Post synthesis alumination of KIT-6 materials with Ia3d symmetry and their catalytic efficiency towards multicomponent synthesis of 1H-pyrazolo[1,2-] phthalazine-5,10-dione carbonitriles and carboxylates

Article abstract of DOI:10.1016/j.molcata.2012.05.003

Alumination of Si-KIT-6 materials with ordered three-dimensional (3D) structure were prepared by post-synthesis method with various Si/Al ratios. The catalysts were characterized by X-ray diffraction analysis (XRD), N₂ porosimetry and FT-IR spectra. The presence of framework and extra framework aluminium was predicted by Aluminium MAS NMR. The strength of the acid sites of the catalysts was studied by NH₃-TPD acidity measurements. The morphology of mesoporous materials was studied by SEM and TEM observation. The metal content of the samples was investigated by ICP-OES. The prepared solid acid catalysts were applied for the multi-component synthesis of 1H-pyrazolo[1,2-]phthalazine-5,10-diones from the reaction of phthalhydrazide, malononitrile/ethylcyano acetate and aromatic aldehyde in ethanol under liquid phase conditions. Activities of the catalysts follow the order: Al-KIT-6 (33) > Al-KIT-6 (56) > Al-KIT-6 (81) > Al-KIT-6 (110) > Nafion-H > Amberlyst-15 HM (12) > Hβ (8) > HY (4). The effects of reaction conditions and different catalysts have been studied. Various advantages associated with these protocols include effective catalysis, simple work-up procedure, short reaction times, high product yields, easy recovery and reusability of the catalysts.

Full text of DOI:10.1016/j.molcata.2012.05.003

Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
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Post synthesis alumination of KIT-6 materials with Ia3d symmetry and their
catalytic efficiency towards multicomponent synthesis of
1H-pyrazolo[1,2-]phthalazine-5,10-dione carbonitriles and carboxylates
G. Karthikeyana, A. Pandurangana,b,∗
a Department of Chemistry, Anna University, Guindy, Chennai 600 025, India
b Institute of Catalysis and Petroleum Technology, CEG, Anna University Chennai, Chennai 600 025, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Alumination of Si-KIT-6 materials with ordered three-dimensional (3D) structure were prepared by post-
synthesis method with various Si/Al ratios. The catalysts were characterized by X-ray diffraction analysis
(XRD), N2 porosimetry and FT-IR spectra. The presence of framework and extra framework aluminium
was predicted by Aluminium MAS NMR. The strength of the acid sites of the catalysts was studied by
NH3-TPD acidity measurements. The morphology of mesoporous materials was studied by SEM and
TEM observation. The metal content of the samples was investigated by ICP-OES. The prepared solid
acid catalysts were applied for the multi-component synthesis of 1H-pyrazolo[1,2-]phthalazine-5,10-
diones from the reaction of phthalhydrazide, malononitrile/ethylcyano acetate and aromatic aldehyde in
ethanol under liquid phase conditions. Activities of the catalysts follow the order: Al-KIT-6 (33) > Al-KIT-6
(56) > Al-KIT-6 (81) > Al-KIT-6 (110) > Nafion-H > Amberlyst-15 ꢀ HM (12) > H␤ (8) > HY (4). The effects of
reaction conditions and different catalysts have been studied. Various advantages associated with these
protocols include effective catalysis, simple work-up procedure, short reaction times, high product yields,
easy recovery and reusability of the catalysts.
Received 6 February 2012
Received in revised form 27 April 2012
Accepted 2 May 2012
Available online 11 May 2012
Keywords:
Al-KIT-6
Mesoporous solid acid catalysts
Three component reaction
1H-pyrazolo[1,2-]phthalazine-5,10-diones
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
symmetric structure with interpenetrating bicontinuous network
of channels [7]. Three-dimensional pore structure of KIT-6 and
Heterogeneous catalysis is emerging technology and they have
attracted considerable attention in organic synthesis due to their
unique catalytic properties. Acid catalysis by mesostructured mate-
rials has attracted due to the large regular pore structure that
make them suitable for liquid-phase acid catalysis by enabling
rapid diffusion of reactants and products through the pores, thus
minimizing consecutive reactions [1–3]. The mesoporous silicate
materials consist of chemically inert silicate framework and in
order to induce a specific catalytic activity, researchers have tried
to incorporate a variety of metals into the mesostructure by either
direct synthesis/ion-exchange or impregnation. The demand for
large pore acid catalysts has prompted greater efforts in both
the academicians and industrialists to synthesise mesoporous
molecular sieves and such acidic forms of porous materials are
important in organic synthesis for a number of catalytic reac-
tions [4–6]. Among the mesoporous materials having uniform
channels, large pore size, high specific surface area and high
thermal stability, KIT-6 exhibits a three-dimensional cubic Ia3d
its resistance against pore blockage of this phase could serve
as an excellent candidate for catalytic applications. Ryoo et al.
recently reported the synthesis routes by low acid concentra-
tions using triblock copolymers as structure-directing agents and
BuOH as a co-agent allowing the formation of great variety of
mesostructures [8]. Direct synthesis of Al-KIT-6 is difficult because,
under strongly acidic conditions during the synthesis, free alu-
minium species exist in cationic form and thus cannot enter
the framework of silica. Post-synthetic routes are preferred for
incorporating aluminium into mesoporous silica matrix and the
resulting materials found to possess structural ordering with bet-
ter catalytic activity. There are numerous applications of transistion
metal supported KIT-6 [9–12], KIT-1 [13–15], SBA-15 [16–18] and
MCM-41 [19–23] those favors organic reactions like esterification,
condensation, isomerisation, acetalization, cyclo-dehyration reac-
tions, hydrodesulfurization and oxidation reactions. Also, certain
multi component reactions (MCRs) involving C C bond forma-
tion, coupling reactions, Knoevenagel condensation reactions, Prins
cyclization, cyclo-addition and dehydrative etherifications pre-
ceded well over a variety of silica modified catalysts [24–27].
Heterocyclic compounds containing phthalazine moiety are
important in medicinal field due to their pharmacological
and biological activities [28,29]. Pyrazolo[1,2-b]phthalazine-dione
∗
Corresponding author at: Department of Chemistry, Anna University, Guindy,
Chennai 600 025, India. Tel.: +91 44 22358653; fax: +91 44 22200660.
E-mail address: pandurangan a@yahoo.com (A. Pandurangan).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.05.003

G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
59
derivatives were reported as anti-inflammatory, analgesic, antihy-
poxic, and antipyretic agents [30]. Novel biologically important
derivatives have been synthesized through MCRs which involve
minimal work trail with quantitative yields of the respective
products [31,32]. In recent times, we have demonstrated het-
erogenous acid catalysis over a variety of MCRs [33,34]. Recently,
1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives have been
synthesised by using pTSA [35] and ultrasound assistance [36].
Considering the above reports, herein we report the synthesis
of 3D cubic mesoporous aluminosilicates (Al-KIT-6) and their
activity as heterogenous solid acid catalysts towards the three
component reaction of phthalhydrazide, malononitrile/ethylcyano
acetate and aromatic aldehyde in ethanol under liquid phase con-
ditions. The reaction was monitored under various solvents and
aluminosilicates guides the multi-component reaction involving
cyclo-condensation pathway to afford the products associated with
easy separation and the recyclability of the catalysts.
and the filtrate was re-crystallized with methanol to get pure prod-
uct. All the products were characterized by 1H NMR, 13C NMR and
IR spectra and have been identified by comparison of the spectral
data with those reported. All yields refer to isolated products. NMR
spectra were recorded on a Bruker 500 MHz and IR spectra were
run on a Perkin-Elmer spectrometer.
2.4. Measurements
The crystalline phase identification and phase purity deter-
mination of the calcined samples of Al-KIT-6 were recorded by
XRD (PAN Analytical, diffractometer) using nickel filtered Cu K␣
˚
radiation (ꢀ = 1.5406 A). The metal content in the catalysts was
measured by inductively-coupled plasma optical emission spec-
troscopy (ICP-OES Optima 5300 DV – PerkinElmer). ASAP-2010
volumetric adsorption analyzer manufactured by the Micromerit-
ics Corporation (Norcross, GA) was used to determine the specific
surface area of the catalysts at liquid nitrogen temperature. Before
the measurement, each sample was degassed at 623 K at 10−5 Torr
overnight in an out gassing station of the adsorption appara-
tus. The full adsorption–desorption isotherm was obtained using
BET method at various relative pressures; the pore size distri-
bution were calculated from the nitrogen adsorption–desorption
isotherms using the BJH algorithm (ASAP-2010 built-in software
from Micromeritics). Mid-infrared spectra were recorded on a Nico-
let (Avatar 360) instrument using a KBr pellet technique. 27Al
MAS NMR spectra were recorded at 104 MHz on a Bruker DRX-
400 spectrometer equipped with a magic angle spin probe at
room temperature. NH3-TPD measurements were carried out in
a flow reactor (Micromeritics Instrument Corporation Chemisoft
TPx V1.02 Unit 1-2750). Samples were activated at 700 ◦C for 1 h
in a flow of helium; subsequently, ammonia was introduced by a
He stream containing 10 vol.% of ammonia at 100 ◦C. The physi-
cally adsorbed NH3 was removed by purging with a helium flow
at 100 ◦C until the baseline was flat. Then the reactor temperature
was ramped at a rate of 10 ◦C/min. SEM micrographs and EDS spec-
tra of the active catalysts was obtained from HITACHI (E-1010) ION
SPUTTER instrument. TEM was performed using a JEOL 3010 elec-
tron microscope operated at 300 kV. This has a filament made up of
LaB6 and the instrument works under a vacuum in the range 10−5
to 10−6 Pa.
2. Experimental
2.1. Materials
Tetraethylorthosilicate, aluminiumisopropoxide and triblock
copolymer (Pluronic P123, EO20PO70EO20; Aldrich: Mol. Wt. 5800)
were purchased from Aldrich (98% pure). Hydrochloric acid (35%)
and n-butanol, as co-solvent, used in the synthesis were AR grade
chemicals. Phthalhydrazide was purchased from Aldrich (99% pure)
and malononitrile, ethylcyanoacetate, various aromatic aldehydes
were purchased from SRL Biochem (India) Ltd. (98% pure) and were
used without further purification.
2.2. Synthesis of Al-KIT-6 materials
Si-KIT-6 materials were synthesized hydrothermally with the
gel composition of 1 TEOS:0.017 P123:1.83 HCl (35%):1.3 n-
BuOH:195 H2O. Pluronic P123 (4 g) was added to 144 g water and
7.9 g 35% HCl in a polypropylene bottle and stirred at 35 ◦C. A
homogenous solution was obtained after 4 h and then n-butanol
(4 g) was then added and the stirring was continued for 1 h. 8.6 g
of TEOS was added at once and the mixture was stirred for 24 h
at 35 ◦C and then the mixture was aged at 100 ◦C for 24 h under
static hydrothermal condition. The solid material was filtered hot
without washing and then dried at 100 ◦C for 12 h in air. The dried
sample was powdered and calcined at 550 ◦C for 8 h in air atmo-
sphere to remove the template. Alumination of siliceous KIT-6 was
done by post synthetic route according to the procedure reported
for SBA-15 in the literature [37]. The method involves the addition
of appropriate amounts of aluminium isopropoxide (for Si/Al: 25,
50, 75 and 100) to 1 g of Si-KIT-6 in hexane (50 ml). The solution
was stirred for 12 h, filtered and dried at 100 ◦C. In order to remove
the extra-framework aluminium, the dried materials were washed
with 1 M HCl and calcined at 550 ◦C for 5 h in air. The samples are
designated as Al-KIT-6 (33), Al-KIT-6 (56), Al-KIT-6 (81) and Al-KIT-
6 (110) with various Si/Al ratios after acid treatment as obtained
from ICP-OES results.
3. Results and discussion
3.1. Characterization of Al-KIT-6
3.1.1. XRD
Low-angle XRD patterns confirm the formation of the
mesophase of the synthesized aluminosilicates. Fig. 1(A) represents
the low angle XRD pattern of the calcined Si-KIT-6 parent material
and Fig. 2 represents the XRD pattern of calcined Al-KIT-6 materi-
als, which shows a sharp intense peak at 2ꢁ = 1.01 corresponding
to (2 1 1) plane and a hump for (2 2 0) plane. The XRD pattern
clearly indicates that the material is well ordered mesostructure
and belongs to bicontinuous cubic space group Ia3d symmetry [37].
The unit cell parameter a0 of calcined sample was calculated from
a0 = 61/2d(2 1 1), in good agreement with the literature and suggests
that mesoporous silica KIT-6 is with body centered cubic symmetry
of the space group Ia3d, with sharp peak due to the (2 1 1) reflection
and these data are presented in Table 1. The d spacing and a0 val-
ues of the fresh aluminosilicates suggests that there is a marginal
difference with varying aluminium content as the insertion of a
heteroatom leading to thickening of the pore wall through tran-
sition metal promoted cross-linking of the amorphous silica walls
[38].
2.3. Catalytic experiments
A mixture of pthalhydrazide (1 mmol), malononitrile or ethyl-
cyanoacetate (1 mmol), aromatic aldehyde (1.1 mmol), 300 mg
of catalyst and solvent (5 ml) was taken in
a magneti-
cally stirred glass vessel fitted with a reflux condenser and
was kept in
a constant temperature oil bath and refluxed
at 60 ◦C for appropriate time (4 h). The completion of the
reaction was monitored by TLC using ethyl acetate and n-hexane as
eluent. After completion of the reaction, the catalyst was removed

60
G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
(211)
(220)
(420)
(211)
(332)
(a)
(b)
(c)
(d)
(e)
(220)
(420)
(332)
A
1
2
3
4
5
6
7
8
2 Theta (deg)
1
2
3
4
5
6
7
8
Fig. 2. X-ray diffraction pattern of Al-KIT-6 [low angle (2ꢁ)]: (a) Al-KIT-6 (33), (b)
Al-KIT-6 (56), (c) Al-KIT-6 (81), (d) Al-KIT-6 (110) and (e) Al-KIT-6 (33) after fourth
cycle for the synthesis of Entry (a).
2 Theta (deg)
Fig. 1. (A) X-ray diffraction pattern of Si-KIT-6 [low angle (2ꢁ)] and inset (B) nitrogen
adsorption–desorption isotherms of Si-KIT-6.
content. Wall thickness was derived using Pw = (ao/2) − Pd (where
Pd is pore diameter and ao the unit cell parameter) is presented in
Table 1 for comparison.
3.1.2. N2 sorption analysis
Nitrogen adsorption–desorption isotherms and the correspond-
ing pore size distributions for the mesoporous KIT-6 materials are
shown in inset of Figs. 1, 3 and 4, respectively. The BET surface
area, pore volume, and average pore size of selected samples are
listed in Table 1. The isotherms are of type IV with a sharp capillary
condensation step at intermediate p/p0 at 0.6–0.7 and a hysteresis
loop characteristic for materials with narrow pore size distribu-
tion. A marginal difference in N2 sorption isotherms was observed
for Al-KIT-6 with Si/Al ratio 33, 56, 81 and 110. This difference sup-
ports the presence of metal in the mesopores. Those have a pore
radius around 3.0–3.1 nm (maximum large pore diameter around
6.2 nm) and a total pore volume from 0.6 to 0.7 cm3/g. The sharp
capillary condensation step indicating a regular pore size distri-
bution at the mesopore level exists in all catalysts. Although the
inclusion of aluminium into KIT-6 was expected to decrease the
specific surface area and the cumulative pore volume, a relatively
high surface area was observed ranging from 653 to 714 m2/g. The
surface area of the materials increased with decreasing aluminium
3.1.3. 27Al MAS NMR
27Al MAS NMR spectra of the Al-KIT-6 (33) materials are shown
Fig. 5. In general, the resonance at 0 ppm is assigned to octa-
hedral aluminium corresponding to extra-framework aluminium
species and resonance at 50 ppm is assigned to framework alu-
minium species in tetrahedral coordination [39]. The spectrum
of the sample shows two resonance peaks around 0 and 50 ppm
and most of the aluminium are in tetrahedral environment. The
single sharp resonance at 54 ppm corresponding to framework
aluminium species is maxima for the spectrum of all Al-KIT-6 mate-
rials. ICP-OES values of the materials with Si/Al ratios: 25, 50, 75 and
100 before the acid treatment was found with Si/Al ratios: 28, 52, 79
and 106. It was evident with the ICP-OES results of the acid treated
Al-KIT-6 materials (final product) that were found with Si/Al ratios:
33, 56, 81 and 110. This indicates that de-alumination occurred
during the acid treatment and the removal of extra-framework
Table 1
Physicochemical characterization and textural properties of various catalysts.
b
b
b
b
Catalysts
Si/Alc
(final product)
XRD
SBET
Pd
Pv
Pw
Acidity
(m2/g)
(nm)
(cm3/g)
(nm)
(mmol/g)e
d spacinga
(A)
ao
a
˚
(nm)
Si-KIT-6
–
33
56
81
110
37
–
–
–
–
–
92.51
83.52
84.28
86.66
91.37
84.15
–
–
–
–
–
22.57
20.42
20.64
21.20
22.30
20.58
–
–
–
–
–
765
653
671
684
714
580
0.02
64
6.2
6.0
6.1
6.1
6.2
6.0
–
–
–
–
–
0.73
0.65
0.67
0.68
0.71
0.61
–
–
–
–
–
5.0
4.2
4.2
4.5
4.9
4.3
–
–
–
–
-
–
Al-KIT-6 (25)
Al-KIT-6 (50)
Al-KIT-6 (75)
Al-KIT-6 (100)
Al-KIT-6 (33)d
Nafion-H
Amberlyst-15
HM (12)
H␤ (8)
0.32
0.27
0.19
0.11
–
0.8
0.75
1.14
0.92
0.58
481
502
367
HY (4)
√
SBET, specific surface area; Pd, pore diameter; Pw, pore wall thickness [ao/2 − Pd (where ao
=
6d)].
a
Values obtained from XRD studies.
b
Values obtained from N2-adsorption results.
Measured by ICP-OES technique.
Fourth cycle for the synthesis of Entry (a).
c
d
e
Values obtained from NH3-TPD results.

G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
61
Adsorption
Desorption
(a)
(b)
(c)
(d)
(e)
0.0
0.2
0.4
0.6
0.8
1.0
Relative pressure (p/p)
o
Fig. 3. Nitrogen adsorption–desorption isotherms of the catalysts: (a) Al-KIT-6 (33),
(b) Al-KIT-6 (56), (c) Al-KIT-6 (81), (d) Al-KIT-6 (110) and (e) Al-KIT-6 (33) after
fourth cycle for the synthesis of Entry (a).
aluminium and other impurities is obvious with the respective
difference in Si/Al ratios [40].
3.1.4. NH3-TPD
Fig. 5. 27Al MAS NMR spectra of catalysts (a) Al-KIT-6 (33), (b) Al-KIT-6 (56), (c)
The temperature-programmed desorption of ammonia (NH3-
TPD) was performed to determine the nature of surface acidity of
the catalysts with various Si/Al ratios as shown in Fig. 6. The spec-
tra shows a well defined high temperature desorption peaks as
the strength of acid sites is related to the corresponding desorp-
tion temperature. Generally, the acid sites are classified into weak
(200 ◦C), medium (200–350 ◦C), and strong (350 ◦C) acid sites [41].
In the given TPD profiles, the area under the peak for Al-KIT-6 (33)
gave 0.32 mmol/g total acidity which is high enough when com-
pared to Al-KIT-6 (1 1 0), i.e. 0.11 mmol/g. Also the acid site density
is 0.49 ␮mol/m2 for Al-KIT-6 (33) and 0.4 ␮mol/m2, 0.27 ␮mol/m2,
0.15 ␮mol/m2 for Si/Al: 56, 81 and 110 respectively. The area of
the TPD peaks implies that the samples have maximum amounts
of weak-medium acid sites and the measured acidity of the solids
is presented in Table 1.
Al-KIT-6 (81) and (d) Al-KIT-6 (110).
3.1.5. Energy dispersive X-ray spectral analysis
The energy dispersive spectra of Al-KIT-6 (33) is illustrated in
Fig. 7 which represents the presence of Si, O and Al for their respec-
tive K␣ signals confirming their presence of aluminium in the KIT-6
material for fresh catalyst. Si/Al ratio calculated from EDX data was
31 and this value was close to the value (33) obtained by ICP-OES.
3.1.6. TEM analysis
The structure and symmetry of the materials were determined
by transmission electron microscopy. The HRTEM images of the
fresh Al-KIT-6 (33) and reused catalyst shows that the material
(a)
(b)
(a)
(c)
(d)
(e)
(f)
(b)
(c)
(d)
(e)
10
20
30
40
50
60
70
80
90
100
100
200
300
400
500
Pore Radius (Å)
Temperature (oC)
Fig. 4. Pore size distribution of the catalysts: (a) Al-KIT-6 (33), (b) Al-KIT-6 (56),
(c) Al-KIT-6 (81), (d) Al-KIT-6 (110) and (e) Al-KIT-6 (33) after fourth cycle for the
synthesis of Entry (a).
Fig. 6. NH3-TPD spectra of (a) Al-KIT-6 (33), (b) Al-KIT-6 (56), (c) Al-KIT-6 (81), (d)
Al-KIT-6 (110) and (e) Si-KIT-6.

62
G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
was further confirmed by 1HNMR spectra; 1H NMR (500 MHz,
DMSO-d6): d = 6.11 (1 H, s, CH), 7.49-7.7 (5 H, m, ArH), 7.82–7.8 (4
H, m, ArH), 8.09 (2 H, s, NH2) ppm as shown in Fig. 10.
3.2.3. Effect of different solvents on product yield
Synthesis
of
1H-pyrazolo[1,2-]phthalazine-5,10-diones
was carried out with different solvents such as ethanol,
methanol, acetonitrile and ethyl acetate. The order
of various solvents over product yield is as follows:
ethanol > acetonitrile > methanol > water ꢀ ethyl acetate respec-
tively as shown in Table 3. Ethanol was found to be good solvent
for all the reactions and frequently pulls out the product through
the pores of the catalyst as the reaction proceeds further with
ease. The less polar solvents showed low product yield since the
solvent would have not been capable of getting the products at the
catalyst surface in that way the deactivation of the active surface
of the catalyst occurs and there was no reaction using solvents
like DMSO, DMF as the solvent plays a negative role by retarding
the multi-component pathway. This might be due to the adsorp-
tion of solvent on the catalyst surface or the solvent–reactant
interactions. The product yield was less when water was used
as solvent and this is due to the solubility problems of the
reactants.
Fig. 7. EDX spectrum of Fresh Al-KIT-6 (33).
consists of the presence of large domains of pure bicontinuous
meso structure (3-D silica–aluminium network) which highlights
the interconnectivity in the pore structure of the Ia3d cubic phase
(Fig. 8(a–d)).
3.2.4. Effect of catalyst and reusability
The
reaction
of
phthalhydrazide,
malononi-
trile/ethylcyanoacetate and aromatic aldehyde was performed
over various catalysts to evaluate the catalytic activity individu-
ally. In the Entries [a–n], the product yields for various catalysts
were compared under the same conditions. All the catalysts were
compared to support the activity based on the product yield,
recovery and reusability. The catalysts takes the order as presented
in Table 4 ; Al-KIT-6 (33) > Al-KIT-6 (56) > Al-KIT-6 (81) > Al-KIT-6
(110) > Nafion-H > Amberlyst-15 ꢀ HM (12) > H␤ (8) > HY (4). All
catalysts showed a good yield of products. Among the mesoporous
alumino silicates, the activity was high with Al-KIT-6 (33) nearly
93% and the isolated yield using Al-KIT-6 (56), KIT-6 (81) and
Al-KIT-6 (110) was 79%, 71% and 64%. This indicates that the
conversion decreases with Si/Al ratios and respectively increases
with acidity of the catalysts. Acidity and mesoporosity of the
3.2. Catalytic studies
3.2.1. Synthesis of 1H-pyrazolo[1,2-]phthalazine-5,10-diones
from phthalhydrazide, malononitrile/ethylcyanoacetate, aromatic
aldehydes
Initially the synthesis of 1H-pyrazolo[1,2-]phthalazine-
5,10-diones was performed by taking
a
mixture of
stoichiometric amount of pthalhydrazide, benzaldehyde
and malononitrile/ethylcyanoacetate along with 300 mg
of catalyst in ethanol and refluxed at 60 ◦C for 4 h. The
reaction involves dehydration and cyclization to yield
the
respective
1H-pyrazolo[1,2-]phthalazine-5,10-diones.
O
O
Ar
Al-KIT-6
NH
NH
N
R
N
N
R
ArCHO
Δ
EtOH
O
NH2
1H-Pyrazolo[1,2-]phthalazine-5,10-diones
1H-pyrazolo[1,2-]phthalazine-5,10-
O
Phthalhydrazide
R
= CN or COOEt
Different
substituted
catalysts is important for the reaction which is evident from the
fact that there was no reaction without the use of any catalyst
or with Si-KIT-6. The lower activity of Al-KIT-6 (110) compared
to other Al-KIT-6 catalysts is due to the low aluminium content
with low acid amount even though the surface area is high. On the
other hand, amberlyst-15 and nafion catalysts offered low yield
which shows that the mesoporosity of silica is indispensable. The
yield of the product was less over zeolites because of the micro-
porosity and high acidity that could hinder the formation of the
required products. The acid sites of Al-KIT-6 catalysts induce the
reaction by proton transfer to afford the products through the
condensation of the aldehyde and active methylene nitriles (mal-
ononitrile/ethylcyano acetate) followed by the cyclization with
phthalhydrazide. The mechanism (as in Fig. 11 ) involves the
formation of carbo-cation by the proton donation by the catalyst
to aldehyde with the removal of water molecule, and in subse-
quent steps, proton goes to catalyst and again proton transfer
diones were prepared changing the aromatic aldehyde
substituents. The para-substituted aldehydes gave good results in
short time compared to the ortho-substituents as there is more
steric hindrance for the ortho substituted aldehydes o-(OCH3, Cl,
Br, NO2) on the product formation than the para-substituted
p-(OCH3, CH3, Cl, Br, NO2) aldehydes with the use of
Al-KIT-6 catalysts. The presence of electron-donating or electron-
withdrawing groups in the aromatic ring of the aldehydes had no
substitution effect on the yield to afford respective products.
3.2.2. Structural determination of isolated products
Primary elucidation of the structures for all the isolated prod-
ucts was done by FT-IR spectra. For Entry [a] – Table 2: a band
at 3361 cm−1 for NH stretching, a band at 3025 cm−1 for alkyl
CH stretching, a band at 2215 cm−1 for nitrile (CN stretching),
1656 cm−1 for C O stretching (Fig. 9). The structure of the product

G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
63
Table 2
Synthesis of 1H-pyrazolo[1,2-]phthalazine-5,10-diones.
Entry
Ar
R
Product
Isolated yield
(%)
O
O
N
N
a
CN
93
CN
CN
o
NH2
Cl
O
Cl
b
CN
N
N
87
o
NH2
Cl
O
Cl
O
c
CN
90
N
N
CN
NH2
Br
o
O
Br
O
O
d
CN
89
N
N
CN
NH2
o
o
O2N
NO2
O
e
CN
84
N
N
CN
NH2
NO2
O
NO2
O
O
f
CN
91
N
N
CN
NH2
o
H3CO
O
N
N
g
CN
90
H3CO
CN
NH2
o
O
OCH3
OCH3
O
O
h
CN
92
N
N
CN
NH2
o

64
G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
Table 2 (Continued)
Entry
Ar
R
Product
Isolated yield
(%)
CH3
CN
O
i
CN
90
N
N
o
o
NH2
O
O
N
N
j
COOEt
90
COOEt
Cl
NH2
O
Cl
O
k
COOEt
82
79
84
N
N
COOEt
o
o
NH2
O
O
l
COOEt
N
N
COOEt
NH2
O
NO2
NO2
O
O
m
COOEt
N
N
COOEt
NH2
o
o
OCH3
OCH3
O
n
COOEt
87
N
N
COOEt
NH2
O
Reaction conditions: mole ratio = 1:1:1.1 (phthalhydrazide:malononitrile/ethylcyanoacetate:benzaldehyde); solvent = ethanol; catalyst = Al-KIT-6 (33); wt. of the cata-
lyst = 300 mg; reaction temperature = 60 ◦C; reaction time = 4 h.
takes place to give the carbo-cation. The addition of the formed
cation to phthalhydrazide takes place with the release of pro-
ton which in turn cyclise to give pyrazolo phthalazine diones. For
all the substituted pyrazolo[1,2-b]phthalazine-2-carbonitrile and
pyrazolo[1,2-b]phthalazine-2-carboxylate derivatives, the meso-
porous aluminosilicates benefits the reactions involving large
organic molecules. The three-dimensional mesopores and high sur-
face area of KIT-6 aluminosilicates with acid centres as a whole
is highly accountable for the expected products in good yields. In
addition they were diffusion resistant for the reactants to react
completely.
liquid-phase reactions. After each experiment, the amount of alu-
minium was determined by ICP after removal of the solid catalyst
by filtration. The extent of reusability was studied by choosing the
model reaction of phthalhydrazide, benzaldehyde and malononi-
trile/ethyl cyanoacetate. The reusability of the Al-KIT-6 catalysts
was tested by recovering the catalysts by filtration from the
solution and washed with acetone and dried to get the material.
The isolated yield of Entry [a], 3-amino-5,10-dihydro-5,10-dioxo-
1-phenyl-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile for four
runs were 93–79% respectively. In the case of Entry [j] ethyl
3-amino-5,10-dihydro-5,10-dioxo-1-phenyl-1H-pyrazolo[1,2-
b]phthalazine-2-carboxylate, the yield percentage for fresh and
up to four recycles were found to be 90–71%. The isolated yield
The extent of leaching of the metal from the support is
important when dealing with heterogeneous-type catalysts in

G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
65
Fig. 8. TEM images of Al-KIT-6 (33): (a and b) fresh and (c and d) recycled catalyst after 4th cycle.
O
O
N
N
NH
2
3361 3025
3500 3000
2215
2000
1656
1500
2500
1000
500
Wavenumber [cm-1]
Fig. 9. [Table 2, Entry (a)]: IR (KBr); 3361 cm−1, 3025 cm−1, 2215 cm−1, 1656 cm−1
.
Fig. 10. 1H NMR (DMSOd6, 500 MHz) spectrum of the compound [Table 3, Entry
(a)].

66
G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
R
O
OH
Ar
-H2O
+
Ar
CH
CH
Ar
CH
C
C
N
H
N
C
R
CH
H
H
O
Al
Si
O
-H
Al-KIT-6
R
R
C
Ar
Ar
O
C
C
C
H
C
N
NH
C
H
NH
NH
O
(Phthalhydrazide)
Ar
Ar
O
O
CH
O
-H
N
N
CH
R
(goes to catalyst)
C
N
R
C
NH
C
NH2
C
O
H
O
HN
Al
Si
Pyrazolo phthalazinedione
O
Fig. 11. Plausible mechanism for the formation of 1H-pyrazolo[1,2-]phthalazine-5,10-diones over Al-KIT-6.
after each cycles are presented in Table 5 . From the observation,
the catalyst Al-KIT-6 (33) showed minor difference in the yield of
the reaction and the ICP analysis showed leaching of aluminium
from 33 to 37 after the last cycle. Also it is clear that on recycling
the catalysts, aluminium still exists without major leaching as to
support that there is a strong interaction with SiO2. The pore wall
thickness was 4.3 nm and surface area decreased to 580 m2/g with
a pore volume 0.61 cm3/g and pore diameter 6.0 nm. Also, for the
determination of the structure and symmetry of the final recycled
catalyst Al-KIT-6 (33), XRD was employed which showed practical
decrease in patterns as shown in Fig. 2 and the data are presented
in Table 1.
Table 4
Effect of various catalysts on 3-amino-5,10-dihydro-5,10-dioxo-1-phenyl-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile over various catalysts.
Sl. no.
Catalysts
Isolated yield (%)
Table 3
Effect of various solvents on the synthesis of 3-amino-5,10-dihydro-5,10-dioxo-1-
phenyl-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile over Al-KIT-6.
1
2
3
4
5
6
7
8
Al-KIT-6 (33)
Al-KIT-6 (56)
Al-KIT-6 (81)
Al-KIT-6 (110)
Nafion-H
Amberlyst-15
HM (12)
H␤ (8)
93
79
71
64
56
41
26
19
12
–
Sl. no.
Solvent
Isolated yield (%)
1
2
3
4
5
6
7
Ethanol
93
72
59
29
15
–
Acetonitrile
Methanol
Water
Ethyl acetate
DMSO
9
10
11
HY (4)
Si-KIT-6
Without catalyst
DMF
–
–
Reaction conditions: mole ratio =1:1:1.1 (phthalhydrazide/malononitrile/
benzaldehyde); solvent = ethanol; catalyst = Al-KIT-6 (33); wt. of the cata-
lyst = 300 mg; reaction temperature = reflux; reaction time = 4 h.
Reaction conditions: mole ratio =1:1:1.1 (phthalhydrazide/malononitrile/
benzaldehyde); solvent = ethanol; wt. of the catalyst = 300 mg; reaction
temperature = 60 ◦C; reaction time = 4 h.

G. Karthikeyan, A. Pandurangan / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 58–67
67
Table 5
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Reusability of Al-KIT-6 (33) catalyst for the synthesis of 3-amino-5,10-
dihydro-5,10-dioxo-1-phenyl-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrilea and
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Post-synthetic implantation of aluminium over Si-KIT-6 was
successfully done under hydrothermal conditions. Acid leach-
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impurities and extra framework aluminium. The mesoporous
aluminosilicates were found to be good recyclable solid acid cata-
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