Which isomer of 1-bromo-3-isopropylcyclohexane reacts faster when refluxed with potassium tert-butoxide

Which isomer of 1-bromo-3-isopropylcyclohexane reacts faster when refluxed with potassium tert-butoxide, the cis isomer or the trans isomer? Draw the structure of the expected product from the faster-reacting compound.

The Correct Answer and Explanation is :

The cis-isomer of 1-bromo-3-isopropylcyclohexane will react faster with potassium tert-butoxide when refluxed. This reaction involves a Williamson ether synthesis mechanism, where the tert-butoxide ion (a strong base) will deprotonate the isopropyl group (if necessary) or participate in an SN2 substitution reaction.

Explanation:

1. Steric hindrance and accessibility: The two isomers (cis and trans) of 1-bromo-3-isopropylcyclohexane differ in the relative orientation of the substituents attached to the cyclohexane ring. In the cis-isomer, the bromine atom at position 1 and the isopropyl group at position 3 are on the same side of the ring. This configuration makes the carbon attached to the bromine (C1) in a more axial position, which is less sterically hindered for an SN2 substitution. Additionally, the isopropyl group is positioned in a more equatorial orientation, reducing any steric strain that would hinder the approach of the nucleophile (tert-butoxide).
2. Trans-isomer: In the trans-isomer, the bromine and isopropyl groups are on opposite sides of the ring, making the C1 position more likely to adopt an equatorial position, but it creates steric interference for the nucleophile in the axial position. As the reaction proceeds, the cis-isomer’s axial position for the leaving group allows for better nucleophilic attack compared to the more hindered trans-isomer.
3. Reaction mechanism: The tert-butoxide ion, being bulky, prefers to attack the more accessible (axial) carbon in the cis-isomer. The reaction proceeds with an SN2 mechanism (since tert-butoxide is a strong nucleophile), with the nucleophile attacking the electrophilic carbon and the leaving group (Br) departing in a single step.

Expected product:

The product formed is an ether with the nucleophile (tert-butoxide) replacing the bromine atom. The expected structure from the faster-reacting cis-isomer would be 3-isopropyl-1-(tert-butoxy)cyclohexane.

Structure of the expected product:

      CH3
       |
CH3-CH2-C-O-CH2-C6H11
       |
      CH3

This reaction illustrates how steric factors influence the rate of nucleophilic substitution, with the cis-isomer being more reactive due to its favorable geometry for the SN2 mechanism.