Solvent-free thiolysis of epoxides under lithium perchlorate catalysis

Article abstract of DOI:10.1007/s00706-005-0458-9

Solvent-free ring opening of 1,2-epoxides with thiols using catalytic amounts of lithium perchlorate affords high yields of β-hydroxy sulfides. Nucleophilic attack of the thiols occurs regioselectively at the sterically less hindered side of the epoxides.

Full text of DOI:10.1007/s00706-005-0458-9

Monatshefte f€ur Chemie (2006)
DOI 10.1007/s00706-005-0458-9
Graphical Abstract
Solvent-Free Thiolysis of Epoxides under
Lithium Perchlorate Catalysis . . . . . . . 000
Mohammad M. Mojtahedi, Hassan Abassi,
M. Saeed Abaee, and Bahareh Mohebali

Monatshefte f€ur Chemie (2006)
DOI 10.1007/s00706-005-0458-9
Solvent-Free Thiolysis of Epoxides
under Lithium Perchlorate Catalysis
ꢀ
Mohammad M. Mojtahedi , Hassan Abassi, M. Saeed Abaee,
and Bahareh Mohebali
Chemistry and Chemical Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran
Received August 4, 2005; accepted (revised) September 1, 2005
Published online April 5, 2006 # Springer-Verlag 2006
Summary. Solvent-free ring opening of 1,2-epoxides with thiols using catalytic amounts of lithium
perchlorate affords high yields of ꢀ-hydroxy sulfides. Nucleophilic attack of the thiols occurs regio-
selectively at the sterically less hindered side of the epoxides.
Keywords. Thiols; Epoxides; Catalytic; Lithium perchlorate; Solvent-free.
Introduction
Ring opening of epoxides with thiols is an important class of organic transforma-
tions and has found many uses in pharmaceutical [1] and natural product chemistry
[2], particularly for the synthesis of leukotrienes [3]. The classical approach for the
synthesis of ꢀ-hydroxy derivatives of sulfides involves thermal or Lewis acid
mediated nucleophilic opening of epoxides with thiols [4] (Scheme 1). In many
of these cases, the ring opening of epoxides is carried out in a halogenated solvent
and normally requires long time treatment under reflux temperatures or environ-
mentally unfriendly conditions.
Prompted by stringent environmental protection laws in recent years, there has
been increasing emphasis on the use and design of eco-friendly reagents, solid state
procedures, and solvent-free reactions [5]. In recent years, lithium perchlorate has
been widely used for various organic transformations [6]. We decided to extend our
previous experiences on the use of lithium perchlorate in synthetic organic chem-
istry [7]. In the present article, an efficient methodology for solvent-free ring open-
ing of epoxides with thiols in the presence of catalytic amounts of lithium
perchlorate at room temperature is described (Scheme 2). To the best of our knowl-
edge, the present procedure is one of the most efficient and reliable methods for the
synthesis of the title compounds.
ꢀ
Corresponding author. E-mail: mojtahedi@ccerci.ac.ir

M. M. Mojtahedi et al.
Scheme 1
Scheme 2
Results and Discussions
We first examined the reaction between 1,2-epoxy-3-phenoxypropane (1a) with
an equimolar amount of thiophenol (2a) in the presence of 20 mol% anhydrous
lithium perchlorate under solvent-free conditions. TLC showed complete disap-
1
pearance of the starting epoxide within a few minutes. The H NMR spectrum
showed the presence of the ꢀ-hydroxy sulfide 3a as the sole compound in the
reaction mixture illustrating that the nucleophilic attack of the thiol occurs
regioselectively on the less hindered side of the epoxide. Extraction of the reac-
tion mixture gave 96% of the desired product (Table 1, entry 1). A control
experiment confirmed the promoting effect of the catalyst. Thus, when a mixture
of thiophenol (2a) and epoxide 1a was stirred at room temperature for 24 h in the
absence of lithium perchlorate, no formation of product was detected and the
starting materials were recovered. Under the same conditions other epoxides
(1b–1e) reacted in a similar manner with thiophenol 2a producing 84–96% of
3b–3e (entries 2–5). The generality of the method was demonstrated by sub-
jecting epoxides 1a–1e to react with p-chlorothiophenol (2b) (entries 6–10).
Consequently, products 3f–3j were obtained in 81–96% yields within a few
minutes.
In conclusion, efficient ring opening of epoxides with thiols using a catalytic
amount of lithium perchlorate and no solvent was observed in less than 5 minutes.
In comparison with other methods existing in literature, the present procedure is
environmentally friendly and affords high yields of the desired products. In addi-
tion, high regioselectivity of the ring opening, rapid completion of the reaction, and
the use of catalytic amounts of Lewis acid are among other advantages of this
protocol.
Experimental
All reported yields are isolated yields. IR spectra were recorded on a FT-IR Bruker Vector 22 infrared
spectrophotometer using KBr disks. NMR spectra were recorded on FT-NMR Bruker AC 500 MHz or
Bruker AC 80 MHz as CDCl3 solutions with TMS as internal reference. GC-MS spectra were obtained
on a Fisons 8000 Trio instrument at an ionization potential of 70eV. Elemental analyses were found to
agree favourably with calculated values.

Solvent-Free Thiolysis of Epoxides
Table 1. Solvent-free thiolysis of 1,2-epoxides using LiClO4
Entry
1
Epoxide
Thiol
Product
Yield=%a Reference
96
[4k]
C6H5SH
2
C6H5SH
95
–
3
4
5
C6H5SH
C6H5SH
C6H5SH
94
84
96
[4l]
[4k]
[4m]
6
7
4-ClC6H4SH
4-ClC6H4SH
93
92
[4j]
–
8
9
4-ClC6H4SH
4-ClC6H4SH
4-ClC6H4SH
81
96
92
[4o]
[4n]
–
10
a
Isolated yields
General Procedure
A mixture of 5.0 mmol epoxide, 5.0 mmol thiophenol, and 1.0 mmol anhydrous LiClO4 was stirred at
room temperature for appropriate length of time (TLC, <5 min). The mixture was extracted 3 times
with 10cm3 portions of ether. The combined etheral phases were washed with H2O and filtered through
a short Na2SO4 column. The solvent was removed under reduced pressure and the product was
fractionated using column chromatography over silica gel or purified with bulb-to-bulb distillation,

M. M. Mojtahedi et al.: Solvent-Free Thiolysis of Epoxides
if necessary. The NMR, IR, and GC-MS spectra of the products were obtained and compared perfectly
to those existing in literature.
1-Isopropoxy-3-(phenylsulfanyl)propan-2-ol (3b, C12H18O2S)
Mp 44ꢁC; 1H NMR (CDCl3, 80 MHz): ꢁ ¼ 1.13 (d, J ¼ 6.5Hz, 6H), 2.55–2.70 (m, 1H), 2.93–3.20 (m,
2H), 3.50–3.95 (m, 4H), 7.10–7.45 (m, 5H) ppm; 13C NMR (CDCl3, 20 MHz): ꢁ ¼ 22.0, 38.1, 69.5,
71.3, 73.0, 127.5, 128.0, 129.3, 137.5 ppm; IR (KBr disk): ꢂꢀ¼ 3431, 1588, 1086, 738 cmꢂ1; MS:
m=z ¼ 226 (Mþ).
1-(4-Chlorophenylsulfanyl)-3-isopropoxypropan-2-ol (3g, C12H17ClO2S)
1H NMR (CDCl3, 80 MHz): ꢁ ¼ 1.18 (d, J ¼ 6.5 Hz, 6H), 3.02–3.20 (m, 2H), 3.45–3.65 (m, 4H),
3.86–3.92 (m, 1H), 7.26–7.45 (m, 4H) ppm; 13C NMR (CDCl3, 20MHz): ꢁ ¼ 21.7, 37.3, 69.0, 70.1,
72.0, 128.8, 130.4, 132.0, 134.4ppm; IR (neat): ꢂꢀ¼ 3443, 1575, 1093, 747 cmꢂ1; MS: m=z ¼ 260 (Mþ).
2-(4-Chlorophenylsulfanyl)-1-phenyl-ethanol (3j, C14H13ClOS)
1H NMR (CDCl3, 80 MHz): ꢁ ¼ 2.57 (br s, 1H), 3.84 (d, J ¼ 6.5 Hz, 2H), 4.20 (d, J ¼ 6.5Hz, 1H),
6.95–7.30 (m, 9H) ppm; 13C NMR (CDCl3, 20 MHz): ꢁ ¼ 55.9, 65.0, 127.6, 127.9, 128.5, 128.8, 129.7,
132.2, 133.6, 138.6ppm; IR (neat): ꢂꢀ¼ 3421, 1573, 1094 cmꢂ1; MS: m=z ¼ 264 (Mþ).
Acknowledgements
We thank Ministry of Science, Research and Technology of Iran for partial financial support of this
work.
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