Mild and Efficient Deoxygenation of Amine-N-oxides with Titanium Tetrachloride-Indium System

Article abstract of DOI:10.1081/SCC-120026845

TiCl₄/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 mild conditions.

Full text of DOI:10.1081/SCC-120026845

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Mild and Efficient Deoxygenation of Amine-N-oxides
with Titanium Tetrachloride-Indium System
a
a
b
b
Professor Byung Woo Yoo , Kwang Hyun Choi , Kyung Il Choi & Joong Hyup Kim
a
Department of Advanced Material Chemistry, Korea University, Jochiwon, Chungnam, South
Korea
b
Biochemicals Research Center, Korea Institute of Science and Technology, Cheongryang,
Seoul, South Korea
Published online: 21 Aug 2006.
To cite this article: Professor Byung Woo Yoo , Kwang Hyun Choi , Kyung Il Choi & Joong Hyup Kim (2003): Mild and Efficient
Deoxygenation of Amine-N-oxides with Titanium Tetrachloride-Indium System, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:24, 4185-4189
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SYNTHETIC COMMUNICATIONS
Vol. 33, No. 24, pp. 4185–4189, 2003
Mild and Efficient Deoxygenation of
Amine-N-oxides with Titanium
Tetrachloride-Indium System
1
,
1
2
Byung Woo Yoo, * Kwang Hyun Choi, Kyung Il Choi,
2
and Joong Hyup Kim
1
Department of Advanced Material Chemistry,
Korea University, Jochiwon, Chungnam, South Korea
2
Biochemicals Research Center,
Korea Institute of Science and Technology,
Cheongryang, Seoul, South Korea
ABSTRACT
4
TiCl /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 mild conditions.
*
Correspondence: Professor Byung Woo Yoo, Department of Advanced
Material Chemistry, Korea University, Jochiwon, Chungnam, 339-700, South
Korea; E-mail: bwyoo@korea.ac.kr.
4
185
DOI: 10.1081/SCC-120026845
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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186
Yoo et al.
Titanium;
Key Words: Deoxygenation;
Chemoselectivity.
N-Oxides;
Indium;
The deoxygenation of amine-N-oxides to amines is an important
transformation in the synthesis of nitrogenous aromatic heterocycles
and an area of considerable interest, particularly when a molecule has
[
other reducible or labile moieties. A number of methods have been
1]
described for the reduction of amine-N-oxides, including agents such
[4]
[
2]
[3]
as: low-valent titanium,
tributyltinhydride,
phosphorous
and sulfur
[7]
compounds,
[8]
[5]
[6]
Pd/C,
NH Cl. However, some of these reagents require relatively long
tetrathiomolybdate,
SmI2,
indium/
[9]
4
reaction times and drastic reaction conditions. Consequently, there is
still a need for introducing mild and efficient reagents for the deoxy-
genation of amine-N-oxides to amines. The chemical reactivity of
TiCl /M system (M ¼ Li, Zn, Mg, Sm) has been the subject of consider-
4
able interest and the reducing ability of these systems has been extensively
[10]
studied. The reduction of TiCl to low-valent titanium species and the
4
[
11]
synthetic utility of such species are well documented in the Lit.
continuation of our efforts towards modified titanium reagents for
In
[12]
organic transformations,
we observed that a combination of TiCl4
with indium could bring about the deoxygenation of amine-N-oxides
under mild conditions. The new reducing system was generated by the
addition of indium powder to a stirred solution of titanium tetrachloride
in THF under nitrogen. We herein wish to report a mild and efficient
method for the deoxygenation of amine-N-oxides using TiCl /In system
4
in THF. 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. The
reactions were fast in all cases with substrates reacting completely
within 5 min at room temperature. The optimum ratio of reagents was
found to be substrate:TiCl :indium ¼ 2:2:1. In order to explore the scope
4
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
TiCl /In
4
N
THF, r. t.
(1)
N
O
1
2

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Deoxygenation of Amine-N-oxides
4187
group tolerance of this deoxygenation system is evident from entries 6–11
which show that bromo, ester, carbonyl, methoxy, and chloro remain
unchanged under the reaction conditions. The generality of the reaction
to various amine-N-oxides is illustrated in Table 1. However, the appli-
cation of this procedure to aliphatic amine-N-oxide proved unsuccessful
and only recovered starting material was isolated. We have been able to
demonstrate the utility of easily accessible TiCl /In system as a convenient
4
reagent for effecting chemoselective deoxygenation of amine-N-oxides.
Table 1. Deoxygenation of amine-N-oxides with TiCl /In.
4
a
Entry
Substrate
Product
Reaction time (min) Yield(%)
1
2
3
4
3-Picoline-N-oxide 3-Picoline
Quinoline-N-oxide Quinoline
Isoquinoline-N-oxide Isoquinoline
5
5
5
5
93
92
86
95
N
N
O
5
6
5
5
85
87
N
N
O
Br
CO
CH
Br
CO2CH3
2
3
N
N
O
7
8
9
CO2CH3
CO2CH3
5
5
5
91
88
95
N
N
O
O
O
N
N
O
OCH
OCH3
3
N
N
O
1
1
0
1
5
5
85
95
N
Cl
N
Cl
O
Br
Br
N
N
O
1
2
N
O
N
5
90
a
Isolated yields.

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188
Yoo et al.
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, titanium(IV) chloride is probably reduced by indium to form
low-valent titanium 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 methodology are the
mild reaction conditions, the short reaction times, the high yields, the
experimental simplicity, and the tolerance of some functional groups.
In conclusion, we believe that the mild, efficient method described
here offers an attractive alternative to the existing methods available for
the reduction of amine-N-oxides to the corresponding amines. Further
investigations of TiCl /In system as reducing agent in organic synthesis
4
are currently in progress.
General Procedure for the Reaction
A typical procedure for the deoxygenation of amine-N-oxide is as
follows: Indium powder (58 mg, 0.5 mmol), titanium tetrachloride
(
226 mg, 1.2 mmol) and THF (10 mL) were mixed under nitrogen
atmosphere and the resulting mixture was stirred at room temperature
for 1 h. A dark-blue solution of the low-valent titanium-indium complex
was obtained and cooled to room temperature. To this solution, 4-tert-
butylpyridine-N-oxide (151 mg, 1.0 mmol) was added. The reaction
mixture turned dark purple almost immediately and was stirred for
5 min at room temperature under nitrogen. The reaction solution was
quenched with dilute HCl and the residue was extracted with ether,
washed with water, dried over anhydrous MgSO . The crude
4
product was purified by silica gel column chromatography to afford
4-tert-butylpyridine (144 mg, 95%).
ACKNOWLEDGMENTS
This work was financially supported by Korea Institute of Science
and Technology (2E16800) and partially by Korea University.
REFERENCES
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Deoxygenation of Amine-N-oxides
4189
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