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Revision as of 21:40, 6 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 13:57, 17 June 2024 edit undoAquoniumH2O4 (talk | contribs)64 editsNo edit summaryTags: Visual edit Mobile edit Mobile web edit
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			{{Short description|Organic ring compound with the formula (CH2)2NH}}
	{{chembox
			{{Chembox
	| Watchedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 410982273
			| verifiedrevid = 443409998
	| ImageFileL1 = Aziridine.svg
			| ImageFileL1 = Aziridine.svg
	| ImageSizeL1 = 100px
	| ImageFileR1 = Aziridine3d.png		| ImageFileR1 = Aziridine3d.png
			| PIN = Aziridine
	| ImageSzieR1 = 100px
			| SystematicName = Azacyclopropane
	| IUPACName = Aziridine
			| OtherNames = Azirane<br />Ethylenimine <br />Aminoethylene <br />Dimethyleneimine <br />Dimethylenimine <br />Ethylimine
	| OtherNames = Azacyclopropane, Ethylene imine
	| Section1 = {{Chembox Identifiers		| Section1 = {{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 8682		| ChemSpiderID = 8682
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
Line 23:		Line 23:
	| CASNo_Ref = {{cascite|correct|CAS}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| CASNo = 151-56-4		| CASNo = 151-56-4
	| EINECS = 205-793-9		| EINECS = 205-793-9
	| PubChem =		| PubChem = 9033
	| ChEBI = 30969		| RTECS = KX5075000
			| UNNumber = 1185
			| UNII = 54P5FEX9FH
			| Beilstein = 102380
			| Gmelin = 616
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 30969
	| SMILES = C1CN1		| SMILES = C1CN1
	}}		}}
	| Section2 = {{Chembox Properties		| Section2 = {{Chembox Properties
	| Formula = | C=2 | H=5 | N=1		| C=2 | H=5 | N=1
			| 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>
	| MolarMass =
			| Odor = ammonia-like<ref name=PGCH/>
	| 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 Evalution of Carcinogenic Risks to Humans |volume=71 |year=1999 |url=http://monographs.iarc.fr/ENG/Monographs/vol71/index.php }}</ref>
	| Density = 0.8321 g/ml 20 °C<ref>{{cite book |author= |title=CRC Handbook of Chemistry and Physics |edition=59th |isbn=0-8493-0549-8 }}</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>
	| MeltingPt = -77.9°C		| MeltingPtC = −77.9
	| BoilingPt = 56°C		| BoilingPtC = 56
	| Solubility = miscible all proportions		| Solubility = miscible
			| VaporPressure = 160 mmHg (20°C)<ref name=PGCH/>
	}}		}}
	| Section3 = {{Chembox Hazards		| Section3 = {{Chembox Hazards
	| MainHazards =		| MainHazards = highly flammable and toxic
	| FlashPt = -11°C		| NFPA-H = 4
	| Autoignition =		| NFPA-F = 3
			| NFPA-R = 3
			| GHSPictograms = {{GHS02}}{{GHS05}}{{GHS06}}{{GHS08}}{{GHS09}}
			| GHSSignalWord = Danger
			| 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}}
			| FlashPtC = -11
			| AutoignitionPtC = 322
			| ExploLimits = 3.6–46%
			| IDLH = Ca <ref name=PGCH>{{PGCH|0274}}</ref>
			| REL = Ca<ref name=PGCH/>
			| PEL = OSHA-Regulated Carcinogen<ref name=PGCH/>
			| LCLo = 25 ppm (guinea pig, 8 hr)<br/>56 ppm (rabbit, 2 hr)<ref name=IDLH>{{IDLH|151564|Ethyleneimine}}</ref>
			| 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
	| OtherFunctn = ],<br> ],<br> ]		| OtherFunction = ]<br />]<br />]
	| Function = heterocycles		| OtherFunction_label = heterocycles
	| OtherCpds =		| OtherCompounds =
	}}		}}
	}}		}}
			{{for|the general class|Aziridines}}
	'''Aziridines''' are ]s containing the aziridine ], a three-membered ] with one ] group and two ] groups.<ref>{{cite book |author=Gilchrist, T.L. |title=Heterocyclic chemistry |isbn=0-582-01421-2 }}</ref><ref>''Epoxides and aziridines - A mini review'' Albert Padwaa and S. Shaun Murphreeb ] (JC-1522R) pp 6-33 </ref> The parent compound is '''aziridine''' (or ethylene imine), with ] {{chem|C|2|H|5|N}}.
			'''Aziridine''' is an ] consisting of the three-membered ] {{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 ] (JC-1522R) pp. 6–33 </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 ].<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 ], are of broader interest in medicinal chemistry.
	== Structure ==		== Structure ==
	The ]s in aziridine are approximately 60°, considerably less than the normal ] bond angle of 109.5°, which results in ] as in the comparable ] and ] molecules. A ] model explains bonding in such compounds. Aziridine is less ] than ] ] amines, with a ] of 7.9 for the ], due to increased ] of the ] ]. ] in aziridine also increases the barrier to ]. This barrier height permits the isolation of separate '''invertomers''', for example the ] and ] invertomers of ''N''-chloro-2-methylaziridine.		The ]s in aziridine are approximately 60°, considerably less than the normal ] bond angle of 109.5°, which results in ] as in the comparable ] and ] molecules. A ] model explains bonding in such compounds. Aziridine is less ] than ] ] amines, with a ] of 7.9 for the ], due to increased ] of the ] ]. ] in aziridine also increases the barrier to ]. This barrier height permits the isolation of separate ''invertomers'', for example the ] and ] invertomers of ''N''-chloro-2-methylaziridine.
			== Synthesis and uses==
	== Synthesis ==<!-- This section is linked from ] -->
			{{multiple image
	There are several ] of aziridines.
			| align = left
			| direction = vertical
			| width = 230
			| image1 = Linear PEI.png
			| caption1 = Linear ] (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 ] via two related routes. The Nippon Shokubai process requires an oxide catalyst and high temperatures to effect the dehydration. In the ], the aminoethanol is converted to the ], 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 ]s (PEI). These and related species are useful ]s and precursors for coatings.<ref name=Ullmann/>
	=== Cyclization of haloamines and amino alcohols ===
	An ] functional group displaces the adjacent ] in an ] ] reaction to generate an aziridine. Amino alcohols have the same reactivity, but the ] group must first be converted into a good ]. The cyclization of an amino alcohol is called a ] (1935), and that of a haloamine the '''Gabriel ethylenimine method''' (1888) <ref></ref>
			==Safety==
	=== Nitrene addition ===
			Aziridine is highly toxic with an ] of 14 mg (oral, rats). It is a skin irritant. As an ], 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>
	] addition to ]s is a well-established method for the synthesis of aziridines. ] or ] of ]s are good ways to generate nitrenes. Nitrenes can also be prepared ''in situ'' from ] and ]s, or the ethoxycarbonylnitrene from the ''N''-sulfonyloxy precursor.<ref>{{cite journal |author=M. Antonietta Loreto, Lucio Pellacani, Paolo A. Tardella, 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 |doi=10.1016/S0040-4039(01)81414-3}}</ref>
			== See also ==
	]
			*], a dimeric form of aziridine
			== References ==
	=== Triazoline decomposition ===
			{{reflist|30em}}
	Thermal treatment or photolysis of ]s expels ], producing an aziridine. Triazolines can be generated by ] of ]s with an ].
			{{Commonscat}}
	===From epoxides===
	One method involves the ] of an ] with ], followed by ] of the ] with ] accompanied by expulsion of nitrogen gas:<ref>{{cite journal |author=Ryan Hili, Andrei K. Yudin |title=Readily Available Unprotected Amino Aldehydes |journal=] |volume=128 |issue=46 |pages=14772–3 |year=2006 |doi=10.1021/ja065898s }}</ref>
	]
	The other method involves the ] of an ] with ]s, followed by ring closing with the ].<ref>{{cite journal |author=B. Pulipaka, Stephen C. Bergmeier |title=Aravinda |journal=Synthesis |issue=9 |pages=1420–30 |year=2008 }}</ref>
	===From oximes===
	The '''Hoch-Campbell ethylenimine synthesis''' is the reaction of certain ]s with ]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, James F. Mckenna |title=The action of Grignard reagents on oximes. i. The action of phenylmagnesium bromide on mixed ketoximes |journal=] |volume=4 |issue=2 |pages=198–205 |year=1939 |doi=10.1021/jo01214a012 }}</ref>:<ref>{{cite journal |author=Kenneth N. Campbell, Barbara Knapp Campbell, Elmer Paul Chaput |title=The reaction of Grignard reagents with oximes. ii. The action of aryl grignard reagents with mixed ketoximes |journal=] |volume=8 |issue=1 |pages=99–102 |year=1943 |doi=10.1021/jo01189a015 }}</ref><ref>{{cite journal |author=Kenneth N. Campbell, Barbara K. Campbell, James F. Mckenna, 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=] |pages=103–9 |year=1943 |doi=10.1021/jo01189a016 |volume=8 }}</ref>
	]
	== Reactions ==<!-- This section is linked from ] -->
	=== Nucleophilic ring opening ===
	Aziridines are reactive substrates in ring-opening reactions with many ]s due to their ]. Alcoholysis and aminolysis are basically the reverse reactions of the cyclizations. Carbon nucleophiles such as ]s and ]s are also effective.
	One application of a ring-opening reaction in ] is that of ] {{chem|TMSN|3}} with an asymmetric ligand<ref>{{cite journal |author=Yuhei Fukuta, Tsuyoshi Mita, Nobuhisa Fukuda, Motomu Kanai, Masakatsu Shibasaki |title=De Novo Synthesis of Tamiflu via a Catalytic Asymmetric Ring-Opening of meso-Aziridines with TMSN3 |journal=] |volume=128 |issue=19 |pages=6312–3 |year=2006 |doi=10.1021/ja061696k }}
	</ref> in ''scheme 2''<ref>The catalyst is based on ] with three ] ]s and the ] a ] (Ph = ]), with 91% ] (ee)</ref> in an ] of ]:
	]
	===1,3-dipole formation===
	Certain N-substituted azirines with ]s on both carbons form ]s in an ] thermal or photochemical ].<ref>{{cite journal |author=Harold W. Heine, Richard Peavy |title=Aziridines XI. Reaction of 1,2,3-triphenylaziridine with diethylacetylene dicarboxylate and ] |journal=] |volume=6 |issue=35 |pages=3123–6 |year=1965 |doi=10.1016/S0040-4039(01)89232-7 }}</ref><ref>{{cite journal |author=Albert Padwa, Lewis Hamilton |title=Reactions of aziridines with dimethylacetylene dicarboxylate |journal=] |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 ] in a ].<ref>{{cite journal |author=Philippe Dauban, Guillaume Malik |title=A Masked 1,3-Dipole Revealed from Aziridines |journal=] |year=2009 |doi=10.1002/anie.200904941 |volume=48 |issue=48 |pages=9026–9 }}</ref>
	:]
	When the N-substituent is an ] such as a ] group, the ] breaks, forming another ] {{chem|TsN|-|–CH|2|–CH|2|+|–R}}<ref>{{cite journal |author=Ioana Ungureanua, Cristian Bologab, Saïd Chayera, André Mann |title=Phenylaziridine as a 1,3-dipole. Application to the synthesis of functionalized pyrrolidines |journal=] |volume=40 |issue=29 |pages=5315–8 |date=16 July 1999 |doi=10.1016/S0040-4039(99)01002-3 }}</ref>
	:]
	This reaction type requires a ] catalyst such as ]. In this way 2-phenyl-''N''-tosylaziridine reacts with alkynes, ]s, ]s and ]s. Certain 1,4-dipoles form from ]s.
	===Other===
	N-unsubstituted ] can be opened with ] in the presence of strong Lewis acid B({{chem||C|6|F|5}}{{chem|)|3}}.<ref>{{cite journal |author=Aravinda B. Pulipaka, Stephen C. Bergmeier |title=A Synthesis of 6-Azabicyclooctanes. The Role of N-Substitution |journal=] |volume=73 |issue=4 |pages=1462–7 |year=2008 |doi=10.1021/jo702444c }}</ref>
	==Human toxicology==
	The toxicology of a particular aziridine compound depends on its structure and activity, although sharing the general characteristics of aziridines. As ]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 |author=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 |author=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.
	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.
	===Carcinogenicity===
	The ] (IARC) has reviewed aziridine compounds and classified them as possibly ] to humans (]).<ref>{{cite book |title=Some Aziridines, N-, S- and O-Mustards and Selenium |series=IARC Monographs on the Evalution of Carcinogenic Risks to Humans |volume=9 |year=1975 |isbn=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 ] which is ] 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 ].
	Respiratory sensitiser — causing occupational asthma
	== References ==
	{{reflist|2}}
	]		]
	]		]
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