Introduction
Epoxides are three-membered rings with one oxygen atom in the centre. Despite the lack of a suitable leaving group, they are connected with high ring tension, which is the basis of their reactivity towards nucleophiles.
While oxygen is a weak leaving group, the epoxide’s ring strain aids in completing the reaction. The ring strain is caused by the carbons’ geometry not being optimal, as the angle between them is 60° instead of 109.5°, as it should be for sp3-hybridized tetrahedral atoms.
Because the ring strain is not as significant as in the three-membered epoxide ring, larger cyclic ethers would not be susceptible to acid-catalyzed or base-catalyzed cleavage under the same conditions.
Read More:
Table of Contents
- Epoxide Ring-Opening Mechanism by Alcoholysis
- Epoxide Ring-Opening Mechanism by Hydrolysis
- Epoxide Ring-Opening Reaction by HX
- Epoxide Ring-Opening by other Nucleophiles
- Additional Ring-Opening Stereochemical Considerations
- Frequently Asked Questions – FAQs
Epoxide Ring-Opening Mechanism by Alcoholysis
Depending on the type of the epoxide and the reaction circumstances, ring-opening reactions can happen via SN2 or SN1 processes. The structure of the result will differ, depending on whether the process dominates if the epoxide is asymmetric.
When an asymmetric epoxide undergoes alcoholysis in basic methanol, an SN2 process opens the rings, and the less substituted carbon becomes the target of the nucleophilic attack, yielding product B:
In acidic methanol, on the other hand, solvolysis happens via a process with strong SN1 characteristics, with the highly substituted carbon serving as the attack site. As a result, product A has the dominant position.
These are both good examples of regioselective reactions.
Basic Epoxide Ring-Opening
Because there is no acid available to protonate the oxygen before ring-opening in the basic SN2 reaction, the leaving group is an alkoxide anion. The ring is unlikely to open without a ‘push’ from the nucleophile since an alkoxide is a poor leaving group.
The nucleophile, a deprotonated, negatively charged methoxide ion, is extremely powerful. When a nucleophilic substitution process involves a weak leaving group and a strong nucleophile, the SN2 mechanism is very likely to be used.
Acid-Catalyzed Epoxide Ring-Opening
The acid-catalyzed epoxide ring-opening process is best described as a hybrid, or cross, of the SN2 and SN1 mechanisms. The oxygen is first protonated, resulting in a suitable leaving group (step 1). The carbon-oxygen bond begins to break (step 2), allowing a positive charge to accumulate on the more substituted carbon.
The nucleophile attacks the electrophilic carbon (step 3) before a complete carbocation intermediate can develop, unlike in an SN1 reaction.
Because the carbon-oxygen bond is still in place to some extent (as in an SN2 reaction), attack preferentially occurs from the backside. The oxygen prevents the attack from the front side.
Epoxide Ring-Opening Mechanism by Hydrolysis
Trans-1,2-diols are formed when epoxides are hydrolysed (1,2 diols are also called vicinal diols or vicinal glycols). The reaction can take place in both acidic and basic environments.
Acid-Catalyzed Hydrolysis
The epoxide oxygen is protonated in aqueous acidic circumstances and then attacked by nucleophilic water. A 1,2-diol product is generated after deprotonation to reconstruct the acid catalyst.
The entering water nucleophile will preferentially attack the more substituted epoxide carbon if the epoxide is asymmetric. The epoxide ring is opened by an SN2-like process, causing the two -OH groups in the product to be trans to each other.
Basic Hydrolysis
During an SN2 reaction in aqueous basic circumstances, the attack of a hydroxide nucleophile opens the epoxide. The epoxide oxygen reacts with water to generate an alkoxide, which is then protonated to form the 1,2-diol product. If the epoxide is asymmetric, the incoming hydroxide nucleophile will attack the epoxide carbon that is less substituted.
The two -OH groups in the result will be trans to each other since the reaction is carried out via an SN2 mechanism.
Epoxide Ring-Opening Reaction by HX
Anhydrous acids (HX) can also open epoxides to generate a trans halohydrin. When both epoxide carbons are primary or secondary, the halogen anion attacks the less substituted carbon in a reaction similar to SN2. In an SN1-like reaction, if one of the epoxide carbons is tertiary, the halogen anion will attack the tertiary carbon first.
Epoxide Ring-Opening by Other Nucleophiles
Amines, hydrides, Grignard reagents, acetylide anions, and hydrides are just a few of the basic nucleophiles that can open the ring of an epoxide. An SN2 mechanism is usually used to open these rings.
Additional Ring-Opening Stereochemical Considerations
The regiochemical regulation of an asymmetrical epoxide’s ring-opening process usually allows for producing only one stereoisomer. However, if the epoxide is symmetrical, each epoxide carbon has nearly the same ability to take the nucleophile. When this happens, the resulting product usually has a mix of enantiomers.
Frequently Asked Questions on Epoxide Reactions
What do you mean by epoxide ring-opening reaction?
During an SN2 reaction in aqueous basic circumstances, the attack of a hydroxide nucleophile opens the epoxide. The epoxide oxygen reacts with water to generate an alkoxide, which is then protonated to form the 1,2-diol product.
How do you synthesise epoxide?
The enantioselective catalytic reduction of an achiral chloromethyl ketone with a chiral oxazaborolidine as catalyst and borane as stoichiometric reductant is a critical step in the manufacturing of chiral phenyloxirane.
What do you mean by regioselective reactions?
The preference of chemical bonding or breaking in one direction over all other potential directions is known as regioselectivity in chemistry. The reaction is selective because one product is preferentially formed over another. This reaction is regioselective because it produces one constitutional isomer instead of the other.
Are epoxide reactions racemic?
Because the two carbons of the epoxide ring are equivalent and attacked by the nucleophile at the same rate, a racemic mixture of enantiomers is generated if an achiral epoxide is used as the starting material.
What is the reagent that makes an epoxide?
An epoxide is formed directly when an alkene is treated with a “peroxyacid” (a carboxylic acid with additional oxygen). m-CPBA [m-chloroperoxybenzoic acid] is a popular peroxyacid for this purpose, but other peroxyacids of the general form RCO3H are also used.
Comments