A mild and selective deoxygenation of N-oxides with ammonium formate as a catalytic hydrogen transfer agent

Article abstract of DOI:10.1081/SCC-120004259

Ammonium formate catalytic transfer hydrogenation in the presence of raney nickel has shown utility for mild and selective deoxygenation of heteroaromatic N-oxides in neutral medium.

Full text of DOI:10.1081/SCC-120004259

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A MILD AND SELECTIVE DEOXYGENATION OF N-OXIDES
WITH AMMONIUM FORMATE AS A CATALYTIC HYDROGEN
TRANSFER AGENT
Roman Balicki a & Grzegorz Maciejewski a
a Pharmaceutical Research Institute , Rydygiera 8, Warszawa, 01-793, Poland
Published online: 16 Aug 2006.
To cite this article: Roman Balicki & Grzegorz Maciejewski (2002) A MILD AND SELECTIVE DEOXYGENATION OF N-OXIDES WITH
AMMONIUM FORMATE AS A CATALYTIC HYDROGEN TRANSFER AGENT, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 32:11, 1681-1683, DOI: 10.1081/SCC-120004259
To link to this article: http://dx.doi.org/10.1081/SCC-120004259
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SYNTHETIC COMMUNICATIONS, 32(11), 1681–1683 (2002)
A MILD AND SELECTIVE
DEOXYGENATION OF N-OXIDES WITH
AMMONIUM FORMATE AS A CATALYTIC
HYDROGEN TRANSFER AGENT
*
Roman Balicki and Grzegorz Maciejewski
Pharmaceutical Research Institute, Rydygiera 8,
01-793 Warszawa, Poland
ABSTRACT
Ammonium formate catalytic transfer hydrogenation in
the presence of raney nickel has shown utility for mild and
selective deoxygenation of heteroaromatic N-oxides in neutral
medium.
Selective and simple deoxygenation of amine N-oxides is still an area
of considerable interest, particularly when a molecule has other reducible or
labile moieties. Asurvey of the literature reveals that many methods have
been reported for reduction of heteroaromatic N-oxides.[1–8] Most of these
methods are deficient in some respects such as relatively drastic reaction
conditions, low yields, poor selectivity or occurrence of side reactions.
In this communication we wish to report on the cheap and selective
method for deoxygenation of nitrogen heteroaromatic N-oxides into the
corresponding bases using catalytic transfer hydrogenation with ammonium
*Corresponding author.
1681
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1682
BALICKI AND MACIEJEWSKI
formate as the hydrogen source, in the presence of raney nickel.[9] The
reaction is carried out within 1–4 h upon addition of the hydrogen donor
to a suspension of raney nickel and the substrate 1 in methanol. In the case
of N-oxides containing alkoxycarbonyl groups, the reaction proceeds at
room temperature, but in most cases, the use of higher temperatures
(40–50ꢀC) is necessary. Thin-layer chromatography of the crude reaction
mixture showed the conversion to be almost quantitative.
The selectivity of our method is demonstrated by several examples
(Table 1). Such reducible substituents as alkoxycarbonyl, alkoxy, carbonyl,
Table 1. Deoxygenation of Heteroaromatic N-Oxides with Ammonium Formate
Reaction Conditions
Substrate 1
Entry
Yieldb
%
R
Temp. (ꢀC)
Time (h)
Product 2a
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
4-t-Bu
3-Me
3-COOMe
4-COOMe
4-Cl
3,5-diBr
4-NO2
3-CH3O
3-CONH2
4-CN
50
50
25
25
40
40
25
50
50
50
50
40
40
40
4
4
1
1
3
3
2
4
3
3
3
2
3
3
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
82
75
88
91
78
74
86c
65
62
77
74
69
87
81
4-COOH
3-COCH3
d
e
aAll products are commercially available and were characterized by comparison of
their IR, MS spectra and TLC with authentic samples.
bYield of isolated product based on a single experiment and not optimized.
c4-aminopyridine was formed.
dQuinoline N-oxide.
eAcridine N-oxide.

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DEOXYGENATION OF N-OXIDES
1683
cyano, and halogens remain unchanged; however, nitro group is readily
reduced under reaction conditions.
In conclusion, this novel and efficient method for the deoxygenation of
nitrogen heteroaromatic N-oxides offers the following advantages: (a) safe
and cheap reducing agent is used, (b) the deoxygenation is very selective
giving the corresponding base in high yields, (c) the procedure is facile and
isolation of the products is easy. For the above reasons, the procedure
described herein may be the method of choice for the deoxygenation of
heteroaromatic N-oxides.
EXPERIMENTAL
Typical procedure: To a stirred suspension of the appropriate N-oxides
1 (2 mmol) and raney nickel (0.1–0.2 g) in methanol (7 cm3) was introduced
anhydrous ammonium formate (2 mmol). The resulting reaction mixture
was stirred at 25–55ꢀC until TLC analysis indicated completion of reaction
(1–4 h). The catalyst was then removed by filtration through celite and
washed with methanol (5 cm3). The residue obtained by evaporation of
solvent was purified by flash column chromatography on silica gel (eluent:
hexane–ethyl acetate, 8 : 1) or crystallized to give pure product 2. The results
are summarized in Table 1.
REFERENCES
1. Emerson, T.R.; Rees, C.W. J. Chem. Soc. 1962, 1917.
2. Howard, E.; Olszewski, W.F. J. Am. Chem. Soc. 1959, 81, 1483.
3. Olah, G.A.; Arvanagdi, M.; Vankar, Y.D. Synthesis 1980, 660.
4. Achremowicz, L. Tetrahedron Lett. 1980, 21, 1675.
5. Den Hertog, H.J.; Overhoff, J. Red. Trav. Chim. Pays-Bas. 1950,
69, 469.
6. McCall, J.M.; Ten Brink, R.E. Synthesis 1975, 335.
7. Aoyagi, E.; Tomomitsu, A.; Ohta, A. Synthesis 1997, 891.
8. Hayashi, E.; Yamanaka, H.; Shimizu, K. Chem. Pharm. Bull. 1958,
6, 323.
9. Gowda, D.C.; Gowda, A.S.P.; Baba, A.R.; Gowda, S. Synth. Commun.
2000, 30, 2889.
Received in the Netherlands April 12, 2001

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