It is, however, found that the substitution of an axial substituent proceeds faster than the substitution of an equatorial substituent. This is because, in the formation of the transition state, the nucleophile attacks the σ*-molecular orbital of the carbon-leaving group (C-X) bond. In the case of an axial attack, this line of attack is hindered by the axial groups at 3 and 5 positions. For an equatorial attack the direction of attack is parallel with the axial groups antiperiplanar to the leaving group and hence much less hindered (Figure 6).
Figure 6
Similarly, the ring closing to form epoxides occurs only in the trans isomer. The cis isomer adopts a conformation where one of the groups is axial (less bulky one), while the other is equatorial. In this conformation the two groups are not antiperiplanar as required for a SN2 reaction. The trans isomer, on the other hand adopts a conformation where both the groups are equatorial to each other. Though, it still seems not suited for a SN2 attack but the attack can take place in the diaxial conformation which may be generated from the diequitorial conformation by ring flipping. Though the former is less stable than the latter, a small amount of the molecule in diaxial conformation may drive the reaction forward (Le Chatelier’s principle) (Scheme 6).
Scheme 6
As with substitution, the elimination reaction in cyclohexane derivatives is also dependent on the conformation. Since E2 reactions can occur only through an antiperiplanar transition state so they must be stereospecific in nature. Thus, in the elimination of trans-1-chloro-2-methyl cyclohexane, the elimination takes place from the diaxial isomer (Scheme 7).
Scheme 7