Silica-supported policresulen as a solid acid catalyst for organic reactions

Article abstract of DOI:10.1016/S1872-2067(15)60910-X

A new type of solid catalyst was prepared by coating a thin layer of policresulen, an inexpensive polymer prepared via condensation of 2-hydroxy-4-methylbenzenesulfonic acid and formaldehyde that has been used as commercially available drug, onto the surface of silica. The policresulen component is insoluble in many organic solvents and can be adsorbed on silica with the aid of hydrogen bonding. The obtained silica/policresulen composite showed remarkable catalytic activity for various organic reactions. In model reactions, the catalyst can be recycled several times without significant loss of activity. The salient features of using this acid catalyst in organic reactions include cost-effectiveness, simple and time-efficient preparation, and the convenience of controlling the acid loading on the solid.

Full text of DOI:10.1016/S1872-2067(15)60910-X

Chinese Journal of Catalysis 36 (2015) 1606–1613
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article (Special Issue for Excellent Research Work in Recognition of Scientists Who Are in Catalysis Field in China)
Silica-supported policresulen as a solid acid catalyst for organic
reactions
Kexing Zeng a,†, Zhipeng Huang a,†, Jie Yang a, Yanlong Gu a,b,
*
a Key Laboratory for Large-Format Battery, Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong Uni-
versity of Science and Technology, Wuhan 430074, Hubei, China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000,
Gansu, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A new type of solid catalyst was prepared by coating a thin layer of policresulen, an inexpensive
polymer prepared via condensation of 2-hydroxy-4-methylbenzenesulfonic acid and formaldehyde
that has been used as commercially available drug, onto the surface of silica. The policresulen com-
ponent is insoluble in many organic solvents and can be adsorbed on silica with the aid of hydrogen
bonding. The obtained silica/policresulen composite showed remarkable catalytic activity for vari-
ous organic reactions. In model reactions, the catalyst can be recycled several times without signifi-
cant loss of activity. The salient features of using this acid catalyst in organic reactions include
cost-effectiveness, simple and time-efficient preparation, and the convenience of controlling the acid
loading on the solid.
Received 25 April 2015
Accepted 22 May 2015
Published 20 September 2015
Keywords:
Acid catalysis
Solid acid
Policresulen
Covalent bond-free immobilization
oxa-Pictet-Spengler reaction
© 2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
waste streams as well as reusability of the catalyst [9–11]. For
this reason, heterogeneous solid acids have been extensively
Acid catalysts have been widely used in both academia and
industry, and can be categorized into two major types: homo-
geneous liquid acids and heterogeneous solid acids [1–3]. Alt-
hough homogeneous mineral acids, such as H2SO4 and HF,
which are corrosive and toxic, have been widely adopted by
chemical industry, with increasing pressure coming from envi-
ronmental protection there is a need to develop green synthetic
systems based on environmentally benign acid catalysts [4–8].
The use of heterogeneous solid acid catalysts has the general
advantages of easier operation, milder conditions, reduced
equipment corrosion, and minimized contamination of the
investigated [12–15], and in some chemical processes, their use
has already contributed to significant improvement of both the
synthetic efficiency and the greenness of the system [16–23].
Despite promising and sometime spectacular results, the prac-
tical application of solid acids in industrial processes is still
hindered by many factors. Among all the methods used to pre-
pare solid acids, the binding of catalysts to organic polymers or
inorganic solids is widely used to produce a stable covalent
bond between the acid center and the solid support, and is
preferable to reduce the chance of leaching [24–26]. The syn-
thesis of some solid acids with this method, however, involves
* Corresponding author. Tel: +86-027-87543032; Fax: +86-027-87544532; E-mail: klgyl@hust.edu.cn
† These authors contributed equally to this work
This work was supported by the National Natural Science Foundation of China (21173089, 21373093), the Fundamental Research Funds for the
Central Universities of China (2014ZZGH019), and the Cooperative Innovation Center of Hubei Province.
DOI: 10.1016/S1872-2067(15)60910-X | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 9, September 2015

Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
1607
several steps which are rather time-consuming. Furthermore,
functionalization of a solid support using covalent bonds often
requires harsh reaction conditions and as a consequence, calls
for both a support and an acid precursor with sufficient chemi-
cal and thermal stability [27]. In many cases, a sophisticated
operational procedure is also needed [28]. Therefore, some
current solid acid catalysts are rather expensive and are there-
fore not widely used in synthesis. There thus exists a need to
develop new, innovative approaches toward the design of re-
coverable and reusable solid acid catalysts.
struct a new heterogeneous acid catalyst using this reagent as a
homogeneous counterpart in conjunction with silica as a sup-
porting material. Thus, we herein report a new solid acid com-
posed of silica and policresulen that displays remarkable cata-
lytic activity in many organic reactions. Compared with con-
ventional solid acids, such as silica-supported sulfonic acid
catalysts and Amberlyst-15, the materials obtained by our
method have several advantages including simple and
time-efficient preparation, low cost, and controllable sulfonic
acid loading as well as tunable catalytic activity.
Recently, the concept of solid-supported liquid phase catal-
ysis has experienced a rekindled interest in the catalytic and
synthetic community for the preparation of efficient heteroge-
neous catalytic materials [29–34]. With the aid of a thin layer of
less volatile fluid coated onto the surface of solid support, some
homogeneous catalysts have been easily immobilized without
employing sophisticated operational procedures. In a selected
reaction, solid form of the catalyst enables an easy recycling,
but the reaction proceeded in microcosmically homogeneous
conditions [35,36]. Inspired by this elegant strategy, we envi-
sion that it may be possible to transfer this concept to the de-
velopment of a solid acid catalyst. To realize this idea, an acidic
species that is amenable to the immobilization step and can
stay stable on the surface of solid support is needed.
Policresulen is prepared by the condensation of meta-
cresolsulfonic acid and formaldehyde and is commercially
available as a clear red-brown solution. It is available at a low
price in a number of countries worldwide [37]. Its systematic
name is 2-hydroxy-3,5-bis(4-hydroxy-2-methyl-5-sulfobenzyl)-
4-methylbenzenesulfonic acid. Policresulen is a topical hemo-
static and antisepticwidely used as medicine for treating com-
mon anal disorders, such as hemorrhoids, and for gynecological
infections [38]. Because the backbone of this reagent contains
many hydroxyl and sulfonic acid groups, it is barely soluble in
many organic solvents, such as toluene, ethyl acetate, and di-
chloroethane. The thermal stability and chemical stability of
policresulen are quite good, making the extension of its appli-
cations to other fields possible. Considering that policresulen is
a strong organic acid, and also taking into account its hydro-
philic properties, we propose that it may be possible to con-
2. Experimental
2.1. Preparation of SiO2/policresulen composite catalysts
1a–1d
In a typical procedure used to prepare silica/policresulen
composite catalyst 1b, silica gel (10 g) was added to a 250-mL
round-bottomed flask containing a mixture of aqueous
policresulen solution (52 wt%, 2.09 g) and ethanol (150 mL).
The suspension was stirred at room temperature for 30 min
prior to the removal of the ethanol and water under reduced
pressure, affording free-flowing solid 1b. Catalysts with differ-
ent amounts of loaded policresulen (1a, 1c, 1d) were prepared
in an analogous way.
2.2. Preparation of TiO2-supported benzenesulfonic acid
catalyst 1f
Titanium oxide (5 g) and toluene (100 mL) were added to a
250-mL round-bottomed flask equipped with magnetic stirring
and
a
Dean-Stark apparatus. After 10
h
of reflux,
4-hydroxybenzenesulfonic acid (3.87 g) dissolved in acetoni-
trile (7 mL) was added to the system and refluxed for another
16 h. At the end of the reaction, the solid was filtered, washed
with ethanol (50 mL × 5) and dried under vacuum conditions,
yielding catalyst 1f. The ion exchange capacity of this catalyst
was measured by titration. The obtained result was in good
agreement with elemental analysis of the sulfur and carbon
content.
Yanlong Gu (Huazhong University of Science and Technology) received the Catalysis Rising
Star Award in 2012, which was presented by The Catalysis Society of China. Professor Yanlong
Gu received his Ph.D. degree in Physical Chemistry from Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, in 2005. He then started a journey as post-doc researcher in the
group of Prof. Shu Kobayashi, The University of Tokyo, Japan, and the group of Prof. Francois
Jerome, The University of Poitiers, France. Since October 2008, Yanlong Gu become a professor
in School of Chemistry and Chemical Engineering, Huazhong University of Science and Tech-
nology. In 2009, he received an award of New Century Excellent Talents in Chinese Universities.
He has a broad interest in homogeneous and heterogeneous catalysis, organic synthesis, bio-
mass valorization and utilization. His research efforts are focusing on (1) catalysis with acids
and ionic liquids; (2) green organic reactions for organic synthesis; and (3) eco-efficient pro-
cesses based on utilization of biomass. He has published more than 80 research papers, 4 re-
views in international peer review journals, and contributed two book chapters in the fields. H
index of his publications reached 31 in 2015. Currently, he is a board member of Current Or-
ganic Chemistry and a committee member of ionic liquid division, Chemical Industry and Engi-
neering Society of China.

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Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
2.3. Reactions
2.4. Spectroscopic data of new compounds
SiO2/policresulen composite catalyzed β-alkylation of styrene
with benzhydrol. All reactions were conducted in a 10-mL
V-type vessel equipped with a triangular magnetic stirrer. In a
typical reaction, benzhydrol (92.1 mg, 0.5 mmol), styrene (62.4
mg, 0.6 mmol), and 1b (20 mg, 2 mol%) were mixed in
1,2-dibromoethane (1.0 mL) and stirred for 5 h at 80 °C. After
the reaction, the mixture was cooled to room temperature and
petroleum ether (3.0 mL) was added prior to centrifugation.
The liquid phase was subjected to isolation with PTLC (PE as
eluent). The desired product, 4a, was obtained in a yield of
92%. As for the solid phase, after washing with PE (3.0 mL × 3)
and drying under vacuum, 1b was used in the next run with a
similar procedure. Tests of the substrate scope were conducted
in the same manner.
SiO2/policresulen composite catalyzed oxa-Pictet-Spengler
reaction. All reactions were conducted in a 10-mL V-type vessel
equipped with a triangular magnetic stirrer. In a typical reac-
tion, 2-(3,4-dimethoxyphenyl)ethanol (91.1 mg, 0.5 mmol),
benzaldehyde (64.8 mg, 0.6 mmol), and 1b (10 mg, 1 mol%)
were mixed in 1,2-dichloroethane (1.0 mL) and stirred for 5 h
at 80 °C. After the reaction, the mixture was cooled to room
temperature and then centrifuged, and the liquid phase was
subjected to isolation with PTLC (eluting solvent: ethyl ace-
tate/petroleum ether = 1/8). The desired product, 7a, was ob-
tained in a yield of 96%. Tests of the substrate scope were
conducted in the same manner. The recycling of 1b was real-
ized after doubling the dose. After washing the solid phase with
PE (3.0 mL × 3) and drying under vacuum, the recovered 1b
was used in the next run with a similar procedure.
(E)-1-chloro-4-(1-(4-methoxyphenyl)-3-phenylallyl)benzene
(4j). Pale yellow liquid; H NMR (400 MHz, CDCl3, 25 °C): δ =
1
7.34 (d, J = 7.4 Hz, 2H), 7.27–7.23 (m, 3H), 7.19 (t, J = 2.7 Hz,
2H), 7.13 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 6.84 (d, J =
8.6 Hz, 2H), 6.58 (dd, Ja = 7.3 Hz, Jb = 15.8, 1H), 6.29 (d, J = 15.9
Hz, 1H), 4.79 (d, J = 7.3 Hz, 1H), 3.75 ppm (s, 3H); 13C NMR (100
MHz, CDCl3): δ = 158.4, 142.4, 137.2, 135.2, 132.4, 132.2, 131.6,
130.1, 129.6, 128.7, 127.5, 126.4, 114.1., 55.3, 52.8 ppm; HRMS
m/z (ESI) calcd. for C22H19ClNaO [M + Na]+: 357.1022, found
357.1020.
(E)-1-fluoro-2-(1-(4-methoxyphenyl)-3-phenylallyl)benzene
1
(4k). Pale yellow liquid; H NMR (400 MHz, CDCl3, 25 °C): δ =
7.36 (d, J = 7.4 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.22–7.12 (m,
5H), 7.10–7.00 (m, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.64 (dd, Ja = 7.2
Hz, Jb = 15.8 Hz, 1H), 6.31 (d, J = 15.8 Hz, 1H), 5.15 (d, J = 7.1 Hz,
1H), 3.76 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 161.9
159.4, 158.3, 137.2, 134.4, 131.6, 131.4, 130.9, 130.8, 130.0,
129.9, 129.5, 128.6, 128.2, 128.1, 127.4, 126.4, 124.2, 124.1,
115.7, 115.5, 113.9, 55.3, 46.2, 46.2 ppm; HRMS m/z (ESI)
calcd. for C22H19FNaO [M + Na]+: 341.1318, found 341.1319.
(E)-1-chloro-2-(1-(4-methoxyphenyl)-3-phenylallyl)benzene
1
(4l). Pale yellow liquid; H NMR (400 MHz, CDCl3, 25 °C): δ =
7.36–7.30 (m, 3H), 7.28–7.22 (m, 3H), 7.19–7.09 (m, 5H), 6.82
(d, J = 8.7 Hz, 1H), 6.59 (dd, Ja = 1.2 Hz, Jb = 15.9 Hz, 1H), 6.24 (d,
J = 15.8 Hz, 1H), 5.33 (d, J = 6.6 Hz, 1H), 3.73 ppm (s, 3H); 13C
NMR (100 MHz, CDCl3): δ = 158.4, 141.3, 137.3, 134.3, 134.2,
131.9, 131.8, 130.2, 129.9, 128.7, 128.6, 127.9, 127.5, 127.0,
126.5, 113.9, 55.3, 49.5 ppm; HRMS m/z (ESI) calcd. for
C22H19ClNaO [M + Na]+: 357.1022, found 357.1025.
SiO2/policresulen composite catalyzed C3-alkenylation of
2-methylindoles with methyl acetoacetate. The reaction was
conducted in a 10-mL V-type vessel equipped with a triangular
magnetic stirrer. In a typical reaction, 2-methylindole (65.6, 0.5
mmol), methyl acetoacetate (116.1 mg, 1.0 mmol), and 1c (50
mg, 10 mol%) were mixed in toluene (1.0 mL) and stirred for
16 h at 100 °C. After the reaction, the mixture was cooled to
room temperature and then centrifuged, and the liquid phase
was subjected to isolation with PTLC. The desired product, 10a,
was obtained in a yield of 90%. After washing the solid phase
with PE (3.0 mL × 3) and drying under vacuum, the recovered
1c was used in the next run with a similar procedure.
SiO2/policresulen composite catalyzed C3-alkenylation of
2-methylindole with phenylacetaldehyde. The reaction was
conducted in a 10-mL of V-type vessel equipped with triangle
magnetic stirring. 2-methylindole (65.6, 0.5 mmol), phenyla-
cetaldehyde (90.1 mg, 0.75 mmol), ethanol anhydrous (50.6
mg, 1.1 mmol) and 1d (33.3 mg, 10 mol%) were mixed in di-
chloromethane (1.0 mL) and stirred for 11 h at room tempera-
ture. After reaction, petroleum ether (3.0 ml) was added prior
to centrifuge, the liquid phase was submitted to isolation with
PTLC. The desired product, 10b, was obtained in a yield of
94%. After washing the solid phase with PE (3.0 mL × 3) and
drying under vacuum, the recovered 1d was used in the next
run with a similar procedure.
(E)-1-chloro-4-(3-phenyl-1-(p-tolyl)allyl)benzene (4m). Pale
yellow liquid; 1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.33 (d, J =
7.2 Hz, 2H), 7.28–7.21 (m, 4H), 7.21–7.16 (m, 1H), 7.15–7.06
(m, 6H), 6.59 (dd, Ja = 7.4 Hz, Jb = 15.8 Hz, 1H), 6.30 (d, J = 15.8
Hz, 1H), 4.79 (d, J = 7.4 Hz, 1H), 2.30 ppm (s, 3H); 13C NMR (100
MHz, CDCl3): δ = 142.4, 140.1, 137.2, 136.3, 132.3, 132.3, 131.7,
130.1, 129.4, 128.7, 128.6, 128.6, 127.5, 126.4, 53.3, 21.1 ppm;
HRMS m/z (ESI) calcd. for C22H19ClNa [M + Na]+: 341.1073,
found 341.1071.
6,7-Dimethoxy-1-phenethyl-isochroman (7k). Yellow liquid;
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.28 (t, J = 7.2 Hz, 2H),
7.22 (d, J = 6.0 Hz, 2H), 7.16 (tt, Ja = 1.6 Hz, Jb = 8.4 Hz, 1H), 6.58
(s, 1H), 6.52 (s, 1H), 4.70 (d, J = 6.4 Hz, 1H), 4.20–4.11 (m, 1H),
3.83 (s, 3H), 3.80 (s, 3H), 3.78–3.71 (m, 1H), 2.98–2.86 (m, 1H),
2.83–2.71 (m, 2H), 2.65–2.56 (m, 1H), 2.23–2.01 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): δ = 147.5, 147.5, 142.4, 129.9,
128.5, 128.3, 126.1, 125.7, 111.5, 107.8, 74.8, 63.2, 56.0, 55.8,
37.8, 31.4, 28.6 ppm; HRMS m/z (ESI) calcd. for C19H22NaO3 [M
+ Na]+: 321.1467, found 321.1465.
1-(4-Trifluoromethyl-phenyl)-1,3,4,9-tetrahydro-pyrano[3,4-
b]indole (7m). Pale yellow liquid; 1H NMR (400 MHz, CDCl3, 25
°C): δ = 7.61 (d, J = 8.1 Hz, 2H), 7. 55 (d, J = 6.8 Hz, 2H), 7.47 (d, J
= 8.0 Hz, 2H), 7.24–7.19 (m, 1H), 7.18–7.09 (m, 2H), 5.82 (s,
1H), 4.36–4.22 (m, 1H), 4.03–3.88 (m, 1H), 3.15–3.01 (m, 1H),
2.89–2.77 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): δ = 143.6,
136.3, 132.7, 131.3, 131.0, 130.0, 128.8, 128.4, 128.0, 127.0,

Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
1609
126.1, 125.9, 125.8, 125.5, 125.4, 122.7, 122.4, 120.0, 118.6,
111.2, 109.2, 75.5, 64.9, 22.3 ppm; HRMS m/z (ESI) calcd. for
C18H14F3NNaO [M + Na]+: 340.0925, found 340.0922.
dicated the existence of aromatic structure in the policre-
sulen/SiO2 catalyst. Meanwhile, the BET surface areas de-
creased with increase of policresulen loading.
After determining that we had successfully synthesized the
desired catalytic materials, we applied them to selected organic
reactions. β-Alkylations of styrene with alcohols are important
C–C bond forming reactions, and many metal complexes or
acids have been investigated as catalysts [43–45]. Because the
only by-product of this type of reaction is water, it has been
considered as a green route for the synthesis of mul-
ti-substituted olefins [46,47]. However, most of the reported
catalysts are homogeneous species and cannot be recycled.
Although a few heterogeneous catalysts have also been em-
ployed [48], they suffer from either a time-consuming prepara-
tion procedure or call for task-specific experimental tools that
are generally inaccessible in a typical organic synthesis lab. To
address these drawbacks, our silica/policresulen catalysts,
which can be prepared within 1 h without using special in-
struments, were employed in the nucleophilic substitution of
benzhydrol 2a with styrene 3a. As shown in Table 1, no prod-
uct was obtained in the absence of catalyst (entry 1). The pre-
sent silica/policresulen composite catalyst was indeed effective
for promoting this reaction. With catalyst 1a, which contained a
low policresulen loading, the desired product 4a was obtained
in only moderate yield after 5 h of reaction at 80 °C in
1,2-dibromoethane (entry 2). The yield of 4a increased with
policresulen loading, and when 1b was used, it reached 92%
under identical conditions (entry 3). However, no significant
improvement in yield was observed when 1b was replaced
with 1c (entry 4). It should be noted that blank SiO2 and TiO2
were proven to be inactive for this reaction (entry 5). There-
fore, the catalytic activity of 1b can be attributed to its coating
of policresulen. The reaction also proceeded smoothly with the
3. Results and discussion
Initially, four SiO2-supported policresulen catalysts were
prepared through a simple procedure, which involved (1) mix-
ing an aqueous solution of policresulen (52 wt%) and silica
together in ethanol solvent; and (2) removing the volatile sol-
vent under reduced pressure after 30 min of stirring. The SO3H
loadings of the catalysts were 0.20, 0.50, 1.00 and 1.50 mmol/g.
The catalysts produced were all fine powders (see the photo in
Fig. 1). It should be noted that, with this method, the obtained
catalysts also contained a small amount of water. Fortunately,
this was easily quantified using the following procedure: (1)
unmodified silica was subjected to TG analysis to determine the
initial amount of absorbed water; (2) the increase in the weight
of the silica material after the immobilization of policresulen
was measured, and the weight contributed by pure policre-
sulen was removed. The water contents of all the catalysts were
found to be nearly the same, ranging from 15wt% to 17 wt% of
the hybrid composite. Two reference catalysts, SiO2-supported
sulfonic acid and TiO2-supported benzenesulfonic acid were
used for comparison in this study. The former was prepared
according to our previous method [39,40], whereas the latter
was prepared based on a modified literature method (see Elec-
tronic Supplementary Information (ESI)) [41,42]. The sche-
matic structures of all the prepared catalysts are shown in Fig.
1. Some physico-chemical properties of the materials are given
in the ESI. Compared with those of the reference material, un-
modified SiO2, a new set of absorption peaks appeared in the IR
spectra of policresulen/SiO2. The bands and their assignments
are as follows: The hydroxyl group stretching vibration v(O−H)
at 3451 cm−1 increased in intensity, indicating the presence of
hydroxyl groups in the structure of policresulen. The absorp-
tion peaks at 1579, 1541, 1491, 1456, and 1408 cm−1 can be
ascribed to stretching vibrations of the aromatic ring
v(C−C)/v(C=C). Peaks appearing at 691, 577, 550 cm−1also in-
Table 1
Nucleophilic substitution of benzhydrol with styrene over different
catalysts.
OH
cat (2 mol %)
+
DBE
o
80 C, 5 h
2a
3a
4a
Entry
1
2
3
4
Catalyst
Yield (%)
—
1a
1b
1c
0
78
92
93
0
5
SiO2 or TiO2
6
7
1e
1f
63
10
46
91
89 (55b)
91
8
Amberlyst-15
9a
10
11c
1b
congener of 1b with PTSA
1b
Reaction conditions: 2a 0.5 mmol, 3a 0.6 mmol, DBE 1.0 mL, 80 °C, 5 h.
a 1b was reused in the fourth run. b the catalyst was reused in the first
run. c 5.0 mmol scale reaction.
Fig. 1. Schematic representation of solid-supported catalysts used in
this study and photo of prepared catalyst 1c.

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Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
SiO2-supported sulfonic acid catalyst 1e. However, the obtained
yield was far inferior to that obtained with 1b (entry 6). To our
surprise, although the acidic species of the TiO2-supported
benzenesulfonic acid catalyst 1f has a similar molecular struc-
ture, a very low yield was obtained with this catalyst (entry 7).
Although we are uncertain as to the reasons behind this dis-
crepancy in performance, the poor catalytic activity of 1f can be
partially ascribed to insufficient contact between the catalyst
and substrate, which is a result of the poor flexibility of the
chemically bonded benzenesulfonic acid. A commonly used
resin-supported acid, Amberlyst-15, was also examined, and
only moderate yield was obtained under identical conditions
(entry 8). These results indicate that silica/policresulen com-
posites are indeed able to act as acid catalysts to promote or-
ganic reactions. Because the policresulen component is insolu-
ble in DBE, the silica/policresulen composite catalyst 1b could
be recovered easily by filtration at the end of the reaction. After
20 min of treatment at 80 °C under vacuum conditions (10
mmHg), the recovered catalyst was subjected to the next run.
With this procedure, 1b could be reused at least four times
without significant loss in its activity (entry 9). A congener of
1b produced using toluenesulfonic acid (PTSA) as the acidic
component (SiO2-PTSA) was also used as a catalyst for the
model reaction. Although good catalytic activity was obtained
in the first run, its recyclability was far from satisfactory (entry
10). This result demonstrated that the policresulen component
was key to rendering this immobilization protocol possible.
Notably, the reaction could also be effectively scaled up by 10
times with similar efficiency (entry 11).
Table 2
Substrate scope of 1b-catalyzed nucleophilic substitution of benzhy-
drols with styrenes.
3
R
4
OH
R
4
1b (2 mol%)
DBE
R
2
R
+
1
3
2
o
R
R
R
80 C, time
1
R
1
2
3
4
4a-4m
2a: R = H, R = H;
3a: R = H, R = H;
1
2
3
4
2b: R = OMe, R = H;
3b: R = Me, R = H;
1
2
3
4
2c: R = OMe, R = 4-Cl;
3c: R = OMe, R = H;
1
2
3
4
2d: R = OMe, R = 2-F;
3d: R = F, R = H;
1
2
3
4
2e: R = OMe, R = 2-Cl;
3e: R = Br, R = H;
1
2
3
t
4
2f : R = Me, R = 4-Cl.
3f: R = Bu , R = H;
3
4
3g: R = H, R = Me;
3
4
3h: R = H, R = Ph.
Entry
1
2
Benzhydrol
Styrene
3a
Time (h) Product Yield (%)
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
5
5
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
92
70
50
3b
3c
3
4
5
6
7
8
9
3d
3e
3f
3g
3h
3a
5
7
1.5
5
1
>99
74
>99
75
>99
86
15
10
11
12
13
3a
3a
3a
3a
9
5
5
5
4j
4k
4l
92
60
90
98
4m
Reaction conditions: 2a 0.5 mmol, 3a 0.6 mmol, 1b 2 mol%, DBE 1 mL,
80 °C.
With the optimized conditions in hand, we probed the scope
of the reaction with respect to both the styrene and the ben-
zhydrol components. As evidenced by the results shown in
Table 2, both electron-rich and moderately electro-poor sty-
renes reacted smoothly with benzhydrol, producing the sub-
stitution products in generally good to excellent yields. Styrene
with methyl or phenyl at the α-position of the double bond was
afforded with the aid of catalyst 1b in moderate or excellent
yield. The scope of the reaction with respect to the benzhydrol
component was then investigated and was found to be good
also. Several benzhydrol derivatives with methyl, methoxy,
fluoro or chloro groups readily participated in the reaction with
styrene, affording the corresponding tri-substituted ethylene in
good to excellent yields.
Tertiary benzyl alcohols can undergo a dehydration reaction
under acidic conditions to form styrene-type products [49].
Based on this mechanism, Han et al. [50] recently developed a
tandem dehydration/nucleophilic substitution reaction in-
volving two different alcohols. We found that this type of
transformation can also be performed in our system with the
aid of 1b. As shown in Scheme 1, two benzhydrol-type alcohols
reacted smoothly under the above-mentioned optimum condi-
tions, providing the expected multi-substituted olefin 4h in
96% yield, which is quite competitive compared with the result
obtained for the condensation reaction of 1,1-diphenylethylene
with benzhydrol over the same catalyst.
OH
OH
1b (2 mol %)
+
DBE, 80 oC, 5 h
4h, 96%
2a
Scheme 1. Tandem dehydration/nucleophilic substitution reaction of
two different alcohols over catalyst 1b.
ca/policresulen composite catalyst to the oxa-Pictet-Spengler
reaction of 2-phenylethanol and benzaldehyde. This type of
condensation relies heavily on the use of acid catalysts [51–55],
and has been extensively used for the synthesis of isochromans.
Although heterogeneous catalysts are preferable from the
viewpoint of green chemistry, they are still rarely used in
oxa-Pictet-Spengler reactions. Until now, there has been only
one report on the use of a solid catalyst, a small pore size zeo-
lite Ersorb-4 [56]. This is a clinoptilolite-type zeolite material
with high Si content (Si:Al ratio 5:1). Unfortunately, this kind of
zeolite is inaccessible to most labs working in organic chemis-
try. We found that, in the presence of a catalytic amount of 1b,
2-(3,4-dimethoxyphenyl)ethanol 5a reacted readily in
1,2-dichloroethane with benzaldehyde 6a at 80 °C, affording
the expected isochroman 7a in 96% yield after 5 h (Table 3,
entry 1). In this reaction, catalyst 1b could also be recycled at
least three times without significant loss in activity. Increasing
Encouraged by the promising results obtained in the
above-mentioned reactions, we then applied the sili-

Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
1611
and tryptophol 5c could also be used as counter substrates of
the aldehyde component. Thus, catalyst 1b was proved again to
be effective for these oxa-Pictet-Spengler reactions (entries 14
and 15).
Table 3
Oxa-Pictet-Spengler reaction catalyzed by solid acid catalysts.
R1
R2
OH
R1
catalyst (1 mol %)
DCE, 80 oC, 5 h
+ R3CHO
O
R2
R3
7a-7m
The silica/policresulen composite catalystwas also used in
the 3-alkenylation of indoles with 1,3-dicarbonyl compounds,
which can produce valuable C3-substituted indoles. The use of
some Lewis or Brønsted acids, such as FeCl3 [57], I2 [58], acidic
ionic liquid [59], and an Au (III) salt catalyst [60] has been ex-
amined for this reaction. However, all these catalysts are ho-
mogeneous and cannot be recycled. Using 1c as the catalyst,
2-methylindole 8a reacted smoothly with methyl acetoacetate
9a in toluene, affording the corresponding C3-alkenylated in-
dole 10a in 90% yield (Scheme 2). At the end of the reaction,
catalyst 1c was easily recovered and reused at least two times
without significant loss in activity. It should be noted that the
same reaction over silica-supported sulfonic acid catalyst 1e
failed to give a satisfactory result. Because only 55% yield was
obtained with catalyst 1b under identical conditions, we de-
duced that the reaction might be significantly influenced by the
catalyst loading. Fortunately, it is very easy to increase the
loading of the policresulen component on the present catalyst.
In contrast, an increase in acid loading with the conventional
silica-supported sulfonic acid catalyst is not easy because it
generally needs a sophisticated procedure and strict control of
the preparation parameters. 2-Methylindole can also readily
undergo an alkenylation with 2-phenylacetaldehyde over 1d
(Scheme 2). A similar reaction using FeCl3 as the catalyst has
been reported by Yang et al. [61]. An excellent yield, 94%, was
obtained after 11 h of stirring at room temperature. In this re-
action, the recovered 1d also showed good recyclability. We
have thus established the first heterogeneous catalytic system
for 3-alkenylation of indoles with 1,3-dicarbonyl compounds
and 2-phenylaldehyde.
5a-5c
MeO
MeO
6a-6l
OH MeO
OH
OH
N
H
5a
5b
5c
Time
(h)
5
Entry Alcohol
R3
Product Catalyst
Yield (%)
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5c
C6H5
C6H5
C6H5
7a
7a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
1b
1e
1f
96(95a, 93b)
5
5
78
41
88
90
98
98
97
96
98
>99
93
98
91
75
4-MeOC6H4
2-MeOC6H4
4-NO2C6H4
2-NO2C6H4
4-ClC6H4
2-ClC6H4
4-BrC6H4
4-CNC6H4
H
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
12
5
3
3
5
5
3
5
5
9
10
11
12
13
14
15
C6H5(CH2)2
C6H5
4-CF3C6H5
16
16
36
7m
Reaction conditions: alcohol 0.5 mmol, aldehyde 0.6 mmol,
1,2-dichloroethane 1.0 mL, 80 °C, 5 h. a 1b was reused in the third run. b
reaction scale 5.0 mmol.
the reaction scale from 0.5 to 5.0 mmol did not significantly
influence the synthetic efficiency. However, when
SiO2-supported sulfonic acid 1e was used as catalyst, the yield
of 7a reached only 78% (entry 2). The reaction with
TiO2-supported benzenesulfonic acid catalyst 1f proceeded
sluggishly, affording 7a in only 41% under identical conditions
(entry 3).
Subsequently, other aldehydes and alcohols were subjected
to the conditions used for entry 1 (Table 3). First, we selected a
set of aldehydes spanning a convenient spectrum of lipophicity
and reactivity and used 5a as the only source of the required
alcohol. When 1b was used as the catalyst, the results for all the
aldehydes, which included both aromatic and aliphatic alde-
hydes, largely paralleled those obtained with benzaldehyde
(entries 4–13). The reaction appeared to be insusceptible to the
presence of a substituent in the C2 position of benzaldehyde;
4. Conclusions
Conventional methods for heterogenizing homogeneous
molecular catalysts must covalently anchor the desired catalyst
molecule on a solid support, and are thus rather complex and
sometimes need sophisticated operations. The present sili-
ca/policresulen system achieves the ultimate goal for moving
from a homogeneous catalyst towards heterogeneous condi-
tions: easy separation of the catalyst and products while main-
taining the same activity. The distinction in our case is that the
catalytically active component, policresulen, could be easily
immobilized on silica without forming chemical bonds. The
unique structure of policresulen is the key factor that renders
this protocol possible. The hydroxyl groups of policresulen
2-methoxybenzaldehyde,
2-nitrobenzaldehyde,
and
2-chlorobenzaldehyde reacted as well as their C4-substituted
congeners (entries 4–9). Under the present conditions, a cyano
group could be delivered into the final product without any
structural damage (entry 11). 3-Methoxyphenethyl alcohol 5b
Scheme 2. C3-Alkenylation of 2-methylindoleover silica/policresulen composite catalyst.

1612
Kexing Zeng et al. / Chinese Journal of Catalysis 36 (2015) 1606–1613
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likely enable the formation of hydrogen bonds that facilitate its
immobilization, while the sulfonic acid ensures a good catalytic
activity of the composite. This catalyst exhibited good perfor-
mance in various organic reactions, including β-alkylation of
styrenes with benzhydrol, oxa-Pictet-Spengler reactions, and
C3-alkenylation of indoles with 1,3-dicarbonyl compounds.
However, we wish to point out that the catalytic reaction might
occur in a homogeneous aqueous phase formed at the surface
of the silica, and that the use of an organic solvent that cannot
dissolve the policresulen component allows the catalyst to re-
main stable on the solid component. Because this unique com-
posite catalyst can be easily prepared without the use of any
special instruments, researchers working in both catalytic re-
action and organic synthesis may find it of use in the future.We
are actively working on exploration of other reactions with this
catalyst with the hope of clarifying its application scope and
limitations.
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Graphical Abstract
Chin. J. Catal., 2015, 36: 1606–1613 doi: 10.1016/S1872-2067(15)60910-X
Silica-supported policresulenas a solidacid catalyst for organic
reactions
Kexing Zeng, Zhipeng Huang, Jie Yang, Yanlong Gu *
Huazhong University of Science and Technology;
Lanzhou Institute of Chemical Physics, Chinese Academy of Science
A new type of solid catalyst was prepared by coating a thin layer of
policresulen, a commercially available drug, onto the surface of silica.
The obtained silica/policresulen composite showed remarkable cata-
lytic activity for various organic reactions.

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