Efficient copper-catalyzed S-arylation of thiols with aryl bromides and chlorides

Article abstract of DOI:10.1055/s-0030-1258234

An efficient copper-catalyzed system for C-S cross-coupling of aromatic thiols with aryl bromides and chlorides has been developed using 1,2,3,4-tetrahydroquinoline-8-ol as a ligand. It is noteworthy that this method is proved to be especially effective for aryl bromides with electron-donating groups. By this protocol, a variety of thioethers as well as symmetrical and unsymmetrical bis-thioethers are obtained in excellent yields with an exceptional level of functional group tolerance and high chemoselectivity. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258234

3602
PAPER
Efficient Copper-Catalyzed S-Arylation of Thiols with Aryl Bromides and
Chlorides
C
opper-Catalyzed
a
S-Arylation
m
of
T
hiols ing Li,* Xiaoying Li, Huifeng Wang, Tao Chen, Yusheng Xie
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116012, P. R. of China
Fax +86(411)39893900; E-mail: yamingli@chem.dlut.edu.cn
Received 8 June 2010; revised 28 July 2010
Furthermore, as shown in Scheme 1, we would be able to
Abstract: An efficient copper-catalyzed system for C–S cross-
achieve several symmetrical bis-thioethers in one-pot
fashion and even obtain unsymmetrical bis-thioethers
based on the activity difference of C–X bonds.
coupling of aromatic thiols with aryl bromides and chlorides has
been developed using 1,2,3,4-tetrahydroquinoline-8-ol as a ligand.
It is noteworthy that this method is proved to be especially effective
for aryl bromides with electron-donating groups. By this protocol, a
variety of thioethers as well as symmetrical and unsymmetrical bis-
thioethers are obtained in excellent yields with an exceptional level
of functional group tolerance and high chemoselectivity.
Br
S
HS
[Cu]
EDG
EDG
+
Key words: copper catalyst, aryl bromides, aryl chlorides, cross-
coupling, organic sulfides
Ar1SH
Ar1
Ar1
S
S
S
S
Ar1
[Cu]
X1
X2
1) Ar1SH
2) Ar2SH
The C–S bonds proverbially exist in compounds with
biological and pharmaceutical impact and in molecules of
useful polymeric materials.1 For example, various aryl
sulfides are used for the treatment of cancer2 and human
immunodeficiency virus diseases.3 The development of
efficient S-arylation methods has been a subject of interest
in synthetic chemistry since Migita first reported the
palladium-catalyzed cross-coupling of aryl halides with
thiols.4 A wide range of transition metals was used to
catalyze this coupling reaction, including palladium,5
nickel,6 cobalt7, copper,8 and indium.9 Among them, the
development of copper-catalyzed methods is attractive
due to the relatively low cost and environmentally nega-
tive influence of the process.
Ar2
Scheme 1 Pathways of experimental design
To optimize the reaction conditions, the coupling reaction
of thiophenol and bromobenzene was used as a model re-
action. When the reaction temperature was raised to
130 °C and the time was prolonged to 48 hours with DMF
as solvent, a significant increase was observed (Table 1,
entry 5). Utilizing the slightly stronger base Cs2CO3
proved to be critical for the reaction (Table 1, entry 7).
Yield was further improved by increasing the amount of
catalyst loading to 20 mol%. Thus, the optimal reaction
conditions were obtained as shown in entry 8.
During the last decade copper-catalyzed cross-coupling
reactions of aryl iodides with thiols have enabled the syn-
thesis of aryl sulfides in good yields under mild reaction
conditions.10 However, only a few reports employed
cheaper and more widely available aryl bromides and
chlorides as arylating agents.10a–f,11 Furthermore, most of
the systems reported in the limited literature were not ev-
idently effective for the aryl bromides with electron-
donating groups. Therefore, it remains a tremendous chal-
lenge to develop an efficient copper-catalyzed method for
the S-arylation with inactivated aryl bromides and aryl
chlorides.
Firstly, with the optimized conditions, the aryl bromides
with electron-donating groups, such as methyl and amino,
gave the prospective diaryl thioethers in excellent yields
(Table 2, 2a, 2b, and 2c). In the case of 4-bromoanisole
with methoxy group, unexpectedly, the GC yield of phe-
nylsulfanylanisole was only 53% (Table 2, 2d). Other by-
products, anisole, phenol, methyl phenyl thioether, and 4-
methoxyphenyl phenyl ether were detected by GC-MS.
Some side-reactions, such as dehalogenation of 4-bro-
moanisole, reaction of anisole and thiophenol resulting in
phenol and methyl phenyl thioether as reported,13 and re-
action of phenol with 4-bromoanisole subsequently to
form 4-methoxyphenyl phenyl ether, were observed (side-
reaction process is described in detail in the Supporting
Information). Heterocyclic bromides such as 2-bromopy-
ridene also could be employed in this coupling reaction
with good to excellent yield (Table 2, 2e). Further, this
catalytic system is highly efficient for aryl chlorides with
electron-withdrawing groups as well, such as cyano,
acetyl, and trifluoromethyl groups (Table 2, 2g, 2i, 2h, 2l,
2m and 2n). Secondly, the sterically hindered ortho-sub-
In our previous copper-catalyzed S-arylation with aryl io-
dides, when p-bromoiodobenzene was used as a substrate,
both coupling reactions of C–I and C–Br bonds with thiols
were observed.12 This encouraged us to extend the method
to inactivated aryl bromides and even to aryl chlorides.
SYNTHESIS 2010, No. 21, pp 3602–3608
x
x.
x
x
.
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0
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0
Advanced online publication: 30.08.2010
DOI: 10.1055/s-0030-1258234; Art ID: F10410SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Copper-Catalyzed S-Arylation of Thiols
3603
Table 1 Optimization of the Reaction Conditionsa
OH
H
N
S
HS
Br
[Cu]/L, base
+
solvent, 48 h
L
Entry
Solvent
[Cu]
Base
[Cu] (mol%)
Temp (°C)
120
Yield (%)
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMF
CuBr
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Cs2CO3
Cs2CO3
20
20
20
20
10
10
10
20
28
18
28
31
61
48
88
97
120
CuCl
CuBr
CuBr
CuBr
CuBr
CuBr
120
120
DMF
130
DMF
130
DMF
130
DMF
130
a Reaction conditions: bromobenzene (0.75 mmol), thiophenol (0.5 mmol), [Cu] (10 or 20 mol%), L (0.1 mmol), base (1.0 mmol), and solvent
(1.5 mL) stirred for 48 h under argon. Yield (GC) was calibrated with diphenyl ether as an internal standard.
stituted aryl bromides and chlorides gave the correspond- chlorophenyl phenyl thioether in good yield by control-
ing products in satisfactory yields (Table 2, 2f and 2g). ling the reaction temperature (Table 2, 2j). On the other
Thirdly, this copper-catalyzed system indicates a high hand, the Ar–Br or Ar–Cl coupled with SH selectively
chemoselectivity. On the one hand, on the basis of differ- without any reaction with NH2 present at the aryl ring of
ence in the activity of C–Br and C–Cl bonds of 4-bromo- the thiol (Table 2, 2k and 2l).
chlorobenzene, we were able to selectively obtain 4-
Table 2 The C–S Coupling Reaction of Aryl Halides and Aromatic Thiolsa
CuBr (20 mol%), L (20 mol%)
X
HS
S
Cs2CO3 (2 equiv)
R1
R2
R1
R2
+
DMF, 130 °C, 48 h
X = Br, Cl
X
Yield (%)b
91
S
Br
2a
S
Br
Br
2b
2c
99
81
S
H2N
S
Br
Br
2d
2e
53c
97
MeO
N
S
Br
2f
75
S
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Y. Li et al.
PAPER
Table 2 The C–S Coupling Reaction of Aryl Halides and Aromatic Thiolsa (continued)
CuBr (20 mol%), L (20 mol%)
X
HS
S
Cs2CO3 (2 equiv)
R1
R2
R1
R2
+
DMF, 130 °C, 48 h
X = Br, Cl
X
Yield (%)b
72
S
Cl
2g
CN
S
Cl
Cl
2h
2i
82
86
F3C
S
O
S
Br
Br
Cl
2j
2k
2l
77d
83
Cl
S
NH2
S
68
F3C
NH2
S
Cl
Cl
2m
2n
57
81
CN
S
O
a Reaction conditions: aryl halides (0.75 mmol), thiols (0.5 mmol), CuBr (20 mol%), L (20 mol%), Cs2CO3 (1 mmol), and DMF (1.5 mL) stirred
at 130 °C for 48 h under argon.
b Isolated yield.
c GC yield.
d At 100 °C.
It was interesting to note that several symmetrical and un- Encouraged by the success of symmetrical bis-thioethers
symmetrical bis-thioethers could be prepared using this achieved, the synthesis of unsymmetrical bis-thioethers
catalytic system. So far, there are only a few scattered lit- from 4-bromoiodobenzene was attempted based on the
erature reports concerning the fact that both halogen difference in the activity between C–I and C–Br bonds. As
groups in aryl dihalides could simultaneously take part in shown in Scheme 2, first, 4-bromophenyl phenyl thio-
the C–S coupling reaction in a one-pot fashion.10f,14,15a ether was prepared first in satisfactory yield by regulating
The optimized reaction conditions for symmetrical bis- the temperature (Scheme 2). Then, 4-bromophenyl phe-
thioethers were somewhat different from those of mono- nyl thioether reacted with other aromatic thiols. Ultimate-
thioethers. The amount of CuBr was reduced to 10 mol%, ly, several unsymmetrical bis-thioethers were obtained in
the quantity of Cs2CO3 was increased to 3 equivalents, good to excellent yields (Scheme 2, 4a–c). In the case of
and the molar ratio of thiophenol to aryl dihalides was p-chlorothiophenol, yield is slightly lower due to the weak
2.2:1. Whether the substrate was para-, meta-, or ortho- nucleophilicity of p-chlorothiophenol and the debromina-
aryl dihalides, the symmetrical bis-thioethers were all ob- tion side-reaction of 4-bromophenyl phenyl thioether.
tained in excellent yields (Table 3, 3a, 3b, and 3c).
Because the aryl chlorides are less reactive, the reaction of
p- or o-dichlorobenzene afforded the corresponding bis-
thioethers in moderate to good yields.
Thus, this reaction offered an easy access to a library of
symmetrical and unsymmetrical bis-thioethers. Besides, it
is found to be much potential in synthesizing PPS oligo-
mers, which have a long history as commercial thermo-
Synthesis 2010, No. 21, 3602–3608 © Thieme Stuttgart · New York

PAPER
Copper-Catalyzed S-Arylation of Thiols
3605
Table 3 The C–S Coupling Reaction of Aryl Dihalides and Thiophenola
CuBr (10 mol%)
L (20 mol%)
Cs2CO3 (3 equiv)
HS
X1
X2
S
S
+
DMF, 130 °C, 48 h
Product
X1
X2
Yield (%)b
Br
Br
Cl
Cl
Cl
I
Br
I
Br
Cl
92
97
95
99
78
S
S
3a
S
S
3b
3c
Br
I
99
Br
Br
Cl
I
Br
Cl
93
99
70c
S
S
a Reaction conditions: aryl dihalides (0.5 mmol), thiophenol (1.1 mmol), CuBr (10 mol%), L (20 mol%), Cs2CO3 (1.5 mmol), and DMF (1.5
mL) stirred at 130 °C for 48 h under argon.
b Isolated yield.
c GC yield; 30% 2-chlorophenyl phenyl thioether was also formed. o-Dichlorobenzene was completely consumed.
S
SH
S
4a, 98%
Br
CuBr (20 mol%)
L (20 mol%)
SH
SH
S
S
Br
I
Cs2CO3 (2 equiv)
DMF, 130 °C, 48 h
CuBr (10 mol%)
L (20 mol%)
Cs2CO3 (2 equiv)
DMF, 70 °C, 24 h
S
S
S
78%
4b, 96%
4c, 67%
Cl
Cl
SH
Scheme 2 Synthesis of unsymmetrical bis-thioethers
plastics and classic sulfur-based polymers because these 1H and 13C NMR spectra were recorded in CDCl3 solvent on a Vari-
an INOVA 400 NMR spectrometer (1H 400 MHz, 13C 100 MHz)
polymers exhibit excellent mechanical properties, high
with respect to internal TMS. GC-MS was obtained on HP 6890GC/
stability, conductivity, energy storage ability, fire retar-
5973MSD spectrometer. MS were recorded on HP1100 HPLC/MS
dant, high refractive index, etc.15
spectrometer. HRMS analyses were performed on UPLC/Q-Tof
In conclusion, we have developed a highly efficient
copper-catalyzed cross-coupling reaction of both aryl bro-
mides and chlorides with aryl thiols. Furthermore, we
successfully achieved symmetrical and unsymmetrical
bis-thioethers in good to excellent yields. In addition, this
catalytic system showed wide functional group tolerance
and well chemoselectivity. We believe that this method
Micro spectrometer. Petroleum ether (PE) used refers to the fraction
boiling in the range 60–90 °C. The 1,2,3,4-tetrahydro-quinoline-8-
ol (L) was prepared as reported in the literature.16
Diphenyl Thioether (2a);17 Typical Procedure
A flame-dried test tube with a magnetic stirring bar was charged
with CuBr (14 mg, 0.1 mmol), ligand (15 mg, 0.1 mmol), Cs2CO3
(326 mg, 1.0 mmol), thiophenol (55 mg, 0.5 mmol), bromobenzene
exhibits the potential in organic synthesis on account of (118 mg, 0.75 mmol), and DMF (1.5 mL) under argon. The mixture
was stirred at 130 °C for 48 h, then cooled to r.t. and the resulting
mixture was extracted with EtOAc (3 × 25 mL). The combined or-
ganic layers were dried (Na2SO4) and concentrated under vacuum.
the low cost and availability of aryl bromides and chlo-
rides.
Synthesis 2010, No. 21, 3602–3608 © Thieme Stuttgart · New York

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Y. Li et al.
PAPER
The residue was purified by column chromatography on silica gel
with PE as eluent; colorless oil (Table 2). CAS: 139-66-2.
1H NMR (400 MHz, CDCl3): d = 7.35–7.21 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 135.6, 130.9, 129.1, 126.9.
GC-MS (EI): m/z = 186 [M]+.
Phenyl 4-(Trifluoromethyl)phenyl Sulfide (2h)19a
The crude product was purified over a silica gel column using PE;
colorless oil. CAS: 53451-90-4.
1H NMR (400 MHz, CDCl3): d = 7.49–7.47 (m, 4 H), 7.41–7.38 (m,
3 H), 7.27–7.25 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 143.0, 133.7 (2 C), 132.6, 129.9
2
(2 C), 128.8, 128.4 (2 C), 128.3 (q, JC,F = 32.6 Hz), 125.9 (d,
p-Tolyl Phenyl Thioether (2b)17
The crude product was purified over a silica gel column using PE;
colorless oil. CAS: 3699-01-2.
3JC,F = 3.5 Hz), 124.2 (q, 1JC,F = 271.6 Hz).
GC-MS (EI): m/z = 254 [M]+.
1H NMR (400 MHz, CDCl3): d = 7.28 (d, J = 8.0 Hz, 2 H), 7.25–
7.14 (m, 5 H), 7.09 (d, J = 8.0 Hz, 2 H) 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 137.6, 137.3, 132.3, 131.5, 130.1,
129.9, 129.1, 126.5, 21.2.
1-[4-(Phenylthio)phenyl]ethanone (2i)5c,20
The crude product was purified over a silica gel column using
EtOAc–PE (1:40); white solid; mp 64–64.8 °C (Lit.20 mp 64–
66 °C). CAS: 10169-55-8.
1H NMR (400 MHz, CDCl3): d = 7.82 (d, J = 8.4 Hz, 1 H), 7.51–
7.48 (m, 2 H), 7.41–7.39 (m, 3 H), 7.20 (d, J = 8.4 Hz, 2 H), 2.55 (s,
3 H).
13C NMR (100 MHz, CDCl3): d = 197.3, 145.1, 134.6, 134.0, 132.2,
129.8, 129.0, 128.9, 127.5, 26.6.
GC-MS (EI): m/z = 228 [M]+.
GC-MS (EI): m/z = 200 [M] +.
4-Aminophenyl Phenyl Thioether (2c)7,18
Following the typical procedure, 2c was prepared from 4-bromoa-
niline and thiophenol. The crude product was purified over a silica
gel column using EtOAc–PE (1:3); pale solid; mp 95.7–96.2 °C
(Lit.18 mp 96–96.5 °C). CAS: 1135-14-4.
1H NMR (400 MHz, CDCl3): d = 7.31 (d, J = 8.4 Hz, 2 H), 7.21 (t,
J = 7.6 Hz, 2 H), 7.13–7.08 (m, 3 H), 6.69 (d, J = 8.4 Hz, 2 H), 3.98
(br s, 2 H).
13C NMR (100 MHz, CDCl3): d = 146.8, 139.7, 136.1, 128.9, 127.6,
125.4, 121.1, 116.1.
4-Chlorophenyl Phenyl Thioether (2j)8d
The crude product was purified over a silica gel column using PE;
colorless oil. CAS: 13343-26-5.
1H NMR (400 MHz, CDCl3): d = 7.35–7.25 (m, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.3, 134.8, 133.2, 132.2, 131.5,
129.49, 129.48, 127.6.
GC-MS (EI): m/z = 201 [M]+.
2-(Phenylthio)pyridine (2e)7
GC-MS (EI): m/z = 220 [M]+, 222 [M + 2]+.
The crude product was purified over a silica gel column using
EtOAc–PE (2:25); colorless oil. CAS: 3111-54-4.
4-Aminophenyl Phenyl Thioether (2k ≡ 2c)
Following the typical procedure, 4-aminophenyl phenyl thioether
was also prepared by reacting bromobenzene with 4-aminothiophe-
nol. The crude product was purified over a silica gel column using
EtOAc–PE (1:3). For analytical and spectral data, see under 2c.
1H NMR (400 MHz, CDCl3): d = 8.41 (d, J = 4.4 Hz, 1 H), 7.60–
7.57 (m, 2 H), 7.46–7.39 (m, 4 H), 6.99–6.96 (t, J = 6.2 Hz, 1 H),
6.87 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 161.6, 149.6, 136.8, 135.0, 131.0,
129.7, 129.2, 121.3, 119.9.
GC-MS (EI): m/z = 186 [M]+.
MS (API): m/z = 188 [M + H]+.
4-[4-(Trifluoromethyl)phenylthio]aniline (2l)21
The crude product was purified over a silica gel column using
EtOAc–PE (1:6); slightly yellow solid; mp 89.6–90.5 °C.
1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 8.4 Hz, 2 H), 7.33 (d,
J = 8.4 Hz, 2 H), 7.11 (d, J = 8.4 Hz, 2 H), 6.72 (d, J = 8.4 Hz, 2 H),
3.98 (br s, 2 H).
13C NMR (100 MHz, CDCl3): d = 147.8, 145.9, 137.1, 126.1, 125.7,
118.4, 116.3.
1-Naphthyl Phenyl Thioether (2f)5c
The crude product was purified over a silica gel column using PE;
colorless oil. CAS: 7570-98-1.
1H NMR (400 MHz, CDCl3): d = 8.39–8.36 (m, 1 H), 7.87–7.83 (m,
2 H), 7.65 (d, J = 7.2 Hz, 1 H), 7.52–7.48 (m, 2 H), 7.41 (t, J = 7.2
Hz, 1 H), 7.22–7.13 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 137.1, 134.4, 133.8, 132.7, 131.4,
129.4, 129.2, 129.1, 128.7, 127.1, 126.6, 126.3, 126.0, 125.8.
GC-MS (EI): m/z = 236 [M]+.
GC-MS (EI): m/z = 269 [M]+.
2-(o-Tolylthio)benzonitrile (2m)22
The crude product was purified over a silica gel column using
EtOAc–PE (1:80); slightly yellow solid; mp 65–65.6 °C.
1H NMR (400 MHz, CDCl3): d = 7.63 (d, J = 7.6 Hz, 1 H), 7.47 (d,
J = 7.6 Hz, 1 H), 7.38–7.34 (m, 3 H), 7.25–7.18 (m, 2 H), 6.84 (d,
J = 8.0 Hz, 1 H), 2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 143.0, 142.2, 135.7, 133.8, 133.1,
131.3, 130.2, 130.0, 128.1, 127.4, 125.8, 117.1, 111.7, 20.9.
2-(Phenylthio)benzonitrile (2g)19a,b
The crude product was purified over a silica gel column using
EtOAc–PE (3:20); slightly yellow solid; mp 56.1–57.1 °C (Lit.19b
mp 56.5–58 °C). CAS: 91804-55-6.
1H NMR (400 MHz, CDCl3): d = 7.64 (d, J = 8.0 Hz, 1 H), 7.49–
7.47 (m, 2 H), 7.43–7.38 (m, 4 H), 7.28–7.24 (m, 1 H), 7.13 (d,
J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 142.4, 133.7, 133.6, 133.0, 132.0,
130.0, 129.8, 129.0, 126.5, 117.0, 113.0.
GC-MS (EI): m/z = 225 [M]+.
1-[4-(o-Tolylthio)phenyl]ethanone (2n)
The crude product was purified over a silica gel column using
EtOAc–PE (1:20); slightly yellow solid; mp 57.7–59 °C.
1H NMR (400 MHz, CDCl3): d = 7.80 (d, J = 8.8 Hz, 2 H), 7.52 (d,
J = 8.0 Hz, 1 H), 7.35–7.34 (m, 2 H), 7.25 (m, 1 H), 7.08 (d, J = 8.4
Hz, 2 H), 2.54 (s, 3 H), 2.37 (s, 3 H).
GC-MS (EI): m/z = 211 [M]+.
Synthesis 2010, No. 21, 3602–3608 © Thieme Stuttgart · New York

PAPER
Copper-Catalyzed S-Arylation of Thiols
3607
13C NMR (100 MHz, CDCl3): d = 197.2, 145.1, 142.4, 136.0, 134.3,
with EtOAc (3 × 25 mL). The combined organic layers were dried
(Na2SO4) and concentrated under vacuum. The residue was purified
by column chromatography on silica gel with PE as eluent to give
4a; white solid; mp 59–60 °C (Lit.25 mp 55.5 °C). CAS: 96802-31-2.
1H NMR (400 MHz, CDCl3): d = 7.34–7.24 (m, 7 H), 7.21 (d,
J = 8.0 Hz, 2 H), 7.16–7.14 (m, 4 H), 2.35 (s, 3 H).
131.3, 130.5, 129.9, 129.1, 127.3, 126.5, 26.6, 20.8.
HRMS (ESI): m/z [M + Na]+ calcd for C15H14OS + Na: 265.0663;
found: 265.0656.
4-Bromophenyl Phenyl Thioether23
This compound was prepared as shown in Scheme 2 employing the
molar ratios of the starting materials used for the preparation of 3a
(see below). The crude product was purified over a silica gel column
using PE; colorless oil. CAS: 65662-88-6.
13C NMR (100 MHz, CDCl3): d = 138.2, 136.7, 135.7, 133.9, 132.9,
131.7, 131.2, 130.6, 130.4, 130.1, 129.4, 127.3, 21.3.
GC-MS (EI): m/z = 308 [M]+.
1H NMR (400 MHz, CDCl3): d = 7.39 (d, J = 8.4 Hz, 2 H), 7.36–
7.24 (m, 5 H), 7.16 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 135.7, 135.0, 132.4, 132.2, 131.7,
129.5, 127.7, 121.0.
1-Phenylsulfanyl-4-o-tolylsulfanylbenzene (4b)
The crude product was purified over a silica gel column using PE as
eluent; colorless oil.
1H NMR (400 MHz, CDCl3): d = 7.34–7.28 (m, 5 H), 7.24–7.20 (m,
5 H), 7.15 (d, J = 8.0 Hz, 1 H), 7.08 (d, J = 8.0 Hz, 2 H), 2.37 (s, 3
GC-MS (EI): m/z = 264 [M]+, 266 [M + 2]+.
H).
1,4-Bis(phenylthio)benzene (3a);15a,24 Typical Procedure
A flame-dried test tube with a magnetic stirring bar was charged
with CuBr (7 mg, 0.05 mmol), ligand (15 mg, 0.1 mmol), Cs2CO3
(489 mg, 1.5 mmol), thiophenol (121 mg, 1.1 mmol), p-dibro-
mobenzene (118 mg, 0.5 mmol), and DMF (1.5 mL) under argon.
The mixture was stirred at 130 °C for 48 h, then cooled to r.t. and
the resulting mixture was extracted with EtOAc (3 × 25 mL). The
combined organic layers were dried (Na2SO4) and concentrated un-
der vacuum. The residue was purified by column chromatography
on silica gel with PE as eluent (Table 3).
White solid; mp 81.6–82.1 °C (Lit.15a mp 81.3 °C). CAS: 3459-94-
7.
1H NMR (400 MHz, CDCl3): d = 7.35 (d, J = 7.2 Hz, 4 H), 7.32–
7.28 (t, J = 7.2 Hz, 4 H), 7.27–7.23 (t, J = 7.2 Hz, 2 H), 7.21 (s, 4 H).
13C NMR (100 MHz, CDCl3): d = 140.0, 135.7, 135.6, 133.8, 133.6,
133.1, 131.7, 131.2, 130.9, 129.9, 129.4, 128.5, 127.3, 127.0, 20.8.
GC-MS (EI): m/z = 308 [M]+.
(4-Chlorophenyl)[4-(phenylthio)phenyl]sulfane (4c)26
The crude product was purified over a silica gel column using PE as
eluent; white solid; mp 92.3–92.8 °C (Lit.26 mp 92–93 °C). CAS:
60420-81-7.
1H NMR (400 MHz, CDCl3): d = 7.37 (d, J = 8.0 Hz, 2 H), 7.32–
7.26 (m, 3 H), 7.24–7.20 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 136.0, 134.7, 134.2, 134.0, 133.5,
132.4, 131.9, 131.7, 131.0, 129.6, 129.5, 127.8.
GC-MS (EI): m/z = 328 [M]+, 330 [M + 2]+.
13C NMR (100 MHz, CDCl3): d = 135.2, 135.1, 131.6, 131.3, 129.5,
127.6.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
GC-MS (EI): m/z = 294 [M]+.
1,3-Bis(phenylthio)benzene (3b)24
Colorless oil. CAS: 2974-10-9.
1H NMR (400 MHz, CDCl3): d = 7.33 (d, J = 7.4 Hz, 4 H), 7.28–
7.20 (m, 7 H), 7.18–7.10 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 137.8, 134.6, 132.0, 131.4, 129.8,
129.4, 128.5, 127.7.
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (Project No. 20876021) and the Education Depart-
ment of Liaoning Province (2009S021).
GC-MS (EI): m/z = 294 [M]+.
References
1,2-Bis(phenylthio)benzene (3c)24
Colorless oil. CAS: 3379-36-0.
1H NMR (400 MHz, CDCl3): d = 7.37–7.21 (m, 10 H), 7.14–7.08
(m, 4 H).
13C NMR (100 MHz, CDCl3): d = 137.5, 134.6, 131.9, 131.5, 129.5,
129.2, 127.6.
GC-MS (EI): m/z = 294 [M]+.
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dure
Following the typical experimental procedure given above for 3a,
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Synthesis 2010, No. 21, 3602–3608 © Thieme Stuttgart · New York

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Y. Li et al.
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