Nitrone
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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.
Contents
• See also
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Structure
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.cite-ref-0-1-1[1]cite-ref-1-2-0[2] The most general reagent used for the oxidation of hydroxylamines is aqueous mercuric oxide:cite-ref-0-1-2[1]cite-ref-3[3]
...but is inhibited if both ketone substituents are bulky.cite-ref-0-1-3[1]
In principle, N-alkylation could produce nitrones from oximes, but in practice electrophiles typically perform a mixture of N- and O-attack.cite-ref-0-1-4[1]cite-ref-1-2-1[2]
Reactions
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.cite-ref-0-1-6[1]cite-ref-1-2-3[2]
1,3-dipolar cycloadditions
As 1,3‑dipoles, nitrones perform [3+2 cycloadditions.cite-ref-yang-synlett-2012-6-0[6] For example, a dipolarophilic alkene combines to form isoxazolidine:
Other ring-closing reactions are known,cite-ref-7[7] including formal [3+3] and [5+2] cycloadditions.cite-ref-yang-synlett-2012-6-1[6]
Isomerization
Deoxygenating reagents, light, or heat all catalyze rearrangement to the amide. Acids catalyze rearrangement to the oxime ether.cite-ref-0-1-8[1]cite-ref-1-2-5[2]
Reduction
Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, SO2) deoxygenate to the imine instead.cite-ref-0-1-9[1]cite-ref-1-2-6[2]
See also
References
cite-note-33. ↑ citerefthiesingmayer1957Thiesing, Jan; Mayer, Hans (1957). "Cyclische Nitrone, II. Über die Polymeren des 2.3.4.5-Tetrahydro-pyridin-N-oxyds und verwandte Verbindungen". Justus Liebigs Ann. Chem. 609: 46-57. doi:10.1002/jlac.19576090105.
cite-note-44. ↑ citerefexner1951Exner, O. (1951). "A New Synthesis of N-methylketoximes". ChemPlusChem. 16: 258-267. doi:10.1135/cccc19510258.
cite-note-55. ↑ citerefthiesingmayer1956Thiesing, Jan; Mayer, Hans (1956). "Cyclische Nitrone I: Dimeres 2.3.4.5-Tetrahydro-pyridin-N-oxyd". Chem. Ber. 89 (9): 2159-2167. doi:10.1002/cber.19560890919.