11.11 : Acid-Catalyzed Ring-Opening of Epoxides

Epoxides are three-membered rings with significant ring strain. The highly strained structure makes epoxides more reactive than other cyclic and acyclic ethers.

Hence, epoxides readily undergo nucleophilic substitution reactions under acidic conditions to alleviate the ring strain.

These acid-catalyzed ring-opening reactions can be accomplished with either halogen acids, or with other weak nucleophiles, such as water and alcohol, under mild acidic conditions.

For instance, hydrolysis of oxirane requires only trace amounts of sulfuric acid.

The reaction mechanism proceeds via proton transfer from the acid catalyst to the epoxide oxygen, forming a bridged oxonium ion intermediate. The protonation thus converts the epoxide oxygen into a better leaving group.

In the second step, the nucleophilic attack by water in an S_N2 manner opens the epoxide ring, forming a protonated alcohol. Notably, the leaving group does not depart; instead, it remains within the same molecule.

Finally, a proton transfer from the protonated alcohol to the solvent completes the reaction.

The regiochemistry of the acid-catalyzed ring-opening reactions is governed by either steric or electronic effects.

In an asymmetrical epoxide, where the carbons are either primary or secondary, the steric effect dominates and favors the nucleophilic attack at the less-substituted primary carbon atom in an S_N2-like manner.

However, when one of the carbons is tertiary, the electronic effect dominates.

A tertiary carbon has more carbocationic character than the primary and thus better stabilizes the partial positive charge on the protonated epoxide.

Thus, the electronic effect favors the nucleophilic attack on the more-substituted tertiary carbon atom in an S_N1-like manner.

The stereochemistry of the acid-catalyzed ring openings is similar to an S_N2 reaction. It involves an inversion of configuration, with the OH and alkoxy groups anti to each other.