Bicyclobutane is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

with the formula C₄H₆. It is a

bicyclic molecule In chemistry, a bicyclic molecule () is a molecule that features two joined rings. Bicyclic structures occur widely, for example in many biologically important molecules like α-thujene and camphor. A bicyclic compound can be carbocyclic (all ...

consisting of two ''

cis Cis or cis- may refer to: Places * Cis, Trentino, in Italy * In Poland: ** Cis, Świętokrzyskie Voivodeship, south-central ** Cis, Warmian-Masurian Voivodeship, north Math, science and biology * cis (mathematics) (cis(''θ'')), a trigonome ...

''-fused cyclopropane rings, and is a colorless and easily condensed gas. Bicyclobutane is noted for being one of the most strained compounds that is isolatable on a large scale — its strain energy is estimated at 63.9 kcal mol⁻¹. It is a nonplanar molecule, with a

dihedral angle A dihedral angle is the angle between two intersecting planes or half-planes. In chemistry, it is the clockwise angle between half-planes through two sets of three atoms, having two atoms in common. In solid geometry, it is defined as the un ...

between the two cyclopropane rings of 123°. The first reported bicyclobutane was the carboxyethyl derivative, C₄H₅CO₂Et, which was prepared by

dehydrohalogenation In chemistry, dehydrohalogenation is an elimination reaction which removes a hydrogen halide from a substrate. The reaction is usually associated with the synthesis of alkenes, but it has wider applications. Dehydrohalogenation from alkyl halid ...

the corresponding bromo

cyclobutane Cyclobutane is a cycloalkane and organic compound with the formula (CH2)4. Cyclobutane is a colourless gas and commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes. Cyclobutane itself is of no commercia ...

carboxylate ester with

sodium hydride Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in co ...

. The parent hydrocarbon was prepared from 1-bromo-3-chlorocyclobutane by conversion of the bromocyclobutanecarboxylate ester, followed by intramolecular

Wurtz coupling In organic chemistry, the Wurtz reaction, named after Charles Adolphe Wurtz, is a coupling reaction whereby two alkyl halides are treated with sodium metal to form a higher alkane. : 2 R−X + 2 Na → R−R + 2 NaX The reaction is of little v ...

using molten

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

. The intermediate 1-bromo-3-chlorocyclobutane can also be prepared via a modified

Hunsdiecker reaction The Hunsdiecker reaction (also called the Borodin reaction or the Hunsdiecker–Borodin reaction) is a name reaction in organic chemistry whereby silver salts of carboxylic acids react with a halogen to produce an organic halide. It is an e ...

from 3-chlorocyclobutanecarboxylic acid using

mercuric oxide Mercury(II) oxide, also called mercuric oxide or simply mercury oxide, is the inorganic compound with the formula Hg O. It has a red or orange color. Mercury(II) oxide is a solid at room temperature and pressure. The mineral form montroydite is v ...

and

bromine Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table ( halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simi ...

: :

A synthetic approach to bicyclobutane derivatives involves ring closure of a suitably substituted 2-bromo-1-(chloromethyl)cyclopropane with magnesium in

THF Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...

. Stereochemical evidence indicates that bicyclobutane undergoes

thermolysis Thermal decomposition, or thermolysis, is a chemical decomposition caused by heat. The decomposition temperature of a substance is the temperature at which the substance chemically decomposes. The reaction is usually endothermic as heat is req ...

to form

1,3-butadiene 1,3-Butadiene () is the organic compound with the formula (CH2=CH)2. It is a colorless gas that is easily condensed to a liquid. It is important industrially as a precursor to synthetic rubber. The molecule can be viewed as the union of two vi ...

with an

activation energy In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules p ...

of 41 kcal mol⁻¹ via a concerted

pericyclic In organic chemistry, a pericyclic reaction is the type of organic reaction wherein the transition state of the molecule has a cyclic geometry, the reaction progresses in a concerted fashion, and the bond orbitals involved in the reaction overlap ...

mechanism (cycloelimination, �2s+σ2a.

Biological synthesis

Multiple research groups have reported success in synthesizing bicyclobutane-containing molecules using enzymes in living cells. One group reported the transformation of

linolenic acid Linolenic acid is a type of naturally-occurring fatty acid. It can refer to either of two octadecatrienoic acids (i.e. with an 18-carbon chain and three double bonds, which are found in the '' cis'' configuration), or a mixture of the two. Lino ...

into a bicyclobutane fatty acid via a protein produced by a strain of the cyanobacterium Anabaena sp. (strain PCC 7120). The other group reported a directed evolution approach, whereby engineered heme protein was expressed in E. coli and successfully optimized for increased rate and yield of biosynthesis of a substituted bicyclobutane derivative.{{Cite journal, last1=Chen, first1=Kai, last2=Huang, first2=Xiongyi, last3=Kan, first3=S. B. Jennifer, last4=Zhang, first4=Ruijie K., last5=Arnold, first5=Frances H., date=6 April 2018, title=Enzymatic construction of highly strained carbocycles, journal=Science, volume=360, issue=6384, pages=71–75, doi=10.1126/science.aar4239, issn=1095-9203, pmc=6104391, pmid=29622650, bibcode=2018Sci...360...71C

References

Cyclopropanes Bicycloalkanes Gases

Biological synthesis

See also

References