A catalyst-free green protocol for the synthesis of pyranopyrazoles using room temperature ionic liquid choline chloride-urea

Article abstract of DOI:10.1002/jhet.1864

An efficient and rapid four component reaction of aldehydes, malanonitrile, β-ketoesters and hydrazine hydrate (or phenyl hydrazine) in environmentally benign room temperature ionic liquid choline chloride-urea has been developed for the synthesis of substituted 4H-pyrano[2,3-c]pyrazoles.

Full text of DOI:10.1002/jhet.1864

Month 2014 A Catalyst-free Green Protocol for the Synthesis of Pyranopyrazoles Using
Room Temperature Ionic Liquid Choline Chloride-urea
Toreshettahally R. Swaroop,a Kothanahally S. Sharath Kumar,a Mariyappan Palanivelu,b Somu Chaitanya,a and
a
*
Kanchugarakoppal S. Rangappa
aDepartment of Studies in Chemistry, University of Mysore, Manasagangothri, Mysore 570 006, India
bDepartment of Chemistry, Gurunanak College, University of Madras, Madras 600042, India
*
E-mail: rangappaks@gmail.com; rangappaks@chemistry.uni-mysore.ac.in
Received July 24, 2012
DOI 10.1002/jhet.1864
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
An efficient and rapid four component reaction of aldehydes, malanonitrile, b-ketoesters and hydrazine
hydrate (or phenyl hydrazine) in environmentally benign room temperature ionic liquid choline chloride-urea
has been developed for the synthesis of substituted 4H-pyrano[2,3-c]pyrazoles.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
been used in the synthesis of microporous crystalline
zeolites [12] carbon dioxide fixation [13] and other
processes [14]. To the best of our knowledge, applicability
of this green IL media in organic synthesis has not
been explored.
As a part of our research aimed at the development of
new synthetic methodologies for biologically important
heterocyclic compounds [15], we have recently reported
the application of this IL in the synthesis of substituted
4H-chromenes [15b].
Substituted 4H-pyrano[2,3-c]pyrazoles represent an
important class of heterocycles that have shown analgesic
[1a], anticancer [1b], anti-inflammatory [1c], molluscidal
[1d], and serine/threonine protein kinase inhibitor activity
[1e]. They have also shown affinity toward A1 and A2a
adenosine receptors [2]. Because of these diverse biological
activities of pyranopyrazoles, many protocols have been
developed for their synthesis. The first reported method
involves the reaction of tetracyanoethylene with 3-methyl-
1H-pyrazoline-5-one in presence of triethylamine [3].
Thereafter, numerous methods have been developed for their
synthesis in ethanol [4], water [5], microwave irradiation [6],
ultrasonic irradiation [7], and solvent-free conditions [8].
In addition, organocatalyzed enantioselective synthesis of
pyranopyrazoles has also been reported [9]. Literature
survey also reveals their synthesis in room temperature ionic
liquid (RTIL) [Bmim]BF4 using L-proline as catalyst [10].
Although the reported methods are effective, they have
limited applicability by the use of toxic and costly catalysts.
Therefore, a catalyst free green protocol that overcomes the
drawbacks of several earlier procedures still attracts a lot of
attention.
RESULTS AND DISCUSSION
The required IL was prepared by heating the mixture of
commercially available choline chloride and urea (Scheme 1)
with a molar ratio of 2:1 at 50ꢀC until a clear homogeneous
liquid was formed [15b], then the temperature of the IL was
bought to room temperature.
As a preliminary test, we investigated the reaction of
benzaldehyde (1a), malanonitrile (2), ethyl acetoacetate
(3a), and hydrazine hydrate (4a) in the aforementioned
prepared RTIL. Surprisingly, the reaction was completed
within 10 min furnishing the product in 95% yield. The
isolated product was found to be 6-amino-3-methyl-4-
phenyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5a)
on the basis of spectral and analytical data. In another
attempt, when the same reaction was carried out in the
absence of IL, the intermediates remain unreacted even
after prolonged stirring at room temperature. This proves
the essential role of IL as a catalyst as well as solvent.
Furthermore, utilization of ILs in chemical synthesis has
attracted much attention because of their advantages over
conventional organic solvents such as negligible vapor
pressure, wide liquid range with melting point around
room temperature, high solubility for many organic,
inorganic, and even polymeric materials [11]. Recently,
ILs based on choline chloride and urea (Scheme 1) has
© 2014 HeteroCorporation

T. R. Swaroop, K. S. Sharath Kumar, M. Palanivelu, S. Chaitanya, and K. S. Rangappa
Vol 000
Scheme 1
The scope of this protocol was extended to the reaction
of other b-ketoesters such as ethyl isobutyroylacetoacetate
(3b) and ethyl benzoylacetoacetate (3c) with aldehydes
(1c, 1e, 1j, 1h, and 1a), 2 and 4a (Scheme 2). All reactions
underwent clearly furnishing pyranopyrazoles (5j–n) in
moderate to good yields (entries 10–14. Table 1). The
present protocol was also found to be effective for phenyl
hydrazine. Thus, phenyl hydrazine reacted smoothly with
aldehydes (1a, 1c, and 1h), 2 and 3 affording pyranopyra-
zoles (5o–q) in moderate yields (entries 15–17, Table 1).
It should be noted that the reactions were clean, all
products were obtained after filtration and washing with water
followed by crystallization from ethanol. All the synthesized
compounds were characterized by IR, 1H NMR, LCMS and
Inspired by this success, we next studied the four compo-
nent reaction of various aldehydes, malanonitrile, ethyl
acetoacetate, and hydrazine hydrate in choline chloride-urea
RTIL (Scheme 2). Thus, the protocol was compatible with
various aryl aldehydes bearing electron donating and
electron-withdrawing substituents, and also with heteroaryl
aldehydes affording the product 6-amino-3-methyl-4-aryl/
heteroaryl-2,4-dihydropyrano[2,3-c]pyraz-ole-5-carbonitrile
(5a–i) in 80–92% yields (entries 1–9, Table 1).
1
elemental analysis. H NMR spectra of pyranopyrazoles
(5a–q) show characteristic peak at 4.10–5.0 ppm. The
Scheme 2
Table 1
Ionic liquid mediated one-pot synthesis of pyranopyrazoles.
Entry
R
1
R1
Time (min)
Producta
% Yieldb
1
2
3
4
5
6
7
8
C6H5
1a
1b
1c
1d
1e
1f
1g
1h
1i
1c
1e
1j
1h
1a
1a
1c
1h
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
(CH3)2CH
(CH3)2CH
(CH3)2CH
(CH3)2CH
C6H5
10
18
10
12
20
14
13
12
10
10
20
15
13
25
30
25
30
5a5c
5b5g
5c5c
5d9
5e9
5f5c
5g9
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
95
88
92
90
85
86
83
80
84
87
82
85
81
75
66
70
62
3,4-(MeO)2C6H3
4-O2N-C6H4
4-Me2N-C6H4
3,4,5-(MeO)3C6H2
4-MeOC6H4
2-Furanyl
3-Pyridinyl
9
N-methylindol-3-yl
4-O2N-C6H4
3,4,5-(MeO)3C6H2
4-EtO-C6H4
3-Pyridinyl
C6H5
C6H5
4-O2N-C6H4
3-Pyridinyl
10
11
12
13
14
15c
16c
17c
CH3
(CH3)2CH
(CH3)2CH
aLiterature reference to the compound.
bIsolated yields. cPhenyl hydrazine (4b) was used in the reaction.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Catalyst-free Green Protocol for the Synthesis of Pyranopyrazoles Using Room
Temperature Ionic Liquid Choline Chloride-urea
mmol) under nitrogen atmosphere was heated to 50ꢀC for 5–10
min with stirring. After the formation of clear viscous liquid
(IL), the reaction mixture was bought to room temperature and
this RTIL was used for the reaction.
possible mechanism for the formation of N-1 unsubstituted
pyranopyrazoles (5a–n) and N-substituted pyranopyrazoles
(5a–p) is depicted in Scheme 3. It might involve Knoevenagel
condensation between 1 and 2 catalyzed by IL and formation
of pyrazolone by reaction between 3 and 4. IL mediated
Michael addition of 7 to 6 followed by cyclization and
tautomerization. We have proposed 2,4-dihydrotautomeric
form for pyranopyrazoles unsubstituted at N-1 position
based on recently reported X-ray crystallographic data
[4,8a] and 1,4-dihydrotautomeric form for N-1 substituted
pyranopyrazoles.
General procedure for the synthesis of pyranopyrazoles
(5).
The mixture of aldehyde (3.0 mmol) and malanonitrile
(3.0mmol) was taken in the earlier prepared IL and stirred for
5 min under nitrogen atmosphere, and then b-ketoester (3.0 mmol)
and hydrazine hydrate (or phenyl hydrazene) (3.0 mmol) were
added, and the reaction mixture was stirred at room temperature
for 5–25min under nitrogen atmosphere. After the reaction, water
was added and solid formed was filtered. The resulting solid was
crystallized from ethanol to obtain pure compounds.
6-Amino-3-methyl-4-phenyl-2,4-dihydropyrano[2,3-c]pyrazole-
5-carbonitrile (5a). White solid. mp 244–246ꢀC. IR (KBr, cmÀ1
)
CONCLUSION
υ: 3350, 3317, 3168, 2182, 1645, 1601, 1495, 1408, 1160, 1149,
1073, 1033, 779, 745, 655, 563. 1H NMR (DMSO-d6, d,
400 ppm): 1.76 (s, 3H); 4.57 (s, 1H); 6.64 (s, 2H); 7.14 (d, 2H,
J = 7.2 Hz); 7.20 (t, 1H, J = 7.2 Hz); 7.30 (t, 2H, J = 7.6 Hz);
12.05 (s, 1H). ESI-MS: m/z 253.2 [M + 1]+. Anal. calcd for
C14H12N4O: C, 66.65; H, 4.79; N, 22.21. Found: C, 66.60; H,
4.75; N, 22.15.
6-Amino-4-(3,4-dimethoxyphenyl)-3-methyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5b). White solid. mp 266–268ꢀC.
IR (KBr, cmÀ1) υ: 3345, 3315, 3160, 2180, 1640, 1600, 1499, 1405,
1166, 1145, 1071, 1030, 775, 741, 654, 560. 1H NMR (DMSO-d6, d,
400 ppm): 1.80 (s, 3H); 3.68 (s, 3H); 3.71 (s, 3H); 4.52 (s, 1H); 6.66
(dd, 1H, J= 8.2Hz, J= 1.8 Hz) 6.73 (d, 1H, J = 2.0 Hz); 6.77 (s, 2H);
6.87 (d, 1H, J = 8.4 Hz); 12.06 (s, 1H). ESI-MS: m/z 313.2 [M + 1]+.
Anal. calcd for C16H16N4O3: C, 61.53; H, 5.16; N, 17.94. Found: C,
61.43; H, 5.26; N, 17.99.
In summary, we have developed an efficient, rapid, first cat-
alyst free green protocol for the synthesis of pyranopyrazoles
by four component cyclocondensation reaction in RTIL
choline chloride-urea. Mild reaction conditions, short
reaction time, ease of work up, high yields and general
applicability of various aldehydes, b-ketoesters and hydra-
zine derivatives such as hydrazine hydrate and phenyl
hydrazine, and simple procedure are the noteworthy features
of this new protocol. In addition, the work presented here is
significant in terms of eco-friendliness, economic viability,
and free from catalyst, thus overcoming the drawbacks such
as use of costly and toxic catalysts in some of the earlier
reported methods. Further application of this methodology
toward enantioselective synthesis of pyranopyrazoles is
underway in our laboratory.
6-Amino-3-methyl-4-(4-nitrophenyl)-2,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile (5c).
White solid. mp 250–252ꢀC. IR
(KBr, cmÀ1) υ: 3335, 3320, 3155, 2195, 1645, 1610, 1505, 1400,
1155, 1140, 1066, 1024, 770, 732, 665, 559. 1H NMR (DMSO-d6,
d, 400 ppm): 1.78 (s, 3H, CH3); 4.80 (s, 1H, CH); 7.04 (s, 2H,
NH2); 7.44 (d, 2H, Ar–H, J = 8.4 Hz); 8.18 (d, 2H, Ar–H,
J= 8.4 Hz); 12.16 (s, 1H, NH). ESI-MS: m/z 298.2 [M + 1]+. Anal.
calcd for C14H11N5O3: C, 56.56; H, 3.73; N, 23.56. Found: C,
56.60; H, 3.79; N, 23.59.
EXPERIMENTAL
NMR spectra were recorded on a Bruker AMX400 spectrometer
in deuterated DMSO solvent with tetramethylsilane as an internal
standard. IR spectra were obtained using a Shimadzu FTIR
8300 spectrometer. Mass spectra and purity were determined on a
LC-MSD-Trap-XCT. Melting points were determined on a Tropical
Labequip apparatus. All analytical thin layer chromatography was
performed with E. Merck silica gel 60F254 aluminum sheets and
was visualized with UV light. Chemicals materials were either
prepared in our laboratory or purchased from Sigma-Aldrich and
Merck Companies (Bangalore, India).
6-Amino-4-(4-(dimethylamino)phenyl)-3-methyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5d). Yellow solid. mp 250–252ꢀC.
IR (KBr, cmÀ1) υ: 3328, 3324, 3150, 2198, 1665, 1620, 1506,
1420, 1145, 1130, 1061, 1029, 755, 731, 655, 549. 1H NMR
(DMSO-d6, d, 400 ppm): 1.77 (s, 3H, CH3); 2.84 (s, 6H, N(CH3)2);
4.42 (s, 1H, CH); 6.63 (d, 2H, Ar–H, J = 8.0 Hz); 6.69 (s, 2H,
NH2); 6.94 (d, 2H, Ar–H, J = 8.0 Hz); 11.98 (s, 1H, NH). ESI-
MS: m/z 295.2 [M + 1]+. Anal. calcd for C16H17N5O: C, 65.07; H,
5.80; N, 23.71. Found: C, 65.15; H, 5.90; N, 23.79.
Preparation of ionic liquid [15b]. A mixture of anhydrous
choline chloride (5g, 35.8 mmol) and anhydrous urea (4.29g, 71.6
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

T. R. Swaroop, K. S. Sharath Kumar, M. Palanivelu, S. Chaitanya, and K. S. Rangappa
Vol 000
6-Amino-3-methyl-4-(3,4,5-trimethoxyphenyl)-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5e). White solid. mp 226-228ꢀC.
IR (KBr, cmÀ1) υ: 3336, 3322, 3150, 2186, 1631, 1600, 1508,
1415, 1145, 1137, 1056, 1029, 773, 739, 666, 555. 1H NMR
(DMSO-d6, d, 400 ppm): 1.85 (s, 3H, CH3); 3.62 (s, 3H, OCH3);
3.69 (s, 6H, (OCH3)2); 4.46 (s, 1H, CH); 6.45 (s, 2H, Ar–H,);
6.81 (s, 2H, NH2); 12.05 (s, 1H, NH). ESI-MS: m/z 343.2
[M+ 1]+. Anal. calcd for C17H18N4O4: C, 59.64; H, 5.30; N,
0.81 (d, 3H, CH3, J = 6.4 Hz ); 0.99 (d, 3H, CH3, J = 7.2 Hz); 2.40
(m, 1H, CH); 3.61 (s, 3H, OCH3); 3.68 (s, 6H, (OCH3)2); 4.57
(s, 1H, CH); 6.42 (s, 2H, Ar–H,); 6.77 (s, 2H, NH2); 12.12
(s, 1H, NH). ESI-MS: m/z 371.2 [M + 1]+. Anal. calcd for
C19H22N4O4: C, 61.61; H, 5.99; N, 15.13. Found: C, 61.66; H,
5.95; N, 15.10.
6-Amino-4-(4-ethoxyphenyl)-3-isopropyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5l). White solid. mp 138–140ꢀC.
IR (KBr, cmÀ1) υ: 3342, 3333, 3166, 2198, 1647, 1611, 1522,
1411, 1132, 1149, 1060, 1039, 785, 679, 551. 1H NMR
(DMSO-d6, d, 400 ppm): 0.75 (d, 3H, CH3, J = 6.8Hz ); 0.94
(d, 3H, CH3, J = 7.2 Hz); 2.48 (m, 1H, CH); 4.51 (s, 1H, CH);
6.72 (s, 2H, NH2); 6.83 (d, 2H, Ar–H, J = 7.6Hz); 7.01 (d,
2H, Ar–H, J = 7.6 Hz); 12.10 (s, 1H, NH). ESI-MS: m/z 325.2
[M+ 1]+. Anal. calcd for C18H20N4O2: C, 66.65; H, 6.21; N,
17.27. Found: C, 66.55; H, 6.27; N, 17.21.
16.37. Found: C, 59.70; H, 5.40; N, 16.41.
6-Amino-4-(4-methoxyphenyl)-3-methyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5f). White solid. mp 212–214ꢀC.
IR (KBr, cmÀ1) υ: 3338, 3331, 3161, 2196, 1642, 1602,
1512, 1419, 1135, 1142, 1057, 1034, 775, 729, 669, 551.
1H NMR (DMSO-d6, d, 400 ppm): 1.76 (s, 3H, CH3); 3.67
(s, 3H, OCH3); 4.51 (s, 1H, CH); 6.77 (s, 2H, NH2); 6.85
(d, 2H, Ar–H, J = 8.8 Hz); 7.05(d, 2H, Ar–H, J = 8.8 Hz);
12.03(s, 1H, NH). ESI-MS: m/z 283.2 [M + 1]+. Anal. calcd
for C15H14N4O2: C, 63.82; H, 5.00; N, 19.85. Found: C,
6-Amino-3-isopropyl-4-(pyridin-3-yl)-2,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile (5m). White solid. mp 170–172ꢀC. IR
(KBr, cmÀ1) υ: 3345, 3322, 3166, 2202, 1647, 1608, 1515, 1425,
63.88; H, 5.11; N, 19.89.
6-Amino-4-(furan-2-yl)-3-methyl-2,4-dihydropyrano[2,3-c]
1
1140, 1061, 1044, 778, 739. H NMR (DMSO-d6, d, 400 ppm):
pyrazole-5-carbonitrile (5g). White solid. mp 233–234ꢀC. IR
(KBr, cmÀ1) υ: 3345, 3339, 3166, 2186, 1645, 1611, 1518,
1418, 1125, 1144, 1067, 1054, 778, 722. 1H NMR (DMSO-
d6, d, 400 ppm): 1.96 (s, 3H, CH3); 4.75 (s, 1H, CH); 6.15
(d, 1H, Ar–H, J = 3.2 Hz);6.34 (t, 1H, Ar–H, J = 3.2 Hz); 6.89
(s, 2H, NH2); 7.50 (d, 1H, Ar–H, J = 0.8 Hz)12.05 (s, 1H, NH).
ESI-MS: m/z 243.2 [M + 1]+. Anal. calcd for C12H10N4O2:
C, 59.50; H, 4.16; N, 23.13. Found: C, 59.55; H, 4.22; N,
0.74 (d, 3H, CH3, J =7.2 Hz ); 0.96 (d, 3H, CH3, J =7.2 Hz); 2.51
(m, 1H, CH); 4.70 (s, 1H, CH); 6.90 (s, 2H, NH2); 7.32 (q, 1H,
Ar–H, J = 4.8Hz); 7.49 (d, 1H, Ar–H, J = 8.0 Hz); 8.43 (d, 1H,
Ar–H); 8.43 (s, 1H, Ar–H); 12.16 (s, 1H, NH). ESI-MS: m/z
282.2 [M+ 1]+. Anal. calcd for C15H15N5O: C, 64.04; H, 5.37; N,
24.90. Found: C, 64.10; H, 5.35; N, 24.95.
6-Amino-3,4-diphenyl-2,4-dihydropyrano[2,3-c]pyrazoleÀ-51-
carbonitrile (5n). White solid. mp 162–164ꢀC. IR (KBr, cm
)
23.19.
υ: 3344, 3311, 3171, 2182, 1645, 1610, 1518, 1420, 1145, 1135,
1061, 1042, 779, 730, 673. 1H NMR (DMSO-d6, d, 400ppm):
4.74 (S, 1H, CH); 7.4 (m, 10H, Ar–H); 12.16 (s, 1H, NH). ESI-
MS: m/z 315.2 [M + 1]+. Anal. calcd for C19H14N4O: C, 72.60; H,
4.49; N, 17.82. Found: C, 72.66; H, 4.55; N, 17.88.
6-Amino-3-methyl-4-(pyridin-3-yl)-2,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile (5h). White solid. mp 150–152ꢀC. IR
(KBr, cmÀ1) υ: 3340, 3336, 3165, 2186, 1645, 1605, 1552,
1429, 1149, 1138, 1067, 1024, 765, 709. 1H NMR (DMSO-
d6, d, 400 ppm): 1.77 (s, 3H, CH3); 4.67 (s, 1H, CH); 6.93
(s, 2H, NH2); 7.32 (q, 1H, Ar–H, J = 5.2 Hz); 7.50 (d, 1H,
Ar–H, J = 8.0 Hz); 8.42 (s, 2H, Ar–H); 12.24 (s, 1H, NH).
ESI-MS: m/z 254.2 [M + 1]+. Anal. calcd for C13H11N5O:
C, 61.65; H, 4.38; N, 27.65. Found: C, 61.69; H, 4.33;
6-Amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile (5o).
White solid. mp 156–158ꢀC. IR
(KBr, cmÀ1) υ: 3341, 3325, 3165, 2210, 1645, 1611, 1514, 1425,
1
1145, 1135, 1065, 1040, 783, 734, 551. H NMR (DMSO-d6, d,
400 ppm): 1.93 (s, 3H, CH3); 4.74 (s, 1H, CH); 7.25 (m, 5H,
Ar–H); 7.35 (m, 5H, Ar–H); 8.56 (s, 2H, NH2). ESI-MS: m/z 329
[M+ 1]+. Anal. calcd for C20H16N4O: C, 73.15; H, 4.91; N, 17.06.
Found: C, 73.25; H, 4.95; N, 17.10.
6-Amino-3-isopropyl-4-(4-nitrophenyl)-1-phenyl-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5p). White solid. mp 148–150ꢀC.
IR (KBr, cmÀ1) υ: 3341, 3339, 3165, 2201, 1645, 1609, 1522,
1420, 1147, 1136, 1061, 1041, 771, 725, 671. 1H NMR (DMSO-
d6, d, 400ppm): 1.31 (d, 6H, CH3); 3.44 (m, 1H, CH); 4.74
(s, 1H, CH); 7.5 (m, 10H, Ar–H); 8.56 (s, 2H, NH2). ESI-MS: m/z
402 [M+ 1]+. Anal. calcd for C22H19N5O3: C, 56.83; H, 4.77; N,
17.45. Found: C, 56.93; H, 4.71; N, 17.49.
6-Amino-3-isopropyl-1-phenyl-4-(pyridin-3-yl)-1,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5q). White solid. mp 178–180ꢀC. IR
(KBr, cmÀ1) υ: 3341, 3339, 3165, 2210, 1645, 1600, 1519, 1425,
1145, 1141, 1061, 1037, 781, 731. 1H NMR (DMSO-d6, d,
400 ppm): 1.31 (d, 6H, CH3); 3.43 (m, 1H, CH); 4.74 (s, 1H, CH);
7.25 (t, 1H, J= 7.0 Hz); 7.50 (m, 6H, Ar–H); 8.4 (m, 2H, Ar–H);
8.56 (s, 2H, NH2). ESI-MS: m/z 358 [M + 1]+. Anal. calcd for
C21H19N5O: C, 70.57; H, 5.36; N, 19.59. Found: C, 70.60; H, 5.45;
N, 19.65.
N, 27.55.
6-Amino-3-methyl-4-(1-methyl-1H-indol-3-yl)-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5i). White solid. mp 170–172ꢀC.
IR (KBr, cmÀ1) υ: 3345, 3321, 3166, 2185, 1652, 1610, 1519,
1
1420, 1142, 1054, 1044, 771. H NMR (DMSO-d6, d, 400 ppm):
1.75 (s, 3H, CH3); 3.72 (s, 3H, NCH3); 4.81 (s, 1H, CH); 6.69
(s, 2H, NH2); 6.88 (t, 1H, Ar–H, J = 7.2 Hz); 7.07 (t, 1H, Ar–H,
J = 8.0 Hz); 7.13 (d, 1H, Ar–H, J = 8.0 Hz); 7.22 (s, 1H, Ar–H);
11.96 (s, 1H, NH). ESI-MS: m/z 306.2 [M+ 1]+. Anal. calcd for
C17H15N5O: C, 66.87; H, 4.95; N, 22.94. Found: C, 66.81; H,
4.89; N, 22.85.
6-Amino-3-isopropyl-4-(4-nitrophenyl)-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5j). White solid. mp 164–166ꢀC.
IR (KBr, cmÀ1) υ: 3348, 3342, 3152, 2186, 1648, 1612, 1502,
1421, 1145, 1125, 1065, 1024, 729, 664. 1H NMR (DMSO-d6, d,
400 ppm): 0.76 (d, 3H, CH3, J = 6.8 Hz ); 0.98 (d,3H, CH3,
J = 6.8 Hz);2.53 (m, 1H, CH); 4.83 (s, 1H, CH); 6.97 (s, 2H,
NH2); 7.43 (d, 2H, Ar–H, J = 8.4Hz); 8.18 (d, 2H, Ar–H,
J = 8.4 Hz); 12.20 (s, 1H, NH). ESI-MS: m/z 326.2 [M+ 1]+. Anal.
calcd for C16H15N5O3: C, 59.07; H, 4.65; N, 21.53. Found: C,
59.15; H, 4.75; N, 21.60.
6-Amino-3-isopropyl-4-(3,4,5-trimethoxyphenyl)-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5k). White solid. mp 140–142ꢀC.
Acknowledgment. We greatly acknowledge the support of this
work by Council of Scientific and Industrial Research, New
Delhi, India for Junior Research Fellowship to T. R. S.
IR (KBr, cmÀ1) υ: 3338, 3342, 3168, 2201, 1652, 1600, 1514,
1
1420, 1144, 1065, 1024, 775. H NMR (DMSO-d6, d, 400 ppm):
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Catalyst-free Green Protocol for the Synthesis of Pyranopyrazoles Using Room
Temperature Ionic Liquid Choline Chloride-urea
[8] (a) Guo, S. B.; Wang, S. X.; Li, J. T. D. Synth Commun
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet