cyclopropane

Cyclopropane was discovered in 1881 by August Freund, who also proposed the correct structure for the substance in his first paper.{{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}} Freund treated 1,3-dibromopropane with sodium, causing an intramolecular Wurtz reaction leading directly to cyclopropane.{{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}} The yield of the reaction was improved by Gustavson in 1887 with the use of zinc instead of sodium.{{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}} Cyclopropane had no commercial application until Henderson and Lucas discovered its anaesthetic properties in 1929;{{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 }} industrial production had begun by 1936.{{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| issue = 10 | year = 1936 | journal = Industrial & Engineering Chemistry}} In modern anaesthetic practice, it has been superseded by other agents.

Cyclopropane was introduced into clinical use by the American anaesthetist 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%{{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}} and a 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".{{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}} For this reason, as well as its high cost and its explosive nature,{{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}} 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.

Cyclopropane is inactive at the GABA_A and glycine receptors, and instead acts as an NMDA receptor antagonist.{{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–}}{{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}} It also inhibits the AMPA receptor and nicotinic acetylcholine receptors, and activates certain K_2P channels.{{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 }}

{{further|Bent bond}}

File:Coulson Moffit Model.png

The triangular structure of cyclopropane requires the bond angles between carbon-carbon covalent bonds to be 60°. The molecule has D_3h molecular symmetry. The C-C distances are 151 pm versus 153-155 pm.{{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}}{{cite book|title=Polymer Mechanochemistry

|editor=Boulatov, Roman |publisher=Springer|year=2015|isbn=978-3-319-22824-2|page =9}}

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 bonds.Eric V. Anslyn and Dennis A. Dougherty. Modern Physical Organic Chemistry. 2006. pages 850-852 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 kcal/mol as compared to cyclobutane (26.2 kcal/mol) with cyclohexane as reference with E_str=0 kcal/mol,S. W. Benson, Thermochemical Kinetics, S. 273, J. Wiley & Sons, New York, London, Sydney, Toronto 1976{{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}}{{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 }} 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.{{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 }}

Cyclopropane was first produced via a Wurtz coupling, in which 1,3-dibromopropane was cyclised using sodium. The yield of this reaction can be improved by the use of zinc as the dehalogenating agent and sodium iodide as a catalyst.{{Ullmann| last1 = Wollweber | first1 = Hartmund | title = Anesthetics, General | year = 2000 | doi = 10.1002/14356007.a02_289}}

:BrCH₂CH₂CH₂Br + 2 Na → (CH₂)₃ + 2 NaBr

The preparation of cyclopropane rings is referred to as cyclopropanation.

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.{{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 }} Hydrohalogenation with hydrohalic acids gives linear 1-halopropanes. Substituted cyclopropanes also react, following Markovnikov's rule.Advanced organic Chemistry, Reactions, mechanisms and structure 3ed. Jerry March {{ISBN|0-471-85472-7}}

:Image:AdditionOfHBrtoCyclopropane.svg

Cyclopropane and its derivatives can oxidatively add to transition metals, in a process referred to as C–C activation.

Cyclopropane is highly flammable. However, despite its strain energy it does not exhibit explosive behavior substantially different from other alkanes.

• Tetrahedrane contains four fused cyclopropane rings that form the faces of a tetrahedron
• Propellane contains three cyclopropane rings that share a single central carbon-carbon bond.
• Spiropentane is two cyclopropane rings fused at a vertex
• Cyclopropene
• Methylenecyclopropane

{{Reflist|2}}

{{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]

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