentration of benzaldehyde during the acid catalyzed deacetalization reaction of benzaldehyde dimethyl acetal followed over time by in-situ Raman
spectroscopy at RT (a), 60 °C (b) and 90 °C (c). Reaction conditions: 1.0 M benzaldehyde dimethyl acetal and 0.5 M CCl4 in 4-propylguaiacol (and 2 wt% silica),
0.1 M HCl in water, total flow 25 μL/mi.
3
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and Science of the government of the Netherlands and by the
Dutch Research Council (NWO).
Keywords: Pickering emulsions • Droplet microfluidics •
Biphasic catalysis • Raman spectroscopy
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(UT) are acknowledged for their input and fruitful discussions.
This work was supported by a VIDI grant of the Dutch Research
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Entry for the Table of Contents
A droplet microfluidic approach was used for Pickering emulsion catalysis (PEC). The setup allowed in-situ analysis using Raman
spectroscopy offering new analytical possibilities to study PEC systems. Pickering stabilization proofed to be beneficial for catalytic
performance.
6
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