Waste-minimised copper-catalysed azide-alkyne cycloaddition in Polarclean as a reusable and safe reaction medium

Article abstract of DOI:10.1039/c7gc03022c

Herein we report the first example of a generally useful organic reaction, namely the copper-catalysed azide-alkyne cycloaddition, performed in a Polarclean/water mixture as a reaction medium. The process is very efficient, affording in 24 out of the 26 tested cases the desired triazole in quantitative yields. Product isolation is also very convenient, since the triazoles either precipitate or form a separate liquid phase, without the need to perform chromatographic separations. Moreover, since the metal catalyst is retained in the Polarclean/water phase, the catalyst/reaction medium can be easily reused for consecutive reaction runs, without an apparent loss in efficiency. This methodology is associated with very limited waste production, as evidenced by calculated E-factors in the range 2.6-3.7.

Full text of DOI:10.1039/c7gc03022c

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ARTICLE
Waste-minimised copper-catalysed azide-alkyne
cycloaddition in Polarclean as a reusable and safe reaction
medium
Received 00th January 20xx,
Accepted 00th January 20xx
Lorenzo Luciani,a Emily Goff,a Daniela Lanari,b Stefano Santoroa and Luigi Vaccaro*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
Herein we report the first example of a generally useful organic reaction, namely the copperꢀcataysed azideꢀalkyne
cyloaddition, performed in a Polarclean/water mixture as reaction medium. The process is very efficient, affording in 24 out
of the 26 tested cases the desired triazole in quantitative yields. Product isolation is also very convenient, since the triazoles
either precipitate or form a separate liquid phase, without the need to perform chromatographic separations. Moreover, since
the metal catalyst is retained in the Polarclean/water phase, the catalyst/reaction medium can be easily reused for
consecutive reaction runs, without apparent loss in efficiency. This methodology is associated with very limited waste
production, as evidenced by calculated Eꢀfactors in the range 2.6ꢀ3.7.
resulted in additional benefits, aside from the expected
advantages in terms of sustainability, such as a reduced metal
leaching from the support when using an heterogeneous catalyst
Introduction
It has been reported that the use of solvents accounts for the
largest part of the waste generated in chemical productions.1
Moreover, life cycle assessments have concluded that most of
the environmental footprint associated with the preparation of
complex organic molecules, such as active pharmaceutical
ingredients, is associated with the use of solvents.2 Thus, the
choice of a particular reaction medium is expected to play a
major role in determining the “greenness” of a chemical
synthesis. This, in turns, justifies the great efforts devoted to the
definition of novel chemical methodologies based on the use of
alternative reaction conditions3 and to the replacement of
common solvents with more sustainable substitutes.4 Most of
the chemicals that find nowadays wide application as reaction
media are derived from nonꢀrenewable fossil resources, which
is obviously far from ideal from the point of view of
sustainability. However, in recent years there has been a
growing interest in the development and in the application of
bioꢀbased solvents, i.e. chemicals derived from biomass
resources used as reaction media.5 In this context, our research
group pioneered the use of γꢀvalerolactone (GVL), a derivative
of lignocellulosic biomass,6 as a promising substitute for
dipolar aprotic solvents such as DMF, DMAc and NMP in by
and consequently improved catalystꢀrecyclability.
a) General copper-catalysed azide-alkyne cycloaddition (CuAAC):
R1
N
Cu(I) catalyst
N
R1
H
+
R2 N3
N
R2
Pros:
Cons:
ꢀ Usually requires chromatography
ꢀ Catalyst and solvent are rarely recycled
ꢀ High Eꢀfactors
+ Prototypical "click" reaction
+ Perfect atom economy
+ Gives access to useful scaffolds
b) This work:
CuSO4—5H2O (2 mol%)
R1
N
Naꢀascorbate (10 mol%)
N
R1
H
+
R2 N3
N
Polarclean
/H2O (4:1)
50 °C, 24 h
R2
Pros:
+ Excellent product yields
+ Very low Eꢀfactor: 2.6ꢀ3.7
+ Easy product isolation
+ No chromatography
+ Both catalyst and reaction media easily recycled
Scheme 1. Features of current work.
We have also been interested in the preparation of 1,2,3ꢀ
triazoles and their chemistry,7c,8 where a central role is played
the
widelyꢀused
copperꢀcatalysed
azideꢀalkyne
cycloaddition (CuAAC).9 This process is well representative of
those reactions that are typically conducted in a mixture of
water and an organic solvent, such as alcohols (EtOH, MeOH,
transitionꢀmetals
functionalisation reactions.7 In several cases the use of GVL
catalysed
crossꢀcoupling
and
C–H
t
ꢀBuOH), tetrahydrofuran, dichloromethane or acetonitrile, and
aLaboratory of Green Synthetic Organic Chemistry, Dipartimento di Chimica,
Biologia e Biotecnologie, Università di Perugia, Via Elce di Sotto 8, 06123 Perugia,
Italy. E-mail: luigi.vaccaro@unipg.it.
is generally catalysed by a Cu(I) species generated in situ from
the reduction of a Cu(II) salt by ascorbic acid or sodium
ascorbate.9
Very recently, within our research program aimed at the
definition of new and safe reaction media, we have proposed
the use of furfuryl alcohol (FA)/water azeotrope, as an effective
biomassꢀderived and easily recoverable reaction medium.8a
bDipartimento di Scienze Farmaceutiche, Università di Perugia Via del Liceo, 1,
06123 Perugia, Italy.
† Electronic Supplementary Informaꢀon (ESI) available: additional experimental
details, full characterization and NMR spectra of all compounds. See
DOI: 10.1039/x0xx00000x
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FA/water azeotrope proved to be crucial for the definition of a
new protocol for CuAAC, very efficient both in terms of
substrate scope and reactivity and of minimization of the waste
generated. This was evidenced by a calculated Eꢀfactor for a
representative reaction as low as 4.3, when typical procedures
have Eꢀfactors in the range of hundreds (Scheme 1).10
Polarclean as a reaction medium in an organic chemical
reaction.
Results and discussion
In CuAAC reactions the use of mixtures of water with a
miscible organic solvent is justified to ensure an adequate
solubility and mixing of the organic reagents and the required
inorganic species (i.e. copper catalyst and additives, such as
sodium ascorbate).
Looking for other chemicals that could find potential
application as green reaction media, we reasoned that
Rhodiasolv® Polarclean could be used as a substitute for
commonlyꢀemployed polar solvents in organic reactions.11
Polarclean (Figure 1), whose principal component is methylꢀ5ꢀ
(dimethylamino)ꢀ2ꢀmethylꢀ5ꢀoxopentanoate, is commercially
available and finds application as solvent or coꢀsolvent and
crystal growth inhibitor in agrochemical formulations. It is
miscible with water and has a boiling point of 278ꢀ282 °C and a
melting point of ꢀ60 °C. Polarclean is industrially produced in a
low carbon footprint process from methyleneglutarodinitrile
(MDN), a byꢀproduct of Nylon 66 manufacturing, otherwise
needed to be disposed.12
We started our investigation by reacting representative 1ꢀ
ethynylꢀ4ꢀmethylbenzene (1a) and azidobenzene (2a) and using
2 mol% of CuSO4ꢁ5H2O as a copper source together with 10
mol% of sodium ascorbate as a reductant (Table 1). First, we
checked the solubility of the reaction mixture in Polarclean,
which confirmed that inorganic reagents were not soluble. Still,
the reaction proceeded at 50 °C for 24 h to give triazole 3a in
70% conversion, although the pure product could only be
isolated by a classic procedure (aqueous workꢀup followed by
column chromatography). When using a 9:1 mixture of
Polarclean and water the reaction mixture was still partially
heterogeneous and led only to a 50% conversion after 24 h at
50 °C.
Table 1. Testing the use of Polarclean as medium for CuAAC
of 1a and 2a
.
N
CuSO4—5H2O (2 mol%)
Naꢀascorbate (10 mol%)
N
N
+
H
N3
Medium
1a
2a
3a
50 °C, 24 h
Medium
Conversion to 3a (%) Isolated Yield
Purification
aquoeus workꢀup/
column chmatography
Polarclean
70
55
35
99
Polarclean/H2O (9:1)
Polarclean/H2O (4:1)
50
column chmatography
Büchner filtration
100
Figure 1. Rhodiasolv® Polarclean structure and properties.
Finally, optimal results were obtained when using a 4:1 mixture
of Polarclean and water (Table 1). This combination of catalytic
system and reaction medium proved extremely efficient in
promoting the selective formation of the desired 1,4ꢀ
disubstituted triazole 3a in 24 h and at a mild temperature (50
°C). Investigating further the substrate scope we found very
satisfactory and consistent results. In fact, the protocol worked
smoothly on all 26 tested combinations of aryl and alkyl
To the best of our knowledge Polarclean has found very little
application as a reaction medium, limited to an example of
metathesis polymerization,13 an attempt of its use , among
many other solvents, in an olefin epoxidation reaction,14 and
also for the fabrication of hollow fibre membranes.15
With the aim of investigating the potential applicability of
Polarclean in useful organic transformations we decided to test
it as a reaction medium in the aboveꢀmentioned CuAAC
reaction. This would also allow for an easy and direct
comparison of the process sustainability with known protocols
and of course with our previously reported methodology based
on the FA/water azeotrope.8a
Therefore, starting from this previous knowledge and also on
the basis of our experience in the field, here we report the first
example of an efficient wasteꢀminimised CuAAC reaction
performed in Polarclean as reaction medium. To the best of our
knowledge this is the first example of a successful use of
acetylenes
1 with aryl and benzyl azides 2, affording the
products in all cases in excellent yields (in 24 of the cases in
quantitative yields) (Scheme 2). Importantly, the presence of
halogens as substituents in aromatic rings of the azide and/or of
the alkyne was in all cases wellꢀtolerated, allowing for
subsequent transformations of these functionalities. The
protocol proved to be very general in terms of substrate scope,
with product yields that are in most of the cases higher or
comparable to those reported in the literature. We also tested
our protocol in the preparation of six new triazoles (see ESI for
2 | J. Name., 2012, 00, 1-3
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Scheme 2. Scope of the copperꢀcatalysed azideꢀalkyne cycloaddition in
Polarclean/water. Reaction conditions: (0.5 mmol), (0.5 mmol), CuSO4ꢁ5H2O
(0.01 mmol, 2 mol%), sodium ascorbate (0.05 mmol, 10 mol%), Polarclean/H2O
4:1 (1 mL), 50 °C, 24h. All yields are isolated yields.
the detailed list of products and for a comparison of product
yields).
1
2
The reaction is operationally extremely easy, not requiring
special conditions such as inert atmosphere and allowing in
general for an easy isolation of the pure products. Mixing of the
reactants and the catalytic system (copper salt and reductant) in
the Polarclean/water phase results in a clear homogeneous
solution. Stirring the mixture at the reaction temperature (50
°C) results, with only one exception (product 3c), in the
A fundamental aspect in the design of a truly sustainable
methodology is the possibility to recycle the catalyst and the
reaction medium, since this generally allows for a dramatic
reduction in waste generation. To test to what extent our
methodology allows for recycling, we repeated the
representative reaction leading to the formation of product 3g
on a larger scale (20 mmol), recovering and reusing the 4:1
Polarclean/water phase at the end of the process (Scheme 3).
Initially we attempted the reuse of the medium by only adding
fresh azide and alkyne reactants, without any further addition of
catalyst or additives. However, this procedure resulted in slow
conversion to the expected triazole. Reasoning that the poor
reactivity could result from the oxidation of copper, rather than
from its depletion from the Polarclean/water phase, we added
additional 5 mol% of sodium ascorbate to the recovered
reaction medium before performing a new run. This modified
procedure allowed to obtain quantitative yields (99%) of
product 3g for at least five consecutive reaction runs (Scheme
3), proving the excellent recyclability of the catalyst/reaction
medium system and supporting our hypothesis that copper is
mostly retained in the Polarclean/water phase.
precipitation of the cycloaddition product 3. This can thus be
isolated by simple filtration, and washing of the solid with
water affords the pure product without need for further
purification. As mentioned, in a single case among our tested
reactions the product (3c) did not spontaneously precipitate
upon formation, forming instead a separated liquid phase. This
required a slightly modified isolation procedure, consisting in
the separation of the two liquid phases and addition of water to
the oily product, which resulted in the immediate formation of a
precipitate. Filtration and washing of the solid with water
allowed isolating the pure product in still excellent yield (90%)
(Scheme 2).
Scheme 3. Recycling of catalyst and reaction medium.
In the context of green chemistry, a quantitative evaluation of
the waste generated is essential to correctly evaluate the
achieved advance in terms of sustainability. We found that the
cumulative Eꢀfactor calculated on the five consecutive reaction
runs is as low as 3.7. The major contributors to this value are
the 4 mL of Polarclean/water eliminated as waste at the end of
the fifth reaction run, and the 2 mL of water used after each
reaction run to wash the solid product. However, it should be
considered that the catalyst/medium system could likely be
used for more than five runs, since even in the last one we
observed full conversion to the desired product in 24 hours.
Increasing the number of reaction runs, the Eꢀfactor could be
further reduced to 2.6, which is the lowest value obtainable for
each run considering full conversion and recovery of the
catalyst/medium system (see ESI for all details about the
recycling procedure and the calculation of the Eꢀfactors).
Comparing these values with those reported in the literature for
other CuAAC cycloaddition protocols, it can be clearly
demonstrated that the procedure reported here is far superior in
terms of reduced waste generation. Typical literature
procedures, in fact, are associated with Eꢀfactors in the range of
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2
3
4
(a) C. JiménezꢀGonzález, A. D. Curzons, D. J. C. Constable
and V. L. Cunningham, Int. J. Life Cycle Assess., 2004, 9,
114–121; (b) D. Cespi, E. S. Beach, T. E. Swarr, F. Passarini,
I. Vassura, P. J. Dunn and P. T. Anastas, Green Chem., 2015,
17, 3390–3400.
(a) Alternative Energy Sources for Green Chemistry, ed. G.
Stefanidis and A. Stankiewicz, RSC Green Chemistry Series,
Cambridge, 2016; (b) Methods and Reagents for Green
Chemistry: An Introduction, ed. P. Tundo, A. Perosa and F.
Zecchini, John Wiley & Sons, Hoboken, 2007.
(a) F. M. Kerton and R. Marriott, Alternative Solvents for
Green Chemistry, RSC Green Chemistry Series, Cambridge,
2nd edn, 2013; (b) A. Jain, R. Vyas, A. Ameta and P. B.
Punjabi, in Green Chemistry: Fundamentals and
Applications, ed. S. C. Ameta and R. Ameta, CRC Press,
2013, pp. 161–198; (c) C. M. Alder, J. D. Hayler, R. K.
Henderson, A. M. Redman, L. Shukla, L. E. Shuster and H. F.
Sneddon, Green Chem., 2016, 18, 3879–3890; (d) L. J.
Diorazio, D. R. J. Hose and N. K. Adlington, Org. Process
Res. Dev., 2016, 20, 760–773; (e) D. Prat, A. Wells, J.
Hayler, H. Sneddon, C. R. McElroy, S. AbouꢀShehada and P.
J. Dunn, Green Chem., 2016, 18, 288–296; (f) D. Prat, J.
Hayler and A. Wells, Green Chem., 2014, 16, 4546–4551; (g)
D. Prat, O. Pardigon, H.ꢀW. Flemming, S. Letestu, V.
Ducandas, P. Isnard, E. Guntrum, T. Senac, S. Ruisseau, P.
Cruciani and P. Hosek, Org. Process Res. Dev., 2013, 17,
1517–1525; (h) P. G. Jessop, Green Chem., 2011, 13, 1391–
1398; (i) R. K. Henderson, C. JiménezꢀGonzález, D. J. C.
Constable, S. R. Alston, G. G. A. Inglis, G. Fisher, J.
hundreds, without considering that usually the products are
purified by column chromatography, which could easily result
in an increase of the Eꢀfactors up to thousands.10 It is worthꢀ
mentioning that also our recently reported procedure based on
the use of the recoverable FA/water azeotrope as reaction
medium8a is associated to slightly higher Eꢀfactor (4.3),
compared to the method reported here.
The Polarclean/water protocol features some evident
advantages compared to our previously reported methodology.
First, it allows for complete catalyst recycling, while in the
FA/water protocol the copper salt had to be added in every
reaction run. Second, the reaction medium is practically fully
recovered at the end of the process by simple filtration of the
solid products. When performing the reaction in FA/water, on
the other hand, the azeotropic reaction medium had to be
recovered by distillation, with inevitable loss of material. This
also contributes to the difference in waste generation between
the FA/water and the Polarclean/water methodologies.
Conclusions
In conclusion, we have shown that a 4:1 mixture of Polarclean
and water can be used as reaction medium for the widelyꢀused
copperꢀcatalysed alkyneꢀazide cycloaddition, providing the
expected triazoles in excellent, and often quantitative, yields
(26 different products prepared). In almost all the cases the
product precipitates in the reaction medium and can thus be
simply isolated by filtration, without the need of timeꢀ
Sherwood, S. P. Binks and A. D. Curzons, Green Chem.
,
2011, 13, 854–862; (j) J. H. Clark and S. J. Tavener, Org.
Process Res. Dev., 2007, 11, 149–155.
(a) S. Santoro, F. Ferlin, L. Luciani, L. Ackermann and L.
Vaccaro, Green Chem., 2017, 19, 1601–1612; (b) A. G.
5
6
consuming
and
wasteꢀgenerating
chromatographic
Corrêa, M. W. Paixão and R. S. Schwab, Curr. Org. Synth.
,
2015, 12, 675–695; (c) Y. Gu and F. Jérôme, Chem. Soc.
purifications. Moreover, the copper catalyst is retained in the
Polarclean/water phase, which allows for an easy and
convenient recycling of the catalyst/reaction medium system
for several reaction runs, without apparent loss of efficiency.
To the best of our knowledge this is the first successful
application of Polarclean as a reaction medium in an organic
process of general interest. Moreover, this is the copperꢀ
catalysed alkyneꢀazide cycloaddition associated with the lowest
generation of waste that we are aware of, as evidenced by the
calculated Eꢀfactors.
Rev., 2013, 42, 9550–9570; (d) I. T. Horváth, Green Chem.
2008, 10, 1024–1028.
(a) P. Pongrácz, L. Kollár and L. T. Mika, Green Chem.
,
,
2016, 18, 842; (b) Z. Zhang, ChemSusChem, 2016, 9, 156–
171; (b) L. Qi, Y. F. Mui, S. W. Lo, M. Y. Lui, G. R. Akien
and I. T. Horváth, ACS Catal., 2014, 4, 1470–1477; (c) E. I.
Gürbüz, J. M. R. Gallo, D. M. Alonso, S. G. Wettstein, W. Y.
Lim and J. A. Dumesic, Angew. Chem. Int. Ed., 2013, 52,
1270–1274; (d) S. G. Wettstein, D. M. Alonso, Y. Chong and
J. A. Dumesic, Energy Environ. Sci., 2012, 5, 8199–8203; (e)
Z.ꢀQ. Duan and F. Hu, Green Chem., 2012, 14, 1581–1583;
(f) L. Qi and I. T. Horváth, ACS Catal., 2012, 2, 2247–2249;
(g) I. T. Horváth, H. Mehdi, V. Fábos, L. Boda and L. T.
Mika, Green Chem., 2008, 10, 238–242.
(a) F. Ferlin, S. Santoro, L. Ackermann and L. Vaccaro,
Green Chem., 2017, 19, 2510–2514; (b) D. Rasina, A.
KahlerꢀQuesada, S. Ziarelli, S. Warratz, H. Cao, S. Santoro,
L. Ackermann and L. Vaccaro, Green Chem., 2016, 18,
5025–5030; (c) X. Tian, F. Yang, D. Rasina, M. Bauer, S.
Warratz, F. Ferlin, L. Vaccaro and L. Ackermann, Chem.
Commun., 2016, 52, 9777–9780; (d) G. Strappaveccia, E.
Ismalaj, C. Petrucci, D. Lanari, A. Marrocchi, M. Drees, A.
Facchetti and L. Vaccaro, Green Chem., 2015, 17, 365–372;
(e) G. Strappaveccia, L. Luciani, E. Bartollini, A. Marrocchi,
F. Pizzo and L. Vaccaro, Green Chem., 2015, 17, 1071–1076;
(f) E. Ismalaj, G. Strappaveccia, E. Ballerini, F. Elisei, O.
Piermatti, D. Gelman and L. Vaccaro, ACS Sustainable
Chem. Eng., 2014, 2, 2461–2464.
Further experiments aimed at investigating the applicability of
Polarclean as reaction medium in other organic processes are
currently ongoing in our laboratory, and will be published in
due course.
7
Acknowledgements
The Università degli Studi di Perugia is acknowledged for
financial support. S.S. gratefully acknowledges the MIUR for
“Programma Giovani Ricercatori, Rita Levi Montalcini”,
fellowship N. PGR123GHQY. Solvay (Rhodiasolv) is
ackowledged for free samples of Polarclean.
Notes and references
8
(a) D. Rasina, A. Lombi, S. Santoro, F. Ferlin and L.
Vaccaro, Green Chem.
, 2016, 18, 6380–6386; (b) A.
1
C. JimenezꢀGonzalez, C. S. Ponder, Q. B. Broxterman and J.
Marrocchi, A. Facchetti, D. Lanari, S. Santoro and L.
Vaccaro, Chem. Sci., 2016, 7, 6298–6308; (c) G.
B. Manley, Org. Process Res. Dev., 2011, 15, 912–917.
4 | J. Name., 2012, 00, 1-3
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ARTICLE
D'Ambrosio, F. Fringuelli, F. Pizzo and L. Vaccaro, Green
Chem., 2005, 7, 874–877; (d) D. Amantini, F. Fringuelli, O.
Piermatti, F. Pizzo, E. Zunino and L. Vaccaro, J. Org. Chem.
2005, 70, 6526–6529.
,
9
(a) F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L.
Noodleman, K. B. Sharpless and V. V. Fokin, J. Am. Chem.
Soc., 2005, 127, 210–216; (b) V. O. Rodionov, V. V. Fokin
and M. G. Finn, Angew. Chem., Int. Ed., 2005, 44, 2210–
2215; (c) V. V. Rostovtsev, L. G. Green, V. V. Fokin and K.
B. Sharpless, Angew. Chem., Int. Ed., 2002, 41, 2596–2599;
(d) C. W. Tornøe, C. Christensen and M. Meldal, J. Org.
Chem., 2002, 67, 3057–3064. For recent applications, see: (d)
X. Zhang, S. Zhi, W. Wang, S. Liu, J. P. Jasinskid and W.
Zhang, Green Chem., 2016, 18, 2642–2646; (e) S. Chassaing,
V. Beneteau and P. Pale, Catal. Sci. Technol., 2016, 6, 923–
957; (f) E. Haldon, M. C. Nicasio and P. J. Pérez, Org.
Biomol. Chem., 2015, 13, 9528–9550; (g) F. Alonso, Y.
Moglie and G. Radivoy, Acc. Chem. Res., 2015, 48, 2516–
2528; (h) A. Qin, Y. Liu and B. Z. Tang, Macromol. Chem.
Phys., 2015, 216, 818–828; (i) H. Wu, H. Li, R. T. R. T. K.
Kwok, E. Zhao, J. Z. Sun, A. Qin and B. Z. Tang, Sci. Rep.
,
2014, 4, 5107–5112; (j) M. Juríček, P. H. J. Kouwer and A.
E. Rowen, Chem. Commun., 2011, 47, 8740–8749; (k) C. R.
Becer, R. Hoogenboom and U. S. Schubert, Angew. Chem.,
Int. Ed., 2009, 48, 4900–4908.
10 Calculated as an average from procedures reported in ref. 9c
and: (a) L. Rinaldi, K. Martina, F. Baricco, L. Rotolo and G.
Cravotto, Molecules, 2015, 20, 2837–2849; (b) B.ꢀY. Lee, S.
R. Park, H. B. Jeon and K. S. Kim, Tetrahedron Lett., 2006,
47, 5105–5109; see ref. 8a for details.
11 (a) O. Jentzer and M. Guglieri, US Pat., US8735324, 2011;
(b) P. Baur, M. Steinbeck, I. Wetcholowsky, T. Auler, A.
Daniels and R. Pontzen, US Pat., US9510589, 2011; (c) O.
Jentzer and M. Guglieri, US Pat., US9392785, 2014; (d) H.
B. Lopez and P. J. Porpiglia, US Pat., US2014031232, 2014;
(e) L. Iannotta, R. Pazhianur, K. M. Shanmuga, J. A. Latting
and T. K. Woodall, US Pat., US2013145806, 2013; (f) A.
Randová, L. Bartovská, P. Morávek, P. Matějka, M. Novotná,
S. Matějková, E. Drioli, A. Figoli, M. Lanč and K. Friess, J.
Mol. Liq., 2016, 224, 1163–1171.
12 http://www.rscspecialitychemicals.org.uk/docs/rscꢀ
symposium/SustainableꢀSolventsꢀProductsꢀandꢀProcessꢀ
Innovations_ThierryꢀVidal_ꢀRSCꢀSymposiumꢀ2012.pdf
(accessed September 2017).
13 T. Lebarbé, A. S. More, P. S. Sane, E. Grau, C. Alfos and H.
Cramail, Macromol. Rapid Commun., 2014, 35, 479–483.
14 A. Mouret, L. Leclercq, A. Mühlbauer and V. NardelloꢀRataj,
Green Chem., 2014, 16, 269–278.
15 N. T. Hassankiadeh, Z. Cui, J. H. Kim, D. W. Shin, S. Y. Lee,
A. Sanguineti, V. Arcella, Y. M. Lee, E. Drioli, J. Membr.
Sci. 2015, 479, 204–212.
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