CuI catalyzed CS bond formation by using nitroarenes

Article abstract of DOI:10.1016/j.catcom.2013.07.019

An efficient, CuI catalyzed, ligand free, synthetic protocol for thioethers has been developed by using nitroarenes. A variety of thiols and nitroarenes was scanned by using this method to produce aryl sulfides. Newly developed method demonstrates a new alternative to existing method which is cost effective approach to synthesize nonsymmetrical aryl thioethers.

Full text of DOI:10.1016/j.catcom.2013.07.019

Catalysis Communications 41 (2013) 123–125
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Catalysis Communications
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Short Communication
CuI catalyzed C\S bond formation by using nitroarenes
Sushilkumar S. Bahekar a, Aniket P. Sarkate b, Vijay M. Wadhai a, Pravin S. Wakte b, Devanand B. Shinde b,
⁎
a
Department of Applied Sciences, MIT College of Engineering, Kothrud, Pune, 411038 MS, India
b
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, 431004 MS, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 May 2013
Received in revised form 9 July 2013
Accepted 10 July 2013
Available online 20 July 2013
An efficient, CuI catalyzed, ligand free, synthetic protocol for thioethers has been developed by using nitroarenes.
A variety of thiols and nitroarenes was scanned by using this method to produce aryl sulfides. Newly developed
method demonstrates a new alternative to existing method which is cost effective approach to synthesize
nonsymmetrical aryl thioethers.
© 2013 Elsevier B.V. All rights reserved.
Keywords:
Catalysis
Ullmann
Nitroarenes
CuI
Sulfides
Ligand free
1. Introduction
2. Experimental
Due to wide-ranging applications in chemical, pharmaceutical
industries [1–3] and as intermediates in organic synthesis [4] sulfides
have emerged as crucial class of organic compounds. Although
transition-metal catalyzed [5–7] carbon heteroatom cross-coupling
reactions have made a great contribution to prepare such moieties,
problems in C\S bond synthesis can be attributed to the sulfur species
rapidly and irreversibly deactivating the catalyst [5,8]. So the efficient
formation of the C\S bond is a most imperative aspect of organic
chemistry.
Typically, the preparation of such compounds involves reaction
of aryl halides with thiophenols by using Pd, [5,9–11] Cu, [12–16]
Ni, [17–19] Fe [20] and other metals as catalysts have been found
more useful. These metal catalysts were used in the presence of
ligand [7,8]. Alternative, literature also has reports about reaction
of boronic acids [21] with thiophenol in the presence of metal
catalyst to produce C\S bond. However, the high cost and air
sensitivity of Pd catalyst systems limit their use in large-scale
practice, and the scope of Cu and other transition-metal catalyst
systems is suitable only for aryl bromides/iodides or triflates. So
the development of a milder environment friendly, cheap and
efficient catalyst system is still desirable. Herein we report the
foremost model of ligand-free, copper-catalyzed synthesis of
nonsymmetrical diaryl sulfides via s-arylation of thiophenols with
nitroarenes (Scheme 1).
All the chemicals and solvents were used from Sigma-Aldrich.
Melting points were uncorrected and recorded on optimelt digital
melting point apparatus. IR spectra were recorded on Bruker alpha E
FTIR spectrophotometer. 1H NMR was recorded on varian 300 MHz
spectrometer by using TMS as internal standard.
2.1. General procedure for the synthesis of compound 3a–3m
To the solution of nitroarene (1 mmol) and thiophenol (1 mmol) in
DMF, anhydrous potassium carbonate (2 mmol) and CuI (0.2 mmol)
were added. The reaction mixture was refluxed at 120 °C in oil bath
until complete consumption (9–12 h) of starting material (TLC). The
reaction mixture was cooled to room temperature, diluted with water
and extracted with ethyl acetate. Combined extract was washed with
water and dried with sodium sulfate, concentrated under vacuum and
the resulting residue was purified by flash column chromatography
(hexane/ethyl acetate) to afford the desired product (Scheme 2).
Spectral data of selected compounds are noted in the references [25].
3. Results and discussion
In the beginning studies, we used 10 mol% of CuI and 2 equivalent of
K2CO3 with 1-methyl-4-nitrobenzene and thiophenol in DMF at 120 °C
(Scheme 1), reaction takes 20 h to complete (TLC, entry 12, Table 1). Re-
action provided 87% isolated yield of the corresponding diaryl thioether.
Furthermore 20 mol% of CuI produces 95% isolated yield in 12 h, we
also optimized the same reaction with 30 mol% of CuI but it produces
near about same result as with 20 mol% of CuI (entry 1 and 11,
⁎
Corresponding author. Tel.: +91 240 2403306; fax: +91 240 2400413.
E-mail address: dbsaniket09@gmail.com (D.B. Shinde).
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.07.019

124
S.S. Bahekar et al. / Catalysis Communications 41 (2013) 123–125
Table 1
Optimization of Cu salt and solvent.
Entry
Cu salt
Solvent
Time (h)
Yield (%)c
1
2
3
4
5
6
7
8
CuI
DMF
DMF
DMF
DMF
12
13
13
14
22
30
30
30
36
30
12
20
48
95
88
89
93
85
88
87
84
82
86
94
87
00
Scheme 1. Synthesis of diaryl thioether.
CuBr
CuCl2
Cu(OTf2)
Cu(OAc)2
CuI
CuI
CuI
CuI
DMF
DMSO
Toluene
Xylene
Acetonitrile
THF
DMF
DMF
DMF
9
10
11
12
13
CuI
CuIa
CuIb
–
Scheme 2. Synthesis of substituted diaryl thioethers.
a
30 mol% of CuI used.
10 mol% of CuI used.
Ioslated yield.
Table 1). The reaction was screened with several copper salts and
solvents to enhance the competence of the coupling reactions and the
results are summarized in (Table 1). It was found that reaction works
with each of Cu salt but it takes more time with Cu (OAc)2 (entry 5,
Table 1). CuBr, CuCl2 and Cu (OTf2) produce thioether in 13–14 h but
yields are less compared to CuI (entries 2–4, Table 1). DMF was turnout
as the best solvent among those examined. It is important to note that
when reaction was carried out without a catalyst not even a trace
amount of thioether formed (entry 13, Table 1).
Numerous literature reports [22–24] suggested that the participa-
tion of copper intermediates plays a key role in Ullmann condensation.
For present approach to explain the possible pathway we would like to
propose a mechanism. We believe that, this reaction may proceed via σ
bond metathesis through a four-center intermediate. (Fig. 1) The first
step in this mechanistic cycle is that nucleophile reacts with the
copper halide to form a Cu\Nu species which acts as a catalyst for the
coupling reaction. Consequently, this copper catalyst coordinates to
the nitroarene via a four-centered intermediate. Due to high electroneg-
ativity of nitro group, coordination is orientated by the partial charges
on Cu+ and on the electronegative nitro group. Hence, the polarization
of the C\NO2 bond creates a partial positive charge on the ipso-carbon
and assists the substitution by the nucleophile to get desired product.
Using the newly optimized conditions, we commence our exploration
into the scope of the CuI catalyzed ligand free Ullmann type coupling of
nitroarenes with thiols and the results are summarized in Table 2. The
C\S bond formation was studied by reacting various nitroarenes with
aryl thiols give corresponding sulfides. In the nitroarenes component
(entries 2–6, Table 2) and thiols with electron donating groups and
electron-withdrawing groups gave the corresponding thioethers in
very high yields. Impressively, irrespective of position (ortho or para)
b
c
of substituents on nitroarenes as well as on thiols, excellent yields of
aryl sulfides were obtained (entries 7–12, Table 2). It is also observed
that heterocyclic nitroarenes also give excellent yield (entry13, Table 2).
However, the presence of electron-withdrawing groups such as
cyano or keto groups drastically increased the yield as well as the reac-
tion rate (entries 6, 7 and 11, Table 2). In comparison with the reported
[9–20] Cu-, Pd- and Ni-catalyzed syntheses of thioethers via the cou-
pling of aryl halides and thiols, the present method offers a very inter-
esting alternative.
4. Conclusions
In summary, the work illustrates the first CuI catalyzed, ligand free
coupling of nitroarenes with thiols to form aryl sulfides under mild
reaction conditions with excellent yields. This new approach underlines
the potential of using nitroarenes as a very user-friendly, inexpensive,
and efficient starting material for C-S bond formation. Further studies
along these lines are underway in our laboratories.
Acknowledgment
The authors are thankful to The Head, Department of Chemical
Technology, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad 431 004 (MS), India, for providing the laboratory
facility.
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Fig. 1. Possible mechanism for the reaction.

S.S. Bahekar et al. / Catalysis Communications 41 (2013) 123–125
125
Table 2
Coupling of nitroarenes with thiols.
Entry
1
Sr. no.
a
Halo arenes
Thiols
Aryl sulfide
Isolated yieldb (%)
93
2
3
b
c
95
91
4
5
d
e
95
89
6
7
f
97a
98a
g
8
h
i
92
9
90
10
j
98a
11
12
k
l
91
93
13
m
88
a
Reaction completed in 9 h.
Isolated yield.
b
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δ
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