Preparation and characterization of nanomagnetic piperidinium benzene-1,3-disulfonate ionic liquid as a novel, green and heterogeneous catalyst and its use in the synthesis of 1H–pyrazolo[1,2-b]phthalazine-5,10-diones and 1H–pyrazolo[1,2-a] pyridazine-5,8-diones under solvent-free conditions

Article abstract of DOI:10.1002/aoc.3717

The one-pot four-component synthesis of 1H–pyrazolo[1,2-b]phthalazine-5,10-diones and 1H–pyrazolo[1,2-a]pyridazine-5,8-diones was carried out from the reaction between various aldehydes, malononitrile, hydrazine hydrate and phthalic anhydride or maleic anhydride at 110?°C in solvent-free conditions using piperidinium benzene-1,3-disulfonate nanomagnetic ionic liquid (NMIL) as a novel and reusable catalyst. Some advantages of the presented procedure are a significant reduction in cost, effective catalysis and reusability of the catalyst. NMIL was thoroughly characterized using Fourier transform infrared spectroscopy, X-ray diffraction, scanning and transmission electron microscopies, thermogravimetry, derivative thermogravimetry, Brunauer–Emmett–Teller analysis, vibrating sample magnetometry and energy-dispersive X-ray spectroscopy. The technique is developed as a suitable and safe method for the synthesis of 1H–pyrazolo[1,2-b]phthalazine-5,10-diones and 1H–pyrazolo[1,2-a]pyridazine-5,8-diones making use of an efficient and reusable green catalyst.

Full text of DOI:10.1002/aoc.3717

Received: 29 September 2016
DOI 10.1002/aoc.3717
Revised: 10 November 2016
Accepted: 25 November 2016
F U L L PA P E R
Preparation and characterization of nanomagnetic piperidinium
benzene‐1,3‐disulfonate ionic liquid as a novel, green and
heterogeneous catalyst and its use in the synthesis of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones and 1H–pyrazolo[1,2‐a]
pyridazine‐5,8‐diones under solvent‐free conditions
Ramin Ghorbani‐Vaghei | Jafar Mahmoodi | Yaser Maghbooli
Faculty of Chemistry, Bu‐Ali Sina University,
Hamedan 6517838683, Iran
The one‐pot four‐component synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐
diones and 1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones was carried out from the
reaction between various aldehydes, malononitrile, hydrazine hydrate and phthalic
anhydride or maleic anhydride at 110 °C in solvent‐free conditions using
piperidinium benzene‐1,3‐disulfonate nanomagnetic ionic liquid (NMIL) as a novel
Correspondence
Ramin Ghorbani‐Vaghei, Faculty of Chemistry,
Bu‐Ali Sina University, Hamedan 6517838683,
Iran.
Email: rgvaghei@yahoo.com
and reusable catalyst. Some advantages of the presented procedure are a significant
reduction in cost, effective catalysis and reusability of the catalyst. NMIL was
thoroughly characterized using Fourier transform infrared spectroscopy, X‐ray
diffraction, scanning and transmission electron microscopies, thermogravimetry,
derivative thermogravimetry, Brunauer–Emmett–Teller analysis, vibrating sample
magnetometry and energy‐dispersive X‐ray spectroscopy. The technique is
developed as a suitable and safe method for the synthesis of 1H–pyrazolo[1,2‐b]
phthalazine‐5,10‐diones and 1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones making use
of an efficient and reusable green catalyst.
KEYWORDS
1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones, 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐
dione, magnetic nanoparticle ionic liquid (NMIL), piperidinium benzene‐1,3‐
disulfonate, solvent‐free conditions
1
|
INTRODUCTION
organic reactions in addition to a decrease in their consump-
tion. The ionic liquids stabilized on MNPs act as heteroge-
neous catalysts in organic reactions. These kinds of
catalysts can be easily separated using a magnet and recycled
after the end of the reaction. Based on these considerations,
MNPs as heterogeneous catalysts have received considerable
attention due to their interesting structures and prominent cat-
alytic activities.[13–18]
The synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐
diones and 1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones has
attracted a great deal of attention because of their biological
and pharmacological actions. Literature reports have already
established that pyrazoles and phthalazines have various
pharmacological properties such as anticancer,[19,20]
In recent years, heterogeneous catalysts have gained
significance because of economic and environmental con-
cerns.[1–9] Among the various heterogeneous catalysts, par-
ticularly ionic liquids as homogeneous, heterogeneous and
recyclable catalysts have attracted much attention in organic
synthesis.[10–12] To overcome some problems, such as high
usage of ionic liquids in organic reactions, lack of economic
efficiency, time‐consuming processes for their recycling,
which causes their waste, and separation from reaction vessel,
which pollutes the environment, ionic liquids are often stabi-
lized on magnetic nanoparticles (MNPs). This method causes
an increase in activity and selectivity of these liquids in
Appl Organometal Chem 2017;e3717.
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Copyright © 2017 John Wiley & Sons, Ltd.
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DOI 10.1002/aoc.3717

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GHORBANI‐VAGHEI ET AL.
antifungal[21,22] anti‐inflammatory,[23] antiviral,[24] antide-
pressant,[25] antibacterial,[26] antipyretic[27] and anticonvul-
sant[28–30] activities. In this paper we present a new class of
ionic liquid, namely piperidinium benzene‐1,3‐disulfonate
nanomagnetic ionic liquid (NMIL; Scheme 1), as a simple,
efficient and novel catalyst, which was successfully used as
a catalyst in the solvent‐free synthesis of 1H–pyrazolo[1,2‐
surface‐modified samples (Figure 1). The FT‐IR spectrum
of Fe3O4 MNPs shows a characteristic absorption peak of
Fe─O bond at about 585 cm−1. The absorption peaks of the
silica shell in the spectrum of SCMNPs at around 1100 and
810 cm−1 are ascribed to the antisymmetric and symmetric
stretching vibrations of Si─O─Si in oxygen–silica tetrahedra,
respectively. Moreover, the absorption peak of the SCMNPs‐
Pr‐Cl core–shell MNPs at 2957 cm−1 is connected to the
stretching vibration of C─H groups. Additionally, the absorp-
tion band at 3408 cm−1 is attributed to the stretching vibra-
tion of N─H of the piperidinium moiety and the peak
appearing at 1645 cm−1 is attributed to the stretching vibra-
tion of the C═C bonds of benzene‐1,3‐disulfonate. Also,
the two peaks observed at 1220 and 1105 cm−1 are related
to the vibrational modes of the sulfonate groups.
b]phthalazine‐5,10‐diones
and
1H–pyrazolo[1,2‐a]
pyridazine‐5,8‐diones via the one‐pot four‐component con-
densation reaction between various aldehydes, malononitrile,
hydrazine hydrate and phthalic anhydride or maleic anhy-
dride (Scheme 2).
2
| RESULTS AND DISCUSSION
A very effective one‐pot synthesis was carried out of a variety
of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐diones and 1H–
pyrazolo[1,2‐a]pyridazine‐5,8‐diones catalysed by the
piperidinium benzene‐1,3‐disulfonate magnetic nanoparticle
ionic liquid under solvent‐free conditions. High yields of
products were achieved using a simple workup.
The structure of NMIL as an efficient, reusable and het-
erogeneous catalyst was characterized through various
methods: Fourier transform infrared (FT‐IR) spectroscopy,
X‐ray diffraction (XRD), scanning electron microscopy
(SEM), transmission electron microscopy (TEM), thermogra-
vimetric analysis (TGA), derivative thermogravimetry
(DTG), Brunauer–Emmett–Teller (BET) analysis, vibrating
sample magnetometry (VSM) and energy‐dispersive X‐ray
spectroscopy (EDX).
FT‐IR spectroscopy was used to compare the produced
Fe3O4 MNPs, SCMNPs and the other core–shell
SCHEME 2 Synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐diones and
1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones in the presence of NMIL catalyst
SCHEME 1 Synthesis of NMIL catalyst

GHORBANI‐VAGHEI ET AL.
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FIGURE 1 FT‐IR spectra: (a) Fe3O4; (b) Fe3O4@SiO2; (c) Fe3O4@SiO2@(CH2)3Cl; (d) Fe3O4@SiO2@(CH2)3‐piperidine; (e) {Fe3O4@SiO2@(CH2)3‐
piperidinium}2benzene‐1,3‐disulfonate
TGA and DTG curves of NMIL as a catalyst display the
mass loss of organic material as it decomposes upon heating
(Figure 2). The MNP catalyst demonstrates two‐step weight
loss behaviour. The weight loss from the NMIL catalyst (room
temperature to 100 °C) is due to the removal of physically
adsorbed water and organic solvents, which were applied in
the process of synthesis of NMIL catalyst. The weight loss
is about 12%. The main weight loss (70%) between 120 and
510 °C occurs mainly due to the thermal decomposition of
the organic layer on the surface of MNPs. Therefore, in the
temperature range between 100 and 510 °C, around 10%
weight loss is observed confirming 0.25 mmol g−1 organic
groups loaded on the SCMNP surface.
The size, shape and morphology of the NMIL catalyst
was investigated via XRD (Figure 3), and SEM and TEM
imaging methods (Figure 4). Considering the intensity ratio
of the main XRD peak detected at 2θ = 35.60°, the
crystalline structure of the magnetic ionic liquid catalyst can
obviously be identified (Table 1). The average crystallite size
D was determined using the Scherrer formula, D= Kλ/
(β cos θ), where K is the Scherrer constant, λ is the X‐ray
wavelength, β is the half‐maximum peak width and θ is the
Bragg diffraction angle. Consequently, the average size of
the magnetic ionic liquid catalyst is found to be about
7.38–33.67 nm. For additional study for determination of par-
ticle size of the NMIL catalyst, we used SEM and TEM anal-
yses. The shapes and dimensions of the particles can be seen
in Figure 4. As expected, the SEM and TEM images of the
NMIL catalyst indicate that the previous calculation of the
particle size is quite accurate and is about 5–35 nm. Both
SEM and TEM techniques corroborate the XRD patterns in
which nano‐sized ionic liquid catalyst was shown using
characteristic peaks. These results support our method for
the synthesis of the NMIL catalyst. The XRD pattern of
Fe3O4 is consistent with the patterns of spinel ferrites
reported in the literature. The position and relative intensities
of all peaks conform well with the standard XRD pattern of
Fe3O4 MNPs (JCPDS card no. 85–1436), indicating the
retention of the crystalline cubic spinel structure of MNPs.
The XRD patterns of the particles display nine characteristic
peaks linked to a cubic iron oxide phase (2θ = 14.80°,
30.10°, 35.50°, 43.10°, 53.00°, 57.00°, 62.80°, 70.50°,
73.90°). These are assigned to the corresponding indices
(1 1 0), (2 2 0), (3 1 1), (4 0 0), (3 3 1), (4 2 2), (5 1 1), (4 4 0)
and (5 3 1), respectively. It is implicit that the resultant
nanoparticles are pure Fe3O4 with a spinel structure and
that the grafting process does not lead to any phase change
of Fe3O4.
EDX analysis of the synthesized NMIL catalyst indicates
the probable elements in the structure of the catalyst, i.e. car-
bon, oxygen, nitrogen and sulfur (Figure 5).
Magnetic measurements of the Fe3O4 nanoparticles and
NMIL catalyst were conducted at room temperature using
VSM. Based on the magnetization curves, the saturation
magnetization of the synthesized NMIL catalyst decreased
from 60 emu g−1 (Fe3O4) to 36 emu g−1. This reduction in
saturation magnetization is owing to the surface coating on
the Fe3O4 MNPs (Figure 6).
To optimize reaction conditions, the condensation
reaction of phthalic anhydride, hydrazine hydrate, 4‐nitro-
benzaldehyde and malononitrile was selected as a model
reaction with various amounts of nanomagnetic catalyst in

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GHORBANI‐VAGHEI ET AL.
4‐nitrobenzaldehyde and malononitrile was used as a model
with 20 mg of NMIL catalyst in a variety of solvents such
as H2O, C2H5OH, CH3CN, CH3CO2Et, CH2Cl2 and toluene
under solvent‐free conditions at 110 °C. The results are sum-
marized in Table 3. As is evident, no solvent is obviously the
best selection for this reaction. Another advantage of choos-
ing solvent‐free conditions for this reaction is the safety,
cheapness and benignity in comparison with organic
solvents.
Encouraged by the important results obtained, and
with the purpose of exhibiting an overview and
determining the scope of this method, a range of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones were synthesized
from the one‐pot four‐component reaction between
phthalic anhydride, malononitrile, hydrazine hydrate and
numerous aldehydes with a catalytic amount of NMIL
catalyst (20 mg) under solvent‐free conditions at 110 °C.
The results are summarized in Table 4. The reaction time
for aromatic aldehydes is rather faster than that for ali-
phatic aldehydes. Also, aromatic aldehydes having elec-
tron‐withdrawing groups react rather faster than those
having electron‐donating groups. Though meta‐ and
para‐substituted aromatic aldehydes give very good
results, ortho‐substituted aromatic aldehydes produce
rather lower yields because of steric effects.
In another experiment, the recyclability and reusability of
the NMIL catalyst were confirmed using the condensation of
4‐chlorobenzaldehyde with malononitrile, ethyl acetoacetate
and hydrazine hydrate. At the end of the reaction, the catalyst
was separated using an external supermagnet, and then the
reaction mixture was decanted and washed with water. After-
wards the NMIL was reused for consecutive catalytic runs
under similar experimental conditions. We found that the cat-
alytic activity of the catalyst was maintained within the limits
of experimental error for seven consecutive runs (Figure 7).
Also, TGA of the NMIL catalyst before and after recycling
shows the thermal stability of the catalyst.
Nitrogen adsorption–desorption measurements were
conducted to investigate the BET specific surface area of
the materials (Figure 8a,b). The BET surface area of the
NMIL is 79.4 m2 g−1 (total pore volume = 0.246 cm3 g−1
;
mean pore diameter = 12.37 nm), and its pore size
distribution is plotted in Figure 8(d). The achieved surface
area for Fe3O4 NNPs is 10.9 m2 g−1 (total pore vol-
ume = 0.047 cm3 g−1; mean pore diameter = 17.25 nm),
and its pore size distribution to plotted in Figure 8(c). In
comparison to Fe3O4 MNPs, the BET surface area of the
NMIL catalyst is greater. The specific surface area of the
NMIL catalyst increases owing to coating of Fe3O4 MNPs
with grafted organic tags (Figure 8). The higher surface area
of the prepared catalyst in comparison to Fe3O4 MNPs core
can be stated as one of the benefits of this catalyst. The pore
sizes of both samples are chiefly between 1 and 10 nm, which
indicates that the samples include both micropores and
mesopores.
FIGURE 2 (a) TGA and DTG curves of NMIL catalyst; (b) TGA of
Fe3O4@SiO2@(CH2)3Cl (I); (c) TGA of piperidine (II)
the range 25–130 °C under solvent‐free conditions (Table 2).
The best results are achieved when the reaction is conducted
using 20 mg of nanomagnetic catalyst at 110 °C (Table 2,
entry 10). No improvement is detected in the yield of reaction
on increasing the amount of the catalyst and temperature
(Table 2, entries 11–13). It is evident that in the absence of
the nanomagnetic catalyst, the product yield is zero or very
low (Table 2, entries 1 and 2).
To compare the results for various conditions and sol-
vents, the reaction of phthalic anhydride, hydrazine hydrate,

GHORBANI‐VAGHEI ET AL.
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FIGURE 3 XRD patterns: (a) Fe3O4; (b) Fe3O4@SiO2; (c) Fe3O4@SiO2@(CH2)3Cl; (d) Fe3O4@SiO2@(CH2)3‐piperidine; (e) {Fe3O4@SiO2@(CH2)3‐
piperidinium}2benzene‐1,3‐disulfonate
To compare the efficacy of {Fe3O4@SiO2@(CH2)3‐
piperidinium}2benzene‐1,3‐disulfonate catalyst with those
of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2@(CH2)3Cl and
Fe3O4@SiO2@(CH2)3‐piperidine in the synthesis of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones, we used these cata-
lysts in the condensation of 4‐nitrobenzaldehyde, phthalic
anhydride, malononitrile and hydrazine hydrate. The results
are summarized in Table 5. The NMIL catalyst strongly
improves the synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐
5,10‐diones in terms of both reaction time and isolated yield.
The reaction times are shorter and the yields are higher when
the MNPs catalyst is used.
A possible mechanism for the synthesis of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones (5) is shown in
Scheme S3 (supporting information).[33] Firstly, NMIL cata-
lyst activates the carbonyl group of phthalic anhydride (1)
and then hydrazine hydrate attacks the oxygen ester group
which affords phthalhydrazide (6). In the next step, NMIL
catalyst activates the carbonyl group of aldehyde (4) and
malononitrile (3). Malononitrile rearranges and then attacks
the carbonyl group of the activated aldehyde which affords
2‐benzylidenemalononitrile (8). Finally, phthalhydrazide
produced in the previous step attacks the 2‐
benzylidenemalononitrile which is activated by NMIL. After
intramolecular attack takes place, the expected 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones are produced as
shown in Scheme S3 (supporting information).[32,34]
In continuation, we investigated the synthesis of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones in the presence of
nanomagnetic catalyst. The efficiency of this catalyst is
comparable to that of some other reported catalysts (Table 6).
Using our catalyst in the synthesis of 1H–pyrazolo[1,2‐b]
phthalazine‐5,10‐diones gives the best results for this
reaction.
3
| CONCLUSIONS
We have reported an efficient and green process for the one‐pot
four‐component synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐
5,10‐diones and 1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones
from the reaction between various aldehydes, malononitrile,

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GHORBANI‐VAGHEI ET AL.
TABLE 1 XRD data for NMIL catalyst
Peak width
(FWHM) (°)
Size
(nm)
Interplanar
distance (nm)
Entry
2θ (°)
1
2
3
4
5
22.80
25.70
35.60
62.80
71.10
0.58
0.35
1.13
0.73
0.29
13.97
23.28
7.38
0.389564
0.346225
0.251885
0.147990
0.132436
12.75
33.67
FIGURE 5 EDX of MNPs with (a) piperidinium benzene‐1,3‐disulfonate
ionic liquid, (b) Fe3O4@SiO2@(CH2)3Cl (I) and (c) piperidine (II)
hydrazine hydrate and phthalic anhydride or maleic
anhydride in the presence of a catalytic amount of NMIL
as an effective, novel, efficient and powerful nanomagnetic
ionic liquid with good to excellent yields under solvent‐free
conditions at 110 °C. The NMIL catalyst was thoroughly
characterized using FT‐IR spectroscopy, XRD, SEM, TEM,
TGA, DTG, BET analysis, VSM and EDX. The chief
advantages of this procedure are the simplicity of the
workup and the products can be isolated without
FIGURE 4 (a, b) SEM images and (c, d) TEM images of new NMIL
catalyst

GHORBANI‐VAGHEI ET AL.
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FIGURE 6 VSM analysis of NMIL catalyst in comparison with Fe3O4 MNPs
TABLE 2 Effect of quantity of catalyst and temperature on synthesis of 1H–
pyrazolo[1,2‐b]phthalazine‐5,10‐diones under solvent‐free conditionsa
chromatography. We propose that the technique has also
numerous benefits such as low consumption of catalyst
and clean reaction, which make it an appropriate and signif-
icant approach for the synthesis of 1H–pyrazolo[1,2‐b]
phthalazine‐5,10‐diones and 1H–pyrazolo[1,2‐a]pyridazine‐
5,8‐diones.
Entry
Catalyst loading
(mg)
Reaction
temperature (°C)
Reaction time
(min)
Yield
(%)b
1
—
—
5
r.t.
110
r.t.
120
120
50
50
50
50
45
45
45
45
45
45
45
—
5
2
3
35
45
45
65
70
60
85
94
94
94
94
4
5
110
r.t.
5
10
10
10
20
20
20
20
30
30
4
| EXPERIMENTAL
6
100
110
r.t.
7
4.1 | Preparation of NMIL Catalyst
8
9
100
110
130
110
130
Firstly, magnetite‐phase Fe3O4 was prepared by adding 3 ml
of FeCl3 (2 M; dissolved in 2 M HCl) to 10.33 ml of double‐
distilled water followed by dropwise addition of 2 ml of
Na2SO3 (1 M) for 3 min under magnetic stirring. When the
solution colour changed from red to light yellow, 80 ml of
an NH3⋅H2O solution (0.85 M) was added under vigorous
stirring. After 30 min, the precipitate of magnetite Fe3O4
was washed to pH < 7.5 with distilled water and separated
with an external magnet. To 1 g of Fe3O4 were added
20 ml of water, 80 ml of ethanol, 3 ml of ammonia and
3 ml of tetraethylorthosilicate (TEOS) under reflux to achieve
Fe3O4@SiO2.[25–28] Subsequently, 3 g of Fe3O4@SiO2 and
(3‐chloropropyl)triethoxysilane (10 mmol) in 80 ml of dry
toluene were refluxed under nitrogen for 12 h. The obtained
Fe3O4@SiO2@(CH2)3Cl was filtered, washed twice with
dry toluene and anhydrous diethyl ether, and dried at 80 °C
for 6 h in vacuum. To synthesize piperidine‐modified MNPs
(pi‐SCMNPs), 1.0 g pf silica‐coated MNPs was added to
50 ml of dry toluene and 3 ml of piperidine. The reaction
mixture was dispersed for 30 min, and then refluxed with stir-
ring for 72 h. The solid phase was filtered, washed with tolu-
ene and ethanol, and dried at 60 °C in vacuum (Scheme 1).
10
11
12
13
aReaction conditions: phthalic anhydride (1 mmol), hydrazine hydrate (1.2 mmol),
4‐nitrobenzaldehyde (1 mmol) and malononitrile (1 mmol).
bIsolated yield
TABLE 3 Effect of solvents on synthesis of 1H–pyrazolo[1,2‐b]
phthalazine‐5,10‐diones at 110°Ca
Entry
Solvent
Reaction time (min)
Yield (%)b
1
2
3
4
5
6
7
Solvent‐free
H2O
45
50
94
88
90
60
65
10
5
C2H5OH
CH3CO2Et
CH3CN
50
90
90
CH2Cl2
120
120
Toluene
aReaction conditions: phthalic anhydride (1 mmol), hydrazine hydrate (1.2 mmol),
4‐nitrobenzaldehyde (1 mmol) and malononitrile (1 mmol).
bIsolated yield.

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GHORBANI‐VAGHEI ET AL.
TABLE 4 Synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐diones and 1H–pyrazolo[1,2‐a]pyridazine‐5,8‐diones using 20 mg of NMIL catalysta
Entry
Aldehyde
3‐Phenylpropanal
Product
Reaction time (min)
Yield (%)b
M.p. (°C)
1
6a
6b
6c
80
65
80
40
60
40
45
40
45
45
45
40
40
40
40
40
60
40
55
40
60
85
70
70
65
70
80 (275 mg)
84 (307 mg)
75 (304 mg)
90 (354 mg)
80 (277 mg)
92 (307 mg)
86 (301 mg)
86 (330 mg)
88 (294 mg)
88 (318 mg)
87 (343 mg)
92 (362 mg)
86 (330 mg)
85 (326 mg)
94 (339 mg)
87 (304 mg)
82 (284 mg)
90 (325 mg)
82 (259 mg)
90 (315 mg)
88 (302 mg)
60 (178 mg)
84 (252 mg)
82 (246 mg)
80 (267 mg)
80 (267 mg)
241–243[31]
266–268[32]
248–250[31]
266–268[33]
250–252[33]
263–265[32]
255–256[33]
274–276[34]
266–268[35]
260–262[33]
267–268[32]
274–276[33]
275–277[34]
233–235[34]
256–258[35]
255–257[33]
253–255[32]
255–257[33]
224–226[33]
254–256[35]
288–290[29]
259–261[29]
272–274[29]
277–279[29]
274–276[29]
274–276[29]
2
2‐Naphthaldehyde
3
3,4,5‐Trimethoxybenzaldehyde
3‐Bromobenzaldehyde
2‐Methoxybenzaldehyde
4‐Fluorobenzaldehyde
2‐Chlorobenzaldehyde
2,3‐Dichlorobenzaldehyde
2‐Fluorobenzaldehyde
2‐Nitrobenzaldehyde
4
6d
6e
5
6
6f
7
6 g
6 h
6i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
6j
2‐Bromobenzaldehyde
4‐Bromobenzaldehyde
2,6‐Dichlorobenzaldehyde
2,4‐Dichlorobenzaldehyde
4‐Nitrobenzaldehyde
6 k
6 l
6 m
6n
6o
6p
6q
6r
3‐Chlorobenzaldehyde
3‐Methoxybenzaldehyde
3‐Nitrobenzaldehyde
Benzaldehyde
6 s
6 t
7a
7b
7c
4‐Chlorobenzaldehyde
2‐Bromobenzaldehyde
2‐Methoxybenzaldehyde
2‐Chlorobenzaldehyde
3‐Chlorobenzaldehyde
2,4‐Dichlorobenzaldehyde
2,6‐Dichlorobenzaldehyde
7d
7e
7f
aReaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), phthalic anhydride or maleic anhydride (1 mmol), hydrazine hydrate (1.2 mmol), solvent free, 110 °C.
bIsolated yield.
An amount of 1.0 g of pi‐SCMNPs was suspended in 50 ml
of acetonitrile and 3 ml of benzene‐1,3‐disulfonic acid was
added to this suspension. The mixture was stirred at room
temperature for 24 h, then filtered and washed twice with ace-
tonitrile and further washed with deionized water and dried at
60 °C in vacuum[33] (Scheme 1).
Then, to this reaction were added aldehyde (1 mmol) and
malononitrile (1 mmol, 0.077 g), and the mixture was stirred
for a specified time. The reaction was monitored using TLC
(n‐hexane–ethyl acetate, 7:3). After the reaction was com-
plete, cold water was added to the reaction mixture and the
catalyst was separated magnetically. The Fe3O4 MNPs were
washed three to four times with ethanol and then dried at
50 °C for 3 h in order to preserve the catalyst for used in sub-
sequent reactions. The products in the aqueous layer were fil-
tered, separated and then washed with hot ethanol. The
obtained products were characterized using TLC and FT‐IR
and NMR spectroscopies. In this study, NMIL as a catalyst
was recycled and reused seven times without any loss of cat-
alytic activity.
4.2 | General procedure for preparation of 1H–
Pyrazolo[1,2‐b]phthalazine‐5,10‐diones
A mixture of phthalic anhydride (1 mmol, 0.148 g), NMIL
(20 mg) and hydrazine hydrate (1.2 mmol, 0.038 g,
0.038 ml) was stirred under solvent‐free conditions at
110 °C for 20 min to form phthalhydrazide as intermediate.

GHORBANI‐VAGHEI ET AL.
9 of 10
TABLE 5 Comparison of efficiency of MNPs catalyst with that of other
catalysts in the reaction of 4‐nitrobenzaldehyde, phthalic anhydride,
malononitrile and hydrazine hydratea
Entry
Catalyst
Catalyst
loading (mg) (min)
Time Yield
(%)b
1
2
3
4
5
MNPs catalyst
20
20
20
20
20
45
120
120
120
120
94
25
20
5
Fe3O4
Fe3O4@SiO2
Fe3O4@SiO2@(CH2)3Cl
Fe3O4@SiO2@(CH2)3‐piperidine
5
aReaction conditions: 4‐nitrobenzaldehyde (1 mmol), phthalic anhydride
(1 mmol), hydrazine hydrate (1 mmol), malononitrile (1 mmol), solvent‐free,
110 °C.
bIsolated yield.
TABLE 6 Comparison of catalytic activity of various catalysts for the
synthesis of 1H–pyrazolo[1,2‐b]phthalazine‐5,10‐dionesa
Entry
Catalyst
Reaction
time (min)
Yield (%)
1
2
3
4
5
6
InCl3 (30 mmol)
120
240
240
240
240
45
84[36]
76[37]
80[37]
85[37]
81[37]
88
MnCl2 (10 mol%)
ZnCl2⋅4H2O (10 mol%)
NiCl2⋅6H2O (10 mol%)
CoCl2⋅6H2O (10 mol%)
NMIL (0.5 mol%)
FIGURE 7 (a) Reusability of NMIL catalyst in 40 min. (b) TGA of NMIL
catalyst after seven recycles
aReaction conditions: phthalic anhydride (1 mmol), hydrazine hydrate (1.2 mmol),
2‐nitrobenzaldehyde (1 mmol) and malononitrile (1 mmol).
ACKNOWLEDGMENTS
The authors thank Bu‐Ali Sina University and Iran National
Science Foundation (INSF) for financial support of our
research group.
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heterogeneous catalyst and its use in the synthesis of
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