Claisen Condensation

Concept: Concept: Claisen Condensation

9m
Video Transcript

In this video, we're going to focus on a specific type of condensation reaction called the Claisen condensation. Esters, like other carbonyls can form enolates. We’ve discussed this in the past. When these esters form enolates, in the absence of other electrophiles, they can react with themselves. When they react with themselves, they're going to condensate into what we call beta-ketoesters. That’s the functional group that we always get at the end. We're just going to go step by step through this mechanism and I'm going to show you guys not only the mechanism, but how to set it up so that it makes the most sense and it’s the easiest for you to predict what the product is going to be.
The first step is to deprotonate your ester to make the enolate. Again, I said this a bunch of times throughout all the videos. Maybe you haven't seen them yet. But what I have said is that whenever you're reacting an ester with an oxide base, what do I have to be careful about? What do I have to know? I have to make sure that my R group is the same as my alkyl r group in the ester. Or what happens? Or I get a transesterification. I'll just put a little bullet here so we can always remember this. You have to keep saying it. Must use alkoxide, if you’re going to use an alkoxide. You don't have to use an alkoxide. But if you use an alkoxide, with same R group as ester. Why? Or you will get transesterification. If you get a transesterification, then you have no idea what happened in your reaction. Instead of getting what you were thinking which would have been a Claisen or whatever, you’re just going to get a transesterification instead. If this word of transesterification sounds totally foreign and you have no idea what I’m talking about, then I would definitely recommend going to the Clutch search bar and searching transesterification because it’s a theme that keeps popping up. It’s probably better that you just know about it now.
Anyway, thankfully here my R groups are both bolded. I guess that means that they’re the same. I pulled off a proton and I got me enolate. Now we're going to do a nucleophilic attack. Remember, we don’t have any other electrophiles around that the negative can react with. Remember how enolates can react with electrophiles and they can attack things. But if we don't have one around, then it’s going to be forced to attack itself. We're going to line up my enolate on the left side. You always put the enolate on the left side. You’re going to line up the electrophile on the right. One thing that's unique about esters is that esters have an OR group. I always want you to draw your OR group. I’m going to put here for the electrophile, draw OR group towards enolate. I'll show you why in a little bit. But it’s very important. To easily predict your products, you should be drawing your R group towards the enolate. With your enolate, you should draw anion towards electrophile. Makes sense? I’ve got what I call me enolate on one side. I've got the non-ionized, the non-enolate electrophile on the right side.
Keep in mind that this molecule, the reason it hasn’t reacted yet is because I used the base on the first one first. I’m just basically saying that I'm using a reacted enolate with one that hasn't reacted yet. We're to start our mechanism. You’re going to get a nucleophilic attack. That CH2 negative is now a pretty strong nucleophile. We're going to attack the carbonyl carbon. We're going to push the electrons up. We’re used to seeing this. But guys, now this mechanism is going to follow a mechanism that we have talked about in other sections of this text, which is that you're kicking up electrons to an O negative, so you’re getting a tetrahedral intermediate. But we also have an OR group present. An OR in your carboxylic acid derivative, part of the Clutch lessons, we define OR as a Z group. Z means it’s electronegative. Z means that it can be kicked out as a leaving group. That means that instead of protonating here like we would expect for nucleophilic addition where it just gets an alcohol and that’s it. We actually reform the double bond and kick out the OR. This is not a nucleophilic addition mechanism. In fact, this is a nucleophilic acyl substitution reaction. This is what NAS means, nucleophilic acyl substitution. This is subject of your carboxylic acid derivatives section of the text.
If you're interested in NAS or what a carboxylic acid derivative is, by all means you can watch my videos and you'll be a pro. Anyway guys, what’s interesting here is that now what we’ve created is we’ve blended two mechanisms into one because we decided to substitute the alpha-position of my enolate. That’s what we’re trying to go for. But we're doing it through an NAS. What we wind up getting is a beta-ketoester. What’s great about beta-ketoesters is that unlike other condensations that sometimes you have alternate products, for example there's a condensation called the aldol condensation where you have two different products that are possible. But Claisen is easier because Claisen, you only have one. You're always just going to have a beta-ketoester. That's it. Why do we call it beta-keto ester? Because you've got an ester with a ketone on the beta-position.
So guys, I just want to show you an example application. It turns out that if you do a Claisen condensation onto, this would be ethyl acetate. Ethyl acetate is the way you name that ester. If you combine ethyl acetate times two in a condensation reaction, what you actually get is called acetoacetic ester. Acetoacetic ester is a huge part of organic synthesis. We're going to spend an entire section talking about how to turn these beta-dicarbonyl esters into other types of compounds like substituted alpha-carbons. It turns out that you can use a Claisen to then make acetoacetic ester, which then we can make other things out of. This a compound that we spend a lot of time with in Organic Chemistry 2. It’s just cool how these thing kind of link together. Awesome. That's it for this video. Let’s move on to the next topic.

Problem: Draw the structure of the Claisen condensation product for each of the following compounds. 

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Problem: Draw the structure of the Claisen condensation product for each of the following compounds. 

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Problem: Give the structure of the ester precursor for the following Claisen condensation product. 

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Claisen Condensation Additional Practice Problems

Complete the following reaction supplying the missing product and showing correct regio- and stereochemistry where applicable. If a racemic or diastereomeric mixture forms show all stereoisomers; if no reaction takes place, write N.R.

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Predict the product when this compound undergoes a Claisen condensation. 

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Fill in the missing reagents and conditions.

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Identify the base you would use for the following transformation. 

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Draw the product for the following Claisen reaction.

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Draw the product for the following Claisen reaction.

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Provide a detailed mechanism for the following transformation.

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Predict the product(s) for the following reaction.

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Indicate the order in which these intermediates would appear during the conversion of  1 into 2.

a) 1 → I → V → 2

b) 1 → II → I → IV → V → 2

c) 1 → III → I → IV → V → 2

d) 1 → III → I → V → 2

e) 1 → II → I → 2

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Indicate the order in which these intermediates would appear during the conversion of 1 into 2.

a) 1 → V → III → I → 2

b) 1 → V → II → I → 2

c) 1 → II → I → 2

d) 1 → IV → 2 + I → 2

e) 1 → III → V → 2 + I → 2

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Provide a mechanism for the following reaction.

 

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Provide an unambiguous structural formula for the condensation product expected when the compound below is treated with sodium ethoxide, then quenched with cold dilute aqueous acid.

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