Nano copper oxide catalyzed synthesis of symmetrical diaryl sulfides under ligand free conditions

Article abstract of DOI:10.3762/bjoc.7.101

Potassium thiocyanate acts as an efficient sulfur surrogate in C-S cross-coupling reactions mediated by recyclable copper oxide nanoparticles under ligand free conditions. This protocol avoids foul smelling thiols, for the synthesis of a variety of symmetrical diaryl sulfides, via the cross-coupling of different aryl halides with potassium thiocyanate, affording corresponding products in moderate to excellent yields.

Full text of DOI:10.3762/bjoc.7.101

Nano copper oxide catalyzed synthesis of
symmetrical diaryl sulfides under
ligand free conditions
K. Harsha Vardhan Reddy, V. Prakash Reddy, A. Ashwan Kumar, G. Kranthi
and Y.V.D. Nageswar*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 886–891.
Organic Chemistry Divison-I, Indian Institute of Chemical Technology,
Hyderabad-500 607, India
doi:10.3762/bjoc.7.101
Received: 18 April 2011
Accepted: 04 June 2011
Published: 30 June 2011
Email:
K. Harsha Vardhan Reddy - Prakashorg1@gmail.com;
V. Prakash Reddy - Prakashorg1@gmail.com; A. Ashwan Kumar -
ashwankumar.10@gmail.com; G. Kranthi -
kranthimpharm@gmail.com; Y.V.D. Nageswar* -
dryvdnageswar@gmail.com
Associate Editor: I. Marek
© 2011 Reddy et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
aryl halides; aryl sulfides; copper oxide; cross-coupling; ligand free;
potassium thiocyanate; recyclable
Abstract
Potassium thiocyanate acts as an efficient sulfur surrogate in C–S cross-coupling reactions mediated by recyclable copper oxide
nanoparticles under ligand free conditions. This protocol avoids foul smelling thiols, for the synthesis of a variety of symmetrical
diaryl sulfides, via the cross-coupling of different aryl halides with potassium thiocyanate, affording corresponding products in
moderate to excellent yields.
Introduction
After the discovery of copper-promoted Ullmann reaction [1-3] During the last decades, transition and boron group metals, such
for the construction of carbon-hetero atom bonds, several as palladium [13-18], nickel [19,20], copper [21-37], iron [38],
protocols have been reported over the years to establish indium [39,40], lanthanum [41] and cobalt [42] have been used
C–N, C–O, and C–S linkages. Carbon–sulfur bonds are wide- in cross-coupling reactions, developed for the formation of
spread, occurring in numerous pharmaceutically and bio- carbon–sulfur bonds. Most of these coupling protocols involve
logically active compounds [4-8]. A large variety of aryl the reaction between thiols and aryl halides, resulting in the for-
sulfides are in use for diverse clinical applications in the treat- mation of C–S bonds. Most of these metal-catalyzed reactions
ment of cancer [9], HIV [10,11], Alzheimer’s and Parkinson’s involve volatile and foul-smelling thiols as the main drawback,
diseases [12].
which leads to environmental and safety problems. To over-
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Beilstein J. Org. Chem. 2011, 7, 886–891.
come these problems, Zhou [43] and coworkers recently
reported an efficient C–S bond formation by the reaction of
potassium thiocyanate and aryl halides in the presence of a
copper catalyst and a ligand in aqueous medium at 130 °C for
48 h. Tao et al. described the synthesis of diaryl sulfides
catalyzed by CuI via cross-coupling between aryl halides and
thioacetamide using Cs2CO3 as the base and DMSO–H2O as
the solvent at 120 °C [44].
Table 1: Screening of copper sources for the cross-coupling reaction
between iodo benzene and potassium thiocyanate.a
Entry
Catalyst
Solvent
Base
T (°) Yield
(%)b
1
2
CuO
CuO
DMSO K2CO3
DMSO K2CO3
DMSO K2CO3
rt
0
46
80
3
CuO
130
51
4
CuO
DMSO Cs2CO3 130
79
5
CuO
DMSO
KOH
130
130
130
130
130
130
130
130
130
130
130
94
These recently developed protocols involve expensive catalytic
systems and ligands [43], long reaction times [43,44], metal
contamination of the final product, and non recyclability of the
catalyst. This leads to increased costs as well as limiting the
scope of the reaction. From the synthetic point of view, it is
desirable to find novel recyclable catalytic systems, especially
under ligand-free conditions, for the synthesis of such highly
useful organic compounds.
6
CuO
DMSO K3PO4
42
7
CuO
Toluene
H2O
KOH
KOH
KOH
KOH
KOH
–
trace
trace
60
8
CuO
9
CuO
PEG
10
11
12
13
14
15
CuO
DMF
70
–
DMSO
DMSO
DMSO
DMSO
DMSO
0c
CuO
0d
CuCl2·2H2O
CuSO4·5H2O
Cu(OAc)·H2O
KOH
KOH
KOH
83
71
In the past few years, considerable efforts have been made in
the area of heterogeneous catalysis for various organic transfor-
mations. In general, heterogeneous catalysts offer higher
surface area and lower coordinating sites, which are
responsible for their higher catalytic activity [45-47]. Further-
more, heterogeneous catalysis has the advantage of high atom
efficiency, easy product purification, and reusability of the cata-
79
aReaction conditions: Iodobenzene (2.0 mmol), potassium thiocyanate
(1.5 mmol), nano CuO (5.0 mol %), solvent (2.0 mL), base (2.0 equiv),
130 °C, 20 h. bIsolated yield. cIn the absence of catalyst. dIn the
absence of base.
lyst. However, up until now, the investigation of nanoparticles First, several copper catalysts were screened (Table 1), and
as catalysts has been limited and will be widely studied in CuO was found to be promising for this tandem reaction
future.
(Table 1, entry 5). Amongst various bases screened, Cs2CO3
and KOH afforded the symmetrical aryl sulfides in excellent
yields (Table 1, entries 4, 5). Other bases such as K2CO3 and
Results and Discussion
In continuation of our investigations on metal-catalyzed cross- K3PO4 gave lesser amounts of the desired product (Table 1,
coupling reactions, we have explored the CuO-catalyzed syn- entries 3, 6). Among the solvents, DMSO yielded the best
thesis of diaryl sulfides under ligand-free conditions results (Table 1, entry 5) whereas PEG and DMF gave the prod-
(Scheme 1). To the best of our knowledge, this is the first re- ucts in moderate yields (Table 1, entries 9 and 10), whilst
cyclable copper oxide nanoparticle-catalyzed cross-coupling of solvents such as toluene and water were ineffective (Table 1,
aryl halides with potassium thiocyanate [46-51].
entries 7 and 8). The coupling reaction did not occur in the
absence of the catalyst (Table 1, entry 11) or base (Table 1,
entry 12). When the reaction was conducted either at room
temperature and 80 °C, no product was obtained or the yield
was very low (Table 1, entries 1 and 2). The ideal temperature
for the reaction was found to be 130 °C.
A study was conducted on C–S cross-coupling reaction using
various sulfur sources under these conditions (Table 2). Among
these sulfur surrogates potassium thiocyanate gave good yields
in this C–S cross-coupling reaction.
Scheme 1: Synthesis of symmetrical aryl sulfides catalyzed by copper
oxide nanoparticles.
Initially, the reaction between potassium thiocyanate and While expanding the scope of this nano CuO catalyzed tandem
iodobenzene was selected as the model reaction for optimizing cross-coupling, the reaction of potassium thiocyanate with
the reaction conditions involving various copper sources, bases, various aryl halides was examined under the optimized condi-
solvents, and temperature (Table 1).
tions. In general, all the reactions were very clean, and the
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Beilstein J. Org. Chem. 2011, 7, 886–891.
symmetrical aryl sulfides were obtained in moderate to good
yields. This protocol efficiently coupled iodobenzenes with
electron donating groups (e.g., Me, OMe and Et) with potas-
sium thiocyanate to produce the corresponding products in
excellent yields (Table 3, entries 4, 6 and 8), whereas in the
presence of an electron withdrawing group (CF3, NO2) a slight
decrease in the yield of the diaryl sulfide (Table 3, entries 12
and 13) was observed. Under these reaction conditions, various
hetero aromatic iodides were reacted with potassium thio-
cyanate and gave the corresponding diaryl sulfides in appre-
ciable yields (Table 3, entries 15, 16 and 17). In case of the
reactions of aromatic and hetero aromatic bromides with potas-
sium thiocyanate, longer reaction times were required in order
to obtain reasonable yields of diaryl sulfides (Table 3, entry 2,
5, 7 and 18). Iodobenzene was found to be a more reactive sub-
strate than bromo, and chloro benzenes (Table 3, entries 1, 2
and 3).
Table 2: Nano CuO catalyzed C–S cross-coupling of iodobenzene with
different sulfur sources.a
Entry
Aryl halide
Sulfur source Yield (%)b
1
2
3
KSCN
94
91
59
NH4SCN
Na2S2O3
4
5
6
KSCN
91
85
54
NH4SCN
Na2S2O3
7
8
9
KSCN
92
81
58
NH4SCN
Na2S2O3
aReaction conditions: Aryl halides (2.0 mmol), sulfur sources
(1.5 mmol), nano CuO (5.0 mol %), DMSO (2.0 mL), KOH (2.0 equiv),
130 °C, 20 h, bIsolated yield.
Table 3: Copper oxide nanoparticles catalyzed synthesis of diaryl sulfidesa.
Entry
Aryl halide
Product
Yield (%)b
94
1
2
3
4
5
6
7
8
63c
trace
91
68c
92
70c
87
9
72
78
10
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Beilstein J. Org. Chem. 2011, 7, 886–891.
Table 3: Copper oxide nanoparticles catalyzed synthesis of diaryl sulfidesa. (continued)
11
12
76
79
13
14
78
75
15
16
66
62
17
18
69
72c
aReaction conditions: Aryl halides (2.0 mmol), potassium thiocyanate (1.5 mmol), nano CuO (5.0 mol %), DMSO (2.0 mL), KOH (2.0 equiv), 130 °C,
20 h. b Isolated yield. cAfter 34 h.
Conclusion
The progress of the reaction was monitored by TLC. When the
We have developed a CuO nanoparticles catalyzed synthesis of reaction was complete, the reaction mixture was allowed to
symmetrical diaryl sulfides via cascade reaction of aryl halides cool, a 1:1 mixture ethyl acetate and water (20 mL) was added
with potassium thiocyanate under ligand free conditions. The and the CuO was removed by centrifugation. The organic layer
reaction avoids foul smelling thiols and the catalyst is eco- was washed successively with brine and water, and dried with
nomical, air stable, functions under ligand free conditions and is Na2SO4. The solvent and volatiles were completely removed
recyclable for up to four cycles without loss of catalytic activity under vacuum to give the crude product, which was purified by
[20,39-41] (Table 4).
column chromatography on silica gel to yield the analytically
pure product in up to 94% yield. The identity and purity of the
product was confirmed by 1H and 13C NMR spectroscopy.
Table 4: Copper oxide reusability of the catalyst.
Recylces
Yield (%)
Catalyst recovery (%)
Supporting Information
Native
94
92
89
86
93
91
88
85
Supporting Information File 1
Experimental details and spectroscopic data for new
compounds.
1
2
3
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-101-S1.pdf]
Experimental
General procedure for the synthesis of diaryl sulfides: A
mixture of aryl iodide (2.0 mmol), potassium thiocyanate
(1.5 mmol), nano CuO (5.0 mol %), and KOH (2.0 equiv) was
stirred at 130 °C under a N2 atmosphere in DMSO (2.0 mL).
Acknowledgements
KHVR and VPR thank CSIR, New Delhi, for the award of
fellowship.
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Beilstein J. Org. Chem. 2011, 7, 886–891.
28.Wang, H.; Jiang, L.; Chen, T.; Li, Y. Eur. J. Org. Chem. 2010, 12, 2324.
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