Amino acid ionic liquid-based titanomagnetite nanoparticles: An efficient and green nanocatalyst for the synthesis of 1,4-dihydropyrano[2,3-c]pyrazoles

Article abstract of DOI:10.1002/aoc.3949

The amino acid ionic liquid tetrabutylammonium asparaginate (TBAAsp) was immobilized on titanomagnetite (Fe_3?xTi_xO₄) nanoparticles in a facile one-pot process using an organosilane compound (TMSP) as spacer. The modified F

Full text of DOI:10.1002/aoc.3949

Received: 17 March 2017
DOI: 10.1002/aoc.3949
Revised: 28 May 2017
Accepted: 9 June 2017
F U L L P A P E R
Amino acid ionic liquid‐based titanomagnetite
nanoparticles: An efficient and green nanocatalyst for the
synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazoles
Davood Azarifar
| Omolbanin Badalkhani | Younes Abbasi
Department of Chemistry, Bu‐Ali Sina
University, 65178 Hamedan, Iran
The amino acid ionic liquid tetrabutylammonium asparaginate (TBAAsp) was
immobilized on titanomagnetite (Fe3−xTi O ) nanoparticles in a facile one‐pot
x
4
Correspondence
process using an organosilane compound (TMSP) as spacer. The modified
@TMSP@TBAAsp magnetic nanoparticles were characterized
Davood Azarifar, Department of
Chemistry, Bu‐Ali Sina University, 65178
Hamedan, Iran.
Fe3−xTi O
x 4
using Fourier transform spectroscopy, scanning electron microscopy,
energy‐dispersive X‐ray spectroscopy, vibrating sample magnetometry and
thermogravimetric analysis. The resulting analytical data clearly verified the
successful immobilization of the ionic liquid on the magnetic substrate. The
magnetic ionic liquid‐based nanoparticles exhibited high catalytic activity in
the synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazole derivatives via a one‐pot
three‐component reaction under mild reaction conditions. The catalyst was eas-
ily recycled and reused for at least six runs without any considerable loss of
activity.
Email: azarifar@basu.ac.ir
KEYWORDS
1
,4‐dihydropyrano[2,3‐c]pyrazoles, amino acid ionic liquid, ionic liquid‐based magnetic nanocatalyst,
one‐pot three‐component synthesis, titanomagnetite nanoparticles
1
| INTRODUCTION
MNPs has been used to prevent their easy oxidation and
also aggregation and to preserve their unique magnetism
and dispersibility. In addition, organofunctional
alkoxysilane linkers act to provide silicon coating of nano-
particles in order to maintain chemical stability and pro-
vide reactive sites on the surface of the nanoparticles for
Recently, nanoparticles have attracted significant interest
as efficient catalysts and supports for numerous organic
reactions and industrial processes because of their unique
size and extraordinary physical and chemical properties
including high surface‐to‐volume ratio and coordinated
parts providing a great number of active sites per unit
area. Metal oxide nanoparticles with significant mag-
netic properties have become very attractive due to their
role as efficient catalysts and alternatives for the immobi-
lization of a wide range of homogeneous catalysts and
ionic liquids (ILs). Nevertheless, these magnetic nano-
particles (MNPs) are aggregated quickly into larger
groupings and thereby lose their unique properties. As
an effective protection strategy, covalent linkage of
organic or inorganic molecules such as organosilanes to
[3,4]
efficient grafting of different groups on their surface.
ILs have become attractive as environmentally
friendly reaction media and catalysts and have been
widely used in organic reactions due to their environ-
mental benignity, high thermal stability, reusability, neg-
[1]
[
5–7]
ligible vapour pressure and easy handling.
Despite
[2]
promising advantages, ILs have disadvantages including
high viscosity resulting in decreased catalytic activity
and
homogeneous
behaviour
in
reactions
making product separation and catalyst recovery more
complicated. To solve such problems, immobilization of
Appl Organometal Chem. 2017;e3949.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3949

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AZARIFAR ET AL.
ILs onto various nanosized solid supports, especially
magnetic nanomaterials, has been the most promising
solution. The obtained IL‐based heterogeneous
nanocatalysts possess advantages including reusability,
easy separation, enhanced stability and catalytic activity
along with retaining the above‐mentioned physical and
be obtained with a single‐step reaction and a variety of
products can be obtained by changing the reaction com-
[
17–19]
ponents.
Dihydropyrano[2,3‐c]pyrazoles and their derivatives
are widely used in synthetic organic and bioorganic chem-
istry because of their pharmacological and therapeutic
properties including insecticidal, diuretic, anticoagulant,
anticancer, antibacterial, analgesic and anti‐inflammatory
[8–11]
chemical properties.
Among nanomaterials employed as supports for vari-
ous catalysts and ILs, MNPs have become popular due
to their high stability, easy synthesis and
[
20]
activities.
There are numerous synthetic procedures
available for the synthesis of 1,4‐dihydropyrano[2,3‐c]
pyrazole derivatives using various catalytic systems and
application of multi‐component reactions under a variety
[12–16]
functionalization and high surface area.
Further-
more, MNPs can be simply separated from a reaction mix-
ture by applying an external magnetic field. This strategy
is more efficient compared to tedious isolation processes
such as filtration or centrifugation.
Considering the advantages of IL‐immobilized MNPs
as designable catalysts, such as environmental friendli-
ness, easy separation and reusability, non‐volatility, high
catalytic efficiency and high thermal stability, we used
[
21–25]
of conditions.
2
2
| EXPERIMENTAL
.1 | Materials and instrumentation
Melting points were determined in open capillaries with a
Buchi 510 apparatus. Fourier transform infrared (FT‐IR)
spectra were recorded in KBr pellets with a Shimadzu
Fe3−xTi O4
MNP‐supported
tetrabutylammonium
x
asparaginate (TBAAsp) IL as an efficient catalyst for the
synthesis of dihydropyrano[2,3‐c]pyrazoles via environ-
mentally benign multi‐component reactions (Scheme 1).
Recently, multi‐component reactions have become popu-
lar as an atom‐economic concept because products can
1
13
435‐U‐04 FT‐IR spectrometer. H NMR and C NMR
spectra were obtained with 250 and 400 MHz Bruker
Avance instruments in DSMO‐d6 as a solvent and
tetramethylsilane as an internal standard. Energy‐
SCHEME 1 (a) Synthesis of amino acid
IL (TBAAsp). (b) Synthesis of
Fe3−xTi
c) Synthesis of 1,4‐dihydropyrano[2,3‐c]
pyrazole derivatives 4a–j catalysed by
Fe3−xTi @TMSP@TBAAsp
x 4
O @TMSP@TBAAsp catalyst.
(
x 4
O

AZARIFAR ET AL.
3 of 10
dispersive X‐ray (EDX) analysis was conducted with a
SAMX instrument. Scanning electron microscopy (SEM)
images were obtained with a KYKYEM‐3200 instrument
operated at an accelerating voltage of 26 kV. Magnetic sus-
ceptibility measurements were performed at room temper-
ature with a vibrating sample magnetometry (VSM)
instrument (model MDKFT). To investigate thermal stabil-
ity, thermogravimetric analysis (TGA) was performed with
a TGA/DTA Linseis‐181a1750 instrument at a heating rate
of 5°C min in the range 25–1000°C under nitrogen flow.
Ultrasonication was performed using a 2200 ETH‐
SONICA ultrasound cleaner with a frequency of 45 kHz.
Mass spectra were recorded with a FINNIGAN‐MAT
added dropwise to the reaction mixture. The resulting
mixture was refluxed at 90°C for 30 min under nitrogen
atmosphere. Then, aqueous solutions of 4 g of NaOH
and 2 g of NaNO in 18 ml of deionized water were added
3
to the mixture and refluxed under vigorous stirring for
1 h. Finally, the reaction mixture was cooled to room tem-
perature to precipitate titanomagnetite nanoparticles
which were separated using a magnetic bar, washed with
water and dried in air.
−
1
2
.4 | Preparation of Fe3−xTi O @TMSP@
x 4
TBAAsp catalyst
8
430 spectrometer operating at an ionization potential of
The surface of the synthesized MNPs (Fe3−xTi O ) was
x 4
7
0 eV.
functionalized using 3‐chloropropyltrimethoxysilane
CPTMS) and TBAAsp IL using a facile one‐pot process.
(
MNPs (0.61 g) were dispersed in 20 ml of pyridine under
ultrasonication for 30 min. Then, a small amount of
sodium metal, 1 ml (5.5 mmol) of CPTMS and a solution
of 2.04 g (5.5 mmol) of TBAAsp in 5 ml of chloroform
were added into the reaction mixture under argon atmo-
sphere and the obtained mixture was ultrasonicated for
a further 15 min. Then, the mixture was stirred under
reflux condition at 110°C for 24 h. The precipitated nano-
particles were separated using a magnetic bar, washed
with ethanol and dried in air to afford about 1.4 g of light
brown powder.
2
.2 | Preparation of TBAAsp IL
TBAAsp IL was fabricated following a modified procedure
reported previously
agine amino acid (2.64 g, 20 mmol) in 20 ml of distilled
water was ultrasonicated for 20–30 min at room tempera-
ture to give an aqueous suspension. Then, 5.2 ml
[26]
(Scheme 1a). A solution of L‐aspar-
(20 mmol) of 40% aqueous tetrabutylammonium hydrox-
ide was added and the resulting mixture was stirred vigor-
ously under reflux condition for 24 h. Following water
removal in air, 10 ml of chloroform was added to the reac-
tion mixture containing unreacted asparagine amino acid
and desired IL. Finally, the remaining amino acid was
separated by filtration and the filtrate was dried in air to
afford the yellow viscous IL. The spectral ( H NMR,
NMR and MS) data for the sample are presented in the
supporting information.
2.5 | Determination of pH value of catalyst
1
13
C
A simple procedure was used for the determination of
the pH value of the catalyst. A mixture of 0.05 g of the
Fe3−xTi O @TMSP@TBAAsp catalyst in distilled water
x
4
−
1
TBAAsp IL. Yellow viscous liquid. IR (KBr, ν, cm ):
(10 ml) was stirred at room temperature for 24 h. Then,
the pH value of the resulting mixture was measured
using a pH meter (Metrohm 827, Herisan, Switzerland)
with a combined glass electrode). As expected, the mea-
sured pH value was found to be 9.37 confirming that
the synthesized catalyst is a basic composite compound.
This result could be explained by the presence of two
amine groups in the grafted TBAAsp IL moiety and the
remaining unreacted hydroxyl groups on the surface of
the catalyst.
3
1
1
4
1
1
383, 3295, 2967, 2941, 2875, 1667, 1578, 1490, 1468,
366. H NMR (400 MHz, DMSO‐d , δ, ppm): 0.95 (t,
2H , 4CH ), 1.31–1.33 (m, 8H , 4CH ), 1.58 (m, 8H ,
CH ), 1.88–1.95 (dd, 1H, H NOC‐CH ), 2.42–2.43 (dd,
H, H NOC‐CH ), 3.17–3.22 (m, 8H , 4CH ), 3.59 (dd,
H , CHNH2), 5.1, 6.32 (4H, 2NH2).
1
6
a
3
b
2
c
2
2
f
2
e
d
2
1
3
CNMR
g
(400 MHz, DMSO‐d , δ, ppm): 13.9 (C H ), 19.7 (‐
6
a
3
C H ), 23.6 (‐C H ), 44.3 (C H ), 54.2 (HC ‐NH ), 57.9
b
2
c
2
h
2
g
2
−
(
‐C H ), 174.9 (OC ‐NH ), 175.4 (C OO ). MS (70 eV):
d
2
e
2
f
m/z = 373.4.
2
.6 | Typical procedure for synthesis of 1,4‐
2
.3 | Fabrication of Fe3−xTi O MNPs
Dihydropyrano[2,3‐c]pyrazoles
x
4
Titanomagnetite nanoparticles were fabricated according
In a flask containing 0.01 g of Fe3−xTi O @TMSP@TBAAsp
x
4
[22]
to our previously reported approach.
In a flask, 3.81 g
catalyst were added aldehyde (1 mmol), malononitrile
(1 mmol) and 3‐methyl‐1‐phenyl‐1H‐2‐pyrazol‐5(4H)‐
one (1 mmol) under solvent‐free conditions. The reaction
mixture was stirred at 100°C for an appropriate time.
Once the reaction was completed, as monitored by
(
13.6 mmol) of FeSO ⋅7H O was dissolved in 18 ml of
4
2
deionized water. The pH of the solution was adjusted to
less than 1 by adding 1 M HCl (7 ml) solution. Then,
1
.6 ml of TiCl and 2 ml of hydrazine monohydrate were
4

4
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AZARIFAR ET AL.
TLC, the mixture was cooled to room temperature,
diluted with 10 ml of ethanol and stirred for 10 min.
Then, an external magnetic field was applied to separate
the catalyst, and the remaining solution was evaporated.
The precipitated solid product was recrystallized from
ethanol to yield pure product. All the synthesized prod-
ucts 4a–j were known compounds which were character-
2.6.4 | 6‐Amino‐4‐(3‐bromophenyl)‐3‐
methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]
pyrazole‐5‐carbonitrile (4d)
White solid; yield 0.358 g (88%); m.p. 162–165°C. IR
−
1
(
1
KBr, ν, cm ): 3453, 3337, 3194, 2823, 2194, 1655,
1
591, 1519, 1390, 1127, 1071, 754.
(400 MHz, DMSO‐d , δ, ppm): 1.81 (s, 3H, CH
(s, 1H, CH), 7.29–7.81 (m, 10H, H‐Ar and NH
NMR (100 MHz, DMSO‐d , δ,ppm): 13.1, 36.8, 57.9,
H
NMR
1
6
3
), 4.75
ized by their melting points and spectral (FT‐IR, H
1
3
1
3
2
).
C
NMR and C NMR) data and compared with the corre-
6
sponding reported data.
9
1
1
8.4, 120.3, 120.5, 122.3, 126.7, 127.5, 129.8, 130.5,
30.9, 135.0, 131.2, 137.9, 144.4, 145.6, 146.9, 160.02,
60.06.
2
.6.1 | 6‐Amino‐3‐methyl‐1,4‐diphenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile
4a)
(
2.6.5 | 6‐Amino‐4‐(2,4‐dichlorophenyl)‐3‐
methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]
pyrazole‐5‐carbonitrile (4e)
White solid; yield: 0.295 g (90%); m.p. 170–173°C. IR (KBr,
−
1
ν, cm ): 3472, 3324, 3194, 3063, 2923, 2198, 1659, 1625,
1
1
592, 1516, 1386, 1265, 1126, 754. H NMR (90 MHz,
Yellow solid; yield 0.353 g (89%); m.p. 184–187°C. IR
−
1
CDCl , δ, ppm): 1.89 (t, 3H, CH ), 4.66–4.69 (3H, CH
(KBr, ν, cm ): 3458, 3325, 2199, 1660, 1591, 1520, 1393,
3
3
13
1
and NH ), 7.28–7.61 (m, 10H, H‐Ar).
C NMR
1269, 1126, 1072, 758. H NMR (90 MHz, CDCl , δ,
2
3
(
1
1
100 MHz, DMSO‐d , δ, ppm): 13.0, 37.2, 58.7, 99.1,
16.5, 120.4, 126.6, 127.5, 128.2, 128.9, 129.7, 137.9,
44.0, 144.3, 145.7, 159.8.
ppm): 1.78 (s, 3H, CH ), 5.16 (s, 1H, CH), 7.32–7.80 (m,
6
3
1
3
10H, H‐Ar and NH2). C NMR (100 MHz, DMSO‐d , δ,
6
ppm): 12.8, 34.0, 56.62, 97.77, 120.0, 120.5, 126.7, 128.6,
1
1
29.4, 129.8, 132.9, 133.0, 133.5, 137.9, 139.7, 144.7,
45.3, 160.3, 160.4.
2
.6.2 | 6‐Amino‐3‐methyl‐4‐(3‐nitrophe-
nyl)‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]
pyrazole‐5‐carbonitrile (4b)
2
.6.6 | 6‐Amino‐4‐(4‐methoxyphenyl)‐3‐
methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]
pyrazole‐5‐carbonitrile (4f)
Cream solid; yield 0.332 g (89%); m.p. 191–193°C. IR
−
1
(
1
KBr, ν, cm ): 3439, 3300, 3191, 3101, 2195, 1649,
White solid; yield 0.315 g (88%); m.p. 177–180°C. IR (KBr,
1
592, 1387, 1263, 1123, 1071, 754. H NMR (250 MHz,
−
1
ν, cm ): 3393, 3323, 3205, 2192, 1661, 1596, 1513, 1393,
DMSO‐d , δ, ppm): 1.77 (s, 3H, CH ), 4.93 (s, 1H,
6
3
1
1
250, 1128, 1074, 813, 759. H NMR (90 MHz, DMSO‐d ,
13
6
CH), 7.29–7.78 (m, 9H, H‐Ar), 8.13 (s, 2H, NH2).
C
δ, ppm): 1.78 (s, 3H, CH ), 3.74 (s, 3H, CH ), 4.62 (s, 1H,
3
3
NMR (100 MHz, DMSO‐d , δ, ppm): 13.1, 35.6, 56.1,
6
13
CH), 6.84–7.82 (m, 11H, H‐Ar and NH2). C NMR
100 MHz, DMSO‐d , δ, ppm): 12.3, 38.1, 54.6, 59.1, 98.2,
9
1
6.6, 120.5, 121.7, 121.9, 130.2, 134.3, 135.9, 146.8,
47.8, 154.6, 160.1.
(
6
113.4, 119.7, 125.5, 128.4, 128.8, 134.9, 137.4, 143.5,
145.2, 158.0, 158.9.
2
.6.3 | 6‐Amino‐4‐(3‐chlorophenyl)‐3‐
methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]
pyrazole‐5‐carbonitrile (4c)
2.6.7 | 6‐Amino‐4‐(3‐ethoxy‐4‐
hydroxyphenyl)‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile
White solid; yield 0.323 g (89%); m.p. 159–162 °C. IR
(4i)
−
1
(KBr, ν, cm ): 3463, 3319, 2193, 1655, 1594, 1391,
1
1
265, 1126, 1070, 756. H NMR (400 MHz, DMSO‐d ,
Yellow solid; yield 0.334 g (86%); m.p. 186–190°C. IR
−
6
1
δ, ppm): 1.81 (s, 3H, CH ), 4.76 (s, 1H, CH), 7.25–
(KBr, ν, cm ): 3420, 3328, 3203, 2923, 2195, 1659, 1596,
3
13
1
7
.81 (m, 10H, H‐Ar and NH2). C NMR (100 MHz,
1514, 1391, 1273, 1125, 758. H NMR (400 MHz, DMSO‐
DMSO‐d , δ, ppm): 13.1 (CH ), 36.9 (CH), 57.9 (C‐
d , δ, ppm): 1.29–1.33 (t, 3H, CH ), 1.83 (s, 3H, CH ),
6
3
6
3
3
CN), 98.4 (CN), 120.3, 120.5, 126.7, 127.1, 127.6,
3.96–4.01 (q, 2H, CH ), 4.57 (s, 1H, CH), 6.61–7.80
2
1
3
1
1
28.0, 129.8, 130.9, 133.6, 137.9, 144.4, 145.6, 146.7,
60.01, 160.05.
(m, 10H, H‐Ar and NH ), 8.85 (s, 1H, OH). C NMR
2
(100 MHz, DMSO‐d , δ, ppm): 13.1, 15.1, 36.7, 59.1, 64.4,
6

AZARIFAR ET AL.
5 of 10
9
1
9.4, 113.9, 115.9, 120.3, 120.6, 126.5, 129.8, 135.0, 138.1,
44.2, 145.0, 146.1, 146.3, 146.8, 146.9, 159.6, 159.7.
120.5, 126.7, 129.0, 130.2, 132.1, 137.9, 143.1, 144.4,
145.6, 159.91, 159.95.
3
| RESULTS AND DISCUSSION
2
.6.8 | 6‐Amino‐3‐methyl‐4‐(4‐
chlorophenyl)‐1‐phenyl‐1,4‐dihydropyrano
2,3‐c]pyrazole‐5‐carbonitrile (4j)
3.1 | Characterization of Fe3−xTi O4
@TMSP@TBAAsp
x
[
White solid; yield 0.341 g (94%); m.p. 178–181°C. IR (KBr,
Following our previous research, herein we synthesized
the hitherto unreported Fe3−xTi O @TMSP@TBAAsp
(Scheme 1b) and investigated its catalytic capability for
−
1
ν, cm ): 3457, 3326, 3259, 3198, 3067, 2920, 2203, 1663,
x
4
1
1
594, 1518, 1393, 1127, 752. H NMR (400 MHz, DMSO‐
d , δ, ppm): 1.80 (s, 3H, CH ), 4.74 (s, 1H, C‐H), 7.28–
the synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazole deriva-
tives (Scheme 1c). Interestingly, the presence of Ti
6
3
13
4+
7
.81 (m, 11H, H‐Ar and NH2). C NMR (100 MHz,
DMSO‐d , δ, ppm): 13.0, 36.5, 58.2, 98.6, 120.3, 120.4,
cations in the structure of the nanoparticles increases
6
x 4 x 4
FIGURE 1 FT‐IR spectra of (a) TBAAsp, (b) Fe3−xTi O MNPs and (c) Fe3−xTi O @TMSP@TBAAsp MNPs

6
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AZARIFAR ET AL.
[27]
the number of surface hydroxyl groups.
This structural
stretching vibrations of O‐H bonds, respectively, which
modification improves the loading capacity of the grafted
functional groups on the surface of titanomagnetite nano-
are bonded to the surface metal atoms. The bands at 735
−
1
and 587 cm are due to the symmetric stretching vibra-
tions of Ti‐O and Fe‐O, respectively. The FT‐IR spectrum
of Fe3−xTi O @TMSP@TBAAsp MNPs (Figure 1c) shows
[22,28]
particles
nanoparticles.
compared with magnetite (Fe O )
3 4
[29,30]
x
4
−
1
As depicted in Scheme 1(a), first we prepared
Fe3−xTi O MNPs based on our previously reported
stretching vibrational peaks at 3410 and 3239 cm (NH),
−
1
−1
2864 and 2934 cm (C‐H), 1700 cm (C═O of amide),
x
4
[
22]
−1
−1
approach.
A mixture of equimolar amounts of
1632 cm
(NH), 1564 cm
(C═O of carboxylate),
−
1
−1
FeSO ⋅7H O and TiCl in acidic solution was reacted with
1300 cm (C‐N), 1114 and 1013 cm (Si‐O‐Si). These
4
2
4
hydrazine hydrochloride in deionized water under reflux
results clearly indicate that the surfaces of Fe3−xTi O
x
4
in nitrogen atmosphere. The produced Fe3−xTi O MNPs
MNPs are successfully functionalized.
The elemental composition of the Fe3−xTi O @
x
4
were magnetically separated from the reaction mixture.
Then, the surface of Fe3−xTi O MNPs was silylated via
x
4
TMSP@TBAAsp MNPs was established using EDX spec-
troscopy. As shown in Figure 2, the EDX pattern obtained
from a typical sample obviously indicates the expected
components (C, N, O, Si, Ti, Fe) and good dispersion of
the Fe3−xTi O @TMSP@TBAAsp MNPs.
x
4
a one‐pot process with CPTMS to prevent aggregation
followed by functionalization with TBAAsp IL in the pres-
ence of a small amount of metallic sodium in chloroform
under
reflux
(Scheme
1b).
The
precipitated
x
4
Fe3−xTi O @TMSP@TBAAsp MNPs were magnetically
The sizes and morphologies of Fe3−xTi O @
x
4
x 4
isolated using a magnetic bar. The structure of the synthe-
sized Fe3−xTi O @TMSP@TBAAsp catalyst was charac-
terized using various analytical techniques such as FT‐
IR spectroscopy, EDX, SEM, TGA and VSM.
TMSP@TBAAsp MNPs were investigated using SEM, as
shown in Figure 3. It can be seen that the size of these
nanoparticles is about 47 nm. The change of particle size
from 22 nm in Fe3−xTi O MNPs to 47 nm in
x
4
x
4
The FT‐IR spectra of TBAAsp IL, Fe3−xTi O MNPs
Fe3−xTi O @TMSP@TBAAsp MNPs clearly indicates the
x 4
x
4
and Fe3−xTi O @TMSP@TBAAsp MNPs are presented in
successful surface functionalization of Fe3−xTi O MNPs.
x 4
x
4
Figure 1. Successful functionalization of Fe3−xTi O4
Also, SEM micrographs reveal that there are major mor-
phological changes in non‐functionalized titanomagnetite
nanoparticles compared to the magnetic IL‐based
x
MNPs is verified by comparison between the FT‐IR spec-
−
1
tra. The bands at 3383, 3295 and 2875–2962 cm in the
[
31]
spectrum of the IL (Figure 1a) are attributed to the
nanoparticles.
Magnetic measurements of Fe3−xTi O
x 4
stretching vibrations of NH and C‐H groups. The absorp-
and
Fe3−xTi O @TMSP@TBAAsp were conducted using a
2
−
1
tion bands at 1667 and 1578 cm
are due to the
x
4
stretching vibrations of C═O bond in amide and carboxyl-
ate moieties, respectively. The FT‐IR spectrum of
Fe3−xTi O MNPs (Figure 1b) exhibits characteristic
broad absorption bands at 3418 and 1630 cm which
can be assigned to the asymmetric and symmetric
VSM instrument at 300 K. The magnetization curves
obtained for these nanoparticles are compared in
Figure 4. The values of the saturation magnetization for
Fe3−xTi O and Fe Ti O @TMSP@TBAAsp are 33.85
x
4
−
1
x
4
3−x
x 4
−
1
and 14.05 emu g , respectively, at +1000 Oe. The
FIGURE 2 EDX pattern of
Fe3−xTi O @TMSP@TBAAsp MNPs
x 4

AZARIFAR ET AL.
7 of 10
FIGURE
5
O
TGA and DTA curves of (a) TBAAsp and
@TMSP@TBAAsp MNPs
(
b) Fe3−xTi
x
4
x 4
FIGURE 3 SEM images of Fe3−xTi O @TMSP@TBAAsp MNPs
reduction in the saturation magnetization provides
evidence for successful formation of the
Fe3−xTi O @TMSP@TBAAsp MNPs. Even with this
reduction in the saturation magnetization, the catalyst
can still be efficiently separated from a solution simply
by applying an external magnetic field.
TGA and derivative thermogravimetric analysis (DTA)
of TBAAsp and Fe3−xTi O @TMSP@TBAAsp MNPs were
x
4
carried out and their thermal decomposition profiles were
obtained as shown in Figure 5. According to Figure 5(a), a
considerable weight loss (80.90%) occurs at 95–258°C
(centred at 176°C) which is attributed to the weight loss
in the synthesized IL sample (TBAAsp) and further
increasing the temperature from 258 to 580°C brings
about the complete decomposition of the corresponding
IL compound. Also, the TGA thermogram of
Fe3−xTi O @TMSP@TBAAsp MNPs (Figure 5b) shows a
x
4
x
4
weight loss of 5.52% at 72–176°C (centred at 110°C) which
can be attributed to the removal of residual water, other
solvents and remaining hydroxyl groups on the catalyst
surface. A significant weight loss of about 11.58% occurs
in the second stage at 176–338°C (centred at 258°C) which
could be due to the removal of the immobilized IL
(
TBAAsp) and organosilane spacer groups (TMSP) grafted
on the surface of Fe3−xTi O MNPs. The third weight loss
x
4
occurs at 338–600°C (centred at 450°C) and probably
FIGURE
4
VSM patterns of (a) Fe3−xTi
x
O
4
MNPs and
results from the complete decomposition of Fe3−xTi O
x
4
(
b) Fe3−xTi
x
O
4
@TMSP@TBAAsp MNPs
MNPs. Therefore, according to the obtained results, the

8
of 10
AZARIFAR ET AL.
thermal stability of the synthesized IL (TBAAsp)
was calculated to be about 258°C. In addition, our synthe-
sized catalyst exhibits a higher grafting capacity of the IL
on the surface of the titanomagnetite nanoparticles
observed that higher amounts of catalyst at 100°C under
solvent‐free conditions inhibit the formation of the prod-
uct (entries 9–11). The catalytic activity of
Fe3−xTi O @TMSP@TBAAsp
was
evaluated
by
x
4
(
11.58%) in comparison to previously reported similar
performing a similar reaction in the absence of the cata-
lyst which gives only a trace amount of product (entry 13).
The generality and scope of the proposed reaction was
extended by using a diverse series of aromatic aldehydes
magnetite (Fe O ) nanoparticles grafted with another IL
3
4
[32]
(6.1%).
1
a–j bearing various substituents under the above‐men-
3
.2 | Evaluation of catalytic activity of
tioned optimal conditions. On the basis of the results sum-
marized in Table 2, the reactions proceed smoothly to
furnish the relevant products in high yields (90–96%)
and short reaction times (15–60 min) regardless of the
substituent nature. The obtained products are all known
compounds and were characterized based on their physi-
Fe3−xTi O @TMSP@TBAAsp in synthesis
of 1,4‐Dihydropyrano[2,3‐c]pyrazole
derivatives
x
4
In view of the beneficial applications of IL‐based hetero-
geneous catalysts in organic reactions, we were encour-
aged to prepare Fe3−xTi O @TMSP@TBAAsp as a new
1
13
cal and spectral (FT‐IR, H NMR and C NMR) data and
x
4
basic IL magnetite and examine its catalytic activity in
the synthesis of dihydropyrano[2,3‐c]pyrazoles under sol-
vent‐free conditions. The one‐pot three‐component reac-
tion between benzaldehyde, malononitrile and 3‐methyl‐
compared with corresponding reported data (Table 2).
3.3 | Catalytic reaction mechanism
1
‐phenyl‐1H‐2‐pyrazol‐5(4H)‐one was chosen as model
A reasonable mechanism is proposed to describe the
one‐pot three‐component reaction between aromatic
aldehydes, malononitrile and 3‐methyl‐1‐phenyl‐1H‐2‐
pyrazol‐5(4H)‐one in the presence of Fe3−xTi O @
TMSP@TBAAsp as a basic catalyst as depicted in
Scheme 2. First, the catalyst accelerates the deproton-
ation of malononitrile into relevant anion which
reaction. The impacts of reaction parameters such as sol-
vent (EtOH, H O), catalyst loading and temperature were
analysed, as summarized in Table 1. The best results in
terms of reaction yield and time are obtained when the
reaction is performed at 100 °C under solvent‐free condi-
tions in the presence of 0.01 g of catalyst (entry 8). It is
2
x
4
a
TABLE 1 Screening reaction parameters for synthesis of 6‐amino‐3‐methyl‐1,4‐diphenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile
b
Entry
Catalyst (g)
Solvent
Temperature (°C)
Time (min)
Yield (%)
1
0.01
H
2
O
Reflux
150
29
2
3
4
5
6
7
8
9
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.03
0.05
0.07
EtOH
Reflux
Reflux
Reflux
Reflux
60
85
140
130
110
65
73
37
EtOH–H
EtOH–H
EtOH–H
2
2
2
O (1:1)
O (2:1)
O (4:1)
45
55
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
73
80
55
82
100
60
90
100
120
135
145
120
180
89
10
11
12
13
100
88
100
74
0.01 (Fe3−xTi
x
O
4
)
100
53
Catalyst‐free
80
Trace
a
Conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), 3‐methyl‐1‐phenyl‐1H‐2‐pyrazol‐5(4H)‐one (1 mmol), solvent (5 ml).
b
Isolated pure yield.

AZARIFAR ET AL.
9 of 10
TABLE 2 Synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazoles catalysed by Fe3−xTi
x
O
4
@TMSP@TBAAsp MNPs under solvent‐free conditions at
a
1
00°C
M.p. (°C)
Yield
Time
(min)
b
Entry
Ar
Product
4a
(%)
Found
Reported
[
[
[
[
[
[
[
[
[
[
25]
33]
33]
22]
33]
22]
33]
34]
33]
34]
1
C
6
H
5
60
40
20
15
25
60
35
45
30
20
90
170–173
168–170
189–191
158–160
160–163
185–187
177–178
187–189
176–178
187–189
177–178
2
3
4
5
6
7
8
9
3‐O
3‐ClC
3‐BrC
2,4‐Cl
4‐MeOC
4‐BrC
4‐MeC
3‐EtO‐4‐HOC
4‐ClC
2
NC
6
H
4
4b
4c
4d
4e
4f
89
89
88
89
88
96
87
86
94
191–193
159–162
162–165
184–187
177–180
190–193
175–178
186–190
178–181
6
H
4
6
H
4
2 6 3
C H
6
H
4
6
H
4
4 g
4 h
4i
6
H
4
6
H
3
1
0
6
H
4
4j
a
Conditions: aldehyde (1 mmol), malononitrile (1 mmol), 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one (1 mmol), solvent‐free, catalyst (0.01 g), 100 °C.
b
Isolated pure yield.
methyl‐1‐phenyl‐2‐pyrazolin‐5‐one to intermediate
1
occurs to give intermediate 2. Finally, tautomerization
of intermediate 2 followed by intermolecular cyclization
affords the respective product.
3.4 | Catalyst reusability
The reusability potential of the Fe3−xTi O @
x
4
TMSP@TBAAsp catalyst was studied in the model reac-
tion between 4‐chlorobenzaldehyde, malononitrile and
3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one under optimal con-
ditions. Once the reaction was completed, the catalyst
was magnetically separated, washed with hot ethanol
and reused for at least six consecutive runs with no con-
siderable loss of catalyst activity (Table 3).
x 4
TABLE 3 Catalytic reusability of Fe3−xTi O @TMSP@TBAAsp
MNPs for synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazole (4j)
a
Run
Time (min)
Yield (%)
1
10
94
2
3
4
5
6
15
18
25
31
35
92
91
89
88
86
SCHEME 2 Possible mechanism for synthesis of 1,4‐dihydro
pyrano [2,3‐c]pyrazoles catalysed by Fe3−xTi O @TMSP@TBAAsp
x 4
MNPs
undergoes an addition reaction with the activated alde-
hyde to produce arylidenemalononitrile intermediate
a
(
1) after dehydration. Then, nucleophilic addition of 3‐
Isolated yield.

10 of 10
AZARIFAR ET AL.
[
[
[
[
15] X. Zheng, S. Luo, L. Zhang, J. P. Cheng, Green Chem. 2009, 11,
4
| CONCLUSIONS
455.
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Catal. B 2009, 58, 103.
In summary, magnetic IL‐based aspargine‐functionalized
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x
4
17] J. Zhu, H. Bienayme, Multicomponent Reactions, Wiley‐VCH,
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pared by a simple procedure using commercially available
non‐toxic materials and characterized using several ana-
lytical techniques. These nanoparticles were probed as
an efficient, versatile and selective heterogeneous catalyst
for the synthesis of 1,4‐dihydropyrano[2,3‐c]pyrazoles.
The high catalytic activity and selectivity, easy magnetic
separation and recyclability of the catalyst, low reaction
times, high product yields, environmentally friendly sol-
vent‐free reaction conditions and simple work‐up place
the presented catalyst in a unique position as an attractive
and promising heterogeneous IL‐based nanocatalyst for
organic syntheses and transformations.
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granted by the Research Council of Bu‐Ali Sina
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