3.12: Stability of Substituted Cyclohexanes

This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.

The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.

For example, in methylcyclohexane, the CH₃ group occupies an axial position in one chair conformation and an equatorial position in another. This leads to an increase in energy of the axial conformation to approximately 7.6 kJ mol⁻¹, making the equatorial conformation more stable with an abundance of 95%.

The reason for such variations in energy and stability is that the methyl hydrogens experience repulsive dispersion interactions with the two parallel and closely positioned axial hydrogens on the same side of the ring. Since the steric strain originates between groups on C1 and C3 or C5, it is called a 1,3-diaxial interaction. These interactions, when shown with the Newman projection, exhibit a gauche relationship. However, if the methyl group is positioned equatorially, it is placed anti to C3 and C5, minimizing the steric repulsion.

As the size of a functional group increases, 1,3-diaxial interactions become more pronounced, increasing the energy difference between the two conformations.

The two chair conformations of cyclohexane, at equilibrium, have identical energies and stabilities, with each conformer representing about 50% of the equilibrium mixture.

Replacing a hydrogen atom with an alkyl group makes the two conformations energetically nonequivalent.

For instance, in methylcyclohexane, the CH₃ group occupies an axial position in one chair conformation and an equatorial position in another.

The axial conformation has an elevated energy of approximately 7.6 kJ mol⁻¹ compared to the equatorial conformation, making the latter more stable.

Consequently, the equatorial conformation comprises about 95% of the equilibrium mixture. The question is — what is the reason for such variations in energy and stability?

Studies reveal that in an axial conformation, the methyl hydrogens experience repulsive dispersion interactions with the two parallel and closely positioned axial hydrogens on the same side of the ring.

This unfavorable steric strain between groups on C1 and C3 or C5 is called 1,3-diaxial interaction, which is a gauche interaction.

Each gauche interaction contributes approximately 3.8 kJ of additional energy.

Such gauche interactions are absent in an equatorial conformation since the methyl group is placed anti to C3 and C5. Hence, the molecules of methylcyclohexane predominantly adopt the low energy, more stable equatorial form.

In monosubstituted cycloalkanes, as the size of the substituent increases, 1,3-diaxial interactions become stronger, causing the energy difference between the two conformations to become more pronounced.

This is particularly evident when the substituent is a tert-butyl group. The low-energy equatorial conformation is much more stable than the axial conformation, with an abundance of 99%.

In disubstituted cycloalkanes — like dimethyl cyclohexane, an increased steric repulsion between methyl groups further reduces the probability of axial conformation in its molecules.