Cyclohexane chair conformations are crucial in understanding molecular structure and stability. These conformations involve axial and equatorial positions, which affect how substituents interact and influence overall molecular stability.

Ring-flipping and substituent positioning play key roles in determining the most stable conformations. Understanding these concepts helps predict molecular behavior and reactivity, essential for grasping organic chemistry principles and applications.

Cyclohexane Chair Conformations

Axial vs equatorial positions

• Axial positions have bonds perpendicular to the plane of the ring alternate up and down with substituents pointing either straight up or straight down (methyl groups)
• Equatorial positions have bonds roughly parallel to the plane of the ring with substituents pointing away from the ring are less sterically hindered than axial substituents (hydroxyl groups)
• Bond angles in cyclohexane are close to the ideal tetrahedral angle of 109.5°, minimizing angle strain

Ring-flipping in cyclohexane

• Ring-flipping is the rapid interconversion between two chair conformations at room temperature involves passing through a higher energy half-chair conformation
• During ring-flipping, axial substituents become equatorial and equatorial substituents become axial (methylcyclohexane)
• The more stable conformation has the bulkier substituents in equatorial positions minimizes steric strain avoids 1,3-diaxial interactions between substituents (tert-butylcyclohexane)

Chair conformations of substituted cyclohexanes

• Monosubstituted cyclohexanes:
  1. Draw the chair conformation with the substituent in both axial and equatorial positions
  2. Label the substituent as either axial or equatorial (chlorocyclohexane)
  3. The equatorial conformation is generally more stable
• Disubstituted cyclohexanes:
  1. 1,2-disubstituted cyclohexanes have cis isomers with both substituents on the same side of the ring and trans isomers with substituents on opposite sides of the ring (1,2-dimethylcyclohexane)
  2. 1,3-disubstituted cyclohexanes have cis isomers with both substituents axial or both equatorial and trans isomers with one substituent axial and one equatorial (1,3-dibromocyclohexane)
  3. 1,4-disubstituted cyclohexanes have both substituents either axial or equatorial and the conformation with both substituents equatorial is more stable (1,4-dihydroxycyclohexane)

Stability and Energy

Compare the stability and energy of axial and equatorial substituents in cyclohexane

• Equatorial substituents are generally more stable than axial substituents as equatorial positions are less sterically hindered while axial positions experience greater steric strain (ethylcyclohexane)
• Axial substituents have higher potential energy than equatorial substituents as 1,3-diaxial interactions between substituents increase strain and potential energy (1,3-diaxial methyl groups)
• The energy difference between axial and equatorial substituents is approximately $1-2 kcal/mol$ per substituent depends on the size and nature of the substituent with larger substituents having a greater preference for equatorial positions (isopropylcyclohexane vs methylcyclohexane)

Conformational Analysis and A-values

• Conformational analysis involves studying the different possible spatial arrangements of atoms in a molecule and their relative energies
• A-values quantify the preference for a substituent to occupy an equatorial position over an axial position in cyclohexane
• Larger A-values indicate a stronger preference for the equatorial position, reflecting greater steric strain in the axial position