Debromination of α-bromoketones and vic-dibromides using indium in the presence of carboxylic acid

Article abstract of DOI:10.1081/SCC-200057259

The debromination of α-bromoketones and vic-dibromides using indium metal in the presence of acetic acid at room temperature effectively afforded the corresponding ketones in excellent yield. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200057259

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Debromination of
α‐Bromoketones and
vic‐Dibromides Using Indium
in the Presence of Carboxylic
Acid
b
a
b
Seung Hwan Lee , Min Young Cho , Mi Hye Nam ,
a
b
b
Young Sang Park , Byung Woo Yoo , Chi‐Woo Lee
b
&
a
Cheol Min Yoon
Graduate School of Biotechnology , Korea
University , Sungbuk‐gu Anamdong 5 ga, Seoul,
South Korea
b
Department of Advanced Material Chemistry ,
Korea University , Jochiwon, Chungnam, South
Korea
Published online: 16 Aug 2006.
To cite this article: Seung Hwan Lee , Min Young Cho , Mi Hye Nam , Young Sang
Park , Byung Woo Yoo , Chi‐Woo Lee & Cheol Min Yoon (2005) Debromination of
α‐Bromoketones and vic‐Dibromides Using Indium in the Presence of Carboxylic Acid,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:10, 1335-1341, DOI: 10.1081/SCC-200057259
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Synthetic Communications , 35: 1335–1341, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200057259
Debromination of a-Bromoketones and
vic-Dibromides Using Indium in the
Presence of Carboxylic Acid
Seung Hwan Lee
Graduate School of Biotechnology, Korea University, Seoul, South Korea
Min Young Cho and Mi Hye Nam
Department of Advanced Material Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
Young Sang Park
Graduate School of Biotechnology, Korea University, Seoul, South Korea
Byung Woo Yoo, Chi-Woo Lee, and Cheol Min Yoon
Department of Advanced Material Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
Abstract: The debromination of a-bromoketones and vic-dibromides using indium
metal in the presence of acetic acid at room temperature effectively afforded the corres-
ponding ketones in excellent yield.
Keywords: a-Bromoketones, debromination, indium, vic-dibromides
The chemical methods of dehalogenation have been important for degrada-
[
tion of halogenated compounds. Many reagents for the dehalogenation of
1]
a-bromoketones and vic-dibromides have been developed and could be
Received in Japan December 9, 2004
Address correspondence to Cheol Min Yoon, Department of Advanced Material
Chemistry, Korea University, Jochiwon, Chungnam 339-700, South Korea.
Tel.: þ82-2-3290-3433; Fax: þ82-2-3290-3433; E-mail: cmyoon@korea.ac.kr
1
335

1336
S. H. Lee et al.
divided in three categories: (1) reducing agents, (2) nucleophilic reducing
agents, and (3) Pd-catalyzed hydrogenation. Indium has been recently intro-
[
2]
duced as one of the reducing agents because of several useful properties.
[3]
However, special conditions such as sonication and heating in aqueous
[
4]
[5]
sodium dodecyl sulfate (SDS)
or aqueous NH Cl–ethanol
4
were
employed for the initiation of the reduction reaction. As a continuous
research of acetic acid as a mild activating additive in the indium-mediated
[6]
reaction, the debrominations using indium in the presence of acetic acid
were examined and found to give the corresponding dehalogenated products
in good yields. The use of acetic acid as an activating additive in the
reduction of a-bromoketones and vic-dibromides using indium in methanol
increased the reaction rate and efficiency at room temperature (Scheme 1).
0
2
,4 -Dibromoacetophenone was chosen for a model study of debromina-
tion to find optimum conditions using various amount of indium in the absence
or presence of various amount of acetic acid in several solvent systems at room
0
temperature. Although the reaction of 2,4 -dibromoacetophenone using an
optimum amount of indium (1.2 equiv.) and acetic acid (5 equiv.) in
0
methanol at room temperature gave 4 -bromoacetophenone within 1 h in
quantitative yield, the reaction in the absence of acetic acid proceeded
slowly, affording the corresponding product after 24 h in 54.8% yield
(Table 1, entry 5). Among solvent systems such as aqueous methanol, THF,
and acetonitrile, methanol was identified to be the choice of solvent. (The
reduction attempted in various solvents (1.5 mL) such as aqueous methanol,
THF and acetonitrile at rt gave the corresponding product in 98.0%, 92.4%,
and 72.6% yields respectively.)
The debrominations of a variety of 2-bromoketones under the conditions
were conducted and the results are summarized in Table 1. The reduction of
primary and secondary 2-bromoketone under the conditions (entries 1 and 2)
Scheme 1.

Debromination Using Indium
1337
a
Table 1. Debromination of a-bromoketones
b
Yield (%)
Entry
1
Substrate
Time (h)
1
87.4
2
3
1
1
83.8
92.4
4
5
6
1
1
98.2
c
98.5 (54.8 )
20 min
93.8
7
8
1
1
84.2
97.6
9
1
1
100.0
87.1
1
0
a
The reactions were conducted with substrate (0.2 mmol), and indium
1.2 equiv.) in the presence of acetic acid (5 equiv.) in methanol (1.5 mL)
at room temperature.
(
b
Isolated yields.
In the absence of acetic acid for 24 h.
c

1338
S. H. Lee et al.
proceeded to give the corresponding brominated products in high yields.
-Bromoacetophenones with electron-donating group (entries 3, 4) and
2
electron-withdrawing groups at phenyl ring (entries 5, 6) were debrominated
to afford the corresponding ketones in high yields. Bromo on phenyl ring
under the reaction condition was remained intact (entry 5) even if the homo-
[7]
coupling of aryl bromide using indium was reported. The bromo group at
alpha position of ester, amide, and cyanide was removed under the reaction
conditions efficiently (entries 7–10).
The bromination of alkenes and subsequent debromination of the
resulting vic-dibromides offer a means for protection of the carbon–carbon
double bond in synthesis and a lot of reagents have been reported for this
[8]
purpose. Our protocol was applied to the debromination reaction of vic-
dibromides. Treatment of 3,4-dibromo-4-phenylbutan-2-one with indium
(1.2 equiv.) and acetic acid (5 equiv.) in methanol (1.5 mL) at room tempera-
ture gave an alkene in 97.1% yield (Table 2, entry 1). Although the dibromides
a
Table 2. Debromination of vic-dibromides
b
c,d
Yield (%)
Entry
1
Substrate
Time (h)
20 min
97.1
87.4
2
3
1
20 min
98.0
4
5
1
75.9
24
No reaction
a
The reactions were conducted with substrate (0.2 mmol), indium
SO (2 equiv.) in the presence of acetic acid
5 equiv.) at room temperature.
(
(
1.2 equiv.), and Na
2
3
b
All dibromides were prepared by bromination of (E)-alkenes with
bromine in CCl
c
4
at rt.
The E or Z form was determined by H NMR spectroscopy.
1
d
Isolated yields.

Debromination Using Indium
1339
with one ester and one ketone functional groups were also debrominated to
provide the corresponding alkenes in good or high yields (entries 2–4),
diethyl 2,3-dibromosuccinate did not proceed at all under the same reaction
condition (entry 5). The result indicates that the debromination of relatively
electron-rich dibromides (entries 1–4) seemed to be more effective than
that of electron-deficient dibromide involving two esters (entry 5) because
of the stabilization of the transition state. Further reduction of the alkenes
[
9]
[10]
[2b]
formed by dehalogenation using Sm, Mg,
under our system.
The nitro group was reported to be reduced to give the amino group by
or In
was not observed
[
6]
0
indium-mediated reaction. When the reaction of 2-bromo-3 -nitroacetophe-
none under our reaction conditions was attempted, the mixture including
unreacted substrate was obtained because of the reduction of nitro group.
After sulfur-containing salt was found by chance to inhibit the reduction of
the nitro group using indium even in the acidic condition, a lot of trials of
debromination using indium in the presence of the sulfur reagents such as
.
[
Na SO , NaHS xH O, NaHSO , and Na S O were conducted and sodium
2 2 3
2
3
2
3
11]
sulfite (Na SO ) was identified to be effective for chemoselective debromi-
2
3
nation in formic acid at room temperature (Scheme 2). (The debromination by
sodium sulfite in the absence of indium in formic acid did not proceed at all.)
0
The debromination of 2-bromo-3 -nitroacetophenone (0.2 mmol) with indium
(
1.2 equiv.) and Na SO (3 equiv.) in formic acid (1.5 mL) at room tempera-
2 3
0
ture afforded 3 -nitroacetophenone in good yield (79.9%). 3,4-Dibromo-4-
2-nitrophenyl)-2-butanone under the same conditions was debrominated to
(
afford the debrominated product in 54.4% and the unreacted substrate was
recovered in 31.1% yield. To the best of our knowledge, this is the first
example on selective debromination of the bromides using indium in the
presence of a nitro functional group. Further studies for the role of the
sulfur reagent in the selective debromination and generality of the reactions
are underway.
In conclusion, aromatic 2-bromoketones are effectively debrominated to
the corresponding ketone by using indium metal in the presence of acetic acid
Scheme 2.

1340
S. H. Lee et al.
at room temperature in excellent yield. The vic-dibromides as a protected form
of alkene were also debrominated by a protocol of indium in the presence of
acetic acid at room temperature in high yields. In particular, the chemo-
selective reduction of the bromides containing a nitro group became
available in formic acid in the presence of sodium sulfite. The exact role of
sulfur-containing salt and the optimum conditions are under investigation.
EXPERMENTAL
To the solution of 0.2 mmol of a-bromoketones or vic-dibromides in 1.5 mL of
methanol was added 1.2 equiv. of indium and 5 equiv. of acetic acid, and the
mixture was stirred at room temperature until the reaction was completed
(
(
monitored by TLC). The reaction was then concentrated and ethyl acetate
10 mL) was added. The solution was washed with saturated sodium bicarbon-
ate (10 mL), water (10 mL ꢀ 2), and brine (10 mL) and dried over anhydrous
magnesium sulfate. Evaporation of the solvent under vacuum gave the
reduced product, which was further purified by silica-gel column chromato-
graphy with a solution of ethyl acetate and hexane (1:10) and characterized
1
by H NMR spectroscopy.
ACKNOWLEDGMENTS
The authors acknowledge the financial support of the Korea Science and
Engineering Foundation (KOSEF-R05-2003-000-11361-0) made in the
program year 2004.
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