A simple, efficient and recyclable catalytic system for carbon-sulfur coupling of aryl halides with thioacetamide

Article abstract of DOI:10.1016/j.molcata.2014.08.010

The carbon-sulfur coupling reaction of aryl halides with thioacetamide using an MCM-41-immobilized bidentate nitrogen copper(I) complex [MCM-41-2N-CuI] as an efficient heterogeneous catalyst is described. Developed catalytic system is found to be effective for the coupling reaction of aryl halides with thioacetamide providing moderate to high yield of diaryl sulfides. This heterogeneous copper catalyst exhibits higher activity than CuI and can be recovered by a simple filtration of the reaction solution and reused for at least 10 consecutive trials without any decreases in activity.

Full text of DOI:10.1016/j.molcata.2014.08.010

Accepted Manuscript
Title: A simple, efficient and recyclable catalytic system for
carbon-sulfur coupling of aryl halides with thioacetamide
Author: Mingzhong Cai Ruiya Yao Lin Chen Hong Zhao
PII:
S1381-1169(14)00357-4
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.08.010
MOLCAA 9225
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
16-12-2013
4-8-2014
5-8-2014
Please cite this article as: M. Cai, R. Yao, L. Chen, H. Zhao, A simple,
efficient and recyclable catalytic system for carbon-sulfur coupling of aryl
halides with thioacetamide, Journal of Molecular Catalysis A: Chemical (2014),
http://dx.doi.org/10.1016/j.molcata.2014.08.010
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A simple, efficient and recyclable catalytic system for carbon-sulfur coupling of aryl halides with
thioacetamide
Mingzhong Caib*, Ruiya Yaoa, Lin Chenb, Hong Zhaoa*
aSchool of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University,
Guangzhou 510006, P. R. China
bKey Laboratory of Functional Small Organic Molecule, Ministry of Education and Department of
Chemistry, Jiangxi Normal University, Nanchang 330022, P. R. China
Corresponding author. Fax: +86 791 88120388; +86 76088207939.
E-mail address: caimingz@tom.com (M. Cai); zhaohong1001@sina.com (H. Zhao)
Research Highlights
► The MCM-41-2N-CuI complex could be conveniently prepared by a simple
procedure.
► This heterogeneous copper catalyst exhibited higher catalytic activity than CuI.
► This copper catalyst can be reused for 10 times without any decrease in activity.
► Our catalytic system provides a practical route for the synthesis of diaryl sulfides.
Abstract
The carbon-sulfur coupling reaction of aryl halides with thioacetamide using an
MCM-41-immobilized bidentate nitrogen copper(I) complex [MCM-41-2N-CuI] as
an efficient heterogeneous catalyst is described. Developed catalytic system is found
1
Page 1 of 23

to be effective for the coupling reaction of aryl halides with thioacetamide providing
moderate to high yield of diaryl sulfides. This heterogeneous copper catalyst exhibits
higher activity than CuI and can be recovered by a simple filtration of the reaction
solution and reused for at least 10 consecutive trials without any decreases in activity.
Keywords: Supported copper catalyst; Carbon-sulfur coupling; Functionalized MCM-41; Diaryl
sulfide; Aryl halide
1. Introduction
The aryl–sulfur bonds proverbially exist in a great number of pharmaceuticals,
biologically active molecules and polymeric materials [1-6]. For example, diaryl
sulfide functionalities have been found in numerous drugs with a broad spectrum of
therapeutic activities such as antidiabetes, anti-inflammatory, anti-Alzheimer’s,
anti-Parkinson’s, anticancer, and anti-HIV [7,8]. However, the related C–S bond
*
formation reactions are less studied compared with C–N and C–O processes, which is
partially caused by the fact that organic sulfur compounds have a tendency to bind to
metals, acting as metal deactivators [9]. Traditional methods for the construction of
aryl–sulfur bonds often require harsh reactions. For instance, coupling of copper
thiolates with aryl halides take place in polar solvents such as HMPA, and at elevated
temperature around 200 °C [10]. Reduction of aryl sulfones or aryl sulfoxides requires
strong reducing agents such as DIBAL-H or LiAlH4 [11-13]. The development of
efficient methods for the formation of aryl–sulfur bonds has been a subject of interest
in synthetic chemistry since Migita et al. first reported cross-coupling reactions of
aryl halides with thiols in the presence of a palladium catalyst [14,15]. A wide range
of transition metals were used to catalyze this coupling reaction, including palladium
2
Page 2 of 23

[16-21], nickel [22,23], cobalt [24], copper [25-31], and indium [32,33]. Among these
methods, the copper-catalyzed cross-coupling is highly attractive due to the relatively
low cost and environmentally negative influence of the process [34].
On the other hand, the common methods for the synthesis of diaryl sulfides are
based on the condensation of aryl halides with thiols, however, the use of volatile and
foul-smelling thiols has been a main drawback, which may bring about safety
problems. In addition, some thiols are too expensive for scale-up operations. In the
meantime, Still and Toste reported that diaryl sulfides could be prepared via the
reaction of samarium thiolates with aryl halides [35]. Firouzabadi et al. described
thioetherification of aryl halides using thiourea as a nonvolatile sulfur source [36].
The copper-catalyzed synthesis of diaryl sulfides from aryl halides with potassium
thiocyanate or thioacetamide has also been reported [31,37]. Although these copper-
catalyzed formation reactions of aryl–sulfur bonds are highly efficient, the problem
with homogeneous catalysis is the difficulty to separate the catalyst from the reaction
mixture and the impossibility to reuse it in consecutive reactions. In addition,
homogeneous catalysis might result in unacceptable copper contamination of the
isolated product, which is a particularly significant drawback for its application in the
pharmaceutical industry. To overcome these problems, the development of highly
active and recyclable heterogeneous catalysts, such as immobilization of catalytically
active species, i.e. organometallic complexes, onto a solid support to produce a
molecular heterogeneous catalyst is essential [38,39]. Heterogeneous catalysis also
helps to minimize wastes derived from reaction workup, contributing to the
3
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development of green chemical processes [40,41]. In spite of tremendous effort
dedicated to the immobilization of homogeneous palladium complexes over the last
two decade [42-44], very few examples of carbon-carbon or carbon-heteroatom bond
formation reactions catalyzed by heterogeneous copper catalysts have appeared
[45-48]. Therefore, the development of a stable heterogeneous copper catalyst that
allows for highly efficient thioetherification of a wide range of aryl halides is
worthwhile.
Developments on the mesoporous material MCM-41 provided a new possible
candidate for a solid support for immobilization of homogeneous catalysts [49].
MCM-41 has a regular pore diameter of ca.5 nm and a specific surface area > 700 m2
g-1 [50]. Its large pore size allows passage of large molecules such as organic reactants
and metal complexes through the pores to reach to the surface of the channel [51-53].
To date, some palladium and rhodium complexes on functionalized MCM-41 support
have been prepared and successfully used in organic reactions [39,54-57]. However,
to the best of our knowledge, no the synthesis of diaryl sulfides catalyzed by immobi-
lization of copper in MCM-41 has been described in the open literature. In continuing
our efforts to develop greener synthetic pathways for organic transformations, our
new approach, described in this paper, was to design and synthesize an MCM-41-
immobilized bidentate nitrogen copper(I) complex (MCM-41-2N-CuI), which was
used as an effective copper catalyst for the carbon-sulfur coupling reaction of aryl
halides with thioacetamide.
2. Experimental
4
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All chemicals were reagent grade and used as purchased. The mesoporous material
MCM-41 was prepared according to a literature procedure [58]. All reactions were
performed under an inert atmosphere of argon using distilled solvents. All coupling
products were characterized by comparison of their spectra and physical data with
authentic samples. IR spectra were determined on a Perkin-Elmer 683 instrument. 1H
NMR spectra (400 MHz) were recorded on a Bruker Avance 400 MHz spectrometer
13
with TMS as an internal standard in CDCl3 as solvent. C NMR spectra (100 MHz)
were recorded on a Bruker Avance 400 MHz spectrometer in CDCl3 as solvent.
Copper content was determined with inductively coupled plasma atom emission
Atomscan16 (ICP-AES, TJA Corporation). X-ray powder diffraction patterns were
obtained on Damx-rA (Rigaka).
2.1. Preparation of MCM-41-2N
A solution of 1.54 g of 3-(2-aminoethylamino)propyltrimethoxysilane in 18 ml of
dry chloroform was added to a suspension of 2.2 g of the MCM-41 in 180 ml of dry
toluene. The mixture was stirred for 24 h at 100 °C. Then the solid was filtered and
washed by CHCl3 (2 × 20 ml), and dried in vacuum at 160 °C for 5 h. The dried white
solid was then soaked in a solution of 3.1 g of Me3SiCl in 100 ml of dry toluene at
room temperature under stirring for 24 h. Then the solid was filtered, washed with
acetone (3 × 20 ml) and diethyl ether (3 × 20 ml), and dried in vacuum at 120 °C for 5
h to obtain 3.49 g of hybrid material MCM-41-2N. The nitrogen content was found to
be 1.84 mmol/g by elemental analysis.
2.2. Preparation of MCM-41-2N-CuI
5
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In a small Schlenk tube, 1.0 g of the above-functionalized MCM-41 (MCM-41-2N)
was mixed with 0.1 g (0.52 mmol) of CuI in 10 ml of dry DMF. The mixture was
stirred at room temperature for 7 h under an argon atmosphere. The solid product was
filtered by suction, washed with DMF and acetone and dried at 40 °C/26.7 Pa under
Ar for 5 h to give 1.066 g of a pale blue copper complex (MCM-41-2N-CuI). The
nitrogen and copper content was found to be 1.67 mmol g-1 and 0.45 mmol g-1,
respectively.
2.3. General procedure for the coupling of aryl halides with thioacetamide
A Schlenk tube was charged with MCM-41-2N-CuI (66 mg, 0.03 mmol),
MeCSNH2 (75 mg, 1.0 mmol), Cs2CO3 (978 mg, 3.0 mmol), and aryl halide (2.5
mmol). The tube was evacuated and backfilled with argon. Then, DMSO-H2O (1
ml/0.5 ml) was added under argon. The tube was sealed, and the reaction mixture was
stirred at 120 °C for 24-48 h. The reaction mixture was cooled to room temperature,
diluted with ethyl acetate (10 ml), and filtered. The MCM-41-2N-CuI complex was
washed with distilled water (2 × 5 ml), ethanol (2 × 5 ml), and Et2O (2 × 5 ml) and
reused in the next run. The filtrate was concentrated under reduced pressure and the
residue was purified by flash column chromatography on silica gel (petroleum/ethyl
acetate = 50:1 to 7:1) to provide the desired product.
3. Results and discussion
An MCM-41-immobilized bidentate nitrogen copper(I) complex (MCM-41-2N-CuI)
was conveniently prepared from commercially available and inexpensive 3-(2-amino-
6
Page 6 of 23

ethylamino)propyltrimethoxysilane and CuI (Scheme 1). Firstly, the mesoporous
material MCM-41 reacted with 3-(2-aminoethylamino)propyltrimethoxysilane in
toluene at 100 °C for 24 h, followed by the silylation with Me3SiCl in toluene at room
temperature for 24 h to give 3-(2-aminoethylamino)propyl-functionalized MCM-41
(MCM-41-2N). The latter was subsequently treated with CuI in DMF at room
temperature for 7 h to generate the MCM-41-immobilized bidentate nitrogen copper(I)
complex (MCM-41-2N-CuI) as a pale blue powder, the copper content of the complex
was found to be 0.45 mmol g-1 according to the ICP-AES measurements. X-ray
powder diffraction (XRD) patterns of the parent MCM-41 and the modified material
MCM-41-2N-CuI are displayed in Figure 1. Small angle X-ray powder diffraction of
the parent MCM-41 gave the peaks corresponding to hexagonally ordered
mesoporous phases. For MCM-41-2N-CuI, the (100) reflection of the parent MCM-41
with decreased intensity was remained after functionalization, while the (110) and
(200) reflections became weak and diffuse, which could be due to contrast matching
between the silicate framework and organic moieties which are located inside the
channels of MCM-41. These results indicated that the basic structure of the parent
MCM-41 was not damaged in the whole process of catalyst preparation.
7
Page 7 of 23

OH
OH
OSiMe3
1. (MeO)3Si(CH2)3NH(CH2)2NH2
Toluene, 100 oC, 24 h
O
Si
N
NH2
H
OH
O
2. Me3SiCl, rt, 24 h
OMe
MCM-41-2N
MCM-41
OSiMe3
O
H
CuI, DMF
r.t., 7 h
Si
N
NH2
O
OMe
CuI
MCM-41-2N-CuI
Scheme 1.
100
1
110
200
2
2
4
6
8
10
2(degrees)
Fig. 1. XRD patterns of the parent MCM-41 (1) and MCM-41-2N-CuI (2)
We started our investigation with iodobenzene as the model substrate to screen the
sulfur source using MCM-41-2N-CuI as a catalyst and DMSO as a solvent, and the
results are listed in Table 1. When thiourea was used as the sulfur source for synthesis
of diphenyl sulfide, the desired product was obtained in 65% yield (entry 1).
Substituted thioureas such as amidothiourea gave poor result (entry 2). We were
delighted to find that the coupling reaction of iodobenzene with thioacetamide
8
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afforded diphenyl sulfide in 84% yield (entry 3). However, the reaction of
iodobenzene with benzothiourea gave diphenyl sulfide in moderate yield (entry 4).
Table 1 Cross-coupling of iodobenzene with various sulfur sources catalyzed by
MCM-41-2N-CuIa
S
S
3 mol% MCM-41-2N-CuI
I
+
DMSO, Cs2CO3, 120 oC, 24 h
NH2
R
Entry
R
Yield b (%) Entry
R
Yield b (%)
1
3
H2N
Me
65
84
2
4
H2NNH
Ph
11
57
a All reactions were performed using 2.5 mmol of iodobenzene, 1.0 mmol of sulfur source, 3.0
mmol of Cs2CO3 and 3 mol% MCM-41-2N-CuI in 1.5 ml of DMSO at 120 °C for 24 h under Ar. b
Isolated yield based on the sulfur source used.
Subsequently, we chose the cross-coupling of iodobenzene with thioacetamide as
model reaction to screen the solvents, bases, and catalyst quantity and the results are
outlined in Table 2. First, using MCM-41-2N-CuI as a catalyst, different solvents
were examined (entries 1-7). Among the solvents examined [DMSO, DMF, THF,
dioxane, and H2O], DMSO was found to be the most effective (entry 1), DMF
afforded moderate yield (entry 2). While no desired product was formed when other
solvents such as THF, dioxane, and H2O were used (entries 3-5). To our delight,
slightly increased yields were observed when mixed solvents such as DMSO-H2O and
DMF-H2O were used (entries 6 and 7). The slightly increased yields may be explained
by the fact that the hydrolysis reaction of the reaction intermediate can be accelerated
due to the introduction of H2O. Next, the influence of different bases on the reaction
9
Page 9 of 23

was tested. Although good yields were also obtained when Na2CO3, K2CO3, and
K3PO4 were used as the base (entries 8-10), Cs2CO3 gave the best result (entry 6). To
verify the effect of the anion of copper(I) salts on the reaction, we also prepared
MCM-41-2N-CuBr and MCM-41-2N-CuCl from CuBr or CuCl instead of CuI
according to Scheme 1. It was found that lower yields were obtained when
MCM-41-2N-CuBr or MCM-41-2N-CuCl was used as the catalyst (entries 11 and 12).
Finally, the amount of supported copper catalyst was also screened, and 3.0 mol%
loading of copper was found to be optimal, a lower yield was observed and a longer
reaction time was required when the amount of the catalyst was decreased (entries 15
and 16). Increasing the amount of copper catalyst could shorten the reaction time, but
did not increase the yield of diphenyl sulfide (entries 13 and 14). Thus, the optimized
reaction conditions for this cross-coupling of iodobenzene with thioacetamide are the
MCM-41-2N-CuI (3 mol%) in DMSO-H2O (2:1) using Cs2CO3 as base at 120 °C
under Ar for 24 h (entry 6).
Table 2 Cross-coupling reaction of iodobenzene with thioacetamide in different
conditionsa
S
S
Heterogeneous copper catalyst
solvent, base, 120 oC
I
+
NH2
Entry Catalyst (mol%)
Solvent (2:1) Base
Time (h) Yieldb (%)
1
2
3
MCM-41-2N-CuI (3)
DMSO
DMF
THF
Cs2CO3 24
84
58
0
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
Cs2CO3 24
Cs2CO3 36
10
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4
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
MCM-41-2N-CuI (3)
Dioxane
Cs2CO3 36
Cs2CO3 36
Cs2CO3 24
Cs2CO3 24
K2CO3 24
Na2CO3 24
K3PO4 24
Cs2CO3 24
Cs2CO3 24
Cs2CO3 18
Cs2CO3 10
Cs2CO3 48
Cs2CO3 72
0
5
H2O
0
6
DMSO-H2O
DMF-H2O
DMSO-H2O
DMSO-H2O
DMSO-H2O
88
63
72
67
75
72
74
87
88
81
76
7
8
9
10
11
12
13
14
15
16
MCM-41-2N-CuBr (3) DMSO-H2O
MCM-41-2N-CuCl (3) DMSO-H2O
MCM-41-2N-CuI (5)
DMSO-H2O
MCM-41-2N-CuI (10) DMSO-H2O
MCM-41-2N-CuI (2)
MCM-41-2N-CuI (1)
DMSO-H2O
DMSO-H2O
a All reactions were performed using 2.5 mmol of iodobenzene, 1.0 mmol of thioacetamide, 3.0
mmol of base in 1.5 ml of solvent at 120 °C under Ar. b Isolated yield based on thioacetamide
used.
S
X
S
3 mol% MCM-41-2N-CuI
R
+
R
R
o
NH2
Cs2CO3, DMSO-H2O (2:1), 120 C
2
1
X= I, Br
Scheme 2.
To examine the scope for this heterogeneous copper-catalyzed coupling reaction,
we have investigated the reactions using a variety of aryl iodides or bromides as the
11
Page 11 of 23

substrates under the optimized reaction conditions (Scheme 2) and the results are
summarized in Table 3. As shown in Table 3, the C–S coupling reactions of a variety
of aryl iodides with thioacetamide proceeded smoothly to afford the corresponding
diaryl sulfides in good to excelent yields. The electron nature of substituents seemed
to have no effect on the results, various electron-donating and electron-withdrawing
substituents such as –CH3, –OCH3, –NH2, –Br, –Cl, –F, –CF3, –CN, –COCH3 and
–NO2 on aryl iodide were well tolerated. This heterogeneous copper catalyst exhibited
higher activity than homogeneous CuI. For instance, in the presence of 3 mol%
MCM-41-2N-CuI, the reactions of iodobenzene and 4-iodoanisole with thioacetamide
in DMSO-H2O (2:1) with Cs2CO3 as base at 120 °C under Ar for 24 h afforded 88%
yield of 2a and 93% yield of 2d, respectively (entries 1 and 4). The same reactions in
the presence of 10 mol% CuI in DMSO-H2O (2:1) with Cs2CO3 as base at 120 °C
under Ar for 24 h gave 83% yield of 2a and 87% yield of 2d, respectively [37]. The
higher activity of MCM-41-2N-CuI over CuI may be explained by the fact that the
chemical bonding between metal complexes and functional groups of the support
maintains the isolated nature of metal complexes, which can influence the catalytic
performance in a manner that the analogous homogeneous complex does not exhibit
in solution [59]. Aryl iodides carrying an ortho substituent were also found to readily
participate in the reaction. For example, the reactions of 2-iodotoluene, 2-iodoanisole,
and 2-iodoaniline with thioacetamide provided good yields of the desired diaryl
sulfides 2c, 2e and 2o under the optimized reaction conditions, respectively (entries 3,
5 and 15), although the effect of steric hindrance on the reaction was observed.
12
Page 12 of 23

Moreover, good yields obtained in the case of 4-chloroiodobenzene, 4-bromo-
iodobenzene and 4-fluoroiodobenzene indicated that there was good chemoselectivity
between iodide, bromide, chloride, and fluoride functional groups (entries 6, 10 and
11). A heteroaryl iodide, such as 3-iodopyridine, could afford the desired diaryl
sulfide 2q in 74% yield (entry 17). The bulky 1-iodonaphthalene also reacted
effectively with thioacetamide to give the corresponding product 2p in 82% yield
(entry 16). The method provides a quite general route for the synthesis of diaryl
sulfides having various functionalities. The results above prompted us to investigate
the reaction of aryl bromides with thioacetamide. The reactivity of aryl bromides was
obviously lower than that of aryl iodides. It was found that nonactivated aryl bromides
such as bromobenzene and 4-bromotoluene were not reactive under the present
reaction conditions (entries 23 and 24). However, the reactions of electron-deficient
aryl bromides with thioacetamide could proceed to give moderate to good yields
(40-79%) of diaryl sulfides (entries 18-22).
Table 3 Heterogeneous copper-catalyzed cross-coupling of aryl iodides or bromides
with thioacetamidea
Entry
Ar
X
I
Time (h)
24
Product
2a
Yieldb (%)
1
2
3
4
5
6
7
Ph
88
89
85
93
72
81
78
4-MeC6H4
2-MeC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
3-CF3C6H4
I
24
2b
I
30
2c
I
24
2d
I
30
2e
I
24
2f
I
24
2g
13
Page 13 of 23

8
9
3-MeC6H4
4-O2NC6H4
4-ClC6H4
I
24
24
24
24
24
24
24
30
24
24
36
36
36
36
36
48
48
86
89
79
76
70
68
85
84
82
74
59
76
79
51
45
Trace
0
2h
2i
I
10
11
12
13c
14
15
16
17
18
19
20
21c
22
23
24
I
2j
4-BrC6H4
I
2k
2l
4-MeCOC6H4
4-CNC6H4
3-O2NC6H4
2-H2NC6H4
1-naphthyl
3-pyridinyl
4-ClC6H4
I
I
2m
2n
2o
2p
2q
2j
I
I
I
I
Br
Br
Br
Br
Br
Br
Br
4-MeCOC6H4
4-O2NC6H4
4-CNC6H4
2-pyridinyl
Ph
2l
2i
2m
2r
2a
2b
4-MeC6H4
a All reactions were performed using 2.5 mmol of aryl halide, 1.0 mmol of thioacetamide, 3.0
mmol of Cs2CO3 and 3 mol% of MCM-41-2N-CuI in DMSO-H2O (1.0 ml/0.5 ml) at 120 °C under
Ar. b Isolated yield based on thioacetamide used. c Solvent: DMSO (1.5 ml).
To verify whether the observed catalysis was due to the heterogeneous catalyst
MCM-41-2N-CuI or to a leached copper species in solution, we performed the hot
filtration test [60]. We focused on the cross-coupling reaction of iodobenzene with
thioacetamide. We filtered off the MCM-41-2N-CuI complex after 10 h of reaction
time and allowed the filtrate to react further. The catalyst filtration was performed at
the reaction temperature (120 °C) in order to avoid possible recoordination or
14
Page 14 of 23

precipitation of soluble copper upon cooling. We found that, after this hot filtration,
no further reaction was observed, indicating that leached copper species from the
catalyst (if any) are not responsible for the observed activity. It was confirmed by
ICP-AES analysis that no copper could be detected in the hot filtered solution. This
result suggests that the copper catalyst remains on the support at elevated temperature
during the reaction. Although the detailed mechanistic studies of copper-catalyzed
couplings of thiols are lacking in the literature, this heterogeneous copper-catalyzed
cross-coupling reaction of aryl halides with thioacetamide may proceed through a
mechanism analogous to that proposed for CuI (Scheme 3) [37]. First, the coupling
reaction of aryl halide (1) with thioacetamide in the presence of MCM-41-2N-CuI
provides aryl ethanimidothioate (A), which is hydrolyzed in the reaction mixture to
afford a thiol (B) along with acetamide as a side product (C) under the basic
conditions. Then the newly generated arylthiol intermediate (B) reacts with aryl halide
(1) under the same catalytic system to give the diaryl sulfide (2).
SH
O
X
S
H2O
MCM-41-2N-CuI
DMSO
R
R
+
+
R
NH2
S
Cs2CO3
NH2
NH
C
B
A
1
X= I, Br
X
R
SH
S
R
R
R
MCM-41-2N-CuI, Cs2CO3
B
2
Scheme 3.
For a heterogeneous transition-metal catalyst, it is important to examine its ease of
15
Page 15 of 23

separation, recoverability and reusability. We also investigated the recyclability of the
MCM-41-2N-CuI by using the coupling reaction of 4-iodoanisole with thioacetamide.
After carrying out the reaction, the catalyst was separated by simple filtration and
washed with distilled water, ethanol and diethyl ether. After being air-dried, it can be
reused directly without further purification. The recovered copper catalyst was used in
the next run, and almost consistent activity was observed for 10 consecutive cycles
(Table 4, entries 1-10). In addition, copper leaching in the immobilized catalyst was
also determined. The copper content of the catalyst was found by ICP analysis to be
0.44 mmol g-1 after ten consecutive runs, only 2% of copper had been lost from the
MCM-41 support. The high stability and excellent reusability of the catalyst should
result from the chelating action of bidentate 2-aminoethylamino ligand on copper and
the mesoporous structure of the MCM-41 support. The result is important from a
practical point of view. The high catalytic activity, excellent reusability and the easy
accessibility of the MCM-41-2N-CuI make it a highly attractive heterogeneous copper
catalyst for the parallel solution phase synthesis of diverse libraries of compounds.
Table 4 Cross-coupling reaction of 4-iodoanisole with thioacetamide catalyzed by
the recycled catalysta
S
S
I
3 mol% MCM-41-2N-CuI
+
DMSO-H2O (2:1), Cs2CO3
120 oC, 24 h
OMe
NH2
MeO
MeO
2d
Cycle
Yieldb (%)
Cycle
Yieldb (%)
1
3
5
93
92
91
2
4
6
92
93
92
16
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7
9
91
91
8
90
90
10
a
Reaction was carried out with 4-iodoanisole (2.5 mmol), thioacetamide (1.0 mmol), MCM-41-
2N-CuI (0.03 mmol), Cs2CO3 (3.0 mmol), DMSO-H2O (1.0 ml/0.5 ml) at 120 °C under Ar for 24
h. b Isolated yield.
4. Conclusion
In summary, we have developed a novel, practical and environmentally friendly
catalyst system for the coupling reaction of aryl halides with thioacetamide by using
an MCM-41-immobilized bidentate nitrogen copper(I) complex [MCM-41-2N-CuI]
as catalyst. This novel heterogeneous copper catalyst can be conveniently prepared by
a simple two-step procedure from commercially available and inexpensive reagents
and exhibits higher catalytic activity than CuI. The reactions generated a variety of
diaryl sulfides in moderate to high yields and were applicable to various aryl iodides
and bromides. In addition, this methodology offers the competitiveness of recycl-
ability of the catalyst without significant loss of catalytic activity, and the catalyst can
be readily recovered by a simple filtration and reused for 10 cycles, thus making this
procedure environmentally more acceptable.
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21272044) and
Scientific Research Fund of Education Department of Jiangxi Province (KJLD13022 )
for financial support.
17
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Captions
1. Scheme 1: Preparation of the MCM-41-2N-CuI
2. Figure 1: XRD patterns of the parent MCM-41 (1) and MCM-41-2N-CuI (2)
3. Table 1: Cross-coupling of iodobenzene with various sulfur sources catalyzed
21
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by MCM-41-2N-CuI
4. Table 2: Cross-coupling reaction of iodobenzene with thioacetamide in different
conditions
5. Scheme 2: Cross-coupling of aryl halides with thioacetamide catalyzed by
MCM-41-2N-CuI
6. Table 3: Heterogeneous copper-catalyzed cross-coupling of aryl iodides or
bromides with thioacetamide
7. Scheme 3: Possible mechanism for heterogeneous copper-catalyzed coupling of
aryl halides with thioacetamide
8. Table 4: Cross-coupling reaction of 4-iodoanisole with thioacetamide catalyzed
by the recycled catalyst
22
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Graphical Abstract
A simple, efficient and recyclable catalytic system for carbon-
sulfur coupling of aryl halides with thioacetamide
Mingzhong Cai*, Ruiya Yao, Lin Chen, Hong Zhao*
S
X
S
3 mol% MCM-41-2N-CuI
R
+
R
R
Cs2CO3, DMSO-H2O (2:1), 120 oC
NH2
2
1
X= I, Br
OSiMe3
O
H
MCM-41-2N-CuI =
Si
N
NH2
O
OMe
CuI
23
Page 23 of 23