{{Short description|Chemical compound containing the functional group R3NO}} {{Use dmy dates|date=May 2023}} thumb|right|170px|General structure of an amine oxide

In chemistry, an '''amine oxide''', also known as an '''amine ''N''-oxide''' or simply '''''N''-oxide''', is a chemical compound that has the chemical formula {{chem2|R3N+\sO-}}. It contains a nitrogen-oxygen coordinate covalent bond with three additional hydrogen and/or substituent-groups attached to nitrogen. Sometimes it is written as {{chem2|R3N→O}} or, alternatively,<ref>{{cite journal | doi=10.1039/C5SC02076J | title=A quantitative definition of hypervalency | date=2015 | last1=Durrant | first1=Marcus C. | journal=Chemical Science | volume=6 | issue=11 | pages=6614–6623 | pmid=30090275 | pmc=6054109}}</ref> as {{chem2|R3N\dO}}.

In the strict sense, the term ''amine oxide'' applies only to oxides of tertiary amines. Sometimes it is also used for the analogous derivatives of primary and secondary amines.

Commonly, amine oxides are white, water-soluble solids: *trimethylamine-''N''-oxide, (m.p. 220&nbsp;°C), an osmolyte found in molluscs *pyridine-''N''-oxide, (m.p. 62–67&nbsp;°C) *''N''-methylmorpholine ''N''-oxide, (m.p. 184–187&nbsp;°C), a nucleophilic oxidant

==Applications== [[image:Imipraminoxide skeletal.svg|thumb|left|120px|Imipraminoxide (aka Imiprex) is used for the treatment of depression.<ref name=Kobus>{{cite journal |last1=Kobus |first1=M. |last2=Friedrich |first2=T. |last3=Zorn |first3=E. |last4=Burmeister |first4=N. |last5=Maison |first5=W. |title=Medicinal Chemistry of Drugs with N-Oxide Functionalities |journal=Journal of Medicinal Chemistry |date=2024 |volume=67 |issue=7 |pages=5168–5184 |doi=10.1021/acs.jmedchem.4c00254 |pmid=38549449 |pmc=11017254 }}</ref>]] Long-chain alkyl amine oxides are used as amphoteric surfactants and foam stabilizers.

Amine oxides are surfactants commonly used in consumer products such as shampoos, conditioners, detergents, and hard surface cleaners.<ref name="OECD">{{cite web|last=Organisation for Economic Co-operation and Development (OECD) |title=Amine Oxides |url=http://webnet.oecd.org/hpv/ui/SIDS_Details.aspx?id=b927b43d-8e91-4ada-80e3-720d634e01c0 |work=OECD Existing Chemicals Database |year=2006 |url-status=dead |archive-url=https://web.archive.org/web/20140222165808/http://webnet.oecd.org/hpv/ui/SIDS_Details.aspx?id=b927b43d-8e91-4ada-80e3-720d634e01c0 |archive-date=22 February 2014}}</ref> Alkyl dimethyl amine oxide (chain lengths C10–C16) is the most commercially used amine oxide.<ref name="Sanderson_2009">{{cite journal|last=Sanderson|first=H|author2=C Tibazarwa |author3=W Greggs |author4=DJ Versteeg |title=High Production Volume Chemical Amine Oxides [C''8''–C''20'']|journal=Risk Analysis|year=2009|volume=29|issue=6|pages=857–867|doi=10.1111/j.1539-6924.2009.01208.x|pmid=19504658|s2cid=45774397}}</ref> They are considered a high production volume class of compounds in more than one member country of the Organisation for Economic Co-operation and Development (OECD); with annual production over {{convert|26000|,|16000|and|6,800|t|ST|abbr=off}} in the US, Europe, and Japan, respectively.<ref name=OECD/> In North America, more than 95% of amine oxides are used in home cleaning products.<ref name="Modler">{{cite web|title=CEH Marketing Research Report: Surfactants, Household Detergents, and their Raw Materials|work=Chemical Economics Handbook|publisher=SRI Consulting|author=Modler, RF|author2=Inoguchi Y|url=http://www.ihs.com/products/chemical/planning/ceh/index.aspx|location=Menlo Park, CA|year=2004}}</ref> They serve as stabilizers, thickeners, emollients, emulsifiers, and conditioners with active concentrations in the range of 0.1–10%.<ref name=OECD/> The remainder (< 5%) is used in personal care, institutional, commercial products<ref name="Sanderson_2006">{{cite journal|last=Sanderson|first=H|author2=Counts JL |author3=Stanton K |author4=Sedlak R |title=Exposure and Prioritization—Human Screening Data and Methods for High Production Volume Chemicals in Consumer Products: Amine Oxides a Case Study.|journal=Risk Analysis|year=2006|volume=26|issue=6|pages=1637–1657|doi=10.1111/j.1539-6924.2006.00829.x|pmid=17184403|doi-access=free}}</ref> and for unique patented uses such as photography.<ref name=OECD/> [[Image:Lauryldimethylamine oxide.png|left|388px|thumb|Lauryldimethylamine oxide, a fatty amine derivative, is a germicidal ingredient in many cosmetics.]]{{clear-left}}

== Properties == Amine oxides are highly polar molecules and have a polarity close to that of quaternary ammonium salts. Small amine oxides are very hydrophilic and have an excellent water solubility and a very poor solubility in most organic solvents.

Amine oxides are moderate bases. For {{chem2|(CH3)3NOH+}}, the p''K''<sub>a</sub> is around 4.<ref name=Kobus/><ref>{{cite book |last1=Maisonneuve |first1=B. |title=Kirk-Othmer Encyclopedia of Chemical Technology |chapter=Amine Oxides |date=2003 |doi=10.1002/0471238961.0113091413010919.a01.pub2 |isbn=978-0-471-48494-3 }}</ref>

== Synthesis == Almost all amine oxides are prepared by the oxidation of either tertiary aliphatic amines or aromatic ''N''-heterocycles. Hydrogen peroxide is the most common reagent both industrially and in academia, however peracids are also important.<ref>{{March6th|page=1779}}</ref> More specialised oxidising agents can see niche use, for instance Caro's acid or ''m''CPBA. Spontaneous or catalysed reactions using molecular oxygen are rare. Certain other reactions will also produce amine oxides, such as the retro-Cope elimination, however they are rarely employed.

Formation of amine oxides can also be an unwanted process, such as the oxidation of amine-based reagents. Amines left exposed to air can undergo oxidation from atmospheric oxygen, slowly reacting with oxygen to form ''N''-oxides. This process can cause the amines to turn a yellowish color and the N-oxides can decompose further into byproducts. Oxidation due to air can be prevented by storing reagents under inert atmosphere.{{cn|date=July 2025}}

== Reactions == Amine oxides exhibit many kinds of reactions.<ref>{{cite journal|title=Synthetic utility of amine ''N''-oxides|author=Albini, Angelo|journal=Synthesis|year=1993|volume=1993|issue=3|pages=263–77|doi=10.1055/s-1993-25843}}</ref><ref name=Kobus/> *Pyrolytic elimination. Amine oxides, when heated to 150–200&nbsp;°C undergo a Cope reaction to form a hydroxylamine and an alkene. The reaction requires the alkyl groups to have hydrogens at the beta-carbon (i.e. works with ethyl and above, but not methyl) *Reduction to amines. Amine oxides are readily converted to the parent amine by common reduction reagents including lithium aluminium hydride, sodium borohydride, hydrogenation, zinc-acetic acid, and iron=acetic acid. Pyridine ''N''-oxides can be deoxygenated by phosphorus oxychloride * Sacrificial catalysis. Oxidants can be regenerated by reduction of ''N''-oxides, as in the case of regeneration of osmium tetroxide by ''N''-methylmorpholine ''N''-oxide in the Upjohn dihydroxylation. * ''O''-Alkylation. Pyridine ''N''-oxides react with alkyl halides to the ''O''-alkylated product{{cn|date=March 2026}} *Lewis bases and ligands * In the Meisenheimer rearrangement, certain ''N''-oxides {{chem2|R^{1}R^{2}R^{3}N+\sO−}} rearrange to alkoxylamines {{chem2|R^{2}R^{3}N\sO\sR^{1}|}} * In the {{vanchor|Polonovski reaction}}, a tertiary ''N''-oxide is cleaved by acetic acid anhydride to the corresponding acetamide and aldehyde:<ref>{{cite journal | last1 = Grierson | first1 = D | year = 1990 | title = The Polonovski Reaction| journal = Org. React. | volume = 39 | page = 85 | doi = 10.1002/0471264180.or039.02 | isbn = 0471264180}}</ref><ref>{{cite journal | last1 =Polonovski | first1 = Max | last2 = Polonovski | first2 = Michel | title = "Sur les aminoxydes des alcaloïdes. III. Action des anhydrides et chlorures d’acides organiques. Préparation des bases nor." | journal = Bull. Soc. Chim. Fr. | volume =41 | year = 1927 | pages = 1190-1208}}</ref><ref>{{cite book|title=Strategic Applications of Named Reactions in Organic Synthesis |edition=paperback |first1=Laszlo |last1=Kürti |first2=Barbara |last2=Czako |year=2005 |publisher=Elsevier Science |isbn=0-12-429785-4}}{{page needed|date=September 2021}}</ref> :650px|Polonovski reaction

== Metabolites ==

Amine oxides are common metabolites of medication and psychoactive drugs. Examples include nicotine, Zolmitriptan, and morphine. Amine oxides of anti-cancer drugs have been developed as prodrugs that are metabolized in the oxygen-deficient cancer tissue to the active drug.

==Human safety== Amine oxides (AO) are not known to be carcinogens, dermal sensitizers, or reproductive toxicants. They are readily metabolized and excreted if ingested. Chronic ingestion by rabbits found lower body weight, diarrhea, and lenticular opacities at a lowest observed adverse effect levels (LOAEL) in the range of 87–150&nbsp;mg AO/kw bw/day. Tests of human skin exposure have found that after 8 hours less than 1% is absorbed into the body. Eye irritation due to amine oxides and other surfactants is moderate and temporary with no lasting effects.<ref name=OECD/>

==Environmental safety== Amine oxides with an average chain length of 12.6 have been measured to be water-soluble at ~410 g/L. They are considered to have low bioaccumulation potential in aquatic species based on log K<sub>ow</sub> data from chain lengths less than C14 (bioconcentration factor < 87%).<ref name=OECD/> Levels of AO in untreated influent were found to be 2.3–27.8&nbsp;ug/L, while in effluent they were found to be 0.4–2.91&nbsp;ug/L. The highest effluent concentrations were found in oxidation ditch and trickling filter treatment plants. On average, over 96% removal has been found with secondary activated sludge treatment.<ref name=Sanderson_2009/> Acute toxicity in fish, as indicated by 96h LC50 tests, is in the range of 1,000–3,000&nbsp;ug/L for carbon chain lengths less than C14. LC50 values for chain lengths greater than C14 range from 600 to 1400&nbsp;ug/L. Chronic toxicity data for fish is 420&nbsp;ug/L. When normalized to C12.9, the NOEC is 310&nbsp;ug/L for growth and hatchability.<ref name=Sanderson_2009/>

== See also ==

* Functional group * Amine, NR<sub>3</sub> * Hydroxylamine, NR<sub>2</sub>OH * Phosphine oxide, PR<sub>3</sub>=O * Sulfoxide, R<sub>2</sub>S=O * Azoxy, RN=N<sup>+</sup>(O<sup>−</sup>)R RN=N<sup>+</sup>RO<sup>−</sup> * Aminoxyl group, radicals with the general structure R<sub>2</sub>N–O• * :Category:Amine oxides, containing all articles on specific amine-oxide compounds

==References== {{reflist}}

== External links == * [https://archive.today/20121212131033/http://www.cem.msu.edu/~reusch/VirtualText/amine2.htm Chemistry of amine oxides] * [http://nanoparticles.org/pdf/Salager-E300A.pdf Surfactants, types and uses] {{Webarchive|url=https://web.archive.org/web/20200731194249/http://nanoparticles.org/pdf/Salager-E300A.pdf |date=31 July 2020}} (pdf) * [http://www.chm.bris.ac.uk/motm/proline/aminehomepage.html The amine oxides homepage] * [https://web.archive.org/web/20120716211320/http://www.chem.qmul.ac.uk/iupac/class/oneN.html Nomenclature of nitrogen compounds] * [http://goldbook.iupac.org/html/A/A00273.html IUPAC definition]

{{DEFAULTSORT:Amine Oxide}} Category:Amine oxides Category:Functional groups