Supported Sulfonic Acids: Solid Catalysts for Batch and Continuous-Flow Synthetic Processes

Article abstract of DOI:10.1002/open.201402148

It's easy being green! In this work, supported sulfonic acids were used as effective catalysts for different classes of reactions. They have the advantage of being cheap, safe, and easy to recycle. Reaction conditions are mild, have good atom economy, and work-up steps are very easy, satisfying essential parameters of the "green chemistry" philosophy. Application of these catalysts to continuous-flow processes resulted in a considerable improvement in efficiency.

Full text of DOI:10.1002/open.201402148

DOI: 10.1002/open.201402148
Supported Sulfonic Acids: Solid Catalysts for
Batch and Continuous-Flow Synthetic
Processes
Calogero G. Piscopo*[a]
Awarding Institute: Università degli Studi di Parma (I), Parma (Italy)
Date Awarded: March 1st, 2012
Supervisors: Prof. Giovanni Sartori, Università degli Studi di Parma, Parma (Italy)
Prof. Raimondo Maggi, Università degli Studi di Parma, Parma (Italy)
In recent years the need to reduce production costs and the increasing regulations in pollution pre-
vention prompted industries and academia to revise old processes for fine chemical and pharmaceuti-
cal synthesis. A powerful tool to enhance the sustainability of chemical processes is, undoubtedly, het-
erogeneous catalysis, which allows a few improvements over homogeneous catalysis and can help de-
velop cleaner, safer, and more economically feasible processes. In the field of heterogeneous catalysis,
two preferential methods have been developed: the use of polymer-supported catalysts and the use
of solid inorganic oxide catalysts. In the last years, much effort has been devoted to the heterogeniza-
tion of catalysts, and different strategies have been developed for the preparation of supported homo-
geneous catalysts.
The ideal supported catalyst should satisfy many requirements in order to combine the advantages
of both homogeneous and heterogeneous catalysis. With careful catalyst design and an appropriate
support choice based on reaction conditions (e.g. solvent, temperature, reactant, etc.) it is possible to
prepare highly efficient supported catalysts. Recently the synthesis of organic compounds using sup-
ported catalysts or reagents has been of great interest in flow systems. This approach represents a rela-
tively new area of study in rapid progress and it promises to improve the ease, efficiency, and automa-
tion of liquid-phase synthesis. The flow systems have several advantages over conventional batch pro-
cesses:
1. They allow for prolonged use of the supported catalyst because physical damage due to magnetic
stirring is minimized.
2. They allow easy or no work-up at the end of the process.
3. The support does not need to be removed from the reaction medium and continuous production
is possible.
Brønsted and Lewis acids are the most important and most common catalysts. Many organic reac-
tions such as aldol condensations, nucleophilic additions, hydrolysis, acylations, etc. are catalyzed by
these acids. However, the use of soluble acids or corrosive mineral acids is associated with a great
number of environmental and economic problems.
[a] Dr. C. G. Piscopo
Clean Synthetic Methodology Group, Dipartimento di Chimica dell’Università
Università degli Studi di Parma, Parco Area delle Scienze 178, 43124 Parma (Italy)
and
Current position: Energetic Materials, Fraunhofer Institute for Chemical Technology (ICT)
Joseph-von-Fraunhoferstr. 7, Pfinztal, 76327 (Germany)
E-mail: calogero.piscopo@ict.fraunhofer.de
The full thesis is available as Supporting Information on the WWW under http://dx.doi.org/10.1002/open.201402148.
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which per-
mits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for
commercial purposes.
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Synthesis and characterization of supported sulfonic acids
Sulfonic acids are organic compounds that exhibit an acid strength comparable to that of sulfuric and
benzenesulfonic acids, which are strong acids frequently used in organic solvents. The synthesis of
silica-supported sulfonic acids can be achieved with different procedures. This thesis deals with the
synthesis and evaluation of the catalytic activity of some supported sulfonic acids as heterogeneous
and reusable catalysts in several organic reactions that are of synthetic interest.
Various supported sulfonic acids were prepared according to well-known literature procedures, with
slight modifications (Scheme 1 and Scheme 2). To probe the acid behavior of the supported species,
Scheme 1. Synthesis of the supported sulfonic acids used in this work. Preparation of propanesulfonic acids tethered onto
a) silica (method A); b) mesoporous silica MCM-41 (method B); c) silica via sol-gel (SG) method.
the materials and the bare support (as a reference), were analyzed using infrared (IR) spectroscopy in
degassed conditions (Figure 1) and under 20 mbar of water vapor (Figure 2). The consequences of the
interaction with water were the depletion of the sulfurylic signal in the 1390–1325 cmÀ1 range and the
appearance of a continuous absorption extended from 3500–1700 cmÀ1. The latter is a kind of “finger-
print” of the formation of H+(H2O)n clusters, and it probes the transfer of protons to the aqueous
layers from ÀSO3H groups, which are converted into ÀSO3À. Thus, it can be stated that the contact
with an aqueous medium results in complete deprotonation of the sulfonic groups.
Subsequently the interaction between the supported sulfonic acids and hydrogen peroxide was in-
vestigated. Hydrogen peroxide is an ideal oxidant for many reasons, mainly due to the fact that it is
cheap, water is theoretically the sole byproduct, and its activation is a challenge that has attracted
many research groups in order to perform oxidation reactions under environment-friendly conditions.
The diffuse reflectance UV/Vis spectra of supported sulfonic acids contacted with an aqueous hydro-
gen peroxide solution suggested the possibility of an electrophilic activation of hydrogen peroxide via
H-bonding.
Supported sulfonic acids as novel catalysts in green oxidation processes
The activity of some supported sulfonic acid catalysts was tested in the Baeyer–Villiger oxidation with
30% aqueous hydrogen peroxide, using cyclohexanone as model substrate and hexafluoroisopropanol
(HFIP) as solvent. In all cases, the cyclohexanone conversion reached comparable high values (80–
90%) independent from the acidity and surface area parameters of the catalyst used. The best catalyst
efficiency was achieved by using a silica-supported propylsulfonic acid prepared by a tethering proce-
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Scheme 2. Synthesis of the supported sulfonic acids used in this work. Preparation of a) butanesulfonic acid tethered onto
amorphous silica; b) arylsulfonic acid tethered onto silica or silica alumina (SA); c) 4-propoxybenzensulfonic acid tethered
onto silica; d) (2-trifluoromethyl)-perfluoroethanesulfonic acid tethered onto silica.
dure (3, Scheme 1a). Kinetic studies demonstrated that the desired lactone is produced through
a spiro-bisperoxide intermediate.
In a flowing-case synthetic study, supported sulfonic acids were evaluated as catalysts in the 1,2-di-
hydroxylation of 1-methylcyclohexene with hydrogen peroxide. The best result in terms of yield (90%)
and selectivity (96%) of 1-methyl-1,2-cyclohexanediol was obtained with the silica-supported 4-ethyl-
phenylsulfonic acid (21, Scheme 2b). To achieve further information on the behavior of these catalysts,
we analyzed the reactions with silica-supported phenylsulfonic, ethylphenylsulfonic, and propoxyphe-
nylsulfonic acids under solvent-free conditions. Variable induction periods were observed with these
supported acids; these induction times are expected to be due to the production of the active species.
This reaction is obviously affected by the sulfonic acid group’s accessibility, which depends on the
length of the arm that binds them to the support surface: propoxyphenyl>ethylphenyl>phenyl.
Another relevant synthetic process that was investigated using supported sulfonic acid catalysts is
the oxidation of methylhydroquinone to methylbenzoquinone with 30% aqueous hydrogen peroxide.
The propylsulfonic acid tethered on both amorphous (3, Scheme 1a<xschr1) and mesoporous MCM-
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Figure 1. IR spectra of samples degassed at beam temperature (ca. 508C) for 1 h: a) bare silica; b) catalyst 16; c) catalyst 24;
d) catalyst 21.
Figure 2. IR spectra of degassed samples and after contact with 20 mbar of water vapor (x, x’): a) bare silica; b) catalyst 16;
c) catalyst 24; d) catalyst 21.
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41 silica (5, Scheme 1a) showed optimal activities. The reusability of SiO2À(CH2)3ÀSO3H was then
checked. The catalyst that is simply recovered by filtration and washed with hot methanol can be
reused twice without loss of activity. The good synthetic results and, in particular, the effective catalyst
recyclability achieved in the batch experiments were further developed on a continuous-flow catalytic
system. The product was obtained in 55% yield, achieving a very high selectivity (95%), which is the
most important parameter in a continuous-flow system.
Similarly the thioanisole oxidation reaction with hydrogen peroxide was examined under continu-
ous-flow conditions. A simple process was set up using a glass column packed with Amberlite IR 120H
as a reactor; and precise control of the flow rate of the reagent solutions was assured by two syringe
pumps. The model reaction was investigated by conducting a systematic variation of experimental pa-
rameters. The desired sulfoxide was obtained in 94% yield and 99% selectivity, using a stoichiometric
amount of 30% aqueous hydrogen peroxide. The promising results achieved in these experiments
suggested the possibility to perform the oxidation of thioanisole with even more dilute hydrogen per-
oxide. For this reason, we used a 3% aqueous hydrogen peroxide solution, which is very cheap and
can be handled safely. The yield was 90%, which, surprisingly, was only a small decrease. Moreover, as
the sulfoxide was the only product, the reaction was completely selective. Finally, the catalyst could be
used for at least 3000 min without any loss of activity. These results represent the first example of the
successful oxidation of aromatic sulfides with 3% aqueous hydrogen peroxide. It must be emphasized
that this process avoids the use of any metals for the activation of the oxidizing reagent.
Catalytic CÀC bond formation promoted by supported sulfonic acid catalysts
CÀC bond formation represents a fundamental transformation in organic synthesis; in fact, the reac-
tions that allow the formation of this bond are key steps in many synthetic routes of valuable organic
chemicals and natural products, as well as in a variety of industrial applications. Thus, these reactions
are important tools for synthetic chemists. In this work two different reactions that allow CÀC bond
formation were explored: the Friedel–Crafts acylation of aromatics and the coupling reaction between
ketones and xanthene through CÀH bond activation.
The acylation reaction of anisole, catalyzed by silica-supported sulfonic acids was carried out. The
above method shows low environmental impact because it avoids the use of halogenated com-
pounds, and acetic acid is the only byproduct. The activity of different catalysts was compared. In all
cases, 4-methoxyacetophenone was the major product. The best result in terms of both yield (71%)
and selectivity (95%) toward the desired product was achieved with the perfluoroalkyl sulfonic acid
tethered onto silica (26, Scheme 2d). The different activities of the tested materials seem to be corre-
lated to the strength of the supported sulfonic acids. In fact, catalyst 26 is undoubtedly a stronger
acid used in this work due to the inductive effect played by the fluorine atoms; on the contrary, cata-
lysts 13 (Scheme 2a) and 21 (Scheme 2b) are weaker acids, and consequently, their activity is lower.
The model reaction was then performed using different aliphatic anhydrides with anisole. Experi-
mental results underline that the anisole conversion and the aromatic ketone yield increase with the
number of carbon atoms of the anhydrides, going from acetic anhydride (two carbon atoms) to valeric
anhydride (five carbon atoms). With longer alkyl chains, the reactivity slightly decreases. This behavior
may be attributed to a hydrophobic positive effect, which can improve the reactivity until the maxi-
mum is reached with valeric anhydride; for longer anhydrides, this effect is overbalanced by a negative
steric influence.
Among the wide panorama of CÀC bond formation reactions, cross-dehydrogenative
coupling (CDC) is becoming a highly attractive example because it can unlock new opportunities for
greener synthetic strategies. To study this area of interest, we selected the CDC between cyclopenta-
none and xanthene as a model reaction. The catalytic tests carried out under an oxygen atmosphere
showed that in all cases, 2-(9H-xanthen-9-yl)cyclopentanone was produced as the only product; in par-
ticular, the silica-supported 4-ethylphenylsulfonic acid (21, Scheme 2b) showed the best catalytic activ-
ity for this reaction (74% yield). Further studies on the parameters affecting the reaction were per-
formed by using Amberlyst-15 as a solid catalyst, being commercially available, more economical, and
safer to handle. The scope and generality of the oxidative coupling process with respect to various nu-
cleophiles was then investigated. Experimental results confirmed the general applicability of the
method to different cyclic and linear ketones and to 1,3-dicarbonyl compounds. Yields of isolated
products are between 55 and 90%, accompanied by excellent selectivity values (83–99%). Finally, the
catalyst recyclability was tested in the reaction between xanthene and cyclohexanone.
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The supported sulfonic acids used in this work showed very good catalytic activity in different
classes of reactions. These catalysts have the advantage of being cheap, safe to handle, and easy to re-
cycle. Reaction conditions are mild, with very good atom economy in most cases, and work-up steps
are very easy, satisfying several essential parameters of the “green chemistry” philosophy. Furthermore
the application of these catalytic systems to continuous-flow processes resulted in a considerable im-
provement in efficiency.
Keywords: continuous-flow synthesis · green chemistry · oxidation · solid acids · sulfonic acids ·
supported catalysts
Publications arising from this work:
*
C. G. Piscopo, S. Bühler, G. Sartori, R. Maggi, Catal. Sci. Technol. 2012, 2, 2449–2452.
*
R. Maggi, G. Martra, C. G. Piscopo, G. Alberto, G. Sartori, J. Catal. 2012, 294, 19–28.
*
R. Maggi, C. G. Piscopo, G. Sartori, L. Storaro, E. Moretti, Appl. Catal. A 2012, 411–412, 146–152.
*
C. G. Piscopo, A. Adorni, R. Maggi, G. Sartori, Chim. Oggi 2011, 29 (Supplement), 6–8.
*
R. Maggi, S. Chitsaz, S. Loebbecke, C. G. Piscopo, G. Sartori, M. Schwarzer, Green Chem. 2011, 13, 1121–1123.
*
C. G. Piscopo, S. Loebbecke, R. Maggi, G. Sartori, Adv. Synth. Catal. 2010, 352, 1625–1629.
Received: December 10, 2014
Published online on January 16, 2015
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