11.9 • The E2 Reaction 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 4.8). The anti periplanar requirement for E2 reactions overrides Zaitsev’s rule and can be met in cyclohexanes only if the hydrogen and the leaving group are trans diaxial (Figure 11.20). If either the leaving group or the hydrogen is equatorial, E2 elimination can’t occur.
The elimination of HCl from the isomeric menthyl and neomenthyl chlorides shown in Figure 11.21 gives a good illustration of this trans-diaxial requirement. Neomenthyl chloride undergoes elimination of HCl on reaction with ethoxide ion 200 times faster than menthyl chloride. Furthermore, neomenthyl chloride yields 3-menthene as the major alkene product, whereas menthyl chloride yields 2-menthene.
The difference in reactivity between the isomeric menthyl chlorides is due to the difference in their conformations. Neomenthyl chloride has the conformation shown in Figure 11.21a, with the methyl and isopropyl groups equatorial and the chlorine axial—a perfect geometry for E2 elimination. Loss of the hydrogen atom at C4 occurs easily to yield the more substituted alkene product, 3-menthene, as predicted by Zaitsev’s rule.
Menthyl chloride, by contrast, has a conformation in which all three substituents are equatorial (Figure 11.21b). To achieve the necessary geometry for elimination, menthyl chloride must first ring-flip to a higher-energy chair conformation, in which all three substituents are axial. E2 elimination then occurs with loss of the only trans-diaxial hydrogen available, leading to the non-Zaitsev product 2-menthene. The net effect of the simple change in chlorine stereochemistry is a 200-fold change in reaction rate and a complete change of product. The chemistry of the molecule is controlled by its conformation.