What Are Epoxides?

Epoxides are a special class of cyclic ethers which are an important functional group in organic chemistry and generate reactive centers due to their unusual high reactivity. Due to their high reactivity, epoxides are considered to be toxic and mutagenic.

Structure of Epoxides

The structure of epoxide is a three-membered ring in which two vertices are with a carbon atom and one vertex is of an oxygen atom, making an equilateral triangle. Due to the presence of oxygen atom between two carbon atoms, these are also called as oxiranes. Among all ethers, epoxides are more reactive due to the presence of ring strain in three membered ring structures. The general structure of an epoxide is given below.

Nomenclature

Generally, organic compounds containing the functional group, epoxide, are named as epoxy, oxirane, epoxide, or ethoxyline. Simple epoxides are generally termed oxides.

Examples:

Epoxide of ethylene $\left({\text{C}}_{\text{2}}{\text{H}}_4\right)$is called ethylene oxide$\left({\text{C}}_{\text{2}}{\text{H}}_{\text{4}}\text{O}\right)$.

Epoxide of benzene $\left({\text{C}}_{\text{6}}{\text{H}}_{\text{6}}\right)$is named as benzene oxide$\left({\text{C}}_{\text{6}}{\text{H}}_{\text{6}}\text{O}\right)$.

Synthesis of Epoxides

Ethylene oxide and propylene oxide are economically important epoxides that are synthesized in a large scale industry. The simplest oxide i.e. ethylene oxide is synthesized by the catalytic oxidation of ethylene in presence of air. In general, many metals such as silver, vanadium, molybdenum, etc., act as the catalyst for the synthesis of epoxide by the oxygenation of its respective alkenes.

Ethylene oxide is the only epoxide that can be synthesized by the direct reaction of alkene in presence of air. Other all epoxides require a peroxide containing reagents such as peroxyl acids, which liberates an oxygen atom and donates to the alkene to form epoxides.

The direct method involves the reaction of an alkene with O₂ in the presence of Ag, leading to the formation of an epoxide.   

Most common and very useful peroxy acid is m-CPBA i.e., meta-chloroperoxy benzoic acid. The weak $\text{O-O}$bonds present in the peroxy acids make them reactive by generating an oxygen atom.

The second method, the indirect method to synthesize epoxides is a two-step process in which the alkenes are treated with halohydrins in presence of a base.

Halohydrin also called as haloalcohol or $\text{β-}$haloalcohol is the functional group in which a halogen group and an $\text{-OH}$group are present on the adjacent carbon atoms. Halohydrin are the species produce when a halogen (Cl, F, Br and so on)and water as solvent are added to an alkene. When this halohydrin is treated with strong bases like $\text{NaOH}$or$\text{KOH}$, deprotonation of $\text{-OH}$ to ${\text{O}}^{-}$occurs which further displaces the halogen from the adjacent carbon atom via${\text{S}}_{\text{N}}\text{2}$ reaction leading to the formation of the respective epoxide.

Reactions of Epoxides

Epoxides undergo various types of reaction and act as starting material for many organic compounds due to the steric hindrance present in the ring. As the epoxide structure is assumed to be an equatorial triangle, epoxides undergo cleavage of $\text{C-O}$bond, the ether bond readily in presence of various acids, aqueous acids, aqueous bases and more.

Epoxides undergo a reduction in presence of lithium aluminum hydride to form respective alcohols. Epoxides undergo deoxygenation in presence of oxophilic reagents, which is a combination of tungsten hexachloride and n-butyllithium to form the respective alkene. Insertion of carbon dioxide can take place by ring expansion of the epoxide to form cyclic carbonates.

Cleavage of Epoxides in Presence of Acid

In general, ether undergoes cleavage of the ether bond in presence of strong acids such as$\text{HI, HBr, HCl}$, etc., and form alcohol and an alkyl halide. Similarly, epoxides are the cyclic ethers which also, undergo cleavage of the ether bond in presence of strong acids leading to opening the ring structure.

Cleavage of Epoxides in Presence of Aqueous Acids and Bases

Ethers such as diethyl ether is found to be inert in presence of aqueous acids such as ${\text{H}}_{\text{3}}{\text{O}}^{\text{+}}{\text{, H}}_{\text{2}}{\text{SO}}_{\text{4}}{\text{/H}}_{\text{2}}\text{O}$etc. In contrast, epoxides undergo cleavage at $\text{C-O}$bond in presence of aqueous acids leading to ring opening and form diols. Similarly, epoxides undergo cleavage even in presence of aqueous bases ${\text{NaOH/H}}_{\text{2}}\text{O}$etc., and form diols by opening up the ring.

Treating Aqueous Base with Epoxide

Here, it needs to note that there is a stereochemistry difference when an epoxide is treated with aqueous acid and aqueous base. On treatment with aqueous acid or aqueous base, the epoxides form anti or vicinal diols. The difference is in the position of the carbon atom on which the nucleophile attacks. This is due to the difference in the mechanism of the reaction taking place.  

In presence of aqueous acid such as${\text{H}}^{\text{+}}{\text{/H}}_{\text{2}}\text{O}$, the nucleophile $\left({\text{H}}_{\text{2}}\text{O}\right)$attacks the epoxide at the most substituted carbon atom leading to the inversion in the stereochemistry.

The intermediate formed is a protonated epoxide, which is a highly reactive compound. The attack of the nucleophile occurs on the most substituted carbon atom as shown in the mechanism.

Similarly, in presence of an aqueous base such as ${\text{NaOH/H}}_{\text{2}}\text{O}$, the nucleophile attacks at the least substituted carbon atom based on the ${\text{S}}_{\text{N}}\text{2}$ displacement mechanism. The stereochemistry of the least substituted carbon atom is inversed in presence of aqueous base. Grignard reagents and organolithium reagents also attack epoxides on the least substituted or steric hindered carbon atom ${\text{S}}_{\text{N}}\text{2}$mechanism and forms alcohols.

Uses of Epoxides 

• Most of the epoxides are used as fumigants.
• The main uses of epoxides, specifically ethylene oxide are in the preparation of ethylene glycol which is used as an anti-freezing agent.
• Ethylene oxide is also widely used in the preparation of various detergents and surfactants.
• Polymerization of an epoxide leads to polyether's.
• Ethylene oxide undergoes polymerization to form polyethylene glycol, which is a widely used surfactant.
• Epoxides act as alkylating agents because of also, they are considered highly toxic.
• Epoxides react with amines leading to the formation of epoxy glues and other structural materials which can be used as hardener.   

Practice Problem

1. Epoxides are formed when halohydrins are treated with base. This reaction involves which type of mechanism?

a. ${\text{S}}_{\text{N}}\text{1}$ mechanism b. ${\text{S}}_{\text{N}}\text{2}$ mechanism c. ${\text{S}}_{\text{N}}\text{i}$ mechanism d. adjacent group participation

Solution: b. ${\text{S}}_{\text{N}}\text{2}$ mechanism

Halohydrins are attacked by the base on the least steric hindered carbon atom which is based on the ${\text{S}}_{\text{N}}\text{2}$ displacement mechanism.

Context and Applications   

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for 

• Bachelors. in Chemistry
• Masters. in Chemistry