In organic chemistry, a nitrone is a functional group consisting of an N-oxide of an imine. The general structure is, 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]
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.[2] The most general reagent used for the oxidation of hydroxylamines is aqueous mercuric oxide:[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.
In principle, N-alkylation could produce nitrones from oximes, but in practice electrophiles typically perform a mixture of N- and O-attack.
Some nitrones oligomerize:[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.
Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.
See main article: Nitrone-olefin 3+2 cycloaddition. As 1,3dipoles, 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.
Deoxygenating reagents, light, or heat all catalyze rearrangement to the amide. Acids catalyze rearrangement to the oxime ether.
Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, ) deoxygenate to the imine instead.