Alkyl nitrite: Difference between revisions
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{{Short description|1=Organic compounds of the form R–O–N=O}} |
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{{About|alkyl nitrites |
{{About|alkyl nitrites in chemical synthesis|their use in medicine and as a recreational drug|Poppers}} |
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[[File:Nitrite- |
[[File:Nitrite-group-2D.svg|200px|General formula of alkyl nitrites|alt=alkyl nitrites|thumb]] |
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''' |
In [[organic chemistry]], '''alkyl nitrites''' are a group of [[organic compound]]s based upon the [[molecular structure]] {{chem2|R\sO\sN\dO}}, where R represents an [[alkyl group]]. Formally they are alkyl [[ester]]s of [[nitrous acid]]. They are distinct from [[nitro compound]]s ({{chem2|R\sNO2}}). |
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The first few members of the series are [[Volatility (chemistry)|volatile]] liquids; [[methyl nitrite]] and [[ethyl nitrite]] are gaseous at room temperature and pressure. The compounds have a distinctive fruity odor. Another frequently encountered nitrite is [[amyl nitrite]] (3-methylbutyl nitrite). |
The first few members of the series are [[Volatility (chemistry)|volatile]] liquids; [[methyl nitrite]] and [[ethyl nitrite]] are gaseous at room temperature and pressure. The compounds have a distinctive fruity odor. Another frequently encountered nitrite is [[amyl nitrite]] (3-methylbutyl nitrite). |
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Alkyl nitrites were initially, and largely still are, used as [[medication]]s and [[chemical reagent]]s, a practice which began in the late 19th century. In their use as medicine, they are often inhaled for relief of [[angina]] and other heart-related symptoms of disease. However, when referred to as " |
Alkyl nitrites were initially, and largely still are, used as [[medication]]s and [[chemical reagent]]s, a practice which began in the late 19th century. In their use as medicine, they are often inhaled for relief of [[angina]] and other heart-related symptoms of disease. However, when referred to as "''[[poppers]]''", alkyl nitrites represent [[recreational drug]]s. |
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== Synthesis and properties == |
== Synthesis and properties == |
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| ⚫ | Organic nitrites are prepared from [[Alcohol (chemistry)|alcohol]]s and [[sodium nitrite]] in [[sulfuric acid]] [[Solution (chemistry)|solution]]. They decompose slowly on standing, the decomposition products being [[oxide]]s of [[nitrogen]], [[water]], the alcohol, and [[polymerization]] products of the [[aldehyde]].<ref>''n-butyl nitrite'' [[Organic Syntheses]], Coll. Vol. 2, p.108 (1943); Vol. 16, p.7 (1936). [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv2p0108 http://www.orgsynth.org/orgsyn/prep.asp?prep=cv2p0108 Link]</ref> They are also prone to undergo homolytic cleavage to form alkyl radicals, the nitrite C–O bond being very weak (on the order of 40–50 kcal ⋅ mol<sup>−1</sup>).{{cn|date=August 2024}} Alkyl nitrites are generally weak [[nitrosation|nitrosating agents]], but nitrosate amines in the presence of a nucleophile catalyst.<ref>{{cite book|title=Nitrosation|first=D. L. H.|last=Williams|publisher=[[Cambridge University Press|Cambridge University]]|location=Cambridge, UK|year=1988|isbn=0-521-26796-X|url=https://archive.org/details/nitrosation0000will|url-access=registration|p=16}}</ref> |
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[[File:Rational harm assessment of drugs radar plot.svg|thumb|Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in [[Delphi method|delphic analysis]] regarding 20 popular recreational drugs. Alkyl nitrites were ranked 20th social and physical harm, and 18th in dependence.<ref>{{cite journal|last1=Nutt|first1=D|last2=King|first2=LA|last3=Saulsbury|first3=W|last4=Blakemore|first4=C|title=Development of a rational scale to assess the harm of drugs of potential misuse.|journal=Lancet|date=24 March 2007|volume=369|issue=9566|pages=1047–53|pmid=17382831|doi=10.1016/s0140-6736(07)60464-4}}</ref>]] |
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| ⚫ | Organic nitrites are prepared from [[alcohol]]s and [[sodium nitrite]] in [[sulfuric acid]] [[solution]]. They decompose slowly on standing, the decomposition products being [[oxide]]s of [[nitrogen]], [[water]], the alcohol, and [[polymerization]] products of the [[aldehyde]].<ref>''n-butyl nitrite'' [[Organic Syntheses]], Coll. Vol. 2, p.108 (1943); Vol. 16, p.7 (1936). [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv2p0108 http://www.orgsynth.org/orgsyn/prep.asp?prep=cv2p0108 Link]</ref> They are also prone to undergo homolytic cleavage to form alkyl radicals, the nitrite C–O bond being very weak (on the order of |
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== Reactions == |
== Reactions == |
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* [[tert-Butyl nitrite|''tert''-Butyl nitrite]] has been shown to be an effective reagent for the selective nitration of [[phenols]]<ref>''Chemoselective Nitration of Phenols with tert-Butyl Nitrite in Solution and on Solid Support'' [[Organic Letters]], Coll. Vol 11, p.4172-4175 (2009)</ref> and [[Sulfonamide (chemistry)|aryl sulfonamides]]<ref>''Chemoselective Nitration of Aromatic Sulfonamides with tert-Butyl Nitrite '' [[Chemical Communications]], {{ |
* [[tert-Butyl nitrite|''tert''-Butyl nitrite]] has been shown to be an effective reagent for the selective nitration of [[phenols]]<ref>''Chemoselective Nitration of Phenols with tert-Butyl Nitrite in Solution and on Solid Support'' [[Organic Letters]], Coll. Vol 11, p.4172-4175 (2009)</ref> and [[Sulfonamide (chemistry)|aryl sulfonamides]]<ref>''Chemoselective Nitration of Aromatic Sulfonamides with tert-Butyl Nitrite '' [[Chemical Communications]], {{doi|10.1039/C2CC37481A}}</ref> |
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* [[Butyl nitrite|''n''-Butyl nitrite]] and [[ammonia]] convert [[phenylhydroxylamine]] to its [[nitrosamine]] derivative [[cupferron]].<ref>''Cupferron'' [[Organic Syntheses]], Coll. Vol. 1, p.177 (1941); Vol. 4, p.19 (1925) [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv1p0177 Link]</ref> Likewise [[pyrrolidine]] is a substrate for ethyl nitrite.<ref>''2-Pyrrolidinemethanol, α,α-diphenyl-, (±)-'' [[Organic Syntheses]], Coll. Vol. 6, p.542 (1988); Vol. 58, p.113 (1978) [http://www.orgsynth.org/orgsyn/pdfs/CV6P0542.pdf Link]</ref> |
* [[Butyl nitrite|''n''-Butyl nitrite]] and [[ammonia]] convert [[phenylhydroxylamine]] to its [[nitrosamine]] derivative [[cupferron]].<ref>''Cupferron'' [[Organic Syntheses]], Coll. Vol. 1, p.177 (1941); Vol. 4, p.19 (1925) [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv1p0177 Link]</ref> Likewise [[pyrrolidine]] is a substrate for ethyl nitrite.<ref>''2-Pyrrolidinemethanol, α,α-diphenyl-, (±)-'' [[Organic Syntheses]], Coll. Vol. 6, p.542 (1988); Vol. 58, p.113 (1978) [http://www.orgsynth.org/orgsyn/pdfs/CV6P0542.pdf Link]</ref> |
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* Alkyl nitrites are also used in the formation of [[oxime]]s with the stronger [[carbon acid]]s and acid or base catalysis for example in the reaction of [[2-butanone]], [[ethyl nitrite]] and [[hydrochloric acid]] forming the oxime,<ref>''Dimethylglyoxime'' [[Organic Syntheses]], Coll. Vol. 2, p.204 (1943); Vol. 10, p.22 (1930) [http://www.orgsynth.org/orgsyn/pdfs/CV2P0204.pdf Link]</ref> the similar reaction with [[phenacyl chloride]],<ref>''Glyoxylyl chloride, phenyl-, oxime'' [[Organic Syntheses]], Coll. Vol. 3, p.191 (1955); Vol. 24, p.25 (1944) [http://www.orgsynth.org/orgsyn/pdfs/CV3P0191.pdf Link]</ref> or the reaction of [[phenylacetonitrile]] with [[methyl nitrite]] and [[sodium hydroxide]].<ref>'' |
* Alkyl nitrites are also used in the formation of [[oxime]]s with the stronger [[carbon acid]]s and acid or base catalysis for example in the reaction of [[2-butanone]], [[ethyl nitrite]] and [[hydrochloric acid]] forming the oxime,<ref>''Dimethylglyoxime'' [[Organic Syntheses]], Coll. Vol. 2, p.204 (1943); Vol. 10, p.22 (1930) [http://www.orgsynth.org/orgsyn/pdfs/CV2P0204.pdf Link]</ref> the similar reaction with [[phenacyl chloride]],<ref>''Glyoxylyl chloride, phenyl-, oxime'' [[Organic Syntheses]], Coll. Vol. 3, p.191 (1955); Vol. 24, p.25 (1944) [http://www.orgsynth.org/orgsyn/pdfs/CV3P0191.pdf Link]</ref> or the reaction of [[phenylacetonitrile]] with [[methyl nitrite]] and [[sodium hydroxide]].<ref>{{OrgSynth|year=1979|volume=59|pages=95|doi=10.15227/orgsyn.059.0095|title=A New Reagent for ''tert''‑Butoxy­carbonylation: 2‑''tert''‑Butoxy­carbonyl­oxy­imino-2‑phenyl­acetonitrile|collvol=6|collvolpages=199|author1=Itoh Masumi|author2=Hagiwara Daijiro|author3=Kamiya Takashi}}</ref> |
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An isolated but classic example of the use of alkyl nitrites can be found in Woodward and Doering's [[quinine total synthesis]]:<ref>''The Total Synthesis of Quinine'' R. B. Woodward and W. E. Doering [[J. Am. Chem. Soc.]]; '''1945'''; 67(5) pp 860 - 874; {{ |
An isolated but classic example of the use of alkyl nitrites can be found in Woodward and Doering's [[quinine total synthesis]]:<ref>''The Total Synthesis of Quinine'' R. B. Woodward and W. E. Doering [[J. Am. Chem. Soc.]]; '''1945'''; 67(5) pp 860 - 874; {{doi|10.1021/ja01221a051}}</ref> |
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:[[File:QuinineNitriteReaction.png|400px|Key step in quinine total synthesis by Woodward / Doering]] |
:[[File:QuinineNitriteReaction.png|400px|Key step in quinine total synthesis by Woodward / Doering]] |
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:[[File:QuinineNitrateMechanism.png|400px|Reaction mechanism for ring opening]] |
:[[File:QuinineNitrateMechanism.png|400px|Reaction mechanism for ring opening]] |
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==Medical use== |
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===Antidote to cyanide poisoning=== |
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[[Amyl nitrite]] is used medically as an [[antidote]] to [[cyanide poisoning]],<ref name="Medsafe">{{cite web|title=Amyl Nitrite |work=Medsafe |publisher=New Zealand Medicines and Medical Devices Safety Authority |date=2000-05-18 |url=http://www.medsafe.govt.nz/Profs/datasheet/a/Amylnitrateinh.htm |access-date=2007-03-15 |archive-url=https://web.archive.org/web/20061111105814/http://www.medsafe.govt.nz/Profs/datasheet/a/Amylnitrateinh.htm |archive-date=2006-11-11 |url-status=dead }}</ref> The light alkyl nitrites cause the formation of [[methemoglobin]] wherein, as an effective antidote to cyanide poisoning, the methemoglobin combines with the cyanide to form nontoxic [[cyanmethemoglobin]].{{Citation needed|date=April 2014}} First responders typically carry a cyanide poison kit containing amyl nitrite. |
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==References== |
==References== |
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{{Nitric oxide signaling}} |
{{Nitric oxide signaling}} |
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{{Functional groups}} |
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{{DEFAULTSORT:Alkyl Nitrites}} |
{{DEFAULTSORT:Alkyl Nitrites}} |
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Latest revision as of 15:31, 1 September 2024
In organic chemistry, alkyl nitrites are a group of organic compounds based upon the molecular structure R−O−N=O, where R represents an alkyl group. Formally they are alkyl esters of nitrous acid. They are distinct from nitro compounds (R−NO2).
The first few members of the series are volatile liquids; methyl nitrite and ethyl nitrite are gaseous at room temperature and pressure. The compounds have a distinctive fruity odor. Another frequently encountered nitrite is amyl nitrite (3-methylbutyl nitrite).
Alkyl nitrites were initially, and largely still are, used as medications and chemical reagents, a practice which began in the late 19th century. In their use as medicine, they are often inhaled for relief of angina and other heart-related symptoms of disease. However, when referred to as "poppers", alkyl nitrites represent recreational drugs.
Synthesis and properties
[edit]Organic nitrites are prepared from alcohols and sodium nitrite in sulfuric acid solution. They decompose slowly on standing, the decomposition products being oxides of nitrogen, water, the alcohol, and polymerization products of the aldehyde.[1] They are also prone to undergo homolytic cleavage to form alkyl radicals, the nitrite C–O bond being very weak (on the order of 40–50 kcal ⋅ mol−1).[citation needed] Alkyl nitrites are generally weak nitrosating agents, but nitrosate amines in the presence of a nucleophile catalyst.[2]
Reactions
[edit]- tert-Butyl nitrite has been shown to be an effective reagent for the selective nitration of phenols[3] and aryl sulfonamides[4]
- n-Butyl nitrite and ammonia convert phenylhydroxylamine to its nitrosamine derivative cupferron.[5] Likewise pyrrolidine is a substrate for ethyl nitrite.[6]
- Alkyl nitrites are also used in the formation of oximes with the stronger carbon acids and acid or base catalysis for example in the reaction of 2-butanone, ethyl nitrite and hydrochloric acid forming the oxime,[7] the similar reaction with phenacyl chloride,[8] or the reaction of phenylacetonitrile with methyl nitrite and sodium hydroxide.[9]
An isolated but classic example of the use of alkyl nitrites can be found in Woodward and Doering's quinine total synthesis:[10]
for which they proposed this reaction mechanism:
References
[edit]- ^ n-butyl nitrite Organic Syntheses, Coll. Vol. 2, p.108 (1943); Vol. 16, p.7 (1936). http://www.orgsynth.org/orgsyn/prep.asp?prep=cv2p0108 Link
- ^ Williams, D. L. H. (1988). Nitrosation. Cambridge, UK: Cambridge University. p. 16. ISBN 0-521-26796-X.
- ^ Chemoselective Nitration of Phenols with tert-Butyl Nitrite in Solution and on Solid Support Organic Letters, Coll. Vol 11, p.4172-4175 (2009)
- ^ Chemoselective Nitration of Aromatic Sulfonamides with tert-Butyl Nitrite Chemical Communications, doi:10.1039/C2CC37481A
- ^ Cupferron Organic Syntheses, Coll. Vol. 1, p.177 (1941); Vol. 4, p.19 (1925) Link
- ^ 2-Pyrrolidinemethanol, α,α-diphenyl-, (±)- Organic Syntheses, Coll. Vol. 6, p.542 (1988); Vol. 58, p.113 (1978) Link
- ^ Dimethylglyoxime Organic Syntheses, Coll. Vol. 2, p.204 (1943); Vol. 10, p.22 (1930) Link
- ^ Glyoxylyl chloride, phenyl-, oxime Organic Syntheses, Coll. Vol. 3, p.191 (1955); Vol. 24, p.25 (1944) Link
- ^ Itoh Masumi; Hagiwara Daijiro; Kamiya Takashi (1979). "A New Reagent for tert‑Butoxycarbonylation: 2‑tert‑Butoxycarbonyloxyimino-2‑phenylacetonitrile". Organic Syntheses. 59: 95. doi:10.15227/orgsyn.059.0095; Collected Volumes, vol. 6, p. 199.
- ^ The Total Synthesis of Quinine R. B. Woodward and W. E. Doering J. Am. Chem. Soc.; 1945; 67(5) pp 860 - 874; doi:10.1021/ja01221a051
External links
[edit]
Media related to Alkyl nitrites at Wikimedia Commons
