One-pot three-component process for the synthesis of substituted pyrano[2,3-c]pyrazoles catalyzed by nanostructured FSM-16-SO3H

Article abstract of DOI:10.1007/s13738-018-1368-1

A three-component process for the one-pot synthesis of 6-amino-4-aryl-5-cyano-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazoles by the reaction of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, and malononitrile in the presence of FSM-16-SO₃

Full text of DOI:10.1007/s13738-018-1368-1

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1368-1
ORIGINAL PAPER
One-pot three-component process for the synthesis of substituted
pyrano[2,3-c]pyrazoles catalyzed by nanostructured FSM-16-SO3H
Somayeh Hashemi‑Uderji1 · Mohammad Abdollahi‑Alibeik1
Received: 7 July 2017 / Accepted: 15 April 2018
© Iranian Chemical Society 2018
Abstract
A three-component process for the one-pot synthesis of 6-amino-4-aryl-5-cyano-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-
c]pyrazoles by the reaction of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, and malononitrile in the presence of
FSM-16-SO3H as an efficient mesoporous catalyst. The FSM-16-SO3H was prepared and characterized by SEM, XRD, BET,
and FT-IR techniques. The advantages of the presented method are high yields, short reaction times, easy purification of
products, easy work-up, and reusability of the catalyst.
Keywords FSM-16 · FSM-16-SO3H · Mesoporous silica · Nanocatalyst · Pyranopyrazoles · Multi-component
Introduction
between pyrazolone, an aldehyde and malononitrile in the
presence of various catalyst such as p-dodecylbenzene sul-
fonic acid (DBSA) [11], triethylbenzylammonium chlo-
ride (TEBA) [12], hexadecyltrimethylammonium bromide
(HTMAB) [13], BF3/MNPs [14], H14[NaP5W30O110] [15],
MgO [16], and KF·2H2O [17].
A multi-component reaction (MCR) or a “Multi-component
Assembly Process” (MCAP) is a convergent reaction, in
which three or more materials incorporate together to form
a single production [1], where basically, all of the atoms par-
ticipate to the newly formed product. MCRs have important
role in the synthesis of chemical compounds.
Heterogeneous catalysis has emerged considerable atten-
tion in organic transformations, especially in organic indus-
try. The greatest advantage of this type of catalyst compound
is the ease of separation. The mesoporous inorganic materi-
als, especially mesoporous silica compounds, are the most
important material for the preparation of heterogeneous
catalyst.
The synthesis of fused pyran derivatives is partial of
multi-component reaction (MCR). Nowadays, substituted
pyrano[2,3-c]pyrazoles are considered as remarkable com-
pounds because of pharmaceutical attributes [2–4]. They
represent a perfect range of biological activities including
anti-inflammatory [5], antimicrobial [6], anticancer [2, 7],
and inhibitors of human Chk1 kinase [8].
Mesoporous silica with highly ordered pores and high
surface area, such as MCM-41 and FSM-16, has attracted
considerable interests in the field of electrochemistry,
adsorption science and catalysis chemistry [18–30].
The first reported method for the synthesis of folded sheet
mesoporous material (FSM-16) includes intercalation of a
layered, kanemite-type sodium silicate with cetyltrimeth-
ylammonium (CTMA) ions [18]. FSM-16 is formed via a
folded sheet mechanism in which the condensation of the
reactive silanol groups available on the vicinal silicate layers
in CTMA kanemite complex terminate to the formation of
a hexagonal array of channels with the same pore size [19].
Acidity of this mesoporous catalyst is not severe. For this
reason, many functional groups have been binded on its sur-
face, to improve the catalytic activity of FSM-16 [31–33].
The first synthetic procedure of this compounds has been
reported by Junek et al. via the reaction of tetracyanoeth-
ylene and 3-methyl-1-phenylpyrazolin-5-one [9]. Another
method for the synthesis of 6-amino-5-cyano-4-aryl-4H-
pyrazolo[3,4-b]pyrans includes the reaction of arylidiene-
malononitrile with 3-methylpyrazoline-5-ones or by the con-
densation of malononitrile and 4-arylidienepyrazoline-5-one
[10]. General method for the synthesis of pyranopyrazole
derivatives using three-component reaction is the reaction
* Mohammad Abdollahi-Alibeik
abdollahi@yazd.ac.ir; moabdollahi@gmail.com
1
Department of Chemistry, Yazd University,
Yazd 89158-13149, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
In this research, we report the preparation and charac-
terization of FSM-16-SO3H as a novel heterogeneous acid
catalyst by functionalization of silanol groups on the surface
of FSM-16 with –SO3H groups (Scheme 1).
Experimental
Materials and methods
The catalytic activity of FSM-16-SO3H was also stud-
ied in the reaction of various types of aldehydes, 3-methyl-
1-phenyl-1H-pyrazol-5(4H)-one and malononitrile for the
synthesis of pyrano[2,3-c]pyrazoles (Scheme 2).
All chemicals were commercial and were used as received.
The reactions were monitored by TLC. The yields of prod-
ucts refer to isolated compounds. Melting points were
obtained by a Buchi B-540 apparatus and are uncorrected.
1H NMR and 13C NMR spectra of pyranopyrazoles were
recorded in DMSO-d6 on a Bruker DRX-400 AVANCE
spectrometer (400 MHz for H and 100 MHz for 13C).
1
Infrared spectra of the reaction products and catalysts were
recorded on a Bruker FT-IR Equinax-55 in KBr disks. The
XRD patterns were recorded on a Bruker D8 ADVANCE
CTAB
Ion-exchange
kanemite
Hexagonal array
Calcination
Si
OSO3H
OSO3H
O
ClSO3H
Si
O
OSO3H
Si
FSM-16-SO3H
FSM-16
Scheme 1 Schematic representation for the preparation of FSM-16-SO3H
Scheme 2 Synthesis of
pyrano[2,3-c]pyrazoles in the
presence of FSM-16-SO3H
CHO
Ph
N
CN
FSM-16-SO3H
Ethanol/Water
N
CN
CN
O
+
+
N
N
O
4
NH2
Ph
1
2
3
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Journal of the Iranian Chemical Society
X-ray diffractometer using Ni-filtered Cu Kα radiation. The
morphology was studied using a KYKY-EM3200 scanning
electron microscope. The BET surface area was measured
using a micromeritics model ASAP2020 from the nitrogen
adsorption–desorption isotherms at 77 K. All samples were
degassed at 120 °C under flowing nitrogen for 2 h. The spe-
cific surface area (SBET) was calculated from the adsorption
General procedure for the synthesis of pyrano[2,3‑c]
pyrazoles
A mixture of aryl aldehyde (1 mmol), malononitrile
(1.1 mmol), 3-methyl-1-phenyl-2-pyrazoline-5-one
(1 mmol), and FSM-16-SO3H (40 mg) was stirred in a mix-
ture of water and ethanol (2 mL, 2:8) at reflux condition.
After completion of the reaction (monitored by TLC, eluent;
n-hexane:ethyl acetate, 7:3), the catalyst was separated by a
centrifuge and then washed with ethanol (2×3 mL). After
evaporation of solvent, the crude products were crystallized
from ethanol to give pure products (4a–o).
data using the BET equation, and the pore volume (Vpore
)
was estimated from the volume of adsorbed N2 at relative
pressure (p/p°) of 0.99. The pore size distribution was calcu-
lated by the Barret–Joyner–Halenda (BJH) method.
Preparation of FSM‑16 nanoparticles
Physical and spectroscopic data for selected
compounds
A typical procedure for the preparation of kanemite was as
follows: to a solution of NaOH (3 g) dissolved in deionized
water (30 mL), tetraethyl orthosilicate (16.6 mL) was added
dropwise and then the mixture was stirred for another 12 h
at room temperature. The solution was transferred into an
oven and heated at 355 K for 4 h. The resultant product was
calcined at 923 K for 5 h to obtain δ-Na2Si2O5 (kanemite).
The kanemite was deliquescent and immediately used for
further treatment. Kanemite (5 g) was dispersed in deionized
water (50 mL) and then stirred for 3 h at 300 K. Then, the
suspension was filtered out to obtain wet kanemite paste. All
of the kanemite pastes were dispersed in an aqueous solu-
tion (40 mL) of cetyltrimethylammonium bromide (CTAB)
(0.125 mol L−1) and then stirred at 343 K for 3 h. The pH
value of the suspension was 11.5–12.5 at this stage. After-
wards, the pH value was adjusted carefully to 8.5 by adding
2 mol L−1 hydrochloric acid with stirring. The suspension
was kept under stirring at 343 K for 3 h with keeping the pH
value at 8–9. After cooling to r.t., the solid was separated by
a centrifuge and washed with distilled water (20 mL) and
dried in oven at 393 K for 2 h to yield mesoporous silicate,
FSM-16, with retaining the template. The product was cal-
cined at 823 K to burn off the surfactant to obtain the final
FSM-16.
6-Amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]-
pyrazole-5-carbonitrile (4a) Yellow solid, mp 178–179 °C
(Lit. [14] 172–174 °C). 1H NMR (400 MHz, DMSO-d6): δ
(ppm) = 7.79 (d, J = 8.0 Hz, 2H), 7.50 (t, J = 8.0 Hz, 2H),
7.33–7.38(m, 3H), 7.25–7.29 (m, 3H), 7.23 (s, NH2), 4.69
(s, 1H), 1.79 (s, 3H); 13C NMR (100 MHz, DMSO-d6): 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.
FT-IR (KBr disk): 733, 1027, 1065, 1125, 1264, 1385, 1444,
1515, 1592, 2198, 3324, 3471 cm−1.
6-Amino-3-methyl-4-(4-chlorophenyl)-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (4b) White
1
solid, mp 180–182 °C (Lit. [14] 178–180 °C). H NMR
(400 MHz, DMSO-d6): δ (ppm)=7.79 (d, J=8.0 Hz, 2H),
7.50 (t, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 7.30–7.35
(m, 3H), 7.27 (s, NH2), 4.74 (s,1H), 1.80 (s, 3H); 13C NMR
(100 MHz, DMSO-d6): δ (ppm)=188.0, 159.3, 145.2, 143.6,
137.5, 129.3, 128.5, 127.8, 127.7, 127.0, 126.1, 119.9, 98.6,
58.1, 36.7, 12.5. FT-IR (KBr disk): 3448, 3323, 2198, 1660,
1519, 1490, 1392, 1128, 756 cm−1.
6-Amino-3-methyl-4-(3-nitrophenyl)-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (4i) White
1
solid, mp 187–189 °C (Lit. [14] 190–191 °C). H NMR
(400 MHz, DMSO-d6): δ (ppm)=8.16–8.17 (m, 2H), 7.79
(m, 3H), 7.68 (t,1H, J = 8.0 Hz), 7.51 (t, 2H, J = 8.0 Hz),
7.38 (s, NH2), 7.34 (t, 1H, J= 8.0 Hz), 4.98 (s, 1H), 1.81
(s, 3H); 13C NMR (100 MHz, DMSO-d6): δ (ppm)=159.7,
147.9, 145.9, 145.1, 144.0, 137.4, 134.7, 130.3, 129.3,
126.3, 122.2, 120.1, 119.7, 97.6, 57.0, 36.1, 12.6. FT-IR
(KBr disk): 3437, 3298, 2194, 1651, 1595, 1517, 1400,
1352,1263, 1122, 1070, 756, 694 cm−1.
Preparation of FSM‑16‑SO3H nanoparticles
FSM-16 (0.278 g) was added to dry CH2Cl2 (3 mL) in a
5 mL round bottom flask equipped with a gas outlet tube and
a dropping funnel containing a solution of chlorosulfonic
acid (0.6 mL) in dry CH2Cl2 (4.5 mL). The chlorosulfonic
acid solution was added dropwise to the obtained suspen-
sion over a period of 30 min at room temperature. After
completion of the reaction, the sediment was separated by a
centrifuge and then washed with deionized water (2×3 mL).
The obtained solid was dried in an oven at 120 °C for 2 h to
obtain FSM-16-SO3H.
6-Amino-3-methyl-4-(4-nitrophenyl)-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (4o) White
1
solid, mp 195–198 °C (Lit. [14] 192–194 °C). H NMR
(400 MHz, DMSO-d6): δ (ppm)=8.24 (d, J=8.8 Hz, 2H),
7.80 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.51 (t,
J = 7.6 Hz, 2H), 7.40 (s, NH2), 7.34 (t, J = 6.4, 1H), 4.94
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Journal of the Iranian Chemical Society
(s, 1H), 1.80 (s, 3H); 13C NMR (100 MHz, DMSO-d6): δ
(ppm) = 181.4, 159.6, 151.2, 146.6, 145.1, 137.4, 129.3,
129.2, 126.3, 123.9, 120.1, 97.6, 66.6, 36.3,12.5. FT-IR
(KBr disk): 3338, 3213, 2191, 1666, 1595, 1517, 1402,
1350, 1132, 821 cm−1.
Results and discussions
The catalyst characterization
The FSM-16 and FSM-16-SO3H were characterized by
FT-IR, SEM, BET, and XRD techniques.
The SEM micrographs of FSM-16 and FSM-16-SO3H are
shown in Fig. 1a, b, respectively. SEM micrographs show
spherical nanoparticles with sizes of about 100 nm. Both
materials have similar texture and there is no significant
difference.
Fig. 2 TEM image of FSM-16-SO3H
Mesostructure of the FSM-16-SO3H sample was studied
by TEM, as shown in Fig. 2. Porosity of the sample is clear
and disordered mesoporous system is due to the insertion
of sulfonic acid groups on the inner surface of the FSM-16
framework that also confirms by XRD data.
The FT-IR spectra of FSM-16 and FSM-16-SO3H
are shown in Fig. 3. The spectrum of FSM-16 (Fig. 3a)
shows characteristic peaks at 1216, 1090, and 804 cm−1
due to symmetric and asymmetric stretching vibrations of
Si–O–Si and the peak of 966 cm−1 due to Si–OH groups.
The peak at 463 cm−1 is assigned to the bending vibration
of Si–O–Si. For FSM-16-SO3H (Fig. 3b), the FT-IR bands
of the O=S=O asymmetric and symmetric stretching modes
(b)
(a)
1084
1090
1200
2000
1600
800
400
Wavenumber (cm-1)
Fig. 1 SEM images of a FSM-16 and b FSM-16-SO3H
Fig. 3 FT-IR spectra of a FSM-16, b FSM-16-SO3H
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Journal of the Iranian Chemical Society
lies in 1120–1230 and 1010–1080 cm−1, respectively, and
that of the S–O stretching mode lies in 600 cm−1. FT-IR
spectrum of FSM-16-SO3H shows the overlap of asymmet-
ric and symmetric stretching bands of SO2 with Si–O–Si
stretching bands in the region of 1000–1250 cm−1, that
resulting in increase of intensity of this peak.
The distribution of both Brønsted and Lewis acid sites
of FSM-16-SO3H was detected using FT-IR spectroscopy
by means of pyridine absorption. Figure 5 shows the pyri-
dine adsorbed spectra of FSM-16-SO3H heated at various
temperatures. The spectrum of pyridine adsorbed FSM-16
shows only peaks of pyridine bonded Lewis acid sites at
1446 and 1598 cm−1 (Fig. 5b). The spectrum of pyridine
adsorbed FSM-16-SO3H before heat treatment (Fig. 5c)
shows the contribution of the pyridine adducts in the region
of 1400–1650 cm−1. The peak at 1487 cm−1 is attributed to
the combination of pyridine bonded to Lewis and Brønsted
acid sites. The peaks appearing at 1530 cm−1 is assigned to
Brønsted acid sites (pyridinum ion). The peak at 1603 cm−1
is attributed to the pyridine bonded Lewis acid sites of the
The low angle XRD patterns of FSM-16 and FSM-
16-SO3H are shown in Fig. 4. The characteristic peaks of
FSM-16 (Fig. 4a) have appeared at 2θ = 2.38°, 4.11° and
4.73° in accordance with the literature [34]. As shown in
Fig. 4b, after surface modification with SO3H groups, the
intensity of the main peak (2θ =2.38°) was decreased and
shifted to the higher angle (2θ=2.76°). Increasing in width
of the main peak of the FSM-16-SO3H is due to the decrease
in the long-range order of the hexagonal mesostructure of
FSM-16 after the incorporation of –SO3H groups into the
channels of FSM-16. The shift of main peak of FSM-16-
SO3H to higher angle is due to decrease in the pore diameter
because of the insertion of sulfonic acid groups on the inner
surface of mesopores.
(a)
(b)
(c)
(d)
(e)
(a)
(b)
1800
1600
1400
1200
1000
Wavenumbers (cm-1)
2
3
4
5
6
7
2
Fig. 5 FT-IR spectra of a FSM-16-SO3H, b pyridine adsorbed
FSM-16 and c FSM-16-SO3H at ambient temperature and pyridine
adsorbed FSM-16-SO3H heated at d 100 °C, e 200 °C
Fig. 4 Low angle XRD patterns of a FSM-16, b FSM-16-SO3H
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Journal of the Iranian Chemical Society
catalyst. The peak at 1633 cm−1 in the spectrum of the cata-
lyst before treatment with pyridine (Fig. 5a) is due to the
presence of water during the preparation of the pellet sam-
ple. This sharp peak overlapped with another weak peak of
Brønsted acid sites at 1642 cm−1. However, these results
confirm distribution of both Brønsted and Lewis acid sites
on the surface of the catalyst. As shown in Fig. 5b–e, with
increasing in temperature, characteristic peaks of Lewis
acid sites at 1603 cm−1 and peaks of Brønsted acid sites
at 1530 cm−1 are still remained. These results confirm that
–SO3H functionalization has strengthened both Brønsted and
Lewis acid sites on the catalyst.
to this method, the initial electrode potential (Ei) indicates
the strength of acid sites and meq of the consumed base
indicates number of acid sites [23]. As shown in Fig. 6, the
very low initial potential of FSM-16 shows that acid strength
of these samples is very low. With placing of –SO3H groups
on the surface of FSM-16, FSM-16-SO3H displays higher
strength than the FSM-16. Owing to more meq of the used
base per gram of the FSM-16-SO3H, this sample has also
higher number of acidic sites than FSM-16.
To investigate the number of –SO3H acidic sites sup-
ported on the FSM-16, the elemental composition of the
FSM-16-SO3H using EDX analysis was determined and
results are shown in Fig. 7 and Table 1. Based on this result,
amount of sulfur in the FSM-16-SO3H is 7.08 wt%, and thus,
the number of –SO3H on the catalyst is 0.87 mmol per gram
of FSM-16-SO3H.
The strength and number of acid sites of the catalysts
were determined by potentiometric titration of samples with
0.02 N solution of n-butylamine in acetonitrile. According
Figure 8 shows the N2 adsorption–desorption isotherms
of the FSM-16 and FSM-16-SO3H catalysts. In the iso-
therms of FSM-16, a mesoporous inflection was observed
at the medium p/p° partial pressure region (p/p°=0.1–0.3),
due to the capillary condensation of N2 in the mesopores. A
sharper hysteresis was observed at higher p/p° (p/p°>0.8)
for both catalysts. The hysteresis in this region is because
of the condensation of N2 within the voids formed by nano-
particles. In the isotherms of FSM-16-SO3H, the curvature
of the mesoporous structure in the area of p/p°=0.2–0.4 is
decreased because of occupation of the hexagonal cavities
by –SO3H groups.
600
(b)
400
200
(a)
0
-200
0.0
0.5
1.0
1.5
meq/g
2.0
2.5
Table 1 Elemental composition
Element
wt%
O
Si
S
of FSM-16-SO3H
61.31 31.60 7.08
Fig. 6 Potentiometric titration of a FSM-16, b FSM-16-SO3H
Fig. 7 Energy-dispersive X-ray
spectrum of FSM-16-SO3H
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Journal of the Iranian Chemical Society
Table 2 Optimization of the reaction conditions for the synthesis of
pyrano[2,3-c]pyrazoles catalyzed by FSM-16-SO3H
Entry Catalyst
Catalyst
amount
(mg)
Solvent
Time
(min)
Yield (%)a
1
FSM-16-
SO3H
40
40
40
40
40
40
40
0
CHCl3
CH2Cl2
MeOH
CH3CN
EtOHb
EtOH
240
310
50
75
78
83
80
80
85
88
60
75
60
71
79
79
80
2
FSM-16-
SO3H
3
FSM-16-
SO3H
4
FSM-16-
60
SO3H
5
FSM-16-
SO3H
270
50
6
FSM-16-
SO3H
7
FSM-16-
SO3H
–
EtOH/
water
40
8
EtOH/
240
105
70
water
9
FSM-16
40
10
20
30
50
60
EtOH/
water
Fig. 8 N2 adsorption–desorption isotherms of a FSM-16, b FSM-16-
SO3H
10
11
12
13
14
FSM-16-
SO3H
EtOH/
water
FSM-16-
EtOH/
water
65
SO3H
Catalytic activity of FSM‑16‑SO3H
FSM-16-
SO3H
EtOH/
55
water
The catalytic activity of FSM-16-SO3H was investigated in
the multi-component reaction of benzaldehyde (1 mmol),
malononitrile (1.1 mmol) and 3-methyl-1-phenyl-1H-pyra-
zol-5(4H)-one (1 mmol) as model reaction for the synthe-
sis of pyrano[2,3-c]pyrazole. The reaction was optimized
for various parameters such as catalyst amount, tempera-
ture, and solvent.
FSM-16-
EtOH/
water
50
SO3H
FSM-16-
SO3H
EtOH/
55
water
Reactions were carried out under reflux condition with benzaldehyde
(1 mmol), malononitrile (1.1 mmol) and 3-methyl-1-phenyl-1H-pyra-
zol-5(4H)-one (1 mmol)
The effect of solvent and temperature was investigated
by performing the model reaction in the presence of 40 mg
catalyst in various solvents and temperatures (Table 2,
entries 1–7). Among them, the mixture of water and etha-
nol was found to be the best solvent under reflux condition
in terms of the reaction time and yield of product (Table 2,
entry 7). The lower yield and longer reaction time was
achieved by performing the model reaction in the presence
of ethanol as the solvent under reflux conditions and at
room temperature (Table 2, entry 5, 6).
aIsolated yield
bReaction was carried out under r.t.
Afterwards, the optimized reaction conditions were
performed for the synthesis of 1,4-dihydropyrano[2,3-c]
pyrazoles using various aromatic aldehydes and results are
summarized in Table 3. It was found that this method is
rather general for both, electron rich and electron poor aryl
aldehydes and the corresponding products were obtained in
good to excellent yields.
To optimize the required catalyst amount, the model
reaction was also performed in the presence of various
amounts of the catalyst and according to the obtained
results (Table 2, entries 8–14) 40 mg of the catalyst was
chosen as the best catalyst amount. Clearly, the FSM-16
support strongly affected the efficiency of the heteroge-
neous catalyst. To show this, the model reaction in the
presence of 40 mg FSM-16 was performed under the same
reaction conditions and lower yield of the product was
obtained after 105 min (Table 2, entry 9).
To investigate the reusability of FSM-16-SO3H, it was
separated from the reaction mixture and washed with etha-
nol. The catalyst was dried in oven at 120 °C for 2 h. The
recycled catalyst was reused in the model reaction. The cata-
lyst was found to be reusable for at least three cycles without
considerable loss of activity (Table 4).
A plausible mechanism for the synthesis of pyrano[2,3-c]
pyrazoles in the presence of FSM-16-SO3H is illustrated in
Scheme 3.
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Journal of the Iranian Chemical Society
Table 3 Synthesis of
pyrano[2,3-c]pyrazoles
catalyzed by FSM-16-SO3H
Entry
a
1
4
Time (min)
40
Yield (%)a
88
CHO
CN
N
N
O
NH2
Ph
Cl
CHO
Cl
b
c
d
30
60
30
82
79
85
CN
N
N
O
NH2
Ph
OMe
CHO
OMe
OMe
CN
OMe
N
N
O
NH2
Ph
Me
CHO
CN
N
Me
N
O
O
O
NH2
Ph
OH
CHO
e
f
27
35
78
81
CN
N
OH
N
NH2
Ph
Cl
CHO
CN
N
Cl
N
NH2
Ph
NMe2
CHO
g
27
85
CN
N
NMe2
N
O
NH2
Ph
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Journal of the Iranian Chemical Society
Yield (%)a
80
Table 3 (continued)
Entry
h
1
4
Time (min)
65
CHO
Cl
CN
Cl
N
N
O
NH2
Ph
NO2
CHO
I
j
25
95
80
76
CN
NO2
N
N
O
NH2
Ph
OMe
CHO
CN
N
OMe
CHO
F
N
O
F
NH2
Ph
k
20
83
CN
N
N
O
O
NH2
Ph
Br
CHO
l
35
82
CN
N
Br
N
NH2
Ph
MeO
CHO
OMe
OMe
CN
m
10
70
MeO
N
N
O
NH2
Ph
OH
CHO
OH
n
o
50
30
78
81
CN
N
N
O
NH2
Ph
NO2
CHO
NO2
CN
N
N
O
NH2
Ph
Reaction conditions: aldehyde (1 mmol), malononitrile (1.1 mmol), 3-methyl-
1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), FSM-16-SO3H (40 mg),
ethanol:water; 8:2 (2 mL), 100 °C
aIsolated yield
1 3

Journal of the Iranian Chemical Society
Table 4 Recycling of FSM-16-
yield and/or reaction time. In addition to this, easy work-
up and using a reusable catalyst are other benefits of this
method.
Run
Yield (%)a
Time
SO3H nanoparticles
1
2
3
88
88
85
40
50
65
Conclusion
Reaction
conditions:
alde-
hyde (1 mmol), malononitrile
(1.1 mmol), 3-methyl-1-phe-
nyl-1H-pyrazol-5(4H)-one
In summary, we have developed a novel, mild and effi-
cient strategy for the synthesis of pyrano[2,3-c]pyrazoles
from aryl aldehydes, malononitrile and 3-methyl-1-phe-
nyl-1H-pyrazol-5(4H)-one using FSM-16-SO3H as solid
acid catalyst. The catalyst was prepared and characterized
by SEM, BET, XRD, pyridine absorption, potentiometric
titration and FT-IR techniques. Results show that FSM-16-
SO3H is an efficient catalyst with easy recoverability and
reusability without significant decrease in catalytic activ-
ity. The methodology is simple, rapid, and relatively inex-
pensive affording good to excellent yields with operational
simplicity.
(1
mmol),
FSM-16-SO3H
(40 mg), ethanol:water; 8:2
(2 mL), 100 °C
aIsolated yield
Table 5 shows the comparison between the activity
of the FSM-16-SO3H and other reported catalysts for
the pyrano[2,3-c]pyrazoles synthesis through reaction
of benzaldehyde, malononitrile and 3-methyl-1-phenyl-
1H-pyrazol-5(4H)-one. Results show that FSM-16-SO3H
is comparable with other catalytic systems in term of
HO
H
CN
NH
δ+
FSM-16-SO3H
-H2O
C
CN
C
H
C
N
+
Knoevenagel
N
condensation
O
CN
H
FSM-16
S
O
δ−
H
O
-H
O
FSM-16
S
O H
O
H
C
NH
O
H
CH
HO
O
CN
NC
C
N
N
HN
H
+H
N
N
FSM-16-SO3H
Ph
Ph
C
N
CN
Ar
Ar
O
Ar
O
Ar
Ar
O
H
H
H
CN
H
CN
CN
NH
CN
FSM-16-SO3H
+H
CN
N
N
N
N
N
C
N
N
N
δ+
O
N
-H
N
NH2
N
O
NH2
Ph
NH
Ph
Ph
Ph
Ph
O
S
H
FSM-16
O
δ−
O
Scheme 3 Plausible mechanism for the synthesis of pyrano[2,3-c]pyrazoles in the presence of FSM-16-SO3H
1 3

Journal of the Iranian Chemical Society
Table 5 Comparative study of
Entry
Catalyst
Solvent
Temp (°C)
Time (min)
Yielda (%)
References
the activity of FSM-16-SO
with other catalysts
3H
1
2
3
4
5
6
7
8
FSM-16-SO3H
DBSA (10 mol%)
H14[NaP5W30O110
HTMAB
Ethanol/water
Water
Ethanol
Water
Reflux
60
Reflux
85–90
90
110
Reflux
Reflux
40
180
60
180
360
90
88
88
84
89
99
92
84
82
This work
[11]
[15]
[13]
[12]
[35]
[36]
[37]
]
TEBA
Water
[Sipim]HSO4
NH4H2PO4/Al2O3
Sulfamic acid
Solvent free
Ethanol
Ethanol
15
600
aIsolated yield
18. T. Yanagisawa, T. Shimizu, K. Kuroda, C. Kato, Bull. Chem.
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Acknowledgements We are thankful to the Yazd University Research
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