5994
M. S. C. Pedras, M. Hossain / Bioorg. Med. Chem. 15 (2007) 5981–5996
mmax (KBr): 3337, 3239, 2993, 2917, 1497, 1452, 1303,
poured into water (25 mL) and extracted with Et O
2
ꢀ1
1
253, 1175, 1085, 932, 750 cm
.
(2· 25 mL). The combined organic extracts were dried
over Na SO and concentrated under reduced pressure.
The residue was subjected to FCC on silica gel (CH Cl /
2 2
2
4
4
.2.6. 6-Fluoro-3-phenylindole (28) and 4-fluoro-3-pheny-
lindole (29). To a solution of 3-fluorophenyl hydrazine
hydrochloride (200 mg, 1.23 mmol) in water (5 mL),
solid Na CO (80 mg, 0.75 mmol) was added. When all
hexane, 1:9) to afford 3-phenylbenzofuran (30, 8 mg,
10% yield based on recovery of starting material) as col-
orless oil. The spectroscopic data of 30 were identical
2
3
1
6b
the Na CO was dissolved, the mixture was extracted
2
with those of reported data.
3
with CH Cl (2· 10 mL), the combined organic extracts
2
2
were dried over Na SO and concentrated under reduced
4.2.8. Methyl (1-b-D-glucopyranosyl-3-hydroxylindol-2-
yl)methyldithiocarbamate (50). HPLC t = 9.5 min; [a]
2
4
pressure. To this residue, phenyl acetaldehyde (47,
08 lL, 0.97 mmol) was added and the mixture was stir-
red for 1 h at room temperature and then for 30 min at
R
D
1
1
ꢀ211 (c 0.12, CH OH); H NMR (500 MHz, CD CN/
3
3
D O, 5.0:0.01, v/v): d 9.57 (br s, D O exchangeable,
2
2
1
2
00 ꢁC. After that a solution of ZnCl2 (376 mg,
1H), 9.25 (br s, D O exchangeable, 1H), 7.66 (d,
2
.91 mmol) in EtOH (3 mL) was added and the mixture
J = 8 Hz, 1H), 7.37 (d, J = 8 Hz, 1H), 7.16 (dd, J = 8,
8 Hz, 1H), 7.08 (dd, J = 8, 8 Hz, 1H), 5.33 (d,
J = 14.5 Hz, 1H), 4.86 (d, J = 14.5 Hz, 1H), 4.56 (d,
J = 8 Hz, 1H), 3.93 (dd, J = 12, 2 Hz, 1H), 3.64 (dd,
J = 12, 7 Hz, 1H), 3.45 (dd, J = 8, 8 Hz, 1H), 3.38 (dd,
was stirred at 100 ꢁC for another 1 h. After cooling, the
mixture was filtered, the solvent was removed under re-
duced pressure, and an aqueous solution of HCl (4%,
1
0 mL) was added. The mixture was extracted with
1
3
CH Cl (2· 15 mL), the combined organic extracts were
dried over Na SO and concentrated under reduced
pressure. The residue was then subjected to FCC on silica
gel (CH Cl /hexane, 1:4) to give a mixture (150 mg, 72%
yield) of 6-fluoro-3-phenylindole (28) and 4-fluoro-3-
phenylindole (29) in equal ratio. Finally, these two
compounds were separated by reverse phase column
chromatography using H O/CH CN (55:45) as eluant.
J = 8, 8 Hz, 1H), 3.31–3.24 (m, 2H), 2.62 (s, 3H).
C
2
2
NMR (125.8 MHz, CD CN): d 201.6 (s), 135.2 (s),
2
4
3
133.9 (s), 126.6 (s), 123.6 (d), 121.6 (s), 120.2 (d), 118.6
(d), 112.9 (d), 105.9 (d), 77.3 (d), 77.1 (d), 74.4 (d),
71.2 (d), 62.7 (t), 41.2 (t), 18.4 (q). HRMS-ESI m/z: mea-
2
2
ꢀ
sured 413.0840 ((Mꢀ1) , calcd 413.0846 for
C H N O S ). FTIR m (KBr): 3359, 2922, 1471,
max
1
7
21
2
6
2
ꢀ
1
1384, 1256, 1072 cm . UV (CH CN) k
(loge): 223
2
3
3
max
1
6
-Fluoro-3-phenylindole (28): HPLC t = 27.4 min; H
R
(4.5), 272 (4.2) nm.
NMR (500 MHz, CD CN): d 9.54 (br s, D O exchange-
able, 1H), 7.87 (dd, J = 5, 9 Hz, 1H), 7.69 (dd, J = 8,
3
2
4.2.9. Methyl (thianaphthen-3-yl-1-S-oxide)methyldithio-
carbamate (51). To a solution of thianaphthene-3-meth-
anamine (40, 19 mg, 0.12 mmol) in CF COOH/CH Cl
1
2
2
Hz, 2H), 7.52 (d, J = 2.5 Hz, 1H), 7.47 (dd, J = 8 Hz,
H), 7.30 (dd, J = 7.5, 7.5 Hz, 1H), 7.24 (dd, J = 10,
Hz, 1H), 6.96 (ddd, J = 10, 9, 2.5 Hz, 1H). C NMR
3
2
2
1
3
(1:2, 0.75 mL) was added H O (30%, 53 lL, 0.47 mmol)
2 2
1
(
(
1
125.8 MHz, CDCl ): d 160.5 (d, J
= 239 Hz), 137.0
C–F
at 0 ꢁC and the reaction mixture was stirred at the same
temperature. After 3 h, the mixture was neutralized with
10% NaHCO and extracted with CH Cl (2· 10 mL).
3
3
d, J
= 12.5 Hz), 135.5, 129.2, 127.9, 126.6, 122.9,
22.2 (d, JC–F = 3.5 Hz), 121.1 (d, JC–F = 10 Hz),
C–F
4
3
3
2
2
2
18.9, 109.4 (d, J
2
= 24 Hz), 98.0 (d, J
1
= 26 Hz).
The combined organic extracts were dried over Na SO
2 4
C–F
C–F
+
HRMS-EI m/z: measured 211.0797 (M , calcd 211.0797
for C H NF). MS-EI m/z (% relative intensity) 211
and concentrated under reduced pressure. The residue
was immediately dissolved in CH Cl (0.5 mL), cooled
1
4
10
2
2
+
(
M , 100), 183 (26). FTIR m
(KBr): 3419, 3054,
to 0 ꢁC, Et N (50 lL) and CS (50 lL) were added,
max
3
2
ꢀ
1
1626, 1601, 1503, 1419, 1222, 1035, 960, 758, 733 cm
4-Fluoro-3-phenylindole (29): HPLC t = 25.8 min; H
.
and the mixture was stirred at 0 ꢁC. After 60 min,
1
CH I (50 lL) was added and the reaction mixture was
R
3
NMR (500 MHz, CD CN): d 9.69 (br s, D O exchange-
stirred for 30 min at room temperature. The reaction
mixture was poured into water (10 mL) and extracted
with CH Cl (2· 10 mL). The combined organic extracts
3
2
able, 1H), 7.64 (dd, J = 8, 1.5 Hz, 2H), 7.43 (dd,
J = 7.5, 7.5 Hz, 2H), 7.41 (d, J = 2.5 Hz, 1H), 7.34 (d,
J = 8 Hz, 1H), 7.31 (dd, J = 7, 7 Hz, 1H), 7.18-7.16 (m,
2
2
were dried over Na SO , concentrated under reduced
2
4
1
3
1
H), 6.83 (dd, J = 8, 12 Hz, 1H).
C
NMR
= 248 Hz), 139.7
pressure, and the residue was applied for FCC on silica
gel (CH Cl /MeOH, 99:1) to afford methyl (thianaph-
then-3-yl-1-S-oxide)methyldithiocarbamate (51, 3 mg,
1
(
(
1
1
1
2
125.8 MHz, CDCl ): d 157.5 (d, J
3 C–F
3
2
2
d, JC–F = 12 Hz), 135.3, 129.2, 129.1, 128.6, 126.6,
3
23.3 (d, J
4
= 8 Hz), 122.9, 118.0 (d, J
= 3 Hz),
C–F
9%) as an off-white solid. HPLC t = 10.8 min; [a]
C–F
R
D
2
15.0 (d, JC–F = 19 Hz), 107.7 (d, JC–F = 3.5 Hz),
4
1
ꢀ252 (c 0.18, MeOH); H NMR (500 MHz, CD OD):
3
2
06.0 (d, = 21 Hz). HRMS-EI m/z: measured
11.0834 (M , calcd 211.0797 for C H NF). MS-EI
m/z (% relative intensity): 211 (M , 100), 183 (21). FTIR
mmax (KBr): 3418, 3054, 1625, 1600, 1546, 1502, 1419,
J
d 7.97 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H),
7.67 (dd, J = 7.5, 7.5 Hz, 1H), 7.61 (dd, J = 7.5,
7.5 Hz, 1H), 7.01 (s, 1H) 5.05 (AB quartet, J = 17,
C–F
+
1
4
10
+
1
3
17 Hz, 2H), 2.65 (s, 3H).
C NMR [125.8 MHz,
ꢀ
1
1
327, 1222, 1035, 758 cm
.
CD OD]: d 201.1 (s), 146.3 (s), 145.6 (s), 136.8 (s),
3
132.7 (d), 131.7 (d), 129.7 (d), 126.4 (d), 123.4 (d),
44.0 (t), 17.2 (q). HRMS-ESI m/z: measured 270.0079
4
phenylvinyl)phenol (49, 98 mg, 0.5 mmol) in DMF
.2.7. 3-Phenylbenzofuran (30). To a solution of o-(1-
1
8
+
([M+1] , calcd 270.0075 for C H NOS ). MS-EI m/z
1
1
12
+
3
(
1.25 mL) were added Cu(OAc) ÆH O (300 mg,
(% relative intensity): 270 ([M+1] , 100). FTIR m
max
(KBr): 3230, 3037, 2922, 1518, 1237, 1121, 1012, 935,
2
2
1
.5 mmol), aqueous LiCl (10 M, 150 lL, 1.5 mmol),
ꢀ1
and aqueous PdCl (0.1 M, 100 lL, 0.01 mmol). After
757 cm . UV (CH OH) k
(loge): 222 (4.4), 246
2
3
max
refluxing at 100 ꢁC for 20 h, the reaction mixture was
(4.1), 270 nm (4.0).