Aldol Condensation: Why is OH a Good LG?

[brake4country]

Homework Statement

In a typical aldol condensation (say 2 aldehydes reacted with NaOH, water, and under heated conditions) why is hydroxide considered a good leaving group in the final step?

Homework Equations

NA

The Attempt at a Solution

I drew out a mechanism with an aldehyde and a ketone, creating the aldol product. From here, heat is added and hydroxide is protonated in solution to leave behind a carbanion on the alpha carbon. Once the double bond is created by the electrons OH is push off. How is OH a good leaving group in this case?

 

[Yanick]

The mechanism you drew is not correct in that the lone pair on the carbanion will not "kick off" the hydroxyl group as there is a methylene group between the two. Re-draw the mechanism from scratch to get a better idea of this reaction.

As far as the hydroxyl leaving group, think about what is in your flask. You even drew the reagent over your arrow in the first step. Leaving group ability is not a binary characteristic but instead is a spectrum from "bad" to "good."

 

[brake4country]

I see what I did wrong. I connected the carbons incorrectly. Does this look better? However, how can OH leave? Isn't it a bad leaving group?

 

[Yanick]

That looks better.

As far as your question goes, refer to the second part of my first post. Good and bad may be used as though they describe a binary phenomenon, but in reality things are not simply yes/no or good/bad. They all fall on a spectrum, so perhaps better terms would be better/worse instead of good bad.

Again think about what is in the flask, you have plenty of hydroxide floating around. It can't be impossible to have hydroxide as a leaving group.

 

[DeeNos]

In the context of an aldol condensation, OH is considered a good leaving group because it is a relatively weak base. This means that it is able to accept a proton more easily than other stronger bases, such as alkoxides or alkyl groups. In the final step of the reaction, the hydroxide group is protonated, forming a water molecule which is a much more stable leaving group. This allows for the formation of the desired product by elimination of the water molecule. Additionally, the resulting carbanion is stabilized by the presence of the alpha carbon and the adjacent carbonyl group, making it more stable and therefore more likely to undergo the elimination reaction. Overall, the use of OH as a leaving group in the aldol condensation reaction allows for efficient and selective formation of the desired product.