Selective and efficient oxidation of sulfides to sulfoxides with N-bromosuccinimide in the presence of β-cyclodextrin in water

Article abstract of DOI:10.1016/j.tetlet.2005.05.011

A simple and highly selective oxidation of sulfides to sulfoxides with N-bromosuccinimide (NBS) catalyzed by β-cyclodextrin in water has been developed. A series of sulfides were oxidized selectively at room temperature in excellent yields. This reaction

Full text of DOI:10.1016/j.tetlet.2005.05.011

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4581–4583
Selective and efficient oxidation of sulfides to sulfoxides with
N-bromosuccinimide in the presence of b-cyclodextrin in waterq
K. Surendra, N. Srilakshmi Krishnaveni, V. Pavan Kumar, R. Sridhar and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 28 February 2005; revised 29 April 2005; accepted 4 May 2005
Available online 23 May 2005
Abstract—A simple and highly selective oxidation of sulfides to sulfoxides with N-bromosuccinimide (NBS) catalyzed by b-cyclo-
dextrin in water has been developed. A series of sulfides were oxidized selectively at room temperature in excellent yields. This reac-
tion proceeds without over-oxidation to sulfones under mild conditions using water as a solvent and has many advantages over the
existing methodologies.
Ó 2005 Published by Elsevier Ltd.
Organic sulfoxides are versatile synthons for C–C bond
formation, molecular rearrangements, functional group
transformations and are also utilized as precursors for
biologically active and chemically important com-
pounds.1 The selective and catalytic oxyfunctionaliza-
with NBS but substrates like pMe-C6H4SMe, etc., gave
no sulfoxide, but instead underwent C–S bond cleavage
under these conditions.11
Cyclodextrins are cyclic oligosaccharides, which catalyze
reactions by supramolecular catalysis involving revers-
ible formation of host–guest complexes by non-covalent
bonding as seen in enzymes. In continuation of our ef-
forts to develop biomimetic approaches for chemical
reactions involving cyclodextrins in water,12 we report
herein an efficient, simple and practical method for the
oxidation of sulfides with NBS catalyzed by b-cyclodex-
trin in water under neutral conditions (Scheme 1).
tion of sulfur is
a pivotal reaction in organic
synthesis.2 Hence, selective oxidation of organic sulfides
is very important from both industrial and green chem-
istry points of view as organosulfur compounds are a
major source of environmental pollution.3 In view of
the importance of sulfoxides, several reagents have been
used for this key transformation such as hypervalent io-
dine compounds,4 H2O2 and its derivatives,5 CAN,6
MnO2–H2SO4/silica gel,7a MnO2–HCl7b and metal
salts,8 photochemical oxidations,9 etc. Though different
approaches have been reported, there are various limita-
tions such as the use of strong acidic or basic conditions,
elevated temperatures, long reaction times, hazardous
organic solvents and reagents, transition metal catalysts,
promoters for the activation of catalysts and low yields.
In general, the reaction was carried out by the in situ
formation of the b-cyclodextrin complex of the substrate
in water followed by the addition of NBS and stirring at
room temperature to give the corresponding sulfoxides
in high yields (Table 1).13 The reaction goes smoothly
at room temperature without the formation of any side
products. No over-oxidation to sulfones was observed.
No stringent conditions were required for these selective
oxidations. Hydrogen bonding may also assist in con-
trolling the chemoselectivity, since cyclodextrin can bind
the product sulfoxide by hydrogen bonding with the
The previously reported use of N-bromosuccinimide for
the oxidation of sulfides has usually been carried out
using anhydrous solvents at various temperatures.10 It
had been shown earlier that certain aromatic sulfides
could be oxidized to sulfoxides in 70% dioxane–water
O
β
-CD/H2O
NBS/rt
R1
R1
S
R2
R2
S
Keywords: Sulfides; Sulfoxides; Oxidation; N-bromosuccinimide;
b-Cyclodextrin; Biomimetic; Water.
q IICT Communication No. 050322.
R1 =aryl, naphthyl; R2 =alkyl
*
Corresponding author. Tel.: +91 4027193164; fax: +91
4027160757; e-mail: drkrrao@yahoo.com
Scheme 1.
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.05.011

4582
K. Surendra et al. / Tetrahedron Letters 46 (2005) 4581–4583
Table 1. Oxidation of sulfides to sulfoxides with NBS in the presence of b-CD in water
O
S
-CD/H O
β
2
R1
R1
R2
S
R2
NBS r t
Entry
R1
R2
b-CD (1.0 mmol)
b-CD (0.1 mmol)
Time (h)
Yield (%)a,b
Time (h)
Yield (%)a,b
1
Ph
Ph
CH3
2.0
2.5
2.5
2.0
2.0
2.0
2.5
2.5
2.5
2.6
2.2
2.5
2.5
2.5
3.0
95
93
92
96
95
94
95
94
92
93
94
92
90
90
92
6.0
8.0
8.0
6.0
6.0
7.0
7.0
8.0
8.0
8.0
6.5
7.0
8.0
8.0
8.0
94
90
90
96
94
94
92
94
90
90
92
90
90
88
90
2
(CH2)2CH3
CH(CH3)2
CH3
3
Ph
4
p-BrC6H4
p-ClC6H4
p-ClC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
o-MeC6H4
p-MeOC6H4
PhCH2
5
CH3
CH2CH3
CH3
6
7
8
CH2CH3
CH(CH3)2
CH3
9
10
11
12
13
14
15
CH3
CH3
PhCH2
PhCH2
CH2CH3
CH(CH3)2
CH3
C
10H7
a All the products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated yields.
oxygen of the sulfoxides, thereby decreasing the nucleo-
philicity of the sulfur and preventing further oxidation
of the sulfoxide to the sulfone.
Acknowledgements
K.S. and N.S.K. thank CSIR, New Delhi, India for the
award of research fellowships.
This methodology is also compatible in the presence of
other functionalities such as chloro, bromo, methoxy
and isopropoxy. These cyclodextrin mediated water
based reactions proceed under mild conditions and are
also useful from the view point of not having to handle
flammable and anhydrous organic solvents. Though
inclusion complexation of sulfides with b-CD takes
place in situ during the reaction, these inclusion com-
plexes have been isolated separately and characterized
References and notes
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1
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NMR, IR and by comparison with known com-
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as the by-products and can be recycled to NBS as de-
scribed in the experimental section. Cyclodextrin was
also recovered and reused. It was also observed that
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much longer (6–8 h). The fact that these reactions do
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In conclusion, our methodology provides a method for
the selective oxidation of sulfides to sulfoxides without
any over-oxidation to sulfones. Moreover, the reaction
proceeds under neutral and mild conditions and can
be carried out easily at room temperature with recycling
of cyclodextrin and regeneration of NBS.
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ethyl acetate and the filtrate was cooled to 5 °C to
recover CD by filtration. The organic layer was dried
over anhydrous Na2SO4 and the solvent was removed
under vacuum to give the products, seen as single
compounds by TLC, which were further purified by
passing through a column of silica gel using ethyl
acetate–hexane (1:1) as eluent. To the filtrate, which
contained succinimide and HBr was added NaBrO3 and
conc. H2SO4 as already reported16 and the mixture
stirred for 30 min, extraction with ethyl acetate giving
NBS in an isolated yield of 75–80%.
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13. b-Cyclodextrin (1 mmol) was dissolved in water (15 ml)
at 60 °C, then the substrate (1 mmol) in acetone (1 ml)
was added slowly with stirring and the mixture cooled to
room temperature. NBS (1 mmol) was added and stirring
at room temperature was continued until the reaction
was complete (Table 1). The mixture was extracted with
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