Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 21
Carboxylic Acid Derivatives
Acid Derivatives
• All can be converted to the carboxylic
acid by acidic or basic hydrolysis.
• Esters and amides common in nature.
=>
Chapter 21
2
Naming Esters
• Esters are named as alkyl carboxylates.
• Alkyl from the alcohol, carboxylate from
the carboxylic acid precursor.
O
CH3CH2
OH
O
+
H
+ HO C CH3
CH3CH2
O C CH3 + H2O
ethanol
ethanoic acid
ethyl ethanoate
ethyl alcohol
acetic acid
ethyl acetate
=>
Chapter 21
3
Name These
CH3
O
O
HCOCH2
CH3CHCH2OCCH3
isobutyl acetate
2-methylpropyl ethanoate
benzyl formate
benzyl methanoate
=>
Chapter 21
4
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
4-hydroxy-2-methylpentanoic acid lactone
-methyl--valerolactone
CH3
=>
Chapter 21
5
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
H
C + H
N
H
H
Bond angles around N
are close to 120.
Chapter 21
6
=>
Classes of Amides
• 1 amide has one C-N bond (two N-H).
• 2 amide or N-substituted amide has
two C-N bonds (one N-H).
• 3 amide or N,N-disubstituted amide
has three C-N bonds (no N-H).
=>
Chapter 21
7
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 Nto indicate their position.
O CH3
CH3CHC N
N-ethyl-N,2-dimethylpropanamide
CH2CH3 N-ethyl-N-methylisobutyramide
CH3
Chapter 21
8
=>
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
9
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 21
10
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 21
11
Acid Halides
• More reactive than acids; the halogen
withdraws e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.
O
C
Br
Cl
O
CH3CHCH2C Br
3-bromobutanoyl bromide
-bromobutyryl bromide
=>
benzoyl chloride
Chapter 21
12
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
O
R C O C
R
=>
Chapter 21
13
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
O
C O C CH3
O
ethanoic anhydride
acetic anhydride
O
CH3
1,2-benzenedicarboxylic anhydride
phthalic anhydride
=>
Chapter 21
14
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 21
15
Boiling Points
Even 3 amides have
strong attractions.
Chapter 21
=>
16
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
m.p. 79C
=>
Chapter 21
17
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 21
=>18
Interconversion of
Acid Derivatives
• Nucleophile adds to the carbonyl to form a
tetrahedral intermediate.
• Leaving group leaves and C=O regenerates.
=>
Chapter 21
19
Reactivity
Reactivity decreases as leaving group
becomes more basic.
=>
Chapter 21
20
Interconversion of Derivatives
More reactive
derivatives can be
converted to less
reactive
derivatives.
=>
Chapter 21
21
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
O
O
R' C O H
R
C
O
- H+
Cl
R
H
C
+O
Cl
R
C
O
O
C
R'
+
HCl
C R'
O
Chapter 21
22
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 21
O
- H+
R
C
O
R' + HCl
23
Acid Chloride to Amide
• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
=>
Chapter 21
24
Anhydride to Ester
• Alcohol attacks one C=O of anhydride.
• Tetrahedral intermediate forms.
• Carboxylate ion leaves, C=O is
restored, H+ is abstracted.
=>
Chapter 21
25
Anhydride to Amide
• Ammonia yields a 1 amide
• A 1 amine yields a 2 amide
• A 2 amine yields a 3 amide
=>
Chapter 21
26
Ester to Amide
• Nucleophile must be NH3 or 1 amine.
• Prolonged heating required.
Surprise!
=>
Chapter 21
27
Leaving Groups
A strong base is not usually a leaving
group unless it’s in an exothermic step.
=>
Chapter 21
28
Transesterification
• One alkoxy group can be replaced by
another with acid or base catalyst.
• Use large excess of preferred alcohol.
Chapter 21
29