Arch. Pharm. Chem. Life Sci. 2016, 349, 1–9
U. M. Kocyigit et al.
ARC HH PHARM
Archiv der Pharmazie
CDCl
3
, ppm): d ¼ 6.33 (t, J ¼ 1.7 Hz, 2H), 3.60 (dd, J ¼ 2.8 Hz;
(2C), 132.8, 131.8 (2C), 127.9 (2C), 122.3 (2C), 112.3, 52.9, 45.9
(2C), 45.7 (2C). IR (KBr, cm ): 3114, 3058, 2983, 1783, 1720,
1490, 1396, 1338, 1290, 1263, 1218, 1191, 1143, 1114, 1083,
1006. Anal. calcd. for C18H13BrN O S: C, 53.88; H, 3.27; N, 6.98;
2 2
S, 7.99. Found: C, 52.37; H, 4.07; N, 5.65; S, 6.54.
ꢁ
1
1
.6 Hz, 2H), 3.53 (m, 2H), 1.81 (dt, J ¼ 9.2; 1.4 Hz, 1H), 1.59 (brd,
13
J ¼ 9.2 Hz, 1H). C-NMR (100 MHz, CDCl
3
, ppm): d ¼ 171.3 (2C),
ꢁ1
135.5 (2C), 52.2, 47.0 (2C), 46.1 (2C). IR (KBr, cm ): 3010, 2981,
879, 1853, 1774, 1450, 1334, 1295, 1230, 1089.
2
Generalprocedureforthesynthesisof2-(4-phenylthiazol-2-
yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-1,3(2H)-
dione derivatives (8a–i)
(3aR,4S,7R,7aS)-2-(4-(4-Chlorophenyl)thiazol-2-yl)-
3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-
dione (8d)
1
To a solution of thiazole derivative 3a (2 mmol) in toluene
Solid, yield: 60%, m.p.: 137–139°C. H NMR (400MHz, CDCl
3
,
(
7.5 mL) was added Et
stirred for about 10 min. Then, dicarboxylic anhydride (7)
2 mmol) in toluene (7.5 mL) was added dropwise into the
3
N (1 mL) and the reaction mixture was
ppm): d ¼ 7.75 (dd, J ¼ 6.8 Hz; 2.0 Hz, 2H), 7.52 (dd, J ¼ 6.8 Hz;
2.0 Hz, 2H), 7.44 (s, 1H), 6.27 (s, 2H), 3.54 (d, J ¼ 1.6 Hz; 2H), 3.52
(d, J ¼ 1.2 Hz; 2H), 1.80 (d, J ¼ 8.8 Hz; 1H), 1.63 (d, J ¼ 8.8 Hz; 1H).
(
1
3
reaction mixture. The reaction mixture was refluxed for 36 h.
Toluene was removed by rotovap. The residue was extracted
with chloroform, organic layer was dried over Na
solvent was removed by rotovap. The crude product was
crystallized in chloroform/hexane (3:7) mixture. The same
methodology was used in the synthesis of following
compounds 2-(4-phenylthiazol-2-yl)-3a,4,7,7a-tetrahydro-1H-
C-NMR (100 MHz, CDCl
3
, ppm): d ¼ 174.3 (2C), 151.4, 151.3,
134.9, 132.8, 131.8 (2C), 127.9 (2C), 122.3, 112.3, 52.3 (2C), 45.9
ꢁ
1
2
SO
4
, and the
(2C),45.7(2C).IR(KBr,cm ):3112,2981,2944,2867,1720,1490,
1394, 1338, 1290, 1218, 1189, 1141, 1070, 1002. Anal. calcd. for
18 2 2
C H13ClN O S:C, 60.59;H, 3.67;Cl, 9.94;N, 7.85; O, 8.97;S, 8.99.
Found: C, 60.69; H, 3.69; Cl, 9.97; N, 7.95; O, 8.87; S, 8.89.
4
,7-methanoisoindol-1,3(2H)-dione (8a–i).
(3aR,4S,7R,7aS)-2-(4-(4-Methoxyphenyl)thiazol-2-yl)-
3
a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-
dione (8e)
3
Solid, yield: 70%, m.p.: 180–182°C. H NMR (400 MHz, CDCl ,
(
3aR,4S,7R,7aS)-2-(4-Phenylthiazol-2-yl)-3a,4,7,7a-
1
tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (8a)
1
Solid, yield: 75%, m.p.: 171–173°C. H NMR (400MHz, CDCl
3
,
ppm): d ¼ 7.82 (dd, J ¼ 6.8 Hz; 2.0 Hz, 2H), 7.33 (s, 1H), 6.94 (dd,
J ¼ 6.8 Hz; 2.0 Hz, 2H), 6.31 (dd, J ¼ 15.6; 1.6 Hz, 2H), 3.85 (s,
3H), 3.56–3.55 (m, 2H), 3.54–3.51 (m, 2H), 1.81 (d, J ¼ 8.8 Hz,
ppm): d ¼ 7.89 (d, J ¼ 7.6 Hz; 2H), 7.46 (s, 1H), 7.42 (t, J ¼ 7.6 Hz;
H), 7.34 (t, J ¼ 7.2 Hz; 1H), 6.28 (bs, 2H), 3.55–3.53 (m, 2H), 3.52
d, J ¼ 1.2 Hz; 2H), 1.81 (d, J ¼ 8.8 Hz; 1H), 1.63 (d, J ¼ 8.8 Hz; 1H).
2
1
3
(
1H), 1.64 (d, J ¼ 8.8 Hz, 2H). C NMR (100 MHz, CDCl
3
, ppm):
1
3
C-NMR (100 MHz, CDCl
3
, ppm): d ¼ 174.4 (2C), 152.7, 151.2,
d ¼ 174.4 (2C), 159.7, 152.5, 151.0, 135.5, 134.9 (2C), 127.7 (2C),
ꢁ1
1
(
34.9 (2C), 133.8, 128.7 (2C), 128.3, 126.3 (2C), 112.1, 52.2, 45.9
114.0, 110.4, 55.3, 52.2 (2C), 45.9 (2C), 45.7 (2C). IR (KBr, cm ):
3106, 3077, 3053, 3002, 2957, 2865, 2842, 1786, 1721, 1672,
1606, 1577, 1520, 1493, 1468, 1439, 1337, 1314, 1257, 1216,
ꢁ
1
2C),45.7(2C).IR(KBr,cm ):3102,3068,3004,2964,2944,2869,
1
1
797, 1722, 1502, 1467, 1446, 1338, 1270, 1214, 1186, 1143,
118, 1095, 1045. Anal. calcd. for C18 S: C, 67.06; H, 4.38;
H
N O
14 2 2
16 2 S
1164, 1140, 1035. Anal. calcd. for C19H N O3 : C, 64.76; H,
N, 8.69; S, 9.95. Found: C, 67.33; H, 4.51; N, 8.72; S, 10.10.
4.58; N, 7.95; S, 9.10. Found: C, 63.69; H, 4.52; N, 7.63; S, 8.88.
(
3aR,4S,7R,7aS)-2-(4-(p-Tolyl)thiazol-2-yl)-3a,4,7,7a-
(3aR,4S,7R,7aS)-2-(4-(3-Methoxyphenyl)thiazol-2-yl)-
3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-
tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (8b)
Solid, yield: 61%, m.p.: 164–166°C. H NMR (400 MHz, CDCl
1
3
,
dione (8f)
1
ppm): d ¼ 7.78 (d, J ¼ 8.4 Hz, 2H), 7.40 (s, 1H), 7.22 (d, J ¼ 8.0 Hz,
Solid, yield: 75%, m.p.: 182–184°C. H NMR (400 MHz, CDCl
3
,
2
3
H), 6,29 (s, 2H), 3.55–3.54 (m, 2H), 3.53–3.51 (m, 2H), 2.38 (s,
ppm): d ¼ 7.48–7.45 (m, 3H), 7.34 (t, J ¼ 8.0 Hz, 1H), 6.92 (ddd,
J ¼ 8.0 Hz; 2.6 Hz; 0.8 Hz, 1H), 6.30 (t, J ¼ 1.6 Hz, 2H), 3.88 (s,
3H), 3.58–3.55 (m, 2H), 3.53 (dd, J ¼ 3.0 Hz; 1.6 Hz, 2H), 1.83 (dt,
13
H), 1.81 (d, J ¼ 9.0 Hz, 1H), 1.63 (d, J ¼ 9.0 Hz, 1H). C NMR
, ppm): d ¼ 174.4 (2C), 152.8, 151.0, 138.2,
34.9 (2C), 131.1, 129.3 (2C), 126.2 (2C), 111.4, 52.2, 45.9 (2C),
(
100 MHz, CDCl
3
1
3
1
4
2
1
4
J ¼ 8.8 Hz; 1.6 Hz, 1H), 1.66 (d, J ¼ 8.8 Hz, 1H).
C NMR
ꢁ
1
5.7 (2C), 21.3. IR (KBr, cm ): 3099, 3068, 3000, 2971, 2948,
871, 1797, 1722, 1502, 1411, 1338, 1292, 1270, 1209, 1184,
(100 MHz, CDCl
3
, ppm): d ¼ 174.3 (2C), 159.9, 152.6, 151.1,
135.2, 134.9, 129.7, 118.8, 114.2, 112.4, 111.8, 55.3, 52.2 (2C),
ꢁ1
141, 1120, 1041. Anal. calcd. for C19
H N
16 2
O
2
S: C, 67.84; H,
45.9 (2C), 45.7 (2C). IR (KBr, cm ): 3108, 3079, 3054, 3000,
2956, 2863, 2844, 1789, 1720, 1670, 1608, 1579, 1521, 1490,
.79; N, 8.33; S, 9.53. Found: C, 67.36; H, 4.93; N, 8.23; S, 9.47.
1
469, 1438, 1338, 1313, 1255, 1218, 1166, 1141, 1033. Anal.
(
3
3aR,4S,7R,7aS)-2-(4-(4-Bromophenyl)thiazol-2-yl)-
a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-
dione (8c)
Solid, yield: 50%, m.p.: 183–185°C. H NMR (400 MHz, CDCl
ppm): d ¼ 7.76 (dt, J ¼ 9.2 Hz; 2.0 Hz, 2H), 7.55–7.53 (m, 2H),
.45 (s, 1H), 6.28 (t, J ¼ 1.6 Hz, 2H), 3.57–3.55 (m, 2H), 3.53–3.52
m, 2H), 1.82 (dt, J ¼ 8.8 Hz; 1.6 Hz, 1H), 1.65 (d, J ¼ 8.8 Hz, 1H).
calcd. for C19 S: C, 64.76; H, 4.58; N, 7.95; S, 9.10.
Found: C, 63.67; H, 4.49; N, 7.43; S, 8.68.
16 2 3
H N O
1
3
,
(3aR,4S,7R,7aS)-2-(8H-Indeno[1,2-d]thiazol-2-yl)-
3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-
dione (8g)
7
1
(
Solid, yield: 85%, m.p.: 196–198°C. H NMR (400 MHz, CDCl
3
,
1
3
C NMR (100 MHz, CDCl
3
, ppm): d ¼ 174.2 (2C), 151.4, 134.9
ppm): d ¼ 7.82 (d, J ¼ 7.6 Hz, 1H), 7.49 (d, J ¼ 7.6 Hz, 1H), 7.37
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