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R.F. George / European Journal of Medicinal Chemistry 47 (2012) 377e386
d6):
d
6.99e7.58 (m,14H, 14 aromatic H), 8.04 (s,1H, ]CH), 9.56,10.61
O), 1659 (amide C]O), 1597 (bending NH), 1512 (C]C); 1H NMR
(s, 2H, NH þ OH exchanged with D2O); MS (m/z, %):439 (Mþ, 5), 438
[(Mþ ꢀ 1), 21], 347 (18), 77 (100); Anal. Calcd. for C25H17N3O3S. H2O
(457.51): C, 65.64; H, 4.19; N, 9.18. Found: C, 65.31; H, 4.64; N, 9.52.
(CDCl3):
d
7.27e7.72 (m, 15H, 14 aromatic H þ NH exchanged with
D2O), 7.90 (s,1H, ]CH); MS (m/z, %): 457 (Mþ,15), 458 [(Mþ þ 1), 6],
459 [(Mþ þ 2), 6], 460 [(Mþ þ 3), 2], 331 (72), 77 (100); Anal. Calcd.
for C25H16ClN3O2S (457.94): C, 65.57; H, 3.52; N, 9.18. Found: C,
65.47; H, 3.82; N, 9.50.
4.1.3.5. (2Z,5Z)
ylidene)-2-cyano-N-(4-methylphenyl)acetamide (4e). Canary yellow
crystals, mp 342e343 ꢃC (dec.), 33% yield; IR (cmꢀ1):
3410 (NH),
2-(5-Benzylidene-4-oxo-3-phenyl-thiazolidin-2-
n
4.1.3.10. (2Z,5Z) N-(4-Chlorophenyl)-2-cyano-2-[5-(4-methoxybenzy-
3050e3020 (aromatic CH), 2924 (aliphatic CH), 2191 (C^N), 1709
(thiazolidinone C]O), 1655 (amide C]O), 1597 (bending NH), 1508
lidene)-4-oxo-3-phenyl-thiazolidin-2-ylidene]acetamide (4j). Canary
yellow crystals, mp 310e311 ꢃC (dec.), 29% yield; IR (cmꢀ1):
n 3398
(C]C); 1H NMR (CDCl3):
d
2.34 (s, 3H, CH3), 7.15e7.72 (m, 14H, 14
aromatic H), 7.81 (s, 1H, NH exchanged with D2O), 7.88 (s, 1H, ]CH);
13C NMR (APT) (DMSO-d6):
20.2 (CH3), 78.8 (C^NeC]C), 112.7
(NH), 3059e3030 (aromatic CH), 2938 (aliphatic CH), 2194 (C^N),
1713 (thiazolidinone C]O), 1659 (amide C]O), 1589 (bending NH),
d
1512 (C]C); 1H NMR (CDCl3):
d 3.91 (s, 3H, OCH3), 7.02e7.85 (m,
(C^N),121.3,128.7,129.1,129.2,129.3,130.2,130.3 (aromatic C),121.2
(C of thiazolidinone attached to olefinic CH), 133.0 (C]CH), 133.2
(aromatic C attached to N of thiazolidinone), 133.3 (aromatic C
attached to NH),134.8 (aromatic C attached to CH3),135.1 (aromatic C
attached to olefinic CH), 161.4 (thiazolidinone C]O), 162.1 (amide
C]O), 166.3 (C^NeC]C); MS (m/z, %):437 (Mþ, 11), 438 [(Mþ þ 1),
8], 331 (39), 77 (100); Anal. Calcd. for C26H19N3O2S (437.52): C, 71.38;
H, 4.38; N, 9.60. Found: C, 71.26; H, 4.19; N, 10.00.
14H, 13 aromatic H þ NH exchanged with D2O), 7.88 (s, 1H, ]CH);
Anal. Calcd. for C26H18ClN3O3S (487.97): C, 64.00; H, 3.72; N, 8.61.
Found: C, 63.87; H, 4.01; N, 8.95.
4.1.3.11. (2Z,5Z) 2-[5-(4-Chlorobenzylidene)-4-oxo-3-phenyl-thiazoli-
din-2-ylidene]-N-(4-chlorophenyl)-2-cyanoacetamide (4k). Yellow
crystals, mp 339e341 ꢃC (dec.), 24% yield; IR (cmꢀ1):
n 3418 (NH),
3050e3024 (aromatic CH), 2191 (C^N), 1713 (thiazolidinone C]O),
1670 (amide C]O), 1597 (bending NH), 1520 (C]C); 1H NMR
4.1.3.6. (2Z,5Z) 2-Cyano-2-[5-(4-methoxybenzylidene)-4-oxo-3-phenyl-
(CDCl3): d 7.27e7.68 (m, 13H, 13 aromatic H), 7.83 (s, 1H, ]CH), 7.90
thiazolidin-2-ylidene]-N-(4-methylphenyl)acetamide
(4f). Canary
3400
(s, 1H, NH exchanged with D2O); MS (m/z, %): 492 (Mþ, 18), 493
[(Mþ þ 1), 4], 494 [(Mþ þ 2), 4], 365 (50), 367 (13), 77 (100); Anal.
Calcd. for C25H15Cl2N3O2S (492.39): C, 60.98; H, 3.07; N, 8.53. Found:
C, 60.87; H, 3.37; N, 8.88.
yellow crystals, mp 325e326 ꢃC (dec.), 53% yield; IR (cmꢀ1):
n
(NH), 3050e3020 (aromatic CH), 2924 (aliphatic CH), 2200 (C^N),
1713 (thiazolidinone C]O), 1643 (amide C]O), 1585 (bending NH),
1504 (C]C); 1H NMR (CDCl3):
d 2.34 (s, 3H, CH3), 3.90 (s, 3H, OCH3),
7.02e7.69 (m, 14H, 13 aromatic H þ NH exchanged with D2O), 7.84 (s,
1H, ]CH); MS (m/z, %):467 (Mþ, 44), 468 [(Mþ þ 1), 14], 361 (93), 77
(100); Anal. Calcd. for C27H21N3O3S (467.55): C, 69.36; H, 4.53; N, 8.99.
Found: C, 69.08; H, 4.38; N, 8.86.
4.1.3.12. (2Z,5Z) N-(4-Chlorophenyl)-2-cyano-2-[5-(2-hydroxybenzy-
lidene)-4-oxo-3-phenyl-thiazolidin-2-ylidene]acetamide (4l). Orange
crystals, mp 269e271 ꢃC (dec.), 30% yield; IR (cmꢀ1):
n 3390 (NH),
3232 (OH), 3059 (aromatic CH), 2199 (C^N), 1690 (thiazolidinone
C]O), 1659 (amide C]O), 1589 (bending NH), 1508 (C]C); 1H NMR
4.1.3.7. (2Z,5Z) 2-[5-(4-Chlorobenzylidene)-4-oxo-3-phenyl-thiazoli-
(DMSO-d6): d 6.98e7.59 (m, 13H, 13 aromatic H), 8.04 (s, 1H, ]CH),
din-2-ylidene]-2-cyano-N-(4-methylphenyl)acetamide (4g). Orange
9.70, 10.63 (s, 2H, NH þ OH exchanged with D2O); Anal. Calcd. for
C25H16ClN3O3S (473.94): C, 63.36; H, 3.40; N, 8.87. Found: C, 63.32; H,
3.61; N, 9.07.
crystals, mp 330e331 ꢃC (dec.), 37% yield; IR (cmꢀ1):
n 3395 (NH),
3059e3028 (aromatic CH), 2920 (aliphatic CH), 2195 (C^N), 1713
(thiazolidinone C]O), 1659 (amide C]O), 1585 (bending NH), 1508
(C]C); 1H NMR (CDCl3):
d
2.34 (s, 3H, CH3), 7.15e7.81 (m, 14H, 13
4.1.4. General procedure for the preparation of compounds 5aee
To a cold solution of appropriate aniline (1 mmol) in dilute
hydrochloric acid (1 ml) was added dropwise a solution of sodium
nitrite (0.07 g in 2 ml water, 1 mmol). This mixture was added to
a suspension of the 4-thiazolidinone derivatives 3a,b (1 mmol) in
DMF (5 ml) and was rendered alkaline with a solution of sodium
acetate (0.24 g, 3 mmol) in water (5 ml). The reaction was stirred
at room temperature overnight and the separated residue was
filtered, washed with water and crystallized from ethanol to
obtain the hydrazono derivatives in pure form.
aromatic H þ NH exchanged with D2O), 7.86 (s, 1H, ]CH); Anal.
Calcd. for C26H18ClN3O2S (471.97): C, 66.17; H, 3.84; N, 8.90. Found:
C, 66.28; H, 3.94; N, 8.65.
4.1.3.8. (2Z,5Z)
2-Cyano-2-[5-(4-hydroxybenzylidene)-4-oxo-3-
phenyl-thiazolidin-2-ylidene]-N-(4-methylphenyl)acetamide (4h).
Orange crystals, mp 276e278 ꢃC (dec.), 28% yield; IR (cmꢀ1):
n
3400 (NH), 3230 (OH), 3059e3030 (aromatic CH), 2920 (aliphatic
CH), 2200 (C^N), 1690 (thiazolidinone C]O), 1655 (amide C]O),
1589 (bending NH), 1512 (C]C); 1H NMR (DMSO-d6):
d 2.26 (s,
3H, CH3), 6.99e7.56 (m, 13H, 13 aromatic H), 8.03 (s, 1H, ]CH),
4.1.4.1. (2Z,5Z)
thiazolidin-2-ylidene]-N-phenylacetamide (5a). Orange crystals, mp
181e183 ꢃC (dec.), 30% yield; IR (cmꢀ1):
3402 (NH), 3055e3012
2-Cyano-2-[4-oxo-3-phenyl-5-(phenylhydrazono)-
9.46, 10.61 (s, 2H, OH þ NH exchanged with D2O); 13C NMR (APT)
(DMSO-d6):
d
20.3 (CH3), 78.7 (C^NeC]C), 113.0 (C^N), 116.2,
n
119.7, 120.5, 120.6, 121.2, 128.7, 128.8, 129.2, 129.4, 130.4 (aromatic
C), 119.5 (aromatic C attached to olefinic CH), 120.3 (C of thiazo-
lidinone attached to olefinic CH), 132.4 (C]CH), 133.2 (aromatic C
attached to N of thiazolidinone), 135.0 (aromatic C attached to
NH), 135.3 (aromatic C attached to CH3), 157.3 (aromatic C
attached to OH), 161.9 (thiazolidinone C]O), 162.3 (amide C]O),
166.1 (C^NeC]C); Anal. Calcd. for C26H19N3O3S (453.52): C,
68.86; H, 4.22; N, 9.27. Found: C, 68.56; H, 4.33; N, 9.37.
(aromatic CH), 2191 (C^N), 1701 (thiazolidinone C]O), 1651
(amide C]O), 1601 (bending NH), 1532 (C]N), 1508 (C]C); 1H
NMR (DMSO-d6):
d 7.10e7.59 (m, 15H, 15 aromatic H), 9.65 (s, 1H,
NH exchanged with D2O), 11.22 (s, 1H, NH exchanged with D2O);
Anal. Calcd. for C24H17N5O2S (439.49): C, 65.59; H, 3.90; N, 15.94.
Found: C, 65.29; H, 4.11; N, 15.81.
4.1.4.2. (2Z,5Z) 2-Cyano-2-[5-(4-methoxyphenylhydrazono)-4-oxo-
3-phenyl-thiazolidin-2-ylidene]-N-phenylacetamide (5b). Red crys-
4.1.3.9. (2Z,5Z)
ylidene)-N-(4-chlorophenyl)-2-cyanoacetamide (4i). Yellow crys-
tals, mp 347e348 ꢃC (dec.), 27% yield; IR (cmꢀ1):
3391 (NH),
3059e3030 (aromatic CH), 2195 (C^N), 1713 (thiazolidinone C]
2-(5-Benzylidene-4-oxo-3-phenyl-thiazolidin-2-
tals, mp 167e170 ꢃC (dec.), 39% yield; IR (cmꢀ1):
n 3406
(NH), 3050e3010 (aromatic CH), 2935 (aliphatic CH), 2199 (C^N),
1736 (thiazolidinone C]O), 1655 (amide C]O), 1601 (bending NH),
n
1543 (C]N), 1501 (C]C); 1H NMR (CDCl3):
d 3.74 (s, 3H, OCH3),