Silica gel-supported tungstic acid (STA): A new, highly efficient and recyclable catalyst for the synthesis of 1 H-pyrazolo[1,2-b[phthalazine-5,10-dione carbonitriles and carboxylates under neat conditions

Article abstract of DOI:10.1016/j.crci.2014.01.026

1H-Pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates possess a broad range of applications as active compounds in the pharmacological and biological fields. We developed an efficient and ecofriendly silica gel-supported tungstic acid (STA)-catalyzed one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates by a three-component reaction of an aldehyde, a malononitrile/ethyl cyanoacetate and a phthalhydrazide under solvent-free conditions. The major advantages of the present method are experimental simplicity, use of an inexpensive and ecofriendly reusable catalyst, good yields, and short reaction times.

Full text of DOI:10.1016/j.crci.2014.01.026

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Contents lists available at ScienceDirect
Comptes Rendus Chimie
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´
Full paper/Memoire
Silica gel-supported tungstic acid (STA): A new, highly
efficient and recyclable catalyst for the synthesis of
1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles
and carboxylates under neat conditions
a
M. Veeranaryana Reddy a, , P. Chenna Rohini Kumar ,
*
G. Chandra Sekhar Reddy b, C. Suresh Reddy a
a Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
b Department of Chemistry, Sri Venkateswara College of Engineering, Tirupati 517 507, India
A R T I C L E I N F O
A B S T R A C T
Article history:
1H-Pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates possess a broad
range of applications as active compounds in the pharmacological and biological fields. We
developed an efficient and ecofriendly silica gel-supported tungstic acid (STA)-catalyzed
one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carbox-
ylates by a three-component reaction of an aldehyde, a malononitrile/ethyl cyanoacetate
and a phthalhydrazide under solvent-free conditions. The major advantages of the present
method are experimental simplicity, use of an inexpensive and ecofriendly reusable
catalyst, good yields, and short reaction times.
Received 11 December 2013
Accepted after revision 30 January 2014
Available online xxx
Keywords:
Silica gel-supported tungstic acid
1H-pyrazolo[1,2-b]phthalazine-5,10-dione
carbonitriles and carboxylates
Phthalhydrazide
´
ß 2014 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Neat reaction
1. Introduction
products and as drug molecules [11–15], the pyra-
zolo[1,2-b]phthalazine-dione and their derivatives are
An increasing number of studies have reported on the
environmentally friendly production of fine chemicals
using recyclable heterogeneous catalysts via multi-com-
ponent reactions (MCRs). They are considered to be
superior synthetic strategies [1–10], with highly efficient
atom economy compared to other organic reactions. Their
advantages in terms of one-pot multi-component reaction,
reaction time, product yield, minimization of waste
production, energy consumption and reproducibility have
been repeatedly exploited in various efficient syntheses of
heterocyclic compounds.
important targets in synthetic organic chemistry. In
particular, pyrazolo[1,2-b]phthalazine-diones are biologi-
cally active and occur in structures of a number of anti-
inflammatory, anti-allergic, analgesic antihypoxic, antic-
onvulsant, cardiotonic, vasorelaxant, antipyretic anti-
hyperglycemic, anti-bacterial, and anti-viral compounds
[16–18]. This core also has been utilized in diverse
pharmaceutical applications, such as in anti-cancer [19]
and anti-diabetes [20] agents.
So far, only a few methods have been reported for the
preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
carbonitriles and carboxylates [21]. However, the above-
mentioned catalysts have one or more disadvantages, such
as long reaction time, high reaction temperature, use of
volatile and hazardous organic solvents, occurrence of side
products, and they were reported in homogenous cata-
lysts. Even though Pandurangan et al. used heterogeneous
catalysts, they reported they worked in solvents, with long
Due to numerous important biological activities as
versatile building blocks for the synthesis of natural
*
Corresponding author.
E-mail addresses: veerupandu@gmail.com, drvnreddym@gmail.com
(M.V. Reddy).
1631-0748/$ – see front matter ß 2014 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2014.01.026
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

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M.V. Reddy et al. / C. R. Chimie xxx (2014) xxx–xxx
Scheme 1. Neat synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates catalyzed by STA.
reaction times [21a]. The use of homogenous catalysts has
received little attention as alternatives to alleviating some
of the limitations. Solid acids as heterogeneous catalysts
have received tremendous attention in different areas of
organic synthesis [22]. Heterogeneous solid acids are
advantageous over conventional homogeneous acid cata-
lysts as they can be easily recovered from the reaction
mixture by simple filtration and can be reused after with or
without activation, thereby making the process economic-
ally more viable. Among them, silica gel-supported
tungstic acid (STA) is a well-known and widely used solid
acid catalyst in synthetic organic chemistry. It has received
considerable attention due to its non-toxicity, cost
effectiveness, air and water compatibility, ease of handling,
good reactivity, recyclability, experimental simplicity,
remarkable ability as a green catalyst to suppress side
reactions in acid-sensitive substrates and as supports for a
wide variety of reactions. Despite its great importance,
only a few publications are reported on its catalytic
application in organic synthesis [23]. It is evident from
recent literature that the solvent-free endorsed STA
reactions are well known as environmentally benign
methods that also usually provide improved selectively,
enhanced reaction rates, cleaner products, and manipula-
tive simplicity [23a,b].
three-component condensation reaction of phthalhydra-
zide, aldehydes and malononitrile/ethyl cyanoacetate in
solvent-free conditions at 70 8C (Scheme 1).
2. Results and discussion
For our initial investigation, the reaction of phthalhy-
drazide (1), 2,3-dihydrobenzo[b][1,4]dioxine-6-carbalde-
hyde (2a), and malononitril (3a) under neat conditions was
chosen as a model reaction. At 70 8C and in the absence of
catalyst, we could not isolate any desired MCR product,
even after 6 h of stirring. After 10 h of stirring, a trace
amount of the corresponding product was obtained
(Table 1, entry 1). Next, the same set of reactions was
performed in the presence of 5 mol% of PS/PTSA. Within
4 h, the corresponding title product 4a was isolated in 40%
product yield (Table 1, entry 2). The product 4a was
confirmed by usual spectroscopic techniques. Encouraged
by this result, we attempted to optimize the yield of the
reaction by screening the same set of reactions with
various heterogeneous catalysts, such as BF3–SiO2, CAN–
SiO2, TiO2–SiO2 and STA, and the results are summarized in
Table 1. Among all the screened catalysts, STA was found
superior with respect to reaction time and product yield
(Table 1, entry 6). Moreover, we found that the yields were
obviously affected by the amount of loaded STA. When
1 mol%, 2 mol%, 5 mol% and 10 mol% of STA were used, the
yields were 58, 70, 93, and 94%, respectively (Table 1,
entries 6–9). Therefore, 5 mol% of STA was sufficient and no
more significant improvement in the reaction rate and
product yield was observed while increasing the amount of
the catalyst from 5 to 10 mol% (Table 1, entry 9).
In continuation of our efforts to develop new green
methodologies and as well as our interest in applications
of heterogeneous-catalyzed organic reactions [24], we
reported herein STA as a new heterogeneous catalytic
system for MCR. The STA catalytic activity was investigated
for the one-pot synthesis of 1H-pyrazolo[1,2-b]phthala-
zine-5,10-dione carbonitriles and carboxylates through a
Table 2
Table 1
Optimal reaction conditions and temperatures for different solvents in
the synthesis of 3-amino-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5,10-
dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 4aa.
Influence of the catalyst for the synthesis of 3-amino-1-(2,3-dihydro-
benzo[b][1,4]dioxin-6-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-
b]phthalazine-2-carbonitrile 4aa.
Entry
Solvent
Temp (8C)
Yield (%)b
Entry
Catalyst (mol%)
Time (min)
Yield (%)b
Catalyst-free
conditions
STA
1
2
3
4
5
6c
7
8
9
Neat
600
240
170
110
130
20
Trace
(5 mol%)
PT/PTSA (5 mol%)
BF3–SiO2 (5 mol%)
CAN–SiO2 (5 mol%)
TiO2–SiO2 (5 mol%)
STA (5 mol%)
40
60
1
2
3
4
5
6
7
8
Toluene
Chlorobenzene
CH2Cl2
110
120
75
33.4
32.2
34.1
30.4
43.6
48.8
57.4
20.5
52.6
48.7
48.4
45.1
50.8
61.4
80.4
93.0
75
66
93, 92, 90, 89
CCl4
75
STA (1 mol%)
100
55
58
70
94
THF
65
STA (2 mol%)
Acetonitrile
Ethanol
65
STA (10 mol%)
20
70
No solvent
70
a
Reaction of 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde (2a,
1 mmol), phthalhydrazide (1, 1 mmol) and malononitrile (3a, 1 mmol)
under neat at 70 8C.
a
Reaction conditions: 3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde
(2a, 1 mmol), phthalhydrazide (1, 1 mmol), and malononitrile (3a,
1 mmol). Reaction times: 20 min.
b
Isolated yield.
c
b
The catalyst was reused four times.
Isolated yield.
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

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3
Then, we investigated the influence of various organic
solvents at different reaction temperatures on the model
reaction with 5 mol% of STA with and without catalyst.
Among various solvents, such as toluene, THF, CH2Cl2,
CH3CN, and DMF, the reaction rate is very slow and
resulted in lower product yields (Table 2, entries 1–6).
Conducting the same reaction in ethanol improved both
the reaction rate and the product yield (Table 2, entry 7).
However, the better product yield was observed in solvent-
free conditions (Table 2, entry 8) and could be explained by
a uniform distribution of the eutectic mixture of reactants,
which are in closer proximity to react. It was concluded
that irrespective of the nature of solvent, even at its boiling
temperature, the optimum conversion rate of the reactants
was always observed, whereas under solvent-free condi-
tions, the maximum conversion rate of the reactants was
only achieved at 70 8C.
of reaction (Table 2, entries 1–7). Irrespective of the nature
of the solvent, even at its boiling temperature, we always
observed an optimum conversion rate of the products
(Fig. 1), but under solvent-free conditions, the maximum
conversion yield was achieved (Table 2, entry 8). The lower
yields in solvent medium may be due to salvation of
reaction medium.
In order to investigate the catalytic activity and the
possibility of catalyst recyclability and reusability, the STA
was recovered from the reaction mixture by simple
filtration in hot EtOH. The separated catalyst was dried
in a vacuum oven at 100 8C and was reused as such for
subsequent experiments under similar reaction condi-
tions. The results showed that the catalyst could be
effectively reused for at least four consecutive cycles
without much appreciable loss in its catalytic activity
(Table 1, entry 6). The recyclability data demonstrate a
high stability of the catalyst under the reaction conditions.
Having optimized the reaction conditions for the
synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
Solvent and temperature variations have also been
tested on the model reaction using 5 mol% of STA in
different solvents at their boiling temperatures for 20 min
Table 3
STA-catalyzed multi-component synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates 4a–t.
Compound
R
X
Yield (%)a
Time (min)
Mp (8C)
Found
Reported
4a
CN
93
20
261–263
4b
CN
90
25
259–261
4c
4d
4e
4f
2-Cl–6-F–C6H3
3,5-F–C6H3
2-F–4-Br–C6H3
3-F–C6H4
CN
CN
CN
CN
CN
CN
CN
CN
91
92
91
93
90
88
89
85
30
26
28
20
26
30
28
32
266–268
272–274
252–254
263–265
260–262
240–242
223–225
245–247
264–266 [21f]
261–263 [21f]
238–240 [21f]
220–222 [21f]
244–246 [21f]
4g
4h
4i
3-F–4-Me-C6H3
C2H5
C3H7
4j
2-thiophene (C4H3S)
4k
CO2Et
91
24
220–222
4l
CO2Et
88
30
211–213
4m
4n
4o
4p
4q
4r
2-Cl–6-F–C6H3
3,5-F–C6H3
2-F–4-Br–C6H3
3-F–C6H4
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
88
90
89
92
90
87
89
90
31
26
32
22
30
35
32
35
217–219
246–248
215–217
228–230
220–222
167–169
151–153
228–230
228–230 [21f]
222–224 [21f]
165–167 [21f]
150–152 [21f]
228–230 [21f]
3-F–4-Me–C6H3
C2H5
4s
C3H7
4t
2-thiophene (C4H3S)
a
Isolated yield.
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

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M.V. Reddy et al. / C. R. Chimie xxx (2014) xxx–xxx
Fig. 1. (Color online.) Product yields at various solvents on model reaction.
carbonitriles and carboxylates using STA as the catalyst
under solvent-free conditions, we subsequently applied
the optimized reaction conditions to various aldehydes to
explore the generality of the reaction system. As shown in
Table 3, multi-component reactions produced excellent
product yields for a wide range of aromatic aldehydes
bearing both electron-donating and electron-withdrawing
substituents. Non-aromatic and heteroaromatic alde-
hydes, however, were less reactive, producing only
moderate yields (Table 3). In a similar manner to what
was observed with malononitrile, ethyl cyanoacetate also
participated in this multi-component reaction to afford the
O
STA
H
R
N
N
C
(2a-t)
N
N
H
C
C
C
(3)
(3)
R
C
HO
STA
R
O
O
H
N
N
STA
STA
CN
CH
N
NC
OH
NH2
(4a-t)
STA
R
O
CN
O
CN
CH
C
H
N
N
H
C
C
HN
HN
C
R
N
STA
O
O
1
H
HN
STA
-H2O
-STA
R
6
C
C
C
CN
STA
N
5
Scheme 2. (Color online.) Schematic presentation of the postulated mechanistic activity of our STA catalyst.
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

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5
corresponding 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
carbonitriles and carboxylates in good yields. In all cases,
the pure product was isolated by simple filtration, without
chromatography or a cumbersome work-up procedure.
After the reaction, the catalyst can be easily separated from
the product and reused without any significant decrease in
its catalytic activity. All new structures were characterized
by 1H NMR, 13C NMR, and HRMS. Data and melting point of
compounds 4f–j and 4p–t coincide with those of the
reported ones.
the catalyst was filtered. The residue was crystallized from
ethanol to afford product 4a (93%). The catalyst was
washed with diethylether, dried at 100 8C for 2 h, and
reused in another reaction.
4.2.1. 3-Amino-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-
5,10-dioxo-5,10-dihydro-1H-pyrazolo-[1,2-b]phthalazine-2-
carbonitrile (4a)
Yield 93%; yellow powder; mp 261–263 8C. 1H NMR
(400 MHz, DMSO-d6):
d 8.25–8.23 (m, 1H), 8.11 (s, 2H),
The role of STA as a catalyst in the synthesis of the title
compounds (4a–t) should be postulated as shown in
Scheme 2. The multi-component reaction should be
proceeding in a stepwise manner. First, the reaction
occurs via a Knoevenagel condensation between the
enolic form of malononitrile (3) and aldehyde (2) in the
presence of acidic STA as a catalyst to form intermediate
5. Here, the solid catalyst can facilitate active hosting sites
for reactant molecules and accelerate the reaction rate.
Second, intermediate 5 immediately transforms into one
more intermediate, 6, by Michael addition of 2,3-
dihydrophthalazine-1,4-dione (1) at the conjugated
C5C bond of 5. Finally, by intramolecular concerted
cyclisation of the adduct, 6 gave the title compounds
(4a–t) in good yields.
8.10–8.06 (m, 1H), 7.96–7.92 (m, 2H), 6.95 (d, J = 8.2 Hz,
1H), 6.82 (d, J = 9.2 Hz, 2H), 6.25 (s, 1H), 4.20 (s, 4H). 13C
NMR (100 MHz, DMSO-d6):
d 156.5, 153.9, 150.5, 146.8,
135.5, 134.5, 133.7, 129.0, 128.4, 127.2, 126.6, 120.5, 117.5,
115.5, 112.8, 64.2, 59.5, 58.3. HRMS (ESI, m/z): calcd for
C
20H14N4O4 (M+H+) 374.1015; found: 374.1011.
4.2.2. 3-Amino-1-(benzo[d][1,3]dioxol-5-yl)-5,10-dioxo-
5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4b)
Yield 90%; yellow powder; mp 259–261 8C. 1H NMR
(400 MHz, DMSO-d6):
8.09–8.05 (m, 1H), 7.97–7.93 (m, 2H), 6.75–6.70 (m, 3H),
6.65 (s, 1H), 6.10 (s, 2H). 13C NMR (100 MHz, DMSO-d6):
d 8.24–8.19 (m, 1H), 8.12 (s, 2H),
d
156.5, 153.5, 152.5, 151.4, 146.6, 144.1, 136.5, 134.6, 133.4,
129.2, 128.5, 127.0, 126.1, 118.5, 115.9, 112.5, 104.5, 59.8,
58.6. HRMS (ESI, m/z): calcd for C19H12N4O4 (M+H+)
360.059; found: 360.059.
3. Conclusion
In conclusion, we have explored the use of the
heterogeneous STA catalyst as an effective and reusable
catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthala-
zine-5,10-dione carbonitriles and carboxylates. The
use of an environmentally friendly and inexpensive
catalyst and solvent-free conditions, along with the
reusability of the catalyst, provides a good example of a
competitive alternative synthetic methodology for these
compounds.
4.2.3. 3-Amino-1-(2-chloro-6-fluorophenyl)-5,10-dioxo-
5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4c)
Yield 91%; yellow powder; mp 266–268 8C. 1H NMR
(400 MHz, DMSO-d6):
d 8.25–8.24 (m, 1H), 8.12 (s, 2H),
8.10–8.06 (m, 1H), 7.98–7.95 (m, 2H), 7.45 (t, J = 8.8 Hz,
1H), 7.30 (dd, J = 2.2, 12.8, Hz, 1H), 7.05 (dd, J = 2.2, 11.0, Hz,
1H), 6.09 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
d 160.4,
156.5, 153.2, 150.4, 134.7, 133.8, 129.7, 129.6, 128.4, 127.5,
126.7, 124.6, 119.7, 117.6, 111.3, 59.9, 57.5. HRMS (ESI, m/
z): calcd for C18H10ClFN4O2 368.0476; found: 368.0470.
4. Experimental
4.1. General
4.2.4. 3-Amino-1-(3,5-difluorophenyl)-5,10-dioxo-5,10-
dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4d)
Yield 92%; yellow powder; mp 272–274 8C. 1H NMR
Chemicals were purchased from Aldrich and Alfa Aesar
Chemical Companies. NMR spectra were recorded in ppm
in DMSO-d6 on a Jeol JNM ECP 400 NMR instrument using
TMS as an internal standard. Mass spectra were recorded
on a Jeol JMS-700 mass spectrometer. All melting points
were determined using open capillaries on an Electro-
thermal-9100 (Japan) instrument.
(400 MHz, DMSO-d6):
d 8.28–8.26 (m, 1H), 8.08–8.06 (m,
1H), 8.05 (s, 2H), 7.88–7.86 (m, 2H), 6.95 (d, J = 7.2 Hz, 2H),
6.74–6.69 (m, 1H), 6.39 (s, 1H). 13C NMR (100 MHz, DMSO-
d6): d 164.2, 159.6, 155.6, 154.4, 151.4, 140.3, 134.7, 133.8,
128.9, 128.1, 127.7, 117.4, 110.4, 104.6, 62.9, 60.8. HRMS
(ESI, m/z): calcd for C18H10F2N4O2 352.077; found:
352.070.
4.2. General procedure for the synthesis of 3-amino-1-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-5,10-dioxo-5,10-dihydro-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4a)
4.2.5. 3-Amino-1-(4-bromo-2-fluorophenyl)-5,10-dioxo-
5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4e)
A mixture of phthalhydrazide (1, 1 mmol, 162 mg), 2,3-
dihydrobenzo[b][1,4]dioxine-6-carbaldehyde (2a, 1 mmol,
164 mg), malononitrile (3a, 1 mmol, 66 mg) and STA
(5 mol%, 21 mg) was stirred at 70 8C under solvent-free
conditions for 20 min (Table 3, entry 1). The progress of the
reaction was monitored by TLC. After completion of the
reaction, the mixture was dissolved in hot ethanol and
Yield 91%; yellow powder; mp 252–234 8C. 1H NMR
(400 MHz, DMSO-d6):
d 8.27–8.24 (m, 1H), 8.12 (s, 2H),
8.11–8.07 (m, 1H), 7.96–7.93 (m, 2H), 7.34 (t, J = 8.8 Hz,
2H), 7.01 (dd, J = 2.2, 12.8, Hz, 1H), 6.30 (s, 1H). 13C NMR
(100 MHz, DMSO-d6):
d 160.5, 156.6, 153.4, 150.8, 134.7,
133.8, 130.5, 129.7, 128.6, 128.4, 127.3, 126.7, 121.4, 119.4,
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

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M.V. Reddy et al. / C. R. Chimie xxx (2014) xxx–xxx
115.7, 59.9, 57.5. HRMS (ESI, m/z): calcd for
18H10BrFN4O2411.997; found: 411.997.
8.09–8.06 (m, 1H), 7.96–7.93 (m, 2H), 7.30 (t, J = 8.8 Hz,
2H), 7.01 (dd, J = 2.2, 12.8, Hz, 1H), 6.23 (s, 1H), 4.00–3.94
(m, 2H), 1.03 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, DMSO-
C
4.2.6. Ethyl 3-amino-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-
yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-
b]phthalazine-2-carboxylate (4k)
d6): d 162.9, 160.0, 156.5, 154.4, 151.8, 134.7, 133.2, 130.2,
128.2, 128.6, 128.3, 127.2, 126.9, 121.4, 118.4, 116.7, 80.5,
58.0, 56.5, 13.9. HRMS (ESI, m/z): calcd for C20H15BrFN3O4
459.023 (M+H+) 459.023; found: 459.023.
Yield 91%; yellow powder; mp 220–222 8C. 1H NMR
(400 MHz, DMSO-d6):
d 8.25–8.23 (m, 1H), 8.10 (s, 2H),
8.08–8.06 (m, 1H), 7.96–7.92 (m, 2H), 6.90 (d, J = 8.2 Hz,
1H), 6.72 (d, J = 9.2 Hz, 2H), 6.05 (s, 1H), 4.20 (s, 4H), 4.02–
3.95 (m, 2H), 1.02 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
Acknowledgements
The authors express their grateful thanks to Depart-
ment of Science and Technology (DST), New Delhi for
providing financial assistance (CS/014/2013 dated 06/05/
2013).
DMSO-d6):
d 163.5, 155.5, 153.6, 149.5, 146.4, 135.0,
133.9, 133.0, 129.3, 128.0, 127.2, 126.8, 120.5, 118.5,
116.5, 112.9, 80.5, 60.2, 59.5, 58.2, 14.2. HRMS (ESI, m/z):
calcd for C22H19N3O6 (M+H+) 421.127; found: 421.121.
4.2.7. Ethyl 3-amino-1-(benzo[d][1,3]dioxol-5-yl)-5,10-
dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-
carboxylate (4l)
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Yield 88%; yellow powder; mp 211–213 8C. 1H NMR
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d 8.27–8.24 (m, 2H), 8.16 (s, 2H),
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4.2.8. Ethyl 3-amino-1-(2-chloro-6-fluorophenyl)-5,10-
dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-
carboxylate (4m)
Yield 88%; yellow powder; mp 217–219 8C. 1H NMR
(400 MHz, DMSO-d6):
d 8.22–8.18 (m, 1H), 8.10 (s, 2H),
8.08–8.04 (m, 1H), 7.94–7.90 (m, 2H), 7.35 (t, J = 8.0 Hz,
1H), 7.20 (d, J = 7.8 Hz, 1H), 7.05 (dd, J = 2.2, 11.0, Hz, 1H),
6.10 (s, 1H), 3.99–3.94 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H). 13
C
NMR (100 MHz, DMSO-d6):
d 163.6, 161.0, 156.5, 153.0,
150.2, 134.7, 133.8, 129.4, 129.0, 128.4, 127.5, 125.7,
124.3, 118.7, 117.6, 112.3, 81.1, 58.9, 56.5, 14.3. HRMS
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(4n)
Yield 90%; Yellow powder; mp 246–248 8C. 1H NMR
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d 8.25–8.22 (m, 1H), 8.12–8.08 (m,
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128.3, 127.7, 117.4, 110.4, 104.6, 80.3, 60.8, 58.4,
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d 8.27–8.24 (m, 1H), 8.10 (s, 2H),
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026

G Model
CRAS2C-3909; No. of Pages 7
M.V. Reddy et al. / C. R. Chimie xxx (2014) xxx–xxx
7
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6071.
Please cite this article in press as: Reddy MV, et al. Silica gel-supported tungstic acid (STA): A new, highly efficient and
recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under
neat conditions. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2014.01.026