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Balicki, Cybulski, and Maciejewski
including agents such as: trivalent phosphorus compounds,[1,2] sulphur or
selenium compounds,[3,4] metals in acids,[5] aluminium iodide,[6] and
catalytic hydrogenation.[7] In general, these traditional procedures often
require severe reaction conditions and prolonged reaction times, and
afford products of insufficient purity in moderate or low yield.
Previously, we reported that amine N-oxides may be easily and efficiently
reduced to the corresponding bases with low-valent titanium, generated
through the reaction TiCl4 with lithium aluminium hydride[8] or stannous
chloride[9] in tetrahydrofuran.
Excellent results were obtained when the deoxygenation of amine
N-oxides was performed in neutral medium using some hydrogen
transfer agents in the presence of palladium on carbon as catalyst.[10,11]
However, our last methods appear to be inappropriate for large-
scale preparation due to necessity of using LiAlH4 or expensive
palladium.
In this communication we report a new and efficient method for
deoxygenation of the N–O function to the corresponding bases using
zinc dust/ammonium formate reagent system. The application of this
cheap and simple agent was till now limited to the reduction of nitro
group[12] and reductive cleavage of azo compounds.[13] A variety of
amine N-oxides were treated with zinc dust/ammonium formate system,
and the corresponding bases were obtained in high yields; the results are
summarized in Table 1. The reaction proceeds readily upon addition of
anhydrous ammonium formate to a suspention of N-oxide and activated
zinc dust in boiling methanol within 2–7 h. The optimum ratio reagent
was found to be 1:3:2 (substrate 1/ammonium formate/ zinc dust) for
monooxides (1a–l) or 1:6:4 for dioxides (1m,n). Acetic acid is also accep-
table solvent in some cases, but the reaction was slower in this medium.
Among the metals tested, zinc appear to be the most effective, while
magnesium and iron powder gave much lower yields. The selectivity
of our method is demonstrated by several examples. Substituents, like
halogen (1b,d), methoxy (1g), cyano (1h), acetyl (1f ) or esters (1i,j)
remained unchanged; however nitro group (1e) was easily reduced
under the reaction conditions to 4-aminopyridine.
The progress of the reaction was monitored by TLC, and the
corresponding products 2 were isolated by the usual work-up and
identified by IR, MS, and TLC.
We believe that the present procedure offers an attractive
alternative for other method available for the reduction of N-oxides.
Its principal advantages are: the ease of manipulation, mild reaction
conditions, selectivity, cheap reagents, and good yields for a wide variety
of heteroaromatic N-oxides.