Mild and efficient deoxygenation of amine-N-oxides with BiCl3/Indium system

Article abstract of DOI:10.1080/00397910902788190

The BiCl3/indium system was found to be a new reagent for deoxygenation of various amine-N-oxides to the corresponding amines in good to excellent yields under mild conditions.

Full text of DOI:10.1080/00397910902788190

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Mild and Efficient
Deoxygenation of Amine-
N-oxides with BiCl3/Indium
System
Byung Woo Yoo a & Jin Woo Choi a
a Department of Advanced Materials Chemistry ,
Korea University , Jochiwon, Chungnam, South
Korea
Published online: 04 Sep 2009.
To cite this article: Byung Woo Yoo & Jin Woo Choi (2009) Mild and Efficient
Deoxygenation of Amine-N-oxides with BiCl3/Indium System, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:19, 3550-3554, DOI: 10.1080/00397910902788190
To link to this article: http://dx.doi.org/10.1080/00397910902788190
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Synthetic Communications1, 39: 3550–3554, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902788190
Mild and Efficient Deoxygenation of
Amine-N-oxides with BiCl3/Indium System
Byung Woo Yoo and Jin Woo Choi
Department of Advanced Materials Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
Abstract: The BiCl3=indium system was found to be a new reagent for
deoxygenation of various amine-N-oxides to the corresponding amines in good
to excellent yields under mild conditions.
Keywords: Bismuth, chemoselectivity, deoxygenation, N-oxides
The deoxygenation of the N-O bond in amine N-oxides in the presence of
other functional groups is an important synthetic transformation that has
received considerable attention.[1] A number of methods have been
developed for the reduction of amine-N-oxides, including agents such
as low-valent titanium,[2] Zn=HCOONH4,[3] InCl3,[4] tributyltinhydride,[5]
Pd=C,[6] SmI2,[7] tetrathiomolybdate,[8] indium=NH4Cl,[9] and Mo(CO)6.[10]
However, many of these reagents often require relatively long reaction
times and harsh reaction conditions and afford products in moderate or
poor yields. Consequently, there is still a need to introduce mild and
efficient reagents for the deoxygenation of amine-N-oxides to amines.
The chemical reactivity of BiCl3=M system (M ¼ Sm, Zn, Al, Mg) has been
the subject of considerable interest, and the reducing ability of these
systems has been extensively studied.[11] In continuation of our efforts
toward metal–metal salt binary systems for organic transformations,[12]
we have found that a combination of BiCl3 with indium brings about
Received November 18, 2008.
Address correspondence to Byung Woo Yoo, Department of Advanced
Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700, South
Korea. E-mail: bwyoo@korea.ac.kr
3550

Deoxygenation of Amine-N-oxides
3551
the deoxygenation of amine-N-oxides under mild conditions. The new
reducing system was generated by the addition of indium to a stirred
solution of bismuth(III) chloride in methanol under sonication. Herein
we report a mild and efficient method for the deoxygenation of
amine-N-oxides using BiCl3=indium system in methanol. Some control
experiments revealed that amine-N-oxides could not be deoxygenated
by BiCl3 or indium alone under the present reaction conditions, and
starting materials were recovered unchanged. The reactions were fast
in all cases with substrates reacting completely within 3 h at room
temperature. The optimum ratio of reagents was found to be
substrate=BiCl3=indium ¼ 1:2:4. To explore the scope and limitation of
this reagent system, we have tested its applicability for selective deoxy-
genation of amine-N-oxides bearing other potentially sensitive functional
groups in the heteroaromatic ring. The functional group tolerance of this
deoxygenation system is evident from entries 6–11, which show that
bromo, ester, ketone, methoxy, and chloro functionalities remain
unchanged under the reaction conditions. The generality of the reaction
to various amine-N-oxides is illustrated in Table 1. We have been able to
demonstrate the utility of an easily accessible BiCl3=indium system as a
convenient reagent for effecting chemoselective deoxygenation of
amine-N-oxides. All the compounds obtained showed infrared (IR),
NMR, and mass spectral (MS) data compatible with the structure.
Although the reaction mechanism is still unclear, it can be rationalized
as the result of a two-stage process. In the first step, bismuth(III) chlor-
ide is probably reduced by indium to form low-valent bismuth species,
which, in the subsequent step, would reductively deoxygenate amine-
N-oxides 1 to give the corresponding amines 2. The reducing property
exhibited by metal–metal salt combinations proceeds through transfer
of one electron from the metal surface to the substrate. We believe that
the present reduction reaction using the BiCl3=indium system proceeds
through a SET (single-electron-transfer) process. The notable advan-
tages of the present methodology are the mild reaction conditions, good
yields, experimental simplicity, and tolerance of some functional
groups.
In conclusion, we believe that the mild and efficient method
described here offers an attractive alternative to the existing methods

3552
B. W. Yoo and J. W. Choi
Table 1. Deoxygenation of amine-N-oxides with BiCl3=indium system
Entry
Substrate
Product
Reaction time (h) Yield (%)a
1
2
3
3-Picoline-N-oxide
Quinoline-N-oxide
Isoquinoline-N-oxide
3-Picoline
Quinoline
Isoquinoline
2.0
1.5
2.0
90b
88b
89b
4
2.0
2.0
95b
87b
5
6
7
3.0
1.5
2.0
3.0
85b
91b
8
90b
9
93b
85b
10
1.5
2.5
11
12
90b
92b
2.0
aIsolated yields.
bThe products are commercially available and were characterized by
comparison of their spectral data with authentic samples.
available for the reduction of amine-N-oxides to the corresponding
amines. Further investigations of the BiCl3=indium system as reducing
agent in organic synthesis are currently in progress.

Deoxygenation of Amine-N-oxides
3553
GENERAL PROCEDURE FOR THE REACTION
A typical procedure for the deoxygenation of amine-N-oxide is as
follows: indium powder (459 mg, 4.0 mmol), bismuth trichloride
(631 mg, 2.0 mmol), and methanol (5 mL) were mixed under a nitrogen
atmosphere, and the resulting mixture was stirred at room temperature
for 1 h under sonication. A dark-blue solution of the low-valent
bismuth–indium complex was obtained. 4-tert-Butylpyridine-N-oxide
(151 mg, 1.0 mmol) was added to this solution. The reaction mixture
was stirred for 2 h at room temperature under nitrogen. The reaction
solution was quenched with 10% NaOH, and the residue was extracted
with ether, washed with water, and dried over anhydrous MgSO4. The
crude product was purified by silica-gel column chromatography to
afford 4-tert-butylpyridine (128 mg, 95%).
ACKNOWLEDGMENT
This work was financially supported by Korea University.
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