An efficient and green synthesis of 6-amino-3-phenyl-4-aryl-1,4- dihydropyrano [2,3-c]pyrazole-5-carbonitrile derivatives under ultrasound irradiation in aqueous medium

Article abstract of DOI:10.1002/jhet.1627

A facile and eco-friendly approach for the synthesis of 6-amino-3-phenyl-4-aryl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile derivatives via four-component reaction of hydrazine, ethyl 3-oxo-3- phenylpropanoate, aldehydes, and malononitrile is described. The reaction is performed in water, without using any catalyst, and under ultrasound irradiation. The developed sonochemical-assisted multi-component reaction provides an improved and accelerated conversion when compared with conventional procedure.

Full text of DOI:10.1002/jhet.1627

Month 2013
An Efficient and Green Synthesis of 6-Amino-3-phenyl-4-aryl-
1,4-dihydropyrano [2,3-c]pyrazole-5-carbonitrile Derivatives under
Ultrasound Irradiation in Aqueous Medium
*
Yi Zou, Yu Hu, Hai Liu, and Da-Qing Shi
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Soochow University, Suzhou 215123, People’s Republic of China
*
E-mail: dqshi@suda.edu.cn
Received August 22, 2011
DOI 10.1002/jhet.1627
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
A facile and eco-friendly approach for the synthesis of 6-amino-3-phenyl-4-aryl-1,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile derivatives via four-component reaction of hydrazine, ethyl 3-oxo-3-phenylpropanoate,
aldehydes, and malononitrile is described. The reaction is performed in water, without using any catalyst, and
under ultrasound irradiation. The developed sonochemical-assisted multi-component reaction provides an im-
proved and accelerated conversion when compared with conventional procedure.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
exothermic reactions, salting in and salting out, and varia-
tion of pH values. Work up and purification can be carried
out by simple phase separation techniques. Also, organic
reactions in water exhibit unique reactivity and selectivity
that are different from reactions in organic solvents.
Industrial chemistry in the new millennium is widely
adopting the concept of “Green Chemistry”[1] to meet the
fundamental scientific challenges of protecting the human
health and environment while maintaining commercial via-
bility. The popularization of ultrasound in life and society
is linked to its widespread usage in medicine [2] and chem-
ical synthesis [3] including materials science, aerogels, food
chemistry, and other research areas assisted by ultrasound
[4]. Recent and innovative applications illustrating the mild-
ness and non-hazardous character of these waves relate to
their potential in Green Chemistry. The role of sonochemistry
in the creation of “benign-by-design” synthetic methods is
clear from the definition: low level of waste, inherently safe,
material-saving and energy-saving, with an optimized use of
non-renewable resources, and a preferential exploitation of
renewable ones. The application of ultrasound in organic
synthesis has become increasing because of its advantages
such as shorter reaction times, milder reaction condition, and
higher yields in comparison with the classical methods [5].
Because in this technique the reaction is carried out normally
at lower temperature relative to the usually thermal methods,
the possibility of occurrence of undesired reactions is reduced
and as a result of a cleaner reaction, the workup is easier. The
generation of many cavities and a dramatic increase in the
temperature and pressure during collapse of the cavities are
the most important effects of ultrasound [6].
Dihydropyrano[2,3-c]pyrazoles play an essential role in
biologically active compounds and therefore represent an
interesting template for medicinal chemistry. They have
been widely used as medicine intermediates due to their
useful biological and pharmacological properties. Many
of those compounds are known as antimicrobial [8], insec-
ticidal [9], and anti-inflammatory [10]. Furthermore, dihy-
dropyrano[2,3-c]pyrazoles showed molluscicidal activity
[11,12] and was identified as a screening hit for Chk1
kinase inhibitor [13]. The first approach to synthesize these
substances was undertaken by Otto [14], in which he initi-
ated the reaction sequence by the base-catalyzed cycliza-
tion of 4-aryliden-5-pyrazolone. Extending the work of
Otto, Klokol, and colleagues [15] performed the direct con-
version of 3-methyl-3-pyrazolin-5-one with malononitrile
in the presence of a weak base. Sharanin et al. [16] devel-
oped a three-component reaction between pyrazolone, an
aldehyde and malononitrile in ethanol using triethylamine
as the catalyst. Shestopalov and co-workers [17] reported
the synthesis of pyrazolopyran via a three-component con-
densation between N-methylpiperidone, pyrazoline-5-one,
and malononitrile in absolute ethanol. Recently, Laufer
and colleagues [18] performed a library of diverse dihydro-
pyrano [2,3-c]pyrazoles in ethanol. However, most of these
synthetic methods suffer from drawbacks such as employ-
ing toxic reagent, strongly basic conditions, expensive and
complex catalysts or reagents, many tedious steps, in most
Designing organic reactions in aqueous media is another
attractive area in green chemistry [7]. Water is an abundant
and environmentally benign solvent. As a reaction
medium, it offers several benefits including control over
© 2013 HeteroCorporation

Y. Zou, Y. Hu, H. Liu, and D.-Q. Shi
Vol 000
cases, low yields of the products, and long reaction times
that restrict their practical applications. As a part of our
interest in using water as solvent for organic synthesis and
expanding the application of ultrasound in the synthesis of
heterocyclic compound [19], herein, we report our prelimi-
nary results on exploring a more ‘green’ and efficient
process for the synthesis of 6-amino-3-phenyl-4-aryl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile derivatives.
electron-donating substituents. In order to verify the effect
of ultrasound irradiation, all previously mentioned reactions
were carried out under the same conditions in the absence of
ultrasound irradiation. The desired products were produced
in relatively lowered yields (67–84%) and with much longer
reaction time (2– 4 h), whereas under ultrasonic irradiation,
the products were obtained in 13–37min with the yields of
70 – 95%. The method to obtain the desired products under
ultrasonic irradiation exhibits several significant advantages
including faster reaction rates, higher yields, and higher
purity (without any additional purification step) particularly
when considering the basic green chemistry concept [22].
Thus, ultrasonic irradiation was found to have bene-
ficial effect on the synthesis of 6-amino-3-phenyl-4-aryl-
1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile derivatives.
In addition, terephthalaldehyde 3l and isophthalaldehyde
3m has also been used in this reaction, respectively
(Scheme 3), and they all gave the desired products in good
yields (Table 3). Unfortunately, the reaction that used
phthalaldehyde as aldehyde failed to yield the
corresponding products because of large steric hindered
effect.
To the best of our knowledge, this new procedure provides
the first example of an efficient and ultrasound-promoted ap-
proach for the synthesis of 6-amino-3-phenyl-4-aryl-1,4-
dihydropyrano [2,3-c]pyrazole-5-carbonitrile derivatives in
water. This method is the most simple and convenient and
would be applicable for the synthesis of different types of
nitrogen-containing heterocyclic compounds. The structures
of all the synthesized compounds were established by their
IR, 1H NMR, 13C NMR, and HRMS spectra.
In this paper, an environmentally benign approach
promoted by the synergy of combined use of water and
ultrasound offers an easy access to 6-amino-3-phenyl-4-
aryl-1,4-dihydropyrano [2,3-c]pyrazole-5-carbonitrile deri-
vatives in excellent yields. Ultrasonic irradiation was found
to have beneficial effect on the synthesis of these com-
pounds. The reactions proceeded to completion almost
instantaneously without the presence of any catalyst, and
pure product was obtained, without using any chromato-
graphic techniques, simply by recrystallization from
ethanol. We hope that this protocol may be of value to
others seeking novel synthetic fragments with unique
properties for medicinal chemistry.
RESULTS AND DISCUSSION
The choice of an appropriate reaction media is of crucial
importance for the successful organic synthesis. To achieve
suitable conditions, we investigated the reaction of hydrazine
1, ethyl 3-oxo-3-phenylpropanoate 2, 4-methylbenzaldehyde
3a, and malononitrile 4 as a model reaction substrate in differ-
ent conditions (Scheme 1). The ultrasonic-assisted reaction to
obtain 5a was examined using different solvents such as etha-
nol, methanol, acetonitrile, tetrahydrofuran (THF), dioxane,
and water, respectively. The results were summarized in
Table 1. The reaction could be efficiently carried out in the
aforementioned solvents, and the reaction in water gave the
best result, affording the desired products not only in good
yield but also with higher reaction rates (86% yield in 1 h)
(Table 1, entry 6). Hence, all further reactions were carried
out using water as solvent, which is considered as the prefer-
ential choice of medium for organic reactions in view of
economic and environmental problems [20].
We also performed three experiments in steadily in-
creased temperature under ultrasonic irradiation (Table 1)
to study the effect of temperature on this reaction. We
found that the reaction at 50ꢀC under ultrasound irradiation
was the optimal condition for this one-pot reaction and
higher temperature did not mean higher yield, because cav-
itation decreases when increasing the temperature (because
of gas evolution) [21].
With this optimum condition in hand, we smoothly syn-
thesized 6-amino-3-phenyl-4-aryl-1,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile derivatives in water under sonication
(Scheme 2). The results were summarized in Table 2. The
reactions proceeded smoothly and a variety of the desired
dihydropyrano[2,3-c]pyrazoles derivatives products 5 were
obtained in good yields whether the aromatic aldehyde 3
is the one bearing electron-withdrawing substituents or
Scheme 1. Model reaction.
CH3
CHO
O
O
H2O
CN
CN
Ph
CN
+
NH2NH2 • H2O
+
+
50°C ))))))
Ph
OC2H5
N
CH3
N
O
NH2
H
1
2
3a
4
5a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
An Efficient and Green Synthesis of 6-Amino-3-phenyl-4-aryl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile Derivatives under Ultrasound Irradiation in Aqueous Medium
Table 1
The model reaction in different conditions under ultrasound irradiation.a
completion of the reaction (monitored by TLC), the reaction
was allowed to cool, the residue was filtered and was
recrystallized from ethanol to produce the desired solid.
Temperature
(ꢀC)
Time
(h)
Isolated yield
(%)
6-Amino-3-phenyl-4-(4-methylphenyl)-1,4-dihydropyrano
Entry
Solvent
[2,3-c]pyrazole-5-carbonitrile (5a).
White powder; mp:
268–270ꢀC; IR (potassium bromide): 3483, 3288, 3114, 2917,
2196, 1639, 1598, 1498, 1400, 1220, 1059, 977, 763 cmꢁ1; H
1
1
2
3
4
5
6
7
8
Ethanol
Methanol
Acetonitrile
THF
Dioxane
Water
30
30
30
30
30
30
50
60
1.5
2
2
2.5
2
1
82
72
31
29
35
86
90
88
NMR (400 MHz, DMSO-d6) d: 2.17 (s, 3H, CH3), 4.93 (s, 1H,
CH), 6.89 (s, 2H, NH2), 6.99 (s, 4H, ArH), 7.25–7.30 (m, 3H,
ArH), 7.45 (d, J = 6.8 Hz, 2H, ArH), 12.88 (s, 1H, NH);
13C NMR (75 MHz, DMSO-d6) d: 21.22, 37.14, 59.22, 98.19,
121.40, 126.80, 127.84, 128.96, 129.28, 129.62, 136.32, 138.50,
142.43, 156.75, 160.67; HRMS Calcd. for C20H16N4ONa
[M+ Na]: 351.1222, found: 351.1232.
6-Amino-4-(4-methoxyphenyl)-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5b). Light yellow powder; mp:
225–227ꢀC (lit.[23] mp: 230ꢀC); IR (potassium bromide): 3411,
3302, 3282, 2192, 1639, 1509, 1449, 1408, 1259, 1170, 1063,
1031 cm-1; 1H NMR (400 MHz, DMSO-d6) d: 3.65 (s, 3H,
CH3O), 4.92 (s, 1H, CH), 6.76 (d, J = 8.4 Hz, 2H, ArH), 6.87
(s, 2H, NH2), 7.02 (d, J = 8.4 Hz, 2H, ArH), 7.24–7.32 (m, 3H,
ArH), 7.45 (d, J = 7.2 Hz, 2H, ArH), 12.87 (s, 1H, NH);
13C NMR (100 MHz, DMSO-d6) d: 41.54, 60.44, 64.22, 103.22,
119.21, 126.25, 131.71, 133.86, 134.13, 142.34, 143.31, 161.56,
163.33, 165.41; HRMS Calcd. for C20H16N4O2Na [M + Na]:
367.1171, found: 367.1166.
Water
Water
0.6
0.6
aReaction conditions: hydrazine (1.5 mmol), ethyl 3-oxo-3-phenylpropanoate
(1 mmol), 4-methylbenzaldehyde (1 mmol), malononitrile (1 mmol), solvent
(15 mL) and the ultrasonic power 250 W, irradiation frequency 40 kHz.
EXPERIMENTAL
Commercial solvents and reagents were used as received. Melting
points are uncorrected. IR spectra were recorded on Varian F-1000
spectrometer (Varian Inc., Palo Alto, State of California, USA) in
KBr with absorptions in cmꢁ1. 1H NMR was determined on Varian
Invoa-400-MHz spectrometer in DMSO-d6 solution. 13C NMR was
determined on Varian Invoa-300/400-MHz spectrometer in DMSO-
d6 solution. J values are in Hz. Chemical shifts are expressed in ppm
downfield from internal standard tetramethylsilane (TMS). HRMS
data were obtained using Bruker microTOF-Q instrument.
6-Amino-4-(4-chlorophenyl)-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5c).
White powder; mp:
254–256ꢀC (lit.[23] mp: 254ꢀC); IR (potassium bromide):
3435, 3290, 3139, 3065, 2189, 1643, 1597, 1493, 1409, 1218,
Ultrasonication was performed in a KQ-250E medical ultra-
sound cleaner with a frequency of 40 kHz and an output power
of 250W (Builtin heating, 30–110ꢀC thermostatically adjustable).
The reaction flask was located at the maximum energy area in the
cleaner, and the surface of the reactants was placed slightly lower
than the level of the water. Observation of the surface of the
reaction solution during vertical adjustment of vessel depth will
show the optimum position by the point at which maximum
surface disturbance occurs. The reaction temperature was controlled
by addition or removal of water from ultrasonic bath.
1
1093, 978, 767 cmꢁ1; H NMR (400 MHz, DMSO-d6) d: 5.06
(s, 1H, CH), 7.00 (s, 2H, NH2), 7.12 (d, J = 8.4 Hz, 2H, ArH),
7.24–7.33 (m, 5H, ArH), 7.45 (d, J = 7.2 Hz, 2H, ArH), 12.94
(s, 1H, NH); 13C NMR (100 MHz, DMSO-d6) d: 41.58, 63.32,
102.48, 126.04, 131.77, 133.84, 133.96, 134.00, 134.16,
134.77, 136.65, 143.57, 149.12, 161.44, 165.65; HRMS
Calcd. for C19H13N4O35ClNa [M + Na]: 371.0676, found:
371.0661.
6-Amino-4-(3-chlorophenyl)-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5d).
241–243ꢀC; IR (potassium bromide): 3461, 3245, 3100, 2923,
2183, 1642, 1594, 1501, 1471, 1408, 1220, 1058, 973, 729 cmꢁ1
White powder; mp:
Classical procedure for the synthesis of 5 in water. A 100-mL
flask was charged with 85% hydrazine hydrate 1 (88 mg, 1.5 mmol),
ethyl 3-oxo-3-phenylpropanoate 2 (192mg, 1 mmol), aldehyde 3
(1mmol), and malononitrile 4 (66 mg, 1 mmol) in water (15 mL).
The mixture was stirred at 50ꢀC. After the completion of the
reaction (monitored by TLC), the reaction was allowed to cool.
The residue was filtered and was recrystallized from ethanol to
produce the desired solid.
;
1H NMR (400 MHz, DMSO-d6) d: 5.08 (s, 1H, CH), 7.02 (s, 2H,
NH2), 7.06 (d, J = 7.6 Hz, 1H, ArH), 7.13–7.33 (m, 6H, ArH),
7.46 (d, J = 7.6 Hz, 2H, ArH), 12.94 (s, 1H, NH); 13C NMR
(75 MHz, DMSO-d6) d: 41.64, 62.92, 102.18, 125.87, 131.54,
131.75, 132.60, 133.84, 133.89, 134.01, 135.66, 138.24, 152.44,
161.25, 165.68; HRMS Calcd. for C19H13N4O35ClNa [M+ Na]:
371.0676, found: 371.0680.
Ultrasound-promoted synthesis of 5 in water.
Another
100-mL flask was charged with 85% hydrazine hydrate 1
(88 mg, 1.5 mmol), ethyl 3-oxo-3-phenylpropanoate 2 (192 mg,
1 mmol), aldehyde 3 (1 mmol), and malononitrile 4 (66 mg,
1 mmol) in water (15 mL). The mixture was sonicated in the
water bath of an ultrasonic cleaner at 50ꢀC. After the
6-Amino-4-(2-chlorophenyl)-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5e).
White powder; mp:
250–251ꢀC; IR (potassium bromide): 3444, 3270, 3122, 2909,
2191, 1638, 1598, 1498, 1397, 1306, 1221, 1058, 977,
Scheme 2. The synthesis of pyrano[2,3-c]pyrazole derivatives 5 under sonication.
R
O
O
Ph
H2O
CN
CN
CN
+
NH2NH2 • H2O
+
RCHO
+
50°C ))))))
Ph
OC2H5
N
NH2
N
O
H
1
2
3
4
5
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Y. Zou, Y. Hu, H. Liu, and D.-Q. Shi
Vol 000
Table 2
Synthesis of pyrano[2,3-c]pyrazole derivatives 5 under sonication and conventional conditions.
With USa
Without USb
Yieldc (%)
Entry
Product
R
Time (min)
Yieldc (%)
Time (h)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-FC6H4
4-BrC6H4
4-NO2C6H4
3,4-OCH2OC6H3
3,4-Cl2C6H3
2-Thienyl
35
37
15
18
21
20
13
20
30
18
22
90
88
95
90
85
88
93
88
70
82
85
3
3.5
2
2
3
3.5
2.5
4
4
3
84
76
80
78
70
67
75
76
69
70
75
10
11
5j
5k
3.5
aReaction in water at 50ꢀC under ultrasound irradiation.
bReaction in water at 50ꢀC under high-stirring condition.
cYields of isolated products.
686 cmꢁ1; 1H NMR (400 MHz, DMSO-d6) d: 5.43 (s, 1H, CH),
7.00 (s, 2H, NH2), 7.10–7.18 (m, 3H, ArH), 7.25–7.31 (m, 4H,
ArH), 7.37 (d, J = 6.8 Hz, 2H, ArH), 12.91 (s, 1H, NH);
13C NMR (75 MHz, DMSO-d6) d: 39.46, 61.93, 102.03,
125.54, 131.50, 132.96, 133.58, 133.92, 134.80, 136.07,
137.45, 143.35, 146.53, 161.62, 165.92; HRMS Calcd. for
C19H13N4O35ClNa [M + Na]: 371.0676, found: 371.0670.
6-Amino-4-(4-fluorophenyl)-3-phenyl-1,4-dihydropyrano
12.91 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6) d: 36.61,
58.78, 97.95, 115.56, 115.56, 115.84, 121.23, 126.93, 129.03,
129.19, 129.24, 129.83, 129.94, 138.68, 141.45, 141.49, 156.56,
159.84, 160.71, 163.06; HRMS Calcd for C19H13N4OFNa
[M + Na]: 355.0966, found: 355.0970.
6-Amino-4-(4-bromophenyl)-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5g).
White powder; mp:
230–232ꢀC; IR (potassium bromide): 3431, 3286, 3135, 2874,
[2,3-c]pyrazole-5-carbonitrile (5f).
White powder; mp:
2187, 1643, 1599, 1499, 1483, 1414, 1219, 1065, 1013,
1
246–248ꢀC; IR (potassium bromide): 3496, 3240, 3095, 2192,
976 cm-1; H NMR (400 MHz, DMSO-d6) d: 5.05 (s, 1H, CH),
1638, 1601, 1587, 1502, 1406, 1222, 1062, 975, 827 cmꢁ1
;
6.99 (s, 2H, NH2), 7.07 (d, J = 8.0 Hz, 2H, ArH), 7.25–7.33
(m, 3H, ArH), 7.38 (d, J = 8.4 Hz, 2H, ArH), 7.46
(d, J = 7.2 Hz, 2H, ArH), 12.93 (s, 1H, NH); 13C NMR
(75 MHz, DMSO-d6) d: 36.78, 58.39, 97.54, 120.34, 121.16,
1H NMR (400 MHz, DMSO-d6) d: 5.04 (s, 1H, CH), 6.96
(s, 2H, NH2), 7.01 (t, J = 8.8 Hz, 2H, ArH), 7.12–7.15 (m, 2H,
ArH), 7.24–7.32 (m, 3H, ArH), 7.44 (d, J = 7.2 Hz, 2H, ArH),
Scheme 3. Synthesis of bispyrano[2,3-c]pyrazole derivatives.
H
H2N
NC
O
N
N
Ph
CHO
CHO
Ph
N
N
H
CN
O
5l
NH2
NH
O
O
3l
H2O
CN
CN
+
NH2NH2 • H2O
+
+
N
50°C ))))))
Ph
OC2H5
CHO
Ph
O
2
1
4
NH2
CHO
CN
CN
3m
Ph
N
N
O
NH2
H
5m
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
An Efficient and Green Synthesis of 6-Amino-3-phenyl-4-aryl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile Derivatives under Ultrasound Irradiation in Aqueous Medium
Table 3
Synthesis of bispyrano[2,3-c]pyrazole derivatives under sonication and conventional conditions.
With US
Time (min)
Without US
Entry
Product
Aldehyde
Yielda (%)
Time (h)
Yielda (%)
1
2
5l
5m
Terephthalaldehyde
Isophthalaldehyde
23
30
92
85
3
5
75
70
aYields of isolated products.
126.88, 129.13, 129.30, 130.26, 131.88, 138.68, 144.67,
156.57, 160.78; HRMS Calcd. for C19H13N4O79BrNa
[M + Na]: 415.0165, found: 415.0159.
4,40-(1,4-Phenylene)bis(6-amino-3-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile) (5l). Yellow powder; mp:
>300ꢀC; IR (potassium bromide): 3293, 3049, 2946, 2188, 1654,
1638, 1589, 1508, 1476, 1277, 1065, 975 cmꢁ1 1H NMR
6-Amino-4-(4-nitrophenyl)-3-phenyl-1,4-dihydropyrano
;
[2,3-c]pyrazole-5-carbonitrile (5h).
White powder; mp:
(400 MHz, DMSO-d6) d: 4.80 (s, 1H, CH), 4.83 (s, 1H, CH), 6.90
(s, 2H, NH2), 6.92 (s, 2H, NH2), 6.99–7.01 (m, 4H, ArH), 7.12–
7.25 (m, 10H, ArH), 12.86 (s, 1H, NH), 12.89 (s, 1H, NH); 13C
NMR (75 MHz, DMSO-d6) d: 37.11, 58.89, 58.94, 97.98, 97.98,
121.23, 121.29, 126.72, 126.88, 128.06, 128.14, 128.89, 129.20,
138.45, 138.71, 143.88, 144.06, 156.66, 160.58, 160.70; HRMS
Calcd. for C32H22N8O2Na [M + Na]: 573.1758, found: 573.1768.
4,40-(1,3-Phenylene)bis(6-amino-3-phenyl-1,4-dihydropyrano
224–226ꢀC; IR (potassium bromide): 3438, 3286, 3122, 2871,
2186, 1646, 1597, 1515, 1419, 1351, 1066, 977, 768 cmꢁ1; H
1
NMR (400 MHz, DMSO-d6) d: 5.27 (s, 1H, CH), 7.12 (s, 2H,
NH2), 7.24–7.32 (m, 3H, ArH), 7.39 (d, J = 8.4 Hz, 2H, ArH),
7.46 (d, J = 7.2 Hz, 2H, ArH), 13.01 (s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6) d: 36.95, 57.54, 96.95, 120.96, 124.35,
126.90, 128.96, 129.22, 129.36, 138.91, 146.87, 152.74,
156.50, 161.04; HRMS Calcd for C19H13N5O3Na [M + Na]:
382.0911, found: 382.0930.
[2,3-c]pyrazole-5-carbonitrile) (5m).
>300ꢀC; IR (potassium bromide): 3477, 3370, 3247, 2194, 1639,
1598, 1499, 1479, 1399, 1216, 1057, 977, 768 cmꢁ1 1H NMR
White powder; mp:
6-Amino-4-(benzo[d][1,3]dioxol-5-yl)-3-phenyl-1,4-
;
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5i).
White
(400 MHz, DMSO-d6) d: 4.76 (s, 1H, CH), 4.84 (s, 1H, CH),
6.76–6.82 (m, 1H, ArH), 6.89–6.93 (m, 5H, ArH and 2 ꢂ NH2),
7.07 (m, 1H, ArH), 7.18–7.31 (m, 11H, ArH), 12.80 (s, 1H, NH),
12.92 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6) d: 37.41,
37.67, 58.85, 58.98, 97.87, 97.92, 121.00, 121.14, 126.34,
126.43, 126.80, 126.99, 127.26, 128.73, 128.91, 129.12, 129.22,
129.35, 138.27, 138.83, 145.49, 145.74, 156.60, 156.93, 160.67;
HRMS Calcd. for C32H22N8O2Na [M + Na]: 573.1758, found:
573.1768.
powder; mp: 231–232ꢀC; IR (potassium bromide): 3481, 3435,
3205, 3132, 2897, 2189, 1633, 1601, 1501, 1446, 1401, 1252,
1041, 926, 728 cmꢁ1 1H NMR (400MHz, DMSO-d6) d: 4.93
;
(s, 1H, CH), 5.91 (d, J = 4.4 Hz, 2H, OCH2O), 6.57–6.61 (m, 2H,
ArH), 6.72 (d, J= 8.0 Hz, 1H, ArH), 6.90 (s, 2H, NH2), 7.27–7.34
(m, 3H, ArH), 7.47 (d, J= 7.6 Hz, 2H, ArH), 12.89 (s, 1H, NH);
13C NMR (75 MHz, DMSO-d6) d: 37.04, 59.10, 98.08, 101.52,
108.19, 108.58, 121.16, 126.90, 129.02, 129.28, 138.52, 139.46,
146.46, 147.83, 156.63, 160.64; HRMS Calcd. for C20H14N4O3Na
[M + Na]: 381.0958, found: 381.0959.
6-Amino-4-(3,4-dichlorophenyl)-3-phenyl-1,4-dihydropyrano
Acknowledgment. We are grateful to the Major Basic Research
Project of the Natural Science Foundation of the Jiangsu Higher
Education Institutions (No. 10KJA150049) and the Foundation
of Key Laboratory of Organic Synthesis of Jiangsu Province
(No. JSK0812) for financial support.
[2,3-c]pyrazole-5-carbonitrile (5j).
White powder; mp:
248–249ꢀC; IR (potassium bromide): 3477, 3250, 3111,
2903, 2190, 1633, 1590, 1500, 1468, 1403, 1218, 1179,
1058, 973, 893, 738 cmꢁ1 1H NMR (400 MHz, DMSO-d6)
;
d: 5.14 (s, 1H, CH), 7.08 (s, 3H, ArH), 7.27–7.48 (m, 7H,
ArH and NH2), 12.97 (s, 1H, NH); 13C NMR (75 MHz,
DMSO-d6) d: 36.45, 57.81, 97.05, 121.12, 127.01, 129.25,
129.95, 130.03, 131.52, 138.97, 146.12, 156.43, 161.02;
HRMS Calcd. for C19H12N4O35Cl2Na [M + Na]: 405.0280,
found: 405.0270.
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6-Amino-3-phenyl-4-(thiophen-2-yl)-1,4-dihydropyrano
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