{{Short description|1=Chemical group (>C=N(O)–)}} {{Distinguish|nitrene}} 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}C\dN+(\sO−)(\sR^{3})}}, where R<sup>3</sup> 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.<ref name=":0">{{Cite journal |last=Hamer |first=Jan |last2=Macaluso |first2=Anthony |date=1964-08-01 |title=Nitrones |url=https://pubs.acs.org/doi/abs/10.1021/cr60230a006 |journal=Chemical Reviews |language=en |volume=64 |issue=4 |pages=473–495 |doi=10.1021/cr60230a006 |issn=0009-2665|url-access=subscription }}</ref>{{Rp|page=474}}

== 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, accelerated by cupric salts.<ref name=":0" />{{Rp|page=476}}<ref name=":1">{{Cite journal |last=Delpierre |first=G. R. |last2=Lamchen |first2=M. |date=1965 |title=Nitrones |url=http://xlink.rsc.org/?DOI=qr9651900329 |journal=Quarterly Reviews, Chemical Society |language=en |volume=19 |issue=4 |pages=329 |doi=10.1039/qr9651900329 |issn=0009-2681|url-access=subscription }}</ref>{{Rp|pages=332-333}}

The most general reagent used for the oxidation of hydroxylamines is aqueous mercuric oxide:<ref name=":0" />{{Rp|page=476}}<ref>{{cite journal |last1=Thiesing |first1=Jan |last2=Mayer |first2=Hans |year=1957 |title=Cyclische Nitrone, II. Über die Polymeren des 2.3.4.5-Tetrahydro-pyridin-N-oxyds und verwandte Verbindungen |journal=Justus Liebigs Ann. Chem. |volume=609 |page=46-57 |doi=10.1002/jlac.19576090105}}</ref> 250px|center However, a hydroxylamine with two α hydrogens may unsaturate on either side. Carbonyl condensation avoids this ambiguity...<ref>{{cite journal|last=Exner|first=O.|title=A New Synthesis of N-methylketoximes|journal=ChemPlusChem|year=1951|volume=16|page=258-267|doi=10.1135/cccc19510258}}</ref>center ...but is inhibited if both ketone substituents are bulky.<ref name=":0" />{{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.<ref name=":0" />{{Rp|page=479}}<ref name=":1" />{{Rp|page=334}}

== Reactions == Some nitrones oligomerize:<ref name=":0" />{{Rp|page=483}}<ref name=":1" />{{Rp|location=334,337-338}}<ref>{{cite journal |last1=Thiesing |first1=Jan |last2=Mayer |first2=Hans |year=1956 |title=Cyclische Nitrone I: Dimeres 2.3.4.5-Tetrahydro-pyridin-N-oxyd |journal=Chem. Ber. |volume=89 |issue=9 |page=2159-2167 |doi=10.1002/cber.19560890919}}</ref> centerSyntheses 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.<ref name=":0" />{{Rp|page=483}}<ref name=":1" />{{Rp|pages=338-340}}

Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.<ref name=":0" />{{Rp|page=491}}<ref name=":1" />{{Rp|page=344}}

=== 1,3-dipolar cycloadditions === {{Main|Nitrone-olefin 3+2 cycloaddition}} As 1,3{{Nbh}}dipoles, nitrones perform [[1,3-dipolar cycloaddition|[3+2] cycloaddition]]s.<ref name="Yang_Synlett_2012">{{cite journal |last=Yang |first=Jiong |year=2012 |title=Recent Developments in Nitrone Chemistry |journal=Synlett |volume=23 |page=2293-97 |doi=10.1055/s-0032-1317096}}</ref> For example, a dipolarophilic alkene combines to form isoxazolidine:

500px|center|Nitrone cycloadditionsOther ring-closing reactions are known,<ref>{{cite journal |last1=Murahashi |first1=Shun-Ichi |last2=Imada |first2=Yasushi |date=15 March 2019 |title=Synthesis and Transformations of Nitrones for Organic Synthesis |journal=Chemical Reviews |volume=119 |issue=7 |pages=4684–4716 |doi=10.1021/acs.chemrev.8b00476 |pmid=30875202 |s2cid=80623450|url=https://tokushima-u.repo.nii.ac.jp/records/2006391 }}</ref> including formal [3+3] and [5+2] cycloadditions.<ref name="Yang_Synlett_2012" />

=== Isomerization === Deoxygenating reagents, light, or heat all catalyze rearrangement to the amide. Acids catalyze rearrangement to the oxime ether.<ref name=":0" />{{Rp|pages=489-490}}<ref name=":1" />{{Rp|pages=345-347}}

=== Reduction === Hydrides add to give hydroxylamines. Reducing Lewis acids (e.g. metals, {{chem2|SO2}}) deoxygenate to the imine instead.<ref name=":0" />{{Rp|page=490}}<ref name=":1" />{{Rp|page=343}}

==See also== * ''N''-Oxoammonium salt * Nitronate

== References == {{reflist}}

Category:Functional groups