Bi(III)-catalyzed C-S cross-coupling reaction

Article abstract of DOI:10.1002/aoc.2871

A direct synthetic route for the C-S coupling of aryl halides with thiophenols is described. This method is tolerant to electron-withdrawing and electron-donating functional groups and also to the presence of functional groups in the ortho position of the aryl iodide or thiophenol. Aryl iodides are coupled with thiophenols without affecting the other functionalities present in the aryl ring. These reactions follow second-order kinetics. Copyright

Full text of DOI:10.1002/aoc.2871

Full Paper
Received: 12 January 2012
Revised: 5 April 2012
Accepted: 7 April 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2871
Bi(III)-catalyzed C-S cross-coupling reaction
Payal Malik and Debashis Chakraborty*
A direct synthetic route for the C-S coupling of aryl halides with thiophenols is described. This method is tolerant to electron-
withdrawing and electron-donating functional groups and also to the presence of functional groups in the ortho position of
the aryl iodide or thiophenol. Aryl iodides are coupled with thiophenols without affecting the other functionalities present
in the aryl ring. These reactions follow second-order kinetics. Copyright © 2012 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: C-S cross-coupling reaction; Bi2O3; aryl halide; thiophenol; water
Introduction
Results and Discussion
C-S Cross-Coupling Reaction
Cross-couplings catalyzed by transition metals historically rely
on a reactive electrophile into which a transition metal inserts,
and a reactive nucleophile that transfers an organic fragment
to the transition metal center. Reductive elimination finally
delivers the product.[1–5] Over time, milder and more selective
conditions for cross-coupling reactions have been developed.
Since the development of metal-catalyzed cross-coupling
reactions in 1970s, numerous efforts have been made to make
cross-coupling reactions more reliable and applicable.[6–8] In
the last decade, transition metal-catalyzed C-S coupling of
diaryl disulfides with aryl halides, boronic acid, aryl silane and
aryl bismuthane have been reported.[9–11] The C-S bond is
important in numerous compounds with biological and pharma-
ceutical impact as well as for precursors required for the
development of molecular materials, making several methods
for its formation indispensable.[12–20] The traditional methods
for C-S bond formation often employ harsh conditions. The
coupling of thiolates with aryl halides takes place in hexamethyl-
phosphoramide at 200ꢀC. The reduction of sulfoxides and
sulfones is carried out with strong reducing agents like DIBAL-H
and LiAlH4.[21,22] To overcome such drawbacks, considerable
research on the development of catalytic systems for the C-S
cross-coupling of thiols with aryl halides have been developed.
For industries, these reactions are attractive because the cost
and environmental impact of the process (E factor) are relatively
The onset of investigations began with a search for the optimal
conditions required for the C-S coupling between various aryl
iodides and thiophenols. The reactions were performed in the
presence of various Bi(III) compounds, solvents, ligands and bases
(Table 1). The optimization results reveal that the 10 mol%
Bi2O3 and N,N-dimethylethane-1,2-diamine with 1 equiv. KOH
in water were the best reaction conditions. In fact, the prod-
uct yield was reduced drastically when less than 10 mol%
Bi2O3 was used.
The results shown in Table 2 indicate that the coupling of
thiophenols with aryl bromides or iodides was successful, leading
to the desired product in excellent yield. In summary, this protocol
is tolerant to electron-withdrawing and electron-donating functional
groups and also to the presence of a functional group in the ortho
position of the aryl iodide or thiophenol. The coupling reaction is
chemoselective. Aryl iodides coupled with thiophenols without
affecting fluoro, chloro, bromo and amino groups present in the aryl
ring. In general the reactions using aryl bromides are slower as
compared to the corresponding iodides and aryl chlorides were
found to be unreactive under the same reaction conditions.
The work-up for these coupling reactions involves extraction of
the aqueous reaction mixture with ethyl acetate, and subsequent
removal of solvent followed by flash chromatography of the
crude product. We are pleased to disclose that the aqueous
phase containing Bi2O3 can be recycled repeatedly without much
loss in activity of the reaction or yield (Table 3). We do not isolate
the Bi2O3 from the aqueous suspension, which is used repeatedly
for subsequent cycles. The requisite amount of KOH was added
along with the starting materials.
low. Palladium-,[23–36] copper-,[37–60] nickel-,[61–67] cobalt-,[68]
[69–72]
and iron-based
catalytic systems have been reported for
this purpose. The high cost and air sensitivity of palladium cata-
lyst systems and tedious procedures for the preparation of
ligands restrict their applications in large-scale processes. Al-
though useful methods are currently available, the requirement
of high temperatures or specially designed phosphine ligands
has prompted a search for new methods. Hence there is a need
for improved procedures for this important reaction in organic
chemistry. Recently, bismuth salts have been employed for vari-
ous organic transformations owing to its benign nature.[73–79]
Our continued interest in green chemistry research prompted
us to explore the capability of bismuth compounds in catalyzing
various organic reactions.[80,81]
*
Correspondence to: Debashis Chakraborty, Department of Chemistry, Indian
Institute of Technology Madras, Chennai-600 036, Tamil Nadu, India. E-mail:
dchakraborty@iitm.ac.in
Department of Chemistry, Indian Institute of Technology Madras, Chennai-600
036, Tamil Nadu, India
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

P. Malik and D. Chakraborty
Table 1. Optimization of reaction conditionsa
Entry
Catalyst
Bi2O3
Ligand
Solvent
Base
KOH
Time (h)b
Yield (%)c
1
1
2
3
4
5
6
7
4
4
4
4
4
4
4
4
4
4
4
4
4
4
H2O
34
39
30
21
24
44
30
30
32
35
40
33
42
50
26
30
34
31
35
28
48
64
53
81
90
85
50
45
60
69
40
30
60
58
50
82
75
71
69
50
60
38
2
Bi2O3
H2O
KOH
3
Bi2O3
H2O
KOH
4
Bi2O3
Bi2O3
H2O
H2O
KOH
KOH
5
6
Bi2O3
H2O
KOH
7
Bi2O3
H2O
KOH
8
Bi2O3
DMSO
DMF
Toluene
CH3CN
H2O
KOH
9
Bi2O3
KOH
10
11
12
13
14
15
16
17
18
19
20
21
Bi2O3
KOH
Bi2O3
KOH
BiCl3
KOH
BiBr3
H2O
KOH
Bi(NO3)3.5H2O
Bi2O3
H2O
KOH
H2O
K3PO4
Cs2CO3
Na2CO3
K2CO3
NaHCO3
NaOH
KOH
Bi2O3
H2O
Bi2O3
H2O
Bi2O3
H2O
Bi2O3
H2O
Bi2O3
H2O
Bi2O3 (5 mol%)
H2O
a4-Methylbenzenethiol (1 mmol) and phenyl iodide (1.2 mmol) were used.
bMonitored using TLC until all the thiophenol was found consumed.
cIsolated yield after column chromatography of the crude product.
The kinetics for the coupling reaction of 2,4-dimethylbenze-
nethiol with phenyl iodide was investigated. High-performance
liquid chromatography (HPLC) was used to determine the various
starting materials and products present as a function of time. The
concentration of thiophenol decreases steadily, while that of the
product increases (see supporting information). We have calcu-
lated the rate of such reactions. The van’t Hoff differential method
was used to determine the order (n) and rate constant (k) (Fig. 1).
The rate of the reaction at different concentrations can be
estimated by evaluating the slope of the tangent at each point
on the curve corresponding to that of 2,4-dimethylbenzenethiol.
With these data, log10(rate) versus log10(concentration) is plotted.
The order (n) and rate constant (k) are given by the slope of the
line and its intercept on the log10(rate) axis. From Fig. 1, it is clear
that this reaction proceeds with second-order kinetics (n = 2.01)
accompanied by elimination of the product and the ligand catalyst
complex is set free to participate in the subsequent cycle. This
mechanism is in accordance with reports available in the literature.
We have concluded from inductively coupled plasma mass
spectrometric studies performed on Bi2O3 that this catalysis is
not a result of impurities (see supporting information). Trace Cu
(II) or Fe(III) was introduced into the reaction mixture in the
absence of Bi2O3. The reaction mixture was stirred for 21 h. HPLC
analysis of the crude after work-up revealed the presence of
the expected product in trace quantities. These studies suggest
that the contribution of product formation due to the presence
of Cu(II) or Fe(III) impurities is negligible.
Conclusions
and the rate constant k = 0.1068 L molÀ1 hÀ1
.
The proposed catalytic cycle (Scheme 1) for this coupling
reaction involves the coordination of the ligand to Bi2O3. The
next step involves the coordination of the aryl bromide or iodide
to this complex, followed by attack of the thiolate anion. This is
A simple and efficient procedure is described for C-S bond forma-
tion by cross-coupling of thiophenols with aryl bromides and
iodides by using a combination of Bi2O3 and N,N-dimethylethane-
1,2-diamine in water. These reactions do not require an inert
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Appl. Organometal. Chem. (2012)

Bi(III) catalyzed C-S grouping
Table 2. Bi2O3 catalyzed C-S cross-coupling reaction of thiophenols with aryl halidesa
Entry
Thiophenol
Halide
Product
Time (h)b
Yield (%)c
Characterization (ref.)d
1
2
27
22
84
87
[82]
[84]
3
20
88
[85]
4
5
26
29
84
85
[82]
[82]
6
7
8
9
17
30
18
17
92
85
88
86
[84]
[84]
[85]
[84]
10
11
12
29
21
30
85
90
88
[86]
[54]
[84]
13
28
90
[83]
14
15
35
31
85
87
[72]
[82]
16
40
78
[72]
17
18
52
27
60
82
[86]
[86]
aReactions of thiophenol (1 mmol) and aryl halide (1.2 mmol) with 10 mol% Bi2O3, 10 mol% N,N-dimethylethane-1,2-diamine and 1 equiv. KOH were
performed in H2O at 100ꢀC.
bMonitored with TLC.
cIsolated yield after column chromatography of the crude product.
dReference for authenticated product characterization.
atmosphere and can be performed at moderate temperatures,
resulting in products in high yield and purity.
(0.011 ml, 10 mol%) and KOH (56 mg, 1 equiv.), aryl halide
(1.2 mmol) were added. The reaction mixture was heated to
reflux and monitored using thin-layer chromatography (TLC) pe-
riodically until all thiophenol was found consumed. The reaction
mixture was extracted repeatedly with ethyl acetate. All the
volatile organics were removed under reduced pressure. The
crude product was purified using flash column chromatography.
The characterization data matched very well with the literature
(Table 2).
Experimental
Typical Procedure for the Coupling of Thiophenol
and Aryl Halide
To a stirred aqueous (2.5 ml) suspension of thiophenol (1 mmol),
Bi2O3 (46 mg, 10 mol %), N,N-dimethylethane-1,2-diamine
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
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P. Malik and D. Chakraborty
Table 3. Results for the coupling of iodobenzene and 4-methyl
Acknowledgments
benzenethiol in different cyclesa
The authors thank the Department of Science and Technology,
New Delhi, for financial support.
Cycle
Time (h)b
Yield (%)c
1
2
3
4
5
21
21
21
21
21
90
90
90
89
89
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