TMSCl-promoted selective oxidation of sulfides to sulfoxides with hydrogen peroxide

Article abstract of DOI:10.1016/j.tetlet.2010.10.171

Selective oxidation of sulfides to sulfoxides is achieved using H ₂O₂ and TMSCl as the promotor. Aromatic and aliphatic sulfides are oxidized to sulfoxides in excellent yields and in short reaction times. Different functional groups including ketone, alkene, ester, and alcohol are tolerated.

Full text of DOI:10.1016/j.tetlet.2010.10.171

Tetrahedron Letters 51 (2010) 6939–6941
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Tetrahedron Letters
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TMSCl-promoted selective oxidation of sulfides to sulfoxides with
hydrogen peroxide
Kiumars Bahrami a, , Mohammad M. Khodaei a, , Behrooz H. Yousefi b, Mehdi Sheikh Arabi a
⇑
⇑
a Department of Chemistry, Razi University, Kermanshah 67149-67346, Iran
b Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, D-81675 Munich, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Selective oxidation of sulfides to sulfoxides is achieved using H2O2 and TMSCl as the promotor. Aromatic
and aliphatic sulfides are oxidized to sulfoxides in excellent yields and in short reaction times. Different
functional groups including ketone, alkene, ester, and alcohol are tolerated.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 1 August 2010
Revised 18 October 2010
Accepted 29 October 2010
Available online 4 November 2010
1. Introduction
tion of sulfides to sulfoxides in excellent yields and in short reac-
tion times (Scheme 1).
Selective oxidation of sulfides to sulfoxides is a very important
reaction in organic synthesis, since they are useful synthetic inter-
mediates for the construction of various chemically and biologi-
cally significant molecules,1 especially drugs and natural
products.2 The direct oxidation of sulfides is an important and
widely studied reaction for the preparation of sulfoxides. Although
a number of methods are available for the conversion of sulfides
into sulfoxides,3–9 there are various limitations such as the use of
strong acidic or basic conditions, elevated temperatures, long
reaction times, hazardous organic solvents and reagents, transition
metal catalysts, the formation of sulfones as side products from
over-oxidation and undesired side reactions occurring on other
functional groups. Hence, there is still a need for the development
of new, efficient, highly selective, and widely applicable methods
for this transformation under mild reaction conditions.
The use of H2O2 as an oxidant has been studied extensively.
Aqueous H2O2 has the advantage that it is a cheap, environmen-
tally benign, and a readily available reagent.10 Since water is the
only expected side product, catalytic oxidation methods using this
reagent are appealing, provided efficient catalysis is accomplished.
This feature has stimulated the development of useful procedures
for H2O2 oxidation, especially with various types of catalyst
systems.11
In order to check the feasibility of the H2O2–TMSCl system in an
organic medium, we performed the oxidation in acetonitrile, tolu-
ene, chloroform, and THF. The best results based on yields and
times were achieved using acetonitrile.
We next performed a set of preliminary experiments on benzyl
phenyl sulfide to examine the effects of different amounts of aque-
ous 30% H2O2 and TMSCl in acetonitrile at 25 °C (Table 1).
It is noteworthy that in a blank experiment (Table 1, entry 1), no
significant oxidation was observed in the absence of TMSCl, and
O
R
S
R'
R
S
R'
R, R' = alkyl, allyl, aryl
Scheme 1. Reagents and conditions: H2O2 (2 equiv), TMSCl (1 equiv), CH3CN, 25 °C.
Table 1
Optimization of the reaction conditions for the oxidation of benzyl phenyl sulfide
using H2O2 and TMSCla
O
S
Ph
Trimethylsilyl chloride (TMSCl) is an efficient Lewis acid which
has found widespread use as a catalyst in organic transforma-
tions.12–14 To the best of our knowledge, there are no reports on
TMSCl-mediated selective oxidation of sulfides.
In continuation of our recent work on the oxidation of sul-
fides,15 herein we report an efficient protocol in which H2O2 has
been used in the presence of TMSCl for the chemoselective oxida-
Ph
S
Ph
Ph
Entry
30% H2O2 (mmol)
TMSCl (mmol)
Yieldb (%)
1
2
3
4
2
2
1
2
0
0.75
1
35c
75
40
98
1
a
b
c
⇑
Reaction conditions: benzyl phenyl sulfide (1 mmol), 2 min, 25 °C.
Isolated yield.
Reaction not complete after 6 h.
Corresponding author. Tel.: +98 831 4274559; fax: +98 831 4274559.
E-mail addresses: Kbahrami2@hotmail.com (K. Bahrami), mmkhoda@razi.ac.ir
(M.M. Khodaei).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.171

6940
K. Bahrami et al. / Tetrahedron Letters 51 (2010) 6939–6941
only a low yield of sulfoxide was obtained in the presence of
2 equiv of H2O2 after 6 h.
allyl, diaryl, dialkyl, cyclic and heterocyclic sulfides could be oxi-
dized to the corresponding sulfoxides in excellent yields. Sulfides
carrying either electron-withdrawing (entry 2) or electron-
donating (entries 3 and 11) substituents gave the corresponding
sulfoxides in excellent yields with high purity. Importantly, this
method was compatible with other functional groups such as
ketone (entry 6), alkene (entry 8), ester (entry 9), and alcohol
(entry 10). Typically, these oxidations could usually be
stopped at the sulfoxide stage without over-oxidation to the
sulfone.
Increasing the temperature to 50 °C reduced the reaction time,
however, 15% of the corresponding sulfone was formed along with
the sulfoxide. Control experiments showed that oxidation with less
30% H2O2 (1 equiv) took longer (40 min) while the use of excess
30% H2O2 (3 equiv) increased sulfone contamination, thereby
reducing the selectivity of the oxidation.
Several functionalized sulfides were selected to examine the
scope and limitations of this procedure (Table 2). Aryl alkyl, aryl
Table 2
Selective oxidation of sulfides to sulfoxides using the H2O2–TMSCl system in CH3CNa
Entry
Sulfide
Sulfoxide
Yieldb (%)/time (min)
98 (2)
Mp (°C)
O
1
120–12216a
S
S
O
S
S
2
3
99 (20)
94 (15)
163–16416b
O2N
Me
O2N
Me
Br
Br
O
S
S
15816c
O
S
4
5
95 (2)
96 (3)
13216d
S
S
O
S
6816d
O
O
6c
94 (10)
199–20116e
S
O
N
S
N
O
S
S
7
8
96 (10)
94 (3)
17215e
N
H
N
H
O
S
S
Oil16f
O
O
S
O
S
S
CH3
CH3
9
93 (35)
98 (3)
Oil16g
O
O
O
S
OH
10
151–15316h
OH
S
O
S
CH3
39–4016d
CH3
11
98 (10)
H3C
H3C
S
O
S
12
13
92 (3)
95 (3)
29–3015c
Oil16i
(CH3)2S
(CH3)2S@O
a
b
c
The purified products were characterized by mp and 1H and 13C NMR spectroscopy.
Yield refers to pure isolated product.
1,4-Dioxane was used as the solvent.

K. Bahrami et al. / Tetrahedron Letters 51 (2010) 6939–6941
6941
Me
Supplementary data
Me
Me Si Cl
Me
Si Me
Me
O
H
O
+
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.171.
H
O
H
O
..
- HCl
A
References and notes
H
O
Me
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the oxygen atom is more electrophilic. Next, nucleophilic attack of
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hydrogen abstraction to yield the corresponding sulfoxide. It is sig-
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water and as a result, does not contaminate the product. Simple
extraction or recrystallization of the product from a mixture of eth-
anol and water afforded pure product.
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2. General procedure for the oxidation of sulfides
In a round-bottomed flask (50 mL) equipped with a stir bar, a
solution of sulfide (2 mmol) in CH3CN (10 mL) was prepared. Aque-
ous 30% H2O2 (4 mmol, 0.4 mL) and TMSCl (2 mmol) were added
and the mixture was stirred at 25 °C for the time period specified
in Table 2. The progress of the reaction was monitored by TLC (elu-
ent: n-hexane/EtOAc, 7:3). After disappearance of the sulfide, the
reaction mixture was quenched by adding H2O (10 mL), extracted
with EtOAc (4 Â 5 mL), and the extract dried with anhydrous
MgSO4. Evaporation gave the corresponding sulfoxide as the only
product. Spectral and physical data for selected compounds can
be found in the Supplementary data.
Acknowledgment
We are thankful to the Razi University Research Council for par-
tial support of this work.