Synthesis of 1(3H)-imino-2-benzothiophene and 1-imino-1H-2-benzothiopyran derivatives by reactions of secondary o-(vinyl)thiobenzamide derivatives with iodine

Article abstract of DOI:10.1246/bcsj.80.763

Efficient methods have been developed for the preparation of 1(3H)-imino-2-benzothiophene and 1-imino-1H-2-benzothiopyran derivatives. Treatment of secondary o-(vinyl)thiobenzamide derivatives with iodine in the presence of sodium hydrogencarbonate in ace

Full text of DOI:10.1246/bcsj.80.763

Ó 2007 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 80, No. 4, 763–767 (2007)
763
Synthesis of 1(3H)-Imino-2-benzothiophene and
1-Imino-1H-2-benzothiopyran Derivatives by Reactions
of Secondary o-(Vinyl)thiobenzamide Derivatives with Iodine
ꢀ
Kazuhiro Kobayashi, Seiki Fujita, Masanori Hase, Osamu Morikawa, and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552
Received September 27, 2006; E-mail: kkoba@chem.tottori-u.ac.jp
Efficient methods have been developed for the preparation of 1(3H)-imino-2-benzothiophene and 1-imino-1H-2-
benzothiopyran derivatives. Treatment of secondary o-(vinyl)thiobenzamide derivatives with iodine in the presence
of sodium hydrogencarbonate in acetonitrile at 0 ꢁC gave the former derivatives. Similar treatment at reflux gave the
latter derivatives.
R2
Br
We have recently reported that iodine-mediated cyclization
of secondary o-vinylbenzamide derivatives affords 3-(iodo-
methyl)isoindolin-1-one derivatives.1 We are interested in
examining the reaction of secondary o-(vinyl)thiobenzamide
derivatives with iodine under similar conditions, which should
give 3-(iodomethyl)isoindolin-1-thione derivatives 6. The re-
action, however, gives 1(3H)-imino-2-benzothiophene deriva-
tives 3. We have also found that 3 can be transformed into 1-
imino-1H-2-benzothiopyran derivatives 5 by elevating the re-
action temperature. This paper reports convenient methods
for the preparation of these heterocycles. Although these deriv-
atives may be of potential interest from a biological point of
view, there have been only a few reports on their syntheses.2,3
Preparation of 3 and 5 was carried out as shown in
Scheme 1. The secondary o-(vinyl)thiobenzamide derivatives
2 were readily prepared by reacting the appropriate isothiocya-
nates with o-vinylphenyllithiums, generated in situ by treating
o-bromostyrene derivatives with butyllithium in diethyl ether
at 0 ꢁC.1 Moderate to good yields of the products 2 were ob-
tained, as summarized in Table 1.
R2
R1
R1
1) n-BuLi, Et2O, 0 °C
2) R3NCS, 0 °C
CSNHR3
1
2
R2
I
R2
CH2I
R1
R1
I2, NaHCO3
reflux
S
S
MeCN, 0 °C, 5 min
R3
N
N
R3
3
4
−HI
R2
R2
R2
CH2I
R1
R1
R1
N R3
N
S
R3
S
S
N
R3
6
7
5
Initially, the reactions of these thioamides 2 with iodine
were carried out in acetonitrile at 0 ꢁC in the presence of so-
dium hydrogencarbonate. They proceeded very smoothly and
were complete within 5 min. After the usual aqueous workup,
followed by purification using preparative TLC on silica gel, 3,
not 6, were obtained in fair to good yields, as shown in Table 1.
One of the possible stereoisomers was obtained as a sole prod-
uct in each reaction. Although the stereochemistry of 1-imino
moiety of 3 is not yet clear, it was tentatively determined to be
Z. The structure of 3 was assigned on the basis of 13C NMR
spectra of 3a and 3h. The spectra had signals assignable to
the imino carbons at ꢀ 165.25 and 164.59, respectively, while
that of 2a showed a signal assignable to the thiocarbonyl car-
bon at ꢀ 198.52. Further confirmation of the structure was car-
ried out by hydrolysis of 3. In other words, subjection acid
hydrolysis of 3a and 3g gave 2-benzothiophene-1(3H)-one
derivatives 8a and 8b, respectively, in good yields, as shown
in Scheme 2.
Scheme 1.
1-ethylimino-4-phenyl-1H-2-benzothiopyran (5d) was found in
the reaction mixture for the preparation of 3d from 2d. It was
hypothesized that 5d was produced due to structural isomeriza-
tion of 3d via intermediate 4 (Scheme 1). Heating of mixtures
of 2, iodine, and sodium hydrogencarbonate in acetonitrile at
reflux resulted in the formation of 5 in moderate to fair yields,
as summarized in Table 2. Thus, it should be possible to trans-
form isolated 3 into 5 under the same reaction conditions. For
example, 3a was heated in acetonitrile at reflux in the presence
of iodine and sodium hydrogencarbonate to give 5a in 86%
yield. In the 13C NMR spectra of 5a, the signal at ꢀ 156.79
could be assigned to the imino carbon atom, which supported
the presence of the 1-imino-1H-2-benzothiopyran structure.
This excludes the possibility of the thiolactam structure 7, as
described for the structure determination of 3. As well, the ster-
eochemistry of the imino moiety, i.e., Z, was only tentative.
During the above investigation, a small quantity (ca. 2%) of
Published on the web April 13, 2007; doi:10.1246/bcsj.80.763

764 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
Synthesis of 1-Imino-1H-2-benzothiopyrans
Table 1. Preparation of 1(3H)-Imino-2-benzothiophene Derivatives 3 via o-(Vinyl)thiobenzamide
Derivatives 2
Entry
1
R3
2 (Yield/%)a)
3 (Yield/%)a)
1
2
3
4
5
6
7
8
9
1a (R1 = H, R2 = Ph)
1a
1a
1a
Ph
m-Tol
4-BrC6H4
Et
2a (81)
2b (77)
2c (77)
2d (68)
2e (53)
2f (56)
2g (76)
2h (72)
2i (59)
2j (79)
2k (71)
3a (69)
3b (56)
3c (61)
3d (62)
3e (73)
3f (51)
3g (50)
3h (86)
3i (56)
3j (78)
3k (77)
1a
1a
c-Hex
Adamantan-1-yl
Ph
1b (R1 = OMe, R2 = Ph)
1c (R1 = H, R2 = 4-ClC6H4)
1c
Ph
c-Hex
Ph
c-Hex
10
11
1d (R1 = H, R2 = Me)
1d
a) Isolated yield.
13C NMR spectra were determined using SiMe4 as an internal ref-
erence 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). High-resolution
MS analyses were performed on a JEOL JMS-AX505 HA spec-
trometer (Faculty of Agriculture, this University). Thin-layer
chromatography (TLC) was carried out using Merck Kieselgel
60 PF254. All of the solvents used were dried over the appropriate
drying agents and distilled under argon prior to use.
CH2I
S
Ph
R
10% aq. HCl
DME, 60 °C
3a,3g
O
8a R = H 78%
8b R = OMe 75%
Scheme 2.
Table 2. Preparation of 1-Imino-1H-2-benzothiopyran De-
rivatives 5
Starting Materials.
1-Bromo-2-(1-phenylethenyl)benzene
(1a),4 (2-bromo-5-methoxyphenyl)phenylmethanone,5 2-bromo-
phenyl(4-chlorophenyl)methanone,6 and 1-bromo-2-(1-methyl-
ethenyl)benzene (1d)7 were prepared by the appropriate reported
methods. All other chemical used in this study were commercially
available.
Entry
2
Time
5 (Yield/%)a)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
0.5 h
0.5 h
0.5 h
10 min
1.5 h
1.5 h
0.5 h
1 h
5a (58)
5b (52)
5c (59)
5d (54)
5e (62)
5f (45)
5g (40)
5h (55)
5i (56)
5j (63)
5k (53)
1-Bromo-4-methoxy-2-(1-phenylethenyl)benzene (1b): This
compound was prepared by the reaction of (2-bromo-5-methoxy-
phenyl)phenylmethanone5 with methylenetriphenylphosphorane
in THF at 0 ꢁC in 68% yield; a pale-yellow oil; Rf 0.35 (1:9
CHCl3–hexane); IR (neat) 1591, 1568, 1464, and 1232 cmꢂ1
;
1H NMR (500 MHz) ꢀ 3.81 (3H, s), 5.27 (1H, d, J ¼ 0:9 Hz), 5.83
(1H, d, J ¼ 0:9 Hz), 6.78 (1H, dd, J ¼ 8:7 and 2.2 Hz), 6.87 (1H,
d, J ¼ 2:2 Hz), 7.25–7.34 (5H, m), and 7.47 (1H, d, J ¼ 8:7 Hz).
Found: C, 62.27; H, 4.64%. Calcd for C15H13BrO: C, 62.30; H,
4.53%.
40 min
1.5 h
2 h
10
11
2j
2k
a) Isolated yield.
1-Bromo-2-[1-(4-chlorophenyl)ethenyl]benzene (1c): This
compound was prepared by the reaction of 2-bromophenyl(4-
chlorophenyl)methanone6 with methylenetriphenylphosphorane
in THF at 0 ꢁC in 73% yield; a colorless oil; Rf 0.71 (cyclohex-
ane); IR (neat) 1616 cmꢂ1; 1H NMR (500 MHz) ꢀ 5.28 (1H, d, J ¼
0:9 Hz), 5.81 (1H, d, J ¼ 0:9 Hz), 7.19 (2H, d, J ¼ 8:7 Hz), 7.22
(1H, ddd, J ¼ 8:2, 7.3, and 1.8 Hz), 7.26 (2H, d, J ¼ 8:7 Hz), 7.30
(1H, dd, J ¼ 7:3 and 1.8 Hz), 7.35 (1H, td, J ¼ 7:3 and 1.4 Hz),
and 7.59 (1H, dd, J ¼ 8:2 and 1.4 Hz). Found: C, 57.18; H, 3.73%.
Calcd for C14H10ClBr: C, 57.27; H, 3.43%.
In conclusion, we showed that the reaction of secondary
o-(vinyl)thiobenzamides with iodine provides a short and effi-
cient route to 1(3H)-imino-2-benzothiophene and 1-imino-1H-
2-benzothiopyran derivatives. To the best of our knowledge,
this is the first report on the general synthesis of these deriva-
tives. The methods have advantages over the previous methods
for the synthesis of these derivatives:2,3 simple manipulations
as well as the ready availability of the starting materials.
Typical Procedure for the Preparation of o-(Vinyl)thiobenz-
amide Derivatives 2. N-Phenyl-2-(1-phenylethenyl)thiobenz-
amide (2a): To a stirred solution of 1a (0.86 g, 3.3 mmol) in
Et2O (10 mL) at 0 ꢁC was added dropwise n-BuLi (1.6 M in hex-
ane; 3.7 mmol) (1 M = 1 mol dmꢂ3). After 1 h, PhNCS (0.49 g,
3.7 mmol) was added, and stirring was continued for an additional
20 min. The reaction mixture was quenched by adding saturated
aqueous NH4Cl (15 mL) and extracted with Et2O three times
(10 mL each). The combined extracts were washed with brine,
Experimental
General. The melting points were determined on a Laboratory
Devices MEL-TEMP II melting-point apparatus and are uncor-
rected. The IR spectra were recorded on a Shimadzu FTIR-8300
spectrometer. The 1H NMR spectra were determined using SiMe4
as an internal reference in CDCl3, unless stated otherwise, with a
JEOL ECP500 FT NMR spectrometer operating at 500 MHz or a
JEOL LA400 FT NMR spectrometer operating at 400 MHz. The

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
765
and dried over anhydrous Na2SO4, and the solvent was evaporat-
ed. The residual solid was recrystallized from Et2O–CH2Cl2 to
give 2a (0.85 g, 81%): a pale-yellow solid; mp 154–159 ꢁC; IR
(KBr disk) 3360 and 1362 cmꢂ1; 1H NMR (500 MHz) ꢀ 5.49 (1H,
d, J ¼ 0:9 Hz), 5.80 (1H, s), 7.20 (1H, tt, J ¼ 7:3 and 1.8 Hz),
7.24–7.29 (9H, m), 7.37 (1H, dd, J ¼ 7:3 and 1.4 Hz), 7.44–7.49
(2H, m), 7.90 (1H, dd, J ¼ 7:3 and 1.4 Hz), and 8.71 (1H, br s);
13C NMR ꢀ 116.10, 122.89, 126.67, 126.88, 128.32, 128.34,
128.43, 128.65, 130.11, 130.39, 130.94, 136.87, 138.58, 139.14,
142.92, 148.78, and 198.52. Found: C, 79.65; H, 5.45; N, 4.43%.
Calcd for C21H17NS: C, 79.96; H, 5.43; N, 4.44%.
and 8.65 (1H, br s). Found: C, 72.03; H, 4.53; N, 3.91%. Calcd
for C21H16ClNS: C, 72.09; H, 4.61; N, 4.00%.
2-[1-(4-Chlorophenyl)ethenyl]-N-cyclohexylthiobenzamide
(2i): A yellow solid; mp 98–100 ꢁC (hexane–Et2O); IR (KBr
disk) 3366 and 1385 cmꢂ1; 1H NMR (500 MHz) ꢀ 0.93–1.00 (2H,
m), 1.08–1.16 (1H, m), 1.28–1.36 (2H, m), 1.55–1.62 (3H, m),
1.82–1.85 (2H, m), 4.17–4.21 (1H, m), 5.41 (1H, s), 5.79 (1H, s),
7.04–7.12 (1H, br), 7.21–7.27 (5H, m), 7.37–7.41 (2H, m), and
7.66–7.70 (1H, m). Found: C, 70.86; H, 6.50; N, 3.87%. Calcd
for C21H22ClNS: C, 70.86; H, 6.23; N, 3.94%.
2-(1-Methylethenyl)-N-phenylthiobenzamide (2j): A yellow
solid; mp 98–100 ꢁC (hexane–Et2O); IR (KBr disk) 3204 and 1373
N-(3-Methylphenyl)-2-(1-phenylethenyl)thiobenzamide (2b):
A yellow solid; mp 69–71 ꢁC (Et2O–CH2Cl2); IR (KBr disk)
cmꢂ1
;
1H NMR (500 MHz) ꢀ 2.10 (3H, s), 5.26 (1H, d, J ¼ 1:4
1
3298, 1609, and 1373 cmꢂ1; H NMR (500 MHz) ꢀ 2.28 (3H, s),
Hz), 5.30 (1H, d, J ¼ 1:4 Hz), 7.25 (1H, dd, J ¼ 7:8 and 1.4 Hz),
7.30 (1H, t, J ¼ 7:3 Hz), 7.36 (1H, ddd, J ¼ 7:8, 7.3, and 1.4 Hz),
7.40 (1H, ddd, J ¼ 7:8, 7.3, and 1.4 Hz), 7.45 (2H, dd, J ¼ 7:8
and 7.3 Hz), 7.79 (2H, d, J ¼ 7:8 Hz), 7.87 (1H, dd, J ¼ 7:8 and
1.4 Hz), and 9.03 (1H, br s). Found: C, 75.85; H, 5.92; N,
5.38%. Calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.53%.
5.47 (1H, s), 5.80 (1H, s), 6.97 (1H, s), 7.01 (1H, d, J ¼ 7:8 Hz),
7.04 (1H, d, J ¼ 7:8 Hz), 7.17 (1H, t, J ¼ 7:8 Hz), 7.25–7.29 (5H,
m), 7.37 (1H, dd, J ¼ 7:3 and 1.4 Hz), 7.42–7.49 (2H, m), 7.89
(1H, dd, J ¼ 7:3 and 1.4 Hz), and 8.65 (1H, br s). Found: C, 80.16;
H, 5.92; N, 4.25%. Calcd for C22H19NS: C, 80.20; H, 5.81; N,
4.25%.
N-Cyclohexyl-2-(1-methylethenyl)thiobenzamide (2k):
A
N-(4-Bromophenyl)-2-(1-phenylethenyl)thiobenzamide (2c):
A yellow solid; mp 111–113 ꢁC (hexane–Et2O); IR (KBr disk)
pale-yellow solid; mp 71–74 ꢁC (hexane–Et2O); IR (KBr disk)
1
3263 and 1387 cmꢂ1; H NMR (500 MHz) ꢀ 1.21–1.31 (3H, m),
3229 and 1362 cmꢂ1
;
1H NMR (500 MHz) ꢀ 5.47 (1H, s), 5.80
1.42–1.50 (2H, m), 1.65–1.68 (1H, m), 1.71–1.75 (2H, m), 2.04
(3H, d, J ¼ 0:9 Hz), 2.11–2.17 (2H, m), 4.48–4.52 (1H, m), 5.13
(1H, q, J ¼ 0:9 Hz), 5.20 (1H, q, J ¼ 0:9 Hz), 7.16 (1H, dd, J ¼
7:3 and 1.4 Hz), 7.29 (1H, td, J ¼ 7:3 and 1.4 Hz), 7.33 (1H, td,
J ¼ 7:3 and 1.4 Hz), 7.44 (1H, br s), and 7.76 (1H, dd, J ¼ 7:3
and 1.4 Hz). Found: C, 73.95; H, 8.41; N, 5.15%. Calcd for
C16H21NS: C, 74.08; H, 8.16; N, 5.40%.
(1H, s), 7.14 (2H, d, J ¼ 8:7 Hz), 7.20–7.28 (5H, m), 7.37–7.40
(3H, m), 7.46 (1H, ddd, J ¼ 7:8, 7.3, and 1.4 Hz), 7.49 (1H,
ddd, J ¼ 7:8, 7.3, and 1.4 Hz), 7.88 (1H, dd, J ¼ 7:8 and 1.4 Hz),
and 8.64 (1H, br s). Found: C, 64.06; H, 4.13; N, 3.46%. Calcd for
C21H16BrNS: C, 63.96; H, 4.09; N, 3.55%.
N-Ethyl-2-(1-phenylethenyl)thiobenzamide (2d): A yellow
solid; mp 69–70 ꢁC (hexane); IR (KBr disk) 3250 and 1387 cmꢂ1
;
Typical Procedure for the Preparation of 2-Benzothiophene
Derivatives 3. 3-Iodomethyl-3-pheny-1(3H)-phenylimino-2-
benzothiophene (3a): To a stirred solution of 2a (0.85 g, 2.7
mmol) in MeCN (20 mL) containing NaHCO3 (0.90 g, 11 mmol)
at 0 ꢁC was added I2 (2.7 g, 11 mmol) in portions. After 5 min,
10% aqueous Na2S2O3 was added dropwise until the color of io-
dine disappeared. The acetonitrile was evaporated, and the organic
materials were extracted with Et2O three times (15 mL each). The
combined extracts were washed with saturated aqueous NaHCO3,
and dried over anhydrous K2CO3, and the solvent was evaporated.
The residue was purified by column chromatography on silica gel
to give 3a (0.82 g, 69%): a yellow viscous oil; Rf 0.30 (14:1 THF–
hexane); IR (neat) 1622 cmꢂ1; 1H NMR (400 MHz) ꢀ 4.21 (1H, d,
J ¼ 10:5 Hz), 4.24 (1H, d, J ¼ 10:5 Hz), 7.14 (2H, d, J ¼ 7:8 Hz),
7.26–7.39 (9H, m), 7.51–7.56 (2H, m), and 8.13 (1H, dd, J ¼ 8:2
and 1.8 Hz); 13C NMR ꢀ 17.82, 66.43, 120.35, 123.88, 124.93,
125.30, 127.05, 127.91, 128.69, 129.03, 129.17, 131.50, 138.22,
140.64, 149.36, 151.55, and 165.25; MS m=z (%) 441 (Mþ,
100). Found: C, 57.09; H, 3.67; N, 3.13%. Calcd for C21H16INS:
C, 57.15; H, 3.65; N, 3.17%.
1H NMR (500 MHz) ꢀ 1.01 (3H, t, J ¼ 7:3 Hz), 3.35–3.40 (2H,
m), 5.41 (1H, s), 5.78 (1H, s), 7.16 (1H, br s), 7.27–7.31 (6H, m),
7.38–7.43 (2H, m), and 7.76 (1H, dd, J ¼ 7:3 and 1.8 Hz). Found:
C, 76.17; H, 6.41; N, 5.19%. Calcd for C17H17NS: C, 76.36; H,
6.41; N, 5.24%.
N-Cyclohexyl-2-(1-phenylethenyl)thiobenzamide (2e):
A
yellow solid; mp 117–120 ꢁC (hexane–Et2O); IR (KBr disk) 3362
and 1387 cmꢂ1; 1H NMR (500 MHz) ꢀ 0.88–1.83 (10H, m), 4.16–
4.20 (1H, m), 5.39 (1H, d, J ¼ 0:9 Hz), 5.84 (1H, d, J ¼ 0:9 Hz),
7.14 (1H, br s), 7.21–7.33 (6H, m), 7.36–7.40 (2H, m), and 7.73–
7.77 (1H, m). Found: C, 78.46; H, 7.27; N, 4.29%. Calcd for
C21H23NS: C, 78.46; H, 7.21; N, 4.36%.
N-(Adamantan-1-yl)-2-(1-phenylethenyl)thiobenzamide (2f):
A yellow solid; mp 40–41 ꢁC (Et2O–CH2Cl2); IR (KBr disk) 3366
1
and 1391 cmꢂ1; H NMR (500 MHz) ꢀ 1.54–1.62 (6H, m), 1.95–
1.99 (9H, m), 5.40 (1H, d, J ¼ 0:9 Hz), 5.90 (1H, d, J ¼ 0:9 Hz),
6.99 (1H, br s), 7.18–7.22 (1H, m), 7.27–7.39 (7H, m), and 7.72–
7.77 (1H, m). Found: C, 80.17; H, 7.45; N, 3.59%. Calcd for
C25H27NS: C, 80.38; H, 7.29; N, 3.75%.
4-Methoxy-N-phenyl-2-(1-phenylethenyl)thiobenzamide (2g):
This product was purified by preparative TLC on silica gel; a yel-
low viscous oil; Rf 0.42 (1:4 THF–hexane); IR (neat) 3343 and
1360 cmꢂ1; 1H NMR (500 MHz) ꢀ 3.89 (3H, s), 5.50 (1H, s), 5.82
(1H, s), 6.87 (1H, d, J ¼ 2:7 Hz), 6.98 (1H, dd, J ¼ 8:7 and 2.7
Hz), 7.16–7.28 (10H, m), 7.96 (1H, d, J ¼ 8:7 Hz), and 8.74 (1H,
br s). Found: C, 76.37; H, 5.66; N, 3.88%. Calcd for C22H19NOS:
C, 76.49; H, 5.54; N, 4.05%.
3-Iodomethyl-1(3H)-(3-methylphenyl)imino-3-phenyl-2-ben-
zothiophene (3b): A yellow viscous oil; Rf 0.26 (1:1 hexane–
1
Et2O); IR (neat) 1615 cmꢂ1; H NMR (400 MHz) ꢀ 2.36 (3H, s),
4.22 (2H, s), 6.94–6.97 (3H, m), 7.23–7.33 (4H, m), 7.37–7.39
(3H, m), 7.51–7.54 (2H, m), and 8.12 (1H, dd, J ¼ 7:7 and
1.5 Hz); MS m=z (%) 455 (Mþ, 86) and 328 (100). Found: m=z
455.0219. Calcd for C22H18INS: M, 455.0205.
1(3H)-(4-Bromophenyl)imino-3-iodomethyl-3-phenyl-2-ben-
zothiophene (3c): A yellow solid; mp 155–158 ꢁC (hexane); IR
2-[1-(4-Chlorophenyl)ethenyl]-N-phenylthiobenzamide (2h):
A yellow solid; mp 128–130 ꢁC (hexane–Et2O); IR (KBr disk)
(KBr disk) 1618 cmꢂ1
;
1H NMR (500 MHz) ꢀ 4.19 (1H, d, J ¼
3364 and 1358 cmꢂ1
;
1H NMR (400 MHz) ꢀ 5.47 (1H, s), 5.75
10:5 Hz), 4.25 (1H, d, J ¼ 10:5 Hz), 7.03 (2H, d, J ¼ 8:7 Hz),
7.25–7.39 (6H, m), 7.48 (2H, d, J ¼ 8:7 Hz), 7.50–7.57 (2H, m),
and 8.10 (1H, dd, J ¼ 7:8 and 1.4 Hz); MS m=z (%) 519 (Mþ,
(1H, s), 7.15 (2H, d, J ¼ 8:6 Hz), 7.19–7.23 (3H, m), 7.31–7.37
(5H, m), 7.44–7.50 (2H, m), 7.86 (1H, dd, J ¼ 7:7 and 2.2 Hz),

766 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
Synthesis of 1-Imino-1H-2-benzothiopyrans
100). Found: C, 48.29; H, 2.98; N, 2.71%. Calcd for C21H15Br-
INS: C, 48.48; H, 2.91; N, 2.69%.
(1H, d, J ¼ 7:8 Hz), 7.49 (1H, t, J ¼ 7:3 Hz), 7.57 (1H, ddd, J ¼
7:8, 7.3, and 1.4 Hz), and 8.05 (1H, d, J ¼ 7:8 Hz); MS m=z (%)
379 (Mþ, 100). Found: C, 50.38; H, 3.73; N, 3.72%. Calcd for
C16H14INS: C, 50.67; H, 3.72; N, 3.69%.
1(3H)-Cyclohexylimino-3-iodomethyl-3-methyl-2-benzothio-
phene (3k): A pale-yellow oil; Rf 0.53 (1:4 THF–hexane); IR
(neat) 1639 and 1622 cmꢂ1; 1H NMR (500 MHz) ꢀ 1.24–1.44 (3H,
m), 1.47–1.59 (2H, m), 1.62–1.69 (1H, m), 1.81–1.92 (4H, m),
1.98 (3H, s), 3.15–3.21 (1H, m), 3.68 (1H, d, J ¼ 10:0 Hz), 3.79
(1H, d, J ¼ 10:0 Hz), 7.37–7.40 (2H, m), 7.47 (1H, td, J ¼ 7:3
and 1.4 Hz), and 7.91 (1H, dd, J ¼ 7:3 and 1.4 Hz); MS m=z (%)
385 (Mþ, 1.2) and 258 (100). Found: m=z 385.0378. Calcd for
C16H20INS: M, 385.0361.
1(3H)-Ethylimino-3-iodomethyl-3-phenyl-2-benzothiophene
(3d): A yellow oil; Rf 0.38 (1:5 Et2O–hexane); IR (neat) 1634
1
cmꢂ1; H NMR (500 MHz) ꢀ 1.40 (3H, t, J ¼ 7:3 Hz), 3.46–3.56
(2H, m), 4.18 (1H, d, J ¼ 12:0 Hz), 4.26 (1H, d, J ¼ 12:0 Hz),
7.26–7.34 (4H, m), 7.40–7.47 (4H, m), and 7.96 (1H, dd, J ¼
7:3 and 1.4 Hz); MS m=z (%) 393 (Mþ, 22) and 266 (100). Found:
C, 51.91; H, 4.17; N, 3.27%. Calcd for C17H16INS: C, 51.92; H,
4.10; N, 3.56%.
1(3H)-Cyclohexylimino-3-iodomethyl-3-phenyl-2-benzothio-
phene (3e): A pale-yellow solid; mp 114–116 ꢁC (hexane–Et2O);
IR (KBr disk) 1632 cmꢂ1; 1H NMR (500 MHz) ꢀ 1.27–1.96 (10H,
m), 3.16–3.21 (1H, m), 4.20 (1H, d, J ¼ 10:5 Hz), 4.25 (1H, d,
J ¼ 10:5 Hz), 7.25–7.34 (4H, m), 7.40–7.45 (4H, m), and 7.98
(1H, dd, J ¼ 6:9 and 2.3 Hz); MS m=z (%) 447 (Mþ, 35) and 320
(100). Found: C, 56.34; H, 5.14; N, 2.98%. Calcd for C21H22INS:
C, 56.38; H, 4.96; N, 3.13%.
1(3H)-(Adamantan-1-yl)imino-3-iodomethyl-3-phenyl-2-ben-
zothiophene (3f): A yellow solid; mp 40–41 ꢁC (hexane–Et2O);
IR (neat) 1624 cmꢂ1 1H NMR (500 MHz) ꢀ 1.69–1.75 (6H, m),
;
2.04–2.15 (9H, m), 4.22 (1H, d, J ¼ 10:5 Hz), 4.24 (1H, d, J ¼
10:5 Hz), 7.25–7.30 (2H, m), 7.32 (2H, dd, J ¼ 7:8 and 7.3 Hz),
7.39–7.44 (4H, m), and 7.94 (1H, dd, J ¼ 7:3 and 1.4 Hz); MS
m=z (%) 499 (Mþ, 9.5), 372 (38), and 135 (100). Found: C,
59.93; H, 5.31; N, 2.84%. Calcd for C25H26INS: C, 60.12; H,
5.25; N, 2.80%.
Typical Procedure for the Preparation of 1H-2-Benzothio-
4-Phenyl-1-phenylimino-1H-2-benzo-
pyran Derivatives 5.
thiopyran (5a): To a stirring mixture of 2a (0.54 g, 1.7 mmol)
in MeCN (12 mL) containing NaHCO3 (0.57 g, 6.8 mmol) at room
temperature was added I2 (1.7 g, 6.8 mmol) in portions; the mix-
ture was heated at reflux for 30 min. After cooling to room temper-
ature, the reaction mixture was worked up in a manner similar to
that described for the preparation of 3a. The crude product was
purified by preparative TLC on silica gel to give 5a (0.31 g,
58%): a white solid; mp 118–119 ꢁC (Et2O–CH2Cl2); IR (KBr
disk) 1564 cmꢂ1 1H NMR (400 MHz) ꢀ 6.54 (1H, s), 6.97 (2H,
;
dd, J ¼ 7:8 and 1.1 Hz), 7.16 (1H, t, J ¼ 7:3 Hz), 7.28 (1H, dd,
J ¼ 7:7 and 1.4 Hz), 7.33 (2H, dd, J ¼ 8:0 and 1.8 Hz), 7.37–7.52
(7H, m), and 8.61 (1H, dd, J ¼ 7:7 and 1.8 Hz); 13C NMR ꢀ
119.61, 119.86, 124.25, 126.21, 127.76, 128.18, 128.53, 128.77,
129.16, 129.38, 129.74, 131.27, 133.20, 134.94, 139.81, 151.03,
and 156.79; MS m=z (%) 313 (Mþ, 100). Found: C, 80.37; H,
4.79; N, 4.40; S, 10.36%. Calcd for C21H15NS: C, 80.48; H,
4.82; N, 4.47; S, 10.23%.
3-Iodomethyl-5-methoxy-3-phenyl-1(3H)-phenylimino-2-ben-
zothiophene (3g): A pale-yellow solid; mp 134 ꢁC (hexane–
1
CH2Cl2); IR (KBr disk) 1618 cmꢂ1; H NMR (500 MHz) ꢀ 3.85
(3H, s), 4.19 (1H, d, J ¼ 10:5 Hz), 4.21 (1H, d, J ¼ 10:5 Hz), 6.85
(1H, d, J ¼ 2:3 Hz), 7.07 (1H, dd, J ¼ 8:7 and 2.3 Hz), 7.11–7.14
(3H, m), 7.26–7.39 (7H, m), and 8.03 (1H, d, J ¼ 8:7 Hz); MS
m=z (%) 471 (Mþ, 88) and 344 (100). Found: C, 56.02; H, 3.91;
N, 3.02%. Calcd for C22H18INOS: C, 56.06; H, 3.85; N, 2.97%.
3-(4-Chlorophenyl)-3-iodomethyl-1(3H)-phenylimino-2-ben-
zothiophene (3h): A yellow solid; mp 84–87 ꢁC (hexane–Et2O);
1-(3-Methylphenyl)imino-4-phenyl-1H-2-benzothiopyran (5b):
A pale-yellow solid; mp 92 ꢁC (Et2O); IR (KBr disk) 1568 cmꢂ1
;
1H NMR (400 MHz) ꢀ 2.38 (3H, s), 6.54 (1H, s), 6.76–6.78 (2H,
m), 6.98 (1H, d, J ¼ 7:3 Hz), 7.26–7.34 (4H, m), 7.39–7.49 (5H,
m), and 8.59 (1H, d, J ¼ 7:3 Hz); MS m=z (%) 327 (Mþ, 99.6)
and 210 (100). Found: C, 80.59; H, 5.31; N, 4.14%. Calcd for
C22H17NS: C, 80.70; H, 5.23; N, 4.28%.
IR (KBr disk) 1620 cmꢂ1 1H NMR (500 MHz) ꢀ 4.16 (1H, d,
;
J ¼ 10:5 Hz), 4.17 (1H, d, J ¼ 10:5 Hz), 7.13 (2H, d, J ¼ 7:8 Hz),
7.16 (1H, t, J ¼ 7:3 Hz), 7.28 (2H, d, J ¼ 8:7 Hz), 7.32 (2H, d,
J ¼ 8:7 Hz), 7.34–7.40 (3H, m), 7.52–7.56 (2H, m), and 8.13
(1H, dd, J ¼ 7:3 and 1.4 Hz); 13C NMR ꢀ 17.08, 65.84, 120.29,
124.06, 125.05, 125.14, 128.55, 128.82, 129.21 (two overlapped
C’s), 131.62, 133.88, 138.09, 139.34, 148.94, 151.43, and 164.59;
MS m=z (%) 475 (Mþ, 11), 348 (72), and 334 (100). Found: C,
52.73; H, 3.22; N, 2.87%. Calcd for C21H15ClINS: C, 53.01; H,
3.18; N, 2.94%.
3-(4-Chlorophenyl)-1(3H)-cyclohexylimino-3-iodomethyl-2-
benzothiophene (3i): A pale-yellow solid; mp 113 ꢁC (decomp)
(hexane–Et2O); IR (KBr disk) 1624 cmꢂ1 1H NMR (500 MHz,
;
DMSO-d6) ꢀ 1.19–1.37 (3H, m), 1.43–1.50 (2H, m), 1.59–1.62
(1H, m), 1.74–1.82 (4H, m), 3.10–3.14 (1H, m), 4.35 (1H, d, J ¼
11:0 Hz), 4.86 (1H, d, J ¼ 11:0 Hz), 7.39 (2H, d, J ¼ 8:7 Hz),
7.43–7.46 (2H, m), 7.48 (2H, d, J ¼ 8:7 Hz), 7.53 (1H, dd, J ¼
7:8 and 7.3 Hz), and 7.78 (1H, d, J ¼ 7:8 Hz); MS m=z (%) 481
(Mþ, 1.1) and 354 (100). Found: C, 52.32; H, 4.40; N, 2.69%.
Calcd for C21H21ClINS: C, 52.35; H, 4.39; N, 2.91%.
1-(4-Bromophenyl)imino-4-phenyl-1H-2-benzothiopyran (5c):
A yellow solid; mp 47–49 ꢁC (hexane–Et2O); IR (KBr disk) 1560
cmꢂ1
;
1H NMR (400 MHz) ꢀ 6.55 (1H, s), 6.86 (2H, d, J ¼ 8:8
Hz), 7.26–7.54 (10H, m), and 8.59 (1H, d, J ¼ 7:3 Hz); MS m=z
(%) 391 (Mþ, 71) and 210 (100). Found: C, 64.18; H, 3.61; N,
3.49%. Calcd for C21H14BrNS: C, 64.29; H, 3.60; N, 3.57%.
1-Ethylimino-4-phenyl-1H-2-benzothiopyran (5d): A yel-
low oil; Rf 0.58 (1:5 Et2O–hexane); IR (neat) 1605 and 1568
cmꢂ1; H NMR (500 MHz) ꢀ 1.47 (3H, t, J ¼ 7:3 Hz), 3.44 (2H,
1
q, J ¼ 7:3 Hz), 6.65 (1H, s), 7.21 (1H, dd, J ¼ 7:8 and 1.4 Hz),
7.35 (2H, dd, J ¼ 7:8 and 1.4 Hz), 7.37–7.45 (5H, m), and 8.46
(1H, dd, J ¼ 7:8 and 1.8 Hz); MS m=z (%) 265 (Mþ, 75) and 210
(100). Found: m=z 265.0946. Calcd for C17H15NS: M, 265.0925.
1-Cyclohexylimino-4-phenyl-1H-2-benzothiopyran (5e):
yellow oil; Rf 0.57 (1:15 THF–hexane); IR (neat) 1605 and
A
1
1573 cmꢂ1; H NMR (500 MHz) ꢀ 1.33–1.48 (3H, m), 1.54–1.61
(2H, m), 1.68–1.71 (1H, m), 1.85–1.87 (4H, m), 3.54–3.58 (1H,
m), 6.61 (1H, s), 7.18 (1H, dd, J ¼ 7:8 and 1.4 Hz), 7.33–7.44
(7H, m), and 8.41 (1H, dd, J ¼ 7:8 and 1.4 Hz); MS m=z (%)
319 (Mþ, 37), 286 (90), and 236 (100). Found: C, 78.55; H,
6.54; N, 4.53%. Calcd for C21H21NS: C, 78.95; H, 6.63; N, 4.38%.
1-(Adamantan-1-yl)imino-4-phenyl-1H-2-benzothiopyran (5f):
A pale-yellow viscous oil; Rf 0.33 (1:7 C6H6–hexane); IR (neat)
3-Iodomethyl-3-methyl-1(3H)-phenylimino-2-benzothiophene
(3j): A yellow oil; Rf 0.37 (1:5 THF–hexane); IR (neat) 1622
1
cmꢂ1; H NMR (500 MHz) ꢀ 1.98 (3H, s), 3.70 (1H, d, J ¼ 10:1
Hz), 3.79 (1H, d, J ¼ 10:1 Hz), 7.13 (2H, dd, J ¼ 8:2 and 1.4 Hz),
7.17 (1H, t, J ¼ 7:3 Hz), 7.40 (2H, dd, J ¼ 8:2 and 7.3 Hz), 7.45

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
767
A
1604 and 1578 cmꢂ1; H NMR (500 MHz) ꢀ 1.72–1.79 (6H, m),
2.12–2.24 (9H, m), 6.58 (1H, s), 7.15 (1H, dd, J ¼ 7:8 and
1.4 Hz), 7.31–7.44 (7H, m), and 8.37 (1H, dd, J ¼ 7:8 and
1.4 Hz); MS m=z (%) 371 (Mþ, 24) and 135 (100). Found: m=z
371.1704. Calcd for C25H25NS: M, 371.1708.
6-Methoxy-4-phenyl-1-phenylimino-1H-2-benzothiopyran
(5g): A yellow solid; mp 178 ꢁC (hexane–Et2O); IR (KBr disk)
1603 and 1556 cmꢂ1 1H NMR (500 MHz) ꢀ 3.74 (3H, s), 6.56
;
(1H, s), 6.74 (1H, d, J ¼ 2:3 Hz), 6.97 (2H, d, J ¼ 8:2 Hz), 7.05
(1H, dd, J ¼ 8:7 and 2.3 Hz), 7.16 (1H, t, J ¼ 7:3 Hz), 7.33–7.45
(7H, m), and 8.58 (1H, d, J ¼ 8:7 Hz); MS m=z (%) 343 (Mþ,
100). Found: C, 76.87; H, 5.05; N, 4.06%. Calcd for C22H17NOS:
C, 76.94; H, 4.99; N, 4.08%.
4-(4-Chlorophenyl)-1-phenylimino-1H-2-benzothiopyran (5h):
A yellow solid; mp 126–128 ꢁC (hexane–Et2O); IR (KBr disk)
1568 cmꢂ1; 1H NMR (500 MHz) ꢀ 6.53 (1H, s), 6.96 (2H, dd, J ¼
8:2 and 0.9 Hz), 7.17 (1H, t, J ¼ 7:3 Hz), 7.24 (1H, dd, J ¼ 7:8
and 1.4 Hz), 7.27 (2H, d, J ¼ 8:2 Hz), 7.40–7.53 (6H, m), and 8.61
(1H, dd, J ¼ 7:8 and 1.4 Hz); MS m=z (%) 347 (Mþ, 100). Found:
C, 72.21; H, 4.11; N, 3.95%. Calcd for C21H14ClNS: C, 72.51; H,
4.06; N, 4.03%.
Calcd for C16H19NS: C, 74.66; H, 7.44; N, 5.44%.
3-Iodomethyl-3-phenyl-2-benzothiophen-1(3H)-one (8a).
1
solution of 3a (0.15 g, 0.35 mmol) in DME/10% aqueous HCl
(3 mL, 2:1) was heated at 60 ꢁC for 2 h. After cooling, the mixture
was diluted by adding Et2O and water (15 mL each), and the lay-
ers were separated. The aqueous layer was extracted with Et2O
twice (5 mL each), and the combined extracts were dried over an-
hydrous K2CO3. Evaporation of the solvent gave a residue, which
was purified by preparative TLC on silica gel to give 8a (0.10 g,
78%): a yellow oil; Rf 0.35 (1:5 Et2O–hexane); IR (neat) 1693
cmꢂ1; 1H NMR (500 MHz) ꢀ 4.24 (1H, d, J ¼ 10:5 Hz), 4.33 (1H,
d, J ¼ 10:5 Hz), 7.29–7.37 (3H, m), 7.39–7.43 (3H, m), 7.54 (1H,
t, J ¼ 7:3 Hz), 7.65 (1H, ddd, J ¼ 7:8, 7.3, and 0.9 Hz), and 7.84
(1H, d, J ¼ 7:8 Hz); MS m=z (%) 366 (Mþ, 0.4) and 239 (100).
Found: C, 49.16; H, 3.30%. Calcd for C15H11IOS: C, 49.20; H,
3.03%.
3-Iodomethyl-5-methoxy-3-phenyl-2-benzothiophen-1(3H)-
one (8b). This compound was prepared by the same procedure as
described above for the preparation of 8a. 8b: a pale-yellow oil;
Rf 0.21 (1:7 THF–hexane); IR (neat) 1682 cmꢂ1 1H NMR (500
;
MHz) ꢀ 3.85 (3H, s), 4.23 (1H, d, J ¼ 11:0 Hz), 4.28 (1H, d, J ¼
11:0 Hz), 6.85 (1H, d, J ¼ 1:8 Hz), 7.05 (1H, dd, J ¼ 8:7 and
1.8 Hz), 7.29–7.37 (3H, m), 7.40 (2H, d, J ¼ 7:8 Hz), and 7.76
(1H, d, J ¼ 8:7 Hz); MS m=z (%) 396 (Mþ, 0.1) and 268 (100).
Found: C, 48.38; H, 3.55%. Calcd for C16H13IO2S: C, 48.50; H,
3.31%.
4-(4-Chlorophenyl)-1-cyclohexylimino-1H-2-benzothiopyran
(5i): A pale-yellow solid; mp 98–100 ꢁC (hexane–Et2O); IR
;
(KBr disk) 1601 and 1574 cmꢂ1 1H NMR (500 MHz) ꢀ 1.24–
1.47 (3H, m), 1.54–1.61 (2H, m), 1.67–1.72 (1H, m), 1.82–1.88
(4H, m), 3.52–3.58 (1H, m), 6.59 (1H, s), 7.12 (1H, dd, J ¼ 7:8
and 1.4 Hz), 7.26 (2H, d, J ¼ 7:8 Hz), 7.37 (1H, ddd, J ¼ 7:8,
7.3, and 1.4 Hz), 7.38–7.47 (3H, m), and 8.40 (1H, dd, J ¼ 7:8
and 1.4 Hz); 13C NMR ꢀ 24.66, 25.91, 32.38, 61.40, 120.10,
126.47, 127.56, 128.69, 128.72, 130.13, 130.18, 130.70, 132.32,
133.62, 133.90, 138.69, and 149.67; MS m=z (%) 353 (Mþ, 29)
271 (100). Found: C, 71.23; H, 5.63; N, 4.05%. Calcd for C21H20-
ClNS: C, 71.27; H, 5.70; N, 3.96%.
We thank Mrs. Miyuki Tanmatsu of this Department for de-
termining mass spectra and performing combustion analyses.
References
1
K. Kobayashi, M. Hase, K. Hashimoto, S. Fujita, M.
Tanmatsu, O. Morikawa, H. Konishi, Synthesis 2006, 2493.
3-Methyl(or Phenyl)-1-imino-3H-benzo[c]thiophenes have
4-Methyl-1-phenylimino-1H-2-benzothiopyran (5j): A yel-
low solid; mp 80–81 ꢁC (hexane); IR (KBr disk) 1562 cmꢂ1
;
2
1H NMR (500 MHz) ꢀ 2.32 (3H, d, J ¼ 1:4 Hz), 6.43 (1H, q, J ¼
1:4 Hz), 6.93 (2H, dd, J ¼ 8:2 and 0.9 Hz), 7.15 (1H, t, J ¼ 7:3
Hz), 7.41 (2H, dd, J ¼ 8:2 and 7.3 Hz), 7.51 (1H, ddd, J ¼ 8:2,
7.3, and 1.4 Hz), 7.58–7.64 (2H, m), and 8.60 (1H, dd, J ¼ 8:2
and 0.9 Hz); 13C NMR ꢀ 21.30, 117.50, 119.64, 124.09, 125.51,
126.28, 128.54, 129.10, 129.69 (two overlapped C’s), 131.50,
135.32, 151.19, and 157.44; MS m=z (%) 251 (Mþ, 83) and 149
(100). Found: C, 76.39; H, 5.50; N, 5.77%. Calcd for C16H13NS:
C, 76.46; H, 5.21; N, 5.57%.
been prepared in low yields by a treatment of 2-(1-hydroxyalkyl)-
benzamide derivatives with Lawesson’s reagent: T. Nishio, H.
Sekiguchi, Tetrahedron 1999, 55, 5017.
3
3-Methyl-1-methylimino-2-benzothiopyran has been pre-
pared in high yield by a reaction of a dianion, generated from
2,N-dimethylthiobenzamide, with acetyl chloride: D. Ach, V.
Reboul, P. Metzner, Eur. J. Org. Chem. 2002, 2573.
4
5
M. E. Jason, Tetrahedron Lett. 1982, 23, 1635.
V. J. Bauer, B. J. Duffy, D. Hoffmann, S. S. Klioze, R. W.
1-Cyclohexylimino-4-methyl-1H-2-benzothiopyran (5k):
A
;
Kosely, Jr., A. R. McFadden, L. L. Martin, H. H. Ong, H. M.
Geyer, III, J. Med. Chem. 1976, 19, 1315.
yellow oil; Rf 0.59 (1:9 THF–hexane); IR (neat) 1571 cmꢂ1
1H NMR (500 MHz) ꢀ 1.29–1.45 (3H, m), 1.49–1.56 (2H, m)
1.66–1.69 (1H, m), 1.82–1.86 (4H, m), 2.28 (3H, d, J ¼ 1:4
Hz), 3.46–3.52 (1H, m), 6.48 (1H, q, J ¼ 1:4 Hz), 7.38–7.41 (1H,
m), 7.48–7.50 (2H, m), and 8.42 (1H, dd, J ¼ 7:3 and 0.9 Hz); MS
m=z (%) 257 (Mþ, 100). Found: C, 74.61; H, 7.49; N, 5.50%.
6
K. Kobayashi, T. Shiokawa, H. Omote, K. Hashimoto, O.
Morikawa, H. Konishi, Bull. Chem. Soc. Jpn. 2006, 79, 1126.
I. Fleming, M. Woolias, J. Chem. Soc., Perkin Trans. 1
1979, 829.
7