Nitrone

Structure

Nitrones, as a tetrasubstituted double bond, admit cis–trans isomerism.

Generation of nitrones

Typical nitrone sources are hydroxylamine oxidation or condensation with carbonyl compounds. Secondary hydroxylamines oxidize to nitrones in air over a timescale of several weeks, a process cupric salts accelerate. The most general reagent used for the oxidation of hydroxylamines is aqueous mercuric oxide:

However, a hydroxylamine with two α hydrogens may unsaturate on either side. Carbonyl condensation avoids this ambiguity...[[File:NitrMech2.png|center]] ...but is inhibited if both ketone substituents are bulky.

In principle, N-alkylation could produce nitrones from oximes, but in practice electrophiles typically perform a mixture of N- and O-attack.

Reactions

Some nitrones oligomerize: [[File:NitrMech3.png|center]]Syntheses with nitrone precursors obviate the issue with increased temperature, to exaggerate entropic factors; or with a nitrone excess.

Carbonyl mimic

Like many other unsaturated functional groups, nitrones activate the α and β carbons towards reaction. The α carbon is an electrophile and the β carbon a nucleophile; that is, nitrones polarize like carbonyls and nitriles but unlike nitro compounds and vinyl sulfur derivatives.

Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.

1,3-dipolar cycloadditions

Main article: Nitrone-olefin 3+2 cycloaddition

As 1,3dipoles, nitrones perform [3+2] cycloadditions. For example, a dipolarophilic alkene combines to form isoxazolidine:

Isomerization

Deoxygenating reagents, light, or heat all catalyze rearrangement to the amide. Acids catalyze rearrangement to the oxime ether.

Reduction

Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, ) deoxygenate to the imine instead.

References

References

1. Hamer, Jan. (1964-08-01). "Nitrones". Chemical Reviews.
2. Delpierre, G. R.. (1965). "Nitrones". Quarterly Reviews, Chemical Society.
3. (1957). "Cyclische Nitrone, II. Über die Polymeren des 2.3.4.5-Tetrahydro-pyridin-N-oxyds und verwandte Verbindungen". [[Justus Liebigs Ann. Chem.]].
4. Exner, O.. (1951). "A New Synthesis of N-methylketoximes". [[ChemPlusChem]].
5. (1956). "Cyclische Nitrone I: Dimeres 2.3.4.5-Tetrahydro-pyridin-N-oxyd". [[Chem. Ber.]].
6. Yang, Jiong. (2012). "Recent Developments in Nitrone Chemistry". [[Synlett]].
7. (15 March 2019). "Synthesis and Transformations of Nitrones for Organic Synthesis". Chemical Reviews.