Chapter 16: Ethers, Epoxides and Sulfides

S_N1 type Reactions of Epoxides

• Before weaker nucleophiles react with epoxides the epoxide must first be protonated so the reaction conditions are acidic.
• Protonation makes the epoxide more electrophilic and creates a better leaving group.
• Examples of  nucleophiles requiring this approach : H₂O, ROH etc.
• The leaving group is the protonated oxygen atom of the epoxide in the form of a neutral alcohol.
• Typically the nucleophile is then deprotonated to give a neutral product.
• For non-symmetrical epoxides, there is a question of regioselectivity :

Scenario 1: The Nu attacks the more substituted C of the epoxide at 180o to the C-O bond that breaks.
Scenario 2: The Nu attacks the least hindered end of the epoxide at 180o to the C-O bond that breaks.

• Experimental results show that scenario 1 is observed under these weaker nucleophiles such as water or alcohols.
• Recall that S_N1 reactions of alkyl halides follow the order 3^o  >  2^o  >  1^o  (i.e. favours the more stable carbocation)
• In order to appreciate this type of reaction we should consider what happens if we break each of the C-O bonds....

• If the more stable carbocation is favoured then the nucleophile attacks the more substituted end of the epoxide.
• This results in the formation of the less highly substituted alcohol.
• Note that although the carbocation does not usually form the carbocation character is important.

In reality it is usually that the epoxide C-O bond to the more substituted center is weaker resulting in carbocation character at that C and the nucleophile attacks there.... because the C-O bond is not totally broken when the nucleophile attacks, it still attacks at 180o with respect to the leaving group.

• This is best described as an S_N1 type of reaction since carbocation character is involved.

• Under acidic conditions, epoxides open in an "S_N1 like" fashion with the nucleophile attacking the more substituted end.

© Dr. Ian Hunt, Department of Chemistry