Conversion of carboxylic acids to esters using acid and alcohols (Fischer Esterification)
Description: When a carboxylic acid is treated with an alcohol and an acid catalyst, an ester is formed (along with water). This reaction is called the Fischer esterification.
Notes: The reaction is actually an equilibrium. The alcohol is generally used as solvent so is present in large excess. Many different acids can be used; it’s common to see just “H+”, although H2SO4 (sulfuric acid) and TsOH (tosic acid) are also often used.
Notes: The byproduct of each of these reactions is water. Note that the fourth example is an intramolecular reaction that forms a cyclic ester. Cyclic esters are also called lactones.
For such a seemingly simple reaction (replacement of OH by OR) there are actually a lot of steps. Protonation of the carbonyl oxygen by acid (Step 1, arrows A and B) makes the carbonyl carbon a much better electrophile. It undergoes 1,2-addition by the alcohol (Step 2, arrows C and D) whereupon the proton from the alcohol is transferred to one of the OH groups (Step 3, arrows E and F). Subsequent 1,2-elimination of water (Step 4, arrows G and H) leads to the protonated ester, and the ester is then deprotonated (Step 5, arrows I and J).
- All of these steps are in equilibrium
- The mechanism for proton transfer can alternatively be drawn as follows:
Note that the acid is a catalyst here (regenerated at the end) and serves two purposes. First, it makes the carbonyl carbon a better electrophile (Setting up step 2) and also allows for the loss of H2O as a leaving group (much better leaving group than HO–)
(Advanced) References and Further Reading
- First example
Emil Fischer, Arthur Speier (1895). “Darstellung der Ester”. Chemische Berichte. 28: 3252–3258
Original paper by Emil Fischer and Arthur Speier describing acid-catalyzed esterification of carboxylic acids and alcohols.
- Protonic States and the Mechanism of Acid‐Catalysed Esterification
Dr. H. Zimmermann Dr. J. Rudolph
Angewandte Chemie Int. Ed., Volume 4, Issue 1, January 1965, Pages 40-49
Considerations of proton mobility in the condensed phase suggest a two-step mechanism of esterification, which proceeds via a tetrahedral intermediate.
- Ethyl Adipate
Org. Synth. Coll. Vol. 2, 264
One of the first procedures in Organic Syntheses, a reliable source for reproducible organic transformations. This uses a Fisher esterification to convert adipic acid, a diacid and precursor to nylon-6,6, to ethyl adipate.