GetWiki

{{Short description|1=Chemical group (>C=N(O)–)}}{{Distinguish|nitrene}}(File:Nitrone-general-structure-2D.png|150px|right|thumb|General structure of a nitrone.)In organic chemistry, a nitrone is a functional group consisting of an N-oxide of an imine. The general structure is {{chem2|R^{1}R^{2}CdN+(sO−)(sR^{3})}}, 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.

Structure

Nitrones, as a tetrasubstituted double bond, admit cis–trans isomerism.JOURNAL, Hamer, Jan, Macaluso, Anthony, 1964-08-01, Nitrones,pubs.acs.org/doi/abs/10.1021/cr60230a006, Chemical Reviews, en, 64, 4, 473–495, 10.1021/cr60230a006, 0009-2665, subscription, {{Rp|page=474}}

Generation of nitrones

Typical nitrones 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.{{Rp|page=476}}JOURNAL, Delpierre, G. R., Lamchen, M., 1965, Nitrones,xlink.rsc.org/?DOI=qr9651900329, Quarterly Reviews, Chemical Society, en, 19, 4, 329, 10.1039/qr9651900329, 0009-2681, {{Rp|pages=332-333}} The most general reagent used for the oxidation of hydroxylamines is aqueous mercury(II) oxide:{{Rp|page=476}}JOURNAL, Thiesing, 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, 10.1002/jlac.19576090105, (File:NitrMech1.png|250px|center)However, a hydroxylamine with two α hydrogens may unsaturate on either side. Carbonyl condensation avoids this ambiguity...JOURNAL, Exner, O., A New Synthesis of N-methylketoximes, ChemPlusChem, 1951, 16, 258-267, 10.1135/cccc19510258, (File:NitrMech2.png|center)...but is inhibited if both ketone substituents are bulky.{{Rp|page=477}}In principle, N-alkylation could produce nitrones from oximes, but in practice electrophiles typically perform a mixture of N- and O-attack.{{Rp|page=479}}{{Rp|page=334}}

Reactions

Some nitrones oligimerize:{{Rp|page=483}}{{Rp|location=334,337-338}}JOURNAL, Thiesing, Jan, Mayer, Hans, 1956, Cyclische Nitrone I: Dimeres 2.3.4.5-Tetrahydro-pyridin-N-oxyd, Chem. Ber., 89, 9, 2159-2167, 10.1002/cber.19560890919, (File:NitrMech3.png|center)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.{{Rp|page=483}}{{Rp|pages=338-340}}Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.{{Rp|page=491}}{{Rp|page=344}}

1,3-dipolar cycloadditions

As 1,3{{Nbh}}dipoles, nitrones perform [3+2] cycloadditions.JOURNAL, Yang, Jiong, 2012, Recent Developments in Nitrone Chemistry, Synlett, 23, 2293-97, 10.1055/s-0032-1317096, For example, a dipolarophilic alkene combines to form isoxazolidine:(File:Nitrone cycloaddition.png|500px|center|Nitrone cycloadditions)Other ring-closing reactions are known,JOURNAL, Murahashi, Shun-Ichi, Imada, Yasushi, 15 March 2019, Synthesis and Transformations of Nitrones for Organic Synthesis, Chemical Reviews, 119, 7, 4684–4716, 10.1021/acs.chemrev.8b00476, 30875202, 80623450, 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.{{Rp|pages=489-490}}{{Rp|pages=345-347}}

Reduction

Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, {{chem2|SO2}}) deoxygenate to the imine instead.{{Rp|page=490}}{{Rp|page=343}}

See also

• N-Oxoammonium salt
• Nitronate

References

{{reflist}}