Reduction pyridine N-oxide

IV. The Chemical Mechanism of Pyridine N-oxide Reduction A. The Initial Step... 

For purposes of pyridine N-oxide reduction, it suffices to say that many examples of Eq. (14) have been explored, including those in which PR3 is displaced contra-thermodynamically (p/TM may be ca. 2) by PyO. Invoking such a step in the catalytic cycle is therefore perfectly acceptable. Actually, the ligand displacement chemistry is a rich and fascinating area in its own right, and for that reason it will be explored independently in Section V. 

Kubota and Miyazaki studied the polarographic reduction of pyridine N-oxides and found a satisfactory correlation with the <7-values. The values increase with increasing pH. 

Both amine oxides related to pyridines and aliphatic amine oxides (/25) are easily reduced, the former the more so. Pyridine N-oxide has been reduced over palladium, platinum, rhodium, and ruthenium. The most active was rhodium, but it was nonselective, reducing the ring as well. Palladium is usually the preferred catalyst for this type of reduction and is used by most workers 16,23,84 158) platinum is also effective 100,166,169). Katritzky and Monrol - ) examined carefully the selectivity of reduction over palladium of a... 

A great deal of chemistry can be done on pyridine N-oxides because the functionality acts as a modifier of ring reactivity. In some cases, the A-oxide functionality needs to be removed after the transformations of interest have been done a selective, mild reduction process would be of value. 

A nonstandard synthesis of the first uranium cluster containing an isopolyoxo-metalate core was reported recently [310b], Reduction of [Cp UCl2] (Cp7 — 1,2,4-/-Bu3C5H2) with two equivalents of KC8 in THF, followed by an addition of two equivalents of pyridine N-oxide, was conducted in an attempt to produce the organometallic dioxo species [Cp7U02]. However, the cluster compound [Cp (bipy)2][U6013] was isolated instead as the main product (54% yield) from this reaction. 

Oxidation of 2,4,4-trimethyl - A1 -py rroline V-oxide with selenium dioxide, followed by treatment with hydrogen chloride, causes ringopening and reclosure to 2,3,4,5-tetrahydro-3,3-dimethyl-5-oxo-pyridine N-oxide (111). Clemmensen reduction of 111 forms 2,4,4-trimethyl-d 1-pyrroline (112) by ring-contraction.334... 

The assumption that it is the O-protonated A -oxide that is reduced is substantiated by the similarity in reduction potential between pyridine N-oxide and A -methoxypyridi-nium ion in acid solution the latter is also reducible in alkaline solution [148]. 

Pyridine-N-oxide is reduced cleanly to pyridine at 25° but further reduction occurs at higher temperatures. Nitro compounds and aromatic halides are not reduced. 

In addition to being more selective, dissolved calcium metal functions in a similar way to lithium and sodium metals towards organic functional groups [45]. Tab. 4.2 lists reductions giving the same products by the three dissolved metals. Among these, calcium affords the highest yields for some substrates (entries 1-3). The compounds in Tab. 4.2 include an aldehyde, indole [46], aryl ketone, enone, naphthalene [47], pyridine N-oxide [48], benzyl alcohol, styrene, and buckminster-fullerene. 

Radiolabeled " C-pirlimycin was readily synthesized from sodium cyanide and 4-ethyl-pyridine N-oxide as shown in Figure 2. The final reduction step produced a 2 1 mixture of desired product and a biologically inactive stereoisomer. Recrystallization preferentially produced pirlimycin HCL in >98% radiochemical purity and >99% chemical purity with an overall radiochemical yield of 25%. 

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