Cu-catalyzed synthesis of diaryl thioethers and S -cycles by reaction of aryl iodides with carbon disulfide in the presence of DBU

Article abstract of DOI:10.1021/jo400709s

Diaryl thioethers and S-cycles were obtained on the basis of the copper-catalyzed reaction of carbon disulfide and aryl iodides in the presence of DBU. This reaction enables the one-pot synthesis of diaryl thioethers by employing cheap, available, and easy-to-handle carbon disulfide with aryl iodides. The reaction was successfully employed in the construction of sulfur-containing cyclic molecules.

Full text of DOI:10.1021/jo400709s

Article
pubs.acs.org/joc
Cu-Catalyzed Synthesis of Diaryl Thioethers and S‑Cycles by Reaction
of Aryl Iodides with Carbon Disulfide in the Presence of DBU
Peng Zhao,† Hang Yin,† Hongxin Gao,† and Chanjuan Xi*,†,‡
†Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing 100084, China
‡State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
S
* Supporting Information
ABSTRACT: Diaryl thioethers and S-cycles were obtained on the
basis of the copper-catalyzed reaction of carbon disulfide and aryl
iodides in the presence of DBU. This reaction enables the one-pot
synthesis of diaryl thioethers by employing cheap, available, and easy-
to-handle carbon disulfide with aryl iodides. The reaction was
successfully employed in the construction of sulfur-containing cyclic
molecules.
catalyzed reaction of CS2 and aryl iodides under ligand-free
conditions.
INTRODUCTION
■
Sulfur-containing organic molecules are a very important motif;
particularly, diaryl thioethers and their derivatives have been
recognized as imperative molecules in biological, pharmaceut-
ical, and material interest.1,2 The traditional methods for the
synthesis of diaryl thioethers involve condensation of
arenethiols with aryl halides3 and treatment of aryl lithium or
Grignard reagents with sulfurated electrophiles.4 However,
these methods often require harsh reaction conditions and are
not suitable for molecules containing sensitive functional
groups.5 The development of transition-metal-catalyzed cou-
pling of arenethiols with aryl halides or pseudohalides has
overcome these difficulties to a great extent. A number of
reactions have been developed for the synthesis of diaryl
thioethers using Pd,6 Cu,7 Fe,8 and other metal catalysts.9
However, these metal-catalyzed reactions require foul-smelling,
expensive, and less available arenethiols. In addition, arenethiols
are prone to undergo oxidative homocoupling to produce
disulfides as byproducts. To solve these drawbacks, persulfides
have been employed,10 but these require a stoichiometric
amount of reductant. Recently, thiourea,11 thiolates,12 and
metal sulfides13,14 have been reported as sulfur sources in the
formation of diaryl thioethers. However, using thiourea and
thiolates as sulfur source are limited to use Pd/P-ligand as
catalyst, and using metal sulfides as sulfur source requires high
temperature and long reaction time. Therefore, the develop-
ment of a foul-smell-free, cheap, and easy-to-handle method
using a sulfur surrogate for the synthesis of diaryl sulfides is still
desirable. As part of our continuous effort toward copper-
catalyzed C−S bond formation and its application in
heterocyclic synthesis using CS2,15 herein, we report a simple,
mild, functional group-tolerant system for the synthesis of the
diaryl thioethers and S-cyclic compounds based on Cu-
RESULTS AND DISCUSSION
■
In the preliminary experiment, we used iodobenzene 1a and
carbon disulfide as starting materials and Cs2CO3 as base in
toluene at 100 °C; diphenyl sulfide 2a was not obtained (Table
1, entry 1). Then several bases were screened under the same
reaction conditions. Clearly, inorganic bases such as K3PO4,
t
KOH, and BuONa as well as organic bases such as Et3N and
1,4-diazabicyclo[2.2.2]octane (DABCO) were ineffective under
the condition (entries 2−6). To our delight, when 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) was used as base, the
reaction proceeded smoothly, and 2a was obtained in 91% yield
(entry 7). We then examined the effect of different solvents,
such as dioxane, THF, MeCN, and dimethyl formamide
(DMF) (entries 8−11). Of all the solvents tested, toluene as
solvent afforded satisfying yield (entry 7). The reactiveness also
depended on reaction temperature. When the reaction
temperature was reduced to 80 °C, the yield of product was
decreased to 21% (entry 12). On the other hand, without CuI,
the reaction did not proceed (entry 13). Furthermore, the effect
of other copper salts was also examined. CuBr and CuCl as
catalyst gave product in 65 and 49% yields, respectively (entries
14−15). CuI proved to be the best choice among the screened
copper salts under the reaction conditions (entry 7). The
reaction also showed a strong dependence on the amount of
DBU. When the DBU was used in 1 and 3 equiv, the desired
product was formed in 27 and 61% yields, respectively (entry
16−17).
Received: April 4, 2013
Published: April 23, 2013
© 2013 American Chemical Society
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idine 1t, 2-iodopyridine 1u, and 2-iodothiophene 1v were
employed to afford the corresponding product in good yields
(entries 20−22). In the cases where p-chloroiodobenzene and
p-bromoiodobenzene were employed, the corresponding diaryl
sulfides were obtained (entries 11−12). This result implied that
there was good chemoselectivity between iodide, bromide, and
chloride functional groups, although bromobenzene and
chlorobenzene did not perform the reaction to afford diphenyl
sulfide under the optimal conditions.
Next, we tried the possibility of applying this catalytic system
in the reaction of two different aryl iodides by using
iodobenzene 1a and 1-iodo-4-methoxybenzene 1i. When the
ratio of two substrates was 1:1, 49% cross-coupling product 2ai
was obtained, while homocoupling products 2a and 2i were
obtained in 22 and 20% yields, respectively (Scheme 1).
Having established an effective catalytic system for the
coupling reactions of aryl iodides with CS2, we also tried a
variety of diiodoaryl compounds. The results are summarized in
Table 3. When 2,2′-diiodobiphenyl 3a and 2-iodo-1-(2-
iodophenyl)-1H-pyrrole 3b were used, the desired product 4a
and 4b were formed in 75 and 62% yields, respectively (entries
1−2). When 1,2-diiodobenzene 3c and 2,2′-oxybis-
(iodobenzene) 3d were employed, thianthrene 4c and
phenoxathiine 4d were formed in 65 and 72% yields,
respectively (entries 3−4). Furthermore, (Z)-1-iodo-2-(2-
iodovinyl)benzene derivatives were used to displace diioaryl
compounds, and benzo[b]thiophene 4e, 4f were obtained in
good yields (entry 5−6). Finally, diiododiene 3g was used in
the reaction, and thiophene 4g was also obtained in 78% yield
(entry 7).
Table 1. Optimization between Iodobenzene 1a and Carbon
Disulfide
a
b
entry
base
solvent
temp (°C)
yield (%)
1
Cs2CO3
K3PO4
KOH
tBuONa
Et3N
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
THF
100
100
100
100
100
100
100
100
100
100
100
80
NR
NR
NR
NR
NR
NR
91 (85)
89 (81)
16
2
3
4
5
6
DABCO
DBU
7
8
DBU
9
DBU
10
11
12
13
14
15
16
17
DBU
CH3CN
DMF
68
DBU
3
DBU
toluene
toluene
toluene
toluene
toluene
toluene
21
c
DBU
100
100
100
100
100
NR
d
DBU
65
e
DBU
49
f
DBU
27
g
DBU
61
a
Reaction condition: 1 mmol of 4-iodobenzene, 1 mmol of carbon
disulfide, 0.1 mmol of CuI, and 2 mmol of base in 1.5 mL of solvent
b
for 12 h. Yield was determined by the GC using n-dodecane as the
c
internal standard; isolated yield was given in brackets. Without using
d
e
CuI. CuBr (10 mol %) was employed. CuCl (10 mol %) was
f
g
employed. DBU (1 mmol) was used. DBU (3 mmol) was used.
On the basis of the above results, the mechanism of this
reaction is proposed as shown in Scheme 2. It is reported that
DBU reacted with CS2 to yield compound 5 and DBUH+SH−
6.16 CuI reacts with DBUH+SH− 6 to generate CuSH 7,7i
which reacts with aryl iodide by oxidative addition to form
intermediate 8. Then the intermediate 8 transforms into
complex 97i via reductive elimination and ligand exchange in
the presence of DBU. Aryl iodide reacts with complex 9 by
oxidative addition to form compound 10, which undergoes
reductive elimination to afford product 2 and releases CuI.
On the basis of these results, the optimal conditions involved
the following parameters: CuI as catalyst, DBU as base, toluene
as solvent, and reaction temperature at 100 °C. Under the
optimized condition, a study on the substrate scope was carried
out, and the representative results are summarized in Table 2.
Different aryl iodides were transformed into corresponding
diaryl sulfides in moderate to excellent yields ranging from 50
to 85%. Both an electron-donating and an electron-withdrawing
group at ortho-position of aryl iodides afforded the correspond-
ing diaryl sulfides in good yields (entries 2−6). To our delight,
the crystal of 2d was suitable for single crystal analysis, and its
structure was fully characterized by X-ray diffraction analysis.
Under the same reaction conditions, 1-iodo-3-methylbenzene
1g and methyl 3-iodobenzoate 1h showed 65 and 67% yields,
respectively (entries 7 and 8). Furthermore, substitution at the
para-position of iodobenze did not affect the reaction either
(entries 9−14). Even with stronger electron-withdrawing group
such as CO2Me or CF3 group on para-position of the
iodobenzene could also succeed to generate desired product
in 65 and 78% isolated yields, respectively (entries 13−14).
When 1-iodonaphthalene 1o was used as a substrate, the
desired product 2o was also formed in 84% yield (entry 15). 4-
Iodo-1,1′-biphenyl 1p also afforded the corresponding diaryl
sulfide in 56% yield (entry 16). Multisubstituent on
iodobenzene could also give the corresponding products in
satisfying yield with prolonged reaction time to 48 h. For
instance, when 1-iodo-2,4-dimethylbenzene 1q and 2-iodo-1,4-
dimethylbenzene 1r were used, the desired product 2q and 2r
were obtained in 70 and 68% yields, respectively (entries 17−
18). Sterically hindered mesityl iodide 1s was transformed into
the corresponding diaryl sulfide 2s in 50% (entry 19). It is
noteworthy that heteroaromatic substrates such as 4-iodopyr-
CONCLUSIONS
■
An efficient methodology for the C−S coupling of aryl iodides
applying carbon disulfide as a cheap, available and easy-to-
handle sulfide surrogate was developed. The new methodology
could be used to synthesize symmetrical diaryl thioethers in
high to excellent yields. The reaction was successfully
transferred to synthesis of dibenzo[b,d]thiophene, benzo[d]-
pyrrolo[2,1-b]thiazole, thianthrene, phenoxathiine, dibenzo-
thiophene, and thiophene in high yields. This unprecedented
reaction provides potential access to valuable structures for
drug discovery and material sciences.
EXPERIMENTAL SECTION
■
General Comments. All the reactions were carried out in predried
screwcapped tubes with Teflon-lined septum under N2 atmosphere.
Unless indicated, all materials were obtained from commercial sources
and used as received. Dioxane, THF, toluene and CH3CN were fresh
distilled, while DMF was dried by molecular sieve. Column
chromatography was performed on silica gel (particle size 200−300
1
mesh). H NMR and 13C NMR spectra were recorded on 300 or 400
MHz at ambient temperature with CDCl3 or DMSO-d6 as the solvent.
Chemical shifts (δ) were given in ppm, referenced to the residual
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a
Table 2. Copper-Catalyzed Reaction of Different Aryl Iodides with CS2
a
Reaction conditions: 1 mmol of aryl iodides, 1 mmol of carbon disulfide, 0.1 mmol of CuI, and 2 mmol of DBU in 1.5 mL of toluene at 100 °C for
b
c
12 h. Isolated yields. Reaction time is 48 h.
Scheme 1. Reaction of Two Different Aryl Iodides and Carbon Disulfide
proton resonance of CDCl3 (7.26), to the carbon resonance of CDCl3
(77.16). Coupling constants (J) were given in Hertz (Hz). The mass
analyzer type was Q-TOF used for the HRMS measurements. The
term m, q, d, s referred to multiplet, quartet, doublet, and singlet. The
reaction progress was monitored by GC. GC yields, using n-dodecane
as the internal standard, were obtained in proportion to the integral
area of n-dodecane signal. 2,2′-Diiodobiphenyl 3a, 2-iodo-1-(2-
iodophenyl)-1H-pyrrole 3b, 2,2′-oxybis(iodobenzene) 3d were formed
according to literature reports.17 (Z)-1-Iodo-2-(4-iodohex-3-en-3-
yl)benzene 3e, (Z)-1-iodo-2-(1-iodo-1-phenylhex-1-en-2-yl)benzene
3f, (3Z,5Z)-4,5-diethyl-3,6-diiodoocta-3,5-diene 3g were obtained
according to literature reports.18
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General Procedure for the Synthesis of Product 2. A sealed
tube was charged with the mixture of aryl iodide 1 (1 mmol), carbon
disulfide (1 mmol), CuI (0.1 mmol), DBU (2 mmol) and then stirred
in toluene (1.5 mL) at 100 °C under nitrogen atmosphere for
indicated time. After completion, H2O (5 mL) was added, and the
mixture was extracted with EtOAc (5 mL × 3) and dried by anhydrous
Na2SO4. Evaporation of the solvent followed by purification on silica
gel (petroleum ether) provided the corresponding product 2.
Diphenyl sulfide (2a).13a Colorless liquid: 158 mg (85% yield); 1H
NMR (300 MHz, CDCl3) δ 7.20−7.36 (m, 10 H); 13C NMR (75
MHz, CDCl3) δ 127.2, 129.3, 131.2, 135.9.
Table 3. Synthesis of Various Sulfide-Containing Cyclic
Compounds
a
2,2′-Thiobis(N,N-dimethylaniline) (2b). Yellow solid: 212 mg (78%
yield), mp 54−56 °C; 1H NMR (300 MHz, CDCl3) δ 2.84 (s, 12 H),
6.93−7.21 (m, 8 H); 13C NMR (75 MHz, CDCl3) δ 44.6, 119.3,
123.4, 127.5, 130.4, 132.5, 153.6; HRMS (ESI positive mode) calcd for
C16H20N2S + H+ 273.1425, found 273.1430; ESI-MS [M + H]+ m/z
273.2.
2,2′-Dimethoxy diphenyl sulfide (2c).13a Yellow liquid: 204 mg
1
(83% yield); H NMR (400 MHz, CDCl3) δ 3.86 (s, 6H), 6.85−6.92
(m, 4H), 7.04−7.07 (m, 2H), 7.22−7.27 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 56.0, 110.9, 121.3, 122.7, 128.5, 132.0, 157.9.
2,2′-Thiodiphenol (2d).19 Light yellow solid: 177 mg (81% yield);
1H NMR (300 MHz, DMSO-d6) δ 6.72−6.77 (m, 2 H), 6.88−6.93
(m, 4 H), 7.08−7.13 (m, 2 H), 9.81 (br, 2 H); 13C NMR (75 MHz,
DMSO-d6) δ 115.4, 119.7, 120.0, 128.3, 131.6, 156.0.
Di-o-tolyl sulfide (2e).13a White solid: 161 mg (75% yield); H
1
NMR (400 MHz, CDCl3) δ 2.39 (s, 6H), 7.05−7.11 (m, 4H), 7.15−
7.19 (m, 2H), 7.24 (d, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ 20.5, 126.8, 127.2, 130.6, 131.2, 134.4, 139.0.
2,2′-Dibromo diphenyl sulfide (2f).13b Light yellow solid: 230 mg
1
(67% yield); H NMR (400 MHz, CDCl3) δ 7.11−7.16 (m, 4 H),
7.21−7.25 (m, 2 H), 7.63 (d, J = 7.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 125.9, 128.3, 128.9, 132.5, 133.6, 135.8.
Di-m-tolyl sulfide (2g).20 Yellow liquid: 137 mg (64% yield); H
1
NMR (400 MHz, CDCl3) δ 2.22 (s, 6H), 6.95 (d, J = 7.3 Hz, 2H),
7.04 (d, J = 7.8 Hz, 2H), 7.34−7.38 (m, 1H), 7.07−7.11 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 21.4, 128.0, 128.2, 129.1, 131.7, 135.7,
139.1.
Bis(m-dimethoxycarbonylphenyl) sulfide (2h). Yellow solid: 202
1
mg (67% yield), mp 79−81 °C; H NMR (400 MHz, CDCl3) δ 3.86
(s, 6H), 7.34−7.37 (m, 2H), 7.47 (d, J = 7.8 Hz, 2H), 7.90 (d, J = 7.8
Hz, 2H), 8.00 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 52.4, 128.6,
129.5, 131.4, 132.2, 135.5, 136.0, 166.3; HRMS (ESI positive mode)
calcd for C16H14O4S + H+ 303.0687, found 303.0685; ESI-MS [M +
Na]+ m/z 325.1.
a
Reaction conditions: 0.5 mmol of diiodoaryls, 1 mmol of carbon
disulfide, 0.1 mmol of CuI, and 2 mmol of DBU in 1.5 mL of toluene
at 100 °C for 12 h. Isolated yields.
b
4,4′-Dimethoxy diphenyl sulfide (2i).13a Yellow liquid: 197 mg
(80% yield); 1H NMR (400 MHz, CDCl3) δ 3.78 (s, 6H), 6.83 (d, J =
8.7 Hz, 4H), 7.28 (d, J = 8.7 Hz, 4H),; 13C NMR (100 MHz, CDCl3)
δ 55.4, 114.9, 127.5, 132.8, 159.1.
Scheme 2. Proposed Mechanism
Di-p-tolyl sulfide (2j).13a White solid: 146 mg (68% yield); 1H
NMR (400 MHz, CDCl3) δ 2.32 (s, 6H), 7.10 (d, J = 7.8 Hz, 2H),
7.22−7.25 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 21.2, 130.0,
131.2, 132.8, 137.0.
4,4′-Dichloro diphenyl sulfide (2k).13a White solid: 178 mg (70%
yield); 1H NMR (400 MHz, CDCl3) δ 7.23−7.29 (m, 8H); 13C NMR
(100 MHz, CDCl3) δ 129.6, 132.4, 133.6, 134.0.
4,4′-Dibromo diphenyl sulfide (2l).13a White solid: 255 mg (74%
1
yield); H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 8.3 Hz, 4H), 7.43
(d, J = 8.3 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 121.6, 132.6,
132.7, 134.6.
Bis(p-dimethoxycarbonylphenyl) sulfide (2m). White solid: 196
1
mg (65% yield), mp 139−141 °C; H NMR (400 MHz, CDCl3) δ
3.89 (s, 6H), 7.36 (d, J = 8.2 Hz, 4H), 7.95 (d, J = 8.2 Hz, 4H); 13C
NMR (100 MHz, CDCl3) δ 52.3, 129.1, 130.5, 140.9, 166.5; HRMS
(ESI positive mode) calcd for C16H14O4S + H+ 303.0689, found
303.0687; ESI-MS [M + Na]+ m/z 325.1.
4,4′-Trifluoromethyl diphenyl sulfide (2n).11 White solid: 251 mg
(78% yield); 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.3 Hz, 2H),
7.59 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 124.1 (q,
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JF−C = 272.2 Hz), 126.4 (q, JF−C = 3.8 Hz), 129.8 (q, JF−C = 33.6 Hz),
131.2, 139.7.
3-Butyl-2-phenylbenzo[b]thiophene (4f).14a Colorless liquid: 90
mg (68% yield); H NMR (400 MHz, CDCl3) δ 0.91 (q, J = 7.2 Hz,
1
Bis(1-naphthyl) sulfide (2o).13a Light yellow solid: 240 mg (84%
yield); 1H NMR (400 MHz, CDCl3) δ 7.31−7.35 (m, 4H), 7.54−7.58
(m, 4H), 7.79−7.81 (m, 2H), 7.90−7.92 (m, 2H), 8.45−7.47 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 125.2, 126.0, 126.5, 126.9, 128.1,
128.7, 130.0, 132.5, 132.7, 134.2.
3H), 1.35−1.47 (m, 2H), 1.64−1.76 (m, 2H), 2.87−2.94 (m, 2H),
7.35 (m, 1H), 7.38−7.44 (m, 2H), 7.47 (m, 2H), 7.55 (m, 2H), 7.78
(m, 1H), 7.83−7.88 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0,
23.0, 26.8, 32.6, 122.4, 122.4, 124.2, 124.2, 128.0, 128.7, 129.8, 132.9,
135.0, 138.3, 139.4, 140.6.
2,3,4,5-Tetraethylthiophene (4g).14a Colorless liquid: 77 mg (78%
yield); 1H NMR (300 MHz, CDCl3) δ 1.12 (t, J = 7.5 Hz, 6 H), 1.28
(t, J = 7.6 Hz, 6 H), 2.50 (q, J = 7.6 Hz, 4 H), 2.76 (q, J = 7.4 Hz, 4
H); 13C NMR (75 MHz, CDCl3) δ 15.7, 16.5, 20.3, 21.4, 136.8, 138.0.
Bis([1,1′-biphenyl]-4-yl) sulfide (2p).21 White solid: 189 mg (56%
1
yield); H NMR (400 MHz, DMSO-d6) δ 7.36−7.40 (m, 2H), 7.45−
7.49 (m, 8H), 7.63−7.72 (m, 8H); 13C NMR (100 MHz, DMSO-d6) δ
126.6, 127.8, 127.8, 129.0, 131.3, 133.9, 139.2, 139.3.
Bis(2,4-dimethylphenyl) sulfide (2q).11 Colorless liquid: 169 mg
1
ASSOCIATED CONTENT
* Supporting Information
(70% yield); H NMR (400 MHz, CDCl3) δ 2.32 (s, 6H), 2.36 (s,
■
6H), 6.91−6.98 (m, 4H), 7.07 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 20.5, 21.1, 127.5, 131.2, 131.3, 131.4, 137.0, 138.8.
S
Copies of spectra for all compounds and the crystallographic
data of product 2d. This material is available free of charge via
the Internet at http://pubs.acs.org.
Bis(2,5-dimethylphenyl) sulfide (2r).11 White solid: 165 mg (68%
yield); 1H NMR (400 MHz, CDCl3) δ 2.25 (s, 6H), 2.36 (s, 6H), 6.92
(s, 2H), 6.99 (d, J = 10.1 Hz, 2H), 7.14 (d, J = 10.1 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 20.1, 21.0, 128.0, 130.4, 131.7, 134.1,
135.8, 136.4.
AUTHOR INFORMATION
Corresponding Author
*E-mail: cjxi@tsinghua.edu.cn.
■
Dimesityl sulfide (2s).22 White solid: 135 mg (50% yield); 1H NMR
(300 MHz, CDCl3) δ 2.20 (s, 12 H), 2.24 (s, 6 H), 6.83 (s, 4 H); 13
NMR (75 MHz, CDCl3) δ 21.0, 21.8, 129.4, 131.2, 136.6, 140.4.
C
Bis(4-pyridyl) sulfide (2t).13b Yellow solid: 141 mg (75% yield); 1H
NMR (400 MHz, CDCl3) δ 7.16 (d, J = 4.6 Hz, 2H), 8.47 (d, J = 4.6
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 124.8, 144.0, 150.4.
Bis(2-pyridyl) sulfide (2u). Red solid: 124 mg (66% yield), mp
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1
218−220 °C; H NMR (300 MHz, CDCl3) δ 7.08−7.13 (m, 2 H),
This work was supported by the National Natural Science
Foundation of China (21032004 and 21272132) and the
National Key Basic Research Program of China (973 program)
(2012CB933402).
7.37−7.40 (m, 2 H), 7.54−7.59 (m, 2 H), 8.47−8.49 (m, 2 H); 13C
NMR (75 MHz, CDCl3) δ 121.8, 125.8, 137.1, 150.2, 156.8, [M + H]+
m/z 189.4.
Bis(2-thiophenyl) sulfide (2v):11 Light yellow liquid: 139 mg (70%
yield); 1H NMR (400 MHz, CDCl3) δ 6.95−6.97 (m, 2H), 7.21−7.22
(m, 2H), 7.33−7.35 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 127.6,
129.8, 132.9, 135.6.
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Hamel, E.; Artico, M.; Silvestri, R. J. Med. Chem. 2006, 49, 947.
(e) Clader, J. W.; Billard, W.; Binch, H.; Chen, L. Y.; Crosby, G.;
Duffy, R. A.; Ford, J.; Kozlowski, J. A.; Lachowicz, J. E.; Li, S. J.; Liu,
C.; McCombie, S. W.; Vice, S.; Zhou, G. W.; Greenlee, W. J. Bioorg.
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General Procedure for the Synthesis of Product 4. A sealed
tube was charged with the mixture of diiodoaryl compound 3 (0.5
mmol), carbon disulfide (1 mmol), CuI (0.1 mmol), DBU (2 mmol)
and then stirred in toluene (1.5 mL) at 100 °C under nitrogen
atmosphere for indicated time. After completion, H2O (5 mL) was
added, and the mixture was extracted with EtOAc (5 mL × 3) and
dried by anhydrous Na2SO4. Evaporation of the solvent followed by
purification on silica gel (petroleum ether) provided the corresponding
product 4.
Dibenzo[b,d]thiophene (4a).14a White solid: 69 mg (75% yield);
1H NMR (400 MHz, CDCl3) δ 7.29−7.33 (m, 2H), 7.70−7.73 (m,
1H), 7.99−8.01 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 121.7,
122.9, 124.4, 126.8, 135.6, 139.5.
Benzo[d]pyrrolo[2,1-b]thiazole (4b).23 White solid: 54 mg (62%
(2) (a) Kaldor, S. W.; Kalish, V. J.; Davies, J. F., II; Shetty, B. V.;
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Reilly, E. B.; Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med.
Chem. 2001, 44, 1202. (c) Martino, G. D.; Edler, M. C.; Regina, G. L.;
Coluccia, A.; Barbera, M. C.; Barrow, D.; Nicholson, R. I.; Chiosis, G.;
Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J. Med. Chem. 2006,
49, 947.
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Shimizu, T.; Asami, Y.; Shiobara, J.; Kato, Y.; Kosugi, M. Bull. Chem.
Soc. Jpn. 1980, 53, 1385. (b) Murata, M.; Buchwald, S. L. Tetrahedron
2004, 60, 7397. (c) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587.
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Chem. Soc. 2006, 128, 2180. (e) Li, G. Y.; Zheng, G.; Noonan, A. F. J.
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1
yield); H NMR (400 MHz, CDCl3) δ 6.22 (d, J = 3.6 Hz, 1 H),
6.58−6.59 (m, 1H), 7.17−7.21 (m, 1H), 7.29−7.33 (m, 1H), 7.42−
7.43 (m, 1H), 7.50 (d, J = 7.8 Hz, 1 H), 7.56 (d, J = 7.8 Hz, 1 H); 13C
NMR (100 MHz, CDCl3) δ 98.9, 110.4, 111.7, 114.9, 123.7, 123.9,
125.5, 127.8, 131.7, 134.7.
Thianthrene (4c).24 White solid: 70 mg (65% yield); 1H NMR (400
MHz, CDCl3) δ 7.15−7.18 (m, 4H), 7.40−7.42 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 127.8, 128.9, 135.7.
Phenoxathiine (4d). White solid: 72 mg (72% yield), mp 54−56
°C; 1H NMR (400 MHz, CDCl3) δ 1.27 (t, J = 7.6 Hz, 3 H), 1.39 (t, J
= 7.5 Hz, 3 H), 2.86 (q, J = 7.6 Hz, 2 H), 2.94 (q, J = 7.5 Hz, 2 H),
7.28−7.33 (m, 1 H), 7.36−7.41 (m, 1 H), 7.69 (d, J = 7.5 Hz, 1 H),
7.82 (d, J = 7.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 117.9,
120.2, 124.6, 126.9, 127.8, 152.3, M+ m/z 200.3.
2,3-Diethylbenzo[b]thiophene (4e).14a Colorless liquid: 70 mg
(74% yield); 1H NMR (300 MHz, CDCl3) δ 1.27 (t, J = 7.6 Hz, 3 H),
1.39 (t, J = 7.5 Hz, 3 H), 2.86 (q, J = 7.6 Hz, 2 H), 2.94 (q, J = 7.5 Hz,
2 H), 7.28−7.33 (m, 1 H), 7.36−7.41 (m, 1 H), 7.69 (d, J = 7.5 Hz, 1
H), 7.82 (d, J = 7.8 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 14.8,
16.4, 19.7, 21.9, 121.3, 122.4, 123.4, 123.8, 132.6, 138.5, 140.2, 141.4.
5005
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