Ionic liquid as reagent. A green procedure for the regioselective conversion of epoxides to vicinal-halohydrins using [AcMIm]X under catalyst- and solvent-free conditions

Article abstract of DOI:10.1021/jo0500885

A variety of structurally diverse epoxides undergo facile cleavages by ionic liquid, [AcMIm]X without any catalyst and solvent to produce the corresponding vicinal halohydrins in high yields. The cleavages are considerably fast and highly regioselective.

Full text of DOI:10.1021/jo0500885

SCHEME 1. Synthesis of Halohydrins
Ionic Liquid as Reagent. A Green
Procedure for the Regioselective
Conversion of Epoxides to
Vicinal-Halohydrins Using [AcMIm]X
under Catalyst- and Solvent-Free
Conditions
Brindaban C. Ranu* and Subhash Banerjee
Department of Organic Chemistry,
Indian Association for the Cultivation of Science,
Jadavpur, Kolkata 700 032, India
Li2CuCl4,13 Lix-TiX4,14 Lix-[Bmim]PF615 are reported to
be more convenient and efficient. However, the presence
of strong Lewis acid and protic acid in these Lix combined
reagent systems often leads to low yields of halohydrins.
As there is a continued interest in the selective ring
opening of epoxides to give halohydrins a milder, more
efficient, and environmentally friendly methodology would
be highly desirable.
ocbcr@iacs.res.in
Received January 15, 2005
The ionic liquids have been the subject of considerable
current interest as environmentally benign reaction
media in organic synthesis because of their unique
properties of nonvolatility, nonflammability, and recy-
clability, among others.16,17 However, the ability of ionic
liquid as a clean catalyst18 and reagent19 has not been
explored to any great extent although it is of much
importance in the context of green synthesis. As a part
of our continuous drive20 to avoid organic solvent, toxic
catalysts, and reagents, we have initiated a new program
to explore the use of ionic liquid as efficient catalyst,
reagent, as well as reaction media for useful organic
transformations. We report here a novel use of an ionic
liquid, acylmethylimidazolium halide ([AcMIm]X),21 for
the cleavage of epoxides to halohydrins without require-
ment of any other catalyst and solvent (Scheme 1). Thus,
[AcMIm]X acts as reagent as well as solvent for this
reaction.
A variety of structurally diverse epoxides undergo facile
cleavages by ionic liquid, [AcMIm]X without any catalyst
and solvent to produce the corresponding vicinal halohydrins
in high yields. The cleavages are considerably fast and highly
regioselective.
The vicinal halohyrins are very useful synthetic inter-
mediates and have found wide applications in organic
transformations and in the synthesis of marine natural
products.1,2 The conventional reagents for epoxide ring
opening to halohydrins are hydrogen halides and hypo-
halite-water.3 However, these procedures are associated
with the disadvantages of intolerance to acid-sensitive
moieties and byproduct formation.4 A variety of other
reagents5 such as ammonium halides in the presence of
metal salts,5a halosilanes,5b haloboranes,5c,d and particu-
larly halides of different elements such as P,6 Al,7 Fe,8
Cu,,9 Ni,10 Sn,11 and Li12 are also available for this
transformation. Among these reagents lithium halides
in combination with various Lewis acids such as
The experimental procedure is very simple. A mixture
of epoxide and [AcMIm]X was heated at 65 °C with
stirring for 1.5-2.0 h (TLC). The reaction mixture was
then quenched with brine and extracted with ether.
(13) Ciaccio, J. A.; Heller, E.; Talbot, A. Synlett 1991, 248.
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5, 44. (b) Ranu, B. C.; Das, A.; Samanta, S. J. Chem. Soc., Perkin Trans.
1 2002, 1520. (c) Ranu, B. C.; Dey, S. S. Tetrahedron Lett. 2003, 44,
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10.1021/jo0500885 CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/12/2005
J. Org. Chem. 2005, 70, 4517-4519
4517

TABLE 1. Synthesis of â-Halohydrins from 1,2-Epoxides with [AcMlm]X
a Yields refer to those of pure isolated products characterized by IR and 1H and 13C NMR spectroscopic data and elemental analysis.
Usual workup followed by short column chromatography
produced the pure product.
A wide range of structurally diverse epoxides under-
went cleavages by this ionic liquid to produce the corre-
sponding halohydrins. Chloro, bromo, and iodo groups
can be introduced with similar efficiency by use of the
corresponding chloride, bromide and iodide derivatives
of the [AcMIm]X. The results are summarized in Table
1. The cleavages are, in general, regio- and stereoselective
going through an SN2 addition path. In case of open chain
terminal epoxides (entries 1-10) less substituted ends
were halogenated. The cyclic epoxides (entries 18-22)
always produced trans halohydrins as indicated by the
observed coupling constants of the ring hydrogens in their
4518 J. Org. Chem., Vol. 70, No. 11, 2005

1H NMR spectra. In R-keto epoxides (entries 24-26),
halogenation occurs at the epoxide juncture R to keto
carbonyl. The â-trisubstituted keto epoxides (entries 27,
28), however, underwent simultaneous dehydration to
give R,â-unsaturated ketones. Interestingly, R-carbo-
methoxy epoxides (entries 29 and 30) leads to halogena-
tion at the â-position producing a single trans stereoiso-
mer as indicated by the coupling constants of 8.7 Hz
(entry 29) and 10.0 Hz (entry 30) due to C2-C3 diaxial
H-interactions and 4.5 Hz (entry 29) and 5.4 Hz (entry
30) due to C2-C3 axial equatorial H-interactions in their
1H NMR spectra. Phenyl-substituted epoxides (entries
11-13) also underwent facile ring cleavages to provide
the corresponding halohydrins. However, diphenyl ep-
oxide (entry 31) underwent rearrangement to give 2-phe-
nylacetophenone. Similar rearrangement was also ob-
served in phenyl-substituted R-carbonyl epoxides (entries
32 and 33). However, the exact reason for the formation
of chlorohydrin as major product in entry 33 is not very
clear to us. Very interestingly, in all of these phenyl-
substituted epoxides only hydride migration occurs in
contrast to Lewis acid catalyzed rearrangements22 where
phenyl migration takes place.
SCHEME 2. Mechanism of Epoxide Cleavage
OCH2Ph, and OCH3, remain unaffected under the present
reaction conditions. Presumably, due to the activation of
the epoxide by the acidic hydrogen of imidazole moiety,
epoxide ring cleavage is facilitated and is then promoted
by the counter halide ion (X-) of [AcMIm]X as depicted
in Scheme 2.
Conclusion
In summary, this procedure provides a novel and green
protocol for epoxide ring cleavage leading to halohydrins
by a simple and inexpensive ionic liquid, [AcMIm]X,
which itself works as reagent, catalyst, and reaction
medium. To the best of our knowledge, we are not aware
of any such use of ionic liquid for epoxide cleavage. The
other significant advantages offered by this method are
operational simplicity, considerably fast reaction (1-2 h),
mild reaction conditions, general applicability to a wide
variety of substrates, regio- and stereoselectivity, and
high isolated yields of products, and thus, it provides a
better and practical alternative to the existing pro-
cedures.3-16 Moreover, this strategy opens up a new area
for further applications of ionic liquid in green synthesis.
Very recently, a synthesis of halohydrins from oxiranes
using LiX in ionic liquid [bmIm]PF6 has been reported
by Yadav and co-workers.15 However, our work is es-
sentially different from theirs as they carried out the
reaction using a conventional halide reagent LiX in ionic
liquid as the reaction medium, whereas in the present
work, the particular ionic liquid, [AcMIm]X, is utilized
as a reagent as well as reaction medium without requir-
ing any other metal halide for the reaction.
Experimental Section
General Experimental Procedure for the Synthesis of
Halohydrins by Ring Cleavage of Epoxide with [AcMIm]X.
Representative Procedure for 1-Chloro-2-octanol. A mix-
ture of 2-hexyloxirane (128 mg, 1 mmol) and [AcMIm]Cl (225
mg, 1.3 mmol) was heated at 65 °C with stirring for 1.5 h (TLC).
The reaction mixture was quenched with saturated brine and
extracted with ether (3 × 10 mL). Evaporation of ether left the
crude product which was purified by column chromatography
over silica gel (hexanes-Et2O 80:20) to provide the pure 1-chloro-
2-octanol as a colorless liquid (155 mg, 95%) whose spectroscopic
data (IR, 1H and 13C NMR) are in good agreement with those of
authentic sample. All of the products except two are known
compounds and are easily identified with their appropriate
stereoconfiguarion (whereever applicable) by comparison of their
NMR spectra with those of authentic samples. The purity of all
In general, the reactions are considerably fast, clean,
and high yielding, leading to the synthesis of halohydrins.
Several functional groups, such as Cl, CO2R, OAc,
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1
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elemental analysis.
Acknowledgment. S.B. is thankful to CSIR, New
Delhi, for the fellowship.
Supporting Information Available: General experimen-
tal requirements and spectroscopic (IR, 1H NMR, and 13C
NMR) data and elemental analysis of the products listed in
entries 29 and 30 of Table 1. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO0500885
J. Org. Chem, Vol. 70, No. 11, 2005 4519