In chair conformation with more than one substituent, where does the larger substituent prefer to be located?

In chair conformation of cyclohexane, the spatial orientation of substituents significantly influences the stability of the molecule. When considering multiple substituents attached to the cyclohexane ring, the larger substituent prefers to be in the equatorial position. This preference arises because the equatorial position allows for more spatial distance from other substituents, minimizing steric hindrance and torsional strain.

In the axial position, substituents are aligned along the axis of the ring, which can lead to 1,3-diaxial interactions with other axial substituents on the same side of the ring. These interactions impose greater steric hindrance, making the molecule less stable. In contrast, the equatorial position positions the larger substituent further away from other groups on the ring, allowing for a more favorable arrangement that reduces steric clashes and contributes to the overall stability of the chair conformation.

Therefore, when multiple substituents are present, positioning the larger substituent equatorially is the most favorable arrangement for achieving a stable conformation of the cyclohexane ring.