Environmentally benign synthesis of pyranopyrazole derivatives by cobalt Schiff-base complexes immobilized on magnetic iron oxide nanoparticles

Article abstract of DOI:10.1016/j.jorganchem.2019.06.030

In this work, an efficient and straight procedure has been described for one-pot three-component synthesis of pyranopyrazole derivatives in the presence of a new cobalt Schiff-base complex immobilized on silica-coated Fe₃O₄ nanoparti

Full text of DOI:10.1016/j.jorganchem.2019.06.030

Accepted Manuscript
Environmentally benign synthesis of pyranopyrazole derivatives by cobalt Schiff-base
complexes immobilized on magnetic iron oxide nanoparticles
Behrouz Shaabani, Hossein Maleki, Jamshid Rakhtshah
PII:
S0022-328X(19)30268-2
DOI:
https://doi.org/10.1016/j.jorganchem.2019.06.030
JOM 20842
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 28 April 2019
Revised Date: 14 June 2019
Accepted Date: 22 June 2019
Please cite this article as: B. Shaabani, H. Maleki, J. Rakhtshah, Environmentally benign synthesis
of pyranopyrazole derivatives by cobalt Schiff-base complexes immobilized on magnetic iron
oxide nanoparticles, Journal of Organometallic Chemistry (2019), doi: https://doi.org/10.1016/
j.jorganchem.2019.06.030.
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ACCEPTED MANUSCRIPT
Environmentally benign synthesis of pyranopyrazole derivatives by cobalt Schiff-base
complexes immobilized on magnetic iron oxide nanoparticles
*
,
Behrouz Shaabani Hossein Maleki and Jamshid Rakhtshah
Department of Inorganic Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
*
Corresponding e-mail address: Shaabani.b@gmail.com
Abstract:
In this work, an efficient and straight procedure has been described for one-pot three-component
synthesis of pyranopyrazole derivatives in the presence of a new cobalt Schiff-base complex
immobilized on silica‐coated Fe O nanoparticles as a reusable catalyst. This new catalyst was
3
4
characterized by different techniques, such as Fourier transform infrared (FT‐IR), X‐ray powder
diffraction (XRD), field‐emission scanning electron microscopy (FE-SEM), energy‐dispersive
X‐ray spectroscopy (EDX), inductively coupled plasma (ICP) and vibrating sample
magnetometry (VSM). The described catalyst was efficiently tested in the synthesis of
pyranopyrazoles via three-component condensation of different aromatic aldehydes,
malononitrile and 3-methyl-1-phenyl-2-pyrazoline-5-one at room temperature with short reaction
times, high yields and TON values up to 388. The considered catalyst can be reused several
times without loss of its catalytic activity. Finally, we compared the results for the synthesis of
desired products in the presence of our nanocatalyst with previously reported catalysts in the
literature.
Keywords:
Immobilized complexes; Fe O nanoparticles; Pyranopyrazoles; Solvent-free.
3
4

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Introduction:
Multicomponent reactions (MCRs) are those reactions in which more than two first materials
react together to form a single product, contains the ingredient of all the components. MCRs
have emerged as a vital field of chemistry and a powerful tool in synthetic organic chemistry [1–
3
]. These reactions are covering unique features like high selectivity, high yield and synthetic
simplicity due to the formation of carbon-carbon and carbon-heteroatom bonds in a single step
4-10].
[
Pyranopyrazoles are biological active heterocyclic compounds that illustrate a wide range
activity like antimicrobial,[11] antitumor,[12] anticancer,[13] anti-inflammatory,[14] and also as
biodegradable agrochemicals [15]. The synthetic contractual method for preparation of
pyranopyrazole derivatives is a three-component reaction of aromatic aldehydes, malononitrile
and 3-methyl-1-phenyl-2-pyrazoline-5-one under various conditions and catalysts such as
DABCO,[16] basic catalysts,[17] nanosized magnesium oxide,[18] bovine serum albumin,[19]
imidazole,[20] CuO/ZrO ,[21] ionic liquids,[22] ultrasound irradiation,[23] aqueous media,[24]
2
H [NaP W O ],[25] and trichloroacetic acid [26].
1
4
5
30 110
Over the past two decades, Schiff bases have been playing a pivotal role in chelating the
intermediate metals, as well as the main group metals, one of the important features of Schiff
bases, are their stability to moisture and high temperature (up to 100 °C) which makes them one
dominant type of organic ligands. They can be used as a catalyst in both homogeneous and
heterogeneous reactions such as reduction [27], oxidation of organic compounds [28],
hydrosilylation of ketones [29] and multi-component reactions [30]. One of the significant
disadvantages of homogeneous catalytic systems is the problem of separation and recovery of the
catalysts from the reaction media [31-33]. In recent years, many attempts have been made to
immobilize Schiff-base complexes on different solid supports such as silica, [34,35], carbon [36]

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and metal oxides [37] to solve these problems. Recently magnetic nanoparticles (MNPs) have
been widely considered for the immobilization of homogeneous catalysts because of their unique
properties likes chemical stability, strong magnetization, high activities and easy recovery in
heterogeneous catalytic processes [38,41]. Iron oxide nanoparticles are unstable under acidic
conditions, and the magnetic core is usually protected with an outer shell such as silica [42,43] or
polymers [44]. Silica is an adequate candidate, which has an excellent chemical affinity and
thermal stability. An advantage of the silica coating is terminating of the surface with abundant
Si–OH bond which facilitates the immobilization of desired compounds on magnetic
nanoparticles.
In continuation of our efforts in the field of synthesis immobilized Schiff-base complexes on
different supports likes MNPs [45,46] and MWCNTs [47,48], we report the synthesis and
characterization of new cobalt Schiff-base complexes supported on Fe O nanoparticles as an
3
4
efficient and recoverable catalyst in the synthesis of pyranopyrazole derivatives.
<Scheme 1.>
Experimental:
Synthesis of magnetite Fe O nanoparticles:
3
4
The Fe O NPs were prepared by chemical co-precipitation technique according to a previously
3
4
published method [49]. A mixture of FeCl .6H O (2 mmol) and FeCl .4H O (1 mmol) in
3
2
2
2
deionized water was added to a three-necked round-bottomed flask (250 mL). The mixture was
stirred for 10 min at 80 °C, then, 15 mL of concentrated ammonia (25%) was added rapidly to
the solution. The black mixture was stirred under N atmosphere for another 2 h then cooled to
2
room temperature. The black precipitate was separated magnetically and washed several times
with water until the pH of the runoff was around 7 and then, dried at 60 °C under vacuum.
Synthesis of silica-coated iron oxide nanoparticle (Fe O @SiO ):
3
4
2
The Fe O @SiO nanoparticles were prepared according to the Stober method [50]. For coating
3
4
2
magnetite nanoparticles with a layer of silica, synthesized nanoparticles (1.0 g) were dispersed

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by ultrasonic vibration in a mixture of 100 mL of ethanol, 10 mL of deionized water and 4 ml of
tetraethylorthosilicate (TEOS). In the following, 2.5 mL of 25 wt% concentrated aqueous
ammonia solution was injected dropwise into the reaction mixture, and the pH value was
controlled in the range 11 ≤ pH ≤ 12. After stirring the mixture for 6 h at room temperature, the
brown precipitate was collected from the solution by using an external magnet, and washed
several times with ethanol and dried under vacuum.
Synthesis of magnetite nanoparticles coated by 3- chloropropyltrimethoxysilane
(
Fe O @SiO @Cl):
3 4 2
1
g of silica coated nanoparticles, synthesized in the previous section, were dispersed in 100 mL
ethanol solution of 3-chloropropyltrimethoxysilane (CPTMS) (2.5 mL) under reflux condition
and N atmosphere for 12 h. The obtained particles were collected using a magnet and
2
subsequently washed with ethanol three times.
Synthesis of cobalt Schiff-base complex (CoSB):
A solution of 2-amino phenol (1 mmol, 0.109 g) in absolute EtOH (10 mL) was added dropwise
to a stirring solution of 2-pyridine carboxaldehyde (1 mmol, 0.107 g) in absolute EtOH (20 mL)
during 10 min at 60 °C. After the addition was completed, the reaction mixture was stirred for 4
h under reflux at 60 °C. The residue was washed with ethanol and dried under vacuum.
Synthesis of cobalt Schiff-base complex immobilized on silica coated Fe O4
3
(
Fe O @SiO @CoSB):
3 4 2
The as-prepared Fe O @SiO @Cl (1g) were dispersed by ultrasonic vibration in ethanol solution
3
4
2
for 20 min, then the cobalt complex was added to the mentioned solution and stirred at 60 °C
under reflux for 24 h. The resulted precipitate was separated from the solution by an external
magnet and washed several times with ethanol and dried in the air.
General procedure for the synthesis of pyranopyrazole derivatives:
Fe O @SiO @CoSB as a magnetic nanocatalyst (8 mg) was added to a mixture of aromatic
3
4
2
aldehyde (1 mmol), malononitrile (0.066 g, 1 mmol) and 3-methyl-1-phenyl-2-pyrazoline-5-one

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(0.174 g, 1 mmol) in an ethanolic medium at room temperature. After completion of the reaction
which was identified by TLC (n-hexane/ethyl acetate: 5/2), the nanocatalyst was recovered
magnetically by adding 5 ml ethyl acetate to solve the product and then it was purified via
recrystallization from ethanol.
6
-amino-4-(2,3-dihydroxyphenyl)-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-
1
carbonitrile (Table 4, entry 10): H NMR (400 MHz, DMSO-d ): δ 9.42 (s, 1H,
̶
OH), 8.06
ArH), 7.33
6
ppm
(
(
(
dd, 1H, J = 8.0, J = 6.0,
̶
ArH), 7.90 (d, 2H, J = 4.0,
OH), 7.09 (t, 1H, J = 8.0, ArH), 6.73 (d, 1H, J = 8.0,
d, 1H, J = 8.0, ArH), 4.51 (s, 1H,
̶
ArH), 7.86 (t, 2H, J = 4.0,
̶
̶
1
2
s, 1H,
̶
̶
̶
ArH), 6.69 (s, 2H,
NH ), 6.62
2
1
̶
̶
CH), 2.33 (s, 3H,
̶
CH ); H NMR (400 MHz, DMSO-d ):
3
6
δppm 158.3, 157.3, 148.6, 144.8, 134.5, 134.1, 130.9, 130.5, 129.5, 126.0, 125.8, 122.1, 119.3,
18.2, 114.3, 114.1, 114.0, 57.3, 36.2.
1
General Procedure for Reusing Experiments:
The reusability of the catalyst was studied in recycling experiments. To regenerate the catalyst,
after finishing each run, 3 ml of hot ethyl acetate was added to the reaction mixture and heated to
dissolve the product. Then, the nanocatalyst was separated from the reaction mixture by an
external magnet and washed with ethanol to reused in the next reaction for eight times.
Results and discussion:
Characterization of cobalt Schiff-base complex immobilized on Fe O as a heterogeneous
3
4
catalyst
A new cobalt Schiff-base complex immobilized on magnetic iron oxide nanoparticles was
prepared from commercially available and inexpensive substrates (Scheme 2).
<Scheme 2.>
The structure of cobalt complex supported on Fe O as a heterogeneous catalyst was studied and
3
4
characterized by Fourier transform infrared (FT-IR), X‐ray powder diffraction (XRD), field -
emission scanning electron microscopy (SEM), energy-dispersive X‐ ray spectroscopy (EDX),
inductively coupled plasma (ICP) and vibrating sample magnetometry (VSM) analysis.

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The prosperous synthesis of iron oxide nanoparticles was confirmed by the particular absorption
-1
−1
peak of Fe-O bond at around 580 cm and also, the band has seen at 3427 cm can be related to
the stretching vibrations of O-H band of the nanoparticles surface (Fig. 1a). The peak at the
−
1
range of 1000-1100 cm verifies the silica modification on the nanoparticles (Fig. 1b). Fig. 1c.
displays the successful reaction between 3‐chloropropyltrimethoxysilane and silica‐coated Fe O4
3
-1
which is concluded by CH stretching vibrations appearing at about 2927 cm (asymmetric CH
2
2
-1
−1
stretch) and 2848 cm (symmetric stretch). The band appeared at 1635 cm exhibit the C=N
stretching vibration band which pertains to attachment the Schiff-base complex on the modified
nanoparticle [30].
<Fig. 1.>
Fig. 2 shows the XRD patterns of initial Fe O and cobalt complex immobilized on silica coated
3
4
Fe O in the range of 10-80°. As represented in Fig. 2a, the XRD pattern exhibit diffraction lines
3
4
of high crystalline nature at 2θ = 18.5, 30.5, 35.6, 43.7, 54, 57, 63 and 74.5. The XRD pattern of
silica-coated magnetite nanoparticles (Figure 2b) exhibited XRD broadened pattern because of
°
its non-crystalline at 2θ = 20-30 which confirm Fe O @SiO structure. The peak width
3
4
2
(
FWHM), size and interplanar distance from the XRD pattern of Fe O @SiO @CoSB were
3 4 2
investigated and the achieved results are summarized in Table 1. The crystallite size of the
desired nanocatalyst was calculated to be (~10 nm) using Scherrer's equation, which was smaller
than the size determined by field emission scanning electron microscopy analysis. The observed
disagreement is dependent on the reality that XRD measurements investigate crystallite sizes of
“coherently diffracting domains” of crystals while grains may contain several of these domains
[
51]. Also, the XRD pattern of cobalt complexes immobilized on Fe O was same with neat
3
4
Fe O , clearly indicating that crystallinity and morphology were not altered after grafting.
3
4
<Table 1. >
<Fig. 2. >

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The morphology of nanocatalyst was studied by scanning electron microscopy (SEM). As can be
seen, Fig. 3. indicated that most of the prepared nanoparticles are spherical shaped and have an
average diameter of about 34 nm. The EDX spectrum of the attained Fe O @SiO @CoSB as
3
4
2
nanocatalyst exhibit, the presence of the anticipated elements in the structure of the catalyst, for
iron (Fe), silicon (Si), oxygen (O), chlorine (Cl) and cobalt (Co) (Figure 4).
Fig. 5 display the EDS-map of the elements in the structure of nanocatalyst. According to the
Figure, it can be concluded that the distribution of elements in the structure of the catalyst is
monotonous and obviously this proves the stable connection of the catalyst into the complex.
ICP analysis of the cobalt showed a value of about 0.315 mmol/g for Fe O @SiO @CoSB.
3
4
2
The magnetic properties of the nanocatalyst were studied using vibrating sample magnetometer
VSM) at room temperature. The magnetization curves measured for Fe O and
(
3
4
Fe O @SiO @CoSB are compared in Fig. 6. According to the magnetization curves, the
3
4
2
−
1
saturation magnetization of the nanoparticles decreases from 53 emu g for the initial Fe O4
3
−
1
sample to 36 emu g for nanocatalyst. According to the above results they are decreasing in
saturation magnetization of the nanocatalyst compared to the bare nanoparticles relevant to the
formation of silica shell and functionalized groups during the modification process. However,
the catalyst still can be efficiently separated easily from the solution with the help of an external
magnetic force.
<Fig. 3.>
<Fig. 4.>
<Fig. 5.>
<Fig. 6.>
Application of Fe O @SiO @CoSB as a heterogeneous catalyst in the synthesis of
3
4
2
pyranopyrazole derivatives:
After successful preparation and characterization of Fe O @SiO @CoSB to find the best
3
4
2
reaction conditions for the synthesis of pyranopyrazole derivatives, the reaction of 4-chloro

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benzaldehyde, malononitrile and 3- methyl-1-phenyl-2-pyrazoline-5-one with an equimolar ratio
was initially examined as a model reaction. The effects of catalyst and temperature were
investigated in the presence of various amounts of Fe O @SiO @CoSB (4–10 mg) at
3
4
2
°
temperatures ranging from 25 to 100 C (Table 2). In the absence of nanocatalyst, a low yield of
the products was achieved after 60, and 40 min (Table 2, entries 1 and 2) and also a further
increase in catalyst amount to 6 mg did not improve the product yield. According to the Table,
the best results were obtained when the reaction was attained in the presence of 8 mg
nanocatalyst at room temperature after 10 min (Table 2, entry 9).
<Table 2.>
The effect of different solvents on the catalytic activity of the Fe O @SiO @CoSB was
3
4
2
investigated in the synthesis of pyranopyrazole derivatives (Table 3). Several solvents such as
H O, ethanol, CH CN, CH Cl , Toluene, and n-Hexane were tested and the highest yield in the
2
3
2
2
shortest reaction time was attained in the ethanol medium.
<Table 3.>
After optimization of the reaction conditions, to estimate the efficiency and scope of the
nanocatalyst, we extended our study using Fe O @SiO @CoSB with different aromatic
3
4
2
aldehydes to prepare a series of pyranopyrazoles (Table 4). A broad range of structurally various
aromatic aldehydes (electron‐donating substituents, electron-withdrawing substituents and
halogens on their aromatic ring) were used in the facile reaction, giving very good to excellent
yields. It is interesting to note that the yield of the reactions with aldehydes which having an
electron‐withdrawing group was a little higher than that for those with an electron‐releasing
group (Table 4, entries 4, 6 and 8). Also it can be concluded that the location of the substituent in
the derivatives are effective in the yield of the reaction. Furthermore, we calculated turn over
numbers (TON) and turn over frequencies (TOF) states on the effectiveness of this nanocatalyst
for the synthesis of all derivatives (Table 4). TON and TOF values for Fe O @SiO @CoSB
3
4
2
were calculated by the equations TON = Yield (%)/Catalyst amount (mol%) and TOF = Yield

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(%)/[Time (min)×Catalyst amount (mol%)] (according to the ICP results, 8 mg of nanocatalyst is
equivalent to 0.252 mol% of catalyst) [52]. The results reveal that the nanocatalyst produces high
TON and TOF values.
<Table 4.>
Furthermore, the additional probability to reuse and recycle the nanocatalyst for several runs was
also studied. The results displayed in Fig. 7, approve that the magnetically separable
nanocatalyst could be reused and recycled eight runs without any significant loss of activity and
even after these runs, the yields remained still high. During the recycling experiment, no
considerable change in the structure of the nanocatalyst was observed from XRD spectral studies
for at least eight successive runs. This data demonstrates the stability of the catalyst and perfect
regeneration capacity of our nanocatalyst in mentioned reaction condition (Fig. 8).
<
Fig. 7.>
Fig. 8.>
<
A plausible mechanism for the synthesis of pyranopyrazole derivatives (VII) in the presence of
Fe O @SiO @CoSB is illustrated in Scheme 3. Initially, the aldehyde is activated using the
3
4
2
cobalt Schiff-base complex moiety of nanocatalyst (I) to resulted (II). At that time, malononitrile
III) attacks to the carbonyl group of the activated aldehyde (II) and gives (IV) by the
(
Knoevenagel condensation and loss of water molecule. The reaction is followed by the Michael
addition of the methylene group of 3‐Methyl‐1‐phenyl‐2‐pyrazolin‐5‐one (V) to an electron
deficient carbon of dicyanoalkene (IV) to afford intermediate (VI), which converts to the
pyranopyrazole (VII) via cyclization followed by tautomerization [53].
<Scheme 3.>
To compare the efficiency and scope of the nanocatalyst with some of those reported in the
literature, a comparative result is presented in Table 4. In comparison with other catalysts
employed for the synthesis of pyranopyrazole, our catalyst showed a much higher
catalytic activity. According to these data, the yield of model reaction in the case of all the

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catalyst (except entries 1 and 3) is lower than Fe O @SiO @CoSB. Also, the comparison of the
3
4
2
required reaction time and temperature for those catalysts listed in the table with our catalyst
indicate that the nanocatalyst synthesized here is convincingly superior to the recently reported
catalytic methods. Additionally, it can be easily separated magnetically after the reaction and has
shown great reusability.
<Table 5.>
Conclusion:
In summary, a new heterogeneous and reusable cobalt Schiff-base complex immobilized on
magnetic Fe O4 nanoparticles was designed and fully characterized by using different
3
techniques. The catalytic applications of the described catalyst were investigated in the synthesis
of pyranopyrazole derivatives under room temperature and ethanol as a green solvent. Notable
advantages of this study are short reaction time, efficiency, the potential for recycling of the
catalyst, high yield, easy experimental work-up, ease of handling of the catalyst with an external
magnet.
Acknowledgements
We would like to thank the University of Tabriz to our research group for financial supports.
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2015) 71402.
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A. Chem. 418 (2016) 54.
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5
1
5
5
7. D. Azarifar, S.M. Khatami, M.A. Zolfigol, R. Nejat-Yami, J. Iran. Chem. Soc. 11 (2014)
223.
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(2008) 278.

ACCEPTED MANUSCRIPT
Scheme 1. The synthesis of pyranopyrazole derivatives using cobalt complex immobilized on silica coated Fe O
3
4
magnetite nanoparticles.

ACCEPTED MANUSCRIPT
Scheme 2. The sequence of events in the preparation of Fe O @SiO @CoSB.
3
4
2

ACCEPTED MANUSCRIPT
OH
-
O
Co
O
I
Fe3O4
Co
O
-
N
III
OH
C
C
H
C ------------ F- e3O4
IV
-
-H+
CN
N
Knoevenagel Condensation
CN
II
Fe O
3
Me
4
Me
H
O
N
O
H
N
Michael Addition
N
N
Ph
V
Ph
Fe3O4
VI
VII
CN
Fe3O4
Me
H
Me
CN
Fe O
3
4
N
Cyclization Followed N
by Tautomerization
C
N
O
N
N
O
NH2
Ph
Ph
Fe3O4
Scheme 3. The probable mechanism for the synthesis of pyranopyrazole derivatives using Fe O @SiO @CoSB as a
3
4
2
nanocatalyst.

ACCEPTED MANUSCRIPT
Fig. 1. FT-IR spectra of Fe O (a), Fe O @SiO (b), Fe O @SiO @Cl(c), Fe O @SiO @CoSB (d) and neat cobalt
3
4
3
4
2
3
4
2
3
4
2
Schiff-base (e).

ACCEPTED MANUSCRIPT
Fig. 2. XRD patterns of Fe O (a) and Fe O @SiO @CoSB (b).
3
4
3
4
2

ACCEPTED MANUSCRIPT
Fig. 3. SEM image of Fe O @SiO @CoSB
3
4
2

ACCEPTED MANUSCRIPT
Fig. 4. EDS diagram of the Fe O @SiO @CoSB
3
4
2

ACCEPTED MANUSCRIPT
Fig. 5. EDS-MAP of the elements in the structure of Fe O @SiO @CoSB
3
4
2

ACCEPTED MANUSCRIPT
Fig. 6. The magnetic hysteresis loops of Fe O MNPs (a) and Fe O @SiO @CoSB (b).
3
4
3
4
2

ACCEPTED MANUSCRIPT
Fig. 7. Reusability of Fe O @SiO @CoSB as a heterogeneous catalyst in 20 minutes.
3
4
2

ACCEPTED MANUSCRIPT
1
0
20
30
40
50
60
70
80
2
θ (Degree)
Fig. 8. Powder XRD pattern of reused Fe O @SiO @CoSB.
3
4
2

ACCEPTED MANUSCRIPT
Table 1. X-ray diffraction (XRD) data for the Fe O @SiO @CoSB as a heterogeneous catalyst.
3
4
2
Peak width
Size
Interplaner
distance (nm)
Entry
2θ
(
FWHM) (°) (nm)
1
2
3
4
5
6
7
18.6
30.5
35.8
43.5
54.0
57.0
63.0
1.24
1.80
1.00
0.30
1.80
1.15
1.05
6.47
4.57
8.35
28.53
4.95
7.88
8.88
0.466532
0.292741
0.250604
0.207795
0.169607
0.161371
0.147509
8
74.0
1.75
5.67
0.127949

ACCEPTED MANUSCRIPT
Table 2. The effect of catalyst amount and temperature on the three-component reaction of 4-chloro benzaldehyde,
a
malononitrile and 3-methyl-1-phenyl-2- pyrazolin-5-one in ethanol as solvent.
o
b
c
Entry
Amount of catalyst (mg)
Reaction temperature ( C)
Reaction time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
—
—
4
4
6
6
6
6
8
8
8
8
10
10
10
10
r.t.
100
r.t.
100
r.t.
50
60
40
30
30
20
20
20
20
10
10
10
10
10
10
10
10
40
38
60
65
85
85
85
85
95
95
95
95
95
95
95
95
75
100
r.t.
50
1
1
1
1
1
1
1
0
1
2
3
4
5
6
75
100
r.t.
50
75
100
a
Reaction conditions: 4-chloro benzaldehyde (1 mmol), malononitrile (1 mmol) and 3-methyl-1-phenyl-2-
b
c
pyrazolin-5-one (1 mmol). This is the temperature of oil bath and not inside the reaction medium. Isolated yield.

ACCEPTED MANUSCRIPT
Table 3. The solvent effect in the reaction between 4-chloro benzaldehyde, malononitrile and 3-methyl-1-phenyl-2-
a
pyrazolin-5-one at room temperature using 8 mg catalyst.
Solvent-free
H O
C H OH
CH CN
CH Cl2
Toluene
40
n-Hexane
2
2
5
3
2
b
Yield (%)
Reaction
80
70
30
95
10
60
40
40
40
45
50
2
0
50
time (min)
a
Reaction conditions: 4-chloro benzaldehyde (1 mmol), malononitrile (1 mmol) and 3-methyl-1-phenyl-2-pyrazolin-
b
5
-one (1 mmol) under room temperature; Isolated yield

ACCEPTED MANUSCRIPT
Table 4. The three-component synthesis of pyranopyrazole derivatives in the presence of 8 mg of nanocatalyst
b
-1 c
d
o
Entry
Product
Time (min) Yield (%) TOF (min )
TON
M.p ( C) [Lit.]
1
10
91
88
36.11
361.11
349.20
170-172 [53]
180-182 [53]
2
3
25
13.96
30
10
85
95
11.24
37.69
337.30
376.98
177-179 [53]
170-172 [54]
4
5
6
15
15
92
94
24.33
24.86
365.07
373.01
150-152 [54]
161-163 [54]
7
8
9
15
10
30
93
98
85
24.60
38.88
11.24
367.58
388.88
337.30
180-182 [55]
200-202 [55]
195-197 [55]

ACCEPTED MANUSCRIPT
e
1
0
25
85
13.49
337.30
165-167
1
1
1
1
2
3
25
15
15
84
90
92
13.33
23.80
24.32
333.33
357.14
365.07
174-176 [53]
234-236 [56]
214-216 [56]
CN
N
N
Ph
O
NH2
1
1
4
5
20
15
90
92
17.85
24.32
357.14
365.07
187-189 [57]
227-228 [57]
a
:
Reaction conditions: different aldehydes (1 mmol), malononitrile (1 mmol) and 3-methyl-1-phenyl-2-pyrazolin-5-
b
c
one (1 mmol), nanocatalyst (8 mg), ethanol as solvent and room temperature Isolated yield; Turnover numbers
(
d
e
TONs); Turnover frequencies (TOFs); New derivative.