In the Fischer esterification, we take a carboxylic acid, add an alcohol and an acid catalyst to the caroboxylic acid and obtain an ester.

Really useful. You can control which ester you form by changing the solvent. So if we use ethanol, we get the ethyl ester. Methanol, the methyl ester.

OK, so how does it work?

Five steps.

1. Protonation (of the carbonyl)
2. Addition (of the alcohol to the carbonyl)
3. Protontransfer (to give OH2+)
4. Elimination (of water)
5. Deprotonation (to give the neutral ester)

P A P E D

Now watch this.  Let’s do the reverse reaction. Start with an ester, and add water and acid catalyst.

Five steps

1. Protonation (of the carbonyl)
2. Addition (of water)
3. Proton transfer (to give ROH+)
4. Elimination (of alcohol)
5. Deprotonation (to give the neutral acid)

P A P E D

OK, so that’s two reaction mechanisms. What if I told you that the same 5 steps underly a completely different reaction – like formation of imines?

rotonation (of the carbonyl)

Protonation (of the carbonyl)

1. Addition (of amine to carbonyl)
2. Proton transfer (to give OH2(+) )
3. Elimination (of water)
4. Deprotonation (to give neutral imine)

P A P E D

I could go on (I do, here). The same PAPED mechanism also covers hydrolysis of imines, formation of enamines, hydrolysis of enamines, formation of anhydrides, acidic hydrolysis of amides… Five steps, all the same.

Point is – just like knowing chords for guitar, if you know these few mechanisms, you can build up a lot of different reaction mechanisms. And a lot of reaction mechanisms that LOOK different are actually EXACTLY THE SAME. 

Bottom line: it’s amazing how efficient it is to divide each mechanism into steps, and keep track of the different steps.

PAPED is a massive time saver.

The title of tomorrow’s post might sound dumb… but trust me, we’ve all made this mistake at some time or another.
Thanks for reading! James

P.S. Reaction Guide – Fischer esterification