Design of a highly efficient and water-tolerant sulfonic acid nanoreactor based on tunable ordered porous silica for the von Pechmann reaction

Article abstract of DOI:10.1021/ol8013107

(Figure Presented) Among a number of different sulfonic acid nanoreactors prepared, 5 having both acidic sites and phenyl groups located inside the mesochannels of SBA-15 was shown to be the most active and reusable catalyst in the von Pechmann reaction. The mesochannels, and covalently anchored organic groups, provide a synergistic means of an efficient approach of the reactants to acidic sites, enough space for the subsequent cyclization, and suitable hydrophobicity to drive out the water byproduct.

Full text of DOI:10.1021/ol8013107

ORGANIC
LETTERS
2008
Vol. 10, No. 18
3989-3992
Design of a Highly Efficient and
Water-Tolerant Sulfonic Acid
Nanoreactor Based on Tunable Ordered
Porous Silica for the von Pechmann
Reaction
Babak Karimi* and Daryoush Zareyee
Department of Chemistry, Institute for AdVanced Studies in Basic Sciences (IASBS),
P.O. Box 45195-1159, GaVa Zang, Zanjan, Iran
karimi@iasbs.ac.ir
Received June 29, 2008
ABSTRACT
Among a number of different sulfonic acid nanoreactors prepared, 5 having both acidic sites and phenyl groups located inside the mesochannels
of SBA-15 was shown to be the most active and reusable catalyst in the von Pechmann reaction. The mesochannels, and covalently anchored
organic groups, provide a synergistic means of an efficient approach of the reactants to acidic sites, enough space for the subsequent
cyclization, and suitable hydrophobicity to drive out the water byproduct.
In recent years, organically functionalized ordered mesopo-
rous silicas1 with a tunable pore structure and tailored
composition have received considerable interest for broad
applications ranging from adsorbent,2 gas separation,3 and
catalysis4 to biological uses.1a,5 These classes of materials
are mainly characterized by very large specific surface areas
(up to 2000 m2·g-1), highly ordered pore systems, and well-
defined and a tunable pore radius from approximately 2 to
50 nm. Moreover, the surface properties (inside the channels)
and, therefore, the chemical functionalities of these materials
can be uniformly modified by covalent anchoring of different
organic moieties.4,1a In other words, they combine in a single
solid both the special chemical reactivity of the organo-
functional groups and attractive properties including a
mechanically stable structure, high surface area, and large
ordered pores with narrow size distribution of an inorganic
backbone. Therefore, it would be reasonable to consider these
materials as numerous combined nanosize vessels with the
same properties, where their size and functions can be pre-
(1) (a) Hoffmann, F.; Cornelius, M.; Morell, J.; Fro¨ba, M. Angew. Chem.,
Int. Ed. 2006, 45, 3216. (b) Stein, A. AdV. Mater. 2003, 15, 763. (c) Lee,
H.; Zones, S. I.; Davis, M. E. Nature 2003, 425, 385. (d) Davis, M. E.
Nature 2002, 417, 813.
(2) (a) Feng, X.; Fryxell, G. E.; Wang, L. Q.; Kim, A. Y.; Liu, J.;
Kemner, K. M. Science 1997, 276, 923. (b) Mori, Y.; Pinnavaia, T. J. Chem.
Mater. 2001, 13, 2173. (c) Mercier, L.; Pinnavaia, T. J. AdV. Mater. 1997,
9, 500. (d) Yoshitake, H. New J. Chem. 2005, 29, 1107.
(3) Harlick, P. J. E.; Sayari, A. Ind. Eng. Chem. Res. 2007, 46, 446.
10.1021/ol8013107 CCC: $40.75
Published on Web 08/15/2008
2008 American Chemical Society

cisely adjusted through an inorganic organic cooperative
mechanism on a molecular level. If such a hypothesis could
be realized in practice, it would be possible to design and
prepare a variety of sophisticated nanoreactors which possess
multiple functional groups (nano reaction media), assembled
in the interior of inorganic mesostructures (nano vessels).6
pH analysis. Table 1 illustrates characteristics of the nan-
oreactors in some detail.8
Table 1. Characterization of Sulfonic Acid Based Nanoreactors
a
c
nanoreactor SBET
R
pore sizeb Vp
proton capacityd
1
2
3
4
5
453
458
586
430
356
-
13.0
12.9
12.9
31.5
27.8
0.24
0.11
0.07
0.67
0.58
1.46
1.17
1.20
1.77
1.61
Mee
Phe
-
Phf
a BET surface area (m2·g-1). b BJH pore size (Å). c Total pore volume
(cm3·g-1). d mmol (-SO3H)·g-1; determined by pH analysis after ion-exchange.
e Loadings of the methyl and phenyl group in 2 and 3 were 0.70 and 0.33
mmol·g-1, respectively, based on TGA and elemental analysis. f Loading
of the phenyl group in 5 was 0.37 mmol·g-1, based on TGA and elemental
analysis.
While several types of solid sulfonic acids, based on
ordered mesoporous silicas, have been created in recent
years,9 there have been only few reports about their applica-
tions as catalysts in chemical transformations. Moreover, to
the best of our knowledge there is no report on the use
of these materials as nanoreactors in the Pechmann conden-
sation. The Pechmann reaction, a two-component (phenol
and ꢀ-ketoester) coupling under acid catalysis, is a valuable
and simple protocol for coumarin ring synthesis.10 In the
conventional production of coumarins by the Pechmann
reaction, concentrated sulfuric acid is used as the catalyst.11
Several other acid catalysts, including Lewis acids, are known
to affect this condensation.12 However, moisture sensitivity
of the majority of Lewis acids to the water produced in the
Pechmann reaction renders them unsuitable for use in large-
scale applications. Other methods may also utilize ionic
liquids13 and microwave irradiation,14 but these methods also
generated strongly acidic wastes and/or they utilize highly
expensive and nonrecyclable reagents. To address the above-
mentioned problems, a number of heterogeneous alternatives
such as Nafion-H,15 zeolite H-BETA, Amberlyst 15,16
Figure 1. Schematic representation for the preparation of sulfonic
acid based nanoreactors 1-5. 1 ) MCM-Pr-SO3H,9d R ) none; 2
) MCM-Me-Pr-SO3H, R ) Me; 3 ) MCM-Ph-Pr-SO3H, R ) Ph;
4 ) SBA-15-Pr-SO3H,9c R ) none; 5 ) SBA-15-Ph-Pr-SO3H, R
) Ph.
Along the line of this hypothesis and in the course of our
investigations into the development of new nanostructured
catalysts,7 herein, we wish to disclose the preparation of five
different sizes of modified sulfonic acid nanoreactors, in
which the propyl sulfonic acid group and two kinds of
organic groups are located inside the channels of both
microporous and mesoporous silicas following published
procedures with slight modifications.8 The preparation
strategy for the nanoreactors 1-5 is shown in Figure 1.8
Nanoreactors 1-5 were characterized by thermogravimet-
ric analysis (TGA), elemental analysis, surface analysis,
transmission electron microscopy (TEM), and ion-exchange
(9) (a) Van Rhijn, W. M.; De Vos, D. E.; Sels, B. F.; Bossaert, W. D.;
Jacobs, P. A. Chem. Commun. 1998, 317. (b) Diaz, I.; Marquez-Alvarez,
C.; Mohino, F.; Perez-Pariente, J.; Sastre, E. J. Catal. 2000, 193, 283. (c)
Margolese, D.; Melero, J. A.; Christiansen, S. C.; Chmelka, B. F.; Stucky,
G. D. Chem. Mater. 2000, 12, 2448. (d) Lim, M. H.; Blanford, C. F.; Stein,
A. Chem. Mater. 1998, 10, 467. (e) Wilson, K.; Lee, A. F.; Macquarrie,
D. J.; Clark, J. H. Appl. Catal., A 2002, 228, 127. (f) Yuan, X.; Lee, H. I.;
Kim, J. W.; Yie, J. E.; Kim, J. M. Chem. Lett. 2003, 32, 560. (g) Shimizu,
K.; Hayashi, E.; Hatamachi, T.; Kodama, T.; Higuchi, T.; Satsuma, A.;
Kitayama, Y. J. Catal. 2005, 231, 131. (h) Karam, A.; Gu, Y.; Je´roˆme, F.;
Doulitz, J.-P.; Barrault, J. Chem. Commun. 2007, 2222. (i) Mbraka, I. K.;
Radu, D. R.; Lin, V. S.-Y.; Shanks, B. H. J. Catal. 2003, 219, 329. (j)
D´ıaz, I.; Mohino, F.; Pariente, J. P.; Sastre, E. Appl. Catal. A: Gen. 2003,
242, 161. For an excellent review on catalytic applications of organosulfonic-
functionalized mesostructured materials, see: (k) Melero, J. A.; van Grieken,
R.; Morales, G. Chem. ReV. 2006, 106, 3790. (l) Jackson, M. A.; Mbraka,
I. K.; Shanks, B. H. Appl. Catal. A: Gen. 2006, 310, 45. (m) Gu, Y.; Karam,
A.; Je´roˆme, F.; Barrault, J. Org. Lett. 2007, 9, 3145.
(4) (a) Corma, A.; Garcia, H. Chem. ReV. 2002, 102, 3837. (b) Mallat,
T.; Baiker, A. Chem. ReV. 2004, 104, 3037. (c) Lu, Z. L.; Lindner, E.;
Mayer, H. A. Chem. ReV. 2002, 102, 3543. (d) Wight, A. P.; Davis, M. E.
Chem. ReV. 2002, 102, 3589.
(5) Hartmann, M. Chem. Mater. 2005, 17, 4577.
(6) During the preparation of this paper, we noticed that a new interesting
nanoreactor based on ordered mesoporous silica (SBA-15) composed of
Keggin-type polyoxometalate H3P12O40 has been reported for ethyl acetate
hydrolysis in water: Inumaru, K.; Ishihara, T.; Kamiya, Y.; Okuhara, T.;
Yamanaka, S. Angew. Chem., Int. Ed. 2007, 46, 7625.
(10) Pechmann, V. H.; Duisberg, C. Chem. Ber. 1884, 17, 929.
(11) Horning, E. C. Organic Synthesis; Wiley: New York, 1955; Vol.
III, p 281.
(7) (a) Karimi, B.; Enders, D. Org. Lett. 2006, 8, 1237. (b) Karimi, B.;
Abedi, S.; Clark, J. H.; Budarin, V. Angew. Chem., Int. Ed. 2006, 45, 4776.
(c) Karimi, B.; Biglari, A.; Clark, J. H.; Budarin, V. Angew. Chem., Int.
Ed. 2007, 46, 7210.
(12) (a) Bose, D. S.; Rudradas, A. P.; Hari Babu, M. Tetrahedron Lett.
2002, 43, 9195. (b) De, S. K.; Gibbs, R. A. Synlett 2005, 1231. (c) Sharma,
G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna, P. R. Tetrahedron Lett.
2005, 46, 6119.
(8) See the Supporting Information for experimental details.
3990
Org. Lett., Vol. 10, No. 18, 2008

Montmorillonite clay,17 and other solid acids18 have been
employed for this purpose in the Pechmann condensation.
Although, these methods are suitable for certain synthetic
conditions, in many of these methods the yields of products
were not always satisfactory and the catalytic activities were
lower than homogeneous catalysts in most cases. Therefore,
it seems that the major task of current research in chemistry
is to replace both homogeneous and less efficient and
traditional heterogeneous acid catalysis procedures by en-
vironmentally more acceptable protocols based on improved
water-tolerant and recoverable catalysts.
reaction can be very difficult to accomplish and hindered
(Table 2, entry 1). Similar results were also obtained with
hydrophobic nanoreactors 2 and 3 (average pore size 12.9
Å), confirming that owing to the size restriction of nanore-
actors the surface hydrophobization does not significantly
improve the catalytic activity for the described reaction
(Table 2, entries 2 and 3). On the other hand, we found that
when nanoreactor 4, with a mesoporous structure (pore
diameter ≈ 31.5 Å), was employed instead, the yield of
∼50% was obtained (Table 2, entry 4). This observation
might be explained by the fact that the large mesochannels
of SBA-15 in 4 can provide enough space to accommodate
the starting materials with the aid of grafted sulfonic acid
and still enough space to promote the cyclization (the
Pechmann) reaction. Although this catalytic activity is better
than the nanoreactors 1-3 having a smaller pore opening, it
is still not satisfactory. We reasoned that under the neat
condition the high affinity of the silica framework of SBA-
15 in 4 for the water byproduct probably allowed a gradual
desorption of the starting materials from the catalyst surface
thus retarding the progress of the reaction. To circumvent
this problem, we then prepared mesoporous nanoreactor 5
in which both sulfonic acid and the phenyl group are
covalently assembled inside the mesochannels of SBA-15.
A BET surface area of 356 m2·g-1, a total pore volume of
0.58 cm3·g-1, and a BJH pore diameter of 27.8 Å were
measured for the material. These values are clearly smaller
than those measured for 4 (Table 1), thus supporting the
nanoreactor model proposed in Figure 1. To our delight,
mesoporous nanoreactor 5 appeared to be much more reactive
than both heterogeneous nanoreactors 1-4 and homogeneous
catalysts (p-TsOH, H2SO4), affording 90% isolated yields
of the desired coumarin (Table 2, entry 5 vs 1-4 and 6, 7).
It was also detected that either mesoporous silica SBA-15
or amorphous silica showed almost no activity under the
same reaction conditions (Table 2, entries 9 and 10).
The catalytic activity of Brønsted acid nanoreactors 1-5
was then tested in the coupling reaction of resorcinol (1,3-
dihydroxyphenol) with ethyl acetoacetate under solvent-free
condition (Table 2).19
Table 2. Pechmann Reaction of Different Substituted Phenols
with Ethyl Acetoacetate Employing Nanoreactors 1-5 as
Catalysts
time
min/[h]c yielda b [%]
,
entry nanoreactor/catalyst
R′
3-OH
1
2
1
2
60
60
60
60
60
60
60
60
60
25
10
25
25
[7]
[5]
[10]
90
[4]
90
30
32
30
50
90
65
60
NR
NR
95
94
92
90
80
83
75
75
65
78
3-OH
3
4
5
6
7
9
10
11
12
13
14
15
16
17
18
19
20
3
4
5
3-OH
3-OH
3-OH
3-OH
3-OH
3-OH
3-OH
2,3-(OH)2
3,5-(OH)2
2-Me-3-OH
3-Me-5-OH
3-Me
3-MeO
3,5-(Me)2
3-NH2
p-TsOH
H2SO4
SBA-15c
silica gelc
5
5
5
5
5
5
5
5
5
5
The scope of this method was then further studied by
conducting it from different substituted phenols using 5 as
a nanoreactor. As summarized in Table 2, a catalytic amount
of 5 (≈7 mol %) efficiently promotes the Pechmann reaction
of a wide range of phenols under solvent-free conditions.
Good to excellent yields of the corresponding coumarins
were obtained regardless of structural variations in the
phenols. It is also interesting to note that in the case of
3-aminophenol the reaction was completely chemoselective
for the formation of a coumarin ring, a feature not observed
with the previous heterogeneous and homogeneous systems
(Table 2, entry 18).12a,b
1-naphthol
4-OH
a Isolated yields of pure products. b Conditions were as follows: phenol
(10 mmol), ethyl acetoacetate (11 mmol), catalyst (∼ 7 mol % equiv to
acidic proton) at 130 °C. c 430 mg of SBA-15 or silica was used.
For the purpose of comparison, Table 2 also summarizes
the catalytic activity of both para-toluenesulfonic acid (p-
TsOH) and H2SO4 under the same reaction conditions (entries
6 and 7). As shown in Table 2, a low isolated yield of ≈
30% for the corresponding coumarin was obtained when the
microporous nanoreactors 1, with an average pore size of
13 Å, were used, probably because of the fact that the
catalytic activity must be related to the -SO3H sites present
within the less accessible micropores where the cyclization
(13) (a) Potdur, M. K.; Mohile, S. S.; Salunkhe, M. M. Tetrahedron
Lett. 2001, 42, 9285. (b) Kandekar, A. C.; Khadikar, B. M. Synlett 2002,
152. (c) Gu, Y.; Zhang, J.; Duan, Z.; Deng, Y. AdV. Synth. Catal. 2005,
347, 512.
(14) Hoz, A. D.; Andres, M.; Vazquez, E. Synlett 1999, 602.
(15) Chaudhari, D. A. Chem. Ind. 1983, 568.
(16) Gunnewegh, E. A.; Hoefnegal, A. J.; Van Bekkum, H. J. Mol. Catal.
A: Chem. 1995, 100, 87.
(17) (a) Frere, S.; Thiery, V.; Besson, T. Tetrahedron Lett. 2001, 42,
2791. (b) Li, T.; Zhang, Z.; Yang, F.; Fu, C. J. Chem. Res. 1998, 38.
(18) Rodriguez-Dominguez, J. C.; Kirsch, G. Tetrahedron Lett. 2006,
47, 3279.
Org. Lett., Vol. 10, No. 18, 2008
3991

The most important issue that should be considered for
practical applications of heterogeneous systems is the lifetime
of the catalyst and its degree of reusability. To resolve this
issue, we designed a set of experiments by conducting
successive condensation of resorcinol with ethyl acetoacetate
(30 mmol scale) using nanoreactor 5 (7 mol % equiv to
-SO3H capacity). After the completion of the first run to
afford the corresponding coumarin in 90% yield (after
purification), the catalyst was thoroughly washed with EtOH
and ethyl ether and finally dried at 100 °C for 3 h. A new
reaction was then accomplished with fresh reactants under
the same reaction conditions. Gratifyingly, the recovered
nanoreactor 5 was successfully used in six successive runs
and exhibited consistent activity to afford an average yield
of 87% (180 mmol total scale) with virtually no significant
loss of performance. It is very important to note that for the
reactions in which water participates as a reactant and
product, only a few solid acids show acceptable performance
and stability.20 High stability of nanoreactor 5 was further
assessed using transmission electron microscopy after the
sixth reaction cycle and showed that the 2D-hexagonal
structure of the catalyst remained intact during the catalysis
and recycling process, while some pore enlargement has
occurred (Figure 2).
15 min and filtered off (∼51% conversion). In the first
experiment, CH2Cl2 was evaporated, and the residue was then
subjected to further heating under solvent-free conditions at
130 °C. We found that no further catalytic activity was
observed upon heating for 2 h, thus supporting the hetero-
geneous nature of the reaction. In the second experiment,
the filtrate was evaporated and then treated with microporous
nanoreactor 2 (≈7 mol %) for 2 h at 130 °C.
Interestingly, we found that although some conversion is
still achieved in this case (≈15% additional conversion after
2 h), the reaction rate decreased significantly due to the
poorer accessibility of the catalytic sites in 2. It is also worth
mentioning that this reaction was not completed even after
prolonged (4 h) heating at 130 °C, thus further confirming
that both 2 and 5 are active nonoreactors through the
proposed model in Figure 1.
In conclusion, we showed that among different kinds of
sulfonic acid based nanoreactors with different pore size and
organic groups nanoreactor 5, in which both acidic sites and
phenyl groups are located inside the mesochannels of SBA-
15, is the most active catalyst in the Pechmann reaction. The
catalyst is even more reactive than the homogeneous strong
acids such as p-TsOH and H2SO4 under the same reaction
conditions. We also demonstrated that uniformly distributed
mesochannels and covalently anchored organic groups might
indeed provide a synergistic means of the efficient approach
of the starting materials to acidic sites, enough space for the
subsequent cyclization, and suitable hydrophobicity to drive
out the water which is formed during the reaction from
mesochannels.21 This approach also opens a pathway to
design and prepare a variety of sophisticated nanoreactors
composed of different types of organic mediators (nanosol-
vents), active sites (nanocatalyst with different properties),
and tunable inorganic nanostructures (nanovessels) for
chemical transformations.
Figure 2. TEM image of nanoreactor 5 perpendicular to the
mesochannels after the sixth reaction cycle. Scale bar: 20 nm.
Acknowledgment. The authors acknowledge IASBS
Research Councils and Iran National Science Foundation
(INSF) for support of this work. We also acknowledge Dr.
Saeed Emadi from IASBS for his help and reading the
manuscript.
To show whether the reaction is actually proceeding in a
heterogeneous pathway inside the nanospace of the catalyst
or whether it is conducting through a homogeneous manner,
two parallel tests were performed, in which the reactions of
resorcinol with ethyl acetoacetate in the presence of nan-
oreactor 5 were quenched (by dilution with CH2Cl2) after
Supporting Information Available: Experimental pro-
cedure and characterization data (TEM, TGA, BET, BJH,
and N2 adsorption-desorption isotherm) for nanoreactors
1-5, general procedure for the Pechmann condensation using
1
nanoreactor 5, and copies of IR, H, and 13C spectra for all
(19) The experimental details for the preparation of nanoreactors 1-5
and their characterization are collected in the Supporting Information.
General procedure for the Pechmann condensation using 5: To the mixture
of the phenolic compound (10 mmol) and ethyl acetoacetate (11 mmol)
was added catalyst 1 (430 mg; ∼7 mol %, -SO3H group) at 130 °C with
constant stirring at the desired time as indicated in Table 2. The reaction
was monitored by TLC. After the completion of the reaction, the reaction
mixture was diluted with ethanol and filtrated to obtain the crude product.
The crude product was purified by column chromatography on silica gel
(hexane:ethyl acetate; 10:1 to 4:1) and then recrystallized from hot ethanol
to afford the pure coumarin derivatives in good to excellent yields (Table
2).
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL8013107
(21) Recently, Shanks and his co-worker made an interesting observation
concerning the strong effect of grafted hydrophobic groups on catalytic
performance of organosulfonic acid mesoporous silicas in the esterification
of fatty acids with methanol: Mbaraka, I. K.; Shanks, B. H. J. Catal. 2005,
229, 365.
(20) Okuhara, T. Chem. ReV. 2002, 102, 3641.
3992
Org. Lett., Vol. 10, No. 18, 2008