Chemistry Letters Vol.33, No.4 (2004)
477
clean and highly regioselective, affording halohydrins in excellent
yields and no side products or decomposition of the products were
observed under the reaction conditions. In the absence of ionic liq-
uid, the reaction was sluggish and most of the unreacted starting
material was recovered. The main advantage of the use of ionic
liquids is that they can be easily recovered while work-up and
reused for three to four runs with consistent in activity. For in-
stance, treatment of 3-phenoxy-1,2-epoxy propane with lithium
iodide in [bmim]PF6 ionic liquid afforded the corresponding iodo-
hydrin in 96, 95, 94, and 95% yields over four cycles. Moreover,
the products thus obtained were of the same purity as in the first
run. Furthermore, the recovery and reuse of [bmim]PF6 is facili-
tated by its hydrophobic nature.12 Although, similar results were
obtained using [bmim]BF4, longer reaction times are required to
achieve complete conversion. In order to compare the efficiency
of ionic liquids, the reactions were also performed in organic sol-
vents such as acetonitrile and tetrahydrofuran.
vents, enhanced reaction rates, improved yields and high regiose-
lectivity are the features obtained by ionic liquids. Owing to the
activation of the epoxide by the acidic hydrogen of imidazole,
the ring-opening of epoxides is facilitated by ionic liquids. This
type of ionic environment cannot be achieved by conventional or-
ganic solvents. Furthermore, ionic liquids induce the ring-opening
of epoxides by lithium halides without the need of any additional
acid catalyst. Both PF6 and BF4 ionic liquids were obtained
from Fluka and used as such without any further purification.
The scope and generality of this process is illustrated with respect
to various epoxides and lithium halides and the results are present-
ed in Table 1.
In conclusion, this paper demonstrates the successful use of
ionic liquids as novel and recyclable solvents for the synthesis
of vic-halohydrins by regioselective ring-opening of epoxides
with lithium halides. Ionic liquids play a dual role of solvent as
well as the promoter thereby avoiding the use of additional acid
catalyst to promote reaction. The epoxides show a significant in-
crease in reactivity, thus reducing the reaction times and improv-
ing the yields significantly. The simple experimental and product
isolation procedures combined with ease of recovery and reuse of
this novel reaction media is expected to contribute to the develop-
ment of green strategies for the preparation of vic-halohydrins.
À
À
In these organic solvents, the epoxides were unreacted even
after long reaction times (6–10 h). In contrast to conventional sol-
Table 1. Synthesis of halohydrins from epoxides using [bmim]PF6/LiX
reagent system
Yield/%b
Time/h
β−Halohydrina
LiX
Entry
Epoxide
OH
BVS, ChSR, KR thank CSIR, New Delhi, for the award of
fellowships.
a
b
c
O
O
91
93
LiBr
LiI
2.0
1.5
Br
OH
I
References and Notes
1
OH
R. E. Erickson, in ‘‘Marine Natural Products,’’ ed. by P. J. Scheuer, Academic
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3.0c
89
O
O
LiCl
LiBr
LiI
Cl
Br
2
a) P. A. Bartlett, in ‘‘Asymmetric Synthesis,’’ ed. by J. D. Morrison, Academic
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d
e
1.5
1.0
2.0
85(12)
87(15)
82(10)
Ph
OH
Ph
Ph
Ph
I
"
"
OH
3
4
Fieser and Fieser’s, in ‘‘Reagents for Organic Synthesis,’’ ed. by J. G. Smith and
M. Fieser, John Wiley & Sons, New York (1990).
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Cl
f
OH
OH
LiCl
LiBr
O
O
g
Br
I
81(13)
3.5
5
a) G. C. Andrews, T. C. Grawford, and L. G. Contilio, Tetrahedron Lett., 22,
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OH
h
i
LiI
3.0
3.0
84(10)
93
"
OH
O
O
Br
I
LiBr
OH
OH
OH
6
7
a) J. S. Bajwa and R. C. Anderson, Tetrahedron Lett., 32, 3021 (1991). b) H. Kot-
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O
O
O
2.5
4.0c
3.0
j
96
90
89
LiI
"
Cl
Br
LiCl
LiBr
k
l
"
O
O
Cl
Cl
OH
OH
O
O
I
91
87
2.5
m
n
LiI
LiCl
LiBr
LiI
8
9
a) M. I. Konaklieva, M. L. Dahl, and E. Turos, Tetrahedron Lett., 33, 7093
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"
Cl
Cl
4.0c
"
Cl
Me
Me
OH
OH
O
O
O
O
Br
I
O
O
91
93
3.0
2.5
2.5
o
p
10 a) R. Sheldon, Chem. Commun., 2001, 2399. b) C. M. Gordon, Appl. Catal., A,
222, 101 (2001).
Me
"
11 Experimental procedure: A mixture of epoxide (1 mmol) and lithium halide
(1.2 mmol) in [bmim]PF6 or [bmim]BF4 (3 mL) was stirred at room temperature
for the appropriate time (see Table). After completion of the reaction, as indicat-
ed by TLC, the reaction mixture was extracted with diethyl ether (3 Â 10 mL).
The combined organic extracts were concentrated in vacuo and the resulting
product was directly charged onto a small silica gel column and eluted with a
mixture of ethyl acetate:n-hexane (1:9) to afford pure halohydrin. The rest of
the ionic liquid was further washed with diethyl ether and recycled in subsequent
runs. The halohydrins thus obtained were identified by comparison of their
NMR, IR, Mass, TLC analysis, and physical data with authentic samples. The
spectral data of all the products were identical with those of authentic samples.6,7
12 The continual reuse of [bmim]PF6 may cause the liberation of most hazardous
HF. Therefore, PF6 based ionic liquid should be recycled with the utmost care.
R. P. Swatloski, J. D. Holbrey, and R. D. Rogers, Green Chem., 5, 361 (2003).
OH
OH
O
O
Br
I
90
92
q
r
LiBr
LiI
MeO
MeO
MeO
2.0
"
OH
s
3.0c
LiCl
O
Cl
89
"
MeO
All products were characterized by 1H NMR, IR and mass spectroscopy.
Yield in paranthesis indicates other regioisomer.
Reactions were carried out at 65 ꢀC.
a
b
c
Published on the web (Advance View) March 23, 2004; DOI 10.1246/cl.2004.476