Synthesis of 2-benzothiophene-1(3H)-thione and isothiochromene-1-thione derivatives by iodine-mediated cyclization of lithium 2-(vinyl)dithiobenzoate derivatives

Article abstract of DOI:10.3987/COM-08-11514

Successive treatment of α-substituted 2-bromostyrenes with butyllithium and carbon disulfide generates lithium 2-(vinyl)dithiobenzoates, which are then allowed to react with iodine to give 3-substituted 3-iodomethyl-2-benzothiophene-1(3H)-thiones and/or 4

Full text of DOI:10.3987/COM-08-11514

HETEROCYCLES, Vol. 78, No. 1, 2009
169
HETEROCYCLES, Vol. 78, No. 1, 2009, pp. 169 – 176. © The Japan Institute of Heterocyclic Chemistry
Received, 4th August, 2008, Accepted, 5th September, 2008, Published online, 8th September, 2008.
DOI: 10.3987/COM-08-11514
SYNTHESIS
ISOTHIOCHROMENE-1-THIONE
IODINE-MEDIATED CYCLIZATION
OF
2-BENZOTHIOPHENE-1(3H)-THIONE
AND
BY
DERIVATIVES
OF
LITHIUM
2-(VINYL)DITHIOBENZOATE DERIVATIVES
Shuhei Fukamachi, Hisatoshi Konishi, and Kazuhiro Kobayashi*
Division of Applied Chemistry, Department of Chemistry and Biotechnology,
Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan
Abstract - Successive treatment of α-substituted 2-bromostyrenes with
butyllithium and carbon disulfide generates lithium 2-(vinyl)dithiobenzoates,
which are then allowed to react with iodine to give 3-substituted
3-iodomethyl-2-benzothiophene-1(3H)-thiones
and/or
4-substituted
isothiochromene-1-thiones in one-pot. Some of the former products can be
transformed into the corresponding latter products on treatment with sodium
hydrogencarbonate in refluxing acetonitrile.
INTRODUCTION
In the course of our studies on the development of new methods for the preparation of benzene-fused
heterocycles utilizing iodine-mediated cyclization of appropriately o-substituted styrene derivatives,1 we
now wish to report a convenient method for the preparation of 2-benzothiophene-1(3H)-thione (5) and
isothiochromene-1-thione derivatives (6) by a treatment of 2-(vinyl)dithiobenzoate derivatives (2) with
iodine. To the best of our knowledge, this is the first report on the iodine-mediated cyclization of
dithiobenzoates. These intermediates (2) can be generated in situ by a successive treatment of
α-substituted 2-bromostyrene derivatives (1) with butyllithium and carbon disulfide. Therefore, the
method allows one-pot access to these sulfur-containing heterocycles from 1. Although these
heterocycles, especially isothiochromene-1-thiones, may be of interest from a biological point of view,
there have been a few reports on the synthesis of these classes of compounds in the literature;2,3 the
methods involve troublesome procedures, and suffer from considerably lower generality.
RESULTS AND DISCUSSION
Our one-pot synthesis of 2-benzothiophene-1(3H)-thione (5) and isothiochromene-1-thione derivatives

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HETEROCYCLES, Vol. 78, No. 1, 2009
R2
Br
R2
R1
R1
1) n-BuLi, Et2O, 0 ˚C
2) CS2, 0 ˚C
S–
1
S
2
R2
a
R2
I+
I
R1
R1
I2, 0 ˚C
b
b
S–
S
S
S
3
4
a R1 = H, R2 = Me
a
– HI
R2
b R1 = H, R2 = Ph
c R1 = H, R2 = p-Tol
d R1 = H, R2 = 4-ClC6H4
e R1 = OMe, R2 = Me
f R1 = OMe, R2 = Ph
R2
R1
I
R1
+
S
S
g R1 = OMe, R2 = 4-ClC6H4
h R1 = OMe, R2 = 4-MeOC6H4
S
S
6a 0%
5a 45%
6b 28%
6c 22%
6d 26%
6e 0%
6f 20%
6g 13%
6h 38%
5b 17%
5c 18%
5d 19%
5e 37%
5f 29%
5g 33%
5h 18%
Scheme 1
(6) was conducted as shown in Scheme 1. Thus, successive treatment of 2-bromostyrene derivatives (1)
with butyllithium and carbon disulfide in diethyl ether at 0 ˚C generated 2-(vinyl)dithiobenzoate
derivatives (2), which were allowed to react with iodine to give, after usual workup followed by
purification using column chromatography on silica gel, 5 and/or 6 in the yields listed in Scheme 1. The
former products, 3-iodomethyl-2-benzothiophene-1(3H)-thiones (5), were produced via iodine-mediated
5-exo ring closure (path a), and the latter products, 4-substituted isothiochromene-1-thione (6), were
produced via iodine-mediated 6-endo ring closure, forming intermediate (4), followed by elimination of
hydrogen iodide (path b). As can be seen from Scheme 1, the reactions generally afforded separable
mixtures of products (5) and (6) in reasonable total yields. However, when 2-bromo-α-methylstyrene
derivatives (1a) and (1e) were used as starting materials, the corresponding
2-benzothiophene-1(3H)-thione derivatives (5) were sole isolated products, and no trace of
isothiochromene-1-thione derivatives (6) were obtained. This may be ascribed to the absence of
conjugation between the 4-methyl substituent and 3,4-double bond of the isothiochromene-1-thione
structure. It should be noted that the ratios of the products were unchanged even when the reactions were

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171
carried out under refluxing conditions.
Some of 3-substituted 3-iodomethyl-2-benzothiophene-1(3H)-thiones (5) proved to be transformed into
the corresponding 4-substituted isothiochromene-1-thione derivatives (6). Thus, mixtures of 5 and
sodium hydrogencarbonate in acetonitrile were heated at reflux temperature to give 6 in good yields as
listed in Scheme 2. When another 3-substituent than iodomethyl was methyl or 4-chlorophenyl (i.e., 5a,
d, e, and g), this transformation reaction did not occur and the starting materials were recovered almost
quantitatively. This transformation is thought to proceed trough equilibrium between the intermediates
(4) and (3), which is generated by treating 5 with sodium hydrogencarbonate. E1-like elimination of
hydrogen iodide from the intermediate (4) gives rise to 6. Although we have no explicit explanation of
the reason for this, methyl and 4-chlorophenyl substituents may make this elimination difficult.
6a 0%
6b 73%
NaHCO3, MeCN, reflux
6c 77%
6d 0%
6e 0%
6f 85%
6g 0%
6h 99%
4
5
3
Scheme 2
In conclusion, a new one-pot synthesis of 2-benzothiophene-1(3H)-thione and isothiochromene-1-thione
derivatives have been achieved. Since the method employs readily available starting materials and is
experimentally simple, it may be of value in organic synthesis. Work on syntheses utilizing reactions of
2-lithiostyrene derivatives with carbon disulfide and related reagents is currently in progress in our
laboratory, and the results will be reported in the near future.
EXPERIMENTAL
The melting points were determined on a Laboratory Devices MEL-TEMP II melting-point apparatus
1
and are uncorrected. The IR spectra were recorded on a Shimadzu FTIR-8300 spectrometer. The H
NMR spectra were determined in CDCl3 using SiMe4 as an internal reference with a JEOL ECP500 FT
NMR spectrometer operating at 500 MHz. The 13C NMR spectrum was determined in CDCl3 using TMS
as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 125 MHz.
Low-resolution MS spectra (EI, 70 eV) were measured by a JEOL JMS-AX505 HA spectrometer.
Thin-layer chromatography (TLC) was carried out on 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 appropriate drying agents and distilled under argon prior to use.

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Starting Materials. 1-Bromo-2-(1-methylethenyl)benzene (1a),4 1-bromo-2-(1-phenylethenyl)benzene
(1b),5 2-bromophenyl(4-methylphenyl)methanone,6 1-bromo-2-[1-(4-chlorophenyl)ethenyl]benzene
(1d),1a
1-bromo-4-methoxy-2-(1-methylethenyl)benzene
(1e),7
1-bromo-4-methoxy-2-(1-
phenylethenyl)benzene (1f),6 and 2-bromo-5-methoxybenzaldehyde4 were prepared by the appropriate
reported procedures. All other chemicals used in this study were commercially available.
1-Bromo-2-[1-(4-methylphenyl)ethenyl]benzene (1c). This compound was prepared by the reaction of
2-bromophenyl(4-methylphenyl)methanone6 with methylenetriphenylphosphorane in THF at 0 ˚C in
1
81% yield; a colorless oil; Rf 0.50 (hexane); IR (neat) 1614 cm–1; H NMR δ 2.34 (3H, s), 5.20 (1H, s),
5.80 (1H, s), 7.11 (2H, d, J = 8.2 Hz), 7.16 (2H, d, J = 8.2 Hz), 7.20 (1H, ddd, J = 7.8, 7.3, 1.8 Hz), 7.30
(1H, dd, J = 7.3, 1.8 Hz), 7.34 (1H, td, J = 7.3, 1.4 Hz), 7.59 (1H, d, J = 7.8 Hz). Anal. Calcd for
C15H13Br: C, 65.95; H, 4.80. Found: C, 65.92; H, 5.00.
2-Bromo-5-methoxyphenyl(4-chlorophenyl)methanol. This compound was prepared by the reaction
of 2-bromo-5-methoxybenzaldehyde4 with 4-chlorophenylmagnesium bromide in THF at 0 ˚C in 92%
yield; a pale-yellow oil; Rf 0.39 (1:2 Et2O–hexane); IR (neat) 3366 cm–1; 1H NMR δ 2.35 (1H, d, J = 3.7
Hz), 3.79 (3H, s), 6.12 (1H, d, J = 3.7 Hz), 6.73 (1H, dd, J = 8.7, 3.2 Hz), 7.12 (1H, d, J = 3.2 Hz), 7.30
(2H, d, J = 8.7 Hz), 7.34 (2H, d, J = 8.7 Hz), 7.42 (1H, d, J = 8.7 Hz). Anal. Calcd for C14H12BrClO2: C,
51.33; H, 3.69. Found: C, 51.32; H, 3.42.
2-Bromo-5-methoxyphenyl(4-chlorophenyl)methanone. This compound was prepared by the PCC
oxidation of 2-bromo-5-methoxyphenyl(4-chlorophenyl)methanol in 1,2-dichloroethane at rt in 77%
yield; a white solid; mp 76–78 ˚C (hexane); IR (KBr) 1668 cm–1; 1H NMR δ 3.81 (3H, s), 6.86 (1H, d, J
= 3.2 Hz), 6.92 (1H, dd, J = 8.7, 3.2 Hz), 7.44 (2H, d, J = 8.7 Hz), 7.52 (1H, d, J = 8.7 Hz), 7.76 (2H, d,
J = 8.7 Hz). Anal. Calcd for C14H10BrClO2: C, 51.65; H, 3.10. Found: C, 51.55; H, 3.13.
1-Bromo-2-[1-(4-chlorophenyl)ethenyl]-4-methoxybenzene (1g). This compound was prepared by
treating 2-bromo-5-methoxyphenyl(4-chlorophenyl)methanone with methylenetriphenylphosphorane in
THF at 0 ˚C in 90% yield; a pale-yellow oil; Rf 0.61 (1:5 Et2O–hexane); IR (neat) 1589 cm–1; 1H NMR δ
3.81 (3H, s), 5.28 (1H, s), 5.80 (1H, s), 6.78 (1H, dd, J = 8.7, 3.2 Hz), 6.85 (1H, d, J = 3.2 Hz), 7.20 (2H,
d, J = 8.7 Hz), 7.27 (2H, d, J = 8.7 Hz), 7.46 (1H, d, J = 8.7 Hz). Anal. Calcd for C15H12BrClO: C,
55.67; H, 3.74. Found: C, 55.62; H, 3.75.
2-Bromo-5-methoxyphenyl(4-methoxyphenyl)methanol. This compound was prepared by the reaction
of 2-bromo-5-methoxybenzaldehyde4 with 4-methoxyphenylmagnesium bromide in THF at 0 ˚C in 90%
yield; a white solid; mp 83–84 ˚C (hexane–Et2O); IR (KBr) 3400, 1611 cm–1; 1H NMR δ 2.26 (1H, d, J =
3.8 Hz), 3.79 (3H, s), 3.80 (3H, s), 6.07 (1H, d, J = 3.8 Hz), 6.71 (1H, dd, J = 8.4, 3.1 Hz), 6.86 (2H, d, J
= 8.4 Hz), 7.22 (1H, d, J = 3.1 Hz), 7.31 (2H, d, J = 8.4 Hz), 7.40 (1H, d, J = 8.4 Hz). Anal. Calcd for
C15H15BrO3: C, 55.75; H, 4.68. Found: C, 55.50; H, 4.50.
2-Bromo-5-methoxyphenyl(4-methoxyphenyl)methanone. This compound was prepared by the PCC

HETEROCYCLES, Vol. 78, No. 1, 2009
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oxidation of 2-bromo-5-methoxyphenyl(4-methoxyphenyl)methanol in 1,2-dichloroethane at rt in 84%
yield; colorless needles; mp 71–73 ˚C (hexane); IR (KBr) 1653, 1603 cm–1; 1H NMR δ 3.80 (3H, s), 3.88
(3H, s), 6.85 (1H, d, J = 2.7 Hz), 6.89 (1H, dd, J = 8.7, 2.7 Hz), 6.94 (2H, d, J = 9.2 Hz), 7.50 (1H, d, J
= 8.7 Hz), 7.81 (2H, d, J = 9.2 Hz). Anal. Calcd for C15H13BrO3: C, 56.10; H, 4.08. Found: C, 55.76; H,
4.35.
1-Bromo-4-methoxy-2-[1-(4-methoxyphenyl)ethenyl]benzene (1h). This compound was prepared by
treating 2-bromo-5-methoxyphenyl(4-methoxyphenyl)methanone with methylenetriphenylphosphorane
in THF at 0 ˚C in 92 % yield; a colorless oil; Rf 0.32 (1:10 THF–hexane); IR (neat) 1606 cm–1; 1H NMR
δ 3.80 (6H, s), 5.15 (1H, s), 5.73 (1H, s), 6.77 (1H, dd, J = 8.7, 3.2 Hz), 6.83 (2H, d, J = 9.2 Hz), 6.86
(1H, d, J = 3.2 Hz), 7.21 (2H, d, J = 9.2 Hz), 7.46 (1H, d, J = 8.7 Hz). Anal. Calcd for C16H15BrO2: C,
60.21; H, 4.74. Found: C, 60.25; H, 4.55.
Typical Procedure for the Preparation of 2-Benzothiophene-1(3H)-thione (5) and
1H-2-Benzothiopyran-1-thione Derivatives (6). 3-Iodomethyl-3-phenyl-2-benzothiophene-1(3H)-
thione (5b) and 4-Phenyl-1H-2-benzothiopyran-1-thione (6b). To a stirred solution of 1b (0.52 g, 2.0
mmol) in Et2O (6 mL) at 0 ˚C was added n-BuLi (1.6 M in hexane; 2.2 mmol) (1 M = 1 mol dm–3)
dropwise; the mixture was stirred for 1 h. To the resulting mixture CS2 (0.18 g, 2.4 mmol) was added.
After 15 min, I2 (1.0 g, 4.0 mmol) was added and stirring was continued for an additional 2 h at the same
temperature before 10% aqueous Na2S2O3 was added until the color of iodine disappeared. The mixture
was diluted with Et2O (6 mL) and the layers were separated. The aqueous layer was extracted with Et2O
twice (5 mL each), and the combined extracts were washed with saturated aqueous NaHCO3 and brine,
and dried over anhydrous Na2SO4. After evaporation of the solvent, the residue was purified by column
chromatography on silica gel to afford 5b (0.13 g, 17%) and 6b (0.14 g, 28%). 5b: a red oil; Rf 0.32
1
(1:10 THF–hexane); IR (neat) 1269, 1051 cm–1; H NMR δ 4.23 (1H, d, J = 10.5 Hz), 4.31 (1H, d, J =
10.5 Hz), 7.30–7.40 (6H, m), 7.53 (1H, ddd, J = 7.8, 7.3, 0.9 Hz), 7.66 (1H, td, J = 7.3, 1.4 Hz), 8.06
(1H, d, J = 7.3 Hz); MS m/z 382 (M+, 33), 255 (100). HR-MS Calcd for C15H11IS2: M, 381.9347. Found:
1
m/z 381.9370. 6b: red needles; mp 101–103 ˚C (hexane); IR (KBr) 1217, 1009 cm–1; H NMR δ 7.05
(1H, s), 7.36 (2H, dd, J = 7.8, 1.4 Hz), 7.44–7.53 (4H, m), 7.60 (1H, ddd, J = 7.8, 7.3, 1.4 Hz), 7.67 (1H,
13
ddd, J = 7.8, 7.3, 1.4 Hz), 9.02 (1H, dd, J = 7.8, 1.4 Hz); C NMR δ 128.05, 128.33, 128.66, 128.73,
129.20, 129.33, 129.37, 132.20, 133.79, 137.18, 137.64, 138.97, 210.53; MS m/z 254 (M+, 100). Anal.
Calcd for C15H10S2: C, 70.83; H, 3.96. Found: C, 70.64; H, 4.09.
3-Iodomethyl-3-methyl-2-benzothiophene-1(3H)-thione (5a): a red oil; Rf 0.33 (1:5 Et2O–hexane); IR
1
(neat) 1271, 1049 cm–1; H NMR δ 2.05 (3H, s), 3.74 (1H, d, J = 10.5 Hz), 3.83 (1H, d, J = 10.5 Hz),
7.48 (1H, d, J = 7.8 Hz), 7.50 (1H, dd, J = 7.8, 7.3 Hz), 7.69 (1H, dd, J = 7.8, 7.3 Hz), 8.00 (1H, d, J =
13
7.8 Hz); C NMR δ 16.18, 27.47, 64.86, 122.93, 125.01, 129.40, 133.05, 142.94, 151.96, 225.07; MS
m/z 320 (M+, 35), 193 (100). HR-MS Calcd for C10H9IS2: M, 319.9190. Found: m/z 319.9185.

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3-Iodomethyl-3-(4-methylphenyl)-2-benzothiophene-1(3H)-thione (5c): a red oil; Rf 0.32 (1:10
THF–hexane); IR (neat) 1269, 1051 cm–1; 1H NMR δ 2.34 (3H, s), 4.21 (1H, d, J = 11.0 Hz), 4.29 (1H, d,
J = 11.0 Hz), 7.15 (2H, d, J = 7.8 Hz), 7.27 (2H, d, J = 7.8 Hz), 7.37 (1H, d, J = 7.8 Hz), 7.52 (1H, ddd,
J = 7.8, 7.3, 0.9 Hz), 7.64 (1H, ddd, J = 7.8, 7.3, 1.4 Hz), 8.05 (1H, d, J = 7.8 Hz); MS m/z 396 (M+, 35),
269 (100). HR-MS Calcd for C16H13IS2: M, 395.9503. Found: m/z 395.9495.
4-(4-Methylphenyl)-1H-2-benzothiopyran-1-thione (6c): red needles; mp 136–138 ˚C (hexane); IR
(KBr disk) 1219, 1007 cm–1; 1H NMR δ 2.44 (3H, s), 7.03 (1H, s), 7.25 (2H, d, J = 8.2 Hz), 7.29 (2H, d,
J = 8.2 Hz), 7.55 (1H, dd, J = 7.8, 1.4 Hz), 7.60 (1H, ddd, J = 8.2, 6.9, 1.4 Hz), 7.66 (1H, ddd, J = 7.8,
6.9, 1.4 Hz), 9.01 (1H, dd, J = 8.2, 1.4 Hz); MS m/z 268 (M+, 100). Anal. Calcd for C16H12S2: C, 71.60;
H, 4.51. Found: C, 71.42; H, 4.80.
3-(4-Chlorophenyl)-3-iodomethyl-2-benzothiophene-1(3H)-thione (5d): a red solid; mp 53–55 ˚C
1
(pentane); IR (KBr) 1267, 1051 cm–1; H NMR δ 4.19 (1H, d, J = 10.5 Hz), 4.25 (1H, d, J = 10.5 Hz),
7.33 (4H, s), 7.52–7.56 (2H, m), 7.66 (1H, ddd, J = 7.8, 7.3, 1.4 Hz), 8.05 (1H, d, J = 7.8 Hz); MS m/z
416 (M+, 34), 269 (100). Anal. Calcd for C15H10ClIS2: C, 43.23; H, 2.42. Found: C, 42.96; H, 2.52.
4-(4-Chlorophenyl)-1H-2-benzothiopyran-1-thione (6d): red needles; mp 113–115 ˚C (hexane–Et2O);
1
IR (KBr) 1217, 1009 cm–1; H NMR δ 7.03 (1H, s), 7.31 (2H, d, J = 8.7 Hz), 7.45–7.48 (3H, m), 7.62
(1H, ddd, J = 7.8, 7.3, 1.4 Hz), 7.68 (1H, ddd, J = 8.2, 7.3, 1.8 Hz), 9.01 (1H, dd, J = 8.2, 1.4 Hz); MS
m/z 288 (M+, 100). Anal. Calcd for C15H9ClS2: C, 62.38; H, 3.14. Found: C, 62.37; H, 3.22.
3-Iodomethyl-5-methoxy-3-methyl-2-benzothiophene-1(3H)-thione (5e): a red solid; mp 103 ˚C
(decomp) (pentane); IR (KBr) 1283, 1047 cm–1; 1H NMR δ 2.02 (3H, s), 3.72 (1H, d, J = 10.5 Hz), 3.78
(1H, d, J = 10.5 Hz), 3.93 (3H, s), 6.90 (1H, d, J = 2.3 Hz), 7.01 (1H, dd, J = 8.7, 2.3 Hz), 7.94 (1H, d, J
= 8.7 Hz); MS m/z 350 (M+, 55), 223 (100). Anal. Calcd for C11H11IOS2: C, 37.72; H, 3.17. Found: C,
37.68; H, 3.22.
3-Iodomethyl-5-methoxy-3-phenyl-2-benzothiophene-1(3H)-thione (5f): a red solid; mp 46–48 ˚C
(pentane); IR (KBr) 1279, 1055 cm–1; 1H NMR δ 3.87 (3H, s), 4.22 (1H, d, J = 11.0 Hz), 4.25 (1H, d, J =
11.0 Hz), 6.80 (1H, d, J = 2.3 Hz), 7.04 (1H, dd, J = 8.7, 2.3 Hz), 7.31–7.40 (5H, m), 8.00 (1H, d, J =
8.7 Hz); MS m/z 412 (M+, 38), 285 (100). Anal. Calcd for C16H13IOS2: C, 46.61; H, 3.18. Found: C,
46.80; H, 3.09.
6-Methoxy-4-phenyl-1H-2-benzothiopyran-1-thione (6f): red needles; mp 170–172 ˚C (hexane–Et2O);
IR (KBr) 1234, 1003 cm–1; 1H NMR δ 3.77 (3H, s), 6.89 (1H, d, J = 2.7 Hz), 7.05 (1H, s), 7.17 (1H, dd,
J = 9.2, 2.7 Hz), 7.36 (2H, dd, J = 7.8, 1.4 Hz), 7.45–7.50 (3H, m), 9.03 (1H, d, J = 9.2 Hz); MS m/z 284
(M+, 100). Anal. Calcd for C16H12OS2: C, 67.57; 4.25. Found: C, 67.51; H, 4.28.
3-(4-Chlorophenyl)-3-iodomethyl-5-methoxy-2-benzothiophene-1(3H)-thione (5g): an orange solid;
1
mp 47–48 ˚C (pentane); IR (KBr) 1285, 1055 cm–1; H NMR δ 3.87 (3H, s), 4.17 (1H, d, J = 11.4 Hz),
4.19 (1H, d, J = 11.4 Hz), 6.77 (1H, s), 7.05 (1H, d, J = 8.7 Hz), 7.33 (4H, s), 7.99 (1H, d, J = 8.7 Hz);

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13C NMR δ 13.28, 56.45, 68.68, 109.77, 116.23, 127.08, 128.53, 128.95, 129.14, 134.40, 137.22, 154.48,
164.44, 222.37; MS m/z 446 (M+, 35), 319 (100). Anal. Calcd for C16H12ClIOS2: C, 43.02; 2.71. Found:
C, 43.16; H, 2.96.
4-(4-Chlorophenyl)-6-methoxy-1H-2-benzothiopyran-1-thione (6g): an orange solid; mp 147–149 ˚C
(hexane–CH2Cl2); IR (KBr) 1234, 1001 cm–1; 1H NMR δ 3.79 (3H, s), 6.81 (1H, d, J = 2.7 Hz), 7.03 (1H,
s), 7.18 (1H, dd, J = 9.2, 2.7 Hz), 7.31 (2H, d, J = 8.7 Hz), 7.47 (2H, d, J = 8.7 Hz), 9.02 (1H, d, J = 9.2
Hz);13C NMR δ 55.68, 111.04, 117.54, 129.06, 129.60, 130.57, 131.86, 132.50, 134.40, 134.50, 136.01,
137.41, 164.37, 207.96; MS m/z 318 (M+, 100). Anal. Calcd for C16H11ClOS2: C, 60.27; 3.48. Found: C,
60.29; H, 3.49.
3-Iodomethyl-5-methoxy-3-(4-methoxyphenyl)-2-benzothiophene-1(3H)-thione (5h): an orange
solid; mp 45–47 ˚C (pentane); IR (KBr) 1281, 1032 cm–1; 1H NMR δ 3.81 (3H, s), 3.86 (3H, s), 4.19 (1H,
d, J = 11.0 Hz), 4.22 (1H, d, J = 11.0 Hz), 6.79 (1H, d, J = 2.3 Hz), 6.87 (2H, d, J = 8.7 Hz), 7.03 (1H,
dd, J = 8.7, 2.3 Hz), 7.30 (2H, d, J = 8.7 Hz), 7.99 (1H, d, J = 8.7 Hz); MS m/z 442 (M+, 10), 314 (100).
Anal. Calcd for C17H15IO2S2: C, 46.16; 3.42. Found: C, 46.03; H, 3.60.
6-Methoxy-4-(4-methoxyphenyl)-1H-2-benzothiopyran-1-thione (6h): an orange solid; mp 179–180
˚C (hexane–CH2Cl2); IR (KBr) 1234, 1001 cm–1; 1H NMR δ 3.78 (3H, s), 3.88 (3H, s), 6.93 (1H, d, J =
2.7 Hz), 7.00 (2H, d, J = 8.7 Hz), 7.03 (1H, s), 7.16 (1H, dd, J = 9.2, 2.7 Hz), 7.28 (2H, d, J = 8.7 Hz),
9.03 (1H, d, J = 9.2 Hz); MS m/z 314 (M+, 34), 269 (100). Anal. Calcd for C17H14O2S2: C, 64.94; 4.49.
Found: C, 65.29; H, 4.23.
Typical procedure for the Transformation of 3-Iodomethyl-2-benzothiophene-1(3H)-thione
derivatives (5) into 1H-2-benzothiopyran-1-thione derivatives (6). A mixture of 5b (99 mg, 0.26
mmol) and NaHCO3 (44 mg, 0.52 mmol) in MeCN (4 mL) was heated at reflux temperature. The
progress of the reaction was monitored by TLC on silica gel (1:10 THF–hexane). After the complete
consumption of the starting material (ca. 3 h), the resulting mixture was worked up in a manner similar
to that described for the preparation of 5b and 6b. Purification of the crude product by column
chromatography on silica gel (1:10 THF–hexane) gave 6b (48 mg, 73%).
ACKNOWLEDGEMENTS
We thank Mrs. Miyuki Tanmatsu of this University for determining mass spectra and performing
combustion analyses.
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