Heteropolyacid-based ionic liquid [Simp]3PW12O40 nanoparticle as a productive catalyst for the one-pot synthesis of 2H-indazolo[2,1-b]phthalazine-triones under solvent-free conditions

Article abstract of DOI:10.1016/j.molliq.2017.06.033

A novel Keggin-type heteropolyacid-based ionic liquid [Simp]₃PW₁₂O₄₀ was developed via the reaction of the as synthesized ionic liquid 3-sulfonic acid 1-imidazolopyridinium hydrogen sulfate [Simp]HSO₄ with an aq

Full text of DOI:10.1016/j.molliq.2017.06.033

Accepted Manuscript
Heteropolyacid-based
ionic
liquid
[Simp]3PW12O40
nanoparticles as a productive catalyst for the one-pot synthesis
of 2H-indazolo[2,1-b]phthalazine-triones under solvent-free
conditions
Reza Tayebee, M. Fattahi Abdizadeh, Behrooz Maleki, Elham
Shahri
PII:
DOI:
Reference:
S0167-7322(17)30650-5
doi: 10.1016/j.molliq.2017.06.033
MOLLIQ 7479
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
24 February 2017
4 June 2017
6 June 2017
Please cite this article as: Reza Tayebee, M. Fattahi Abdizadeh, Behrooz Maleki, Elham
Shahri , Heteropolyacid-based ionic liquid [Simp]3PW12O40 nanoparticles as a
productive catalyst for the one-pot synthesis of 2H-indazolo[2,1-b]phthalazine-triones
under solvent-free conditions, Journal of Molecular Liquids (2017), doi: 10.1016/
j.molliq.2017.06.033
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ACCEPTED MANUSCRIPT
Heteropolyacid-based ionic liquid [Simp]3PW12O40 nanoparticles as a productive catalyst
for the one-pot synthesis of 2H-indazolo[2,1-b]phthalazine-triones under solvent-free
conditions
Reza Tayebeea,c, M. Fattahi Abdizadehb*, Behrooz Malekia, Elham Shahric
aDepartment of Chemistry, Hakim Sabzevari University, Sabzevar, 96179-76487, Iran
bCellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
cDepartment of Chemistry, Payame Noor University (PNU), Tehran, 19395-4697, Iran
Abstract
A novel Keggin-type heteropolyacid-based ionic liquid [Simp]3PW12O40 was developed via the
reaction of the as synthesized ionic liquid 3-sulfonic acid 1-imidazolopyridinium hydrogen
sulfate [Simp]HSO4 with an aqueous solution of H3PW12O40. Then, the formulated
[Simp]3PW12O40 was changed to the nano-form via solvothermal processing in tetralin at 220 ºC.
After that, the provided powdered solid nanomaterial was characterized by FT-IR,1H-NMR,
XRD, SEM, EDX and TGA analyses. Then, the focused nanomaterial was handled as a
productive and encouraging nanocatalyst for the establishment of 2H-indazolo[2,1-
b]phthalazine-1,6,11(13H)-trione attendants through one-pot, multi-component contraction of
aldehydes, phthalhydrazide, and dimedone under solventless status and the generality and
practical tolerance of this useful and environmentally benign method are illustrated. The simple
work-up, smooth reaction conditions, good to excellent yields, and reasonably short reaction
times are the particular benefits of this protocol. Besides, the new nano-powdered ionic liquid
was a successful and modest catalyst that could definitely be recycled and reused several times
without apparent decrease in its catalytic activity.
Keywords: ionic liquid; heterogeneous; [Simp]3PW12O40; phthalazine-triones
Corresponding authors:
Reza
Tayebee
and
Mojtaba
Fattahi Abdizadeh, Emails:
Rtayebee@hsu.ac.ir,
mojtabafattahi@gmail.com.

ACCEPTED MANUSCRIPT
1. Introduction
The use of green catalysts and gentle situations in synthetic reactions hold out critical
considerations throughout organic synthesis approaches. This consideration can be credited to
the lessening of natural squanders and the worth of the applied techniques. Multi-component
reactions have been proved to be strikingly fruitful in producing molecular complexity in a single
synthetic operation [1-5]. In the interim, ionic liquids have been evaluated as green disclosures in
organic synthesis because of their great particular properties, for example poor vapor pressure,
tunable polarity, wide liquid range, good solvating ability, high thermal stability, and simplicity
of recyclability and common reusability without considerable decrease in their activities [6].
Among a wide range of ionic liquids, acidic counterparts, essentially ionic liquids including N-
substituted reagents, are the most imperative ones which have been effectively utilized for the
speeding up of various sorts of organic transformations via the multi-component reactions [7,8].
Heteropolyacids (HPAs) as an important class of inorganic transition-metal oxide clusters
included an extensive variety of fabulous properties such as high stability, relatively non-
toxicity, crystallinity, and ease of handling; which, have pulled in special interests in medicine,
biology, catalysis and materials science [9-12]. Recently, ionic liquids involving
polyoxometalates, which are comprised of heteropolyanions and appropriate organic cations,
have attracted impressive interests as a new family of ionic liquids [13] and have been emerged
as potential compounds in nanotechnology, electrochemistry, and catalysis [14–16].
Heterocycles containing phthalazine moiety have critical pharmacological properties such
as anti-inflammatory [17], anti-convulsant [18], anti-microbial [19], anti-fungal [20] and anti-
cancer [21] activities. Accordingly, synthesis of 2H-indazolo[2,1- b]phthalazine-triones has been
the concentration of enthusiasm for as far back as decade and distinctive types of mediators such
as silica sulfuric acid [22], trimethylsilyl chloride [23],
cyanuric chloride [24],
dodecylphosphonic acid [25], p-TSA [26], H3PW12O40 in 1-butyl-3-methylimidazolium
tetrafluoroborate [27], Mg(HSO4)2 [28], H2SO4 in water–ethanol [29], silica-supported poly
phosphoric acid [30], N-halo sulfonamides [31], sulfonated poly(ethylene glycol) [32], wet
cyanuric chloride [33], 1,1,1,3,3,3-hexafluoro-2-propanol [34], Fe(III)-based dicationic ionic
liquid, [C4(mim)2](FeCl4)2 [35], Fe3O4@silica sulfuric acid nanoparticles [36], phosphomolybdic
acid (PMA/SiO2) [37], and tungstosilicic acid [38] have been applied for this transformation.

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Taking into account disadvantages of the existing protocols, such as low product yields, long
reaction times, costly motivators, poisonous reagents and solvents, and trouble in recovery and
reuse of the catalysts, extension of new effective and environmentally benign methodology
permitting simple synthesis of phthalazine heterocycles is therefore necessary.
As of late,
a
new ionic liquid [Simp]HSO4 (3-sulfonic acid 1-
imidazolopyridinium hydrogensulfate) is investigated and applied as catalyst; in any case, liquid
nature of this catalyst made work-up and reuse troublesome [39, 40]. Herein, we wish to
introduce devising, characterization, and application of a new heterogeneous catalyst
[Simp]3PW12O40 with upgraded catalytic activity in promoting synthesis of 2H-indazolo[2,1-
b]phthalazine-trione derivatives (Scheme 1). The solid catalyst was set up by blending an
aqueous solution of H3PW12O40 with the liquid [Simp]HSO4.
R1
O
H
O
O
O
O
[Simp]3PW12O40, 0.03 g
Solvent-free, 100 oC
O
N
N
NH
NH
+
+
R2
O
R1
R2
R2
O
R2
R2=CH3, H
R1=halogen, electron withdrawing (releasing) group
Scheme 1. Typical formulation for the synthesis of different phthalhydrazide-triones.
2. Experimental
2.1. Materials
Materials and reagents were obtained from Merck, Fluka, and Aldrich. All yields allude to the
isolated products which were identified by comparison of their physical data and also their FT-IR
1
and H-NMR spectra with the previously reported and authentic. The purity assurance of the
substrates and reaction monitoring were joined by TLC on silica gel polygram SILG/UV 254
plates. Solid state FT-IR spectra were recorded utilizing the KBr disk strategy on an 8700

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1
13
Shimadzu Fourier Transform spectrophotometer. H and C NMR (300 and 100 MHz) spectra
were reported on a Bruker-Avance spectrometer. Scanning electron microscope (SEM)
micrographs were attained using a KYKY-EM3200 microscope (acceleration voltage 26 kV).
Crystallinity was assessed by powder X-ray diffraction (XRD) on a PW1800-PHILIPS
diffractometer with Cu Kα radiation (λ = 1.5418 Ǻ) at 40 kV and 30 mA. Thermogravimetric
(TGA) analysis was performed on a Bahr STA-503 instrument in air at a heating rate of 10
°C/min−1. A freeze dryer, Model FD-10, Pishtaz Equipment Engineering Co, Iran, was used for
occasional drying of the prepared nanocatalyst. Melting points were obtained in open capillaries
on a Bamstead electrothermal type 9200 melting point apparatus.
2.2. Preparation of 3-sulfonic acid 1-imidazolopyridinium hydrogen sulfate [Simp]HSO4
Caffeine (0.9710 g, 5 mmol) in dry CH2Cl2 (50 ml) was added to a round-bottomed flask. Then,
chlorosulfonic acid (0.59 g, 5.1 mmol) was included drop-wise for 20 min at ambient
temperature. Then, the reaction mixture was stirred for 12 h. The residue was washed with dry
CH2Cl2 (3×50 ml) and dried to give 3-sulfonic acid imidazolopyridinium chloride [Simp]Cl as a
viscous thick yellow-brown oil. At that point, sulfuric acid (0.49 g, 5 mmol) was added drop-
wise to [Simp]Cl (1.155 g, 5 mmol) over a period of 5 min at room temperature to remove the
produced HCl during the reaction. At long last, the subsequent mixture was stirred for 24 h at 60
°C under aerobic conditions to give [Simp]HSO4 as a viscous yellow oil. FT-IR (KBr, cm−1) υmax
582, 886, 1012, 1174, 1683, and 2395–3480.
:
2.3.Synthesis of 3-sulfonic acid 1-imidazolopyridinium tungstophosphate [Simp]3PW12O40
[Simp]3PW12O40 was prepared by following the procedure detailed by Ammam and Fransaer
[41]. In an average arrangement, phosphotungstic acid (H3PW12O40, 1.5 g) was dissolved in 5 ml
deionized water. Then, [Simp]HSO4 (0.7 g) was gradually added to the above solution with
continuous stirring. Then, the reaction mixture was stirred at room temperature for 24 h to form a
yellowish powder. The precipitate was filtered, washed with deionized water and dried under
aerobic conditions. The resulting solid product was characterized by spectroscopic techniques
and formulated as [Simp]3PW12O40. To fragmentize the obtained ionic liquid particles to the
nanoparticles, solvothermal technique was used. For this purpose, 0.2 g of [Simp]3PW12O40 was
added to 70 ml of tetralin with strong stirring for 30 min. Thereafter, the mixture was transferred

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to Teflon steel autoclave and the closed container was heated to 220 °C for 24 h. Finally, the
container was gradually cooled to room temperature and the separated solid material was dried at
80 °C for 12 h. To study effect of drying conditions on the catalytic efficacy of [Simp]3PW12O40,
the prepared final material was dried under freeze conditions. Results showed no obvious
improvements in the catalytic activity of this sample with the one dried under usual thermal
conditions as described above.
2.4. General route for the synthesis of 2H-indazolo[1,2-b]phthalazine-triones
1,3-Diketones (0.25 mmol), phthalhydrazide (0.25 mmol), aromatic aldehydes (1 mmol), and the
heterogeneous catalyst [Simp]3PW12O40 (0.03 g) were thoroughly mixed in a test tube and heated
at 100 °C in an oil-bath under solvent-free conditions for the required time. Fulfillment of the
reaction was observed by TLC: n-hexane: ethyl acetate (8:2). After completion, the reaction
mixture was cooled to room temperature and chloroform was added. After a minute, the
heterogeneous catalyst was filtered and chloroform was dissipated from the residue. At that
point, 5 ml of hot ethanol was added to the reaction mixture and stirred for 5 min. After wards,
the reaction mixture was cooled to 5 °C and the acquired phthalazine-trione precipitate was
separated. Further re-crystallization in ethanol afforded the highly pure product. All products
1
13
were known compounds and were described by FT-IR, H NMR, C NMR, and determination
of their melting points [27, 31, 38–40].
2.5. Spectral data for some representative 2H-indazolo[1,2–b]phthalazine-1,6,11(13H)-triones
3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione
(Table 6, entry 1): IR (KBr) 2958, 1664, 1576 cm-1; 1H NMR (300 MHz, CDCl3): δ (ppm) 1.24
(s, 6H), 2.45 (s, 2H), 3.23 and 3.45 (d, AB system, J = 18.0 Hz, 2H), 6.45 (s, 1H), 7.32-8.35 (m,
13
9H, Ph); C NMR (100 MHz, CDCl3): δ (ppm) 28.4, 28.6, 34.7, 38.2, 50.9, 64.8, 118.2, 127.1,
127.6, 127.8, 128.7, 128.9, 129.1, 133.6, 134.5, 136.4, 150.9, 154.3, 156.2, 192.3.
3,4-dihydro-3,3-dimethyl-13-(4-chlorophenyl)-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-
1
trione (Table 6, entry 3): IR (KBr) 2957, 2931, 1688, 1654, 1622 cm-1; H NMR (300 MHz,
CDCl3): δ (ppm) 1.22 (s, 6H, 2Me), 2.33 (s, 2H, CH2C), 3.22-3.44 (AB system, J =19.2 Hz, 2H,
CHaHbCO), 6.41 (s, 1H, CHN), 7.28-7.38 (dd, J= 8.4 Hz, 4H, ArCl), 7.84-8.38 (m, 4H, Ph); 13C

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NMR (100 MHz, CDCl3): δ (ppm) 28.5, 28.7, 34.7, 38.0, 50.9, 64.31, 118.5, 127.1, 127.7, 127.8,
128.6, 128.6, 128.8, 129.1, 133.4, 134.5, 136.3, 150.8, 154.4, 156.0, 192.2.
3,4-dihydro-3,3-dimethyl-13-(4-nitrophenyl)-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-
1
trione (Table 6, entry 3): IR (KBr) 2965, 2375, 1666 cm-1; H NMR (300 MHz, CDCl3): δ
)ppm) 8.29–8.08 (m, 4H), 7.80–7.79 (m, 2H), 7.53 (d, J = 8.4 Hz, 2H), 6.41 (s, 1H), 3.35–3.15
(AB system, J = 19.2 Hz, 2H), 2.25 (s, 2H), 1.13 (s, 3H), 1.10 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 192.1, 155.9, 154.5, 151.7, 147.8, 143.4, 134.8, 133.9, 128.9, 128.5, 128.2,
128.0, 127.7, 124.0, 117.2, 64.1, 50.7, 37.9, 34.7, 28.6, 28.3.
3,4-dihydro-3,3-dimethyl-13-(2-chlorophenyl)-2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-
1
trione (Table 6, entry 4): IR (KBr) 3058, 2957, 2894, and 1662 cm-1; H NMR (300 MHz,
CDCl3): δ (ppm) 1.21 (s, 3H), 1.23 (s, 3H), 2.34 (s, 2H), 3.26 and 3.45 (d, AB system, J = 19.1
Hz, 2H), 6.66 (s, 1H), 7.24-8.41 (m, 8H, Ph); 13C NMR (100 MHz, CDCl3): δ (ppm) 28.3, 28.7,
34.5, 37.9, 50.8, 63.9, 116.6, 127.1, 127.5, 127.9, 128.6, 129.0, 129.8, 130.4, 132.5, 133.0, 133.5,
134.4, 151.8, 154.1, 156.1, 192.0.
3,4-dihydro-3,3-dimethyl-13-(4-methylphenyl)-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-
trione (Table 6, entry 5): IR (KBr) 2897, 1663, 1654, 1603, 1600, 1497, 1085, 827, 790, 687,
1
627, 495 cm-1; H NMR (300 MHz; CDCl3): δ (ppm) 1.17 (s, 6H), 2.25 (s, 3H), 2.28 (s, 2H),
3.18-3.37 (AB system, s, 2H, J = 18.85 Hz), 6.36 (s, 1H), 7.08–7.2 (m, 4H), 7.8 (m, 2H), 8.2–8.3
13
(m, 2H); C NMR (100 MHz, CDCl3,): δ (ppm) 21.6, 28.8, 29.1, 35.0, 38.4, 51.3, 65.1, 118.9,
127.4, 128.0, 128.3, 129.3, 129.5, 129.7, 133.8, 134.8, 138.8, 151.1, 154.6, 156.3, 192.4.
3. Results and Discussion
An acidic ionic liquid is characterized as a low melting ionic salt involving Brönsted, Lewis, or
a combination of Brönsted and Lewis acidic characteristics. The acidic function(s) or group(s)
can be either in the cation, anion, or both [6]. Apparently, in [Simp]3PW12O40, Simp+ cation and
heteropolyoxometalate anion carry on as Brönsted and Lewis acid sites, individually. Scheme 1
provides the general pathway for the preparation of [Simp]3PW12O40 from the reaction of
[Simp]HSO4, with the heteropolyacid H3PW12O40. As indicated by our previous work,
[Simp]HSO4 was fabricated from the reaction of caffeine with chlorodulfonic acid in dry
dichloromethane with subsequent substitution of the chloride counter ion with hydrogen sulfate.

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Then, the prepared high dense ionic liquid [Simp]HSO4 was separated and treated with
H3PW12O40 in the second step to afford a pale yellow precipitate of [Simp]3PW12O40 as an
immaculate powder. From that point, this new fabricated catalyst was performed in the
preparation of indazolophthalazine-trione derivatives. The structure of [Simp]3PW12O40 provides
functional Brønsted acidic hydrogen sulfate sites along with Lewis acidic sites of W+6 in the
framework of Keggin anion. Subsequently, [Simp]3PW12O40 behaved as an ideal acid catalyst in
the desired organic transformation.
O
O
O
CH3
CH3
H
CH3
H3C
O
N
N
H3C
O
H3C
O
dry CH2Cl2
ClSO3H
N
N
H2SO4
-HCl
N
N
N
N
N
-
H
Cl-
HSO4
H
N
N
N
SO3H
SO3H
CH3
CH3
CH3
caffeine
[Simp]Cl
[Simp]HSO4
(dense brownish liquid)
O
CH3
H3C
N
N
[Simp]HSO4
+
H
H3PW12O40
N
O
N
PW12O40
SO3H
CH3
3
(powdered yellow solid)
Scheme 2. A general route for the synthesis of 3-sulfonic acid 1-imidazolium hydrogen sulfate
[Simp]HSO4 and the heteropoly anion substituted [Simp]3PW12O40.
3.1. Structural identification of [Simp]3PW12O40
The infrared spectra of H3PW12O40 and [Simp]3PW12O40 are appeared in Fig. 1. PW12O403- with
m+
(80−12m−n)−
the Keggin structure is communicated by the general formula of [Xn+M12 O40]
(heteroatom X= P, As, Si, etc., polyatom M= W, Mo, etc.) and provided strong peaks at 1080,
980, 892, and 812 cm-1 due to the four sorts of oxygen atoms P-Oi, W-Ot, W-Ob-W, and W-Oc-
W, respectively (Fig. 1a). In the FT-IR spectrum of [Simp]3PW12O40 (Fig. 1b) the strong
stretching vibrations at 1100-800 cm-1 are distinctively credited to the above Keggin structure
[41]. Hence, the Keggin structure is retained after exchanging of the protons with the
imidazolopyridinium cation. In examination with the parent anion PW12O403- in H3PW12O40, the
vibration frequencies of the polyoxometalate in the ionic liquid has slight shifts, which showed

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that the bonds of the heteropoly anion are fortified or weakened owing to the interaction with the
organic cation. The FT-IR spectrum of [Simp]3PW12O40 showed a broad peak at 3000–3700 cm−1
which can be related to the stretching of OH, SO3H, and the adsorbed water molecules.
Moreover, the C–H stretching vibrations are covered with above broad band. The strong peaks
observed at 886, and 597 cm−1 related to the S–OH bending and symmetric S–O stretching
vibrations, respectively [42,43]. Furthermore, the band at 887 cm−1 would be related to the N–
SO2 vibrations [44]. The bands at 1595 and 1638 cm−1 were due to C=N and C=C ring vibration
1
of the imidazole part of the ionic liquid. The H NMR spectrum of [Simp]3PW12O40 showed the
acidic hydrogen of -SO3H at 7.81 ppm in acetone.

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Fig. 1. FT-IR spectra of H3PW12O40 (a) and [Simp]3PW12O40 (b).
1
In the H-NMR spectrum of [Simp]3PW12O40 in DMSO, the number of the signals fitted
l
exactly with the structure of ionic liquid (Fig. 2) which afforded four H signals due to three
methyl groups at 3.33, 3.44 and 3.88 and one proton attached to the aromatic ring at 8.02 δ ppm.

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Fig. 2. 1H-NMR spectrum of [Simp]3PW12O40.
The synthesized nanopowdered ionic liquid [Simp]3PW12O40 was likewise investigated
by SEM with different amplifications for determining the particle size, shape, and surface
morphology (Fig. 3). These pictures demonstrated that in view of synthetic alteration, formation
of nanoparticles of [Simp]3PW12O40 would provide an extended heterogeneous surface as
catalyst for the targeted multi-component organic transformation. EDX investigation was
additionally confirmed combination of the heteropoly anion with [Simp]+. The peaks in the XRD
patterns of H3PW12O40 and [Simp]3PW12O40 are situated at the wide-angle region of 2θ= 10–50°.
Clearly, comparison of the two patterns confirms that a phase change is happened as a result of
the substitution of the secondary structure protons in H3PW12O40 with the organic cations. (Fig.
4).

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Fig. 3. SEM micrographs (up) and EDX (bottom) analysis of [Simp]3PW12O40 nanoparticles.

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Fig. 4. XRD patterns of H3PW12O40 (a) and [Simp]3PW12O40 nanoparticles (b).
The heteropolyacid H3PW12O40 in its non-reduced structures is generally characterized by
oxygen-to-metal (O–M) charge transfer bands, which show up in the UV district around 265 nm.
They are trademark bands of the Keggin structure, and relate to the charge transfer from the
bridge oxygen atoms (Ob, Oc) to the metal atoms [41]. Be that as it may, it should be mentioned
that the electronic transitions of n-σ* and π-π* due to nitrogen atoms and carbonyl groups in
caffeine fragment provide an unmistakable absorption band at about 265-270 nm in the UV-Vis

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spectrum of [Simp]HSO4 and [Simp]3PW12O40. Furthermore, a little difference between the
maximum absorption bands of [Simp]HSO4 and [Simp]3PW12O40 in Fig. 5, indicating that the
wavelength of the band does not significantly vary with the counter cation.
Fig. 5. UV-vis spectra of [Simp]HSO4 (a), [Simp]3PW12O40 (b), H3PW12O40 (C).
The thermogravimetric behaviour of [Simp]3PW12O40 is shown in Fig. 6. The initial low
temperature weight loss was due to the removal of water molecules that occurred below 200 °C.
The second step was for the beginning of the decomposition of organic parts that occurred in the
range of 380–450 °C. The rapid weight loss started above 450 °C was mainly due to the
decomposition of Keggin heteropolyacid moiety to WO3 and P2O5 [45]. The thermal stability of
the Keggin units have been affected because of their interaction with the imidazolopyridinium
moieties.

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Fig. 6. TGA of [Simp]3PW12O40 molecular nanohybrid material.
3.2. Performance of [Simp]3PW12O40 in the catalytic preparation of different indazolo-
phthalazine-triones
3.2.1. Effect of the heteropolyacid nature and structure
Catalytic activity of Keggin H3PW12O40 was compared with some illustrative heteropolyacids in
the
preparation
of
2,2-dimethyl-13-phenyl-2,3-dihydro-1H-indazolo[2,1-b]phthalazine-
4,6,11(13H)-trione (DMP) (Table 1). Almost, all the examined Keggin and Wells-Dawson
heteropolyacids are strong acids and showed good catalytic activity in the desired
transformation. Results uncovered that both Keggin and Wells-Dawson heteropolyacids behaved
as efficient catalysts and prompted to 82-85% yield after 20 min. Notwithstanding, the Keggin
H3PMo12O40 and the transition metal substituted Wells-Dawson H7FeP2W17O61 showed lower
activity and gave 60 and 75% of conversion, respectively.

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Table 1. Effect of the heteropolyacid nature and structure on the efficacy of the preparation of
DMP.a
Catalyst
Structure type
Keggin
Time (min)
Yield (%)b
H3PMo12O40
H3PW12O40
20
20
20
20
20
60
82
75
83
85
Keggin
H7FeP2W17O61 Wells-Dawson
H5PW10V2O40
H6P2W18O62
Keggin
Wells-Dawson
a0.03 g of catalyst was added to a mixture of phthalhydrazide (0.25 mmol), aldehyde (0.25
mmol), and dimedone (0.25 mmol) and the mixture was stirred at 100 ºC for 20 min. bIsolated
yields.
3.2.2. Optimization of the reaction conditions
Condensation of benzaldehyde (0.25 mmol), dimedone (0.25 mmol) and phthalhydrazide (0.25
mmol) to 2H-indazolo[2,1-b]phthalazine-4,6,11(13H)-trione was chosen to afford the ideal
conditions. In the first place, impact of [Simp]3PW12O40 concentration was considered. It was
found that 2H-indazolo[2,1-b]phthalazine-trione was created in a trace amount after 20 min in
the absence of catalyst; whereas, 0.01g of catalyst led to 50% yield after 20 min. As appeared in
Table 2, this transformation needs presence of catalyst; along these lines, the optimum amount of
0.03g was decided for the preparation of the desired phthalazine-triones. It should be noticed that
higher amounts (>0.03 g) have no constructive outcome on the reaction time or yield%.
Table 2. Effect of the catalyst amount on the preparation of DMP. a
Entry
[Simp]3PW12O40
Time (min)
Yield (%)b
1
0
20
20
20
20
20
0
2
3
4
5
0.01
0.02
0.03
0.04
50
61
85
83

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aGeneral reaction conditions are as described below Table 1. bIsolated yields
3.2.3. Effect of reaction temperature, time, and solvent on the catalytic system
Effect of reaction temperature was researched in the synthesis of 3,4-dihydro-3,3-dimethyl-13-
phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione (DMP) in the sight of 0.03 g of
[Simp]3PW12O40(Figs. 7-8). Findings uncovered that yield% was expanded with improving
º
reaction temperature from 25 to 100 C. Impact of reaction time was also inspected. Findings
showed that yield% was improved with time and the finest yield was gained after 20 min and no
better outcomes were acquired under continued times.
Fig. 7. Effect of temperature on the preparation of DMP.

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Fig. 8. Effect of time on the preparation of DMP.
Despite the way that this system is under solvent free conditions, even though, effects of
some familiar solvents with various polarity were contemplated on the model reaction and the
obtained results were compared with the solvent free case (Table 3). This study was carried out
under reflux conditions for each solvent. Clearly, the solvent free approach was found to be more
powerful than the solvent system considering both the reaction time and yield%.
Table 3. Effect of different solvents on the condensation of benzaldehyde, phthalhydrazide and
dimedone.a
Entry
Solvent
Condition
Time (min)
Yield (%)b
1
2
3
4
5
H2O
Reflux
Reflux
Reflux
Reflux
100 °C
120
120
120
120
20
48
35
45
46
85
CH2Cl2
Chloroform
Toluene
Free-solvent
General reaction conditions are as described below Table 1. bIsolated yields

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3.3. Exploring condensation of phthalhydrazide and aromatic aldehydes with different diketones
To study impact of diketone structure on the condensation reaction, different acyclic diketones
were chosen to react with phthalhydrazide and benzaldehyde in the presence of [Simp]3PW12O40
(Table 4). Among the examine diketones, 5,5-dimethyl-1,3-cyclohexane-dione (dimedone) and
1,3-cyclohexanedione prompted to the best yield (85 and 90% respectively). The two other linear
dikenones, i.e 2, 5-hexane-dione and 3, 5-hexane-dione were clearly less compelling than the
cyclic ones and led to 23 and 37% yield, respectively, after 20 min. Also, only a trace amount of
the desired product was attained for ethyl acetoacetate as substrate.
Table 4. Studying reactivity of cyclic and linear hexanediones towards the condensation
reaction.a
Diketone
Structure
Time (min) Yield (%)b
O
5,5-dimethyl-1,3-cyclohexane-dione
1,3-cyclohexane-dione
20
20
85
89
O
O
O
O
2,5-hexane-dione
20
23
O
3,5-hexane-dione
ethyl acetoacetate
20
20
37
O
O
O
trace
OEt
O
aGeneral reaction conditions are as described below Table 1. bIsolated yields.

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3.4. Comparison of the catalytic activity of [Simp]3PW12O40 with some reported catalysts
Catalytic activity of [Simp]3PW12O40 was compared with some revealed catalysts as portrayed in
Table 5. The general condensation reaction of dimedone, phthalhydrazide, and benzaldehyde was
considered as a delegate illustration and the correlation was in terms of mol% or measure of the
catalyst, reaction time, temperature, and yield%. The present new catalytic system behaved as
one of the best protocols considering simplicity and cost of the procedure. Albeit, some of the
introduced mediators catalyzed the reaction at a reduced temperature, however, they require
toxic and costly solvents, higher amounts of catalyst, and longer reaction times.
Table 5. Comparison of the catalytic efficiency of [Simp]3PW12O40 with some reported catalysts.
Entry
Catalyst and Conditions
Time
(min)
Yielda
(%)
Ref.
H2SO4[bmim][BF4], 80 ºC
1
2
3
4
5
30
120
35
86
94
29
33
36
CAN, Solvent free, 50 ºC
Fe3O4@Silica sulfuric acid, Solvent free, 100 ºC
PMA–SiO2 (0.05 mmol), Solvent-free, 80 ºC
[Simp]3PW12O40
88
30
85
37
This work
20
85
aIsolated yields.
3. 5. Synthesis of substituted phthalazine-triones
All inclusive statement of the present convention was surveyed by applying condensation
reaction with various substituted benzaldehydes. In all cases, the reactions provided the desired
products in good to excellent yields. As shown in Table 6, a series of aromatic aldehydes
containing either electron-withdrawing or electron-donating substituents effectively responded
and afforded the corresponding pure products under the selected conditions. Although, aldehydes
bearing electron-deficient groups led to better yields, however, the reactions proceeded easily

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and equally for both electron-withdrawing and electron-donating substituted. Therefore, the
nature and electronic aspects of the substituents had no an evident and essential impact on the
rate and reaction yield.
Table 6. Synthesis of different 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones in the
presence of [Simp]3PW12O40 under solvent-free conditions.
R1
O
H
O
O
O
O
O
[Simp]3PW12O40, 0.03 g
Solvent-free, 100 oC
O
N
N
NH
NH
+
+
R2
O
R1
R2
R2
R2
Enty
R1
R
Time (min)
Yield (%)a
m.p. / lit. m.p.
(ºC)
Ref.
1
2
Ph
4-FPh
4-ClPh
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
20
80
80
80
50
60
60
60
80
60
40
20
20
15
85
80
83
82
75
68
74
66
70
73
70
89
90
92
205-207/204-206
220-222/218-220
261-263/261-263
223-225/223-225
264-266/264-266
208-210/210-211
218-220/220-221
225-227/227-229
256-258/257-259
205-207/207-209
235-237/238-240
220-222/222-225
280-282/279-282
230-232/228-231
22
22
22
22
22
23
24
22
34
28
32
25
25
25
3
4
4-NO2Ph
2-ClPh
5
6
3-OMePh
4-OMePh
4-Me-Ph
4-(CH3)2NPh
3-ClPh
7
8
9
10
11
12
13
14
2-NO2Ph
Ph
4-BrPh
H
3-NO2Ph
H
aYields point out to the isolated neat products. The desired pure products were described by
comparison of their physical data with those of known samples.

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3.6. Hot filtration test
With a specific end goal to affirm that the catalytic activity was started from the ionic liquid
catalyst [Simp]3PW12O40 and not from the drained segments (if possible) in the reaction mixture,
a hot filtration test was done. In this technique, the condensation reaction of benzaldehyde was
performed at 100 °C for 10 min in the presence of the [Simp]3PW12O40. Then, the reaction
mixture was cooled to room temperature and the yield of 59% was accomplished as depicted in
the experimental section. A short time later, the heterogeneous catalyst was filtered and
chloroform was evaporated from the residue and the reaction was continued with the filtrate at
100 °C for another 20 min (total time 30 min). However, no corresponding increase in the
product yield beyond 59% was watched. This outcome affirmed the heterogeneous nature of the
catalyst and that no leaching of the components occurred during the course of the reaction. FT-
IR, XRD, UV-Vis, and 1H NMR of the recycled catalyst after 4th run were compared to the fresh
one. In agreement with the results of recyclability, no observable spectral changes were detected
for the recycled catalyst.
3.7. Reusability and reproducibility of [Simp]3PW12O40
The reusability of the catalyst was tested in the synthesis of DMP, as shown in Fig. 9. The
catalyst was recouped after each run, washed three times with chloroform, dried in an oven at 80
ºC for 4 h and tested in a subsequent run. The catalyst was approved for 5 runs. It was observed
that the catalyst displayed very good reusability. Additionally, to ensure reproducibility of the
transformation, duplicated typical experiments were carried out under similar reaction
conditions. The obtained yields were observed to be reproducible within ±3% variation.

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Fig. 9. Yield% vs of reusability of [Simp]3PW12O40 catalyst.
4. Conclusion
In outline, a new ionic nanomaterial [Simp]3PW12O40 was fabricated and utilized as a proficient
impetus for the one-vessel synthesis of 2H-indazolo-phthalazine-triones via the contraction of
dimedone, phthalhydrazide and aromatic aldehydes. The catalytic reactions were adjusted under
thermal solventless conditions in brief times. Besides, the catalyst could be profitably renewed
and reused at least for five runs without serious loss of activity. The one-pot feature and
utilization of heterogeneous solid acid catalyst, as an eco-friendly mediator, provided the current
protocol suitable for multi-step approaches. This methodology bears significant improvements
such as the heterogeneous impetus of the catalyst, scope of the transformation, accessible
operation and simple work up.
5. Acknowledgments
Partial financial support from the Research Councils of Sabzevar University of Medical Sciences
and Hakim Sabzevari University is greatly appreciated.

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Graphical abstract

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Highlights


Preparation of a new powdered ionic liquid [Simp]3PW12O40
The catalyst was an inexpensive and efficient catalyst with high recycle ability without
significant loss of activity

The entire synthetic sequence is cost-effective, environmentally friendly, and possesses
acceptable generality