In organic chemistry, a nitrone is a functional group consisting of an Amine 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 group mimic.
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
Copper compounds accelerate.
The most general reagent used for the oxidation of hydroxylamines is aqueous
mercuric oxide:
However, a hydroxylamine with two
Locant 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 Oxime, but in practice Electrophile typically perform a mixture of N- and O-attack.
Reactions
Some nitrones oligomerize:
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
Locant towards reaction. The α carbon is an electrophile and the β carbon a nucleophile; that is, nitrones
Polar bond like carbonyls and nitriles but unlike
Nitro compound and vinyl sulfur derivatives.
Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.
1,3-dipolar cycloadditions
As 1,3dipoles, nitrones perform [1,3-dipolar cycloaddition]]s.
For example, a dipolarophilic
alkene combines to form
isoxazolidine:
ring-closing reactions are known,
Isomerization
Deoxygenating reagents,
Photochemistry, or heat all catalyze rearrangement to the
amide. Acids catalyze rearrangement to the
Oxime.
Reduction
Hydrides add to give
hydroxylamines.
Redox Lewis acids (e.g.
metals,
Sulfur dioxide)
Deoxygenation to the
imine instead.
See also
