Claisen-Schmidt Condensation - Online Tutor, Practice Problems & Exam Prep

The Claisen Schmidt reaction is a specific type of crossed aldol reaction involving an enolizable aldehyde and ketone. Unlike typical crossed aldol reactions, where one carbonyl is non-enolizable, both reactants here can form enolates. However, aldehydes are more reactive towards nucleophilic addition, leading to a predominant product. This reaction exemplifies how the reactivity of functional groups influences product formation, emphasizing the importance of understanding nucleophilicity and electrophilicity in organic synthesis.

Claisen-Schmidt Reaction

Hey everyone. Now we're going to talk about a very specific type of crossed aldol reaction called a Claisen Schmidt reaction. The Claisen Schmidt condensation is what happens when you have an enolizable aldehyde plus ketone. This means that we're kind of breaking the rules. Remember that I told you is if you have a crossed aldol, then you should have one non-enolizable carbonyl. But this is the reaction that happens when you have specifically an enolizable aldehyde and an enolizable ketone, both together. It turns out that you actually get kind of lucky if you mix an aldehyde and a ketone together that are enolizable because theoretically, they could both react and you would get a cross product. But what happens in real life is that one product does actually predominate. Why? Because it turns out that aldehydes are more susceptible to nucleophilic addition than ketones. It's going to favor one of the enolates over the other. Basically, what I'm trying to say here is that you've got your ketone, let's say, and you've got your aldehyde. Theoretically, both of these could form enolates. I could form an enolate on A. I could form an enolate on B and I would start getting a mess. I would get my Punnett square again. But what actually happens is that you only form the enolate on A. Why? Because B happens to be an aldehyde, so it's a group that is easier to do nucleophilic addition with. Then it would prefer to be attacked and be the electrophile instead of being the enolate. With Claisen-Schmidt, it's the one example where you actually can have enolizable cross products and or cross reagents and you're still just going to get one product. Make sense? You guys got this. Go ahead and predict the major product of the following Claisen Schmidt condensation. Notice I have a ketone and aldehyde. Notice they're both enolizable. Try to predict it and then I'll show you guys what the answer is.

Predict the Major Product

Which one did you choose as the enolate? By definition, if I have a mixed ketone and aldehyde, the ketone is going to want to be the enolate so that it can attack the aldehyde. I'm going to bring this ketone down to my left side and draw it as my enolate. Remember that you always want the anion to face towards the electrophile. I'm going to react that with my aldehyde which I'll keep drawn exactly the way it is because I want the H, the smallest group to face towards the negative charge. I'm going to do my reaction. I'm going to get a molecule that looks like this. My enolate is there. Now I have OH carbon. I am skipping a few steps like for example, I skipped the protonation step because this isn't a mechanism question. This is a predictive product. But you guys know that you could protonate that with the conjugate of your base because your base would have an extra proton. It pulled a proton off the ketone. Now we know that what these things like to do, your beta-hydroxycarbonyls, what's wrong? It's going to be very difficult to keep this as a beta-hydroxycarbonyl because we've got an irreversible dehydration hanging around. Once you dehydrate, it can't go back to the original ketone. What we're going to wind up getting is a dehydration product. Awesome. There you go. That's going to be pretty much my final product. Notice it's between the alpha and the beta. This is my enone and we're done. That's it for the Claisen-Schmidt. As you guys can see, how it fits into the idea of crossed aldol. It just happens to be lucky that the aldehyde is less willing to be an enolate than the ketone. Awesome. Let's move on to the next topic.

Here’s what students ask on this topic:

What is the Claisen-Schmidt condensation reaction?

The Claisen-Schmidt condensation is a specific type of crossed aldol reaction involving an enolizable aldehyde and an enolizable ketone. Unlike typical crossed aldol reactions, where one carbonyl compound is non-enolizable, both reactants in this reaction can form enolates. However, due to the higher reactivity of aldehydes towards nucleophilic addition, the reaction predominantly yields a single product. This reaction is significant in organic synthesis for forming α,β-unsaturated carbonyl compounds.

Why do aldehydes predominate in Claisen-Schmidt condensation reactions?

Aldehydes predominate in Claisen-Schmidt condensation reactions because they are more reactive towards nucleophilic addition compared to ketones. This higher reactivity is due to the aldehyde's carbonyl carbon being less sterically hindered and more electrophilic. As a result, the aldehyde tends to act as the electrophile, while the ketone forms the enolate, leading to a predominant product.

What are the typical products of a Claisen-Schmidt condensation reaction?

The typical products of a Claisen-Schmidt condensation reaction are α,β-unsaturated carbonyl compounds. These products result from the nucleophilic addition of the enolate (formed from the ketone) to the carbonyl group of the aldehyde, followed by dehydration. The reaction generally yields a single predominant product due to the higher reactivity of the aldehyde.

How does the reactivity of functional groups influence the Claisen-Schmidt condensation?

The reactivity of functional groups significantly influences the Claisen-Schmidt condensation. Aldehydes are more reactive towards nucleophilic addition than ketones due to their less sterically hindered and more electrophilic carbonyl carbon. This reactivity difference ensures that the aldehyde acts as the electrophile, while the ketone forms the enolate, leading to a predominant product. Understanding nucleophilicity and electrophilicity is crucial for predicting the outcome of this reaction.

Can both reactants form enolates in a Claisen-Schmidt condensation reaction?

Yes, both reactants in a Claisen-Schmidt condensation reaction can form enolates. This reaction involves an enolizable aldehyde and an enolizable ketone. However, despite the potential for both to form enolates, the aldehyde typically acts as the electrophile due to its higher reactivity towards nucleophilic addition, leading to a predominant product.