A new and efficient method for the synthesis of thiiranes from oxirane-β-cyclodextrin complexes and thiourea in water

Article abstract of DOI:10.1016/j.tetlet.2004.06.111

Oxiranes react smoothly with thiourea in the presence of β-cyclodextrin in water at room temperature under neutral conditions to afford the corresponding thiiranes in excellent yields; the β-cyclodextrin can be recycled.

Full text of DOI:10.1016/j.tetlet.2004.06.111

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6523–6526
A new and efficient method for the synthesis of thiiranes from
oxirane–b-cyclodextrin complexes and thiourea in waterq
K. Surendra, N. Srilakshmi Krishnaveni and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 1 March 2004; revised 11 June 2004; accepted 18June 2004
Available online 19 July 2004
Abstract—Oxiranes react smoothly with thiourea in the presence of b-cyclodextrin in water at room temperature under neutral con-
ditions to afford the corresponding thiiranes in excellent yields; the b-cyclodextrin can be recycled.
Ó 2004 Elsevier Ltd. All rights reserved.
Thiiranes, which are the simplest sulfur heterocycles and
occur in nature, are useful from both theoretical and
synthetic points of view. They are used in the pharma-
ceutical, polymer, pesticide and herbicide industries.1
A variety of methods have been developed for the prep-
aration of thiiranes.2 Amongst these, the most impor-
tant method is the conversion of oxiranes to thiiranes
by an oxygen–sulfur exchange reaction. Various sulfur
introducing reagents such as inorganic thiocyanates,3
phosphine sulfide,4 3-methylbenzothiazole-2-thiirane,5
dimethylthioformamide in the presence of trifluoro ace-
tic acid,6 silica gel supported potassium thiocyanate,7
indium halides/KSCN8 and polymeric cosolvent/
NH4SCN,9 together with solvent-free conditions10 and
ionic liquids,11 etc., have been reported to produce thiir-
anes from oxiranes. However, many of these methods
suffer from undesirable side reactions due to rearrange-
ment or polymerization of the oxiranes resulting in low
yields of the thiiranes especially for the conversion of
cyclohexene oxide to cyclohexene sulfide, and styrene
oxide to styrene sulfide as well as the synthesis of other
higher thiiranes.2
control of pH was important if the episulfide was to be
obtained without polymerization.13,2b Epoxides have
been transformed to episulfides by the action of thiourea
in aqueous acidic solutions followed by basic workup in
methanolic solutions.14 So far no success has been
achieved in carrying out these reactions exclusively in
water under neutral conditions.15 Water as a solvent is
safe, economical and environmentally benign.16 In view
of the advantages of using water as a solvent, we ex-
plored the synthesis of thiiranes from oxiranes and thio-
urea in water in the presence of b-cyclodextrin.
Cyclodextrins are cyclic oligosaccharides possessing
hydrophobic cavities, which bind substrates and cata-
lyze chemical reactions with high selectivity. They cata-
lyze reactions by supramolecular catalysis involving
reversible formation of host–guest complexes by nonco-
valent bonding as seen in enzymes. Complexation de-
pends on the size, shape and hydrophobicity of the
guest molecule. This mimicking of biochemical selectiv-
ity, which involves orientation of the substrate by com-
plex formation thereby positioning only certain regions
for favourable attack, is superior to chemical selectivity
where the attack is due to the intrinsic reactivity of the
substrate at different regions. Our earlier expertise in
the field of biomimetic modelling of organic chemical
reactions involving cyclodextrins,17 prompted us to at-
tempt the regioselective ring opening of oxiranes with
thiourea in the presence of b-cyclodextrin (b-CD)
(Schemes 1 and 2).
Although thiourea has been one of the most widely used
reagents for this transformation,12 it suffers from vari-
ous disadvantages such as long reaction times, low
yields and desulfuration of the resulting episulfide to ole-
fin in some cases.12f In reports with aqueous solvents the
Keywords: Oxiranes; Thiiranes; b-Cyclodextrin; Thiourea; Water.
q IICT Communication No. 040602.
Reactions were carried out by the in situ formation of
the b-cyclodextrin complex of the epoxide 1 in water
followed by the addition of thiourea 2 and stirring at
*
Corresponding author. Tel.: +91-40-27193164; fax: +91-40-271-
60757; e-mail: drkrrao@yahoo.com
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.111

6524
K. Surendra et al. / Tetrahedron Letters 45 (2004) 6523–6526
room temperature to give the corresponding thiiranes 3
−
β CD/H2O
in impressive yields.18 These reactions take place at
room temperature and no side product or rearrange-
ment was observed. The b-cyclodextrin can be recovered
and reused. The reactions also take place using a-cyclo-
dextrin with the same results. However, b-cyclodextrin
was chosen as the catalyst since it is inexpensive and
readily available. When a catalytic amount of cyclodex-
trin (0.1mmol per 1.0mmol of substrate) was used in the
reaction, the yields were only 15%.
O
S
thiourea/rt
n
n
1
2
3
n=0,1
Scheme 1.
O
CD/H O
S
−
β
2
The reactions are clean and high yielding compared to
conventional methods. The reaction with styrene epox-
ides (Table 1, entries 3–4), trans-cinnamyl epoxides
(Table 1, entries 5–6) and phenoxy-epoxides (Table 1,
entries 7–13) were complete within 4h whereas the cyclic
epoxides (Table 1, entries 1–2) required 6h. Reactions
were carried out on a wide range of epoxides. All
thiourea/rt
R1
R1
R
R
1
2
3
R=aryl, aryloxy, hexyl
R1=H, CH2OH, CH2OTBDMS
Scheme 2.
Table 1. b-Cyclodextrin catalyzed synthesis of thiiranes from oxiranes and thiourea in water
Entry 1
Substrate
Producta
Time (h)
6.0
Yield (%)b
80
1
O
S
2
6.0
82
O
S
S
O
3
4
3.5
3.5
93
94
Ph
Ph
O
S
p-Cl-Ph
p-Cl-Ph
O
S
H
OH
OH
5
6
H
Ph
4.0
4.0
85
81
H
H
H
Ph
O
S
OTBDMS
OTBDMS
H
Ph
H
H
Ph
S
O
7
8
3.0
3.0
94
96
PhO
PhO
O
S
p-Cl-PhO
p-Me PhO
p-MeO PhO
p-
Cl
p-Me
MeO
p-Ac-PhO
MeOEt-PhO
-
PhO
PhO
PhO
O
O
S
S
9
3.5
4.0
96
91
-
-
10
-
p-
-
O
S
11
12
13
14
4.0
3.5
4.0
3.5
90
94
88
91
p-Ac-PhO
O
S
p-MeOEt-PhO
p-
O
S
p
-NO2-PhO
p
-
NO2
-
PhO
S
O
p-MeO-Ph
p
-
MeO-Ph
O
S
15
16
4.0
6.0
94
80
Ph
O
Ph
O
S
O
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated yields after purification.

K. Surendra et al. / Tetrahedron Letters 45 (2004) 6523–6526
6525
1
products were characterized by H NMR, MS, IR and
elemental analysis or by comparison with known com-
pounds.6,7,11
Thus, it can be seen that the reaction takes place
through supramolecular catalysis. An upfield shift of
the H-3 and H-5 protons was also observed in the
b-CD-cyclohexene epoxide complex.
These reactions do not take place in the absence of
cyclodextrin. It appears that cyclodextrin not only
activates the epoxide but also forms a cyclodextrin–
epoxide complex through hydrogen bonding. Evidence
for association between the epoxide and cyclodextrin is
Acknowledgements
K.S. thanks CSIR, New Delhi, India, for the award of a
research fellowship.
1
supported by H NMR spectroscopy. The studies were
undertaken with p-chlorophenoxy epoxide as a repre-
1
sentative example. A comparison of the H NMR spec-
References and notes
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from the spectra of the reaction mixtures of the b-CD-
epoxide complex and thiourea (after 3h) that the com-
plex retains the upfield character of the H-3 and H-5
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K. Surendra et al. / Tetrahedron Letters 45 (2004) 6523–6526
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