Chapter 11
Carboxylic Acid Derivatives
Chapter 11
1
Acid Derivatives
• All acid derivatives can be converted to the
carboxylic acid by acidic or basic hydrolysis.
• Esters and amides are common in nature.
Chapter 11
2
Naming Esters
IUPAC Nomenclature
As usual the long chain will contain the carbonyl carbon.
Drop the “e” then add oate suffix. The remaining carbon
chain is named as substituent and used as a prefix.
Common Nomenclature
Esters are named from the common name of the acid used
to form them. Drop the “oic acid” from the common acid
name and att the suffix “ate”. The other carbon group is
named as a substituent.
O
CH3CH2
OH
CH3CH2
+ HO C CH3
ethanol
ethanoic acid
ethyl alcohol
acetic acid
O
+
H
Chapter 11
O C CH3 + H2O
3
Naming Esters
IUPAC Nomenclature
As usual the long chain will contain the carbonyl carbon.
Drop the “e” then add oate suffix. The remaining carbon
chain is named as substituent and used as a prefix.
Common Nomenclature
Esters are named from the common name of the acid used
to form them. Drop the “oic acid” from the common acid
name and att the suffix “ate”. The other carbon group is
named as a substituent.
O
CH3CH2
OH
CH3CH2
+ HO C CH3
ethanol
ethanoic acid
ethyl alcohol
acetic acid
O
+
H
O C CH3 + H2O
ethyl ethanoate
Chapter 11
ethyl acetate
4
Name These
CH3
O
CH3CHCH2OCCH3
O
HCOCH2
Chapter 11
5
Name These
CH3
O
O
CH3CHCH2OCCH3
HCOCH2
(Common)
Chapter 11
6
Name These
CH3
O
O
CH3CHCH2OCCH3
HCOCH2
isobutyl acetate (Common)
Chapter 11
7
Name These
CH3
O
O
CH3CHCH2OCCH3
HCOCH2
isobutyl acetate (Common)
benzyl formate (common)
Chapter 11
8
Name These
CH3
O
O
CH3CHCH2OCCH3
HCOCH2
isobutyl acetate (Common)
2-methylpropyl ethanoate (IUPAC)
benzyl formate (common)
Chapter 11
9
Name These
CH3
O
O
CH3CHCH2OCCH3
HCOCH2
isobutyl acetate (Common)
2-methylpropyl ethanoate (IUPAC)
benzyl formate (common)
benzyl methanoate (IUPAC)
Chapter 11
10
Cyclic Esters
• Reaction of -OH and -COOH on same molecule
produces a cyclic ester, lactone.
• To name, add word lactone to the IUPAC acid name
or replace the -ic acid of common name with olactone.
O
H3C
O
CH3
4-hydroxy-2-methylpentanoic acid lactone
Chapter 11
11
Cyclic Esters
• Reaction of -OH and -COOH on same molecule
produces a cyclic ester, lactone.
• To name, add word lactone to the IUPAC acid name
or replace the -ic acid of common name with olactone.
O
H3C
O
CH3
4-hydroxy-2-methylpentanoic acid lactone
-methyl--valerolactone
Chapter 11
12
Amides
• Product of the reaction of a carboxylic acid
and ammonia or an amine.
• Not basic because the lone pair on nitrogen
is delocalized by resonance.
_
O
C
H
O
N
H
C + H
N
H
H
H
Bond angles around N
are close to 120.
Chapter 11
13
Classes of Amides
• 1 amide has one C-N bond (two N-H).
• 2 amide or N-substituted amide has two CN bonds (one N-H).
• 3 amide or N,N-disubstituted amide has
three C-N bonds (no N-H).
Chapter 11
14
Naming Amides
• For 1 amide, drop -ic or -oic acid from the
carboxylic acid name, add -amide.
• For 2 and 3 amides, the alkyl groups
bonded to nitrogen are named with N- to
indicate their position.
O CH3
CH3CHC N CH2CH3
CH3
Chapter 11
15
Naming Amides
• For 1 amide, drop -ic or -oic acid from the
carboxylic acid name, add -amide.
• For 2 and 3 amides, the alkyl groups
bonded to nitrogen are named with N- to
indicate their position.
O CH3
CH3CHC N CH2CH3
N-ethyl-N,2-dimethylpropanamide
N-ethyl-N-methylisobutyramide
CH3
Chapter 11
16
Cyclic Amides
• Reaction of -NH2 and -COOH on same molecule
produces a cyclic amide, lactam.
• To name, add word lactam to the IUPAC acid name or
replace the -ic acid of common name with -olactam.
O
N H
CH3
Chapter 21
17
Cyclic Amides
• Reaction of -NH2 and -COOH on same molecule
produces a cyclic amide, lactam.
• To name, add word lactam to the IUPAC acid name or
replace the -ic acid of common name with -olactam.
O
N H
CH3
4-aminopentanoic acid lactam
-valerolactam
Chapter 21
18
Nitriles
• -CN can be hydrolyzed to carboxylic acid, so
nitriles are acid derivatives.
• Nitrogen is sp hybridized, lone pair tightly
held, so not very basic (pKb about 24).
Chapter 11
19
Naming Nitriles
• For IUPAC names, add -nitrile to the alkane
name.
• Common names come from the carboxylic
acid. Replace -ic acid with -onitrile.
Br
C N
CH3CHCH2CH2CH2CN
Chapter 11
20
Naming Nitriles
• For IUPAC names, add -nitrile to the alkane
name.
• Common names come from the carboxylic
acid. Replace -ic acid with -onitrile.
Br
C N
CH3CHCH2CH2CH2CN
5-bromohexanenitrile
-bromocapronitrile
Cyclohexanecarbonitrile
Chapter 11
21
Acid Halides
• More reactive than acids; the halogen
withdraws e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.
O
C
Br
O
CH3CHCH2C Br
Cl
Chapter 11
22
Acid Halides
• More reactive than acids; the halogen
withdraws e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.
O
C
Br
O
CH3CHCH2C Br
Cl
3-bromobutanoyl bromide
-bromobutyryl bromide
benzoyl chloride
Chapter 11
23
Acid Anhydrides
• Two molecules of acid combine with the loss
of water to form the anhydride.
• Anhydrides are more reactive than acids, but
less reactive than acid chlorides.
• A carboxylate ion is the leaving group in
nucleophilic acyl substitution reactions.
O
R C O H
O
O
H O C
R
Chapter 11
O
R C O C
R
24
Naming Anhydrides
• The word acid is replaced with anhydride.
• For a mixed anhydride, name both acids.
• Diacids may form anhydrides if a 5- or 6membered ring is the product.
O
O
CH3
O
C O C CH3
O
O
=>
Chapter 11
25
Naming Anhydrides
• The word acid is replaced with anhydride.
• For a mixed anhydride, name both acids.
• Diacids may form anhydrides if a 5- or 6membered ring is the product.
O
O
CH3
O
C O C CH3
O
ethanoic anhydride
acetic anhydride
O
1,2-benzenedicarboxylic anhydride
phthalic anhydride
Chapter 11
=>
26
Multifunctional Compounds
• The functional group with the highest
priority determines the parent name.
• Acid > ester > amide > nitrile > aldehyde >
ketone > alcohol > amine > alkene > alkyne.
O
C
OCH2CH3
CN
Chapter 11
27
Multifunctional Compounds
• The functional group with the highest
priority determines the parent name.
• Acid > ester > amide > nitrile > aldehyde >
ketone > alcohol > amine > alkene > alkyne.
O
C
OCH2CH3
ethyl o-cyanobenzoate
CN
Chapter 11
28
Boiling Points
Even 3 amides have
strong attractions.
Chapter 11
29
Melting Points
• Amides have very high melting points.
• Melting points increase with increasing
number of N-H bonds.
m.p. -61C
m.p. 28C
Chapter 11
m.p. 79C
30
Solubility
• Acid chlorides and anhydrides are too reactive
to be used with water or alcohol.
• Esters, 3 amides, and nitriles are good polar
aprotic solvents.
• Solvents commonly used in organic reactions:
– Ethyl acetate
– Dimethylformamide (DMF)
– Acetonitrile
Chapter 11
31
Interconversion ofAcid Derivatives
• Nucleophile adds to the carbonyl to form a
tetrahedral intermediate.
• Leaving group leaves and C=O regenerates.
Chapter 11
32
Reactivity
Reactivity decreases as leaving group
becomes more basic.
Chapter 11
33
Interconversion of Derivatives
More reactive
derivatives can be
converted to less
reactive
derivatives.
Chapter 11
34
Acid Chloride to Anhydride
• Acid or carboxylate ion attacks the C=O.
• Tetrahedral intermediate forms.
• Chloride ion leaves, C=O is restored, H+ is
abstracted.
O
R' C O H
_
O
R
C
O
Cl
R
H
C
+O
O
- H+
Cl
R
C
O
O
C
R'
+
HCl
C R'
O
Chapter 11
35
Acid Chloride to Ester
• Alcohol attacks the C=O.
• Tetrahedral intermediate forms.
• Chloride ion leaves, C=O is restored, H+ is
abstracted.
_
O
R'
O H
R
C
O
Cl
R C Cl
+O
H
R'
Chapter 11
O
- H+
R
C
O
R' + HCl
36
Acid Chloride to Amide
• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
Chapter 11
37
Anhydride to Ester
• Alcohol attacks one C=O of anhydride.
• Tetrahedral intermediate forms.
• Carboxylate ion leaves, C=O is restored, H+
is abstracted.
Chapter 11
38
Anhydride to Amide
• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
Chapter 11
39
Ester to Amide
• Nucleophile must be NH3 or 1 amine.
• Prolonged heating required.
Surprise!
Chapter 11
40
Leaving Groups
A strong base is not usually a leaving group
unless it’s in an exothermic step.
Chapter 11
41
Transesterification
• One alkoxy group can be replaced by
another with acid or base catalyst.
• Use large excess of preferred alcohol.
Chapter 11
42
TRANSESTERIFICATION OF COCAINE
N
N
O
O
OCH3
OCH2CH3
CH3CH2OH
H
H
Ph
Ph
0
0
O
Cocaine
O
Cocaethylene
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 11
44
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 11
45
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 11
46
Hydrolysis of Amides
Prolonged heating in 6 M HCl or 40% aqueous
NaOH is required.
Chapter 11
47
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 11
48
Reduction to Alcohols
Lithium aluminum hydride reduces acids, acid
chlorides, and esters to primary alcohols.
Chapter 11
49
Acid Chloride Synthesis
• Use thionyl chloride, SOCl2, or oxalyl
chloride, (COCl)2.
• Other products are gases.
Chapter 11
50
Acid Chloride Reactions (1)
acid
ester
amide
acid anhydride
Chapter 11
51
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 11
O
52
Anhydride Reactions
acid
ester
amide
acylbenzene
AlCl3
Chapter 11
53
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
CH3CH2OH
C OH
O
Chapter 11
O
54
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
O
+
H
R C OR' + RCOOH
R C O C R + R'OH
acid anhydride
O
R C OH + CH2N2
O
R C OCH3 + N2
methyl ester
Chapter 11
55
Synthesis of Amides
O
R C OH + R'NH2
O
heat
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
Chapter 11
O
R C NH2
56
Reactions of Amides
acid and amine
amine
1° amine
nitrile
Chapter 11
57
CHAPTER 11 REVIEW
Chapter 11
58
Name
O
C
CH3CH2
OCH2CH2CH3
a. Ethyl ethanoate
b.Propyl propanoate
c. Ethyl propanoate
d.Propyl ethanoate
e.Propyl butanoate
Answer
a. Ethyl ethanoate
b.Propyl propanoate
c. Ethyl propanoate
d.Propyl ethanoate
e.Propyl butanoate
The longest chain is three carbons. Propyl is
the alkoxy group.
Name
O
O
a. 3-Hydroxybutanoic acid lactone
b.4-Hydroxybutanoic acid lactone
c. 4-Hydroxypentanoic acid lactone
d.5-Hydroxypentanoic acid lactone
Answer
a. 3-Hydroxybutanoic acid lactone
b.4-Hydroxybutanoic acid lactone
c. 4-Hydroxypentanoic acid lactone
d.5-Hydroxypentanoic acid lactone
A lactone is a cyclic ester. The hydroxy is on
the fifth carbon.
Name
O
C
CH3CH2
a.
b.
c.
d.
e.
NHCH2CH3
Pentanamide
Butanamide
N-Ethylethanamide
N-Ethylpropanamide
N-Methylethanamide
Answer
a.
b.
c.
d.
e.
Pentanamide
Butanamide
N-Ethylethanamide
N-Ethylpropanamide
N-Methylethanamide
Ethyl is attached to the nitrogen. The longest
chain is three carbons.
21.4 Name
O
N
a. 3-Aminobutanoic acid lactam
b.4-Aminobutanoic acid lactam
c. 4-Aminopentanoic acid lactam
d.5-Aminopentanoic acid lactam
Answer
a. 3-Aminobutanoic acid lactam
b.4-Aminobutanoic acid lactam
c. 4-Aminopentanoic acid lactam
d.5-Aminopentanoic acid lactam
A lactam is a cyclic amide. The amino group is
on the fifth carbon.
Name
(CH3)2CHCH2C
a. Pentanenitrile
b.Butanenitrile
c. Propanenitrile
d.2-Methylbutanenitrile
e.3-Methylbutanenitrile
N
Answer
a. Pentanenitrile
b.Butanenitrile
c. Propanenitrile
d.2-Methylbutanenitrile
e.3-Methylbutanenitrile
The longest chain has four carbons. The
methyl is on the third carbon.
Name
O
C
CH3CH
Cl
Cl
a. 1-Chloroethanoyl chloride
b.2-Chloroethanoyl chloride
c. 1-Chloropropanoyl chloride
d.2-Chloropropanoyl chloride
Answer
a. 1-Chloroethanoyl chloride
b.2-Chloroethanoyl chloride
c. 1-Chloropropanoyl chloride
d.2-Chloropropanoyl chloride
The longest chain has three carbons.
Chlorines are on the second carbon and the
carbonyl carbon.
Name
CH3CH2
O
O
C
C
O
CH3
a. Ethanoic methanoic anhydride
b.Methanoic propanoic anhydride
c. Ethanoic anhydride
d.Ethanoic propanoic anhydride
e.Propanoic anhydride
Answer
a. Ethanoic methanoic anhydride
b.Methanoic propanoic anhydride
c. Ethanoic anhydride
d.Ethanoic propanoic anhydride
e.Propanoic anhydride
The three-carbon chain is on the left. A
two-carbon chain is on the right.
CH3CH2
O
O
C
C
Cl
+
HO
CH3
a. Ethanoic methanoic anhydride
b.Methanoic propanoic anhydride
c. Ethanoic anhydride
d.Ethanoic propanoic anhydride
Answer
a. Ethanoic methanoic anhydride
b.Methanoic propanoic anhydride
c. Ethanoic anhydride
d.Ethanoic propanoic anhydride
An acid halide reacts with a carboxylic acid
to form an anhydride.
O
C
CH3CH2
Cl
+ CH3OH
a. Methyl ethanoate
b.Methyl propanoate
c. Ethyl ethanoate
d.Ethyl propanoate
Answer
a. Methyl ethanoate
b.Methyl propanoate
c. Ethyl ethanoate
d.Ethyl propanoate
An acid halide reacts with an alcohol to form
an ester.
O
C
CH3CH2
a.
b.
c.
d.
Cl
+ 2 (CH3)2NH
N-Methylethanamide
N-Methylpropanamide
N,N-Dimethylethanamide
N,N-Dimethylpropanamide
Answer
a. N-Methylethanamide
b. N-Methylpropanamide
c. N,N-Dimethylethanamide
d. N,N-Dimethylpropanamide
An acid halide reacts with an amine to form an
amide.
O
O
C
CH3CH2
CH3OH
C
O
CH2CH3
a. Ethanoic acid + ethanol
b.Propanoic acid + methyl ethanoate
c. Ethanoic acid + ethyl ethanoate
d.Propanoic acid + methyl propanoate
e.Ethanoic acid + ethyl propanoate
Answer
a. Ethanoic acid + ethanol
b.Propanoic acid + methyl ethanoate
c. Ethanoic acid + ethyl ethanoate
d.Propanoic acid + methyl propanoate
e.Ethanoic acid + ethyl propanoate
An anhydride reacts with an alcohol to give a
carboxylic acid and an ester.
O
O
C
CH3CH2
a.
b.
c.
d.
CH3CH2NH2
C
O
CH2CH3
N,N-Diethylpropanamide + propanoic acid
N-Ethylpropanamide + propanoic acid
N-Ethylethanamide + ethanoic acid
N,N-Diethylethanamide + ethanoic acid
Answer
a.
b.
c.
d.
N,N-Diethylpropanamide + propanoic acid
N-Ethylpropanamide + propanoic acid
N-Ethylethanamide + ethanoic acid
N,N-Diethylethanamide + ethanoic acid
An anhydride reacts with an amide to form an
amide and a carboxylic acid.
O
CH3CH2CH2NH2
C
CH3CH2
a.
b.
c.
d.
e.
OCH3
N-Propyl propanamide + methanol
N-Propyl ethanamide + ethanol
N-Ethyl propanamide + methanol
N-Ethyl ethanamide + ethanol
N-Ethyl ethanamide + propanol
Answer
a.
b.
c.
d.
e.
N-Propyl propanamide + methanol
N-Propyl ethanamide + ethanol
N-Ethyl propanamide + methanol
N-Ethyl ethanamide + ethanol
N-Ethyl ethanamide + propanol
An ester reacts with an amine to produce an
amide and an alcohol.
O
H2SO4
C
CH3CH2
NHCH3
a. Propanal + ammonia
b.Ethanoic acid + ammonia
c. Propanoic acid + methylamine
d.Ethanoic acid + methylamine
Answer
a. Propanal + ammonia
b.Ethanoic acid + ammonia
c. Propanoic acid + methylamine
d.Ethanoic acid + methylamine
An amide is hydrolyzed under acidic
conditions to form a carboxylic acid and an
amine.
H2SO4
CH3CH2C
N
a. Propylamine
b.Propanamide
c. Propanoic acid
d.Butanoic acid
e.No reaction
heat
Answer
a. Propylamine
b.Propanamide
c. Propanoic acid
d.Butanoic acid
e.No reaction
A nitrile is hydrolyzed to a carboxylic acid in
the presence of acid and heat.
O
1. LiAlH4
C
CH3CH2
OCH3
2. H3O+
a. Methanol + ethanol
b.Methanol + propanol
c. Ethanol + propanol
d.Ethanol
Answer
a. Methanol + ethanol
b.Methanol + propanol
c. Ethanol + propanol
d.Ethanol
An ester is reduced to two alcohols.
O
1. LiAlH4
C
CH3CH2
NHCH3
2. H2O
a. Ethyl methyl amine
b.Ethyl propyl amine
c. Methyl propyl amine
d.Methyl amine + propanoic acid
e.Ethyl amine + propanoic acid
Answer
a. Ethyl methyl amine
b.Ethyl propyl amine
c. Methyl propyl amine
d.Methyl amine + propanoic acid
e.Ethyl amine + propanoic acid
An amide is reduced to an amine with lithium
aluminum hydride.
O
1. 2 CH3MgBr
C
CH3CH2
Cl
2. H3O+
a. 2-Methyl-2-butanol
b.3-Methyl-3-pentanol
c. 1-Butanol
d.3-Methyl-2-butanol
e.3-Ethyl-3-pentanol
Answer
a. 2-Methyl-2-butanol
b.3-Methyl-3-pentanol
c. 1-Butanol
d.3-Methyl-2-butanol
e.3-Ethyl-3-pentanol
Two methyl groups add to the carbon of the
carbonyl. Hydrolysis yields the tertiary alcohol.
O
1. 2 CH3MgBr
C
CH3CH2
OCH2CH3 2. H3O+
a. 2-Methyl-2-butanol + ethanol
b.2-Methyl-2-butanol + methanol
c. 2-Butanone + ethanol
d.2-Methyl-2-butanol + ethanol
Answer
a. 2-Methyl-2-butanol + ethanol
b.2-Methyl-2-butanol + methanol
c. 2-Butanone + ethanol
d.2-Methyl-2-butanol + ethanol
The reaction of an ester with a Grignard
reagent forms a tertiary alcohol and an
alcohol.
End of Chapter 11
Chapter 11
97