Reduction of pyridine N-oxides

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. 

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. 

Deoxygenation of N-oxides,4 TiCl4 -NaBH4 (1 2) in DME reduces the N-oxide of pyridine and mcthylpyridines (picolines) to the corresponding heterocycles in high yield. However the N-oxide of quinolines and isoquinolines is reduced further to dihydro derivatives of the hetcrocyclcs. Pyridine, quinoline, and isoquinoline themselves are not reduced by this low-valent titanium species. Reduction of heterocyclic N-oxides with TiCI, has been reported (6, 588). 

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. 

Related reductions using Sml2 have also been reported. For example, Zhang described the rapid reduction of pyridine IV-oxides and azobenzenes using Sml2 with MeOH,43 whereas Natale used Sml2 to cleave the N-O bond in isoxazoles.44... 

Various new procedures have been reported for the reduction of pyridine iV-oxides, including the use of TiCU with NaBH4 of (MeO)3P with of SO, generated in situ and of M0CI5 with zinc dust. Irradiation of pyridine N-oxide in the presence of sodium hydroxide yields the anion of 5-hydroxypenta-2,4-dienenitrile if the irradiation is carried out in the presence of secondary amines, derivatives of 5-aminopenta-2,4-dienenitrile are obtained. ... 

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. 

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... 

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