Study Guides › Conformational Analysis

Conformational Analysis

This guide is an early version — the text is complete, and a few figures are still being redrawn. Spotted something unclear? Let us know.

The question this page answers: What is the actual 3D nature of organic molecules? Are they static or flexible?

Deeper reading: Clayden 2e: Chapter 16 Page 360–379 — see our chapter-by-chapter practice map for Clayden.

Conformations and bond rotation

What relates conformational isomers?

Molecules exist in various conformations (or conformational isomers) that are related by bond rotation.

Here are some examples:

Here are some examples:

Being able to identify the most stable conformation of a molecule is central to understanding its properties and behavior.

The ratio between conformations can be estimated with the rule of thumb that 1.4 kcal/mol at 298 K is worth roughly one order of magnitude in equilibrium constant K.

Newman projections

How do we visualize bond rotation?

Newman projections are a drawing method that help with visualizing this bond rotation.

Newman projections are drawn from the perspective of looking directly down a C–C bond. Here are a couple examples:

Newman projections are drawn from the perspective of looking directly down a C–C bond. Here are a couple examples:

Notice the terminology of “staggered” vs. “eclipsed” to describe how the groups attached to the carbon atoms are rotated with respect to each other.

Why conformations differ in energy

What sets a conformation's energy?

Different conformations of a molecule have different energies because of the balance between stabilizing delocalization or destabilizing repulsion.

Here is an energy diagram for conformations of ethane from Prof. Tim Wallace (Manchester):

Figure coming soon — being redrawn for this guide.

The increased energy in eclipsed conformations comes from destabilizing torsional strain that arises from repulsion between electron clouds of the two C–H bonds. Additionally, in the staggered conformation there is stabilizing hyperconjugation interaction between the σ C–H orbital and the parallel anti-bonding σ* C–H orbital:

The increased energy in eclipsed conformations comes from destabilizing torsional strain that arises from repulsion between electron clouds of the two

Syn-periplanar, anti-periplanar, and gauche

Naming butane conformations

When there are more substituents, things go more complicated. Here is an energy diagram for butane, also by Prof. Tim Wallace (Manchester):

Figure coming soon — being redrawn for this guide.

Notice that the added nomenclature of syn-periplanar and anti-periplanar help refer to specific instances where the largest groups are eclipsed or staggered. You will also hear these referred to as syn-coplanar and anti-coplanar. The gauche conformation is the one where the Newman projection is staggered, but the largest groups are still close to each other.

The steric strain between methyl groups arises from repulsion when the H atoms try to occupy the same space.

The cyclohexane chair flip

What is a chair flip?

Cyclohexanes undergo a series of conformation changes that can be summarized as a chair flip.

In the chair conformation of cyclohexane, half the substituents on the C atoms are axial and the other half are equatorial. Upon a chair flip, everything axial switches to becoming equatorial and vice versa:

In the chair conformation of cyclohexane, half the substituents on the C atoms are axial and the other half are equatorial. Upon a chair flip, everyth

The most significant intermediate conformation during the chair flip process is the boat conformation. Here is a numbered depiction on how to interconvert these conformations:

The most significant intermediate conformation during the chair flip process is the boat conformation. Here is a numbered depiction on how to intercon

Even though the chair conformation is the lowest energy conformation, there are still repulsive interactions, of which 1,3-diaxial strain is the most important:

Even though the chair conformation is the lowest energy conformation, there are still repulsive interactions, of which 1,3-diaxial strain is the most

Translating line-angle drawings to chairs

Draw the chair both ways

It is important to be able to translate fluidly between line-angle drawing and perspective-style cyclohexane chairs.

Here are some examples, note that these chairs are not all in the same conformation:

Here are some examples, note that these chairs are not all in the same conformation:

A-values and the equatorial preference

Axial or equatorial?

Because of diaxial strain, a general trend is that the lowest energy conformation of a cyclohexane has its largest group equatorial, not axial.

Here are some examples:

Here are some examples:

This preference can be quantified by A-values, which indicate the energy cost of placing a group axial instead of equatorial:

Figure coming soon — being redrawn for this guide.

The chair conformation with the lower total A-value will likely be the lowest energy conformation of the molecule:

The chair conformation with the lower total A-value will likely be the lowest energy conformation of the molecule:

In this case, we would predict the difference in energies of the chair forms would be ~3.5 kcal, which would correspond to an equilibrium ratio of ~368 to 1 at 298 K.

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