CeCl3-promoted one-pot synthesis of multisubstituted bispyrano[2,3-c]pyrazole derivatives

Article abstract of DOI:10.1007/s00706-013-1104-6

A simple and efficient method was developed for the synthesis of multisubstituted bispyrano[2,3-c]pyrazole derivatives via one-pot reaction of β-keto esters, hydrazine (or phenylhydrazine), terephthalaldehyde, and malononitrile in the presence of CeCl₃·7H₂O (10 mol%) as a catalyst. This method provides the products in good yields after a simple workup procedure without further purification. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1104-6

Monatsh Chem (2014) 145:491–496
DOI 10.1007/s00706-013-1104-6
ORIGINAL PAPER
CeCl3-promoted one-pot synthesis of multisubstituted
bispyrano[2,3-c]pyrazole derivatives
•
•
•
Keyume Ablajan Li-Ju Wang Zulipiya Maimaiti
Yong-Ting Lu
Received: 6 May 2013 / Accepted: 13 October 2013 / Published online: 30 November 2013
Ó Springer-Verlag Wien 2013
Abstract A simple and efficient method was developed
for the synthesis of multisubstituted bispyrano[2,3-c]pyra-
zole derivatives via one-pot reaction of b-keto esters,
hydrazine (or phenylhydrazine), terephthalaldehyde, and
malononitrile in the presence of CeCl3ꢀ7H2O (10 mol%) as
a catalyst. This method provides the products in good
yields after a simple workup procedure without further
purification.
an important raw material and intermediate that is widely
used for the preparation of bioactive compounds including
medicinally active compounds and agrochemicals. Because
of their wide range of applications, pyrano[2,3-c]pyrazoles
are produced in large quantities. Therefore, the develop-
ment of new methods for their synthesis has received
considerable attention.
The combinatorial synthesis of small molecule hetero-
cyclic libraries has emerged as a valuable tool in the search
for novel lead structures. As a result, the performance of
one-pot methods in the synthesis of various chemicals has
recently been summarized [10–12]. Multicomponent reac-
tions (MCRs) have attracted considerable attention because
of their valuable features such as atom economy,
straightforward reaction design, energy savings, and
reduced waste. Highly functionalized small organic mole-
cules and new heterocyclic compounds can be synthesized
using MCRs. Multicomponent one-pot synthesis is of
particular interest because of its wide applicability [13–17].
In recent decades, many synthetic approaches for the
preparation of pyrano[2,3-c]pyrazole compounds have
been reported, wherein various improvements and modifi-
cations of the reaction have been made. These methods
include the two-component reaction of benzylidenemal-
ononitrile and pyrazole-5-one catalyzed by cinchona
alkaloid derivatives [18], the electrocatalyzed three-
component reaction of substituted piperidin-4-ones, mal-
ononitrile, and pyrazolin-5-ones [3], as well as a simple
and eco-friendly noncatalytic synthesis of both pyranopy-
razoles and N1-phenyl-substituted pyranopyrazoles
[19–23]. In addition, the four-component one-pot method is
widely used for the synthesis of pyrano[2,3-c]pyrazole
derivatives. For example, piperidine-catalyzed consecutive
one-pot synthesis of trifluoromethylated spiro[indole-3,40-
pyrano[2,3-c]pyrazole] derivatives has been reported [24].
Keywords Multicomponent reaction ꢀ
One-pot synthesis ꢀ CeCl3-promoted ꢀ
Bispyrano[2,3-c]pyrazole ꢀ Heterocycles
Introduction
Pyrano[2,3-c]pyrazoles are an important class of com-
pounds that include pharmaceuticals and biodegradable
agrochemicals. Many have been previously reported in the
literature as biologically important compounds with
potential anticancer [1], antibacterial [2, 3], antiherpetic
[4], anti-inflammatory [5, 6], and molluscicidal activity [7].
They have also been identified as promising inhibitors of
human Chk1 kinase in computer-based screening and kinase
inhibition assays [8, 9]. Furthermore, terephthalaldehyde is
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1104-6) contains supplementary
material, which is available to authorized users.
K. Ablajan (&) ꢀ L.-J. Wang ꢀ Z. Maimaiti ꢀ Y.-T. Lu
Key Laboratory of Oil and Gas Fine Chemicals, Ministry of
Education and Xinjiang Uyghur Autonomous Region, College of
Chemistry and Chemical Engineering, Xinjiang University,
Urumqi, China
e-mail: ablajan209@hotmail.com
123

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K. Ablajan et al.
Scheme 1
Four-component one-pot syntheses of multisubstituted bispyrano[2,3-c]pyrazoles
acetoacetate using CeCl3ꢀ7H2O as a catalyst [31]. Here, we
describe a facile and scalable four-component one-pot
synthesis of multisubstituted bispyrano[2,3-c]pyrazoles in
the presence of CeCl3ꢀ7H2O (10 mol%) as a catalyst in
ethanol (Scheme 1). The products are obtained in good
yield and chemical purity without further purification.
Table 1 Optimization of the reaction conditions and solvent
screening for the synthesis of 5a and 6a
Entry Reaction conditionsa
Solvent
Yieldb/%
5a 6a
1
No catalyst, reflux, 1 h
Ce(NO3)2 (10 mol%), reflux
InCl3 (10 mol%), reflux
ZnCl2 (10 mol%), reflux
EtOH
EtOH
EtOH
EtOH
5
8
2
60 62
55 60
45 48
76 75
78 77
18 15
35 32
3
Results and discussion
4
5
CeCl3ꢀ7H2O (10 mol%), reflux EtOH
CeCl3ꢀ7H2O (20 mol%), reflux EtOH
CeCl3ꢀ7H2O (10 mol%), 80 °C No solvent
CeCl3ꢀ7H2O (10 mol%), reflux H2O
In order to determine the optimum reaction conditions for
the synthesis of 5a via the one-pot route, we initially
investigated the reaction of methyl acetoacetate (1a),
hydrazine hydrate (2a), terephthalaldehyde (3), and mal-
ononitrile (4) under different reaction conditions
(Scheme 1). Also, we conducted the reaction of 1a, phen-
ylhydrazine (2b), 3, and 4 for the synthesis of 6a. The
detailed results are listed in Table 1.
6
7
8
9
CeCl3ꢀ7H2O (10 mol%), reflux EtOH/H2O (1:1) 55 50
10
11
12
13
14
CeCl3ꢀ7H2O (10 mol%), rt, 12 h EtOH
CeCl3ꢀ7H2O (10 mol%), reflux DMF
CeCl3ꢀ7H2O (10 mol%), reflux MeCN
CeCl3ꢀ7H2O (10 mol%), reflux MeOH
CeCl3ꢀ7H2O (10 mol%), reflux CH2Cl2
20 15
65 60
60 63
65 60
55 50
As shown in Table 1, when the reaction was conducted
without any catalyst, products 5a and 6a were obtained in 5
and 8 % yield using EtOH as a solvent, respectively, and
prolonged refluxing did not increase the product yield
(Table 1, entry 1). Other catalysts such as Ce(NO3)2, InCl3,
and ZnCl2 also catalyzed the reaction to give the products
in low yields (Table 1, entries 2–5). However, good yields
of products 5a (76 %) and 6a (75 %) were obtained when
CeCl3ꢀ7H2O was used as the catalyst in refluxing EtOH
(Table 1, entry 5). In addition, it is notable that the product
yield did not change significantly with increased amounts
of CeCl3ꢀ7H2O (Table 1, entry 6). In another attempt, when
the reaction was carried out at room temperature, only
a small amount of the product was obtained (Table 1,
entry 10).
Product 5a was obtained from the reaction of methyl acetoacetate
(2.0 mmol), hydrazine hydrate (2.0 mmol), terephthalaldehyde
(1.0 mmol), and malononitrile (2.0 mmol) in 15 cm3 of solvent;
product 6a was obtained using the same conditions with phen-
ylhydrazine (2.0 mmol) in place of hydrazine hydrate
a
Except entries 1 and 10, reaction time of all experiments is 20 min
b
Isolated yields
However, the systematic synthesis of multisubstituted bis-
pyrano[2,3-c]pyrazoles via a one-pot reaction route has not
been reported.
CeCl3ꢀ7H2O is a cheap, non-toxic, and ‘‘friendly’’
reagent [25–29], which has been utilized as an efficient
Lewis acid catalyst for the three-component coupling
of aldehydes, aromatic amines, and diethylphosphite
to produce a-aminophosphonates [30]. A series of 1,4-
dihydropyridines were efficiently synthesized by the reac-
tion of aldehydes with ammonium acetate and ethyl
Next, the effect of the reaction solvent was evaluated.
As shown in Table 1, low yields of products 5a (55–65 %)
and 6a (50–60 %) were obtained when the mixture was
refluxed in the presence of CeCl3ꢀ7H2O (10 mol%) as a
123

CeCl3-promoted one-pot synthesis
493
onto C=N and tautomerization generated the expected
target product.
Table 2 Synthesis of multisubstituted bispyrano[2,3-c]pyrazole
derivatives 5a–5f and 6a–6f
Entry Product R1
Reactant Time/min; yielda/%
R2 = CH3 R2 = C2H5
Experimental
1
5a
5b
5c
5d
5e
5f
CH3
2a
2a
2a
20/76
30/79
35/90
40/81
45/75
40/85
45/75
50/76
60/72
50/75
45/78
50/76
20/70
30/75
35/84
40/75
45/70
40/78
45/70
50/70
60/65
50/70
45/72
50/70
Melting points were measured in open end capillary tubes
on a Bu¨chi B-2540 digital melting point apparatus. Infrared
(IR) spectra were recorded on a Bruker EQUINOX 55
spectrophotometer as KBr pellets. 1H and 13C NMR spectra
were obtained on a Varian INOVA-400 instrument using
DMSO-d6 as a solvent. Chemical shifts are given in ppm
relative to TMS as an internal standard. ESI–MS spectra
were determined on an HP 1100 LC–MS (ESI). HRMS
(ESI) data were obtained on Micromass Q-Tof Global mass
spectrometer. Silica gel (GF-254) was used for TLC. All
chemical reagents were of analytical grade and used
without further purification.
2
C2H5
n-C3H7
3
4
iso-C3H7 2a
5
Ph
2a
2a
2b
2b
2b
6
CF3
7
6a
6b
6c
6d
6e
6f
CH3
C2H5
n-C3H7
8
9
10
11
12
a
iso-C3H7 2b
Ph
2b
2b
CF3
Isolated yields
Synthesis of the multisubstituted bispyrano[2,3-c]
pyrazole derivatives 5a–5f and 6a–6f
catalyst in different solvents such as DMF, MeCN, MeOH,
and CH2Cl2 (Table 1, entries 8–11). These results revealed
that using EtOH as the solvent afforded the best yields.
The optimized reaction conditions were tested for the
synthesis of other multisubstituted bispyrano[2,3-c]pyra-
zole derivatives via the four-component one-pot synthesis
route using CeCl3ꢀ7H2O (10 mol%) as a catalyst in re-
fluxing EtOH. In all cases, products 5a–5f and 6a–6f were
obtained in good yields (Table 2). The structures of the
To a mixture of b-keto ester (1, 2.0 mmol) and hydrazine
hydrate (85 %) or phenylhydrazine (2, 2.0 mmol) in
15 cm3 ethanol were added terephthalaldehyde (3,
1.0 mmol) and malononitrile (4, 2.0 mmol), followed by
CeCl3ꢀ7H2O (10 mol%). The reaction mixture was then
refluxed for 20–60 min. After the reaction reached com-
pletion, the mixture was cooled and large amounts of a
precipitate formed. The precipitate was filtered off and
washed thoroughly with EtOH to give the desired product.
1
products were confirmed on the basis of H NMR, IR, and
ESI–MS spectral analyses. The corresponding spectral data
were in agreement with the proposed structures of all target
compounds. Moreover, all reactions were complete within
60 min and all products could be purified by filtration of
the formed precipitate and washed thoroughly with EtOH
without recrystallization. Furthermore, the reaction was
also investigated using other ethyl b-keto esters. As shown
in Table 2, slightly lower yields of the products were
afforded when ethyl acetoacetates (1b) were used instead
of methyl acetoacetates (1a). Nonetheless, twelve products,
5a–5f and 6a–6f, were obtained under the optimized con-
ditions mentioned above.
The Ce3? ions from the CeCl3ꢀ7H2O catalyst may have
facilitated both the condensation reaction and the nucleo-
philic attack. A plausible reaction mechanism for the
synthesis of compound 5 is shown in Scheme 2. At first,
the condensation of the b-keto esters 1 with hydrazine
hydrate (2a) forms intermediate pyrazole-5-one A, and the
Knoevenagel condensation between terephthalic aldehyde
(3) and malononitrile (4) affords intermediate B. Then,
Michael reaction between intermediates A and B yields
C. Subsequent intramolecular nucleophilic attack of OH
4,40-(1,4-Phenylene)bis(6-amino-3-methyl-2,4-dihydro-
pyrano[2,3-c]pyrazole-5-carbonitrile) (5a, C22H18N8O2)
Light yellow crystals; yield 324 mg (76 %); m.p.: 300 °C;
ꢀ
IR (KBr): m = 3,231, 3,120, 2,187, 1,641, 1,593,
1,489 cm-1 1H NMR (400 MHz, DMSO-d6): d = 1.74
;
(s, 6H, 2 CH3), 4.57 (s, 2H, 2 CH), 6.84 (s, 4H, 2 NH2),
7.11 (s, 4H, C6H4), 12.08 (s, 2H, 2 NH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 9.58 (2C), 35.81 (2C), 57.04
(2C), 97.59 (2C), 120.64 (2C), 127.51 (4C), 135.47 (2C),
142.62 (2C), 154.60 (2C), 160.71 (2C) ppm; MS (ESI):
m/z = 427 ([M?H]?), 449 ([M?Na]?); HR-MS (ESI): calcd
for C22H18N8O2 ([M?H]?) 427.1553, found 427.1556.
4,40-(1,4-Phenylene)bis(6-amino-3-ethyl-2,4-dihydro-
pyrano[2,3-c]pyrazole-5-carbonitrile) (5b, C24H22N8O2)
White crystals; yield 359 mg (79 %); m.p.: [300 °C; IR
(KBr): m = 3,479, 3,243, 3,115, 2,970, 2,195, 1,638, 1,603,
1,488 cm-1; 1H NMR (400 MHz, DMSO-d6): d = 0.74 (t,
6H, 2 CH3), 2.09–2.15 (m, 4H, 2 CH2), 4.57 (s, 2H, 2 CH),
6.82 (s, 4H, 2 NH2), 7.10 (s, 4H, C6H4), 12.10 (s, 2H, 2
NH) ppm; 13C NMR (100 MHz, DMSO-d6): d = 12.34
123

494
K. Ablajan et al.
Scheme 2
3
_
_
Ce
R1
N
NC
H2O
R2OH
O
O
CeCl3·7H2O
Reflux
O
O
H2N
+
C
N
3
R1
OR2
Ce
R1
OR2
H2O
O
3
Ce
1
N
H
H
N
O
NH2
A
N
2a
Knoevenagel
condensation
R1
NC
C
N
OHC
A
CHO
H2O
NC
B
CN
3
4
H
N
R1
N
R1
NH
N
NC
NH
O
CN
3
HN
C
Ce
3
_
O
O
Ce
H
TM
H
O
5
C
NH
3
Ce
HN
CN
N
R1
NC
R1
HN
N
H
N
C
A plausible one-pot reaction mechanism for the synthesis of compound 5
(2C), 17.64 (2C), 35.90 (2C), 57.34 (2C), 96.90 (2C),
120.57 (2C), 127.51 (4C), 140.44 (2C), 143.16 (2C),
154.55 (2C), 160.50 ppm; MS (ESI): m/z = 455
([M?H]?), 477 ([M?Na]?); HR-MS (ESI): calcd for
C24H22N8O2 ([M?H]?) 455.1866, found 455.1873.
160.25 (2C) ppm; MS (ESI): m/z = 483 ([M?H]?), 505
([M?Na]?); HR-MS (ESI): calcd for C26H26N8O2
([M?H]?) 483.2,179, found 483.2169.
4,40-(1,4-Phenylene)bis(6-amino-3-phenyl-2,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitrile) (5e, C32H22N8O2)
Yellowish brown crystals; yield 414 mg (75 %); m.p.:
[300 °C; IR (KBr): m = 3,251, 3,130, 2,184, 1,641, 1,618,
1,499 cm-1; 1H NMR (400 MHz, DMSO-d6): d = 4.82 (s,
2H, 2 CH), 6.87 (s, 4H, 2 NH2), 6.98–7.00 (m, 4H, C6H4),
7.13–7.25 (m, 10H, 2 C6H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 18.40 (2C), 36.49 (2C), 58.55 (2C), 97.30
(2C), 120.26 (2C), 126.19 (4C), 127.29 (4C), 128.45 (6C),
137.96 (2C), 143.19 (2C), 155.90 (2C), 159.95 (2C) ppm;
MS (ESI): m/z = 551 ([M?H]?), 573 ([M?Na]?); HR-MS
(ESI): calcd for C32H22N8O2 ([M?H]?) 551.1866, found
551.1871.
4,40-(1,4-Phenylene)bis(6-amino-3-propyl-2,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitrile) (5c, C26H26N8O2)
White crystals; yield 434 mg (90 %); m.p.: 238–240 °C;
IR (KBr): m = 3,486, 3,233, 3,111, 2,967, 2,198, 1,633,
1,594 cm-1; 1H NMR (400 MHz, DMSO-d6): d = 0.59 (t,
6H, 2 CH3), 1.07–1.21 (m, 4H, 2 CH2), 1.99–2.17 (m, 4H,
2 CH2), 4.55 (s, 2H, 2 CH), 6.82 (s, 4H, 2 NH2), 7.09 (s,
4H, C6H4), 12.09 (s, 2H, 2 NH) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 13.28 (2C), 20.83 (2C), 26.11 (2C), 36.00
(2C), 57.39 (2C), 97.23 (2C), 120.52 (2C), 127.48 (4C),
139.64 (2C), 143.12 (2C), 154.32 (2C), 160.49 (2C) ppm;
MS (ESI): m/z = 483 ([M?H]?), 505 [M?Na]?; HR-MS
(ESI): calcd for C26H26N8O2 ([M?H]?) 483.2179, found
483.2166.
4,40-(1,4-Phenylene)bis(6-amino-3-trifluoromethyl-2,4-di-
hydropyrano[2,3-c]pyrazole-5-carbonitrile)
(5f, C22H12F6N8O2)
4,40-(1,4-Phenylene)bis(6-amino-3-isopropyl-2,4-dihydro-
pyrano[2,3-c]pyrazole-5-carbonitrile)
White crystals; yield 453 mg (85 %); m.p.: [300 °C; IR
(KBr): m = 3,245, 3,122, 2,207, 1,639, 1,582, 1,494 cm-1
;
(5d, C26H26N8O2)
Light yellow crystals; yield 391 mg (81 %); m.p.:
[300 °C; IR (KBr): m = 3,488, 3,248, 3,107, 2,970,
1H NMR (400 MHz, DMSO-d6): d = 0.64 (t, 6H, 2 CH3),
1.12–1.23 (m, 4H, 2 CH2), 1.99–2.13 (m, 4H, 2 CH2), 4.55
(s, 2H, 2 CH), 6.82 (s, 4H, 2 NH2), 7.09 (s, 4H, C6H4),
12.09 (s, 2H, 2 NH) ppm; 13C NMR (100 MHz, DMSO-
d6): d = 51.05 (2C), 73.04 (2C), 97.59 (2C), 116.52 (2C),
2,877, 2,195, 1,638, 1,603 cm-1 1H NMR (400 MHz,
;
DMSO-d6): d = 0.75 (d, 6H, 2 CH3), 1.04 (d, 6H, 2 CH3),
2.49–2.52 (m, 2H, 2 CH), 4.57 (s, 2H, 2 CH), 6.79 (s, 4H, 2
NH2), 7.08 (s, 4H, C6H4), 12.10 (s, 2H, 2 NH) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 20.39 (2C), 21.13 (2C),
24.91 (2C), 36.09 (2C), 57.73 (2C), 96.10 (2C), 120.52
(2C), 127.50 (4C), 143.50 (2C), 144.84 (2C), 154.62 (2C),
1
120.53 (q, JCF = 261 Hz, 2 CF3), 127.51 (4C), 137.47
(2C), 142.62 (2C), 154.20 (2C), 167.71 (2C) ppm; MS
(ESI): m/z = 535 ([M?H]?), 557 ([M?Na]?); HR-MS
(ESI): calcd for C22H12F6N8O2 ([M?H]?) 535.0987, found
535.0981.
123

CeCl3-promoted one-pot synthesis
495
4,40-(1,4-Phenylene)bis(6-amino-3-methyl-1-phenyl-1,4-di-
hydropyrano[2,3-c]pyrazole-5-carbonitrile)
(6a, C34H26N8O2)
(d, 6H, 2 CH3), 0.99 (d, 6H, 2 CH3), 1.97–2.41 (m, 2H, 2
CH), 4.70 (s, 2H, 2 CH), 7.07 (s, 4H, 2 NH2), 7.07–7.96
(m, 14H, C6H4 ? 2 C6H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 20.25 (2C), 21.39 (2C), 26.72 (2C), 36.34
(2C), 59.22 (2C), 97.31 (2C), 119.50 (2C), 120.10 (4C),
127.85 (4C), 129.12 (4C), 137.63 (4C), 142.86 (2C),
143.94 (2C), 153.81 (2C), 158.93 (2C) ppm; MS (ESI): m/
z = 635 ([M?H]?), 657 ([M?Na]?); HR-MS (ESI): calcd
for C38H34N8O2 ([M?H]?) 635.2805, found 634.2815.
White crystals; yield 433 mg (75 %); m.p.: 238–240 °C;
IR (KBr): m = 3,474, 3,325, 3,260, 3,193, 2,194, 1,660,
1,595, 1,518 cm-1
;
1H NMR (400 MHz, DMSO-d6):
d = 1.29 (s, 6H, 2 CH3), 4.70 (s, 2H, 2 CH), 7.21 (s, 4H,
2 NH2), 7.24–8.02 (m, 14H, C6H4 ? 2 C6H5) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 12.40 (2C), 51.54 (2C),
108.75 (2C), 112.28 (2C), 119.87 (2C), 126.06 (2C),
127.93 (4C), 128.64 (4C), 129.22 (4C), 137.41 (4C),
142.19 (2C), 143.67 (2C), 159.30 (2C) ppm; MS (ESI): m/
z = 579 [M?H]?; 601 ([M?Na]?); HR-MS (ESI): calcd
for C34H26N8O2 [M?H]? 579.2179, found 578.2171.
4,40-(1,4-Phenylene)bis(6-amino-1,3-diphenyl-1,4-dihydro-
pyrano[2,3-c]pyrazole-5-carbonitrile) (6e, C44H30N8O2)
Yellowish brown crystals; yield 547 mg (78 %); m.p.:
260–261 °C; IR (KBr): m = 3,459, 3,320, 3,201, 3,059,
2,192, 1,653, 1,591, 1,511 cm-1 1H NMR (400 MHz,
;
4,40-(1,4-Phenylene)bis(6-amino-3-ethyl-1-phenyl-1,4-di-
hydropyrano[2,3-c]pyrazole-5-carbonitrile)
(6b, C36H30N8O2)
DMSO-d6): d = 4.62 (s, 2H, 2 CH), 6.79 (s, 4H, 2 NH2),
7.05–7.97 (m, 20H, 4 C6H5), 7.08 (s, 4H, C6H4), 12.10 (s,
2H, 2 NH) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 40.75 (2C), 58.22 (2C), 94.31 (2C), 116.50 (2C),
121.83 (4C), 127.45 (2C), 127.89 (4C), 128.15 (2C),
128.55 (4C), 129.12 (4C), 131.18 (2C), 132.63 (4C),
140.16 (4C), 149.94 (2C), 154.81 (2C), 160.93 (2C) ppm;
MS (ESI): m/z = 703 ([M?H]?), 725 ([M?Na]?); HR-MS
(ESI): calcd for C44H30N8O2 ([M?H]?) 703.2492, found
702.2482.
White crystals; yield 460 mg (76 %); m.p.: 294–295 °C;
IR (KBr): m = 3,466, 3,323, 3,192, 2,963, 2,196, 1,662,
1,594, 1,516 cm-1
;
1H NMR (400 MHz, DMSO-d6):
d = 0.79 (t, 6H, 2 CH3), 2.06–2.31 (m, 4H, 2 CH2), 4.75
(s, 2H, 2 CH), 7.23 (s, 4H, 2 NH2), 7.27–8.06 (m, 14H,
C6H4 ? 2 C6H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 12.40 (2C), 18.69 (2C), 57.54 (2C), 107.85 (2C),
112.22 (2C), 119.76 (2C), 126.26 (2C), 127.83 (4C),
128.94 (4C), 129.32 (4C), 137.51 (4C), 143.09 (2C),
143.37 (2C), 159.69 (2C) ppm; MS (ESI): m/z = 607
([M?H]?), 629 ([M?Na]?); HR-MS (ESI): calcd for
C36H30N8O2 ([M?H]?) 607.2492, found 607.2486.
4,40-(1,4-Phenylene)bis(6-amino-3-trifluoromethyl-1-phe-
nyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile)
(6f, C34H20F6N8O2)
Yellow crystals; yield 521 mg (76 %); m.p.: 259–261 °C;
IR (KBr): m = 3,498, 3,248, 3,130, 2,986, 2,898, 2,190,
4,40-(1,4-Phenylene)bis(6-amino-3-propyl-1-phenyl-1,4-di-
hydropyrano[2,3-c]pyrazole-5-carbonitrile)
(6c, C38H34N8O2)
1,625, 1,602 cm-1 1H NMR (400 MHz, DMSO-d6):
;
d = 6.74–7.21(m, 10H, 2 C6H5), 7.65 (s, 4H, C6H5),
7.86 (s, 2H, NH2), 10.40 (s, 2H, 2 NH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 44.41 (2C), 58.54 (2C), 98.75
(2C), 116.28 (2C), 121.87 (4C), 122.67 (q, 1JCF = 265 Hz,
2 CF3), 126.06 (4C), 127.93 (4C), 129.04 (2C), 132.51
(4C), 140.15 (4C), 159.30 (2C) ppm; MS (ESI):
m/z = 687 ([M?H]?), 709 ([M?Na]?); HR-MS (ESI):
calcd for C34H20F6N8O2 ([M?H]?) 687.1613, found
686.1605.
Yellowish brown crystals; yield 456 mg (72 %); m.p.:
273–274 °C; IR (KBr): m = 3,466, 3,324, 3,194, 2,952,
2,193, 1,657, 1,592, 1,515 cm-1 1H NMR (400 MHz,
;
DMSO-d6): d = 0.74 (t, 6H, 2 CH3), 1.20–1.34 (m, 4H, 2
CH2), 2.0–2.32 (m, 4H, 2 CH2), 4.68 (s, 2H, 2 CH), 7.17 (s,
4H, 2 NH2), 7.21–7.96 (m, 14H, C6H4 ? 2 C6H5) ppm; 13
C
NMR (100 MHz, DMSO-d6): d = 13.58 (2C), 20.56 (2C),
28.79 (2C), 36.54 (2C), 58.43 (2C), 98.15 (2C), 119.92
(2C), 126.03 (4C), 127.87 (4C), 129.20 (4C), 137.49 (4C),
142.55 (2C), 143.71 (2C), 148.96 (2C), 159.10 (2C) ppm;
MS (ESI): m/z = 635 ([M?H]?), 657 ([M?Na]?); HR-MS
(ESI): calcd for C38H34N8O2 ([M?H]?) 635.2,805, found
634.2817.
Acknowledgments We gratefully acknowledge the Natural Science
Foundation of China (No. 21162028) and the Natural Science
Foundation of Xinjiang Science Technology Agency (No. 2009
211A02).
References
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