Carboxylic Acid Derivatives
By James Ashenhurst
Carbonyl Chemistry: Learn Six Mechanisms For the Price Of One
Last updated: May 21st, 2019
So at some point during Org 2, you will probably be expected to learn a whole slew of mechanisms.
- Conversion of carboxylic acids to esters (Fischer esterification)
- Hydrolysis of esters to carboxylic acids
- Hydrolysis of amides to carboxylic acids
- Formation of imines from ketones/aldehydes and amines
- Hydrolysis of imines to ketones/aldehydes and amines.
- Formation of anhydrides from carboxylic acids
Six different mechanisms. That means writing out and learning a whole bunch of different steps for each of these reactions.
Sounds like a lot of work, doesn’t it?
What if you could cut down the amount of time you spent doing these mechanisms by a factor of six? That would be worth learning, right?
Well, you’re in luck. The six reactions listed might look different, but they actually have EXACTLY THE SAME MECHANISM. So if you’ve learned how one of them works – you’ve actually learned them all. Let’s break it down using the first reaction (formation of esters from alcohols and carboxylic acids) as an example.
Step 1: Protonation
The reaction begins with protonation on the oxygen of the C=O (or C=N) bond. This means the oxygen (or nitrogen) has less electron density to share with the carbonyl carbon. Being more electron-poor, the carbonyl carbon has now become a better electrophile, which sets up…
1,2-addition (step 2)
Whereby the nucleophile adds to the carbonyl carbon, forming a new bond and breaking the [PI] bond beween the carbon and oxygen. Note that the neutral nucleophile is positively charged and the (former) carbonyl oxygen is neutral. An acid base reaction can now ensue, a fancy name for which is….
Proton transfer (step 3)
where a proton is transferred from the atom which previously acted as a nucleophile to a different atom on the molecule (either O or N). Once the proton has been transferred, the group becomes much less basic, which also means that it will be a much better leaving group. So one of the lone pairs from an adjacent atom forms a new Pi bond with the carbon, resulting in…
1,2-elimination (step 4),
ejecting a neutral molecule (such as H2O or NH3) as a leaving group. There’s just one more step to go. The atom participating in the new Pi bond has a positive charge, which means we have to remove it in order to get a neutral species – a step we call…
Deprotonation (step 5)
And that’s it. Note that the acid is not consumed – it’s a catalyst here, and can meet up with another molecule of our starting material back in Step 1.
Although the material is spread out over several chapters, the hidden pattern in their mechanism should come in handy when it comes to exam time.
Just remember this: Protonation / 1,2-Addition / Proton transfer / 1,2-Elimination / Deprotonation.
I’ve been trying to come up with a good mnemonic for this. Piranhas Attack People Every Day? Here’s a random mnemonic generator.
PS – Here are the six mechanisms I’m talking about, broken down this way: