Editing Rotamer (section)

==Conformation-dependent reactions==
Reaction rates are highly dependent on the conformation of the reactants. In many cases the dominant product arises from the reaction of the ''less prevalent'' conformer, by virtue of the [[Curtin–Hammett principle|Curtin-Hammett principle]]. This is typical for situations where the conformational equilibration is much faster than reaction to form the product. The dependence of a reaction on the stereochemical orientation is therefore usually only visible in [[Configurational analysis]], in which a particular conformation is locked by substituents. Prediction of rates  of many reactions involving the transition between sp2 and sp3 states, such as ketone reduction, alcohol oxidation or [[SN2 reaction|nucleophilic substitution]] is possible if all conformers and their relative stability ruled by their [[Strain (chemistry)|strain]] is taken into account.<ref>Schneider, H.-J.; Schmidt, G.; Thomas F. J. Am. Chem. Soc., 1983, 105, 3556.
https://pubs.acs.org/doi/pdf/10.1021/ja00349a031</ref>

One example where the rotamers become significant is  [[elimination reaction]]s, which involve the simultaneous removal of a proton and a [[leaving group]] from vicinal or ''anti''periplanar positions under the influence of a base.

[[Image:E2 elimination reaction.svg|center|thumb|350px|Base-induced bimolecular dehydrohalogenation (an E2 type reaction mechanism). The optimum geometry for the transition state requires the breaking bonds to be antiperiplanar, as they are in the appropriate staggered conformation]]

The mechanism requires that the departing atoms or groups follow antiparallel trajectories. For open chain substrates this geometric prerequisite is met by at least one of the three staggered conformers. For some cyclic substrates such as cyclohexane, however, an antiparallel arrangement may not be attainable depending on the substituents which might set a conformational lock.<ref>{{cite web|title=Cycloalkanes |url=http://www.ch.ic.ac.uk/local/organic/conf/c1_rings.html|publisher=Imperial College London|access-date=|first =Henry S. |last =Rzepa|date = 2014}}</ref> Adjacent [[substituent]]s on a cyclohexane ring can achieve antiperiplanarity only when they occupy trans [[wikt:diaxial|diaxial]] positions (that is, both are in axial position, one going up and one going down). {{citation needed|date=January 2025}}

One consequence of this analysis is that ''trans''-4-''tert''-butylcyclohexyl chloride cannot easily eliminate but instead undergoes substitution (see diagram below) because the most stable conformation has the bulky ''t''-Bu group in the equatorial position, therefore the chloride group is not antiperiplanar with any vicinal hydrogen (it is gauche to all four). The thermodynamically unfavored conformation has the ''t''-Bu group in the axial position, which is higher in energy by more than 5 kcal/mol (see [[A value]]).<ref name="dougherty a value">{{cite book|last1=Dougherty|first1=Eric V. Anslyn |last2= Dennis|first2= A.|title=Modern Physical Organic Chemistry|url=https://archive.org/details/modernphysicalor00ansl|url-access=limited|year=2006|publisher=University Science Books|location=Sausalito, CA|isbn=978-1-891389-31-3|page=[https://archive.org/details/modernphysicalor00ansl/page/n131 104]|edition=Dodr.}}</ref> As a result, the ''t''-Bu group "locks" the ring in the conformation where it is in the equatorial position and substitution reaction is observed. On the other hand, ''cis''-4-''tert''-butylcyclohexyl chloride undergoes elimination because antiperiplanarity of Cl and H can be achieved when the ''t''-Bu group is in the favorable equatorial position.

{{multiple image
| align = center
| image1 = Seven-atom interaction 1-(tert-butyl)-4-chlorocyclohexane.svg
| width1 = 230
| alt1 =
| caption1 = Thermodynamically unfavored conformation of ''trans''-4-''tert''-butylcyclohexyl chloride where the ''t''-Bu group is in the axial position exerting 7-atom interactions.
| image2 = E2 1-(tert-butyl)-4-chlorocyclohexane.svg
| width2 = 500
| alt2 =
| caption2 = The ''trans'' isomer can attain antiperiplanarity only via the unfavored axial conformer; therefore, it does not eliminate. The ''cis'' isomer is already in the correct geometry in its most stable conformation; therefore, it eliminates easily.
| footer =
}}

The repulsion between an axial ''t''-butyl group and hydrogen atoms in the 1,3-diaxial position is so strong that the cyclohexane ring will revert to a [[cyclohexane conformation|twisted boat]] conformation. The strain in cyclic structures is usually characterized by deviations from ideal [[bond angles]] ([[Baeyer strain]]), ideal [[torsional angle]]s ([[Pitzer strain]]) or [[transannular strain|transannular]] (Prelog) interactions.