Crossed Aldol Condensation: Videos & Practice Problems

In a crossed aldol condensation involving different aldehydes, multiple enolates can form, leading to a complex mixture of products. Each aldehyde can react with itself or with the other, resulting in various compounds that differ in structure despite having the same number of carbons. To avoid this synthetic challenge, one should use a non-enolizable aldehyde, which lacks an alpha proton, ensuring a single product formation. Examples include formaldehyde and benzaldehyde, which simplify the reaction by acting solely as electrophiles.

Crossed Aldol

In this video, we're going to explore what happens when you try to run an aldol condensation on a mixture of different aldehydes. Whenever you run a condensation on 2 different ketones or 2 different aldehydes, mixed products are going to be difficult to avoid because what's going to happen is that we've got 2 different enolates that are possible, not within the same ketone or aldehyde, but on different aldehydes. That opens up a big can of worms because for example, let's say we have aldehyde A that can form an enolate here and aldehyde B that can form an enolate here. We've got an issue because it turns out that once you form enolate A, A can react with itself to give you A. A negative could attack A, the actual protonated version of A to give you A A negative could also attack B, so the non enolate version of B to give you a B condensation product. B negative, so the enolate of B could attack A to give you B A which by the way, AB and B A look like they're similar but they're not. They're actually going to be different compounds because you have different numbers of carbons in each. Finally, B negative could react with B to give you B_B. What's going to happen? You're going to get this terrible Punnett square of aldol products and it's just going to be a disaster. For the sake of teaching purposes, I am going to fill in this square, so you guys can see all the possibilities. But typically, this is not something that we would ever do in a classroom. You would never draw all 4 aldol products because it's just it's a synthetically useless reaction. No one wants that high of a mixture of products. But for the sake of learning, let's just see what each of these combinations would look like.

Always remember that the first letter, I'm using as the enolate. I'm doing enolate, enolate, enolate, enolate. I'm doing my whole left right thing. Let's start off with AB. And I am going to you might need to gr

Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol condensation reaction. 

• A.
• B.
• C.
• D.

Answer: (B)

Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol reaction. 

• A.
• B.
• C.
• D.

Answer: (B)

What product can be isolated from the following aldol condensation reaction? 

• A.
• B.
• C.
• D.

Answer: (A)

Here’s what students ask on this topic:

What is a crossed aldol condensation?

A crossed aldol condensation is a reaction between two different aldehydes or ketones, leading to the formation of multiple products. This occurs because each aldehyde or ketone can form an enolate, which can then react with itself or the other aldehyde/ketone. This results in a complex mixture of products, making the reaction synthetically challenging. To simplify the reaction and obtain a single product, one of the reactants should be a non-enolizable aldehyde, which lacks an alpha proton and can only act as an electrophile.

How can you avoid multiple products in a crossed aldol condensation?

To avoid multiple products in a crossed aldol condensation, use a non-enolizable aldehyde or ketone. Non-enolizable compounds lack an alpha proton, preventing them from forming enolates. Examples include formaldehyde and benzaldehyde. By using a non-enolizable aldehyde, it ensures that only one enolate is formed, which will react with the non-enolizable aldehyde, leading to a single product. This approach simplifies the reaction and avoids the formation of a complex mixture of products.

What are some examples of non-enolizable aldehydes used in crossed aldol condensations?

Examples of non-enolizable aldehydes used in crossed aldol condensations include formaldehyde and benzaldehyde. These compounds lack an alpha proton, which means they cannot form enolates. As a result, they act solely as electrophiles in the reaction, ensuring that only one product is formed. This simplifies the reaction and avoids the formation of multiple products, which is a common issue in crossed aldol condensations involving enolizable aldehydes or ketones.

Why is a crossed aldol condensation considered synthetically challenging?

A crossed aldol condensation is considered synthetically challenging because it involves multiple enolates that can form from different aldehydes or ketones. Each enolate can react with itself or with the other aldehyde/ketone, leading to a complex mixture of products. This makes it difficult to isolate a single desired product. To overcome this challenge, chemists often use non-enolizable aldehydes, which lack an alpha proton and can only act as electrophiles, simplifying the reaction and ensuring the formation of a single product.

What is the role of an enolate in a crossed aldol condensation?

In a crossed aldol condensation, an enolate acts as a nucleophile that attacks the carbonyl carbon of another aldehyde or ketone. The enolate is formed by deprotonating the alpha carbon of an aldehyde or ketone. This nucleophilic enolate can react with the carbonyl group of another molecule, leading to the formation of a β-hydroxy carbonyl compound. However, when multiple enolates are possible, it can result in a complex mixture of products, making the reaction synthetically challenging.