Cyclohexane ring flip

Substituent groups on the steroid ring system can be either axial or equatorial. As with simple cyclohexanes (Section 4.7), equatorial substitution is generally more favorable than axial substitution for steric reasons. The hydroxyl group at C3 of cholesterol, for example, has the more stable equatorial orientation. Unlike what happens with simple cyclohexanes, however, steroids are rigid molecules whose geometry prevents cyclohexane ring-flips. 

In a monosubstituted cyclohexane, the substituent can be either in an equatorial or axial position. Equatorial positions are more spacious and in substituted cyclohexanes they are preferred. Cyclohexane rings flip between chair forms and establish an equilibrium. In the process of flipping, all equatorial positions become axial and all axial positions become equatorial. The equilibrium favors the chair in which substituents are equatorial. In monosubstituted cyclohexanes, the conformation in which the substituent is equatorial is favored. In disubstituted cyclohexanes where one group is axial and one equatorial, the equilibrium favors the chair form where the larger group occupies the more spacious equatorial position. 

Axial hydrogens (Section 5.2) The set of six straight up and down hydrogens in chair cyclohexane. Ring flip interconverts these hydrogens with the set of equatorial hydrogens. 

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 hy 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. 

We have seen that when a cyclohexane ring flips, all equatorial bonds become axial and all axial bonds become equatorial. Now lets consider the consequences of flipping a substituted cyclohexane ring. The chair—chair interconversion of monosubstituted cyclohexanes occurs very rapidly. However, the two conformations of monosubstituted cyclohexanes, unlike those of cyclohexane, are not equally stable. 

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