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A. M. Farag, Yehya M. Elkholy and K. A. Ali
Vol 45
Synthesis of 5-(2-Phenyl-2-oxoethyl)-1,3,4-triphenyl-4,5-
Ethyl 5-(hydrazinocarbonyl)-5-[2-(4-methylphenyl)-2-oxo-
ethyl]-1-(4-methylphenyl)-1-phenyl-1,4-dihydropyrazole-3-
carboxylate (6f). Yield 85%; mp 120 °C; ir (KBr) ꢀ/max cm-1
dihydro-1H-pyrazole 5-carbohydrazide and Ethyl 5-(hydra-
zinocarbonyl)-5-[2-phenyl-2-oxoethyl]-1,4-diphenyl-4,5-
dihydro-1H-pyrazole-3-carboxylate derivatives 6a,b and 6c-
f. General Procedure. Hydrazine hydrate (80%, 2 mL) was
added to a stirred solution of the appropriate spiropyrazolo-
furanone derivatives 5a-f (0.5 gm) in absolute ethanol (20 mL)
and the reaction mixture was stirred for 4 hours. The color of
spiropyrazolofuranone derivative disappears and white
precipitate was formed. The precipitated solid was collected by
filtration, washed with ethanol and crystalized from absolute
ethanol.
5-(2-Phenyl-2-oxoethyl)-1,3,4-triphenyl-4,5-dihydro-1H-
pyrazole-5-carbohydrazide (6a). Yield 80%; mp 175 °C; ir
(KBr) ꢀ/max cm-1 3300-3430 (NH, NH2), 1710, 1680 (2 C=O); 1H
nmr (ꢁ, ppm,CDCl3): 8.76 (s, 1H, NH), 3.75 (s, 2H, NH2), 4.15
(s, 2H, CH2), 4.83 (s, 1H, CH pyrazole), 7.25-7.51 (m, 20H,
ArHs). MS (m/z): 474 (M+), 456, 415, 336, 309, 194, 130, 91,
77, 51. Anal. Calcd for C30H26N4O2 (474.559): C, 75.92; H,
5.47; N, 11.80%. Found: C, 76.30; H, 5.70; N, 11.90%.
5-[2-(4-Methylphenyl)-2-oxoethyl]-1,3,4-triphenyl-4,5-
dihydro-1H-pyrazole-5-carbohydrazide (6b). Yield 82%;
mp.130 °C; ir (KBr) ꢀ/max cm-1 3300-3430 (NH, NH2), 1710
(C=O), 1680 (C=O). 1H nmr (ꢁ, ppm, CDCl3): 2.15 (s, 3H, CH3),
8.78 (s, 1H, NH), 3.78 (s, 2H, NH2), 4.16 (s, 2H, CH2), 4.84 (s,
1H, CH pyrazole), 7.25-7.50 (m, 19H, ArHs). Anal. Calcd for
C31H28N4O2 (488.58): C, 76.20; H, 5.77; N, 11.46%. Found: C,
76.60; H, 6.00; N, 11.60%.
1
3494, 3352 (NH, NH2), 1705, 1689 (2C=O); H nmr (ꢁ, ppm,
CDCl3): 1.15 (t, 3H, ester-CH3), 2.29 (s, 6H, 2CH3), 2.74 (s, 1H,
NH), 3.87 (s, 2H, NH2), 4.16 (s, 2H, CH2), 4.18 (q, 2H, ester-
CH2), 4.84 (s, 1H, CH pyrazole), 6.9-7.82 (m, 13H, ArHs).
Anal. Calcd for C29H30N4O4 (498.62): C, 69.86; H, 6.01; N,
11.23%. Found: C, 70.10; H, 6.21; N, 11.40 %.
Cyclization of 5-(2-Phenyl-2-oxoethyl)-1,3,4-triphenyl-4,5-
dihydro-1H-pyrazole-5-carbohydrazide. Synthesis of 1,3,4,9-
tetraphenyl-1,2,7,8-tetrazaspiro[4.5]deca-2,9-diene-6-one (10).
A mixture of glacial acetic acid (5 mL), hydrochloric acid (34%,
10 mL) and pyrazole-5-carbohydrazide 6a (20 mmol) was
refluxed for 5 hour. The reaction mixture was allowed to cool
and poured into ice-cold water. The precipitated solid was
collected by filtration, washed with water and crystallized from
ethanol. Yield 50%; mp 158 °C; ir (KBr) ꢀ/max cm-1 3417 (NH),
1
1744 (C=O); H nmr (ꢁ, ppm, DMSO-d6): 3.46 (s, 1H, CH-
pyridazine), 5.80 (s, 1H, CH-pyrazole), 7.31-7.88 (m, 20H,
ArHs), 8.66 (s, 1H, NH), 12.23 (s, 1H, NH). Anal. Calcd for
C30H24N4O (456.54): C, 78.92; H, 5.30; N, 12.27%. Found: C,
79.10; H, 4.90; N, 12.53%. 13C nmr (ꢁ, ppm, DMSO-d6): 47.81,
70.54, 95.62, 114.83, 115.18, 116.31, 122.12, 125.07, 126.81,
126.93, 127.09, 127.34, 127.65, 128.07, 128.26, 128.50, 128.72,
128.86, 129.26, 129.56, 129.88, 131.97, 132.69, 133.77, 135.85,
136.97, 137.65, 142.41, 148.52, 177.88.
Ethyl 5-(hydrazinocarbonyl)-5-[2-phenyl-2-oxoethyl]-1,4-
diphenyl-4,5-dihydro-1H-pyrazole-3-carboxylate (6c). Yield
70%; mp 128 °C; ir (KBr) ꢀ/max cm-1 3394, 3317 (NH, NH2),
REFERENCES
[1] Lim, S-G; Kwon, B-I; Choi, M-G ; Jun; C-H, Synlett,
2005, 1113.
1
1712, 1689 (2 C=O); H nmr (ꢁ, ppm, CDCl3): 1.13 (s, 3H,
ester-CH3), 2.67 (s, 2H, CH2), 2.74 (s, 1H, NH), 3.64 (s, 1H,
CH-pyrazole), 3.87 (s, 2H, NH2), 4.12 (q, 2H, ester-CH2), 7.25-
7.41 (m, 15H, ArHs). MS (m/z): 470 (M+), 452, 411, 390, 365,
233, 130, 105, 77, 51. 13C nmr (ꢁ, ppm, CDCl3): 13.91, 39.79,
58.10, 60.59, 75.26, 89.27, 119.72, 122.09, 124.09, 125.10,
127.87,128.25, 128.37, 128.59, 128.84,128.90, 129.17, 129.30,
129.65, 131.86, 134.49, 140.95, 141.92, 141.97, 161.66, 170.63.
Anal. Calcd for C27H26N4O4 (470.52): C, 68.92; H, 5.57; N,
11.90%. Found: C, 69.10; H, 6.01 N, 12.00%.
[2] Zaleso V. V.; Rubtsov A. E. Chemistry of Heterocyclic
compounds, 2004, 40, 133.
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compounds, 2002, 38, 1319.
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Waisser, K. Bioorg. Med Chem Lett., 2000, 10, 1893.
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Tetrahedron, 1998, 54, 135.
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Ethyl 5-(hydrazinocarbonyl)-5-[2-phenyl)-2-oxoethyl]-1(4-
methylphenyl)-4-phenyl-1H-pyrazole-3-carboxylate (6d).
Yield 75%; mp 160 °C; ir (KBr) ꢀ/max cm-1 3355, 3300 (NH,
NH2), 1712, 1687 (2C=O). 1H nmr (ꢁ, ppm, CDCl3): 1.15 (t, 3H,
ester-CH3), 2.74 (s, br, 1H, NH), 2.54 (s, 3H, CH3), 3.87 (s, 2H,
NH2),4.16 (s, 2H, CH2), 4.18 (q, 2H, ester-CH2), 4.94 (s, br, 1H,
CH-pyrazole), 7.17-7.29 (m, 14H, ArHs). Anal. Calcd for
C28H28N4O4 (484.55).: C, 69.40; H, 5.82; N, 11.56%. Found:
C, 69.80; H, 6.10; N, 11.80%.
[7] Yonetoku, Y.; Kubota, H.; Okamoto, Y.; Ishikawa, J.;
Takeuchi, M.; Ohta, M.; Tsukamoto, S. Bioorg Med Chem 2006, 14,
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Xie, X. Q. J. Med. Chem. 2006, 49, 625.
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P.; Kubota, H.; Kinet, J. P; Fleig, A.; Yamada T.; Penner, R. Mol.
Pharmacol. 2006, 69, 1413.
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Heterocyclic Chem., 2007, 44, 177.
Ethyl 5-(hydrazinocarbonyl)-5-[2-(4-methylphenyl)-2-oxo-
ethyl]-1,4-diphenyl-1H-pyrazole-3-carboxylate (6e). Yield
83%; mp 198 °C; ir (KBr) ꢀ/max cm-1 3327, 3276 (NH, NH2),
1718, 1697 (2C=O). 1H nmr (ꢁ, ppm, CDCl3): 1.14 (t, 3H, ester-
CH3), 2.32 (s, br, 1H, NH), 2.62 (s, 3H, CH3), 3.87 (s, 2H, NH2),
4.13 (s, 2H, CH2), 4.18 (q, 2H, ester-CH2), 4.80 (s, br., 1H, CH-
pyrazole), 7.17-7.38 (m, 14H, ArHs). 13C nmr (ꢁ, ppm, CDCl3):
13.94, 20.92, 39.89, 59.47, 60.94, 89.12, 120.10, 124.31, 124.98,
127.90, 128.62, 129.11, 129.21, 129.28, 134.52, 138.28, 13880,
141.06, 142.00, 161.63, 170.46. Anal. Calcd for C28H28N4O4
(484.55): C, 69.40; H, 5.82; N, 11.56%. Found: C, 69.70; H,
5.60; N, 11.70%.
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