# Nitrone

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Chemical group (>C=N(O)–)

Not to be confused with [nitrene](/source/Nitrene).

General structure of a nitrone.

In [organic chemistry](/source/Organic_chemistry), a **nitrone** is a [functional group](/source/Functional_group) consisting of an [*N*-oxide](/source/Amine_oxide) of an [imine](/source/Imine). The general structure is R1R2C=N+(−O−)(−R3), where R3 is not a [hydrogen](/source/Hydrogen). Their primary application is [intermediates](/source/Chemical_Intermediate) in [chemical synthesis](/source/Chemical_synthesis). A nitrone is a [1,3-dipole](/source/1%2C3-dipole) used in [cycloadditions](/source/1%2C3-dipolar_cycloaddition), and a [carbonyl](/source/Carbonyl_group) mimic.

## Structure

Nitrones, as a tetrasubstituted [double bond](/source/Double_bond), admit [*cis*–*trans* isomerism](/source/Cis%E2%80%93trans_isomerism).[1]: 474

## Generation of nitrones

Typical nitrone sources are [hydroxylamine](/source/Hydroxylamine) oxidation or [condensation](/source/Alkylimino-de-oxo-bisubstitution) with [carbonyl compounds](/source/Carbonyl_compounds). Secondary hydroxylamines oxidize to nitrones in air over a timescale of several weeks, accelerated by [cupric salts](/source/Copper_compounds).[1]: 476[2]: 332–333

The most general reagent used for the oxidation of hydroxylamines is aqueous [mercuric oxide](/source/Mercuric_oxide):[1]: 476[3]

However, a hydroxylamine with two [α](/source/Locant) hydrogens may unsaturate on either side. Carbonyl condensation avoids this ambiguity...[4]

...but is inhibited if both ketone substituents are bulky.[1]: 477

In principle, *N*-[alkylation](/source/Alkylation) could produce nitrones from [oximes](/source/Oxime), but in practice [electrophiles](/source/Electrophile) typically perform a mixture of *N*- and *O*-attack.[1]: 479[2]: 334

## Reactions

Some nitrones oligomerize:[1]: 483[2]: 334,337-338[5]

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](/source/Unsaturated_compound) functional groups, nitrones activate the [α and β carbons](/source/Locant) towards reaction. The α carbon is an electrophile and the β carbon a nucleophile; that is, nitrones [polarize](/source/Polar_bond) like carbonyls and nitriles but unlike [nitro compounds](/source/Nitro_compound) and vinyl sulfur derivatives.[1]: 483[2]: 338–340

Nitrones hydrolyze extremely easily to the corresponding carbonyl and N-hydroxylamine.[1]: 491[2]: 344

### 1,3-dipolar cycloadditions

Main article: [Nitrone-olefin 3+2 cycloaddition](/source/Nitrone-olefin_3%2B2_cycloaddition)

As [1,3‑dipoles](/source/1%2C3-dipole), nitrones perform [\[3+2\] cycloadditions](/source/1%2C3-dipolar_cycloaddition).[6] For example, a dipolarophilic [alkene](/source/Alkene) combines to form [isoxazolidine](/source/Isoxazolidine):

Nitrone cycloadditions

Other [ring-closing reactions](/source/Ring_closing_reaction) are known,[7] including formal [3+3] and [5+2] [cycloadditions](/source/Cycloaddition).[6]

### Isomerization

[Deoxygenating reagents](https://en.wikipedia.org/w/index.php?title=Deoxygenating_reagent&action=edit&redlink=1), [light](/source/Photochemistry), or heat all catalyze rearrangement to the [amide](/source/Amide). Acids catalyze rearrangement to the [oxime ether](/source/Oxime).[1]: 489–490[2]: 345–347

### Reduction

[Hydrides](/source/Hydrides) add to give [hydroxylamines](/source/Hydroxylamines). [Reducing](/source/Redox) [Lewis acids](/source/Lewis_acids_and_bases) (e.g. [metals](/source/Metals), [SO2](/source/Sulfur_dioxide)) [deoxygenate](/source/Deoxygenation) to the [imine](/source/Imine) instead.[1]: 490[2]: 343

## See also

- [*N*-Oxoammonium salt](/source/N-Oxoammonium_salt)

- [Nitronate](/source/Nitronate)

## References

1. ^ [***a***](#cite_ref-:0_1-0) [***b***](#cite_ref-:0_1-1) [***c***](#cite_ref-:0_1-2) [***d***](#cite_ref-:0_1-3) [***e***](#cite_ref-:0_1-4) [***f***](#cite_ref-:0_1-5) [***g***](#cite_ref-:0_1-6) [***h***](#cite_ref-:0_1-7) [***i***](#cite_ref-:0_1-8) [***j***](#cite_ref-:0_1-9) Hamer, Jan; Macaluso, Anthony (1964-08-01). ["Nitrones"](https://pubs.acs.org/doi/abs/10.1021/cr60230a006). *Chemical Reviews*. **64** (4): 473–495. [doi](/source/Doi_(identifier)):[10.1021/cr60230a006](https://doi.org/10.1021%2Fcr60230a006). [ISSN](/source/ISSN_(identifier)) [0009-2665](https://search.worldcat.org/issn/0009-2665).

1. ^ [***a***](#cite_ref-:1_2-0) [***b***](#cite_ref-:1_2-1) [***c***](#cite_ref-:1_2-2) [***d***](#cite_ref-:1_2-3) [***e***](#cite_ref-:1_2-4) [***f***](#cite_ref-:1_2-5) [***g***](#cite_ref-:1_2-6) Delpierre, G. R.; Lamchen, M. (1965). ["Nitrones"](http://xlink.rsc.org/?DOI=qr9651900329). *Quarterly Reviews, Chemical Society*. **19** (4): 329. [doi](/source/Doi_(identifier)):[10.1039/qr9651900329](https://doi.org/10.1039%2Fqr9651900329). [ISSN](/source/ISSN_(identifier)) [0009-2681](https://search.worldcat.org/issn/0009-2681).

1. **[^](#cite_ref-3)** 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.](/source/Justus_Liebigs_Ann._Chem.)* **609**: 46-57. [doi](/source/Doi_(identifier)):[10.1002/jlac.19576090105](https://doi.org/10.1002%2Fjlac.19576090105).

1. **[^](#cite_ref-4)** Exner, O. (1951). "A New Synthesis of N-methylketoximes". *[ChemPlusChem](/source/ChemPlusChem)*. **16**: 258-267. [doi](/source/Doi_(identifier)):[10.1135/cccc19510258](https://doi.org/10.1135%2Fcccc19510258).

1. **[^](#cite_ref-5)** Thiesing, Jan; Mayer, Hans (1956). "Cyclische Nitrone I: Dimeres 2.3.4.5-Tetrahydro-pyridin-N-oxyd". *[Chem. Ber.](/source/Chem._Ber.)* **89** (9): 2159-2167. [doi](/source/Doi_(identifier)):[10.1002/cber.19560890919](https://doi.org/10.1002%2Fcber.19560890919).

1. ^ [***a***](#cite_ref-Yang_Synlett_2012_6-0) [***b***](#cite_ref-Yang_Synlett_2012_6-1) Yang, Jiong (2012). "Recent Developments in Nitrone Chemistry". *[Synlett](/source/Synlett)*. **23**: 2293-97. [doi](/source/Doi_(identifier)):[10.1055/s-0032-1317096](https://doi.org/10.1055%2Fs-0032-1317096).

1. **[^](#cite_ref-7)** Murahashi, Shun-Ichi; Imada, Yasushi (15 March 2019). ["Synthesis and Transformations of Nitrones for Organic Synthesis"](https://tokushima-u.repo.nii.ac.jp/records/2006391). *Chemical Reviews*. **119** (7): 4684–4716. [doi](/source/Doi_(identifier)):[10.1021/acs.chemrev.8b00476](https://doi.org/10.1021%2Facs.chemrev.8b00476). [PMID](/source/PMID_(identifier)) [30875202](https://pubmed.ncbi.nlm.nih.gov/30875202). [S2CID](/source/S2CID_(identifier)) [80623450](https://api.semanticscholar.org/CorpusID:80623450).

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