M.-X. Song et al. / European Journal of Medicinal Chemistry 54 (2012) 403e412
407
(s, 1H, CH), 6.89e7.74 (m, 8H, AreH), 10.37 (s, 1H, NH). MS m/z 424
(M þ 1). Anal. Calcd. for C18H11Cl2NO3S2: C, 50.95; H, 2.61; N, 3.30.
Found: C, 51.22; H, 2.75; N, 3.52.
NH). MS m/z 386 (M þ 1). Anal. Calcd. for C19H15NO4S2: C, 59.20; H,
3.92; N, 3.63. Found: C, 59.36; H, 4.15; N, 3.51.
5.4.13. (Z)-5-(4-(2-(4-methoxyphenyl)-2-oxoethoxy)benzylidene)-
2-thioxothiazolidin-4-one (I-m)
5.4.5. (Z)-5-(4-(2-(2-bromophenyl)-2-oxoethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-e)
Yield 87%; m.p.190e192 ꢁC. IR (KBr) cmꢂ1: 3225 (NH), 1689 (C]
Yield 87%; m.p. 144e146 ꢁC. IR (KBr) cmꢂ1: 3220 (NH), 1686 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 3.86 (s, 3H, OCH3), 5.19 (s,
2H, COCH2), 7.75 (s, 1H, CH), 6.91e8.06 (m, 8H, AreH), 10.46 (s, 1H,
NH). MS m/z 386 (M þ 1). Anal. Calcd. for C19H15NO4S2: C, 59.20; H,
3.92; N, 3.63. Found: C, 59.04; H, 3.98; N, 3.53.
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
5.05 (s, 2H, COCH2), 7.76
(s, 1H, CH), 6.91e7.87 (m, 8H, AreH), 10.47 (s, 1H, NH). MS m/z 434
(M þ 1). Anal. Calcd. for C18H12BrNO3S2: C, 49.78; H, 2.78; N, 3.22.
Found: C, 49.53; H, 2.94; N, 3.06.
5.5. General procedure for the preparation of compounds II
5.4.6. (Z)-5-(4-(2-(3-bromophenyl)-2-oxoethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-f)
A mixture of 3 (3 mmol), 2-(4-oxo-2-thioxothiazolidin-3-yl)
acetic acid (3 mmol), 10 drops glacial acetic acid and 10 drops
piperidine in ethanol (20 mL) was refluxed for 4 h. After cooling,
a precipitate was obtained by filtration, which was further recrys-
tallized from ethanol to provide a yellow solid IIa-m.
Yield 82%; m.p. 210e212 ꢁC. IR (KBr) cmꢂ1: 3218 (NH), 1685 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 5.06 (s, 2H, COCH2), 7.76
(s, 1H, CH), 6.92e8.13 (m, 8H, AreH), 10.46 (s, 1H, NH). MS m/z 434
(M þ 1). Anal. Calcd. for C18H12BrNO3S2: C, 49.78; H, 2.78; N, 3.22.
Found: C, 49.99; H, 2.84; N, 3.36.
5.5.1. (Z)-2-(5-(4-(2-(2-chlorophenyl)-2-oxoethoxy)benzylidene)-
4-oxo-2-thioxothia-zolidin-3-yl)acetic acid(II-a)
5.4.7. (Z)-5-(4-(2-(3-bromophenyl)-2-oxoethoxy)benzylidene)-2-
thioxothiazolidin-4- one (I-g)
Yield 91%; m.p. 152e154 ꢁC. IR (KBr) cmꢂ1: 3413 (OH), 1702 (C]
Yield 84%; m.p. 177e178 ꢁC. IR (KBr) cmꢂ1: 3217 (NH), 1683 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 4.35 (s, 2H, COCH2), 5.53
(s, 2H, OCH2), 7.14e7.90 (m, 8H, AreH), 7.77 (s, 1H, CH), 9.12 (s, 1H,
COOH). MS m/z 448 (M þ 1). Anal. Calcd. for C20H14ClNO5S2: C,
53.63; H, 3.15; N, 3.13. Found: C, 53.41; H, 3.24; N, 3.22.
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
5.22 (s, 2H, COCH2), 7.75
(s, 1H, CH), 6.90e8.01 (m, 8H, AreH), 10.46 (s, 1H, NH). MS m/z 434
(M þ 1). Anal. Calcd. for C18H12BrNO3S2: C, 49.78; H, 2.78; N, 3.22.
Found: C, 49.53; H, 2.93; N, 3.40.
5.5.2. (Z)-2-(5-(4-(2-(3-chlorophenyl)-2-oxoethoxy)benzylidene)-
4-oxo-2-thioxothia-zolidin-3-yl)acetic acid (II-b)
5.4.8. (Z)-5-(4-(2-(2-fluorophenyl)-2-oxoethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-h)
Yield 89%; m.p. 272e274 ꢁC. IR (KBr) cmꢂ1: 3414 (OH), 1700 (C]
Yield 86%; m.p. 170e171 ꢁC. IR (KBr) cmꢂ1: 3213 (NH), 1672 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 4.51 (s, 2H, COCH2), 5.75
(s, 2H, OCH2), 7.18e8.08 (m, 8H, AreH), 7.81 (s, 1H, CH), 9.21 (s, 1H,
COOH). MS m/z 448 (M þ 1). Anal. Calcd. for C20H14ClNO5S2: C,
53.63; H, 3.15; N, 3.13. Found: C, 53.79; H, 3.27; N, 3.19.
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
5.11 (s, 2H, COCH2), 7.76
(s, 1H, CH), 6.91e7.96 (m, 8H, AreH), 10.46 (s, 1H, NH). MS m/z 374
(M þ 1). Anal. Calcd. for C18H12FNO3S2: C, 57.90; H, 3.24; N, 3.75.
Found: C, 58.17; H, 3.36; N, 3.48.
5.5.3. (Z)-2-(5-(4-(2-(4-chlorophenyl)-2-oxoethoxy)benzylidene)-
4-oxo-2-thioxothia-zolidin-3-yl)acetic acid (II-c)
5.4.9. (Z)-5-(4-(2-(4-fluorophenyl)-2-oxoethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-i)
Yield 90%; m.p. 202e204 ꢁC. IR (KBr) cmꢂ1: 3411 (OH), 1699 (C]
Yield 81%; m.p. 245e246 ꢁC. IR (KBr) cmꢂ1: 3215 (NH), 1676 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 4.36 (s, 2H, COCH2), 5.73
(s, 2H, OCH2), 7.16e8.06 (m, 8H, AreH), 7.77 (s, 1H, CH), 9.31 (s, 1H,
COOH). MS m/z 448 (M þ 1). Anal. Calcd. for C20H14ClNO5S2: C,
53.63; H, 3.15; N, 3.13. Found: C, 53.87; H, 3.18; N, 3.27.
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
5.70 (s, 2H, COCH2), 7.61
(s, 1H, CH), 7.12e8.13 (m, 8H, AreH), 13.78 (s, 1H, NH). MS m/z 374
(M þ 1). Anal. Calcd. for C18H12FNO3S2: C, 57.90; H, 3.24; F, 5.09; N,
3.75. Found: C, 58.08; H, 3.31; N, 3.53.
5.5.4. (Z)-2-(5-(4-(2-(2,4-dichlorophenyl)-2-oxoethoxy)
benzylidene)-4-oxo-2-thioxoth-iazolidin-3-yl)acetic acid (II-d)
Yield 84%; m.p. 238e240 ꢁC. IR (KBr) cmꢂ1: 3408 (OH), 1696
5.4.10. (Z)-5-(4-(2-oxo-2-phenylethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-j)
Yield 87%; m.p. 194e196 ꢁC. IR (KBr) cmꢂ1: 3210 (NH), 1672 (C]
(C]O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
4.52 (s, 2H, COCH2),
5.52 (s, 2H, OCH2), 7.14e7.96 (m, 7H, AreH), 7.81 (s, 1H, CH), 9.52
(s,1H, COOH). MS m/z 482 (M 1). Anal. Calcd. for
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 5.25 (s, 2H, COCH2), 7.76
(s, 1H, CH), 6.91e8.08 (m, 9H, AreH), 10.46 (s, 1H, NH). MS m/z 356
(M þ 1). Anal. Calcd. for C18H13NO3S2: C, 60.83; H, 3.69; N, 3.94.
Found: C, 60.67; H, 3.74; N, 4.09.
þ
C20H13Cl2NO5S2: C, 49.80; H, 2.72; N, 2.90. Found: C, 49.97; H,
2.90; N, 2.75.
5.4.11. (Z)-5-(4-(2-oxo-2-(p-tolyl)ethoxy)benzylidene)-2-
thioxothiazolidin-4-one (I-k)
5.5.5. (Z)-2-(5-(4-(2-(2-bromophenyl)-2-oxoethoxy)benzylidene)-
4-oxo-2-thioxothia-zolidin-3-yl)acetic acid (II-e)
Yield 83%; m.p. 247e249 ꢁC. IR (KBr) cmꢂ1: 3217 (NH), 1685 (C]
Yield 87%; m.p. 186e188 ꢁC. IR (KBr) cmꢂ1: 3398 (OH), 1703 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
2.49 (s, 3H, CH3), 5.21 (s,
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d 4.35 (s, 2H, COCH2), 5.50
2H, COCH2), 7.75 (s, 1H, CH), 6.90e8.22 (m, 8H, AreH), 10.45 (s, 1H,
NH). MS m/z 370 (M þ 1). Anal. Calcd. for C19H15NO3S2: C, 61.77; H,
4.09; N, 3.79. Found: C, 61.95; H, 4.02; N, 3.84.
(s, 2H, OCH2), 7.16e7.87 (m, 8H, AreH), 7.77 (s, 1H, CH), 9.14 (s, 1H,
COOH). MS m/z 492 (M þ 1). Anal. Calcd. for C20H14BrNO5S2: C,
48.79; H, 2.87; N, 2.84. Found: C, 48.66; H, 2.59; N, 3.01.
5.4.12. (Z)-5-(4-(2-(3-methoxyphenyl)-2-oxoethoxy)benzylidene)-
2-thioxothiazolidin-4-one (I-l)
5.5.6. (Z)-2-(5-(4-(2-(3-bromophenyl)-2-oxoethoxy)benzylidene)-
4-oxo-2-thioxothia-zolidin-3-yl)acetic acid (II-f)
Yield 88%; m.p. 193e195 ꢁC. IR (KBr) cmꢂ1: 3221 (NH), 1687 (C]
Yield 86%; m.p. 254e256 ꢁC. IR (KBr) cmꢂ1: 3396 (OH),1707 (C]
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
3.84 (s, 3H, OCH3), 5.23 (s,
O). 1H NMR (DMSO-d6, 300 MHz, ppm):
d
4.33 (s, 2H, COCH2), 5.75
2H, COCH2), 7.76 (s, 1H, CH), 6.91e7.76 (m, 8H, AreH), 10.46 (s, 1H,
(s, 2H, OCH2), 7.18e8.20 (m, 8H, AreH), 7.76 (s, 1H, CH), 12.49 (s, 1H,