Vol. 28, No. 7 (2016)
Synthesis of Some Pyridazine Based Pyrazolines 1411
phenylprop-2-en-1-one (5) m.p.: 110-114 °C, 3-(4-nitoro-
phenyl)-1-phenylprop-2-en-1-one (6) m.p.: 155-157 °C.
3-Chloro-6-[5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-
1H-pyrazol-1-yl]pyridazine (10): It was obtained from the
reaction of an equimolar quantities (3.46 mmol) of 3-chloro-
6-hydrazinylpyridazine (0.5 g), 3-(4-chlorophenyl)-1-phenyl-
prop-2-en-1-one (5) (0.83 g) and piperidine 1 mL in 10 mL
Pyrazolines (7-11)
MethodA:An equimolar quantity (3.46 mmol) of 3-chloro-
6-hydrazinylpyridazine [7] (0.5 g), an appropriate chalcone
(2-6) (0.72 g) and 10 mL ethanol was heated under reflux for
6 h. The reaction mixture was cooled and diluted with 20 mL
water, the precipiate formed were filtered, dried at room tempe-
rature and was purified by column chromatography on basic
aluminium oxide, using benzene as an eluent.
Method B: The mixture of reactants was heated under
reflux in toluene for 6 h. the same product was obtained as in
method A.
Method C: The mixture of reactants was heated under
reflux in ethanol in the presence of 1 mL piperidine for 6 h.
The best results were obtained from method C, hence the
rest of the reactions of 3-chloro-6-hydrazinyl pyridazine and
other chalcones were performed following this method.
3-Chloro-6-(3,5-diphenyl-2,3-dihydro-1H-pyrazol-1-
yl)pyridazine (7): It was obtained from the reaction of an
equimolar quantities (3.46 mmol) of 3-chloro-6-hydrazinyl-
pyridazine (0.5 g), (2) (0.55 g) and piperidine 1 mL in 10 mL
ethanol.
ethanol.Yield: 1.0 g (78 %); m.p.: 173-175 °C; IR (KBr, νmax
,
cm-1), 1624, 1463, 3054, 2999, 2935, 1582,1565 and 1443.MS
m/z 370 [M+,100], 371 [M+ 33], 372 [M+ 22]. 1H NMR (CDCl3)
δ: 7.26 (s, 1H, 5-H pyrazole), 7.28 (d, J = 4.2 Hz, 2H, 4-H
pyrazole), 7.39-7.49 (m, 5H, 3-phenyl), 7.51 (d, J = 9.5 Hz,
1H, 4-H pyridazine), 7.60 (d, J = 9.5 Hz, 1H, 5-H pyridazine),
7.71-7.77 (m, 4H, 5-(4-chlorophenyl).
3-Chloro-6-[5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-
1H-pyrazol-1-yl]pyridazine (11): It was obtained from the
reaction of an equimolar quantities (3.46 mmol) of 3-chloro-
6-hydrazinylpyridazine (0.5 g) and 3-(4-nitorophenyl)-1-
phenylprop-2-en-1-one (6) (0.87 g) and piperidine 1.0 mL in
10 mL ethanol. Yield: 0.74 g (57 %); m.p.: 163-168 °C; IR
(KBr, νmax, cm-1): 1537, 1355 (-NO2) 1619, 1490, 3276 2945,
2880 and 1420. MS m/z %: 379 [M+, 100] 381 [M+, 33].
RESULTS AND DISCUSSION
Pyrazolines (7-11) were prepared in good yields by
the reaction of respective chalcones (2-6) with 3-chloro-6-
hydrazinylpyridazine. These were characterized through their
Yield: 0.70 g (60 %); m.p.: 188-190 °C; IR (KBr, νmax
,
cm-1): 1617, 1584, 3058, 2999, 2920 &1445. MS m/z % 332
[M+, 100] 334 [33 %]; Elemental analysis for C19H13N4Cl:
Calculated: C, 68.57; H, 3.94; N, 16.84. Found: C, 68.28; H,
1
spectral data (IR, H NMR and mass) while (7) in addition
gave the expected elemental analysis. The IR spectra displayed
the absorption bands for the OH or the NO2 functionalities.
1
3.92; N, 16.20 %; H NMR (DMSO-d6): δ: 5.9 (s, 2H, 4-H
1
The H NMR data was also consistent with the designated
pyrazole), 7.24-7.34 (m, 5H, 2,3,4,5,6-H 3-phenylpyrazole),
7.51 (d, J = 9.0 Hz, 1H, 4-H pyridazine), 7.60 (d, J = 9.0 Hz,
1H, 5-H pyridazine), 7.69 (m, 5H, 5-phenyl pyrazole).
Method B:Yield 16 %; Method C: Yield 60 %.
structures. The mass spectra of these pyrazolines showed the
molecular ion as the base peak together with the M+2 due to
37Cl isotope with the proportionate intensity (3:1).
3-Chloro-6-(3-ethyl-5-phenyl-2,3-dihdro-1H-pyrazol-
1-yl)pyridazine (8): It was obtained from the reaction of an
equimolar quantities (3.46 mmol) of 3-chloro-6-hydrazinyl-
pyridazine, 1-phenylpent-1-en-3-one (3) (0.55 g) and piperi-
dine 1 mL in 10 mL ethanol. Yield: 0.5 g (51 %); m.p.: 102-
104 °C; IR (KBr, νmax, cm-1):1611, 1495, 1382, 1478, 3023,
2966, 2926, 1581 and 1565. MS m/z %: 286 [M+, 100], 288
[M+, 33].
R1
N
N
R2
N
N
4-[1-(6-Chloropyridazin-3-yl)-5-phenyl-2,3-dihydro-
1H-pyrazol-3-yl]phenol (9): It was obtained from the reaction
of an equimolar quantities (3.46 mmol) of 3-chloro-6-hydra-
zinylpyridazine (0.5 g), 1-(4-hydroxyphenyl)-3-phenylprop-
2-en-1-one (4) (0.76 g) and piperidine 1.0 mL in 10 mL
ethanol. Yield: 0.6 g (49.58 %); m.p.: 150-155 °C; IR (KBr,
Cl
7-11
(7) R1= R2= C6H5 (8) R1= C2H5, R2= C6H5 (9) R1= 4-OHC6H4, R2= C6H5
(10) R1= C6H5, R2= 4-ClC6H4 (11) R1= C6H5, R2= 4-NO2C6H4
Antibacterial activity: These pyrazolines were tested,
by disc diffusion method, for their antibacterial properties
against various organisms. The results are presented in Table-1.
ν
max, cm-1): 3297, 1611, 1495, 3276 (-OH str.) 2945, 2889 and
1424.; MS m/z %:252 [M+, 100], 254 [M+ 33].
TABLE-1
ANTIBACTERIAL ACTIVITY OF 1,3,5-TRISUBSTITUTED PYRAZOLINES
Inhibition (%)
Code
S. aureus
E. coli
S. typhi
11.45
26.31
54.24
19.65
26.28
97.13
P. aureuginosa
15.63
B. subtilis
S. sonnei
7
8
9
10
11
45.54
31.21
52.64
47.56
46.86
96.13
3.12
31.80
52.20
18.57
31.13
12.17
96.48
31.31
29.45
46.02
15.93
19.49
98.01
14.97
48.77
27.07
14.95
94.14
90.28
89.26
90.56
64.51
Ciprofloxacin
91.16