Amelioration of H4[W12SiO40] by nanomagnetic heterogenization: For the synthesis of 1H–pyrazolo[1,2-b]phthalazinedione derivatives

Article abstract of DOI:10.1002/aoc.4001

We conveniently coated silicotungstic acid (STA, H₄[W₁₂SiO₄₀]) on amino-functionalized Si–magnetite nanoparticles, as surface functionalization of magnetic nanoparticles is an excellent way for green and efficient catalysis. The nanoparticles were structurally characterized using various techniques. The catalytic activity and recyclability of the STA–amine–Si–magnetite nanoparticles were probed through synthesis of 1H–pyrazolo[1,2-b]phthalazinedione derivatives. The reaction proceeds smoothly to provide products in excellent yields and short reaction times. The catalyst could be readily recovered using a simple external magnet and reused several times without any significant loss in activity. Herein, we report a comparison of the activity of H₄[W₁₂SiO₄₀] as a homogeneous and heterogeneous catalyst, the latter being found to be more efficient. The findings offer effective methods for environmentally friendly synthesis of pyrazolo[1,2-b]phthalazinedione derivatives.

Full text of DOI:10.1002/aoc.4001

Received: 7 March 2017
DOI: 10.1002/aoc.4001
Revised: 27 May 2017
Accepted: 29 June 2017
F U L L P A P E R
Amelioration of H4[W12SiO40] by nanomagnetic
heterogenization: For the synthesis of 1H–pyrazolo[1,2‐b]
phthalazinedione derivatives
Priya Arora
| Jaspreet Kaur Rajput
Department of Chemistry, Dr B. R.
Ambedkar National Institute of
Technology, Jalandhar 144011, Punjab,
India
We conveniently coated silicotungstic acid (STA, H4[W12SiO40]) on amino‐
functionalized Si–magnetite nanoparticles, as surface functionalization of mag-
netic nanoparticles is an excellent way for green and efficient catalysis. The
nanoparticles were structurally characterized using various techniques. The
catalytic activity and recyclability of the STA–amine–Si–magnetite nanoparti-
cles were probed through synthesis of 1H–pyrazolo[1,2‐b]phthalazinedione
derivatives. The reaction proceeds smoothly to provide products in excellent
yields and short reaction times. The catalyst could be readily recovered using
a simple external magnet and reused several times without any significant loss
in activity. Herein, we report a comparison of the activity of H4[W12SiO40] as a
homogeneous and heterogeneous catalyst, the latter being found to be more
efficient. The findings offer effective methods for environmentally friendly syn-
thesis of pyrazolo[1,2‐b]phthalazinedione derivatives.
Correspondence
Priya Arora, Department of Chemistry, Dr
B. R. Ambedkar National Institute of
Technology, Jalandhar 144011, Punjab,
India.
Email: priyaarora89@yahoo.co.in
KEYWORDS
heterogeneous catalysis, heteropoly acids, magnetic separation, pyrazolo[1,2‐b]phthalazinediones,
silicotungstic acid (H4[W12SiO40]), STA–amine–Si–magnetite
1 | INTRODUCTION
synthesis have been reported.[6,7] These protocols have
their own advantages as well as limitations like expensive
Heterocyclic unit‐containing molecules are of keen inter-
est to scientists because of their significant medicinal prop-
erties and their use as precursors for the library of natural
products and drug molecules.[1] Heterocycles containing
bridgehead hydrazine,[2] e.g. pyrazoles, reported by Knorr
in 1883,[3] show multiple biological activities like anti‐
inflammatory, anti‐allergic, analgesic, vasorelaxant, anti-
bacterial, antiviral, anti‐diabetes and anti‐hypoxic activi-
ties. For example, the pyrazolo[1,2‐b]phthalazinedione
core has been utilized in multiple pharmaceutical applica-
tions.[4] Pyrazoles are key structures for many drugs like
Viagra, celecoxib, pyrazofurine, etc.[5] A perusal of the lit-
erature reveals that the general method of their synthesis
is condensation of aldehydes and active methylene com-
pounds with phthalhydrazide. Several strategies for their
catalysts or reagents, low yields, occurrence of several side
products, long reaction times and harsh reaction condi-
tions. In spite of their extensive utility range, very few effi-
cient methods have been developed for the synthesis of N‐
heterocycles containing phthalazine moiety.
Nowadays many organic reactions are carried out
using acid catalysts, like Friedel–Crafts alkylations, acyla-
tions and sulfonations, aromatic halogenations, nitra-
tions, isomerizations and oligomerizations.[8] Due to
numerous disadvantages of mineral acids (hydrochloric
acid and sulfuric acid), such as the requirement of expen-
sive separation processes, treatment of waste streams for
disposal to remove harmful acids and also expensive
equipment to handle corrosive liquid acids, they have
been replaced by solid acid catalysts. Heteropoly acids
Appl Organometal Chem. 2017;e4001.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4001

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ARORA AND RAJPUT
are Brønsted acid catalysts[9] in the solid state and these are
stronger acids as compared to conventional acids.[10]
Heteropoly acids have attracted the attention of scien-
tists[11] because they possess many positive properties like
strong acidity, high catalytic stability and excellent water
tolerance.[12] The strong acidity of heteropoly acids is due
to weak interactions between polyanion and compensating
proton. Keggin‐type heteropoly acids are generally repre-
sented by [XM12O40]n−, where X is the heteroatom (most
commonly P5+, Si4+ or B3+), M is the addenda atom (the
most common are molybdenum and tungsten atoms) and
O represents oxygen.[13] The common disadvantage associ-
ated with heteropoly acids is their solubility in polar media.
Further to meet the need of today's research interests,
i.e. to develop stable, reusable and highly active solid
acids and also to circumvent difficulties in catalyst separa-
tion,[14] heteropoly acids have been replaced by their het-
erogeneous counterparts. Magnetically separable systems
facilitate the efficient separation of catalyst from solution
upon completion of the reaction by just applying a simple
external magnet. Nowadays, there is growing interest in
the development of this type of catalyst support[15] as sur-
face functionalization of magnetic nanoparticles[16] is a
smart way to bridge the gap between heterogeneous and
homogeneous catalysis. And also the properties of mag-
netic nanoparticles, like high surface area‐to‐volume ratio
and small size, aid their use as supports as they can carry
a large amount of active catalyst which is easily accessible
to the reactants. Magnetic nanoparticles have also been
widely used as supports in various biological fields like
silica‐coated magnetite nanoparticles (STA‐Amine‐Si‐
Magnetite). Thereby, an efficient, economical and recycla-
ble magnetically separable catalyst was structured for the
first time which resolves the issues of cumbersome sepa-
ration of catalyst from reaction mixture. The synthesis of
the catalyst follows the principles of green chemistry
and omits the use of extra energy consumption in this pro-
tocol. The activity of the catalyst was evidenced from the
synthesis of pyrazolo derivatives in good yields. A very
small loading of STA (0.035 mmol g−1) resulted in effi-
cient results for this protocol and hence eliminating the
need of higher amounts of catalysts as given in already
reported methods.
2 | EXPERIMENTAL
2.1 | Materials
All chemicals were purchased from various companies.
Ammonium hydroxide (NH4OH, 25% weight as NH3), fer-
ric sulfate (Fe2(SO4)3), ferrous sulfate (FeSO4⋅7H2O),
H4[W12SiO40], hydrazine hydrate, anisaldehyde, 3‐
nitrobenzaldehyde, N,N‐dimethylcinnamaldehyde and
benzaldehyde were purchased from Loba Chemie.
Tetraethylorthosilicate,
5‐methylfurfural
and
phthalamide were from Merck Millipore. APTMS and 9‐
anthracenecarboxaldehyde were from Acros Organics.
Vanillin, 3,4‐dimethoxybenzaldehyde and syringaldehyde
were bought from SD Fine‐Chem Limited. Malononitrile
and other substituted aldehydes were purchased from
Avra Synthesis Private Ltd. All chemicals were used with-
out any further purification.
magnetic
resonance
imaging,
hyperthermia,
bioseparation, drug delivery, etc. But the use of magnetic
nanoparticles has some problems, one of which is agglom-
eration.[17] Gratifyingly this can be precluded by coating
the catalyst surface with various organic or inorganic
shells, like silica, polymers, biomolecules, metals, etc. Sil-
ica is the best choice due to its inherent properties like
thermal stability against degradation, biocompatibility,
high stability in aqueous media, large surface area and
hence higher loading of active sites.[18]
In conjunction with our studies of functionalized mag-
netite nanoparticles[19,20] and also their efficient use as a
magnetically separable catalyst,[21] a study of acidic func-
tionalized magnetite nanoparticles has been initiated.
Silicotungstic acid (STA, H4[W12SiO40]) has been coated
over amine‐functionalized magnetite nanoparticles for
the first time, which has increased its activity as compared
to pure H4[W12SiO40], and the catalytic scope in the syn-
thesis of pyrazolo[1,2‐b]phthalazinediones has been
examined. The main objective of the work reported was
to improve the catalytic properties of heteropoly acid,
i.e. STA. To accomplish this goal STA was coated over
2.2 | Instrumentation
Fourier transform infrared (FT‐IR) spectra of nanoparti-
cles were recorded using a PerkinElmer Spectrum RX‐I
FT‐IR spectrophotometer using KBr pellets in the range
400–4000 cm−1 and FT‐IR spectra of all products were
obtained with an Agilent Cary 600 spectrometer using
the attenuated total reflection sampling technique. The
crystalline phase of the nanoparticles was characterized
by means of X‐ray diffraction (XRD) measurements using
Cu Kα radiation (λ = 0.154 nm) with a PANalytical X'Pert
PRO (NDP) X‐ray diffractometer in the 2θ range 10–80°.
The morphology, nanostructure and particle size of the
functionalized nanoparticles was studied using transmis-
sion electron microscopy (TEM) with a Hitachi S7500
instrument. Samples were prepared by dispersing a small
amount of solid nanoparticles in ethanol and then depos-
iting on carbon‐coated Cu grids by drop casting and
followed by drying. Magnetic measurements were carried
out for dried samples to evaluate magnetic properties of
aminopropyltrimethoxysilane
(APTMS)‐functionalized

ARORA AND RAJPUT
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multifunctional nanoparticles at room temperature.
For this, vibrating sample magnetometry (VSM) was
carried out with a Princeton Applied Research model
155. The surface morphology and elemental composi-
tion of the nanoparticles were studied using scanning
electron microscopy (SEM) and elemental dispersive
X‐ray spectroscopy (EDX). SEM images were obtained
with a JEOL JSM‐6610LV instrument. Thermogravi-
metric analysis (TGA) curves were recorded using an
EXSTAR6000TG/DTA 6300 instrument at a heating
rate of 10 °C min−1 under nitrogen atmosphere. The
surface area, pore volume and pore diameter of nano-
particles were obtained using a Micromeritics ASAP
2010 accelerated surface area and porosimetry system.
57Fe Mössbauer measurements were carried out in
transmission mode with a 57Co/Rh radioactive source
in constant acceleration mode using a standard PC‐
based Mössbauer spectrometer equipped with Weissel
velocity drive. Velocity calibration was done with the
natural iron absorber. A PE optima 5300 DV was used
for inductively coupled plasma optical emission spec-
troscopy (ICP‐OES) analysis. The organic products
and stirred continuously overnight at room temperature.
Finally, the nanoparticles were washed thrice with
CH3OH. The nanoparticles were separated with a magnet
and dried at 50 °C.
2.4 | Catalytic experiments
One of the reactants, i.e. phthalhydrazide, was synthe-
sized using a reported method.[22] An amount of 1 g
(6.8 mmol) of phthalamide was dissolved by refluxing
in a water bath in 20 ml of EtOH. Then 331.13 μl
(6.8 mmol) of hydrazine hydrate was added, and
white precipitates of phthahydrazide were seen after
16 min. The precipitates were filtered and washed
with EtOH three times to remove unreacted reactants.
The final product was recrystallized from EtOH.
Phthalhydrazide formation was confirmed using 1H
NMR spectroscopy.
1
Phthalhydrazide: H NMR (400 MHz, DMSO‐d6, δ,
ppm): 7.80–7.84 (m, 2.09), 8.08–8.13 (m, 2.0), 11.45 (bs,
2.33). 13C NMR (400 MHz, DMSO‐d6, δ, ppm): 125,
127.36, 131.90, 154.87.
1
were characterized using H NMR and 13C NMR spec-
troscopy at 400 MHz with the aid of a Bruker
Advance II 400 NMR spectrophotometer using
tetramethylsilane as the internal standard and deuter-
ated dimethylsulfoxide (DMSO‐d6) and CDCl3 as
solvents.
To a mixture of phthalhydrazide (1; 0.0405 g,
0.25 mmol), malononitrile (2; 15.72 μl, 0.25 mmol) and
aromatic aldehyde (3; 0.25 mmol) in 10 ml of CH3OH
was added a catalytic amount of STA‐Amine‐Si‐Magnetite
nanoparticles (10 mg). The resulting mixture was heated at
70 °C with a water bath for around 45–60 min. After com-
pletion of the reaction, as monitored by TLC, the solid
product was dissolved in hot CH3OH. The catalyst is insol-
uble and could be removed by applying an external mag-
net at the wall of the flask. The pure products 4a–z and
4a′ were obtained by recrystallization from hot EtOH.
The remaining catalyst was washed with ethanol and then
with acetone to remove any remaining product. Then it
was dried at 50 °C for 1 h. The physical and spectral (FT‐
2.3 | Catalyst preparation
Magnetite nanoparticles were prepared by modified co‐
precipitation aided by the sonication method and silica
coating was carried out using the Stöber method, as
described in our previous work.[19,20] For coating of
APTMS over Si‐Magnetite, 0.5 g of Si‐Magnetite nano-
particles was dispersed in 125 ml of water and sonicated
for 30 min. Then the solution was turned basic by
adding NH4OH (25%) dropwise to reach pH ≈ 10.5.
The resulting solution was again subjected to sonication
for 15 min for homogeneous mixing. APTMS
(0.071 mol, 12.5 ml) was then added dropwise to the
stirring mixture at 55 °C. The stirring was continued
for 3.5 h at 300 rpm. The Amine‐Si‐Magnetite nanopar-
ticles were then purified by three repeated washings
with water and centrifugation and finally dried at
50 °C for 24 h.[20]
1
IR, H NMR, 13C NMR) data for compounds are given
below.
2.5 | Spectral data for compounds
2.5.1 | 4a. 3‐Amino‐5,10‐dihydro‐1‐(4‐
hydroxy‐3‐methoxyphenyl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
1
STA‐Amine‐Si‐Magnetite nanoparticles were then
prepared using an impregnation method in which two
solutions, i.e. 0.45 g of Amine‐Si‐Magnetite nanoparticles
in 25.5 ml of CH3OH and an organic solution of
H4[W12SiO40] (0.2188 mmol, 0.63 g in 45 ml of CH3OH),
were sonicated for 30 min. After that, they were mixed
Yellow solid. H NMR (400 MHz, DMSO‐d6, δ, ppm): 3.7
(s, 3), 6.94 (d, 1), 7.48–7.49 (d, 2), 7.62 (s, 1), 7.87–7.89
(m, 4), 8.06 (bs, 2), 8.22 (s, 1). 13C NMR (400 MHz,
DMSO‐d6, δ, ppm): 56.6, 58.1, 75.3, 114.3, 118.2, 125.4,
127.3, 129.4, 133, 144.3, 149.1, 162.3. FT‐IR (cm−1): 3377,
2894, 2224, 1660, 1588.

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ARORA AND RAJPUT
2.5.2 | 4b. 3‐Amino‐1‐(4‐(dimethylamino)
phenyl)‐5,10‐dihydro‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
2.5.8 | 4h. 1‐(4‐(Dimethylamino)styryl)‐3‐
amino‐5,10‐dihydro‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
1
Orange solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 3.10
(s, 6), 6.85–6.87 (d, 3), 7.88–7.89 (m, 6), 8.06 (bs, 2). FT‐IR
(cm−1): 2890, 2208, 1658, 1608, 1491.
Shiny red solid. H NMR (400 MHz, DMSO‐d6, δ, ppm):
3.05 (s, 6), 6.75–6.77 (d, 2), 6.93–7.00 (m, 1), 7.48–7.5 (d,
1), 7.59–7.61 (d, 2), 7.87–7.89 (m, 3), 8.07–8.10 (bs + s,
4). 13C NMR (400 MHz, DMSO‐d6, δ, ppm): 40.2, 73.5,
109.6, 112.5, 114, 115.9, 117.2, 118.3, 120.1, 121.9, 125.4,
132.4, 133, 153.5, 162.5. FT‐IR (cm−1): 2901, 2214, 2122,
1664, 1529.
2.5.3 | 4c. 3‐Amino‐5,10‐dihydro‐1‐(4‐
methoxyphenyl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 3.88 (s, 3), 7.04 (d, 1), 7.18–7.20 (d, 2), 7.80 (d, 1),
7.87–7.89 (m, 2), 7.97–7.99 (d, 2), 8.08 (bs, 2), 8.41 (s, 1).
FT‐IR (cm−1): 2895, 2120, 1659, 1557, 1492.
2.5.9 | 4i. 3‐Amino‐5,10‐dihydro‐1‐(4‐
hydroxyphenyl)‐5,10‐dioxo‐1H‐pyrazolo[1,2‐
b]phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.03 (s, 1), 6.93–6.95 (d, 4), 7.87–7.89 (m, 4), 8.05–
8.07 (bs, 2), 9.52 (bs, 1). FT‐IR (cm−1): 3353, 3016, 2892,
2232, 1660, 1580.
2.5.4 | 4d. 3‐Amino‐1‐(2‐chlorophenyl)‐
5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.45 (s, 1), 7.34–7.36 (m, 3), 7.46 (d, 1), 7.58–7.60
(dd, 1), 7.97–7.99 (m, 2), 8.0 (m, 2), 8.15 (bs, 2). FT‐IR
(cm−1): 3375, 3174, 2211, 1656, 1606.
2.5.10 | 4j. 3‐Amino‐1‐(3,4‐
dimethoxyphenyl)‐5,10‐dioxo‐5,10‐dihydro‐
1H‐pyrazolo[1,2‐b]phthalazine‐2‐
carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 3.79 (s, 3), 3.89 (s, 3), 7.22–7.24 (d, 1), 7.60–7.65
(m, 3), 7.88–7.89 (m, 3), 8.07 (bs, 2), 8.37 (s, 1). 13C NMR
(400 MHz, DMSO‐d6, δ, ppm): 56, 56.6, 77.2, 112.5,
114.5, 115.3, 124.6, 125.6, 127.7, 133, 137.58, 149.3, 155,
161.2. FT‐IR (cm−1): 2897, 2117, 1660, 1563, 1495.
2.5.5 | 4e. 3‐Amino‐1‐(4‐chlorophenyl)‐
5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.14 (s, 1), 7.50–8.55 (m, 10). FT‐IR (cm−1): 3365,
2197, 1657, 1581, 1490.
2.5.11 | 4k. 3‐Amino‐5,10‐dioxo‐1‐phenyl‐
5,10‐1H‐pyrazolo[1,2‐b]phthalazine‐2‐
carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.13 (s, 1), 7.31–7.38 (m, 4), 7.44–7.46 (m, 3),
7.86–8.06 (m, 2), 8.07 (bs, 2). FT‐IR (cm−1): 3014, 2895,
2227, 1657, 1603, 1492.
2.5.6 | 4f. 3‐Amino‐5,10‐dihydro‐1‐(3‐nitro-
phenyl)‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 6.34
(s, 1), 7.66–7.70 (t, 1), 7.87–7.89 (m, 2), 7.96–7.98 (m, 2),
8.06–8.07 (m, 2), 8.20 (bs, 2), 8.26–8.28 (m, 1). FT‐IR (cm
−1): 3364, 2193, 1651, 1537.
2.5.7 | 4g. 3‐Amino‐5,10‐dihydro‐1‐(3‐
methylfuran‐2‐yl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
2.5.12 | 4l. 3‐Amino‐1‐(anthracen‐9‐yl)‐
5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
1
1
Brown solid. H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.5
Orange solid. H NMR (400 MHz, DMSO‐d6, δ, ppm):
(s, 3), 6.60–6.61 (d, 1), 6.88 (s, 1), 7.38–7.39 (d, 1), 7.86–
7.89 (m, 4), 8.07 (bs, 2). 13C NMR (400 MHz, DMSO‐d6,
δ, ppm): 14.6, 64.5, 110.7, 112.6, 121.6, 124.5, 125.7
133.1, 135.6, 144.5, 153.2. FT‐IR (cm−1): 2895, 2219,
1607, 1548, 1492.
7.64–7.7 (m, 4), 7.88–7.89 (m, 4), 8.162 (bs, 2), 8.18–8.23
(m, 4), 8.89 (s, 1), 9.66 (s, 1). 13C NMR (400 MHz,
DMSO‐d6, δ, ppm): 92.5, 112.7, 113.8, 116.3, 119.7, 125.3,
126.6, 128.3, 128.9, 129.6, 130.9, 131.9, 133, 138.2, 163.1.
FT‐IR (cm−1): 2897, 2124, 1662, 1576, 1494.

ARORA AND RAJPUT
5 of 18
2.5.13 | 4m. 3‐Amino‐1‐(4‐bromophenyl)‐
5,10‐dioxo‐5,10‐dihydro‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
2.5.14 | 4n. 3‐Amino‐5,10‐dihydro‐1‐
(naphthalen‐2‐yl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.12 (s, 1), 7.464 (d, 1), 7.55 (d, 1), 7.81–7.83 (d, 1),
7.88 (m, 1), 7.9 (m, 1), 8.07 (bs, 2), 8.35 (m, 1), 8.54 (s,
1), 8.71 (s, 1). FT‐IR (cm−1): 3452, 2887, 2121, 1656, 1487.
Yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 6.29
(s, 1), 7.5 (m, 1), 7.6 (m, 1), 7.87 (m, 2), 8.03–8.13 (m, 6),
8.48 (s, 2), 8.68 (1). FT‐IR (cm−1): 3323, 2898, 2194,
1654, 1585.
2.5.15 | 4o. 3‐Amino‐1‐(2‐nitrophenyl)‐
5,10‐dioxo‐5,10‐dihydro‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light brown solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm):
6.60 (s, 1), 7.88–8.33 (m, 10). FT‐IR (cm−1): 2898, 2214,
1654, 1493.
2.5.16 | 4p. 3‐Amino‐1‐(4‐nitrophenyl)‐
5,10‐dioxo‐5,10‐dihydro‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light brown solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm):
6.29 (s, 1), 7.87–7.89 (m, 6), 8.06 (bs, 4). FT‐IR (cm−1):
3436, 2892, 2122, 1656, 1491.
2.5.17 | 4q. 3‐Amino‐5,10‐dihydro‐1‐(4‐
hydroxy‐3,5‐dimethoxyphenyl)‐5,10‐dioxo‐
1H‐pyrazolo[1,2‐b]phthalazine‐2‐
carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 3.79 (s, 6), 7.15–7.20 (d, 1), 7.37 (s, 2), 7.87–7.89
(m, 3), 8.075 (bs, 2), 8.2 (s, 1), 10.24 (bs, 1). 13C NMR
(400 MHz, DMSO‐d6, δ, ppm): 56.5, 65.4, 87.6, 106.3,
FIGURE 1 FT‐IR spectra of (a) magnetite, (b) Si‐Magnetite, (c)
Amine‐Si‐Magnetite and (d) STA‐Amine‐Si‐Magnetite nanoparticles
FIGURE 2 XRD patterns for 2θ in the
range 10–90° of (a) JCPDS card no. 19–
0629, (b) magnetite, (c) Si‐Magnetite, (d)
Amine‐Si‐Magnetite and (e) STA‐Amine‐
Si‐Magnetite nanoparticles

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ARORA AND RAJPUT
109.7, 115.7, 125.6, 133.1, 148.5, 168.8. FT‐IR (cm−1):
3337, 2901, 2224, 1601, 1502.
(m, 6), 8.65 (s, 2). 13C NMR (400 MHz, DMSO‐d6, δ,
ppm): 85.9, 103.5, 113.1, 114.1, 115, 115.8, 118.4, 125.6,
128.2, 131.1, 133.1, 133.7, 135.6, 160.2. FT‐IR (cm−1):
3323, 2207, 2118, 1661, 1584, 1474.
2.5.18 | 4r. 3‐Amino‐5,10‐dihydro‐5,10‐
dioxo‐1‐(3‐phenoxyphenyl)‐1H–
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.13 (s, 1), 6.9–8.5 (m, 15). 13C–NMR (400 MHz,
DMSO‐d6, δ, ppm): 63, 93.6, 98, 116.4, 117.7, 118.4, 119,
122.1, 124, 127.3, 127.8, 130.5, 133.2, 134.3, 135.1, 141.3,
151.1, 152.5. FT‐IR (cm−1): 3376, 2200, 1657, 1568, 1485.
2.5.22 | 4v. 3‐Amino‐5,10‐dihydro‐1‐(3‐
methoxyphenyl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
Yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 3.86
(s, 3), 6.19 (s, 1), 6.87–6.89 (m, 1), 6.99–7.02 (m, 1), 7.03 (s,
1), 7.16–7.18 (m, 1), 7.40–7.49 (m, 4), 7.7 (s, 1), 7.86–7.89
(m, 1). FT‐IR (cm−1): 2921, 2230, 2121, 1659, 1569, 1466.
2.5.19 | 4s. 3‐Amino‐1‐(4‐fluorophenyl)‐
5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 6.15
(s, 1), 7.18 (s, 2), 7.50 (s, 2), 7.88–8.10 (m, 4), 8.54 (s, 2).
FT‐IR (cm−1): 3370, 2896, 2195, 1640.
2.5.20 | 4t. 3‐Amino‐5,10‐dihydro‐1‐(3‐
hydroxyphenyl)‐5,10‐dioxo‐1H‐pyrazolo[1,2‐
b]phthalazine‐2‐carbonitrile.
Yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 5.97
(s, 1), 6.64–6.80 (t, 1), 7.03 (s, 1), 7.32 (s, 3), 7.88–8.02 (m,
3), 8.20 (s, 2), 9.40 (s, 1). FT‐IR (cm−1): 3369, 2238, 2117,
1650, 1575.
FIGURE 4 Room temperature magnetization curves of (a)
magnetite and (b) STA‐Amine‐Si‐Magnetite nanoparticles
2.5.21 | 4u. 3‐Amino‐1‐(4‐cyanophenyl)‐
5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light yellow solid. 1H NMR (400 MHz, DMSO‐d6, δ,
ppm): 6.22 (s, 1), 7.72 (s, 1), 7.84–7.88 (d, 1), 8.04–8.11
FIGURE
5
TEM
image
of
STA‐Amine‐Si‐Magnetite
nanoparticles. White arrows show magnetite nanoparticles and
black arrows show coatings
FIGURE 3 Mössbauer spectra of core nanoparticles

ARORA AND RAJPUT
7 of 18
(d, 3), 7.85–7.89 (m, 5), 8.0694 (bs, 2). FT‐IR (cm−1):
2917, 2090, 1667, 1425.
2.5.23 | 4w. 3‐Amino‐5,10‐dihydro‐5,10‐
dioxo‐1‐(thiophen‐2‐yl)‐1H–pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
1
2.5.27 | 4a′. 3‐Amino‐5,10‐dihydro‐5,10‐
dioxo‐1H‐pyrazolo[1,2‐b]phthalazine‐2‐
carbonitrile.
Light yellow solid. H NMR (400 MHz, CDCl3, δ, ppm):
6.59 (s, 1), 7.26–7.28 (t, 1), 7.80–7.81 (d, 2), 7.87–7.89 (d,
4), 8.3 (bs, 2). FT‐IR (cm−1): 2920, 2223, 1660, 1570, 1492.
1
Yellow solid. H NMR (400 MHz, DMSO‐d6, δ, ppm):
3.64–3.81 (m, 1), 4.70 (s, 1), 7.82 (s, 2), 7.94–8.02 (m, 2),
8.20–8.24 (m, 2). 13C NMR (400 MHz, DMSO‐d6, δ,
ppm): 48.5, 54.5, 55.3, 127, 127.8, 128.8, 134.1, 135.2,
152.4. FT‐IR (cm−1): 3340, 2922, 2209, 1647, 1603, 1436.
2.5.24 | 4x. 3‐Amino‐5,10‐dihydro‐5,10‐
dioxo‐1‐(1H–pyrrol‐2‐yl)‐1H–pyrazolo[1,2‐b]
phthalazine‐2‐carbonitrile.
Light green solid. 1H NMR (400 MHz, DMSO‐d6, δ, ppm):
6.52 (s, 1), 7.35–7.36 (d, 2), 7.52 (s, 2), 7.88–7.99 (m, 3),
8.06 (bs, 2), 12.13 (bs, 1). 13C NMR (400 MHz, DMSO‐d6,
δ, ppm): 63.5, 112.3, 114.6, 124.9, 127.2, 131.9, 132.4,
133,8, 154.7, 162.9. FT‐IR (cm−1): 3367, 2919, 2216, 1661,
1587, 1419.
3 | RESULTS AND DISCUSSION
The magnetite nanoparticles were prepared using a
modified co‐precipitation method combined with
ultrasonication without any use of an additive. The final
nanocatalyst, i.e. STA‐Amine‐Si‐Magnetite nanoparti-
cles, was synthesized using a wet impregnation method
with (H4SiW12O40)⋅xH2O as a precursor. Both the sup-
port and final nanocatalyst were characterized using
various techniques like FT‐IR spectroscopy, XRD,
TGA, VSM, TEM, SEM, Brunauer–Emmett–Teller
(BET) measurements, etc. We report an efficient and
convenient procedure for the synthesis of pyrazolo
derivatives from aldehydes, malanonitrile and
phthalhydrazide using the STA‐Amine‐Si‐Magnetite
nanoparticles as catalyst.
2.5.25 | 4y. 3‐Amino‐5,10‐dihydro‐1‐(2,4‐
dimethoxyphenyl)‐5,10‐dioxo‐1H‐
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
1
Yellow solid. H NMR (400 MHz, DMSO‐d6, δ, ppm):
3.71–3.79 (s, 6), 6.26 (s, 1), 6.72–6.73 (d, 1), 6.77–6.79 (d,
1), 7.21–7.23 (d, 1), 8.02–8.03 (m, 4), 8.26 (s, 2). 13C
NMR (400 MHz, DMSO‐d6, δ, ppm): 56.6, 56.8, 98.9,
108.3, 113.7, 114.4, 115.7, 125.6, 131.1, 133.1, 154.4. FT‐
IR (cm−1): 2920, 2197, 2120, 1669, 1567, 1466.
3.1 | Characterization of catalyst
2.5.26 | 4z. 3‐Amino‐5,10‐dihydro‐1‐(4‐
isopropylphenyl)‐5,10‐dioxo‐1H‐
The characteristic bands of octahedral and tetrahedral
Fe─O vibrations at 590 and 633 cm−1 corresponding to
Fe3O4 can be obviously observed in the FT‐IR spectruma
of magnetite nanoparticles (Figure 1). Appearance of
new peaks at 476, 801 and 1097 cm−1 due to stretching
pyrazolo[1,2‐b]phthalazine‐2‐carbonitrile.
1
Yellow solid. H NMR (400 MHz, DMSO‐d6, δ, ppm):
1.20–1.22 (d, 6), 2.93–2.95 (m, 1), 5.16 (bs, 1), 7.35–7.37
FIGURE 6 SEM analysis and EDX
signal of STA‐Amine‐Si‐Magnetite
nanoparticles

8 of 18
ARORA AND RAJPUT
and deformation vibrations of SiO2 testify to the success-
ful coating of SiO2 on the magnetite nanoparticles. The
retention of Keggin unit after coating is confirmed by
the presence of characteristic peaks[23,24] of H4[SiW12O40]
at 800, 897, 952, 1116 cm−1 which are due to W─O─W,
W═O and Si─O vibrations.[25,26] A broad band at around
3300–3450 cm−1 is due to absorption of OH bonds on the
surface of all materials synthesized.[27]
The diffractograms of magnetite, Si‐Magnetite,
Amine‐Si‐Magnetite and STA‐Amine‐Si‐Magnetite are
shown in Figure 2. All the peaks for magnetite were
consistent with JCPDS card no. 19–0629[28] with face‐
centred cubic structure and Fd‐3 m space group. No
additional peaks at 2θ = 23.8° and 26.1° were observed
which confirmed the formation of magnetite rather
than maghemite. Also, a lattice parameter value of
8.374 Å was calculated which corresponds to magne-
tite.[29] The XRD patterns of all materials have the same
peaks which confirmed the retention of the crystalline
structure of parental Fe3O4. A very broad peak at
2θ = 20–25° was observed which is a characteristic peak
of amorphous materials. No characteristic sharp peak of
pure STA was observed which indicated the good
dispersion of STA in the synthesized catalyst.[25,30,31]
The core nanoparticles were characterized using
Mössbauer spectroscopy at room temperature to confirm
whether in our method magnetite or maghemite have
been formed. The Mossbauer spectrum (Figure 3) was
obtained which confirmed that Fe3O4 had been
successfully synthesized[32] with a paramagnetic doublet
suggesting its superparamagnetic properties.[33–37] The
broadening of the sextet lines reaffirms the
superparamagnetic behaviour of the nanoparticles. The
fitted parameter of the spectrum, isomer shift of 0.24(1)
mm s−1, is similar to that of magnetite nanoparticles.[38,39]
The magnetic properties of magnetite and STA‐
Amine‐Si‐Magnetite nanoparticles were measured using
VSM at room temperature by cycling the field between
−10 000 and +10 000 Oe. As indicated in Figure 4, the
graph clearly reveals the superparamagnetic nature of
the materials with almost non‐measurable remanence
and coercivity. The saturation magnetization value of
STA‐Amine‐Si‐Magnetite nanoparticles was found to be
7.90 emu g−1 which is lower than that of magnetite nano-
particles which is found to be 53.96 emu g−1. The reason
could be the presence of non‐magnetic shell over mag-
netic core. This observed magnetization is sufficient to
allow the magnetic nanoparticles to be attracted by a
small magnet of surface field of 42 MGs Oe. And also
the fine hysteresis loop (Hc (Fe3O4) = 22.42 Oe, Hc
(STA‐Amine‐Si‐Magnetite) = 5.2 Oe) confirms the
superparamagnetic properties as suggested by Mössbauer
spectra.
FIGURE 7 Surface area plots of (a) magnetite, (b) Si‐Magnetite,
(c) Amine‐Si‐Magnetite and (d) STA‐Amine‐Si‐Magnetite
nanoparticles. Insets show the Type V isotherm plots

ARORA AND RAJPUT
9 of 18
TABLE 1 BET analysis of magnetite, Si‐Magnetite, Amine‐Si‐Magnetite and STA‐Amine‐Si‐Magnetite nanoparticles
Nanoparticle
Surface area (m2 g−1
)
Pore volume (cm3 g−1
)
Pore diameter (Å)
Magnetite
118.08
0.305
103.229
Si‐Magnetite
7.2464
8.5458
2.6949
0.01186
0.02998
0.006458
65.455
140.333
95.8571
Amine‐Si‐Magnetite
STA‐Amine‐Si‐Magnetite
Thermal properties of pure H4[W12SiO40] and STA‐
Amine‐Si‐Magnetite nanoparticles were investigated and
compared using TGA which was performed under nitro-
gen atmosphere from 45 to 700 °C at a heating rate of
10 °C min−1 (Figure 8). In the case of pure H4[W12SiO40],
an initial loss of 10% was observed up to 90 °C due to
moisture. After that, a weight loss of 3.6% weight was
observed from 90 to 217 °C, which is due to loss of struc-
tural water. After that, a very small loss of weight, i.e. only
around 2%, was observed to 527 °C, beyond which no loss
was observed. In comparison, in the case of STA‐Amine‐
Si‐Magnetite nanoparticles, initial loss due to moisture
was found to be 4.5% up to 229 °C, after which a loss of
only 5% was observed to 600 °C. This indicates that
H4[W12SiO40] has been stabilized thermally to some
extent on functionalizing it on the amine‐coated magne-
tite nanoparticles and it can be effectively used after coat-
ing even at higher temperatures. Quantitative
determination of the amino group coating was done using
TGA of Amine‐Si‐Magnetite nanoparticles and a loading
of 7.93 mmol g−1 was obtained[40] (Figure S1).
To determine the extent of STA loading on Amine‐Si‐
Magnetite nanoparticles, the tungsten content was deter-
mined using ICP‐OES. An amount of 0.06 g of catalyst
was suspended in 4 ml of conc. HNO3 and 2 ml of conc.
HCl and was placed in a microwave digestion system.
After digestion, the contents were cooled and made up
to a known volume in a 100 ml standard flask with deion-
ized water. Analysis of the solution using ICP‐OES
showed the presence of 20.81 ppm of tungsten in the sam-
ple, which corresponds to 0.035 mmol g−1 STA on the
Amine‐Si‐Magnetite nanoparticles.
FIGURE 8 TGA curves of (a) pure STA and (b) STA‐Amine‐Si‐
Magnetite nanoparticles under nitrogen atmosphere
A TEM image of STA‐Amine‐Si‐Magnetite nanoparti-
cles is shown in Figure 5. The nanoparticles have sizes
in the range 40–45 nm. Monodisperse nanoparticles in
non‐aggregated form are discernible which are almost
spherical in shape. The presence of STA shell on the sur-
face of multiple ferrites is clearly visible as marked by
black arrows in the figure whereas white arrows indicate
the magnetite nanoparticles. The spherical shape of nano-
particles is confirmed from SEM analysis (Figure 6). The
presence of elements like Si, W, O and Fe confirms that
STA‐Amine‐Si‐Magnetite nanoparticles have been suc-
cessfully synthesized. EDX analysis confirmed a loading
of 7.2 wt% of STA in STA‐Amine‐Si‐Magnetite nanoparti-
cles and the results were consistent with that of 7.6 wt% of
STA calculated using ICP‐OES.
To confirm the surface modification, BET surface area,
pore volume and pore diameter measurements were made
for all the layers of nanoparticles, as shown in Figure 7.
Each inset shows the Type V isotherm plot for each layer
which confirms that surfaces of all the layers are mesopo-
rous in nature. BET surface area, single point total pore
volume and average pore diameter values of nanoparticles
are summarized in Table 1. From pore diameter, we can
conclude that all the particles are mesoporous in nature.
3.2 | Application of STA‐amine‐Si‐
magnetite catalyst in synthesis of 1H–
Pyrazolo[1,2‐b]phthalazinedione
derivatives
Several experiments were preliminarily conducted to opti-
mize the conditions for the synthesis of 1H–pyrazolo[1,2‐
b]phthalazinedione derivatives. Initial optimization stud-
ies were done using phthalhydrazide, malanonitrile and
benzaldehyde as standard substrates. As evident from
Table 2, when no catalyst was used, the yield of the

10 of 18
ARORA AND RAJPUT
TABLE 2 Optimization of conditions for synthesis of 1H–pyrazolo[1,2‐b]phthalazinedione derivativesa
Entry
Catalyst (mg)
Solvent
Time (min)
Yield (%)
TONb
TOF (min−1 c
)
1
—
EtOH–H2O (1:1)
435
55.32
—
—
2
Magnetite (10)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH
180
195
210
48 min
135
330
62
49.62
58.93
60.43
84.25
41.10
42.03
63.76
72.15
68.88
70.38
93.40
98.2
2
3
0.01
3
Si‐Magnetite (10)
0.01
0.05
4
Amine‐Si‐Magnetite (10)
STA‐Amine‐Si‐Magnetite (10)
CoFe2O4 (10)
3
5
601
2
12.5
6
0.01
7
Fe3O4@cyclodextrin (10)
STA‐Amine‐Si‐Magnetite (2.5)
STA‐Amine‐Si‐Magnetite (5)
STA‐Amine‐Si‐Magnetite (7.5)
STA‐Amine‐Si‐Magnetite (12.5)
STA‐Amine‐Si‐Magnetite (10)
STA‐Amine‐Si‐Magnetite (10)
STA‐Amine‐Si‐Magnetite (10)
STA‐Amine‐Si‐Magnetite (10)
STA‐Amine‐Si‐Magnetite (10)
Pure H4[W12SiO40] (10)
2
0.007
8
1821
1030
656
402
667
701
463
—
29.3
9
62
16.6
13.6
8.3
10
11
12
13
14
15
16
17
18
48
48
60
11.1
15.5
5.1
CH3OH
45
CH3OH–H2O (1:1)
DMSO
90
64.88
—
—
—
DMF
—
—
—
—
CH3OH
120
—
65.60
—
46
0.39
—
Pure H4[W12SiO40] (1)
CH3OH
—
aReaction conditions: phthalhydrazide 1 (0.25 mmol), malononitrile 2 (0.25 mmol), benzaldehyde 3 (0.25 mmol), 10 ml of solvent, STA‐Amine‐Si‐Magnetite
nanoparticles (10 mg), refluxing.
bTurnover number.
cTurnover frequency.
reaction was 55.32% in 435 min. Using bare magnetite
nanoparticles in the reaction gave 49% yield. Other exper-
iments using the Si‐Magnetite and Amine‐Si‐Magnetite
nanoparticles gave only 58.93 and 60.43% yields, respec-
tively, in around 210 min. Similarly, CoFe2O4 nanoparti-
cles and cyclodextrin‐coated magnetite nanoparticles
gave yields of 41.10% in 135 min and 42.03% in 330 min,
respectively. But using the STA‐Amine‐Si‐Magnetite
nanoparticle catalyst gave 84.25% yield in 48 min. This
clearly showed that the reaction was catalysed by the
STA moiety. A synergistic effect is thus observed on
immobilization of STA on Amine‐Si‐Magnetite nanoparti-
cles.[41–44] An increase in catalytic activity on
heterogenizing has been well demonstrated by the results.
After that, the effect of catalyst loading on the reaction
was studied. Neither an increase nor decrease in catalyst
loading (to 2.5 or to 12.5 mg) gave any benefit to the yield
(Table 2, entries 8–11). Further, the same reaction was
carried out in various solvents (Table 2, entries 12–16)
and significant solvent effects were observed, giving a
yield of 98.2% and a trace amount of product with CH3OH
and dimethylformamide (DMF), respectively. The reaction
cannot be carried out at room temperature or at tempera-
tures lower than 60 °C and this can be attributed to the
insolubility of phthalhydrazide at low temperatures.
Therefore all the reactions have been carried out at 60 °C.
This requires appropriate refluxing of solvent for solubility.
To study further the merit of the designed catalyst as com-
pared to a conventional one, reaction with pure
H4[W12SiO40] (10 mg) was carried out, which gave desired
product but in moderate yield, i.e. 65%, and after 120 min of
reaction period (Table 2, entry 17). A reaction with pure

ARORA AND RAJPUT
11 of 18
TABLE 3 Scope of reaction with various aldehydes
Yield
(%)
Time
(min)
M.p.
(°C)
Lit.
m.p. (°C)
TOF
(min−1
)
Entry
R
Product
TON
4a
4‐Hydroxy‐3‐methoxy
92.4
33
272–276
—
660
20
4b
p‐N,N‐dimethyl
98.88
75
289–290
294–296[45]
706
9.4
4c
4‐Methoxy
97.68
67
235–238
240–242[46]
697
10.4
4d
4e
2‐Chloro
4‐Chloro
98.1
25
27
250–252
268–270
257–259[47]
700
689
28
96.57
270–272[47]
25.5
4f
3‐nitro
95.08
99.08
60
60
269–270
232–236
269–271[47]
679
707
11.3
11.7
4g
5‐Methylfurfural
—
(Continues)

12 of 18
ARORA AND RAJPUT
TABLE 3 (Continued)
Yield
(%)
Time
(min)
M.p.
(°C)
Lit.
m.p. (°C)
TOF
(min−1
)
Entry
R
Product
TON
4h
p‐N,N‐Dimethylcinnamaldehyde
91.95
16
220
—
656
41
4i
4j
4‐Hydroxy
97.13
99.87
50
21
268–270
233–237
270–272[1]
693
713
13.8
33.9
3,4‐dimethoxy
—
4k
4l
H
95.13
90.73
45
29
272–276
218–220
276–278[47]
679
648
15.1
22.3
9‐Anthracenecarboxaldehyde
—
4m
4‐Bromo
77.82
95.28
19
31
272–274
272–274
265–267[46]
555
680
29.2
21.9
4n
2‐Napthaldehyde
276–278[47]
(Continues)

ARORA AND RAJPUT
13 of 18
TABLE 3 (Continued)
Yield
(%)
Time
(min)
M.p.
(°C)
Lit.
m.p. (°C)
TOF
(min−1
)
Entry
R
Product
TON
4o
2‐nitro
95.28
68
268–270
265–266[48]
680
10
4p
4q
4‐nitro
90.91
20
264–268
264–266[46]
649
702
32.4
17.1
4‐Hydroxy‐3,5‐dimethoxy
98.35
41
292–294
—
4r
4s
3‐Phenoxy
4‐Fluoro
92.71
97.36
120
>300
—
662
695
5.5
23
262
263–265[2]
30.2
4t
3‐Hydroxy
4‐Cyano
95.73
92.74
90
25
230–234
279–280
232–236[45]
683
662
7.5
4u
—
26.4
(Continues)

14 of 18
ARORA AND RAJPUT
TABLE 3 (Continued)
Yield
(%)
Time
(min)
M.p.
(°C)
Lit.
m.p. (°C)
TOF
(min−1
)
Entry
R
Product
TON
4v
3‐Methoxy
96.42
70
260–262
264–266[49]
688
9.8
4w
4x
4y
Thiophen‐2‐carboxaldehyde
Pyrrole‐2‐carboxaldehyde
2,4‐dimethoxy
88.94
94.71
97.97
330
50
254–258
258–260
286–288
254–258
635
676
699
1.9
—
13.5
9.2
76
—
4z
4‐isopropyl
75.73
32
260–262
264–266[1]
540
16.9
4a′
Formaldehyde
93.33
32
250–252
—
666
20.8
H4[W12SiO40] (1 mg, same as that of 0.035 mmol g−1) was
also carried out and no results were obtained even after 6 h
of refluxing. The better results for designed catalyst are
due to a change in properties on conversion to nanometric
counterpart. More surface atoms in the designed catalyst
as compared to the conventional one increases the activity
of the catalyst. This observation testifies to the efficiency of
the designed catalyst in our protocol.
STA‐Amine‐Si‐Magnetite catalyst was found to be versa-
tile. Various substituted aldehydes, regardless of
With the optimized conditions in hand, we extended
the scope of this reaction to a wide range of aldehydes
(Table 3). As evident from the results in Table 3, the
SCHEME 1 Synthesis of 4a–z and 4a′

ARORA AND RAJPUT
15 of 18
electron‐donating or electron‐withdrawing substituents,
reacted efficiently to give the desired products in excellent
yields. The reactions of sterically hindered aromatic alde-
hydes
such
as
2‐chlorobenzaldehyde and 2‐
nitrobenzaldehyde also proceeded smoothly to give the
desired products 4d and 4o in high yields. In addition to
aromatic aldehydes, heterocyclic aldehydes like 3‐
phenoxybenzaldehyde, 2‐thiophenecarboxaldehyde and
pyrrole‐2‐carboxaldehyde also gave desired products 4r,
4w and 4x under the optimized reaction conditions with
92.71, 88.94 and 94.71% yields, respectively. Reactions with
aliphatic aldehydes such as formaldehyde, crotonaldehyde
and glutaraldehyde were also carried out. No products
were obtained with glutaraldehyde and crotonaldehyde,
whereas formaldehyde gave desired product (Table 3, entry
4a′). A library of pyrazolo derivatives was synthesized using
this protocol (Scheme 1) and the products were character-
ized using FT‐IR, 1H NMR and 13C NMR spectroscopy.
FIGURE 10 FT‐IR spectrum of recycled STA‐Amine‐Si‐
Magnetite nanoparticles after five cycles
has been preserved as confirmed from the FT‐IR spectrum
of recycled STA‐Amine‐Si‐Magnetite nanoparticles after
five cycles (Figure 10). Because of covalent bonding, hydro-
gen bonding and acid–base interactions between STA and
NH2 of Amine‐Si‐Magnetite nanoparticles, leaching of
STA from the nanoparticles is unlikely. In order to check
the leaching of the STA from the catalyst, an experiment
was conducted,[20] in which after completion of the reac-
tion, the reaction mixture was filtered and the catalyst col-
lected using magnetic separation was thoroughly washed
with plenty of water. The leaching of heteropolyanion from
STA‐Amine‐Si‐Magnetite nanoparticles into methanol
upon reflux during reaction was determined using UV–visible
spectroscopy as STA shows a charge transfer band corre-
sponding to O → W in UV spectra.[42] An amount of 10 mg
of catalyst was refluxed for 2–3 h in 10 ml of MeOH followed
by separation of supernatant and catalyst with the aid of an
external magnet. Two aliquots after 45 min and 2 h refluxing
were separated. Further, the supernatant solutions were
diluted with 1 N H2SO4 to set pH = 1. The amount of
heteropolyanion leached is found to be 4.02 and 4.7% after
45 min and 2 h refluxing, respectively. After 2 h refluxing,
the leaching of heteropolyanion is found to be almost the
same as after 45 min.[50]
3.3 | Recyclability of catalyst
From the green chemistry and industrial points of view,
recyclability of heterogeneous catalysts is of great impor-
tance. To check the recyclability of the catalyst, after the
completion of reaction, 10 ml of CH3OH was added to the
reaction mixture and heated to dissolve the product. The
catalyst was then separated from the clear solution of the
reaction mixture by applying an external magnet to the wall
of the beaker. The catalyst was then washed with CH3OH
and acetone and dried in an oven at 50 °C for 1 h. The cat-
alyst was then used for the next reaction. Experiments
revealed almost the same catalytic activity of recycled
STA‐Amine‐Si‐Magnetite nanoparticle catalyst as the fresh
one (Figure 9). The negligible loss in activity which is
observed could be due to loss of the catalyst during the
extraction process. This means that the catalyst structure
A mechanism of the synthesis of 1H–pyrazolo[1,2‐b]
phthalazinedione derivatives catalysed by the STA‐
Amine‐Si‐Magnetite nanoparticles is proposed, as shown
in Scheme 2. Heteropoly acids play a role similar to that
of Brønsted acids in catalysis.[23,51,52] Initially, STA proton-
ates the carbonyl group of the aldehyde[53] which further
undergoes Knoevenagel condensation with malanonitrile.
Further, Michael addition of phthalhydrazide to C═C
bond of the Knoevenagel product followed by cyclization
results in the formation of desired product.
FIGURE 9 Recycling experiment of STA‐Amine‐Si‐Magnetite
nanoparticles up to five cycles

16 of 18
ARORA AND RAJPUT
SCHEME 2 Plausible mechanism of
synthesis of 1H–pyrazolo[1,2‐b]
phthalazinedione derivatives catalysed by
STA‐Amine‐Si‐Magnetite nanoparticles
TABLE 4 Comparison of STA‐Amine‐Si‐Magnetite nanoparticles with other catalyst in the synthesis of product 4 k
Time Yield
Entry Catalyst used
Amount (min) (%)
Solvent Temperature Ref.
[54]
1
2
3
4
5
6
7
8
Al‐KIT‐6
300 mg
5 mol%
240
50
93
92
87
88
92
65
89
94
EtOH
60 °C
[55]
[56]
[46]
[2]
CAN
PEG400 45 °C
NiCl2⋅6H2O
0.1 mmol 180
1 mmol 35
EtOH
—
Reflux
120 °C
50 °C
NaHCO3
Et3N + ultrasonication
0.02 g
0.1 g
60
EtOH
—
[57]
[58]
[59]
PBBS (poly(N‐bromo‐N‐ethylbenzene‐1,3‐disulfonamide))
RH@[SiPrDABCO@BuSO3−]HSO4
40
80 °C
0.15 g
180
EtOH
—
Reflux
100 °C
PTSA (p‐toluenesulfonic acid) in ionic liquid 1‐butyl‐3‐
0.3 mmol 180
methylimidazolium bromide {[bmim]Br}
[60]
[49]
9
[Bmim]OH + microwave (100 W)
SBA‐Pr‐SO3H
0.2 ml
—
4
94
90
98
—
—
45 °C
80 °C
10
11
20
45
STA‐Amine‐Si‐Magnetite
10 mg
CH3OH Reflux (60 °C) Present
work
(Table 4). It is evident from the comparison that only a
very small amount of STA‐Amine‐Si‐Magnetite nanopar-
ticles, i.e. 10 mg, is enough for conversion of reactants to
products as compared to other catalysts which are
required in large amounts for the conversion to take
3.4 | Comparison of Present Work with
Reported Methods
In order to exhibit the merits of the present work, it has
been compared with some previously reported studies

ARORA AND RAJPUT
17 of 18
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H4[W12SiO40] catalyst supported on Amine‐Si‐Magnetite
nanoparticles for the synthesis of 1H–pyrazolo[1,2‐b]
phthalazinedione derivatives in the presence of various
aldehydes under relatively mild operating conditions. A
simple procedure for designing the catalyst has been used
without applying any inert conditions and with inexpen-
sive reagents and high catalytic activity has been attained.
A library of around 27 pyrazolo derivatives has been syn-
thesized with excellent yields. In addition to its good
activity, this protocol also offers easy catalyst separation
using an external magnet and very good recyclability of
the catalyst of up to five cycles without any significant loss
in activity, thus making this procedure more environmen-
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ACKNOWLEDGEMENTS
We are grateful to SAIF, Panjab University Chandigarh
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1
for FT‐IR, TEM and H NMR, IIT Ropar for SEM–EDX,
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XRD and H NMR, CSMCRI Bhavnagar and BIT Benga-
84658.
luru for BET, and CIL IIT Roorkee for VSM, and DST‐
FIST New Delhi for financial assistance in acquiring the
FT‐IR data at NIT Jalandhar. One of the author (P.A.) is
grateful to MHRD and NIT Jalandhar for providing
research fellowships. We would like to thank Mr.
Harminder Singh and Miss Jigyasa Badhan for their valu-
able suggestions in manuscript writing.
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How to cite this article: Arora P, Rajput JK.
Amelioration of H4[W12SiO40] by nanomagnetic
heterogenization: For the synthesis of 1H–
pyrazolo[1,2‐b]phthalazinedione derivatives. Appl
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