Cyclopropane

Cyclopropane is the cycloalkane with the molecular formula (CH₂)₃, consisting of three methylene groups (CH₂) 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 of its derivatives - cyclopropanes - are of commercial or biological significance.<ref name=Faust>Template:Cite journal</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>Template:Cite journal</ref> Freund treated 1,3-dibromopropane with sodium, causing an intramolecular Wurtz reaction leading directly to cyclopropane.<ref name=Freund82>Template:Cite journal</ref> The yield of the reaction was improved by Gustavson in 1887 with the use of zinc instead of sodium.<ref name=Gustavson>Template:Cite journal</ref> Cyclopropane had no commercial application until Henderson and Lucas discovered its anaesthetic properties in 1929;<ref>Template:Cite journal</ref> industrial production had begun by 1936.<ref name=Ind-prod>Template:Cite journal</ref> In modern anaesthetic practice, it has been superseded by other agents.

Anaesthesia

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%<ref>Template:Cite journal</ref> 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".<ref>Template:Cite journal</ref> For this reason, as well as its high cost and its explosive nature,<ref>Template:Cite journal</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.

Pharmacology

Cyclopropane is inactive at the GABA_A and glycine receptors, and instead acts as an NMDA receptor antagonist.<ref name="HemmingsHopkins2006">Template:Cite book</ref><ref name="Hemmings2009">Template:Cite book</ref> It also inhibits the AMPA receptor and nicotinic acetylcholine receptors, and activates certain K_2P channels.<ref name="HemmingsHopkins2006" /><ref name="Hemmings2009" /><ref name="pmid12459679">Template:Cite journalTemplate:Dead link</ref>

Structure and bonding

File:Coulson Moffit Model.png

Orbital overlap in the bent bonding model of cyclopropane

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.<ref>Template:Cite journal</ref><ref>Template:Cite book</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 bonds.<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 kcal/mol as compared to cyclobutane (26.2 kcal/mol) with cyclohexane as reference with E_str=0 kcal/mol,<ref>S. W. Benson, Thermochemical Kinetics, S. 273, J. Wiley & Sons, New York, London, Sydney, Toronto 1976</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</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>Template:Cite journal</ref>

Synthesis

Cyclopropane was first produced via a Wurtz coupling, in which 1,3-dibromopropane was 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">Template:Ullmann</ref>

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

The preparation of cyclopropane rings is referred to as cyclopropanation.

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>Template:Cite journal</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 Template:ISBN</ref>

Electrophilic addition of HBr to cyclopropane

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

Safety

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

See also

• 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

External links

• Synthesis of Cyclopropanes and related compounds
• Carbon triangle