Convenient synthesis of 3-substituted benzo[b]thiophenes by iodine-mediated cyclization of α-substituted 2-(1-Phenylethylthio)styrenes

Article abstract of DOI:10.1246/bcsj.80.1780

A new and convenient method for the preparation of 3-substituted benzo[b]thiophenes was developed. α-Substituted 2-(1-phenylethylthio) styrenes, which could easily be prepared from 2-mercaptophenyl ketones or benzenethiols in two or three steps, respectively, underwent 5-endo cyclization on treatment with iodine in the presence of sodium hydrogencarbonate in acetonitrile at room temperature to give 3-substituted benzo[b]thiophenes in fair to good yields.

Full text of DOI:10.1246/bcsj.80.1780

1780 Bull. Chem. Soc. Jpn. Vol. 80, No. 9, 1780–1784 (2007)
Ó 2007 The Chemical Society of Japan
Convenient Synthesis of 3-Substituted Benzo[b]thiophenes
by Iodine-Mediated Cyclization of ꢀ-Substituted
2-(1-Phenylethylthio)styrenes
ꢀ
Osamu Morikawa, and Hisatoshi Konishi
Kazuhiro Kobayashi, Daizo Nakamura, Kazuna Miyamoto,
Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552
Received January 5, 2007; E-mail: kkoba@chem.tottori-u.ac.jp
A new and convenient method for the preparation of 3-substituted benzo[b]thiophenes was developed. ꢀ-Substi-
tuted 2-(1-phenylethylthio)styrenes, which could easily be prepared from 2-mercaptophenyl ketones or benzenethiols
in two or three steps, respectively, underwent 5-endo cyclization on treatment with iodine in the presence of sodium
hydrogencarbonate in acetonitrile at room temperature to give 3-substituted benzo[b]thiophenes in fair to good yields.
In a previous paper, we have reported an efficient synthesis
of 1-aryl-1H-indoles by iodine-mediated cyclization of 2-(aryl-
amino)styrene derivatives1 and now wish to describe an appli-
cation of this cyclization reaction to the synthesis of benzo[b]-
thiophenes.2 We have found that 3-substituted benzo[b]thio-
phenes 7 are obtained in reasonable yields by treating ꢀ-sub-
stituted 2-(1-phenylethylthio)styrenes 3 with iodine.3 Benzo-
[b]thiophene derivatives are an important class of hetero-
cycles, because a number of molecules having this skeleton
have been shown to exhibit a variety of biological activities.4
The starting ꢀ-substituted 2-(1-phenylethylthio)styrenes 3
were easily prepared according to the two sequences stated
below. First, readily available 2-mercaptophenyl ketones 15–7
were S-1-phenylethylated with (1-bromoethyl)benzene and
sodium hydride. The resulting 2-(1-phenylethylthio)phenyl
ketones 2 were subjected to a Wittig reaction with methylene-
triphenylphosphorane to give 3a–3f (Scheme 1). Secondly,
lithiation of 4-alkylbenzenethiols 4 by butyllithium under the
conditions reported by Martin et al.,8 followed by reaction of
the resultant lithium 2-lithiobenzenethiolates with acetone,
afforded 2-(4-alkyl-2-mercaptophenyl)propan-2-ols 5, which
were S-1-phenylethylated with (1-bromoethyl)benzene and
sodium hydride to afford 2-[4-alkyl-2-(1-phenylethylthio)phen-
yl]propan-2-ols 6. Sequential dehydration of these 2-(2-mer-
captophenyl)propan-2-ols 6 with a catalytic amount of concen-
trated sulfuric acid in acetic anhydride afforded 5-substituted
ꢀ-methyl-2-(1-phenylethylthio)styrenes 3g and 3h (Scheme 2).
ꢀ-Substituted 2-(1-phenylethylthio)styrene derivatives 3,
thus obtained, smoothly underwent 5-endo cyclization reaction
on treatment with iodine in the presence of sodium hydrogen
carbonate in acetonitrile at room temperature to provide the
desired 3-substituted benzo[b]thiophenes 7 in fair to good
yields, as summarized in Scheme 3. It indicates that both 3-
alkyl- and 3-aryl-benzo[b]thiophenes can be prepared, whereas
3-arylindole derivatives can not be obtained in the indole syn-
SH
Me
OH
SH
1) 2 n-BuLi, 2 TMEDA
SH
SCHMePh
NaH
R2
R2
2) acetone
R1
R1
PhCHBrMe
Me
4
O
5g 69%
5h 57%
O
1
2a 79%
2b 78%
2c 78%
SCHMePh
Me
NaH
2d 76%
2e 88%
PhCHBrMe
R2
2f 76%
OH
Me
a R1 = Me
b R1 = n-Bu
g R2 = Me
SCHMePh
6g 74%
6h 77%
Ph3P=CH2
c R1 = sec-Bu
h R2 = t-Bu
d R1 = Ph
e R1 = m-Tol
SCHMePh
R1
3a 88%
f R1 = 4-ClC6H4
H2SO4
Ac2O
R2
3b 75%
3c 76%
3d 77%
3e 60%
3f 77%
Me
3g 65%
3h 55%
Scheme 1.
Scheme 2.
Published on the web September 13, 2007; doi:10.1246/bcsj.80.1780

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 9 (2007) 1781
rected. The IR spectra were recorded on a Shimadzu FTIR-8300
spectrometer. 1H NMR spectra were determined using SiMe4 as
an internal reference in CDCl3 with a JEOL ECP500 FT NMR
spectrometer operating at 500 MHz. 13C NMR spectra were deter-
mined using SiMe4 as an internal reference with a JEOL ECP500
FT NMR spectrometer operating at 125 MHz in CDCl3. Low-
resolution mass spectra were recorded on a JEOL AUTOMASS
20 spectrometer (Center for Joint Research and Development,
this University). Thin-layer chromatography (TLC) was carried
out using Merck Kieselgel 60 PF254. Column chromatography
was performed using Merck Kieselgel 60 (0.063–0.200 mm). All
of the solvents used were dried over the appropriate drying agents
and distilled under argon prior to use.
Starting Materials. 1-(2-Mercaptophenyl)ethanone,5 (2-mer-
captophenyl)phenylmethanone,6 (2-mercaptophenyl)(3-methyl-
phenyl)methanone,7 and (4-chlorophenyl)(2-mercaptophenyl)-
methanone7 were prepared according to reported procedures. All
other chemicals used in this study were commercially available.
1-(2-Mercaptophenyl)pentan-1-one.9 This compound was
prepared from 2-mercaptobenzoic acid and butyllithium under
same conditions as reported for the preparation of 1-(2-mercapto-
phenyl)ethanone5 in 68% yield; a white solid; mp 44–45 ꢁC (hex-
ane–Et2O) (lit.,9 mp 46–47 ꢁC).
SCHMePh
S
I2, NaHC O3
MeCN, rt
R2
R2
R1
R1
7a 77%
7b 64%
7c 61%
7d 58%
7e 54%
7f 57%
7g 65%
7h 56%
3
a R1 = Me, R2 = H
b R1 = n-Bu, R2 = H
c R1 = sec-Bu, R2 = H
d R1 = Ph, R2 = H
e R1 = m-Tol, R2 = H
f R1 = 4-ClC6H4, R2 = H
g R1 = R2 = Me
h R1 = Me, R2 = t-Bu
Scheme 3.
Me
Ph
I
Me
Ph
I
S
S
I2
3
R2
I
R2
I
R1
R1
8
9
Me
Ph
1-(2-Mercaptophenyl)-2-methylbutan-1-one.
This com-
I
pound was prepared from 2-mercaptobenzoic acid and sec-butyl-
lithium under same conditions as reported for the preparation of
1-(2-mercaptophenyl)ethanone5 in 73% yield; a yellow liquid;
;
bp 120 ꢁC/120 Pa; IR (neat) 2550 and 1666 cmꢂ1 1H NMR ꢂ
− HI
S
− PhCHIMe
7
R2
R1
10
0.92 (3H, t, J ¼ 7:3 Hz), 1.20 (3H, d, J ¼ 6:9 Hz), 1.46–1.55
(1H, m), 1.79–1.88 (1H, m), 3.34–3.40 (1H, m), 4.25 (1H, s),
6.99–7.34 (3H, m), and 7.83 (1H, dd, J ¼ 7:8 and 1.4 Hz). Calcd
for C11H14OS: C, 68.00; H, 7.26%. Found: C, 67.88; H, 7.25%.
Typical Procedure for the Preparation of 2-(1-Phenylethyl-
thio)phenyl Ketones 2. 1-[2-(1-Phenylethylthio)phenyl]etha-
none (2a): To a stirred suspension of NaH (60% in oil; 0.12 g,
2.9 mmol) in THF (6 mL) at 0 ꢁC was added a solution of 1-(2-
mercaptophenyl)ethanone (1a)5 (0.44 g, 2.9 mmol) in THF (6 mL)
dropwise. After 15 min, (1-bromoethyl)benzene (0.54 g, 2.9 mmol)
was added, and stirring was continued an additional 1 h at the
same temperature. Saturated aqueous NH4Cl (15 mL) was added,
and the mixture was extracted with Et2O twice (15 mL each). The
combined extracts were washed with brine, and dried over anhy-
drous Na2SO4, and the solvent was evaporated. The residue was
purified by column chromatography on silica gel to give the title
compound (0.58 g, 79%): a pale-yellow oil; Rf 0.59 (3:1 hexane–
Scheme 4.
thesis previously reported by us.1 Unfortunately, however, the
possibility of the preparation of 2,3-disubstituted 3-aryl-
benzo[b]thiophenes could not be examined, because the re-
spective ꢀ,ꢁ-disubstituted 2-(1-phenylethylthio)styrene deriv-
atives could not be prepared by reactions of 2-(1-phenylethyl-
thio)phenyl ketones with alkylidenetriphenylphosphoranes. It
should be noted that, when ꢀ-phenyl-2-(phenylmethylthio)-
styrene was subjected to the iodocyclization reaction under
the same conditions as described above, a considerably smaller
amount (39%) of the desired 3-phenylbenzo[b]thiophene (7d)
was isolated from a rather complex reaction mixture.
The formation of the benzo[b]thiophenes 7 from the 2-(1-
phenylethylthio)styrenes 3 is thought to proceed as illustrated
in Scheme 4. Treatment of 3 with iodine generates the iodo-
nium ion intermediates 8. A 5-endo attack of the lone pair
electrons of the sulfur atom on the iodonium ion moiety gives
the sulfonium ion intermediate 9. Sequential elimination of
hydrogen iodide from 9 gives the benzothiophenium ion inter-
mediate 10, from which loss of (1-iodoethyl)benzene gives 7.
In summary, the results detailed herein demonstrate that 3-
substituted benzo[b]thiophenes can be conveniently prepared
from readily available starting materials using simple manipu-
lations. Work on the utilization of this and related methodolo-
gies for the syntheses of other thiophene-fused heterocycles
are in progress in our laboratory and will be described at a
later date.
EtOAc); IR (neat) 1663 cmꢂ1
;
1H NMR ꢂ 1.65 (3H, d, J ¼ 6:9
Hz), 2.57 (3H, s), 4.22 (1H, q, J ¼ 6:9 Hz), 7.15–7.23 (2H, m),
7.27–7.30 (3H, m), 7.33 (1H, dd, J ¼ 7:8 and 1.4 Hz), 7.38 (2H,
d, J ¼ 7:3 Hz), and 7.61 (1H, dd, J ¼ 7:8 and 1.4 Hz). Calcd for
C16H16OS: C, 74.96; H, 6.29%. Found: C, 74.91; H, 6.20%.
1-[2-(1-Phenylethylthio)phenyl]pentan-1-one (2b): A yellow
solid; mp 59–60 ꢁC (hexane–Et2O); IR (KBr disk) 1670 cmꢂ1
;
1H NMR ꢂ 0.93 (3H, t, J ¼ 7:3 Hz), 1.39 (2H, sextet, J ¼ 7:3
Hz), 1.63 (3H, d, J ¼ 6:9 Hz), 1.68 (2H, quintet, J ¼ 7:3 Hz),
2.86 (2H, t, J ¼ 7:3 Hz), 4.38 (1H, q, J ¼ 6:9 Hz), 7.16–7.21
(2H, m), 7.23–7.28 (3H, m), 7.31 (1H, d, J ¼ 7:8 Hz), 7.34 (2H,
d, J ¼ 7:3 Hz), 7.51 (1H, dd, J ¼ 7:3 and 1.4 Hz); 13C NMR ꢂ
13.94, 22.38, 22.60, 26.37, 41.53, 47.16, 125.62, 127.14, 127.25
(two overlapped C’s), 128.33, 128.47 (two overlapped C’s),
130.69, 131.11, 143.12, and 204.13. Calcd for C19H22OS: C,
76.46; H, 7.43%. Found: C, 76.43; H, 7.52%.
Experimental
General. The melting points were determined on a Laboratory
Devices MEL-TEMP II melting-point apparatus and are uncor-
2-Methyl-1-[2-(1-phenylethylthio)phenyl]butan-1-one (2c):

1782 Bull. Chem. Soc. Jpn. Vol. 80, No. 9 (2007)
Synthesis of Benzo[b]thiophenes
A yellow oil; a mixture of diastereomers (ca. 1:1); Rf 0.45 (1:2
THF–hexane); IR (neat) 1693 cmꢂ1 1H NMR ꢂ 0.91 (3H, t,
;
Hz each), 2.45–2.54 (1H, m), 4.37 (1H, q, J ¼ 6:9 Hz), 4.88 (1H,
t, J ¼ 1:4 Hz), 5.15 (1H, t, J ¼ 1:4 Hz), 7.02–7.05 (1H, m), 7.08–
7.14 (2H, m), 7.16–7.21 (1H, m), 7.23–7.31 (5H, m). Calcd for
C20H24S: C, 81.02; H, 8.16%. Found: C, 80.75; H, 8.13%.
J ¼ 7:3 Hz), 1.15 and 1.16 (3H, 2d, J ¼ 6:9 Hz each), 1.39–1.48
(1H, m), 1.61 (3H, d, J ¼ 6:9 Hz), 1.73–1.83 (1H, m), 3.15–3.24
(1H, m), 4.38 (1H, q, J ¼ 6:9 Hz), 7.19 (2H, dd, J ¼ 7:8 and
7.3 Hz), 7.23–7.27 (3H, m), 7.29–7.33 (3H, m), and 7.43 (1H, d,
J ¼ 7:3 Hz). Calcd for C19H22OS: C, 76.46; H, 7.43%. Found:
C, 76.31; H, 7.37%.
1-(1-Phenylethenyl)-2-(1-phenylethylthio)benzene (3d):
A
pale-yellow oil; Rf 0.72 (5:1 hexane–EtOAc); IR (neat) 1614 and
1601 cmꢂ1; 1H NMR ꢂ 1.44 (3H, d, J ¼ 6:9 Hz), 4.19 (1H, q, J ¼
6:9 Hz), 5.16 (1H, d, J ¼ 1:4 Hz), 5.78 (1H, d, J ¼ 1:4 Hz), 7.16–
7.24 (10H, m), and 7.26–7.30 (4H, m); 13C NMR ꢂ 22.27, 47.11,
115.74, 126.60, 126.68, 126.95, 127.28, 127.49, 127.74, 128.14,
128.23, 130.56, 132.29, 134.58, 140.70, 143.28, 144.21, and
148.67. Calcd for C22H20S: C, 83.50; H, 6.37%. Found: C,
83.37; H, 6.62%.
1-[1-(3-Methylphenyl)ethenyl]-2-(1-phenylethylthio)benzene
(3e): A yellow oil; Rf 0.83 (4:1 hexane–CH2Cl2); IR (neat) 1614
and 1601 cmꢂ1; 1H NMR ꢂ 1.44 (3H, d, J ¼ 6:9 Hz), 2.31 (3H, s),
4.18 (1H, q, J ¼ 6:9 Hz), 5.14 (1H, d, J ¼ 0:9 Hz), 5.77 (1H, d,
J ¼ 0:9 Hz), 7.01 (1H, d, J ¼ 7:8 Hz), 7.08 (2H, d, J ¼ 7:8 Hz),
7.15–7.22 (9H, m), and 7.27 (1H, ddd, J ¼ 7:8, 6.9, and 1.8 Hz).
Calcd for C23H22S: C, 83.59; H, 6.71%. Found: C, 83.54; H,
6.43%.
Phenyl[2-(1-phenylethylthio)phenyl]methanone (2d): A pale-
yellow oil; Rf 0.39 (10:1 pentane–Et2O); IR (neat) 1668 cmꢂ1
;
1H NMR ꢂ 1.52 (3H, d, J ¼ 6:9 Hz), 4.31 (1H, q, J ¼ 6:9 Hz),
7.15–7.21 (4H, m), 7.26–7.37 (5H, m), 7.43 (2H, dd, J ¼ 8:2 and
7.3 Hz), 7.57 (1H, tt, J ¼ 7:3 and 1.4 Hz), and 7.72 (2H, dd, J ¼
8:2 and 1.4 Hz). Calcd for C21H18OS: C, 79.21; H, 5.70%. Found:
C, 79.21; H, 5.90%.
(3-Methylphenyl)[2-(1-phenylethylthio)phenyl]methanone
(2e): A yellow oil; Rf 0.75 (5:1 hexane–EtOAc); IR (neat) 1666
and 1601 cmꢂ1; 1H NMR ꢂ 1.52 (3H, d, J ¼ 6:9 Hz), 2.38 (3H, s),
4.31 (1H, q, J ¼ 6:9 Hz), 7.15–7.21 (4H, m), 7.27–7.34 (6H, m),
7.38 (1H, d, J ¼ 7:3 Hz), 7.47 (1H, d, J ¼ 7:3 Hz), and 7.58 (1H,
s). Calcd for C22H20OS: C, 79.48; H, 6.06%. Found: C, 79.45; H,
6.19%.
1-[1-(4-Chlorophenyl)ethenyl]-2-(1-phenylethylthio)benzene
(3f): A pale-yellow oil; Rf 0.70 (10:1 hexane–Et2O); IR (neat)
1614 cmꢂ1; 1H NMR ꢂ 1.47 (3H, d, J ¼ 7:3 Hz), 4.23 (1H, q, J ¼
7:3 Hz), 5.22 (1H, s), 5.73 (1H, s), 7.09 (2H, d, J ¼ 8:2 Hz), and
7.11–7.32 (11H, m). Calcd for C22H19ClS: C, 75.30; H, 5.46%.
Found: C, 75.06; H, 5.54%.
(4-Chlorophenyl)[2-(1-phenylethylthio)phenyl]methanone
(2f): A yellow oil; Rf 0.37 (10:1 pentane–Et2O); IR (neat) 1667
1
cmꢂ1; H NMR ꢂ 1.53 (3H, d, J ¼ 6:9 Hz), 4.30 (1H, q, J ¼ 6:9
Hz), 7.16–7.20 (2H, m), 7.21–7.36 (5H, m), 7.39 (1H, d, J ¼
8:2 Hz), 7.42 (2H, d, J ¼ 8:7 Hz), 7.63 (1H, d, J ¼ 8:2 Hz), and
7.71 (2H, d, J ¼ 8:7 Hz). Calcd for C21H17ClOS: C, 71.48; H,
4.86%. Found: C, 71.17; H, 5.05%.
2-(2-Mercapto-5-methylphenyl)propan-2-ol (5g). This com-
pound was prepared by the reaction of lithium 2-lithio-4-methyl-
benzenethiolate, which was generated from 4-methylbenzenethiol
(4g) by the method of Martin et al.,8 with acetone; a white solid;
Typical Procedure for the Preparation of 2-(1-Phenylethyl-
thio)styrenes 3a–3f. 1-(1-Methylethenyl)-2-(1-phenylethylthio)-
benzene (3a): To a stirred suspension of methyltriphenylphos-
phonium iodide (0.77 g, 1.9 mmol) in THF (5 mL) at 0 ꢁC was
mp 40–42 ꢁC (hexane–Et2O); IR (KBr disk) 3290 and 2544 cmꢂ1
;
1H NMR ꢂ 1.70 (6H, s), 2.30 (3H, s), 2.53 (1H, s), 3.96 (1H, s),
6.92 (1H, dd, J ¼ 7:8 and 1.4 Hz), 7.18 (1H, d, J ¼ 7:8 Hz), and
7.19 (1H, d, J ¼ 1:4 Hz). Calcd for C10H14OS: C, 65.89; H,
7.74%. Found: C, 65.85; H, 7.78%.
added n-BuLi (1.5 M in hexane; 1.9 mmol) (1 M = 1 mol dmꢂ3
)
dropwise. After 15 min, a solution of 2a (0.33 g, 1.3 mmol) in
THF (6 mL) was added, and stirring was continued for an addi-
tional 4 h at the same temperature. The resulting mixture was
worked up in a manner similar to that described above, and the
crude product was purified by preparative TLC on silica gel to
give 3a (0.29 g, 88%): a pale-yellow oil; Rf 0.73 (5:1 hexane–
2-[5-Methyl-2-(1-phenylethylthio)phenyl]propan-2-ol. (6g).
This compound was prepared by 1-phenylethylation of 5g as de-
scribed for the preparation of 2a. 6g: Rf 0.31 (8:1 hexane–AcOEt);
1
IR (neat) 3435 cmꢂ1; H NMR ꢂ 1.60 (3H, s), 1.648 (3H, d, J ¼
1
EtOAc); IR (neat) 1639 and 1601 cmꢂ1; H NMR ꢂ 1.60 (3H, d,
6:9 Hz), 1.649 (3H, s), 2.32 (3H, s), 4.33 (1H, q, J ¼ 6:9 Hz), 4.98
(1H, s), 6.93 (1H, dd, J ¼ 7:8 and 1.4 Hz), 7.17 (1H, d, J ¼ 7:8
Hz), and 7.23–7.33 (6H, m). Calcd for C18H22OS: C, 75.48; H,
7.74%. Found: C, 75.33; H, 7.79%.
J ¼ 7:3 Hz), 2.09 (3H, d, J ¼ 0:9 Hz), 4.38 (1H, q, J ¼ 7:3 Hz),
4.85 (1H, quint, J ¼ 0:9 Hz), 5.20 (1H, quint, J ¼ 0:9 Hz), 7.08–
7.16 (4H, m), 7.19 (1H, tt, J ¼ 7:3 and 1.4 Hz), 7.26 (2H, dd, J ¼
7:8 and 7.3 Hz), and 7.30 (2H, dd, J ¼ 7:8 and 1.4 Hz); 13C NMR
ꢂ 22.30, 24.20, 47.38, 115.68, 126.62, 127.05, 127.18, 127.23,
128.34, 128.66, 131.96, 132.90, 143.26, 145.88, and 146.38. Calcd
for C17H18S: C, 80.26; H, 7.13%. Found: C, 79.99; H, 7.18%.
4-Methyl-2-(1-methylethenyl)-1-(1-phenylethylthio)benzene
(3g). This compound was prepared by the treatment of 6g with a
catalytic amount of sulfuric acid in Ac2O at 0 ꢁC; a yellow oil; Rf
1
0.80 (8:1 hexane–AcOEt); IR (neat) 1638 cmꢂ1; H NMR ꢂ 1.58
1-(1-Butylethenyl)-2-(1-phenylethylthio)benzene (3b):
A
;
(3H, d, J ¼ 6:9 Hz), 2.08 (3H, s), 2.28 (3H, s), 4.32 (1H, q, J ¼
6:9 Hz), 4.83 (1H, d, J ¼ 1:4 Hz), 5.17 (1H, d, J ¼ 1:4 Hz), 6.93–
6.94 (2H, m), 7.16–7.20 (2H, m), and 7.24–7.30 (4H, m). Calcd
for C18H20S: C, 80.54; H, 7.51%. Found: C, 80.40; H, 7.59%.
2-[5-(1,1-Dimethylethyl)-2-mercaptophenyl]propan-2-ol (5h).
This compound was prepared by reacting acetone with lithium 4-
(1,1-dimethylethyl)-2-lithiobenzenethiolate, which was generated
from 4-(1,1-dimethylethyl)benzenethiol (4h) by the method of
Martin et al.;8 a yellow solid; mp 54–57 ꢁC (hexane–Et2O); IR
yellow oil; Rf 0.80 (1:3 AcOEt–hexane); IR (neat) 1636 cmꢂ1
1H NMR ꢂ 0.88 (3H, t, J ¼ 7:3 Hz), 1.31–1.34 (4H, m), 1.59 (3H,
d, J ¼ 6:9 Hz), 2.43 (2H, t, J ¼ 6:9 Hz), 4.38 (1H, q, J ¼ 6:9 Hz),
4.85 (1H, s), 5.17 (1H, d, J ¼ 1:4 Hz), 7.05 (1H, dd, J ¼ 6:9 and
1.8 Hz), 7.08–7.13 (2H, m), 7.18 (1H, t, J ¼ 7:3 Hz), 7.24–7.27
(3H, m), and 7.30 (2H, d, J ¼ 7:3 Hz). Calcd for C20H24S: C,
81.02; H, 8.16%. Found: C, 80.80; H, 8.16%.
1-[1-(1-Methylpropyl)ethenyl]-2-(1-phenylethylthio)benzene
(3c): A yellow oil; a mixture of diastereomers (ca. 1:1); Rf 0.83
1
(neat) 3400 and 2557 cmꢂ1; H NMR ꢂ 1.30 (9H, s), 1.55 (1H, br
1
(1:3 AcOEt–hexane); IR (neat) 1631 and 1603 cmꢂ1; H NMR ꢂ
s), 1.72 (6H, s), 3.96 (1H, s), 7.12 (1H, dd, J ¼ 8:2 and 1.8 Hz),
7.21 (1H, d, J ¼ 8:2 Hz), and 7.42 (1H, d, J ¼ 1:8 Hz). Calcd for
C13H20OS: C, 69.59; H, 8.98%. Found: C, 69.52; H, 9.01%.
2-[5-(1,1-Dimethylethyl)-2-(1-phenylethylthio)phenyl]pro-
0.88 and 0.90 (combined 3H, 2t, J ¼ 7:3 Hz each), 1.07 and 1.09
(combined 3H, 2d, J ¼ 6:9 Hz each), 1.20–1.30 (1H, m), 1.52–
1.62 (combined 4H, m including 2d at 1.58 and 1.59, J ¼ 6:9

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 9 (2007) 1783
pan-2-ol (6h). This compound was prepared by 1-phenylethyla-
tion of 5h as described for the preparation of 3a. 6h: a yellow oil;
Rf 0.38 (2:1 hexane–Et2O); IR (neat) 3440 cmꢂ1; 1H NMR ꢂ 1.30
(9H, s), 1.63 (3H, s), 1.66 (3H, d, J ¼ 6:9 Hz), 1.67 (3H, s), 4.35
(1H, q, J ¼ 6:9 Hz), 4.94 (1H, s), 7.14 (1H, dd, J ¼ 8:2 and 2.3
Hz), 7.23–7.27 (2H, m), 7.29–7.33 (4H, m), and 7.45 (1H, d,
J ¼ 2:3 Hz). Calcd for C21H28OS: C, 76.78; H, 8.59%. Found:
C, 76.50; H, 8.80%.
4-(1,1-Dimethylethyl)-2-(1-methylethenyl)-1-(1-phenylethyl-
thio)benzene (3h). This compound was prepared from 6h as de-
scribed for the preparation of 3g. 3h: a pale-yellow oil; Rf 0.81
(10:1 hexane–THF); IR (neat) 1639 cmꢂ1 1H NMR ꢂ 1.28 (9H,
;
s), 1.59 (3H, d, J ¼ 7:3 Hz), 2.10 (3H, d, J ¼ 1:4 Hz), 4.34 (1H,
q, J ¼ 7:3 Hz), 4.86 (1H, d, J ¼ 0:9 Hz), 5.19 (1H, d, J ¼ 0:9
Hz), 7.11 (1H, d, J ¼ 2:3 Hz), 7.14 (1H, dd, J ¼ 8:2 and 2.3 Hz),
7.18–7.21 (2H, m), 7.26 (2H, dd, J ¼ 7:8 and 7.3 Hz), and 7.31
(2H, d, J ¼ 7:8 Hz). Calcd for C21H26S: C, 81.23; H, 8.44%.
Found: C, 80.99; H, 8.67%.
768 cmꢂ1; 1H NMR ꢂ 2.42 (3H, d, J ¼ 0:9 Hz), 2.50 (3H, s), 7.04
(1H, s), 7.18 (1H, d, J ¼ 8:2 Hz), 7.51 (1H, s), 7.72 (1H, d, J ¼
8:2 Hz); MS m=z (%) 162 (Mþ, 100).
5-(1,1-Dimethylethyl)-3-methylbenzo[b]thiophene (7h):13
A
colorless oil; Rf 0.71 (pentane); IR (neat) 3076, 2962, 1448, 1363,
1256, 877, 835, 812, 768, and 656 cmꢂ1; 1H NMR ꢂ 1.41 (9H, s),
2.45 (3H, d, J ¼ 0:9 Hz), 7.05 (1H, q, J ¼ 0:9 Hz), 7.43 (1H, dd,
J ¼ 8:2 and 1.8 Hz), 7.68 (1H, d, J ¼ 1:8 Hz), and 7.78 (1H, d,
J ¼ 8:2 Hz); MS m=z (%) 204 (Mþ, 100).
Determination of mass spectra and performance of combus-
tion analyses by Mrs. Miyuki Tanmatsu of this Department are
gratefully acknowledged.
References
1
K. Kobayashi, K. Miyamoto, T. Yamase, D. Nakamura, O.
Morikawa, H. Konishi, Bull. Chem. Soc. Jpn. 2006, 79, 1580.
For recent general synthesis of benzo[b]thiophene deriva-
Typical Procedure for the Preparation of Benzo[b]thio-
phenes 7. 3-Methylbenzo[b]thiophene (7a):10 To a stirring
mixture of 3a (0.12 g, 0.48 mmol) and NaHCO3 (0.12 g, 1.4 mmol)
in MeCN (2 mL) at 0 ꢁC was added iodine (0.37 g, 1.4 mmol) por-
tionwise; the mixture was then stirred for 4 h at room temperature.
Ten percent aqueous Na2S2O3 was added until the color of iodine
disappeared and the mixture was extracted with Et2O twice
(10 mL each). The combined extracts was washed with saturated
aqueous NaHCO3 and then brine, and dried over anhydrous
K2CO3. After evaporation of the solvent, the residue was purified
by preparative TLC on silica gel to give 7a (55 mg, 77%): a pale-
yellow liquid; Rf 0.76 (8:1 hexane–EtOAc); the 1H NMR spec-
trum of this product was identical to that reported previously.10
3-Butylbenzo[b]thiophene (7b):10 A pale-yellow oil; Rf 0.69
2
tives: a) C. Mukherjee, A. De, Synlett 2002, 325. b) M. G.
Cabiddu, S. Cabbidu, E. Cadoni, S. Demontis, C. Fattuoni, S.
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3
Iodine-mediated cyclization of (2-benzylthiophenyl)acety-
lenes leading to the synthesis of 3-iodobenzo[b]thiophenes has
been reported previously: B. L. Flynn, P. Verdier-pinard, E.
Hamel, Org. Lett. 2001, 3, 651.
1
(8:1 hexane–EtOAc); the H NMR spectrum of this product was
identical to that reported previously.10
4
a) G. De Nanteuil, C. Lila-Ambroise, A. Rupin, M. O.
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3-(1-Methylpropyl)benzo[b]thiophene (7c):11 A pale-yellow
oil; Rf 0.71 (pentane); IR (neat) 3067, 2963, 1456, 1427, 762, and
1
733 cmꢂ1; H NMR ꢂ 0.93 (3H, t, J ¼ 7:3 Hz), 1.35 (3H, d, J ¼
6:9 Hz), 1.62–1.71 (1H, m), 1.80–1.89 (1H, m), 3.10 (1H, sextet,
J ¼ 7:3 Hz), 7.07 (1H, s), 7.33 (1H, ddd, J ¼ 8:2, 7.3, and 1.4 Hz),
7.37 (1H, ddd, J ¼ 7:8, 7.3, and 1.4 Hz), 7.78 (1H, d, J ¼ 7:8 Hz),
and 7.86 (1H, dd, J ¼ 8:2 and 1.4 Hz); MS m=z (%) 190 (Mþ,
100).
3-Phenylbenzo[b]thiophene (7d):10 A pale-yellow oil; Rf
1
0.69 (8:1 hexane–EtOAc); the H NMR spectrum of this product
was identical to that reported previously.10
3-(3-Methylphenyl)benzo[b]thiophene (7e): A colorless oil;
Rf 0.57 (pentane); IR (neat) 3048, 2920, 1605, 1427, 777, 760,
732, and 698 cmꢂ1
;
1H NMR ꢂ 2.44 (3H, s), 7.23 (1H, d, J ¼
6:9 Hz), 7.36–7.41 (6H, m), and 7.91–7.93 (2H, m); 13C NMR ꢂ
21.51, 122.88, 122.99, 123.22, 124.25, 124.35, 125.78, 128.30,
128.59, 129.41, 135.94, 137.96, 138.20, 138.36, and 140.67; MS
m=z (%) 224 (Mþ, 100). Calcd for C15H12S: C, 80.31; H, 5.39%.
Found: C, 80.27; H, 5.67%.
3-(4-Chlorophenyl)benzo[b]thiophene (7f): A pale-yellow
oil; Rf 0.62 (10:1 hexane–EtOAc); IR (neat) 3059, 1585, 1521,
;
1481, 1090, 1014, 825, 762, and 734 cmꢂ1 1H NMR ꢂ 7.38–
7.41 (3H, m), 7.46 (2H, d, J ¼ 8:7 Hz), 7.52 (2H, d, J ¼ 8:7 Hz),
7.85 (1H, dd, J ¼ 7:3 and 0.9 Hz), and 7.92 (1H, dd, J ¼ 7:8 and
1.4 Hz); MS m=z (%) 244 (Mþ, 100). Calcd for C14H9ClS: C,
68.71; H, 3.71%. Found: C, 68.69; H, 3.89%.
3,5-Dimethylbenzo[b]thiophene (7g):12 A colorless oil; Rf
0.67 (pentane); IR (neat) 3062, 2918, 1445, 1290, 835, 800, and

1784 Bull. Chem. Soc. Jpn. Vol. 80, No. 9 (2007)
Synthesis of Benzo[b]thiophenes
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