Elimination Reactions and Cyclohexane Conformation

Anti periplanar geometry for E2 reactions is particularly important in cyclohexane rings, where chair geometry forces a rigid relationship between the substituents on neighboring carbon atoms (Section 4.9). As pointed out by Derek Barton in a landmark 1950 paper, much of the chemical reactivity of substituted cyclohexanes is controlled by their conformation. Let s look at the E2 dehydrohalogenation of chlorocyclohexanes to see an example of such conformational control. 

The geometric requirement for E2 reaction in a cyclohexane. The leaving group and the hydrogen must both be axial for anti perlplanar elimination to be possible. 

Oehydrochlorination of menthyl and neomenthyl chlorides, (a) Neomenthyl chloride loses HCl from its more stable conformation, but (b) menthyl chloride must first ring ftip before HCl loss can occur. 

Problem 11.19 Which isomer would you expect to undergo E2 elimination faster, 2rans-l-bromo-4- tert-butylcyclohexane or cis-l-bromo-4- er -butylcyclohexane Draw each molecu in its more stable chair conformation, and explain your answer. 

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Elimination Reactions and Cyclohexane Conformation The Deuterium Isotope Effect 420 The El Reaction 421... 

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. 

The six-membered rings in these T.S.s are more flexible than the five-membered T.S.—(81) above—and need not be planar (cf cyclohexanes v. cyclopentanes). Elimination may thus proceed, in part at least, from conformations other than the syn-periplanar, with the result that the degree of SYN stereoselectivity in these eliminations may sometimes be lower than that observed in the Cope reaction. Both reactions require higher temperatures than for the Cope reaction, carboxylic esters particularly so. 

The reaction fails if the proton to be removed is sterically hindered — either tertiary as in 21 or neopentyl-like as in 226,). In six membered rings, the ds, syn hydrogen must be axial for elimination. In the parent cyclohexyl system 23, a mixture of 24 and 25 results29 whereas, in a conformationally rigid cyclohexane... 

More evidence comes from the reactions of substituted cyclohexanes. You saw in Chapter 18 that substituents on cyclohexanes can be parallel with one another only if they are both axial. An equatorial C-X bond is anti-periplanar only to C-C bonds and cannot take part in an elimination. For unsubstituted cyclohexyl halides treated with base, this is not a problem because, although the axial conformer is less stable, there is still a significant amount present (see the table on p. 462), and elimination can take place from this conformer. 

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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