Synthesis of 4-aryl-2-sulfenyl-2H-1-benzothiopyran derivatives by cyclization of [2-(1-aryl-2-methoxyvinyl)phenylthio][methyl(or phenyl)-thio]methyllithiums

Article abstract of DOI:10.1246/bcsj.79.1977

4-Aryl-2-methyl(or phenyl)thio-2H-1-benzothiopyrans have been prepared in satisfactory yields from the corresponding 1-(1-aryl-2-methoxyethenyl)-2- {[methyl(or phenyl) thiomethyl]thio}benzenes via lithiation of the carbon atom between the two sulfur atoms

Full text of DOI:10.1246/bcsj.79.1977

Short Articles
Bull. Chem. Soc. Jpn. Vol. 79, No. 12, 1977–1979 (2006) 1977
i) 2 equiv. n-BuLi
DME, –78 to 0 °C
S
SR
SCH2SR
OMe
Synthesis of 4-Aryl-2-sulfenyl-2H-
1-benzothiopyran Derivatives by
Cyclization of [2-(1-Aryl-2-methoxy-
vinyl)phenylthio][methyl(or phenyl)-
thio]methyllithiums
ii) H3O+
Ar
Ar
2a 76%
2b 71%
2c 63%
2d 59%
2e 67%
2f 57%
1
a Ar = Ph, R = Me
b Ar = Ph, R = Ph
c Ar = p-Tol, R = Me
d Ar = p-Tol, R = Ph
e Ar = 4-ClC6H4, R = Me
f Ar = 4-ClC6H4, R = Ph
Scheme 1.
ꢀ
Kazuna Miyamoto, Osamu Morikawa,
Kazuhiro Kobayashi, Mai Horiuchi,
SCHSR
OMe
n-BuLi
and Hisatoshi Konishi
2
1
Ar
Department of Materials Science, Faculty of Engineering,
Tottori University, 4-101 Koyama-minami, Tottori 680-8552
3
3
Me
Received June 8, 2006; E-mail: kkoba@chem.tottori-u.ac.jp
S
SR
S
SMe
MeI
H3O+
2
R = Me, Ar = Ph
4-Aryl-2-methyl(or phenyl)thio-2H-1-benzothiopyrans
have been prepared in satisfactory yields from the corre-
sponding 1-(1-aryl-2-methoxyethenyl)-2-{[methyl(or phen-
yl)thiomethyl]thio}benzenes via lithiation of the carbon
atom between the two sulfur atoms, followed by intramolec-
ular cyclization with loss of lithium methoxide.
Ar
Ph
5 61%
4
Scheme 2.
two sulfur atoms is first lithiated by butyllithium to generate
the sulfur-stabilized carbanion 3. This carbanion is cyclized
to 2, the 2-proton of which is removed upon reaction with 3
to generate benzothiopyran-2-yl carbanion 4, and 3 reverts to
1. Compound 1 is again converted into 2 by another butyl-
lithium. The conversion of 2 into 4 may occur via the second
equivalent of butyllithium. The carbanion 4 was protonated
upon aqueous workup to give 2. The existence of 4 in the re-
action mixture was confirmed by the production of 2-methyl-2-
methylthio-4-phenyl-2H-1-benzothiopyran (5). In other words,
when the reaction between 1a and two molar amounts of butyl-
lithium was quenched with iodomethane, 5 was afforded in fair
yield, as shown in Scheme 2. The formation of 5 was support-
Compounds having a 2H-1-benzothiopyran skeleton are in-
teresting from a biological point of view, because compounds
with related skeletons exhibit a variety of biological activities.1
However, only a few works on the synthesis of 2H-1-benzo-
thiopyran derivatives have been reported to date.2 Recently,
Kaye and Nocanda reported a convenient Baylis–Hillman syn-
thesis of 3-substituted 2H-1-benzothiopyrans.2b Accordingly,
we became interested in developing a general method for the
preparation of 2H-1-benzothiopyran derivatives. We now re-
port a facile synthetic route to 4-aryl-2-sulfenyl-2H-1-benzo-
thiopyrans 2.3
Our procedure to construct the 2H-1-benzothiopyran skel-
eton is based on base-mediated cyclization of 1-(1-aryl-2-
methoxyethenyl)-2-(sulfenylmethylthio)benzenes 1,4 which
were easily prepared from readily available 2-mercaptobenzo-
phenone5,6 in two steps, as illustrated in Schemes 1 and 2.
Thus, compounds 1 were treated with two molar amounts of
butyllithium at ꢁ78 ꢂC to generate the carbanions stabilized
by two sulfur atoms 3, and these carbanions were allowed to
attack intramolecularly the ꢀ-carbon of the methoxyvinyl moi-
ety by raising the reaction temperature to 0 ꢂC to afford via the
corresponding benzyl anion intermediates with loss of methox-
ide, products 2 in generally fair-to-good yields, as summarized
in Scheme 1. The use of two molar amounts of butyllithium
was essential for complete conversion. When the reaction
was carried out using an equimolar amount of butyllithium,
a low yield of 2 was obtained and a considerable amount of
1 was recovered.
1
ed by its H NMR spectrum, which has the signal for 3-H at
ꢁ 6.10. This value is very close to those of compounds 2. If
methylation occurred at the 4-position, the signal for 3-H
would appear in further upfield.
In summary, we have demonstrated that a new type of 2H-1-
benzothiopyran derivatives can be prepared conveniently. This
synthesis may find some value in the synthesis of this type of
heterocycles because of the ready availability of the starting
materials and the ease of operations.
Experimental
{2-[(Methylthiomethyl)thio]phenyl}phenylmethanone. This
compound was prepared by S-(methylthio)methylation of (2-mer-
captophenyl)phenylmethanone5 with chloromethyl methyl sulfide
using NaH as a base in THF at 0 ꢂC in 76% yield: a pale-yellow
oil; Rf 0.41 (hexane–AcOEt 5:1); IR (neat) 1668 cmꢁ1; H NMR
1
(500 MHz, CDCl3) ꢁ 2.08 (3H, s), 3.92 (2H, s), 7.32–7.40 (2H,
m), 7.44–7.50 (3H, m), 7.59 (1H, tt, J ¼ 7:3 and 1.4 Hz), 7.62
(1H, d, J ¼ 7:3 Hz), and 7.80 (2H, dd, J ¼ 8:3 and 1.4 Hz). Calcd
for C15H14OS2: C, 65.66; H, 5.14; S, 23.37%. Found: C, 65.59; H,
5.24; S, 23.47%.
The need for two molar amounts of butyllithium can be ex-
plained as follows (see, Scheme 2). The carbon atom between
Published on the web December 13, 2006; doi:10.1246/bcsj.79.1977

1978 Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006)
Ó 2006 The Chemical Society of Japan
1-(2-Methoxy-1-phenylethenyl)-2-[(methylthiomethyl)thio]-
benzene (1a). This compound was prepared by treatment of {2-
[(methylthiomethyl)thio]}phenylmethanone with (methoxymeth-
ylene)triphenylphosphoran in THF at 0 ꢂC in 66% yield: a pale-
yellow oil; Rf 0.27 (hexane–Et2O 8:1); E:Z = ca. 1:1; IR (neat)
(500 MHz, CDCl3) ꢁ 2.41 (3H, s), 4.27 (2H, s), 7.18–7.25 (5H,
m), 7.32–7.38 (4H, m), 7.46 (1H, ddd, J ¼ 7:8, 6.9, and 1.8 Hz),
7.62 (1H, d, J ¼ 7:8 Hz), 7.67 (2H, d, J ¼ 8:2 Hz). Calcd for
C21H18OS2: C, 71.96; H, 5.18; S, 18.30%. Found: C, 71.65; H,
5.31; S, 18.15%.
1633 cmꢁ1
;
1H NMR (500 MHz, CDCl3) ꢁ 2.04 (1.5H, s), 2.06
1-[1-(4-Methylphenyl)-2-methoxyethenyl]-2-[(phenylthio-
methyl)thio]benzene (1d). This compound was prepared from 4-
methylphenyl{2-[(phenylthiomethyl)thio]phenyl}methanone as
described for the preparation of 1a in 57% yield; a colorless oil;
a mixture of stereoisomers (E:Z = 4:6); Rf 0.30 (hexane–Et2O
(1.5H, s), 3.73 (1.5H, s), 3.80 (1.5H, s), 3.84 (1H, s), 3.88 (1H, s),
6.23 (0.5H, s, vinyl-H of E-isomer), 6.69 (0.5H, s, vinyl-H of
Z-isomer), 7.11–7.43 (8.5H, m), and 7.50 (0.5H, dd, J ¼ 7:8 and
0.9 Hz). Calcd for C17H18OS2: C, 67.51; H, 6.00; S, 21.20%.
Found: C, 67.37; H, 6.05; S, 21.27%.
10:1); IR (neat) 1634 cmꢁ1 1H NMR (500 MHz, CDCl3) ꢁ 2.30
;
Phenyl{2-[(phenylthiomethyl)thio]phenyl}methanone. This
compound was prepared from (2-mercaptophenyl)phenylmetha-
none5 and chloromethyl phenyl sulfide in a manner similar to that
described for the preparation of {2-[(methylthiomethyl)thio]phen-
yl}phenylmethanone in 76% yield; a pale-yellow oil; Rf 0.15
(3H, s), 3.67 (1.8H, s), 3.74 (1.2H, s), 4.18 (1.2H, s), 4.23 (0.8H,
s), 6.16 (0.4H, s, vinyl-H of E-isomer), 6.61 (0.6H, s, vinyl-H of
Z-isomer), 6.99–7.06 (3H, m), 7.17–7.35 (9H, m), 7.45 (0.4H, d,
J ¼ 7:8 Hz), and 7.52 (0.6H, dd, J ¼ 7:3 and 1.8 Hz). Calcd for
C23H22OS2: C, 72.97; H, 5.86; S, 16.94%. Found: C, 72.95; H,
6.01; S, 16.93%.
(hexane–AcOEt 5:1); IR (neat) 1666 cmꢁ1 1H NMR (500 MHz,
;
CDCl3) ꢁ 4.28 (2H, s), 7.18–7.26 (3H, m), 7.32–7.37 (3H, m),
7.39 (1H, dd, J ¼ 7:8 and 1.8 Hz), 7.42–7.49 (3H, m), 7.57 (1H,
ddd, J ¼ 7:8, 7.3, and 1.4 Hz), 7.63 (1H, dd, J ¼ 7:8 and 0.9 Hz),
and 7.77 (2H, dd, J ¼ 8:2 and 1.4 Hz). Calcd for C20H16OS2: C,
71.39; H, 4.79; S, 19.06%. Found: C, 71.36; H, 4.92; S, 19.22%.
1-(2-Methoxy-1-phenylethenyl)-2-[(phenylthiomethyl)thio]-
benzene (1b). This compound was prepared from phenyl{2-
[(phenylthiomethyl)thio]phenyl}methanone as described for the
preparation of 1a in 60% yield; a pale-yellow oil; Rf 0.48 (hex-
4-Chlorophenyl{2-[(methylthiomethyl)thio]phenyl}metha-
none. This compound was prepared from 4-chlorophenyl(2-mer-
captophenyl)methanone6 and chloromethyl methyl sulfide as de-
scribed for the preparation of {2-[(methylthiomethyl)thio]phen-
yl}phenylmethanone in 68% yield; a pale-yellow oil; Rf 0.28
(hexane–THF 5:1); IR (neat) 1666 cmꢁ1 1H NMR (500 MHz,
;
CDCl3) ꢁ 2.08 (3H, s), 3.92 (2H, s), 7.35–7.37 (2H, m), 7.43 (2H,
d, J ¼ 8:7 Hz), 7.46–7.52 (1H, m), 7.62 (1H, d, J ¼ 7:8 Hz), and
7.74 (2H, d, J ¼ 8:7 Hz). Calcd for C15H13ClOS2: C, 58.33; H,
4.24; S, 20.76%. Found: C, 58.31; H, 4.51; S, 20.89%.
ane–AcOEt 5:1); E:Z = ca. 1:1; IR (neat) 1634 cmꢁ1 1H NMR
;
(500 MHz, CDCl3) ꢁ 3.69 (1.5H, s), 3.76 (1H, s), 4.18 (1H, s),
4.23 (1.5H, s), 6.20 (0.5H, s, vinyl-H of E-isomer), 6.65 (0.5H,
s, vinyl-H of Z-isomer), 7.09–7.39 (13H, m), 7.46 (0.5H, d,
J ¼ 8:2 Hz), and 7.53 (0.5H, dd, J ¼ 7:8 and 1.4 Hz). Calcd for
C22H20OS2: C, 72.49; H, 5.53; S, 17.59%. Found: C, 72.10; H,
5.56; S, 17.39%.
1-[1-(4-Chlorophenyl)-2-methoxyethenyl]-2-[(methylthio-
methyl)thio]benzene (1e). This compound was prepared from
4-chlorophenyl-2-{[(methylthiomethyl)thio]phenyl}methanone as
described for the preparation of 1a in 57% yield; a pale-yellow
oil; Rf 0.24 (hexane–CH2Cl2 2:1); a mixture of stereoisomers
(E:Z = ca. 7:3); IR (neat) 1634 cmꢁ1; 1H NMR (500 MHz, CDCl3)
ꢁ 2.05 and 2.07 (combined 3H, 2s), 3.73, 3.81, 3.86, and 3.89 (com-
bined 5H, 4s), 6.23 (0.7H, s, vinyl-H of E-isomer), 6.67 (0.3H,
s, vinyl-H of Z-isomer), 7.05 (0.6H, d, J ¼ 8:7 Hz), 7.16–7.27
(3.8H, m), 7.29–7.35 (2.6H, m), 7.42 (0.7H, d, J ¼ 7:8 Hz), and
7.50 (0.3H, dd, J ¼ 7:8 and 1.4 Hz). Calcd for C17H17ClOS2: C,
60.61; H, 5.09; S, 19.04%. Found: C, 60.52; H, 5.11; S, 19.72%.
4-Chlorophenyl{2-[(phenylthiomethyl)thio]phenyl}metha-
none. This compound was prepared from 4-chlorophenyl(2-mer-
captophenyl)methanone6 and chloromethyl phenyl sulfide as de-
scribed for the preparation of {2-[(methylthiomethyl)thio]phen-
yl}phenylmethanone in 67% yield; a pale-yellow oil; Rf 0.28
4-Methylphenyl{2-[(methylthiomethyl)thio]phenyl}metha-
none. This compound was prepared from 2-mercaptophenyl(4-
methylphenyl)methanone6 and chloromethyl methyl sulfide as de-
scribed for the preparation of {2-[(methylthiomethyl)thio]phen-
yl}phenylmethanone in 64% yield; a pale-yellow oil; Rf 0.35
1
(hexane–THF 5:1); IR (neat) 1661 and 1605 cmꢁ1; H NMR (500
MHz, CDCl3) ꢁ 2.08 (3H, s), 2.42 (3H, s), 3.91 (2H, s), 7.25 (2H,
d, J ¼ 7:8 Hz), 7.32–7.37 (2H, m), 7.46 (1H, ddd, J ¼ 7:8, 6.9,
and 2.3 Hz), 7.61 (1H, d, J ¼ 8:2 Hz), and 7.70 (2H, d, J ¼ 7:8
Hz). Calcd for C16H16OS2: C, 66.63; H, 5.59; S, 22.23%. Found:
C, 66.32; H, 5.61; S, 22.32%.
1-[1-(4-Methylphenyl)-2-methoxyethenyl]-2-[(methylthio-
methyl)thio]benzene (1c). This compound was prepared from
4-methylphenyl{2-[(methylthiomethyl)thio]phenyl}methanone as
described for the preparation of 1a in 60% yield; a colorless oil;
a mixture of stereoisomers (E:Z = ca. 6:4); Rf 0.42 (hexane–Et2O
5:1); IR (neat) 1634 cmꢁ1; 1H NMR (500 MHz, CDCl3) ꢁ 2.06 and
2.08 (combined 3H, 2s), 2.30 (3H, s), 3.72, 3.79, 3.86, and 3.89
(combined 5H, 4s), 6.19 (0.6H, s, vinyl-H of E-isomer), 6.65
(0.4H, s, vinyl-H of Z-isomer), 7.01–7.07 (3H, m), 7.18–7.32 (4H,
m), 7.42 (0.6H, d, J ¼ 8:2 Hz), and 7.50 (0.4H, d, J ¼ 7:8 Hz).
Calcd for C18H20OS2: C, 68.31; H, 6.37; S, 20.26%. Found: C,
68.36; H, 6.38; S, 22.16%.
(hexane–THF 5:1); IR (neat) 1666 cmꢁ1 1H NMR (400 MHz,
;
CDCl3) ꢁ 4.27 (2H, s), 7.20–7.50 (10H, m), 7.62 (1H, d, J ¼ 7:7
Hz), and 7.69 (2H, d, J ¼ 8:4 Hz). Calcd for C20H15ClOS2: C,
64.76; H, 4.08; S, 17.29%. Found: C, 64.50; H, 4.09; S, 17.13%.
1-[1-(4-Chlorophenyl)-2-methoxyethenyl]-2-[(phenylthio-
methyl)thio]benzene (1f). This compound was prepared from
4-chlorophenyl{2-[(phenylthiomethyl)thio]phenyl}methanone as
described for the preparation of 1a in 59% yield; a pale-yellow
oil; a mixture of stereoisomers (E:Z = ca. 1:1); Rf 0.28 (hex-
ane–CH2Cl2 3:1); IR (neat) 1636 cmꢁ1 1H NMR (400 MHz,
;
CDCl3) ꢁ 3.69 (1.5H, s), 3.76 (1.5H, s), 4.19 (1H, s), 4.23 (1H, s),
6.19 (0.5H, s, vinyl-H of E-isomer), 6.62 (0.5H, s, vinyl-H of Z-
isomer), 7.00 (1H, d, J ¼ 8:8 Hz), 7.15–7.34 (11H, m), and 7.44
(0.5H, d, J ¼ 7:3 Hz), and 7.51 (0.5H, dd, J ¼ 7:7 and 1.4 Hz).
Calcd for C22H19ClOS2: C, 66.23; H, 4.80; S, 16.07%. Found:
C, 66.22; H, 4.86; S, 15.97%.
4-Methylphenyl{2-[(phenylthiomethyl)thio]phenyl}metha-
none. This compound was prepared from 2-mercaptophenyl(4-
methylphenyl)methanone6 and chloromethyl phenyl sulfide as de-
scribed for the preparation of {2-[(methylthiomethyl)thio]phen-
yl}phenylmethanone in 70% yield; a pale-yellow oil; Rf 0.33
Typical Procedure for the Preparation of 2. 2-Methylthio-4-
phenyl-2H-1-benzothiopyran (2a). To a stirred solution of 1a
(hexane–THF 10:1); IR (neat) 1661 and 1605 cmꢁ1 1H NMR
;

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006) 1979
(0.14 g, 0.48 mmol) in DME (6 mL) at ꢁ78 ꢂC was added n-BuLi
(1.55 M in hexane; 1.0 mmol) (1 M ¼ 1 mol dmꢁ3) dropwise. Af-
ter 5 min, the temperature was gradually raised to 0 ꢂC before
the reaction was quenched by adding saturated aqueous NH4Cl
(10 mL). The usual workup followed by purification using prepar-
ative TLC on silica gel (hexane–AcOEt 50:1) gave 2a (96 mg,
75%); a pale-pink solid; mp 91–92 ꢂC (hexane–Et2O); IR (KBr
7.24–7.27 (3H, m), 7.34–7.38 (3H, m), and 7.48–7.50 (2H, m);
MS (CI) m=z (%) 367 [ðM þ 1Þþ, 27] and 257 (100). Calcd for
C21H15ClS2: C, 68.74; H, 4.12; S, 17.48%. Found: C, 68.72; H,
4.13; S, 17.48%.
2-Methyl-2-methylthio-4-phenyl-2H-1-benzothiopyran (5).
After 1a was treated with 2 molar amounts of n-BuLi in a manner
similar to that described above for the preparation of 2a, MeI
(2 molar amounts) was added. After 30 min, similar workup as
described above followed by purification of the crude product by
preparative TLC on silica gel gave 2b: a reddish-brown oil; Rf
0.31 (hexane–CH2Cl2 3:1); IR (neat) 1602, 1598, 1492, 1469,
disk) 1464 and 1348 cmꢁ1 1H NMR (500 MHz, CDCl3) ꢁ 2.11
;
(3H, s), 4.74 (1H, d, J ¼ 7:3 Hz), 6.10 (1H, d, J ¼ 7:3 Hz), 7.05–
7.10 (2H, m), 7.20 (1H, ddd, J ¼ 7:8, 6.0, and 2.3 Hz), 7.30–7.33
(2H, m), and 7.36–7.40 (4H, m); MS (EI) m=z (%) 270 (Mþ, 0.26),
269 (0.57), and 223 (100). Calcd for C16H14S2: C, 71.07; H, 5.22;
S, 23.72%. Found: C, 70.95; H, 5.23; S, 23.65%.
1
1443, 1433, and 1367 cmꢁ1; H NMR (500 MHz, CDCl3) ꢁ 1.78
(3H, s), 2.42 (3H, s), 6.10 (1H, s), 7.03–7.06 (1H, m), 7.14–7.17
(2H, m), 7.18–7.22 (3H, m), and 7.26–7.29 (3H, m); MS (EI)
m=z (%) 284 (Mþ, 9.9) and 269 (100). Calcd for C17H16S2: C,
71.78; H, 5.67; S, 22.55%. Found: C, 71.86; H, 5.54; S, 22.48%.
4-Phenyl-2-phenylthio-2H-1-benzothiopyran (2b): A pale-
pink solid; mp 102–103 ꢂC (hexane–Et2O) (lit.,7 101 ꢂC). Spectral
data (IR and 1H NMR) were identical to those reported previously.7
4-(4-Methylphenyl)-2-methylthio-2H-1-benzothiopyran (2c):
A reddish-brown oil; Rf 0.33 (hexane–AcOEt 50:1); IR (neat)
We thank Mrs. Miyuki Tanmatsu of this Department for de-
termining mass spectra and performing combustion analyses.
1510, 1463, 1431, and 1346 cmꢁ1 1H NMR (500 MHz, CDCl3)
;
ꢁ 2.10 (3H, s), 2.40 (3H, s), 4.73 (1H, d, J ¼ 7:3 Hz), 6.09 (1H,
d, J ¼ 7:3 Hz), 7.05–7.09 (2H, m), 7.18–7.22 (5H, m), and 7.38
(1H, d, J ¼ 7:8 Hz); MS (EI) m=z (%) 284 (Mþ, 0.02), 283 (0.06),
and 237 (100). Calcd for C17H16S2: C, 71.78; H, 5.67; S, 22.55%.
Found: C, 71.61; H, 5.70; S, 22.22%.
References
1
a) W. R. Chao, C. T. Helmes, M. I. Dawson, Cancer
Lett. 1985, 29, 43. b) L. W. Spruce, J. B. Gale, K. D. Berlin,
A. K. Verma, T. R. Breitman, X. H. Ji, D. van der Helm, J.
Med. Chem. 1991, 34, 430. c) H. Nakazumi, Y. Kobara, T. Kitao,
J. Heterocycl. Chem. 1992, 29, 135. d) D. M. Benbrook,
M. M. Madler, L. W. Spruce, P. J. Birckbichler, E. C. Nelson,
S. Subramanian, G. M. Weerasekare, J. B. Gale, M. K. Patterson,
Jr., B. Wang, W. Wang, S. Lu, T. C. Rowland, P. DiSivestro, C.
Lindamood, D. L. Hill, K. D. Berlin, J. Med. Chem. 1997, 40,
3567.
4-(4-Methylphenyl)-2-phenylthio-2H-1-benzothiopyran (2d):
A pale-pink solid; mp 134–135 ꢂC (hexane–Et2O); IR (KBr disk)
1
1606, 1508, 1472, and 1437 cmꢁ1; H NMR (500 MHz, CDCl3) ꢁ
2.40 (3H, s), 5.04 (1H, d, J ¼ 7:3 Hz), 6.14 (1H, d, J ¼ 7:3 Hz),
7.02 (1H, dd, J ¼ 8:2 and 1.4 Hz), 7.04 (1H, td, J ¼ 7:3 and
1.4 Hz), 7.16–7.22 (5H, m), 7.25–7.27 (3H, m), 7.37 (1H, d, J ¼
7:3 Hz), and 7.49–7.51 (2H, m); 13C NMR (125 MHz, CDCl3) ꢁ
21.20, 48.87, 120.39, 125.57, 128.14, 128.22, 128.41, 128.60,
128.65, 128.93, 129.05, 130.12, 132.77, 134.57 (two overlap-
ped C’s), 137.26, 137.65, and 141.53; MS (CI) m=z (%) 347
[ðM þ 1Þþ, 34] and 237 (100). Calcd for C22H18S2: C, 76.26; H,
5.24; S, 18.51%. Found: C, 76.01; H, 5.51; S, 18.46%.
2
a) K. Kobayashi, R. Nakahashi, A. Shimizu, T. Kitamura,
O. Morikawa, H. Konishi, J. Chem. Soc., Perkin Trans. 1 1999,
1547. b) P. T. Kaye, X. W. Nocanda, Synthesis 2001, 2389, and
references cited therein.
4-(4-Chlorophenyl)-2-methylthio-2H-1-benzothiopyran (2e):
A reddish-brown oil; Rf 0.29 (hexane–Et2O 5:1); IR (neat) 1487,
1433, and 1348 cmꢁ1; 1H NMR (500 MHz, CDCl3) ꢁ 2.10 (3H, s),
4.73 (1H, d, J ¼ 7:3 Hz), 6.09 (1H, d, J ¼ 7:3 Hz), 7.02 (1H, d,
J ¼ 7:8 Hz), 7.09 (1H, dd, J ¼ 7:8 and 7.3 Hz), 7.21 (1H, dd, J ¼
7:8 and 7.3 Hz), 7.25 (2H, d, J ¼ 7:8 Hz), 7.36 (2H, d, J ¼ 7:8
Hz), and 7.39 (1H, d, J ¼ 7:8 Hz); MS (EI) m=z (%) 304 (Mþ,
0.03), 303 (0.09), and 257 (100). Calcd for C16H13ClS2: C,
63.04; H, 4.30; S, 21.04%. Found: C, 62.83; H, 4.41; S, 20.82%.
4-(4-Chlorophenyl)-2-phenylthio-2H-1-benzothiopyran (2f):
A pale-pink solid; mp 123–125 ꢂC (hexane–Et2O); IR (KBr disk)
3
been prepared in low yield by a rather complicated procedure:
A. Banihashemi, A. Rahmatpour, Tetrahedron 1999, 55, 7271.
7-Methyl-2-(4-methylphenyl)thio-1H-2-benzothiopyran has
4
isomers. Their stereochemistries were determined on the basis
These compounds were obtained as mixtures of stereo-
1
of H NMR spectra; the signals of the vinyl protons of E-isomers
were observed in higher magnetic field compared to those of
Z-isomers.
5
S. W. McCombie, J. R. Tagat, W. A. Metz, D. Nazareno,
M. S. Puar, Tetrahedron 1993, 49, 8073.
K. Kobayashi, H. Umakoshi, A. Matsunaga, M. Tanmatsu,
O. Morikawa, H. Konishi, Bull. Chem. Soc. Jpn. 2004, 77, 2095.
B. D. Tilak, G. T. Panse, Indian J. Chem. 1969, 7, 315.
6
1
1582, 1486, and 1437 cmꢁ1; H NMR (500 MHz, CDCl3) ꢁ 5.03
(1H, d, J ¼ 7:8 Hz), 6.14 (1H, d, J ¼ 7:8 Hz), 6.95 (1H, d, J ¼
7
7:8 Hz), 7.05 (1H, dd, J ¼ 7:8 and 7.3 Hz), 7.19–7.22 (3H, m),