Facile and Efficient Deoxygenation of Amine-N-oxides with Gallium in Water

Article abstract of DOI:10.1081/SCC-200028619

A facile and efficient procedure for the deoxygenation of amine-N-oxides with gallium metal in water is described. The experimental procedure is quite simple and the products are obtained in high yields without any activating agent.

Full text of DOI:10.1081/SCC-200028619

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Facile and Efficient
Deoxygenation of
Amine‐N‐oxides with Gallium
in Water
Jung Hwa Han a , Kyung Il Choi b , Joong Hyup Kim
b & Byung Woo Yoo a
a Department of Advanced Materials Chemistry,
Korea University, Jochiwon, Chungnam, 339‐700,
Korea
b Biochemicals Research Center, Korea Institute
of Science and Technology, Cheongryang, Seoul,
130‐650, Korea
Version of record first published: 12 Jan 2011
To cite this article: Jung Hwa Han, Kyung Il Choi, Joong Hyup Kim & Byung Woo Yoo
(2004): Facile and Efficient Deoxygenation of Amine‐N‐oxides with Gallium in Water,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:17, 3197-3201
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 17, pp. 3197–3201, 2004
Facile and Efficient Deoxygenation of
Amine-N-oxides with Gallium in Water
Jung Hwa Han,1 Kyung Il Choi,2 Joong Hyup Kim,2
and Byung Woo Yoo1,
*
1Department of Advanced Materials Chemistry, Korea University,
Jochiwon, Chungnam, Korea
2Biochemicals Research Center, Korea Institute of Science and
Technology, Cheongryang, Seoul, Korea
ABSTRACT
A facile and efficient procedure for the deoxygenation of amine-N-oxides
with gallium metal in water is described. The experimental procedure is
quite simple and the products are obtained in high yields without any acti-
vating agent.
Key Words: Deoxygenation; Amine-N-oxides; Amine; Gallium.
The deoxygenation of amine-N-oxides to amines in the presence of other
functional groups is an important transformation in the synthesis of nitrogenous
*
Correspondence: Byung Woo Yoo, Department of Advanced Materials Chemistry,
Korea University, Jochiwon, Chungnam, 339-700, Korea; E-mail: bwyoo@korea.ac.kr.
3197
DOI: 10.1081/SCC-200028619
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3198
Han et al.
aromatic heterocycles.[1] A number of reagents have been reported to be effec-
tive in mediating the deoxygenation of amine-N-oxides. Examples include
low-valent titanium,[2] phosphorous[3] and sulfur[4] compounds, tributyltinhy-
dride,[5] Pd/C,[6] tetrathiomolybdate,[7] SmI2,[8] etc. However, many of these
reagents require relatively long reaction times, drastic reaction conditions, and
are sensitive to both air and moisture. Consequently, there is still a need for
introducing mild and efficient reagents for the deoxygenation of amine-N-
oxides to amines. Recently, it was reported that indium metal could be used
for the deoxygenation of various amine-N-oxides.[9] Because of the close
resemblance of gallium to indium in several respects, including first ionization
potential and reduction potential (Ga: FIP, 5.99 eV, E8, Ga3þ/Ga ¼ 20.56 V;
In: FIP, 5.79 eV, E8, In3þ/In ¼ 20.345 V), we envisaged that gallium metal
could also be a potential reducing agent. In this communication we report a
novel method for the deoxygenation of amine-N-oxides using gallium metal
in water at reflux, which occurs to afford the corresponding amines. Although
gallium has been used in carbonyl addition
reactions,[10,12] its use in other domains has not been investigated. This
prompted us to initiate an investigation into the reduction of amine-N-
oxides by gallium metal and we have found that various amine-N-oxides 1
on treatment with gallium metal in water are smoothly converted into the
corresponding amines 2 in high yields without activating agents such as
ammonium chloride or hydrochloric acid (Eq. (1)). The results of reduction
of amine-N-oxides using gallium metal are summarized in Table 1. Recently,
growing interest has been focused on synthetic organic reactions in aqueous
media from both economical and ecological points of view. The use of
water as a solvent to carry out organic reactions offers practical convenience
as it alleviates the need to handle flammable and anhydrous organic solvents.
Particularly metal-mediated organic reactions in aqueous media (such as In,
Zn, Bi, Sn, Sm, etc.) have received considerable attention in organic synthesis
over the last decade.[11] However, the reactions promoted by gallium in
aqueous media have not been widely studied.[12] To determine the optimum
conditions, the reaction was performed under several reaction conditions.
The best result was obtained when the reaction was carried out using
gallium (3 equiv) in water at reflux in terms of yields and reaction times.
The reaction was not significantly improved by increasing the quantity of
metallic gallium and the reaction time. It was also found that at room tempera-

Deoxygenation of Amine-N-oxides with Gallium in Water
3199
Table 1. Deoxygenation of amine-N-oxides with gallium metal.
Reaction
time (hr)
Yield
(%)a
Entry
1
Substrate
Product
0.5
90
2
4
83
3
4
4
3
88
85
5
6
0.5
7
96
84
7
8
8
7
81
95
9
3
92
0
10
24
11
12
24
24
0
0
aIsolated yields.

3200
Han et al.
ture no significant formation of the desired product was observed even after
prolonged stirring. In order to explore the scope and limitations of this
reagent we have tested its applicability for selective deoxygenation of
amine-N-oxides bearing other potentially sensitive functional groups in the
aromatic ring. Unfortunately the application of this approach to aliphatic-N-
oxide proved unsuccessful and only recovered starting material was isolated
(entries 10, 11, and 12). The high yields of the reduction products demonstrate
the efficiency of this new method. The functional group tolerance of this deox-
ygenation system is evident from the table, which shows that halogen,
hydroxy, ester, cyano, methoxy, and amino remain unchanged under the
present reaction conditions. All the compounds obtained showed IR, NMR,
and mass spectral data compatible with the structure. Thus, we have been
able to demonstrate the utility of easily accessible gallium metal as a reducing
agent for effecting chemoselective deoxygenation of amine-N-oxides. The
notable advantages of the present methodology are high isolated yields of pro-
ducts, operational simplicity, tolerance of other labile functional groups, and
environmentally friendly reaction conditions. Although the mechanism of the
reaction is not yet clear, it may be assumed that these reductions are also going
through a single electron transfer (SET) process like other metal-mediated
reactions in aqueous media.
In conclusion, we have demonstrated that gallium is an effective metal for
the reduction of aromatic amine-N-oxides in water. Further studies to develop
other new reactions using gallium metal in aqueous media are currently in
progress.
GENERAL PROCEDURE FOR THE REACTION
A typical procedure for the deoxygenation of amine-N-oxide is as
follows: Gallium metal (104 mg, 1.5 mmol) in water (1 mL) was stirred for
1 hr under sonication and then to this solution 4-cyanopyridine-N-oxide
(60 mg, 0.5 mmol) in water (2 mL) was added slowly. The resulting mixture
was heated under reflux for 30 min. After completion of the reaction, as indi-
cated by TLC, the resultant mixture was filtered through Celite and extracted
with ether (4ꢀ10 mL). The organic layer was washed with saturated brine and
dried over anhydrous MgSO4. After evaporation of the solvent in vacuo, the
crude product was purified by silica gel column chromatography (ethyl
acetate : hexane ¼ 1 : 1) to afford 4-cyanopyridine (47 mg, 90%).
Spectroscopic data of 2-amino-3-cyano-5-chloromethylpyrazine (entry
9): pale yellow solid, mp 1528C–1548C. 1H NMR (DMSO-d6): d 4.54 (s, 2H,
CH2CI), 7.36 (br s, 2H, NH2), 8.21 (s, 1H, Harom). IR (KBr) 3410–3210 (NH2),
2230 (CN) cm21
.

Deoxygenation of Amine-N-oxides with Gallium in Water
3201
ACKNOWLEDGMENTS
This work was financially supported by Korea Institute of Science and
Technology (2E16800) and partially by Korea University.
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Received in Japan March 31, 2004