Epoxidation

This reaction adds a 3-membered cycle ether (epoxide functional group) to an alkene using reagents called peroxy acids. These epoxides are highly strained, so they can react in very useful ring-opening reactions, which we will discuss later. 

Epoxides from Peroxy Acids

Concept: General properties of epoxidation.     

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Video Transcript

So, now we're going to talk about another addition reaction and this one only adds oxygen by itself to a double bond to form a completely new functional group called an epoxide. Needless to say, the name of this reaction is called epoxidation.
Before we can even get started, I kind of want to define what is an epoxide because some of you guys might now know. An epoxide is a functional group that is just made of a cyclic three-membered ether. What that means is that remember that the definition of an ether was ROR, that was an ether. Well, an epoxide is just going to be a cyclic ether. So what that means is it's an O with two R groups on both sides, but they're attached to each other. So this would be an epoxide.
Epoxidation, needless to say, is going to add that one oxygen to the double bond in order to make it into that three-membered ring. So how do we add epoxides to double bonds? Well, we do it by using a type of molecule called a peroxy acid. Peroxy acids are the molecules that are used to make them. And this is the general formula of a peroxy acid.
What you're going to notice is that it actually looks a lot like a carboxylic acid. Remember that carboxylic acid looks like this, OH. So really it's the same thing as a carboxylic acid except it has one more O. So remember that the definition of a carboxylic acid is CO2H. That's the condensed formula. Well, for a peroxy acid it's going to be RCO3H. So what you're going to notice is that it's really the same exact thing except I've just added one more oxygen, so it's CO3H. So that's the first thing.
Now you could use any peroxy acid you want to make an epoxide, but the common ones that are used are MCPBA and MMPP. These are two reagents that you don't need to know exactly what they look like as long as you can recognize that these are types of peroxy acids. The only thing that changes is the R group, but the COOOH is the same. 

Peroxy acids are compounds with the general molecular formula RCO3H. The most common examples are MCPBA and MMPP. These are essentially the same molecule, just with different –R groups. 

Concept: The mechanism of how peroxy acids make epoxides.   

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You typically won’t need to know this entire mechanism, but here is the first step:

General Reaction:

Epoxides from Halohydrins

Concept: The mechanism of how halohydrins make epoxides via intramolecular SN2.  

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Video Transcript

Now there's actually one more way that we can make epoxides and that's by using halohydrins. Now remember that in the addition section, addition reactions, halohydrin is one of the addition reactions that we can use. It turns out that halohydrins are also good at making epoxides. How? Through an intramolecular SN2 reaction. Remember that a SN2 is just a back side attack.
So here's the way it works. Basically, remember that I've got a double bond and that double bond is exposed to diatomic halogen and water. What's going to wind up happening is that I get a halohydrin. You guys should all be able to follow to this point. Notice that the stereochemistry is once again anti. Cool.
Now, also, because this didn't have – it was perfectly symmetrical, it doesn't matter which side I put the OH and the X on, you could have picked either one.
But now here's the interesting part, once I have a halohydrin, I can react that with any base I want. And if I react that with a base, what's going to happen is that the base is going to wind up deprotonating my alcohol.
So what I'm going to wind up getting is a nucleophile on one side of the molecule and a leaving group on the other side. What we've basically done is we've made an oxide. We've basically made a nucleophile out of the alcohol. So what's going to happen here is that we're going to get an intramolecular reaction where this O does and attack on that X, on that carbon, and kicks out the X.
So what winds up happening is that we wind up forming a ring that looks like this. We wind up forming that this ring stays the same, but now this O is attached here and attached there because this new bond that I'm drawing in blue right here is the one that was created by the back side attack here. And then plus I would get my leaving group, X-.
So these are two different ways to make epoxides. Your professor may teach just the epoxidation with the peroxy acids. He may teach halohydrins as well. I want you guys to be responsible for both because I've seen them often enough that it's just important for you to know both of them. 

Halohydrins can be deprotonated using a base to become a nucleophilic OH-. Once this anion is created, it can participate in intramolecular SN2 reaction with the halogen next to it, making a three-membered ring closure. 

Epoxidation Additional Practice Problems

Using line-angle ONLY, draw the MAJOR product expected from the following reaction. Be sure to show stereochemistry if appropriate. If no reaction occurs write NR.

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Propose a detailed mechanism for the proposed conversion of A to B. Show the key intermediates and the products obtained after each step.

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For the reaction below, draw the structure of the appropriate compound. Indicate stereochemistry where it is pertinent.

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Predict the product of the following reaction: 

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Through what mechanism can a 1,2-halohydrin be converted into an epoxide?

A) electrophilic addition

B) E2

C) SN2

D) SN1

E) polymerization

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Provide a reasonable mechanism to account for the following transformations:

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Consider the strucutres below and answer the following questions. 

i. Which compound(s) would react with RCO3R and then NaOH to form a meso compound. (An achiral molecule with chirality centers?) 

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Which reaction(s) would produce the epoxide shown?

1) A only

2) B only

3) A and B

4) B and C

5) All of them will work

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When trans-2-bromo-cyclohexan-1-ol is reacted with sodium hydroxide in water, an epoxide is formed. When cis-2-bromo-cyclohexan-1-ol is reacted with sodium hydroxide in water, an epoxide is NOT formed. Using complete sentences and Lewis structures, explain why an epoxide is not formed with the cis-compound.

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Draw the chemical structure for mCPBA.

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Predict the organic product(s) of the following reaction. When appropriate, be sure to indicate stereochemistry. Be sure to indicate the major product if more than one product is formed. Draw all answers in skeletal form. 

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Supply a structural formula for the major organic product ; if no reaction occurs, write N.R. Give the best possible answer. Be sure to show stereoisomers properly when necessary.

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Draw the structural formula of the major organic product(s) in the box for the following reaction.

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Williamson ether synthesis of epoxides.

a) Draw the structure of products B and D, showing the stereochemistry.

b) Circle the product (B or D), which has an [α] D = +98°.

c) What kind of isomers are B and D.

d) Draw the structure of the isomer of B and D, which has an [α]  D = -98°.

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If cis-2-butene is treated with meta-chloroperbenzoic acid what is the final product?

A) I 

B) II

C) III

D) IV

E) None of the above

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