Facile deoxygenation of amine-N-oxides with CoCl2·6H 2O-indium system

Article abstract of DOI:10.1080/00397910500382941

CoCl₂·6H₂O/In 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 sonication. Copyright Taylor & Francis Group, LLC.

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Facile Deoxygenation of Amine‐N‐oxides With
CoCl2 · 6H2O–Indium System
Jung Hwa Han a , Kyung Il Choi b , Joong Hyup Kim b , Cheol Min Yoon a &
Byung Woo Yoo a
a Department of Advanced Materials Chemistry , Korea University ,
Jochiwon, Chungnam, South Korea
b Biochemicals Research Center , Korea Institute of Science and
Technology , Cheongryang, Seoul, South Korea
Published online: 19 Aug 2006.
To cite this article: Jung Hwa Han , Kyung Il Choi , Joong Hyup Kim , Cheol Min Yoon & Byung Woo Yoo (2006)
Facile Deoxygenation of Amine‐N‐oxides With CoCl2 · 6H2O–Indium System, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:4, 415-419, DOI:
10.1080/00397910500382941
To link to this article: http://dx.doi.org/10.1080/00397910500382941
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Synthetic Communicationsw, 36: 415–419, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500382941
Facile Deoxygenation of Amine-N-oxides
.
With CoCl2 6H2O–Indium System
Jung Hwa Han
Department of Advanced Materials Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
Kyung Il Choi and Joong Hyup Kim
Biochemicals Research Center, Korea Institute of Science and
Technology, Cheongryang, Seoul, South Korea
Cheol Min Yoon and Byung Woo Yoo
Department of Advanced Materials Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
.
Abstract: CoCl2 6H2O/In 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 sonication.
Keywords: Amine-N-oxides, cobalt, deoxygenation, indium
The deoxygenation of amine-N-oxides to amines is an important transform-
ation in the synthesis of nitrogenous aromatic heterocycles.[1] A number of
methods have been described 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] and indium/
NH4Cl.[9] However, these deoxygenations often require prolonged reaction
times and severe reaction conditions. Some of these are associated with limit-
ations regarding selectivity and compatibility with other functional groups, are
Received in Japan May 12, 2005
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
415

416
J. H. Han et al.
hazardous, and are sensitive to both air and moisture. Consequently, there
is still a need for introducing selective, mild, and cheap reagents for the
deoxygenation of amine-N-oxides to amines. The reduction of CoCl2 to
low-valent cobalt species and the synthetic utility of such species are well
documented in the literature.[10] In continuation of our efforts to find low-
valent metal reagents for organic transformations,[11] we observed that a com-
bination of CoCl2 with indium could bring about the deoxygenation of amine-
N-oxides
under mild conditions. To the best of our knowledge, to date there are no
.
reports of the use of the CoCl2 6H2O/In system for the deoxygenation of
amine-N-oxides in the literature. The new reducing system was generated
by the addition of indium powder to a stirred solution of cobalt(II) chloride
hexahydrate in MeOH under sonication. We herein report a mild and
efficient method for the deoxygenation of amine-N-oxides using a
.
CoCl2 6H2O/In system in MeOH. A variety of amine N-oxides were
.
treated with the CoCl2 6H2O/In system, and the corresponding amines
were obtained in high yields. The results are summarized n Table 1. The
reactions proceed readily in all cases with substrates reacting completely
within 2 h at room temperature. The optimum ratio of reagents was found to
be 1:2:4 (substrate–CoCl2–indium). Some control experiments revealed
that amine-N-oxides could not be deoxygenated by indium alone under
the present reaction conditions, and starting materials were recovered
unchanged. To explore the scope and limitation of this reagent system we
have tested its applicability for selective deoxygenation 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 the table, which shows that cyano, bromo, ester, and methoxy substitu-
ents remain unchanged under the reaction conditions. However, the appli-
cation of this procedure to aliphatic amine-N-oxide proved unsuccessful,
and only the recovered starting material was isolated. We have been able to
.
demonstrate the utility of an easily accessible CoCl2 6H2O/In system as a
convenient reagent for effecting chemoselective deoxygenation of amine-N-
oxides. All the compounds obtained showed IR, NMR, and mass spectral
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, cobalt(II) chloride is probably reduced by indium to form low-
valent cobalt species, which, in the subsequent step, would reductively
deoxygenate amine-N-oxides 1 to give the corresponding amines 2. The
notable advantages of the present procedure are the mild reaction conditions,

Deoxygenation of Amine-N-oxides
417
.
Table 1. Deoxygenation of amine-N-oxides with CoCl2 6H2O/In system
Reaction
time (h)
Yield
(%)a
Entry
Substrate
Product
Quinnoline
Isoquinnoline
1
2
3
Quinnoline-N-oxide
Isoquinnoline-N-oxide
4-t-Butylpyridine-N-oxide
2.0
2.0
2.0
92
90
85
4-t-Butylpyridine
4
5
2.0
1.5
90
95
6
2.0
90
7
8
9
2.0
1.5
0.5
85
91
88
10
11
2.0
1.0
80
82
aIsolated yields.
the short reaction times, the excellent yields, and the tolerance of some labile
functional groups.
.
In conclusion, we believe that the use of the CoCl2 6H2O/In system
offers an attractive alternative to the existing methods available for the

418
J. H. Han et al.
reduction of amine-N-oxides to the corresponding amines. Further investi-
.
gations of the CoCl2 6H2O/In system as a reducing agent in organic
synthesis are currently in progress.
EXPERIMENTAL
1
The H NMR spectra were recorded on an FT-Bruker AF-300 (300 MHz for
1H NMR) using TMS as an internal standard. Infrared spectra were
obtained on a Perkin Elmer 16F PC FT-IR Shimadzu. TLC analysis was
performed on silica-gel plates (Merck, 60 F-254). All products were purified
by flash column chromatography using silica gel 60 (79–230 mesh, Merck).
General Procedure for the Reaction
A typical procedure for the deoxygenation of amine-N-oxide is as follows:
Indium powder (230 mg, 2.0 mmol), cobalt(II) chloride hexahydrate
(238 mg, 1.0 mmol), and MeOH (1 mL) were mixed under sonication. The
resulting mixture was stirred at room temperature for 1 h, and a solution of
the low-valent cobalt–indium complex was obtained. 4-tert-Butylpyridine-
N-oxide (76 mg, 0.5 mmol) was added dropwise to this solution. The
reaction mixture was stirred for 2 h at room temperature under sonication.
The solvent was evaporated under reduced pressure, and the residue was
extracted with ether, washed with brine, and dried over anhydrous MgSO4.
The crude product was purified by silica-gel column chromatography
(hexane–ethyl acetate ¼ 1:1) to afford 4-tert-butylpyridine (65 mg, 85%).
ACKNOWLEDGMENTS
This work was financially supported by the Korea Institute of Science and
Technology (2E16800) and partially by Korea University.
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