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J. Safaei-Ghomi et al. / Chinese Chemical Letters 25 (2014) 401–405
R
O
R
O
O
CN
CuI NP
S
+
O
.
+
+
NH -NH H O
2
2
2
N
N
X
solvent-free
X
O
CHO
X= CN, COOEt
H N
2
1
2
3
4
5
Scheme 1. Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives.
(solvent-free) [40], AL-KIT-6(ethanol, 60 8C, 4 h) [41], NiCl2ꢀ6H2O
(ethanol/reflux) [42] InCl3 [43].
mp 247–249 8C, IR (KBr, cmꢁ1):
1H NMR (400 MHz, DMSO-d6):
n
d
max 3383, 3300, 2207, 1659, 1603;
2.43 (3H, s, CH3), 6.30 (1H, s, CH),
Herein, we report the use of CuI nanoparticles as an efficient
catalyst for the preparation of 1H-pyrazolo[1,2-b]phthalazine-
5,10-diones by the four-component condensation reactions of
phthalic anhydride, hydrazine monohydrate, aromatic aldehydes
and malononitrile or ethyl cyanoacetate under solvent-free
conditions in good to excellent yields (Scheme 1).
7.17–7.28 (4H, m, Ar), 7.96–8.25 (6H, m, Ar and NH2); 13C NMR
(100 MHz, DMSO-d6): d 18.65, 61.2, 62.5, 122.0, 126.8, 127.2, 127.8,
128.0, 128.3, 128.5, 128.7, 130.5, 133.8, 134.8, 135.2, 136.5, 153.7,
154.2, 156.6. Anal. Calcd. for C19H14N4O2: C 69.09, H 4.27, N 16.95,
Found: C 68.98, H 4.25, N 16.98, MS (EI) (m/z): 330.
3-Amino-1-(3-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (5b): Yellow powder;
mp 250–252 8C, IR (KBr, cmꢁ1):
1H NMR (400 MHz, DMSO-d6):
nmax 3361, 3259, 2194, 1658, 1570;
2. Experimental
d
2.27 (3H, s, CH3), 6.05 (1H, s, CH),
7.12–7.24 (4H, m, Ar), 7.96–8.26 (6H, m, Ar and NH2); 13C NMR
2.1. Preparation of CuI nanoparticles
(100 MHz, DMSO-d6): d 24.0, 61.3, 63.2, 122.1, 122.3, 127.2, 127.4,
127.8, 128.2, 128.6, 128.9, 131.4, 134.0, 134.6, 135.6, 136.3, 154.0,
154.5, 157.3. Anal. Calcd. for C19H14N4O2: C 69.09, H 4.27, N 16.95,
Found: C 69.15, H 4.15, N 16.87, MS (EI) (m/z): 330.
The CuI nanoparticles were prepared according to the proce-
dure reported in the literature [44]. Where the catalyst was
prepared by ultrasonic irradiation approach. Firstly, the copper
substrate (CuSO4) (1 mmol) is cleaned ultrasonically for 20 s in
acetone and then in a 2 mol/L HCl solution, followed by repeated
rinsing with distilled water. After drying, the substrate is dipped
slowly into a solution of KI (2 mmol) in 40 mL of distilled water,
sonicated and allowed to react for 30 min. When the reaction was
completed, a gray precipitate was obtained. The solid was filtered
and washed with distilled water, ethanol and dried at room
temperature for 48 h.
3-Amino-1-(4-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (5c): Yellow powder;
mp 253–255 8C, IR (KBr, cmꢁ1):
1H NMR (400 MHz, DMSO-d6):
n
d
max 3361, 3259, 2196, 1656, 1569;
2.28 (3H, s, CH3), 6.07 (1H, s, CH),
7.14–7.33 (4H, m, Ar), 7.94–8.25 (6H, m, Ar and NH2); 13C NMR
(100 MHz, DMSO-d6):
d 21.2, 62.3, 64.0, 123.1, 1234, 127.4, 127.6,
127.9, 128.1, 128.7, 130.2, 130.8, 133.3, 134.6, 135.0, 136.5, 153.0,
154.7, 157.0. Anal. Calcd. for C19H14N4O2: C 69.09, H 4.27, N 16.95,
Found: C 69.11, H 4.19, N 16.90, MS (EI) (m/z): 330.
3-Amino-1-(4-isopropylphenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (5d): Yellow powder;
2.2. General procedure for the preparation of 1H-pyrazolo[1,2-
b]phthalazine-5,10-dione derivatives
mp 265–267 8C, IR (KBr, cmꢁ1):
1H NMR (400 MHz, DMSO-d6):
nmax 3368, 3264, 2191, 1659, 1569;
d
1.18 (6H, d, J = 6.8 Hz), 2.92 (1H,
Hydrazine monohydrate (1 mmol) and phthalic anhydride
(1 mmol) were mixed at 70 8C (15 min). Then, aromatic aldehydes
(1 mmol), malononitrile or ethyl cyanoacetate (1 mmol) and CuI
nanoparticles (10% mol), as catalyst, was added and stirred at 70 8C
under solvent-free conditions for the specific time (Table 1). After
completion of the reaction, the reaction mixture was recrystallized
from MeOH to afford the pure product.
m), 6.09 (1H, s, CH), 7.23–7.35 (4H, m, Ar), 7.95–8.24 (6H, m, Ar and
NH2); 13C NMR (100 MHz, DMSO-d6):
24.3, 33.6, 61.3, 63.4, 116.1,
d
126.9, 127.32, 127.7, 129.1, 133.6, 134.21, 148.4, 150.6, 153.4,
156.8. Anal. Calcd. for C21H18N4O2: C 70.36, H 5.06, N 15.63, Found:
C 70.29, H 4.99, N 15.67, MS (EI) (m/z): 358.
3-Amino-1-(4-hydroxyphenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (5e): Yellow powder;
3-Amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (5a): Yellow powder;
mp 270–272 8C, IR (KBr, cmꢁ1):
1H NMR (400 MHz, DMSO-d6):
J = 8 Hz, Ar), 7.22–7.24 (2H, d, J = 8 Hz, Ar), 7.95–8.24 (6H, m, Ar
and NH2), 9.51 (1H, s, OH); 13C NMR (100 MHz, DMSO-d6):
61.4,
nmax 3372, 3259, 2197, 1663, 1568;
d
6.02 (1H, s), 6.70–6.72 (2H,d,
Table 1
The model reaction was carried out by various catalystsa
d
62.6, 115.0, 116.2, 126.6, 127.3, 128.3, 128.6, 128.8, 133.6, 134.5,
150.5, 153.5, 156.6, 157.6. Anal. Calcd. for C18H12N4O3: C 65.06, H
3.64, N 16.85, Found: C 64.98, H 3.57, N 16.80, MS (EI) (m/z): 332.
3-Amino-1-(4-chlorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyr-
azolo[1,2-b]phthalazine-2-carbonitrile (5g): Yellow powder; mp
Entry
Catalyst
Mol%
Time (min)
Yieldb (%)
1
2
FeCl3
MgO
15
10
10
20
10
10
15
5
80
80
40
50
35
45
55
61
75
82
93
92
3
GaCl3
Et3N
100
180
45
4
5
CuCl
270–272 8C, IR (KBr, cmꢁ1):
NMR (400 MHz, DMSO-d6):
n
d
max 3375, 3259, 2194, 1659, 1655; 1H
6.14 (1H, s, CH), 7.39–7.52 (4H, m, Ar),
6
CuBr
45
7
CuI
40
7.94–8.26 (6H, m, Ar and NH2); 13C NMR (100 MHz, DMSO-d6):
d
8
CuI NPs
CuI NPs
CuI NPs
25
61.3, 62.8, 116.3, 127.2, 127.7, 128.8, 129.3, 133.3, 134.3, 135.1,
137.9, 151.2, 154.1, 157.2. Anal. Calcd. for C18H11N4O2Cl: C 61.64,
H 3.16, N 15.97, Found: C 61.51, H 3.13, N 16.01, MS (EI) (m/z): 350.
Ethyl 3-amino-5,10-dihydro-1(4-isopropylphenyl)-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5i): Yellow powder;
9
10
15
25
10
25
a
Phthalic anhydride (1 mmol), hydrazine monohydrate (1 mmo1), benzaldehyde
(1 mmol) and malononitrile (1 mmol).
b
Isolated yield.