A new, efficient, and simple method for the synthesis of thiiranes from epoxides under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2003.11.099

A simple, efficient, and new method has been developed for the synthesis of thiiranes from epoxides through a one-pot reaction of epoxides with diethyl phosphite in the presence of ammonium acetate or ammonium hydrogen carbonate/sulfur/ and acidic alumina under solvent-free conditions using microwave irradiation.

Full text of DOI:10.1016/j.tetlet.2003.11.099

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1283–1285
A new, efficient, and simple method for the synthesis of thiiranes
from epoxides under solvent-free conditions
Babak Kaboudin* and Hamid Norouzi
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45195-159, Iran
Received 29 September 2003; revised 8 November 2003; accepted 21 November 2003
Abstract—Asimple, efficient, and new method has been developed for the synthesis of thiiranes from epoxides through a one-pot
reaction of epoxides with diethyl phosphite in the presence of ammonium acetate or ammonium hydrogen carbonate/sulfur/ and
acidic alumina under solvent-free conditions using microwave irradiation.
Ó 2003 Elsevier Ltd. All rights reserved.
Since organic sulfur compounds have become increas-
ingly useful and important in organic synthesis, the
development of convenient and practical methods for
the preparation of thiiranes are desirable. Thiiranes are
the simplest sulfur heterocycles and occur in Nature.
They have been used advantageously in the pharma-
ceutical, polymer, pesticide, and herbicide industries.1
The most important method for the synthesis of thiir-
anes is the conversion of alkene oxides (epoxides) to
thiiranes with thiourea, thioamides, phosphine sulfide,
or dimethylthioformamide in the presence of trifluoro-
acetic acid or using inorganic thiocyanates or related
compounds.2 Although there are many classical meth-
ods for synthesizing thiiranes, these involve long reac-
tion times, the use of strongly acidic or oxidizing
conditions, high-temperature reaction conditions,
expensive reagents, give poor yields, involve the for-
mation of several by-products due to rearrangement or
polymerization of the oxiranes and use moisture sensi-
tive, and foul smelling reagents, which must be handled
with care.3 On the other hand, thiiranes cannot be pre-
pared from some alkene oxides such as styrene oxide,
stilbene oxide, and cycloalkene oxides using thiourea
and thiocyanates.4 Recently the use of recyclable ionic
liquids for the conversion of oxiranes to epoxides has
been reported.5 Despite a wide range of synthetic
methods for the conversion of epoxides to thiiranes, no
attempt has been made to use readily accessible sulfur
for this conversion. In recent years, the use of reagents
and catalysts immobilized on solid supports has received
considerable attention. Such reagents not only simplify
purification processes but also help prevent release of
reaction residues into the environment. Reagents sup-
ported on organic polymers and within and/or on the
surface of inorganic matrices have all been reported.6
Recently we reported a new method for the synthesis of
phosphorothioates of alkyl halides using a mixture
of alumina/ammonium acetate/sulfur in the presence of
diethylphosphite under microwave irradiation.7 Here we
report a new procedure for the conversion of epoxides
into thiiranes using a mixture of alumina/ammonium
acetate or ammonium hydrogen carbonate/sulfur in the
presence of diethylphosphite under microwave irradia-
tion. Initially, we carried out the experiment with 2-
phenoxymethyl oxirane in a mixture of alumina/
ammonium acetate/sulfur in the presence of diethyl-
phosphite under microwave irradiation to afford the
corresponding episulfide in 78% yield after 2 min
(Scheme 1). When this reaction was carried out in
ethanol for 3 h it afforded the corresponding thiirane in
56% yield. Ammonium formate (NH4CO2H) was not as
O
S
O
H
P(OEt)2
NH4X/S/Al2O3
Keywords: Thiiranes; Epoxides; Diethylphosphite; Ammonium acetate;
Microwave.
PhO
PhO
* Corresponding author. Tel.: +98-241-4242239; fax: +98-241-42490-
23; e-mail: kaboudin@iasbs.ac.ir
Scheme 1.
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.099

1284
B. Kaboudin, H. Norouzi / Tetrahedron Letters 45(2004) 1283–1285
Table 1. The reaction of 2,3-epoxypropyl phenyl ether with diethyl
phosphite in the presence of ammonium salts/sulfur/alumina
These results prompted us to extend this process to
other epoxides. Interestingly, aryl, alkyl, and sterically
hindered epoxides reacted smoothly with sulfur under
these reaction conditions to produce the corresponding
thiiranes in good to excellent yields (Table 2 and Scheme
2). As shown in Table 2, epoxides in the presence of
ammonium acetate or ammonium hydrogen carbonate/
sulfur/alumina reacted with diethyl phosphite to give the
required products in good to excellent yields. Similarly,
cyclohexyl oxide was converted into the corresponding
thiirane in a good yield. Styrene oxide in the presence of
ammonium acetate or ammonium hydrogen carbonate/
sulfur/alumina reacted with diethyl phosphite, giving the
corresponding thiirane in an excellent yield.8
Entry
Ammonium
salt
Reaction
conditions
Reaction
Yield
time (min) (%)a
a
b
c
d
e
f
NH4OAc
NH4OAc
NH4CO2H
NH4HCO3
NH4NO3
NH4I
Microwave
Reflux-EtOH 180
2
78
56
––
58
––
5
Microwave
Microwave
Microwave
Microwave
Microwave
Microwave
Microwave
5
3
4
4
4
4
4
g
h
i
NH4Cl
NH4PF6
NH4Br
––
––
––
a Isolated yields.
In summary, simple work-up, low use of solvents, fast
reaction rates, mild reaction conditions, good yields,
and the relatively clean reactions with no tar formation
make this method an attractive and a useful contribu-
tion to present methodologies. Indeed, a wide range of
epoxides was converted into the corresponding thiiranes
using this method.
effective as ammonium acetate or ammonium hydrogen
carbonate and failed to give the required product (Table
1). Other ammonium salts (NH4Cl, NH4Br, NH4PF6,
and NH4NO3) were not effective and did not give any
product. The reaction with ammonium iodide gave only
5% of the desired product.
Table 2. Conversion of epoxides to thiiranes using diethyl phosphite in the presence of ammonium acetate or ammonium hydrogen carbonate/sulfur/
alumina with or without microwave irradiation
Entry
Epoxide
Conversiona (%)
NH4OAc
Yieldb (%)
NH4HCO3
Yieldb (%)
Time (min)
0.5
Time (min)
0.5
O
a
98
82
80
Ph
O
b
c
98
98
30c
83
80
––
––
––
––
Ph
O
180d
Ph
d
e
O
77
87
3
2
69
78
3
3
61
58
O
PhO
H2C
O
O
f
71
4
62
4
57
O
CH3
CH3
O
g
h
48
65
3
4
42
60
4
4
40
57
H3C
O
O
H3C(CH2)11
a Conversions were determined by GC analysis.
b Yields refer to the isolated pure products after column chromatography.
c Shaking without microwave irradiation.
d Reflux in ethanol or methanol.

B. Kaboudin, H. Norouzi / Tetrahedron Letters 45(2004) 1283–1285
1285
O
R
-O
O
O
+NH4-S P(OEt)2
NH4OAc/S/Al2O3
Microwave
R
O
H
P(OEt)2
O
P
S
R
S P(OEt)2
O-
EtO
OEt
-S
R
O
S
O
+NH4-O P(OEt)2
+
O
P(OEt)2
R
Scheme 2.
5. Yadav, J. S.; Reddy, B. V. S.; Reddy, Ch. S.; Rajasekhar,
K. J. Org. Chem. 2003, 68, 2525.
Acknowledgements
6. (a) Danks, T. N.; Desai, B. Green Chem. 2002, 4, 179, and
references cited therein; (b) Kaboudin, B.; Nazari, R.
Tetrahedron Lett. 2001, 42, 8211; (c) Kaboudin, B. Chem.
Lett. 2001, 880.
The Institute for Advanced Studies in Basic Sciences
(IASBS) is thanked for supporting this work.
7. Kaboudin, B. Tetrahedron Lett. 2002, 43, 8713.
References and notes
8. This solvent-free reaction is operationally simple. The
reagent (10 mmol) was prepared by the combination of
ammonium acetate (10 mmol, finely ground), sulfur (10
mmol), and alumina (Al2O3, acidic, 2.5 g) in a mortar and
pestle by grinding them together until a fine, homogeneous,
powder was obtained (5–10 min). Diethyl phosphite
(10 mmol) was added to this mixture and the mixture was
irradiated in a microwave for 1 min using 720 W. The
epoxide (9 mmol) was added to this reagent and the mixture
was irradiated in a microwave for 0.5–4 min using 300–
450 W. (Akitchen-type microwave was used in all exper-
iments.) The mixture was then washed with 200 mL CHCl3.
All of the ammonium salts were removed by washing with
an aq solution of sodium carbonate and then water.
Chromatography through a plug of silica gel with EtOAc/
n-hexane (1:9) and evaporation of the solvent under
reduced pressure gave the pure products in 42–83% yields.
The procedure was the same in the case of ammonium
hydrogen carbonate. All the products gave satisfactory
spectral data in accordance with the assigned structures.
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