Simple and highly efficient catalyst- and waste-free ring opening of epoxides with Na2S in water

Article abstract of DOI:10.1007/s00706-010-0261-0

Water was found to be a highly efficient and green catalyst and solvent for ring-opening reaction of epoxides with Na₂S at room temperature to give substituted bis(hydroxyethyl)thioethers in high yields.

Full text of DOI:10.1007/s00706-010-0261-0

Monatsh Chem (2010) 141:323–326
DOI 10.1007/s00706-010-0261-0
ORIGINAL PAPER
Simple and highly efficient catalyst- and waste-free ring opening
of epoxides with Na2S in water
•
•
•
Najmedin Azizi Elham Akbari Frough Ebrahimi
Mohammad R. Saidi
Received: 2 May 2009 / Accepted: 23 January 2010 / Published online: 26 February 2010
Ó Springer-Verlag 2010
Abstract Water was found to be a highly efficient and
green catalyst and solvent for ring-opening reaction of
epoxides with Na2S at room temperature to give substituted
bis(hydroxyethyl)thioethers in high yields.
are also versatile building blocks for synthesis of cyclic
sulfides [14, 15], benzoxathiepines, benzothiazepines, and
thioketones [16–18]. Therefore, their syntheses have been
extensively investigated with different methods in recent
years [19–25].
Keywords Epoxide ꢀ Sodium sulfide ꢀ Catalyst-free ꢀ
Water chemistry ꢀ Bis(hydroxyethyl)thioethers
However, among the reactions of sulfur nucleophiles
with epoxides, to the best of our knowledge there are no
reports in the literature that allow direct access to thi-
obis(alcohols) by reaction of epoxides with Na2S without
catalyst in water. Recently hexamethyldisilathiane has
been used as sulfur nucleophile for ring opening of epox-
ides in the presence of tetrabutylammonium fluoride
(TBAF) as catalyst to produce bis(hydroxyethyl)thioethers
in tetrahydrofuran (THF) [26].
Introduction
Epoxides are very useful intermediates and starting mate-
rials in organic synthesis due to their versatility and
reactivity with a wide range of nucleophiles [1, 2]. They
are important functional groups of natural products [3–5],
and medicinal [6], polymer [7, 8], and supramolecular
[2, 9] compounds. Thiolysis of 1,2-epoxides by sulfur
nucleophiles is a convenient, practical, and widely
employed strategy for synthesis of b-hydroxy sulfides,
which are important intermediates in synthesis of drugs,
pharmaceuticals [10–12], and natural products [13]. They
Over the last decade governmental policies have been
aimed at limiting use of hazardous solvents released into
the environment, and their replacement with water is rec-
ommended. In this context, environmentally benign
chemical processes in water have attracted more attention
due to its being a relatively green and cheap media for
organic reactions [27–31].
Results and discussion
In continuation of our research interest in developing
green organic chemistry by using water as reaction
medium [32–35] or by performing organic transforma-
tions under solvent-free conditions [36–38], herein we
report an efficient, environmentally benign, and simple
ring-opening reaction of epoxides with Na2S under mild
conditions. By omitting any organic solvent or catalyst,
and reducing the amount of waste, the reaction can be
carried out under cleaner reaction conditions at room
temperature in water.
N. Azizi (&)
Chemistry and Chemical Engineering Research Center of Iran,
P.O. 14335-186, Tehran, Iran
e-mail: azizi@ccerci.ac.ir
E. Akbari ꢀ F. Ebrahimi ꢀ M. R. Saidi (&)
Department of Chemistry,
Sharif University of Technology,
P.O. Box 11465-9516, 11365 Tehran, Iran
e-mail: saidi@sharif.edu
123

324
N. Azizi et al.
Scheme 1
O
Na2S, Solvent
rt, 4 h
O
PhO
OPh
OH
S
OH
Solvent
CH2Cl2 ClCH2CH2Cl
CH3CN
35
Ether Solvent-free Water
40 70 97
Yield (%)
0
0
We wished to explore the applicability of Na2S, which
might act as an acceptable, nontoxic, low cost, and odorless
sulfur nucleophile for ring-opening reaction of epoxides,
while giving interesting biological compounds. First, we
embarked upon a series of experiments to establish the
optimum conditions for thiolysis of an epoxide. The reac-
tion between glycidyl phenyl ether and Na2S was chosen,
and the results are presented in Scheme 1. First findings
indicated that water was an excellent solvent for thiolysis
of glycidyl phenyl ether without using any catalyst or
promoter at room temperature to give bis(hydroxyethyl)
thioethers with excellent yield. As mentioned above, this
reaction yields bis(hydroxyethyl)thioethers, and in order to
obtain mono epoxide addition, subsequent reactions with
glycidyl phenyl ether were carried out using different
amounts of Na2S. This variation did not change the product
distribution, and only in some cases were trace amounts
of hydroxyethylthiols observed. We also investigated the
effects of common organic solvents, in particular their
influence on the rate and course of these reactions. In
CH2Cl2 or ClCH2CH2Cl the reaction did not take place and
the starting materials were recovered, and low yield of the
product was observed in acetonitrile and diethyl ether
(Scheme 1).
yields. The regioselectivity in the reaction of unsymmet-
rical epoxides is governed by both steric and electronic
effects. The regioselectivity was determined by 1H
nuclear magnetic resonance (NMR). Unsymmetrical ox-
iranes underwent cleavage by Na2S with preferential
attack at the less substituted carbon of the epoxide,
affording a single product in high to quantitative yields.
The only exception was styrene oxide, from which two
regioisomers were formed (Scheme 2).
Furthermore, in the case of cyclic epoxides such as
cyclohexene oxide (Table 1, entry 12), trans products were
obtained (Scheme 3). However, there was no significant
selectivity for one of the diastereoisomers, and a mixture of
two diastereoisomers was obtained (Fig. 1).
In summary, this simple and easily reproducible coupling
of epoxides with Na2S under catalyst-free conditions in green
and abundant solvent affords various bis(hydroxyethyl)
thioethers of potentially high synthetic utility in high yield,
without the formation of any undesirable side-products.
Experimental
General procedure for aqueous ring opening
of epoxides with Na2S
Having established optimal conditions for the reaction
between glycidyl phenyl ether and Na2S, we were keen to
expand the scope of this reaction and determine whether it
would prove equally successful with a range of other
epoxides. We therefore examined the reaction of Na2S with
a variety of epoxides under the optimized conditions, and
the results are shown in Table 1.
To a stirred solution of 0.4 cm3 glycidyl phenyl ether
(3 mmol) in 2 cm3 water in a test-tube was added 0.2 g
Na2S (3 mmol), and the resulting mixture was stirred at
room temperature for 4–8 h. In the case of solid
bis(hydroxyethyl)thioethers, pure products were isolated
by filtration. The liquid bis(hydroxyethyl)thioethers were
extracted by ethyl acetate and dried over anhydrous
Na2SO4. Evaporation of the solvent afforded the desired
pure product in most cases. In a few cases, the crude
product was further purified by flash column chroma-
tography to provide the corresponding pure product. All
The range of suitable epoxides explored includes
commercially available aliphatic epoxides such as glyc-
idyl phenyl ether, propylene oxide, butylene oxide,
cyclohexene oxide, and styrene oxide. The results indicate
the usefulness of this method. The substituents do not
show any significant effects on reaction time or product
123

Simple and highly efficient catalyst- and waste-free ring opening of epoxides
325
Table 1 Water-accelerated reaction of epoxides with Na2S
R
R
Na2S, Solvent
rt, 4-8 h
O
S
R
OH
OH
1
2
Entry
1
Epoxide
Product
Yielda
Ref.
[25]
2a
80 (82:18)b
O
Ph
Ph
S
Ph
OH
OH
OH
OH
OH
OH
2
3
4
5
2b
2c
2d
2e
82
78
72
78
[26]
[25]
[20]
[20]
O
S
S
S
S
OH
OH
OH
OH
O
O
O
O
O
O
6
7
2f
95
88
[25]
[22]
O
O
O
O
S
S
O
O
OH
OH
OH
OH
2g
O
O
8
2h
82
[25]
O
O
S
O
O
OH
OH
9
2i
97 (R=H)
[25]
[25]
O
O
O
S
10
11
O
2j
2k
95 (R=Me)
92 (R=OMe)
Ar
OH
OH
Ar
[21, 25]
R
12
2l
70
[25]
OH
O
S
OH
a
Nuclear magnetic resonance (NMR) yields
See Scheme 2
b
123

326
N. Azizi et al.
Scheme 2
Ph
Ph
Na2S, Solvent
rt, 8 h, 80 %
Ph
Ph
O
S
+
S
Ph
OH
OH
OH
OH
82%
18%
10. Corey EJ, Clark DA, Goto G, Marfat A, Mioskowski C, Same-
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JJ (1987) J Med Chem 30:1609
12. Kesavan V, Bonnet-Delpon D, Be0gue0 JP (2000) Tetrahedron
Lett 41:2895 and references therein
OH
Na2S
O
Water, rt, 8h
S
OH
70 %
13. Ozaki E, Matsui H, Yoshinaga H, Kitagawa S (2000) Tetrahedron
Lett 41:2621
Scheme 3
14. Aifheli CG, Kaye PT (1996) Synth Commun 26:4459
15. Scwartz A, Madan PB, Mohacsi E, O’Brien JP, Todaro E, Coffen
DL (1992) J Org Chem 57:851
16. Behrens CH, Ko SY, Sharpless KB, Walker F (1985) J Org Chem
50:5687
17. Forristal I, Lawson KR, Rayner CM (1999) Tetrehedron Lett
40:7015
18. Yamada O, Ogassawara K (1995) Synlett 427
19. Fringuelli F, Pizzo F, Tortoioli S, Zuccaccia C, Vaccaro L (2006)
Green Chem 8:191
20. Fringuelli F, Pizzo F, Tortoioli S, Vaccaro L (2004) J Org Chem
69:2315
R
S
R
R
(meso)
OH
OH
R
S
(R,S)
OH
Fig. 1 Possible diastereoisomers
OH
21. Fringuelli F, Pizzo F, Tortoioli S, Vaccaro L (2002) Adv Synth
Catal 344:379
22. Azizi N, Saidi MR (2006) Catal Commun 7:224
23. hivani R, Chakraborti AK (2007) J Mol Catal A Chem 263:137
and references cited therein
compounds were characterized on the basis of their
spectroscopic data (IR and NMR).
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180:1929
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Acknowledgments Financial support of this work by the Chemistry
and Chemical Research Center of Iran and Sharif University of
Technology is gratefully appreciated.
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29. Khatik GL, Kumar R, Chakraborti AK (2006) Org Lett 8:2433
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