Conformations

Conformations of Alkanes and Cycloalkanes

General Overview

  • Conformations are different rotational arrangements of a molecule, particularly in the context of alkanes and cycloalkanes.
  • Molecules with different conformations are called conformers or conformational isomers.

Bond Rotations

  • Bond rotations occur between sp³-hybridized carbons.
  • The cylindrical symmetry of the σ bond allows for these rotations.

Alkane Conformations

  • Molecular models help visualize the conformations of alkanes.

Representing Conformations

  • Conformation: A three-dimensional arrangement of atoms in a molecule resulting from rotation about a single bond.
  • Newman Projection: A method to visualize a molecule by looking along a carbon-carbon bond; it represents the dihedral (torsion) angle of the molecule's atoms.
  • Torsional Strain: Repulsions between groups on adjacent atoms when they rotate closer together.

Staggered vs Eclipsed Conformations

  • Staggered Conformation: Bonds on adjacent carbon atoms are furthest apart, resulting in the least torsional strain.
  • Eclipsed Conformation: Bonds on adjacent carbon atoms are closest together, which results in the most torsional strain. This conformation has higher energy because it takes energy to bring the atoms closer together.

Conformations of Ethane

  • Eclipsed Conformation has a torsional strain of approximately 2.9 kcal/mol (12 kJ/mol).

Steric Strain

  • Steric Strain: Occurs due to repulsive forces when atoms that are not bonded are forced closer together (electron cloud repulsion).
  • Gauche Conformation: Substituents are 60° apart, which may lead to steric strain.
  • Anti Conformation: Substituents are 180° apart; thus, no torsional strain nor steric strain (~3.8 kJ/mol).

Strain in Alkane Conformers

  • Examples of strain in conformers include:
    • Torsional strain: 4 kJ/mol
    • Torsional and steric strain combinations range from 6 kJ/mol to 11 kJ/mol.

Conformations of Butane

  • Discusses steric strain resulting from the proximity of electron clouds and various conformational isomers.

Cycloalkane Structures

  • Bond Rotations in Cycloalkanes: Cycloalkanes (sp³ C atoms in a ring) have less flexibility than open-chain alkanes.

Angle Strain in Cycloalkanes

  • Angle Strain: Arises from bond angles that do not permit maximum orbital overlap; ideal angle is 109.5°.
  • Rings larger than three atoms will not be flat and will adopt non-planar conformations to minimize angle and torsional strain.

Specific Cycloalkanes

  • Cyclopropane:

    • 3-membered ring must be planar, leading to a bond angle of 60°.
    • Results in reduced orbital overlap due to bent δ bonds and significant torsional strain since all C-H bonds are eclipsed.

  • Cyclobutane:

    • Expected to be more angle strain-free than cyclopropane but suffers from increased torsional strain.
    • The butterfly conformation helps alleviate torsional strain.

  • Cyclopentane:

    • A planar structure would produce no angle strain but significant torsional strain.
    • Non-planar structure offers little ring strain and reduced torsional strain (envelope conformation).

  • Cyclohexane:

    • Substituted cyclohexane rings are common (e.g., cholesterol) and are free from angle strain and torsional strain.
    • The chair conformation forms tetrahedral angles, alleviating all strain.

Representing Cyclohexane Chair Conformations

  • Top-View and Side-View representations show the non-planar chair conformation of cyclohexane.

Axial and Equatorial Positions

  • In the chair conformation:
    • 6 axial positions (perpendicular to the ring plane)
    • 6 equatorial positions (along the ring plane)
  • Each carbon atom has one axial and one equatorial position, which alternate in orientation.

Drawing Cyclohexane Chair Conformations

Step 1: Draw C-C bonds

  • Procedure to illustrate the C-C bonds in cyclohexane.

Step 2: Draw Axial and Equatorial Groups

  • Axial Substituents: Vertical orientations, alternating structure.
  • Equatorial Substituents: Parallel to ring bond and also alternate up and down.

Cyclohexane Conformation Mobility

  • The chair conformations interconvert through “chair-flip”, redistributing axial and equatorial positions.
  • After the flip, axial positions become equatorial, and equatorial become axial. Up and down orientations are preserved through the flip.

1,3-Diaxial Interactions

  • Two conformations of monosubstituted cyclohexanes are not equally stable due to 1,3-diaxial interactions.
  • These interactions create steric strain; the substituent's size influences the magnitude of steric strain, favoring equatorial positions for bulkier groups.
  • Example values of steric strain for substituents:
    • R = CH3: ∆G° = +3.8 kJ/mol
    • Substituent sizes escalate the steric strain from 1.0 for Cl or Br to 11.4 for t-butyl groups.

Stereoisomers in Cycloalkanes

  • Stereoisomers: Compounds connected in the same order but differing spatially; commonly occur in cycloalkanes with multiple substituents.

Analysis of Disubstituted Cyclohexanes

  • Cis and trans forms exist, where:
    • Cis: Substituents on the same face of the ring
    • Trans: Substituents on opposite faces of the ring

Examples Include:

  • cis-1,2-Dimethylcyclohexane
  • trans-1,2-Dimethylcyclohexane

Take-Home Problems

  1. Determine cis/trans isomerism in provided structures.
  2. Draw chair conformations for trans-1-tert-butyl-3-methylcyclohexane and identify the most stable conformation utilizing equatorial positions for larger substituents.
  3. Analyze chair conformations for the synthetic opioid Tramadol and determine stability.