Nitrone

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.

Nitrones, as a tetrasubstituted double bond, admit cis–trans isomerism.^1: 474

Typical nitrone sources are hydroxylamine oxidation or condensation with carbonyl compounds. Secondary hydroxylamines oxidize to nitrones in air over a timescale of several weeks, accelerated by cupric salts.^{1: 476 2: 332–333}

The most general reagent used for the oxidation of hydroxylamines is aqueous mercuric oxide:^1: 476 3

However, a hydroxylamine with two α hydrogens may unsaturate on either side. Carbonyl condensation avoids this ambiguity...⁴

...but is inhibited if both ketone substituents are bulky.^1: 477

In principle, N-alkylation could produce nitrones from oximes, but in practice electrophiles typically perform a mixture of N- and O-attack.^{1: 479 2: 334}

Some nitrones oligomerize:^{1: 483 2: 334,337-338 5}

Syntheses with nitrone precursors obviate the issue with increased temperature, to exaggerate entropic factors; or with a nitrone excess.

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.^{1: 483 2: 338–340}

Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.^{1: 491 2: 344}

As 1,3‑dipoles, nitrones perform [3+2] cycloadditions.⁶ For example, a dipolarophilic alkene combines to form isoxazolidine:

Other ring-closing reactions are known,⁷ including formal [3+3] and [5+2] cycloadditions.⁶

Deoxygenating reagents, light, or heat all catalyze rearrangement to the amide. Acids catalyze rearrangement to the oxime ether.^{1: 489–490 2: 345–347}

Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, SO₂) deoxygenate to the imine instead.^{1: 490 2: 343}