Alumina-supported molybdenum (VI) oxide: An efficient and recyclable heterogeneous catalyst for regioselective ring opening of epoxides with thiols, acetic anhydride, and alcohols under solvent-free conditions

Article abstract of DOI:10.1246/cl.2008.620

An efficient and simple protocol for regioselective ring opening of epoxides with thiols, acetic anhydride, and alcohols using 16wt% MoO₃ supported on alumina as a recyclable catalyst is described. Copyright

Full text of DOI:10.1246/cl.2008.620

620
Chemistry Letters Vol.37, No.6 (2008)
Alumina-supported Molybdenum (VI) Oxide: An Efficient and Recyclable Heterogeneous Catalyst
for Regioselective Ring Opening of Epoxides with Thiols, Acetic Anhydride,
and Alcohols under Solvent-free Conditions
Sweety Singhal, Suman L. Jain, and Bir SainÃ
Chemical and Biotechnology Division, Indian Institute of Petroleum, Dehradun-248005, India
(Received March 24, 2008; CL-080315)
An efficient and simple protocol for regioselective ring
SR'
OH
16wt % MoO3/Al2O3 (2 mol %)
10–30 min
opening of epoxides with thiols, acetic anhydride, and alcohols
using 16 wt % MoO3 supported on alumina as a recyclable
catalyst is described.
or
OH
SR'
R
R
R'SH, r.t.
2
3
OAc
O
16wt % MoO3/Al2O3 (2 mol %)
Ac2O, r.t.
OAc
R
25–35 min
R
4
1
Epoxides are highly versatile synthetic intermediates in
organic synthesis as they undergo ring-opening reactions with
various nucleophiles to afford 1,2-difunctionalized compounds.
ꢀ-Hydroxysulphides, 1,2-diacetates, and ꢀ-alkoxyalcohols
are valuable synthones and being extensively used as key inter-
mediates in the synthesis of various biologically active natural
and synthetic products.1 The easiest and straightforward ap-
proach for their synthesis involves the ring opening of epoxides
with appropriate nucleophile under acidic or basic conditions.
Since alcohols, thiols, and acetic anhydride are comparatively
poor nucleophiles than amines, therefore require strong acidic
or basic conditions, high temperature, and large excess of nucle-
ophile. These limitations led to the development of mild catalyt-
ic methodologies involving the use of metal salts/complexes,2
metal triflates,3 microwave irradiation,4 ionic liquids,5 and
solvent-free protocols. However, most of the existing methods
suffer from one or more drawbacks such as the use of expensive
reagents, toxic/volatile organic solvents, homogeneous nature of
the catalyst, low regioselectivity, extended reaction times, and
poor yields. Recent developments have focused considerable
attention towards the use of heterogeneous catalysts due to their
ease of handling, facile recovery from the reaction mixture,
higher stability and recyclability. Further, solventless synthetic
methods are valuable not only for green chemistry reasons but
also for simplicity in procedure and provide high yield of the
desired product.6
OR"
OH
16wt % MoO3/Al2O3 (2 mol %)
R"OH, r.t.
or
OH
OR"
R
R
15–45 min
5
6
R = alkyl, aryl, cycloalkyl
R' = aryl, benzyl
R" = alkyl, benzyl
Scheme 1.
(overnight) and finally calcined at 550 ꢀC for 6 h. Physicochem-
ical characterization data of the prepared catalyst are given in
another literature report.12
Initially, we studied the reaction of styrene oxide with ben-
zenethiol in the presence of catalytic amount of 16 wt % MoO3/
Al2O3 (2 mol %) at room temperature under solvent-free reac-
tion condition. The reaction was completed within 10 min and
yielded 2a regioselectively in a nearly quantitative yield being
formed by the cleavage at benzylic position (Table 1, Entry 1).
The reaction did not occur neither in the absence of the
MoO3/Al2O3 nor with the use of thermally treated pure Al2O3
as catalyst. Whereas the reaction was found to be slow with
the use of thermally treated pure MoO3 (Aldrich) as a catalyst
and led to the product in a very poor yield even after prolonged
reaction time. We assume that the higher catalytic activity of
16 wt % MoO3/Al2O3 is probably due to the increased Lewis
acidity of the Mo oxide dispersed on alumina support.
To generalize the reaction, we carried out the thiolysis of
various alkyl, aryl, and cycloalkyl epoxides with a variety of thi-
ols under similar reaction conditions.13 In all cases, the reaction
was found to be regioselective in nature and afforded very good
to excellent yields of the corresponding ꢀ-hydroxysulfide. These
results are presented in Table 1. We observed that aryl epoxides
underwent cleavage at the benzylic position (Table 1, Entries 1,
2, 8–11, 15, and 16), probably due to the formation of stabilized
benzylic cation as reactive intermediate, while alkyl epoxides
such as epichlorohydrin 3a and 3b underwent ring opening with
the preferential attack at terminal position. Nevertheless, Posner
and Rogers reported the Woelm 200 neutral chromatographic
alumina catalyzed nucleophilic ring opening of epoxides under
mild reaction conditions.14 However, the use of excess alumina
(7.5 g for 1 mmol of epoxide) as well as nucleophile (>4 mmol/
mmol of epoxide), comparatively lower product yields and need
to use large amount of solvent (diethyl ether) for the reaction as
well as work-up makes its utility limited.
In this context, heterogeneous catalysts such as mesoporous
aluminosilicates,7 HBF4–SiO2,8 ammonium 12-molybdophos-
phate,9 and aluminododecatungstoposphate (AlPW12O40)10 have
been utilized for the regioselective ring opening of epoxides by
using thiols, alcohols, and acetic anhydride as nucleophiles.
However, the drawbacks associated with most of these methods
are tedious preparation of catalysts and longer reaction times.
In the present letter we wish to report that MoO3 supported
on alumina, an easily accessible, stable catalyst can efficiently be
applied as a recyclable heterogeneous catalyst for the regioselec-
tive ring opening of epoxides with thiols, acetic anhydride
and alcohols to afford corresponding ꢀ-hydroxysulphides, 1,2-
diacetates, and ꢀ-alkoxyalcohols in a very good to excellent
yields under solvent-free conditions (Scheme 1).
16 wt % MoO3/Al2O3 catalyst was prepared on ꢁ-Al2O3
support by the incipient wet impregnation method using ammo-
.
nium heptamolybdate [(NH4)6Mo7O24 4H2O] salt following the
literature procedure.11 The prepared catalyst was dried at 110 ꢀC
To extend the scope of the protocol developed we also stud-
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.6 (2008)
621
Table 1. 16 wt % MoO3/Al2O3 catalyzed ring opening of
epoxides with various nucleophilesa,b
be recovered from the reaction mixture by simple filtration and
reused as such for subsequent four runs without loss in catalytic
activity.
Entry
Epoxide
Nucleophile
Product Time Yieldc
/min
10
15
25
15
45
30
40
/%
97
89
96
96
80
90
91
1
To check the leaching of metal during the reaction, the
catalyst was separated by filtration and the filtrate so obtained
was analyzed by inductively coupled plasma atomic emission
spectroscopy (ICP-AES). There was no solved molybdate
detected, establishing that the reaction is completely heterogene-
ous in nature.
The merits of the protocol developed reflected by the
fact that MoO3 supported on alumina is an easy accessible,
inexpensive, and versatile catalyst which can efficiently be
applied for the regioseelctive ring opening of epoxides with
various nucleophiles in high yields under solvent-free condition
and could be recycled without loss in activity.
O
1
2
3
4
5
6
7
PhSH
PhCH2SH
Ac2O
2a
2b
4a
5a
5b
5c
5d
MeOH
PhCH2OH
i-PrOH
t-BuOH
8
9
PhSH
PhCH2SH
p-CH3C6H4SH
p-ClC6H4SH
Ac2O
15
25
15
15
30
15
35
94
88
92
89
95
94
91
2c
2d
2e
2f
4b
5e
5f
O
10
11
12
13
14
Me
MeOH
i-PrOH
We kindly acknowledge the Director, IIP for his kind
permission to publish these results and SS, SJ are thankful to
CSIR for their research fellowships.
15
16
17
18
19
PhSH
p-BrC6H4SH
Ac2O
MeOH
i-PrOH
15
20
30
20
30
96
90
97
97
93
2g
2h
4c
5g
5h
O
Cl
References and Notes
20
21
22
23
24
25
PhSH
PhCH2SH
p-ClC6H4SH
Ac2O
MeOH
i-PrOH
20
30
20
35
40
45
90
85
89
89
90
89
1
J. R. Luly, N. Yi, J. Soderquist, H. Stein, J. Cohen, T. J. Perun,
J. J. Plattner, J. Med Chem. 1987, 30, 1609; E. J. Corey, D. A.
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Hammarstrom, J. Am. Chem. Soc. 1980, 102, 1436; P. G.
Williams, W. Y. Yoshida, R. E. Moore, V. J. Paul, J. Nat. Prod.
2002, 65, 29.
3a
3b
3c
4d
6a
6b
O
Cl
2
3
Shivani, A. K. Chakraborti, J. Mol. Catal. A: Chem. 2007, 263,
137; W. Su, J. Chen, H. Wu, C. Jin, J. Org. Chem. 2007, 72,
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Graham, Tetrahedron Lett. 2007, 48, 4723.
26
27
28
29
PhSH
p-ClC6H4SH
Ac2O
15
20
30
30
97
88
94
91
3d
3e
4e
6c
O
i-PrOH
O
30
31
32
33
34
PhSH
C6H5CH2SH
Ac2O
MeOH
i-PrOH
15
20
30
15
15
96
88
94
93
90
3f
3g
4f
6d
6e
4
5
6
O
35
36
37
38
PhSH
C6H5CH2SH
Ac2O
25
30
15
20
90
87
90
90
3h
3i
4g
6f
C6H5
O
7
8
9
MeOH
aReaction condition: Epoxide 1 (2 mmol), nucleophile 2 (2.2
mmol), 16 wt % MoO3/Al2O3 (2 mol %) at room temperature.
B. P. Bandgar, A. V. Patil, O. S. Chavan, V. T. Kamble, Catal.
Commun. 2007, 8, 1065.
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6865.
bFor alcoholysis 4 mmol of alcohol was used. Isolated yields.
c
ied the ring opening of epoxides with acetic anhydride under
similar reaction conditions. In all cases, the conversion was com-
pleted in 25–35 min and yielded exclusively 1,2-diacetates in
high yields (Table 1, Entries 3, 12, 17, 23, 28, 32, and 37). Sim-
ilarly, the procedure worked well for alcoholysis of epoxides
with a variety of benzylic, primary, secondary, and tertiary alco-
hols under the same experimental conditions. All the reactions
were found to be selective and afforded corresponding ꢀ-alkoxy-
alcohols in very good to excellent yields. These results are pre-
sented in Table 1 (Entries 4–7, 13, 14, 18, 19, 24, 25, 29, 33, 34,
and 38). In contrast to most of the reported methods, which are
effective only with primary alcohols, the present methodology
worked equally well with secondary and tertiary alcohols and
afforded high yields of the products 5c, 5d, 5f, 5h, 6b, 6c, and
6e being formed via regioselective ring opening of epoxides.7
Next we checked the recycling of the catalyst using the
reaction of styrene oxide and benzenethiol as a representative
example. At the end of the reaction, the catalyst could easily
10 H. Firouzabadi, N. Iranpoor, A. A. Jafari, S. Makarem, J. Mol.
Catal. A: Chem. 2006, 250, 237.
11 B. M. Reddy, E. P. Reddy, S. T. Srinivas, J. Catal. 1992, 136, 50.
12 S. Singhal, S. L. Jain, V. V. D. N. Prasad, B. Sain, Eur. J. Org.
Chem. 2007, 2051.
13 General experimental procedure: Into a stirred mixture of an ep-
oxide (2 mmol) and 16 wt % MoO3/Al2O3 (2 mol %) contained
in a 25-mL round-bottomed flask was added nucleophile
(2.2 mmol, in case of alcoholysis 4 mmol of alcohol was used).
The reaction was further continued at room temperature with
stirring for the time period as mentioned in the Table 1. After
completion of the reaction, reaction mixture was dissolved in
Et2O (5 mL) and catalyst was recovered by filtration. The organic
layer was washed with water (3 Â 10 mL), dried over anhydrous
Na2SO4 and concentrated under vacuum. The crude product was
purified by flash chromatography to yield pure 1,2-difunctional-
ized products. The recovered catalyst was washed with Et2O,
dried under vacuum and reused for further experiments.
14 G. H. Posner, D. Z. Rogers, J. Am. Chem. Soc. 1977, 99, 8208;
G. H. Posner, Angew. Chem., Int. Ed. Engl. 1978, 17, 487.
Published on the web (Advance View) May 3, 2008; doi:10.1246/cl.2008.620