596
M. A.-H. Zahran et al.
Arch. Pharm. Chem. Life Sci. 2007, 340, 591–598
by column chromatography, eluting with chloroform-ethylace-
tate (9 : 1) to afford the cycloadduct products 5a–c, 6a, b.
General synthetic procedure for 7a–d
Microwave irradiation conditions
To a mixture of pyrazolon-4-carbaldehyde 1a, d (1 mmol), few
drops of glacial acetic acid (5-6 drops), silica gel (0.75 g) and a sol-
ution of ethylcyanoacetate, malononitrile, respectively
(1 mmol), were added; the solvent was evaporated and then irra-
diated in a microwave oven at 350 W for the appropriate time
(Table 1). After irradiation, the product was dissolved in metha-
nol, filtered off, the filtrate concentrated, and the final product
was separated in pure form.
4-(8-Chloro-3a,4,5,9b-tetrahydro-3H-
cyclopenta[c]quinolin-4-yl)-5-phenyl-2,4-dihydro-3H-
pyrazol-3-one 5a
Green crystals, Yield 40%, Mp. 132-1338C ; IR (KBr): 3260 (NH),
1675 (C=O) cm– 1; 1H-NMR (300 MHz, CDCl3), (d ppm): 1.30 (m, 2H,
CH2 of cyclopentene), 4.23 (m, 4H, CH of cyclopentene, quino-
line), 6.62 (m, 1H, HC=C of cyclopentene), 7.1 (m, 1H, C=CH of
cyclopentene), 7.30–7.73 (m, 8H, Harom), 8.10 (s, 1H, CH of pyra-
zole); MS (EI) m/z (%) = 363 [M+] (1.4), 251 (2.5), 167 (15), 149 (100).
C21H18N3OCl (363.84). Anal. Calcd.: C; 69.32, H; 4.99, N; 11.55.
Found: C; 69.14, H; 5.13, N; 11.47%.
Conventional heating method
To a mixture of pyrazolon-4-carbaldehyde 1a, d (1 mmol) and a
solution of ethylcyanoacetate, malononitrile, respectively
(1 mmol), in ethanol (15 mL) and few drops of glacial acetic acid
(5–6 drops) were added. The reaction mixture was refluxed for
the appropriate time (Table 1). After cooling, the product was fil-
tered off and recrystallized from the appropriate solvent.
4-(8-Nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-
4-yl)-5-phenyl-2,4-dihydro-3H-pyrazol-3-one 5b
Yellowish green crystals; Yield 48%, Mp. 168–1708C; IR (KBr):
3480 (NH), 3360 (NH), 1632 (C=O) cm– 1 1H-NMR (300 MHz,
;
CDCl3), (d ppm): 1.27 (m, 2H, CH2 of cyclopentene), 4.35 (m, 4H,
CH of cyclopentene, quinoline), 6.65 (m, 2H, HC=CH of cyclopen-
tene), 7.3–8.07 (m, 8H, Harom), 8.10 (s, 1H, CH of pyrazole); MS (EI)
m/z (%) = 374 [M+] (8), 138 (42), 108 (81), 65 (100). C21H18N4O3
(374.39). Anal. Calcd.: C; 67.37, H; 4.85, N; 14.96. Found: C; 67.20,
H; 4.70, N; 14.91%.
Ethyl-2-cyano-3-(5-oxo-3-phenyl-4,5-dihydro-1H-pyrazol-
4-yl)acrylate 7a
Yellow crystals (ethanol); IR (KBr): 3238 (NH), 2209 (CN), 1759
1
(C=O), 1681 (C=O) cm– 1; H-NMR (300 MHz, DMSO-d6), (d ppm):
1.29 (t, 3H, J = 7.05 Hz, CH3-CH2-), 4.26 (q, 2H, J1 = 7.2 Hz J2
=
14.1 Hz, CH3-CH2-), 7.57–7.82 (m, 5H, Ph), 7.85 (s, 1H, CH of pyra-
zole), 8.73 (s, 1H, HC=C), 14.1 (s, 1H, NH); MS (EI) m/z (%) = 284 [M+]
(100), 239 (87), 77 (31). C15H13N3O3 (283.28). Anal. Calcd.: C; 63.60,
H; 4.63, N; 14.83. Found: C; 63.88, H; 4.45, N; 14.53%.
4-(8-Methoxy-3a,4,5,9b-tetrahydro-3H-
cyclopenta[c]quinolin-4-yl)-5-phenyl-2,4-dihydro-3H-
pyrazol-3-one 5c
Yellowish green crystals; Yield 41%, Mp. 151–1538C; IR (KBr):
[(5-Oxo-3-phenyl-4,5-dihydro-1H-pyrazol-4-
yl)methylene]malononitrile 7b
3254 (NH), 1673 (C=O) cm– 1 1H-NMR (300 MHz, DMSO-d6), (d
;
ppm): 1.28 (m, 2H, CH2 of cyclopentene), 3.61 (s, 3H, OCH3), 4.55
(m, 4H, CH of cyclopentene, quinoline), 6.50 (m, 1H, HC=C of
cyclopentene), 6.65 (m, 1H, C=CH of cyclopentene), 6.96–7.3 (m,
8H, Harom), 7.70 (s, 1H, CH of pyrazole); MS (EI) m/z (%) = 360 [M+1]
(13), 313 (34), 149 (43), 57 (100). C22H21N3O2 (359.42). Anal. Calcd.:
C; 73.52, H; 5.89, N; 11.69. Found: C; 73.80, H; 5.76, N; 11.68%.
Yellow crystals (ethanol); IR (KBr): 3181 (NH), 2219 (CN), 1714
(C=O) cm– 1; 1H-NMR (300 MHz, DMSO-d6), (d ppm): 7.28–7.60 (m,
5H, Ph), 7.67 (s, 1H, CH of pyrazole), 8.61 (s, 1H, HC=C), 13.1 (s,
1H, NH); MS (EI) m/z (%) = 237 [M+1] (20), 186 (71), 77 (100).
C13H8N4O (236.22). Anal. Calcd.: C; 66.1, H; 3.41, N; 23.72. Found:
C; 66.12, H; 4.26, N; 23.42%.
5-Phenyl-4-(6,6a,7,9a-tetrahydro-5H-cyclopenta[c]-1,6-
Ethyl-2-cyano-3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-
dihydro-1H-pyrazol-4-yl)acrylate 7c
naphthyridin-6-yl)-2,4-dihydro-3H-pyrazol-3-one 6a
Yellow crystals; Yield 43%, Mp. 173–1748C; IR (KBr): 3415 (NH),
1615 (C=O) cm– 1;1H-NMR (300 MHz, CDCl3), (d ppm): 1.25 (m, 2H,
CH2 of cyclopentene), 4.23 (m, 4H, CH of cyclopentene, naphthyr-
idine), 5.67 (m, 2H, HC=CH of cyclopentene), 7.27–7.55 (m, 8H,
Harom), 7.69 (s, 1H, CH of pyrazole). C20H18N4O (330.38). Anal.
Calcd.: C; 72.71, H; 5.49, N; 16.96. Found: C; 72.60, H; 5.00, N;
16.99%.
Yellow crystals (ethanol); IR (KBr): 2213 (CN), 1708 (C=O), 1679
(C=O) cm– 1; 1H-NMR (300 MHz, DMSO-d6), (d ppm): 1.27 (t, 3H, J =
7.05 Hz, CH3-CH2-), 2.51 (s, 3H, CH3), 3.39 (s, 3H, -NCH3), 4.24 (q,
2H, J1 = 6.9 Hz, J2 = 14.1 Hz, CH3-CH2-), 7.35–7.56 (m, 5H, Ph), 7.91
(s, 1H, HC=C); MS (EI) m/z (%) = 311 [M+] (89), 239 (38), 56 (100).
C17H17N3O3 (311.33). Anal. Calcd.: C; 65.58, H; 5.5, N; 13.5. Found:
C; 65.28, H; 5.91, N; 13.37%.
5-Phenyl-4-(6,6a,7,9a-tetrahydro-5H-cyclopenta[c]-1,5-
[(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-
naphthyridin-6-yl)-2,4-dihydro-3H-pyrazol-3-one 6b
Yellow crystals; Yield 36%, Mp. 142–1448C; IR (KBr): 3419 (NH),
1617 (C=O) cm– 1; 1H-NMR (300 MHz, DMSO-d6), (d ppm): 1.23 (m,
2H, CH2 of cyclopentene), 4.54 (m, 4H, CH of cyclopentene, naph-
thyridine), 5.65 (m, 2H, HC=CH of cyclopentene), 7.39–7.90 (m,
8H, Harom), 8.16 (s, 1H, CH of pyrazole), 9.76 (s, 1H, NH); MS (EI) m/
z (%) = 330 [M+] (100), 77 (45). C20H18N4O (330.38). Anal. Calcd.: C;
72.71, H; 5.49, N; 16.96. Found: C; 71.97, H; 5.8, N; 16.97%.
yl)methylene]malononitrile 7d
Yellow crystals (ethanol); IR (KBr): 2213 (CN), 1684 (C=O) cm– 1
;
1H-NMR (300 MHz, DMSO-d6), (d ppm): 2.51 (s, 3H, CH3), 3.39 (s,
3H, -NCH3), 7.35–7.59 (m, 5H, Ph), 7.81 (s, 1H, HC=C); MS (EI) m/z
(%) = 264 [M+] (100), 172 (71), 56 (52). C15H12N4O (264.28). Anal.
Calcd.: C; 68.17, H; 4.58, N; 21.20. Found: C; 68.25, H; 4.66, N;
21.53%.
i 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim