Magnesium hydrogensulfate: A cheap and efficient catalyst for the conversion of epoxides into β-alkoxy alcohols, vicinal-diols, and thiiranes

Article abstract of DOI:10.1081/SCC-120022479

The nucleophilic ring opening reactions of epoxides by aliphatic alcohols and water are achieved efficiently in the presence of catalytic amounts of magnesium hydrogensulfate, Mg(HSO₄)₂, with high degree of regioselectivity. The reactions are chemoselective and many of the other functional groups such as ethereal carbon oxygen bonds as well as carbon-carbon double bond remain intact under the reaction conditions. Epoxides also react with thiourea or ammonium thiocyanate in the presence of Mg(HSO ₄)₂ to afford the corresponding thiiranes in good to excellent yields.

Full text of DOI:10.1081/SCC-120022479

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Magnesium Hydrogensulfate: A Cheap and Efficient
Catalyst for the Conversion of Epoxides into β-Alkoxy
Alcohols, Vicinal-Diols, and Thiiranes
Peyman Salehi a , Mohammad Mahdi Khodaei b , Mohammad Ali Zolfigol c & Afsaneh Keyvan b
a Department of Phytochemistry, Medicinal Plants Research Institute, Shahid Beheshti
University, Evin, Tehran, Iran
b Department of Chemistry, Faculty of Science, Razi University, Kermanshah, Iran
c Department of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, Iran
Published online: 21 Aug 2006.
To cite this article: Peyman Salehi , Mohammad Mahdi Khodaei , Mohammad Ali Zolfigol & Afsaneh Keyvan (2003): Magnesium
Hydrogensulfate: A Cheap and Efficient Catalyst for the Conversion of Epoxides into β-Alkoxy Alcohols, Vicinal-Diols, and
Thiiranes, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
33:17, 3041-3048
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 17, pp. 3041–3048, 2003
Magnesium Hydrogensulfate: A Cheap and
Efficient Catalyst for the Conversion of Epoxides
into b-Alkoxy Alcohols, Vicinal-Diols,
and Thiiranes
2,
Peyman Salehi,1, Mohammad Mahdi Khodaei,
*
*
Mohammad Ali Zolfigol,3 and Afsaneh Keyvan2
1Department of Phytochemistry, Medicinal Plants
Research Institute, Shahid Beheshti University,
Evin, Tehran, Iran
2Department of Chemistry, Faculty of Science,
Razi University, Kermanshah, Iran
3Department of Chemistry, Faculty of Science,
Bu-Ali Sina University, Hamadan, Iran
*Correspondence: Peyman Salehi, Department of Phytochemistry, Medicinal
Plants Research Institute, Shahid Beheshti University, Evin, Tehran, Iran;
E-mail: p-salehi@cc.sbu.ac.ir; Mohammed Mahdi Khodaei, Department
of Chemistry, Faculty of Science, Razi University, Kermanshah, Iran; E-mail:
khodaei@razi.ac.ir.
3041
DOI: 10.1081/SCC-120022479
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3042
Salehi et al.
ABSTRACT
The nucleophilic ring opening reactions of epoxides by aliphatic
alcohols and water are achieved efficiently in the presence of catalytic
amounts of magnesium hydrogensulfate, Mg(HSO4)2, with high
degree of regioselectivity. The reactions are chemoselective and
many of the other functional groups such as ethereal carbon-
oxygen bonds as well as carbon–carbon double bond remain intact
under the reaction conditions. Epoxides also react with thiourea or
ammonium thiocyanate in the presence of Mg(HSO4)2 to afford the
corresponding thiiranes in good to excellent yields.
Key Words: Magnesium hydrogensulfate; Epoxides; b-alkoxy alco-
hols; Vicinal diols; Thiiranes.
b-alkoxy alcohols are commonly synthesized by the alcoholysis of
epoxides under acidic conditions.[1–9] Hydrolysis of epoxides is an impor-
tant route to prepare vicinal diols in high yields.[3,4,8] Epoxides are also
considered as the most convenient starting materials for the synthesis of
thiiranes through their reactions with inorganic thiocyanates, thiourea or
thioamides in acidic conditions in which oxygen atom is replaced by
sulfur.[10] When an aqueous solvent is used, control of pH is important
to avoid the polymerization of the produced thiiranes.[11] Recently,
several acidic reagents have been used for this purpose.[12–17] Butmost
of these methods suffer from unavailability or high cost of the reagent.
In continuation of our studies on the application of magnesium
hydrogensulfate in organic synthesis,[18] we wish to report a very efficient
and catalytic method for regioselective ring opening of epoxides by
alcohols and water.
The reaction of epoxides with primary, secondary, and tertiary
alcohols in the presence of 0.01–0.2 molar equivalents of Mg(HSO4)2
was investigated and the corresponding b-alkoxy alcohols were obtained
in good to excellent yields with high degree of regio- and chemoselectivity
(Sch. 1, Table 1).
In the case of styrene oxide, the nucleophiles attacked the more
hindered carbon (Table 1, Entries 1–5). The alcoholysis reaction of cyclo-
hexene oxide ended up with the formation of trans-b-alkoxy alcohols in
high yields (Table 1, Entries 6–10). In other model compounds in which
electron withdrawing groups were attached to the epoxide ring, the elec-
tronic and steric effects act in the same direction and the products of the
attack of nucleophiles to the less hindered carbon atoms were obtained
(Table 1, Entries 11–29).

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Magnesium Hydrogensulfate
3043
Scheme 1.
The reactions were chemoselective and cleavage of other carbon-
oxygen and carbon-halogen bonds was notobserved in any case. Also
the double bond in allyl glycidyl ether remained intact under the reaction
conditions.
We have also investigated the hydrolysis reactions of epoxides in the
presence of catalytic amounts of magnesium hydrogensulfate (Sch. 2,
Table 2).
The reactions were carried out in acetone–water (3/1:v/v) as solvent
and the corresponding vicinal diols were obtained in excellent yields. In
the case of cyclohexene oxide, trans-1,2-dihydroxy cyclohexane was
obtained in 95% yield (Table 2, Entry 2).
Different kinds of epoxides were also converted into thiiranes by the
reaction with ammonium thiocyanate or thiourea in dry acetonitrile in
the presence of 0.5 molar equivalent of magnesium hydrogensulfate
(Sch. 3, Table 3).
As shown in Table 3, epoxides bearing electron releasing groups as
well as electron withdrawing groups underwent the oxygen–sulfur
exchange in high yields. No polymerization product was obtained. The
reactions with ammonium thiocyanate took place in 10–30 min while
similar reactions with thiourea had taken place in longer periods. This

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3044
Salehi et al.
Table 1. The reaction of epoxides with aliphatic alcohols in the presence of
magnesium hydrogensulfate at room temperature.
Mg(HSO4)2/sub.
(mole ratio)
Time
(min) [h]
Yield
(%)
Entry
R1
R2
Product
1
2
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1d
1d
1d
1d
1d
1e
1e
1e
1e
1e
1f
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.02
0.01
0.1
(1)
(5)
91
87
83
80
85
85
80
83
72
78
85
91
89
81
85
93
91
83
85
80
95
82
95
85
87
82
80
85
79
Me
n-Pr
i-Pr
2a
2a
3
(5)
2a(3a trace)
2a(3a trace)
2a
4
(10)
(5)
t-Bu
Allyl
Me
5
6
(1)
2
OR
7
(10)
(10)
(40)
(30)
(30)
[1]
n-Pr
i-Pr
8
9
t-Bu
Allyl
Me
OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
3c
3c
3c
3c
3c
3d
3d
3d
3d
3d
3e
3e
3e
3e
3e
3f
0.1
0.1
n-Pr
i-Pr
[1.5]
[2]
0.1
0.1
t-Bu
Allyl
Me
[1.3]
(45)
[2]
0.1
0.1
n-Pr
i-Pr
0.1
0.1
[1.5]
[2]
t-Bu
Allyl
Me
0.1
0.1
[1]
[1]
0.1
0.1
[3.5]
[2.5]
[5.5]
[1.5]
[3.5]
[4]
n-Pr
i-Pr
0.1
0.1
t-Bu
Allyl
n-Pr
i-Pr
0.2
0.2
1f
3f
1f
0.2
0.2
[8.5]
[3]
t-Bu
Allyl
3f
1f
3f
could be due to the higher nucleophilicity of thiocyanate ion in compar-
ison with thiourea.
In conclusion, catalytic nature of the reactions, high degree of regio-
and chemoselectivity, cheapness and ease of handling of the reagent are
among the outstanding features that make magnesium hydrogensulfate
the reagent of choice for the synthesis of b-alkoxy alcohols, vicinal diols
and thiiranes from epoxides.

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Magnesium Hydrogensulfate
3045
1 (a-f )
4 (a-f )
Scheme 2.
Table 2. Hydrolysis of epoxides in the presence of magnesium hydrogensulfate.
Mg(HSO4)3/sub.
(mole ratio)
Time
(min) [h] Temp.
Yield
(%)
Entry R1
Product
1
2
1a
1b
0.01
0.01
(1)
(1)
rt93
rt95
4a
Trans-1,2-
cyclohexandiol
3
4
5
6
1c
1d
1e
1f
0.05
0.01
0.1
[1.5]
(30)
[2]
reflux
reflux
reflux
reflux
89
91
93
90
4c
4d
4e
4f
0.1
[1.8]
1 (a-f )
5 (a-f)
Scheme 3.
EXPERIMENTAL
All of the products are known compounds and were characterized by
comparison of their spectral data (1H NMR, IR) and physical properties
with those reported in the literature.[3,6,13,15] 1H NMR spectra were
run on a Bruker Avance 500 MHz spectrometer. IR spectra were
obtained by a Shimadzu 470 spectrophotometer. The reaction monitoring

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3046
Salehi et al.
Table 3. Conversion of epoxides into thiiranes by the reaction with ammonium
thiocyanate or thiourea in the presence of magnesium hydrogensulfate.
Time Yield
Nucleophile (min) [h] (%)
Entry
R1
Product
1
2
1a
1b
1c
NH4SCN
NH4SCN
NH4SCN
(10)
(20)
(30)
(20)
(30)
(25)
[2.5]
[2]
97
95
89
92
85
90
80
87
81
90
85
78
5a
5b
3
5c
5[R1¼CH3(CH2)5CH2]
4
CH3(CH2)5CH2 NH4SCN
5
1e
1f
NH4SCN
NH4SCN
5e
6
5f
5a
7
1a
1b
1c
H2NCSNH2
H2NCSNH2
H2NCSNH2
8
5b
5c
9
[7]
[5]
10
11
12
CH3(CH2)5CH2 H2NCSNH2
5[R1¼CH3(CH2)5CH2]
1e
1f
H2NCSNH2
H2NCSNH2
[7]
[6]
5e
5f
was accomplished by TLC on SIL G/UV 254 sheets or by GC on a
Shimadzu 8A gas chromatograph. All yields refer to isolated products.
General Procedure for the Alcoholysis of Epoxides
Magnesium hydrogensulfate (0.02–0.4 mmol) was added to a solu-
tion of epoxide (2 mmol) in alcohol (7 mL). The mixture was stirred
magnetically at room temperature for the appropriate period of time
(Table 1). The progress of the reaction was followed by GC or TLC.
After completion of the reaction, solvent was evaporated under reduced
pressure. Water (20 mL) was added and the mixture extracted with
diethyl ether (3 ꢀ 20 mL). The organic layer was separated and dried
(Na2SO4). Evaporation of the solvent followed by purification on a
shortsilica gel column gave hte desired b-alkoxy alcohols in 73–95%
yields.
General Procedure for the Hydrolysis of Epoxides
To a solution of epoxide (2 mmol) in acetone–water (3/1:v/v, 7 mL),
magnesium hydrogensulfate (0.02–0.2 mmol) was added. The reaction
mixture was stirred magnetically at the optimum temperature for the

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Magnesium Hydrogensulfate
3047
appropriate period (Table 2). Solvent was evaporated under reduced
pressure. Diethyl ether (50 mL) was added and the mixture passed
through a silica gel pad followed by washing the pad with ether.
Ethereal solution was dried (Na2SO4) and concentrated to afford the
corresponding vicinal diols in 82–92% yields.
General Procedure for the Conversion of Epoxides
into Thiiranes
In a round-bottomed flask equipped with a condenser and a mag-
netic stirrer, a solution of epoxide (2 mmol) in acetonitrile (7 mL) and
ammonium thiocyanate/ or thiourea (6 mmol) was prepared. Magnesium
hydrogensulfate (1 mmol) was added and the mixture was stirred magne-
tically under reflux conditions for the appropriate period (Table 3).
Progress of the reaction was monitored by TLC (eluent:
n-hexane/EtOAc:4/1). Solvent was evaporated on a rotary evaporator.
Water (15 mL) was added and the mixture extracted with chloroform
(3 ꢀ 15 L). The organic layer was separated and dried (MgSO4).
Evaporation of the solvent followed by chromatography on a short
column of silica gel gave the pure thiiranes.
ACKNOWLEDGMENT
We are grateful to Razi University Research Council for financial
supportof ht is work.
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Received in the Netherlands October 30, 2002