Ch. 20 - Carboxylic Acid Derivatives: NAS WorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

Fischer Esterification is an acid-catalyzed method to turn carboxylic acids into esters through nucleophilic acyl substitution.


General Reaction:

Fischer esterification (aka Fischer-Speier esterification and acid-catalyzed esterification) is a great way to take a carboxylic acid and convert it into an ester. All that’s required is a carboxylic acid, a strong acid catalyst, and an alcohol. Let’s go ahead and use acetic acid, H3O(same as writing H+), and ethanol to demonstrate the mechanism. To be clear, any acid like H2SO4 or HCl works just fine; we’re just going to use protonated water here.

Mechanism:

Starting material reagents and productStarting material, reagents, and product

protonationProtonation
The first step of this reaction is the protonation of the carbonyl oxygen to form an electrophilic carbon. Either resonance form can be used for the rest of the mechanism.

nucleophilic attackNucleophilic attack

The alcohol then comes in and attacks the carbon to form a tetrahedral intermediate.

Proton transferProton transfer

Next an intramolecular proton transfer occurs to form a hydronium ion.

reform-the-carbonylReform the carbonyl

Once that happens, the carbonyl is reformed and water is kicked off.

DeprotonationDeprotonation

All that’s left to do is deprotonate the carbonyl.


Now that you've learned about Fischer esterification, you know the game plan for nucleophilic acyl substitution (NAS). NAS can be used to make tons of molecules like benzoic acid and aspirin!

Summary:

Notice that we ended up with our acid again? That’s why this is considered an acid-catalyzed mechanism. Of course, there’s also base-catalyzed esterification. Be sure to check out my lesson dedicated to carboxylic acid derivatives. Good luck studying!



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.


Additional Problems
Which of the following is (are) tetrahedral intermediate(s) in the acid catalyzed esterification of benzoic acid with ethanol?
In the acid catalyzed esterification of compound  1, several possible intermediates are shown. Indicate the order in which these intermediates would appear during the conversion of 1 into 2. a) 1 → I → IV → V→ III → 2 b) 1 → II → IV → 2 c) 1 → III → IV → I→ V → 2 d) 1 → III → I → V→ IV → 2 e) 1 → I → III → IV → 2  
Draw a reasonable mechanism for the reaction below.
Provide a detailed reaction mechanism for the following transformation. This is an intramolecular version of what type of reaction?
Provide a detailed mechanism for the esterification reaction below.
What is the best choice of reagent(s) to perform the following transformation? a CH3OH, H2SO4 b CH3I, H2SO4 c NaOCH3 d CH3Li e CH3MgBr
Draw the organic product(s) for the following reaction. Indicate stereochemistry where appropriate. Assume an aqueous workup, when necessary. A reasonable answer may be “ No Reaction.”
Predict the product. NOTE: the product has 6 oxygens
Draw reasonable mechanisms for the reaction below.
Provide an electron push mechanism for the following transformation. Be sure you use the correct arrow formalism and correct non-zero formal charges.
Predict the product(s) for each of the following reaction. When appropriate, label them major and minor.
Draw the structural formula of the reactant(s), reagents(s) or the major organic product(s) in the boxes 
Predict the product(s) for the following reaction. When appropriate, label them major and minor. 
Draw the structure of the major organic product(s) of the reaction. 
What product would you expect to obtain from the following reaction?
Draw the structures of the major organic products of the following reaction.