2.14 Conformations of Monosubstituted Cyclohexanes

Even though cyclohexane rings flip rapidly between chair conformations at room temperature, the two conformations of a monosubstituted cyclohexane aren’t equally stable. In methylcyclohexane, for instance, the equatorial conformation is more stable than the axial conformation by 7.6 kJ/mol (1.8 kcal/mol). The same is true of other monosubstituted cyclohexanes: a substituent is almost always more stable in an equatorial position than in an axial position.

The energy difference between axial and equatorial conformations is due to steric strain caused by 1,3-diaxial interactions. The axial methyl group on C1 is too close to the axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kJ/mol of steric strain (Figure 2.22).Figure 2.22 Interconversion of axial and equatorial methylcyclohexane, represented in several formats. The equatorial conformation is more stable than the axial conformation by 7.6 kJ/mol.

The 1,3-diaxial steric strain in substituted methylcyclohexane is already familiar—we saw it previously as the steric strain between methyl groups in gauche in Section 2.8. Gauche butane is less stable than anti butane by 3.8 kJ/mol (0.9 kcal/mol) because of steric interference between hydrogen atoms on the two methyl groups. Comparing a four-carbon fragment of axial methylcyclohexane with gauche butane shows that the steric interaction is the same in both (Figure 2.23). Because axial methylcyclohexane has two such interactions, it has 2 × 3.8 = 7.6 kJ/mol of steric strain. Equatorial methylcyclohexane has no such interactions and is therefore more stable.

Figure 2.23 The origin of 1,3-diaxial interactions in methylcyclohexane. The steric strain between an axial methyl group and an axial hydrogen atom three carbons away is identical to the steric strain in gauche butane. (To display clearly the diaxial interactions in methylcyclohexane, two of the equatorial hydrogens are not shown.)

The exact amount of 1,3-diaxial steric strain in a given substituted cyclohexane depends on the nature and size of the substituent. Not surprisingly, the amount of steric strain increases through the series H₃C− < CH₃CH₂− < (CH₃)₂CH–<< (CH₃)₃C−, paralleling the increasing size of the alkyl groups.

Problem 2.30
Why do you suppose an axial cyano (–CN) substituent causes practically no 1,3-diaxial steric strain (0.4 kJ/mol)?