Thiol-free route to diaryl sulfides by Cu catalyzed coupling of sodium thiosulfate with aryl halides

Article abstract of DOI:10.1016/S1872-2067(16)62486-5

A method for the synthesis of diaryl sulfides from aryl halides in polyethylene glycol was reported. Inodorous Na₂S₂O₃·5H₂O, which is readily available as a stable salt, is an effective source of sulfur in the presence of CuI as catalyst.

Full text of DOI:10.1016/S1872-2067(16)62486-5

Chinese Journal of Catalysis 37 (2016) 1550–1554
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Thiol‐free route to diaryl sulfides by Cu catalyzed coupling of
sodium thiosulfate with aryl halides
Najmeh Nowrouzi*, Mohammad Abbasi, Hadis Latifi
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A method for the synthesis of diaryl sulfides from aryl halides in polyethylene glycol was reported.
Inodorous Na2S2O3·5H2O, which is readily available as a stable salt, is an effective source of sulfur in
the presence of CuI as catalyst.
Received 6 May 2016
Accepted 14 June 2016
Published 5 September 2016
© 2016, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Copper catalyst
Sulfide
Thiol
Sodium thiosulfate
1. Introduction
used for the in situ generation of thiol or thiolate. In 2013,
Jiang’s group [52] reported the first Pd catalyzed coupling reac‐
Nowadays, organosulfur chemistry attracts extensive atten‐
tion because sulfur containing building blocks are present in
many natural products and pharmaceuticals [1–8]. The search
for new methods for the synthesis of sulfides is a subject of
much current interest. Traditional sulfide construction involves
thiol alkylation or arylation [9–18], or the treatment of an or‐
ganometallic reagent with a disulfide molecule [19–23]. How‐
ever, the drawbacks of these methods include the utilization of
environmentally unfavorable and odorous thiols as starting
materials or generating them as byproducts. Thiols are also air
sensitive and are readily oxidized by atmospheric oxygen. To
overcome these problems, various sulfur‐transfer reagents for
in situ generation of thiols have been employed such as thiou‐
rea [24–28], potasium thioacetate [29], carbon disulfide
[30–34], metal sulfides [35,36], sulfonyl hydrazide [37,38],
ethyl xanthogenate [39], thiocyanate [40], thioacetamide [41],
and S8 [42–51]. Recently, Na2S2O3, which is readily available as
a stable solid and does not have any smell, was successfully
tion using Na2S2O3 as the sulfur reagent to get a substituted
1,4‐benzothiazine derivate.
Since then, this group has studied several intramolecular or
intermolecular C–S bond formation reactions using Na2S2O3 in
the presence of different metal catalysts. In 2014, they devel‐
oped a method for making aromatic sulfides by Pd catalyzed
cross coupling of aryl halides, alkyl halides, and Na2S2O3·5H2O
[53]. They also introduced a practical approach to construct
thioethers using aromatic amines and alkyl halides as starting
materials along with
a catalyst system composed of
CuSO4·5H2O/bipy/Na2S2O3·5H2O [54]. In another work, Jiang
and coworkers [55] developed a procedure for sulfide synthe‐
sis by cross coupling of 1‐aryltriazenes, Na2S2O3 and alkyl hal‐
ides, which employed CuSO4 as a catalyst, BF3‐Et2O as a pro‐
moter and water as solvent at room temperature under air. In
2014, a combination of Pd(dppf)Cl2 and dppf using odorless
Na2S2O3 as the sulfur source in DMF at 140 °C was used by Hou
et al. [56] to synthesize 2‐aminobenzo[b]‐thiophene com‐
* Corresponding author. Tel: +98‐77‐31222341; Fax: +98‐77‐33441494; E‐mail: nowrouzi@pgu.ac.ir, nnoroozy@yahoo.com
DOI: 10.1016/S1872‐2067(16)62486‐5 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 37, No. 9, September 2016

Najmeh Nowrouzi et al. / Chinese Journal of Catalysis 37 (2016) 1550–1554
1551
pounds. Lately, Rostami et al. [42] reported the thio‐arylation
reactions of alkyl halides with nitroarenes using Na2S2O3·5H2O
as a sulfide surrogate and Cu salts as catalyst. In most of these
methods, Pd complex catalysts were employed for the
thio‐arylation of aryl halides. In this regard, developing a cata‐
lyst system other than Pd is of interest. To date, thioetherifica‐
tion of aryl halides in the presence of a copper based catalyst
system and Na2S2O3·5H2O as a convenient and environmentally
friendly source of sulfur has not been reported.
(4‐dimethylaminopyridine) (20 mo%) as ligand in DMSO at
120 °C under atmospheric conditions. The desired product was
obtained in 95% yield after 12 h (Table 1, entry 1). Performing
the reaction in toluene, CH3CN and H2O under reflux conditions
did not result in the desired product, but left the starting mate‐
rials intact (Table 1, entries 2–4). Moreover, when the reaction
was performed in polyethylene glycol (PEG‐200), which is an
eco‐friendly media, similar results were obtained to the DMSO
results (Table 1, entry 5). Polyethylene glycols (PEGs) and their
derivatives are non‐toxic, cheap and easily available, and ther‐
mally stable and recoverable, and are a suitable medium for
environmentally friendly and safe chemical reactions. There‐
fore, the subsequent reactions were performed in PEG‐200.
Lowering the temperature from 120 to 100 °C resulted in a
longer reaction time and a lower yield (Table 1, entry 6). When
the temperature of the reaction was raised to 140 °C, no im‐
provement of the product yield and reaction rate was observed
(Table 1, entry 7). Control experiments confirmed that no con‐
version occurred without a catalyst (Table 1, entry 8). It was
further observed that increasing the catalyst loading beyond 20
mol% did not affect the reaction appreciably, while in the
presence of 10 mol% of the catalyst, the reaction did not reach
completion even after 24 h (Table 1, entries 9 and 10). The
presence of a ligand was necessary for the reaction and the
reaction did not occur under ligand‐free conditions (Table 1,
entry 11). The reaction was also tested with other ligands such
as L‐proline and DABCO. While L‐proline gave 30% of yield
(Table 1, entry 12), DABCO failed to give any product (Table 1,
entry 13).
2. Experimental
2.1. General
All chemicals used were purchased from the Fluka, Merck,
or Aldrich chemical companies. The products were character‐
ized by the comparison of their spectral and physical data with
those of reference samples.
2.2. Typical procedure for the synthesis of diphenylsulfane from
iodobenzene
A mixture of Na2S2O3·5H2O (1.1 mmol, 0.273 g), iodoben‐
zene (2.0 mmol, 0.22 mL), CuI (20 mol%, 0.038 g) and DMAP
(20 mol%, 0.024 g) was added to a flask containing PEG‐200 (1
mL). The mixture was heated at 120 °C with stirring and the
reaction was followed by TLC analysis. After completion of the
reaction, which was detected by TLC (12 h), the mixture was
cooled to room temperature and the coupled product was ex‐
tracted with ethyl acetate (3×3 mL). The solvent was evapo‐
rated and the crude mixture was purified by column chroma‐
tography over silica gel using n‐hexane as the eluent to give
pure diphenylsulfane as a colourless liquid in 94% yield.
Having identified the optimal conditions (Table 1, entry 5),
the substrate scope of this reaction was investigated. As shown
in Table 2, aryl iodides bearing both electron‐withdrawing and
electron‐donating groups, such as the nitro (Table 2, entry 5),
methyl (Table 2, entry 2), methoxy (Table 2, entry 3) and amino
1
Diphenylsulfane (Table 2, entry 1). H NMR (250 MHz,
CDCl3): H = 7.25–7.16 (m, 10H). Anal. Calcd. for (C12H10S): C,
77.38; H, 5.41; S, 17.21. Found: C, 77.30; H, 5.35; S, 17.35.
Di‐p‐tolylsulfane (Table 2, entry 2). 1H NMR (250 MHz,
CDCl3): H = 7.20–7.16 (m, 4H), 6.77–6.71 (m, 4H), 2.33 (s, 6H).
Anal. Calcd. for (C14H14S): C, 78.46; H, 6.58; S, 14.96. Found: C,
78.61; H, 6.52; S, 14.87.
Bis(4‐methoxyphenyl)sulfane (Table 2, entry 3). 1H NMR
(250 MHz, CDCl3): H = 7.38–7.30 (m, 4H), 6.78–6.74 (m, 4H),
3.72 (s, 6H). Anal. Calcd. for (C14H14O2S): C, 68.26; H, 5.73; S,
13.02. Found: C, 68.16; H, 5.70; S, 13.15.
4,4’‐Thiodibenzonitrile (Table 2, entry 10). 1H NMR (250
MHz, CDCl3): H = 7.56–7.52 (m, 4H), 7.36–7.32 (m, 4H). Anal.
Calcd. for (C14H8N2S): C, 71.16; H, 3.41; N, 11.86; S, 13.57.
Found: C, 71.28; H, 3.37; N, 11.95; S, 13.40.
Table 1
Optimization of the reaction parameters for the reaction of iodoben‐
zene (2.0 mmol) with Na2S2O3·5H2O (1.1 mmol) in the presence of CuI
as catalyst.
S
I
CuI, Ligand
.
Na2S2O3 5H2O
+
Solvent, 
Ligand Time Yield*
Catalyst
(mol%)
Entry
Solvent
T (°C)
(20 mol%) (h)
(%)
1
2
3
4
5
6
7
8
20
20
20
20
20
20
20
—
30
10
20
20
20
DMSO
Toluene
CH3CN
H2O
PEG
PEG
PEG
PEG
PEG
PEG
120
Reflux
Reflux
100
120
100
140
120
120
120
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
—
12
24
24
24
12
24
12
24
12
24
24
24
24
95
—
—
—
94
50
94
—
95
60
—
30
—
3. Results and discussion
9
As a continuation of our ongoing research on organosulfur
chemistry [57–62], we were interested in examining CuI as the
pre‐catalyst for the thio‐arylation of aryl halides in the pres‐
ence of Na2S2O3·5H2O. To test this, we performed the reaction
of iodobenzene (2.0 mmol) with Na2S2O3·5H2O (1.1 mmol) in
the presence of CuI (20 mol%) as catalyst and DMAP
10
11
12
13
PEG
PEG
PEG
120
100
L‐proline
140
DABCO
* Isolated yield.

1552
Najmeh Nowrouzi et al. / Chinese Journal of Catalysis 37 (2016) 1550–1554
ONa
Table 2
S
S
O
Synthesis of diaryl sulfides from aryl halides catalyzed by CuI in the
presence of Na2S2O3·5H2O in PEG‐200.
III
Ph
ONa
Cu
X
S
X
I
CuI, DMAP
PhX
.
Na2S2O3 5H2O
PEG200, 120 oC
NaX
ONa
Z
Z
Z
Entry
ArX
Time (h) Yield * (%)
Ref.
I
O
I
CuI
Ph Cu
S
S
1
2
3
12
14
15
94
85
85
[28]
[28]
[28]
O
I
I
I
NaX
O
O
O
S
Cu
S
O
S
Ph
S
ONa
H3C
H3CO
H2N
Ph
O
I
II
III
Ph
I
Cu
X
I
I
Cu
S
4
5
15
11
80
90
[41]
[28]
SO3
I
Ph
III
CuI
PhX
O2N
CH3
PhSPh
I
6
48
—
—
Scheme 1. Mechanism for symmetric sulfide synthesis.
Br
Slightly longer reaction times compared with the io‐
do‐analogues were required (Table 2, entries 7–11). This cata‐
lyst system was not efficient for chloro arenes. When the cata‐
lyst system was applied for 4‐chlorobenzonitrile, the reaction
did not proceed at all and the starting material was isolated
intact after an appropriate reaction time (Table 2, entry 12).
On the basis of the literature [53–55], a reaction pathway is
presented in Scheme 1. First, a Cu(III) species was generated by
the oxidative addition of Cu(I) to the C–X bond of aryl halide.
The Cu(III) species subsequently reacted with Na2S2O3 to give
intermediate I. Reductive elimination of intermediate I pro‐
duced the aryl thiolsulfate along with the CuI catalyst. Then, the
aryl thiolsulfate reacted with the arylated Cu(III) halide (gen‐
erated in situ from aryl halide and CuI) to give intermediate II,
which was transform to III by releasing SO3. Finally, the subse‐
quent reductive elimination from III yielded diaryl sulfide and
regenerated the CuI catalyst.
7
8
14
15
93
81
[28]
[28]
Br
Br
H3C
H2N
9
17
12
85
88
[41]
[41]
[28]
Br
Br
Cl
10
NC
O2N
NC
11
12
12
48
89
—
Reaction conditions: aryl halide (2.0 mmol), Na2S2O3·5H2O (1.1 mmol),
DMAP (20 mol%), CuI (20 mol%), PEG‐200 (1 mL), 120 °C.
* Isolated yield.
4. Conclusions
Cu catalyzed coupling of aryl halides and Na2S2O3·5H2O was
developed which gave symmetrical diaryl sulfides in excellent
yields. A variety of functional groups on the aryl halides were
tolerated. Na2S2O3·5H2O was used as a sulfur source. This is an
odorless, stable, commercially available, easily handled and
environmentally friendly salt. This route to sulfides avoids the
use of thiol as the coupling partner or byproduct, which avoid‐
ed its facile oxidation and unpleasant smell. The use of a green
solvent and an inexpensive catalyst are the other advantages of
this system.
groups (Table 2, entry 4) all worked well to give products in
excellent yields. However, in case of electron‐releasing groups,
a slightly longer reaction time was required for the completion
of the reaction. As shown in entry 6 in Table 2, the target prod‐
uct was not obtained in the case of 2‐methyliodobenzene even
after prolonged reaction time, which was probably due to the
steric hindrance on the substrate. Aryl bromides bearing elec‐
tron‐withdrawing and electron-donating groups as well as aryl
iodides afforded the desired products in excellent yields.

Najmeh Nowrouzi et al. / Chinese Journal of Catalysis 37 (2016) 1550–1554
1553
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Graphical Abstract
Chin. J. Catal., 2016, 37: 1550–1554 doi: 10.1016/S1872‐2067(16)62486‐5
Thiol‐free route to diaryl sulfides by Cu catalyzed coupling of sodium thiosulfate with aryl halides
Najmeh Nowrouzi *, Mohammad Abbasi, Hadis Latifi
Persian Gulf University, Iran
Cu catalyzed coupling of aryl halides and Na2S2O3·5H2O was developed to make symmetrical diaryl sulfides.

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