May 2010
Synthesis of Some New Pyridazin-3-one Derivatives and Their Utility
in Heterocyclic Synthesis
537
water. The precipitate was collected by filtration, and the solid
product was recrystallized from methanol.
Synthesis of 4-(4-methylphenyl)-2-{[6-(4-methylphenyl)-
4,5-dihydropyrimidin-2-yl]thio}-4-oxobutanoic acid 12. A
mixture of 1b (0.01 mol) and compound 11 (0.01 mol) was
refluxed in dry benzene (30 mL) containing few drops of
pipredine for 6 h. The solution was evaporated and the product
was collected and recrystallized from ethanol.
12. Pale yellow (58%), m.p. 183ꢁC, mmax/cmꢀ1 (KBr) 1682,
1642 (2C¼¼O), 1355 (CASAC); 1H NMR (DMSO) d ¼ 2.11
ppm (s, 6H, 2CH3), 2.12–2.35 (broad s, 6H, 3CH2), 3.11 (d,
1H, CH), 6.94–8.23 (m, 8H, ArH), 12.44 (s, 1H, COOH); m/z
394 (Calcd. for C22H22N2O3S: C, 66.98; H, 5.62; N, 7.10; S,
8.13%. Found: C, 67.11; H, 5.33; N, 6.99; S, 8.00%).
7a. Brown (77%), m.p. 199ꢁC, mmax/cmꢀ1 (KBr) 1612
(C¼¼N), (Calcd. for C10H6N2ClBr: C, 44.56; H, 2.24; N,
10.39% Found: C, 44.24; H, 2.22; N, 10.41.00%).
7b. Gray (65%), m.p. 165C, mmax/cmꢀ1 (KBr) 1612 (C¼¼N),
m/z 204 (Calcd. for C11H9N2Cl: C, 64.56; H, 4.43; N, 13.69%
Found: C, 64.68; H, 4.18; N, 13.22%).
Synthesis of 3-(4-bromo- (methyl)phenyl)-6-hydrazino-
pyridazine 8a,b. A mixture of compounds 7a,b (0.01 mol)
and hydrazine hydrate (0.015 mol) was refluxed for 6 h in n-
butanol (50 mL), and the solid obtained was collected and
recrystallized from suitable solvent.
8a. Pale brown (75%), m.p. 184ꢁC, from MeOH, mmax/cmꢀ1
(KBr) 3319–3199 (NH, NH2), m/z 265 (Calcd. for C10H9N4Br:
C, 45.30; H, 3.42; N, 21.13% Found: C, 45.00; H, 3.69; N,
20.98%).
8b. Yellow (71%), m.p. 155ꢁC, from EtOH, mmax/cmꢀ1
(KBr) 3314–3195 (NH, NH2), m/z 200 (Calcd. for C11H12N4:
C, 65.98; H, 6.04; N, 27.98% Found: C, 66.02; H, 6.11; N,
27.68%).
REFERENCES AND NOTES
[1] Meki, N.; Lomioka, H.; Fujumot, K.; Jmahese, T.; Mekya, K.
Jpn Kokau Tokkyo Jpo2 1990, 45, 471; Chem Abstr 1990, 113, 54361.
[2] Ywan, B.; Liu, C.; Lian Gaodeng, G. Xuexws Huaxue Xue-
bao 1989, 10, 543; Chem Abstr 1990, 112, 158175.
[3] Bettarini, F.; Lapuzzi, L.; Massimini, S.; Castoro, P.; Cap-
riale, V. Eur. Pat. Appl. Ep. 391390(CL CO 7D 23716) 1990; Chem
Abstr 1991, 114, 12239.
Synthesis
of
2-[6-(4-bromophenyl)pyridazin-3-yl]-5-
methyl-2,4-dihydro-3H-pyrazol-3-one 9. A mixture of equiv-
alent amounts of compound 8a (0.01 mol) and ethylacetoace-
tate in 50 mL ethanol was refluxed for 6 h. The reaction mix-
ture was concentrated to separate the solid product, filtered
off, and recrystallized from ethanol.
[4] Snmez, M.; Berber, I.; Akbaꢀs, E. Eur J Med Chem 2006,
41, 101.
[5] Freud, W.; Hawprecht, G.; Wuozer, B.; Westphslen, K. O.;
Weyer, M. Ger. Offen. DE 3807896 (CL CO 7D 237/14) 1989; Chem
Abstr 1990, 113, 23935.
9. White (62%), m.p. 235ꢁC,
m
max/cmꢀ1 (KBr), 1643
[6] Wriede, V.; Wuerzer, B.; Meyer, N.; Westphalen, K. O.
Ger. Offen DE 3825468 (CL CO 7D 237/22), 1990; Chem Abstr 1990,
113, 23936.
(C¼¼O), 1582 (C¼¼N); 1H NMR (DMSO) d ¼ 2.04 (s, 3H,
CH3), 2.23 (s, 2H, CH2), 7.41–8.22 (m, 6H, ArH); m/z 331
(Calcd. for C14H11N4OBr: C, 50.77; H, 3.35; N, 16.92%
Found: C, 50.25; H, 3.45; N, 16.65%).
[7] Barlogova, S.; Guint, J. Cesk Hyg 1975, 20, 5.
[8] Bergmann, R.; Gericke, R. J Med Chem 1990, 33, 492.
[9] Schoen, W. Eur. Pat. Appl. EP 347987(CL CO 7K 5/02),
1989; Chem Abstr 1991, 114, 229391.
Synthesis
of
6-(4-bromophenyl)-3-methyl[1,2,4]tria-
zolo[4,3-b]pyridazine 10. Method A. A mixture of 8a (0.01
mol) and acetic acid (30 mL) was refluxed for 8 h. The reac-
tion mixture was left to cool, and the precipitated solid product
was collected by filtration and recrystallized from ethanol.
Method B. A mixture of 8a (0.01 mol) and acetohydrazide
(0.01 mol) was refluxed for 5 h in absolute ethanol (20 mL).
The reaction mixture was diluted by water, collected by filtra-
tion, and recrystallized from ethanol.
[10] Blaschhe, H.; Straissing, H.; Fillier, H.; Enznhofer, R. Eur.
Pat. Appl. E. P. 372305(CL CO 7D 403/12), 1990; Chem Abstr 1990,
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[11] Rabat, C.; Coudert, P.; Tronche, P.; Bastide, J.; Bastide, P.;
Privat, A. M. Chem Pharm Bull 1989, 37, 2832.
[12] Baddar, F. G.; El-Habashi, A.; Fateen, A. K. J Chem Soc
1965, 3342.
1
10. Brown (56%), m.p. 212ꢁC, H NMR (DMSO) d ¼ 1.98
[13] Juranic, Z.; Stevaic, L.; Dra kulic, B.; Stano, T.; Kovic, J.;
Radularic, S.; Juranic, I. J Serb Chem Soc 1990, 64, 505.
[14] El-Mobayad, M.; Sayed, G. H.; El-Shekeil, A. G.; Abd El-
Ghani, E. Indian J Chem Sect B 1990, 29, 72.
ppm (s, 3H, CH3), 7.00–8.23 (m, 6H, C6H4, HC¼¼CH); m/z
289 (Calcd. for C12H9N4Br: C, 49.85; H, 3.14; N, 19.38%.
Found: C, 49.95; H, 3.33; N, 19.01%).
[15] El-Mobayad, M.; Sayed, G. H.; El-Shekeil, A. G.; Abd El-
Ghani, E. Egypt J Chem 1991, 34, 73.
Synthesis of 6-(4-methylphenyl)-2-thioxo-2,3,4,5-tetrahy-
dropyrimidine-4-carboxylic acid 11. Compound 1b (0.01
mol) was refluxed with thiourea (0.01 mol) in 30 mL acetic
acid for 3 h. The reaction mixture was cooled, left at room
temperature over night, and filtered off to give pale yellow
needles of the product that was recrystallized from ethanol.
11. Yellow (64%), m.p. 250ꢁC, mmax/cmꢀ1 (KBr) 3242
[16] Juralg, Z.; Sterovic, L. J.; Drokulic, B.; Stano Jkovic, T.;
Radulovic, S.; Jurovic, I. J Serb Chem Soc 1999, 64, 505.
[17] Wasfy, A. F.; Arief, M. H.; Amine, M. S.; Donia, S. G.;
Aly, A. A.; Z Nat forsch 2002, 57b, 668.
[18] Cromwell, N. H.; Cook, K. E.; Greger, P. L. J Am Chem
Soc 1965, 78, 4416.
1
(NH), 1678 (C¼¼O), 1491 (C¼¼S); H NMR (DMSO) d ¼ 2.12
[19] Dixon, S.; Gregory, H.; Wiggins, L. F. J Chem Soc 1949,
2139.
ppm (s, 3H, CH3), 2.23 (s, 2H, CH2), 3.34 (s, 1H, CH), 6.88–
7.81 (m, 4H, ArH), 8.78 (s, 1H, NH), 12.41 (s, 1H, COOH);
m/z 248 (Calcd. for C12H12N2O2S: C, 58.05; H, 4.87; N,
11.28; S, 12.91%. Found: C, 58.24; H, 5.01; N, 11.28; S,
12.84%).
[20] Ji, J. G.; Li, T.; Mortell, K. H.; Schrimpf, M. R.; Nersesian,
D. L.; Pan, L. P. PCT W.O. Pat. 2006065233, 2006.
[21] Cao, L. H.; Wang, C. F.; Tao, J. Chin J Organic Chem
2006, 26, 1686.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet