Synthesis of pyranopyrazoles using nano-Fe-[phenylsalicylaldiminemethylpyranopyrazole]Cl2 as a new Schiff base complex and catalyst

Article abstract of DOI:10.1002/aoc.3968

By the condensation reaction of benzaldehyde with ethyl acetoacetate, malononitrile and hydrazine hydrate in the presence of FeCl₂, a pyranopyrazole derivative was prepared which was then reacted with salicylaldehyde to afford nano-Fe-[phenylsalicylaldiminemethylpyranopyrazole]Cl₂ (nano-[Fe-PSMP]Cl₂). The prepared nano-Schiff base complex was fully characterized using Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, differential thermogravimetry, scanning electron microscopy and UV–visible spectroscopy, and was used as an efficient and catalyst for the preparation of pyranopyrazoles.

Full text of DOI:10.1002/aoc.3968

Received: 27 April 2017
DOI: 10.1002/aoc.3968
Revised: 4 June 2017
Accepted: 19 June 2017
F U L L P A P E R
Synthesis of pyranopyrazoles using nano‐Fe‐
phenylsalicylaldiminemethylpyranopyrazole]Cl as a new
[
2
Schiff base complex and catalyst
Ahmad Reza Moosavi‐Zare
| Hamid Goudarziafshar | Khadijeh Saki
Sayyed Jamaleddin Asadabadi University,
Asadabad 6541835583, Iran
By the condensation reaction of benzaldehyde with ethyl acetoacetate, malo-
nonitrile and hydrazine hydrate in the presence of FeCl , a pyranopyrazole
2
Correspondence
derivative was prepared which was then reacted with salicylaldehyde to afford
Ahmad Reza Moosavi‐Zare, Sayyed
Jamaleddin Asadabadi University,
Asadabad 6541835583, Iran.
Email: moosavizare@yahoo.com
nano‐Fe‐[phenylsalicylaldiminemethylpyranopyrazole]Cl
(nano‐[Fe‐PSMP]
2
Cl ). The prepared nano‐Schiff base complex was fully characterized using
2
Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetric
analysis, differential thermogravimetry, scanning electron microscopy and
UV–visible spectroscopy, and was used as an efficient and catalyst for the
preparation of pyranopyrazoles.
Funding information
Sayyed Jamaleddin Asadabadi University
KEYWORDS
2
nano‐[Fe‐PSMP]Cl , pyranopyrazole, Schiff base complex, tandem reaction
A tandem reaction is a chemical process in which at least
two consecutive reactions are carried out continuously
without isolation of any intermediates, changing reaction
conditions and adding reagents. Clean reaction condi-
tions, high atom economy and low generated waste are
1 | EXPERIMENTAL
All chemicals were purchased from Merck or Fluka.
Known products were identified by comparison of their
melting points and spectral data with those reported in
the literature.
[1–4]
some of the advantages of such a reaction.
Pyranopyrazole derivatives are an important class of
heterocyclic compounds. They have been introduced as
1
.1 | Procedure for synthesis of Nano‐[Fe‐
[5]
[6]
[7]
bactericidal, vasodilatory
and anticancer
agents.
PSMP]Cl2
These compounds have various applications such as phar-
maceutical ingredients and biodegradable agrochemi-
A mixture of ethyl acetoacetate (0.13 g, 1 mmol), hydra-
zine hydrate (1.25 mmol) and isonicotinic acid (0.1 mmol,
0.0123 g, 10 mol%) was added to a 10 ml round‐bottomed
flask connected to a reflux condenser, and stirred at 85 °C for
5 min and then benzaldehyde (1 mmol) and malononitrile
(0.066 g, 1 mmol) were added to the reaction mixture.
After the completion of the reaction, as monitored by
TLC, the reaction mixture was cooled to room tempera-
ture. Water was added to the reaction mixture to dissolve
isonicotinic acid and the aqueous layer was separated from
the reaction mixture. Afterwards, the solid residue (crude
product) was triturated with a mixture of ethanol and
[
8]
cals.
Additionally, pyrano[2,3‐c]pyrazoles have been
[9]
shown to act as potential insecticidal and molluscicidal
agents.
[
10,11]
For these reasons, considerable attention has
been focused on the development of new procedures for
[12–19]
the synthesis of these compounds.
Having the above considerations in mind, we have
designed and identified nano‐Fe‐[phenylsalicylaldimine-
methylpyranopyrazole]Cl2 (nano‐[Fe‐PSMP]Cl2), the
structure of which is shown in Figure 1, and used it as
an active complex and efficient and catalyst for the
preparation of pyranopyrazoles (Scheme 1).
Appl Organometal Chem. 2017;e3968.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3968

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MOOSAVI‐ZARE ET AL.
catalyst by filtration (the product is soluble in warm etha-
nol; however, the catalyst is not soluble in this solvent).
Then, the ethanol was evaporated and the solid residue
(
crude product) was triturated with a mixture of ethanol
and water (9:1) to give the pure product. The recivered cat-
alyst was washed with ethanol and dried to use for another
reaction. The spectral data of compounds are reported in
the supporting information.
FIGURE 1 Proposed structures of nano‐[Fe‐PSMP]Cl
2
2
| RESULTS AND DISCUSSION
water (9:1) to afford 6‐amino‐3‐methyl‐4‐phenyl‐2,4‐
dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile as an
The prepared amine (1 mmol) and
FeCl ⋅4H O (1 mmol) were pulverized in a mortar for
Nano‐[Fe‐PSMP]Cl2 was prepared by the reaction of
benzaldehyde with ethyl acetoacetate, malononitrile and
[
17]
amine product.
hydrazine hydrate to give related pyranopyrazole accord-
2
2
[17,20]
ing to previous literature
and then reacted with
1
0 min, and then transferred to a 25 ml round‐bottomed
salicylaldehyde and FeCl ⋅4H O to afford nano‐[Fe‐
2
2
flask containing salicylaldehyde (1.5 mmol), connected
to a reflux condenser, and stirred at 120 °C for 24 h. After
this time, the reaction was continued with excess
salicylaldehyde for 48 h under the previous reaction
conditions. Finally, the reaction mixture was cooled
and washed with ethyl acetate three times to purify
PSMP]Cl as a nano‐Schiff base complex (Scheme 2).
2
The structure of nano‐[Fe‐PSMP]Cl was confirmed using
2
Fourier transform infrared (FT‐IR) spectroscopy, X‐ray
diffraction (XRD), Scanning electron microscopy (SEM),
thermogravimetric analysis (TGA), differential thermo-
gravimetry (DTG), UV–visible spectroscopy and mass
analysis.
nano‐[Fe‐PSMP]Cl from excess salicylaldehyde.
2
At first, (E)‐6‐(2‐hydroxybenzylideneamino)‐3‐methyl‐
4
‐phenyl‐2,4‐dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile
1
.2 | General procedure for synthesis of
(
PSMP) as a Schiff base was prepared alone and its struc-
Pyranopyrazoles
1
13
ture confirmed from H NMR and C NMR spectra. The
corresponding spectra are reported in the supporting
information.
A mixture of ethyl acetoacetate (0.26 g, 2 mmol), hydra-
zine hydrate (2.5 mmol) and nano‐[Fe‐PSMP]Cl (4 mol
2
%
) was added to a 25 ml round‐bottomed flask connected
The FT‐IR spectrum of the catalyst (Figure 2) showed
−
1
to a reflux condenser and stirred at 100 °C for 5 min, and
then aromatic aldehyde (2 mmol) and malononitrile
a broad peak at 3000–3600 cm which can be related to
O―H stretching of OH group and the peak observed at
−
1
(0.132 g, 2 mmol) were added to the reaction mixture.
1653 cm corresponds to stretching mode of C¼N bond
After the completion of the reaction, as monitored by
TLC, the reaction mixture was cooled to room temperature
and the product and remaining starting materials were
extracted with warm ethanol (20 ml) to separate from the
of azomethine.
The XRD pattern of nano‐[Fe‐PSMP]Cl was obtained
2
in the range 0–90° (Figure 3). As can be seen, the XRD
pattern exhibits a broad peak in the range 10–30°.
SCHEME 1 Preparation of
pyranopyrazoles using nano‐[Fe‐PSMP]Cl
2

MOOSAVI‐ZARE ET AL.
3 of 8
SCHEME 2 Preparation of nano‐[Fe‐PSMP]Cl
2
FIGURE 2 FT‐IR spectrum of nano‐[Fe‐PSMP]Cl
2
Scanning electron microscopy (SEM) images of the
catalyst were also obtained. It is evident that the parti-
cles of the prepared catalyst were of nanometric size
from that for some other species applied for the synthesis
of nano‐[Fe‐PSMP]Cl2.
In order to optimize the reaction conditions, we
selected the reaction of hydrazine hydrate (2.2 mmol),
ethyl acetoacetate (2 mmol), malononitrile (2 mmol) and
4‐chlorobenzaldehyde (2 mmol) as a model reaction. This
reaction was studied in the presence of different amounts
(Figure 4).
TGA and DTG of the nano‐[Fe‐PSMP]Cl2 catalyst
were also conducted. The corresponding results are
shown in Figures 5 and 6. As can be seen, that nano‐
[
Fe‐PSMP]Cl catalyst was decomposed after 300 °C.
of nano‐[Fe‐PSMP]Cl at temperatures ranging between
2
2
UV–visible spectra were obtained as further evidence
85 and 120 °C under solvent‐free conditions (Table 1).
to confirm the preparation of nano‐[Fe‐PSMP]Cl . UV
2
spectra were recorded in dimethylsulfoxide (DMSO) as
solvent. The maximum of absorption for amine, Schiff
base (PSMP), nano‐[Fe‐PSMP]Cl2 and FeCl ⋅4H O
2
2
appeared at 295, 372, 326 and 392 nm, respectively
(Figure 7). Therefore, λmax for the complex is different
FIGURE 3 XRD pattern of nano‐[Fe‐PSMP]Cl
2
FIGURE 4 SEM micrograph of nano‐[Fe‐PSMP]Cl
2

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MOOSAVI‐ZARE ET AL.
2
TABLE 1 Effect of amount of nano‐[Fe‐PSMP]Cl and tempera-
ture on reaction between hydrazine hydrate, ethyl acetoacetate,
malononitrile and 4‐chlorobenzaldehyde
Catalyst
(mol%)
Temp.
(°C)
Time
(min)
Yield
(%)
a
Entry
1
10
8
100
100
100
100
85
30
10
20
5
50
47
70
85
70
50
2
3
4
5
6
6
4
4
10
20
4
120
a
Isolated yield.
FIGURE 5 TGA curve of nano‐[Fe‐PSMP]Cl
a temperature increase rate of 10 °C min
2
at of 0–600 °C, with
[Fe‐PSMP]Cl2 under reflux conditions. The results
showed that solvent‐free condition was the best for this
reaction (Table 2).
−
1
After optimization of the reaction conditions, we
investigated the efficacy of nano‐[Fe‐PSMP]Cl2 in the
synthesis of a series of 6‐amino‐4‐(4‐methoxyphenyl)‐
5
‐cyano‐3‐methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyra-
zoles. This was achieved using various aldehydes
including aldehydes with electron‐releasing substitu-
(
ents, electron‐withdrawing substituents and halogens
on the aromatic ring) in the reaction with hydrazine
hydrate, ethyl acetoacetate and malononitrile to afford
the corresponding products in high yields and in short
reaction times. The results are summarized in Table 3.
These results indicate that the corresponding products
were produced in high yields and in short reaction
times.
In a proposed mechanism (Scheme 3) which is sup-
[
16–19]
FIGURE 6 DTG analysis of nano‐[Fe‐PSMP]Cl
2
ported by the literature,
at first, ethyl acetoacetate
was activated by nano‐[Fe‐PSMP]Cl2 and hydrazine
attacked the carbonyl group of the activated ethyl
acetoacetate. Then, loss of H O, and intramolecular
2
nucleophilic attack by another NH group of hydrazine
2
to the next carbonyl group of ethyl acetoacetate afforded
5‐methyl‐2,4‐dihydropyrazol‐3‐one (I) after removing
TABLE 2 Reaction between hydrazine hydrate, ethyl aceto-
acetate, malononitrile and 4‐chlorobenzaldehyde catalysed by nano‐
2
[Fe‐PSMP]Cl (4 mol%) in various solvents (15 ml) under reflux
conditions
FIGURE 7 UV–visible spectra of amine, Schiff base (PSMP),
nano‐[Fe‐PSMP]Cl and FeCl ⋅4H O in DMSO
a
2
2
2
Entry
Solvent
Time (min)
Yield (%)
1
EtOH
20
50
The reaction was most efficient with 4 mol% of the cata-
lyst at 100 °C, and it afforded the expected products in
high yield within a short reaction time (Table 1, entry
2
3
4
CH
3
2
CN
Cl
25
25
20
30
40
40
CH
2
Acetone
4
). In the next step, the model reaction was conducted
a
in the presence of several solvents using 4 mol% nano‐
Isolated yield.

MOOSAVI‐ZARE ET AL.
5 of 8
2
TABLE 3 Preparation of pyranopyrazoles using nano‐[Fe‐PSMP]Cl as catalyst at 100 °C
a
Entry
Product
Time (min)
Yield (%)
M.p., °C (lit.)
[
19]
1
5
87
257–260 (261–263
)
[
17]
2
3
4
5
6
5
10
10
5
85
80
90
88
88
243 (245–247
220 (226–228
230–240
)
[
19]
)
242–246
[
21]
5
249–250 (249–252
)
[
19]
7
8
10
10
80
89
214–216 (212–214
220–226 (255–257
)
[
16]
)
(Continues)

6
of 8
MOOSAVI‐ZARE ET AL.
TABLE 3 (Continued)
a
Entry
Product
Time (min)
Yield (%)
M.p., °C (lit.)
[
16]
9
10
89
218–220 (217
)
[
19]
1
0
5
85
253–256 (258–259
)
[
16]
1
1
2
10
10
84
80
252–256 (255
)
[
12]
1
218–220 (217–219
)
[
17]
1
1
3
4
10
86
88
256–260 (260–263
212–216 (211–212
)
[
22]
5
)
[
17]
1
5
5
85
210–215 (215–217
)
[
17]
1
6
5
90
190–198 (206–208
)
(Continues)

MOOSAVI‐ZARE ET AL.
7 of 8
TABLE 3 (Continued)
a
Entry
Product
Time (min)
Yield (%)
M.p., °C (lit.)
[
18]
1
7
5
92
230–233 (240–242
)
a
Isolated yield.
SCHEME 3 Proposed mechanism for synthesis of pyranopyrazoles using nano‐[Fe‐PSMP]Cl
2
one molecule of EtOH. In the next step, by the reaction of
aromatic aldehyde, which was activated by nano‐[Fe‐
(2.2 mmol), ethyl acetoacetate (2 mmol), malononitrile
(2 mmol) and 4‐chlorobenzaldehyde (2 mmol). After the
completion of the reaction, the reaction mixture was
extracted with warm ethanol (20 ml) to separate from
the catalyst by filtration (the product is soluble in warm
ethanol; however, the catalyst is not soluble in this
solvent). Then, the ethanol was evaporated and the solid
residue (crude product) was triturated with a mixture of
ethanol and water (9:1) to give the pure product. The
PSMP]Cl , with malononitrile, cyanoolefin compound
2
(
II) was prepared. Finally, by the tandem Michael addi-
tion–cyclization reaction of 5‐methyl‐2,4‐dihydropyrazol‐
‐one with prepared cyanoolefin compound, the expected
3
pyranopyrazole was synthesized.
The recyclability of the catalyst was also examined in
the condensation reaction of hydrazine hydrate

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MOOSAVI‐ZARE ET AL.
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use for another reaction.
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ACKNOWLEDGMENT
[
17] M. A. Zolfigol, M. Tavasoli, A. R. Moosavi‐Zare, P. Moosavi,
The authors gratefully acknowledge Sayyed Jamaleddin
Asadabadi University for providing support for this work.
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, 25681.
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Ahmad Reza Moosavi‐Zare
321-9326
http://orcid.org/0000-0003-
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2
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Additional Supporting Information may be found online
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