Efficient α-chlorination and α-bromination of carbonyl compounds using N-halosuccinimides/UHP in ionic liquid

Article abstract of DOI:10.1080/00397910600978168

A facile and efficient method for the α-halogenation of carbonyl compounds utilizing N-halosuccinimides (NXS) in the presence of urea-hydrogen peroxide (UHP) in [bmim]BF4 has been newly developed. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600978168

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Efficient α‐Chlorination and α‐Bromination
of Carbonyl Compounds Using
N‐Halosuccinimides/UHP in Ionic Liquid
a
a
Jong Chan Lee & Hyun Jung Park
a
Department of Chemistry, Chung‐Ang University, Seoul, South Korea
Version of record first published: 25 Jul 2007.
To cite this article: Jong Chan Lee & Hyun Jung Park (2007): Efficient α‐Chlorination and α‐Bromination
of Carbonyl Compounds Using N‐Halosuccinimides/UHP in Ionic Liquid, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:1, 87-90
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Synthetic Communications , 37: 87–90, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600978168
Efficient a-Chlorination and a-Bromination
of Carbonyl Compounds Using
N-Halosuccinimides/UHP in Ionic Liquid
Jong Chan Lee and Hyun Jung Park
Department of Chemistry, Chung-Ang University, Seoul, South Korea
Abstract: A facile and efficient method for the a-halogenation of carbonyl compounds
utilizing N-halosuccinimides (NXS) in the presence of urea–hydrogen peroxide (UHP)
in [bmim]BF has been newly developed.
4
Keywords: bromination, chlorination, ionic liquid, ketones, peroxide
a-Halogenated carbonyl compounds are widely used in organic synthesis as
[
valuable reaction intermediates. Among others, a-chloro and a-bromoaryl
1]
ketones receive attention because of their versatile uses in organic transfor-
[
mations. There is a wealth of reported methods concerning preparation of
2]
a-haloaryl ketones. For instance, a-bromoaryl ketones can be obtained from
[3]
[4]
the reaction of aryl ketones with bromine, copper(II) bromide, and tetra-
[
butylammonium tribromide. The a-chloroaryl ketones can be prepared by
5]
[
6]
[7]
the reaction of aryl ketones with sulfuryl chloride, copper(II) chloride,
[8]
and benzyltrimethylammonium dichloroiodate. However, these methods
generally provide undesirable a,a-dihalogenated side products and require
drastic reaction conditions. Among other halogenating agents, the N-halosuc-
cinimides (NXSs) should be considered the reagent of first choice because
of their ready availability and ease of handling. In recent years, the NXSs
have been successfully utilized in the preparation of a-halocarbonyl
[
9–11]
compounds. However, reported methods for the N-halosuccinimide-
induced alpha halogenation of carbonyl compounds invariably require use
Received in Japan June 1, 2006
Address correspondence to Jong Chan Lee, Department of Chemistry, Chung-Ang
University, Seoul 156-756, South Korea. E-mail: jclee@cau.ac.kr
87

8
8
J. C. Lee and H. J. Park
of strong acid activators. Thus, the development of a more convenient method
that avoids the use of strong acids for the NXS (X ¼ Cl, Br) mediated prep-
aration of a-halocarbonyl compounds is still being pursued.
Herewith, we have attempted to develop a novel and facile method for the
preparation of a-haloaryl ketones using NXS/urea–hydrogen peroxide (UHP)
in an ionic liquid medium. UHP is a stable, neutral, and nontoxic reagent and
[12,13]
can be used as a viable substitute for hydrogen peroxide.
To the best of
our knowledge, there has been no example of the utilization of hydrogen
peroxide to activate NXS for the halogenation reactions. Our new protocol
involves reaction of aryl ketones with NXS in the presence of UHP in
1-butyl-3-methylimidazolium tetrafluoroborate, [bmim]BF , an ionic liquid
medium. Treatment of an aryl ketone with N-halosuccinimide (2.0 equiv)
4
and UHP (1.2 equiv) in 1 mL of [bmim]BF at 608C for 1–20 h readily
4
gave the corresponding a-haloaryl ketone product (Scheme 1). In the
present protocol, both aryl methyl ketones and aryl methylene ketones were
converted equally well into the a-haloaryl ketones in high yields.
Ring-halogenated products are not obtained in all of the cases studied.
The results of the current studies are summarized in Table 1.
In recent years, halogenation to the 2-position of 1,3-dicarbonyl
compounds received much attention because of versatile utilities of 2-halo-
[11,14]
1,3-dicarbonyl compounds in organic synthesis.
The present procedure
was successfully applied to the a-halogenation of 1,3-dicarbonyl
compounds, and a-halogenated products were obtained in high yields
(
entries 9 and 10). Most probably, the present halogenation reactions are
mediated by hypohalous acid (HOX) in situ formed from the reaction of
NXS with UHP.
In summary, a-halogenation of aryl ketones and 1,3-dicarbonyl
compounds are achieved in an efficient manner utilizing a NXS/UHP in
ionic liquid. The protocol is brief but highly efficient and does not require
the use of strong acids in the activation of NXS, which should make this
method a useful alternative to the existing methods.
EXPERIMENTAL
The 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) was
obtained from Fluka. Merck silica gel 60 (230–400 mesh) was used for
flash-column chromatography.
Scheme 1.

Efficient a-Chlorination and a-Bromination
89
Table 1. Preparation of a-halocarbonyl compounds
a
Yield (%)
Entry
Substrate
Product
X ¼ CI X ¼ Br
1
78
76
76
68
90
70
94
98
76
86
77
74
89
78
76
85
2
3
4
5
6
7
8
9
78
95
96
97
1
0
a
Isolated yield.
General Procedure for Halogenation Reaction of Ketones
NXS (2.0 mmol) and UHP (0.113 g, 1.2 mmol) were added to a solution of
aryl ketone (1.0 mmol) in [bmim]BF (1 mL). The mixture was stirred at
4
6
08C for 1–20 h. After completion of the reaction, the product was
extracted with dichloromethane (2 Â 25 mL), washed with aqueous sodium
sulfite (40 mL), and dried over MgSO . The solvent was removed in vacuo,
4
and the crude mixture was purified by silica-gel chromatography using
dichloromethane as eluent to give the pure a-haloaryl ketone.
ACKNOWLEDGMENT
This work was supported by the Seoul R&BD Program.

9
0
J. C. Lee and H. J. Park
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