A new synthesis of benzo[b]thiophenes utilizing an interrupted Pummerer reaction

Article abstract of DOI:10.1016/j.tet.2009.01.084

A convenient synthesis of 3-arylbenzo[b]thiophenes utilizing an interrupted Pummerer reaction of 2-(1-arylvinyl)phenyl ethyl sulfoxides is described. Thus, treatment of these sulfoxides, which were readily prepared from 2-sulfanylphenyl ketones or 2-fluor

Full text of DOI:10.1016/j.tet.2009.01.084

Tetrahedron 65 (2009) 2430–2435
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A new synthesis of benzo[b]thiophenes utilizing an interrupted
Pummerer reaction
*
Kazuhiro Kobayashi , Mai Horiuchi, Shuhei Fukamachi, Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2009
Received in revised form 20 January 2009
Accepted 20 January 2009
Available online 29 January 2009
A convenient synthesis of 3-arylbenzo[b]thiophenes utilizing an interrupted Pummerer reaction of 2-(1-
arylvinyl)phenyl ethyl sulfoxides is described. Thus, treatment of these sulfoxides, which were readily
prepared from 2-sulfanylphenyl ketones or 2-fluoro-5-methoxybenzaldehyde, with acetic anhydride at
100 ꢀC afforded 3-arylbenzo[b]thiophenes in reasonable yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Benzo[b]thiophenes
Interrupted Pummerer reaction
Sulfoxides
Acetic anhydride
Ring closure
1. Introduction
ketones 15 or commercially available 2-fluoro-5-methoxy-
benzaldehyde. In the first procedure, S-ethylation of 1 with
Literature survey has revealed that many molecules having
the benzo[b]thiophene skeleton exhibit a wide variety of bi-
ological activities.1 Therefore, many research groups2 including
us3 have been developing a number of new methods for the
preparation of benzo[b]thiophene derivatives. In this paper we
wish to report a new and efficient method for the synthesis of
benzo[b]thiophenes. We anticipated that reaction of 2-(1-
arylvinyl)phenyl ethyl sulfoxides 5 with acetic anhydride would
afford 3-arylbenzo[b]thiophenes 6, via an interrupted Pum-
merer reaction,4 because Bates et al. have reported that
pyrrolo[2,1-b]benzothiazole is formed by treating alkyl 2-(pyr-
rol-1-yl)phenyl sulfoxides with trifluoroacetic anhydride.4a
They have offered an interrupted Pummerer pathway for its
formation.
iodoethane using sodium hydride as a base produced the cor-
responding 2-(ethylsulfanyl)phenyl ketones 2a–c in good yields,
as shown in Scheme 1. In the second procedure, aryl(2-fluoro-5-
methoxyphenyl)methanones 3, which were readily prepared
from 2-fluoro-5-methoxybenzaldehyde via reaction with aryl-
magnesium bromide followed by the PCC oxidation in good
yields (see Experimental section), were allowed to react with
ethanethiol using sodium hydride as a base to give aryl 2-
ethylsulfanyl-5-methoxyphenyl ketones 2d–i in generally
good yields, as shown in Scheme 2. A somewhat low yield
was obtained with (2-fluoro-5-methoxyphenyl)(4-methoxy-
phenyl)methanone (3g). We reasoned that 4-methoxyphenyl
substituent might lower the reactivity of 3g toward sodium
ethanethiolate.
2. Results and discussion
O
O
2-(1-Arylvinyl)phenyl sulfoxides
from aryl 2-ethylsulfanylphenyl ketones 2, which were obtained
by two different procedures starting with aryl 2-sulfanylphenyl
5 were readily prepared
NaH, EtI
Ar
Ar
SH
SEt
1a Ar = Ph
2a Ar = Ph 79%
2b Ar = p-Tol 78%
2c Ar = 4-ClC6H4 81%
1b Ar = p-Tol
1c Ar = 4-ClC6H4
* Corresponding author. Tel./fax: þ81 857 31 5263.
Scheme 1.
E-mail address: kkoba@chem.tottori-u.ac.jp (K. Kobayashi).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.084

K. Kobayashi et al. / Tetrahedron 65 (2009) 2430–2435
2431
O
F
O
products were obtained, though no products arising from normal
Pummerer reaction were isolated.
MeO
MeO
NaSEt
Ar
Ar
SEt
A limitation of the aforementioned method is that 3-alkylben-
zo[b]thiophenes cannot be prepared. Thus, the treatment of ethyl
2-(1-methylethenyl)phenyl sulfoxide with acetic anhydride under
conditions similar to those described above for the preparation of 3-
arylbenzo[b]thiophenes 6 resulted in almost quantitative recovery
of the starting sulfoxide; even the normal Pummerer product could
not be formed, though we have no explanation of the reason for this.
A probable pathway leading to 3-arylbenzo[b]thiophenes 6 from
2-(1-arylethenyl)phenyl ethyl sulfoxides 5 is outlined in Scheme 4.
This is parallel to that reported by Bates et al. for the formation of
pyrrolo[2,1-b]benzothiazole from alkyl 2-(pyrrol-1-yl)phenyl sul-
foxides.4a Thus, treatment of 5 with acetic anhydride generates an S-
3
2d 82%
d Ar = o-Tol
2e 82%
2f 85%
2g 48%
2h 80%
2i 88%
e Ar = m-Tol
f Ar = p-Tol
g Ar = 4-MeOC6H4
h Ar = 2-Thienyl
i Ar = 1-Naphthyl
Scheme 2.
We conducted the conversion of 2, thus obtained, into 3-aryl-
benzo[b]thiophenes 6 as outlined in Scheme 3, and the results are
summarized in Table 1. Thus, the reaction of compounds 2 with
methylene- or ethylene-triphenylphosphorane gave 2-(ethyl-
sulfanyl)styrene derivatives 4, which was then oxidized with an
equimolar amount of sodium metaperiodate to give 2-(1-arylvi-
nyl)phenyl ethyl sulfoxides 5. As can be seen from the Table, these
conversions were carried out generally in good yields.
acetoxylated sulfonium ion intermediate 7. The alkene
p-electrons
attackintramolecularlyonthesulfurcationcenterwithalossofacetic
acid to afford a benzothiophenium ion intermediate 8. Ethyl acetate
are eliminated from this intermediate to give rise to 6. The lower
yields in the reactions with ethyl (1-propenyl)phenyl sulfoxides 5c
and 5f–ii thought to be due to unfavorable steric interaction between
the methyl substituent and the ethyl group in the intermediate 8.
Ar
Ar
R1
R2
Ph3P=CHR2
R1
R2
2
Ac2O
5
SEt
SEt
OAc OAc
4
7
Ar
R1
R2
NaIO4
Ar
R1
– AcOH
– AcOEt
R2
S(O)Et
6
S
Et
OAc
5
8
Ar
S
R1
Scheme 4.
Ac2O, Δ
R2
In conclusion, the above-mentioned experiments have demon-
strated that the treatment of 2-(1-arylethenyl)phenyl sulfoxides
with acetic anhydride results in the formation of 3-arylbenzo[b]-
thiophenes. As the present method starts with readily available
materials and involves very simple manipulations, it may be of
value in organic synthesis. Studies on the synthesis of sulfur-con-
taining heterocycles utilizing this type of reaction are now under
way in our laboratory.
6
Scheme 3.
We were able to obtain 3-arylbenzo[b]thiophenes 6 by simply
heating the sulfoxides 5 in acetic anhydride at 100 ꢀC. We found
that the reactions proceeded smoothly to give the desired products
-substituents of 5 were phenyl, p-tolyl, 4-
methoxyphenyl, 2-thienyl, or 1-naphthyl, and the
in good yields, when the
a
b
-substituent
was hydrogen (entries 1, 2, 4–6, and 8–10). Poor yields were
obtained, however, with ethyl (1-propenyl)phenyl sulfoxides 5c
and 5f–ii (entries 3 and 7). Rather complicated mixtures of
3. Experimental
3.1. General
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were
determined with a Shimadzu FTIR-8300 spectrophotometer. The 1H
NMR spectra were determined in CDCl3 using TMS as an internal
reference with a JEOL ECP500 FT NMR spectrometer operating at
500 MHz or a JEOL LA400 FT NMR spectrometer operating at
400 MHz. The 13C NMR spectra were determined in CDCl3 using
TMS as an internal reference with a JEOL ECP500 FT NMR spec-
trometer operating at 125 MHz. Low-resolution MS spectra
(EI, 70 eV) were measured by a JEOL JMS AX505 HA spectrometer.
TLC was carried out on a Merck Kieselgel 60 PF254. Column chro-
matography was performed using Merck Kieselgel 60 (0.063–
0.200 mm). All of the organic solvents used in this study were dried
over appropriate drying agents and distilled prior to use.
Table 1
Preparation of benzo[b]thiophenes 6 from 2-(ethylsulfanyl)phenyl ketones 2
Entry
2
R2
4 (Yielda/%)
5 (Yielda/%)
6 (Yielda/%)
1
2
3
4
5
6
7
8
9
10
2a
2b
2c
2d
2e
2f
H
H
Me
H
H
H
Me
H
H
H
4a (73)
4b (75)
4c (85)
4d (59)
4e (81)
4f–i (81)
4f–ii (51)
4g (75)
4h (66)
4i (76)
5a (74)
5b (87)
5c (95)
5d (96)
5e (83)
5f–i (93)
5f–ii (78)
5g (81)
5h (78)
5i (92)
6a (77)
6b (62)
6c (20)
6d (67)
6e (59)
6f–i (75)
6f–ii (29)
6g (86)
6h (82)
6i (78)
2f
2g
2h
2i
a
Isolated yields.

2432
K. Kobayashi et al. / Tetrahedron 65 (2009) 2430–2435
3.2. Starting materials
6.95 (d, J¼8.7 Hz, 2H), 6.99–7.03 (m, 2H), 7.07 (t, J¼8.7 Hz, 1H), 7.85
(d, J¼8.7 Hz, 2H). Anal. Calcd for C15H13FO3: C, 69.22; H, 5.03.
Aryl(2-sulfanylphenyl)methanones 1 were prepared by a pre-
viously reported our procedure.5 All other chemicals used in this
study were commercially available.
Found: C, 68.96; H, 4.98.
3.2.1.9. (2-Fluoro-5-methoxyphenyl)(2-thienyl)methanol. Yield: 89%;
a yellow oil; Rf 0.32 (1:2 Et2O–hexane); IR (neat) 3396 cmꢁ1; 1H NMR
3.2.1. Aryl(2-fluoro-5-methoxyphenyl)methanones 3d–i
These compounds were prepared by the reaction of 2-fluoro-5-
methoxybenzaldehyde with arylmagnesium bromides in THF at
0 ꢀC, followed by the PCC oxidation of the resulting alcohols in
CH2Cl2 at room temperature.
(500 MHz)
d
2.50 (d, J¼4.6 Hz,1H), 3.79 (s, 3H), 6.33 (d, J¼4.6 Hz,1H),
6.79 (ddd, J¼8.7, 4.1, 3.7 Hz, 1H), 6.92–6.95 (m, 2H), 6.98 (dd, J¼9.1,
8.7 Hz, 1H), 7.12 (dd, J¼5.5, 3.2 Hz, 1H), 7.27 (d, J¼1.4 Hz, 1H). Anal.
Calcd for C12H11FO2S: C, 60.49; H, 4.65. Found: C, 60.46; H, 4.81.
3.2.1.10. (2-Fluoro-5-methoxyphenyl)(2-thienyl)methanone (3h). Yield:
3.2.1.1. (2-Fluoro-5-methoxyphenyl)(2-methylphenyl)methanol. Yield:
92%; a pale-yellow oil; Rf 0.23 (1:3 Et2O–hexane); IR (neat)
88%; a yellow oil; Rf 0.33 (1:3 Et2O–hexane); IR (neat) 1645 cmꢁ1
;
1H NMR (500 MHz)
d
3.82 (s, 3H), 7.01–7.06 (m, 2H), 7.10 (dd, J¼9.1,
3364 cmꢁ1; 1H NMR (500 MHz)
d
2.17 (d, J¼4.1 Hz, 1H), 2.32 (s, 3H),
8.7 Hz, 1H), 7.15 (dd, J¼4.6, 4.1 Hz, 1H), 7.57–7.59 (m, 1H), 7.76 (dd,
J¼4.6, 1.4 Hz, 1H). Anal. Calcd for C12H9FO2S: C, 61.00; H, 3.84.
Found: C, 60.95; H, 3.95.
3.74 (s, 3H), 6.29 (d, J¼4.1 Hz, 1H), 6.77 (dd, J¼8.7, 3.2 Hz, 1H), 6.87
(dd, J¼3.2, 2.6 Hz,1H), 6.96 (dd, J¼9.1, 8.7 Hz,1H), 7.15–7.23 (m, 3H),
7.45 (d, J¼7.3 Hz, 1H). Anal. Calcd for C15H15FO2: C, 73.15; H, 6.14.
Found: C, 73.12; H, 6.18.
3.2.1.11. (2-Fluoro-5-methoxyphenyl)(naphthalen-1-yl)methanol. Yield:
89%; a colorless viscous oil; Rf 0.23 (1:3 Et2O–hexane); IR (neat)
3.2.1.2. (2-Fluoro-5-methoxyphenyl)(2-methylphenyl)methanone
3381 cmꢁ1; 1H NMR (500 MHz)
d
2.38 (d, J¼4.7 Hz,1H), 3.70 (s, 3H),
(3d). Yield: 82%; a pale-yellow oil; Rf 0.48 (1:3 Et2O–hexane); IR
6.78 (ddd, J¼8.7, 3.6, 2.7 Hz, 1H), 6.86–6.88 (m, 2H), 7.01 (dd, J¼9.2,
8.7 Hz, 1H), 7.47–7.52 (m, 3H), 7.63 (d, J¼7.3 Hz, 1H), 7.82 (d,
J¼8.2 Hz,1H), 7.87 (dd, J¼7.3, 2.3 Hz,1H), 8.08 (dd, J¼7.3,1.8 Hz,1H).
Anal. Calcd for C18H15FO2: C, 76.58; H, 5.36. Found: C, 76.49; H, 5.58.
(neat) 1668 cmꢁ1 1H NMR (500 MHz)
; d 2.49 (s, 3H), 3.82 (s, 3H),
7.00–7.07 (m, 2H), 7.13 (dd, J¼7.3, 2.7 Hz, 1H), 7.23 (dd, J¼7.8, 7.3 Hz,
1H), 7.29 (d, J¼7.8 Hz, 1H), 7.38–7.42 (m, 2H). Anal. Calcd for
C15H13FO2: C, 73.76; H, 5.36. Found: C, 73.69; H, 5.40.
3.2.1.12. (2-Fluoro-5-methoxyphenyl)(naphthalen-1-yl)methanone
3.2.1.3. (2-Fluoro-5-methoxyphenyl)(3-methylphenyl)methanol. Yield:
68%; a pale-yellow oil; Rf 0.29 (1:3 Et2O–hexane); IR (neat) 3408,
(3i). Yield: 81%; a white solid; mp 105–107 ꢀC (hexane–Et2O); IR
(KBr) 1649, 1614 cmꢁ1 1H NMR (500 MHz)
; d 3.84 (s, 3H), 7.03 (t,
1607 cmꢁ1;1H NMR (500 MHz)
d
2.29 (d, J¼4.1 Hz,1H), 2.34 (s, 3H), 3.78
J¼9.2 Hz, 1H), 7.07 (ddd, J¼9.2, 4.1, 3.2 Hz, 1H), 7.22 (dd, J¼5.5,
3.2 Hz, 1H), 7.48 (dd, J¼8.2, 7.3 Hz, 1H), 7.56 (ddd, J¼7.8, 7.3, 1.4 Hz,
1H), 7.60 (td, J¼7.3, 1.4 Hz,1H), 7.67 (d, J¼7.3 Hz,1H), 7.93 (dd, J¼7.8,
1.4 Hz, 1H), 8.03 (d, J¼8.2 Hz, 1H), 8.53 (d, J¼8.2 Hz, 1H). Anal. Calcd
for C18H13FO2: C, 77.13; H, 4.67. Found: C, 77.02; H, 4.74.
(s, 3H), 6.07 (d, J¼4.1 Hz,1H), 6.75 (dt, J¼8.7, 3.7 Hz,1H), 6.93 (dd, J¼9.2,
8.7 Hz, 1H), 7.06–7.09 (m, 2H), 7.19–7.24 (m, 3H). Anal. Calcd for
C15H15FO2: C, 73.15; H, 6.14. Found: C, 72.98; H, 6.13.
3.2.1.4. (2-Fluoro-5-methoxyphenyl)(3-methylphenyl)methanone
(3e). Yield: 79%; a pale-yellow oil; Rf 0.50 (1:3 Et2O–hexane); IR
3.3. Aryl[2-(ethylsulfanyl)phenyl]methanones 2a–c
(neat) 1668 cmꢁ1 1H NMR (500 MHz)
; d 2.41 (s, 3H), 3.82 (s, 3H),
7.02–7.10 (m, 3H), 7.36 (dd, J¼7.8, 7.3 Hz, 1H), 7.42 (d, J¼7.3 Hz, 1H),
7.62 (d, J¼7.8 Hz, 1H), 7.68 (s, 1H). Anal. Calcd for C15H13FO2: C,
73.76; H, 5.36. Found: C, 73.81; H, 5.62.
These compounds were prepared by successive treatment of
aryl(2-sulfanylphenyl)methanones 1 with sodium hydride and
iodoethane in THF at 0 ꢀC.
3.2.1.5. (2-Fluoro-5-methoxyphenyl)(4-methylphenyl)methanol. Yield:
74%; a pale-yellow oil; Rf 0.26 (1:3 Et2O–hexane); IR (neat) 3391,
3.3.1. [2-(Ethylsulfanyl)phenyl]phenylmethanone (2a)
A yellow oil; Rf 0.30 (1:8 THF–hexane). The spectral data (IR and
1H NMR) were identical to those reported previously.6
1614 cmꢁ1; 1H NMR (500 MHz)
d
2.21 (d, J¼4.6 Hz, 1H), 2.33 (s, 3H),
3.78 (s, 3H), 6.07 (d, J¼4.6 Hz, 1H), 6.74 (ddd, J¼9.2, 3.7, 3.2 Hz, 1H),
6.92 (t, J¼9.2 Hz, 1H), 7.07 (dd, J¼6.0, 3.2 Hz, 1H), 7.15 (d, J¼8.2 Hz,
2H), 7.29 (d, J¼8.2 Hz, 2H). Anal. Calcd for C15H15FO2: C, 73.15; H,
6.14. Found: C, 73.08; H, 5.87.
3.3.2. [2-(Ethylsulfanyl)phenyl](4-methylphenyl)methanone (2b)
A yellow oil; Rf 0.33 (1:8 THF–hexane); IR (neat) 1660, 1605 cmꢁ1
;
1H NMR (500 MHz)
d
1.23 (t, J¼7.3 Hz, 3H), 2.42 (s, 3H), 2.88 (q,
J¼7.3 Hz, 2H), 7.24–7.27 (m, 3H), 7.34 (dd, J¼7.3, 1.4 Hz, 1H), 7.43 (ddd,
J¼7.8,7.3,1.4 Hz,1H), 7.48(d,J¼7.8 Hz,1H), 7.69 (d, J¼8.2 Hz, 2H). Anal.
Calcd for C16H16OS: C, 74.96; H, 6.29. Found: C, 74.80; H, 6.31.
3.2.1.6. (2-Fluoro-5-methoxyphenyl)(4-methylphenyl)methanone
(3f). Yield: 82%; a white solid; mp 67–70 ꢀC (hexane–Et2O); IR
(KBr) 1668, 1607 cmꢁ1 1H NMR (500 MHz)
; d 2.44 (s, 3H), 3.82 (s,
3H), 7.01–7.09 (m, 3H), 7.28 (d, J¼8.2 Hz, 2H), 7.76 (d, J¼8.2 Hz, 2H).
3.3.3. (4-Chlorophenyl)[2-(ethylsulfanyl)phenyl]methanone (2c)
A yellow oil; Rf 0.43 (1:8 THF–hexane); IR (neat) 1667 cmꢁ1; 1H
Anal. Calcd for C15H13FO2: C, 73.76; H, 5.36. Found: C, 73.72; H, 5.53.
NMR (400 MHz)
d
1.23 (t, J¼7.3 Hz, 3H), 2.87 (q, J¼7.3 Hz, 2H), 7.27
3.2.1.7. (2-Fluoro-5-methoxyphenyl)(4-methoxyphenyl)methanol. Yield:
83%; a pale-yellow oil; Rf 0.18 (1:2 Et2O–hexane); IR (neat) 3418,
(ddd, J¼7.7, 7.3, 1.5 Hz, 1H), 7.33 (dd, J¼7.7, 1.5 Hz, 1H), 7.41 (d,
J¼8.8 Hz, 2H), 7.44 (ddd, J¼7.7, 7.3, 1.5 Hz, 1H), 7.48 (dd, J¼7.7,
1.5 Hz, 1H), 7.72 (d, J¼8.8 Hz, 2H). Anal. Calcd for C15H13ClOS: C,
65.09; H, 4.73. Found: C, 65.15; H, 4.73.
1612 cmꢁ1; 1H NMR (500 MHz)
d
2.20 (d, J¼3.7 Hz, 1H), 3.78 (s, 3H),
3.79 (s, 3H), 6.06 (d, J¼3.7 Hz, 1H), 6.75 (ddd, J¼8.7, 3.7, 3.2 Hz, 1H),
6.87 (d, J¼8.7 Hz, 2H), 6.92 (dd, J¼9.2, 8.7 Hz, 1H), 7.08 (dd, J¼6.0,
3.2 Hz, 1H), 7.32 (d, J¼8.7 Hz, 2H). Anal. Calcd for C15H15FO3: C,
68.69; H, 5.76. Found: C, 68.82; H, 5.90.
3.4. Aryl[2-(ethylsulfanyl)-5-methoxyphenyl]methanones
2d–i
3.2.1.8. (2-Fluoro-5-methoxyphenyl)(4-methoxyphenyl)methanone
These compounds were prepared by reacting aryl(2-fluoro-5-
methoxyphenyl)methanones 3 with ethanethiol in DMF in the
presence of sodium hydride at room temperature.
(3g). Yield: 77%; a yellow oil; Rf 0.25 (1:2 Et2O–hexane); IR (neat)
1661 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 3.82 (s, 3H), 3.89 (s, 3H),

K. Kobayashi et al. / Tetrahedron 65 (2009) 2430–2435
2433
3.4.1. (2-Ethylsulfanyl-5-methoxyphenyl)(2-methylphenyl)-
methanone (2d)
(m, 9H). Anal. Calcd for C16H16S: C, 79.95; H, 6.71. Found: C, 79.83;
H, 6.75.
A yellow oil; Rf 0.52 (1:3 Et2O–hexane); IR (neat) 1668 cmꢁ1; 1H
NMR (500 MHz)
d
1.17 (t, J¼7.3 Hz, 3H), 2.56 (s, 3H), 2.74 (q,
3.5.2. 1-Ethylsulfanyl-2-[1-(4-methylphenyl)ethenyl]benzene (4b)
A pale-yellow oil; Rf 0.53 (1:2 CH2Cl2–hexane); IR (neat)
J¼7.3 Hz, 2H), 3.79 (s, 3H), 6.92 (d, J¼2.7 Hz, 1H), 6.99 (dd, J¼8.7,
2.7 Hz, 1H), 7.17 (dd, J¼7.8, 7.3 Hz, 1H), 7.25–7.30 (m, 2H), 7.38 (ddd,
J¼7.8, 7.3, 1.4 Hz, 1H), 7.40 (d, J¼8.7 Hz, 1H). Anal. Calcd for
C17H18O2S: C, 71.30; H, 6.34. Found: C, 71.20; H, 6.57.
1611 cmꢁ1; 1H NMR (500 MHz)
d
1.20 (t, J¼7.3 Hz, 3H), 2.33 (s, 3H),
2.82 (q, J¼7.3 Hz, 2H), 5.20 (s, 1H), 5.79 (d, J¼0.9 Hz, 1H), 7.09 (d,
J¼7.8 Hz, 2H), 7.17–7.21 (m, 4H), 7.28–7.33 (m, 2H). Anal. Calcd for
C17H18S: C, 80.26; H, 7.13. Found: C, 80.05; H, 7.36.
3.4.2. (2-Ethylsulfanyl-5-methoxyphenyl)(3-methylphenyl)-
methanone (2e)
3.5.3. 1-[1-(4-Chlorophenyl)prop-1-enyl]-2-(ethylsulfanyl)-
benzene (4c)
A yellow oil; Rf 0.40 (1:3 Et2O–hexane); IR (neat) 1668 cmꢁ1; 1H
NMR (500 MHz)
d
1.14 (t, J¼7.3 Hz, 3H), 2.39 (s, 3H), 2.73 (q,
A pale-yellow oil; a mixture of stereoisomers (E/Z¼ca. 6:4); Rf
J¼7.3 Hz, 2H), 3.81 (s, 3H), 6.85 (d, J¼2.7 Hz, 1H), 6.98 (dd, J¼8.2,
2.7 Hz,1H), 7.32 (dd, J¼7.8, 7.3 Hz,1H), 7.39 (d, J¼7.3 Hz,1H), 7.47 (d,
J¼8.2 Hz, 1H), 7.54 (d, J¼7.8 Hz, 1H), 7.65 (s, 1H). Anal. Calcd for
C17H18O2S: C, 71.30; H, 6.34. Found: C, 71.28; H, 6.31.
0.57 (1:3 CH2Cl2–hexane); IR (neat) 1635 cmꢁ1; 1H NMR (400 MHz)
d
1.20 (t, J¼7.3 Hz, 1.8H), 1.22 (t, J¼7.3 Hz, 1.2H), 1.62 (d, J¼6.9 Hz,
1.2H), 1.89 (d, J¼6.9 Hz, 1.8H), 2.78 (q, J¼7.3 Hz, 1.2H), 2.84 (q,
J¼7.3 Hz, 0.8H), 5.83 (q, J¼6.9 Hz, 0.6H), 6.30 (q, J¼6.9 Hz, 0.4H),
7.06–7.34 (m, 8H). Anal. Calcd for C17H17ClS: C, 70.69; H, 5.93.
Found: C, 70.54; H, 5.77.
3.4.3. (2-Ethylsulfanyl-5-methoxyphenyl)(4-methylphenyl)-
methanone (2f)
A yellow oil; Rf 0.53 (1:3 Et2O–hexane); IR (neat) 1668,
3.5.4. 1-Ethylsulfanyl-4-methoxy-2-[1-(2-methylphenyl)ethenyl]-
benzene (4d)
1605 cmꢁ1; 1H NMR (500 MHz)
d
1.14 (t, J¼7.3 Hz, 3H), 2.42 (s, 3H),
2.73 (q, J¼7.3 Hz, 2H), 3.81 (s, 3H), 6.85 (d, J¼2.7 Hz, 1H), 6.98 (dd,
J¼8.7, 2.7 Hz, 1H), 7.25 (d, J¼8.2 Hz, 2H), 7.46 (d, J¼8.7 Hz, 1H), 7.70
(d, J¼8.2 Hz, 2H). Anal. Calcd for C17H18O2S: C, 71.30; H, 6.34. Found:
C, 71.21; H, 6.37.
A pale-yellow oil; Rf 0.41 (1:3 CH2Cl2–hexane); IR (neat)
1591 cmꢁ1; 1H NMR (500 MHz)
d
1.10 (t, J¼7.3 Hz, 3H), 2.25 (s, 3H),
2.61 (q, J¼7.3 Hz, 2H), 3.78 (s, 3H), 5.46 (d, J¼1.8 Hz, 1H), 5.51 (d,
J¼1.8 Hz, 1H), 6.79 (d, J¼2.7 Hz, 1H), 6.81 (dd, J¼8.2, 2.7 Hz, 1H),
7.09–7.18 (m, 4H), 7.30 (d, J¼8.2 Hz,1H). Anal. Calcd for C18H20OS: C,
76.01; H, 7.09. Found: C, 75.80; H, 7.12.
3.4.4. (2-Ethylsulfanyl-5-methoxyphenyl)(4-methoxyphenyl)-
methanone (2g)
A yellow oil; Rf 0.31 (1:2 Et2O–hexane); IR (neat) 1661 cmꢁ1; 1H
3.5.5. 1-Ethylsulfanyl-4-methoxy-2-[1-(3-methylphenyl)-
ethenyl]benzene (4e)
NMR (500 MHz)
d
1.14 (t, J¼7.3 Hz, 3H), 2.73 (q, J¼7.3 Hz, 2H), 3.81
(s, 3H), 3.87 (s, 3H), 6.84 (d, J¼2.7 Hz, 1H), 6.92 (d, J¼9.2 Hz, 2H),
6.97 (dd, J¼8.7, 2.7 Hz, 1H), 7.46 (d, J¼8.7 Hz, 1H), 7.78 (d, J¼9.2 Hz,
2H). Anal. Calcd for C17H18O3S: C, 67.52; H, 6.00. Found: C, 67.48;
H, 6.02.
A pale-yellow oil; Rf 0.40 (1:3 CH2Cl2–hexane); IR (neat)
1593 cmꢁ1; 1H NMR (500 MHz)
d
1.10 (t, J¼7.3 Hz, 3H), 2.31 (s, 3H),
2.67 (q, J¼7.3 Hz, 2H), 3.81 (s, 3H), 5.21 (d, J¼0.9 Hz, 1H), 5.79 (d,
J¼0.9 Hz, 1H), 6.82 (d, J¼3.2 Hz, 1H), 6.87 (dd, J¼8.7, 3.2 Hz, 1H),
7.06–7.07 (m, 2H), 7.11 (s, 1H), 7.17 (dd, J¼7.8, 7.3 Hz, 1H), 7.35 (d,
J¼8.7 Hz, 1H). Anal. Calcd for C18H20OS: C, 76.01; H, 7.09. Found: C,
75.76; H, 7.20.
3.4.5. (2-Ethylsulfanyl-5-methoxyphenyl)(2-thienyl)-
methanone (2h)
A yellow oil; Rf 0.44 (1:2 Et2O–hexane); IR (neat) 1645 cmꢁ1; 1H
NMR (500 MHz)
d
1.17 (t, J¼7.3 Hz, 3H), 2.78 (q, J¼7.3 Hz, 2H), 3.82
3.5.6. 1-Ethylsulfanyl-4-methoxy-2-[1-(4-methylphenyl)-
ethenyl]benzene (4f–i)
(s, 3H), 6.96 (d, J¼2.7 Hz, 1H), 6.99 (dd, J¼8.7, 2.7 Hz, 1H), 7.11 (dd,
J¼5.0, 4.1 Hz, 1H), 7.41 (dd, J¼4.1, 1.4 Hz, 1H), 7.47 (d, J¼8.7 Hz, 1H),
7.73 (dd, J¼5.0, 1.4 Hz, 1H). Anal. Calcd for C16H14O2S2: C, 60.40; H,
5.07. Found: C, 60.36; H, 5.07.
A
colorless oil; Rf 0.28 (1:3 CH2Cl2–hexane); IR (neat)
1591 cmꢁ1; 1H NMR (400 MHz)
d
1.11 (t, J¼7.3 Hz, 3H), 2.33 (s, 3H),
2.67 (q, J¼7.3 Hz, 2H), 3.80 (s, 3H), 5.17 (s, 1H), 5.76 (s, 1H), 6.82 (d,
J¼2.9 Hz,1H), 6.86 (dd, J¼8.4, 2.9 Hz,1H), 7.09 (d, J¼8.0 Hz, 2H), 7.17
(d, J¼8.0 Hz, 2H), 7.34 (d, J¼8.4 Hz, 1H). Anal. Calcd for C18H20OS: C,
76.01; H, 7.09. Found: C, 75.76; H, 7.36.
3.4.6. (2-Ethylsulfanyl-5-methoxyphenyl)(naphthalen-1-yl)-
methanone (2i)
A yellow oil; Rf 0.45 (1:3 Et2O–hexane); IR (neat) 1661 cmꢁ1; 1H
NMR (500 MHz)
d
1.13 (t, J¼7.3 Hz, 3H), 2.72 (q, J¼7.3 Hz, 2H), 2.78
3.5.7. 1-Ethylsulfanyl-4-methoxy-2-[1-(4-methylphenyl)prop-1-
enyl]benzene (4f–ii)
(s, 3H), 7.00 (d, J¼2.7 Hz, 1H), 7.03 (dd, J¼8.7, 2.7 Hz, 1H), 7.42 (dd,
J¼8.2, 7.8 Hz, 1H), 7.44 (d, J¼8.7 Hz, 1H), 7.54 (dd, J¼8.2, 0.9 Hz, 1H),
7.57 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H), 7.63 (ddd, J¼8.2, 7.3, 1.4 Hz,
1H), 7.91 (d, J¼7.8 Hz, 1H), 8.00 (d, J¼8.2 Hz, 1H), 8.77 (d, J¼8.2 Hz,
1H). Anal. Calcd for C20H18O2S: C, 74.50; H, 5.63. Found: C, 74.69; H,
5.78.
A colorless oil; a mixture of stereoisomers (E/Z¼ca. 6:4); Rf 0.28
(1:3 CH2Cl2–hexane); IR (neat) 1591 cmꢁ1 1H NMR (400 MHz)
;
d
1.10 (t, J¼7.3 Hz, 1.2H), 1.15 (t, J¼7.3 Hz 1.8H), 1.62 (d, J¼6.9 Hz,
1.8H), 1.90 (d, J¼6.9 Hz, 1.2H), 2.30 (s, 1.8H), 2.33 (s, 1.2H), 2.61 (q,
J¼7.3 Hz, 1.2H), 2.71 (q, J¼7.3 Hz, 0.8H), 3.789 (s, 1.2H), 3.794 (s,
1.8H), 5.77 (q, J¼6.9 Hz, 0.4H), 6.28 (q, J¼6.9 Hz, 0.6H), 6.69 (d,
J¼2.7 Hz, 0.4H), 6.77–6.80 (m, 1.2H), 6.87 (dd, J¼8.7, 2.7 Hz, 0.4H),
7.05 (d, J¼7.8 Hz, 2H), 7.11 (d, J¼7.8 Hz, 2H), 7.24 (d, J¼8.7 Hz, 0.4H),
7.34 (d, J¼8.2 Hz, 0.6H). Anal. Calcd for C19H22OS: C, 76.46; H, 7.43.
Found: C, 76.22; H, 7.31.
3.5. 1-(1-Arylvinyl)-2-(ethylsulfanyl)benzenes 4
These compounds were prepared by treating 2 with methylene-
or ethylene-triphenylphosphorane in THF at 0 ꢀC.
3.5.8. 1-Ethylsulfanyl-4-methoxy-2-[1-(4-methoxyphenyl)-
ethenyl]benzene (4g)
3.5.1. 1-Ethylsulfanyl-2-(1-phenylethenyl)benzene (4a)
A pale-yellow oil; Rf 0.31 (1:5 CH2Cl2–hexane); IR (neat)
A pale-yellow oil; Rf 0.21 (1:3 CH2Cl2–hexane); IR (neat)
1615 cmꢁ1
;
1H NMR (400 MHz)
d
1.19 (t, J¼7.3 Hz, 3H), 2.81 (q,
1606 cmꢁ1
;
1H NMR (500 MHz)
d
1.12 (t, J¼7.3 Hz, 3H), 2.70
J¼7.3 Hz, 2H), 5.26 (d, J¼1.0 Hz, 1H), 5.82 (d, J¼1.0 Hz, 1H), 7.17–7.34
(q, J¼7.3 Hz, 2H), 3.80 (s, 3H), 3.81 (s, 3H), 5.12 (d, J¼0.9 Hz, 1H),

2434
K. Kobayashi et al. / Tetrahedron 65 (2009) 2430–2435
5.71 (d, J¼0.9 Hz, 1H), 6.81–6.84 (m, 3H), 6.87 (dd, J¼8.7, 2.7 Hz,
1H), 7.21 (d, J¼9.2 Hz, 2H), 7.34 (d, J¼8.7 Hz, 1H). Anal. Calcd for
C18H20O2S: C, 71.96; H, 6.71. Found: C, 71.91; H, 6.62.
3.6.5. Ethyl 4-methoxy-2-[1-(3-methylphenyl)ethenyl]phenyl
sulfoxide (5e)
A pale-yellow oil; Rf 0.20 (1:2 THF–hexane); IR (neat) 1589,
1047 cmꢁ1; 1H NMR (500 MHz)
d
1.07 (t, J¼7.3 Hz, 3H), 2.32 (s, 3H),
3.5.9. 1-Ethylsulfanyl-4-methoxy-2-[1-(2-thienyl)ethenyl]-
benzene (4h)
2.52 (dq, J¼13.3, 7.3 Hz, 1H), 2.63 (dq, J¼13.3, 7.3 Hz, 1H), 3.86 (s,
3H), 5.28 (d, J¼0.9 Hz, 1H), 5.80 (d, J¼0.9 Hz, 1H), 6.84 (d, J¼2.7 Hz,
1H), 6.98–7.12 (m, 4H), 7.20 (t, J¼7.8 Hz, 1H), 7.90 (d, J¼8.7 Hz, 1H).
Anal. Calcd for C18H20O2S: C, 71.96; H, 6.71. Found: C, 72.02; H, 6.62.
A
pale-yellow oil; Rf 0.42 (1:3 CH2Cl2–hexane); IR (neat)
1593 cmꢁ1 1H NMR (500 MHz)
;
d
1.15 (t, J¼7.3 Hz, 3H), 2.74 (q,
J¼7.3 Hz, 2H), 3.81 (s, 3H), 5.08 (s, 1H), 5.77 (s, 1H), 6.66 (dd, J¼3.7,
1.4 Hz,1H), 6.85(d, J¼2.7 Hz,1H), 6.88(dd, J¼8.7, 2.7 Hz,1H), 6.91 (dd,
J¼5.0, 3.7 Hz, 1H), 7.20 (dd, J¼5.0, 1.4 Hz, 1H), 7.37 (d, J¼8.7 Hz, 1H).
Anal. Calcd for C15H16OS2: C, 65.18; H, 5.83. Found: C, 64.87; H, 6.02.
3.6.6. Ethyl 4-methoxy-2-[1-(4-methylphenyl)ethenyl]phenyl
sulfoxide (5f–i)
A pale-yellow oil; Rf 0.44 (1:1 THF–hexane); IR (neat) 1587,
1040 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
1.07 (t, J¼7.3 Hz, 3H), 2.34 (s,
3.5.10. 1-Ethylsulfanyl-4-methoxy-2-[1-(naphthalen-1-yl)-
ethenyl]benzene (4i)
3H), 2.52 (dq, J¼14.7, 7.3 Hz, 1H), 2.65 (dq, J¼14.7, 7.3 Hz, 1H), 3.86 (s,
3H), 5.25 (s, 1H), 5.78 (s, 1H), 6.83 (d, J¼2.7 Hz, 1H), 7.09 (dd, J¼8.7,
2.7 Hz,1H), 7.11(d, J¼8.7 Hz, 2H), 7.15(d, J¼8.7 Hz, 2H), 7.90(d, J¼8.7 Hz,
1H). Anal. Calcd for C18H20O2S: C, 71.96; H, 6.71. Found: C, 71.93; H, 6.63.
A pale-yellow oil; Rf 0.41 (1:3 CH2Cl2–hexane); IR (neat)
1591 cmꢁ1
;
1H NMR (500 MHz)
d
1.06 (t, J¼7.3 Hz, 3H), 2.62 (q,
J¼7.3 Hz, 2H), 3.75 (s, 3H), 5.69 (d, J¼0.9 Hz, 1H), 5.71 (d, J¼0.9 Hz,
1H), 6.82 (dd, J¼8.7, 2.7 Hz, 1H), 6.86 (d, J¼2.7 Hz, 1H), 7.30 (d,
J¼7.3 Hz, 1H), 7.33 (d, J¼8.7 Hz, 1H), 7.38 (d, J¼7.8 Hz, 1H), 7.40–7.46
(m, 2H), 7.76 (d, J¼8.2 Hz, 1H), 7.83 (d, J¼7.8 Hz, 1H), 8.26 (d,
J¼8.2 Hz, 1H). Anal. Calcd for C21H20OS: C, 78.71; H, 6.29. Found: C,
78.50; H, 6.33.
3.6.7. Ethyl 4-methoxy-2-[1-(4-methylphenyl)prop-1-enyl]phenyl
sulfoxide (5f–ii)
A pale-yellow oil; a mixture of stereoisomers (E/Z¼ca. 6:4); Rf
0.41 (1:1 THF–hexane); IR (neat) 1589, 1065 cmꢁ1
;
1H NMR
(500 MHz)
d
1.04 (t, J¼7.3 Hz, 3H), 1.68 (br s, 1.2H), 1.91 (d, J¼6.9 Hz,
1.8H), 2.31 (s, 1.2H), 2.34 (s, 1.8H), 2.36–2.40 (m, 2H), 3.86 (s, 1.8H),
3.87 (s, 1.2H), 5.87 (q, J¼6.9 Hz, 0.6H), 6.32 (br s, 0.4H), 6.73 (br s,
0.4H), 6.82 (d, J¼2.3 Hz, 0.6H), 6.98–7.13 (m, 5H), 7.80 (d, J¼8.7 Hz,
0.6H), 7.92 (d, J¼8.7 Hz, 0.4H). Anal. Calcd for C19H22O2S: C, 72.57;
H, 7.05. Found: C, 72.56; H, 7.28.
3.6. Ethyl 2-(1-arylvinyl)phenyl sulfoxides 5
These compounds were prepared by treating 4 with NaIO4 in
aqueous MeOH at room temperature.
3.6.1. Ethyl 2-(1-phenylethenyl)phenyl sulfoxide (5a)
3.6.8. Ethyl 4-methoxy-2-[1-(4-methoxyphenyl)ethenyl]phenyl
sulfoxide (5g)
A pale-yellow oil; Rf 0.29 (1:2 THF–hexane); IR (KBr) 1614,
1034 cmꢁ1
;
1H NMR (400 MHz)
d
1.08 (t, J¼7.3 Hz, 3H), 2.49–2.58
A pale-yellow oil; Rf 0.33 (1:1 THF–hexane); IR (neat) 1589,
(m, 1H), 2.65–2.74 (m, 1H), 5.33 (s, 1H), 5.83 (s, 1H), 7.22–7.25 (m,
2H), 7.30–7.32 (m, 4H), 7.50 (ddd, J¼7.7, 7.3, 1.1 Hz, 1H), 7.59 (ddd,
J¼7.7, 7.3, 1.1 Hz, 1H), 8.01 (1H, d, J¼7.7 Hz, 1H). Anal. Calcd for
C18H16OS: C, 74.96; H, 6.29. Found: C, 75.06; H, 6.41.
1034 cmꢁ1
;
1H NMR (500 MHz)
d
1.08 (t, J¼7.3 Hz, 3H), 2.53 (dq,
J¼14.7, 7.3 Hz, 1H), 2.66 (dq, J¼14.7, 7.3 Hz, 1H), 3.81 (s, 3H), 3.86 (s,
3H), 5.19 (s, 1H), 5.72 (s, 1H), 6.83–6.84 (m, 3H), 7.09 (dd, J¼8.7,
2.7 Hz, 1H), 7.19 (d, J¼8.7 Hz, 2H), 7.90 (d, J¼8.7 Hz, 1H). Anal. Calcd
for C18H20O3S: C, 68.33; H, 6.37. Found: C, 68.20; H, 6.45.
3.6.2. Ethyl 2-[1-(4-methylphenyl)ethenyl]phenyl sulfoxide (5b)
A pale-yellow oil; Rf 0.30 (1:3 THF–hexane); IR (neat) 1609,
3.6.9. Ethyl 4-methoxy-2-[1-(thienyl)ethenyl]phenyl sulfoxide (5h)
A pale-yellow oil; Rf 0.17 (1:2 THF–hexane); IR (neat) 1591,
1334 cmꢁ1; 1H NMR (500 MHz)
d
1.08 (t, J¼7.3 Hz, 3H), 2.34 (s, 3H),
2.55 (dq, J¼14.7, 7.3 Hz, 1H), 2.72 (dq, J¼14.7, 7.3 Hz, 1H), 5.27 (d,
J¼0.9 Hz, 1H), 5.79 (d, J¼0.9 Hz, 1H), 7.11 (d, J¼8.7 Hz, 2H), 7.13 (d,
J¼8.7 Hz, 2H), 7.30 (dd, J¼7.8, 1.4 Hz, 1H), 7.49 (td, J¼7.3, 1.4 Hz, 1H),
7.58 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H), 7.80 (dd, J¼7.8, 1.4 Hz, 1H). Anal.
Calcd for C17H18OS: C, 75.51; H, 6.71. Found: C, 75.60; H, 6.80.
1045 cmꢁ1
;
1H NMR (500 MHz)
d
1.10 (t, J¼7.3 Hz, 3H), 2.57 (dq,
J¼14.7, 7.3 Hz, 1H), 2.74 (dq, J¼14.7, 7.3 Hz, 1H), 3.86 (s, 3H), 5.15 (s,
1H), 5.79 (s, 1H), 6.70 (dd, J¼3.7, 0.9 Hz, 1H), 6.87 (d, J¼2.7 Hz, 1H),
6.93 (dd, J¼5.0, 3.7 Hz, 1H), 7.11 (dd, J¼8.7, 2.7 Hz, 1H), 7.25 (dd,
J¼5.0, 0.9 Hz, 2H), 7.92 (d, J¼8.7 Hz, 1H). Anal. Calcd for C15H16O2S2:
C, 61.61; H, 5.52. Found: C, 61.53; H, 5.49.
3.6.3. 2-[1-(4-Chlorophenyl)prop-1-enyl]phenyl ethyl sulfoxide (5c)
A pale-yellow oil; a mixture of stereoisomers (E/Z¼ca. 6:4); Rf
3.6.10. Ethyl 4-methoxy-2-[1-(naphthalen-1-yl)ethenyl]phenyl
sulfoxide (5i)
0.31 (1:2 THF–hexane); IR (neat) 1634, 1035 cmꢁ1
;
1H NMR
(500 MHz)
d
1.09 (t, J¼7.3 Hz, 3H), 1.68 (d, J¼6.4 Hz, 1.2H), 1.91 (d,
A pale-yellow viscous oil; Rf 0.46 (1:1 THF–hexane); IR (neat)
J¼7.3 Hz, 1.8H), 2.44–2.58 (m, 2H), 5.93 (q, J¼7.3 Hz, 0.6H), 6.35 (br,
0.4H), 7.08 (d, J¼8.7 Hz, 2H), 7.25–7.29 (m,1H), 7.30 (d, J¼8.7 Hz, 2H),
7.46 (ddd, J¼7.8, 7.3, 1.4 Hz, 0.6H), 7.52 (ddd, J¼7.8, 7.3, 1.4 Hz, 0.6H),
7.55 (ddd, J¼7.8, 7.3, 1.4 Hz, 0.4H), 7.61 (ddd, J¼7.8, 7.3, 1.4 Hz, 0.4H),
7.93 (dd, J¼7.8,1.4 Hz, 0.6H), 8.03 (dd, J¼7.8,1.4 Hz, 0.4H). Anal. Calcd
for C17H17ClOS: C, 66.98; H, 5.62. Found: C, 66.80; H, 5.61.
1589, 1045 cmꢁ1
;
1H NMR (500 MHz)
d
0.87 (t, J¼7.3 Hz, 3H), 2.20
(dq, J¼14.7, 7.3 Hz, 1H), 2.30 (dq, J¼14.7, 7.3 Hz, 1H), 3.90 (s, 3H),
5.71 (d, J¼0.9 Hz, 1H), 5.80 (d, J¼0.9 Hz, 1H), 7.06 (dd, J¼8.7, 2.3 Hz,
1H), 7.09 (d, J¼2.3 Hz, 1H), 7.28 (dd, J¼7.3, 1.4 Hz, 1H), 7.40 (dd,
J¼8.2, 7.3 Hz, 1H), 7.43 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H), 7.47 (ddd, J¼7.8,
7.3, 1.4 Hz, 1H), 7.82 (d, J¼8.2 Hz, 1H), 7.84 (d, J¼8.7 Hz, 1H), 7.86 (d,
J¼7.8 Hz, 1H), 8.08 (d, J¼7.8 Hz, 1H). Anal. Calcd for C21H20O2S: C,
74.97; H, 5.99. Found: C, 74.83; H, 6.17.
3.6.4. Ethyl 4-methoxy-2-[1-(2-methylphenyl)ethenyl]phenyl
sulfoxide (5d)
A pale-yellow oil; Rf 0.48 (1:1 THF–hexane); IR (neat) 1589,
3.7. Typical procedure for the preparation of
benzo[b]thiophenes 6
1045 cmꢁ1; 1H NMR (500 MHz)
d
1.03 (t, J¼7.3 Hz, 3H), 2.18 (s, 3H),
2.24–2.37 (m, 2H), 3.88 (s, 3H), 5.48 (d, J¼1.4 Hz, 1H), 5.56 (d,
J¼1.4 Hz, 1H), 6.95 (d, J¼2.7 Hz, 1H), 7.04 (dd, J¼8.7, 2.7 Hz, 1H), 7.12
(td, J¼7.3, 1.4 Hz, 1H), 7.15 (d, J¼7.3 Hz, 2H), 7.21 (td, J¼7.3, 1.4 Hz,
1H), 7.86 (d, J¼8.7 Hz, 1H). Anal. Calcd for C18H20O2S: C, 71.96; H,
6.71. Found: C, 72.04; H, 6.75.
3.7.1. 3-Phenylbenzo[b]thiophene (6a)7
A solution of 5a (0.16 g, 0.64 mmol) in Ac2O (1 mL) was heated at
100 ꢀC until the spot of the starting material had disappeared by
TLC analyses (1:3 THF–hexane; 9 h). After removal of Ac2O under

K. Kobayashi et al. / Tetrahedron 65 (2009) 2430–2435
2435
reduced pressure, the residue was purified by preparative TLC on
silica gel to give 6a (0.10 g, 77%); a pale-yellow oil; Rf 0.72 (1:10
THF–hexane). The spectral (IR and 1H NMR) data of this product
were identical to those reported previously.7
(500 MHz)
J¼1.8 Hz, 1H), 7.331 (s, 1H), 7.51 (d, J¼8.7 Hz, 2H), 7.76 (d, J¼8.7 Hz,
1H); 13C NMR
55.35, 55.57, 105.19, 114.20, 114.53, 123.49, 123.92,
128.63, 129.65, 132.97, 137.39, 139.17, 157.67, 159.08; MS m/z 270
(Mþ, 100). Anal. Calcd for C16H14O2S: C, 71.08; H, 5.22. Found: C,
70.84; H, 5.41.
d 3.84 (s, 3H), 3.88 (s, 3H), 7.02–7.05 (m, 3H), 7.330 (d,
d
3.7.2. 3-(4-Methylphenyl)benzo[b]thiophene (6b)7
Apale-yellowoil;Rf 0.65 (1:20 THF–hexane). The spectral (IR and 1H
NMR) data of this product were identical to those reported previously.7
3.7.9. 5-Methoxy-3-(2-thienyl)benzo[b]thiophene (6h)
A pale-yellow oil; Rf 0.25 (hexane); IR (neat) 3090, 1599, 1456,
3.7.3. 3-(4-Chlorophenyl)-2-methylbenzo[b]thiophene (6c)
1434, 1261, 1232, 1026, 777, 698 cmꢁ1; 1H NMR (500 MHz)
d 3.88 (s,
A pale-yellow oil; Rf 0.59 (1:30 THF–hexane); IR (neat) 3057,1589,
3H), 7.05 (dd, J¼8.7, 2.3 Hz, 1H), 7.17 (dd, J¼5.0, 3.7 Hz, 1H), 7.32 (d,
1435, 1090, 833, 760, 733 cmꢁ1
;
1H NMR (500 MHz)
d
2.48 (s, 3H),
J¼3.7 Hz, 1H), 7.36 (d, J¼5.0 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J¼2.3 Hz,
2.88–7.31 (m, 2H), 7.33 (d, J¼8.7 Hz, 2H), 7.44–7.49 (m, 3H), 7.79–7.81
1H), 7.75 (d, J¼8.7 Hz, 1H); 13C NMR
d 55.57, 105.17, 114.98, 123.50,
(m,1H); 13C NMR
d
14.47,122.00,122.14,123.91,124.25,128.79,131.33,
124.76, 125.00, 125.25, 127.58, 130.22, 132.84, 137.46, 138.44, 157.90;
MS m/z 246 (Mþ, 100). Anal. Calcd for C13H10OS2: C, 63.38; H, 4.09.
Found: C, 63.24; H, 4.09.
132.53, 133.24, 133.70, 136.52, 138.18, 140.02; MS m/z 258 (Mþ, 100).
Anal. Calcd for C15H11ClS: C, 69.62; H, 4.28. Found: C, 69.50; H, 4.09.
3.7.4. 5-Methoxy-3-(2-methylphenyl)benzo[b]thiophene (6d)
A pale-yellow oil; Rf 0.69 (1:40 THF–hexane); IR (neat) 3060,
3.7.10. 5-Methoxy-3-(naphthalen-2-yl)benzo[b]thiophene (6i)
A pale-yellow oil; Rf 0.30 (hexane); IR (neat) 3055, 1599, 1454,
1599, 1456, 1261, 1229, 1028, 790 cmꢁ1
;
1H NMR (500 MHz)
d
2.19
1435, 1269, 1219, 1024, 779 cmꢁ1; 1H NMR (500 MHz)
d 3.64 (s, 3H),
(s, 3H), 3.76 (s, 3H), 6.86 (d, J¼2.3 Hz, 1H), 7.03 (dd, J¼8.7, 2.3 Hz,
1H), 7.27–7.36 (m, 5H), 7.77 (d, J¼8.7 Hz,1H); MS m/z 254 (Mþ,100).
Anal. Calcd for C16H14OS: C, 75.55; H, 5.55. Found: C, 75.30; H, 5.69.
6.83 (d, J¼2.3 Hz, 1H), 7.04 (dd, J¼8.7, 2.3 Hz, 1H), 7.38 (dd, J¼7.8,
7.3 Hz, 1H), 7.48 (s, 1H), 7.49 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H), 7.54 (dd,
J¼7.3, 1.4 Hz, 1H), 7.58 (dd, J¼8.2, 7.3 Hz, 1H), 7.73 (d, J¼8.2 Hz, 1H),
7.82 (d, J¼8.7 Hz, 1H), 7.94 (d, J¼7.8 Hz, 2H); 13C NMR
d 55.47,
3.7.5. 5-Methoxy-3-(3-methylphenyl)benzo[b]thiophene (6e)
A yellow oil; Rf 0.57 (1:10 THF–hexane); IR (neat) 3091, 1601,
105.47, 114.86, 123.31, 125.46, 125.98, 126.04, 126.21, 126.31, 127.73,
128.24 (two overlapped C’s), 132.32, 132.35, 133.71, 133.78, 136.05,
140.57, 157.57; MS m/z 290 (Mþ, 100). Anal. Calcd for C19H14OS: C,
78.59; H, 4.86. Found: C, 78.47; H, 5.13.
1454, 1435, 1267, 1221, 1029, 847, 775 cmꢁ1 1H NMR (500 MHz)
;
d
2.44 (s, 3H), 3.84 (s, 3H), 7.04 (dd, J¼8.7, 2.3 Hz, 1H), 7.23 (dd,
J¼7.8, 1.8 Hz, 1H), 7.36 (d, J¼2.3 Hz, 1H), 7.38–7.40 (m, 4H), 7.77 (d,
J¼8.7 Hz, 1H); MS m/z 254 (Mþ, 100). Anal. Calcd for C16H14OS: C,
75.55; H, 5.55. Found: C, 75.49; H, 5.59.
Acknowledgements
We wish to thank Mrs. Miyuki Tanmatsu of this university for
determining mass spectra and performing combustion analyses.
3.7.6. 5-Methoxy-3-(4-methylphenyl)benzo[b]thiophene (6f–i)
A pale-yellow solid mp 73–75 ꢀC (hexane–CH2Cl2); IR (KBr)
3088, 1601, 1497, 1454, 1427, 1263, 1235, 1028, 820, 779 cmꢁ1 1H
;
NMR (500 MHz)
d
2.44 (s, 3H), 3.83 (s, 3H), 7.04 (dd, J¼8.7, 2.7 Hz,
References and notes
1H), 7.30 (d, J¼8.7 Hz, 2H), 7.35 (d, J¼2.7 Hz, 1H), 7.37 (s, 1H), 7.48
(d, J¼8.7 Hz, 2H), 7.76 (d, J¼8.7 Hz, 1H); MS m/z 254 (Mþ, 100). Anal.
Calcd for C16H14OS: C, 75.55; H, 5.55. Found: C, 75.58; H, 5.79.
1. Pinto, E.; Queiroz, M. R. P.; Vale-Silva, L. A.; Oliveira, J. F.; Begouin, A.; Begouin,
J.-M.; Kirsch, G. Bioorg. Med. Chem. Lett. 2008, 16, 8172–8177 See also pertinent
references cited in Ref. 3.
2. (a) Yoshida, S.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 5573–5576; (b)
Aoyama, T.; Orito, M.; Takido, T.; Kodomari, M. Synthesis 2008, 2089–2099 See
also pertinent references cited in Ref. 3.
3.7.7. 5-Methoxy-2-methyl-3-(4-methylphenyl)benzo[b]thiophene
(6f–ii)
3. (a) Kobayashi, K.; Nakamura, D.; Miyamoto, K.; Morikawa, O.; Konishi, H. Bull.
Chem. Soc. Jpn. 2007, 80, 1780–1784; (b) Kobayashi, K.; Nakamura, D.; Miyamoto,
K.; Fukamachi, S.; Morikawa, O.; Konishi, H. Heterocycles 2008, 75, 919–924.
4. (a) Bates, D. K.; Thomas Winters, R.; Picard, J. A. J. Org. Chem. 1992, 57, 3094–
3097; (b) Toru, T.; Watanabe, Y.; Mase, N.; Tsusaka, M.; Hayakawa, T.; Ueno, Y.
Pure Appl. Chem. 1996, 68, 711–714; (c) Amat, M.; Hadida, S.; Pshenichnyi, G.;
Bosch, J. J. Org. Chem. 1997, 62, 3158–3175; (d) Chen, L.-C.; Wang, H.-M.; Kang,
I.-J. Heterocycles 1999, 51, 1437–1441; (e) Wang, H.-M.; Huang, H.-Y.; Kang, I.-J.;
Chen, L.-C. Heterocycles 2001, 55, 1231–1235.
A pale-yellow oil; Rf 0.37 (1:10 THF–hexane); IR (neat) 1597,
1456, 1441, 1269, 1231, 1151, 1030, 826 cmꢁ1 1H NMR (500 MHz)
;
d
2.44 (s, 3H), 2.47 (s, 3H), 3.77 (s, 3H), 6.93 (dd, J¼8.7, 2.3 Hz, 1H),
6.97 (d, J¼2.7 Hz, 1H), 7.28 (d, J¼8.2 Hz, 2H), 7.30 (d, J¼8.2 Hz, 2H),
7.64 (d, J¼8.7 Hz, 1H); MS m/z 268 (Mþ, 100). Anal. Calcd for
C17H16OS: C, 76.08; H, 6.01. Found: C, 76.02; H, 6.12.
5. Kobayashi, K.; Umakoshi, H.; Matsunaga, A.; Tanmatsu, M.; Morikawa, O.; Ko-
nishi, H. Bull. Chem. Soc. Jpn. 2004, 77, 2095–2096.
6. Toyota, S.; Oki, M. J. Organomet. Chem. 1997, 534, 1–6.
3.7.8. 5-Methoxy-3-(4-methoxyphenyl)benzo[b]thiophene (6g)
A pale-yellow solid; mp 118–120 ꢀC (hexane–CH2Cl2); IR (KBr)
3086, 1609, 1497, 1454, 1425, 1247, 1177, 1031 cmꢁ1
;
1H NMR
7. Keegatra, M. A.; Brandsma, L. Synthesis 1988, 888–890.