Cyclohexanes with two substituents come in cis and trans forms, each with unique conformations. These structures affect stability due to steric interactions and substituent positioning. Understanding these conformations is key to predicting molecular behavior and reactivity.

Energy differences between conformations depend on substituent size and position. By calculating these differences, we can determine the most stable conformation and predict conformational equilibrium. This knowledge is crucial for understanding cyclohexane chemistry and its applications.

Conformations of Disubstituted Cyclohexanes

Cis vs trans disubstituted cyclohexanes

• Cis disubstituted cyclohexanes have both substituents on the same side of the ring (above or below the plane) can exist in either diaxial (both substituents axial) or diequatorial (both substituents equatorial) conformations
• Trans disubstituted cyclohexanes have substituents on opposite sides of the ring exist in either axial-equatorial (one substituent axial, the other equatorial) or equatorial-axial (one substituent equatorial, the other axial) conformations

Stability of cyclohexane conformations

• Steric interactions influence conformation stability 1,3-diaxial interactions (steric strain) destabilize the conformation when two axial substituents are separated by two carbon atoms
  • Equatorial substituents generally experience less steric strain than axial substituents
• Cis disubstituted cyclohexanes diequatorial conformation more stable than diaxial
  • Diaxial has two 1,3-diaxial interactions causing significant steric strain (methyl groups)
  • Diequatorial minimizes steric strain by placing both substituents in equatorial positions (chloro groups)
• Trans disubstituted cyclohexanes axial-equatorial and equatorial-axial conformations are equally stable
  • Both have one axial and one equatorial substituent resulting in similar steric strain (bromo and ethyl)
• Conformational analysis considers the effects of ring strain and substituent effects on overall stability

Energy differences in chair conformations

• Energy difference between conformations depends on substituent size larger substituents (tert-butyl) increase the energy difference while smaller substituents (fluoro) result in smaller differences
• Approximate energy differences for common substituents in kcal/mol per substituent:
  1. Methyl (CH3): 1.7
  2. Ethyl (CH2CH3): 1.8
  3. Isopropyl (CH(CH3)2): 2.2
  4. tert-Butyl (C(CH3)3): 4.9
  5. Chloro (Cl): 0.5
  6. Bromo (Br): 0.6
• Total energy difference calculated by adding individual substituent contributions
  • Example: cis-1,3-dimethylcyclohexane
    1. Diaxial conformation: $2 × 1.7 = 3.4$ kcal/mol higher in energy than diequatorial
    2. Diequatorial conformation more stable by 3.4 kcal/mol
• A-values quantify the energy difference between axial and equatorial positions for specific substituents

Conformational Equilibrium

• Conformational equilibrium describes the distribution of different conformations in a mixture
• Factors affecting equilibrium include temperature, solvent, and the relative energies of conformations
• The position of equilibrium can be influenced by the magnitude of ring strain and substituent effects