nme o me ho oh meo oh me o o o - colby college 19.pdfcarboxylic acid derivatives: reaction at the...
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OHO OH
NMe
OMeO OH
NMe
OO O
NMe
Me
O
Me
O
OHO OH
NMe
OMeO OH
NMe
OO O
NMe
Me
O
Me
O
morphine codine heroin
O
OHMe
O
ClMe
O
OMe Me
Me O
OMe Me
OO
NH
MeMe
acetic acid acetyl chlorideN-methyl acetamideisopropyl acetate acetic anhydride
O
NMeMe
Me
N,N-dimethyl acetamide
Naming Carboxylic Acid Derivatives
O
OHMe
O
ClMe
O
OMe Me
MeO
OMe Me
OO
NH
MeMe
Acids
Acid Chlorides AmidesEstersAcid Anhydrides
Most reactive (electrophilic) Least reactive (electrophilic)
O
ClR
O
OR R
O
O
OHR
O
ORR
O
NH2R
Carboxylic Acid Derivatives: Reaction at the α-Position
O
Me
H
O
OMe
H
O
NH
H
Me
O
OH
H
pKa = 19 pKa = 24 pKa = 25 pKa = 24
Carboxylic Acid Derivatives: Reaction at the α-Position
O
Me
H
O
OMe
H
O
NH
H
Me
O
OH
H
LDA
O
Me
LDA LDA LDA
O
OMe
O
N
H
Me
O
O
H
pKa = 18
pKa = 5
No longer easily deprotonated
LDA
O
O
pKa = 30
Carboxylic Acid Derivatives: Reaction at the α-Position
O
Me
H
O
OMe
H
O
N
H
Me
O
OH
H
LDA
O
Me
LDA LDA LDA
O
OMe
O
NMe
O
O
H
pKa = 5
LDA
O
O
pKa = 30
Me
No acidic hydrogens
Me
All of these are enolates, and will react at the α-postition with electrophiles.
pKa = 25
Condensation of Ester Enolates: The Claisen Condensation
O
OMe
H
O
OMe
NaOMe
MeOH
O
OMeMeO
MeOMe
O
OMe
O
Me
O
OMe
H
O
Me
O
OMe
pKa = 10
NaOMe
O
Me
O
OMe
H3O+ workup
a β-keto ester
Intramolecular Condensation of Ester Enolates: The Dieckmann Condensation
MeOOMe
O
O
NaOMe, MeOHOMe
OO
MeOOMe
O
O
MeOOMe
O
OOMe
OO OMeNaOMe
OMe
OO
NaOMe
OMe
OO
OMe
OOH3O+ workup
Crossed Condensation of Ester Enolates: The Crossed Claisen Condensation
EtO
ONaOEt, EtOH
Me MeO
O
+EtO
O O
Me
Only enolate possibleNeed excess of this ester
+ EtO
O O
Me
Me
major minor
O
EtOMe
Me
NaOEt, EtOH
The following Claisen condensation fails. Why?
No Reaction
Crossed Condensation of Ester Enolates: The Crossed Claisen Condensation
EtOMe
O
Me
NaOEt, EtOHNo Reaction
O
OMe
Me
O
OMe
NaOMe
MeOH
O
OMe O
OMe
O
OMe
O O
OMe
MeH
Me
MeMe
Me
Me
Me
MeMe
Me
Me
Me Me
No α-hydrogens left, reaction cannot be driven to completion by deprotonation
Decarboxylation of Acids with β-Carbonyl Groups
O
R
O
O
HO
R
H O
R Me
(heat)
CO2
O
HO
O
OH
Me
O
HO
Me
30 °C
O
O
OH
O
30 °C O
O
The Chemistry of Nitriles
R C N
H3O+
or–OH
O
NH2R
O
OHR
H3O+
or–OH
R C NOH2
NHR
R C N H
H3O+
OH2
OH
NHR
tautomerize O
NH2R
The Chemistry of Nitriles
Me C NR Li
R MgCl
LiAlH4
H2, Pd or Pt
Me C N
Me C N
Me C N
N
RMe
N
RMe
Li
MgCl
N
HMe
Li
H3O+ workup
H3O+ workup
O
RMe
O
RMe
LiAlH4N
HMe
LiH2Al
H
H3O+ workupMe NH2
Me NH2
The Chemistry of Nitriles
NR
H
pKa = 25
LDAN
R CN
R
NR MeI
NR
Me
"Enolates" of nitriles react like other enolates that you have seen: