One-pot synthesis of quinoline-2(1H)-thiones from 2-isocyanostyrenes via electrocyclic reaction of the corresponding 2-isothiocyanatestyrenes

Article abstract of DOI:10.1055/s-0029-1216949

The reaction of a-substituted 2-isocyanostyrenes, which could be readily prepared from commercially available 2-aminophenyl ketones or 2-aminobenzonitriles, with sulfur in the presence of a catalytic amount of selenium proceeded smoothly to give the corre

Full text of DOI:10.1055/s-0029-1216949

3378
PAPER
One-Pot Synthesis of Quinoline-2(1H)-thiones from 2-Isocyanostyrenes via
Electrocyclic Reaction of the Corresponding 2-Isothiocyanatestyrenes
O
ne-Pot Synthesis
a
of
Q
uinoli
z
ne-2(
1
H
)-th
u
ione
s
from
2
h
-Isocyanosty
i
renes ro Kobayashi,* Seiki Fujita, 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
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 8 May 2009; revised 15 June 2009
cedure reported by Hanson et al.,6 as illustrated in
Abstract: The reaction of a-substituted 2-isocyanostyrenes, which
Scheme 1. Thus, treatment of 1 with formic acid in reflux-
ing toluene afforded the corresponding N-(2-aroylphe-
nyl)formamides 2, which were then dehydrated with
could be readily prepared from commercially available 2-ami-
nophenyl ketones or 2-aminobenzonitriles, with sulfur in the pres-
ence of a catalytic amount of selenium proceeded smoothly to give
the corresponding 2-isothiocyanatestyrenes. The latter spontane- phosphoryl chloride in the presence of triethylamine in
THF at 0 °C7 to afford 2-isocyanophenyl ketones 3. Wittig
reaction between 3 and methylene- or ethylenetriphe-
nylphosphoranes afforded a-substituted 2-isocyanosty-
ously underwent the electrocyclic reaction to afford 4-substituted
quinoline-2(1H)-thiones in one-pot with isolated yields ranging
from 37 to 91%.
Key words: quinoline-2(1H)-thiones, isocyanides, electrocyclic
renes 4.
reaction, isothiocyanates, sulfur
R3
R3
R1
R2
R1
R2
O
O
We have previously reported that quinoline-2(1H)-ones
can be readily prepared by reacting a-substituted 2-isocy-
anostyrenes with m-chloroperbenzoic acid (mCPBA).1
The method involves oxidation of 2-isocyanostyrenes to
the corresponding 2-isocyanatostyrenes, which spontane-
ously undergo the electrocyclic reaction to provide 4-sub-
stituted quinoline-2(1H)-ones. As an extension of this
synthesis, we decided to develop a one-pot preparation of
quinoline-2(1H)-thiones and found that treatment of 2-
isocyanostyrenes with sulfur in the presence of a catalytic
amount of selenium led to the formation of the desired
products, via probably the electrocyclic reaction of the
corresponding 2-isothiocyanatestyrenes. We wish to de-
scribe the results of our investigation which offer a new
and facile method for the preparation of quinoline-2(1H)-
thiones. Few methods for the preparation of this class of
heterocycles have been reported, which are based on the
reaction of 2-haloquinolines with thiourea2a or sodium
sulfide,2b and the reaction of quinolin-2(1H)-ones with
HCO2H
toluene, reflux
NH2
NHCHO
1
2
R3
R3
R1
R2
R1
R2
R4
Ph3P=CHR4
THF, 0 °C
POCl3, Et3N
THF, 0 °C
O
NC
NC
3
4
R3
N
R1
R4
sulfur, cat. selenium, Et3N, THF, reflux
S
C
R2
5
R3
R1
R2
R4
S
3a
P2S5 or Lawesson’s reagent.3b However, these are of
limited generality. Recently, Otani and Saito have report-
ed a synthesis by an indium-promoted Friedel–Crafts alk-
enylation-cyclization of 2-alkynylphenyl isothiocyanates
at higher temparature.4 A report on the utilization of quin-
oline-2(1H)-thiones to the synthesis of more complex and
important heterocycles has appeared.5
N
H
6
Scheme 1 Preparation of quinoline-2(1H)-thiones
In general, the 2-isocyanostyrenes 4, thus obtained, were
allowed to react with 1.2 molar amounts of sulfur in THF
in the presence of 2.4 molar amounts of triethylamine and
0.03 molar amount of selenium at reflux temperature.8
The conversion of 4 into the corresponding isothiocyan-
ates 5 and the subsequent electrocyclic reaction proceeded
smoothly. Quinoline-2(1H)-thiones 6 were obtained by
simply evaporating THF and triethylamine after cooling,
and subsequently recrystallizing the residual solids from
Our synthesis of 4-substituted quinoline-2(1H)-thiones 6
started mainly from 2-aminophenyl aryl ketones 1, which
are commercially available or readily obtained from the
reaction of 2-aminobenzonitriles with arylmagnesium
bromide followed by acid hydrolysis according to the pro-
SYNTHESIS 2009, No. 20, pp 3378–3382
x
x.
x
x
.
2
0
0
9
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216949; Art ID: F09809SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of Quinoline-2(1H)-thiones from 2-Isocyanostyrenes
3379
Table 1 Preparation of Quinoline-2(1H)-thiones 6 from 2-Isocyanostyrenes 4
Entry
4
Conditionsa
Time
20 min
2.5 h
6 (Yield, %)b
6a-i (81)
6a-ii (74)
6b (79)
1
2
3
4
5
6
7
8
4a-i (R1 = R2 = R4 = H, R3 = Ph)
4a-ii (R1 = R2 = H, R3 = Ph, R4 = Me)
4b (R1 = R2 = R4 = H, R3 = p-Tol)
4c (R1 = R2 = R4 = H, R3 = 4-MeOC6H4)
4d [R1 = R2 = R4 = H, R3 = 3,4-(MeO)2C6H3]
4e (R1 = R2 = R4 = H, R3 = Me)
4f (R1 = Cl, R2 = R4 = H, R3 = p-Tol)
4g (R1 = R2 = OMe, R3 = Ph, R4 = H)
A
B
A
A
A
A
A
A
1.5 h
25 min
40 min
1.5 h
6c (89)
6d (91)
6e (37)
1.5 h
6f (45)
1.5 h
6g (58)
a A: THF, reflux; B: diglyme, 100 °C.
b Isolated yields.
ed in CDCl3 using TMS as an internal reference on 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 recorded in CDCl3 using TMS as an internal reference on a
JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low-
and high-resolution MS spectra (EI, 70 eV) were recorded on a
JEOL JMS AX505 HA spectrometer. TLC was carried out on a
Merck Kieselgel 60 PF254. Column chromatography was performed
using Merck Kieselgel 60 (0.063–0.200 mm). All organic solvents
used in this study were dried over appropriate drying agents and dis-
tilled prior to use. (2-Amininophenyl)phenylmethanone (1a) was
commercially available. (2-Aminophenyl)(4-methylphenyl)metha-
none (1b) was prepared according to the procedure reported by
Hanson et al.6 (2-Isocyanophenyl)phenylmethanone (3a) was pre-
pared from 1a via N-(2-benzoylphenyl)formamide (2a) as described
appropriate solvents. The reaction conditions and results
are summarized in Table 1, which indicates that the yields
of the products were generally fair to good, while the sub-
strates bearing chloro or methoxy substituents 4f or 4g af-
forded the desired products 6f or 6g in somewhat
diminished yields (entries 7 or 8, respectively). The re-
duced yields of 6f and 6g may be attributable to the insta-
bility of the starting isocyanides 4f and 4g. The yield of 4-
methylisoquinoline-2(1H)-thione (6e) was also rather low
(entry 6). Probably, the high electron density of the vinyl
moiety facilitates the electrocyclic reaction. Therefore, 1-
ethenyl-2-isocyanobenzene (R3 = R4 = H in 4) would give
the corresponding desired product in a much lower yield.
1-Isocyano-2-(1-phenylpropen-1-yl)benzene (4a-ii) was previously.9 1-Isocyano-2-(1-methylethenyl)benzene (4e) was pre-
pared from 2-(1-methylethenyl)benzenamine by the procedure re-
first treated with sulfur under the conditions mentioned
ported previously by us.10 All other chemicals used in this study
above. However, no desired product, 3-methyl-4-phe-
nylquinoline-2(1H)-thione (6a-ii), was produced, though
were commercially available.
TLC analyses for monitoring the progress of the reaction
Aryl(2-aminophenyl)methanones 1
indicated that the starting isocyanide was consumed com-
pletely and that the corresponding isothiocyanate precur-
sor 5a-ii was produced almost quantitatively; the methyl
substituent at the b-position of the styrene moiety may
make the electrocyclic reaction difficult. Fortunately, the
synthesis of 6a-ii was accomplished by heating the reac-
tion mixture in diethyleneglycol dimethyl ether (diglyme)
at 100 °C in fair-to-good yield (entry 2).
These compounds, except for 1a and 1e, were prepared by treating
2-aminobenzonitriles with arylmagnesium bromides, followed by
acidic hydrolysis, according to the procedure reported by Hanson et
al.6
(2-Aminophenyl)(4-methoxyphenyl)methanone (1c)11
Yield: 88%; yellow solid; mp 75–76 °C (hexane–Et2O) (Lit.11 mp
76 °C).
IR (KBr): 3470, 3358, 1614 cm–1.
In summary, the present work demonstrates that quino-
line-2(1H)-thiones can be prepared by treating 2-isocy-
anostyrenes with sulfur in the presence of a catalytic
amount of selenium. This method has advantages of sim-
ple manipulations as well as ready availability of the start-
ing materials and may find some value in organic
synthesis. Investigations on the possibility of the synthe-
sis of derivatives related to quinoline-2(1H)-thiones by
applying the present procedure are in progress in our lab-
oratory.
1H NMR (500 MHz): d = 3.88 (s, 3 H), 5.85 (br s, 2 H), 6.63 (ddd,
J = 7.8, 7.3, 0.9 Hz, 1 H), 6.74 (d, J = 7.8 Hz, 1 H), 6.95 (d, J = 8.7
Hz, 2 H), 7.28 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.46 (dd, J = 7.8, 1.4
Hz, 1 H), 7.68 (d, J = 8.7 Hz, 2 H).
Anal. Calcd for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C,
73.85; H, 5.75; N, 6.04.
(2-Aminophenyl)(3,4-dimethoxyphenyl)methanone (1d)12
Yield: 89%; yellow solid; mp 79–81 °C (hexane) (Lit.12 mp 78–80
°C).
The spectral (IR and 1H NMR) data of this product were identical to
those reported previously.12
All melting points were obtained on a Laboratory Devices MEL-
TEMP II and are uncorrected. IR spectra were recorded on a Shi-
madzu FTIR-8300 spectrophotometer. The 1H NMR spectra record-
(2-Amino-4-chlorophenyl)(4-methylphenyl)methanone (1f)
Yield: 76%; yellow solid; mp 115–116 °C (hexane).
Synthesis 2009, No. 20, 3378–3382 © Thieme Stuttgart · New York

3380
K. Kobayashi et al.
PAPER
IR (KBr): 3452, 3344, 1634, 1605 cm–1.
J = 7.8 Hz, 2 H), 8.46 (s, 1 H), 8.49 (d, J = 1.4 Hz, 1 H), 11.28 (br
s, 1 H).
1H NMR (500 MHz): d = 2.43 (s, 3 H), 6.10 (br s, 2 H), 6.57 (dd,
J = 8.7, 1.8 Hz, 1 H), 6.73 (d, J = 1.8 Hz, 1 H), 7.26 (d, J = 7.8 Hz,
2 H), 7.39 (d, J = 8.7 Hz, 1 H), 7.53 (d, J = 7.8 Hz, 2 H).
Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C,
67.36; H, 5.51; N, 4.69.
Anal. Calcd for C14H12ClNO: C, 68.44; H, 4.92; N, 5.70. Found: C,
68.17; H, 4.98; N, 5.40.
2-Isocyanophenyl Ketones 3
These compounds, except for 3e, were prepared by treating 2 with
POCl3–Et3N in THF at 0 °C under the conditions described previ-
ously.7 Data for new compounds follow.
(2-Amino-4,5-dimethoxyphenyl)phenylmethanone (1g)12
Yield: 72%; yellow oil; Rf = 0.47 (2:3 THF–hexane).
The spectral (IR and 1H NMR) data for this compound were identi-
(2-Isocyanophenyl)(4-methylphenyl)methanone (3b)
Yield: 79%; yellow needle; mp 116–117 °C (hexane–Et2O).
cal to those reported previously.12
IR (KBr): 2124, 1655 cm–1.
1H NMR (500 MHz): d = 2.44 (s, 3 H), 7.29 (d, J = 8.2 Hz, 2 H),
7.49–7.57 (m, 4 H), 7.72 (d, J = 8.2 Hz, 2 H).
N-(2-Aroylphenyl)formamides 2
These compounds, except for 2e, were prepared by treating 1 with
HCO2H in refluxing toluene under azeotropic conditions as de-
scribed prepviously.9 Data for new compounds follow.
Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C,
81.27; H, 5.16; N, 6.17.
N-[2-(4-Methylbenzoyl)phenyl]formamide (2b)
Yield: 85%; white solid; mp 68–70 °C (hexane).
IR (KBr): 3300, 3277, 1703, 1618, 1603 cm–1.
(2-Isocyanophenyl)(4-methoxyphenyl)methanone (3c)
Yield: 84%; yellow oil; Rf = 0.54 (1:2 EtOAc–hexane).
1H NMR (500 MHz): d = 2.46 (s, 3 H), 7.13 (ddd, J = 7.8, 7.3, 0.9
Hz, 1 H), 7.29 (d, J = 7.8 Hz, 2 H), 7.56–7.59 (m, 2 H), 7.63 (d,
J = 7.8 Hz, 2 H), 8.48 (d, J = 1.4 Hz, 1 H), 8.64 (d, J = 8.2 Hz, 1 H),
10.62 (br s, 1 H).
IR (neat): 2124, 1661 cm–1.
1H NMR (500 MHz): d = 3.89 (s, 3 H), 6.97 (d, J = 8.9 Hz, 2 H),
7.49–7.56 (m, 4 H), 7.80 (d, J = 8.9 Hz, 2 H).
Anal. Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C,
76.04; H, 4.92; N, 5.64.
Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C,
75.29; H, 5.78; N, 5.83.
(2-Isocyanophenyl)(3,4-dimethoxyphenyl)methanone (3d)
Yield: 78%; yellow solid; mp 126–128 °C (dec.) (hexane–THF).
IR (KBr): 2129, 1643 cm–1.
1H NMR (400 MHz): d = 3.96 (s, 6 H), 6.86 (d, J = 8.4 Hz, 1 H),
7.22 (dd, J = 8.4, 1.8 Hz, 1 H), 7.48–7.57 (m, 4 H), 7.58 (d, J = 1.8
Hz, 1 H).
N-[2-(4-Methoxybenzoyl)phenyl]formamide (2c)
Yield: 77%; yellow oil; Rf = 0.43 (1:2 EtOAc–hexane).
IR (neat): 3317, 1693, 1634 cm–1.
1H NMR (500 MHz): d = 3.90 (s, 3 H), 6.98 (d, J = 8.7 Hz, 2 H),
7.15 (dd, J = 7.8, 7.3 Hz, 1 H), 7.55–7.58 (m, 2 H), 7.75 (d, J = 8.7
Hz, 2 H), 8.46 (s, 1 H), 8.60 (d, J = 7.8 Hz, 1 H), 10.42 (br s, 1 H).
Anal. Calcd for C16H13NO3: C, 71.90; H, 4.90; N, 5.24. Found: C,
71.64; H, 4.94; N, 5.34.
Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.53; H, 5.18; N, 5.40.
(4-Chloro-2-isocyanophenyl)(4-methylphenyl)methanone (3f)
Yield: 92%; yellow oil; Rf = 0.70 (1:5 EtOAc–hexane).
IR (neat): 2124, 1668, 1605 cm–1.
1H NMR (500 MHz): d = 2.45 (s, 3 H), 7.30 (d, J = 7.8 Hz, 2 H),
7.46 (d, J = 8.7 Hz, 1 H), 7.50 (dd, J = 8.7, 1.8 Hz, 1 H), 7.51 (s, 1
H), 7.69 (d, J = 7.8 Hz, 2 H).
N-[2-(3,4-Dimethoxybenzoyl)phenyl]formamide (2d)
Yield: 68%; white solid; mp 139–141 °C (hexane–THF).
IR (KBr): 3377, 1697, 1638 cm–1.
1H NMR (500 MHz): d = 3.94 (s, 3 H), 3.98 (s, 3 H), 6.91 (d, J = 8.7
Hz, 1 H), 7.16 (dd, J = 7.8, 7.3 Hz, 1 H), 7.32 (dd, J = 8.7, 1.8 Hz,
1 H), 7.39 (d, J = 1.8 Hz, 1 H), 7.56–7.59 (m, 2 H), 8.46 (d, J = 1.4
Hz, 1 H), 8.59 (d, J = 7.8 Hz, 1 H), 10.34 (br s, 1 H).
This compound was rather unstable and decomposed during the iso-
lation procedure (distillation and chromatography on silica gel), so
it was used in the next step after workup without any purification.
Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C,
67.31; H, 5.32; N, 4.88.
(2-Isocyano-4,5-dimethoxyphenyl)(4-methylphenyl)metha-
none (3g)
Yield: 72%; yellow solid; mp 122–124 °C (hexane–Et2O).
IR (KBr): 2127, 1652 cm–1.
1H NMR (500 MHz): d = 3.91 (s, 3 H), 3.97 (s, 3 H), 6.93 (s, 1 H),
7.01 (s, 1H), 7.50 (dd, J = 7.8, 7.3 Hz, 2 H), 7.63 (tt, J = 7.3, 1.4 Hz,
1 H), 7.81 (dd, J = 7.8, 1.4 Hz, 2 H).
N-[5-Chloro-2-(4-Methylbenzoyl)phenyl]formamide (2f)
Yield: 90%; yellow solid; mp 123–125 °C (hexane–Et2O).
IR (KBr): 3227, 1699, 1624 cm–1.
1H NMR (500 MHz): d = 2.46 (s, 3 H), 7.11 (dd, J = 8.5, 1.6 Hz, 1
H), 7.30 (d, J = 8.0 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 1 H), 7.59 (d,
J = 8.0 Hz, 2 H), 8.48 (s, 1 H), 8.77 (d, J = 1.6 Hz, 1 H), 10.78 (br
s, 1 H).
Anal. Calcd for C16H13NO3: C, 71.90; H, 4.90; N, 5.24. Found: C,
71.72; H, 5.12; N, 5.23.
Anal. Calcd for C15H12ClNO2: C, 65.82; H, 4.42; N, 5.12. Found: C,
65.89; H, 4.45; N, 5.02.
2-Isocyanostyrenes 4
N-(4,5-Dimethoxy-2-benzoylphenyl)formamide (2g)
These compounds, except for 4e, were prepared by treating 3 (30
mmol) with methylenetriphenylphosphorane or ethylenetriphe-
nylphosphorane (4.5 mmol) in THF (10 mmol) at 0 °C. Workup
(Et2O/H2O) and subsequent purification by recrystallization or col-
umn chromatography on silica gel gave the products.
Yield: 84%; yellow solid; mp 119–121 °C (hexane–THF).
IR (KBr): 3227, 1684, 1616 cm–1.
1H NMR (500 MHz): d = 3.73 (s, 3 H), 4.02 (s, 3 H), 7.06 (s, 1 H),
7.50 (dd, J = 7.8, 7.3 Hz, 2 H), 7.59 (t, J = 7.3 Hz, 1 H), 7.67 (d,
Synthesis 2009, No. 20, 3378–3382 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Quinoline-2(1H)-thiones from 2-Isocyanostyrenes
3-Methyl-4-phenylquinoline-2(1H)-thione (6a-ii)
3381
1-Isocyano-2-(1-phenylethenyl)benzene (4a-i)10
Yield: 74%; yellow oil; Rf = 0.66 (1:4 Et2O–hexane).
Yellow solid; mp 225–229 °C (dec.) (hexane–Et2O).
The spectral (IR and 1H NMR) data for this product were identical
IR (KBr): 3192, 1618, 1065 cm–1.
to those reported previously.10
1H NMR (500 MHz): d = 2.33 (s, 3 H), 7.13 (d, J = 7.8 Hz, 1 H),
7.21 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.23 (dd, J = 7.8, 1.4 Hz, 2 H),
7.49 (tt, J = 7.3, 1.4 Hz, 1 H), 7.53–7.56 (m, 4 H), 12.22 (br s, 1 H).
13C NMR (125 MHz): d = 19.65, 115.56, 124.02, 124.39, 127.21,
128.25, 128.56, 128.78, 130.14, 135.16, 136.81, 137.49, 145.67,
181.62.
1-Isocyano-2-(1-phenylprop-1-enyl)benzene (4a-ii)1
Yield: 68%; a mixture of stereoisomers (E/Z = ca. 8:2); yellow oil;
Rf = 0.67 (1:3 Et2O–hexane).
IR (neat): 2122 cm–1.
1H NMR (500 MHz): d = 1.69 (d, J = 7.3 Hz, 2.4 H), 1.93 (d, J = 6.9
Hz, 0.6 H), 6.02 (q, J = 6.9 Hz, 0.2 H), 6.39 (q, J = 7.3 Hz, 0.8 H),
7.16–7.47 (m, 9 H).
MS: m/z (%) = 251 (66, [M+]), 250 (100).
Anal. Calcd for C16H13NS: C, 76.46; H, 5.21; N, 5.57. Found: C,
76.40; H, 5.31; N, 5.67.
1-Isocyano-2-[1-(4-methylphenyl)ethenyl]benzene (4b)13
Yield: 76%; pale-yellow oil; Rf = 0.55 (1:9 Et2O–hexane).
IR (neat): 2122, 1618 cm–1.
1H NMR (500 MHz): d = 2.35 (s, 3 H), 5.34 (s, 1 H), 5.84 (s, 1 H),
7.13 (d, J = 8.2 Hz, 2 H), 7.15 (d, J = 8.2 Hz, 2 H), 7.34–7.37 (m, 2
H), 7.39–7.42 (m, 2 H).
4-(4-Methylphenyl)quinoline-2(1H)-thione (6b)
Yellow solid; mp 229–230 °C (dec.) (hexane–THF).
IR (KBr): 3109, 1620, 1111 cm–1.
1H NMR (500 MHz): d = 2.46 (s, 3 H), 7.29 (ddd, J = 7.8, 7.3, 1.4
Hz, 1 H), 7.33 (d, J = 7.8 Hz, 2 H), 7.37 (d, J = 7.8 Hz, 2 H), 7.45
(s, 1 H), 7.55 (dd, J = 7.8, 1.4 Hz, 1 H), 7.59 (ddd, J = 7.8, 7.3, 1.4
Hz, 1 H), 7.69 (d, J = 7.8 Hz, 1 H), 12.02 (br s, 1 H).
1-Isocyano-2-[1-(4-methoxyphenyl)ethenyl]benzene (4c)10
Yield: 61%; yellow oil; Rf = 0.64 (1:2 Et2O–hexane).
MS: m/z (%) = 251 (100, [M+]).
The spectral (IR and 1H NMR) data for this product were identical
Anal. Calcd for C16H13NS: C, 76.46; H, 5.21; N, 5.57. Found: C,
76.19; H, 5.29; N, 5.60.
to those reported previously.10
1-Isocyano-2-[1-(3,4-dimethoxyphenyl)ethenyl]benzene (4d)10
Yield: 50%; yellow oil; Rf = 0.50 (1:2 Et2O–hexane).
4-(4-Methoxyphenyl)quinoline-2(1H)-thione (6c)
Yellow solid; mp 225–228 °C (dec.) (hexane–THF).
IR (KBr): 3196, 1620, 1113 cm–1.
1H NMR (500 MHz): d = 3.90 (s, 3 H), 7.05 (d, J = 8.7 Hz, 2 H),
7.30 (ddd, J = 8.2, 7.3, 1.8 Hz, 1 H), 7.42 (s, 1 H), 7.45 (d, J = 8.7
Hz, 2 H), 7.57–7.61 (m, 2 H), 7.72 (d, J = 8.2 Hz, 1 H), 12.14 (br s,
1 H).
13C NMR (125 MHz): d = 55.41, 114.22, 116.49, 122.51, 124.63,
126.86, 128.38, 130.43, 130.82, 131.24, 139.49, 147.78, 160.44,
179.70.
The spectral (IR and 1H NMR) data for this product were identical
to those reported previously.10
1-Chloro-3-isocyano-4-[1-(4-methylphenyl)ethenyl]benzene
(4f)
Yield: 45%; yellow oil; Rf = 0.73 (1:9 Et2O–hexane).
IR (neat): 2122 cm–1.
1H NMR (500 MHz): d = 2.35 (s, 3 H), 5.34 (s, 1 H), 5.84 (s, 1 H),
7.13 (s, 4 H), 7.29 (d, J = 8.2 Hz, 1 H), 7.38 (dd, J = 8.2, 1.8 Hz, 1
H), 7.40 (d, J = 1.8 Hz, 1 H).
MS: m/z (%) = 267 (100, [M+]).
Anal. Calcd for C16H13NOS: C, 71.88; H, 4.90; N, 5.24. Found: C,
71.75; H, 4.86; N, 5.14.
HRMS: m/z calcd for C16H12ClN (M+): 253.0658; found: 253.0678.
1-Isocyano-4,5-dimethoxy-2-[1-(4-methylphenyl)ethenyl]ben-
zene (4g)
Yield: 60%; white solid; mp 99–100 °C (hexane).
IR (KBr): 2120, 1606 cm–1.
1H NMR (500 MHz): d = 3.87 (s, 3 H), 3.91 (s, 3 H), 5.40 (s, 1 H),
5.86 (s, 1 H), 6.75 (s, 1 H), 6.89 (s, 1 H), 7.27–7.35 (m, 5 H).
HRMS: m/z calcd for C17H15NO2 (M+): 265.1103; found: 265.1084.
4-(3,4-Dimethoxyphenyl)quinoline-2(1H)-thione (6d)
Yellow solid; mp 195–199 °C (dec.) (hexane–THF).
IR (KBr): 3167, 1616, 1113 cm–1.
1H NMR (400 MHz): d = 3.92 (s, 3 H), 3.97 (s, 3 H), 6.99 (d, J = 1.8
Hz, 1 H), 7.00 (d, J = 8.4 Hz, 1 H), 7.06 (dd, J = 8.4, 1.8 Hz, 1 H),
7.31 (ddd, J = 8.1, 7.3, 1.1 Hz, 1 H), 7.47 (s, 1 H), 7.53 (d, J = 8.1
Hz, 1 H), 7.60 (ddd, J = 8.1, 7.3, 1.1 Hz, 1 H), 7.76 (d, J = 8.1 Hz,
1 H), 11.83 (br s, 1 H).
13C NMR (125 MHz): d = 56.05, 56.13, 111.22, 112.14, 116.62,
121.94, 122.54, 124.74, 126.89, 128.67, 130.85, 131.32, 139.59,
147.93, 149.19, 149.95, 179.66.
4-Phenylquinoline-2(1H)-thione (6a-i);14 Typical Procedure
A solution of 4a (0.21 g, 1.0 mmol) in THF (6 mL) containing Et3N
(0.24 g, 2.4 mmol), sulfur (powder; 39 mg, 1.2 mmol), and selenium
(powder; 2.3 mg, 0.030 mmol) was heated at reflux temperature for
30 min. After cooling, THF and Et3N were evaporated. The residual
solid was recrystallized from hexane–THF to give 6a-i as yellow
needles; yield: 0.19 g (81%); mp 221–224 °C (dec.) (Lit.4 mp 224–
227 °C).
MS: m/z (%) = 297 (100, [M+]).
Anal. Calcd for C17H15NO2S: C, 68.66; H, 5.08; N, 4.71. Found: C,
68.52; H, 5.23; N, 4.47.
4-Methylquinoline-2(1H)-thione (6e)2
IR (KBr): 3445, 1620, 1117 cm–1.
Yellow solid; mp 226–228 °C (dec.) [Lit.2 mp 266 °C (dec.)].
1H NMR (500 MHz): d = 7.30 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.47–
7.48 (m, 3 H), 7.51–7.53 (m, 3 H), 7.57 (dd, J = 7.8, 1.4 Hz, 1 H),
7.61 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.66 (d, J = 7.8 Hz, 1 H), 12.15
(br s, 1 H).
IR (KBr): 3206, 1622, 1109 cm–1.
1H NMR (500 MHz): d = 2.51 (s, 3 H), 7.37 (ddd, J = 7.8, 7.3, 1.4
Hz, 1 H), 7.39 (s, 1 H), 7.49 (d, J = 7.8 Hz, 1 H), 7.59 (ddd, J = 7.8,
7.3, 1.4 Hz, 1 H), 7.76 (dd, J = 7.8, 1.4 Hz, 1 H), 11.84 (br s, 1 H).
Synthesis 2009, No. 20, 3378–3382 © Thieme Stuttgart · New York

3382
K. Kobayashi et al.
PAPER
(2) (a) Nakano, S.; Yoshida, T.; Taniguchi, H.; Suzuki, N.
6-Chloro-4-(4-methylphenyl)quinoline-2(1H)-thione (6f)
Yellow solid; mp 240–243 °C (dec.) (hexane–THF).
IR (KBr): 3161, 1614, 1123 cm–1.
1H NMR (500 MHz): d = 2.46 (s, 3 H), 7.23 (dd, J = 8.7, 1.8 Hz, 1
H), 7.34 (s, 4 H), 7.41 (s, 1 H), 7.48 (d, J = 1.8 Hz, 1 H), 7.61 (d,
J = 8.7 Hz, 1 H), 11.64 (br s, 1 H).
Chem. Pharm. Bull. 1977, 25, 1658. (b) Nandeshwarappa,
B. P.; Kumar, D. B. A.; Naik, H. S. B.; Mahadevan, K. M.
Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 1997.
(3) (a) Albert, A.; Barlin, G. B. J. Chem. Soc. 1959, 2384.
(b) Boberg, F.; Bruchmann, B.; Garming, A.; Nink, G.
Phosphorus, Sulfur Silicon Relat. Elem. 1990, 53, 313.
(4) Otani, T.; Kunimatsu, S.; Nihei, H.; Abe, Y.; Saito, T. Org.
Lett. 2007, 9, 5513.
MS: m/z (%) = 285 (100, [M+]).
Anal. Calcd for C16H12ClNS: C, 67.24; H, 4.23; N, 4.90. Found: C,
67.15; H, 4.23; N, 4.60.
(5) Fujita, R.; Hoshino, M.; Tomisawa, H. Chem. Pharm. Bull.
2006, 54, 334.
(6) Chalender, S. A.; Hanson, P.; Taylor, A. B.; Walton, P. H.;
Timms, A. W. J. Chem. Soc., Perkin Trans. 2 2001, 214.
(7) (a) Ito, Y.; Kobayashi, K.; Seko, N.; Saegusa, T. Bull. Chem.
Soc. Jpn. 1984, 57, 73. (b) Ugi, I.; Meyr, R. Org. Synth.
Coll. Vol. 5; Wiley: New York, 1973, 1060.
(8) The conversion of isocyanides into isothiocyanates under
these conditions and the role of selenium in this conversion
have been reported: Fujiwara, S.; Shin-Ike, T.; Sonoda, N.;
Aoki, M.; Okada, K.; Miyoshi, N.; Kambe, N. Tetrahedron
Lett. 1991, 32, 3503.
(9) Kobayashi, K.; Yoneda, K.; Miyamoto, K.; Morikawa, O.;
Konishi, H. Tetrahedron 2004, 60, 11639.
(10) Kobayashi, K.; Takagoshi, K.; Kondo, S.; Morikawa, O.;
Konishi, H. Bull. Chem. Soc. Jpn. 2004, 77, 553.
(11) DeTar, D. F.; Relyea, D. I. J. Am. Chem. Soc. 1954, 76,
1680.
5,6-Dimethoxy-4-phenylquinoline-2(1H)-thione (6g)
Yellow solid; mp 214–217 °C (dec.) (hexane–THF).
IR (KBr): 3186, 1622, 1115 cm–1.
1H NMR (500 MHz): d = 3.78 (s, 3 H), 4.04 (s, 3 H), 7.00 (s, 1 H),
7.25 (s, 1 H), 7.26 (s, 1 H), 7.41–7.56 (m, 5 H), 13.24 (br s, 1 H).
MS: m/z (%) = 297 (100, [M+]).
Anal. Calcd for C17H15NO2S: C, 68.66; H, 5.08; N, 4.71. Found: C,
68.62; H, 5.10; N, 4.72.
Acknowledgment
We are grateful to Mrs. Miyuki Tanmatsu of this university for her
assistance in determining mass spectra and performing combustion
analyses.
(12) Butin, A. V.; Smirnov, S. K.; Stroganova, T. A.; Bender, W.;
Krapivin, G. D. Tetrahedron 2007, 63, 474.
(13) Kobayashi, K.; Yonemori, J.; Matsunaga, A.; Morikawa, O.;
References
Konishi, H. Heterocycles 2001, 55, 33.
(1) Kobayashi, K.; Kitamura, T.; Yoneda, K.; Morikawa, O.;
(14) Kuenzle, F. M.; Schmutz, J. Helv. Chim. Acta 1970, 53, 798.
Konishi, H. Chem. Lett. 2000, 798.
Synthesis 2009, No. 20, 3378–3382 © Thieme Stuttgart · New York