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{{Short description|Organic ring compound with the formula (CH2)2NH}}
{{chembox
{{Chembox
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 443409998
| verifiedrevid = 443409998
| ImageFileL1 = Aziridine.svg
| ImageFileL1 = Aziridine.svg
| ImageFileR1 = Aziridine3d.png
| ImageFileR1 = Aziridine3d.png
| IUPACName = Aziridine
| PIN = Aziridine
| OtherNames = Azacyclopropane, Ethylene imine, Aminoethylene, Azirane, Dimethyleneimine, Dimethylenimine, Ethylimine
| SystematicName = Azacyclopropane
|Section1={{Chembox Identifiers
| OtherNames = Azirane<br />Ethylenimine <br />Aminoethylene <br />Dimethyleneimine <br />Dimethylenimine <br />Ethylimine
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8682
| ChemSpiderID = 8682
Line 32: Line 34:
| SMILES = C1CN1
| SMILES = C1CN1
}}
}}
|Section2={{Chembox Properties
| Section2 = {{Chembox Properties
| C=2 | H=5 | N=1
| C=2 | H=5 | N=1
| Appearance = Clear colorless oily liquid<ref>{{cite book |chapter=Aziridine |chapter-url=http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-12.pdf |title=Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=71 |year=1999 |url=http://monographs.iarc.fr/ENG/Monographs/vol71/index.php }}</ref>
| Appearance = Colorless oily liquid<ref>{{cite book |chapter=Aziridine |chapter-url=http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-12.pdf |title=Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=71 |year=1999 |url=http://monographs.iarc.fr/ENG/Monographs/vol71/index.php }}</ref>
| Odor = ammonia-like<ref name=PGCH/>
| Odor = ammonia-like<ref name=PGCH/>
| Density = 0.8321 g/mL 20 °C<ref>{{cite book |author= Weast, Robert C.|title=CRC Handbook of Chemistry and Physics |edition=59th |year=1978 |publisher=CRC Press |location=West Palm Beach, FL |id={{Listed Invalid ISBN|0-8493-0549-7}} |display-authors=etal}}</ref>
| Density = 0.8321 g/mL 20 °C<ref>{{cite book |author= Weast, Robert C.|title=CRC Handbook of Chemistry and Physics |url= https://archive.org/details/crchandbookofche00clev|url-access= registration|edition=59th |year=1978 |publisher=CRC Press |location=West Palm Beach, FL |id={{Listed Invalid ISBN|0-8493-0549-7}} |display-authors=etal}}</ref>
| MeltingPtC = −77.9
| MeltingPtC = −77.9
| BoilingPtC = 56
| BoilingPtC = 56
| Solubility = miscible
| Solubility = miscible
| VaporPressure = 160 mmHg (20° C)<ref name=PGCH/>
| VaporPressure = 160 mmHg (20°C)<ref name=PGCH/>
}}
}}
|Section3={{Chembox Hazards
| Section3 = {{Chembox Hazards
| MainHazards = highly flammable and toxic
| MainHazards = highly flammable and toxic
| NFPA-H = 4
| NFPA-H = 4
Line 49: Line 51:
| GHSPictograms = {{GHS02}}{{GHS05}}{{GHS06}}{{GHS08}}{{GHS09}}
| GHSPictograms = {{GHS02}}{{GHS05}}{{GHS06}}{{GHS08}}{{GHS09}}
| GHSSignalWord = Danger
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|225|300|310|314|318|330|340|350|411}}
| HPhrases = {{H-phrases|225|300|310|314|330|340|350|411}}
| PPhrases = {{P-phrases|201|202|210|233|240|241|242|243|260|262|264|270|271|273|280|281|284|301+310|301+330+331|302+350|303+361+353|304+340|305+351+338|308+313|310|320|321|322|330|361|363|370+378|391|403+233|403+235|405|501}}
| PPhrases = {{P-phrases|201|202|210|233|240|241|242|243|260|262|264|270|271|273|280|281|284|301+310|301+330+331|302+350|303+361+353|304+340|305+351+338|308+313|310|320|321|322|330|361|363|370+378|391|403+233|403+235|405|501}}
| FlashPtC = -11
| FlashPtC = -11
Line 60: Line 62:
| LC50 = 250 ppm (rat, 1 hr)<br/>250 ppm (guinea pig, 1 hr)<br/>62 ppm (rat, 4 hr)<br/>223 ppm (mouse, 2 hr)<br/>56 ppm (rat, 2 hr)<br/>2236 ppm (mouse, 10 min)<ref name=IDLH/>
| LC50 = 250 ppm (rat, 1 hr)<br/>250 ppm (guinea pig, 1 hr)<br/>62 ppm (rat, 4 hr)<br/>223 ppm (mouse, 2 hr)<br/>56 ppm (rat, 2 hr)<br/>2236 ppm (mouse, 10 min)<ref name=IDLH/>
}}
}}
|Section8={{Chembox Related
| Section8 = {{Chembox Related
| OtherFunction = [[Borirane]]<br />[[Ethylene oxide]]<br />[[Thiirane]]
| OtherFunction = [[Borirane]]<br />[[Ethylene oxide]]<br />[[Thiirane]]
| OtherFunction_label = heterocycles
| OtherFunction_label = heterocycles
Line 67: Line 69:
}}
}}


{{for|the general class|Aziridines}}
'''Aziridines''' are [[organic compound]]s containing the aziridine [[functional group]], a three-membered [[heterocycle]] with one [[amine|amine group]] (-NH-) and two [[methylene bridge]]s (-{{chem|CH|2}}-).<ref>{{cite book |author=Gilchrist, T.L. |title=Heterocyclic chemistry |isbn=978-0-582-01421-3 }}</ref><ref>''Epoxides and aziridines – A mini review'' Albert Padwaa and S. Shaun Murphreeb [[Arkivoc]] (JC-1522R) pp. 6–33 [http://www.arkat-usa.org/ark/journal/2006/I03_Coxon/1522/JC-1522R.asp Online article]</ref> The parent compound is '''aziridine''' (or ethylene imine), with [[molecular formula]] {{chem|C|2|H|5|N}}.

'''Aziridine''' is an [[organic compound]] consisting of the three-membered [[heterocycle]] {{chem2|C2H5N}}.<ref>{{cite book |author=Gilchrist, T.L. |title=Heterocyclic chemistry |year=1987 |publisher=Longman Scientific & Technical |isbn=978-0-582-01421-3 }}</ref><ref>''Epoxides and aziridines – A mini review'' Albert Padwa, S. Shaun Murphree [[Arkivoc]] (JC-1522R) pp. 6–33 [http://www.arkat-usa.org/ark/journal/2006/I03_Coxon/1522/JC-1522R.asp Online article]</ref> It is a colorless, toxic, volatile liquid that is of significant practical interest.<ref name=Ullmann>{{Ullmann|doi=10.1002/14356007.a03_239.pub2|title=Aziridines|year=2006|last1=Steuerle|first1=Ulrich|last2=Feuerhake|first2=Robert|isbn=3527306730}}</ref> Aziridine was discovered in 1888 by the chemist [[Siegmund Gabriel]].<ref>{{Cite journal|last=Gabriel|first=S.|date=1888|title=Ueber Vinylamin und Bromäthylamin. (II.)|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/cber.18880210287|journal=Berichte der Deutschen Chemischen Gesellschaft|language=en|volume=21|issue=2|pages=2664–2669|doi=10.1002/cber.18880210287|issn=1099-0682}}</ref> Its derivatives, also referred to as [[aziridines]], are of broader interest in medicinal chemistry.


== Structure ==
== Structure ==
The [[bond angle]]s in aziridine are approximately 60°, considerably less than the normal [[hydrocarbon]] bond angle of 109.5°, which results in [[Ring strain|angle strain]] as in the comparable [[cyclopropane]] and [[ethylene oxide]] molecules. A [[banana bond]] model explains bonding in such compounds. Aziridine is less [[base (chemistry)|basic]] than [[Open chain compound|acyclic]] [[aliphatic]] amines, with a [[pKa]] of 7.9 for the [[conjugate acid]], due to increased [[orbital hybridization|s character]] of the [[nitrogen]] [[free electron pair]]. [[Angle strain]] in aziridine also increases the barrier to [[nitrogen inversion]]. This barrier height permits the isolation of separate ''invertomers'', for example the [[cis isomer|''cis'']] and [[trans isomer|''trans'']] invertomers of ''N''-chloro-2-methylaziridine.
The [[bond angle]]s in aziridine are approximately 60°, considerably less than the normal [[hydrocarbon]] bond angle of 109.5°, which results in [[Ring strain|angle strain]] as in the comparable [[cyclopropane]] and [[ethylene oxide]] molecules. A [[banana bond]] model explains bonding in such compounds. Aziridine is less [[base (chemistry)|basic]] than [[Open chain compound|acyclic]] [[aliphatic]] amines, with a [[pKa]] of 7.9 for the [[conjugate acid]], due to increased [[orbital hybridization|s character]] of the [[nitrogen]] [[free electron pair]]. [[Angle strain]] in aziridine also increases the barrier to [[nitrogen inversion]]. This barrier height permits the isolation of separate ''invertomers'', for example the [[cis isomer|''cis'']] and [[trans isomer|''trans'']] invertomers of ''N''-chloro-2-methylaziridine.


== Synthesis and uses==
== Synthesis ==<!-- This section is linked from [[Organic reaction]] -->
{{multiple image
There are several [[organic synthesis|syntheses]] of aziridines ('''aziridination''').
| align = left
| direction = vertical
| width = 230
| image1 = Linear PEI.png
| caption1 = Linear [[polyethylenimine]] (PEI) fragment, derived from aziridine.
| image2 = Branched PEI.png
| caption2 = Typical branched PEI fragment, derived from aziridine.
| background color = #FFFFFF
}}
Aziridine is produced industrially from [[aminoethanol]] via two related routes. The Nippon Shokubai process requires an oxide catalyst and high temperatures to effect the dehydration. In the [[Wenker synthesis]], the aminoethanol is converted to the [[sulfate ester]], which undergoes base-induced sulfate elimination. Older methods entailed amination of 1,2-dichloroethane and cyclization of 2-chloroethylamine.<ref name=Ullmann/>


Aziridine forms a wide variety of polymeric derivatives, known as [[polyethylenimine]]s (PEI). These and related species are useful [[crosslinking agent]]s and precursors for coatings.<ref name=Ullmann/>
=== Cyclization of haloamines and amino alcohols ===
An [[amine]] functional group displaces the adjacent [[halide]] in an [[intramolecular]] [[nucleophilic substitution]] reaction to generate an aziridine. Amino alcohols have the same reactivity, but the [[Hydroxyl|hydroxy]] group must first be converted into a good [[leaving group]]. The cyclization of an amino alcohol is called a [[Wenker synthesis]] (1935), and that of a haloamine the '''Gabriel ethylenimine method''' (1888).{{citation needed|date=September 2015}}


==Safety==
=== Nitrene addition ===
Aziridine is highly toxic with an [[LD50|LD<sub>50</sub>]] of 14 mg (oral, rats). It is a skin irritant. As an [[alkylation|alkylating agent]], it is also a mutagen.<ref name=Ullmann/> It is reactive toward DNA, potentially relevant to its mutagenicity. Aziridine containing compounds also appear to be similarly dangerous.<ref>{{cite journal |vauthors=Kanerva L, Keskinen H, Autio P, Estlander T, Tuppurainen M, Jolanki R |title=Occupational respiratory and skin sensitization caused by polyfunctional aziridine hardener |journal=Clin Exp Allergy |volume=25 |issue=5 |pages=432–9 |date=May 1995 |pmid=7553246 |doi=10.1111/j.1365-2222.1995.tb01074.x |s2cid=28101810 }}</ref><ref>{{cite journal |vauthors=Sartorelli P, Pistolesi P, Cioni F, Napoli R, Sisinni AG, Bellussi L, Passali GC, Cherubini Di Simplicio E, Flori L |title=Skin and respiratory allergic disease caused by polyfunctional aziridine |journal=Med Lav |volume=94 |issue=3 |pages=285–95 |year=2003 |pmid=12918320 }}</ref><ref>{{cite journal |author=Mapp CE |title=Agents, old and new, causing occupational asthma |journal=Occup. Environ. Med. |volume=58 |pages=354–60 |year=2001 |pmid=11303086 |doi=10.1136/oem.58.5.354 |issue=5 |pmc=1740131 }}</ref>
[[Nitrene]] addition to [[alkene]]s is a well-established method for the synthesis of aziridines. [[Photolysis]] or [[thermolysis]] of [[azide]]s are good ways to generate nitrenes. Nitrenes can also be prepared ''in situ'' from [[iodosobenzene diacetate]] and [[Sulfonamide (chemistry)|sulfonamide]]s, or the ethoxycarbonylnitrene from the ''N''-sulfonyloxy precursor.<ref>{{cite journal |author=M. Antonietta Loreto |author2=Lucio Pellacani |author3=Paolo A. Tardella|author4=Elena Toniato |title=Addition reactions of ethoxycarbonylnitrene and ethoxycarbonylnitrenium ion to allylic ethers |journal=Tetrahedron Letters |volume=25 |issue=38 |pages=4271–4 |year=1984 |url=http://www.sciencedirect.com/science?_ob=ArticleURL&_aset=V-WA-A-W-AV-MsSAYZW-UUW-U-AAWZCZYECB-AAWVAVEDCB-WYWCZUAZV-AV-U&_rdoc=11&_fmt=summary&_udi=B6THS-42H2CKG-1YM&_coverDate=12%2F31%2F1984&_cdi=5290&_orig=search&_st=13&_sort=d&view=c&_acct=C000051225&_version=1&_urlVersion=0&_userid=1065764&md5=781fe50f70e6397001e321945b9fd3db |archive-url=https://archive.today/20120909011017/http://www.sciencedirect.com/science?_ob=ArticleURL&_aset=V-WA-A-W-AV-MsSAYZW-UUW-U-AAWZCZYECB-AAWVAVEDCB-WYWCZUAZV-AV-U&_rdoc=11&_fmt=summary&_udi=B6THS-42H2CKG-1YM&_coverDate=12/31/1984&_cdi=5290&_orig=search&_st=13&_sort=d&view=c&_acct=C000051225&_version=1&_urlVersion=0&_userid=1065764&md5=781fe50f70e6397001e321945b9fd3db |dead-url=yes |archive-date=2012-09-09 |doi=10.1016/S0040-4039(01)81414-3}}</ref>

[[File:Nitreneaddition.png|center|450px|Nitrene addition]]

*The nitrogen lacks its lone pair ":N:", and should be shown for a nitrene.

=== Triazoline decomposition ===
Thermal treatment or photolysis of [[triazoline]]s expels [[nitrogen]], producing an aziridine. Triazolines can be generated by [[cycloaddition]] of [[alkene]]s with an [[azide]].

===From epoxides===
One method involves the [[ring-opening reaction]] of an [[epoxide]] with [[sodium azide]], followed by [[organic reduction]] of the [[azide]] with [[triphenylphosphine]] accompanied by expulsion of nitrogen gas:<ref>{{cite journal |author=Ryan Hili |author2=Andrei K. Yudin |title=Readily Available Unprotected Amino Aldehydes |journal=[[J. Am. Chem. Soc.]] |volume=128 |issue=46 |pages=14772–3 |year=2006 |doi=10.1021/ja065898s |pmid=17105264 }}</ref>

[[File:AziridineSynthesisFromEpoxide.png|center|500px|Aziridine synthesis Hili 2006]]

The other method involves the [[ring-opening reaction]] of an [[epoxide]] with [[amine]]s, followed by ring closing with the [[Mitsunobu reaction]].<ref>{{cite journal |author=B. Pulipaka |author2=Stephen C. Bergmeier |title= Synthesis of Hexahydro-1 H -benzo[ c ]chromen-1-amines via the Intramolecular Ring-Opening Reof Aziridines by π-Nucleophiles |journal=Synthesis |issue=9 |pages=1420–30 |year=2008 | doi = 10.1055/s-2008-1072561 |volume=2008}}</ref>

===From oximes===
The '''Hoch-Campbell ethylenimine (Aziridine) synthesis''' is the reaction of certain [[oxime]]s with [[Grignard reagent]]s:<ref>Hoch, Compt. rend., 196, 1865 ('''1934'''); (a), ibid., aOS, 799 (1936); (e), ibid., 204, 358 (1937).</ref><ref>{{cite journal |author=Kenneth N. Campbell |author2=James F. Mckenna |title=The action of Grignard reagents on oximes. i. The action of phenylmagnesium bromide on mixed ketoximes |journal=[[J. Org. Chem.]] |volume=4 |issue=2 |pages=198–205 |year=1939 |doi=10.1021/jo01214a012 }}</ref><ref>{{cite journal |author=Kenneth N. Campbell |author2=Barbara Knapp Campbell |author3=Elmer Paul Chaput |title=The reaction of Grignard reagents with oximes. ii. The action of aryl grignard reagents with mixed ketoximes |journal=[[J. Org. Chem.]] |volume=8 |issue=1 |pages=99–102 |year=1943 |doi=10.1021/jo01189a015 }}</ref><ref>{{cite journal |author=Kenneth N. Campbell |author2=Barbara K. Campbell |author3=James F. Mckenna|author4=Elmer Paul Chaput |title=The action of Grignard reagents on oximes. iii. The mechanism of the action of arylmagnesium halides on mixed ketoximes. A new synthesis of ethyleneimines |journal=[[J. Org. Chem.]] |pages=103–9 |year=1943 |doi=10.1021/jo01189a016 |volume=8 }}</ref>
[[File:Hoch-Campbell Ethylenimine Synthesis.svg|center|Hoch-Campbell Ethylenimine Synthesis]]

===From alkenes using DPH===
In 2014, a new method was described to produce aziridines by reacting a mono-, di-, tri- or tetra- substituted alkene (olefin) with O-(2,4-dinitrophenyl)hydroxylamine (DPH) via homogeneous rhodium catalysis, alone. This method is operationally simple (i.e., [[one-pot synthesis|one-pot]]) with excellent yield.

Alkene + DPH <math>\xrightarrow{Rh_2(CO_2R)_4}</math> Aziridine

For instance, Ph-Aziridine-Me can be synthesyzed by this method and then converted by [[#Nucleophilic ring opening|ring opening reaction]] to (D)-amphetamine and (L)-amphetamine (the two active ingredients in [[Adderall]]).<ref>{{Cite journal|last=Jat|first=Jawahar L.|last2=Paudyal|first2=Mahesh P.|last3=Gao|first3=Hongyin|last4=Xu|first4=Qing-Long|last5=Yousufuddin|first5=Muhammed|last6=Devarajan|first6=Deepa|last7=Ess|first7=Daniel H.|last8=Kürti|first8=László|last9=Falck|first9=John R.|date=2014-01-03|title=Direct Stereospecific Synthesis of Unprotected N-H and N-Me Aziridines from Olefins|url=http://science.sciencemag.org/content/343/6166/61|journal=Science|language=en|volume=343|issue=6166|pages=61–65|doi=10.1126/science.1245727|issn=0036-8075|pmc=4175444|pmid=24385626}}</ref>

== Reactions ==<!-- This section is linked from [[Organic reaction]] -->

=== Nucleophilic ring opening ===
Aziridines are reactive substrates in ring-opening reactions with many [[nucleophile]]s due to their [[ring strain]]. Alcoholysis and aminolysis are basically the reverse reactions of the cyclizations. Carbon nucleophiles such as [[organolithium reagent]]s and [[organocuprate]]s are also effective.

One application of a ring-opening reaction in [[asymmetric synthesis]] is that of [[trimethylsilylazide]] {{chem|TMSN|3}} with an asymmetric ligand<ref>{{cite journal |author=Yuhei Fukuta |author2=Tsuyoshi Mita |author3=Nobuhisa Fukuda|author4=Motomu Kanai |author5=Masakatsu Shibasaki |title=De Novo Synthesis of Tamiflu via a Catalytic Asymmetric Ring-Opening of meso-Aziridines with TMSN3 |journal=[[J. Am. Chem. Soc.]] |volume=128 |issue=19 |pages=6312–3 |year=2006 |doi=10.1021/ja061696k |pmid=16683784 }}</ref> in ''scheme 2''<ref>The catalyst is based on [[yttrium]] with three [[isopropyloxy]] [[substituent]]s and the [[ligand]] a [[phosphine oxide]] (Ph = [[phenyl]]), with 91% [[enantiomeric excess]] (ee)</ref> in an [[organic synthesis]] of [[Oseltamivir total synthesis|oseltamivir]]:

[[File:TamifluSynthesisII.png|center|600px|Scheme 2. Synthesis of Tamiflu via a Catalytic Asymmetric Ring-Opening of meso-Aziridines with TMSN3]]

===1,3-dipole formation===
Certain N-substituted azirines with [[electron withdrawing group]]s on both carbons form [[azomethine ylide]]s in an [[electrocyclic reaction|electrocyclic]] thermal or photochemical [[ring-opening reaction]].<ref>{{cite journal |author=Harold W. Heine |author2=Richard Peavy |title=Aziridines XI. Reaction of 1,2,3-triphenylaziridine with diethylacetylene dicarboxylate and maleic anhydride |journal=[[Tetrahedron Letters]] |volume=6 |issue=35 |pages=3123–6 |year=1965 |doi=10.1016/S0040-4039(01)89232-7 |title-link=maleic anhydride }}</ref><ref>{{cite journal |author=Albert Padwa |author2=Lewis Hamilton |title=Reactions of aziridines with dimethylacetylene dicarboxylate |journal=[[Tetrahedron Letters]] |volume=6 |issue=48 |pages=4363–7 |year=1965 |doi=10.1016/S0040-4039(00)71101-4 }}</ref> These ylides can be trapped with a suitable [[dipolarophile]] in a [[1,3-dipolar cycloaddition]].<ref>{{cite journal |author=Philippe Dauban |author2=Guillaume Malik |title=A Masked 1,3-Dipole Revealed from Aziridines |journal=[[Angew. Chem. Int. Ed.]] |year=2009 |doi=10.1002/anie.200904941 |volume=48 |issue=48 |pages=9026–9 |pmid=19882612}}</ref>

:[[File:Aziridine ring opening.svg|665px|Aziridine ring opening]]

When the N-substituent is an [[electron-withdrawing group]] such as a [[tosyl]] group, the [[carbon-nitrogen bond]] breaks, forming another [[zwitterion]] {{chem|TsN|-|–CH|2|–CH|2|+|–R}}<ref>{{cite journal |author=Ioana Ungureanua |author2=Cristian Bologab |author3=Saïd Chayera|author4=André Mann |title=Phenylaziridine as a 1,3-dipole. Application to the synthesis of functionalized pyrrolidines |journal=[[Tetrahedron Letters]] |volume=40 |issue=29 |pages=5315–8 |date=16 July 1999 |doi=10.1016/S0040-4039(99)01002-3 }}</ref>

:[[File:2-phenyl-N-tosyl-aziridine cycloadditions.svg|566px|2-phenyl-N-tosyl-aziridine cycloadditions]]

This reaction type requires a [[Lewis acid]] catalyst such as [[boron trifluoride]]. In this way 2-phenyl-''N''-tosylaziridine reacts with alkynes, [[nitrile]]s, [[ketone]]s and [[alkene]]s. Certain 1,4-dipoles form from [[azetidine]]s.

===Other===
N-unsubstituted [[aziridines]] can be opened with [[olefins]] in the presence of strong Lewis acid B({{chem||C|6|F|5}}{{chem|)|3}}.<ref>{{cite journal |author=Aravinda B. Pulipaka |author2=Stephen C. Bergmeier |title=A Synthesis of 6-Azabicyclo[3.2.1]octanes. The Role of N-Substitution |journal=[[J. Org. Chem.]] |volume=73 |issue=4 |pages=1462–7 |year=2008 |doi=10.1021/jo702444c |pmid=18211092 }}</ref>

==Human toxicology==

The toxicology of a particular aziridine compound depends on its structure and activity, although sharing the general characteristics of aziridines. As [[electrophile]]s, aziridines are subject to attack and ring-opening by endogenous nucleophiles such as nitrogenous bases in DNA base pairs, resulting in potential mutagenicity.<ref>{{cite journal |vauthors=Kanerva L, Keskinen H, Autio P, Estlander T, Tuppurainen M, Jolanki R |title=Occupational respiratory and skin sensitization caused by polyfunctional aziridine hardener |journal=Clin Exp Allergy |volume=25 |issue=5 |pages=432–9 |date=May 1995 |pmid=7553246 |doi=10.1111/j.1365-2222.1995.tb01074.x }}</ref><ref>{{cite journal |vauthors=Sartorelli P, Pistolesi P, Cioni F, Napoli R, Sisinni AG, Bellussi L, Passali GC, Cherubini Di Simplicio E, Flori L |title=Skin and respiratory allergic disease caused by polyfunctional aziridine |journal=Med Lav |volume=94 |issue=3 |pages=285–95 |year=2003 |pmid=12918320 }}</ref><ref>{{cite journal |author=Mapp CE |title=Agents, old and new, causing occupational asthma |journal=Occup. Environ. Med. |volume=58 |pages=354–60 |year=2001 |pmid=11303086 |doi=10.1136/oem.58.5.354 |issue=5 |pmc=1740131 }}</ref>

===Exposure===

Inhalation and direct contact are exposure routes.
Some reports note that the use of gloves has not prevented permeation of aziridine. It is therefore important that users check the breakthrough permeation times for gloves, and pay scrupulous attention to avoiding contamination when degloving. Workers handling azidrine are expected to be provided with, and required to wear and use, a half-mask filter-type respirator for dusts, mists and fumes.<ref>[https://www.cdc.gov/niosh/npg/nengapdxe.html Appendix E - OSHA Respirator Requirements for Selected Chemicals]</ref>

There is relatively little human exposure data on aziridine. This is because it is considered extremely dangerous. In industrial settings, class A pressure suits are preferred when exposure is possible.

===Carcinogenicity===

The [[International Agency for Research on Cancer]] (IARC) has reviewed aziridine compounds and classified them as possibly [[carcinogenic]] to humans ([[List of IARC Group 2B carcinogens|IARC Group 2B]]).<ref>{{cite book |title=Some Aziridines, N-, S- and O-Mustards and Selenium |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=9 |year=1975 |isbn=978-92-832-1209-6 |format=PDF |url= http://monographs.iarc.fr/ENG/Monographs/vol9/volume9.pdf}}</ref> In making the overall evaluation, the IARC Working Group took into consideration that aziridine is a direct-acting [[alkylating agent]] which is [[mutagenic]] in a wide range of test systems and forms DNA adducts that are promutagenic.

'''Irritancy'''

Aziridines are irritants of mucosal surfaces including eyes, nose, respiratory tract and skin.

'''Sensitization'''

Aziridine rapidly penetrates skin on contact.

Skin sensitizer — causing allergic contact dermatitis and [[urticaria]].

Respiratory sensitiser — causing occupational asthma


== See also ==
== See also ==
Line 161: Line 99:
== References ==
== References ==
{{reflist|30em}}
{{reflist|30em}}

{{Commonscat}}


[[Category:Functional groups]]
[[Category:Functional groups]]
[[Category:IARC Group 2B carcinogens]]
[[Category:IARC Group 2B carcinogens]]
[[Category:Aziridines]]
[[Category:Aziridines]]
[[Category:Substances discovered in the 19th century]]

Latest revision as of 13:57, 17 June 2024

Aziridine
Names
Preferred IUPAC name
Aziridine
Systematic IUPAC name
Azacyclopropane
Other names
Azirane
Ethylenimine
Aminoethylene
Dimethyleneimine
Dimethylenimine
Ethylimine
Identifiers
3D model (JSmol)
102380
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.268 Edit this at Wikidata
EC Number
  • 205-793-9
616
KEGG
RTECS number
  • KX5075000
UNII
UN number 1185
  • InChI=1S/C2H5N/c1-2-3-1/h3H,1-2H2 checkY
    Key: NOWKCMXCCJGMRR-UHFFFAOYSA-N checkY
  • InChI=1/C2H5N/c1-2-3-1/h3H,1-2H2
    Key: NOWKCMXCCJGMRR-UHFFFAOYAE
  • C1CN1
Properties
C2H5N
Molar mass 43.069 g·mol−1
Appearance Colorless oily liquid[1]
Odor ammonia-like[2]
Density 0.8321 g/mL 20 °C[3]
Melting point −77.9 °C (−108.2 °F; 195.2 K)
Boiling point 56 °C (133 °F; 329 K)
miscible
Vapor pressure 160 mmHg (20°C)[2]
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 highly flammable and toxic
GHS labelling:
GHS02: FlammableGHS05: CorrosiveGHS06: ToxicGHS08: Health hazardGHS09: Environmental hazard
Danger
H225, H300, H310, H314, H330, H340, H350, H411
P201, P202, P210, P233, P240, P241, P242, P243, P260, P262, P264, P270, P271, P273, P280, P281, P284, P301+P310, P301+P330+P331, P302+P350, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P310, P320, P321, P322, P330, P361, P363, P370+P378, P391, P403+P233, P403+P235, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 4: Very short exposure could cause death or major residual injury. E.g. VX gasFlammability 3: Liquids and solids that can be ignited under almost all ambient temperature conditions. Flash point between 23 and 38 °C (73 and 100 °F). E.g. gasolineInstability 3: Capable of detonation or explosive decomposition but requires a strong initiating source, must be heated under confinement before initiation, reacts explosively with water, or will detonate if severely shocked. E.g. hydrogen peroxideSpecial hazards (white): no code
4
3
3
Flash point −11 °C (12 °F; 262 K)
322 °C (612 °F; 595 K)
Explosive limits 3.6–46%
Lethal dose or concentration (LD, LC):
250 ppm (rat, 1 hr)
250 ppm (guinea pig, 1 hr)
62 ppm (rat, 4 hr)
223 ppm (mouse, 2 hr)
56 ppm (rat, 2 hr)
2236 ppm (mouse, 10 min)[4]
25 ppm (guinea pig, 8 hr)
56 ppm (rabbit, 2 hr)[4]
NIOSH (US health exposure limits):
PEL (Permissible)
 OSHA-Regulated Carcinogen[2]
REL (Recommended)
 Ca[2]
IDLH (Immediate danger)
 Ca [100 ppm][2]
Related compounds
Related heterocycles
 Borirane
Ethylene oxide
Thiirane
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
For the general class, see Aziridines.

Aziridine is an organic compound consisting of the three-membered heterocycle C2H5N.[5][6] It is a colorless, toxic, volatile liquid that is of significant practical interest.[7] Aziridine was discovered in 1888 by the chemist Siegmund Gabriel.[8] Its derivatives, also referred to as aziridines, are of broader interest in medicinal chemistry.

Structure

[edit]

The bond angles in aziridine are approximately 60°, considerably less than the normal hydrocarbon bond angle of 109.5°, which results in angle strain as in the comparable cyclopropane and ethylene oxide molecules. A banana bond model explains bonding in such compounds. Aziridine is less basic than acyclic aliphatic amines, with a pKa of 7.9 for the conjugate acid, due to increased s character of the nitrogen free electron pair. Angle strain in aziridine also increases the barrier to nitrogen inversion. This barrier height permits the isolation of separate invertomers, for example the cis and trans invertomers of N-chloro-2-methylaziridine.

Synthesis and uses

[edit]
Linear polyethylenimine (PEI) fragment, derived from aziridine.
Typical branched PEI fragment, derived from aziridine.

Aziridine is produced industrially from aminoethanol via two related routes. The Nippon Shokubai process requires an oxide catalyst and high temperatures to effect the dehydration. In the Wenker synthesis, the aminoethanol is converted to the sulfate ester, which undergoes base-induced sulfate elimination. Older methods entailed amination of 1,2-dichloroethane and cyclization of 2-chloroethylamine.[7]

Aziridine forms a wide variety of polymeric derivatives, known as polyethylenimines (PEI). These and related species are useful crosslinking agents and precursors for coatings.[7]

Safety

[edit]

Aziridine is highly toxic with an LD50 of 14 mg (oral, rats). It is a skin irritant. As an alkylating agent, it is also a mutagen.[7] It is reactive toward DNA, potentially relevant to its mutagenicity. Aziridine containing compounds also appear to be similarly dangerous.[9][10][11]

See also

[edit]

References

[edit]
  1. ^ "Aziridine" (PDF). Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 71. 1999.
  2. ^ a b c d e NIOSH Pocket Guide to Chemical Hazards. "#0274". National Institute for Occupational Safety and Health (NIOSH).
  3. ^ Weast, Robert C.; et al. (1978). CRC Handbook of Chemistry and Physics (59th ed.). West Palm Beach, FL: CRC Press. ISBN 0-8493-0549-7.
  4. ^ a b "Ethyleneimine". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  5. ^ Gilchrist, T.L. (1987). Heterocyclic chemistry. Longman Scientific & Technical. ISBN 978-0-582-01421-3.
  6. ^ Epoxides and aziridines – A mini review Albert Padwa, S. Shaun Murphree Arkivoc (JC-1522R) pp. 6–33 Online article
  7. ^ a b c d Steuerle, Ulrich; Feuerhake, Robert (2006). "Aziridines". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a03_239.pub2. ISBN 3527306730.
  8. ^ Gabriel, S. (1888). "Ueber Vinylamin und Bromäthylamin. (II.)". Berichte der Deutschen Chemischen Gesellschaft. 21 (2): 2664–2669. doi:10.1002/cber.18880210287. ISSN 1099-0682.
  9. ^ Kanerva L, Keskinen H, Autio P, Estlander T, Tuppurainen M, Jolanki R (May 1995). "Occupational respiratory and skin sensitization caused by polyfunctional aziridine hardener". Clin Exp Allergy. 25 (5): 432–9. doi:10.1111/j.1365-2222.1995.tb01074.x. PMID 7553246. S2CID 28101810.
  10. ^ Sartorelli P, Pistolesi P, Cioni F, Napoli R, Sisinni AG, Bellussi L, Passali GC, Cherubini Di Simplicio E, Flori L (2003). "Skin and respiratory allergic disease caused by polyfunctional aziridine". Med Lav. 94 (3): 285–95. PMID 12918320.
  11. ^ Mapp CE (2001). "Agents, old and new, causing occupational asthma". Occup. Environ. Med. 58 (5): 354–60. doi:10.1136/oem.58.5.354. PMC 1740131. PMID 11303086.
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