Improving the selectivity toward three-component biginelli versus hantzsch reactions by controlling the catalyst hydrophobic/hydrophilic surface balance

Article abstract of DOI:10.1002/cctc.201300739

The catalytic activities and selectivities of two kinds of mesoporous solid acids SBA-15-PrSO₃H 1, SBA-15-Ph-PrSO₃H 2, and a periodic mesoporous organosilica (PMO) based solid acid Et-PMO-Me-PrSO₃H 3 that comprise differen

Full text of DOI:10.1002/cctc.201300739

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DOI: 10.1002/cctc.201300739
Improving the Selectivity toward Three-Component
Biginelli versus Hantzsch Reactions by Controlling the
Catalyst Hydrophobic/Hydrophilic Surface Balance
[
a]
[a]
[a]
[b]
Babak Karimi,* Akbar Mobaraki, Hamid M. Mirzaei, Daryoush Zareyee, and
Hojatollah Vali
[c]
The catalytic activities and selectivities of two kinds of meso-
the three-component coupling reaction of benzaldehyde, me-
tylacetoacetate and urea in the presence of 1 result in the gen-
eration of a mixture of Hantzsch dihydropyridine 4 (ꢀ37%)
and Biginelli dihydropyrimidinone 5 (ꢀ49%), whereas the
same reaction with 2 (catalyst loading of 1 mol% as well) fur-
nishes the corresponding aldolic product methyl-2-benzyli-
dene-3-oxobutanoate 6 as the major product (ꢀ80%) with
concomitant formation of small amounts of 5 (<10%) under
essentially the same reaction conditions that are employed
with catalyst 3. Water adsorption–desorption analysis of the
catalysts is employed to possibly relate the observed selectivity
to the difference in physicochemical properties of the
materials.
porous solid acids SBA-15-PrSO H 1, SBA-15-Ph-PrSO H 2, and
3
3
a periodic mesoporous organosilica (PMO) based solid acid Et-
PMO-Me-PrSO H 3 that comprise different physicochemical sur-
3
face properties were compared in an environmentally benign
one-pot, three-component Biginelli reaction of aldehydes, b-ke-
toesters and urea or thiourea under solvent-free conditions.
Among these mesoporous solid acid catalysts, 3, which has
a hydrophobic/hydrophobic balance in the nanospaces (meso-
channels) in which the active sites are located, is found to be
a significantly more selective catalytic system in the Biginelli
reaction; it produces the corresponding 3,4-dihydropyrimidin-
2-one\thione (DHPM) 5 derivatives in good to excellent yields
and excellent selectivities. Notably, in the case of conducting
Introduction
Ordered mesoporous silica (OMS) materials have gained in-
creasing interest because of their high surface area, narrow
pore size distribution, adjustable mesopore diameter, and
highly tunable physicochemical properties by varying the
For example, it is well documented that if all reacting partners
(starting materials) are lipophilic, the product formation is
more favorable in the case of employing the catalyst that has
more surface hydrophobicity in close proximity to the active
[
1]
[2,3]
nature and extent of the surface functionalization. In catalytic
applications, these characteristics render OMS materials as
a versatile platform in preparing novel sophisticated materials,
which display enhanced catalytic performance; these include
the activity and/or the selectivity. Therefore, a critical stage in
designing a high-performance catalytic system based on OMS
materials is directly concerned with a better understanding of
the surface physicochemical properties and their relationship
with the reaction partners, as well as with the reaction profile.
sites.
A more interesting case is the reaction profiles that involve
both hydrophobic and hydrophilic reaction partners; these
should first diffuse onto the catalyst surface (the system pores
in the case of an OMS-based catalyst) and then react at the
available active sites. In these circumstances, it is often neces-
sary to have an optimum hydrophobic/hydrophilic characteris-
tic inside the system pores to equally accommodate both the
hydrophilic and hydrophobic substrates, thus improving the
[2,3]
reaction rate.
In contrast, because of the inorganic nature
and thus inherent hydrophilic character of the mesoporous
silica network, if there are one or more polar constituents, the
activity of the silica-based catalysts would tend to decrease
through extended physical adsorption of these polar mole-
cules onto the catalyst surface. Therefore, the control of the
hydrophobic/hydrophilic balance in the solid catalysts might
indeed influence their catalytic performance and durability as
well. Based on our experience in design and application of
[
a] Prof. Dr. B. Karimi, A. Mobaraki, H. M. Mirzaei
Department of Chemistry
Institute for Advanced Studies in Basic Sciences (IASBS)
Zanjan 45137-6731 (Iran)
Fax: (+98)241-415-3232
E-mail: karimi@iasbs.ac.ir
[b] Dr. D. Zareyee
Department of Chemistry
Islamic Azad University, Qaemshahr Branch (Iran)
[3,4]
[
c] Prof. H. Vali
novel nanostructured catalysts in recent years,
we discov-
Anatomy and Cell Biology and Facility for Electron Microscopy Research
McGill University
ered that the concomitant control of hydrophobic and acidic
properties in the interior of mesochannels of sulfonic acid-
functionalized OMS can remarkably facilitate diffusion of the
reactants and products for a number of selected acid-catalyzed
3
450 University St, Montreal, Quebec, H3A 2A7 (Canada)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300739.
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reactions, thus improving the overall catalyst efficien-
[
3]
cy and/or sometimes the selectivity. These results
stimulated our interest in finding whether hydropho-
bic channels would be able to influence the catalytic
performance of OMS-based sulfonic acid catalysts in
the Biginelli reaction. We have chosen the Biginelli re-
action because it consists of triple condensation of
both hydrophilic (urea or one of its derivative) and
hydrophobic (an aldehyde and 1,3-dicarbonyl) starting materi-
als and produces two equivalents of water (Scheme 1).
Figure 1. Solid sulfonic acid catalysts based on OMS and PMO.
properties of mesoporous-based sulfonic acid could also influ-
ence the selectivity of the Biginelli reaction. Thus, we first pre-
pared three different solid sulfonic acid-based catalysts on
either OMS (SBA-15) or periodic mesoporous organosilica
(PMO), which followed the reported protocols with slight
[
5]
Since the initial Biginelli reports in 1891, a plethora of pro-
tocols and/or catalytic systems have been developed for this
important synthetic transformation. Along this line, many
Brønsted and Lewis acids have been used to promote the Bigi-
[9]
modifications (Figure 1).
[
6,7]
nelli reaction.
In spite of these advances; most of these pro-
tocols require a high loading of expensive and nonrecoverable
Results and Discussion
The structural parameters of all materials were determined by
employing N adsorption–desorption analysis at T=77 K. All
2
samples show N adsorption isotherms of type IV, which indi-
2
cates the formation of mesopores. The nitrogen isotherm pat-
terns of mesoporous solid acid 1 and 2 exhibit a sharp H1 hys-
teresis loop, which is the characteristic pattern for mesoporous
materials with a narrow pore size determination (PSD) (Fig-
Scheme 1. Representation of the Biginelli reaction.
[3a,b]
ure S2 and S7, Supporting Information).
Conversely, ethane-
bridged PMO-based sulfonic acid 3 displays an indistinct H2
hysteresis loop, which points to the fact that the structure con-
sists of mesopores with a relatively broad PSD (Figure S16,
catalysts and require prolonged reaction times in many instan-
ces. In addition, the selectivity of the three-component Biginelli
reaction toward dihydropyrimidinones (DHPMs) is not always
satisfactory owing to the significant formation of unwanted di-
hydropyridine (DHP) derivatives through the competitive
Hantzsch reaction, which often imposes further separation
steps and strongly limits the scope of this process, a feature
not often highlighted in the literature by the researchers. The
loss of the reaction selectivity may be unambiguously caused
by the in situ decomposition of urea (or urea derivatives) by
the byproduct water to give ammonia, which can subsequent-
ly react with the other reaction partners (aldehyde and 1,3-di-
carbonyl), thus furnishing the corresponding Hantzsch adduct.
Therefore, it is expected that in the case of using a catalytic
system that has a suitable hydrophobic/hydrophilic balance,
the byproduct water in this process can in principle be driven
out from the catalyst surface (active sites) as soon as it is pro-
duced, thereby preventing its subsequent reaction with urea
to ammonia at the active sites, and suppressing the Hantzsch
reaction. In recent years, several
[3e]
Supporting Information). The amount adsorbed at the rela-
tive pressure 0.99 was used to estimate the total pore
[10]
volume. The specific surface area and average PSD were cal-
culated by using the Brunauer–Emmett–Teller (BET) and Bar-
rett–Joyner–Halenda (BJH) methods, respectively (Table 1). The
thermogravimetric analysis and differential thermal analysis
(TGA/DTA) were concomitantly employed with elemental
(sulfur) analysis in all cases to estimate the loading of function-
alized groups in the materials. Moreover, the precise sulfonic
acid function in the catalyst 1–3 (acid capacity) was measured
by using pH analysis of an ion-exchange sample with saturated
[11]
aqueous NaCl solution (Table 1).
To get additional insight into the structural feature of the
materials, they were studied by means of transmission electron
microscopy (TEM).
As can be clearly seen all materials show a well-defined 2D-
hexagonal mesoporous structure, a feature which is in good
[
2,8]
[3]
groups,
including ours, have
Table 1. Characterization of functionalized PMOs.
discovered that the catalytic per-
formance of OMS-based catalysts
and thus their selectivity in
some organic reactions markedly
depends on the nature and the
extent of surface functionaliza-
tion of these materials. Along
the line of these achievements,
we were interested to determine
whether the physicochemical
[a]
[b]
[c]
[d]
[e]
Entry
Solid acid
S
BET
2
V
p
Pore size
[nm]
Sulfur content
Acid capacity
[ mmolH g
À1
3
À1
À1
+
À1
[m g
]
[cm g
]
[mmolg
]
]
1
2
3
4
5
Et-PMO-Me-PrSH
3
3 (recycled)
2
1
213
318
83
356
430
0.24
0.27
0.10
0.58
0.67
3.5
3.4
5.2
5.4
6.2
–
0.8
–
–
–
–
0.50
0.40
1.61
1.77
[
[
a] BET surface area. [b] Total pore volume. [c] BJH pore size. [d] Sulfur content measured by elemental analysis.
e] Determined by titration after ion-exchange (mmolH
+
À1
g ) (see the Supporting Information).
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agreement with the ordered mesoporous structure estimated
sulfonic acid catalyst indeed have a significant and somewhat
interesting impact on both the efficiency and the selectivity of
the titled reaction under the described reaction conditions. Al-
though the performance of the three-component coupling re-
action of benzaldehyde, metylacetoacetate and urea in the
by N -sorption analyses of the materials (Figure 2).
2
After the initial characterization of the materials 1–3, their
catalytic performance (both selectivity and activity) was then
compared in the three-component reaction of methylacetoace-
tate (1 mmol), benzaldehyde (1 mmol), urea (1.2 mmol) under
solvent-free conditions at T=908C in the presence of 1 mol%
of the catalyst within 1.5 h (Scheme 2). Although, the use of
presence of SBA-15-PrSO H 1 (1 mol%) results in the genera-
3
tion of a mixture of Hantzsch dihydropyridine 4 (ꢀ37%) and
Biginelli dihydropyrimidinone 5 (ꢀ49%), the same reaction
with 1 (1 mol% as well) furnishes the corresponding aldolic
product methyl-2-benzylidene-3-oxobutanoate 6 as the major
product (ꢀ80%) with concomitant formation of a trace
amount of 5 (<10%). Most interestingly, if the PMO-based sul-
fonic acid 3 (Et-PMO-Me-PrSO H) is used as the catalyst rather
3
than 1 and 2 under otherwise the same reaction conditions,
a substantial changeover of the product selectivity toward the
formation of DHPM 5 in excellent yields of 91% occurs
(
Scheme 2). To the best of our knowledge there are no reports
of such a changeover in the product selectivity in a similar
three-component reaction by changing the surface physico-
chemical properties of the employed solid catalysts.
If this observed variation in the product selectivity can be
amenable to matching the physicochemical properties in the
nanospaces of the mesoporous support, in which the acidic
sites are located, with the hydrophobic/hydrophilic nature of
the reaction constituents (reactant and products) it would be
a remarkable advance in the field. For this reason, we were in-
terested to get more insight into this issue. To do this, we pro-
ceeded to measure the water adsorption–desorption isotherm
of the catalysts 1–3 in the gas phase at T=258C (Figure 3).
Figure 2. TEM images of the catalyst: a) 1 (scale bar 100 nm), b) 2 (scale bar
20 nm), c) 3 (scale bar 100 nm). For further images see the Supporting Infor-
mation.
solid sulfonic acids based on either OMS or PMO are well-
documented in several important functional group transforma-
1 exhibits a large water adsorption at P/P that ranges from
0
[
2,12,13]
tions,
to our knowledge there is no precedent example
0.6–0.8, which indicates that the nanospaces of this material
have a significant hydrophilic nature. Conversely, the organo-
of the effect of surface physicochemical properties of these
materials in the selectivity control of multicomponent reactions
such as the Biginelli reaction. Our preliminary investigations re-
vealed that the physicochemical properties of the employed
functionalized SBA-15-Ph-PrSO H 2 shows almost no water
3
uptake under the same conditions, which demonstrates that
the nanospaces of 1 become extremely hydrophobic upon
Scheme 2. Three-component reaction of methylacetoacetate (1 mmol),
benzaldehyde (1 mmol), and urea (1.2 mmol) in the presence of solid acid
catalysts 1–3 at 908C within 1.5 h under solvent-free conditions.
Figure 3. Water adsorption–desorption isotherms of solid acid catalysts
1 (
&
), 2 (*), and 3 (~).
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functionalization with the phenyl group. In contrast, the
amount of water uptake in the case of 3 is much lower than
for 1, whereas this value is much higher than the value mea-
sured for 2. These observation can be attributed to the fact
that whereas the nanospaces in material 3 have considerable
hydrophobic character, they are still hydrophilic enough com-
pared to those of material 2, a feature which seems to be cru-
cial for allowing both the hydrophobic and hydrophilic starting
materials to readily diffuse into the nanospaces of the catalyst,
where the acidic sites are located.
tivity toward the formation of dihydropyrimidinone in the
three-component Biginelli reaction. By obtaining the appropri-
ate catalytic system (catalyst 3), we were next interested in in-
vestigating the scope of this catalytic system in the Biginelli re-
action of various aldehydes, b-ketoesters, and urea as well as
thiourea. To do this we thus managed to find the optimum re-
action conditions for this process. The impact of catalyst load-
ing, and reaction temperature on the Biginelli reaction of ben-
zaldehyde (1 mmol), methylacetoacetate (1 mmol) and urea
(1.2 mmol) as model substrates are summarized in Table 2.
At this stage, a critical question is this: how do the physico-
chemical properties of the nanospaces in mesoporous solid
acids 1–3 influence the observed product selectivities demon-
strated in Scheme 2? On the basis of the fact that the three–
component Biginelli reaction consists of both hydrophilic (urea
or thiourea) and hydrophobic (aldehyde and b-ketoester) start-
ing materials, facile diffusion of these physically divergent reac-
tants into the system pore of the catalyst is an important cata-
lytic implication that should be resolved. It thus appears that
faster adsorption of, for example, more hydrophobic starting
materials onto the catalyst surface would certainly prohibit the
penetration of reactants that have a higher hydrophilic nature
and vice versa, thus, strongly suppressing the Biginelli reaction.
It is thereby reasonable that an optimum hydrophobic/hydro-
philic balance in the nanospaces of the catalyst is necessary for
favorable penetration of all reactants into the system pores to
achieve high catalytic activity and, in particular, the product se-
lectivity. Based on this explanation, the high hydrophobic char-
acter of sulfonic acid catalyst 2 may indeed provide a means
of faster diffusion of benzaldehyde as well as ethylacetoacetate
Table 2. Effects of reaction temperature and the loading of the Et-PMO-
Me-PrSO
3
H solid acid on the Biginelli reaction with urea.
[a]
Entry
Mol
[%]
T
[8C]
t
Yield
[%]
[h[min]]
1
2
3
4
5
6
7
8
9
1
1
1
0.5
0.3
1.5
1
0.5
0.3
–
50
70
80
80
80
90
90
90
90
80
90
8
56
86
91
93
91
95
93
92
92
59
63
7[30]
2[30]
4
5
1
1[20]
1[45]
2[15]
9
10
11
–
4
[
a] Yields refer to the isolated pure products. (R=H, X=O).
In the presence of catalyst 3 (1 mol%), we stirred the afore-
(
but not urea) to the active sites provided by open mesopores,
mentioned components at T=508C for 8 h; this afforded the
corresponding dihydropyrimidin-2-one in only 56% isolated
yield (Table 2, entry 1). As expected, it is found that by increas-
ing the reaction temperature the yield of the desired dihydro-
pyrimidin-2-one is remarkably increased at a constant catalyst
loading of 1 mol% (Table 2, entries 2–3 and 7). At the same
time, a decrease in the amount of catalyst does not show any
significant impact on the product yields at T=908C (Table 2,
entries 7–9). We also examined the reaction in catalyst-free
conditions. This gives the expected product in a moderate
yield at T=808C after prolonging the reaction time (Table 2,
entries 10–11). Taken together, among the examined reaction
conditions, this three-component reaction can be most effi-
ciently catalyzed by 0.3 mol% of 3 at T=908C for 135 min
under solvent-free conditions (Table 2, entry 9). Our next objec-
tive was to apply the present procedure for the synthesis of
thiopyrimidin-2-ones by employing thiourea as one of the re-
action partners instead of urea because thiopyrimidin-2-ones
are important pharmacophores with regard to biological activi-
ty.
thus shifting the reaction selectivity toward the formation of
aldolic adduct 6 as the major product in the absence of urea
derivatives (Scheme 2). This model may also explain the signifi-
cant selectivity changeover of the process toward the forma-
tion of dihydropyrimidinone 5 if PMO-based sulfonic acid 3 is
employed rather than mesoporous solid acids 1 and 2. This ob-
servation most likely originates from a hydrophobic/hydrophil-
ic balance in the system pores (mesochannels) of 3, which in-
evitably renders its mesoporous environment favorable to in-
teract with both hydrophobic and hydrophilic starting materi-
als, thus increasing their concentration in near proximity to sul-
fonic acid moieties, which causes efficient and selective
formation of dihydropyrimidinone 5. Based on this model, the
concomitant formation of 4 and 5 in the case of employing
1
might be also ascribed to the pronounced hydrophilic
nature of system pores in 1, which arise from a relatively high
concentration of silanol groups; these can strongly interact
with both urea and the byproduct water and facilitate the un-
wanted hydrolysis of urea (or thiourea) to produce ammonia
to a greater extent, thereby gradually shifting the process se-
lectivity toward the production of Hantzsch dihydropyridine
upon subsequent condensation with bezaldehyde and ethyla-
cetoacetate (Scheme 2). From these unprecedented observa-
tions, it is particularly conspicuous that the hydrophobic/hy-
drophilic balance in the mesoporous environments of the em-
ployed catalyst has a decisive role in achieving the high selec-
An initial assessment demonstrated that the aforementioned
optimized conditions were not successful for the three-compo-
nent Biginelli condensation reaction in the presence of thiour-
ea. Therefore, the reaction was performed at a higher tempera-
ture and concentration of catalyst (T=110 8C, 0.7 mol%) to
ensure that excellent yields were also achieved for various thi-
opyrimidin-2-one derivatives (Table 3).
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entries 3–8), which indicates that the position of the electron-
withdrawing substituent has no significant effect on the yields
of DHPM adducts. A similar behavior is observed with electron-
releasing groups. Meta-methyl (Table 4, entries 9–10), 3,5-di-
methyl (Table 4, entries 11–12), para-isopropyl (Table 4, en-
tries 13–14), and para-methoxy (Table 4, entries 15–16) benzal-
dehydes produce the expected DHPMs in good quantities.
Also, the bulky aromatic naphthyl group gives the desired
product in good yields (Table 4, entries 17–18). Furthermore,
under similar reaction conditions, 3-phenylpropionaldehyde as
a model for an aliphatic and enolizable aldehyde gives the cor-
responding DHPMs in high yield but longer reaction times are
required to obtain high yields of the corresponding condensa-
tion products (Table 4, entries 19–20). Notably, the methodolo-
gy is also successfully employed for heterocyclic aldehydes
such as furfural (Table 4, entries 21–22), which gives the re-
spected DHPM adducts in good yields. It is also found that the
use of ethyl acetoacetate instead of methyl acetoacetate in the
three-component reaction gives the corresponding products in
excellent yields (Table 4, entries 23–24). These results are quite
comparable to recent interesting reports by Bhaumik and co-
Table 3. Effects of reaction temperature and loading of catalyst 3 on the
Biginelli reaction with thiourea.
[
a]
Entry
Mol
%]
T
[8C]
t
[h]
Yield
[%]
[
1
2
3
4
5
6
0.3
0.3
0.3
0.5
0.7
–
90
100
110
110
110
110
5
5
7
7
7
7
53
59
74
83
91
43
[a] Yields refer to the isolated pure products.(R=H, X=S).
With the optimized reaction conditions in hand, to study the
generality of the procedure, the scope of the Biginelli-like scaf-
folds reaction was investigated with various aldehydes, b-ke-
toester and urea or thiourea, and a library of substituted
DHPMs was obtained in good to excellent yields in appropriate
time under solvent-free conditions (Table 4). Both electron-
withdrawing as well as electron-donating substituents on the
aldehyde aryl ring are tolerated and react with methyl acetoa-
cetate and urea under the optimized conditions. Meta- and
para-fluoro and meta-bromobenzaldehydes successfully pro-
duce the desired products in similarly excellent yields (Table 4,
[6k]
[6l]
workers and Alvim et al., in which they employ a novel
functionalized Fe O @mesoporous SBA-15 and several types of
3
4
ionic liquid-based systems, respectively, as the catalysts in the
Biginelli reaction with urea to synthesize DHPMs with more or
less close turnover numbers (TONs) and selectivities.
Table 4. Yields of various substituted DHPM derivatives on Et-PMO-Me-
3
PrSO H.
Reusability of the Et-PMO-Me-PrSO H (3) catalyst
3
[a,b]
Entry Aldehyde
R
X
t
Yield
group substituent [h[min]] [%]
The recovery of catalyst 3 in the Biginelli reaction of benzalde-
hyde (1 mmol) with methylacetoacetate (1 mmol) and urea
(1.2 mmol) with 0.3 mol% catalyst loading of the catalyst
under solvent-free conditions at T=908C was also tested. The
catalyst is easily recovered from the reaction mixture by filtra-
tion, then washed with acetonitrile, water and ethanol and fi-
nally dried at T=110 8C for 2 h before another reaction is per-
formed. During the recycling experiment with fresh reactants
under the same reaction conditions, no considerable change in
the activity of the catalyst for at least 8 consecutive runs is ob-
served, which clearly demonstrates the stability of the catalyst
for these conditions in the Biginelli reaction (Figure 4).
1
2
3
4
5
6
7
8
9
0
benzaldehyde
benzaldehyde
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
O
S
O
S
O
S
O
S
O
S
O
S
O
S
O
S
O
S
O
S
O
S
O
S
2[15]
7
2
5[55]
2[5]
6[10]
2[10]
6[50]
2[25]
7
2[20]
6[55]
2[35]
7[15]
2[40]
7[10]
1[50]
5[30]
3[40]
8[35]
1[45]
5[35]
2[25]
7[45]
92
91
93
92
91
89
93
89
90
88
89
90
90
91
88
89
92
91
89
87
83
79
90
89
3-fluorobenzaldehyde
3-fluorobenzaldehyde
4-fluorobenzaldehyde
4-fluorobenzaldehyde
3-bromobenzaldehyde
3-bromobenzaldehyde
3-methylbenzaldehyde
3-methylbenzaldehyde
1
1
1
3,5-dimethylbenzaldehyde Me
3,5-dimethylbenzaldehyde Me
4-isopropylbenzaldehyde Me
4-isopropylbenzaldehyde Me
1
1
1
1
1
1
1
1
2
2
2
2
2
2
3
4
5
6
7
8
9
0
1
2
3
4
We also performed N -sorption analysis and acid-base titra-
2
4-methoxybenzaldehyde
4-methoxybenzaldehyde
naphthaldehyde
Me
Me
Me
Me
tion of catalyst 3 after the tenth reaction cycle to determine if
any structural changes and leaching of the sulfonic acid sites
naphthaldehyde
had occurred in the catalyst or not. Both N -sorption diagrams
2
3-phenylpropionaldehyde Me
3-phenylpropionaldehyde Me
(
(
see S20, the Supporting Information) and the TEM image
Figure 5) of the recovered catalyst show little (almost ignora-
2-furfuraldehyde
2-furfuraldehyde
benzaldehyde
benzaldehyde
Me
Me
Et
ble) changes in the morphology of the catalyst after recovery.
Although, the catalyst does not show significant structural
changes, to show the overall stability of catalyst 3, the acidic
capacity was measured by titration of ion-exchanged catalysts
after the tenth reaction cycles. Our studies reveal that the sul-
fonic acid loading in catalyst 3 is slightly reduced from 0.5 to
Et
[
(
a] Aldehyde (1 mmol), methyl acetoacetate (1 mmol), urea or thiourea
1.2 mmol) and catalyst 3 (0.3 mol%) at T=908C. [b] Reaction was per-
formed at T=110 8C by using 0.7 mol% of catalyst 3. Yields refer to the
isolated pure products based on the aldehydes. Structures of the prod-
ucts were confirmed by H and C NMR and IR spectral data. The melting
points of the products were also compared with authentic samples that
were prepared according to the known procedures (see the Supporting
Information).
+
À1
1
13
0.40 mmolH g (ꢀ80% survival), which is still quite interest-
ing. Notably, for the reactions in which water participates as
a byproduct, only a few solid acids show acceptable perfor-
[2a,14]
mance and stability.
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with both hydrophobic (aldehyde and b-ketoester molecules)
and hydrophilic (urea or thiourea) starting materials, thus in-
creasing their concentration in near proximity to sulfonic acid
moieties and causing efficient and selective formation of dihy-
dropyrimidinone 5. In the same way, the concomitant forma-
tion of 4 and 5 in the case of employing 1 might be also as-
cribed to the pronounced hydrophilic nature of system pores
in 1, which arise from a relatively high concentration of silanol
groups; these can strongly interact with both urea and the by-
product water and facilitate the unwanted hydrolysis of urea
(
or thiourea) to produce ammonia to a greater extent, thereby
gradually shifting the process selectivity toward the production
of Hantzsch dihydropyridine upon subsequent condensation
with bezaldehyde and ethylacetoacetate. To the best of our
knowledge, there are no precedent reports of such a change-
over in the product selectivity in a similar three-component re-
action by changing the surface physicochemical properties of
the employed solid catalysts. Work is underway to expand the
application of this approach in other important chemical trans-
formations. It is believed that this finding will stimulate the
creation of new areas in designing novel solid acid catalysts
that have an appropriate surface hydrophobic/hydrophilic bal-
ance to control the selectivity of a typical transformation in
a designated pathway.
Figure 4. Recyclability of catalyst 3 in the Biginelli reaction of benzaldehyde,
methylacetoacetate, and urea at T=908C under solvent-free conditions.
Yield (&) and Time (&)
Experimental Section
Preparation of SBA-15-PrSH
The synthesis of SBA-15-PrSH was achieved by using the procedure
[9c]
described by Stucky and co-workers. This procedure involved
a synthetic strategy based on the co-condensation of tetraethoxy-
silane (TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) in
the presence of Pluronic P123 (EO PO EO ) as the structure-di-
Figure 5. TEM images of catalyst 3 (scale bar 100 nm) after the tenth
reaction cycle.
20
70
20
recting agent. In a typical preparation procedure, Pluronic P123
1
(
(
4.0 g, Aldrich, average Mw = 5800) was dissolved in HCl solution
4
125 g, 1.9m) with stirring at room temperature. The solution was
Conclusions
heated to T=408C before TEOS (6.83 g) was added. After 3 h pre-
hydrolysis of TEOS, the thiol precursor MPTMS (1.6 g) was added.
The resultant solution was stirred for 20 h at T=408C, after which
the mixture was aged at T=1008C for 24 h under static conditions.
The solid was recovered by filtration and air dried at room temper-
ature overnight. The template was removed from the as-synthe-
sized material by washing with ethanol by using a Soxhlet appara-
tus for 24 h.
In summary, the preparation and characterization of two kinds
of mesoporous solid acids SBA-15-PrSO H 1, SBA-15-Ph-PrSO H
3
3
2
, and a periodic mesoporous organosilica (PMO) based solid
acid Et-PMO-Me-PrSO H 3 are described. The catalytic perfor-
3
mance (both activity and selectivity) of these catalytic systems
is compared in the three-component Biginelli condensation re-
action of aldehydes, b-ketoesters, and urea as well as thiourea.
Amongst them, catalyst 3 is found to be significantly more se-
lective in the Biginelli reaction, which affords the correspond-
ing DHPM derivatives in good to excellent yields and excellent
selectivities without the formation of any detectable dihydro-
pyridine (DHP, Hantzch adduct) and/or aldolic products. This
remarkable and unprecedented selectivity improvement of the
Preparation of SBA-15-Ph-PrSH
PhSi(OEt) (PTES, 4 mmol) was added to a suspension of SBA-15-
3
PrSH (3 g) in dry toluene. The resulting mixture was first stirred at
room temperature for 1 h and then heated under reflux for a fur-
ther 24 h. The solid materials were filtered off and successively
washed with toluene, EtOH, and Et O, and dried overnight at T=
2
Et-PMO-Me-PrSO H catalyst in the Biginelli reaction versus the
3
1208C to afford the corresponding SBA-15-Ph-Pr-SH.
Hantzsch reaction and/or aldolic products most likely owes to
the hydrophobic/hydrophilic balance in the nanospaces (meso-
channels) of the material in which the active sulfonic acid
groups are located. It is assumed that this hydrophobic/hydro-
philic balance in the system pores (mesochannels) of 3, ren-
ders its mesoporous environment favorable for interaction
Preparation of SBA-15-PrSO H (1) and SBA-15-Ph-PrSO H (2)
3
3
The conversion of the thiol groups of the catalysts to sulfonic acid
moieties was accomplished by using hydrogen peroxide. Typically,
the solid materials (0.3 g) were suspended in aqueous H O (10 g,
2
2
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3
0 wt%). These suspensions were stirred at room temperature in
Acknowledgements
an argon atmosphere for 24 h. After the oxidation treatment, the
resulting solutions were filtered and washed separately with water
and ethanol. Finally the wet materials were suspended in H SO4
The authors acknowledge the IASBS Research Council and Iran
National Science Foundation (INSF) for supporting this work.
2
(
1m) solution for 2 h, washed several times with water and etha-
nol, and dried at T=608C under vacuum overnight to give the cor-
responding 1 and 2 catalysts.
Keywords: heterogeneous catalysis · mesoporous materials ·
organocatalysis · solid-state reactions · surface chemistry
Preparation of Et-PMO-Me-PrSO H (3)
3
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