Cyclohexane rings can adopt different shapes, with substituents in axial or equatorial positions. These conformations have different energies due to steric and torsional strain. Understanding these differences is crucial for predicting molecular behavior and reactivity.

Larger substituents prefer the equatorial position to minimize unfavorable interactions. This preference is quantified by the A-value, which measures the energy difference between axial and equatorial conformations. Polar groups also tend to favor the equatorial position.

Conformations of Monosubstituted Cyclohexanes

Energy of cyclohexane conformations

• Monosubstituted cyclohexanes exist in two conformations axial and equatorial
  • Axial conformation substituent is perpendicular to the ring plane (e.g., axial methylcyclohexane)
  • Equatorial conformation substituent is parallel to the ring plane (e.g., equatorial methylcyclohexane)
• Energy difference between axial and equatorial conformations denoted as $\Delta G°$
  • $\Delta G° = G°{axial} - G°{equatorial}$
  • More stable conformation has a lower $G°$ value
• Factors affecting energy difference
  • Steric strain bulky substituents prefer equatorial position to minimize 1,3-diaxial interactions (e.g., t-butylcyclohexane)
  • Torsional strain substituents with lone pairs or multiple bonds prefer equatorial position to minimize eclipsing interactions (e.g., hydroxycyclohexane)
• Energy difference typically expressed in kcal/mol or kJ/mol
  • Magnitude of $\Delta G°$ depends on nature of substituent
  • Larger, bulkier substituents have greater preference for equatorial position, resulting in larger $\Delta G°$ (e.g., isopropylcyclohexane vs methylcyclohexane)
  • The preference for the equatorial position is quantified by the A-value, which represents the free energy difference between axial and equatorial conformations

Effects of 1,3-diaxial interactions

• 1,3-Diaxial interactions occur when two axial substituents are located on same side of cyclohexane ring, separated by two carbon atoms
  • Interactions are unfavorable due to steric repulsion between substituents
  • Larger substituents lead to greater steric strain and less stable conformation (e.g., di-tert-butylcyclohexane)
• In monosubstituted cyclohexanes, 1,3-diaxial interactions occur when substituent is in axial position
  • Axial substituent experiences steric repulsion with axial hydrogens at 3 and 5 positions
  • Interaction destabilizes axial conformation relative to equatorial conformation
• Magnitude of 1,3-diaxial interactions depends on size of substituent
  • Larger substituents experience greater steric repulsion, making axial conformation less favorable (e.g., t-butylcyclohexane)
  • Smaller substituents experience less steric repulsion, reducing energy difference between axial and equatorial conformations (e.g., methylcyclohexane)

Preferred conformations of substituted cyclohexanes

• Preferred conformation of monosubstituted cyclohexane is one with lower energy (more stable)
  • Usually conformation that minimizes steric strain and torsional strain
• Substituent size affects preferred conformation
  1. Larger substituents prefer equatorial position to minimize 1,3-diaxial interactions (t-butyl, isopropyl)
  2. Smaller substituents have smaller preference for equatorial position (methyl, ethyl)
• Substituent polarity affects preferred conformation
  1. Polar substituents with lone pairs or multiple bonds prefer equatorial position to minimize torsional strain (-OH, -NH2, -C≡N)
  2. Equatorial position allows better alignment of substituent with C-H bonds, reducing eclipsing interactions
• Examples of preferred conformations
  • Methylcyclohexane small preference for equatorial conformation due to small size of methyl group
  • t-Butylcyclohexane strong preference for equatorial conformation due to large size of t-butyl group and significant 1,3-diaxial interactions in axial conformation
  • Hydroxycyclohexane preference for equatorial conformation due to polar nature of -OH group and desire to minimize torsional strain

Conformational Analysis Techniques

• Chair conformation is the most stable form of cyclohexane, with all bonds staggered
• Ring flip is the process by which a cyclohexane molecule converts between two chair conformations, interchanging axial and equatorial positions
• Newman projections can be used to visualize and analyze the staggered and eclipsed conformations of cyclohexane and its derivatives