The E2 Reaction and Cyclohexane Conformation

Mechanism of the El reaction. Two steps are involved, the first of which is rate-limiting, and a carbocation intermediate is present. 

T he difference in reactivity between the isomeric menthvl chlorides is due 

Which isomer would you expect to undergo E2 elimination faster, fm/rs-l-bromo-4-fev/-butylcyclohexane or c/s-l-bromo-4-terf-butylcyclohexane Draw each molecule in its more stable chair conformation, and explain your answer. 

O Spontaneous dissociation of the tertiary alkyl chloride yields an intermediate carbocation in a slow, rate-limiting step. 

El eliminations begin with the same unimolecular dissociation we saw in the Sf I reaction, but the dissociation is followed by loss of ll from the adjacent carbon rather than by substitution. In fact, the Ei and Sis l reactions normally occur together whenever an alkyl halide is treated in a protic solvent with a non-basic nucleophile. Thus, the best El substrates are also the best S 1 substrates, and mixtures of substitution and elimination products are usually obtained. For example, when 2-chloro-2-mcthylpropane is warmed tc 65 °C in 80% aqueous ethanol, a 64 36 mixture of 2-methvi-2-propanol (Sj,jT) and 2-mcthylpropene (F1) results. 

Predicting the Double-Bond Stereochemistry of the Product in an E2 Reaction 

What stereochemistry do you expect for the alkene obtained by E2 elimination of (lS,25)-l,2-dibromo-l,2-diphenylethane  

Strategy Draw (15,25)-l,2-dibromo-l,2-diphenylethane so that you can see its stereochemistry and so that the —H and —Br groups to be eliminated are anti periplanar. Then carry out the elimination while keeping all substituents in approximately their same positions, and see what alkene results. 

Solution Anti periplanar elimination of HBr gives (Z)-l-bromo-l,2-diphenylethylene. 

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Nearly all cyclohexanes are most stable in chair conformations. In the chair, all the carbon-carbon bonds are staggered, and any two adjacent carbon atoms have axial bonds in an anti-coplanar conformation, ideally oriented for the E2 reaction. (As drawn in the following figure, the axial bonds are vertical.) On any two adjacent carbon atoms, one has its axial bond pointing up and the other has its axial bond pointing down. These two bonds are trans to each other, and we refer to their geometry as trans-diaxial. 

If this principle is taken to its ultimate conclusion, there should be halo-cyclohexanes for which an E2 reaction is impossible. 2,6-Dimethyl-l-bromocy-clohexane (34) is such a case. To satisfy the relative stereochemistry of the two methyl groups (cis to each other) and the bromine anti to the two methyl groups), the bromine atom must be axial in one chair conformation with two axial methyl groups (34A), but equatorial in the other chair conformation that has two equatorial methyl groups (34B). Only conformation 34A has an axial bromine atom required for an E2 reaction, but both P-hydrogen atoms (Hg and Hb) are equatorial. No P-hydrogen atoms are trans, diaxial to an axial bromine, so there is no E2 reaction. When 34 is heated with ethanol KOH, there is no E2 reaction. The carbon bearing the bromide in 34 is very sterically hindered, so an Sn2 reaction is very unlikely certainly the substitution will be very slow. 

Substituted cyclohexanes only undergo E2 reactions from the chair conformation in which the leaving group and the proton both occupy axial positions. 

Abstract This chapter emphasises on the important aspects of steric and stereo-electronic effects and their control on the conformational and reactivity profiles. The conformational effects in ethane, butane, cyclohexane, variously substituted cyclohexanes, and cis- and tra/ ,v-decalin systems allow a thorough understanding. Application of these effects to E2 and ElcB reactions followed by anomeric effect and mutarotation is discussed. The conformational effects in acetal-forming processes and their reactivity profile, carbonyl oxygen exchange in esters, and hydrolysis of orthoesters have been discussed. The application of anomeric effect in 1,4-elimination reactions, including the preservation of the geometry of the newly created double bond, is elaborated. Finally, a brief discussion on the conformational profile of thioacetals and azaacetals is presented. 

As shown in Scheme 7.38 for menthyl chloride [(li ,3i ,45 )-3-chloro-4-(l-methylethyl)methyl-cyclohexane], the isomer in which all of the substituents are (preferentially) equatorial, antiperiplanar elimination can only occur when the ring flexes into the less stable conformation where all groups are axial. As shown in the scheme, there is only one proton that is both axial and p to the chlorine. Thus, there is only one E2 elimination product on reaction with sodium hydroxide in ethanol. 

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