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Chemistry Letters Vol.34, No.9 (2005)
Chemoselective Oxidation of Sulfides to Sulfoxides Using N-t-Butyl-N-chlorocyanamide
Vinod Kumar and Mahabir Parshad Kaushikꢀ
Process Technology Development Division, Defence R & D Establishment,
Jhansi Road, Gwalior-474002 (MP), India
(Received May 19, 2005; CL-050667)
A simple, efficient and highly chemoselective method
This protocol uses 2 as positive chlorine donor for the oxi-
dation of sulfides to sulfoxides in a mixed acetonitrile–water
solution (Scheme 1). The reaction was almost instantaneous at
25 ꢁC and took less than a minute for complete transformation
of sulfides to sulfoxides. A series of experiments established that
one mol of 2 per mol of sulfides were required to obtain maxi-
mum yield of the sulfoxides. Using standard conditions, the ox-
idation of a series of sulfides was examined (Table 1). Many fac-
tors such as change in the alkyl aryl group and the choice of the
reaction medium also have profound effect on the progress of the
reaction. The sulfides were chosen to reflect a variety of structur-
al types. Dialkyl, alkyl aryl, diaryl, cyclic, dibenzothiophene and
sulfide with ester moiety reacted with 2 under these reaction con-
ditions to produce the corresponding sulfoxides in excellent
yields in less than a min along with quantitative recovery of
t-butylcyanamide 4. The reactivity was almost the same for all
the sulfides used in this study. The choice of reaction medium is
important. The best results were obtained in acetonitrile–water
(1:1). However, in case of phenyl methyl sulfide, 4-chlorophenyl
methyl sulfide, diphenyl sulfide, and dibezothiophene (Table 1,
Entrys 1, 2, 4, and 13) which are insoluble in 1:1 acetonitrile–
water solution, this solution in the ratio of 7:3 was used to get
maximum yield. Generally, electron-withdrawing group attach-
ed to sulfides reduces the reactivity against oxidation. The nota-
ble feature of this method is the efficient oxygenation of even
those sulfides, which are linked to electron-withdrawing group
(Table 1, Entry 5). The formation of sulfoxide is thought to
proceed via the formation of sulfonium ion 5, which is formed
by the attack of sulfur on the electrophilic chlorine, which then
has been developed for the synthesis of sulfoxides from sulfides
using N-t-butyl-N-chlorocyanamide as an oxidant in a mixed
acetonitrile–water solution with a 1:1 mol ratio of oxidant to
sulfides. N-t-butyl-N-chlorocyanamide, a source of positive
chlorine, has been used for conversion of the variety of sulfides
into their corresponding sulfoxides in quantitative yields.
Sulfoxides have attracted the attention of organic chemists
for a long time owing to their varied reactivity as a functional
group for the transformations into variety of organosulfur com-
pounds. These transformations are useful for the synthesis of
drugs and sulfur-substituted natural products.1,2 Sulfoxides are
also useful for the stereocontrol in the construction of chemically
and biologically important molecules.3–5 These compounds are
usually prepared by the oxidation of sulfides and several oxida-
tive procedures are applicable for this transformation.6,7 Gener-
ally, it is important to stop the oxidation at the sulfoxide stage by
controlling the electrophilic character of the oxidant, but this
requirement is often hard to meet and the failure results in
over-oxidation of sulfoxides to sulfones. Therefore, there is still
considerable interest in the development of selective oxidants for
this important transformation.6 There is significant difference in
the nuleophilicity of the sulfides compared to the sulfoxides,8
although several methods are known6,7 for oxidizing sulfides
to sulfoxides, very few are sufficiently selective to terminate
oxidation at the sulfoxides stage and prevent over-oxidation to
sulfones.9 The most recent reports on sulfoxides synthesis
include formation from thionyl chloride and arenes employing
trifluoromethanesulfonic acid10 or scandium triflate11 as the
catalyst. The direct preparation of sulfoxides often suffers from
the formation of mixture of the products containing sulfonium
salt and chlorinated by-products along with desired sulfoxides.12
Copper-catalyzed (TEMPO) oxidation of sulfides to sulfoxides
has just been reported.13 No doubt this method works at ambient
temperature with improved selectivity, but time-consuming. A
variety of the existing methods have disadvantages of being
expensive, using toxic chemicals, or suffering from moderate
selectivity. In the course of our studies on N-t-butyl-N-chloro-
cyanamide14 2 for oxidation of sulfides, we have explored a
rapid, efficient, economic, and easy-to-use method for chemose-
lective and quantitative transformation of sulfides to their corre-
sponding sulfoxide.
Table 1. Preparation of sulfoxides15 by 2
Entry
R
R0
Yield/%b
1a
2a
3
CH3
CH3
C6H5
94
95
95
96
94
96
94
96
92
94
95
95
92
90
p-Cl-C6H5
C6H5
C6H5
i-C3H7
C6H5
4a
5
p-Ac-C6H5
C3H7
i-C3H7
p-Ac-C6H5
C3H7
i-C3H7
6
7
8
C4H9
C4H9
(CH2)2-OH
C2H5
9
(CH2)2-OH
(CH2)2-OH
C2H5
10
11
12
13a
14
COOMe
—
—
Tetrahydrothiophene
Dibenzothiophene
1,4-Dithiane
CN
O
S
ACN:H O, (1:1)
2
N
R
R'
N
H
CN
1,4-Dithiane-1-oxide
S
R
R'
Cl
All products had satisfactory spectroscopic data and were com-
pared with authentic samples.
1
2
3
4
b
aAcetonitrile–water ratio is 7:3. Isolated yield.
Scheme 1. Synthesis of sulfoxides from sulfides.
Copyright Ó 2005 The Chemical Society of Japan