A new inorganic-organic hybrid material Al-SBA-15-TPI/H6P2W18O62 catalyzed one-pot, three-component synthesis of 2H-indazolo[2,1-b]phthalazine-triones

Article abstract of DOI:10.1039/c4dt03504f

A new inorganic-organic hybrid material Al-SBA-15-TPI/H₆P₂W₁₈O₆₂ was prepared and fully characterized by SEM, XRD, FT-IR, TGA-DTA, and UV-Vis spectroscopic techniques. Then, the prepared nanomaterial was used as a simple, cost-effective, and reusable heterogeneous catalyst for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives by a one-pot, three-component condensation reaction of phthalhydrazide, cyclic diones, and aromatic aldehydes under solvent free conditions at 100°C in a short time. This methodology has proven to be efficient and environmentally benign in terms of high yields and low reaction times and offers significant improvements with regard to the scope of transformation and simplicity of operation by avoiding expensive or corrosive catalysts.

Full text of DOI:10.1039/c4dt03504f

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A new inorganic-organic hybrid material Al-SBA-15-TPI/H6P2W18O62 catalyzed one-
pot, three-component synthesis of 2H-Indazolo[2,1-b]phthalazine-triones
a
R. Tayebee∗ , M. M. Aminib, S. Pouyamanesha, A. Aliakbari b
aDepartment of Chemistry, School of Sciences, Hakim Sabzevari University, Sabzevar 96179ꢀ76487,
Iran
bDepartment of Chemistry, Shahid Beheshti University, G.C., Tehran 1983963113, Iran
Abstract
A new inorganicꢀorganic hybrid material AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 was prepared and was
fully characterized by SEM, XRD, FTꢀIR, TGAꢀDTA, and UVꢀVis spectroscopic techniques.
Then, the prepared nanomaterial was used as a simple, costꢀeffective, and reusable
heterogeneous catalyst for the synthesis of 2Hꢀindazolo[2,1ꢀb]phthalazineꢀ1,6,11(13H)ꢀtrione
derivatives by a oneꢀpot, threeꢀcomponent condensation reaction of phthalhydrazide, cyclic
diones, and aromatic aldehydes under solvent free conditions at 100 ºC in a short time. This
methodology proves to be efficient and environmentally benign in terms of high yields and
low reaction times and offers significant improvements with regard to the scope of
transformation and simplicity in operation by avoiding expensive or corrosive catalysts.
Keywords: Nanohybrid catalyst; H6P2W18O62; Phthalazineꢀtriones; Heterogeneous.
1. Introduction
Study of hybrid organicꢀinorganic materials is an attractive prolific enterprise. Today
fabrication, characterization, modification, and technological applications of organicꢀ
inorganic hybrid nanomaterials constitute an emerging prominent field in nanoscience and
nanotechnology.1,2 Synergism between hydrophobic and hydrophilic properties of the main
components of hybrid materials exploited extraordinary properties and allow their
applications in many fields. The design of novel hybrid nanocatalysts with new or improved
properties has been the subject of attractive research fields in recent years.
Heterogenization of the heteropolyacids in an organic matrix and innovation of new
organicꢀinorganic hybrid catalysts has been a recent trend in heterogeneous catalysis.3,4
Therefore, hybridization of heteropolyacids offers new routes to generate wellꢀdefined,
∗ Corresponding author: Reza Tayebee, Email: Rtayebee@hsu.ac.ir; Tel:+98ꢀ51ꢀ44410310; Fax: +98ꢀ51ꢀ44410300
† Electronic supplementary information (ESI) is available.
1

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functionalized molecular and supramolecular architectures through anchoring of
heteropolyacids with an organic linker. Among different types of heteropolyacids, Wellsꢀ
Dawson polytungsticacids are effective catalysts, which could be loaded on the surface of
mesoporous materials such as SBAꢀ15 to achieve a heterogeneous and reusable catalyst.
In the past few decades, heterocyclic chemistry has been one of the most profound
disciplines in organic synthesis and pharmaceutical chemistry.5 Heterocycles involving
phthalazine moieties, which are capable to generate a bridgehead hydrazine, possess a wide
range of implementations in pharmacology, such as anticonvulsant, vasorelaxant, and
antitumor agent.6 Moreover, fused phthalazines are effective envoys for inhibition of p38
MAP kinase, selective binding of GABA receptor, and as antianxiety drug.7
Although, different methods have been offered for preparation of phthalazine
derivatives,8,9 their broad utility range has accentuated the need to develop more efficient
synthetic routes for the scaffold manipulation of phthalazine derivatives. Most protocols
directed toward designing structural motifs containing phthalazine ring fragment, usually
employ multiꢀcomponent condensation of aldehydes and active methylene compounds such
as malononitrile, ethyl cyanoacetate, and dimedone.10 However, many of these protocols have
their own limitations, such as use of expensive catalyst or toxic organic solvents, strong
acidic conditions, and harsh reaction conditions. Moreover, considering importance of
solventꢀfree organic reactions, new catalytic approaches should be taking into account for
reduction of environmental wastes and energy cost. The possibility of performing
multicomponent reactions under solvent free conditions with an efficient heterogeneous
catalyst could enhance their efficacy from an economic as well as ecologic viewpoint.
In extension of our investigations to explore more effective catalysts in green organic
synthesis by using simple and cost effective nanohybrid materials,11ꢀ13 AlꢀSBAꢀ15ꢀ
TPI/H6P2W18O62 as a new inorganicꢀorganic hybrid material was prepared, characterized, and
used as an efficient catalyst in the synthesis of 2Hꢀindazolo[2,1ꢀb] phthalazineꢀtrione
derivatives via oneꢀpot, threeꢀcomponent condensation of phthalhydrazide, aromatic
aldehydes, and dimedone under solvent free conditions (Scheme 1).
2

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R1
O
O
H
O
O
O
O
O
Al-SBA-15-TPI/H6P2W18O62
NH
N
N
+
+
Solvent-free , 100 oC
NH
R
O
R
R1
R
R
R= H, Me
R1= electron withdrawing (donating), halogen, H
Scheme 1 General formulation for the preparation of different phthalhydrazideꢀtriones.
2. Experimental section
2.1. Materials and methods
All starting materials and solvents were obtained from commercial sources and used as
received. Fresh aluminium triꢀsecꢀbutoxide (Al(OꢀSBu)3) was prepared according to the
literature procedure14 and purified by vacuum distillation (167 °C/5 mmHg). Scanning
electron microscope (SEM) micrographs were taken using a KYKYꢀEM3200 microscope
(acceleration voltage 26 kV). The crystalline structures of the samples were evaluated by Xꢀ
ray diffraction (XRD) analysis on a STOE diffractometer with Cu Kα radiation (λ = 1.5418
Ǻ) at 40 keV and 40 mA with a scanning rate of 3° min−1 in the 2θ range from 0.5 to 80°.
Fourier transform infrared (FTꢀIR) spectra were recorded on a 8700 Shimadzu Fourierꢀ
Transform spectrophotometer in the region of 250 to 4000 cm−1 using KBr pellets.
Thermogravimetric and differential thermal analysis (TGAꢀDTA) were carried out on a Bahr
STAꢀ503 instrument in air at a heating rate of 10 °C minꢀ1. Ultravioletꢀvisible spectra were
obtained on a Shimadzu Model UVꢀ2550 spectrophotometer. Elemental analyses were
performed with a Thermo Finnigan Flashꢀ1112EA microanalyzer. Progress of the reactions
was monitored by thinꢀlayer chromatography (TLC). Melting points were recorded on a
1
Bamstead electrothermal type 9200 melting point apparatus. H and 13C NMR spectra were
recorded on a Bruker AVANCE 300ꢀMHz instrument using TMS as internal reference. All
products were identified by comparison of their spectral and physical data with those
previously reported. WellsꢀDawson H6P2W18O62.24H2O acid catalyst (HPA) was prepared
according to the previously reported methods.15 Synthesis of AlꢀSBAꢀ15 and pyridineꢀ
functionalized AlꢀSBAꢀ15ꢀTPI are described in the supporting information.
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2.2. Immobilization of Wells-Dawson diphosphooctadecatungsticacid on Al-SBA-15-TPI
For the immobilization of H6P2W18O62.24H2O on AlꢀSBAꢀ15ꢀTPI, 50 ml of methanol
containing 0.4 g of H6P2W18O62.24H2O was added to a freshly prepared AlꢀSBAꢀ15ꢀTPI (0.8
g) and the mixture was refluxed for 4 h. Then, the heterogeneous catalyst was filtered off and
washed with methanol several times and thereafter dried at room temperature. Amount of
H6P2W18O62.24H2O loading on AlꢀSBAꢀ15ꢀTPI was found to be 0.11 mmol/g, as determined
by UVꢀVis spectroscopy. This result was confirmed by thermogravimetric analysis. UVꢀVis
studies showed that 9.64% of pyridine groups on the surface of AlꢀSBAꢀ15 were coordinated
to the WellsꢀDawson heteropolyacid. The functionalized AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 did not
leach significantly after prolonged contact with aqueous solution, as confirmed by UVꢀVis
spectroscopy. Therefore, Nꢀ[3ꢀ(triethoxysilyl)propyl]isonicotinamide (TPI) linker was a
suitable agent for the immobilization process and provided anchoring of the heteropolyacid
onto the functionalized support. A schematic for the preparation of AlꢀSBAꢀ15ꢀTPI/HPA
nanocatalyst is shown in Scheme 2.
OH
O
OH
OH
OH
EtO
EtO
Toluene
N
Si
N
+
H
Reflux
(24h)
OEt
(TPI)
OH
O
OH
Si
O
O
N
N
H
(H6P2W18O62)
Methanol
O
OH
O
N
Si
N
H
O
OH
O
n+
OH
NH+
O
O
OH
Si
N
n-
H2
H(6-n)P2W18O62
O
NH+
O
O
Si
N
H2
OH
(Al-SBA-15-TPI/H6P2W18O62
)
Scheme 2 A schematic for preparation of AlꢀSBAꢀ15ꢀTPI/HPA nanocatalyst.
4

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2.3. General procedure for preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-
triones
To a mixture of aldehyde (0.25 mmol), phthalhydrazide (0.25 mmol) and dimedone (0.25
mmol), AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 (0.02 g) was added and the mixture was heated to 100
ºC for appropriate time. Completion of the reaction was monitored by TLC. After
completion, hot ethanol (5 ml) was added to the reaction mixture and stirred for 5 min. Then,
the heterogeneous solid catalyst was quickly filtered off and the filtrate was cold to 5 ºC to
precipitate the desired product. Finally, the solid product was further purified by reꢀ
crystallization in aqueous EtOH (25%). The desired pure products were characterized by
comparison of their physical data with those of known 2Hꢀindazolo[2,1ꢀb]phthalazineꢀ
1,6,11(13H)ꢀtriones.
2.4. Spectral data for some representative 2H-indazolo[1,2–b]phthalazine-1,6,11(13H)-
36, 43
triones
3,3ꢀDimethylꢀ13ꢀphenylꢀ3,4ꢀdihydroꢀ2Hꢀindazolo[2,1b]phthalazineꢀ1,6,11(13H)ꢀtrione
(Table 6, Entry 1): Yellow powder; m.p: 206ꢀ208 °C; IR (KBr) (vmax, cmꢀ1) 2956, 1665,
1574; 1H NMR (300 MHz, CDCl3): δ (ppm) 1.21 (s, 6H, 2Me), 2.33 (s, 2H, CH2C), 3.22ꢀ3.47
(AB system, J = 18.9 Hz, 2H, CHaHbCO), 6.44 (s, 1H, CHN), 7.29ꢀ8.36 (m, 9H, Ph); 13C
NMR (100 MHz, CDCl3): δ (ppm) 28.3, 28.7, 34.8, 38.1, 50.9, 64.8, 118.7, 127.0ꢀ127.9,
128.6ꢀ129.1, 134.5, 136.4, 150.8, 154.2, 156.0, 192.1.
3,3ꢀDimethylꢀ13ꢀ(2ꢀhydroxyphenyl)ꢀ3,4ꢀdihydroꢀ2Hꢀindazolo[1,2ꢀb]phthalazineꢀ1,6,11ꢀ
(13H)ꢀtrione (Table 6, Entry 3): Yellow solid; m.p: 184–188 °C; IR (KBr, νmax cm–1) 2897,
1
1661, 1492, 1378, 1328, 1262, 1082, 791. H NMR (300 MHz, CDCl3): δ (ppm) 10.98 (br s,
1H, OH), 8.25–8.34 (m, 2H), 7.83–7.85 (m, 2H), 6.97–7.56 (m, 4H, ArH), 6.33 (s, 1H,
ArCH), 2.43 and 2.60 (ABꢀq system, J = 17.3 Hz, 2H), 2.32 (s, 2H), 1.03 (s, 3H, CH3), 0.97
(s, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ (ppm) 201.1, 196.1, 169.3, 161.5, 150.8,
137.1, 133.4, 131.7, 128.7, 128.1, 127.5, 124.5, 120.6, 115.8, 111.1, 52.2, 43.3, 41.5, 27.3,
26.4.
3,3ꢀDimethylꢀ13ꢀ(3ꢀnitrophenyl)ꢀ3,4ꢀdihydroꢀ2Hꢀindazolo[1,2ꢀb]phthalazineꢀ1,6,11(13H)ꢀ
trione (Table 6, Entry 4): Yellow powder; m.p: 268ꢀ271 °C; IR (KBr) (vmax, cmꢀ1) 2973,
1
1683, 1661, 1625; H NMR (300 MHz, CDCl3): δ (ppm) 1.23 (s, 6H, Me), 2.34 (s, 2H,
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CH2C), 3.23ꢀ3.47 (AB system, J =18.9 Hz, 2H, CHaHbCO), 6.53 (s, 1H, CHN), 7.54ꢀ8.4 (m,
8H, Ph); 13C NMR (100 MHz, CDCl3): δ (ppm) 28.4, 28.8, 34.8, 38.1, 50.8, 64.1, 117.2,
121.5, 123.8, 127.7, 128.1, 128.6, 128.9, 129.6, 133.9, 134.7, 138.4, 148.5, 150.7, 154.3,
155.9, 192.1.
13ꢀ(4ꢀchlorophenyl)ꢀ3,3ꢀDimethylꢀ3,4ꢀdihydroꢀ2Hꢀindazolo[1,2ꢀb]phthalazineꢀ1,6,11(13H)ꢀ
trione (Table 6, Entry 7): Yellow powder; m.p: 262ꢀ264 °C; IR (KBr) (vmax, cmꢀ1) 2957,
1
2931, 1688, 1654, 1622; H NMR (300 MHz, CDCl3): δ (ppm) 1.22 (s, 6H, 2Me), 2.33 (s,
2H, CH2C), 3.22ꢀ3.44 (AB system, J =19.2 Hz, 2H, CHaHbCO), 6.41 (s, 1H, CHN), 7.28ꢀ7.38
(dd, J= 8.4 Hz, 4H, ArCl), 7.84ꢀ8.38 (m, 4H, Ph); 13C 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.
3,3ꢀDimethylꢀ13ꢀ(4ꢀmethylphenyl)ꢀ3,4ꢀdihydroꢀ2Hꢀindazolo[2,1ꢀb]phthalazineꢀ1,6,11(13H)ꢀ
trione (Table 6, Entry 15): Yellow powder; m.p: 226ꢀ228 °C ; IR (KBr) (vmax, cmꢀ1) 2958,
1667, 1631; 1H NMR (300 MHz, CDCl3): δ (ppm) 1.21 (s, 6H, 2Me), 2.20 (s, 3H, CH3), 2.33
(s, 2H, CH2C), 3.21ꢀ3.45 (AB system, J =18.9 Hz, 2H, CHaHbCO), 6.43 (s, 1H, CHN), 7.12ꢀ
7.32 (dd, J =7.8 Hz, 4H, ArMe) 7.83ꢀ8.36 (m, 4H, Ph); 13C NMR (100 MHz, CDCl3): δ
(ppm) 21.3, 28.4, 28.6, 34.6, 38.1, 50.9, 64.7, 118.7, 127.1, 127.7, 128.9, 129.1, 129.4,
133.4, 134.4, 138.3, 148.5, 150.7, 154.1, 156.1, 192.1.
13ꢀisobutylꢀ3,3ꢀDimethylꢀ3,4ꢀdihydroꢀ1Hꢀindazolo[1,2ꢀb]phthalazineꢀ1,6,11(2H,13H)ꢀtrione
(Table 6, Entry 16): Yellow powder; m.p: 135ꢀ137 °C; IR (KBr) (vmax, cmꢀ1) 2959, 2872,
1
1663, 1631; H NMR (300 MHz, CDCl3): δ (ppm) 0.86ꢀ0.87 (d, 3H, Me), 0.94 (d, 3H,
Me),1.21 (s, 3H, Me), 1.25 (s, 3H, Me), 1.68ꢀ1.75 (m, 1H, CH), 2.01ꢀ2.05 (m, 1H, CH), 2.14ꢀ
2.18 (m, 1H, CH), 2.35ꢀ2.45 (AB system, J =15 Hz, 2H), 3.14ꢀ3.35 (AB system, J =19 Hz,
2H), 5.7 (m, 1H, CHN), 7.85ꢀ7.93 (m, 2H, Ph), 8.34ꢀ8.38 (m, 2H, Ph); 13C NMR (100 MHz,
CDCl3): δ (ppm) 23.1, 24.1, 25.3, 28.8, 29.0, 34.8, 38.5, 39.8, 51.5, 62.2, 118.7, 127.8,
128.3, 129.8, 129.4, 133.8, 134.8, 151.7, 155.3, 156.5, 193.3.
3. Results and discussion
Organicꢀinorganic hybrid silicaꢀbased porous materials have been extensively contemplated,
because of their glamorous properties such as regular mesostructure, thermal and mechanical
stability, tuneable pore size, high adsorption capacity, as well as extraordinarily wide
possibilities of functionalization with organic linkers.16,17 Therefore, development of porous
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silicaꢀbased materials with large specific surface areas is currently an area of extensive
research, particularly with regard to potential applications in areas such as adsorption,
chromatography, catalysis, sensor technology, and gas storage.
In spite of good catalytic applications reported for hybrid materials composed of
SBAꢀ15, its surface acidity is not sufficient and introducing metal ions, such as aluminium, in
the neutral silica framework, directed to generation of more surface acidic sites.18 Generally,
incorporation of heteroatoms, such as aluminium, into the mesoporous materials introduces a
charge imbalance in the framework which is balanced by protons, thus generating bridging
hydroxyl groups (SiꢀOHꢀAl, as Bronsted acidic sites) on the surface of these materials.19
Among the metalꢀsubstituted mesoporous materials, aluminium incorporated mesoporous
silicas have great potential in moderate acid catalyzed reactions for large molecules.20 There
are different strategies for the direct synthesis of aluminiumꢀsubstituted mesoporous silica
under acidic conditions.20 Prehydrolysis of the alkoxysilicanes before addition of aluminium
alkoxide, is generally more utilized. In this strategy, aluminium triꢀsecꢀbutoxide is used as the
ꢀ
aluminium source, and hydrolyzed rapidly to monomeric Al(OH)4 under acidic or basic
conditions. Hydrolysis of aluminium triꢀsecꢀbutoxide under high acidic conditions, resulted in
formation of soluble tetrahedral coordinated aluminium precursors, which favour
incorporation of aluminium into the mesoporous materials.
3.1. Structural characterization of Al-SBA-15-TPI/HPA nanocatalyst
3.1.1. X-ray diffraction (XRD) studies
Lowꢀangle Xꢀray diffraction patterns of AlꢀSBAꢀ15, AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀ
TPI/HPA are shown in Fig. S1†. All patterns present a very intense peak at 2θ ~0.9º which
can be indexed to the (100) hkl reflection. This peak is associated with the P6mm hexagonal
symmetry typical of SBAꢀ15 material and indicating a significant degree of longꢀrange
ordering in the structure and a wellꢀformed hexagonal lattice.21 Diffraction patterns indicated
that the primary structure of AlꢀSBAꢀ15 was maintained after modification with TPI and
anchoring with the heteropolyacid. Due to the grafting of pyridine groups, the diffraction
peak of AlꢀSBAꢀ15 was slightly shifted to higher angle and became weaker compared with
that of the unmodified one. These results indicated that the mesoporous phase of the
composite was maintained, while integrity of the mesopore structure was affected by the
incorporation of TPI as functionalizing agent.22 A slight shift of the characteristic reflection
of AlꢀSBAꢀ15ꢀTPI/HPA in the lowꢀangle XRD pattern indicated that H6P2W18O62 mostly
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occupied mesoporous channels.23 HPA loading induced a striking effect on the width and
intensity of the main reflection at d100 spacing and this line became broader and weaker with
a marginal shift indicating a noticeable decrease in the order of AlꢀSBAꢀ15 and occupation of
the mesopore channels with H6P2W18O62.24 Bulk HPA crystal phase did not appear in the
HPA supported AlꢀSBAꢀ15ꢀTPI material, indicating that HPA was finely dispersed on the
surface of AlꢀSBAꢀ15ꢀTPI. Furthermore, the highꢀangle XRD pattern of H6P2W18O62
immobilized on AlꢀSBAꢀ15ꢀTPI showed that H6P2W18O62 diffraction peaks were collapsed
and only a broad peak was observed at 2θ about 22° after incorporation with the
functionalized support. This finding confirmed that the heteropolyacid was well dispersed
onto the AlꢀSBAꢀ15 mesopore. This is in agreement with the XRD pattern of other
heteropolyacids used in other supports.25
3. 1. 2. UV-Vis spectroscopy
UVꢀVis spectrum of the Wells–Dawson heteropolyacid showed two types of ligand→metal
chargeꢀtransfer bands originating from different oxygen atoms.26 The highest energy
absorption band at about 220 nm was assigned to Od→W chargeꢀtransfer band due to the
terminal oxygen atoms. Other weak bands at~260 and ~310 nm are characteristic bands for
diphosphooctadecatungsticacid and are attributed to the Ob→W or Oc→W chargeꢀtransfer
bands originating from the bridging oxygen atoms.
To determine the extent of HPA which can be loaded on the support, 0.8 g of Alꢀ
SBAꢀTPI was suspended in a 50 ml methanol solution of HPA with an initial
concentration 8000 ppm. The suspension was refluxed for 4 h; absorption spectrum was
recorded for the solution after removing the solid catalyst by filtration (Fig. 1). After 240 min
refluxing and comparison with the standard solutions, the heteropolyacid concentration had
declined to 250 ppm which corresponded to 0.11 mmolg−1 loading of HPA on the support.
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Fig. 1 UVꢀVis spectral changes after addition of H6P2W18O62 to AlꢀSBAꢀ15ꢀTPI under reflux
for 4 h.
3. 1. 3. Studying morphology (SEM) of Al-SBA-15-TPI/HPA nanocatalyst
Morphology of AlꢀSBAꢀ15ꢀTPI/HPA nanocatalyst was investigated by SEM (Fig. 2). The
sphericalꢀelliptical particles in this micrograph are attributed to AlꢀSBAꢀ15ꢀTPI/HPA.
Actually, by introducing aluminium into the silica, the robeꢀlike morphology, which is
consistent with known SBAꢀ15 structure, was changed to some extent. However,
functionalization with Nꢀ(3ꢀ(triethoxysilyl) propyl) isonicotinamide and anchoring HPA had
no significant effect on the structure of pure AlꢀSBAꢀ15.
Fig. 2 SEM micrograph of the AlꢀSBAꢀ15ꢀTPI/HPA nanocatalyst
.
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3. 1. 4. FT-IR spectroscopy
To ascertain covalent binding of TPI and anchoring of HPA into the surface of AlꢀSBAꢀ15
mesopores, FTꢀIR spectroscopy was used for characterization of the ordered mesoporous Alꢀ
SBAꢀ15, AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀTPI/HPA (Fig. 3). TPI was attached to the surface
of SBAꢀ15 by condensation of the silanol groups of aluminaꢀsilica and the ethoxy groups of
TPI under refluxing in toluene. Presence of organic groups is confirmed by observation of Cꢀ
H aromatic, CꢀH aliphatic, C=O, and C=N groups around 3050, 2800ꢀ2950, 2652, 1650 and
1550 cmꢀ1 region, respectively. Broad NꢀH stretching bands were superimposed to those of
water, in the 3000–3500 cmꢀ1 range.27 These findings proved that pyridine groups have been
successfully grafted to the surface of AlꢀSBAꢀ15. Furthermore, FTꢀIR spectra of AlꢀSBAꢀ15,
AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀTPI/HPA revealed the typical SiꢀOꢀSi bands of the
inorganic framework; symmetric stretching vibration mode around 800 cmꢀ1 and asymmetric
stretching vibration around 1080–1100 cmꢀ1.28
The absorption peak of the SiꢀOH bands at 960 cmꢀ1 in AlꢀSBAꢀ15 weaken upon
functionalization, indicating that the TPI agents are substituted with some of the surface
silanol groups. The broad band in 3000–3700 cm−1 region and the band at 1630ꢀ1650 cmꢀ1
can be attributed to the symmetrical stretching and bending vibrations of the adsorbed water
molecules, respectively. In comparison with the pure SBAꢀ15, there is a slight shift toward
higher frequencies for the bands in which attributed to SiꢀOꢀSi, as a result of longer AlꢀO
bond distance than SiꢀO.
Wells–Dawson structure of H6P2W18O62 consists of two half units composed of a
central PO4 tetrahedron surrounded by nine WO6 octahedral. Therefore, the H6P2W18O62
structure involves four kinds of oxygen atoms. The first is P–Oa in which the oxygen atom
connects with the tungsten atoms, the second is W–Ob–W oxygen bridges (cornerꢀsharing
oxygen bridges between different W3O13groups), the third is W–Oc–W oxygen bridges (edgeꢀ
sharing oxygen bridge within W3O13 groups), and the last is W–Od terminal oxygen atoms.
The four characteristic bands of H6P2W18O62 were appeared at νas(W–Od): 965 cm−1; νas(W–
Ob–W): 912 cm−1; νas(W–Oc–W): 776 cm−1 and νas(P–Oa): 1093 cm−1.29
In the FTꢀIR spectrum of AlꢀSBAꢀ15ꢀTPI/HPA observation of HPA was hindered as a
result of the strong background of aluminaꢀsilica support. Actually, from four characteristic
bands of HPA, W–Oc–W and P–Oa bands overlap with those of SiꢀOꢀSi stretching vibrations
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of mesoporous supports and only the bands corresponding to W–Od (961 cm−1) and W–Ob–
W (914 cmꢀ1) were discernable after immobilization. Appearance of HPA characteristic bands
in the FTꢀIR spectrum of AlꢀSBAꢀ15ꢀTPI/HPA revealed that the WellꢀDawson structure
remained intact after immobilization.
HPA
C-H aromatic
C-H aliphatic
C=N
Silanol groups(Si-O-H)
Si-OH
Si-O-Si
Fig. 3 FTꢀIR spectra of AlꢀSBAꢀ15, AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀTPI/HPA.
3. 1. 5. Thermal analysis
The thermal stability of AlꢀSBAꢀ15 support, AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀTPI/HPA
nanocatalyst were investigated by carrying out TGA analysis (Fig. 4a). Moreover, the thermal
stability of AlꢀSBAꢀ15ꢀTPI/HPA nanocatalyst was investigated by carrying out TGA–DTA
analysis (Fig. 4b). TGA curve of aluminaꢀsilica support contains two steps of weight loss.
The first weight loss (~9%) in the temperature range of 25–125 °C which is accompanied
with endothermic peaks in DTA curve was attributed to the release of physically adsorbed
water and the second one (3.5%) in the range of 125–800 °C was due to the dehydroxylation
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of OH groups. TGA profile of AlꢀSBAꢀ15ꢀTPI and AlꢀSBAꢀ15ꢀTPI/HPA both showed a
weight loss of 23 and 16%, respectively. This occurred in the temperature range of 300ꢀ800
°C, which is accompanied by a broad exothermic peak between 370 °C and 510 °C in the
DTA curve (Fig. 4b), corresponding to the combustion of the organic part of TPI. The 23%
weight loss in AlꢀSBAꢀ15ꢀTPI gave TPI concentration as 1.14 mmol/g in the aluminaꢀsilica
mesopore which was in agreement with CHN analysis.
(a)
(b)
Fig. 4 (a) TGA curves of AlꢀSBAꢀ15, AlꢀSBAꢀ15ꢀTPI, and AlꢀSBAꢀ15ꢀTPI/HPA. (b) TGA
and DTA of AlꢀSBAꢀ15ꢀTPI/HPA.
Although the apparent thermogram curves of AlꢀSBAꢀ15ꢀTPI and AlꢀSBAꢀ15ꢀ
TPI/HPA are similar, the amount of weight loss is higher for pyridine functionalized aluminaꢀ
silica mesopore. Indeed, the presence of heteropolyacid, which was retained intact at the high
temperature on AlꢀSBAꢀ15ꢀTPI, decreased organic moiety percentage on the resulting
nanocatalyst, so the amount of weight loss is declined in HPA anchored mesopore compared
to AlꢀSBAꢀ15ꢀTPI. Furthermore, according to thermal analysis, the prepared nanocatalyst
was stable up to 300 °C.
3. 2. Catalytic tests
Multiꢀcomponent reactions (MCRs) have attracted extensive interest in organic syntheses and
in pharmaceutical chemistry. This strategy has provided more facile, fast, atom efficient and
environmentally benign processes by mixing different starting materials in a single step and
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avoiding the complicated isolation and purification of intermediates.30 Therefore, MCRs have
been considered as a practical, economic, and green approach to access diverse structures of
complex products. Now, the catalytic activity of new heteropolyacid based inorganicꢀorganic
nanonanohybrid catalyst AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 is assessed for the preparation of 2Hꢀ
indazolo[2,1ꢀb]phthalazineꢀ1,6,11(13H)ꢀtriones under heterogeneous solvent free conditions.
3. 2. 1. Effect of the heteropolyacid nature and structure on the efficacy of the catalytic
system
Catalytic activity of H6P2W18O62 was compared with other indicative familiar
heteropolyacids in the preparation of 2,2ꢀdimethylꢀ13ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindazolo[2,1ꢀ
b]phthalazineꢀ4,6,11(13H)ꢀtrione (Table 1). Almost, all the introduced Keggin and Wellsꢀ
Dawson heteropolyacids are strong acids and behaved as good catalysts in the respective
transformation.31 Although, Kegginꢀtype heteropolyacids have shown better catalytic activity
than WellsꢀDawson counterparts in many acid catalyzed organic transformations, however,
WellsꢀDawson type polytungsticacid H6P2W18O62 clearly showed higher reactivity in the
preparation of phthalazineꢀtrione derivatives. Many factors such as acidity of the
heteropolyacid, negative charge density smeared over oxygen atoms, structural composition
and distortions, and absorption of the substrate molecule into the bulk of the heteropolyacid
would contribute to the catalytic efficiency of the heteropolyacids under the reaction
conditions.31
Table 1 Effect of the heteropolyacid nature and structure on the efficacy of the preparation
of 2,2ꢀdimethylꢀ13ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindazolo[2,1ꢀb]phthalazineꢀ4,6,11(13H)ꢀtrione
Catalyst
Structure type
Keggin
Time (min)
Yield (%)
H3PMo12O40
H3PW12O40
H6P2W18O62
H6P2Mo18O62
H4SiW12O40
H4SiW9Mo2O40
25
20
10
25
20
25
60
81
86
73
50
78
Keggin
WellsꢀDawson
WellsꢀDawson
Siꢀsubstituted Keggin
Siꢀsubstituted mixed
metal Keggin
H4SiW9Mo3O40
35
80
Siꢀsubstituted mixed
metal Keggin
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H14NaP5W30O110
20
68
Preyssler
To a mixture of aldehyde (0.25 mmol), phthalhydrazide (0.25 mmol) and dimedone (0.25 mmol), catalyst (0.75
mol%) was added and the mixture was heated to 100 ºC for the required time. Progress of the reaction was
monitored with TLC. Workꢀup was carried out as described in the experimental section. Yield% refers to the
isolated yield.
3. 2. 2. Effect of catalyst amount on the catalytic efficiency
In next step, a study set out to determine the optimal amount of H6P2W18O62 and AlꢀSBAꢀ15ꢀ
TPI/H6P2W18O62 in the preparation of 2,2ꢀdimethylꢀ13ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindazolo[2,1ꢀ
b]phthalazineꢀ4,6,11(13H)ꢀtrione. Therefore, the reaction was carried out by varying amount
of the catalyst (Table 2). Maximum yield of 86% was attained with 0.75 mol% (0.033 g) of
H6P2W18O62 after 10 min; whereas, only 0.021 g of the nanocatalyst AlꢀSBAꢀ15ꢀ
TPI/H6P2W18O62 (involving 0.224 mol% of H6P2W18O62) led to 82% yield after a very short
period of time of time (5 min). Clearly, AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 was more effective than
H6P2W18O62 and fewer amount of the heteropolyacid was needed to reach the maximum yield
in a very short reaction time. Moreover, further increase in the amount of the catalyst in the
aforementioned reaction did not a significant effect on the product yield and reaction time.
Table 2 Effect of the catalyst amount on the condensation of benzaldehyde, phthalhydrazide,
and dimedone under solventꢀfree conditions
Entry
Al-SBA-15-TPI/
H6P2W18O62 (g)
H6P2W18O62 (mol%)
Time (min)
Yield (%)
1
2
3
4
5
6
0
0
120
5
21
72
75
78
82
86
0.007
0.010
0.014
0.021
ꢀ
0.074
0.112
0.149
0.224
0.75
5
5
5
10
General reaction conditions are as described below Table 1.
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3. 2. 3 Effect of reaction time on the catalytic efficiency
Effect of reaction time was also investigated to explore minimum time required to obtain the
maximum yield in the preparation of 2,2ꢀdimethylꢀ13ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindazolo[2,1ꢀ
b]phthalazineꢀ4,6,11(13H)ꢀtrione catalyzed by H6P2W18O62 (0.75 mol%). As illustrated in
Fig. S2†, only 5 min is sufficient to get 84% yield. No obvious increase in yield% was
detected after a prolonged reaction time. However, a slight decrease was observed after 15
min.
3. 3. Studying catalytic efficiency of different (support-organic linker/heteropolyacid)
hybrid materials
Several reports declared that electrostatic attachment of heteropolyacids to the solid
supporting materials via a suitable linker is a beneficial strategy to overcome leaching of the
catalytically active catalyst from the surface of supporting material. Thus, effect of the kind
and nature of some organic modifiers, as linkers between solid supporting material and the
heteropolyacid, was studied in this research. Results revealed that these organic linkers
significantly affected the catalytic efficiency of H5PW10V2O40 (Table 3). Mesoporous silica
SBAꢀ15 with the wellꢀordered hexagonal arrays of cylindrical channels, and a large number
of silanol groups at the surface,32 was served as an intriguing support for this study. This
material led to much better results than Fe3O4 in this study.
Table 3 Effect of different organic linkers on the catalytic efficiency.
Catalyst
Amount (g)
Time (min)
Yield (%)
Ref.
SBAꢀ15ꢀpipꢀ
H5PW10V2O40
0.005
10
73
23
AlꢀSBAꢀ15ꢀ
TPI/H6P2W18O62
0.01
0.01
5
78
34
this work
4
Fe3O4ꢀ
20
TPI/H5PW10V2O40
Fe3O4ꢀ
0.01
20
36
26
TPI/H6P2W18O62
AlꢀSBAꢀ15
SBAꢀ15
0.01
0.01
25
35
70
57
this work
32
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General reaction conditions are as described below Table 1. All reactions were carried out at 100 ºC.
Effects of the kind of solid support material, organic linker, and the catalytically
active heteropolyacid on the efficacy of the prepared inorganicꢀorganic hybrid material are
also shown in Table 3. MCMꢀ41 mesoporous silica was obviously more effective than Fe3O4
as the solid support. MCMꢀ41ꢀNH2ꢀH5PW10V2O40 led to 86% yield after 20 min; whereas, the
Fe3O4 counterpart produced only 33% of product during the same time and under similar
conditions. Moreover, nature of the organic linker was ineffective in Fe3O4ꢀlinkerꢀ
H5PW10V2O40. Both Fe3O4ꢀNH2ꢀH5PW10V2O40 and Fe3O4ꢀTPIꢀH5PW10V2O40 led to ~33%
yield after 20 min. However, the WellsꢀDawson H6P2W18O62 was substantially more effective
than the Keggin vanadium substituted H5PW10V2O40. Carbon nanotube modified with TPI
was also used as the supporting material. Although, this new heterogeneous catalyst attracted
the interest of several research groups, however, it was significantly less effective than the
target heterogeneous catalyst used in this study, AlꢀSBAꢀ15ꢀTPIꢀH6P2W18O62.
The catalytic activity of the ingredients comprising the organic–inorganic nanohybrid
material AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 was investigated. Results showed that incorporation of
15% aluminum into the framework of SBAꢀ15 significantly increased efficacy of the
supporting material. 0.01 g of SBAꢀ15 produced 57% yield after 35 min; whereas, the same
amount of AlꢀSBAꢀ15 led to 70% yield after 25 min. Moreover, anchoring of the Wellsꢀ
Dawson H6P2W18O62 to the modified AlꢀSBAꢀ15 led to 78% yield after 5 min. Clearly, the
new synthesized nanohybrid material AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 behaved as a unique and
effective catalyst in the desired condensation reaction.
3. 4. Studying condensation of phthalhydrazide and aromatic aldehydes with different
diketones
To further explore the scope of this protocol, we decided to investigate condensation reaction
of phthalhydrazide and aromatic aldehydes with other cyclic and acyclic diketones in the
presence of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 (0.02 g). Among the examined diketones (Table 4),
dimedone, 5,5ꢀdimethylꢀ1,3ꢀcyclohexaneꢀdione, led to the best yield%; whereas, the
unsubstituted 1,3ꢀcyclohexaneꢀdione was less effective. Cyclohexaneꢀ1,3ꢀdione afforded the
corresponding condensation product with 74% yield after 15 min. It seems that electron
releasing nature of the two methyl substituents in dimedone would activate the diketone
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toward condensation reaction. Two linear hexane diones, i.e 2, 5ꢀhexaneꢀdione and 2, 3ꢀ
hexaneꢀdione were also tested. Obviously, linear diones were clearly less effective than the
cyclic ones and both linear hexane diones led to 38ꢀ43% yield after 45ꢀ50 min; whereas, the
cyclic diones provided 74ꢀ82% of products after shorter times 5ꢀ15 min.
Table 4 Studying reactivity of cyclic and linear hexanediones towards the desired
condensation reaction.
Diketone
Structure
Time (min)
Yield (%)
O
5,5ꢀdimethylꢀ1,3ꢀcyclohexaneꢀdione
5
82
O
O
1,3ꢀcyclohexaneꢀdione
15
74
O
O
O
2,5ꢀhexaneꢀdione
2,3ꢀhexaneꢀdione
50
45
38
43
O
O
General reaction conditions are as described below Table 1.
3. 5. Comparison of the catalytic activity of Al-SBA-15-TPI/H6P2W18O62 nanocatalyst
with some reported catalysts
Comparison of the efficacy of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 catalyst with some reported
catalysts in the literature is presented in Table 5. The model reaction of dimedone,
phthalhydrazide, and benzaldehyde was considered as a representative example and the
comparison was in terms of mol% or amount of the catalyst, temperature, reaction time, and
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percentage yields. Obviously, the present new nanohybrid catalyst (AlꢀSBAꢀ15ꢀTPI/
H6P2W18O62) was more effective than most of the conventional catalysts listed in Table 5.
The present methodology utilized a very low amount of the heterogeneous catalyst under
solventꢀfree conditions. Although, some of the introduced additives catalyzed the reaction,
even though at a lower temperature, they required toxic and expensive solvents, higher mol%
of catalyst, and longer reaction times.
Table 5 Comparison of the catalytic efficiency of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 nanocatalyst
with some reported catalysts.
Entry
Catalyst and Conditions
PSA, Solvent free, 100 C, 7 mol%
H4SiW12O40, Solvent free, 100 C, 1 mol%
H2SO4[bmim][BF4], 80 C, 15 mol%
CAN, Solvent free, 50 C, 5 mol%
Citric acid, Solvent free, 80 C, 3 mol%
MNPsꢀguanidine, Solvent free, 70 C, 2.34 mol%
[C4(min)2](FeCl4)2, Solvent free, 100 C, 20 mol%
Fe3O4@Silica sulforic acid, Solvent free, 100 C, 0.075 g
Iodine / ))))*, Solvent free, 25ꢀ30 C, 10 mol%
AlꢀSBAꢀ15ꢀTPI/H6P2W18O62, Solvent free, 100
Time (min) Yield (%) Ref.
1
2
10
16
30
120
20
35
10
35
10
5
91
92
94
94
92
93
89
88
92
82
33
34
35
36
37
38
39
40
41
º
º
3
4
º
º
5
º
6
º
7
º
8
º
9
º
10
This
º
C, 0.02g
work
3. 6. Synthesis of different phthalazine-triones
The generality of this method was examined using several types of aldehydes. In all cases,
the reactions gave the corresponding products in good to excellent yields (Table 6).
Although, the nature and electronic properties of aldehydes would affect yield%, the
reactions proceeded smoothly and equally well for electronꢀwithdrawing as well as electronꢀ
donating substituents on aldehydes to afford the corresponding phthalazineꢀtriones.
Moreover, aromatic aldehydes reacted faster and led to higher yields% than their aliphatic
counterparts.
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Table 6 Synthesis of different 2Hꢀindazolo[2,1ꢀb]phthalazineꢀ1,6,11(13H)ꢀtriones in the
presence of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 under solventꢀfree conditions.
R1
O
O
O
O
O
O
Al-SBA-15-TPI/H6P2W18O62
Solvent-free , 100 oC
NH
NH
N
N
C
+
O
+
R
R1
H
R
R
O
R
R= H, Me
R1= aromatic, aliphatic chain
Entry
1
R1
Ph
R
Me
Time (min)
5
Yield (%)
82
Ref.
43
m.p. / lit. m.p. (
205ꢀ207/206ꢀ208
º
C)
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
4ꢀFPh
2ꢀOHPh
3ꢀNO2Ph
4ꢀNO2Ph
2ꢀClPh
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
20
10
10
20
12
20
15
20
15
35
10
15
30
15
60
66
76
78
84
78
80
75
74
69
72
79
82
74
72
56
222ꢀ224/221ꢀ224
185ꢀ187/184ꢀ188
269ꢀ271/268ꢀ271
223ꢀ225/222ꢀ225
267ꢀ269/266ꢀ268
261ꢀ263/262ꢀ264
259ꢀ261/260ꢀ262
242ꢀ243/242ꢀ243
207ꢀ209/206ꢀ208
186ꢀ188/185ꢀ186
224ꢀ227/224ꢀ226
266ꢀ267/266ꢀ268
203ꢀ205/204ꢀ206
225ꢀ227/226ꢀ228
135ꢀ137/135ꢀ137
39
36
43
43
41
43
44
45
38
35
38
41
42
43
43
4ꢀClPh
2, 6ꢀCl2Ph
2ꢀOMePh
3ꢀOMePh
3, 4ꢀ(OMe)2Ph
3ꢀBrPh
4ꢀBrPh
4ꢀisopropylPh
4ꢀMeꢀPh
(CH3)2CHꢀ
CH2ꢀ
17
18
19
20
21
(CH3)2CHꢀ
CH3ꢀCH2ꢀ
Ph
2, 6ꢀCl2Ph
4ꢀMeꢀPh
Me
Me
H
H
H
120
65
15
40
25
52
45
74
67
58
133ꢀ135/132ꢀ134
146ꢀ148/145ꢀ147
222ꢀ224/223ꢀ224
285ꢀ287/>280
43
43
34
44
38
245ꢀ246/244ꢀ246
Yields refer to the isolated pure products. The desired pure products were characterized by comparison of their
physical data with those of known compounds.
3. 7. Hot filtration test
In order to confirm that the catalytic activity was generated from the conjugated AlꢀSBAꢀ15ꢀ
TPI/HPA and not from the leached components (if possible) in the reaction mixture, a hot
filtration test was carried out. In this technique, the condensation reaction was performed at
100 °C for 2 min in the presence of the AlꢀSBAꢀ15ꢀTPI/HPA nanocatalyst. At this stage,
yield of the product was 60%. The catalyst was then filtered off under hot conditions, and
with the filtrate, which was obtained after separation of the catalyst, the reaction was
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continued for another 10 min at the same reaction temperature. However, no corresponding
increase in the product yield beyond 60% was observed. This result confirmed the
heterogeneous nature of the nanocatalyst and that no leaching of the heteropolyacid occurred
during the course of the reaction.
3. 8. Reusability and reproducibility of Al-SBA-15-TPI/H6P2W18O62 nancatalyst
The reusability of the nanocatalyst was tested in the synthesis of 2,2ꢀdimethylꢀ13ꢀphenylꢀ2,3ꢀ
dihydroꢀ1Hꢀindazolo[2,1ꢀb]phthalazineꢀ4,6,11(13H)ꢀtrione, as shown in Fig. 5. The catalyst
was recovered after each run, washed three times with ethanol, dried in an oven at 90 ºC for 4
h and tested in the subsequent run. The nanocatalyst was tested for 8 runs. It was observed
that the catalyst displayed very good reusability. Moreover, to ensure reproducibility of the
transformation, repeated typical experiments were carried out under identical reaction
conditions. The obtained yields were found to be reproducible within ±2% variation.
Fig. 5 Yield% as a function of reusability of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 nanocatalyst.
3. 9. Proposed reaction pathway for the heterogeneous catalytic system
A plausible reaction pathway for the reaction of benzaldehyde, phthalhydrazide, and
dimedone in the presence of AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 nanohybrid catalyst is presented in
Scheme 3. It seems that the reaction starts by Knoevenagel condensation of 1,3ꢀdione and
aldehyde, followed by Michael addition of the phthalhydrazide, and subsequent cyclization to
afford the product. It is conceivable that H+ from the heteropolyacid first bound to the
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carbonyl oxygen of the aromatic aldehyde and increased its Lewis acidity. Then, nuleophilic
addition of dimedone to the carbonyl group of aldehyde led to the generation of (I) and
followed by loss of H2O afforded (II). As reported in the literature, the Knoevenagel type
coupling of arylaldehyde with active methylene compounds such as dimedone gives 2ꢀ
benzylideneꢀ5,5ꢀdimethylcyclohexaneꢀ1,3ꢀdione.46ꢀ48 Therefore, subsequent 1,4ꢀconjugate
Michaelꢀtype addition of phthalhydrazide to the olefin followed by cyclization affords the
corresponding product.
O
O
OH
CH
O
Ar
CH
H
OH
A lꢀS B A ꢀ15ꢀT P I/H
P
W
O
OH
6
2
1 8 6 2
..
OH
R
R
O
Ar
O
O
Ar
O
Ar
OH
2
ꢀH
O
2
H
O
OH
(I)
(II)
H
..
O
N
NH
M ichaelꢀtype fashion
O
O
Ar
O
O
O
Ar
O
N
ꢀH
O
2
N
HN
Intram olecular cyclization
OH
N
O
Scheme 3 Proposed mechanism for the synthesis of 2Hꢀindazolo[1,2ꢀb]phthalazineꢀ
triones.
4. Conclusion
In summary, a new inorganicꢀorganic nanohybrid material AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 was
fabricated and used as an efficient catalyst for the oneꢀpot preparation of 2Hꢀindazolo[2,1ꢀ
b]phthalazineꢀ1,6,11(13H)ꢀtrione derivatives from the threeꢀcomponent condensation
reaction of phthalhydrazide, dimedone, and aromatic aldehydes. The catalyst was fully
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characterized and the catalytic reactions were carried out under thermal solvent free
conditions in short times. Furthermore, the catalyst could be successfully recovered and
reused at least for eight runs without significant loss of activity. The oneꢀpot nature and the
use of heterogeneous solid acid material as an ecoꢀfriendly catalyst make the present protocol
an interesting alternative to multiꢀstep approaches. This methodology offers significant
improvements with regard to the heterogeneous nature of the catalyst, scope of the
transformation, simplicity in operation and work up.
Acknowledgements
Partial financial support from the Research Councils of Hakim Sabzevari and Shahid
Beheshti Universities is greatly appreciated.
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Graphical Abstract
(Al-SBA-15/TPI/H6P2W18O62)
O
O
R1
NH
NH
O
O
O
+
H
O
N
N
O
+
R
R1
R
R
O
R
Al-SBA-15
+
n
O
+
+
N
NH
H
2
O
+
+
N
NH
H
2
R
=
PI/H6P2W18O62
AlꢀSBAꢀ15ꢀTPI/H6P2W18O62 is introduced as an effective catalyst for the oneꢀpot synthesis
of indazoloꢀphthalazineꢀtriones. The catalyst could be easily separated without noticeable
reduction in activity.
25