Mild and efficient deoxygenation of amine-N-oxides with MoCl5/NaI system

Article abstract of DOI:10.1080/00397910801929739

The MoCl5/NaI 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. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801929739

This article was downloaded by: [Pennsylvania State University]
On: 25 August 2012, At: 00:52
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Mild and Efficient Deoxygenation of
Amine‐N‐oxides with MoCl /NaI System
5
a
a
Byung Woo Yoo & Min Chol Park
a
Department of Advanced Materials Chemistry, Korea University, Jochiwon,
Chungnam, South Korea
Version of record first published: 24 Apr 2008
To cite this article: Byung Woo Yoo & Min Chol Park (2008): Mild and Efficient Deoxygenation of
Amine‐N‐oxides with MoCl /NaI System, Synthetic Communications: An International Journal for Rapid
5
Communication of Synthetic Organic Chemistry, 38:10, 1646-1650
To link to this article: http://dx.doi.org/10.1080/00397910801929739
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

w
Synthetic Communications , 38: 1646–1650, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801929739
Mild and Efficient Deoxygenation of Amine-
N-oxides with MoCl /NaI System
5
Byung Woo Yoo and Min Chol Park
Department of Advanced Materials Chemistry, Korea University,
Jochiwon, Chungnam, South Korea
Abstract: The MoCl /NaI system was found to be a new reagent for deoxygenation of
5
various amine-N-oxides to the corresponding amines in good to excellent yields under
mild conditions.
Keywords: Chemoselectivity, deoxygenation, molybdenum, N-oxides
The deoxygenation of amine-N-oxides to amines is an important transformation
in the synthesis of nitrogenous aromatic heterocycles and an area of consider-
able interest, particularly when a molecule has other reducible or labile
[
1]
moieties. A number of methods have been described for the reduction
[2]
of amine-N-oxides, including agents such as low-valent titanium,
[
Zn/HCOONH , InCl3, tributyltinhydride, Pd/C, SmI2, tetrathio-
3]
[4]
[5]
[6]
[7]
4
[
8]
[9]
[10]
molybdate, indium/NH Cl, and Mo(CO)6.
However, some of these
4
reagents require relatively long reaction times and drastic reaction conditions.
Consequently, there is still a need for introducing mild and efficient reagents
for the deoxygenation of amine-N-oxides to amines. In continuation of our
efforts toward the development of the low-valent metal reagents for organic
Received in Japan June 21, 2007
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
1
646

Amine-N-oxide-Deoxygenation with MoCl /NaI
5
1647
[
11]
transformations,
iodide could bring about the deoxygenation of amine-N-oxides under mild
we observed that a combination of MoCl with sodium
5
conditions. The new reducing system was generated
by the addition of sodium iodide to a stirred solution of molybdenum pen-
tachloride in acetonitrile under nitrogen. We herein report a mild and
efficient method for the deoxygenation of amine-N-oxides using a MoCl5/
NaI system in acetonitrile. Some control experiments revealed that amine-
N-oxides could not be deoxygenated by MoCl alone under the present
5
reaction conditions, and starting materials were recovered unchanged. The
reactions proceeded smoothly in all cases with substrates reacting completely
within 1–3 h at room temperature.
The optimum ratio of reagents was found to be 1:2:4 (MoCl5–
substrate–NaI). 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 heteroaro-
matic ring. The functional group tolerance of this deoxygenation system is
evident from entries 5–15, which show that cyano, bromo, ester, carbonyl,
methoxy, amide, chloro, and carboxyl substituents remain unchanged
under the reaction conditions. The generality of the reaction to various
amine-N-oxides is illustrated in Table 1. However, the application 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 the easily accessible MoCl /NaI system as a convenient reagent
5
for effecting chemoselective deoxygenation of amine-N-oxides. All the
compounds obtained showed infrared spectroscopy (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, molybdenum(V) chloride is probably
reduced by sodium iodide to form low-valent molybdenum 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, high yields, experimental sim-
plicity, 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 investi-
gations of the MoCl /NaI system as reducing agent in organic synthesis are
5
currently in progress.

1
648
B. W. Yoo and M. C. Park
Table 1. Deoxygenation of amine-N-oxides with MoCl
5
/NaI system
Reaction
time (h)
a
Entry
Substrate
Product
3-Picoline
Quinoline
Yield (%)
b
1
2
3
4
3-Picoline-N-oxide
Quinoline-N-oxide
2.0
3.0
1.5
1.0
93
92
b
b
Isoquinoline-N-oxide
4-t-Butylpyridine-N-oxide
Isoquinoline
4-t-Butylpyridine
86
95
b
b
85
5
2.0
[
12a]
6
3.0
87
b
7
8
9
1.5
2.0
1.0
91
[
12a]
88
b
b
95
1
1
0
1
2.5
3.0
85
[
12a]
95
b
1
1
2
3
2.0
2.0
90
b
91
[
12b]
1
1
4
5
3.0
2.0
86
b
83
a
b
Isolated yields.
The products are commerically available and were characterized by comparison of
their spectral data with authentic samples.

Amine-N-oxide-Deoxygenation with MoCl /NaI
5
1649
GENERAL PROCEDURE FOR THE REACTION
A typical procedure for the deoxygenation of amine-N-oxide is as follows:
Sodium iodide (300 mg, 2.0 mmol), molybdenum pentachloride (136 mg,
0
.5 mmol), and CH CN (10 mL) were mixed under a nitrogen atmosphere,
3
and the resulting mixture was stirred at room temperature for 30 min. To
this solution, 4-tert-butylpyridine-N-oxide (151 mg, 1.0 mmol) was added.
The reaction mixture was stirred for 1 h at room temperature under
nitrogen. The reaction solution was quenched with water, and the residue
was extracted with ether, washed with brine, and dried over anhydrous
MgSO . The crude product was purified by silica-gel column chromatography
4
(hexane–ethyl acetate ¼ 1:1) to afford 4-tert-butylpyridine (129 mg, 95%).
ACKNOWLEDGMENTS
This work was supported by the Brain Korea 21 Project in 2007.
REFERENCES
1. Ochiai, E. In Aromatic Amine Oxides; Elsevier: Amsterdam, 1967; pp. 184–209.
2. (a) Malinoswaki, M. Titanium(0) reagents, 1: A facile deoxygenation of unfunc-
4
tionalized aromatic N-oxides. Synthesis 1987, 732; (b) Balicki, R. TiCl /NaI—
A novel, efficient reagent for mild reduction of the N-O bond in amine N-oxides
and nitrones. Chem. Ber. 1990, 647; (c) Balicki, R.; Kaczmarek, L.;
Malinnowski, M. Selective reduction of the N-O bond in heteroaromatic N-
4 2
oxides by TiCl /SnCl . Synth. Commun. 1989, 19, 897.
3
4
. Balicki, R.; Cybulski, M.; Maciejewski, G. An efficient deoxygenation of hetero-
aromatic N-oxides using zinc dust/ammonium formate reagent system. Synth.
Commun. 2003, 33, 4137.
. Ilias, M. H.; Barman, D. C.; Prajapati, D.; Sandhu, J. S. An indium mediated
efficient chemoselective deoxygenation of N-oxides and nitrons. Tetrahedron
Lett. 2002, 43, 1877.
5
6
7
8
9
. Jousseaume, B.; Chanson, E. Mild selective deoxygenation of amine oxides by
tin-tin bonded derivatives. Synthesis 1987, 55.
. Balicki, R. Efficient deoxygenation of heteroaromatic N-oxides with ammonium
formate as a catalytic hydrogen transfer agent. Synthesis 1989, 645.
. Zhang, Y.; Lin, R. Some deoxygenation and reduction reactions with samarium
diiodide. Synth. Commun. 1987, 17, 329.
. Ilankumaran, P.; Chandrasekara, S. Chemoselective deoxygenation of nitrones and
N-oxides with tetrathiomolybdate. Tetrahedron Lett. 1995, 36, 4881.
. Yadav, J. S.; Subba Reddy, B. V.; Muralidhar Reddy, M. Indium-mediated deoxy-
genation of amine-N-oxides in aqueous media. Tetrahedron Lett. 2000, 41, 2663.
1
0. Yoo, B. W.; Choi, J. W.; Yoon, C. M. A facile and efficient deoxygenation of
amine-N-oxides with Mo(CO) . Tetrahedron Lett. 2006, 47, 125.
6
11. (a) Choi, K. H.; Choi, K. I.; Kim, J. H.; Yoon, C. M.; Yoo, B. W. Mild and
efficient deoxygenation of epoxides with bis(cyclopentadienyl)titanium(IV)

1
650
B. W. Yoo and M. C. Park
dichloride–indium system. Bull. Korean Chem. Soc. 2005, 26, 1495;
b) Han, J. H.; Choi, J. W.; Choi, K. I.; Kim, J. H.; Yoon, C. M.; Yoo, B. W. A
facile deoxygenation of amine-N-oxide with NiCl 6H O/indium system. Bull.
(
2
2
Korean Chem. Soc. 2005, 26, 1921; (c) Han, J. H.; Choi, J. W.; Choi, K. I.;
Kim, J. H.; Yoo, B. W. A facile and efficient reduction of nitroarenes with
NiCl
d) Han, J. H.; Choi, K. I.; Kim, J. H.; Yoon, C. M.; Yoo, B. W. Facile deoxygena-
tion of amine-N-oxide with CoCl 6H O–indium system. Synth. Commun. 2006,
6, 415.
2 2
6H O/indium system. Bull. Korean Chem. Soc. 2006, 27, 1115;
(
2
2
3
1
2. (a) Yoo, B. W.; Choi, J. W.; Kim, D. Y.; Hwang, S. K.; Choi, K. I.; Kim, J. H. Mild
and efficient deoxygenation of amine-N-oxide with with bis(cyclopentadienyl)-
titanium(IV) dichloride–indium system. Bull. Korean Chem. Soc. 2002, 23, 797;
(
b) Han, J. H.; Choi, K. I.; Kim, J. H.; Yoon, C. M.; Yoo, B. W. Facile and
efficient deoxygenation of amine-N-oxides with gallium in water. Synth.
Commun. 2004, 17, 3197.