Pyridine-N-oxide

Structure

The structure of pyridine-N-oxide is very similar to that of pyridine with respect to the parameters for the ring. The molecule is planar. The N–O distance is 1.34Å. The C–N–C angle is 124°, 7° wider than in pyridine.

Synthesis

The oxidation of pyridine can be achieved with a number of peroxy acids, including peracetic acid and peroxybenzoic acid. Oxidation can also be effected by a modified Dakin reaction using a urea–hydrogen peroxide complex, and sodium perborate or, using methylrhenium trioxide () as catalyst, with sodium percarbonate.

Reactions

Pyridine N-oxide is five orders of magnitude less basic than pyridine: the pKa of protonated pyridine-N-oxide is 0.8. Protonated derivatives are isolable, e.g., [C5H5NOH]Cl. Further demonstrating its (feeble) basicity, pyridine-N-oxide also serves as a ligand in coordination chemistry. A host of transition metal complexes of pyridine-N-oxides are known.

Some electrophilic substitutions on pyridine rings are usefully effected using pyridine N-oxide followed by deoxygenation. Addition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed, e.g., using zinc dust.

Related pyridine-''N''-oxides

Pyridine-N-oxides are uncommon in nature. 2-(Methyldithio)pyridine-N-oxide and related compounds have been isolated from species of Allium.

The N-oxides of various pyridines are precursors to useful drugs:

• Nicotinic acid N-oxide, derived from nicotinic acid is a precursor to niflumic acid and pranoprofen.
• 2,3,5-Trimethylpyridine N-oxide is a precursor to the drug omeprazole
• 2-Chloropyridine N-oxide is a precursor to the fungicide zinc pyrithione

Safety

The compound is a skin irritant.

References

References

1. Meisenheimer, Jakob. (1926). "Über Pyridin-, Chinolin- und Isochinolin-''N''-oxyd". [[Ber. Dtsch. Chem. Ges.]].
2. (20 September 2015). "Pyridine ''N''-Oxide". [[John Wiley & Sons]].
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4. (1953). "Pyridine-''N''-oxide". Org. Synth..
5. (1999). "The Urea−Hydrogen Peroxide Complex: Solid-State Oxidative Protocols for Hydroxylated Aldehydes and Ketones (Dakin Reaction), Nitriles, Sulfides, and Nitrogen Heterocycles". [[Org. Lett.]].
6. (1989). "Further functional group oxidations using sodium perborate". [[Tetrahedron (journal).
7. (2006). "Rhenium-Catalyzed Highly Efficient Oxidations of Tertiary Nitrogen Compounds to ''N''-Oxides Using Sodium Percarbonate as Oxygen Source". [[Synlett]].
8. (1996). "Studies on correlations of acid-base properties of substituted pyridine ''N''-oxides in solutions. Part 1. Correlations of the p ''Ka'' values in non-aqueous solvents and water". Analytica Chimica Acta.
9. Scriven, E. F. V.. (1984). "Comprehensive Heterocyclic Chemistry: The Structure, Reactions, Synthesis and Uses of Heterocyclic Compounds". [[Pergamon Press]].
10. (2011). "Synthesis of 2-aryl Pyridines By Palladium-catalyzed Direct Arylation of Pyridine ''N''-oxides". Org. Synth..
11. (2009). "Bioactive Pyridine- ''N'' -oxide Disulfides from ''Allium stipitatum''". Journal of Natural Products.
12. {{Ullmann. (2000)