A heteropolyacid-based ionic liquid immobilized onto magnetic fibrous nano-silica as robust and recyclable heterogeneous catalysts for the synthesis of tetrahydrodipyrazolopyridines in water

Article abstract of DOI:10.1039/c6ra15766a

The application of a heteropolyacid containing an ionic liquid based organosilica (Fe₃O₄/KCC-1/IL/HPW) catalyst for the synthesis of tetrahydrodipyrazolopyridines is demonstrated. Because of the amplification effect of the IL, high l

Full text of DOI:10.1039/c6ra15766a

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A heteropolyacid-based ionic liquid immobilized
onto magnetic fibrous nano-silica as robust and
recyclable heterogeneous catalysts for the
synthesis of tetrahydrodipyrazolopyridines in
water†
Cite this: RSC Adv., 2016, 6, 75973
Seyed Mohsen Sadeghzadeh
The application of a heteropolyacid containing an ionic liquid based organosilica (Fe3O4/KCC-1/IL/HPW)
catalyst for the synthesis of tetrahydrodipyrazolopyridines is demonstrated. Because of the amplification
effect of the IL, high loading capacities of the heteropolyacid were achieved. The catalyst system could
be successfully recovered and reused several times without any significant decrease in activity and
selectivity. The synthesized Fe3O4/KCC-1/IL/HPW nanocatalyst exhibited excellent catalytic activity in
multicomponent reactions under mild conditions due to the easy accessibility of the active sites.
Received 17th June 2016
Accepted 27th July 2016
DOI: 10.1039/c6ra15766a
www.rsc.org/advances
a recyclable strong ionic liquid in organic reactions is oen
considered to follow the principles of green chemistry, i.e.,
Introduction
these catalyzed processes consume a minimum amount of
energy and reagents or auxiliaries and minimize waste. There-
fore, in order to reduce these problems, a supported IL catalyst
as a novel solid catalyst combining the advantageous charac-
teristics of ILs has been designed for catalyzed reactions. In
recent years, the use of solid ionic liquid catalysts has offered
important advantages in organic synthesis, for example, oper-
ational simplicity, environmental compatibility, non-toxicity,
reusability, low cost, and ease of isolation. In this regard,
a solid ionic liquid, a product that is easily synthesized from
ionic liquids on ordered and non-ordered silica gel, has shown
immense potential as an efficient and easily retrievable solid
support/catalyst in various important organic syntheses.3–7
Mesoporous poly(ionic liquid)s (MPILs) simultaneous combine
the features of mesoporous materials, polymers and ionic
liquids (ILs), providing numerous new functionalities that can
be applied in the elds of adsorption, separation, and catalysis.
The practical performances of MPILs are closely related to their
pore structures, which motivates the development of various
pore formation strategies.8–11 Mesoporous silica materials are
known as good supports for uorescence probes, which is due
to their unique characteristics such as excellent solvent dis-
persibility, good optical transparency in the visible region,
favorable biocompatibility, large surface area and open pore
structure, and abundant functionalization sites in the silica
network.12–14 Some silica-based mesoporous materials, such as
SBA-15, MCM-41, MCM-48, and HMS, have been reported as
inorganic carriers of chemosensors.15–21 However, most of these
optical nanoprobes have some limitations, which include the
requirement of using organic or aqueous–organic solvent
Ionic liquids are essential and efficient catalysts for the
production of industrially important chemicals. Millions of
tons of ionic liquids are annually consumed as catalysts, which
require costly and inefficient separation of the catalysts from
homogeneous reaction mixtures. Moreover, ionic liquids have
received considerable interest as eco-friendly solvents, catalysts
and reagents in organic synthesis because of their unique
properties such as low volatility, non-ammability, high
thermal stability, negligible vapor pressure and ability to
dissolve a wide range of materials.1,2 Though ILs possess
promising advantages, their widespread practical application
are still prevented by several disadvantages such as high
viscosity, which results in ILs taking only a minor part in the
catalyzed reactions for chemical production; homogeneous
reactions are difficult to conduct due to the separation and
reuse procedures, which consequently result in high cost due to
the use of relatively large amounts of ILs as opposed to
economic criteria. To address these disadvantages, supported
IL materials have become more interesting and have found
desirable applications as solid organocatalysts. This class of
advanced materials possesses the properties of ILs and behaves
as bulk ILs. The supported ionic liquid has a better performance
in numerous elds with the merits of both a homogeneous
ionic liquid and heterogeneous solid material. The use of
Department of Chemistry, College of Sciences, Sina Masihabadi Student Research, P.
O. Box 97175-615, Neishabour, Iran. E-mail: seyedmohsen.sadeghzadeh@gmail.
com; Fax: +98 561 2502065; Tel: +98 561 2502065
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra15766a
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FTIR spectra were obtained on a VERTEX 70 spectrometer
(Bruker) in the transmission mode in spectroscopic grade KBr
pellets for all the powders. The particle size and structure of the
nanoparticles were observed using a Philips CM10 transmission
electron microscope operating at 100 kV. Powder X-ray diffrac-
tion data were obtained using a Bruker D8 Advance model with
Cu ka radiation. Thermogravimetric analysis (TGA) was carried
Scheme 1 Synthesis of tetrahydrodipyrazolopyridines in the presence
of Fe3O4/KCC-1/IL/HPW MNPs.
À1
ꢀ
out on a NETZSCH STA449F3 at a heating rate of 10 C min
under nitrogen. 1H and 13C NMR spectra were observed on
a BRUKER DRX-300 AVANCE spectrometer at 300.13 and 75.46
MHz, BRUKER DRX-400 AVANCE spectrometer at 400.22 and
100.63 MHz, respectively. Elemental analyses for C, H, and N
were performed using a Heraeus CHN–O-Rapid analyzer. The
purity determination of the products and reaction monitoring
were accomplished by TLC on silica gel polygram SILG/UV 254
plates. Mass spectra were acquired on a Shimadzu GCMS-
QP5050 Mass Spectrometer.
mixtures, poor performance for removal of metal ions, and poor
accessibility of analytes to sensing sites inside the pores.
Recently, Vivek Polshettiwar reported the synthesis of a new
brous silica nanosphere (KCC-1) with a high surface area, large
open pore structure, and high thermal and hydrothermal
stabilities.22 KCC-1 has a unique brous morphology, and the
high surface area is attributed to its brous morphology and not
to pores, which can be valuable in the design of silica-supported
catalysts, hydrogen storage, drug delivery, as a chromatography
support, and in versatile composite materials.23–27
General procedure for the preparation of Fe3O4 nanoparticles
The synthesis procedure is illustrated as follows: (1) 0.01 mol
FeCl2$4H2O and 0.03 mol FeCl3$6H2O were dissolved in 200 mL
of distilled water, followed by the addition of polyethylene
glycol (PEG) (1.0 g, MW 6000). (2) Sodium hydroxide (NaOH)
was added to the solution and the pH value was controlled in
the range 12 # pH # 13. (3) Different amounts of hydrazine
hydrate (N2H4$H2O, 80% concentration) were added to the
abovementioned suspension. The reaction was continued for
about 24 h at room temperature. During this period, the pH
value was adjusted by NaOH and kept in the range 12 # pH #
13. The black Fe3O4 NPs were then rinsed several times with
deionized water.
Pyrazoles exist in some compounds that are used as phar-
maceuticals and agrochemicals. A number of pyrazole con-
taining compounds such as Celebrex, Viagra and Acomplia have
been successfully commercialized.28,29 Pyrazoles have also
found applications in the agrochemical industry as ultraviolet
stabilizers and energetic materials and in the eld of photo-
protectors.30–33 Numerous methods have been employed for the
synthesis of pyrazole derivatives, e.g., the use of microwave
irradiation,34,35 ionic liquids,36 TMSCl–NaI,37 metal triates,38,39
molecular iodine,40,41 SiO2–NaHSO4,42 SiO2–HClO4,43 ceric
ammonium nitrate,44 phenylboronic acid,45 PTSA–SDS,46 and
organocatalysts.47
In our previous research, we prepared
a novel IL-
functionalized ordered mesobers organosilica (KCC-1/IL)
material using ionic liquid and tetramethoxysilane as silica
precursors. The KCC-1/IL material was then used as an efficient
support for the immobilization of heteropolyacid (KCC-1/IL/
HPW) and as a catalyst.48 However, isolation and recovery of
these tiny nanocatalysts from the reaction mixture is not easy.
Conventional techniques (such as ltration) are not efficient
because of the nano size of the catalyst particles. This limitation
hampers the economics and sustainability of this nanocatalyst.
To overcome this issue, the use of magnetic nanoparticles has
emerged as a viable solution; their insoluble and paramagnetic
nature enables easy and efficient separation of the catalysts from
the reaction mixture with an external magnet. In continuation of
our studies in this eld, we reported the use of Fe3O4/KCC-1/IL/
HPW nanocatalysts as an efficient catalyst for the synthesis of
tetrahydrodipyrazolopyridine derivatives (Scheme 1).
General procedure for the preparation of Fe3O4/KCC-1 MNPs
The Fe3O4/KCC-1 core–shell microspheres were synthesized
according to the previously reported method.49 0.02 mol of
Fe3O4 MNPs was dispersed in a mixture of 80 mL of ethanol, 20
mL of deionized water and 2.0 mL of a 28 wt% concentrated
ammonia aqueous solution (NH3$H2O), followed by the addi-
tion of 0.20 g of tetraethyl orthosilicate (TEOS). Aer vigorous
stirring for 24 h, the nal suspension was repeatedly washed,
ltered several times and dried at 60 ꢀC in air. Fe3O4/SiO2 (0.25
g) was dispersed in an aqueous solution (30 mL) containing
urea (0.3 g) to form solution A under ultrasonication for 1 h.
Cetylpyridinium bromide (CPB) (0.5 g) was added to 0.75 mL of
n-pentanol and 30 mL cyclohexane to form solution B. Solution
A was added to solution B under stirring at room temperature.
Then, 1.25 g TEOS was added dropwise to the abovementioned
solution. The resulting mixture was continually stirred for 1 h at
room temperature and then maintained at 120 ꢀC for 5 h, thus
inciting the reaction. Aer the reaction was completed, the
mixture was allowed to cool to room temperature, and the
Fe3O4/KCC-1 core–shell microspheres were isolated by strong
Experimental
Materials and methods
Chemical materials were purchased from Fluka and Merck in magnetic suction, then washed with deionized water and
high purity. Melting points were determined in open capillaries acetone, and dried overnight in a drying oven at 40 ꢀC. This
ꢀ
using an Electrothermal 9100 apparatus and are uncorrected. material was then calcined at 550 C for 5 h in air.
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General procedure for the preparation of Fe3O4/KCC-1/3-
chloropropylsilane MNPs
Fe3O4/KCC-1 NPs (2 mmol) and THF (20 mL) were mixed
together in a beaker, and then NaH (20 mmol) was dispersed
into the mixture by ultrasonication. 3-Chloropropyltriethox-
ysilane (22 mmol) was added dropwise at room temperature and
stirred for another 16 h at 60 ꢀC. The resultant product was
collected and washed with ethanol and deionized water, and
ꢀ
then dried under vacuum at 60 C for 2 h for further use.
General procedure for the preparation of Fe3O4/KCC-1/IL/
HPW MNPs
Fig. 1 TEM image of the fresh Fe3O4/KCC-1/IL/HPW MNPs (a) and
Fe3O4/KCC-1/IL/HPW MNPs after ten reuses (b).
First, 1-methylimidazole (100 mmol) and Fe3O4/KCC-1/3-
chloropropyltriethoxysilane (5 mmol) were dissolved in dry
ethanol (50 mL) under stirring. The resulting mixture was
reuxed for 24 h under nitrogen protection. Aer removal of
ethanol in vacuum, the solid residue was dissolved in water. The
obtained solution was concentrated under vacuum and then
extracted with ethanol–tetrahydrofuran. Subsequently, ion
exchange with H3PW12O40 (110 mmol) in ethanol/water was
performed for 72 h at ambient temperature. Aer the solvent
was removed, the resulting mixture was ꢀltered, aer which the
ltrate was dried under vacuum at 100 C.48
that KCC-1 could be easily functionalized with 3-chloropropyl-
triethoxysilane to form Fe3O4/KCC-1/3-chloropropylsilane
MNPs. Then,
a magnetic brous nano-silica supported
heteropolyacid-based ionic liquid (Fe3O4/KCC-1/IL/HPW) was
realized.
The size and structure of the Fe3O4/KCC-1/IL/HPW MNPs
were evaluated using transmission electron microscopy (TEM)
(Fig. 1). The average size of the Fe3O4 MNPs is about 30–40 nm.
Uniform and monodisperse Fe3O4/KCC-1/IL/HPW materials
with radial-like channels were synthesized successfully. The
length of the silica bres coming out of the centre of the Fe3O4/
KCC-1/IL/HPW and distributed in all directions was estimated
to be 220–250 nm (Fig. 1a). Comparison of TEM images of the
used catalyst (Fig. 1b) with those of the fresh catalyst (Fig. 1a)
showed that the morphology and structure of Fe3O4/KCC-1/IL/
HPW MNPs remained intact aer ten recoveries. Very low
agglomeration of Fe3O4/KCC-1/IL/HPW MNPs can be observed.
The FT-IR spectra of KCC-1 and Fe3O4/KCC-1/IL/HPW are
presented in Fig. 2. For KCC-1, the broad absorption bands at
1089 cmÀ1 and 3654 cmÀ1 are attributed to Si–O–Si unsym-
metrical stretching and OH, respectively. The two peaks at 799
cmÀ1 and 467 cmÀ1 are from the Si–O–Si symmetrical stretching
and bending, respectively (Fig. 2a). Compared to the spectrum
of KCC-1, three new peaks at approximately 1642, 3024, and
3219 cmÀ1 appeared in the spectrum of Fe3O4/KCC-1/IL/HPW,
corresponding to the ring vibration of imidazole and stretch-
ing vibrations of the saturated and unsaturated C–H bonds on
the imidazole ring, respectively (Fig. 2b). These results indi-
cated that the imidazolium IL had been successfully introduced
onto the sÀurface of KCC-1. The characteristic IR bands of
H2PW12O40 at 963, 657, 590, and 467 cmÀ1 were clearly
observed in the IR spectrum of the as-prepared Fe3O4/KCC-1/IL/
HPW MNPs catalyst (Fig. 2b). These facts are consistent with the
General procedure for the preparation of tetrahydrodipyrazolo
pyridine
A 50 mL conical ask was charged with a mixture of hydrazine
hydrate (2.0 mmol), ethyl acetoacetate (2.0 mmol), and Fe3O4/
KCC-1/IL/HPW MNPs (0.1 mg) in H2O (15 mL). The mixture was
stirred for 2 min at room temperature followed by the addition
of aldehyde (1.0 mmol) and ammonium acetate (3.0 mmol). The
reaction mixture was stirred at room temperature for 30 min.
Aer completion of the reaction and monitored by TLC, the
catalyst Fe3O4/KCC-1/IL/HPW MNPs were separated by an
external magnet. The precipitate was washed with EtOH to
afford the pure product and then dried well under vacuum
pump.
Results and discussion
The synthesis of Fe3O4/KCC-1/IL/HPW nanocatalysts involved
several steps (Scheme 2). The bers of the magnetic KCC-1 have
numerous Si–OH groups on the surface; thus, it was expected
À
synthesis design and conrm that the H2PW12O40 units are
highly dispersed or were taken up on the net cross-linking
chitosan in the single molecule form.
The powder X-ray diffraction patterns of KCC-1, Fe3O4/KCC-
1, and Fe3O4/KCC-1/IL/HPW are shown in Fig. 3. As can be
observed, all samples possess the typical diffraction peaks at
(220), (311), (400), (422), (511) and (440), which are in good
agreement with the data for a standard Fe3O4 sample, as
Scheme 2 Schematic for the synthesis of Fe3O4/KCC-1/IL/HPW.
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Fig. 4 TGA diagram of Fe3O4/KCC-1/IL/HPW NPs.
encapsulated brous nano-silica, ionic liquid, heteropolyacid,
and obtain information on their thermal stability. As seen in
Fig. 4, three weight loss stages were observed in ow air. About
2.0 wt% weight loss was observed in the rst stage (40–250 ꢀC)
corresponding to the loss of small molecules such as physically
absorbed water. In the second stage (250–550 ꢀC), the weight
loss is about 10.5 wt% and can be attributed to the pyrolysis of
cross-linking organic group derivatives. The weight loss in the
third stage (550–610 ꢀC) is about 14.0 wt%, which should be
assigned to the further decomposition of chitosan residues and
the release of H2O from the thermal decomposition of HPW or
its relevant ammonium salts formed by the electrostatic inter-
action between the amino group cations in chitosan and
Fig. 2 FTIR spectra of Fe3O4/KCC-1 NPs (a) and Fe3O4/KCC-1/IL/HPW
NPs (b).
À
H2PW12O40 anions.
The magnetic properties of the nanoparticles were charac-
terized using a vibrating sample magnetometer (VSM). The
magnetization curves of the obtained nanocomposite, regis-
tered at 300 K, showed that nearly no residual magnetism was
detected (Fig. 5), which means that the nanocomposite exhibi-
ted paramagnetic characteristics. Magnetic measurements
show that pure Fe3O4 and Fe3O4/KCC-1/IL/HPW have saturation
magnetization values of 55.4 and 23.1 emu gÀ1, respectively.
These nanocomposites with paramagnetic characteristics and
high magnetization values can quickly respond to the external
Fig. 3 XRD analysis of (a) Fe3O4, (b) Fe3O4/KCC-1, and (c) Fe3O4/KCC-
1/IL/HPW MNPs.
reported in the JCPDS card (no. 19-0629) (Fig. 3a). In addition to
the peaks of iron oxide, the XRD pattern of Fe3O4/SiO2/KCC-1
core–shell nanoparticles presented a broad featureless XRD
peak at low diffraction angles, which corresponded to the
amorphous silica (Fig. 3b). Fig. 3c shows a typical XRD pattern
for the Fe3O4/KCC-1/IL/HPW MNPs. There was no change in it.
Furthermore, the diffraction peaks ascribed to crystalline
tungstophosphoric acid were observed in the XRD pattern of the
as-prepared Fe3O4/KCC-1/IL/HPW MNPs. By contrast with the
XRD pattern of Fe3O4/KCC-1 MNPs (Fig. 3b), it was found that
an envelope peak centered at 20.4ꢀ in the XRD pattern of Fe3O4/
KCC-1/IL/HPW MNPs (Fig. 3c) was the peculiar diffraction peak
of the amorphous chitosan.
TGA experiments were carried out by heating the samples
under air up to 800 ꢀC in order to check the amount of
Fig. 5 Room-temperature magnetization curves of the nano catalysis.
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Table 1 The effect of heteropoly acid on the synthesis of tetrahy- Table 2 The effect of solvent and temperature for synthesis of tet-
drodipyrazolo pyridinea
rahydrodipyrazolo pyridinea
Entry
Heteropoly acid
Yielda,b (%) Entry
Solvent
Temp. (ꢀC)
Yieldb (%)
1
2
3
H3PW12O40
H3SiW12O40
H3PMo12O40
96
87
81
1
2
3
4
5
6
7
8
EtOH
H2O
H2O
H2O
r.t.
r.t.
60
61
96
96
96
96
33
24
29
45
22
25
16
10
16
9
80
a
Reaction conditions: hydrazine hydrate (2.0 mmol), ethyl acetoacetate
(2.0 mmol), benzaldehyde (1.0 mmol) and ammonium acetate (3.0
H2O
CH3CN
THF
CH2Cl2
EtOAc
DMF
Toluene
n-Hexane
Benzene
CCl4
Cyclohexane
CHCl3
DMSO
MeOH
Dioxane
i-PrOH
Solvent-free
100
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
b
mmol), water (3 mL), catalyst (0.5 mg), heating under reux, 1 h. GC
yields [%].
9
10
11
12
13
magnetic eld and quickly redisperse once the external
magnetic eld is removed. These results reveal that the nano-
composites exhibit a good magnetic response, which suggests 14
15
16
17
18
potential applications for targeting and separation.
40
34
63
20
53
20
Preliminary investigations involved screening for three
different heteropoly acids in the catalyst structure, namely,
tungstophosphoric acid (H3PW12O40), silicotungstic acid
(H3SiW12O40) and molybdophosphoric acid (H3PMo12O40), for 20
the synthesis of tetrahydrodipyrazolo pyridine. The experiments
19
21
a
were carried out at room temperature. Analysis of the reaction
Reaction conditions: hydrazine hydrate (2.0 mmol), ethyl acetoacetate
(2.0 mmol), benzaldehyde (1.0 mmol) and ammonium acetate (3.0
mixture on TLC showed complete conversion of the starting
material. According to the results, we chose H3PW12O40 for the
synthesis of tetrahydrodipyrazolo pyridine (Table 1).
b
mmol), catalyst (0.1 mg), 30 min. GC yields [%].
We examined the effect of solvent on the synthesis of tetra-
hydrodipyrazolo pyridine using the Fe3O4/KCC-1/IL/HPW MNPs
by heating under reux (Table 2). The solvent does affect the
performance of the catalyst. n-Hexane, benzene, CCl4, and
cyclohexane, which are non-polar solvents, gave tetrahy-
drodipyrazolo pyridine in a lower yield than that obtained
under solvent-free conditions (Table 2, entry 12–15). CH3CN,
THF, CH2Cl2, DMF, toluene, dioxane, CHCl3, EtOAc, and DMSO,
all aprotic polar solvents, also gave tetrahydrodipyrazolo pyri-
dine in low yields. The reaction did better in protic solvents. i-
PrOH and ethanol gave tetrahydrodipyrazolo pyridine in
average yields (Table 2, entries 1 and 20). In contrast, the use of
methanol resulted in an increased yield of 70%, whereas the
yield was remarkably increased up to 96% when H2O was used
as the solvent in the presence of Fe3O4/KCC-1/IL/HPW MNPs. In
this study, it was found that water was more efficient (Table 2,
entry 2) over other organic solvents. A solvent that stabilizes one
of the two competing transition states and controls the selec-
tivity should enhance the selectivity of the product obtained via
the stabilized transition state. For example, in multicomponent
reactions, higher reaction rates and selectivities are oen ob-
tained in polar solvents compared to non-polar solvents, which
has been attributed to enhanced hydrogen bonding between the
solvent and the transition state, as well as enforced hydro-
phobic interactions when conducted in water, which facilitates
alignment of the substrates.50 The ability to use water as the
reaction medium greatly increases the green credentials of the
method. We also investigated the crucial role of temperature in
temperature. The best temperature for this reaction was at room
temperature. Temperatures greater than room temperature do
not cause changes in the efficiency of the reaction (Table 2,
entry 2–5).
Then, the amount of catalyst necessary to promote the
reaction efficiently was examined. It was observed that the
variation in the Fe3O4/KCC-1/IL/HPW MNP amount had an
effective inuence. The best amount of Fe3O4/KCC-1/IL/HPW
MNP was 0.1 mg, which afforded the desired product in 96%
yields (Fig. 6). Under the optimal conditions, the reaction
Fig.
6 Optimization of the conditions for synthesis of tetrahy-
the synthesis of tetrahydrodipyrazolo pyridine in the presence
of Fe3O4/KCC-1/IL/HPW MNPs as the catalyst. Results clearly
indicated that the catalytic activity is not sensitive to reaction
drodipyrazolo pyridines: hydrazine hydrate (2.0 mmol), ethyl acetoa-
cetate (2.0 mmol), benzaldehyde (1.0 mmol) and ammonium acetate
(3.0 mmol), water (3 mL), at room temperature, 1 h.
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Table 4 The loading amount of HPW in Fe3O4/KCC-1/IL/HPW and
Fe3O4/SiO2/IL/HPW
Entry
Catalyst
wt%
1
2
3
4
Fe3O4/SiO2/IL/HPW
Fe3O4/KCC-1/IL/HPW
Fe3O4/SiO2/IL/HPW aer ten reuses
Fe3O4/KCC-1/IL/HPW aer ten reuses
3.1
6.9
1.7
6.8
catalyst dramatically, mimicking homogeneous catalysts.
Moreover, the activity and selectivity of the nano-catalyst can be
manipulated by tailoring the chemical and physical properties
such as size, shape, composition and morphology. As a result,
Fe3O4/KCC-1/IL/HPW was used in the subsequent investiga-
tions because of its high reactivity, high selectivity and easy
separation.
Fig. 7 Effect of time on yield of tetrahydrodipyrazolo pyridines:
hydrazine hydrate (2.0 mmol), ethyl acetoacetate (2.0 mmol), benz-
aldehyde (1.0 mmol) and ammonium acetate (3.0 mmol), catalyst (0.1
mg), water (3 mL), at room temperature.
To assess the exact impact of the presence of KCC-1 in the
catalyst, Fe3O4/KCC-1/IL/HPW was compared with Fe3O4/SiO2/
IL/HPW. The loading amount of HPW in Fe3O4/KCC-1/IL/HPW
and Fe3O4/SiO2/IL/HPW were determined by inductively
coupled plasma mass spectrometry (ICP-MS). The amount of
HPW in Fe3O4/KCC-1/IL/HPW was more than double that of the
Fe3O4/SiO2/IL/HPW. It is interesting that the amount of HPW
aer reuse of the catalyst for ten consecutive cycles was more
than quadruple in the Fe3O4/KCC-1/IL/HPW compared to the
Fe3O4/SiO2/IL/HPW. This remarkable ability of the Fe3O4/KCC-
1/IL/HPW mesostructure may be attributed to KCC-1 units
that effectively manage the reaction through preventing HPW
agglomeration and releasing and recapturing HPW during the
reaction process (Table 4).
We compared the catalytic performance of our catalyst with
literature reported catalysts for synthesis of tetrahydrodipyr-
azolo pyridine (Table S1†). Table S1† clearly demonstrates that
the highest efficiency for the synthesis of tetrahydrodipyrazolo
pyridine was found using Fe3O4/KCC-1/IL/HPW MNPs, whereas
an appropriate, highly perfect performance of the present
catalyst was observed for this reaction. Table S1† clearly
demonstrates that lower temperature, minimum catalyst
amount, shorter reaction time and the use of water as a solvent,
i.e., the requirements for the green synthesis of tetrahy-
drodipyrazolo pyridine, were met using our catalyst, whereas an
appropriate, highly perfect performance of the present catalyst
was observed for this reaction.
progress in the presence of 0.1 mg of Fe3O4/KCC-1/IL/HPW
MNPs was monitored by GC. Using this catalyst system, excel-
lent yields of tetrahydrodipyrazolo pyridine can be achieved in
30 min (Fig. 7). No apparent by-products were observed by GC in
all the experiments and tetrahydrodipyrazolo pyridine was ob-
tained in a 96% yield.
To further evaluate the efficiency of the catalyst, different
control experiments were performed and the obtained data are
shown in Table 3. Initially, a standard reaction was carried out
using Fe3O4 and Fe3O4/KCC-1; no product formation was
observed aer a reaction time of 1 h. The result of this study
showed that the desired product was not formed in any amount
(Table 3, entries 1 and 2). When Fe3O4/KCC-1/IL was used as the
catalyst, a reaction was observed, although the yield of the
desired product was average (Table 3, entries 3). The ILs could
not give satisfactory catalytic activity under mild reactions.
Based on these results, we continued the research to improve
the yield of the product by adding HPW to the catalyst. Notably,
there was not much difference in the reaction yields when the
reaction was carried out using Fe3O4/KCC-1/IL/HPW and IL/
HPW catalyst (Table 3, entries 4 and 5). The nano-sized parti-
cles increased the exposed surface area of the active site of the
catalyst, thereby enhancing the contact between reactants and
Aer optimization of the reaction conditions, to delineate
this approach, particularly in regard to library construction, this
methodology was evaluated using hydrazine hydrate, ethyl
acetoacetate, and ammonium acetate, and a variety of different
substituted aldehydes in the presence of Fe3O4/KCC-1/IL/HPW
MNPs under similar conditions. As can be seen from Table 5,
electronic effects and the nature of substituents on the aromatic
ring did not show strongly obvious effects in terms of yields
under the reaction conditions. Aromatic aldehydes containing
electron-withdrawing groups or electron-donating were
employed and reacted well to afford the desired products in
excellent yields with high purity.
Table 3 Influence of different catalysts for the synthesis of tetrahy-
drodipyrazolo pyridinea
Entry
Catalyst
Yieldb (%)
1
2
3
4
5
Fe3O4
—
—
58
96
96
Fe3O4/KCC-1
Fe3O4/KCC-1/IL
Fe3O4/KCC-1/IL/HPW
IL/HPW
a
Reaction conditions: hydrazine hydrate (2.0 mmol), ethyl acetoacetate
(2.0 mmol), benzaldehyde (1.0 mmol) and ammonium acetate (3.0
b
mmol), water (3 mL), at room temperature, 30 min. Isolated yield.
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Table 5 Synthesis of tetrahydrodipyrazolo pyridines in the presence of
Conclusions
the Fe3O4/KCC-1/IL/HPW catalyst in watera
In summary, the design and preparation of a novel HPW con-
taining an IL-based ordered mesobers magnetic organosilica
Entry
R
Yieldb (%)
MP (ꢀC)
1
2
3
4
5
6
7
8
9
H
Cl
F
NO2
MeO
Me
HO
NC
Me2N
96
95
97
98
92
93
90
95
91
237–239 (ref. 51) (Fe3O4/KCC-1/IL/HPW) and its catalytic application for the
251–253 (ref. 52)
synthesis of tetrahydrodipyrazolo pyridines have been
described. The catalyst could be recovered and reused at least
ten times with no decrease in its activity and selectivity. Based
on these results, we conclude that although the Fe3O4/KCC-1/IL
258–260 (ref. 51)
>300 (ref. 51)
181–183 (ref. 51)
245–247 (ref. 52)
269–271 (ref. 51) nanostructure acts as cobweb for the soluble HPW species, it
287–240 (ref. 51)
238–240 (ref. 51)
can also operate as a nanoscaffold to retake the HPW into the
mesobers, thereby avoiding wide agglomeration of the HPW.
a
Reaction conditions: hydrazine hydrate (2.0 mmol), ethyl acetoacetate This superior effectiveness of the Fe3O4/KCC-1/IL/HPW nano-
(2.0 mmol), aldehydes (1.0 mmol) and ammonium acetate (3.0 mmol),
catalyst may be ascribed to the isolated IL units incorporated in
the mesobers, which could control the reaction mechanism by
catalyst (0.1 mg), water (15 mL), at room temperature, 30 min.
b
Isolated yields (%).
preventing the formation of agglomerated HPW as well as
stabilizing the active catalytic HPW species.
The recovery and reuse of a catalyst are highly preferable for
a catalytic process. In this regard, the recyclability of the Fe3O4/
Acknowledgements
KCC-1/IL/HPW MNPs was investigated in a model reaction of
I thank Dr Majid Younesi and Dr Hassan Atashin for their
hydrazine hydrate, ethyl acetoacetate, benzaldehyde, and
helpful editing of my manuscript.
ammonium acetate under optimized reaction conditions. The
recovered catalyst was washed with ethylacetate, dried at room
temperature and reused for a similar reaction. It is worth noting
that the heterogeneous property of the Fe3O4/KCC-1/IL/HPW
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