G.H. Al-Ansary et al. / European Journal of Medicinal Chemistry 68 (2013) 19e32
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(ύ max, cmꢂ1): 3120 (NH), 2890 (CeH aliphatic), 1700 (C]O); MS
(Mwt.: 392.88): m/z 394 (Mþ2, 6.3%), 392 (Mþ, 15%), 168 (100%).
Anal. Calcd for C17H13ClN2O3S2: C, 51.97; H, 3.34; N, 7.13; Found: C,
51.62; H, 3.58; N, 6.94.
C16H10Cl2N2O3S2: C, 46.50; H, 2.44; N; 6.78; Found: C, 46.78; H,
2.65; N; 7.13.
5.1.5.10. (Z)-2-(4-Fluorobenzenesulfonamido)-5-(4-methoxyphenyl-
methylene)thiazol-4-(5H)-one (6h). The titled compound was
separated as bright yellow crystals (2.51 g, 65%); mp 243e245 ꢁC;
5.1.5.4. (Z)-2-(4-Methylbenzenesulfonamido)-5-(4-methoxyphenyl-
methylene)thiazol-4-(5H)-one (6b). The titled compound was
separated as yellow crystals (3.51 g, 81%); mp > 300 ꢁC; 1H NMR
1H NMR (300 MHz, DMSO):
d
7.98 (m, 2H, Ar),
7.46 (t, J ¼ 8.8 Hz, 2H, Ar),
d
3.84 (s, 3H, eOCH3); FT-IR (ύ max, cmꢂ1): 3100
d
7.75 (s, 1H, olefin),
d
7.63 (d, J ¼ 8.7 Hz, 2H, Ar),
d
d
7.09 (d,
(300 MHz, DMSO):
7.76 (m, 4H, Ar),
d
7.91 (d, J ¼ 7.8 Hz, 2H, Ar),
d
7.82 (s, 1H, olefin),
2.35 (s, 3H,
J ¼ 8.7 Hz, 2H, Ar),
d
d
7.51 (m, 3H, Ar), 7.43 (m, 4H, Ar),
d
d
(NH), 2900 (CeH aliphatic), 1720 h(C]O); MS (Mwt.: 392.42): m/z
392 (Mþ, 2%), 235 (50%), 164 (100%). Anal. Calcd for C17H13FN2O4S2:
C, 52.03; H, 3.34; N, 7.14; Found: C, 51.84; H, 3.21; N, 7.46.
CH3); FT-IR (ύ max, cmꢂ1): 3310 (NH), 2860 (CeH aliphatic), 1670
(C]O); MS (Mwt.: 434.53): m/z 434 (Mþ, 20%), 210 (100%). Anal.
Calcd for C23H18N2O3S2: C, 63.57; H, 4.18; N, 6.45; Found: C, 63.22;
H, 3.85; N, 6.73.
5.1.5.11. (Z)-2-(4-Fluorobenzenesulfonamido)-5-(2-chlorophenylme-
thylene)thiazol-4-(5H)-one (6i). The titled compound was sepa-
rated as buff crystals (2.96 g, 75%); mp 272e274 ꢁC; 1H NMR
5.1.5.5. (Z)-5-(2-Chlorophenylmethylene)-2-(4-methylbenzenesul-
fonamido)thiazol-4-(5H)-one (6c). The titled compound was
separated as pale yellow crystals (2.51 g, 70%); mp 192e194 ꢁC; 1H
(300 MHz, DMSO):
d 9.25 (br,1H, NH), d 7.97e7.61 (m, 4H, Ar), d 7.58
(s, 1H, olefin),
d
7.56e7.45 (m, 4H, Ar); FT-IR (ύ max, cmꢂ1): 3120
NMR (300 MHz, DMSO):
d
10.16 (br, 1H, NH),
8.25 (d, J ¼ 8.7 Hz, 1H, Ar),
7.68 (s, 1H, olefin),
7.48 (d, J ¼ 8.1 Hz, 2H, Ar),
d
8.96 (s, 1H, Ar),
(NH), 1730 (C]O); MS (Mwt.: 396.84): m/z 398 (Mþ2, 5%), 396
d
8.72 (d, J ¼ 5.4 Hz, 1H, Ar),
d
d
7.85 (t,
(12%), 203 (36%), 170 (43%), 168 (100%). Anal. Calcd for
J ¼ 6.6 Hz, 1H, Ar),
d
d
C16H10ClFN2O3S2: C, 48.42; H, 2.54; N, 7.06; Found: C, 48.13; H, 2.87;
N, 7.39.
d
7.11 (d, J ¼ 7.8 Hz, 2H, Ar),
d
2.28 (s, 3H, CH3); FT-IR (ύ max,
cmꢂ1): 3400 (NH), 2900 (CeH aliphatic), 1620 (C]O); MS (Mwt.:
359.42): m/z 359 (Mþ, 4%), 205 (67%), 135 (100%). Anal. Calcd for
5.1.6. (Z)-4-Acetamidophenylsulfonamido-5-(arylmethylene)
thiazol-4(5H)-one (7a, b)
C
16H13N3O3S2: C, 53.47; H, 3.65; N, 11.69; Found: C, 53.21; H, 3.93;
N, 11.50.
5.1.6.1. General procedure. To a mixture of the corresponding 4-
acetamidobenzenesulphonyl chloride (2.32 g, 10 mmol) in THF
(10 mL) and TEA (3 mL, 30 mmol), 5c, d (10 mmol) was added. The
reaction mixture was refluxed for 24 h. THF was evaporated under
vacuum leaving a solid material which was collected and dissolved
in dil. HCl. The mixture was stirred at rt for 10 h to dissolve any
unreacted material. The solid precipitate was filtered off, washed
with water and dried over anhydrous calcium chloride. Recrystal-
lization from methanol afforded the titled products (7a, b).
5.1.5.6. (Z)-5-(4-Biphenylmethylene)-2-(4-methylbenzenesulfon-
amido)thiazol-4-(5H)-one (6d). The titled compound was separated
as pale yellow crystals (2.87 g, 74%); mp 192e194 ꢁC; 1H NMR
(300 MHz, DMSO):
d
9.84 (br, 1H, NH),
7.61 (d, J ¼ 7.2 Hz, 2H, Ar),
3.69 (s, 3H, -OCH3), d
d
7.84 (d, J ¼ 7.2 Hz, 2H, Ar),
7.40 (d, J ¼ 6.9 Hz,
2.37 (s,
d
7.71 (s, 1H, olefin),
d
d
2H, Ar),
d
7.12 (d, J ¼ 8.1 Hz, 2H, Ar),
d
3H, CH3); FT-IR (ύ max, cmꢂ1): 3450 (NH), 2850 (CeH aliphatic),
1680 (C]O); MS (Mwt.: 388.46): m/z 388 (Mþ, 45%), 234 (50%),164
(100%). Anal. Calcd for C18H16N2O4S2: C, 55.65; H, 4.15; N, 7.21;
Found: C, 56.08; H, 4.43; N, 7.56.
5.1.6.2. (Z)-4-Acetamidophenylsulfonamido-5-(2-chlorophenylme-
thylene)thiazol-4(5H)-one (7a). TLC system (CHCl3/MeOH 9.5:0.5).
The product was separated as white crystals, (2.95 g, 68%);
mp > 280 ꢁC.
5.1.5.7. (Z)-2-(4-Chlorobenzenesulfonamido)-5-(pyridin-3-ylmeth-
ylene)thiazol-4-(5H)-one (6e). The titled compound was separated
as orange crystals (2.42 g, 64%); mp 220e222 ꢁC; 1H NMR
5.1.6.3. (Z)-4-Acetamidophenylsulfonamido-5-(4-biphenylmethyle-
ne)thiazol-4(5H)-one (7b). TLC system (CHCl3/MeOH 9.5:0.5). The
product was separated as white crystals, (2.96 g, 62%); mp > 280 ꢁC.
(300 MHz, DMSO):
d
8.92 (s, 1H, Ar),
d
8.69 (d, 1H, Ar),
d
8.12 (d, 1H,
7.35 (d,
Ar), 7.91 (t, 1H, Ar),
d
d
7.83 (s, 1H, olefin),
d
7.58 (d, 2H, Ar), d
2H, Ar); FT-IR (ύ max, cmꢂ1): 3080 (NH), 1690 (C]O); MS (Mwt.:
379.84): m/z 380 (Mþ, 5%), 231 (56%), 174 (83%), 74 (100%). Anal.
Calcd for C15H10ClN3O3S2: C, 47.43; H, 2.65; N, 11.06; Found: C,
47.06; H, 2.83; N, 10.78.
5.1.7. (Z)-4-Aminophenylsulfonamido-5-(arylmethylene)thiazol-
4(5H)-ones (8a, b)
5.1.7.1. General procedure. The respective 7a, b (10 mmol) was
refluxed in 2 N HCl (20 mL) for 2 h. The reaction mixture was left to
cool then filtered to get rid of any unreacted material. Na2CO3 was
added to the filtrate until effervescence stopped. Herein, the crude
product precipitated. The mixture was kept in the refrigerator
overnight, then it was filtered, the residue washed with water
(2 ꢄ 10 mL) and dried over anhydrous calcium chloride. Recrys-
tallization from ether afforded the titled products 8a, b.
5.1.5.8. (Z)-2-(4-Chlorobenzenesulfonamido)-5-(4-methoxyphenyl-
methylene)thiazol-4-(5H)-one (6f). The titled compound was
separated as yellow crystals (2.88 g, 72%); mp 176e178 ꢁC; 1H NMR
(300 MHz, DMSO):
2H, Ar), 7.68 (s, 1H, olefin),
J ¼ 8.7 Hz, 2H, Ar),
3.84 (s, 3H, eOCH3); FT-IR (ύ max, cmꢂ1): 3220
d
7.90 (d, J ¼ 8.4 Hz, 2H, Ar),
d
7.73 (d, J ¼ 8.7 Hz,
d
d
7.54 (d, J ¼ 8.4 Hz, 2H, Ar),
d
7.11 (d,
d
(NH), 2800 (CeH aliphatic), 1710 (C]O); MS (Mwt.: 408.88): m/z
408 (Mþ, 2%), 231 (26%),148 (100%). Anal. Calcd for C17H13ClN2O4S2:
C, 49.94; H, 3.20; N, 6.85; Found: C, 49.62; H, 3.11; N, 7.24.
5.1.7.2. (Z)-4-Aminophenylsulfonamido-5-(2-chlorophenylmeth-
ylene)thiazol-4(5H)-one (8a). The titled compound was separated
as orange crystals (2.82 g, 72%); mp 180e182 ꢁC; 1H NMR (300 MHz,
5.1.5.9. (Z)-2-(4-Chlorobenzenesulfonamido)-5-(2-chlorophenyl-
methylene)thiazol-4-(5H)-one (6g). The titled compound was
separated as white crystals (3.34 g, 81%); mp 195e197 ꢁC; 1H NMR
DMSO):
d
12.73 (br, 2H, -NH2),
d 7.92 (s,1H, olefin), d 7.64 (d, 2H, Ar),
d
7.55 (d, 2H, Ar),
d
7.52e7.47 (m, 4H, Ar), FT-IR (ύ max, cmꢂ1): 3280
(NH2), 1690 (C]O); MS (Molecular formula: C16H12ClN3O3S2, Mwt.:
393.87): m/z 394 (Mþ, 6%), 204 (51%), 168 (100%).
(300 MHz, DMSO):
d
9.58 (br, 1H, NH),
7.68 (d, J ¼ 8.7 Hz, 2H, Ar),
d
7.90 (d, J ¼ 8.7 Hz, 2H, Ar),
d
7.78 (s, 1H, olefin),
d
d
7.48 (m, 4H, Ar);
FT-IR (ύ max, cmꢂ1): 3240 (NH),1680 (C]O); MS (Mwt.: 413.3): m/z
413 (Mþ, 3%), 202 (35%), 174 (7%), 167 (100%). Anal. Calcd for
5.1.7.3. (Z)-4-Aminophenylsulfonamido-5-(4-biphenylmethylene)
thiazol-4(5H)-one (8b). The titled compound was separated as pale