Apropos of nothing, here’s a post about a series of reactions that is a common source of student difficulties. It’s called the malonic ester synthesis, and it’s an interesting way of making substituted carboxylic acids. There’s an essentially identical process called the acetoacetic ester synthesis and it makes substituted ketones; the only difference between the two processes is the choice of starting material.
Here’s an example of both processes. Pay attention to the bonds that form and the bonds that break.
Before going into the mechanism, see if you can identify the common pattern for each of these malonic ester syntheses. Follow the different colors of atoms. Where does each come from? Where do each of them go?
The cool thing about this process is how it’s built from a series of simple reactions. Again, mechanisms in organic chemistry are a lot like music – from a small number of parts, we can build up something complex.
Let’s walk through the mechanism (focusing on the malonic ester synthesis for brevity – the acetoacetic ester synthesis mechanism is identical except we’re starting with a different compound).
These processes are built out of four reactions in total:
- deprotonation of the ester to form an enolate
- SN2 of the enolate upon an alkyl halide, forming a new C-C bond
- acidic hydrolysis of the ester to give a carboxylic acid
- decarboxylation of the carboxylic acid
In the first step, a base (CH3O– in this case) removes the most acidic proton from the ester (on C2 here, with a pKa of about 13) to give anenolate. The resulting enolate can be drawn as one of two resonance forms.
Secondly, it’s also possible to do two alkylations before doing the aqueous hydrolysis step. Can you figure out how to make B from a malonic ester synthesis?
[If you’ve read this far, worked on these problems, and would like an answer, leave a comment!]