Why can cyclohexane rings cause some complications with elimination reactions?

Question

Elias Aguila · Accepted Answer

Cyclohexane rings can cause complications because E2 eliminations must be antiperiplanar.

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule.

An example is the dehydrobromination of bromoethane.

The H atom must come from the β carbon atom — the carbon next to the one bearing the leaving group.

Also, the bonds to the β H and to the leaving group LG must be antiperiplanar.

Consider the dehydrohalogenation of menthyl chloride, (#1S,2R,4R#)-2-chloro-1-isopropyl-4-methylcyclohexane.

If we ignore stereochemistry, we identify β H atoms at C-1 and C-3. The major product should be the more stable Zaitsev product, 1-isopropyl-4-methylcyclohexene.

But this product forms in 0 % yield. Only the less stable Hofmann product forms, but slowly.

This makes sense if we consider the stereochemistry of menthyl chloride.

In the most stable chair form, the bulky isopropyl group must be in the equatorial position. This makes the Cl also equatorial.

The ring must flip to the less stable form. That makes both isopropyl and Cl axial.

But then only the β H atom at C-3 is axial and antiperiplanar to the Cl.

So the only observed product is 3-isopropyl-6-methylcyclohexene.

Easton Jones · Answer

undefined Cyclohexane rings can cause complications with elimination reactions due to the potential formation of stable products through different elimination pathways. The geometry of the cyclohexane ring can lead to steric hindrance, making it difficult for reactants or intermediates to adopt the necessary conformation for the reaction to proceed. Additionally, the possibility of multiple substitution patterns on the ring can result in different regioselectivities and product distributions. These factors can make it challenging to control the outcome of elimination reactions involving cyclohexane rings.