Epoxidation

Core Concepts

This article gives an introduction to the epoxidation reaction. We will discuss its general concepts, reaction mechanism, and applications in organic chemistry.

What is Epoxidation?

Epoxidation is a type of reaction that leads to the formation of an epoxide, a cyclic ether with a three-membered ring made up of two carbon atoms and an oxygen atom. This is done through the addition of a singular oxygen atom to an alkene.

This addition reaction occurs by breaking the C=C pi bond of the alkene, leading to the formation of two new C-O sigma bonds. Most often, this type of reaction is done with a peroxyacid, an acid which contains an acidic -OOH group. This leads to the cleavage of the reagent’s O-O bond when reacted. In addition to epoxide formation, a carboxylic acid is also produced.

Epoxidation is a stereoselective reaction, with a syn addition of the oxygen atom. This means that both C-O bonds are formed on the same side, meaning that cis and trans alkenes give varied stereoisomers. Cis alkenes lead to epoxides with cis substituents, and trans alkenes lead to epoxides with trans substituents.

How it works

Epoxidation reactions occur in a concerted mechanism, where all bonding events occur in a single step. The 5-arrow mechanism shown below displays the cleavage of the weak pi bond of the alkene. This leads to the attack on the oxygen of the electrophilic hydroxyl group, which is the oxygen atom used for the two new epoxide C-O bonds formed. These bonds are formed using an electron pair from the broken pi bond and a lone pair from the peroxyacid. The weak O-O bond of the peroxyacid is broken. This reaction is particularly unstable due to the fact that there are three pairs of electrons in motion, meaning that there is no intermediate state. Everything, including all bond breaking and forming, occurs at the same time. Following this arrow pushing mechanism, a final epoxide and carboxylic acid product are synthesized.

Applications

Epoxidation reactions are essential in organic chemistry since they can then be intermediates in stepwise reactions or reacted with different nucleophiles leading to the synthesis of of a wide set of compounds. Albuterol, a compound used in the treatment of asthma, is an example of a compound that is synthesized from the opening of an epoxide ring.

Practice Problems

Problem 1. Which of the following would be the correct epoxide formed from the following reaction with mCPBA, a common peroxyacid used in laboratories