Download Chapter 21 Carboxylic Acid Derivatives

Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 21
Carboxylic Acid Derivatives
(continued)
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2006, Prentice Hall
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
Industrial Synthesis
of Acetic Anhydride
• Four billion pounds/year produced.
• Use high heat (750°C) and triethyl
phosphate catalyst to produce ketene.
O
CH3 C OH
H
H
heat
(EtO)3P O
H
C C O
H
O
O
C C O + CH3 C OH
O
CH3 C O C CH3
=>
Chapter 21
15
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
=>
16
Anhydride Reactions
acid
ester
amide
acylbenzene
AlCl3
=>
Chapter 21
17
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
=>
18
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
=>
19
Reactions of Esters
acid
ester
amide
1° alcohol
Chapter 21
3° alcohol
=>
20
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
21
Polyesters
• Dacron® thread
• Mylar® tape
• Glyptal resin
• PET bottles
Chapter 21
=>
22
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
23
Reactions of Amides
acid and amine
amine
1° amine
nitrile
=>
Chapter 21
24
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
25
-Lactams
• Highly reactive, 4-membered ring.
• Found in antibiotics isolated from fungi.
Amide  ester !!
=>
Chapter 21
26
Polyamides
Nylon 6.6
=>
Chapter 21
27
Synthesis of Nitriles
O
R C NH2
POCl3
R C N
1° amide
R X
NaCN
+ R C N + Na X
alkyl halide
Ar
+
N N
diazonium salt
O
R C R'
aldehyde
or ketone
CuCN
Ar
CN + N2
HO CN
HCN
R C R'
KCN cyanohydrin
Chapter 21
=>
28
Reactions of Nitriles
amide
acid
1° amine
ketone
Chapter 21
=>
29
Thioesters
More reactive than esters because:
-S-R is a better leaving group than -O-R
Resonance overlap is not as effective.
=>
Chapter 21
30
Carbonic Acid Esters
• CO2 in water contains some H2CO3.
• Diesters are stable.
• Synthesized from phosgene.
O
Cl C Cl
phosgene
O
+
2 CH3CH2OH
CH3CH2OCOCH2CH3
diethyl carbonate
=>
Chapter 21
31
Urea and Urethanes
• Urea is the diamide of carbonic acid.
• Urethanes are esters of a monoamide
of carbonic acid.
O
O
Cl
C Cl
+
N C O
H2O
H2N C NH2
urea
2 NH3
O
O
NH C OH
NH C OR
a carbamic acid
Chapter 21
ROH
=>
a urethane
32
Polycarbonates
Long-chain esters of carbonic acid
=>
Chapter 21
33
Polyurethanes
A diol reacts with a diisocyanate.
=>
Chapter 21
34
End of Chapter 21
Chapter 21
35