Environmentally benign synthesis of methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c] pyrazole-3-carboxylates using CeO2 nanoparticles as a reusable and robust catalyst

Article abstract of DOI:10.1515/znb-2016-0119

In this work, we report the synthesis and characterization of CeO₂ nanoparticles as an efficient catalyst for the preparation of methyl 6-amino-5-cyano-4-aryl-2,4- dihydropyrano[2,3-c]pyrazole-3-carboxylates via one-pot four-component condensation reaction of dimethyl acetylenedicarboxylate, hydrazine hydrate, malononitrile, and aldehydes in aqueous medium. The use of a non-hazardous organic solvent, easy recovery of the catalyst, compatibility with various functional groups, and high yield of the products make the protocol attractive, greener, and economic.

Full text of DOI:10.1515/znb-2016-0119

Z. Naturforsch. 2016; aop
Javad Safaei-Ghomi*, Mehrnoosh Asgari-Kheirabadi and Hossein Shahbazi-Alavi
Environmentally benign synthesis of methyl
6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]
pyrazole-3-carboxylates using CeO2 nanoparticles
as a reusable and robust catalyst
DOI 10.1515/znb-2016-0119
reactions. Based on the two-component synthesis, Shara-
nina et al. in 1982 developed the three-component syn-
thesis of pyrano[2,3-c]pyrazoles from the reaction of
substituted pyrazol-5-ones, aldehydes, and malononitrile
in the presence of morpholine as a catalyst [5]. Synthesis
of bioactive compounds should be facile, flexible, and
green in organic synthesis. Therefore, looking for efficient
and concise methods for the synthesis of pyranopyrazoles
is considered very important. Multicomponent reactions
supply a practical method for the synthesis of various
compounds with pharmaceutical and biological activities
[6]. The combination of multicomponent reactions with a
heterogeneous catalyst could improve their effectiveness
Received May 11, 2016; accepted June 14, 2016
Abstract: In this work, we report the synthesis and char-
acterization of CeO2 nanoparticles as an efficient catalyst
for the preparation of methyl 6-amino-5-cyano-4-aryl-2,4-
dihydropyrano[2,3-c]pyrazole-3-carboxylates via one-pot
four-component condensation reaction of dimethyl acety-
lenedicarboxylate, hydrazine hydrate, malononitrile, and
aldehydes in aqueous medium. The use of a non-hazardous
organic solvent, easy recovery of the catalyst, compatibility
with various functional groups, and high yield of the prod-
ucts make the protocol attractive, greener, and economic.
Keywords: catalytic activity; CeO2 nanoparticles; multi- from operating cost and environmental points of view.
component reactions; nanoparticles; one-pot; pyrano[2,3-
The chemical synthesis productivity can be increased
by nano-sized catalysts due to small size and high surface
to volume ratios [7]. Among various nanoparticles (NPs),
cerium NPs have received considerable attention because
of their unique properties and potential applications
in diverse fields [8]. CeO2 has received much attention
c]pyrazole.
1 Introduction
Pyranopyrazoles are important classes of organic com- because of its many attractive characteristics, such as
pounds due to their wide range of biological and pharma- unique UV absorption ability [9], ferromagnetic properties
cological activities. The synthesis of pyranopyrazoles is [10], and major part of catalyst formulation for the dehy-
an interesting challenge because compounds with these drogenation of ethylbenzene to styrene [11].
scaffolds were reported to possess a multiplicity of phar-
There are many methods for the preparation of CeO2
macological properties such as anticancer activity against NPs such as sol–gel method [12], thermal hydrolysis [13],
several cell lines [1], analgesic [2], Chk1 inhibitors [3], and homogeneous precipitation [14], and so on. In the present
molluscicidal activities [4]. Pyrano[2,3-c]pyrazole is iso- research, CeO2 NPs were fabricated by a simple co-precip-
meric with pyrano[4,3-c]pyrazole, pyrano[3,2-c]pyrazole, itation technique. Compared with other techniques, the
and pyrano[3,4-c]pyrazole. Practically, the construction co-precipitation method is a simple and attractive proce-
of pyrano[2,3-c]pyrazole structures has been established dure for the preparation of CeO2 NPs. Recently, γ-alumina
through different modes of reaction and cyclization: [15], piperidine [16], imidazole [17], glycine [18], l-proline
two-component, three-component, and four-component or KF-alumina [19], and triethylamine (under solvent-
free conditions) [20] were reported for the synthesis of
pyrano[2,3-c]pyrazole derivatives.
*Corresponding author: Javad Safaei-Ghomi, Department of Organic
Herein, we report the use of CeO2 NPs as an efficient
Chemistry, Faculty of Chemistry, University of Kashan, PO Box
catalyst for the preparation of methyl 6-amino-5-cyano-
87317-51167, Kashan, I.R. Iran, e-mail: safaei@kashanu.ac.ir
4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates
Mehrnoosh Asgari-Kheirabadi and Hossein Shahbazi-Alavi:
Department of Organic Chemistry, Faculty of Chemistry, University of
Kashan, PO Box 87317-51167, Kashan, I.R. Iran
by the four-component reaction of dimethyl acety-
lenedicarboxylate, hydrazine hydrate, malononitrile,
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ꢀꢀꢀꢁ
2ꢀ ꢀJ. Safaei-Ghomi et al.: Methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates
and aromatic aldehydes in water at room temperature reaction was carried out using CeO2 bulk and CeO2 NPs as
(Scheme 1).
the catalyst, the product could be obtained in a moderate
to good yield. As expected, the increased surface area due
to small particle size increased the reactivity of the cata-
lyst. This factor is responsible for the accessibility of the
substrate molecules on the catalyst surface. The catalyst
2 Results and discussion
The catalyst was prepared by the co-precipitation method was recovered from the reaction mixture by either filtration
using aqueous ammonia solution as the precipitating or centrifugation and washed successively with ethanol
agent. Ce(NO3)3·6H2O was used as a starting material for and water. The recycling of the nano-CeO2 catalyst was
the synthesis of CeO2 NPs. This method is easy and inex- examined, and it was found that product yields decreased
pensive. The XRD pattern for CeO2 NPs is shown in Fig. 1.
The pattern agrees well with the reported pattern for 3, 90%; run 4, 89%; run 5, 88%, run 6, 87%, run 7, 87%).
CeO2 NPs (JCPDS No. 43-1002). The crystalline size was cal- With these promising results in hand, we turned to
culated from full-width at half-maximum (FWHM) using explore the scope of the reaction using diverse aromatic
Scherrer’s formula and was observed to be 11 nm. aldehydes as substrates under the optimized reaction
to a small extent on each reuse (run 1, 91%; run 2, 91%; run
In order to optimize the reaction conditions for conditions (Table 2). As is shown in Table 2, aromatic
the synthesis of pyrano[2,3-c]pyrazoles, the reaction of aldehydes bearing electron-donating or -withdrawing
4-nitrobenzaldehyde with dimethyl acetylenedicarboxy- substituents gave the desired methyl 6-amino-5-cyano-4-
late, hydrazine hydrate, and malononitrile was used as a aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates in
model reaction at room temperature. Several reactions good to excellent yields and short reaction times. Several
were scrutinized using different solvents, such as ethanol, groups such as F, OMe, Me, and NO2 are compatible with
acetonitrile, water, and dichloromethane. In the presence the reaction conditions.
of water the products were obtained in high yield. The
model reaction was considered in the presence of different
catalysts. The best result was obtained in using CeO2 NPs.
2.1 The proposed reaction mechanism
To optimize the catalyst quantity, the reaction was carried
A plausible mechanism for the preparation of methyl
out with different quantities of the CeO2 NPs and 6 mol%
6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-
of CeO2 NPs was found to be optimal (Table 1). When the
3-carboxylates using CeO2 NPs is shown in Scheme 2. First,
we assumed that the reaction occurs via a Knoevenagel
O
condensation between malononitrile and aldehyde to form
Ar
CO2CH3
H
CO2C
NH2
NH2
NC
NC
3
NC
+
+
+
Ar
H
NH
Table 1:ꢀOptimization of reaction condition using different catalysts.a
N
H2N
O
Mol, %ꢁ Time, minꢁ Yield, %b
5a−i
Entryꢁ Solventꢁ Catalyst
ꢁ
H
CO2C
3
1
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
CH2Cl2
ꢂ
InCl3
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
3ꢂ
20ꢂ
10ꢂ
5ꢂ
90ꢂ
70ꢂ
65ꢂ
60ꢂ
65ꢂ
55ꢂ
55ꢂ
55ꢂ
40ꢂ
25ꢂ
25ꢂ
25ꢂ
25ꢂ
33
37
41
44
49
51
53
48
60
76
84
91
91
4
1
2
3
2
CH3CN ꢂ Et3N
3
EtOH
EtOH
H2O
ꢂ
ꢂ
ꢂ
CuO
CaO
ZrO2
Scheme 1:ꢀSynthesis of pyrano[2,3-c]pyrazoles using CeO2 NPs.
4
5
10ꢂ
3ꢂ
6
CH3CN ꢂ Ce(NO3)3
CH3CN ꢂ (NH4)2Ce(NO3)6 ꢂ
7
3ꢂ
8
H2O
H2O
EtOH
H2O
H2O
H2O
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
Nd2O3
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
5ꢂ
9
CeO2 bulk
CeO2 NPs
CeO2 NPs
CeO2 NPs
CeO2 NPs
8ꢂ
10
11
12
13
6ꢂ
3ꢂ
6ꢂ
9ꢂ
aReaction conditions: hydrazine hydrate (1 mmol), malononitrile
(1 mmol), dimethyl acetylenedicarboxylate (1 mmol), and 4-nitroben-
zaldehyde (1 mmol).
bIsolated yields.
Bold text signifies best yield in 25 min for the reaction.
Fig. 1:ꢀThe XRD pattern of CeO2 NPs.
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ꢁꢀꢀꢀ
J. Safaei-Ghomi et al.: Methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylatesꢃ ꢃ3
Table 2:ꢀSynthesis of pyrano[2,3-c]pyrazole-3-carboxylates with CeO2 NPs.a
Entryꢁ
Ar
ꢁ
Productꢁ
Time, min
ꢁ Yield, %b
ꢁ
M.p., °Cꢁ
M.p., °C [Ref.]
1
2
3
4
5
6
7
8
9
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
4-NO2-C6H4
2-F-C6H4
4-OMe-C6H4
4-Me-C6H4
3-NO2-C6H4
C6H5
2,3-(OMe)2-C6H3 ꢂ
2-OMe-C6H4
4-Br-C6H4
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
5a
5b
5c
5d
5e
5f
5g
5h
5i
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
25
28
34
32
29
31
39
36
32
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
91
88
84
88
89
85
82
84
85
ꢂ 242–243ꢂ
ꢂ 248–250ꢂ
ꢂ 238–240ꢂ
ꢂ 242–244ꢂ
ꢂ 234–235ꢂ
ꢂ 231–232ꢂ
ꢂ 239–241ꢂ
ꢂ 210–212ꢂ
ꢂ 245–247ꢂ
244–245 [21]
–
–
–
236–237 [21]
231–232 [21]
–
212–214 [21]
247–248 [21]
ꢂ
ꢂ
aAll the reactions were carried out in water.
bIsolated yields.
the intermediate I and concomitant formation of pyrazole These compounds will provide promising candidates for
derivative II by the reaction of hydrazine hydrate and dime- biological applications and drug discovery. The attrac-
thyl acetylenedicarboxylate. Finally, Michael addition of tive features of this protocol are the simple procedure, use
I, II, followed by cyclization and tautomerization to give of recyclable nanocatalyst, easy workup, and the use of
the pyranopyrazoles. CeO2 NPs coordinate with the active water as a solvent that is considered to be relatively envi-
groups (particular Cꢀ=ꢀO, C≡N, and active H), thus increas- ronmentally benign.
ing the reactivity of the groups. Theoretically, nanoscale
heterogeneous catalysts should present higher surface
areas which are mainly responsible for their catalytic activ-
4 Experimental
ity. These surface atoms behave as the centers where the
chemical reactions could be catalytically activated.
4.1 Chemicals and instruments
3 Conclusions
All organic materials were purchased commercially from
Sigma-Aldrich and Merck and were used without further
In conclusion, we have developed a straightforward and purification. Ce(NO3)3·6H2O (99.999%) was obtained from
efficient approach to methyl 6-amino-5-cyano-4-aryl-2,4- Sigma-Aldrich.
dihydropyrano[2,3-c]pyrazole-3-carboxylates by a simple
All melting points are uncorrected and were determined
one-pot four-component condensation reaction of dime- in capillary tubes on a Boetius melting point microscope.
thyl acetylenedicarboxylate, hydrazine hydrate, malonon- FT-IR spectra were recorded with KBr pellets using a Magna-
itrile, and aldehydes using CeO2 NPs in aqueous medium. IR 550 Nicolet spectrometer. NMR spectra were recorded on a
NC
O
+
C
N
NC
Ar
CN
Ar
O
Ar
H
CO2Me
NH
I
NC
CO2Me
H
O
N
NH2
H2N
H2N
+
NH
N
O
MeO2C
OMe
II
Scheme 2:ꢀSchematic mechanism for the catalytic activity of CeO2 NPs in the synthesis of title compounds 5a–i.
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ꢀꢀꢀꢁ
4ꢀ ꢀJ. Safaei-Ghomi et al.: Methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates
Bruker 400 MHz spectrometer with tetramethylsilane as an MHz, [D6]DMSO): δ (ppm)ꢁꢀ=ꢀꢁ3.63 (3H, s, OMe), 4.69 (1H, s,
internal standard. Powder XRD was carried out on a Philips CH), 7.18–7.25 (4H, m, H-Ar), 7.49 (2H, NH2), 13.69 (1H, s,
X’pert diffractometer with monochromatized CuKα radiation NH). – 13C NMR (100 MHz, [D6]DMSO): δ (ppm)ꢁꢀ=ꢀꢁ37.88
(λꢁꢀ=ꢀꢁ1.5406 Å). The microscopic morphology of products was (CH), 52.22 (OMe), 58.46 (C), 104.87 (C), 120.84 (CN), 127.69
visualized by SEM (MIRA 3 TESCAN).
(2CH), 127.91 (C), 129.27 (2CH), 136.16 (C), 145.47 (C), 155.82
(C), 158.88 (C), 160.65 (Cꢀ=ꢀO). – Analysis for C15H11N5O5:
calcd. C 52.79, H 3.25, N 20.52; found C 52.83, H 3.21, N 20.61.
4.2 Preparation of CeO2 nanoparticles
CeO2 NPs were prepared according to the procedure
reported in the literature [22] with some modification by
a co-precipitation technique with post-annealing in air.
Briefly, 3 g of highly pure Ce(NO3)3·6H2O was dissolved in
the mixture of 50 mL deionized water and 20 mL alcohol.
Then, the appropriate amount of aqueous ammonia solu-
tion (28 wt%) was added to the above solution till the pH
value reached 8. Thereafter, the mixture was stirred for 4 h
at room temperature and then dried at 80°C for 6 h. The
solid was treated at 700°C for 2 h to obtain the CeO2 NPs.
The pattern agrees well with the reported pattern for CeO2
NPs (JCPDS No. 43-1002). The crystalline size was calcu-
lated from FWHM using Scherrer’s formula and resulted
in an average diameter of 11 nm.
4.4.2 Methyl 6-amino-5-cyano-4-(2-fluorophenyl)-2,4-
dihydropyrano[2,3-c]pyrazole-3-carboxylate (5b)
Colorless crystals; m.p. 248–250°C. – IR (KBr): ν ꢁ=ꢁ 3427,
3299, 3187, 2956, 2193, 1723, 1637, 1601, 1489, 1400, 1044cm−1.
1
– H NMR (400 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 3.59 (3H, s,
OMe), 5.00 (1H, s, CH), 7.08–7.24 (4H, m, CH), 7.23 (2H,
13
NH2), 13.76 (1H, s, NH). – C NMR (100 MHz, [D6]DMSO):
δ (ppm) ꢀ=ꢀ 31.66 (CH), 52.19 (OMe), 56.61 (C), 103.45 (C),
115.65 (CH), 115.87 (CN), 120.57 (CH), 124.82 (CH), 129.19
(CH), 129.27 (C), 130.50 (C), 131.72 (C), 158.79 (C), 159.14 (C),
160.97 (Cꢀ=ꢀO). – Analysis for C15H11FN4O3: calcd. C 57.33, H
3.53, N 17.83; found C 57.27, H 3.46, N 17.76.
4.4.3 Methyl 6-amino-5-cyano-4-(4-methoxylphenyl)-2,4-
4.3 General procedure for the preparation
of methyl 6-amino-5-cyano-4-aryl-
2,4-dihydropyrano[2,3-c]pyrazole-3-
carboxylate derivatives (5a–i)
dihydropyrano[2,3-c]pyrazole-3-carboxylate (5c)
Colorless crystals; m.p. 238–240°C. – IR (KBr): ν ꢁ=ꢁ 3428,
3323, 3214, 2924, 2194, 1728, 1639, 1602, 1475, 1392,
1110 cm−1. – 1H NMR (400 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 3.64
(3H, s, OMe), 3.69 (3H, s, OMe), 4.67 (1H, s, CH), 6.81 (2H,
A mixture of malononitrile (1 mmol), and aldehydes
(1 mmol), hydrazine hydrate (1 mmol), dimethyl acety-
lenedicarboxylate (1 mmol), and 6 mol% CeO2 NPs in H2O
(4 mL) was stirred at room temperature for the specific
time. The reaction was monitored by thin-layer chromatog-
raphy. After cooling, the precipitated solid was filtered and
washed with H2O. The product was dissolved in hot metha-
nol and the catalyst was filtered. After cooling, the crude
products were precipitated. The precipitate was washed
with methanol to afford the pure product and dried well in
vacuo. The structures of the products were fully established
on the basis of their 1H NMR, 13C NMR, and FT-IR spectra.
13
NH2), 7.00–7.20 (4H, m, CH), 13.70 (1H, s, NH). – C NMR
(100 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 36.70 (CH), 52.21 (OCH3
ester), 55.41 (OMe), 58.59 (C), 105.05 (C), 114.02 (CN), 120.84
(2CH), 128.87 (2CH), 129.14 (C), 137.53 (C), 155.78 (C), 158.36
(C), 158.90 (C), 160.53 (Cꢀ=ꢀO). – Analysis for C16H14N4O4:
calcd. C 58.89, H 4.32, N 17.17; found C 58.80, H 4.28, N,
17.26.
4.4.4 Methyl 6-amino-5-cyano-2,4-dihydropyrano-4-
(p-tolyl)pyrano[2,3-c]pyrazole-3-carboxylate (5d)
4.4 Physical and spectroscopic data
Colorless crystals, m.p. 242–244°C. – IR (KBr): ν ꢁ=ꢁ 3390,
3325, 3215, 2952, 2194, 1724, 1645, 1605, 1480, 1393, 1393,
1049 cm−1. – 1H NMR (400 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 2.22
(3H, s, Me), 3.63 (3H, s, OMe), 4.67 (1H, s, CH), 6.99–7.15
4.4.1 Methyl 6-amino-5-cyano-2,4-dihydro-4-
(4-nitrophenyl)pyrano[2,3-c]pyrazole-3-
carboxylate (5a)
13
(4H, m, CH, 2H, NH2), 13.69 (1H, s, NH). – C NMR (100
MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 21.07 (CH3), 37.08 (CH), 52.21
Colorless crystals; m.p. 242–243°C. – IR (KBr): νꢀꢁ=ꢁꢀ3385, (OCH3), 58.40 (C), 104.87 (C), 120.79 (CN), 127.69 (2CH),
3324, 3265, 2955, 2201, 1488, 1390, 1027 cm−1. – 1H NMR (400 129.27 (2CH), 136.16 (C), 142.47 (C), 155.82 (C), 158.88 (C),
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ꢃ5
J. Safaei-Ghomi et al.: Methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylatesꢃ
160.60 (Cꢀ=ꢀO). – Analysis for C16H14N4O3: calcd. C 61.93, H 4.4.8 Methyl 6-amino-5-cyano-2,4-dihydro-4-
4.55, N 18.06; found C 61.96, H 4.62, N 18.11.
(2-methoxyphenyl)pyrano[2,3-c]pyrazole-3-
carboxylate (5h)
4.4.5 Methyl 6-amino-5-cyano-2,4-dihydro-4-
(3-nitrophenyl)pyrano[2,3-c]pyrazole-3-
carboxylate (5e)
Colorless crystals; m.p. 210–212°C. – IR (KBr): ν ꢁ=ꢁ 3412,
3323, 3269, 2939, 2196, 1719, 1651, 1610, 1488, 1390, 1027 cm−1.
1
– H NMR (400 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 3.57 (3H, s,
OMe), 3.67 (3H, s, OMe), 4.99 (1H, s, CH), 6.89–7.17 (4H,
13
Colorless crystals, m.p. 234–235°C. – IR (KBr): ν ꢁ=ꢁ 3399, m, H-Ar), 7.02 (2H, NH2), 13.76 (1H, s, NH). – C NMR (100
1
3326, 3265, 2955, 2201, 1488 cm−1. – H NMR (400 MHz, MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 37.31 (CH), 52.25 (CH3 ester),
[D6]DMSO) : δ (ppm) ꢀ=ꢀ 3.68 (3H, s, OMe), 4.71 (1H, s, CH), 55.37 (OMe), 57.94 (C), 104.51 (C), 111.99 (CN), 113.90 (CH),
7.20–7.27 (4H, m, H-Ar), 7.51 (2H, NH2), 13.70 (1H, s, NH). 119.93 (CH), 120.75 (CH), 125.98 (C), 129.09 (CH), 129.84.71
–
13C NMR (100 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 37.91 (CH), (C), 146.96 (C), 158.85 (C), 159.44 (C), 160.70 (Cꢀ=ꢀO). – Anal-
52.30 (OMe), 58.47 (C), 104.89 (C), 120.88 (CN), 127.69 (CH), ysis for C16H14N4O4: calcd. C 58.89, H 4.32, N 17.17; found:
127.91 (C), 128.8 (CH), 129.31 (CH), 131.12 (CH), 136.26 (C), C 58.95, H 4.27, N 17.26.
145.52 (C), 155.90 (C), 158.91 (C), 160.79 (Cꢀ=ꢀO). – Analysis
for C15H11N5O5: calcd. C 52.79, H 3.25, N 20.52; found C 52.70,
H 3.18, N 20.61.
4.4.9 Methyl 6-amino-4-(4-bromophenyl)-5-cyano-2,4-
dihydropyrano[2,3-c]pyrazole-3-carboxylate (5i)
4.4.6 Methyl 6-amino-5-cyano-4-phenyl-2,4-
dihydropyrano[2,3-c]pyrazole-3-
carboxylate (5f)
Colorless crystals; m.p. 245–247°C. – IR (KBr): ν ꢁ=ꢁ 3405,
3329, 3265, 2966, 2209, 1729, 1654, 1616 cm−1. – 1H NMR (400
MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 3.63 (3H, s, OMe), 4.69 (1H,
s, CH), 7.20–7.28 (4H, m, H-Ar), 7.50 (2H, NH2), 13.68 (1H,
13
Colorless crystals; m.p. 231–232°C. – IR (KBr): ν ꢁ=ꢁ 3389, s, NH). – C NMR (100 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 37.46
3329, 3268, 2960, 2209, 1729, 1654, 1613 cm−1. – 1H NMR (400 (CH), 52.19 (OCH3), 58.19 (C), 104.66 (C), 118.73 (CN), 127.14
MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 3.59 (3H, s, OMe), 4.690 (1H, s, (CH), 127.79 (C), 128.69 (CH), 129.19 (C), 145.37 (C), 155.89
CH), 7.05–7.28 (5H, m, CH), 7.24 (2H, NH2), 13.74 (1H, s, NH). (C), 158.85 (C), 160.61 (Cꢀ=ꢀO). – Analysis for C15H11BrN4O3:
–
13C NMR (100 MHz, [D6]DMSO): δ (ppm) ꢀ=ꢀ 37.45 (CH), calcd. C 48.02, H 2.96, N 14.93; found C 48.11, H 2.90,
52.16 (OCH3), 58.17 (C), 104.65 (C), 120.73 (CN), 127.10 (CH), N 14.89.
127.79 (CH), 128.68 (CH), 129.18 (C), 145.36 (C), 155.87 (C),
158.84 (C), 160.61 (Cꢀ=ꢀO). – Analysis for C15H12N4O3: calcd. C Acknowledgment: The authors are grateful to University of
60.81, H 4.08, N 18.91; found C 60.73, H 4.16, N 18.96.
Kashan for supporting this work by Grant No.: 463562/VI.
4.4.7 Methyl 6-amino-5-cyano-2,4-dihydro-4-
(2,3-dimethoxyphenyl)pyrano[2,3-c]pyrazole-3-
carboxylate (5g)
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Z. Naturforsch.ꢃ
ꢃ2016 | Volume x | Issue x(b)
Graphical synopsis
Javad Safaei-Ghomi, Mehrnoosh
Asgari-Kheirabadi and Hossein
Shahbazi-Alavi
Environmentally benign synthesis
of methyl 6-amino-5-cyano-4-aryl-
2,4-dihydropyrano[2,3-c]pyrazole-3-
carboxylates using CeO2 nanoparticles
as a reusable and robust catalyst
DOI 10.1515/znb-2016-0119
Z. Naturforsch. 2016; x(x)b: xxx–xxx
- 10.1515/znb-2016-0119
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