Design and development of a new functionalized cellulose-based magnetic nanocomposite: preparation, characterization, and catalytic application in the synthesis of diverse pyrano[2,3-c]pyrazole derivatives

Article abstract of DOI:10.1007/s13738-019-01610-9

In this work, a facile protocol for the preparation of a new cellulose-based functionalized magnetic nanocomposite catalyst is described. The structure and morphology of the prepared nanomaterial was characterized by scanning electron microscopy, energy-d

Full text of DOI:10.1007/s13738-019-01610-9

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-019-01610-9
ORIGINAL PAPER
Design and development of a new functionalized cellulose-based
magnetic nanocomposite: preparation, characterization, and catalytic
application in the synthesis of diverse pyrano[2,3-c]pyrazole
derivatives
Ali Maleki1 · Vahid Eskandarpour1
Received: 7 July 2018 / Accepted: 23 January 2019
© Iranian Chemical Society 2019
Abstract
In this work, a facile protocol for the preparation of a new cellulose-based functionalized magnetic nanocomposite catalyst is
described. The structure and morphology of the prepared nanomaterial was characterized by scanning electron microscopy,
energy-dispersive X-ray analysis, X-ray diffraction patterns, and Fourier transform infrared spectroscopy analyses. Then, its
catalytic activity was investigated in the synthesis of 2,4-dihydropyrano[2,3-c]pyrazole and spiro[indoline-3,4′-pyrano[2,3-c]
pyrazole derivatives through a one-pot four-component reaction between isatin or aldehydes or acetophenones, ethylacetoac-
etate, hydrazine hydrate, and malononitrile or ethylcyanoacetate in short reaction times, high yields, and mild conditions.
The nanocomposite was simply separated by an external magnet and reused several times without remarkable loss of activity.
Keywords Cellulose composite · Magnetic bionanostructure · Heterogeneous nanocatalyst · Spiroindoline ·
Pyranopyrazoles
Introduction
used [7–11]. In the 4-CR, carbonyl compounds, hydrazine
hydrate, β-keto-ester, and malononitrile condensed in the
presence of a catalyst. Different catalysts have been reported
for these reactions such as tetraethylammonium [12],
[(CH2)4SO3HMIM][HSO4] [13] and Al2O3 [14].
Multicomponent reactions (MCRs) are an important tool to
efficiently synthesis of various complex molecules in one-
pot conditions starting from at least three simple and readily
available raw materials. In the recent years, researchers have
increased their interest in MCRs and used this strategy for
pharmaceutical and drug discovery research [1, 2].
One of the most important challenges in pharmaceutical
chemistry is the synthesis of biologically active molecules
via economical protocols [3]. Dihydropyrano[2,3-c]pyra-
zoles play an important role in the synthesis of biologically
active compounds. These compounds have many properties
such as antimicrobial [4], insecticidal [5], and anti-inflam-
matory activities [6].
The indole moiety is one of the most important hetero-
cycles which is involved in a variety of natural products
and medicinal agents [15–19]. Compounds carrying the
indole moiety exhibit antibacterial and antifungal activi-
ties [15–19]. Furthermore, it has been reported that C-3
spiroindoline derivatives highly enhance biological activity
of chemical compounds [16–19].
Most of the reported protocols for the synthesis of
both these products, especially in the case of spiroindo-
line–pyranopyrazoles, were suffering from disadvantages
such as expensive reagents, long reaction times, low yields,
toxic reagents, and harsh reaction conditions. Hence, devel-
opment of an effective method for the synthesis of these
scaffolds is significant. The preparation of an efficient
catalyst is also necessary. In the past decade, functional-
ized magnetic catalysts have been the center of attentions
due to their diverse advantages such as a broad range of
applications, reusability, high stability, availability, and easy
In the synthesis of pyranopyrazoles, three-component
(3-CR) or four-component (4-CR) reactions are often
* Ali Maleki
maleki@iust.ac.ir
1
Catalysts and Organic Synthesis Research Laboratory,
Department of Chemistry, Iran University of Science
and Technology, Tehran 16846-13114, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
separation [20]. As a result, nanocatalysts are reliable and
a promising option for chemists to be utilized in organic
reactions.
surface of the nanoparticles. The average size of nanoparti-
cles was about 25–55 nm.
Figure 3 shows the Fourier transform infrared (FT-IR)
spectra of γ-Fe2O3@cellulose-OSO3H in comparison with
cellulose and cellulose-OSO3H. A broad band at 3350 cm−1
was observed which is attributed to σ O−H stretching vibra-
tions of OH groups on cellulose structure that due to the
structure of each spectrum, the substrate cellulose nanocom-
posite structure proved to be designed. Hydrogen bonding
is the reason of the broadness of this band. Due to the pres-
ence of nanoparticles between hydrogen bonds in the cel-
lulose or cellulose-OSO3H structure, the OH band of the
nanocomposite is lower than them. In the IR spectrum of
nanocomposite, a new band at 437 cm−1 is related to Fe–O
bonds in Fe2O3 nanoparticles that can prove the nanoparti-
cle synthesis on cellulose surface. In addition, the decrease
in the height of OH broadband also is another reason for
why Fe2O3 nanoparticles have been placed on the cellulose
surface. Other important bands, which must be appeared at
580 and 634 cm−1, are not distinguished because of over-
lapping with cellulose bands. The stretching vibrations of
S=O bands should have been seen at 1032 cm−1 related to
SO3H is not seen due to the overlapping with cellulose bands
In the past decades, functionalized magnetic catalysts
have been the center of attention due to their diverse advan-
tages such as a broad range of application, reusability, high
stability, availability, and easy separation [21]. In connec-
tion with our previous works on the introduction of novel
protocols in MCRs and bionanostructure catalysts [22–26],
herein, the preparation and characterization of γ-Fe2O3@
cellulose-OSO3H as a new bionanocomposite that catalyzes
the effective synthesis of 2,4-dihydropyrano[2,3-c]pyrazole
(Fig. 1, path A) and spiro[indoline-3,4′-pyrano[2,3-c]pyra-
zole] (Fig. 1, path B) at room temperature are described.
This nanocatalyst can remove simply after completion of the
reaction by an external magnetic field.
Reported methods hint different disadvantages, such as
expensive reagents, long reaction times, low yields, and use
of the toxic reagents in both of the reactions, especially, for
spiroindoline–pyranopyrazoles production. Therefore, the
use of effective catalysts will be an important approach to
reduce these issues.
located at 1046 cm−1
.
Results and discussion
To determine the elements composition in the nanocom-
posite structure, the γ-Fe2O3@cellulose–OSO3H was ana-
lyzed by energy-dispersive X-ray (EDX) analysis. As shown
in Fig. 4, elements C, O, F, and S were indicated. Cellulosic
surface structure confirms the elements C and O as well as
Fe and O in the synthesis of nanoparticles on the surface. In
addition, existence of SO3H groups on the nanocomposite
structure was confirmed by sulfur element on this analysis.
X-ray powder diffraction (XRD) pattern was also used
to determine the structure of the nanocatalyst. The XRD
Catalyst characterization
Initially, γ-Fe2O3 nanoparticles were synthesized by co-
precipitation method using cellulose microcrystals. As indi-
cated in Fig. 2, the size and morphology of the nanoparti-
cles were studied by scanning electron microscopy (SEM).
SEM images proved the homogeneous structure of the cata-
lyst. The cellulose layer was coated homogeneously on the
Fig. 1 Synthesis of 2,4-dihydropyrano[2,3-c]pyrazoles
1
and
derivatives, malononitrile or ethylcyanoacetate, ethyl acetoacetate and
hydrazine hydrate catalyzed by γ-Fe2O3@cellulose-OSO3H
spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives
2
through
four-component reactions of isatin or aldehyde or acetophenone
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Journal of the Iranian Chemical Society
Fig. 2 SEM images of γ-Fe2O3@cellulose-OSO3H showing the layered structure of cellulose with γ-Fe2O3 nanoparticles on its surface in differ-
ent magnifications
Fig. 3 FT-IR spectra of the γ-Fe2O3@cellulose-OSO3H in comparison with cellulose and cellulose–OSO3H
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Journal of the Iranian Chemical Society
Fig. 4 EDX analysis of the γ-Fe2O3@cellulose–OSO3H nanocatalyst
follows: 2θ=30.3°, 35.8°, 43.35°, 53.7°, 57.3°, and 62.91°
and XRD pattern of cellulose fibers shows two peaks at
2θ=22.7° and 16.7°. According to the above results, it can
be figured out that the patterns resulted from γ-Fe2O3@cel-
lulose–OSO3H nanocomposite was in accordance with cel-
lulose and γ-Fe2O3 patterns. This confirms the synthesis of
γ-Fe2O3 nanoparticles inside cellulose sulfuric acid matrix.
The average size of the nanoparticles is about 32 nm which
is obtained via Scherrer equation:
Kꢀ
d =
.
ꢁ cos Ø
Inspection of the catalytic activity of γ‑Fe2O3@cel‑
lulose–OSO3H in the synthesis of pyranopyrazole
and spiro‑indole‑pyranopyrazole derivatives
Synthesis of pyranopyrazole compounds using γ-Fe2O3@
cellulose–OSO3H as catalyst
Fig. 5 XRD pattern of γ-Fe2O3@cellulose–OSO3H, cellulose, and
γ-Fe2O3
To optimize the reaction conditions, we considered the reac-
tion of 3-nitrobenzaldehyde, ethylacetoacetate, malononi-
trile, and hydrazine hydrate (molar ratios of 1:1:1:1) as a
model reaction (Fig. 6). First, this reaction was attempted
under catalyst-free conditions, but after 1 h, the product was
obtained in low yield. Therefore, the presence of catalyst for
completion of this reaction is necessary. A number of cata-
lysts such as Al2O3, [14] tetraethylammonium bromide [12],
[(CH2)4SO3HMIM] [HSO4] [13], and meglumine [37] were
reported. Some of these catalysts need heating at refluxing
and provide low yields after long reaction times. In com-
parison with those catalysts, new nanocomposite (γ-Fe2O3@
cellulose–OSO3H) proved to be the most efficient one which
gave higher yield (96%) in 3 min with a very small amount
pattern of the γ-Fe2O3@cellulose-OSO3H nanocomposite is
shown in Fig. 5. The peak in region 2θ =20 degree, which
is a curved peak, represents the cellulose substrate and cel-
lulose XRD. The sharp peaks in the region of 30–65° are
related to γ-Fe2O3 nanoparticles on its surface. This could
easily be proven by comparing with the γ-Fe2O3 pattern.
The XRD pattern of the γ-Fe2O3, along with its relationship
with the crystalline planes of each signal, corresponds per-
fectly with nanocomposite crystalline signals. These results
showed that γ-Fe2O3@cellulose-OSO3H has been success-
fully synthesized. The γ-Fe2O3 peaks at XRD pattern are
as follows: 2 2 0, 3 3 1, 4 0 0, 4 2 2, 5 1 1, and 4 4 0. The
XRD pattern peaks of the obtained nanocomposite are as
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Journal of the Iranian Chemical Society
Fig. 6 Model reaction of the
pyranopyrazole synthesis
Table 1 Screening of γ-Fe2O3@cellulose–OSO3H and solvent effects
compounds which contain electron-withdrawing groups
react better and require short reaction time when compared
to those containing of electron-donating groups. Because of
the presence of methyl group in acetophenones and steric
hindrance of this group, reaction time with acetophenone is
longer than aldehydes. In the case of malononitrile deriva-
tives (malononitrile or ethylcyanoacetate), no differences
were observed in reaction time.
on the model reaction
Entry
Solvent
Catalyst
Time (min)
Yielda (%)
amount (g)
1
2
3
4
5
6
7
8
9
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Water
–
60
3
3
3
3
3
3
3
3
trace
70
96
96
97
97
80
90
70
0.001
0.005
0.01
Table 2 clearly shows that the reaction of various aro-
matic aldehydes or acetophenones, malononitrile, ethyl ace-
toacetate, and hydrazine hydrate in ethanol as a solvent and
the nanocomposite provided the corresponding pyranopyra-
zole in high yields and short reaction time. Some of these
derivatives were produced for the first time, and for ensure
of formation of them, these compounds were analyzed with
melting point, IR, and NMR spectral data.
0.02
0.025
0.005
0.005
0.005
Acetonitrile
Chloroform
aReaction conditions: 1 mmol of 3-nitrobenzaldehyde, 1 mmol of
ethyl acetoacetate, 1 mmol malononitrile and 1 mmol of hydrazine
hydrate
To show the efficiency of γ-Fe2O3@cellulose–OSO3H as
appropriate catalyst for pyranopyrazole synthesis, we com-
pared our results with other results which have been reported
using various catalysts in Table 3. To compare the catalytic
activity of γ-Fe2O3 nanoparticles or SO3H, cellulose sulfuric
acid and γ-Fe2O3@cellulose were synthesized and applied
in model reaction. The results showed, in the presence both
these catalysts, that reaction time was longer and reaction
yield was lower. However, in the presence of this new nano-
composite [with Lewis acid (γ-Fe2O3) and Brønsted–Lowry
acid (SO3H)], the results were better.
of catalyst. The results are shown in Table 1. The progress
of the reaction was monitored by TLC. In summary, the
reaction time and yield of model reaction at room temper-
ature and ethanol as a solvent in the presence of 0.005 g
nanocatalyst were the best condition. Therefore, some other
pyranopyrazole derivatives were synthesized with aforemen-
tioned mole ratio and in optimized condition utilized from
the model reaction. These results persuaded us to other car-
bonyl compounds (aldehyde, acetophenone, and malononi-
trile derivatives (malononitrile or ethylcyanoacetate) for the
synthesis of pyranopyrazole compounds. This reaction has
the advantages of easy separation of catalyst by an external
magnet, use of acetophenone derivatives, the first report of
using ethylcyanoacetate instead of malononitrile, high yield
and short reaction time, excellent recyclability of catalyst,
use of the eco-friendly solvent, and easy workup.
Synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]
derivatives using γ- Fe2O3@cellulose–OSO3H
To optimize the reaction conditions, we considered the
reaction of isatin, ethylacetoacetate, malononitrile, and
hydrazine hydrate (mole ratios 1:1:1:1) as a model reaction
(Table 4). The progress of the reaction was monitored by
TLC. According to results that were showed in this table,
because of trace yield of spiro[indoline-3,4′-pyrano[2,3-c]
pyrazole], the presence of catalyst is necessary for the effec-
tive reaction progress and gaining high yield. A few reports
observed for this reaction. Triethanolamine, meglumine,
piperidine, 4-DMAP, and NaBr/electricity passed (F/mol)
We investigated aldehydes and acetophenones containing
both electron-withdrawing and electron-donating groups and
also malonitrile derivatives (malononitrile and ethylcyanoac-
etate). Due to very short reaction time in aldehyde deriva-
tives, effects of these groups are not comprehensible and in
reactivity of acetophenons, steric hindrance effects of groups
are not salient, either. However, in case of acetophenones,
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Journal of the Iranian Chemical Society
Table 2 Synthesis of pyranopyrazole derivatives using γ-Fe2O3@cellulose–OSO3H
Entry
Aldehyde
CH-acid
Product
Time
Yielda (%)
Mp (°C) Mp (°C, refs)
(min)
1
3
96
244–246 250–252 [16,
17, 18, 19]
2
3
2
4
92
86
226–228 214–216 [27]
241–243 233–235 [31]
4
5
4
3
95
84
244–245
245 [30]
176–178 178–180 [16,
17, 18, 19]
6
7
4
2
95
96
184–186 175–177 [20]
249–251
250 [20]
8
4
89
198–199 208–209 [16,
17, 18, 19]
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Journal of the Iranian Chemical Society
Table 2 (continued)
9
4
89
184–186 184–186 [28]
10
4
90
218–220 188–190 [27]
11
3
3
3
94
98
95
211–213
220 [30]
12
198–199 196–198 [27]
13
217–218 222–224 [29]
14
15
2
2
96
99
235
196–198 [16,
17, 18, 19]
200–201 181–183 [20]
16
17
3
3
92
94
227–228 223–224 [32]
218–219 200–202 [21]
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Journal of the Iranian Chemical Society
Table 2 (continued)
18
4
3
3
88
93
99
190–192 190–191 [32]
19
238–230 218–220 [27]
184–186 222–224 [27]
20
21
3
99
219
244
244–245 [33]
22
23
4
3
98
99
250 [30]
238.5–
239.5
Not reported
24
3
94
189–191 189–191 [34]
25
26
7
8
88
89
174–176 174–175 [32]
220–221 181–183 [28]
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Journal of the Iranian Chemical Society
Table 2 (continued)
27
6
2
94
90
193–195 Not reported
244–246 Not reported
28
29
3
4
90
88
156–158 Not reported
30
166–168
153–154
130 [41]
143 [41]
31
32
4
3
88
91
189–191 Not reported
33
3
95
> 300
300 [40]
aReaction conditions: aldehyde or acetophenone (1 mmol), malononitrile or ethylcyanoacetate (1 mmol), ethyl acetoacetate (1 mmol), hydrazine
hydrate (1 mmol) and 0.005 g γ-Fe2O3@cellulose-OSO3H, room temperature, 2 mL ethanol
are some of catalysts applied for this reaction. Almost all
of these catalysts were used once, so they do not have reus-
ability in organic synthesis and organocatalysts, such as
piperidine, are poison, too. Some of these catalysts need dif-
ficult conditions such as electricity passed, ultrasonic, high
temperature, or low yields in long reaction time. Hence, a
new catalyst that eliminates these problems is necessary.
γ-Fe2O3@cellulose–OSO3H is effective and catalyzed this
reaction in high yield and low reaction time and its sepa-
ration from reaction pot, by an external magnetic field is
very simple. In the pilot reaction, according to the results
that showed conditions, the efficiency and yields of the
products in ethanol as a green solvent at room temperature
were higher than other solvent. 0.01 g of the catalyst was
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Journal of the Iranian Chemical Society
Table 4 Screening of γ-Fe2O3@cellulose–OSO3H and solvent effects
for the synthesis of 6′-amino-3′-methyl-2-oxo-2′H-spiro[indoline-3,4′-
pyrano[2,3-c]pyrazole]-5′-carbonitrile
Entry
Solvent
Catalyst
Time (min)
Yielda (%)
amount (g)
1
2
3
4
5
6
7
8
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Water
Acetonitrile
Chloroform
–
120
–
0.005
0.01
0.02
0.025
0.01
0.01
0.01
40
40
40
40
40
40
40
80
93
93
88
–
–
–
aReaction conditions: 1 mmol of isatin, 1 mmol of ethylacetoacetate,
1 mmol malononitrile, and 1 mmol of hydrazine hydrate
an optimized amount of the catalyst for this reaction. More
or lower amounts of catalyst decrease the yield in the same
reaction time.
Then, we decided to develop this optimized condi-
tions to other isatins and ethylcyanoacetate as a malon-
onitrile derivative for the synthesis of spiro[indoline-
3,4′-pyrano[2,3-c]pyrazole] derivatives (Table 5). We
investigated isatins containing NO2 or Cl on benzene ring
and N–R derivatives of isatins. According to results that
are listed in Table 5, in the presence of electron-withdraw-
ing groups on the benzene of isatin, its chemical activity
increases but with larger group on nitrogen of isatin, its
activity decreases. In general, isatins which contain elec-
tron-withdrawing groups require shorter reaction time in
comparison with those with N–R derivatives of isatin. This
is also related to steric hindrance effects of alkyl groups.
To develop the optimized conditions, other isatins and
ethylcyanoacetate as a malononitrile derivative were used
for the synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyra-
zole] derivatives. According to results shown in Table 5,
isatins which contain electron-withdrawing groups require
shorter reaction times than those with N–R derivate of
isatin. This may also be related to steric hindrance effects
of alkyl groups.
To show the ability of γ-Fe2O3@cellulose–OSO3H
as a useful catalyst for the synthesis of spiro[indoline-
3,4′-pyrano[2,3-c]pyrazole] derivatives through one-pot
four-component reaction, we compared our outcomes with
other results which has been reported using various cata-
lysts under different conditions (Table 6).
To investigate the recoverability and reusability of
γ-Fe2O3@cellulose–OSO3H catalyst, it was tested in
the reaction of 3-nitrobenzaldehyde, ethylacetoacetate,
malononitrile, and hydrazine hydrate (mole ratio 1:1:1:1)
and isatin, ethylacetoacetate, malononitrile, and hydra-
zine hydrate (mole ratio 1:1:1:1) as pilot reactions. After
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Journal of the Iranian Chemical Society
Table 5 Synthesis of
spiro[indoline-3,4′-
Entry
1
Isatin
CH-acid
Product
Time
(min)
40
Yield
(%)a
93
Mp (°C) Mp (°C, refs)
pyrano[2,3-c]pyrazole]
derivatives using γ-Fe2O3@
cellulose–OSO3H
294–295 285–286 [35]
2
3
35
42
95
94
270–271
218–222
270 [39]
210 [36]
4
5
42
42
94
93
180–182 176–178 [39]
268–269 270–272 [35]
296–297 297–298 [35]
6
7
35
42
93
92
180
170–172 [36]
8
48
92
133–135 125–128 [36]
9
45
40
89
92
183–185 180–182 [39]
280–282 Not reported
10
11
40
91
265
Not reported
aReaction conditions: isatin derivatives (1 mmol), malononitrile or ethyl cyanoacetate (1 mmol), ethyl
acetoacetate (1 mmol), hydrazine hydrate (1 mmol), 0.01 g of γ-Fe2O3@cellulose–OSO3H, room tem-
perature, 2 mL of EtOH
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Table 6 Comparison of
Entry Catalyst
Amount of catalyst Reaction conditions Time (min) Yield (%)
the catalytic efficiency of
γ-Fe2O3@cellulose–OSO3H
with other catalysts for the
synthesis of spiro[indoline-3,4′-
pyrano[2,3-c]pyrazole]
1
2
3
4
5
6
7
Triethanolamine [36]
20 mmol
10 mol%
10 mol%
10 mol%
50 mg
EtOH/reflux
EtOH:H2O/r.t
H2O/r.t
EtOH/60 °C
EtOH/ultrasonic
EtOH/electricity
EtOH r.t
120
25–40
300
60
60
64
43–68
85–93
80–97
75–87
69–93
51–98
89–95
Meglumine [37]
Piperidine [39]
4-DAP [38]
Piperidine [25]
NaBr [38]
0.01 g
γ-Fe2O3@cellulose-OSO3H 0.01 g
30–42
Fig. 7 Examination of γ-Fe2O3/
Cu@cellulose reusability in the
synthesis of 6′-amino-3′-methyl-
2-oxo-2′H-spiro[indoline-
3,4′-pyrano[2,3-c]
pyrazole]-5′-carbonitrile
and 6-amino-3-methyl-
4-(3-nitrophenyl)-2,4-
dihydropyrano[2,3-c]pyrazole-
5-carbonitrile
completion of the reaction, the nanocatalyst was simply
separated by an external magnet. Then washed with hot
ethanol and dried at room temperature. The catalyst was
used and recycled five times without significant loss of
activity (Fig. 7).
Experimental section
General
All solvents, chemicals, and reagents were purchased from
Merck or Aldrich and used as received. Melting points
were determined using an Electrothermal 9100 apparatus.
FT-IR spectra were recorded as KBr pellets on a Shimadzu
FT-IR-8400S spectrometer. Analytical TLC was carried
out using Merck 0.2 mm silica gel 60 F-254 Al-plates. 1H
and 13C NMR spectra were obtained using Bruker DRX-
500 Avance spectrometers. The powder X-ray diffraction
pattern was recorded using a X-PERT-PRO diffractometer
with Cu Kα, (λ=1.54 Å) irradiation, in the range of 5 to 80
(2θ) with a scan step of 0.026. The morphology of catalyst
was studied with scanning electron microscopy using SEM
(AIS2300C SEI) on gold-coated samples. Elemental analysis
of the nanocomposite was provided by TESCAN-VEGA II
energy-dispersive X-ray (EDX) analysis.
Conclusions
In summary, a new protocol was developed for the prepara-
tion of γ-Fe2O3@cellulose–OSO3H bionanostructure catalyst.
The structure and morphology of the prepared nanocomposite
were well confirmed by SEM, EDX, XRD, and FT-IR analy-
ses. Then, its catalytic activity was investigated in two impor-
tant syntheses of pyranopyrazoles and spiroindoline–pyrano-
pyrazoles. This nanocomposite was easily separated by an
external magnet and was effective reusable at least five times
without remarkable loss of catalytic activity. The syntheses of
pyranopyrazoles and spiroindoline–pyranopyrazoles were car-
ried out through one-pot four-component reactions between
isatin or aromatic aldehyde or acetophenone derivatives, ethy-
lacetoacetate, hydrazine hydrate, and malononitrile or ethylcy-
anoacetate. This protocol had many advantages such as short
reaction times, high yields, mild reaction conditions, and low
requirement of the catalyst amount.
Preparation of γ‑Fe2O3@cellulose‑OSO3H
At first, the cellulose microcrystal (5.00 g) was added to 20 mL
of CHCl3 and stirred vigorously. Then, 1.00 g of chlorosul-
fonic acid diluted in 5 mL of chloroform was added drop-
wise at 0 °C during 2 h. When the addition was completed,
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Journal of the Iranian Chemical Society
the mixture was stirred for 2 h until HCl was removed from
reaction vessel. Finally, the mixture was filtered and washed
with methanol (3*10 mL) and dried at room temperature to
afford cellulose sulfuric acid. In second, an aqueous solution
of NaOH, urea, and H2O was prepared with material ratios
7:12:81, respectively. Then, the temperature was decreased
to -12 °C by use of ice and salt (NaCl). After that, 2.0 g of
the synthesized cellulose sulfuric acid was added. Next, 0.5 g
of FeCl2.4H2O and 1.0 g of FeCl3. 6H2O were dissolved in
50 mL of deionized water and added dropwise to the cellulose
sulfuric acid solution. Finally, the resulted mixture was filtered
and washed with water, ethanol and acetone and dried at room
temperature to afford γ-Fe2O3 nanoparticles coated on cellu-
lose sulfuric acid as a brown composite powder.
γ-Fe2O3@cellulose–OSO3H
IR (KBr) cm− 1: 3353, 2894, 1633, 1423, 1367, 1201,
1155, 1062, 1027, 663, 565, 437.
6-Amino-3,4-dimethyl-4-(4-nitrophenyl)-2,4-dihydropyran
o[2,3-c]pyrazole-5-carbonitrile (Table 2, Entry 27)
White powders (94%): mp 193–195 °C. IR (KBr) cm− 1
:
3481, 3223, 3122, 2189, 1641, 1596, 1490, 1470, 1352.
1H NMR (500.13 MHz, DMSO-d6) δ: 1.7 (3H, s, CH3), 1.7
(3H, s, CH3), 6.9 (2H, br s, NH2), 7.5 (2H, d, J = 8.9 Hz,
H–Ar), 8.1 (2H, d, J = 8.9 Hz, H–Ar), 12.1 (1H, s, NH).
6-Amino-4-(4-methoxy-3-(phenoxymethyl)phenyl)-3-me-
thyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(Table 2, Entry 24)
General procedure for the synthesis of pyranopyra‑
zole derivatives
A mixture of an aldehyde 1 (1 mmol), malononitrile 2
(1 mmol), ethylacetoacetate 3 (1 mmol), hydrazine hydrate 4
(1 mmol), and γ-Fe2O3@cellulose-OSO3H (0.005 g) in 2 mL
of ethanol was vigorously stirred in a 5 mL round bottom flask
at room temperature. The reaction progress was monitored by
TLC. After completion of the reaction, the catalyst was sepa-
rated by an external magnet. The pure products were obtained
by recrystallization from ethanol.
White powders (94%): mp 189–191 °C. 1H NMR
(500.13 MHz, DMSO-d6) δ: 1.7 (3H, s, CH3), 3.7 (3H,
s, OCH3), 4.5 (1H, s, CH), 5.0 (2H, s, CH2), 6.8–7.4
(10H, m, H–Ar and NH2). 12.065 (1H, s, NH). 13C NMR
(125.61 MHz, DMSO-d6) δ: 9.7, 35.7, 39.5, 55.5, 57.3,
69.9, 97.6, 111.9, 113.21, 120.0, 127.9, 128.3, 135.6,
136.8, 137.0, 147.3, 148.0, 154.7, 160.7.
6′-Amino-5-chloro-3′-methyl-5′-propionyl-2′H-spiro[indoli
ne-3,4′-pyrano[2,3-c]pyrazol]-2-one (Table 5, Entry 10)
General procedure for the synthesis of spiro[indolin
e‑3,4′‑pyrano[2,3‑c]pyrazole] derivatives
White powder (92%); mp 280–282 °C; IR (KBr) cm− 1
:
A mixture of isatin 1 (1 mmol), malononitrile or ethylcyanoac-
etate 6 (1 mmol), ethyl acetoacetate 7 (1 mmol), hydrazine
hydrate (1 mmol), and γ-Fe2O3@cellulose–OSO3H (0.01 g) in
2 mL of ethanol was stirred vigorously in a 5 mL round bottom
flask at room temperature. Reaction progression was moni-
tored by TLC. The reaction progress was monitored by TLC.
After completion of the reaction, the catalyst was separated by
an external magnet. The catalyst was washed by hot ethanol,
dried and reused in subsequent reactions. The pure products
were obtained by recrystallization from ethanol.
1
3417, 3311, 3240, 1695, 1666, 1475, 1292, 1199. H
NMR (500.13 MHz, DMSO-d6) δ: 0.7 (3H, t, J = 7.1 Hz,
CH3), 1.6 (3H, s, CH3), 3.6–3.8 (2H, m, CH2), 6.8 (1H, d,
J = 8.2 Hz, H–Ar), 6.8 (1H, d, J= 1.8 Hz, H–Ar), 7.1 (1H,
dd, J = 5.1 and 2.1 Hz, H–Ar), 8.0 (2H, br s, NH2), 10.5
(1H, s, NH), 12.2 (1H, s, NH).
Acknowledgements The authors gratefully acknowledge partial sup-
port from the Research Council of the Iran University of Science and
Technology.
Spectral data
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