P. Manojkumar et al. / European Journal of Medicinal Chemistry 44 (2009) 4690–4694
4693
Table 2
Characterisation data of compounds (3a–g and 5a–g).
Comp.
R
Mol. formula
M.p [ꢁC]
Yield [%]
Analysis. (%) found (calc.)
C
H
N
3a
3b
3c
3d
3e
3f
3g
5a
5b
5c
5d
5e
5f
2,4-(CH3)2
4-Br
4-NO2
4-Cl
3-NO2
4-COOH
2-COOH
2,4-(CH3)2
4-Br
4-NO2
4-Cl
3-NO2
4-COOH
2-COOH
C25H24N4O4
C23H19BrN4O4
C23H19N5O6
C23H19ClN4O4
C23H19N5O6
C24H20N4O6
C24H20N4O6
C24H22N4O5
208–210
258–260
218–220
266–268
268–270
242–244
216–218
254–256
195–197
190–192
248–250
250–253
185–188
175–177
54
66
65
70
62
64
62
48
62
58
65
55
64
45
67.45(67.55)
55.82(55.77)
59.92(59.87)
61.32(61.27)
59.92(59.87)
62.37(62.60)
62.37(62.60)
64.23(64.57)
52.94(53.13)
56.99(57.02)
57.96(58.35)
56.96(57.02)
59.64(59.74)
59.68(59.74)
5.48(5.44)
3.85(3.87)
4.18(4.15)
4.22(4.25)
4.13(4.15)
4.32(4.38)
4.47(4.38)
4.88(4.97)
3.39(3.45)
3.68(3.70)
3.76(3.78)
3.83(3.70)
3.83(3.92)
3.95(3.92)
12.59(12.60)
11.26(11.31)
15.13(15.18)
12.38(12.43)
15.29(15.18)
12.08(12.17)
11.99(12.17)
12.34(12.55)
11.18(11.27)
15.25(15.11)
7.94(7.83)
C22H17BrN4O5
C22H17N5O7
C22H17ClN4O5
C22H17N5O7
C23H18N4O7
C23H18N4O7
15.02(15.11)
12.26(12.12)
12.01(12.12)
5g
single spot on the TLC plates. The solvent system used was tolue-
ne:methanol (3:7).
OCH2), 6.25 (s, 1H, CH), 6.90–8.43 (m, 7H, Ar-H); mass (%): MHþ
462.2 (22), 257.6 (75), 175.4 (36), 137.0 (62), 121.2 (100).
Compound 3a: IR (KBr,
n
cmꢃ1): 2927 (CH), 1693 (C]O), 1610
Compound 3f: IR (KBr,
n
cmꢃ1): 3422 (OH), 2817 (CH), 1681
(C]N), 1287 (C–O–C); 1H NMR (DMSO-d6)
d
ppm: 2.42 (s, 3H,
(C]O), 1594 (C]N), 1206 (C–O–C); 1H NMR (DMSO-d6)
d ppm: 2.12
0
coumarin CH3), 2.50 (s, 3H, aromatic C2 –CH3), 2.51 (s, 3H, aromatic
0
(s, 3H, coumarin CH3), 2.25 (s, 3H, pyrazole C3–CH3), 3.14 (s, 3H,
pyrazole C5–CH3), 4.51 (s, 2H, OCH2), 6.01 (s, 1H, CH), 7.41–7.85 (m,
7H, Ar-H), 13.45 (COOH); mass (%): MHþ 461.3 (16), 256.3 (72),
219.4 (100), 136.8 (15), 123.2 (20).
C4 –CH3), 3.33 (s, 3H, pyrazole C3–CH3), 3.58 (s, 3H, pyrazole C5–
CH3), 4.78 (s, 2H, OCH2), 6.30 (s, 1H, CH), 6.98–7.74 (m, 6H, Ar-H);
ppm: 18.12 (coumarin CH3), 38.59 (CH3 of
pyrazole C5), 39.42 (CH3 of pyrazole C3), 39.70 (CH3 of aromatic C2 ),
13C NMR (DMSO-d6)
d
Compound 3g: IR (KBr,
n
cmꢃ1): 3446 (OH), 2922 (CH), 1650
ppm: 2.27
0
40.25 (CH3 of aromatic C4 ), 66.16 (OCH2), 101.62 (coumarin C8),
(C]O),1587 (C]N),1247 (C–O–C); 1H NMR (DMSO-d6)
d
0
102.25 (coumarin C6), 102.87 (coumarin C3), 104.12 (coumarin C10),
(s, 3H, coumarin CH3), 2.51 (s, 3H, pyrazole C3–CH3), 3.37 (s, 3H,
pyrazole C5–CH3), 4.78 (s, 2H, OCH2), 6.25 (s, 1H, CH), 6.97–8.04 (m,
7H, Ar-H), 10.32 (COOH); mass (%): MHþ 461.3 (18), 256.3 (65),
219.2 (100), 136.8 (22), 121.8 (26).
0
0
105.37 (aromatic C1 ), 106.11 (aromatic C5 ), 107.25 (coumarin C5),
0
0
0
107.87 (aromatic C6 ), 108.49 (aromatic C3 ), 109.12 (aromatic C2 ),
0
109.81 (aromatic C4 ), 110.10 (coumarin C9), 110.56 (coumarin C7),
113.68 (pyrazole C4), 126.49 (pyrazole C5), 153.28 (pyrazole C3),
154.45 (coumarin C4), 160.54 (coumarin C2), 166.16 (pNC]O); mass
(%): Mþ 444.0 (13), 217.0 (10), 189.1 (12), 137.1 (55), 123.2 (100).
6.3. Synthesis of 1-(4-methylcoumarinyl-7-oxyacetyl)-3-methyl-4-
(substituted phenyl) hydrazono-2-pyrazolin-5-one (5a–g)
Compound 3b: IR (KBr,
n
cmꢃ1): 2921 (CH), 1720 (C]O), 1621
ppm: 2.40 (s, 3H,
(C]N), 1282 (C–O–C); 1H NMR (DMSO-d6)
d
Ethyl-2-(substituted phenyl) hydrazono-3-oxobutyrate (4a–g)
coumarin CH3), 2.50 (s, 3H, pyrazole C3–CH3), 3.30 (s, 3H, pyrazole
C5–CH3), 4.78 (s, 2H, OCH2), 6.25 (s, 1H, CH), 6.86–7.74 (m, 7H, Ar-
(0.02 mol) was dissolved in glacial acetic acid (20 ml) acid and
4-methylcoumarinyl-7-oxyacetic acid hydrazide
1
(0.496 g,
H); 13C NMR (DMSO-d6)
d
ppm: 18.12 (coumarin CH3), 38.62 (CH3
0.002 mol) in glacial acetic acid (20 ml) was added and the mixture
was refluxed for 4 h, cooled and then allowed to stand overnight.
The resultant solid was dried and then recrystallised from ethanol
.The purity of all the compounds was established by single spot on
the TLC plates. The solvent system used was methanol:toluene
(7:3).
at C5 of pyrazole), 40.29 (CH3 at C3 of pyrazole), 66.19 (OCH2),
101.62 (coumarin C8), 102.25 (coumarinC6), 102.87 (coumarin C3),
0
0
104.12 (coumarin C10), 105.37 (aromatic C4 ), 106.62 (aromatic C1 ),
0
0
107.24 (coumarin C5), 107.87 (aromatic C2 ,C6 ), 109.12 (aromatic
0
0
C3 ,C5 ), 111.47 (coumarin C9), 112.55 (coumarin C7), 113.67 (pyr-
azole C4), 126.49 (pyrazole C5), 153.37 (pyrazole C3), 154.46
(coumarin C4), 160.55 (coumarin C2), 166.15 (pNC]O); mass (%):
(MH þ 2)þ 497.6 (15), MHþ 495.9 (17), 291.1 (86), 189.0 (42), 137.5
(62), 121.2 (100).
Compound 5a: IR (KBr,
n
cmꢃ1): 3172 (NH), 3053 (Ar.CH),
2971 (Aliph.CH), 1722 (C]O), 1510 (NH–N]C), 1243 (C–O–C); 1H
NMR (DMSO-d6)
d
ppm: 2.41 (s, 3H, coumarin CH3), 2.49 (s, 3H,
0
0
aromatic C2 –CH3), 2.51 (s, 3H, aromatic C4 –CH3), 3.36 (s, 3H,
pyrazolone CH3), 4.78 (s, 2H, OCH2), 6.25 (s, 1H, CH), 7.00–7.74
Compound 3c: IR (KBr,
n
cmꢃ1): 2925 (CH), 1672 (C]O), 1596
ppm: 2.24 (s, 3H,
(C]N), 1262 (C–O–C); 1H NMR (DMSO-d6)
d
(m, 6H, Ar-H), 10.32 (s, 1H, NH); 13C NMR (DMSO-d6)
d
ppm:
coumarin CH3), 2.48 (s, 3H, pyrazole C3–CH3), 3.44 (s, 3H, pyrazole
C5–CH3), 4.87 (s, 2H, OCH2), 6.22 (s, 1H, CH), 6.93–8.36 (m, 7H, Ar-
H); mass (%): MHþ 462.4 (20), 257.2 (90), 175.4 (34), 137.0 (58),
121.4 (100).
18.12 (coumarin CH3), 38.90 (pyrazolone CH3), 39.73 (CH3 of
0
0
aromatic C2 ), 40.29 (CH3 of aromatic C4 ), 66.19 (OCH2), 101.62
(coumarin C8), 111.46 (coumarin C6), 112.58 (coumarin C3),
0
112.94 (coumarin C10), 113.52 (aromatic C6 ), 113.59 (aromatic
Compound 3d: IR (KBr,
n
cmꢃ1): 2810 (CH), 1681 (C]O), 1604
ppm:
0 0
C5 ), 113.66 (coumarin C5), 114.45 (aromatic C4 ), 114.48 (pyrazole
(C]N), 1286 (C–O–C), 1078 (Ar–Cl); 1H NMR (DMSO-d6)
d
C4), 115.92 (aromatic C2 ), 116.14 (aromatic C3 ), 116.97 (aromatic
0
0
0
2.41 (s, 3H, coumarin CH3), 2.51 (s, 3H, pyrazole C3–CH3), 3.37 (s,
3H, pyrazole C5–CH3), 4.67 (s, 2H, OCH2), 6.25 (s, 1H, CH), 7.01–7.79
(m, 7H, Ar-H); mass (%): (MH þ 2)þ 453.1 (7), MHþ 450.9 (22), 246.2
(80), 189.3 (16), 123.2 (100).
C1 ), 117.36 (coumarin C9), 126.49 (coumarin C7), 153.36 (pyr-
azolone C3), 154.46 (coumarin C4), 160.03 (coumarin C2), 160.55
(pyrazolone C5) 166.14 (pNC]O); mass (%): (M-1)þ 445.3 (15),
287.2 (40), 219.2 (84) and 175.4 (100).
Compound 3e: IR (KBr,
O–C); 1H NMR (DMSO-d6)
(s, 3H, pyrazole C3–CH3), 3.37 (s, 3H, pyrazole C5–CH3), 4.78 (s, 2H,
n
cmꢃ1): 2945 (CH), 1598 (C]N), 1287 (C–
ppm: 2.36 (s, 3H, coumarin CH3), 2.51
Compound 5b: IR (KBr,
2971 (Aliph.CH), 1718 (C]O), 1517 (NH–N]C), 1260 (C–O–C);
1H NMR (DMSO-d6)
ppm: 2.41 (s, 3H, coumarin CH3), 2.51
n
cmꢃ1): 3164 (NH), 3058 (Ar.CH),
d
d