Substitution Reactions coupled with Acid/base reaction
Major concepts
 Weaker nucleophiles can be made into stronger nucleophiles by deprotonation
 Two common carbon nucleophiles are enolates and acetonides
Vocabulary
 Enolate
 Acetonide
 LDA, t-butoxide
Students should be able to:
 Recognize whether a base is strong enough to deprotonate a weak nucleophile to make a strong
nucleophile
 Apply nucleophilic substitution mechanisms to carbon nucleophiles
 Recognize nucleophiles and electrophiles and predict the products of substitution reactions
 Predict the products and provide reagents for carbon-based nucleophiles in substitution
Daily Problems
1. If these compounds are treated with a strong enough base, they will be deprotonated and made into
a nucleophile. Draw the structure of this nucleophile.
2. Draw these structures.
A. LDA
B. an enolate ion
C. Acetylide
3. Provide an arrow mechanism with all intermediate structures for the following substitution reaction.
4. In the table, put a check next to each base that is capable of completely deprotonating the
compound to make it a good nucleophile.
Potassium t-butoxide
Sodium hydride
OH
O
H
H3C
O
C
CH
O
OH
5. Predict the major product(s) of the following substitution reactions.
LDA
6. Provide the necessary reagents.
Cumulative Problems
7. Label each reaction as addition, elimination, or substitution if it is not already given. Predict the
major product of each of these reactions.
8. Explain why these reactions will not take place as written.
9. Propose a substitution reaction that would lead to the formation of SAM. Draw the necessary
arrows. (Hint: Indicate the new bond in the product. Which two atoms are now connected? Which
was the electrophile? Which was the substrate?)
NH2
N
O
HO
P
O
O
O-
P
N
O
O
P
O
N
O
N
O-
O-
OH
OH
CO2-
S
NH2
NH2
N
SAM
-
OOC
S
O
N
N
N
+ triphosphate
NH2
OH
OH
Why would SAM be a good methylating reagent? (Why is it willing to donate a methyl group to another
molecule?)