Stereo- and regioselective thiolysis of 1,2-epoxides in water

Article abstract of DOI:10.1080/00397910701548100

A simple, efficient, stereoselective, and highly regioselective procedure for the synthesis of β-hydroxy sulfides by thiolysis of various 1,2-epoxides in water as a solvent, using no catalyst and under very mild conditions, is described. Copyright Taylor

Full text of DOI:10.1080/00397910701548100

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Stereo‐ and Regioselective Thiolysis of
1,2‐Epoxides in Water
Barahman Movassagh a b & Mohammad Soleiman‐Beigi a
a Department of Chemistry , K. N. Toosi University of Technology , Tehran,
Iran
b Kermanshah Oil Refining Company , Kermanshah, Iran
Published online: 10 Sep 2007.
To cite this article: Barahman Movassagh & Mohammad Soleiman‐Beigi (2007) Stereo‐ and Regioselective
Thiolysis of 1,2‐Epoxides in Water, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:18, 3239-3244, DOI: 10.1080/00397910701548100
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Synthetic Communicationsw, 37: 3239–3244, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701548100
Stereo- and Regioselective Thiolysis
of 1,2-Epoxides in Water
Barahman Movassagh
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran and Kermanshah Oil Refining Company, Kermanshah, Iran
Mohammad Soleiman-Beigi
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran
Abstract: A simple, efficient, stereoselective, and highly regioselective procedure for
the synthesis of b-hydroxy sulfides by thiolysis of various 1,2-epoxides in water as a
solvent, using no catalyst and under very mild conditions, is described.
Keywords: epoxides, b-hydroxy sulfides, thiols, thiolysis, water
INTRODUCTION
To minimize the amount of toxic waste and by-products generated by
chemical processes, new and more environmentally friendly synthetic
methods using fewer toxic substances need to be developed. Many organic
solvents are harmful and should be used as little as possible or not at all.
Alternatives being investigated for organic reactions include water,[1] super-
critical gases (particularly CO2[2]), and solvent-free conditions (SFC).[3]
Water is usually avoided as a medium for organic reactions because of
the insolubility, and occasionally decomposition, of the reactants and
the incompatibility of intermediates with water.[4] In recent years,
Received in the U.K. October 4, 2006
Address correspondence to Barahman Movassagh, Department of Chemistry, K. N.
Toosi University of Technology, P. O. Box 16315-1618, Tehran, Iran. E-mail:
bmovass1178@yahoo.com
3239

3240
B. Movassagh and M. Soleiman-Beigi
however, there have been several reports of the use of water in organic
reactions.[5]
Nucleophilic ring-opening reactions of epoxides are among the most
important reactions in these small-ring systems.[6] Most ring-opening
reactions of epoxides occur by SN2 nucleophilic displacements at carbon; a
very wide range of carbanions and heteroatom nucleophiles have been
shown to react in this way. The opening of the epoxide ring by sulfur nucleo-
philes to yield b-hydroxy sulfides is an important tool in organic chemistry,[7]
particularly for the synthesis of leukotrienes[8] in pharmaceutical[9] and
natural products.[10]Thiolysis of epoxides has been extensively studied in
organic solvents[11] and can be promoted by acids, a Lewis catalyst or metal
salts,[9,12] or bases (NaOH or Et3N) in a protic solvent (i-PrOH or
MeOH).[10,13] Recently, thiolysis in water was studied by Fringuelli and col-
leagues,[14] with the formation of b-hydroxy sulfides promoted by Lewis acids
such as ZnCl2[5g,15]and InCl3.[14] Another group[16] reported microwave-
promoted synthesis of these compounds in water under basic (NaOH)
conditions.
RESULTS AND DISCUSSION
In a previous study,[17] we investigated the regioselective ring opening of
epoxides by a zinc thiolate intermediate. The reaction was generated from dis-
ulfides in the presence of a Zn/AlCl3 system in dimethylformamide at 658C to
afford the corresponding b-hydroxy sulfides. In the current study, we
examined stereo- and regio-selective ring opening of 1,2-epoxides with
thiols in water at 25 and 508C, in the absence of any catalyst (Scheme 1).
The results are summarized in Table 1.
Initially, we treated glycidyl phenyl ether (R1 ¼ CH2OPh, Scheme 1) with
an equimolar amount of thiophenol in the absence of a catalyst in water at
258C. After 19 h, as monitored by thin-layer chromatography (TLC), the
isolated yield of the corresponding b-hydroxy sulfide 3 was 75%. Under the
same reaction conditions, we performed two other experiments using molar
ratios of thiophenol–glycidyl phenyl ether of 1:1.2 and 1.5:1; the reaction
times and isolated yields were 16.5 h (77%) and 19 h (84%), respectively.
Given the latter result, we decided to use a thiol–epoxide molar ratio
Scheme 1.
.

Thiolysis of 1,2-Epoxides
3241
Table 1. Reaction of epoxides with thiols (1.5 mol. equiv.) in water as solvent and in
the absence of a catalyst
Time (h)/
temp (8C)
Yield
(%)b
Entry R1 or epoxide
R2
Producta
Ref.
1
2
3
4
5
6
CH3
PhOCH2
HOCH2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
17/25
19/25
4/25
6/25
17/25
3
3
85
84
9
9
3
72
79
5g
9
4/3c
3
CH3CH2
74
28 (74)d
12a
9
25/25 (50)
7
8
ClCH2
PhOCH2
ClCH2
CH3CH2
PhOCH2
ClCH2
CH3
Ph
6.5/25
21/25 (50)
7/25 (50)
16/25
3
3
91
55 (81)d
79 (81)d
71
34 (85)d
43 (97)d
93
9
18
19
20
19
19
9
4-ClC6H4
4-ClC6H4
4-CH3C6H4
9
3
10
11
12
13
14
15
16
3
2-Naphthyl 16/25 (50)
2-Naphthyl 10/25 (50)
PhCH2
PhCH2
3
3
19/25
19/25
13/25
15/25
3
ClCH2
Ph
PhOCH2
3
70
97
9
HOCH2CH2
HOCH2CH2
4/3e
3
18
18
84
aAll products were known and identified by comparison of their physical and
spectral data with those of authentic samples.
bIsolated yields.
cRatio 4/3 ¼ 1.8:1.
dYields at 508C.
eRatio 4/3 ¼ 2.1:1.
of 1.5:1 (Table 1). In all cases, the ring opening was completely anti-
stereoselective. The only products obtained were the trans-b-hydroxy
sulfides, as shown by the reaction carried out on cyclohexene oxide (entry
1
6, Table 1), where no trace of the syn adduct was detected by H NMR
spectroscopy. In such a cyclic system, a strong preference to approach from
the axial direction may outweigh other factors.
As can be seen from Table 1, in the case of unsymmetrical epoxides, the
reactions were completely regioselective and proceeded via an SN2
mechanism with an attack of the thiol at the less-hindered site. The only
exception was in the case of styrene oxide, where mixtures of the two
regioisomers were obtained; when styrene oxide reacted with thiophenol
(entry 4, Table 1), regioisomers 4 and 3 were obtained in yields of 51 and
28%, respectively (79% total isolated yield). Treatment of this epoxide with
2-mercaptoethanol (entry 15, Table 1) yielded regioisomers 4 and 3 at 66

3242
B. Movassagh and M. Soleiman-Beigi
and 31%, respectively (97% total isolated yield); this is due to partial stabil-
ization of the developing positive charge at the more hindered site of the
epoxide. Lower yields of the products in some experiments (entries 6, 8, 9,
11, and 12, Table 1) prompted us to also examine the reactions at 508C.
The product obtained under both conditions was found to be the regioisomer
3. The nucleophilic addition of water was not observed in either case.
We hypothesized that the following mechanism is involved in these
reactions: it is likely that the thiol undergoes a small amount of dissociation,
to thiolate anion and a proton, which protonates the epoxide to facilitate attack
by the thiolate anion.
In summary, the new method demonstrated here shows that water is an
effective reaction medium in the thiolysis of 1,2-epoxides in the absence of
any catalyst. The reactions were highly regio- and stereoselective, and
trans-b-hydroxy sulfides were produced in good to excellent yields under
very mild conditions.
EXPERIMENTAL
Chemicals were purchased from Merck and Aldrich chemical companies.
Yields refer to isolated products. Melting points were determined by a
Bu¨chi B-540 apparatus. IR spectra were run on an ABB FTLA 2000 instru-
ment. The 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on a Bruker AQS-300 Avance NMR spectrometer. The progress of
the reaction was followed by TLC using silica-gel SILG/UV 254 plates.
Products were characterized by comparing their physical and spectral data
with those of the authentic samples.[5g,9,12a,18–20]
Typical Procedure for Preparation of 1-(4-Methylphenylthio)butan-
2-ol (T1–10)[20]
A mixture of 1,2-epoxybutane (1.0 mmol, 0.072 g), 4-methylbenzenethiol
(1.5 mmol, 0.186 g), and water (1 mL) was placed in a test tube. The
reaction mixture was magnetically stirred at room temperature for 16 h.
The course of the reaction was monitored by TLC until the starting material
had completely disappeared. Then, water (1 mL) was added, and the
organic materials were extracted with diethyl ether (3 Â 3 mL). The organic
layer was separated and then dried over anhydrous Na2SO4, and the solvent
was removed at reduced pressure. The residue was purified by preparative
TLC (silica gel, eluent n-hexane–EtOAc ¼ 4:1) to afford 0.139 g (71%) of
pure 1-(4-methylphenylthio)butan-2-ol as pale yellow oil; IR ymax (neat):
1
3394, 1492, 1456, 804 cm21. H NMR (CDCl3): d 0.97 (t, 3H, J ¼ 7.5 Hz),
1.57 (quint, 2H, J ¼ 7.2 Hz), 2.34 (s, 3H), 2.60 (s, 1H), 2.81 (dd, 1H,
J ¼ 13.6, 8.8 Hz), 3.12 (dd, 1H, J ¼ 13.6, 3.4 Hz), 3.56–3.62 (m, 1H), 7.12

Thiolysis of 1,2-Epoxides
3243
(d, 2H, J ¼ 8.1 Hz), 7.35 (d, 2H, J ¼ 8.1 Hz). 13C NMR (CDCl3): d 10.0, 21.1,
28.9, 42.5, 70.5, 129.9, 130.9, 131.5, 136.9.
Supplementary Data
1-(4-Chlorophenylthio)-3-phenoxypropan-2-ol (T1-8).[18] Colorless oil, IR
ymax (neat): 3417, 1597, 1476, 1243 cm21.1H NMR (CDCl3): d 2.54 (br s,
1H), 3.14 (dd, 1H, J ¼ 13.9, 6.7 Hz), 3.24 (dd, 1H, J ¼ 13.9, 5.4 Hz),
4.00–4.06 (m, 2H), 4.08–4.17 (m, 1H), 6.88 (d, 2H, J ¼ 8.7 Hz), 6.98
(t, 1H, J ¼ 7.4 Hz), 7.23–7.35 (m, 6H). 13C NMR (CDCl3): d 37.7, 68.7,
70.0, 114.5, 121.4, 129.3, 129.6, 131.1, 132.6, 133.9, 158.3.
1-Chloro-3-(2-naphthalenethio)propan-2-ol (T1-12).[19] White solid; mp
141–1428C (lit.[19] mp 1428C); IR ymax (KBr): 3404, 1624, 1501,
1
1423 cm21. H NMR (CDCl3): d 2.88 (br s, 1H), 3.20 (dd, 1H, J ¼ 13.9,
7.0 Hz), 3.29 (dd, 1H, J ¼ 13.9, 5.6 Hz), 3.72 (d, 2H, J ¼ 5.2 Hz), 4.01 (br
m, 1H), 7.47–7.54 (m, 3H), 7.77–7.87 (m, 4H). 13C NMR (CDCl3): d 38.1,
48.1, 69.6, 126.2, 126.8, 127.2, 127.7, 127.8, 128.3, 128.9, 132.1, 132.1,
133.7.
1-Benzylthio-propan-2-ol (T1-13).[9] Pale yellow oil; IR ymax (neat): 3400,
1600, 1454 cm21.1H NMR (CDCl3): d 1.22 (d, 3H, J ¼ 6.2 Hz), 2.40 (dd,
1H, J ¼ 13.4, 8.7 Hz), 2.47 (br s, 1H), 2.61 (dd, 1H, J ¼ 13.4, 3.6 Hz), 3.75
(s, 2H), 3.80–3.86 (m, 1H), 7.23–7.34 (m, 5H). 13C NMR (CDCl3): d 22.0,
36.2, 40.7, 65.4, 127.2, 128.6, 128.9, 138.1.
ACKNOWLEDGMENTS
The K. N. Toosi University of Technology Research Council and Kermanshah
Oil Refining Company are thanked for financial support of this work.
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