cyclopropane

[sahy-kluh-proh-peyn, sik-luh-]

cyclopropane, C₃H₆, a gaseous hydrocarbon. It is a cyclic alkane, its three carbon atoms being joined together in a ring. The angle between successive carbon-carbon bonds in the ring is only 60°, much less than that between successive carbon-carbon bonds in a normal open-chain alkane; the cyclopropane molecule is thus said to be "strained." Many reactions of cyclopropane involve breaking one of the carbon-carbon bonds in the ring, which opens the ring and relieves the strain. Cyclopropane is prepared commercially by the reaction of 1,3-dichloropropane with zinc. It is a potent inhalation anesthetic, that once enjoyed wide use, but has been replaced by less combustible gases. Cyclopropane allowed the transport of more oxygen to the tissues than did other common anesthetics and also produced greater skeletal muscle relaxation. It is not irritating to the respiratory tract. Because of the low solubility of cyclopropane in the blood, postoperative recovery was usually rapid but nausea and vomiting were common. See anesthesia.

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Cyclopropane

Cyclopropane is a cycloalkane molecule with the molecular formula C₃H₆, consisting of three carbon atoms linked to each other to form a ring, with each carbon atom bearing two hydrogen atoms.

The bonds between the carbon atoms are considerably weaker than in a typical carbon-carbon bond, yielding reactivity similar to or greater than alkenes. The angle strain from the 60° angle between the carbon atoms (less than the normal angle of 109.5° for bonds between atoms with sp³ hybridised orbitals) reduces the compound's carbon-carbon bond energy, making it more reactive than other cycloalkanes such as cyclohexane and cyclopentane. The molecule also has torsional strain due to the eclipsed conformation of its hydrogen atoms. It is somewhat stabilized by some pi character in its carbon-carbon bonds, indicated by the Walsh orbital description whereas it is modeled as a three-center-bonded orbital combination of methylene carbenes.

The smallest polycyclic compounds contain multiple fused cyclopentane rings. Tetrahedrane contains four fused cyclopropane rings which form the faces of a tetrahedron. [[Propellane|[1.1.1]Propellane]] contains three cyclopropane rings which share a single central carbon-carbon bond.

Cyclopropane is an anaesthetic when inhaled. In modern anaesthetic practice, it has been superseded by other agents, due to its extreme reactivity under normal conditions: when the gas is mixed with oxygen there is a significant risk of explosion.

History

Cyclopropane was discovered in 1881 by August Freund, who also proposed the right structure for the new substance in his first paper. Freund reacted 1,3-dibromopropane with sodium, the reaction is a intramolecular Wurtz reaction leading directly to cyclopropane. The yield of the reaction can be improved by the use of zinc instead of sodium. Cyclopropane had no commercial application until Henderson and Lucas discovered its anaesthetic properties in 1929; industrial production had begun by 1936.

Safety

Because of the strain in the carbon-carbon bonds of cyclopropane, the molecule has an enormous amount of potential energy. In pure form, it will break down to form linear hydrocarbons, including "normal", non-cyclic propene. This decomposition is potentially explosive, especially if the cyclopropane is liquified, pressurized, or contained within tanks. Explosions of cyclopropane and oxygen are even more powerful, because the energy released by the formation of normal propane is compounded by the energy released via the oxidation of the carbon and hydrogen present. At room temperature, sufficient volumes of liquified cyclopropane will self-detonate. To guard against this, the liquid is shipped in cylinders filled with tungsten wool, which prevents high-speed collisions between molecules and vastly improves stability. Pipes to carry cyclopropane must likewise be of small diameter, or else filled with unreactive metal or glass wool, to prevent explosions. Even if these precautions are followed, cyclopropane is dangerous to handle and manufacture, and is no longer used for anaesthesia.

Cyclopropanes

Cyclopropanes are a class of organic compounds sharing the common cyclopropane ring, in which one or more hydrogens may be substituted. These compounds are found in biomolecules; for instance, the pyrethrum insecticides (found in certain Chrysanthemum species) contain a cyclopropane ring.

Organic synthesis

Cyclopropanes can be prepared in the laboratory by organic synthesis in various ways and many methods are simply called cyclopropanation:

addition of sodium to 1,3-dibromopropane in the Freund reaction (1881) or zinc to 1,3-dichloropropane in the Gustavson reaction(1887)
addition to an alkene of a zinc carbenoid in the Simmons-Smith reaction (1958) for example to cinnamyl alcohol. In one adaptation an amide is reacted with two equivalents of dichloromethane aided by titanium tetrachloride and magnesium:

a possible reaction mechanism for this cyclopropanation was proposed:

addition to an alkene of a carbene such as dibromocarbene in the synthesis of propellane or methyl diazoacetate The Walsh orbital description of the molecule facilitates this reaction.
nucleophilic displacement of a leaving group by a carbon nucleophile in a 1,3 relationship, for example the synthesis of cyclopropylacetylene from 5-chloro-1-pentyne. Another example can be found in the Bingel reaction. An asymmetric reaction creating three stereocenters is demonstrated in a reaction of cyclohexenone with bromonitromethane assisted by trans-2,5-dimethylpiperazine as a base and a pyrrolidine based tetrazole organocatalyst:

an intramolecular Wurtz coupling for example in the synthesis of bicyclo[1.1.0]butane
Rearrangement reaction of certain cyclobutane compounds for instance the conversion of 1,2-cyclobutanediol to cyclopropanecarboxaldehyde
photochemical rearrangement reaction of 1,4-dienes to vinylcyclopropanes in the di-pi-methane rearrangement
reaction of esters with Grignards in presence of a titanium alkoxide in the Kulinkovich reaction
extrusion of nitrogen in certain pyrazolines in the so called Kishner cyclopropane synthesis

Organic reactions

Although cyclopropanes are formally cycloalkanes, they are very reactive due to considerable strain energy and due to double bond character.

Cyclopropyl groups participate in cycloaddition reaction such as the formal [5+2]cycloaddition shown below:

This asymmetric synthesis is catalyzed by a rhodium BINAP system with 96% enantiomeric excess.

Cyclopropyl groups also engage in many rearrangement reactions. An extreme example is found in the compound bullvalene. A cyclopropane ring is an intermediate in the Favorskii rearrangement. Certain methylenecyclopropanes are found to convert to cyclobutenes:

This reaction is catalyzed by platinum(II) chloride in a carbon monoxide environment. The proposed reaction mechanism is supported by deuterium labeling.

In another version of the same reaction the catalyst is PdBr₂ is prepared in situ from palladium(II) acetate and copper(II) bromide and the solvent is toluene.