New magnetic nanocomposites of ZrO2-Al2O 3-Fe3O4 as green solid acid catalysts in organic reactions

Article abstract of DOI:10.1039/c3cy00572k

A series of magnetic solid acid nano-catalysts were designed and prepared through a facile co-precipitate approach. The original nanocomposites ZrO ₂-Al₂O₃-Fe₃O₄ were characterized by means of ICP-AES

Full text of DOI:10.1039/c3cy00572k

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New magnetic nanocomposites of ZrO2–Al2O3–Fe3O4
as green solid acid catalysts in organic reactions
Cite this: Catal. Sci. Technol., 2014,
4, 71
*
*
Anqi Wang, Xiang Liu, Zhongxing Su and Huanwang Jing
A series of magnetic solid acid nano-catalysts were designed and prepared through a facile co-precipitate
approach. The original nanocomposites ZrO2–Al2O3–Fe3O4 were characterized by means of ICP-AES, BET,
XRD, TEM, HRTEM, VSM, FT-IR, NH3-TPD and TG. Their catalytic behaviours were investigated via esterification,
the synthesis of bis-indolylmethanes, Hantzsch reaction, Biginelli reaction and Pechmann reaction. In all of
these organic reactions, the corresponding products were obtained in moderate to excellent yields. The
optimal catalyst was ZAF-16/16, which retained catalytic activity after several recycles.
Received 2nd August 2013,
Accepted 24th September 2013
DOI: 10.1039/c3cy00572k
www.rsc.org/catalysis
(MNPs) are one of the most widely studied materials in
multi-disciplinary research, covering magnetic resonance
Introduction
Acid-catalyzed organic reactions are topics of overwhelming
interest in view of vast applications in the chemical industry.
Conventional liquid inorganic acids, such as H2SO4, HCl,
H3PO4 and HF have been developed and applied to various
organic syntheses. However, these homogeneous acids are
not suitable for industrial processes due to separation prob-
lems and environmental issues. In the last few decades,
many types of solid acids have emerged as potential alternate
catalysts to the mineral acids, including sulfated metal
oxides, zeolites, heteropolyacids, metal phosphates, inorganic
oxides, etc.1–5 The preparation and use of solid acid catalysts
are active research fields for esterification,6,7 isomerization,8,9
acylation,10,11 alkylation,12,13 nitration,14,15 as well as other
important organic transformations.16–21 It is well known
that the solid superacid catalysts of sulfated metal oxides
(SO42−–MxOy) offer new opportunities for developing environ-
mentally benign and friendly processes in organic syntheses.
However, the SO42−–MxOy catalysts suffer from the disadvan-
tage of deactivation in practical applications, possibly due to
sulfur reduction during the reaction process, or the forma-
tion of coke on the surface of catalysts.22–24 Therefore, a more
stable solid acid catalyst capable of resisting deactivation
needs to be developed.
imaging (MRI),25 magnetic storage media,26 biotechnology,27
ferrofluids,28 etc. Among magnetic materials, Fe3O4 nano-
particles have been used as a versatile support for a variety of
heterogeneous catalysts in diverse classes of organic
transformations.29
Based on the above fundamental understandings, we
designed and prepared a series of green magnetic solid acid
nano-catalysts ZrO2–Al2O3–Fe3O4 (ZAF) that have been
applied in various organic reactions. Esterification of carbox-
ylic acids with alcohols are classical chemical reactions. The
synthesis of n-butyl acetate was selected as a probe reaction
to evaluate the catalytic activities of the prepared magnetic
solid acid nano-catalysts, ZAF. Heterocyclic compounds con-
stitute a paramount group of natural products with various
pharmaceutical properties and biological activities, as well as
other applications. Recently, numerous methods describing
the preparation of bis-indolylmethanes (BIMs) have been
reported in the literature employing protic acids and
Lewis acids catalysts.21,30,31 The Hantzsch reaction, which
provides 1,4-dihydropyridines (1,4-DHPs),32–34 and the
Biginelli synthesis, which generates 3,4-dihydropyrimidinones
(3,4-DHPMs),35–37 are two remarkable multicomponent reac-
tions that could be catalyzed by acidic catalysts. Moreover,
the acid-catalyzed Pechmann reaction is a method commonly
used for synthesizing coumarin derivatives.19,38,39 Herein, the
prepared ZrO2–Al2O3–Fe3O4 nanocomposites acted as efficient
and versatile catalysts in these reactions, and the excellent
results were disclosed in this paper.
In general, the traditional heterogeneous catalyst separa-
tion methods, such as filtration or centrifugation, become
tedious and hamper complete separation of the catalysts.
Consequently, a great amount of research work has been
devoted to the development of readily separable heteroge-
neous catalysts for organic reactions. Magnetic nanoparticles
Results and discussion
Characterization of catalysts
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and
Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Gansu,
Lanzhou, 730000, PR China. E-mail: liuxiang@lzu.edu.cn, hwjing@lzu.edu.cn;
Fax: +86 0931 8912582; Tel: +86 0931 8912585
The ICP-AES data indicated that only small differences
between the actual and controlled molar ratio of Zr–Al–Fe3O4
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Table 1 The composition and BET surface areas of prepared catalysts
35.4°, 37.0°, 43.0°, 53.3°, 56.9°, 62.5° and 73.9° could be
ascribed to reflections from (111), (220), (311), (222), (400),
(422), (511), (440) and (533) planes of Fe3O4, respectively. In
contrast, the diffraction peaks of both Fe3O4 and ZrO2 were
observed in Fig. 1b–d. Besides the corresponding peaks of
Fe3O4, the 2θ values at 50.7°, 60.5°, 82.8° and 85.8° were
attributed to the characteristic reflections from (202), (311),
(133) and (042) planes of tetragonal ZrO2, respectively. It was
notable that the separate diffraction peaks of Al2O3 were
absent in the XRD profiles. This might suggest that the alu-
mina component had homogeneously dispersed into the
structure of ZrO2–Al2O3, forming the uniform bi-component
of ZrO2–Al2O3 nanocomposites that was coated on the surface
of the Fe3O4 MNPs. However, samples with higher ZrO2–Al2O3
contents, namely, the catalysts ZAF-12/12, ZAF-16/16 and
ZAF-20/20, revealed no evident diffraction peaks except a
broadened peak around 30° (Fig. 1e–g). It was concluded that
the content of ZrO2–Al2O3 would deeply affect the crystalline
phase of ZAF catalysts.
Zr : Al : Fe3O4 (molar ratio)
SBET
(m2 g−1
)
Entry
Catalyst
Controlled
Measured a
1
2
3
4
5
6
7
8
ZAF-2/2
ZAF-4/4
ZAF-8/8
ZAF-12/12
ZAF-16/16
ZAF-20/20
ZAF-16/0
2 : 2 : 1
4 : 4 : 1
8 : 8 : 1
12 : 12 : 1
16 : 16 : 1
20 : 20 : 1
16 : 0 : 1
16 : 8 : 1
16 : 12 : 1
16 : 24 : 1
16 : 32 : 1
—
2 : 1.9 : 1
3.9 : 3.6 : 1
7.8 : 7.6 : 1
11.8 : 11.4 : 1
15.2 : 14.8 : 1
18.2 : 17.4 : 1
15.8 : 0 : 1
15.4 : 7.9 : 1
15.1 : 10.8 : 1
14.7 : 20.8 : 1
14.9 : 29.1 : 1
—
48
57
95
141
165
167
92
144
157
187
199
46
ZAF-16/8
9
ZAF-16/12
ZAF-16/24
ZAF-16/32
ZAF-16/16 (400)
ZAF-16/16 (500)
ZAF-16/16 (600)
ZAF-16/16 (700)
10
11
12
13
14
15
—
—
—
—
—
—
26
23
16
a
Determined by ICP-AES analysis.
were observed in ZAF catalysts (Table 1, entries 1–11). Using
N2 adsorption technology, the specific surface areas of the
prepared magnetic solid acid nano-catalysts were obtained
and are listed in Table 1. It could be seen that the composi-
tion of ZAF catalysts had an obvious impact on the specific
surface areas (SBET). There was an appreciable variation in
SBET with the increase of ZrO2–Al2O3 contents, represented by
the SBET of ZAF-20/20 being much higher than that of ZAF-2/2
(Table 1, entry 6 vs. 1). On the other hand, addition of alu-
mina component to the catalysts resulted in an increased
trend of the specific surface areas (Table 1, entries 5, 7–11).
The catalyst ZAF-16/0 showed lower specific surface area
(92 m2 g−1), while the catalyst ZAF-16/32 revealed the highest
specific surface area (199 m2 g−1). Thus, the SBET increased
along with the increased amount of alumina component.
Additionally, the specific surface area of catalyst ZAF-16/16
declined sharply after the catalyst was calcined at tempera-
tures from 400 to 700 °C, and the SBET of all the calcined cat-
alysts were reduced below 50 m2 g−1 (Table 1, entries 12–15).
The XRD patterns of amine-functionalized Fe3O4 MNPs
are shown in Fig. 1a. The diffraction peaks at 18.2°, 30.0°,
Fig. 2 shows that the crystalline phase of the nano-
composites changed with increasing alumina content in ZAF
catalysts. It could be observed from Fig. 2a that the diffrac-
tion peaks of both Fe3O4 and tetragonal ZrO2 were detected
in ZAF-16/0 where there was not any alumina component.
Otherwise, the 2θ values of ZAF-16/8 were unaltered com-
pared to ZAF-16/0 except the peak intensity of tetragonal ZrO2
grew slightly and that of Fe3O4 declined (Fig. 2b). But when
the alumina content further increased, the separate diffrac-
tion peaks of Fe3O4 and tetragonal ZrO2 gradually diminished
while the amorphous phase replaced the crystalline phase
(Fig. 2c–f).
The effect of calcination temperature on the crystalline
structure of the catalyst ZAF-16/16 is shown in Fig. 3. It could
be seen that the ZAF-16/16 (400) and ZAF-16/16 (500) kept an
almost constant structure, which was similar to the
uncalcined catalyst ZAF-16/16 (Fig. 3a and b). However, fur-
ther increase in calcination temperature (600 and 700 °C)
resulted in an appearance of some characteristic reflections
of Fe3O4 and tetragonal ZrO2 (Fig. 3c and d).
The morphology and fine structure of amine-
functionalized Fe3O4 MNPs and catalyst ZAF-16/16 were
Fig. 1 XRD patterns of amine-functionalized Fe3O4 and ZAF catalysts
with different contents of ZrO2–Al2O3.
Fig. 2 XRD patterns of ZAF catalysts with various contents of Al2O3.
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Fig. 5 Magnetic hysteresis loops of (a) Fe3O4 MNPs, (b) ZAF-16/16.
Fig. 3 XRD patterns of catalyst ZAF-16/16 after calcination at different
temperatures.
Fig.
6 FT-IR spectra of (a) Fe3O4 MNPs, (b) ZAF-16/16 without
pyridine adsorption, (c) ZAF-16/16 with pyridine adsorption.
ZAF-16/16 could be explained by the presence of a surface
coating of ZrO2–Al2O3 nanocomposites.
Fig. 6a presents the strong IR band at 577 cm−1 character-
istic of the Fe–O vibrations, while the transmissions around
1623, 1480 and 872 cm−1 were well matched with that from
free 1,6-hexanediamine, indicating the existence of –NH2
group on the amine-functionalized Fe3O4.40 The IR spectrum
for catalyst ZAF-16/16 without pyridine adsorption is illus-
trated in Fig. 6b. It was clear to see that the vibration peak of
Zr–O band was at 712 cm−1,41 and the characteristic band of
1620 cm−1 could be ascribed to –NH2 originating from the
Fe3O4 surface. The IR spectrum of pyridine adsorbed on mag-
netic solid acid nano-catalyst ZAF-16/16 in Fig. 6c shows char-
acteristic bands in the range of 1400–1650 cm−1. Namely, the
bands at 1456 and 1542 cm−1 could be assigned to Lewis and
Brønsted acid sites, respectively. Moreover, an additional
broad and intense band at 3403 cm−1 corresponding to
stretching vibrations of hydroxyl groups and absorbed water
accompanied by the 1627 cm−1 band were observed.42,43
Fig. 4 TEM and HRTEM images of (a, b) amine-functionalized Fe3O4
and (c, d) ZAF-16/16.
examined by TEM and HRTEM. It was clear to see in Fig. 4a
that the Fe3O4 MNPs had a size range of 200–300 nm. Fig. 4b
indicated that the interplanar distance was 0.48 nm, attrib-
uted to the (111) lattice planes of Fe3O4. Additionally, Fig. 4c
confirmed the presence of a ZrO2–Al2O3 coating. Compared
with Fe3O4 MNPs, there was a conspicuous increase in the
particle size of catalyst ZAF-16/16. Meanwhile, the detailed
structural information of ZAF-16/16 was amorphous, which
was also evidenced by HRTEM (Fig. 4d). These observations
were in good agreement with the XRD results (Fig. 1a and f).
The magnetic properties of as-synthesized Fe3O4 and
ZAF-16/16 were measured at room temperature. As shown in
Fig. 5a, the saturation magnetization value of Fe3O4 was
20.5 emu g−1. After being coated by the ZrO2–Al2O3 layer, the
saturation magnetization value of ZAF-16/16 was 18.7 emu g−1
(Fig. 5b). The slight decrease in magnetic saturation for
Temperature-programmed
desorption
of
ammonia
(NH3-TPD) was used to compare the acidic characteristics of
the catalysts ZAF-16/16 and ZAF-16/0. Fig. 7 showed that each
catalyst exhibited a broad NH3 desorption peak starting from
100 °C and extending beyond 800 °C. It was observed in
Fig. 7a and b that there were three distinct desorption peaks
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structure water of Zr(OH)4. The TG curves revealed that the
total mass loss of ZAF-16/16 (38.2%) was higher than that of
ZAF-16/0 (22.4%). We inferred that the addition of alumina
component was beneficial to enlarge the surface area of cata-
lyst ZAF-16/16, which resulted in more hydroxyl groups
existing in ZAF-16/16.
Esterification
Esterification is a fundamental organic reaction which can be
catalyzed by both homogeneous and heterogeneous acidic
catalysts. n-Butyl acetate is widely used as a solvent and in
plasticizers, perfumes and flavors, and also as an organic
feedstock and intermediate.45,46 The synthesis of n-butyl ace-
tate was chosen as a model reaction to examine the catalytic
performance of the prepared magnetic solid acid nano-
catalysts and the results are listed in Table 3. It could be seen
that the reaction was quite difficult to take place in the
absence of catalyst (Table 3, entry 1). However, when the
esterification was catalyzed by the series of ZrO2–Al2O3–Fe3O4
catalysts the n-butyl acetate was formed as a single product
(Table 3, entries 2–11). The catalysts with various contents of
ZrO2–Al2O3 revealed different activities during the reaction
process, and the catalytic activity of ZAF-16/16 was much
higher compared to the other catalysts (Table 3, entry 6). On
the other hand, the calcination temperatures had a bearing
on the catalytic activity of ZAF-16/16. The catalyst ZAF-16/16
after calcination at temperatures from 400–700 °C displayed
lower activities than the initial precipitated catalyst, and the
conversion of n-butyl alcohol decreased sharply with increas-
ing calcination temperatures (Table 3, entries 12–15). It was
worthy to mention that the catalyst ZrO2–Al2O3, which did
not contain a magnetic component, was less effective than
ZAF-16/16 (Table 3, entry 16 vs. 6); meanwhile, a trace
amount of n-butyl acetate was formed when the reaction was
catalyzed by Fe3O4 MNPs (Table 3, entry 17). We could infer
that the Fe3O4 MNPs not only acted as a magnetic compo-
nent for separation, but also participated in the catalysis. The
control experiments showed that the conversions were obvi-
ously declined when ZrO2–Fe3O4 (ZAF-16/0), Al2O3–Fe3O4
(ZAF-0/16), ZrO2 and Al2O3 acted as catalysts in the esterifica-
tion (Table 3, entries 18–21), which verified the synergy effect
in the tri-component nanocomposites of ZrO2–Al2O3–Fe3O4
catalysts. Consequently, the original precipitated catalyst of
ZAF-16/16 was determined as the optimal catalyst for the next
catalytic reactions. Compared to some solid acid catalysts
that have been reported in the literature, the optimal catalyst
ZAF-16/16 revealed higher activity in a shorter reaction time
and at a lower temperature (Table 3, entry 6 vs. entries
22–27). We also carried out the reaction using prepared ZAF-
16/16 as the catalyst under the same reaction conditions of
literature studies and the results showed that the ZAF-16/16
was more active than the reported solid acid catalysts
(Table 3, entries 22–27, data in parentheses). According to
the literature, the esterification mechanism involved both
Lewis and Brønsted acid sites.48
Fig. 7 NH3-TPD profiles of catalysts (a) ZAF-16/16, (b) ZAF-16/0.
at the range of 100–300 °C, 300–400 °C and 400–700 °C,
which demonstrated that both of the two catalysts contained
weak, moderate and strong acid sites.44 The amounts of acid
sites on the catalysts and the peak temperature of the TPD
profiles are also listed in Table 2. The data showed that the
total amount of acid sites on ZAF-16/16 (2.77 mmol g−1) was
higher than that of ZAF-16/0 (1.61 mmol g−1). This phenome-
non could be interpreted as the acid strength of catalyst
ZAF-16/16 being much stronger, indicating that the addition
of alumina component led to the increase in catalyst acidity.
The thermal properties of the catalysts ZAF-16/16 and
ZAF-16/0 were determined by TG analyses and the results are
illustrated in Fig. 8. Generally, the weight loss of the catalyst
could be explained by the following reasons: the gradient that
appeared at a lower temperature below 200 °C was ascribed
to desorption of water adsorbed on the surface of catalysts,
whereas the gradient that emerged above 200 °C
corresponded to the release of crystal water and the chemical
Table 2 NH3-TPD data of the catalysts
NH3 adsorption (mmol g−1
100–300 °C 300–400 °C 400–700 °C Total
)
Entry Catalyst
1
2
ZAF-16/16 1.15
ZAF-16/0 0.16
0.28
0.32
1.34
1.13
2.77
1.61
Fig. 8 TG profiles of catalysts (a) ZAF-16/16, (b) ZAF-16/0.
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Table 3 Esterification of acetic acid and n-butyl alcohol catalyzed by a series of ZrO2–Al2O3–Fe3O4 nano-catalystsa
Entry
Catalyst
Conv.b (%)
Entry
Catalyst
Conv. (%)
1
2
3
4
5
6
7
8
No trace
21.2
32.5
75.9
84.4
90.0
86.2
27.7
51.1
40.7
26.2
80.4
68.9
45.0
15
16
17
18
19
20
21
ZAF-16/16 (700)
ZA-16/16
Fe3O4
ZAF-16/0
ZAF-0/16
ZrO2
39.2
85.1
2.4
22.5
17.1
20.2
14.8
ZAF-2/2
ZAF-4/4
ZAF-8/8
ZAF-12/12
ZAF-16/16
ZAF-20/20
ZAF-16/8
ZAF-16/12
ZAF-16/24
ZAF-16/32
ZAF-16/16 (400)
ZAF-16/16 (500)
ZAF-16/16 (600)
Al2O3
22c
23c
24d
25d
26e
27e
SO42−/ZrO2
SiO2–Al2O3
Al2O3
63 (91.4)f
34 (91.4)f
32.2 (90.4)f
62.6 (90.4)f
58 (88.5)f
86 (88.5)f
9
10
11
12
13
14
V2O5–Al2O3
ZrO2–WO3
SO42−/ZrO2–WO3
a
b
Reaction conditions: catalysts 0.50 g, acetic acid 0.15 mol, n-butyl alcohol 0.10 mol, cyclohexane 25 mL, reflux, 1.5 hours. Determined by
c
d
e
f
GC with FID detector, n-butyl acetate selectivity > 99%. See ref. 6. See ref. 47. See ref. 48. The numbers in parentheses represented the
results of control experiments that catalyzed by ZAF-16/16 under the identical reaction conditions in references.
Synthesis of bis-indolylmethanes
Brønsted acid sites on the catalysts.49–51 In this work, the
magnetic solid acid nano-catalyst ZAF-16/16 revealed an
excellent catalytic efficiency in the synthesis of BIMs. From
the results in Table 4, it could be seen that benzaldehyde
reacted smoothly with indole to produce BIMs in excellent
yield (98.4%) under refluxing in methanol, while the blank
experiment showed that the reaction could barely occur in
the absence of catalyst (Table 4, entries 2 vs. 1). In addition,
Bis-indolymethane derivatives have been reported to be iso-
lated from natural products, which display important biologi-
cal activity. Typical approaches involve the reaction of indole
with aldehydes under Lewis and protic acid catalytic systems,
and the plausible mechanism of BIMs synthesis revealed that
the substrate aldehydes could be activated by both Lewis and
Table 4 Synthesis of bis-indolylmethanes catalyzed by ZAF-16/16a
Entry
R
Yieldb (%)
Entry
R
Yield (%)
1c
2
Ph
Ph
Trace
98.4
85d
13
14
3,4-(CH3)2C6H3
2-ClC6H4
73.5
98.5
3e
4e
5e
6e
7
8
9
10
11
12
Ph
Ph
Ph
Ph
97.5
98.0
97.6
97.1
64.6
92.7
64.6
58.7
62.0
92.1
15
16
17
18
19
20
21
22
23
24f
3-ClC6H4
4-ClC6H4
83.0
91.5
84.9
59.0
53.4
97.4
98.1
88.9
93.4
51.4
2,4-Cl2C6H3
2-BrC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-HOC6H4
Ph–CHCH
C3H7
2-CH3OC6H4
3-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3
3-CH3C6H4
4-CH3C6H4
a
b
Reaction conditions: catalyst ZAF-16/16 0.20 g, aldehyde 1.25 mmol, indole 2.5 mmol, methanol 10 mL, reflux, 1.5 hours. Isolated yield.
In the absence of catalyst. d See ref. 21. e Recycled ZAF-16/16 was used. f Reaction time was 3 hours.
c
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aromatic aldehydes with electron-donating as well as
electron-withdrawing substituents also gave good yields
(Table 4, entries 7–23). However, under identical reaction
conditions, n-butyl aldehyde did not give any product until
the reaction time was doubled to 3 hours (Table 4, entry 24).
The reaction of benzaldehyde and indole was chosen as a
model to examine the recyclability of catalyst ZAF-16/16. The
recycling results showed that the magnetic solid acid nano-
catalyst ZAF-16/16 could retain almost its initial activity up to
five reaction cycles. Meanwhile, the loss of the nano-catalyst
during the separation process was negligible (the total loss
was about 1% in weight).
poor yield (8.5%). Based on the proposed mechanism of
Hantzsch reaction reported in the literature, the synthesis of
1,4-DHPs involved
cyclocondensation.55
a protocol of Lewis-acid catalyzed
Biginelli reaction
More than one century ago, the Italian chemist Pietro
Biginelli reported one-pot cyclocondensation reaction
a
between aldehydes, β-ketoesters and urea to generate 3,4-
dihydropyrimidinones under strongly acidic conditions. Since
then, the development of efficient and versatile catalytic sys-
tems for the Biginelli reaction has become an active ongoing
research area.35–37 To further extend the application scopes
of the as-prepared magnetic solid acid nano-catalysts, the
optimal catalyst ZAF-16/16 was also applied in the Biginelli
reaction. On the basis of the results in Table 6, the reaction
hardly proceeded in the absence of catalyst (Table 6, entry 1).
Furthermore, the solvents played an important role in the
synthesis of 3,4-DHPMs. Several classical solvents were cho-
sen as the reaction media for comparison (Table 6, entry 2).
It was found that the best result was obtained in ethylene gly-
col. The reaction was completed within 5 hours and the
expected product was isolated in 82.4% yield. A class of aro-
matic aldehydes were reacted with ethyl acetoacetate and
urea under the same conditions. In all cases, the aromatic
aldehydes with either electron-donating or electron-
withdrawing groups participated in the condensation reac-
tion readily. The nature and the position of substitution on
the aromatic ring did not have much effect on the reaction
(Table 6, entries 3–19). To our delight, the reaction also
proceeded smoothly when thiourea was used in place of urea
to afford the corresponding 3,4-dihydropyrimidinthiones in
moderate yields (Table 6, entries 20–35). The mechanism of
the Biginelli reaction showed that the Brønsted acid sites
on the solid acid catalysts played an important role in this
typical procedure.1
Hantzsch reaction
Multicomponent reactions (MCRs) are one of the most pow-
erful emerging synthetic tools for the creation of molecular
structure complexity and diversity.52,53 The Hantzsch reac-
tion, which affords 1,4-dihydropyridines as products, is one
of the earliest and best known MCRs. In recent decades, con-
siderable attention has been paid to the synthesis of 1,4-
DHPs owing to their pivotal pharmaceutical and biological
activities.54 We have introduced the catalyst ZAF-16/16 into
the Hantzsch reaction and the results are summarized in
Table 5. In all cases, the corresponding products were
obtained in the presence of a catalytic amount of ZAF-16/16.
Compared with the substituted aromatic aldehydes, the
unsubstituted benzaldehyde achieved the highest yield
(94.5%). Moreover, the aryl group substituted with different
groups and the same group located at different positions on
the aromatic ring did not present much effect on the forma-
tion of the final products and afforded the target products in
good yields (Table 5, entries 3–17). We also carried out the
reaction without any catalyst but the product was isolated in
Table 5 Hantzsch reaction catalyzed by ZAF-16/16a
Pechmann reaction
Coumarins are widely distributed in the families of rutaceae
and umbelliferae, and were obtained from these plants by vir-
tue of various extraction methods in earlier years. Chemically,
several protocols have been developed for the syntheses of
coumarins, including Pechmann, Perkin, Knoevenagel, Wit-
tig, Reformatsky and Claisen reactions.19,56–58 Among these,
the acid-catalyzed Pechmann reaction is simple and com-
monly used for synthesizing 7-hydroxyl-4-methyl coumarin
from ethyl acetoacetate and m-dihydroxybenzene. Accord-
ingly, the optimal catalyst ZAF-16/16 was applied in the
Pechmann reaction instead of the conventional liquid acid
catalyst. When toluene was used as a water-carrying agent, a
65.1% isolated yield of 7-hydroxyl-4-methyl coumarin was
Entry
R
Yieldb (%) Entry
R
Yield (%)
1c
2
3
4
5
6
7
8
9
Ph
Ph
8.5
10
11
12
13
14
15
16
17
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3 82.7
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-HOC6H4
78.3
77.3
94.5 95d
77.7
2-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3 83.3
3-CH3C6H4
4-CH3C6H4
3,4-(CH3)2C6H3
2-ClC6H4
73.6
77.7
53.8
80.3
65.8
83.8
85.4
60.0
75.5
Ph–CHCH 64.0
accomplished after
4 hours (Scheme 1). As previously
a
Reaction conditions: catalyst ZAF-16/16 0.05 g, aldehyde 5 mmol,
ethyl acetoacetate 10 mmol, ammonium acetate 10 mmol, ethanol
reported in the literature, the Pechmann reaction is catalyzed
by the Brønsted acid site of the catalyst. A possible mecha-
nism for the formation of 7-hydroxyl-4-methyl coumarin is
b
c
10 mL, reflux, 1.5 hours. Isolated yield. In the absence of catalyst.
d
See ref. 55.
76 | Catal. Sci. Technol., 2014, 4, 71–80
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Table 6 Biginelli reaction catalyzed by ZAF-16/16a
Entry
1c
R
X
Yieldb (%)
Entry
19
R
X
Yield (%)
81.6
Ph
O
Trace
82.4
80d
Ph–CHCH
O
11.9e
13.7f
8.2g
2
Ph
O
20
Ph
S
63.4
19.5h
25.4i
37.1j
35.5k
54.6
51.9
68.2
75.6
53.7
80.4
71.5
40.1
67.0
66.6
68.5
64.6
78.7
79.7
75.4
36.8
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2-CH3OC6H4
3-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3
3-CH3C6H4
4-CH3C6H4
3,4-(CH3)2C6H3
2-ClC6H4
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
2-CH3OC6H4
3-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3
3-CH3C6H4
4-CH3C6H4
3,4-(CH3)2C6H3
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
2-NO2C6H4
3-NO2C6H4
2,4-(NO2)2C6H3
Ph–CHCH
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
46.2
49.3
57.1
45.3
44.1
59.0
54.7
35.5
40.9
54.8
43.0
34.5
48.9
37.2
47.1
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
2-BrC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2,4-(NO2)2C6H3
a
Reaction conditions: catalyst ZAF-16/16 0.20 g, aldehyde 5 mmol, ethyl acetoacetate 5 mmol, urea or thiourea 7.5 mmol, ethylene glycol 10
b
c
d
e
f
g
mL, 140 °C, 5 hours. Isolated yield. In the absence of catalyst. See ref. 36. Methanol 10 mL, reflux. Ethanol 10 mL, reflux. Acetonitrile
h
i
j
10 mL, reflux. Tetrahydrofuran 10 mL, reflux. N,N-Dimethylformamide (DMF) 10 mL, 140 °C. N-Methyl-2-pyrrolidone (NMP) 10 mL, 140 °C.
k
Mixed solvents of dioxane 5.7 mL and i-propanol 4.3 mL, reflux.
found over the catalyst ZAF-16/16, which gave a 90.0% yield
of n-butyl acetate. In addition, the optimal catalyst ZAF-16/16
was also used to catalyze several organic reactions, such as
the synthesis of bis-indolylmethanes, Hantzsch reaction,
Biginelli reaction and Pechmann reaction, facilitating the
formation of diverse pharmacological and biological activities
Scheme 1 Synthesis of 7-hydroxyl-4-methyl coumarin.
heterocyclic compounds. In these organic reactions, the
target products were obtained in moderate to good yields.
Meanwhile, simple magnetic removal and recycling of
ZAF-16/16 is shown to proceed without obvious loss of either
catalyst and activity.
the chemisorption of the carbonyl group of ethyl acetoacetate
on the Brønsted acid site of the catalyst.59
Experimental section
Materials
Conclusions
In summary, we have designed and synthesized a series of
magnetic separable nanocomposites ZrO2–Al2O3–Fe3O4 that
are used as green solid acid catalysts in various organic reac-
tions. Both Lewis and Brønsted acid sites are present on the
ZAF catalysts. The catalytic activities of all the prepared cata-
lysts were evaluated via the esterification reaction between
acetic acid and n-butyl alcohol. The maximum activity was
All reagents were obtained from commercial sources and
used as received without further purification.
Preparation of magnetic Fe3O4 nanoparticles
The amine-functionalized magnetic nanoparticles were pre-
pared via the versatile solvothermal reaction reported by Li.40
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Preparation of magnetic solid acid catalysts
measured on a Linseis STA PT 1600 thermoanalyzer. The
analyses were carried out in N2 atmosphere from room
temperature to 800 °C with a heating rate of 10 °C min−1.
A series of magnetic solid acid nano-catalysts ZrO2–Al2O3–Fe3O4
were prepared via a simple co-precipitation method at room
temperature. The model catalyst was labelled as ZAF-16/16,
which means the feeding mole ratios of ZrOCl2·8H2O and
AlCl3·6H2O were 16 : 16. A typical procedure is described as
follows: Fe3O4 nanoparticles (1 mmol, 0.2315 g) were dis-
persed into deionized water (20 mL) with ultrasound for
30 min, then ZrOCl2·8H2O (16 mmol, 5.1562 g) and
AlCl3·6H2O (16 mmol, 3.8629 g) were dissolved in deionized
water (60 mL) to obtain a clear solution that was added into
the above system in one portion. After that, ammonia hydrox-
ide (NH3·H2O) was added dropwise with vigorous mechanical
stirring until the pH value of the solution reached 9 and
began to precipitate. After continuous stirring for 8 hours at
room temperature, the precipitate was filtered and washed
with deionized water until no chloride ions could be
detected. Finally, the precipitate was dried at 100 °C in a vac-
uum. To verify the effect of calcination temperature on the
catalytic performance of the magnetic solid acid nano-
catalysts, the model catalyst ZAF-16/16 was also calcined in a
muffle furnace for 3 hours at temperatures from 400 to
700 °C. These calcined catalysts were named as ZAF-16/16
(400–700) where the numbers in parentheses indicate the dif-
ferent calcination temperatures.
General procedure for the esterification
The reaction was performed in a three-neck flask equipped
with a condenser and water separator. A mixture of n-butanol
(0.10 mol, 9.2 mL), acetic acid (0.15 mol, 8.6 mL), and nano-
catalysts ZrO2–Al2O3–Fe3O4 (0.50 g) was heated at reflux in
cyclohexane (25 mL) for 1.5 hours. After completion of the
reaction (no water-drops appeared in the water separator),
the catalysts could be recovered by an external magnet. The
reaction mixture was analyzed by GC to give the conversion
of substrate n-butanol and the selectivity of target product
n-butyl acetate.
General procedure for the synthesis of bis-indolylmethanes
A mixture of aldehyde (1.25 mmol), indole (2.5 mmol,
0.2929 g) and nano-catalyst ZAF-16/16 (0.20 g) was heated at
reflux in methanol (10 mL) for the appropriate time. After
completion of the reaction (monitored by TLC), the mixture
was cooled to room temperature. The nano-catalyst ZAF-16/16
could be separated by an external magnet. Then the reaction
mixture was poured into ice water (20 mL). The resulting
solid precipitate was filtered and recrystallized from metha-
nol and water to afford pure products. To examine the reus-
ability of the catalyst, the used catalyst ZAF-16/16 was washed
with acetone and dried at 80 °C for the next cycle.
Catalysts characterization
ICP-AES was performed on an IRIS Advantage ER/S instru-
ment (American TJA Company) for determining the composi-
tion of the catalysts. The specific surface areas of the
obtained catalysts were determined on a ChemiSorb 2750
apparatus by N2 adsorption at 77 K. Powder X-ray diffraction
(XRD) patterns were recorded on X'Pert PRO (Holland
PANalytical Company), in the range of 2° ≤ 2θ ≤ 90° at a
scanning rate of 8° min−1, using Cu Kα radiation (λ = 1.5406 Å).
TEM and HRTEM images were collected on a field emission
transmission electron microscope (Tecnai-G2-F30). Magnetic
hysteresis loops were conducted on a vibrating sample mag-
netometer (Lake Shore 7304) at room temperature. FT-IR
spectra were recorded on a Nicolet Fourier-transform infrared
spectrometer (NEXUS 670) in the range of 400–4000 cm−1
with a resolution of 4 cm−1. The pretreatment of catalyst that
was adsorbed with pyridine is described as follows: the cata-
lyst sheet was evacuated at 300 °C for 2 hours under a vac-
uum of 10−2 Pa, then cooled to room temperature. After
pyridine adsorption for 30 min and evacuation at 200 °C for
1 hour, the IR spectrum was recorded. NH3-TPD measure-
ments were carried out on a TP-5080 instrument. The sample
(100 mg) was swept by an Ar flow (20 mL min−1) at 450 °C for
1 hour and then exposed to NH3 at room temperature for
1 hour. After adsorption of NH3 on the sample, the carrier
gas Ar (20 mL min−1) was allowed to flow over the sample at
120 °C. Once a stable baseline of NH3 was obtained, the
sample was heated from room temperature to 850 °C at a
rate of 20 °C min−1. Thermal gravimetric (TG) analyses were
General procedure for the Hantzsch reaction
A mixture of aldehyde (5 mmol), ethyl acetoacetate (10 mmol,
1.26 mL), ammonium acetate (10 mmol, 0.7708 g) and nano-
catalyst ZAF-16/16 (0.05 g) was heated at reflux in ethanol
(10 mL) for the appropriate time. After completion of the
reaction (monitored by TLC), the mixture was cooled to room
temperature. The nano-catalyst ZAF-16/16 could be recovered
by an external magnet. The solvent was evaporated under
reduced pressure to yield the crude product, which was then
purified by recrystallization from ethanol and water to
provide the pure product.
General procedure for the Biginelli reaction
A mixture of aldehyde (5 mmol), ethyl acetoacetate (5 mmol,
0.63 mL), urea (7.5 mmol, 0.4505 g) or thiourea (7.5 mmol,
0.5709 g) and nano-catalyst ZAF-16/16 (0.20 g) was heated at
140 °C in ethylene glycol (10 mL) for the appropriate time.
After completion of the reaction (monitored by TLC), the
mixture was cooled to room temperature. The nano-catalyst
ZAF-16/16 could be removed by an external magnet. Then
the reaction mixture was poured into ice water (20 mL). The
resulting solid precipitate was filtered and recrystallized from
ethanol and water to give pure products.
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General procedure for the Pechmann reaction
20 R. Fazaeli, S. Tangestaninejad, H. Aliyan and M. Moghadam,
Appl. Catal., A, 2006, 309, 44–51.
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The reaction was performed in a three-neck flask equipped
with
a condenser and water separator. A mixture of
m-dihydroxybenzene (5 mmol, 0.5506 g), ethyl acetoacetate
(5 mmol, 0.63 mL) and nano-catalyst ZAF-16/16 (1.00 g) was
heated at reflux in toluene (25 mL). After completion of the
reaction (no water-drops appeared in the water separator),
the mixture was cooled to room temperature, and hot metha-
nol (40 mL) was added to dissolve all the products. The
nano-catalyst ZAF-16/16 could be separated by an external
magnet. Subsequently, the solvent was evaporated under
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