View source for Cyclopropane

{{Chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 438532196
| Name           = Cyclopropane
| Reference      = <ref>''Merck Index'', 11th Edition, '''2755'''.</ref>
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageFile3     = Liquid_Cyclopropane.jpg
| ImageFileL1    = Cyclopropane-stereo.svg
| ImageNameL1    = Cyclopropane - displayed formula
| ImageClassL1   = skin-invert
| ImageFileR1_Ref = {{chemboximage|correct|??}}
| ImageFileR1    = Regular triangle.svg
| ImageSizeR1    = 80px
| ImageClassR1   = skin-invert
| ImageNameR1    = Cyclopropane - skeletal formula
| ImageFileL2    = Cyclopropane-3D-balls.png
| ImageClassL2 = bg-transparent  
| ImageFileR2    = Cyclopropane-3D-vdW.png
| ImageClassR2 = bg-transparent  
| OtherNames     = 
| IUPACName      = 
| PIN            = Cyclopropane<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 137 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4| chapter = Front Matter }}</ref>
| SystematicName = 
| Section1       = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6111
| PubChem = 6351
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1796999
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 99TB643425
| InChIKey = LVZWSLJZHVFIQJ-UHFFFAOYAL
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C3H6/c1-2-3-1/h1-3H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LVZWSLJZHVFIQJ-UHFFFAOYSA-N
| CASNo = 75-19-4
| CASNo_Ref = {{cascite|correct|CAS}}
| InChI = 1/C3H6/c1-2-3-1/h1-3H2
| SMILES = C1CC1
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 30365
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03627
| UNNumber = 1027
  }}
| Section2       = {{Chembox Properties
| Formula = C<sub>3</sub>H<sub>6</sub>
| Appearance = Colorless gas
| Odor = Sweet, ethereal
| MolarMass = 42.08 g/mol
| Density = 1.879 g/L (1 atm, 0&nbsp;°C)<br>680 g/L (liquid)
| MeltingPtC = -128
| BoilingPtC = -32.9
| Solubility = 502 mg/L
| pKa = ~46
| MagSus = −39.9·10<sup>−6</sup> cm<sup>3</sup>/mol
| VaporPressure = 640 kPa (20&nbsp;°C)<br>1350 kPa (50&nbsp;°C)
  }}
| Section3       = 
| Section4       = 
| Section5       = 
| Section6       = 
| Section7       = {{Chembox Hazards
| ExternalSDS = [https://sg.airliquide.com/sites/al_sg/files/2020/08/03/sds-038-clp_cyclopropane.pdf Air Liquide]
| MainHazards = Highly flammable<br/>Asphyxiant
| NFPA-H = 1
| NFPA-F = 4
| NFPA-R = 0
| NFPA-S = SA
| FlashPt =
| GHSSignalWord = Danger
| GHSPictograms = {{GHS02}}
| ExploLimits = 2.4 % (lower)<br>10.4 % (upper)
| AutoignitionPtC = 495
  }}
}}
{{For|the functional group|Cyclopropanes}}

'''Cyclopropane''' is the [[cycloalkane]] with the molecular formula (CH<sub>2</sub>)<sub>3</sub>, consisting of three [[methylene group]]s (CH<sub>2</sub>) linked to each other to form a triangular ring. The small size of the ring creates substantial [[ring strain]] in the structure. Cyclopropane itself is mainly of theoretical interest, but many [[Cyclopropanes|cyclopropane derivatives]] are of commercial or biological significance.<ref name=Faust>{{cite journal |doi=10.1002/1521-3773(20010618)40:12<2251::AID-ANIE2251>3.0.CO;2-R|title=Fascinating Natural and Artificial Cyclopropane Architectures|year=2001|last1=Faust|first1=Rüdiger|journal=Angewandte Chemie International Edition|volume=40|issue=12|pages=2251–2253|pmid=11433485}}</ref> 

Cyclopropane was used as a clinical [[inhalational anesthetic]] from the 1930s through the 1980s. The substance's high flammability poses a risk of fire and explosions in operating rooms due to its tendency to accumulate in confined spaces, as its density is higher than that of air.

==History==
Cyclopropane was discovered in 1881 by [[August Freund]], who also proposed the correct structure for the substance in his first paper.<ref name=Freund81>{{Cite journal | title = Über Trimethylen | trans-title = On trimethylene | author = August Freund | volume = 26 | issue = 1 | year = 1881 | doi = 10.1002/prac.18820260125 | journal = Journal für Praktische Chemie | pages = 367–377 |url = https://books.google.com/books?id=WSzzAAAAMAAJ&pg=PA367}}</ref> Freund treated [[1,3-Dibromopropane|1,3-dibromopropane]] with [[sodium]], causing an intramolecular [[Wurtz reaction]] leading directly to cyclopropane.<ref name=Freund82>{{cite journal | title = Über Trimethylen | trans-title = On trimethylene | author = August Freund | volume = 3 | issue = 1 | year = 1882 | doi = 10.1007/BF01516828 | journal = Monatshefte für Chemie | pages = 625–635 | s2cid = 197767176 |url = https://books.google.com/books?id=b448AAAAIAAJ&pg=PA625}}</ref> The yield of the reaction was improved by Gustavson in 1887 with the use of [[zinc]] instead of sodium.<ref name=Gustavson>{{cite journal
| author = G. Gustavson
| title = Ueber eine neue Darstellungsmethode des Trimethylens
| trans-title = On a new method of preparing trimethylene
| journal = Journal für Praktische Chemie
| volume = 36
| pages = 300–305
| year = 1887  
| url =http://gallica.bnf.fr/ark:/12148/bpt6k90799n/f308.table
| doi=10.1002/prac.18870360127}}</ref> Cyclopropane had no commercial application until Henderson and Lucas discovered its anaesthetic properties in 1929;<ref>{{cite journal
| title = A New Anesthetic: Cyclopropane : A Preliminary Report |author1=G. H. W. Lucas |author2=V. E. Henderson | journal = Can Med Assoc J | volume = 21 | issue = 2 | pages = 173–5 |date=1 August 1929 | pmid = 20317448 | pmc=1710967 }}</ref> industrial production had begun by 1936.<ref name=Ind-prod>{{cite journal | title = Synthesis of Cyclopropane |author1=H. B. Hass |author2=E. T. McBee |author3=G. E. Hinds | pages = 1178–81 | doi = 10.1021/ie50322a013 | volume = 28 | issue = 10 | year = 1936 | journal = Industrial & Engineering Chemistry}}</ref> In modern anaesthetic practice, it has been superseded by other agents.

===Anaesthesia===
Cyclopropane was introduced into clinical use by the American anaesthetist [[Ralph M. Waters|Ralph Waters]] who used a closed system with carbon dioxide absorption to conserve this then-costly agent.
Cyclopropane is a relatively potent, non-irritating and sweet smelling agent with a [[minimum alveolar concentration]] of 17.5%<ref>{{cite journal|last=Eger|first=Edmond I.|author2=Brandstater, Bernard |author3=Saidman, Lawrence J. |author4=Regan, Michael J. |author5=Severinghaus, John W. |author6= Munson, Edwin S. |title=Equipotent Alveolar Concentrations of Methoxyflurane, Halothane, Diethyl Ether, Fluroxene, Cyclopropane, Xenon and Nitrous Oxide in the Dog|journal=Anesthesiology|year=1965|volume=26|issue=6|pages=771–777|doi=10.1097/00000542-196511000-00012|pmid=4378907|doi-access=free}}</ref> and a [[Blood:gas partition coefficient|blood/gas partition coefficient]] of 0.55. This meant induction of anaesthesia by inhalation of cyclopropane and oxygen was rapid and not unpleasant. However at the conclusion of prolonged anaesthesia patients could suffer a sudden decrease in blood pressure, potentially leading to [[cardiac dysrhythmia]]: a reaction known as "cyclopropane shock".<ref>{{cite journal|last=JOHNSTONE|first=M|author2=Alberts, JR|title=Cyclopropane anesthesia and ventricular arrhythmias.|journal=British Heart Journal|date=July 1950|volume=12|issue=3|pages=239–44|pmid=15426685|doi=10.1136/hrt.12.3.239|pmc=479392}}</ref> For this reason, as well as its high cost and its explosive nature,<ref>{{cite journal|last=MacDonald|first=AG|title=A short history of fires and explosions caused by anaesthetic agents.|journal=British Journal of Anaesthesia|date=June 1994|volume=72|issue=6|pages=710–22|pmid=8024925|doi=10.1093/bja/72.6.710|doi-access=free}}</ref> it was latterly used only for the induction of anaesthesia, and has not been available for clinical use since the mid-1980s.
Cylinders and flow meters were colored orange (now orange is used for the anesthetic gas [[enflurane]]).

===Pharmacology===
Cyclopropane is inactive at the [[GABAA receptor|GABA<sub>A</sub>]] and [[glycine receptor]]s, and instead acts as an [[NMDA receptor antagonist]].<ref name="HemmingsHopkins2006">{{cite book|author1=Hugh C. Hemmings|author2=Philip M. Hopkins|title=Foundations of Anesthesia: Basic Sciences for Clinical Practice|url=https://books.google.com/books?id=xaXu1wHmENoC&pg=PA292|year=2006|publisher=Elsevier Health Sciences|isbn=978-0-323-03707-5|pages=292–}}</ref><ref name="Hemmings2009">{{cite book|last1=Hemmings|first1=Hugh C.|chapter=Molecular Targets of General Anesthetics in the Nervous System |series=Contemporary Clinical Neuroscience |title=Suppressing the Mind|year=2009|pages=11–31|doi=10.1007/978-1-60761-462-3_2|isbn=978-1-60761-463-0}}</ref> It also inhibits the [[AMPA receptor]] and [[nicotinic acetylcholine receptor]]s, and activates certain [[KCNK2|K<sub>2P</sub> channel]]s.<ref name="HemmingsHopkins2006" /><ref name="Hemmings2009" /><ref name="pmid12459679">{{cite journal | vauthors = Hara K, Eger EI, Laster MJ, Harris RA | title = Nonhalogenated alkanes cyclopropane and butane affect neurotransmitter-gated ion channel and G-protein-coupled receptors: differential actions on GABAA and glycine receptors | journal = Anesthesiology | volume = 97 | issue = 6 | pages = 1512–20 | date = December 2002 | pmid = 12459679 | doi = 10.1097/00000542-200212000-00025 | s2cid = 21160239 | doi-access = free }}{{Dead link|date=November 2019 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

==Structure and bonding==
{{further|Bent bond}}
[[File:Coulson Moffit Model.svg|150px|thumb|left|Orbital overlap in the bent bonding model of cyclopropane]]
The triangular structure of cyclopropane requires the [[bond angle]]s  between carbon-carbon covalent bonds to be 60°. The molecule has D<sub>3h</sub> [[molecular symmetry]]. The C-C distances are 151 [[picometer|pm]] versus 153-155 pm.<ref>{{cite journal|last=Allen|first=Frank H.|author2=Kennard, Olga |author3=Watson, David G. |author4=Brammer, Lee |author5=Orpen, A. Guy |author6= Taylor, Robin |title=Tables of bond lengths determined by X-ray and neutron diffraction. Part 1. Bond lengths in organic compounds|journal=Journal of the Chemical Society, Perkin Transactions 2|year=1987|issue=12|pages=S1–S19|doi=10.1039/P298700000S1|url=http://pubs.rsc.org/en/content/articlelanding/1987/p2/p298700000s1|url-access=subscription}}</ref><ref>{{cite book|title=Polymer Mechanochemistry
|editor=Boulatov, Roman |publisher=Springer|year=2015|isbn=978-3-319-22824-2|page =9}}</ref>

Despite their shortness, the C-C bonds in cyclopropane are weakened by 34 kcal/mol vs ordinary C-C bonds.  In addition to ring strain, the molecule also has torsional strain due to the [[eclipsed conformation]] of its hydrogen atoms. The C-H bonds in cyclopropane are stronger than ordinary C-H bonds as reflected by NMR coupling constants.

Bonding between the carbon centres is generally described in terms of [[bent bond]]s.<ref>Eric V. Anslyn and Dennis A. Dougherty. ''Modern Physical Organic Chemistry.'' 2006. pages 850-852</ref> In this model the carbon-carbon bonds are bent outwards so that the inter-orbital angle is 104°.

The unusual structural properties of cyclopropane have spawned many theoretical discussions.  One theory invokes σ-[[aromaticity]]: the stabilization afforded by delocalization of the six electrons of cyclopropane's three C-C σ bonds to explain why the strain of cyclopropane is "only" 27.6&nbsp;kcal/mol as compared to [[cyclobutane]] (26.2&nbsp;kcal/mol) with [[cyclohexane]] as reference with E<sub>str</sub>=0&nbsp;kcal/mol,<ref>S. W. Benson, Thermochemical Kinetics, S. 273, J. Wiley & Sons, New York, London, Sydney, Toronto 1976</ref><ref>{{cite journal | last1 = Dewar | first1 = M. J. | year = 1984 | title = Chemical Implications of σ Conjugation | journal = J. Am. Chem. Soc. | volume = 106 | issue = 3| pages = 669–682 | doi=10.1021/ja00315a036}}</ref><ref>{{cite journal | last1 = Cremer | first1 = D. | year = 1988 | title = Pros and Cons of σ-Aromaticity | doi = 10.1016/s0040-4020(01)86238-4 | journal = Tetrahedron | volume = 44 | issue = 2| pages = 7427–7454 }}</ref> in contrast to the usual π aromaticity, that, for example, has a highly stabilizing effect in [[benzene]]. Other studies do not support the role of σ-aromaticity in cyclopropane and the existence of an induced ring current; such studies provide an alternative explanation for the energetic stabilization and abnormal magnetic behaviour of cyclopropane.<ref>{{cite journal | last1 = Wu | first1 = Wei | last2 = Ma | first2 = Ben | last3 = Wu | first3 = Judy I-Chia | last4 = von Ragué | first4 = Schleyer |last5 = Mo | first5 = Yirong | year = 2009 | title = Is Cyclopropane Really the σ-Aromatic Paradigm? | journal = Chemistry: A European Journal | volume = 15 | issue = 38| pages = 9730–9736 | doi = 10.1002/chem.200900586 | pmid = 19562784 | doi-access = free }}</ref>

==Synthesis==
Cyclopropane was first produced via a [[Wurtz coupling]], in which  [[1,3-dibromopropane]] was [[cyclisation|cyclised]] using [[sodium]].<ref name=Freund81/> The yield of this reaction can be improved by the use of [[zinc]] as the dehalogenating agent and sodium iodide as a catalyst.<ref name="Wollweber2000">{{Ullmann| last1 = Wollweber | first1 = Hartmund | title = Anesthetics, General | year = 2000 | doi = 10.1002/14356007.a02_289}}</ref>
:BrCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>Br  +  2 Na  →  (CH<sub>2</sub>)<sub>3</sub>  +  2 NaBr

==Reactions==
Owing to the increased π-character of its C-C bonds, cyclopropane is often assumed to add bromine to give 1,3-dibromopropane, but this reaction proceeds poorly.<ref>{{cite journal |doi=10.1021/ed044p461 |title=Halogenation and olefinic nature of cyclopropane |year=1967 |last1=Gordon |first1=Arnold J. |journal=Journal of Chemical Education |volume=44 |issue=8 |page=461 }}</ref>  [[Hydrohalogenation]] with [[hydrohalic acids]] gives linear 1-halopropanes. Substituted cyclopropanes also react, following [[Markovnikov's rule]].<ref>Advanced organic Chemistry, Reactions, mechanisms and structure 3ed. Jerry March {{ISBN|0-471-85472-7}}</ref> 
:[[Image:Addition of HBr to Cyclopropane.svg|Electrophilic addition of HBr to cyclopropane|class=skin-invert]]

Cyclopropane and its derivatives can [[Oxidative addition|oxidatively add]] to [[transition metals]], in a process referred to as [[Cyclopropane carbon-carbon bond activation|C–C activation]].

==Safety==
Cyclopropane is highly flammable. However, despite its strain energy  it does not exhibit explosive behavior substantially different from [[Flammability limit#Examples|other alkanes]].

==See also==
* [[Tetrahedrane]] contains four fused cyclopropane rings that form the faces of a [[tetrahedron]]
* [[1.1.1-Propellane|Propellane]] contains three cyclopropane rings that share a single central carbon-carbon bond.
* [[Spiropentane]] is two cyclopropane rings fused at a vertex
* [[Cyclopropene]]
* [[Methylenecyclopropane]]

==References==
{{Reflist|2}}

==External links==
{{Commons category}}
*[https://www.organic-chemistry.org/synthesis/C1C/cyclic/alkanes/cyclopropanes.shtm Synthesis of Cyclopropanes and related compounds]
*[https://web.archive.org/web/20140729132503/http://www.org-chem.org/yuuki/triangle/triangle_en.html Carbon triangle]

{{Cycloalkanes}}
{{General anesthetics}}
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[[Category:General anesthetics]]
[[Category:Cyclopropanes| ]]
[[Category:NMDA receptor antagonists]]
[[Category:Nicotinic antagonists]]
[[Category:AMPA receptor antagonists]]
[[Category:Cycloalkanes]]
[[Category:Gases]]