Download Decarboxylation

Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Decarboxylation
O
R H
R
OH
Reaction type: Elimination
+
CO2
O
O
HO
OH
H H
Malonic acid
Mechanism:
O H O
HO
O
H H
HO
H H
235
HO
H H
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Nucleophilic Acyl Substitution
O
Nu
+
O
LG
Nu
+
LG
Two events in a nucleophilic acyl substitution reaction:
In nucleophilic substitution (e.g. for alkyl halides) the nucleophile cannot
attack until the leaving group leaves, why is there a difference ?
Nucleophilic Acyl Substitution : Reactive Systems
Nucleophile:
Electrophile:
O
O
Nu
LG
Nu
LG
LG
Nu
Nucleophilic Acyl Substitution : Less Reactive
Nucleophile:
Electrophile:
Activate the Nucleophile:
Activate the Electrophile:
O
H B
LG
B
Nu H
LG
LG

236
O
+
B H
Nu
LG
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Interconversion Reactions of Acyl Chlorides:
Acid
anhydrides
O
O
R'
+
OR" R
O
Esters
Cl
Acids
R
O
O
O
H2O +
Amides
+ Cl
OR
R
Cl
O
O
NHR2 +
R
+ Cl
OR'
R
Cl
R
R' + R"O
O
BASE
R'OH +
R
O
O
R
Cl
+ HCl
NR2
Reaction type:
Friedel-Crafts Acylation of Benzene
O
O
R
+
AlCl3
Cl
Reaction type:
Reagent :
Limitation:
237
R + HCl
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Interconversion Reactions of Acid Anhydrides
Esters R'OH +
R
Acids
R
Amide NHR2 +
R
R
R'
O
O
R
OH
O
O
+
R
R'
O
O
+
O
O
O
R
OR'
R
R'
O
O
+
O
O
O
H2O +
O
O
O
R
NR2
O
Reaction type:
Interconversion Reactions of Esters
O
Esters
R'OH +
R
H2O +
R
O
R
OR"
O
Acids
H+
O
NHR2 +
R
OR'
O
H+
+ R"OH
or OHOR
OR" then H+R
O
Amides
+ R"OH
Cl
BASE
Reaction type:
Transesterification:
Hydrolysis:
Amide preparation:
BASIC conditions:
ACIDIC conditions:
238
R
+ R"OH
NR2
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Reduction of Esters
O
LiAlH4
+
OH
+ ROH
H
H
Reactions usually in Et2O or THF followed by H3O+ work-ups
Reaction type:
R'
R'
OR
Overall Reaction:
Reagents:
Mechanism:
Li
H3Al H
O
O
OR
+
H
Li
H3Al H
OH
H
OH
H
H
Reactions of RLi and RMgX with Esters
2 LiR"
or
2 MgBrR"+ R'
O
OH
+ ROH
H
H
Reaction usually in Et2O followed by H3O+ work-up
Reaction type:
OR
239
R'
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Nucleophilic Addition to Nitriles
Nu
H+ N C R
Reaction type:
Strong nucleophiles:
Further reaction
R

H+
Nu
+

Weak nucleophiles:
N
N
C R
R
R

N
N
N
C
C
C
C
R
R
H
R
N
N
C
C
R
R
240
R
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Hydrolysis of Nitriles
N Strong Acid
or Base
C
H2O
C
HEAT
R
R
Reaction type:
Mechanism:
N
N H
H2O
HEAT
O
R
N H
C
C
R
R
R
O
N H
H2O
H
C
C
N H
H 2O
C
HO
C
HO
R
R
H
H
HN H
H O
HN H
H
C
O
R
HN H
H O
C
C
HO
R
R
H
H N H
HN H
H 2O
R
O
H OH
R
N H
AMIDE
H2O
H
HN H
H 2O
C
H
H
HO
H
H N H
H
R
O
HO
R
OH
OH2
R
O
241
OH
H
H N H
O
R
H
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Reduction of Nitriles
LiAlH4
R CH2 NH2
R C
N
Reactions usually in Et2O or THF followed by H3O+ work-up
Reaction type:
Products:

Reagents:
Reactions of RLi or RMgX with Nitriles
O
1) RLi or RMgX
C
N
R'
R
2) H3O
Reaction usually in Et2O or THF
R'
Reaction type:
Products:
R'
C
N
1) RLi or RMgX
NMgX 2) H3O
R'
R
Nitriles are less reactive than aldehydes and ketones.
O
R'
R
Why doesn’t the Grignard reagent continue to react at the ketone
stage?
242
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Reactions of Amides
Hydrolysis of Amides
O
C
R'2N
R
Reaction type:
Strong
acid or base
O
H O
heat
+
R'2NH
H
HO R
O
R
Reagents:
Mechanism basic:
O
R2N
C
O
OH
R2N
R
H
C O
O
OH R
R
R
N
+
O
R
R
NH
+
R
Mechanism acidic:
O
H
C
HN
R
H
O H
C
H N
H
H2O
R
OH
H
H
N
R
H O H
H2O
OH
O
H
O
H N H
H
R
OH
R H
HO
R
HO
H N H
H
243
O
HN H
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Reduction of Amides
H
O
+ LiAlH4
R NR2
R NR2
H
Reactions usually in Et2O or THF followed by H3O+ work-ups
Reaction type:
Products:
Reagents:
Primary
amine
Secondary
amine
Tertiary
amine
H
O
R
NH2
O
R
R
+ LiAlH4
NHR
R
+ LiAlH4
R
O
R
+ LiAlH4
NR2
H
H
H
H
H
NH2
NHR
NR2
Mechanism:
Li
Li
Li
AlH3
AlH
3
O
AlH3
HO
H
R2N
R2N
H
H
H
C
C
H
R2N
C
R R2N
CH
R
R
R
Why do we get the amine rather than the alkane?
244
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Spectroscopy
1
IR
13
H NMR
Carboxylic OH
C=O
Acids
C-O
C NMR
–COOH
H-C-COOH

Acyl
Halides
Anhydrides
H-COC
H-C-C=O
Esters
Amides
Nitriles
UV-VIS


245
Exam 3 notes
LSW S04
Organic Chemistry
Carboxylic Acids and Derivatives
Mass Spec
Carboxylic
Acids
Acyl
Halides
Acid
Anhydrides
acylium ions
Esters
Amides
Nitriles

246