BF3 bonded nano Fe3O4 (BF3/MNPs): An efficient magnetically recyclable catalyst for the synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives

Article abstract of DOI:10.1039/c5ra11343a

A simple and efficient procedure for the synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives has been developed by a one-pot three-component reaction of various aldehydes with malononitrile and 3-methyl-1-phenyl-2-pyrazoline-5-one in the presence of

Full text of DOI:10.1039/c5ra11343a

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: M. Abdollahi-
Alibeik, A. Moaddeli and K. Masoomi, RSC Adv., 2015, DOI: 10.1039/C5RA11343A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
BF bonded nano Fe O (BF /MNPs): an efficient magnetically recyclable
1
2
3
3
4
3
catalyst for the synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives
3
4
∗
Mohammad AbdollahiꢀAlibeik , Ali Moaddeli, Kianoosh Masoomi
a
Department of Chemistry, Yazd University, Yazd 89158-13149, Iran
5
6
7
Abstract
Simple and efficient procedure for the synthesis of 1,4ꢀdihydropyrano[2,3ꢀc]pyrazole
derivatives has been developed by oneꢀpot threeꢀcomponent reaction of various aldehydes
8
9
with malononitrile and 3ꢀMethylꢀ1ꢀphenylꢀ2ꢀpyrazolineꢀ5ꢀone in the presence BF
3
/MNPs as
/MNPs
10
11
12
13
14
15
16
a novel nanostructured, heterogeneous and reusable catalyst. In this research, BF
3
nanoparticles were prepared at three calcination temperature and characterized by various
techniques. The characterization and optimization results show that the catalyst with
calcination temperature of 450 °C has the best catalytic activity. The nanoꢀsized magnetite
catalyst were recovered by simple separation with an external magnet and reused for several
cycles without considerable loss of activity.
1
7
Keywords: magnetite nano particles; solid acid catalyst; magnetite recoverable catalyst;
18
19
pyrane; multiꢀcomponent reaction.
Introduction
20
Many conventional liquid inorganic acids, such as HNO , BF and H SO have been replaced
21
22
23
24
25
26
3
3
2
4
by heterogeneous solid acid catalysts in acidꢀcatalyzed organic transformations.
Environmental pollution and difficulties in handling and separation of such homogeneous
catalyst and also contamination of the products by residual catalyst, greatly restrict their
applications from a process and economic point of view. Immobilization of inorganic acid on
solid supports is a suitable way to improvement of mentioned drawbacks and this way
∗Corresponding author
Mohammad AbdollahiꢀAlibeik, Department of Chemistry, Yazd University, Yazd 89158ꢀ13149, Iran Tel.: +98ꢀ
35ꢀ31232659; fax: +98ꢀ35ꢀ38210644
Eꢀmail address: abdollahi@yazd.ac.ir, moabdollaho@gmail.com
1

RSC Advances
Page 2 of 18
View Article Online
DOI: 10.1039/C5RA11343A
combine high surface area with the additional benefit of relatively facile recovery and
1
1
regeneration.
2
Solidꢀsupported catalysts are an important and growing arena in heterogeneous catalysis.
Therefore, a key challenge is to use a suitable and stable support with a large surface area to
reach high accessibility to maximum active catalytic sites and maximum catalyst loading.
3
4
5
2
, 3
4, 5
6
7
8, 9
Nanoꢀsized solidꢀsupports such as ZrO
2
, TiO
2
, Al
2
O
3
, ZnO and SiO
2
have
6
attracted much attention due to their versatile physical surface and catalytic properties and
applications in catalysis. However, conventional separation methods for these tiny support
particles may become inefficient.
7
8
9
Magnetite nanoparticles are one of the most widely studied materials in multiꢀdisciplinary
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
1
0
11
12
research including biotechnology , biomedicine , magnetic resonance imaging (MRI) ,
1
3
14, 15
targeted drug delivery
and catalysis
. As the catalyst, magnetite has been used in
1
6
several important commercial processes such as ammonia synthesis , water gas shift
17
18
reaction
and FischerꢀTropsch reaction , which are important routes to get high value
intermediates for chemical and petrochemical industries.
Recently, nanoꢀmagnetite has found versatile applications as a solidꢀsupport for preparation
1
9
of recyclable catalysts in the development of sustainable methodologies . Surface
functionalization of magnetic nanoparticles is a wellꢀdesigned way to bridge the gap between
2
0ꢀ22
heterogeneous and homogeneous catalysis to increase catalytic activity of MNPs
. Due to
its magnetic properties, it is also useful as component of several catalysts and adsorbents for
different applications, allowing its separation from medium after reaction.
Fused pyran derivatives represent an important class of compounds which possess high
23
activity profile due to their wide range of biological activities such as antimicrobial
,
2
4
25
antiviral
and cancer therapy . Fused Pyrans to pyrazoles as pyranopyrazoles are an
important class of heterocyclic compounds. They find applications as biodegradable
2
6
27, 28
agrochemicals
and pharmaceutical ingredients
. The first synthetic method of this
nucleus has been reported by Junek and coꢀworkers by the reaction between 3ꢀmethylꢀ1ꢀ
2
9
phenylpyrazolinꢀ 5ꢀone and tetracyanoethylene . Afterward, various precursors and various
3
0, 31
27, 32ꢀ34
acidic
or basic
catalysts has been introduced for the synthesis of pyranopyrazoles.
on Fe and bonded it to the support using thermal
In this research, we supported BF
3
3 4
O
operations at various temperature as a novel solid acid and magnetically recoverable catalyst
for the synthesis of pyranopyrazoles through multiꢀcomponent reaction of 3ꢀmethylꢀ1ꢀ
phenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone, malononitrile and various aromatic aldehydes (Scheme 1).
3
4
2

Page 3 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
Scheme 1.
1
2
3
2
. Experimental
4
5
2. 1. Materials and methods
All chemicals were commercial products. All reactions were monitored by (Thin Layer
6
1
13
Chromatography) TLC and all yields refer to isolated products. H and C NMR spectra
7
1
were recorded in DMSOꢀd
6
on a Bruker DRXꢀ400 AVANCE (400 MHz for H and 100 MHz
8
1
3
for C) spectrometer. Infrared spectra of the catalysts and reaction products were recorded on
a Bruker FTꢀIR Equinoxꢀ55 spectrophotometer in KBr disks. XRD patterns were recorded on
a Bruker D8 ADVANCE Xꢀray diffractometer using nickel filtered Cu Kα radiation (λ =
9
10
11
12
13
14
1
.5406 Å). Scanning electron microscopy (SEM) was performed using KYKYꢀEM3200
instrument. Potentiometric data was collected using pH/mV meter, AZ model 86502ꢀ
pH/ORP. ICP analysis was performed by VARIAN model Vistaꢀpro instrument.
1
5
2. 2. Preparation of MNPs
16
3
5
Fe O ꢀMN was prepared by coꢀprecipitation method as reported . In a typical procedure 0.5
17
18
19
20
21
3
4
M ferrous chloride (10 mL) and 0.5 M ferric chloride (10 mL) were mixed in a glass beaker.
To this solution, 12 M NH OH (60 mL) was added drop by drop with continuous stirring.
The resulting black precipitate was kept for 2 h. The precipitate was washed three times with
deionized water (20 mL) to remove excess NH
4
3
.
2
2
3
2. 3. Preparation of BF /MNPs
23
A mixture of MNPs (1 g), toluene (10 mL) and BF
3
·Et
2
O (3 mmol) was stirred for 2 h at
24
25
26
27
28
room temperature. The suspension was separated by centrifuge and washed with toluene (10
mL). The solid was dried in an oven at 120 °C for 1 h and then calcined at 350, 400 or 450 °C
for 2 h. The samples were labeled as BF
temperature.
3
/MNPsꢀX where X is the final calcination
2
3
9
0
3

RSC Advances
Page 4 of 18
View Article Online
DOI: 10.1039/C5RA11343A
Scheme 2. Preparation of the BF
3
/MNPs catalyst
1
2
3
2. 4. General procedure for the synthesis of derivatives
A mixture of aryl aldehyde 1 (1 mmol), 3ꢀMethylꢀ1ꢀphenylꢀ2ꢀpyrazolineꢀ5ꢀone (1 mmol)
4
5
6
7
8
9
1
malononitrile 4 (1 mmol) and BF /MNPs (100 mg) was stirred in ethanol (5 mL) at 80 °C for
3
mentioned times in Table 2. After completion of the reaction (monitored by TLC), the
catalyst was separated from solid product by an external magnet, and product washed with
small amounts of water (10 mL) and ethanol (5 mL) then recrystallized from ethanol to give
the pure products 4aꢀj.
0
2. 5. Physical and spectroscopic data for selected compounds
11
6
-amino-3-methyl-4-(4-chlorophenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-
12
13
carbonitrile (4a):
1
H NMR (400 MHz, DMSOꢀd
6
) : δ (ppm) = 7.79 (d, , J = 8 Hz, 2H), 7.50 (t, J = 8 Hz, 2H),
14
15
16
17
18
1
3
7
.42 (d, , J = 8 Hz, 2H), 7.30ꢀ7.35 (m, 3H), 7.27 (s, NH ), 4.74 (s, 1H), 1.80 (s, 3H); C NMR
2
(100 MHz, DMSOꢀd
6
): δ (ppm) = 188.0, 159.3, 145.2, 143.6, 137.5, 129.3, 128.5, 127.8, 127.7,
1
27.0, 126.1, 119.9, 98.6, 58.1, 36.7, 12.5. FTꢀIR (KBr disk): 3448, 3323, 2198, 1660, 1519,
ꢀ1
1
490, 1392, 1128, 756 cm
.
6
-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (4b)
19
20
21
22
23
24
1
6
H NMR (400 MHz, DMSOꢀd ) : δ (ppm) = 7.79 (d, J = 8 Hz, 2H), 7.50 (t, J = 8 Hz, 2H),
1
3
7.33ꢀ7.38 ( m, 3H), 7.25ꢀ7.29 (m, 3H), 7.23 (s, NH ), 4.69 (s ,1H), 1.79 (s ,3H); C NMR
2
(100 MHz, DMSOꢀd
6
): δ (ppm) = 181.0, 159.4, 145.2, 143.6, 137.5, 129.3, 128.5, 127.8,
127.0, 126.1, 119.9, 109.5, 98.6, 58.1, 36.7, 12.5. FTꢀIR (KBr disk): 733, 1027, 1065, 1125,
ꢀ1
1264, 1385, 1444, 1515, 1592, 2198, 3324, 3471 cm .
6
-amino-3-methyl-4-(4-nitrophenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-
25
26
carbonitrile (4c)
1
H NMR (400 MHz, DMSOꢀd
6
) : δ (ppm) = 8.24 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.4 Hz,
27
28
29
2
4
H), 7.59 ( d, J = 8.8 Hz 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.40 (s, NH ), 7.34 (t, J = 6.4 , 1H),
2
1
3
.94 (s ,1H), 1.80 (s ,3H); C NMR (100 MHz, DMSOꢀd ): δ (ppm) = 181.4, 159.6, 151.2,
6
4

Page 5 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
1
46.6, 145.1, 137.4, 129.3, 129.2, 126.3, 123.9, 120.1, 97.6, 66.6, 36.3, 12.5. FTꢀIR (KBr
1
2
3
4
5
6
7
8
9
1
ꢀ1
disk): 3338, 3213, 2191, 1666, 1595, 1517, 1402, 1350, 1132, 821 cm .
-amino-3-methyl-4-(3-nitrophenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-
6
carbonitrile (4j)
1
H NMR (400 MHz, DMSOꢀd
6
) : δ (ppm) = 8.16ꢀ8.17 (m, 2H), 7.79 (m, 3H), 7.68 (t, 1H,
), 7.34 (t, 1H, J=8Hz), 4.98 (s, 1H), 1.81 (s, 3H) );
): δ (ppm) = 159.7, 147.9, 145.9, 145.1, 144.0, 137.4, 134.7,
30.3, 129.3, 126.3, 122.2, 120.1, 119.7, 97.6, 57.0, 36.1, 12.6. FTꢀIR (KBr disk): 3437,
J=8Hz), 7.51 (t, 2H, J=8Hz), 7.38 (s, NH
1
2
3
C NMR (100 MHz, DMSOꢀd
6
1
3
ꢀ1
298, 2194, 1651, 1595, 1517, 1400, 1352, 1263, 1122, 1070, 756, 694 cm .
0
3
. Results and discussions
11
12
3. 1. The catalyst characterization
Fig. 1 represents the results of scanning electron microscopy (SEM) in order to investigate
the particle size and morphology of the catalysts. The SEM of the MNPs and BF /MNPs
shows spherical nanoparticles with sizes of <100 nm. In the case of BF /MNPs, partial
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3
3
agglomeration is observed due to BF treatment on MNPs surface and also calcination, but
3
this treatment has not dramatically effect on the nanoparticle shapes. To investigate the
elemental component of the BF
c. Presence of the Fe and O related to the MNPs is obvious. In addition, EDX analysis
shows considerable content of the F. Moreover the loading level of boron on the surface of
3
/MNPsꢀ450, EDX analysis was performed and shown in Fig.
3
ꢀ1
BF
3
/MNPsꢀ450 was estimated to be at about 0.5 mmol g with an ICP method and the
ꢀ1
fluoride contents of BF
3
/MNPsꢀ450 was estimated to be at about 0.75 mmol g and it was
measured by a potentiometric method using a fluoride ionꢀselective electrode. These results
verify presence of BꢀF species in the catalyst and the obtained B/F molar ratio of 3/2 shows
that boron species on the MNPs surface. The B/F molar ratio of 3/2 suggests that a covalent
bond between oxygen of Fe
calcination.
3
O
4
and boron is created due to evolution of HF during
2
8
5

RSC Advances
Page 6 of 18
View Article Online
DOI: 10.1039/C5RA11343A
1
2
Fig. 1. SEM images of a) MNPs b) BF
3
/MNPsꢀ450 and c) EDX Analysis of BF
3
/MNPsꢀ450
3
4
TEM image of the BF
3
/MNPsꢀ450 is shown in Fig. 2. This image demonstrates nearly
5
6
uniform size of the particles and spherical shape of them.
6

Page 7 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
1
2
3
Fig. 2. TEM image of the BF /MNPsꢀ450
3
XRD pattern of magnetite nanoparticles is shown in Fig. 3. Both Fe
show diffraction peaks at 2θ = 30.3, 35.6, 43.3, 53.8, 57.4 and 62.9º that are indexed to the
crystalline cubic inverse spinel structure of Fe nanoparticles.
3
O
4
and BF
3
/MNPsꢀ450
4
5
6
3
O
4
7
8
Fig. 3. XRD patterns of a) MNPs and b) BF /MNPsꢀ450
3
9
Fig. 4 shows the IR spectra of MNPs and BF
3
/MNPs at different calcination temperatures
10
11
12
13
14
ꢀ1
over the 400–4000 cm region. As shown in Fig. 4, all the samples show characteristic peaks
−1
at 560 and 638 cm , which are assigned to FeꢀO stretching modes. The peak at 1083 is
assigned to CꢀO (the residue of ether) that is not observed in the calcined samples. Apart
−1
from the main peaks of MNPs, there is a wide peak at ~1400 cm , which is assigned to B–O
7

RSC Advances
Page 8 of 18
View Article Online
DOI: 10.1039/C5RA11343A
36
stretching . This peak is observed before calcination of the catalyst and also is observed in
all calcined samples but with less intensity and partly broadening. Surprisingly, this peak has
a larger relative intensity respect to the other calcined samples.
1
2
3
a)
b)
c)
d)
e)
2000
1600
1200
800
400
ꢀ1
Wavenumber (cm )
4
Fig. 4. FTꢀIR spectra of a) MNPs and BF
3
/MNPs b) Before calcination c) calcination at 350
5
6
°C d) calcination at 400 °C d) calcination at 450 °C
7
The catalyst acidity characters, including the acidic strength and the total number of acid sites
were determined by potentiometric titration. According to this method, the initial electrode
8
9
3
7
potential (Ei) indicates the maximum acid strength of the surface sites . Therefore, a
suspension of the catalyst in acetonitrile was potentiometrically titrated with a solution of
10
11
12
13
0.02 M
n
ꢀbutylamine. As shown in Fig. 5, BF /MNPsꢀ450 displays higher strength than the
3
MNPs.
1
4
8

Page 9 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
4
00
00
0
2
a)
-
-
-
-
200
400
600
800
b)
0.0
0.2
0.4
meq/g
0.6
0.8
1.0
1
Fig. 5. Potentiometric titration of a) MNPs and b) BF
3
/MNPsꢀ450
2
3
Fig. 6 shows the magnetization versus applied field of the catalyst that was obtained by VSM.
4
5
6
7
8
−
1
The saturation magnetization value was measured to be ~60 emu g for Fe
3
O
4
and ~50 emu
/MNPsꢀ50. The results show that surface modification of MNPs has insignificance
effect on the magnetic properties of MNPs.
−
1
g for BF
3
9

RSC Advances
Page 10 of 18
View Article Online
DOI: 10.1039/C5RA11343A
60
40
20
0
a)
b)
-
-
-
20
40
60
-
8000
-4000
0
4000
8000
Applied field (Oe)
1
2
3
Fig. 6. VSM test of the a) MNPs and b) BF /MNPsꢀ450
3
4
5
Fig. 7. Representation of catalyst separation with an external magnet
6
After characterization of the prepared catalysts, to determination of the best catalytic activity,
they have been used in the multiꢀcomponent reaction of 4ꢀchlorobenzaldehyde, malononitrile
and 3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone as model reaction. The reaction was optimized
for various parameters such as temperature, solvent and catalyst loading. We first,
investigated effect of the calcination temperature on the catalytic behavior of prepared
7
8
9
10
11
12
13
samples. In the presence of an equal amount of the catalyst (100 mg), BF /MNPsꢀ450 show
3
the better catalytic activity in term of the yield of desired product and time of completion of
1
0

Page 11 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
model reaction in ethanol as the reaction solvent. Therefore, other reaction parameters has
1
2
3
4
5
been optimized in the presence of BF /MNPsꢀ450. To optimize the catalyst amount, the
3
model reaction was performed in the presence of various amounts of the catalyst and
according to the obtained results (Table 1, entries 1ꢀ4) 100 mg of the catalyst was chosen as
the best catalyst amount.
Table 1. Screening of reaction parameters for the synthesis of 1,4ꢀdihydropyrano[2,3ꢀ
6
7
c]pyrazole.
c
Catalyst
Yield
(%)
86
b
Entry
Catalyst
Time (min)
amount (mg)
1
2
3
4
5
6
7
8
BF
BF
BF
BF
3
/MNPsꢀ450
/MNPsꢀ450
/MNPsꢀ450
/MNPsꢀ450
50
75
30
20
15
25
60
60
180
35
3
3
3
89
100
125
100
100
100
7
96
79
BF
3
/MNPsꢀ400
85
BF /MNPsꢀ350
83
3
MNPs
40
BF
3
.Et
2
O
86
a
All reactions were carried out with 4ꢀchlorobenzaldehyde (1 mmol), malononitrile (1.1 mmol), 3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ
pyrazolꢀ5(4H)ꢀone (1 mmol), ethanol (5 mL) and BF /MNPsꢀx as the catalyst at 80 °C.
8
9
3
1
0
The effect of solvent was also investigated by performing the model reaction in the presence
of 100 mg catalyst in various solvents (Table 2, entries 1ꢀ5). Among them, ethanol was found
to be the best solvent in reflux condition (80 °C) in terms of the reaction time and yield of
desired product (Table 2, entry 1). The model reaction in the presence of ethanol as the
solvent was also performed at the lower temperature (70 °C) and also the less yield and
longer reaction time was obtained (Table 2, entry 6). To investigate efficiency of the support
11
12
13
14
15
16
17
18
19
20
3 3 2
on the catalytic activity of BF the model reaction was performed in the presence of BF .Et O
(7 mg, equal to loading amount of boron on the 100 mg catalyst) and results shows lower
activity than BF /MNPsꢀ450. MNPs was also applied as the catalyst in the model reaction
3
and results show that MNPs lacks catalytic activity in this type of reaction.
2
2
1
2
1
1

RSC Advances
Page 12 of 18
View Article Online
DOI: 10.1039/C5RA11343A
Table 2. Screening of solvents at variable temperature
1
Entry
Catalyst amount Solvent
mg)
Temp. (°C)
Time
(min)
15
Yield (%)
(
1
2
3
4
5
6
100
100
100
100
100
100
EtOH
80
100
80
96
60
90
53
65
80
H
2
O
45
DMF
THF
15
65
15
MeOH
EtOH
65
25
70
30
a
All reactions were carried out with 4ꢀchlorobenzaldehyde (1 mmol), malononitrile (1.1 mmol), 3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ
pyrazolꢀ5(4H)ꢀone (1 mmol) and BF /MNPsꢀ450 as the catalyst.
2
3
3
4
5
6
7
8
9
Thereafter, the above optimized reaction conditions were explored for the synthesis of 1,4ꢀ
dihydropyrano[2,3ꢀc]pyrazole derivatives and the results are summarized in Table 3. As
exemplified in Table 3, this protocol is rather general for a wide variety of electronꢀrich as
well as electronꢀdeficient aromatic aldehydes.
1
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
8
9
0
1
2

Page 13 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
1
2
a
3
Table 3. BF /MNPsꢀ450 catalyzed synthesis of 1,4ꢀdihydropyrano[2,3ꢀc]pyrazole
b
c
ref
Entry
a
Substrate 1
Product 4
Time (min)
Yield (%)
M.p. (°C)
3
8
15
96
178ꢀ180
3
8
8
b
c
5
88
90
172ꢀ174
3
10
192ꢀ194
3
8
8
d
e
15
60
85
93
172ꢀ173
175ꢀ177
3
3
4
9
0
f
15
15
87
84
160ꢀ161
175ꢀ177
g
1
3

RSC Advances
Page 14 of 18
View Article Online
DOI: 10.1039/C5RA11343A
2
3
7
8
h
i
60
20
90
88
195ꢀ197
213ꢀ214
4
0
j
15
91
190ꢀ191
CHO
O N
2
a
All reactions were carried out with 4ꢀchlorobenzaldehyde (1 mmol), malononitrile (1.1 mmol), 3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ
pyrazolꢀ5(4H)ꢀone (1 mmol) in ethanol (5 mL) and BF /MNPsꢀ450 as the catalyst at 80 °C.
1
2
3
3
4
5
6
7
A Plausible mechanism for the synthesis of pyranopyrazoles catalyzed by BF
3
/MNPs is
explained in scheme 3.
Scheme 3. Plausible mechanism for the synthesis of pyranopyrazoles catalyzed by BF /MNPs
3
8
9
Reusability of the catalyst was investigated in the model reaction under the optimized
reaction conditions. The catalyst was separated from the model reaction and reused four times
with negligible loss of the catalytic activity (Table 4). Partial loss of activity may be due to
blockage of active sites of the catalyst and/or partial leaching of boron from the catalyst.
10
11
12
1
4

Page 15 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
Table 4. Reusability test of BF
3
/MNPsꢀ450 in the model reaction at the optimized conditions
1
Fresh catalyst
First cycle
Second cycle Third cycle
Fourth cycle
Time (min)
Yield (%)
15
95
15
90
15
88
15
85
15
80
2
A comparative study of this work with other methods has performed. Table 5 presents other
reported methods for the synthesis of pyranopyrazole derivatives. Although Table 5 contains
various methods such as fourꢀcomponent synthesis of pyranopyrazoles, we can say that our
method is comparable with other reported method in terms of yield and reaction time. The
most significance of our method is use of the magnetite heterogeneous solid acid catalyst
with good catalyst recoverability and ease of separation from reaction media. In addition, use
of commercial available precursors, green solvent and easy workꢀup make this method
attractive for the synthesis of pyranopyrazole derivatives.
3
4
5
6
7
8
9
10
1
1
Table 5. Comparison of this work with other similar works for synthesis of pyranopyrazoles
12
Entry
Catalyst
Solvent Temp.(°C) Time (min)
yields%
4
1
1
2
Uncapped SnO
2
QDs
H
2
O
RT
90ꢀ150
15ꢀ25
88ꢀ98
88ꢀ95
40
silica‐bonded N‐
propylpiperazine
piperidine
EtOH
Reflux
27
3
4
H O
RT
5ꢀ10
5ꢀ60
67ꢀ94
2
BF
/MNPs
EtOH
Reflux
84ꢀ96[this work]
3
1
1
3
4
Conclusion
15
16
17
18
19
20
21
22
23
24
25
In conclusion, we prepared BF /MNPs as a novel magnetite recoverable catalyst and it has
3
been characterized using various techniques such as SEM, TEM, EDX, XRD, FTꢀIR and
3
VSM. In this study immobilization of BF on the MNPs was performed through thermal
treatment (calcination) and it was observed that calcination temperature have important effect
on the catalysis activity of the catalyst. The catalytic activity of the prepared catalysts at the
different calcination temperature was investigated in the synthesis of 1,4ꢀdihydropyrano[2,3ꢀ
c]pyrazole derivatives through oneꢀpot multiꢀcomponent reaction of aldehyde, malononitrile
3
and 3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone and BF /MNPsꢀ450 showed better catalytic
activity respect to the other samples. From the synthetic method point of view, use of a
reusable catalyst, moderate to good yield of products, he simple experimental procedure, easy
1
5

RSC Advances
Page 16 of 18
View Article Online
DOI: 10.1039/C5RA11343A
workup and ease of the magnetite catalyst recovery make this method attractive for the
synthesis of 1,4ꢀdihydropyrano[2,3ꢀc]pyrazole derivatives.
1
2
3
4
5
Acknowledgment
We are thankful to the Yazd University Research Council for partial support of this work.
6
7
References:
1
2
3
4
T. Vijai Kumar Reddy, G. Sandhya Rani, R. B. N. Prasad and B. L. A. Prabhavathi Devi,
RSC Advances, 2015, 5, 40997ꢀ41005.
8
9
Y. R. Girish, K. S. Sharath Kumar, U. Muddegowda, N. K. Lokanath, K. S. Rangappa and
S. Shashikanth, RSC Adv., 2014, 4, 55800ꢀ55806.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
M. AbdollahiꢀAlibeik and E. Shabani, Journal of the Iranian Chemical Society, 2014, 11,
3
51ꢀ359.
H. Tian, X. L. Zhang, J. Scott, C. Ng and R. Amal, Journal of Materials Chemistry A
014, 2, 6432.
N. D. Tran, M. Besson and C. Descorme, New J. Chem., 2011, 35, 2095ꢀ2104.
S. Fuentes, N. E. Bogdanchikova, G. Diaz, M. Peraaza and G. C. Sandoval, Catal. Lett.
997, 47, 27ꢀ34.
M. HosseiniꢀSarvari, Z. Razmi and M. M. Doroodmand, Appl. Catal., A, 2014, 475, 477ꢀ
86.
,
2
5
6
,
1
7
4
8 M. AbdollahiꢀAlibeik and A. Moaddeli, New J. Chem., 2015, 39, 2116ꢀ2122.
9 M. AbdollahiꢀAlibeik and A. Moaddeli, RSC Advances, 2014, 4, 39759ꢀ39766.
10 T. Matsunaga, in Iron Biominerals, eds. R. Frankel and R. Blakemore, Springer US,
1
991, DOI: 10.1007/978ꢀ1ꢀ4615ꢀ3810ꢀ3_6, ch. 6, pp. 79ꢀ95.
1 R. K. Singh, T. H. Kim, K. D. Patel, J. C. Knowles and H. W. Kim, J Biomed Mater Res
, 2012, 100, 1734ꢀ1742.
1
1
1
1
A
2 C. Y. Haw, F. Mohamed, C. H. Chia, S. Radiman, S. Zakaria, N. M. Huang and H. N.
Lim, Ceram. Int., 2010, 36, 1417ꢀ1422.
3 T. Neuberger, B. Schöpf, H. Hofmann, M. Hofmann and B. von Rechenberg, J. Magn.
Magn. Mater., 2005, 293, 483ꢀ496.
4 S. Ko and J. Jang, Angew Chem Int Ed Engl, 2006, 45, 7564ꢀ7567.
1
6

Page 17 of 18
RSC Advances
View Article Online
DOI: 10.1039/C5RA11343A
15 V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara and J. M. Basset, Chem Rev
,
1
2011, 111, 3036ꢀ3075.
2
16 A. Baiker, H. Baris and R. Schlögl, J. Catal., 1987, 108, 467ꢀ479.
17 C. R. F. Lund, J. E. Kubsh and J. A. Dumesic, 1985, 279, 313ꢀ338.
18 K. R. P. M. Rao, F. Huggins, V. Mahajan, G. Huffman and V. U. S. Rao, Hyperfine
Interact., 1994, 93, 1745ꢀ1749.
3
4
5
6
1
2
2
2
2
2
9 K. Debnath, K. Singha and A. Pramanik, RSC Advances, 2015, 5, 31866ꢀ31877.
0 A. KhalafiꢀNezhad, M. Nourisefat and F. Panahi, RSC Advances, 2014, 4, 22497.
1 M. Kotani, T. Koike, K. Yamaguchi and N. Mizuno, Green Chem., 2006, 8, 735.
7
8
9
2 M. B. Gawande, P. S. Branco and R. S. Varma, Chem. Soc. Rev., 2013, 42, 3371ꢀ3393.
3 N. J. Thumar, Arkivoc, 2010, 2009, 363.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
4 P. W. Smith, S. L. Sollis, P. D. Howes, P. C. Cherry, I. D. Starkey, K. N. Cobley, H.
Weston, J. Scicinski, A. Merritt, A. Whittington, P. Wyatt, N. Taylor, D. Green, R.
Bethell, S. Madar, R. J. Fenton, P. J. Morley, T. Pateman and A. Beresford, J. Med.
Chem., 1998, 41, 787ꢀ797.
25 J. Skommer, D. Wlodkowic and J. Pelkonen, Experimental Hematology, 2006, 34, 463ꢀ
4
74.
6 H. V. Chavan, S. B. Babar, R. U. Hoval and B. P. Bandgar, Bull. Korean Chem. Soc.
011, 32, 3963ꢀ3966.
2
,
2
2
2
2
3
7 G. Vasuki and K. Kumaravel, Tetrahedron Lett., 2008, 49, 5636ꢀ5638.
8 M. Babaie and H. Sheibani, Arabian Journal of Chemistry, 2011, 4, 159ꢀ162.
9 H. Junek and H. Aigner, Chem. Ber., 1973, 106, 914ꢀ921.
0 S. Pal, M. N. Khan, S. Karamthulla, S. J. Abbas and L. H. Choudhury, Tetrahedron Lett.
013, 54, 5434ꢀ5440.
,
2
3
1 M. A. Zolfigol, M. Tavasoli, A. R. MoosaviꢀZare, P. Moosavi, H. G. Kruger, M. Shiri
and V. Khakyzadeh, RSC Advances, 2013, 3, 25681.
3
2 B. Maheshwar Rao, G. N. Reddy, T. V. Reddy, B. L. A. P. Devi, R. B. N. Prasad, J. S.
Yadav and B. V. S. Reddy, Tetrahedron Lett., 2013, 54, 2466ꢀ2471.
33 Y. Zou, Y. Hu, H. Liu and D. Shi, ACS Combinatorial Science, 2012, 14, 38ꢀ43.
34 S. H. S. Azzam and M. A. Pasha, Tetrahedron Lett., 2012, 53, 6834ꢀ6837.
35 R. Ghosh, L. Pradhan, Y. P. Devi, S. S. Meena, R. Tewari, A. Kumar, S. Sharma, N. S.
Gajbhiye, R. K. Vatsa, B. N. Pandey and R. S. Ningthoujam, J. Mater. Chem., 2011, 21,
13388.
1
7

RSC Advances
Page 18 of 18
View Article Online
DOI: 10.1039/C5RA11343A
3
6 M. AbdollahiꢀAlibeik and A. RezaeipoorꢀAnari, Catal. Sci. Technol., 2014, 4, 1151ꢀ
159.
7 L. R. Pizzio, P. G. Vázquez, C. V. Cáceres and M. N. Blanco, Appl. Catal., A, 2003, 256,
25ꢀ139.
1
1
2
3
3
1
4
38 H. S. Sohal, A. Goyal, R. Sharma, R. Khare and S. Kumar, 2013, 2013, 4.
5
39 M. Farahi, B. Karami, I. Sedighimehr and H. M. Tanuraghaj, Chin. Chem. Lett., 2014,
6
2
5, 1580ꢀ1582.
0 K. Niknam, N. Borazjani, R. Rashidian and A. Jamali, Chinese. j. catal., 2013, 34, 2245ꢀ
254.
1 S. Paul, K. Pradhan, S. Ghosh, S. K. De and A. R. Das, Tetrahedron, 2014, 70, 6088ꢀ
099.
7
4
4
8
2
9
10
11
6
1
2
1
8