D.I. Othman et al.: Novel benzofuran derivativesꢀꢂꢁꢁꢁꢀ5
General method for the synthesis
-(4-(benzofuran-2-yl)thiazol-2-ylamino)-
-(substituted phenyl)thiazolidin-4-
ones 3a–f
Synthesis of 4-(benzofuran-2-yl) thiazol-
3
2-amine (4)
2
A solution of 2-bromoacetylbenzofuran (1.35 g, 0.01 mol) and thio-
urea (0.4 g, 0.01 mol) in ethanol (10 mL) was heated under reflux for
3
h and then neutralized with 10% K CO . The separated solid was
2 3
2-(2-Hydrazinylthiazolyl)benzofuran (0.5 g, 1 mmol) and an aromatic
filtered, dried and crystallized from ethanol/water (9:1) [27]: yield 1.1
aldehyde (1 mmol) were stirred in THF for 5 min, followed by addition
of mercaptoacetic acid (1.1 mmol) and molecular sieves 4 Å. The mix-
ture was stirred under reflux, until TLC showed disappearance of the
starting materials. The molecular sieves were removed by filtration.
The filtrate was concentrated in vacuo and the residue was triturated
1
g (90%); mp 214°C; H NMR: δ 6.99 (s, 2H, NH , D O exchangeable),
2
2
7
.05 (s, 1H, C3′-H), 7.20–7.35 (m, 3H, C5′-H, C6′-H and C4-H), 7.55 (d,
1
H, C4′-H, J = 8 Hz); 7.65 (d, 1H, C7′-H, J = 8Hz).
with 5% NaHCO . The crude product 3a–f was filtered and crystal-
3
lized from petroleum ether/diethyl ether (2:1).
General procedure for the synthesis
of 3-(4-(benzofuran-2-yl)thiazol-2-yl)-
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(4-hydroxyphenyl)
2
-(substituted phenyl)-thiazolidin-4-ones
thiazolidin-4-one (3a) Yield 0.14 g (84%); mp 155°C; IR: 748, 1511,
-1 1
1567, 1627, 2931, 3137, 3401 cm ; H NMR: δ 3.65 (s, 1H, br OH), 3.73 (s,
2H, C5-H), 4.21 (br s, 1H, NH), 6.76 (s, 1H, C2-H ), 7.39–8.02 (m, 10H, Ar-
5
a–e
+
+
H); MS: m/z 410 (16.10, M +1), 409 (15, M ), 231 (100), 143 (74). Anal. A solution of 2-(2-aminothiazolyl)benzofuran (1.2 g, 1 mmol) and an
Calcd for C H N O S (409.48): C, 58.66; H, 3.69; N, 10.26. Found: C, aromatic aldehyde (1 mmol) in toluene or THF was stirred and treated
2
0
15
3
3 2
58.35; H, 3.55; N, 10.18.
with mercaptoacetic acid (1.1 mmol) and molecular sieves 4 Å. The
mixture was stirred under reflux until TLC showed disappearance of
starting materials. The molecular sieves were removed by filtration.
The filtrate was concentrated in vacuo and the residue was triturated
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(2-hydroxyphenyl)
thiazolidin-4-one (3b) Yield 0.108 g (72%); mp 145–147°C; IR: 740,
-1
1
with 5% NaHCO . The crude product 5a–e was filtered and crystal-
1
511, 1567, 1627, 2931, 3137, 3401 cm ; H NMR: δ 3.65 (s, 1H, br OH);
3
lized from petroleum ether/diethyl ether (2:1).
3
.73 (s, 2H, C5-H); 4.21 (br s, 1H, NH), 6.76 (s, 1H, C2-H), 7.39–8.02
+
(
m, 10H, Ar-H); MS: m/z 409 (13, M ), 198 (100), 175 (25). Anal. Calcd
for C H N O S (409.48): C, 58.66; H, 3.69; N, 10.26. Found: C, 58.45; 3-(4-(Benzofuran-2-yl)thiazol-2-yl)-2-(4-hydroxyphenyl)thiazoli-
2
0
15
3
3 2
H, 3.36; N, 10.19.
din-4-one (5a) Yield 0.177 g (88%); mp 125°C; IR: 770, 1511, 1567, 1627,
-1 1
2
931, 3401 cm ; H NMR: δ 3.65 (s, 1H, br OH), 3.99 (s, 2H, C5-H), 6.76
+
(
s, 1H, C2-H), 7.20–7.89 (m, 10H, Ar-H); MS: m/z 395 (1.42, M +1), 31
100), 215 (50). Anal. Calcd for C H N O S (394.47): C, 60.90; H, 3.58;
N, 7.10. Found: C, 59.10; H, 3.55; N, 7.19.
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(3,4-dimethoxy-
(
phenyl)thiazolidin-4-one (3c) Yield 0.116 g (70%); mp 110–112°C;
20 14
2
3 2
-1
1
IR: 685, 1516, 1585, 1679, 2929, 3131 cm ; H NMR: δ 3.80 (s, 2H, C5-
H), 3.90 (s, 6H, 2OCH ), 7.05–7.70 (m, 9H, Ar-H), 8.00 (s, 1H, C2-H);
3
+
MS: m/z 454 (58, M ), 379 (11), 216 (100). Anal. Calcd for C H N O S
3-(4-(Benzofuran-2-yl)thiazol-2-yl)-2-(2-hydroxyphenyl)thiazo-
2
2
19
3
4
2
(
453.53): C, 58.26; H, 4.22; N, 9.27. Found: C, 58.13; H, 4.40; N, 9.17.
lidin-4-one (5b) Yield 0.103 g (57%); mp 140–142°C; IR: 687, 1518,
-
1
1
1
(
(
580, 1660, 2920, 3405 cm ; H NMR: δ 3.99 (s, 2H, C5-H), 7.00–7.70
m, 10H, Ar-H), 10.80 (s, 1H, br OH), 10.20 (s, 1H, C2-H); MS: m/z 395
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(4-hydroxy-3-meth-
+
+
0.4, M +1), 394 (0.5, M ), 63 (100), 78 (95). Anal. Calcd for C H N O S
oxyphenyl) thiazolidin-4-one (3d) Yield 0.104 g (65%); mp 160°C;
20 14
2
3 2
-1
1
(394.47): C, 60.90; H, 3.58; N, 7.10. Found: C, 60.88; H, 3.65; N, 7.16.
IR: 710, 1520, 1570, 1627, 2931, 3137, 3401 cm ; H NMR: δ 3.52 (s, 1H,
br OH); 3.75 (s, 2H, C5-H); 3.90 (s, 3H, OCH ); 6.90–7.89 (m, 10H, 9Ar-
H, C2-H); MS: m/z 440 (1.32, M ), 216 (100), 174 (46). Anal. Calcd for 3-(4-(Benzofuran-2-yl)thiazol-2-yl)-2-(3,4-dimethoxyphenyl)thi-
C H N O S (439.51): C, 57.39; H, 3.90; N, 9.56. Found: C, 57.23; H, 3.88; azolidin-4-one (5c) Yield 0.13 g (65%); mp 98–100°C; IR: 1001, 1511,
N, 9.31.
3
+
2
1
17
3
4 2
-
1 1
1589, 1683, 2925 cm ; H NMR: δ 3.78 (s, 6H, 2OCH ), 3.87 (s, 2H, C5-H),
3
+
7
.05–7.89 (m, 9H, Ar-H), 9.66 (s, 1H, C2-H); MS: m/z 439 (15, M +1), 438
+
(
52, M ), 151 (100), 165 (90). Anal. Calcd for C H N O S (438.52): C,
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(4-methoxyphenyl)
22 18 2 4 2
6
0.26; H, 4.14; N, 6.39. Found: C, 60.44; H, 4.28; N, 6.59.
thiazolidin-4-one (3e) Yield 0.085 g (55%); mp 156–158°C; IR: 1002,
-1
1
1
509, 1585, 1679, 2929, 3131 cm ; H NMR: δ 3.77 (s, 2H, C5-H), 3.80
+
(
s, 3H, OCH ), 6.68–7.69 (m, 11H, 10Ar-H, C2-H); MS: m/z 424 (2, M ), 3-(4-(Benzofuran-2-yl)thiazol-2-yl)-2-(4-hydroxy-3-methoxyphe-
3
4
3 (100). Anal. Calcd for C H N O S (423.51): C, 59.56; H, 4.05; N, nyl)thiazolidin-4-one (5d) Yield 0.107 g (55%); mp 110–112°C; IR:
2
1
17
3
3 2
-1 1
9.92. Found: C, 59.43; H, 3.98; N, 9.71.
710, 1525, 1567, 1627, 2929, 3401 cm ; H NMR: δ 3.52 (s, 1H, br OH), 3.77
(
s, 2H, C5-H), 3.90 (s, 3H, OCH ), 6.90–7.89 (m, 10H, 9Ar-H, C2-H); MS:
3
+
m/z 424 (1, M ), 43 (100), 78 (30). Anal. Calcd for C H N O S (424.49):
3
-(4-(Benzofuran-2-yl)thiazol-2-ylamino)-2-(4-(dimethylamino)
21 16
2
4 2
C, 59.42; H, 3.80; N, 6.60. Found: C, 59.64; H, 3.68; N, 6.89.
phenyl)thiazolidin-4-one (3f) Yield 0.119 g (45%); mp 96–98°C; IR:
-1
1
6
80, 1510, 1580, 1685, 2930, 3130 cm ; H NMR: δ 3.87 (s, 2H, C5-H),
3
.78 (s, 6H, N (CH ) ), 6.68–7.69 (m, 11H, 10Ar-H, C2-H); MS: m/z 437 3-(4-(Benzofuran-2-yl)thiazol-2-yl)-2-(4-(dimethylamino)phe-
3
2
+
+
(
1, M +1), 436 (1, M ), 145 (100), 118 (76). Anal. Calcd for C H N O S
nyl)thiazolidin-4-one (5e) Yield 0.148 g (76%); mp 116–117°C; IR:
-1 1
2
2
20
4
2 2
(
436.55): C, 60.53; H, 4.62; N, 12.83. Found: C, 59.99; H, 4.38; N, 12.61.
690, 1550, 1569, 1663, 2930 cm ; H NMR: δ 3.87 (s, 2H, C5-H), 3.78 (s,
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