Conformational isomerism

Conformers of butane. The gauche and anti forms are staggered conformations. The eclipsed conformation of butane is unstable because it is at an energy maximum.

In chemistry, conformational isomerism is a form of stereoisomerism in which molecules with the same structural formula (same connectivity) exist as different conformational isomers or conformers in 3-D due to rotations about one or more σ bonds. ^[1] Conformations are not superimposable in three dimensions and can be characterized by their dihedral angles, the angle between two planes formed by atom₁-atom₂-atom₃ and atom₂-atom₃-atom₄ in a sequence of atoms, atom₁-atom₂-atom₃-atom₄. The dihedral angle can also be seen as the angle between the two vectors formed by atom₂→atom₁ and atom₃→atom₄. Rotamers are conformers that differ by rotation about only a single σ bond.^[2]. That is, only one dihedral angle will be different between rotamers. Conformers can differ by rotations about many sigma bonds or just one (i.e. a rotamer is a conformer). The rotational barrier, or barrier to rotation, is the activation energy required to convert from one rotamer to another rotamer.

Different conformers can interconvert by rotation around single bonds, without breaking chemical bonds. The existence of more than one conformation, usually with different energies, is due to hindered rotation about sp³ hybridised σ bonds. The comparative stabilities of different conformers of a molecule are usually explained through differences in a combination of steric repulsion and electronic effects. A simplified example is that of a butane molecule viewed in the Newman projection shown - i.e. as if viewed down the central C2-C3 bond with relative rotations of C1 and C4 illustrated. The only unique gauche conformer in case of butane has a dihedral angle of 60°, anti is 180°, and eclipsed is 0° in the CH₃-CH₂-CH₂-CH₃. In the case of 1-fluoropropane F-CH₂-CH₂-CH₃, there is a gauche⁺ and a gauche^- rotamer, with dihedral angles of +60 and -60 respectively. Butane does not have both because of symmetry.

Important examples of conformational isomerism include:

1. Linear alkane conformations with staggered, eclipsed and gauche conformers, and
2. Ring conformation
   • Cyclohexane conformations with chair and boat conformers.
   • Carbohydrates
   • Steroids
3. Atropisomerism- due to restricted rotation about a bond, a molecule can become chiral
4. Folding of molecules, where some shapes are stable and functional, but others are not.

Equilibrium Population of Conformers

Boltzmann distribution % of lowest energy conformation at various temperatures (degrees Celsius, color) and energy difference in kcal/mol (x-axis)

The population of different conformers follows a Boltzmann distribution:

The left hand side is the equilibrium ratio of conformer i to the total. E_rel is the relative energy of the i-th conformer from the minimum energy conformer. R is the molar ideal gas constant equal to 8.31 J/(mol·K) and T is the temperature in kelvins (K). The denominator of the right side is the partition function.

Consequences

If the eclipsed conformations of an isomer have high enough potentials, they may prevent rotation of substituents to different staggered conformations at sufficiently low energy levels. This will result in a racemic mixture of conformations that may or may not have different reactivities in situations such as enzymatic reactions in which molecular shape is usually a key factor of operation.

Conformer dependent reactions

The E2 elimination mechanism relies on the base- or acid-attacked substituent being in an antiperiplanar configuration along a bond with respect to the leaving group. This prerequisite for reaction is important in understanding organic elimination reaction pathways, especially those involving halogenated cyclic alkanes such as cyclohexanes. Two adjacent substituents on a cyclic alkane can only undergo an E2 elimination if they are both axial to the ring and hence antiperiplanar. A combination of axial and equatorial substituents cannot react through an E2 mechanism, though ring flips (with associated reconformation) may allow reactions to occur if they are not precluded by an energy barrier or steric lock through isopropyl or larger substituents.

Conditions

Conformational isomerism only occurs around single bonds because double or triple bonds have one or two pi bonds that prevent rotation about the longitudinal axis. Conformers sufficiently constrained to exhibit measurable isomerism are unique from various flavours of stereoisomers in the fact that changes in stereochemistry are independent from any mechanism and instead rely only on molecular energy.

References

1. ^ http://goldbook.iupac.org/C01258.html|IUPAC definition of a conformer.
2. ^ International Union of Pure and Applied Chemistry (1996). "Rotamer". Compendium of Chemical Terminology Internet edition.

See also

• Isomer
• Steric effects
• Molecular configuration

External links

• Polymer structure: configuration and conformation