P. Dallemagne et al. / Bioorg. Med. Chem. 10 (2002) 2185–2191
2189
1
,3-Dimethyl-6-oxo-5,6-dihydro-4H-cyclopenta[c]thien-4-
was purified by column chromatography (3.50ꢄ30 cm,
ylammonium chloride (1g). This was prepared by reflux-
ing for 12 h a solution of 2 g (0.006 mol) of 10g in
silica gel 60, 0.063–0.200 mm) with petroleum ether-
EtOAc (80:20) as the eluent, resulting in a colorless oil
1
1
00 mL of a 10 N aqueous HCl solution. After eva-
poration of the reaction mixture, the resulting crystals
81%) were recrystallized from isopropanol: White
(70%): H NMR (DMSO-d ) d 8.07 (d, J=2 Hz, 1H,
6
H-3), 7.55 (d, J=2 Hz, 1H, H-1), 5.65 (dd, J=7, 2 Hz,
1H, H-6), 5.1 (bs, 1H, OH), 3.25 (dd, J=19, 7 Hz, 1H,
H-5a), 2.67 (dd, J=19, 2 Hz, 1H, H-5b). Anal. calcd for
C H O S: C, 54.53; H, 3.92; S, 20.80. Found: C, 54.69;
(
ꢀ
1
crystals, mp >260 C; H NMR (DMSO-d ) d 8.7 (bs,
3
H-5a), 2.90 (dd, J=19, 4 Hz, 1H, H-5b), 2.61 (s, 3H,
6
H, NH ), 4.8 (bs, 1H, H-4), 3.44 (dd, J=19, 8 Hz, 1H,
3
7
6
2
H, 4.08; S, 21.02.
1
3
CH ), 2.56 (s, 3H, CH ); CNMR (DMSO- d ) d 193.9
3
3
6
(
C-6), 144.3 (C-6a), 139.9 (C-1), 139.1 (C-3), 132.9
C-3a), 49.2 (C-4), 42.6 (C-5), 12.8 (CH ), 12.7 (CH ).
1,3,6-Trichloro-5,6-dihydro-4H-cyclopenta[c]thiophen-4-
one (3a). This was prepared by refluxing for 15 min,
0.7 g (0.003 mol) of 2a in 10 mL of thionyl chloride.
After evaporation, the resulting oil was dissolved in
(
Anal. calcd for C H NOClS: C, 49.65; H, 5.56; N, 6.43.
Found: C, 49.45; H, 5.58; N, 6.52.
3
3
9
12
30 mL of Et O and the solution was washed with water.
The organic layer was separated, dried over MgSO and
2
1,3-Dichloro-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thio-
phen-4-one (2a). This was prepared by adding at 0 C,
7
4
ꢀ
g (0.102 mol) of NaNO2 to a solution of 4.5 g
0.017 mol) of 1a in 100 mL of a 20% aqueous AcOH
the solvent was removed to afford crystals (68%) which
were recristallized from ether–petroleum ether (50:50):
ꢀ
J=8, 2 Hz, 1H, H-6), 3.61 (dd, J=20, 8 Hz, 1H, H-5a),
1
(
Beige crystals, mp 75 C; H NMR (CDCl ) d 5.27 (dd,
3
solution. The reaction mixture was then stirred at room
temperature for 4 h. Crystals (80%) were formed, fil-
tered, washed with water, dried and recrystallized from
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3
3.20 (dd, J=20, 2 Hz, 1H, H-5b); CNMR (CDCl 3) d
192.0 (C-4), 147.21 (C-3a), 138.0 (C-6a), 132.0 (C-3),
121.0 (C-1), 54.6 (C-5), 46.1 (C-6). Anal. calcd for
C H OCl S: C, 34.81; H, 1.25; S, 13.28. Found: C,
ꢀ
1
Et O: Beige crystals, mp 73 C; H NMR (DMSO-d ) d
2
6
5
(
.8 (bs, 1H, OH), 5.06 (dd, J=7, 1 Hz, 1H, H-6), 3.31
dd, J=19, 7 Hz, 1H, H-5a), 2.68 (dd, J=19, 1 Hz, 1H,
7
3
3
34.66, H, 1.32; S, 13.05.
1
3
H-5b); CNMR (DMSO- d ) d 192.7 (C-4), 149.9
6
(
C-3a), 138.2 (C-6a), 126.9 (C-3), 121.8 (C-1), 63.4
C-5), 53.6 (C-6). Anal. calcd for C H O Cl S: C, 37.69;
6-Bromo-1,3-dichloro-5,6-dihydro-4H-cyclopenta[c] thio-
phen-4-one (4a). This was prepared by adding at 0 C,
ꢀ
0.25 mL of bromine (0.005 mol) to a suspension of 1.2 g
(
H, 1.81; S, 13.76. Found: C, 37.46; H, 2.21; S, 13.69.
7
4
2
2
(0.005 mol) of 2a in 30 mL of AcOH. The reaction mix-
1
,3-Dibromo-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thio-
phen-4-one (2b). This was prepared from 1b using the
ture was stirred at room temperature for 5 h and then
poured into 100 mL of cold water. Crystals (50%) were
formed, filtered, washed with water, dried and recrys-
same method and concentrations as for the synthesis of
2a. Crystals (76%) were formed, filtered, washed with
water, dried and recrystallized from Et O: Beige crys-
ꢀ
1
tallized from Et O: Yellow crystals, mp 82 C; H NMR
2
(DMSO-d ) d 5.50 (dd, J=8, 2 Hz, 1H, H-6), 3.74 (dd,
2
6
ꢀ
1
tals, mp 75 C; H NMR (DMSO-d ) d 5.7 (bs, 1H,
J=20, 8 Hz, 1H, H-5a), 3.10 (dd, J=20, 2 Hz, 1H,
H-5b). Anal. calcd for C H OBrCl S: C, 29.40; H, 1.06;
S, 11.21. Found: C, 29.35; H, 1.30; S, 11.49.
6
OH), 5.00 (dd, J=7, 2 Hz, 1H, H-6), 3.31 (dd, J=19,
Hz, 1H, H-5a), 2.67 (dd, J=19, 2 Hz, 1H, H-5b); 13
7
3
2
7
C
NMR (DMSO-d ) d 192.5 (C-4), 158.1 (C-3a), 154.1
6
(C-6a), 115.0 (C-3), 111.8 (C-1), 64.4 (C-5), 63.2 (C-6).
Anal. calcd for C H O Br S: C, 26.95; H, 1.29; S, 10.28.
Found: C, 26.74; H, 1.37; S, 10.35.
6-Benzylamino-1,3-dichloro-5,6-dihydro-4H-cyclopenta
[c]thiophen-4-one (5a). This was prepared by refluxing
for 3 h a solution of 0.6 g (0.003 mol) of 9a and 0.4 g
7
4
2
2
(0.0037 mol) of benzylamine in 20 mL of chloroform.
After evaporation of the reaction mixture, the resulting
oil was dissolved in 30 mL of Et O and the solution was
2
1-Bromo-6-hydroxy - 5,6 - dihydro - 4H - cyclopenta[c]thio-
phen-4-one (2c). This was prepared by adding at 0 C,
5
ꢀ
.5 g (0.08 mol) of NaNO2 to a solution of 2.7 g
0.01 mol) of 1c in 50 mL of a 20% aqueous AcOH
washed with water. The organic layer was separated and
dried over MgSO . After filtration and evaporation, the
(
4
solution. The reaction mixture was stirred at room
temperature for 6 h, neutralized with NaHCO3 and
extracted with CHCl . The organic layer was separated,
crude oil was purified by column chromatography
(3.5ꢄ30 cm, silica gel 60, 0.063–0.200 mm) with petro-
leum ether–EtOAc (90:10) as the eluent, resulting in a
1
3
dried over CaCl and evaporated. The resulting brown
2
yellow oil (20%): H NMR (CDCl ) d 7.30 (m, 5H,
3
oil was purified by column chromatography (3.5ꢄ30 cm,
phenyl), 4.40 (m, 1H, H-6), 4.2 (bs, 1H, NH), 3.80 (m,
2H, CH ), 3.21 (dd, J=19, 7 Hz, 1H, H-5a), 2.88 (dd,
silica gel 60, 0.063–0.200 mm) with petroleum ether–
EtOAc (80:20) as the eluent, resulting in a colorless oil
2
1
3
J=19, 3 Hz, 1H, H-5b); C NMR (CDCl ) d 193.4
3
1
(
70%): H NMR (DMSO-d ) d 8.12 (s, 1H, H-3), 5.7
(C-4), 149.7 (C-3a), 139.3 (C-6a), 137.5 (C-3), 128.6
(C-2a and C-6a), 128.5 (C-1 ), 128.2 (C-3 and C-5 ),
6
0
127.4 (C-4 ), 119.0 (C-1), 51.6 (CH ), 51.2 (C-5), 51.1
0
0
(bs, 1H, OH), 5.04 (dd, J=7, 2 Hz, 1H, H-6), 3.35 (dd,
J=19, 7 Hz, 1H, H-5a), 2.67 (dd, J=19, 2 Hz, 1H,
0
(C-6). Anal. calcd for C H NOCl S: C, 53.86; H, 3.55;
N, 4.49. Found: C, 53.97; H, 3.52; N, 4.42.
2
H-5b). Anal. calcd for C H O BrS: C, 36.07; H, 2.16; S,
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5
2
14 11
2
1
3.76. Found: C, 36.02; H, 2.04; S, 13.58.
6
-Hydroxy-5,6-dihydro-4H-cyclopenta[c]thiophen-4-one (2d).
6-Anilino-1,3-dichloro-5,6-dihydro-4H-cyclopenta[c] thio-
phen-4-one (6a). This was prepared from 9a and aniline
using the same method as for the synthesis of 5a.
This was prepared from 1d using the same method and
concentrations as for the synthesis of 2c. The crude oil