M.S. Karthikeyan et al. / European Journal of Medicinal Chemistry 42 (2007) 30e36
35
Table 3
Antifungal activities of hydroxy pyrazolines (7aeo)
Compd no.
Aspergillus fumigatus
Aspergillus flavus
Trichophyton mentagrophytes
Penicillium marneffei
Candida albicans
7a
14 (12.5)
11 (12.5)
13 (12.5)
21 (6.25)
12 (12.5)
19 (6.25)
18 (6.25)
19 (6.25)
e
9 (25)
11 (25)
15 (12.5)
18 (12.5)
e
7 (25)
10 (25)
10 (25)
12 (12.5)
15 (6.25)
20 (6.25)
12 (12.5)
20 (6.25)
18 (6.25)
17 (6.25)
e
e
7b
7c
15 (12.5)
10 (25)
19 (6.25)
e
11 (25)
19 (6.25)
10 (25)
7d
7e
7f
7g
16 (12.5)
16 (12.5)
15 (12.5)
10 (25)
e
16 (12.5)
12 (25)
9 (25)
18 (6.25)
19 (6.25)
20 (6.25)
12 (12.5)
17 (12.5)
20 (12.5)
19 (12.5)
e
7h
7i
7j
e
10 (25)
18 (6.25)
e
e
7k
7l
20 (6.25)
e
18 (6.25)
10 (25)
e
19 (6.25)
e
7m
7n
7o
e
e
10 (25)
e
e
20 (6.25)
e
10 (25)
e
18 (12.5)
23 (6.25)
e
20 (6.25)
e
14 (12.5)
22 (6.25)
12 (25)
21 (6.25)
Standard
‘‘e’’ Indicates bacteria are resistant to the compounds at concentration > 100 mg/ml; MIC values are given in brackets; MIC (mg/ml) ¼ minimum inhibitory con-
centration, i.e., lowest concentration to completely inhibit fungal growth; zone of inhibition is expressed in mm.
6.3. General procedure for the preparation of aryloxy
acid hydrazide (5)
proton, JHeF meta ¼ 6.6 Hz), 7.45e7.51 (m, 3H, phenyl pro-
tons), 7.71 (d, 1H, dichlorofluorophenyl proton, JHeF ortho
9.9 Hz), 7.74e7.77 (m, 2H, phenyl protons). Mass (m/z, %):
526 (Mþ, 25), 493 (76), 460 (28), 191 (12).
¼
Aryloxy acid was prepared from respective phenols. The
resulting acid was esterified by treating with absolute ethanol
in the presence of few drops of conc. H2SO4. Further treatment
with hydrazine hydrate yielded aryloxy acid hydrazide (5) in
good yields.
Compound 7d: IR (KBr) n/cmꢀ1: 3313 (OH), 3099 (Are
H), 2925 (CeH), 1604 (C]N), 1465 (C]C). 1H NMR
(CDCl3) d: 3.56 (s, 2H, OCH2), 3.87 (s, 3H, OCH3), 4.72 (s,
1H, OH), 5.06 (d, 1H, CH2, J ¼ 16.4 Hz), 5.13 (d, 1H, CH2,
J ¼ 16.4 Hz), 6.86 (d, 2H, p-chlorophenoxy protons,
J ¼ 9 Hz), 6.97 (d, 2H, p-anisyl protons, J ¼ 8.8 Hz), 7.21
(d, 2H, p-chlorophenoxy protons, J ¼ 9 Hz), 7.43 (d, 1H, di-
6.4. Procedure for the synthesis of 1-aryloxy-3-aryl-5-
hydroxy-5-aryl pyrazolines (7)
chlorofluorophenyl proton, JHeF
¼ 6.5 Hz), 7.67e7.71
meta
(m, 3H, dichlorofluorophenyl proton and p-anisyl protons).
Compound 7e: IR (KBr) n/cmꢀ1: 3317 (OH), 3091 (AreH),
2922 (CeH), 1666 (amide C]O), 1606 (C]N), 1465
To a mixture of chalcone dibromides (4) (0.01 mol) in ab-
solute ethanol (75 ml) aryloxy acid hydrazides (5) (0.01 mol)
and triethylamine (10 ml) were added. The reaction mixture
was heated under reflux for w12 h on a water bath. The con-
tents were reduced, cooled and poured onto crushed ice and
kept overnight. The resulting hydroxy pyrazolines (7) were
collected by filtration and recrystallised from suitable solvents.
Compound 7b: IR (KBr) n/cmꢀ1: 3303 (OH), 3039 (Are
H), 2916 (CH2), 1668 (amide C]O), 1593 (C]N), 1465
1
(C]C). H NMR (CDCl3) d: 3.55 (s, 2H, OCH2), 3.87 (s,
3H, OCH3), 4.83 (s, 1H, OH), 5.04 (d, 1H, CH2,
J ¼ 16.5 Hz), 5.13 (d, 1H, CH2, J ¼ 16.5 Hz), 6.83 (d, 2H,
p-cresyloxy protons, J ¼ 8.4 Hz), 6.97 (d, 2H, p-anisyl pro-
tons, J ¼ 8.7 Hz), 7.06 (d, 2H, p-cresyloxy protons,
J ¼ 8.4 Hz), 7.41 (d, 1H, dichlorofluorophenyl proton, JHeF
¼ 6.5 Hz), 7.68e7.72 (m, 3H, dichlorofluorophenyl pro-
meta
ton and p-anisyl protons). 13C NMR (CDCl3) d: 20.4, 47.9,
55.4, 65.4, 90.9, 114.3, 116.1, 116.3, 122.9, 125.8, 126.8,
128.4, 128.8, 129.9, 130.6, 131.0, 132.4, 139.7, 154.2,
155.5, 155.9, 158.0, 161.8, 167.5.
1
(C]C). H NMR (CDCl3) d: 2.27 (s, 3H, CH3), 3.58 (s, 2H,
OCH2), 4.77 (s, 1H, OH), 5.07 (d, 1H, CH2, J ¼ 16.5 Hz),
5.15 (d, 1H, CH2, J ¼ 16.5 Hz), 6.83 (d, 2H, p-cresyloxy pro-
tons, J ¼ 8.2 Hz), 7.06 (d, 2H, p-cresyloxy protons,
J ¼ 8.2 Hz), 7.42 (d, 1H, dichlorofluorophenyl proton, JHeF
Compound 7f: IR (KBr) n/cmꢀ1: 3315 (OH), 3099 (AreH),
2937 (CeH), 1676 (amide C]O), 1595 (C]N), 1469
¼ 6.6 Hz), 7.44e7.49 (m, 3H, phenyl protons), 7.69 (d,
meta
1
(C]C). H NMR (CDCl3) d: 3.55 (s, 2H, OCH2), 3.87 (s,
1H, dichlorofluorophenyl proton, JHeF
7.75e7.78 (m, 2H, phenyl protons).
¼ 9.9 Hz),
ortho
3H, OCH3), 4.68 (s, 1H, OH), 5.15 (d, 1H, CH2,
J ¼ 16.5 Hz), 5.21 (d, 1H, CH2, J ¼ 16.5 Hz), 6.79 (d, 1H, di-
chlorophenoxy protons, J ¼ 8.8 Hz), 7.13 (dd, 1H, dichloro-
phenoxy protons, J ¼ 2.4 Hz), 7.36 (d, 1H, dichlorophenoxy
protons, J ¼ 2.5 Hz), 7.44 (m, 3H, dichlorofluorophenyl proton
and p-anisyl protons), 7.68 (d, 2H, dichlorofluorophenyl pro-
ton and p-anisyl protons). Mass (m/z, %): 556 (Mþ, 15), 461
(25), 353 (5), 191 (5).
Compound 7c: IR (KBr) n/cmꢀ1: 3398 (OH), 3099 (AreH),
1
1670 (amide C]O), 1571 (C]N), 1471 (C]C). H NMR
(CDCl3) d: 3.58 (s, 2H, OCH2), 4.82 (s, 1H, OH), 5.17 (d,
1H, CH2, J ¼ 16.5 Hz), 5.23 (d, 1H, CH2, J ¼ 16.5 Hz), 6.80
(d, 1H, dichlorophenoxy protons, J ¼ 8.8 Hz), 7.13 (dd, 1H, di-
chlorophenoxy protons, J ¼ 2.4 Hz), 7.36 (d, 1H, dichlorophe-
noxy protons, J ¼ 2.5 Hz), 7.43 (d, 1H, dichlorofluorophenyl