Nitrone

Not to be confused with nitrene.

In organic chemistry, a nitrone is a functional group consisting of an N-oxide of an imine. The general structure is R¹R²C=N⁺(−O⁻)(−R³), where R³ is not a hydrogen. Their primary application is intermediates in chemical synthesis. A nitrone is a 1,3-dipole used in cycloadditions, and a carbonyl mimic.

General structure of a 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...

...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:

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

Nitrone cycloadditions

Other ring-closing reactions are known, including formal [3+3] and [5+2] cycloadditions.

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, SO₂) deoxygenate to the imine instead.

See also

• N-Oxoammonium salt
• Nitronate