Download Chapter 21 Carboxylic Acid Derivatives

Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 21
Carboxylic Acid Derivatives
(continued)
Hydrolysis of Acid
Chlorides and Anhydrides
• Hydrolysis occurs quickly, even in moist air
with no acid or base catalyst.
• Reagents must be protected from moisture.
=>
Chapter 21
2
Acid Hydrolysis of Esters
• Reverse of Fischer esterification.
• Reaches equilibrium.
• Use a large excess of water.
O
CH3
C OCH3 + HOH
O
+
H
CH3
C OH
+ CH3OH
=>
Chapter 21
3
Saponification
• Base-catalyzed hydrolysis of ester.
• “Saponification” means “soap-making.”
• Soaps are made by heating NaOH with
a fat (triester of glycerol) to produce the
sodium salt of a fatty acid - a soap.
• One example of a soap is sodium
stearate, Na+ -OOC(CH2)16CH3.
=>
Chapter 21
4
Hydrolysis of Amides
Prolonged heating in 6 M HCl or 40%
aqueous NaOH is required.
=>
Chapter 21
5
Hydrolysis of Nitriles
• Under mild conditions, nitriles hydrolyze
to an amide.
• Heating with aqueous acid or base will
hydrolyze a nitrile to an acid.
Chapter 21
=>
6
Reduction to Alcohols
Lithium aluminum hydride reduces acids,
acid chlorides, and esters to primary
alcohols.
=>
Chapter 21
7
Reduction to Aldehydes
Acid chlorides will react with a weaker
reducing agent to yield an aldehyde.
=>
Chapter 21
8
Reduction to Amines
• Lithium aluminum hydride reduces amides
and nitriles to amines.
• Nitriles and 1 amides reduce to 1 amines.
• A 2 amide reduces to a 2 amine.
• A 3 amide reduces to a 3 amine.
=>
Chapter 21
9
Organometallic Reagents
Grignard reagents and organolithium
reagents add twice to acid chlorides and
esters to give alcohols after protonation.
=>
Chapter 21
10
Grignard Reagents
and Nitriles
A Grignard reagent or organolithium reagent
attacks the cyano group to yield an imine
which is hydrolyzed to a ketone.
=>
Chapter 21
11
Acid Chloride Synthesis
• Use thionyl chloride, SOCl2, or oxalyl
chloride, (COCl)2.
• Other products are gases.
=>
Chapter 21
12
Acid Chloride Reactions (1)
acid
ester
amide
acid anhydride
=>
Chapter 21
13
Acid Chloride Reactions (2)
3° alcohol
ketone
1° alcohol
aldehyde
acylbenzene
=>
Chapter 21
AlCl3
14
Lab Synthesis
of Anhydrides
• React acid chloride with carboxylic acid
or carboxylate ion.
O
C Cl
O
O
O
C O C CH
3
_
+ CH3 C O
• Heat dicarboxylic acids to form cyclic
O
O
anhydrides.
C OH
O
C OH
O
Chapter 21
O
=>
15
Anhydride Reactions
acid
ester
amide
acylbenzene
AlCl3
=>
Chapter 21
16
Anhydride vs. Acid Chloride
• Acetic anhydride is cheaper, gives a
better yield than acetyl chloride.
• Use acetic formic anhydride to produce
formate esters and formamides.
• Use cyclic anhydrides to produce
a difunctional molecule.
O
O
C OCH CH
2
3
O
O
CH3CH2OH
Chapter 21
C OH
O
=>
17
Synthesis of Esters
O
O
+
R C OH
+ R'OH
H
R C OR'
+ HOH
acid
O
O
R C Cl
R C OR' + HCl
+ R'OH
acid chloride
O
O
R C O C R + R'OH
O
+
H
R C OR' + RCOOH
acid anhydride
O
R C OH + CH2N2
O
R C OCH3 + N2
methyl ester
Chapter 21
=>
18
Reactions of Esters
acid
ester
amide
1° alcohol
Chapter 21
3° alcohol
=>
19
Lactones
• Formation favored for five- and sixmembered rings.
OH
H+
O
+ H2O
COOH
O
• For larger rings, remove water to
shift equilibrium toward products
OH
+
O
H
COOH
+
H2O
O
=>
Chapter 21
20
Polyesters
• Dacron® thread
• Mylar® tape
• Glyptal resin
• PET bottles
Chapter 21
=>
21
Synthesis of Amides
O
O
heat
R C OH + R'NH2
R C NHR' + HOH
acid
O
O
R C NR'2 + R'2NH2+Cl-
R C Cl + 2 R'2NH
acid chloride
O
O
O
R C NR'2 + RCOOH
R C O C R + R'2NH
acid anhydride
O
O
R C OR'' + R'NH2
R C NHR' + R''OH
ester
+
R C N + H2O
-
H or OH
nitrile
O
R C NH2
=>
Chapter 21
22
Reactions of Amides
acid and amine
amine
1° amine
nitrile
=>
Chapter 21
23
Lactam Formation
• Five- and six-membered rings can be
formed by heating - and -amino acids.
• Smaller or larger rings do not form readily.
=>
Chapter 21
24
End of Chapter 21
Chapter 21
25