A copper-catalyzed synthesis of symmetrical diarylsulfanes

Article abstract of DOI:10.1055/s-0033-1340985

A room-temperature, copper-catalyzed synthesis of symmetrical diarylsulfanes has been developed. The reaction proceeds from aryl iodides and elemental sulfur (S₈) by the action of copper(I) salts in the presence of N-ethyl-N-isopropylpropan-2-amine to afford the corresponding diarylsulfanes in good yields. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340985

LETTER
▌1121
lAetteCr opper-Catalyzed Synthesis of Symmetrical Diarylsulfanes
Copper-Catalyzed Synthesis of Symmetrical Diarylsulfanes
Issa Yavari,* Majid Ghazanfarpour-Darjani, Yazdan Solgi
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
Fax +98(21)82883455; E-mail: yavarisa@modares.ac.ir
Received: 25.01.2014; Accepted after revision: 19.02.2014
Table 1 Synthesis of Diarylsulfanes 2a
Abstract: A room-temperature, copper-catalyzed synthesis of sym-
metrical diarylsulfanes has been developed. The reaction proceeds
from aryl iodides and elemental sulfur (S8) by the action of cop-
per(I) salts in the presence of N-ethyl-N-isopropylpropan-2-amine
to afford the corresponding diarylsulfanes in good yields.
I
S
copper source, ligand
base, solvent
S8
+
2
1
Key words: S-arylation, copper(I) iodide, diarylsulfanes, sulfur
O
O
O
O
O
O
MeO
OMe
Ph
Ph
L3
L1
L2
Cross-coupling reactions performed between aryl halides
and various nucleophiles in the presence of copper cata-
lysts are powerful methods for carbon–heteroatom bond
formation.1,2 The importance of the aryl–sulfur bond
stems from its presence in molecules of pharmaceutical
and material interest. For example, diarylthioether moi-
eties have been found in numerous drugs.3 A common
method for the synthesis of diarylsulfanes is the transi-
tion-metal-catalyzed cross-coupling reaction between
aryl halides and thiophenoles. Different transition metals
including palladium,4,5 nickel,6,7 iron,8,9 and copper10–13
have been reported to catalyze the formation of diarylsul-
fanes. Less common strategies for the synthesis of thio-
ether moieties involve the use of thioureas,14 disulfides,15
2-(iodoaryl)thioureas,16 thoicyanates,17 and aryl halides in
the presence of copper catalysts. Recently, we have devel-
oped an efficient copper-catalyzed C–N cross-coupling.18
Herein, we report a route to C–S cross-coupling at room
temperature. To the best of our knowledge, no synthetic
routes by copper catalysis at ambient temperature aimed
to the synthesis of symmetrical diarylsulfanes have been
reported.
O
O
H
N
Me
Me
N
H
N
N
L4
L5
L6
Catalyst
Ligand
Base
Solvent
Yield (%)
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
CuBr
Cu2O
CuI
CuI
CuI
CuI
L1
L2
L3
L4
L5
L6
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
EIPA
Et3N
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
87
33
49
76
62
62
64
32
9
NMP
MeCN
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
–
54
47
58
71
43
61
10
Initially, the reaction between iodobenzene (3 mmol) and
elemental sulfur (1.1 mmol), in the presence of copper(I)
iodide (10 mol%), acetylacetone (1.1 mmol), and N-ethyl-
N-isopropylpropan-2-amine (EIPA, 2 mmol) in DMSO at
25 °C was selected as a model for the synthesis of sym-
metrical diarylsulfanes (Table 1). Changing the solvent to
DMSO led to good yields, but the use of other solvents re-
sulted in significantly reduced yields. Bases other than
EIPA afforded lower yields, and copper catalysts other
than copper(I) iodide exhibited reduced activities. Among
the ligands tested, acetylacetone showed a superior effect
on the reaction yields (Table 1).
DABCO
DBU
Cs2CO3
a Reactions conditions: iodobenzene (2 mmol), S8 (1.1 mmol), copper
source (0.10 mmol), ligand (1.1 mmol), base (2.0 mmol), solvent (2
mL), 25 °C, 8 h, under argon.
After the optimized reaction conditions were established,
a number of aryl iodides was examined to explore the
scope of this reaction. As summarized in Table 2, various
aryl iodides were converted into the corresponding diaryl-
sulfanes in good yields.19
SYNLETT 2014, 25, 1121–1123
Advanced online publication: 10.04.2014
In conclusion, a novel copper-mediated procedure was de-
veloped for the preparation of symmetrical diarylsulfanes
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340985; Art ID: ST-2014-D0069-L
© Georg Thieme Verlag Stuttgart · New York

1122
I. Yavari et al.
LETTER
(3) Liu, G.; Huth, J. R.; Olejniczak, E. T.; Mendoza, F.;
DeVries, P.; Leitza, S.; Reilly, E. B.; Okasinski, G. F.; Fesik,
S. W.; Von Geldern, T. W. J. Med. Chem. 2001, 44, 1202.
(4) Nielsen, S. F.; Nielsen, E. Ø.; Olsen, G. M.; Liljefors, T.;
Peters, D. J. Med. Chem. 2000, 43, 2217.
Table 2 Copper-Catalyzed C–S Coupling of Aryl Iodides with Ele-
mental Sulfur
Entry ArX
Product
Yield
(%)
(5) Murata, M.; Buchwald, S. L. Tetrahedron 2004, 60, 7397.
(6) Fernandez, M. A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc.
2006, 128, 2180.
(7) Zhang, Y.; Ngeow, K. N.; Ying, J. Y. Org. Lett. 2007, 9,
3495.
(8) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. Int. Ed.
2008, 47, 2880.
(9) Buchwald, S. L.; Bolm, C. Angew. Chem. Int. Ed. 2009, 48,
5586.
S
I
1
87
84
1a
2a
2b
S
I
2
(10) Sperotto, E.; van Klink, G. P. M.; de Vries, J. G.; van Koten,
G. J. Org. Chem. 2008, 73, 5625.
1b
(11) Xu, H.; Zhao, X.; Fu, Y.; Feng, Y. Synlett 2008, 3063.
(12) Xu, R.; Wan, J.; Mao, H.; Pan, Y. J. Am. Chem. Soc. 2010,
132, 15531.
S
I
3
71
(13) Prasad, D.; Sekar, G. Synlett 2010, 79.
(14) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M. Adv. Synth.
Catal. 2010, 352, 119.
(15) Wang, H.; Jiang, L.; Chen, T.; Li, Y. Eur. J. Org. Chem.
2010, 2324.
(16) Ramana, T.; Saha, P.; Das, M.; Punniyamurthy, T. Org. Lett.
2010, 12, 84.
(17) Ke, F.; Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X. Org. Lett.
2011, 13, 454.
1c
2c
S
I
4
68
91
72
MeO
OMe
NO2
MeO
1d
2d
I
S
(18) Yavari, I.; Ghazanfarpour-Darjani, M.; Ahmadian, S.; Solgi,
Y. Synlett 2011, 1745.
5
O2N
O2N
(19) General Procedure for the Synthesis of Products 2
A mixture of aryl iodide (2 mmol), CuI (0.10 mmol), ligand
(1.1 mmol), and S8 (1.1 mmol) were added to an oven-dried
reaction tube equipped with a septum. The reaction tube was
evacuated and back-filled with argon. Under a counterflow
of argon, EIPA (0.258 g, 2 mmol) and DMSO (2 mL) were
added, and the mixture stirred at r.t. for 8 h. After complete
disappearance of aryl iodide (monitored by TLC), H2O (5
mL) was added, and the mixture was extracted with CH2Cl2
(3 × 5 mL). The combined organic phases were dried (on
MgSO4) and filtered before evaporation of the solvent. The
residue was purified on silica gel, eluting with PE–EtOAc
(20:1), to give product 2. Analytical and spectroscopic data
for all derivatives, except 2g–i have been reported
previously.19
1e
2e
S
I
6
Br
Br
Br
1f
2f
CF3
CF3
CF3
S
I
7
71
1g
2g
F3C
S
CF3
F3C
I
8
9
81
80
Bis(2-trifluoromethylphenyl)sulfane (2g)
Colorless oil; yield: 0.23 g (71%). IR (KBr): νmax = 2915,
1591, 1443, 1313, 1264, 1170, 1128, 1034, 756 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 7.24 (2 H, d, 3J = 8.0 Hz, 2
CH), 7.36–7.44 (4 H, m, 4 CH), 7.74 (2 H, d, 3J = 7.5 Hz, 2
CH). 13C NMR (125.7 MHz, CDCl3): δ = 123.6 (2 CF3, q,
1JCF = 272.0 Hz), 126.9 (2 CH, q, 3JCF = 5.5 Hz), 127.5 (2
CH), 131.0 (2 C, q, 2JCF = 30.2 Hz), 132.4 (2 CH), 134.7 (2
CH), 134.8 (2 C, q, 3JCF = 5.0 Hz). MS (EI, 70 eV): m/z (%)
= 322 [M + 1], 301 (55), 252 (33), 233 (99), 184 (59), 157
(50), 133 (17), 108 (36).
1h
2h
S
I
NC
CN
NC
1i
2i
from aryl iodides at ambient temperature. This protocol,
allowing the formation of two C–S bonds in a one-pot re-
action, is distinguished by avoiding the use of foul smell-
ing thiophenols and strong inorganic bases.
Bis(3-trifluoromethylphenyl)sulfane (2h)
Colorless oil; yield: 0.26 g (81%). IR (KBr): νmax = 2928,
1589, 1422, 1316, 1145, 755 cm–1. 1H NMR (500 MHz,
CDCl3) δ = 7.46 (2 H, d, 3J = 7.2 Hz, 2 CH), 7.49–7.55 (4 H,
m, 4 CH), 7.62 (2 H, s, 2 CH). 13C NMR (125.7 MHz,
CDCl3): δ = 123.6 (2 CF3, q, 1JCF = 271 Hz), 124.4 (2 CH, q,
3JCF = 3.5 Hz), 127.7 (2 CH, q, 3JCF = 3.7 Hz), 129.9 (2 CH),
131.9 (2 C, q, 2JCF = 32.4 Hz), 134.2 (2 CH), 136.2 (2 C). MS
(EI, 70 eV): m/z (%) = 322 [M + 1], 301 (26), 233 (69), 184
(35), 157 (40), 133 (11), 108 (25).
References and Notes
(1) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108,
3054.
(2) Monnier, F.; Taillefer, M. Angew. Chem. Int. Ed. 2009, 48,
2.
Synlett 2014, 25, 1121–1123
© Georg Thieme Verlag Stuttgart · New York

LETTER
Bis(4-cyanophenyl)sulfane (2i)
Copper-Catalyzed Synthesis of Symmetrical Diarylsulfanes
1123
CDCl3): δ = 110.9 (2 C), 118.1 (2 CN), 126.5 (4 CH), 132.8
(4 CH), 142.1 (2 C). MS (EI, 70 eV): m/z (%) = 236 [M + 1],
204 (14), 166 (11), 134 (100), 107 (30), 90 (51), 82 (15), 75
(24), 69 (45), 63 (46), 57 (16), 51 (16).
Colorless solid; mp 174–176 °C; yield: 0.19 g (80%). IR
(KBr): νmax = 3424, 2370, 2218, 1582, 1482, 818 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 7.55 (4 H, d, 3J = 8.4 Hz, 4
CH), 7.61 (4 H, d,3J = 8.4 Hz, 4 CH).13C NMR (125.7 MHz,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1121–1123

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