A reinforced Pickering emulsion for cascade reactions

Article abstract of DOI:10.1039/c8cc07644h

Based on an interfacial sol-gel process, a novel reinforced Pickering emulsion has been developed successfully for one-pot cascade reactions involving incompatible catalysts.

Full text of DOI:10.1039/c8cc07644h

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
A reinforced Pickering emulsion for cascade
reactions†
Cite this: Chem. Commun., 2018,
54, 13014
Nan Xue,‡ Gaihong Zhang,‡ Xiaoming Zhang and Hengquan Yang
*
Received 22nd September 2018,
Accepted 24th October 2018
DOI: 10.1039/c8cc07644h
rsc.li/chemcomm
Based on an interfacial sol–gel process, a novel reinforced Pickering
emulsion has been developed successfully for one-pot cascade
reactions involving incompatible catalysts.
Living cells, as an ingenious outcome of nature evolution, are
an excellent platform to perform multistep cascade reactions
with unsurpassed efficiency and specificity.1–5 Among several
tactics employed to reconcile different reaction pathways,
‘‘compartmentalization’’ is one of the key strategies. Due to
the compartmentalization, incompatible substrates and bio-
catalytic species are spatially isolated, and undesired inter-
ferences between multiple species can be avoided.5–9
Scheme 1 (I) Procedures for the preparation of reinforced Pickering
emulsion droplets. (II) Schematic description of a one-pot cascade reaction
based on a reinforced Pickering emulsion. a represents an acid-containing
reinforced Pickering droplet. b represents a base-containing reinforced
Pickering emulsion droplet. A is a starting substrate. B represents an
intermediate, and C is a final product.
Inspired by living cells, many artificially compartmentalized
systems have been explored for one-pot cascade reactions. The
reported strategies mainly rely on the immobilization or encap-
sulation of different catalytic species on/within polymers or sol– this system is the requirement of laminating two Pickering
gel materials to avoid direct contact.8–20 Although encouraging emulsions, which ensures sufficiently long distances between
results are obtained, these methods often entail quite complex droplets containing incompatible reagents. These inherent limita-
immobilization/encapsulation procedures.4,8–11 Moreover, these tions severely hinder the practical application of the concept.
systems are still embryonic because of the inability to mimic the
fundamental aspects of cellular systems.
Herein, we report a novel approach for conducting one-pot
cascade reactions based on a reinforced Pickering-emulsion. As
Pickering emulsions, namely particle-stabilized emulsions, shown in Scheme 1(I), water-in-oil Pickering emulsion droplets
are emerging as an ideal platform for mimicking natural are reinforced through cross-linking of emulsifier particles,
systems.6,21–30 The spatially separated small droplets of lami- forming an inorganic shell around the droplets. [The emulsifiers
nated Pickering emulsions have recently been explored to serve were prepared by surface modification of 60–80 nm silica nano-
as microcompartments to compartmentalize different incom- spheres with methyltriethoxysilane, as shown in transmission
patible reagents, while the continuous phase (outside droplets) electron microscopy (TEM) images in Fig. S1 in the ESI;† their
allows other reactants to diffuse freely and to access the com- water contact angle was 921 as shown in Fig. S2 in the ESI†]
partmentalized reagents for chemical reactions.28 However, due to Tetramethoxysilane (TMOS) is used as the cross-linking reagent
the thermodynamic instability, droplet coalescence and Ostwald because it can be hydrolyzed and condensed under relatively
ripening occur unavoidably, leading to the contact of incom- mild conditions (detailed procedures included in the ESI†). If an
patible reagents during the reaction.31 Another disadvantage of acid (for example, H2SO4) or a base (for example, NH2CH2CH2NH2,
which is denoted as EDA hereafter) is added into the water phase
School of Chemistry and Chemical Engineering, Shanxi University,
before formulating the Pickering emulsions, one can get an acid-
containing reinforced Pickering emulsion or a base-containing
reinforced Pickering emulsion. These two reinforced Pickering
Wucheng Road 92, Taiyuan 030006, China. E-mail: hqyang@sxu.edu.cn
† Electronic supplementary information (ESI) available: Experimental section;
TEM images; N2 sorption analysis; EDX spectrum; XPS spectrum. See DOI:
emulsions are brought together and well mixed, leading to an
acid/base-coexisting biphasic system, as shown in Scheme 1(II).
10.1039/c8cc07644h
‡ These authors attributed equally to this work.
13014 | Chem. Commun., 2018, 54, 13014--13017
This journal is ©The Royal Society of Chemistry 2018

View Article Online
Communication
ChemComm
During the reaction, reactant A in the oil phase can be converted to hydrolysis rate, and the self-condensation of the siliceous
intermediate B upon contact with the acid catalyst, which is moieties took place more easily.
subsequently transformed to the final product C after contact with
The porosity of the shell of the reinforced droplets was
the base catalyst. The good shell permeability of the reinforced determined by nitrogen-sorption measurements. Before measure-
droplets ensures contact of the reactants/intermediate with the ments, the inner liquid was also washed off. As shown in Fig. S4
acid/base catalysts. Since the presence of an inorganic shell around (ESI†), the microcapsules derived from the acid-containing
each droplet avoids the thermodynamically driven droplet coales- droplets show a type-IV isotherm, and the microcapsules derived
cence and Ostwald ripening, the acid and base can co-exist in the from the base-containing droplets display a type-II isotherm. The
same vessel for a long period of time. Moreover, due to the high BET specific surface area of the former is as high as 537 m2 gÀ1
stability of the reinforced droplets, the lamination procedures used and that of the latter is 188 m2 gÀ1. Their pore size distributions
in the previous method can be avoided completely.28
calculated by the BJH method are 4–6 nm and 20–30 nm,
,
As shown in Fig. 1a, the prepared Pickering emulsion droplets respectively. The formation of high surface areas and large pores
containing the acid or base are spherical and somewhat poly- is very interesting since no surfactants were used as the template
disperse with a mean diameter of 17 or 39 mm (for the droplet size during the cross-linking process. These results confirm that the
distribution, see Fig. S3 in the ESI†). After cross-linking, the reinforced droplets have a porous shell, which helps the mole-
obtained acid-containing or base-containing reinforced Pickering cules to communicate with the external medium.
emulsion droplets have a size distribution similar to that of their
We next checked the ability of the reinforced Pickering emul-
mother droplets. Upon washing thoroughly with ethanol, the sion to confine opposing reagents (H2SO4 and EDA) in the same
structural integrity of the empty microcapsule was well preserved system. Congo red was used as the indicator to visualize the
(Fig. 1b). In contrast, without cross-linking, the droplets were pH changes of the water droplets because it is water-soluble but
broken after ethanol washing, which was due to ethanol-induced oil-insoluble and its color varies as the pH changes (azure at
demulsification. Scanning electron microscopy (SEM) indicated pH o 3.0 and red at pH 4 5.0). Acid-containing reinforced
that the hollow microcapsules were structurally robust under droplets were prepared by using 0.5 M H2SO4 (0.80 mL) in the
vacuum. Their shell was several micrometers in thickness (Fig. 1c presence of Congo red. The resultant reinforced Pickering emul-
and d). From the magnified SEM image, one can find that the sion is azure in color (Fig. 2a, a1). This reinforced Pickering
silica emulsifiers were closely packed on the outer surface of the emulsion was then mixed thoroughly with the EDA-containing
microcapsules. Interestingly, the microcapsules derived from the reinforced Pickering emulsion. If only a small portion of EDA
acid-containing Pickering emulsion and the microcapsules diffuse out from the reinforced droplets and cross the oil phase to
derived from the base-containing Pickering emulsion differ signi- react with H2SO4 within the neighbouring reinforced droplets,
ficantly in surface morphology. The former was broadly spherical, the color of the mixture should change. As seen, at the beginning,
while the latter was spheres with apparent wrinkles. This differ- the mixture was azure (Fig. 2a, a1). After standing for 5 min, the
ence might be attributed to the difference in the hydrolysis and reinforced droplets settled down and the color remained azure.
condensation rates.32–34 With acid as the catalyst, the condensa- After 30 min, the color still had no visible change, indicating
tion rate is slower, and the hydrolysed siliceous moieties first the survival of the acid and base in the same system. For
condensate with the silanols on the emulsifier surfaces, resulting comparison, the same procedure was implemented to mix the
in a relatively holonomic spherical shell structure. With base acid-containing and the base-containing Pickering emulsions
as the catalyst, the condensation rate is faster than the
Fig. 2 (a) Comparison of the confining ability of the reinforced Pickering
Fig. 1 Optical microscopy images of the H2SO4-containing reinforced
Pickering emulsion before (a1) and after (b1) cross-linking with TMOS.
Optical microscopy images of the EDA-containing Pickering emulsion
before (a2) and after (b2) cross-linking with TMOS, the scale bar is 100 mm.
SEM images of the microcapsules derived from the H2SO4-containing (c) and
the EDA-containing (d) reinforced Pickering emulsions. (c1 and d1) The
morphology of the microcapsules. (c2 and d2) A single microcapsule at high
magnification. (c3 and d3) A deliberately broken particle. (c4 and d4) The
surface of the shell at high magnification.
emulsion (a1) and the Pickering emulsion (without cross-linking, a2).
(b) Appearance of the columns filled with Cargo red and the H2SO4-
containing reinforced Pickering emulsion in the lower layer and the EDA-
containing reinforced Pickering emulsion in the upper layer (b1) and the
corresponding Pickering emulsion system (without cross-linking, b2).
(c) The fluorescence microscopy images of the FITC-dextran-stained
reinforced Pickering emulsion in a Nile Red solution and (c1) the reinforced
Pickering emulsion in a Nile Red solution (c2). Well-mixed c1 and c2 over
time (c3–c6). The scale bar is 50 mm.
This journal is ©The Royal Society of Chemistry 2018
Chem. Commun., 2018, 54, 13014--13017 | 13015

View Article Online
ChemComm
Communication
without cross-linking (Fig. 2a, a2). A rapid color change from in which deacetalization requires an acid as the catalyst and
azure to red was observed once they were brought together, Knoevenagel condensation requires a base as the catalyst.28 The
which was a result of acid–base reactions.
cascade reaction system was formulated by mixing together an
In order to further evaluate the ability of the reinforced acid-containing reinforced Pickering emulsion, a base-containing
droplets to confine acid or base, we packed a column reactor reinforced Pickering emulsion, and the reactants.
with these two reinforced Pickering emulsions in the lower layer
To validate the examination, we conducted a set of control
(acid-containing) and in the upper layer (base-containing), experiments. In the first control experiment, only a H2SO4-
respectively. Due to the presence of Congo red, the lower layer containing reinforced Pickering emulsion was present in the
was azure. To make the experiment more sensitive, the upper reaction system (without EDA). After 3 h, the content of benz-
layer was allowed to contain an excess of EDA (4 mL, 500 mM) in aldehyde dimethylacetal in the reaction mixture was determined
comparison to its opposing reagent H2SO4 (4 mL, 5 mM) in the to be less than 0.5%, and that of the intermediate product was
lower layer. If a trace of the base flows down with the oil phase, more than 99%, and no final product was detected (Fig. 3). In the
the lower layer would change its color. Initially, a clear boundary second control experiment, the reaction system consisted of only
between these two layers was discerned. After the oil phase an EDA-containing reinforced Pickering emulsion without
flowed for 10 h (2 mL hÀ1), a red layer appeared, which resulted H2SO4. After the same period of time, the content of benzalde-
from acid–base neutralization. After 96 h of continuous flow, hyde dimethylacetal in the reaction mixture was also more than
about 1.1 cm of the reinforced Pickering emulsion changed from 85% and the second reaction did not occur. These two control
azure to red. The reason for the escape of EDA from the experiments suggest that the combination of H2SO4 and EDA is
reinforced droplets is its slight miscibility with toluene. Under absolutely necessary for this chosen cascade reaction. In the
the same conditions, the color change length of the Pickering third control experiment, a H2SO4-containing Pickering emul-
emulsion (without cross-linking) was 1.9 cm, which is about 1.7 sion and an EDA-containing Pickering emulsion (both without
fold larger than that of the reinforced Picking emulsion system. cross-linking) were mixed together. Under the same reaction
These comparisons underscore that the reinforced Picking emul- conditions, only 30% of benzaldehyde dimethylacetal was con-
sion has enhanced confinement ability.
verted to the intermediate benzaldehyde and the final product
Also, we used confocal fluorescence microscopy to observe was approximately 20%. This outcome suggests that a Pickering
whether the fluorescent molecules transfer between the reinforced emulsion without cross-linking has no ability to process this
droplets. A water-soluble dye (toluene-insoluble), fluorescein iso- cascade reaction. For the reinforced Pickering emulsion system,
thiocyanate (FITC-dextran), was loaded into a reinforced Picking benzaldehyde dimethylacetal was fully transformed to the final
emulsion during the preparation. Its oil phase (toluene) was also product via a deacetalization-Knoevenagel cascade after the
stained with another dye, fluorescein Nile red (water-insoluble). same period of time (Fig. 3 and Table 1, entry 1). This set of
As seen in Fig. 2c, the fluorescence images reveal that the FITC- experiments confirms the effectiveness of the reinforced
dextran is distributed within the interior of the reinforced droplets Pickering emulsion in performing one-pot cascade reactions
as evidenced by green zones. After mixing the FITC-dextran/Nile involving opposing reagents.
red co-stained reinforced Picking emulsion with only the Nile red-
The cascade reaction system is applicable to other sub-
stained reinforced Picking emulsion, green and black zones were strates, as summarized in Table 1 (entries 3 and 4). Benzalde-
observed concomitantly. After standing for 7 h, this situation hyde dimethylacetal was also transformed to the final product
remained almost unchanged. That is to say, the FITC-dextran with 96.6% of conversion within 6 h at 70 1C. For less reactive
molecules did not initially enter the dye-free reinforced droplets.
These findings further confirm that the reinforced droplets have
good ability to compartmentalize molecules within their interiors
and prevent the transport of oil-phase-insoluble molecules
between different reinforced droplets.
To evaluate the stability of the reinforced Pickering emulsion
against coalescence, a thermal treatment was implemented. As
shown in Fig. S5 (ESI†), after thermal treatment at 100 1C for 3 h,
the reinforced droplets remained almost the same as those before
the thermal treatment, whereas the droplets of the Pickering
emulsion (without cross-linking) were completely destroyed. This
difference indicates that the cross-linking was indeed successful
Fig. 3 Comparison of the compositions in different reaction systems for
the p-anisaldehyde dimethyl acetal deacetalization–Knoevenagel cascade
and the resulting reinforced droplets have high stability against
coalescence.
As demonstrated above, the coupling of good compart-
mentalization ability with excellent shell permeability probably
enables one-pot cascade reactions in this reinforced Pickering
emulsion. To test this potential, a deacetalization–Knoevenagel
reaction. (a) Only a H2SO4-containing reinforced Pickering emulsion was
present in the reaction system (without EDA). (b) Only an EDA-containing
reinforced Pickering emulsion without H2SO4. (c) A H2SO4-containing
Pickering emulsion and an EDA-containing Pickering emulsion (both without
cross-linking) were mixed together. (d) The mixed acid- and base-containing
reinforced Pickering emulsion systems. Reaction conditions: 0.4 mL H2SO4
(0.5 M), 1.0 mL EDA (0.5 M), 2 mmol p-anisaldehyde dimethyl acetal, 3 mmol
condensation cascade reaction was chosen for investigation, methyl cyanoacetate, and 70 rpm rotating.
13016 | Chem. Commun., 2018, 54, 13014--13017
This journal is ©The Royal Society of Chemistry 2018

View Article Online
Communication
ChemComm
Table 1 Results of deacetalization–Knoevenagel cascade reactions of the reinforced Pickering emulsions
Entry
Reactions
Intermediates
Products
T/1C
Timee (h)
Yield f (%)
Yieldg (%)
1a
2b
3c
50
50
70
3
8
6
0.0
o20
3.1
499.9
480.0
96.6
4d
80
12
3.6
85.5
Reaction conditions: 0.4 mL H2SO4 (0.5 M), 1.0 mL EDA (0.5 M), 70 rpm.a 2 mmol p-anisaldehyde dimethyl acetal and 3 mmol methyl cyanoacetate.
b
c
The second reaction cycle of the reinforced Pickering emulsion under the same conditions as those of the case of a. 2 mmol benzaldehyde
d
e
dimethylacetal and 3 mmol methyl cyanoacetate. 1 mmol benzaldehyde propylene glycol acetal and 1.5 mmol methyl cyanoacetate. Reaction
time. Yield of the intermediates. Yield of the final target product.
f
g
3 M. Marguet, C. Bonduelle and S. Lecommandoux, Chem. Soc. Rev.,
2013, 42, 512–529.
4 R. J. R. W. Peters, I. Louzao and J. C. M. van Hest, Chem. Sci., 2012, 3,
335–342.
5 M. Weitz, A. Mu¨ckl, K. Kapsner, R. Berg, A. Meyer and F. C. Simmel,
J. Am. Chem. Soc., 2013, 136, 72–75.
6 M. Zhang, L. J. Wei, H. Chen, Z. P. Du, B. P. Binks and H. Q. Yang,
J. Am. Chem. Soc., 2016, 138, 10173–10183.
7 J. Lu, J. Dimroth and M. Weck, J. Am. Chem. Soc., 2015, 137,
12984–12989.
8 R. J. R. W. Peters, M. Marguet, S. Marais, M. W. Fraaije, J. C. van Hest
and S. Lecommandoux, Angew. Chem., Int. Ed., 2014, 53, 146–150.
9 M. Kim, S. J. Yeo, C. B. Highley, J. A. Burdick, P. J. Yoo, J. Doh and
D. Lee, ACS Nano, 2015, 9, 8269–8278.
10 B. Helms, S. J. Guillaudeu, Y. Xie, M. McMurdo, C. J. Hawker and
J. M. Frechet, Angew. Chem., Int. Ed., 2005, 44, 6384–6387.
11 Y. G. Chi, S. T. Scroggins and J. M. Frechet, J. Am. Chem. Soc., 2008,
130, 6322–6323.
12 A. V. Biradar, V. S. Patil, P. Chandra, D. S. Doke and T. Asefa, Chem.
Commun., 2015, 51, 8496–8499.
13 F. Zhang, H. Y. Jiang, X. Y. Li, X. T. Wu and H. X. Li, ACS Catal.,
2013, 4, 394–401.
14 M. Filice and J. M. Palomo, ACS Catal., 2014, 4, 1588–1598.
15 A. C. Marr and P. C. Marr, Dalton Trans., 2011, 40, 20–26.
16 Y. Yang, X. Liu, X. B. Li, J. Zhao, S. Y. Bai, J. Liu and Q. H. Yang,
Angew. Chem., Int. Ed., 2012, 51, 9164–9168.
17 P. Li, C. Y. Cao, Z. Chen, H. Liu, Y. Yu and W. G. Song, Chem.
Commun., 2012, 48, 10541–10543.
18 Z. F. Jia, K. W. Wang, B. E. Tan and Y. L. Gu, ACS Catal., 2017, 7,
3693–3702.
19 M. L. Hossain, K. Wang, F. Ye, Y. Zhang and J. Wang, Chin. J. Catal.,
2017, 38, 115–122.
20 Z. H. Weng, T. Y. Yu and F. Zaera, ACS Catal., 2018, 8, 2870–2879.
21 L. J. Wei, M. Zhang, X. M. Zhang, H. C. Xin and H. Q. Yang, ACS
Sustainable Chem. Eng., 2016, 4, 6838–6843.
22 S. Crossley, J. Faria, M. Shen and D. E. Resasco, Science, 2010, 327, 68.
23 X. M. Yang, X. N. Wang and J. S. Qiu, Appl. Catal., A, 2010, 382, 131–137.
24 Z. Y. Xie, H. L. Ge, J. Y. Du, T. Duan, G. C. Yang and Y. He, Anal.
Chem., 2018, 90, 11665–11670.
25 Q. Zhang, R. X. Bai, T. Guo and T. Meng, ACS Appl. Mater. Interfaces,
2015, 7, 18240–18246.
acetals such as benzaldehyde propylene glycolacetal, the con-
tent of the final products was determined to be 85.5% within
12 h at 80 1C. These findings further demonstrate the effective-
ness of the Pickering emulsion based encapsulation strategy.
Furthermore, the reinforced droplets can easily settle down
at the bottom of the vessel soon after stopping the rotation,
which allows their recovery for multiple reaction cycles. As
listed in Table 1 (entry 1), in the second run, above 80% yield
of the final product could still be obtained after prolonging the
reaction time to 8 h. Though the recyclability is not very good, it
is the first time to realize the recycling of incompatible liquid
acid and base co-involved cascade reactions, which is otherwise
unattainable for the reported system. The shell of the reinforced
droplets plays an important role in this success.
In summary, taking advantaging of the interfacial sol–gel
(cross-linking) process, a reinforced Pickering emulsion has
first been developed successfully for the construction of cascade
reaction systems. This method was shown to enable the facile
encapsulation of liquid acid and base catalysts within the reinforced
droplets. The grown shell is proven to be able to compartmentalize
incompatible reagents to avoid mutual interferences even in the
same vessel, while its porous shell allows the reactant molecules to
diffuse freely to access the compartmentalized catalysts. These
merits constitute the key features of biomimetic multistep
synthesis to some extent. The investigation of the deacetalization–
Knoevenagel cascade reaction demonstrates the applicability of
our strategy in processing one-pot cascade reactions involving
incompatible reagents. The present approach will serve as a plat-
form for mimicking biocatalytic systems.
This work was supported by the National Natural Science
Foundation of China (21733009, 21573136, and U1510105), and
the Program for Youth Sanjin Scholar.
26 H. Jiang, Y. X. Li, L. Z. Hong and T. Ngai, Chem. – Asian J., 2018, DOI:
10.1002/asia.201800853.
27 L. C. Lee, J. Lu, M. Weck and C. W. Jones, ACS Catal., 2016, 6, 784–787.
28 H. Q. Yang, L. M. Fu, L. J. Wei, J. F. Liang and B. P. Binks, J. Am.
Chem. Soc., 2015, 137, 1362–1371.
Conflicts of interest
`
29 Z. Zhang, K. C. Tam, X. S. Wang and G. Sebe, ACS Sustainable Chem.
Eng., 2018, 6, 2583–2590.
30 J. S. Xu and M. Antonietti, J. Am. Chem. Soc., 2017, 139, 6026–6029.
31 R. Aveyard, B. P. Binks and J. H. Clint, Adv. Colloid Interface Sci.,
2003, 100, 503.
There are no conflicts to declare.
32 L. J. Wei, S. Yan, H. H. Wang and H. Q. Yang, NPG Asia Mater., 2018,
10, 899–911.
Notes and references
1 C. M. Agapakis, P. M. Boyle and P. A. Silver, Nat. Chem. Biol., 2012, 8, 33 Z. G. Feng, Y. S. Li, D. C. Niu, L. Li, W. R. Zhao, H. R. Chen, L. Li,
527–535. J. H. Gao, M. L. Ruan and J. L. Shi, Chem. Commun., 2008, 2629–2631.
2 M. Fischlechner, Y. Schaerli, M. F. Mohamed, S. Patil, C. Abell and 34 D. K. Shen, J. P. Yang, X. M. Li, L. Zhou, R. Y. Zhang, W. Li, L. Chen,
F. Hollfelder, Nat. Chem., 2014, 6, 791–796.
R. Wang, F. Zhang and D. Y. Zhao, Nano Lett., 2014, 14, 923–932.
This journal is ©The Royal Society of Chemistry 2018
Chem. Commun., 2018, 54, 13014--13017 | 13017