Bicyclobutane

{{Chembox

|ImageFile = Bicyclobutane-2.svg

|PIN = Bicyclo[1.1.0]butane

|Section1={{Chembox Identifiers

|CASNo = 157-33-5

|CASNo_Ref = {{cascite|correct|CAS}}

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = YK26N2Z3VC

|PubChem = 135973

|ChemSpiderID = 119751

|InChI=1S/C4H6/c1-3-2-4(1)3/h3-4H,1-2H2

|InChIKey = LASLVGACQUUOEB-UHFFFAOYSA-N

|SMILES = C1C2C1C2}}

|Section2={{Chembox Properties

|Formula = C₄H₆

|C=4 | H=6

|Appearance = colorless gas

|BoilingPt = 8.3 ± 0.2 °C

}}

}}

Bicyclo[1.1.0]butane is an organic compound with the formula C₄H₆. It is a bicyclic molecule consisting of two cis-fused cyclopropane rings, and is a colorless and easily condensed gas.{{cite journal |first1= K. B. |last1= Wiberg |authorlink1= Kenneth B. Wiberg |first2= G. M. |last2= Lampman |first3= R. P. |last3= Ciula |first4= D. S. |last4= Connor |first5= P. |last5= Schertler |first6= J. |last6= Lavanish |title= Bicyclo[1.1.0]butane |journal= Tetrahedron |year=1965 |volume= 21 |issue= 10 |pages= 2749–2769 |doi= 10.1016/S0040-4020(01)98361-9}} 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 between the two cyclopropane rings of 123°.{{cite book|title = Advances in Alicyclic Chemistry|volume = 2|editor1-first = H.|editor1-last = Hart|editor2-first = G. J.|editor2-last = Karabatsos|year = 1968|first = K. B.|last = Wiberg|authorlink = Kenneth B. Wiberg|chapter = Small Ring Bicyclo[n.m.0]alkanes|publisher = Academic Press|isbn = 9781483224213|pages = 185–254|chapter-url = https://books.google.com/books?id=9h0SBQAAQBAJ&pg=PA191}}

The first reported bicyclobutane was the ethyl carboxylate derivative, C₄H₅CO₂Et, which was prepared by dehydrohalogenation the corresponding bromocyclobutanecarboxylate ester with sodium hydride. The parent hydrocarbon was prepared from 1-bromo-3-chlorocyclobutane by conversion of the bromocyclobutanecarboxylate ester, followed by intramolecular Wurtz coupling using molten sodium.{{OrgSynth|first1 = Gary M.|last1 = Lampman|first2 = James C.|last2 = Aumiller|title = Bicyclo[1.1.0]butane|year = 1971|volume = 51 |pages = 55|doi = 10.15227/orgsyn.051.0055}} The intermediate 1-bromo-3-chlorocyclobutane can also be prepared via a modified Hunsdiecker reaction from 3-chlorocyclobutanecarboxylic acid using mercuric oxide and bromine:{{OrgSynth|year = 1971|title = Mercury(II) oxide-modified Hunsdiecker reaction: 1-Bromo-3-chlorocyclobutane|last1 = Lampman|first1 = Gary M.|last2 = Aumiller|first2 = James C.|volume = 51|pages = 106|doi = 10.15227/orgsyn.051.0106}}

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A synthetic approach to bicyclobutane derivatives involves ring closure of a suitably substituted 2-bromo-1-(chloromethyl)cyclopropane with magnesium in THF.{{cite journal|title = New synthesis of bicyclo[1.1.0]butane hydrocarbons|first1 = A. I.|last1 = D'yachenko|first2 = N. M.|last2 = Abramova|first3 = S. V.|last3 = Zotova|first4 = O. A.|last4 = Nesmeyanova|first5 = O. V.|last5 = Bragin|journal =Bulletin of the Academy of Sciences of the USSR |year = 1985|volume = 34|issue = 9|pages = 1885–1889|doi = 10.1007/BF00953929|s2cid = 96988412}} Substituted bicyclo[1.1.0]butanes can also be prepared from the reaction of iodo-bicyclo[1.1.1]pentanes with amines, thiols, and sulfinate salts.{{cite journal |last1=Mandler |first1=Michael D. |last2=Mignone |first2=James |last3=Jurica |first3=Elizabeth A. |last4=Palkowitz |first4=Maximilian D. |last5=Aulakh |first5=Darpandeep |last6=Cauley |first6=Anthony N. |last7=Farley |first7=Christopher A. |last8=Zhang |first8=Shasha |last9=Traeger |first9=Sarah C. |last10=Sarjeant |first10=Amy |last11=Paiva |first11=Anthony |last12=Perez |first12=Heidi L. |last13=Ellsworth |first13=Bruce A. |last14=Regueiro-Ren |first14=Alicia |title=Synthesis of Bicyclo[1.1.0]butanes from Iodo-Bicyclo[1.1.1]pentanes |journal=Organic Letters |date=10 November 2023 |volume=25 |issue=44 |pages=7947–7952 |doi=10.1021/acs.orglett.3c01417 |url=https://pubs.acs.org/doi/10.1021/acs.orglett.3c01417 |publisher=American Chemical Society |issn=1523-7060}} Bicyclo[1.1.0]butanes are explored in medicinal chemistry as covalent reactive groups.{{Cite journal |last1=Tokunaga |first1=Keisuke |last2=Sato |first2=Mami |last3=Kuwata |first3=Keiko |last4=Miura |first4=Chizuru |last5=Fuchida |first5=Hirokazu |last6=Matsunaga |first6=Naoya |last7=Koyanagi |first7=Satoru |last8=Ohdo |first8=Shigehiro |last9=Shindo |first9=Naoya |last10=Ojida |first10=Akio |date=2020-10-28 |title=Bicyclobutane Carboxylic Amide as a Cysteine-Directed Strained Electrophile for Selective Targeting of Proteins |url=https://pubs.acs.org/doi/10.1021/jacs.0c07490 |journal=Journal of the American Chemical Society |language=en |volume=142 |issue=43 |pages=18522–18531 |doi=10.1021/jacs.0c07490 |pmid=33047956 |issn=0002-7863}}

:File:SchemeBCBs.svg

Stereochemical evidence indicates that bicyclobutane undergoes thermolysis to form 1,3-butadiene with an activation energy of 41 kcal mol⁻¹ via a concerted pericyclic mechanism (cycloelimination, [σ2s+σ2a]).{{cite journal|last1 = Woodward|first1 = Robert B.|authorlink1 = Robert Burns Woodward|last2 = Hoffmann|first2 = Roald|authorlink2 = Roald Hoffmann|year = 1969|title = The Conservation of Orbital Symmetry|journal = Angewandte Chemie International Edition|volume = 8|issue = 11|pages = 781–853|doi = 10.1002/anie.196907811}}