Efficient recyclable CuI-nanoparticle-catalyzed S-arylation of thiols with aryl halides on water under mild conditions

Article abstract of DOI:10.1039/c2ob06795a

CuI nanoparticles efficiently catalyzed the C-S cross coupling of aryl and alkyl thiols with aryl halides in the absence of ligands on water under mild conditions. A wide range of diaryl sulfides and aryl alkyl sulfides are synthesized in good to excellent yields utilizing this protocol. This procedure is particularly noteworthy given its mild conditions, avoiding the undesired formation of disulfides through oxidation of thiols. The recovery and successful reutilization of the catalyst is described. Furthermore, the directed synthesis of bisarylated product is presented. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2ob06795a

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 2562
www.rsc.org/obc
PAPER
Efficient recyclable CuI-nanoparticle-catalyzed S-arylation of thiols with aryl
halides on water under mild conditions†
Hua-Jian Xu,*a Yu-Feng Liang,a Xin-Feng Zhoua and Yi-Si Feng*b
Received 25th October 2011, Accepted 19th January 2012
DOI: 10.1039/c2ob06795a
CuI nanoparticles efficiently catalyzed the C–S cross coupling of aryl and alkyl thiols with aryl halides in
the absence of ligands on water under mild conditions. Awide range of diaryl sulfides and aryl alkyl
sulfides are synthesized in good to excellent yields utilizing this protocol. This procedure is particularly
noteworthy given its mild conditions, avoiding the undesired formation of disulfides through oxidation of
thiols. The recovery and successful reutilization of the catalyst is described. Furthermore, the directed
synthesis of bisarylated product is presented.
requirement of microwave irradiation,7r–t poor efficiency with
Introduction
aliphatic thiols,7u–w and more critical is that the majority of them
do not suitable for aryl bromide.7s–t,w–ad Otherwise, of the
Catalytic methods for the formation of carbon–sulfur bonds are
of great important in general organic synthesis as well as in
materials science applications and in the pharmaceutical indus-
try.1 Transition-metal-catalyzed cross-coupling of aryl halides
with thiols for the formation of aryl sulfides is one of the most
powerful tools.2 A variety of Pd,3 Co,4 Ni,5 In,6 Cu7 and Fe8
catalysts have been studied for the development of efficient, ben-
eficial and environmentally friendly conditions for S-arylation.
However, S-arylation has been comparatively less studied than
N-arylation and O-arylation due to the tendency of thiols to
undergo oxidative homocoupling S–S reactions.8a
From an industrial viewpoint, the development of Cu-
catalyzed methods for arylation of thiols with aryl halides is still
attractive owing to the advantages of copper over other metals,
like its ready availability and low toxicity.9 The traditional
copper-mediated reactions suffer from many drawbacks such as
high reaction temperature, the usual requirement of stoichio-
metric copper salts, long reaction time, sensitivity to functional
groups on the aryl halide and irreproducibility. In fact, only in
recent years have considerable efforts been made to improve the
efficiency of this reaction and they have made a great contri-
bution with the use of copper salts in the presence of several
ligands.7a–q Some ligand-free copper-catalyzed C–S coupling
reactions have also been developed.7r–ad However, many of these
ligand-free methods still have certain shortcomings, as of the
limited number of methods available employing copper catalysts,
most involve the use of a non-reusable catalytic system and toxic
organic solvents.
Metal nanoparticles have received much attention due to the
advantages offered by these “semi-heterogeneous catalysts”.
They both have the characteristics of heterogeneous catalysis
(recovery and recyclability) and those of homogeneous catalysis
(relatively low catalyst loadings and good selectivity). In
addition, because of their large surface area, metal nanoparticles
usually showed enhanced reactivity under mild conditions.10
Thus, transition-metal nanoparticles have been used widely as
catalyst for organic synthesis.11
The development of environmentally friendly catalytic
systems, in particular using water as the reaction medium, has
drawn much attention in recent years due to this green solvent
being non-toxic, low cost, widely available and giving greater
chemoselectivity, as compared with organic solvents.12 Con-
sidering our experience in this field with the application of
“on-water chemistry” to selective synthesis of phenols, anilines
and thiophenols from aryl halides catalyzed by CuI nanoparti-
cles,13 we judged it certainly appealing to explore and extend
the scope of such advantageous protocol. Herein, we report that
CuI nanoparticles efficiently catalyzed the C–S cross-coupling of
aryl and alkyl thiols with aryl halides on water under mild
conditions.
aSchool of Medical Engineering, Hefei University of Technology, Hefei
230009, P. R. China
Results and discussion
bSchool of Chemical Engineering, Hefei University of Technology and
Anhui Key Laboratory of Controllable Chemistry Reaction & Material
Chemical Engineering, Hefei 230009, P. R. China. E-mail: hjxu@hfut.
edu.cn; Fax: +86-551-2904405; Tel: +86-551-2904353
†Electronic supplementary information (ESI) available: Experimental
details and spectral data. See DOI: 10.1039/c2ob06795a
In the first stage of the study, the coupling reaction was carried
out with iodobenzene and benzenethiol in the presence of
1.5 mol% CuI nanoparticles using nBu4NOH as the base on
water at room temperature for 24 h, and the corresponding
2562 | Org. Biomol. Chem., 2012, 10, 2562–2568
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 1 CuI nanoparticles catalyzed C–S cross-coulping of thiophenol
with aryl halides on watera
Entry
X
[Cu] (mol%)
Base
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
I
I
I
I
I
I
I
I
I
I
I
I
I
I
Br
Br
Br
Br
Cl
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (np(1.5))
CuI (10)
nBu4NOH
nBu4NOH
nBu4NOH
CsOH
KOH
Cs2CO3
NEt3
Me4NOH
Et4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
nBu4NOH
r.t.
40
50
50
50
50
50
50
50
50
50
50
50
50
50
80
90
80
80
51
79
93
11
9
Trace
7
67
78
27
19
17
21
Trace
21
61
45
trace
trace
9
10
11
12
13
14
15c
16c
17c
18c
19c
CuBr (10)
CuCl (10)
Cu2O (10)
—
CuI (np(3.0))
CuI (np(3.0))
CuI (np(5.0))
CuI (10)
CuI (np(5))
Scheme 1 CuI nanoparticle catalyzed S-arylation of aryl iodides with
aryl thiols on water. CuI nanoparticles (1.5 mol%), Ar–I (1.0 mmol),
Ar–SH (1.2 mmol), 40% nBu4NOH aq. (2.0 mL/3.0 equiv) at 50 °C
under Ar for 24 h; isolated yield. At room temperature.
a Reaction conditions: halogenated benzene (1.0 mmol), benzenethiol
(1.2 mmol), base (3.0 equiv), H2O (2.0 mL) under Ar for 24 h.
b Determined by GC (average of two GC runs). c Reaction time is 48 h.
np = nanoparticles. r.t. = room temperature.
coupling product was obtained in 51% yield (Table 1, entry 1).
Surprisingly, when the temperature was elevated to 50 °C, the
yield increased to 93% (Table 1, entry 3). It’s noteworthy that
the low temperature presumably greatly reduced the amount of
disulfide byproducts (<4%) through the facile oxidation of
thiols.14 Among the bases studied, CsOH, KOH, Cs2CO3, NEt3,
Me4NOH and Et4NOH, provided lower yields than nBu4NOH
(Table 1, entries 4–9). Of the copper catalysts investigated, CuI
nanoparticles were significantly superior to CuI, CuBr, CuCl and
Cu2O (Table 1, entries 10–13). Only a trace amount of the
product was observed in the absence of the catalyst (Table 1,
entry 14).
In order to extend the scope of this catalytic system, we exam-
ined a wide array of aryl iodides and aryl thiols. As shown in
Scheme 1, the presence of electron donating methyl or methoxy
groups or electron withdrawing carboxyl or chloro groups on the
phenyl rings both in the aryl iodides and the aryl thiols did not
cause significant changes in yields. Sterically more hindered
substrates such as 2-methyliodobenzene, 2-chloro-iodobenzene
and 2,6-dimethylbenzenethiol were also proved to be excellent
substrates. In addition, the coupling reaction between heteroaryl
iodides and aryl thiols were successfully performed and the cor-
responding heteroaromatic sulfides in excellent yields were
obtained. 4-iodo-1,2-dimethylbenzene, 4-fluoroiodo-benzene, 4-
iodobiphenyl and 1-iodonaphthalene can react with aryl thiols
even at room temperature in moderate to good yields.
Scheme 2 CuI nanoparticle catalyzed S-arylation of aryl iodides with
alkyl thiols on water. CuI nanoparticles (1.5 mol%), Ar–I (1.0 mmol),
R′-CH2SH (1.2 mmol), 40% nBu4NOH aq. (2.0 mL/3.0 equiv) at 50 °C
under Ar for 24 h; isolated yield. At room temperature.
dodecanethiol all afforded the corresponding products
(Scheme 2). However, an increase in the size of the alkyl chain
led to a slight decrease in the yield of the aryl alkyl sulfides.
Aliphatic secondary thiols also reacted. For example, cyclohexa-
nethiol reacted with 2-methyliodobenzene to give the product in
92% yield. Aryl iodides containing heteroatoms also reacted to
Interestingly, the methodology described herein was not
limited to the use of aryl thiols. Indeed, these reaction conditions
were also suitable for the coupling of alkyl thiols with aryl
iodides. Butane-, pentane-, hexane-, heptanes-, octane-, and
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2562–2568 | 2563

View Article Online
Scheme 4 Synthesis of bisarylated product.
1,4-didiiodobenzene underwent the cross-coupling reaction with
phenthiol, hexane-1-thiol and cyclohexanethiol to give 1,4-bis-
(phenylthio)benzene, 1,4-bis(hexylthio)benzene and 1,4-bis-
(cyclohexylthio)benzene in 97%, 95% and 91% yield. The two
mercapto groups of hexane-1,6-dithiol could react with iodo-
benzene, 1-iodonaphthalene and 2-iodopyridine to product 1,6-
bis(phenylthio)-hexane, 1,6-bis(naphthalen-1-ylthio)hexane and
1,6-bis(pyridin-2-ylthio)hexane in 93%, 94% and 93% yield,
respectively.
Scheme 3 CuI nanoparticle catalyzed S-arylation of aryl bromides
with aryl thiols and alkyl thiols on water. CuI nanoparticles (3.0 mol%),
Ar–Br (1.0 mmol), R′-SH (1.2 mmol), 40% nBu4NOH aq. (2.0 mL/3.0
equiv) at 80 °C under Ar for 48 h; isolated yield.
Finally, the catalyst was recyclable with slight loss of activity
(Table 2). We consider the loss of catalyst during the separation
process was the main factor responsible for the slight decrease of
catalytic activity during the recycling tests, and thus the runs
were made in 10 mmol scale in order to facilitate the catalyst
recovery. After completion of S-arylation of phenthiol with
4-fluoroiodobenzene, the catalyst was recovered from the reaction
mixture by centrifugation and reused for the fresh reaction. It
was found that the catalyst could be reused at least four times
with a slight decrease in activity. In case of cross-coupling of
phenthiol with 4-fluorobromobenzene, the reuse runs also pro-
ceeded well for each cycle. In the TEM analysis of CuI nanopar-
ticles (Fig. S1a, b†), interestingly, the shape and size of the
nanoparticles remained unchanged before and after the reaction.
Furthermore, the XRD analysis exhibited identical peaks for
both the fresh and recovered CuI nanoparticles (Fig. S1c, d†).
give the corresponding aryl alkyl sulfides. The C–S bond for-
mation of iodobenzene with hexane-1-thiol and cyclohexanethiol
can be accomplished at room temperature in 83% and 69%
yields respectively.
With regard to aryl bromides, elevation of the reaction temp-
erature to 80 °C, accretion of the amount of the catalyst to 3 mol
% and prolongation of the reaction time to 48 h were required to
obtain satisfactory yields. Under these revised conditions, aryl
bromides could couple with a variety of aryl thiols in yields
between 47% and 94% (Scheme 3). For electron-poor aryl bro-
mides, such as 4-trifluoromethylbromobenzene, 4-fluoro-bromo-
benzene and 4-bromobenzoic acid, high yields were obtained. In
the case of electron-rich aryl bromides, moderate isolated yields
could be obtained. The coupling reaction of sterically hindered
aryl bromides with aryl thiols could occur, although the yields
were lower than those of iodides analogs. To our delight, aryl
bromides also could be coupled successfully with alkyl thiols
in moderate to good yields under this improved condition.
Butanethiol, pentanethiol, hexanethiol and phenyl-methanethiol
were S-arylated in good yields. An ortho-substituted bromoben-
zene and heteroaryl bromide were compatible in this coupling
reaction.
Conclusions
To sum up, we have developed a reusable and efficient CuI
nanoparticle catalytic system for the C–S bond formation of both
aryl and alkyl thiols with aryl iodides and aryl bromides without
ligand assisted on water under relative low temperature (no
higher than 80 °C). A variety of diaryl sulfides and aryl alkyl
sulfides are synthesized with good chemoselectivity and func-
tional group tolerance. Many aryl iodides could translate even at
room temperature. The formation of disulfide side product
through the facile oxidation of thiols was repressed efficiently
due to the very mild conditions. Synthesis of bisarylated product
Unfortunately, when aryl chlorides were employed, very low
yields were obtained. For example, the reactions of 4-trifluoro-
methylchlorobenzene and 4-nitrochlorobenzene with phenthiol
with 5 mol% CuI nanoparticles at 80 °C for 72 h giving the cor-
responding product in only 21% and 16% yields, respectively.
This catalytic system can also be applied to synthesis
of bisarylated product (Scheme 4). Both iodine groups of
2564 | Org. Biomol. Chem., 2012, 10, 2562–2568
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 2 Reuse studies of CuI nanoparticles in 10 mmol scalea
dried over Na2SO4, filtered and concentrated in vacuum to yield
the crude product. The obtained crude was purified by column
chromatography on silica gel and the product was dried under
vacuum for at least 0.5 h.
Diphenylsulfane (5a).8a Iodobenzene was allowed to react
with benzenethiol, column chromatography (petroleum ether/
ethyl acetate 100/1), isolated as a colorless oil (173 mg, 93%
yield). 1H NMR (300 MHz, CDCl3): δ 7.35–7.30 (m, 5H),
7.29–7.19 (m, 5H) ppm. 13C NMR (75 MHz, CDCl3): δ 135.8,
131.0, 129.2, 127.0 ppm. HRMS calcd for C12H10S (M+):
186.0503; found: 186.0541. Elemental analysis: calcd C, 77.37;
H, 5.41; S, 17.21%; found C, 77.35; H, 5.37; S, 17.16%.
Catalyst recovery (%)
Product yieldc (%)
Run
X = I
X = Br
X = I
X = Br
1
96
94
93
92
97
94
93
93
94
92
92
90
86
84
84
84
2b
3b
4b
a X = I: CuI nanoparticles (1.5 mol%), 4-fluoroiodobenzene (10 mmol),
phenthiol (12 mmol), 40% nBu4NOH aq. (20 mL/3.0 equiv) at 50 °C
under Ar for 24 h; X = Br: CuI nanoparticles (3.0 mol%), 4-
fluorobromobenzene (10 mmol), phenthiol (12 mmol), 40% nBu4NOH
aq. (20 mL/3.0 equiv) at 80 °C under Ar for 48 h. b The recovered
catalyst was used under identical reaction conditions to those for the first
run. c Determined by GC.
Biphenyl-4-yl(p-tolyl)sulfane
(5q). 4-Iodobiphenyl
was
allowed to react with 4-methylbenzenethiol, column chromato-
graphy (petroleum ether/ethyl acetate 100/1), isolated as a white
solid (252 mg, 91% yield). M.p. = 106–108 °C. 1H NMR
(300 MHz, CDCl3): δ 7.59–7.56 (d, J = 7.2 Hz, 2H), 7.53–7.50
(d, J = 8.4 Hz, 2H), 7.47–7.42 (t, J = 7.5 Hz, 2H), 7.38–7.34
(m, 5H), 7.19–7.17 (d, J = 7.8 Hz, 2H), 2.38 (s, 3H) ppm. 13C
NMR (75 MHz, CDCl3): δ 140.4, 139.4, 137.7, 136.3, 132.4,
131.3, 130.2, 130.1, 128.8, 127.7, 127.4, 126.9, 21.2 ppm.
HRMS calcd for C19H16S (M+): 276.0973; found: 276.0976.
Elemental analysis: calcd C, 82.56; H, 5.83; S, 11.60%; found
C, 82.47; H, 5.71; S, 11.53%.
has also been demonstrated. The catalyst can be easily recovered
and reused.
Experimental section
General procedure for preparation of CuI nanoparticles
Biphenyl-4-yl(4-chlorophenyl)sulfane(5r). 4-Iodobiphenylwas
allowed to react with 4-chlorobenzenethiol, column chromato-
graphy (petroleum ether/ethyl acetate 100/1), isolated as a white
solid (290 mg, 98% yield). M.p. = 122–125 °C. 1H NMR
(300 MHz, CDCl3): δ 7.55–7.50 (t, J = 8.4 Hz, 4H), 7.43–7.32
(m, 5H), 7.30–7.19 (m, 4H) ppm. 13C NMR (75 MHz, CDCl3):
δ 140.4, 140.2, 134.6, 134.2, 133.1, 132.1, 131.6, 129.4, 128.9,
128.0, 127.6, 127.0 ppm. HRMS calcd for C18H13ClS (M+):
296.0426; found: 296.0432. Elemental analysis: calcd C, 72.84;
H, 4.41; Cl, 11.94; S, 10.80%; found C, 72.76; H, 4.35; Cl,
11.83; S, 10.70%.
0.464 g (4 mmol) of dimethylglyoxime (dmgH) and 0.400 g
(2 mmol) of Cu(OAc)2·H2O were added into 50 ml of absolute
ethanol in sequence, which was stirred at 0 °C for 30 min to get
brown precipitates Cu(dmg)2. Then the collected precipitates dis-
persed in 50 ml of absolute ethanol again, 0.664 g (4 mmol) KI
was added and stirred vigorously for 2 h. After that, the mixture
was transferred into 60 mL Teflon-lined stainless steel autoclave.
The autoclave was sealed and heated at 180 °C for 6 h, and then
the reactor bomb is allowed to cool to room temperature. Black
precipitates were obtained, then centrifugalized and washed
with ethanol and deionized water for three times to ensure the
removal of the impurities. The final product was then dried in a
vacuum oven at room temperature for 12 h.
3-(o-Tolylthio)pyridine (5t). 3-Iodopyridine was allowed
to react with 2-methylbenzenethiol, column chromatography
(petroleum ether/ethyl acetate 20/1), isolated as a colorless oil
(175 mg, 87% yield). 1H NMR (300 MHz, CDCl3): δ 8.44–8.39
(m, 2H), 7.44–7.40 (m, 1H), 7.35–7.32 (d, J = 7.5 Hz, 1H),
7.27–7.22 (m, 2H), 7.19–7.13 (m, 2H), 2.38 (s, 3H) ppm. 13C
NMR (75 MHz, CDCl3): δ 149.8, 147.1, 140.5, 136.3, 134.0,
133.7, 131.8, 130.9, 128.7, 127.0, 123.8, 20.6 ppm. HRMS
calcd for C12H11NS (M+): 201.0612; found: 201.0612. Elemen-
tal analysis: calcd C, 71.60; H, 5.51; N, 6.96; S, 15.93%; found
C, 71.33; H, 5.45; N, 6.48; S, 15.82%.
General procedure for C–S coupling catalyzed by CuI
nanoparticles on water
After standard cycles of evacuation and back-filling with dry and
pure argon, an oven-dried Schlenk tube equipped with a mag-
netic stirring bar was charged with CuI nanoparticles (1.5–5 mol
%), the aryl halides if a solid (1 mmol), aryl thiols if a solid
(1.2 mmol). The tube was evacuated and backfilled with argon
(this procedure was repeated three times). Under a counter flow
of argon, aryl halides if a liquid (1 mmol), aryl thiols if a liquid
(1.2 mmol) and degassed 40% tetra-n-butylammonium hydrox-
ides water solution (2.0 mL, 3.0 equiv) were added by syringe.
The tube was sealed and the mixture was allowed to stir at r.t.
−80 °C for 24–72 h. The reaction mixture was then allowed to
cool to ambient temperature. Then, the mixture was quenched by
the addition of a saturated NH4Cl solution (3 mL) and extracted
with ethyl acetate (3 × 10 mL). Organic layers were gathered,
Benzyl(phenyl)sulfane (6a).7y Iodobenzene was allowed
to react with phenylmethanethiol, column chromatography
(petroleum ether/ethyl acetate 100/1), isolated as a colorless oil
(194 mg, 97% yield). 1H NMR (300 MHz, CDCl3): δ 7.31–7.16
(m, 10H), 4.10 (s, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ
137.5, 136.5, 129.9, 129.5, 128.9, 128.5, 127.2, 126.4,
39.1 ppm. HRMS calcd for C13H12S (M+): 200.0660; found:
200.0662. Elemental analysis: calcd C, 77.95; H, 6.04; S,
16.01%; found C, 77.40; H, 6.17; S, 16.33%.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2562–2568 | 2565

View Article Online
Benzyl(3,4-dimethylphenyl)sulfane (6g). 4-Iodo-1,2-dimethyl-
benzene was allowed to react with phenylmethanethiol, column
chromatography (petroleum ether/ethyl acetate 100/1), isolated
268.1286; found: 268.1288. Elemental analysis: calcd
C, 80.54; H, 7.51; S, 11.95%; found C, 80.44; H, 7.37; S,
11.98%.
1
as a colorless oil (224 mg, 98% yield). H NMR (300 MHz,
1-(4-(m-Tolylthio)phenyl)ethanone (5ah). 1-(4-Iodophenyl)-
ethanone was allowed to react with 3-methylbenzenethiol,
column chromatography (petroleum ether/ethyl acetate 100/1),
isolated as a yellow solid (218 mg, 90% yield). 1H NMR
(300 MHz, CDCl3): δ 7.82–7.80 (d, J = 8.7 Hz, 2H), 7.32
(s, 1H), 7.30–7.28 (d, J = 5.4 Hz, 2H), 7.22–7.19 (d, J = 8.7 Hz,
3H), 2.54 (s, 3H), 2.36 (s, 3H) ppm. 13C NMR (75 MHz,
CDCl3): δ 197.0, 145.2, 139.6, 134.5, 134.4, 131.6, 130.9,
129.6, 129.5, 128.8, 127.3, 26.4, 21.2 ppm. HRMS calcd
for C15H14OS (M+): 242.0765; found: 242.0742. Elemental
analysis: calcd C, 74.34; H, 5.82; O, 6.60; S, 13.23%; found C,
74.22; H, 5.93; O, 6.25; S, 13.17%.
CDCl3): δ 7.45–7.34 (m, 6H), 7.23–7.14 (m, 2H), 4.21 (s, 2H),
2.34 (s, 6H) ppm. 13C NMR (75 MHz, CDCl3): δ 137.9, 137.2,
135.2, 131.8, 130.1, 129.4, 128.9, 128.4, 128.0, 127.0, 39.7,
19.6, 19.3 ppm. HRMS calcd for C15H16S (M+): 228.0973;
found: 228.0975. Elemental analysis: calcd C, 78.90; H, 7.06; S,
14.04%; found C, 78.77; H, 7.18; S, 14.06%.
Hexyl(phenyl)sulfane (6k).7y Iodobenzene was allowed to
react with hexane-1-thiol, column chromatography (petroleum
ether/ethyl acetate 100/1), isolated as a colorless oil (190 mg,
1
98% yield). H NMR (300 MHz, CDCl3): δ 7.32–7.24 (m, 4H),
7.16–7.12 (t, J = 7.2 Hz, 1H), 2.93–2.88 (t, J = 7.2 Hz, 2H),
1.69–1.59 (m, 2H), 1.46–1.37 (m, 2H), 1.30–1.25 (m, 4H),
0.90–0.85 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
δ 137.1, 128.9, 128.8, 125.6, 33.6, 31.3, 29.1, 28.5, 22.5,
14.0 ppm. HRMS calcd for C12H18S (M+): 194.1129; found:
194.1136. Elemental analysis: calcd C, 74.16; H, 9.34; S,
16.50%; found C, 74.28; H, 9.17; S, 16.30%.
2-(Hexylthio)pyridine (6ad). 2-Bromopyridine was allowed to
react with hexane-1-thiol, column chromatography (petroleum
ether/ethyl acetate 10/1), isolated as a colorless oil (127 mg,
1
65% yield). H NMR (300 MHz, CDCl3): δ 8.41–8.39 (d, J =
6.3 Hz, 1H), 7.46–7.34 (t, J = 8.1 Hz, 1H), 7.15–7.13 (d, J = 8.1
Hz, 1H), 6.95–6.91 (t, J = 4.8 Hz, 1H), 3.17–3.12 (t, J = 7.2 Hz,
2H), 1.74–1.64 (m, 2H), 1.48–1.39 (m, 2H), 1.33–1.25 (m, 4H),
0.90–0.85 (t, J = 6.9 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
δ 158.6, 148.3, 134.7, 121.1, 118.0, 30.3, 29.0, 28.3, 27.6, 21.5,
12.9 ppm. HRMS calcd for C11H17NS (M+): 195.1082; found:
195.1080. Elemental analysis: calcd C, 67.64; H, 8.77; N, 7.17;
S, 16.42%; found C, 67.38; H, 8.77; N, 7.15; S, 16.31%.
(3,4-Dimethylphenyl)(octyl)sulfane (6o). 4-Iodo-1,2-dimethyl-
benzene was allowed to react with octane-1-thiol, column
chromatography (petroleum ether/ethyl acetate 100/1), isolated
1
as a colorless oil (213 mg, 85% yield). H NMR (300 MHz,
CDCl3): δ 7.14 (s, 1H), 7.11–7.08 (d, J = 7.8 Hz, 1H),
7.06–7.03 (d, J = 7.8 Hz, 1H), 2.90–2.85 (t, J = 7.5 Hz, 2H),
2.24–2.23 (d, J = 3.3 Hz, 6H), 1.68–1.58 (m, 2H), 1.45–1.27
(m, 10H), 0.91–0.86 (t, J = 6.3 Hz, 3H) ppm. 13C NMR
(75 MHz, CDCl3): δ 137.1, 134.4, 133.4, 131.0, 130.1, 127.1,
34.3, 31.8, 29.3, 29.2, 29.1, 28.8, 22.6, 19.7, 19.2, 14.0 ppm.
HRMS calcd for C16H26S (M+): 250.1755; found: 250.1757.
Elemental analysis: calcd C, 76.73; H, 10.46; S, 12.80%; found
C, 76.37; H, 10.31; S, 12.59%.
1,4-Bis(phenylthio)benzene. 1,4-Diiodobenzene was allowed
to react with benzenethiol, column chromatography (petroleum
ether/ethyl acetate 100/1), isolated as a white solid (286 mg,
1
97% yield). M.p. = 86–89 °C. H NMR (300 MHz, CDCl3): δ
7.37–7.31 (m, 5H), 7.30–7.23 (m, 5H), 7.21 (s, 4H) ppm. 13C
NMR (75 MHz, CDCl3): δ 135.1, 134.9, 131.4, 131.2, 129.3,
127.4 ppm. HRMS calcd for C18H14S2 (M+): 294.0537; found:
294.0532. Elemental analysis: calcd C, 73.43; H, 4.79; S,
21.78%; found C, 73.16; H, 4.83; S, 21.95%.
Cyclohexyl(3,4-dimethylphenyl)sulfane
(6q). 4-Iodo-1,2-
dimethylbenzene was allowed to react with cyclohexanethiol,
column chromatography (petroleum ether/ethyl acetate 100/1),
isolated as a colorless oil (214 mg, 97% yield). 1H NMR
(300 MHz, CDCl3): δ 7.22 (s, 1H), 7.19–7.16 (d, J = 7.8 Hz,
1H), 7.07–7.05 (d, J = 7.8 Hz, 1H), 3.06–2.98 (m, 1H), 2.24
(s, 6H), 1.99–1.96 (m, 2H), 1.79–1.75 (m, 2H), 1.38–1.25
(m, 6H) ppm. 13C NMR (75 MHz, CDCl3): δ 137.0, 135.5,
134.0, 131.4, 130.2, 130.0, 47.0, 33.4, 26.1, 25.8, 19.7,
19.4 ppm. HRMS calcd for C14H20S (M+): 220.1286; found:
220.1286. Elemental analysis: calcd C, 76.30; H, 9.15; S,
14.55%; found C, 76.40; H, 9.16; S, 14.28%.
1,4-Bis(hexylthio)benzene. 1,4-Diiodobenzene was allowed to
react with hexane-1-thiol, column chromatography (petroleum
ether/ethyl acetate 50/1), isolated as a white solid (295 mg, 95%
1
yield). M.p. = 33–34 °C. H NMR (300 MHz, CDCl3): δ 7.09
(s, 4H), 2.76–2.71 (t, J = 6.6 Hz, 4H), 1.54–1.44 (m, 4H),
1.32–1.22 (m, 4H), 1.21–1.07 (m, 8H), 0.76–0.72 (t, J = 6.9 Hz,
6H) ppm. 13C NMR (75 MHz, CDCl3): δ 134.4, 129.6, 33.9,
31.3, 29.0, 28.4, 22.4, 13.9 ppm. HRMS calcd for
C18H30S2 (M+): 310.1789; found: 310.1796. Elemental analysis:
calcd C, 69.61; H, 9.74; S, 20.65%; found C, 69.28; H, 9.82; S,
20.73%.
Biphenyl-4-yl(cyclohexyl)sulfane (6r). 4-Iodobiphenyl was
allowed to react with cyclohexanethiol, column chromatography
(petroleum ether/ethyl acetate 100/1), isolated as a white solid
1,4-Bis(cyclohexylthio)benzene. 1,4-Diiodobenzene was allowed
to react with cyclohexanethiol, column chromatography (pet-
roleum ether/ethyl acetate 50/1), isolated as a white solid
1
(255 mg, 95% yield). M.p. = 36–37 °C. H NMR (300 MHz,
CDCl3): δ 7.60–7.58 (d, J = 7.2 Hz, 2H), 7.55–7.52 (d, J = 8.4
Hz, 2H), 7.48–7.42 (m, 4H), 7.37–7.32 (t, J = 7.2 Hz, 1H),
3.20–3.13 (m, 1H), 2.06–2.03 (d, J = 11.1 Hz, 2H), 1.83–1.80
(m, 2H), 1.48–1.26 (m, 6H) ppm. 13C NMR (75 MHz, CDCl3):
δ 140.5, 139.5, 134.4, 132.1, 128.8, 127.4, 127.3, 126.9, 46.6,
33.4, 26.1, 25.8 ppm. HRMS calcd for C18H20S (M+):
1
(278 mg, 91% yield). M.p. = 66–68 °C. H NMR (300 MHz,
CDCl3): δ 7.28 (s, 4H), 3.11–3.04 (m, 2H), 2.05–1.91 (m, 4H),
1.77–1.68 (m, 4H), 1.62–1.55 (m, 2H), 1.42–1.22 (m, 10H)
ppm. 13C NMR (75 MHz, CDCl3): δ 133.5, 131.8, 46.5, 33.2,
25.9, 25.6 ppm. HRMS calcd for C18H26S2 (M+): 306.1476;
2566 | Org. Biomol. Chem., 2012, 10, 2562–2568
This journal is © The Royal Society of Chemistry 2012

View Article Online
(e) U. Schopfer and A. Schlapbach, Tetrahedron, 2001, 57,
3069; (e) Z. Jiang, J. She and X. Lin, Adv. Synth. Catal., 2009,
351, 2558; (f) M. Murata and S. L. Buchwald, Tetrahedron, 2004, 60,
7397; (g) T. Itoh and T. Mase, Org. Lett., 2004, 6, 4587;
(h) C. Mispelaere-Canivet, J.-F. Spindler, S. Perrio and P. Beslin,
Tetrahedron, 2005, 61, 5253; (i) J.-Y. Lee and H. L. Phil, J. Org. Chem.,
2008, 73, 7413; ( j) C. C. Eichman and J. P. Stambuli, J. Org. Chem.,
2009, 74, 4005; (k) C.-F. Fu, Y.-H. Liu, S.-M. Peng and S.-T. Liu,
Tetrahedron, 2010, 66, 2119; (l) G. Y. Li, Angew. Chem., Int. Ed., 2001,
40, 1513.
found: 306.1470. Elemental analysis: calcd C, 70.53; H, 8.55; S,
20.92%; found C, 70.47; H, 8.39; S, 20.98%.
1,6-Bis(phenylthio)hexane. Iodobenzene was allowed to react
with hexane-1,6-dithiol, column chromatography (petroleum
ether/ethyl acetate 100/1), isolated as a white solid (281 mg,
1
93% yield). M.p. = 62–64 °C. H NMR (300 MHz, CDCl3): δ
7.24–7.16 (m, 8H), 7.10–7.05 (t, J = 6.9 Hz, 2H), 2.84–2.79
(t, J = 7.2 Hz, 4H), 1.58–1.54 (m, 4H), 1.38–1.33 (m, 4H) ppm.
13C NMR (75 MHz, CDCl3): δ 135.8, 127.9, 127.7, 124.6, 32.4,
27.9, 27.2 ppm. HRMS calcd for C18H22S2 (M+): 302.1163;
found: 302.1163. Elemental analysis: calcd C, 71.47; H, 7.33; S,
21.20%; found C, 71.27; H, 7.35; S, 21.17%.
4 (a) Y.-C. Wong, T. T. Jayanth and C.-H. Cheng, Org. Lett., 2006, 8, 5613;
(b) M.-T. Lan, W.-Y. Wu, S.-H. Huang, K.-L. Luo and F.-Y. Tsai, RSC
Adv., 2011, 1, 1751.
5 (a) J. Zhang, C. M. Medley, J. A. Krause and H. Guan, Organometallics,
2010, 29, 6393; (b) S. Jammi, P. Barua, L. Rout, P. aha and
T. Punniyamurthy, Tetrahedron Lett., 2008, 49, 1484; (c) C. Millois and
P. Diaz, Org. Lett., 2000, 2, 1705; (d) H. J. Cristau, B. Chabaud,
A. Chêne and H. Christol, Synthesis, 1981, 892; (e) K. Takagi,
Chem. Lett., 1987, 2221; (f) V. Percec, J.-Y. Bae and D. H. Hill, J. Org.
Chem., 1995, 60, 6895; (g) N. J. Taniguchi, J. Org. Chem., 2004, 69,
6904.
1,6-Bis(naphthalen-1-ylthio)hexane. 1-Iodonaphthalene was
allowed to react with hexane-1,6-dithiol, column chromato-
graphy (petroleum ether/ethyl acetate 30/1), isolated as a white
solid (373 mg, 94% yield). M.p. = 100–101 °C. 1H NMR
(300 MHz, CDCl3): δ 8.45–8.43 (d, J = 8.1 Hz, 2H), 7.87–7.85
(d, J = 7.8 Hz, 2H), 7.75–7.72 (d, J = 8.4 Hz, 2H), 7.59–7.49
(m, 6H), 7.44–7.39 (t, J = 8.1 Hz, 2H), 3.00–2.95 (t, J = 7.2 Hz,
4H), 1.70–1.60 (m, 4H), 1.49–1.44 (m, 4H) ppm. 13C NMR
(75 MHz, CDCl3): δ 134.0, 133.8, 132.8, 128.4, 127.5, 126.8,
126.1, 126.0, 125.4, 124.9, 34.0, 28.9, 28.2 ppm. HRMS calcd
for C26H26S2 (M+): 402.1476; found: 402.1476. Elemental
analysis: calcd C, 77.56; H, 6.51; S, 15.93%; found C, 77.66; H,
6.52; S, 15.83%.
6 (a) V. P. Reddy, A. V. Kumar, K. Swapna and K. R. Rao, Org. Lett.,
2009, 11, 1697; (b) V. P. Reddy, K. Swapna, A. V. Kumar and K. R. Rao,
J. Org. Chem., 2009, 74, 3189.
7 (a) Y.-B. Huang, C.-T. Yang, J. Yi, X.-J. Deng, Y. Fu and L. Liu, J. Org.
Chem., 2011, 76, 800; (b) D. J. C. Prasad and G. Sekar, Synthesis, 2010,
79; (c) W. Deng, Y. Zou, Y.-F. Wang, L. Liu and Q.-X. Guo, Synlett,
2004, 1254; (d) Y.-J. Chen and H.-H. Chen, Org. Lett., 2006, 8, 5609;
(e) D. Zhu, L. Xu, F. Wu and B. Wan, Tetrahedron Lett., 2006, 47, 5781;
(f) X. Lu and W. Bao, J. Org. Chem., 2007, 72, 3863; (g) H. Zhang,
W. Cao and D. Ma, Synth. Commun., 2007, 37, 25; (h) H.-J. Xu,
X.-Y. Zhao, J. Deng, Y. Fu and Y.-S. Feng, Tetrahedron Lett., 2009, 50,
434; (i) M. T. Herrero, R. SanMartin and E. Domínguez, Tetrahedron,
2009, 65, 1500; ( j) C. Palomo, M. Oiarbide, R. Lopez and
E. Gomez-Bengoa, Tetrahedron Lett., 2000, 41, 1283; (k) C. G. Bates,
R. K. Gujadhur and D. Venkataraman, Org. Lett., 2002, 4, 2803;
(l) F. Y. Kwong and S. L. Buchwald, Org. Lett., 2002, 4, 3517;
(m) H. Yang, C. Xi, Z. Miao and R. Chen, Eur. J. Org. Chem., 2011,
3353; (n) M. Carril, R. SanMartin, E. Domínguez and I. Tellitu,
Chem.–Eur. J., 2007, 13, 5100; (o) C. Enguehard-Gueiffier, I. Thery,
A. Gueiffier and S. L. Buchwald, Tetrahedron, 2006, 62, 6042;
(p) A. K. Verma, J. Singh and R. Chaudhary, Tetrahedron Lett., 2007, 48,
7199; (q) Y. Feng, H. Wang, F. Sun, Y. Li, X. Fu and K. Jin, Tetrahedron,
2009, 65, 9737; (r) Y.-J. Wu and H. He, Synlett, 2003, 1789;
(s) B. C. Ranu, A. Saha and R. Jana, Adv. Synth. Catal., 2007, 349, 2690;
(t) C. Gonzalez-Arellano, R. Luque and D. J. Macquarrie, Chem.
Commun., 2009, 1410; (u) L. Rout, P. Saha, S. Jammi and
T. Punniyamurthy, Eur. J. Org. Chem., 2008, 640; (v) S. Bhadra,
B. Sreedhar and B. C. Ranu, Adv. Synth. Catal., 2009, 351,
2369; (w) E. Sperotto, G. P. M. van Klink, J. G. deVries and G. van
Koten, J. Org. Chem., 2008, 73, 5625; (x) C.-K. Chen, Y.-W. Chen,
C.-H. Lin, H.-P. Lin and C.-F. Lee, Chem. Commun., 2010, 46, 282;
(y) L. Rout, T. K. Sen and T. Punniyamurthy, Angew. Chem., Int. Ed.,
2007, 46, 5583; (z) Y.-S. Feng, Y.-Y. Li, L. Tang, W. Wu and H.-J. Xu,
Tetrahedron Lett., 2010, 51, 2489.(aa) H. J. Xu, X. Y. Zhao, J. Deng,
Y. Fu and Y. S. Feng, Synlett, 2008, 3063; (ab) S. Kovács and Z. Novák,
Org. Biomol. Chem., 2011, 9, 711; (ac) J. She, Z. Jiang and Y. Wang,
Tetrahedron Lett., 2009, 50, 593; (ad) P. Buranaprasertsuk,
J. W. W. Chang, W. Chavasiri and P. W. H. Chan, Tetrahedron Lett.,
2008, 49, 202.
1,6-Bis(pyridin-2-ylthio)hexane. 2-Iodopyridine was allowed
to react with hexane-1,6-dithiol, column chromatography (pet-
roleum ether/ethyl acetate 20/1), isolated as a colorless oil
(282 mg, 93% yield). 1H NMR (300 MHz, CDCl3): δ 8.40–8.38
(d, J = 4.8 Hz, 2H), 7.45–7.39 (t, J = 7.5 Hz, 2H), 7.14–7.12 (d,
J = 8.1 Hz, 2H), 6.94–6.90 (t, J = 6.3 Hz, 2H), 3.17–3.12 (t, J =
7.2 Hz, 4H), 1.75–1.66 (m, 4H), 1.50–1.45 (m, 4H) ppm. 13C
NMR (75 MHz, CDCl3): δ 159.3, 149.3, 135.6, 122.0, 119.0,
29.8, 29.1, 28.3 ppm. HRMS calcd for C16H20N2S2 (M+):
304.1068; found: 304.1082. Elemental analysis: calcd C, 63.12;
H, 6.62; N, 9.20; S, 21.06%; found C, 63.17; H, 6.86; N, 9.26;
S, 21.47%.
Acknowledgements
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 20802015, 21072040,
21071040).
8 (a) A. Correa, M. Carril and C. Bolm, Angew. Chem., Int. Ed., 2008, 47,
2880; (b) J.-R. Wu, C.-H. Lin and C.-F. Lee, Chem. Commun., 2009,
4450; (c) V. K. Akkilagunta, V. P. Reddy and K. R. Rao, Synlett, 2010,
1260; (d) W.-Y. Wu, J.-C. Wang and F.-Y. Tsai, Green Chem., 2009, 11,
326.
9 For reviews, see: (a) S. V. Ley and A. W. Thomas, Angew. Chem., Int.
Ed., 2003, 42, 5400; (b) K. Kunz, U. Scholz and D. Ganzer, Synlett,
2003, 2428; (c) I. P. Beletskaya and A. V. Cheprakov, Coord. Chem. Rev.,
2004, 248, 2337.
Notes and references
1 (a) E. Block, Reactions of Organosulfur Compounds, Academic Press,
New York, 1978; (b) P. S. Herradura, K. A. Pendola and R. K. Guy, Org.
Lett., 2000, 2, 2019; (c) A. Gangjee, Y. Zeng, T. Talreja, J. J. McGuire,
R. L. Kisliuk and S. F. Queener, J. Med. Chem., 2007, 50, 3046;
(d) A.-M. Faucher, P. W. White, C. Brochu, C. G. Maitre, J. Rancourt and
G. Fazal, J. Med. Chem., 2004, 47, 18.
2 (a) Metal-Catalyzed Cross-Coupling Reactions, ed. F. Diederich and
A. de Meijere, Wiley-VCH, Weinheim, 2004; (b) T. Kondo and
T. Mitsudo, Chem. Rev., 2000, 100, 3205.
10 D. Astruc, F. Lu and J. R. Aranzaes, Angew. Chem., Int. Ed., 2005, 44,
7852.
3 (a) M. A. Fernández-Rodríguez and J. F. Hartwig, Chem.–Eur. J., 2010,
16, 2355; (b) C. S. Bryan, J. A. Braunger and M. Lautens,
Angew. Chem., Int. Ed., 2009, 48, 7064; (c) M. A. Fernández-Rodríguez,
Q. Shen and J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 2180;
11 (a) M. B. Thathagar, J. Beckers and G. Rothenberg, J. Am. Chem. Soc.,
2002, 124, 11858; (b) M. B. Thathagar, J. Beckers and G. Rothenberg,
Green Chem., 2004, 6, 215; (c) L. Rout, T. K. Sen and T. Punniyamurthy,
Angew. Chem., Int. Ed., 2007, 46, 5583; (d) L. Rout, S. Jammi and
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2562–2568 | 2567

View Article Online
T. Punniyamurthy, Org. Lett., 2007, 9, 3397; (e) S. Jammi, S. Sakthivel,
L. Rout, T. Mukherjee, S. Mondal, R. Mitra, P. Saha and
T. Punniyamurthy, J. Org. Chem., 2009, 74, 1971; (f) B. Sreedhar,
R. Arundhathi, P. L. Reddy and M. L. Kantam, J. Org. Chem., 2009, 74,
7951.
M. Komatsu, Chem. Rev., 2009, 109, 711; (d) N. Mase and C. F. Barbas,
Org. Biomol. Chem., 2010, 8, 4043.
13 H.-J. Xu, Y.-F. Liang, Z.-Y. Cai, H.-X. Qi, C.-Y. Yang and Y.-S. Feng,
J. Org. Chem., 2011, 76, 2296.
14 The yield of diphenyldisulfane in this optimal reaction system was 1.9%,
the highest yield of disulfides in all reactions was 3.7%. When the
reaction was performed in air, the yield of oxidative coupling product
(R-S-S-R) can be up to ∼30%.
12 (a) P. A. Grieco, Organic Synthesis in Water, Blackie A & P, London,
1998; (b) D. G. Blackmond, A. Armstrong, V. Coomber and A. Wells,
Angew. Chem., Int. Ed., 2007, 46, 3798; (c) S. Minakata and
2568 | Org. Biomol. Chem., 2012, 10, 2562–2568
This journal is © The Royal Society of Chemistry 2012