Nucleophilic Acyl Substitution—weak Nu
Major concepts
 Nucleophilic acyl substitutions can occur with weak nucleophiles under basic conditions, but
only if the carboxylic acid derivative is very reactive
 Nulceophilic acyl substitutions can occur with weak nucleophiles under acidic conditions
 Carboxylic acids can be esterified with alcohols under acidic conditions
Vocabulary
 Fisher esterification
Students should be able to:
 Draw a mechanism for nucleophilic acyl substitution under acidic conditions (Fisher
esterification)
 Determine functional groups that undergo nucleophilic acyl substitution reactions
 Predict the products of nucleophilic acyl substitutions
 Predict the direction of equilibrium and draw energy diagrams for the mechanisms of
nucleophilic acyl substitution taking into account Le Chatlier’s principle

Daily Problems
1. Draw a mechanism for this Fisher esterification. What byproduct is produced?
O
CH3OH
O
H+
+
OCH 3
OH
H2O
byproduct
-H+
OH
O
OH
CH3OH
OH
CH3OH
O
H
O
O
HO
OH
HO
HO
OH
H
OHCH 3
OH2
2. Although the stability of the starting materials and products are about the same in the reaction
above, the equilibrium lies far to the right. Explain how this is possible. How could this reaction be
forced back to the left? (Hint: What is the byproduct of the reaction?)
This equilibrium is possible through the addition of acid to the electrophile, making it a better
electrophile. This means it does not need as strong of a nucleophile to react. The reaction could be
forced back to the left is water was added.
3. These reactive carboxylic acid derivatives will react with these weak nucleophiles. Predict the
product, and explain what the purpose of the triethylamine (TEA) and pyridine (pyr) is in each reaction.
Triethylamine and pyridine are bases that “soak up” the byproduct (acid).
4. Predict the products of these nucleophilic acyl substitution reactions.
Cumulative problems:
5. Label each reaction as a nucleophilic substitution, a nucleophilic addition, or a nucleophilic acyl
substitution. Then predict the product.