Conformational isomerism 2.

In the case of cyclic compounds full rotation around a bond is already not possible and the conformation is highly dependent on the devation of the geometry from that of the ideal one. To get tetrahedral geometries for the carbons, the ring must be nonplanar. Especially in small rings (cyclopropane and cyclobutane) the valence angles of carbons are far from the ideal 109.3°, therefore these rings have a high ring strain (Bayer-strain). The cyclopentane is nearly free of angle strain (108°). Cyclohexane can adopt the ideal geometry without any strain and so do the higher membered rings. However, the latter can also be strained when unsaturated.

Cyclohexane has three stable conformations: chair (having the lowest energy of the three), twisted boat and the metastable boat confomations:

The energy differences between the chair and the other forms are quite small, nevertheless it is high enough to force the molecule to adopt ~99.9% of chair conformation in equilibrium. The chair forms can freely interconvert (flip) at room temperature.

Question:

Bearing in mind the interactions described in the previous page, why have the boat conformations of cyclohexane higher energy than the chair ones?

Answer...

In the chair conformation the bonds (and the corresponding bonded atoms) of 2-2 atoms are in eclipsed position. This strain leads to higher energy content. There are other effects, though, see later.



The examination of the 12 hydrogens (or substituents) of cyclohexane reveals that these are of two types: the six equatorial substituents and their bonds are positioned roughly in the plane of the ring, while the six axial ones are oriented above and below the plane.
Notice that ring flip (chair → boat → chair) causes equatorial hydrogens or substituents to become axial, and vice-versa.

Substituents larger than hydrogen experience greater steric crowding when they are axial rather than equatorial (Van der Waals strain or "flagpole" interaction).

In the case of 1-methyl-cylohexane the energie difference is about 1.7 kcal/mol. This cannot prevent the ring from flipping, however, it will preferentially adopt conformations with the methyl group in the equatorial orientation (~95:5). This effect is more pronounced in molecules with large subtituents, these can even fix the conformation of the molecule.

If several substituents are present, the molecule tends to adopt a conformation with the most possible substituents in equatorial positions. For example all of the substituents of the D-glucose molecule are in equatorial position.
There are other factors to influence conformations, their energies and distributions, for example the possible hydrogen bonds between the substituents.


For disubstituted cyclohexanes stereoisomerism is possible, the cis-trans nomenclature is preferred to distinguish the isomers. For example, the two configurations of 1,2-disubstituted cyclohexanes can exist in 2-2 conformations respectively, as each substituents may be axial or equatorial:


Questions:

Of the four isomers of the 1,2-difluorocyclohexane drawn above which one is energetically the most favoured one?

Answer...

Based on the above discussion, the trans diequatorial (eq-eq) isomer is more stable by 1-2 kcal/mol than the other three ones.


Why is the right conformation of 1-tert-buthyl-1-methyl-cyclohexane more stable than the left one?


Answer...

The molecule tends to adopt the conformation with the larger substituent in the equatorial position.


When two cyclohexan rings are joined to obtain the decalin molecule (named also decahydronaphthalene or bicyclo[4.4.0]decane), there are two possibilities for the fusion: the new atoms can be added either in ax-eq/eq-ax or in eq-eq positions. In other words, the two fluorine atoms of the above difluoro-cyclohexane is replaced with a ‑CH2CH2CH2CH2‑ chain. The new ring cannot be added in axial-axial manner because this would be geometrically impossible. Therefore cis-decaline is a mixture of two conformers, while the ring system of trans-decaline is fixed and rigid:

cis-Decalin and trans-decalin in 3D:


Question:

How many axial and equatorial hydrogen atoms are in the cis- and trans-decalin molecules?

Answer...

trans-Decalin has 10 axial and 8 equatorial hydrogens. In the case of cis-decaline it cannot be answered is unambiguously, because the two common hydrogens of the rings are equatorial in one ring while axial in the other one.