Master Organic Chemistry

Acetoacetic

In organic chemistry, you’ve probably seen (what seems like) a million examples by now of how a series of simple processes can build into something more complicated.

This is especially true in the chemistry of aldehydes, ketones, and carboxylic acid derivatives, where reactions and mechanisms can build on each other like a pyramid.

Today’s example goes by two different names, but the process is simply a combination of several different reactions you’ve already encountered.
They are:

  1. enolate formation
  2. enolate alkylation (with an alkyl halide)
  3. ester hydrolysis to give a carboxylic acid (with aqueous acid)
  4. heating to give decarboxylation.

This process goes by two different names, depending on what you start with.

If you start with a di-ester with a carbon in the middle (a 3 carbon di-ester) this is called a malonic ester, and the process is called the malonic ester synthesis. 

If you start with a 4 carbon chain with an ester at one end and a ketone two carbons over, this is called an “acetoacetonate ester” (knowing the name isn’t crucial) and the process is called the acetoacetic acid synthesis. 

Let’s look at these two:

  • In the first step, base removes a proton from the central carbon.  Note that both enolates are very easy to form,  since there are two carbonyls next to the enolate that can stabilize it through resonance (either C-2 or C-3).
  • In the second step, we add an alkyl halide, performing an alkylation on the enolate.
  • In the third step, aqueous acid hydrolyzes the ester to the carboxylic acid.
  • In the fourth step, heating helps to decarboxylate the beta-keto acid into an enol, which then tautomerizes.

So what we end up doing is forming a carboxylic acid (in the top example) or a ketone (in the bottom example).

So if you learn to recognize the key patterns here – how the product is derived from the starting materials – it will make your life a lot easier. Because each of the steps we talk about here are reactions we’ve learned before – we’re just putting them together in a new combination.

Thanks for reading! James

Tomorrow: let’s wrap up the week.