19.13
Reactions of Carboxylic Acids:
A Review and a Preview
Reactions of Carboxylic Acids
Reactions already discussed
Acidity (Sections 19.4-19.9)
Reduction with LiAlH4 (Section 15.3)
Esterification (Section 15.8)
Reaction with Thionyl Chloride (Section 12.7)
Reactions of Carboxylic Acids
New reactions in this chapter
a-Halogenation
Decarboxylation
But first we revisit acid-catalyzed esterification
to examine its mechanism.
19.14
Mechanism of Acid-Catalyzed Esterification
Acid-catalyzed Esterification
(also called Fischer esterification)
O
H+
COH + CH3OH
O
COCH3 + H2O
Important fact: the oxygen of the alcohol is
incorporated into the ester as shown.
Mechanism of Fischer Esterification
The mechanism involves two stages:
1) formation of tetrahedral intermediate
(3 steps)
2) dissociation of tetrahedral intermediate
(3 steps)
Mechanism of Fischer Esterification
The mechanism involves two stages:
1) formation of tetrahedral intermediate
(3 steps)
2) dissociation of tetrahedral intermediate
(3 steps)
OH
C
OCH3
OH
tetrahedral intermediate in esterification
of benzoic acid with methanol
First stage: formation of tetrahedral intermediate
O
COH + CH3OH
H+
OH
C
OH
OCH3
methanol adds to the
carbonyl group of the
carboxylic acid
the tetrahedral
intermediate is
analogous to a
hemiacetal
Second stage: conversion of tetrahedral
intermediate to ester
O
COCH3 + H2O
H+
this stage corresponds
to an acid-catalyzed
dehydration
OH
C
OH
OCH3
Mechanism of formation
of
tetrahedral intermediate
Step 1
CH3
••
O ••
H
H
C
•O
•
••
O ••
+
H
Step 1
CH3
••
O ••
H
O ••
+
H
C
•O
•
••
••
+O
H
CH3
H
H
C
•• O
••
•• O •
•
H
Step 1
••
•• O
H
C
+O
••
••
+O
H
H
C
•• O
••
H
carbonyl oxygen is
protonated because
cation produced is
stabilized by electron
delocalization
(resonance)
Step 2
••
+O
H
•• O •
•
C
•• O
••
CH3
H
H
Step 2
••
•• OH
+
O ••
C
•• OH
••
••
+O
CH3
H
H
•• O •
•
C
•• O
••
CH3
H
H
Step 3
••
•• OH
C
•• OH
••
+
O ••
CH3
CH3
H
•• O •
•
H
Step 3
••
•• OH
C
+
O ••
CH3
CH3
H
•• OH
••
•• O •
•
H
••
•• OH
C
•• OH
••
CH3
O ••
••
+
H O ••
CH3
H
Tetrahedral intermediate
to
ester stage
Step 4
••
•• OH
C
H
O ••
••
••
OCH3
••
Step 4
••
•• OH
C
H
O ••
••
••
OCH3
CH3
••
H
O ••
+
H
Step 4
••
•• OH
C
H
+
O
••
••
CH3
OCH3
••
•• O •
•
H
H
••
•• OH
C
H
O ••
••
••
OCH3
CH3
••
H
O ••
+
H
Step 5
••
•• OH
C
H
+
O
••
••
OCH3
••
H
Step 5
••
•• OH
••
C
H
OCH3
+
O
••
••
H
••
•• OH
+
C
+ ••
OCH3
••
••
H
O
••
H
Step 5
••
•• OH
C
+ ••
OCH3
••
••
+ OH
C
••
OCH3
••
Step 6
H
O+
••
O ••
C
••
CH3
H
••
O
••
••
OCH3
••
H
••
+O
C
••
H
OCH3
••
CH3
Key Features of Mechanism
Activation of carbonyl group by protonation of
carbonyl oxygen
Nucleophilic addition of alcohol to carbonyl group
forms tetrahedral intermediate
Elimination of water from tetrahedral intermediate
restores carbonyl group
19.15
Intramolecular Ester Formation:
Lactones
Lactones
Lactones are cyclic esters
Formed by intramolecular esterification in a
compound that contains a hydroxyl group and
a carboxylic acid function
Examples
O
HOCH2CH2CH2COH
4-hydroxybutanoic acid
O
+
O
4-butanolide
IUPAC nomenclature: replace the -oic acid
ending of the carboxylic acid by -olide
identify the oxygenated carbon by number
H2O
Examples
O
HOCH2CH2CH2COH
4-hydroxybutanoic acid
O
+
O
H2O
4-butanolide
O
HOCH2CH2CH2CH2COH
5-hydroxypentanoic acid
O + H2 O
O
5-pentanolide
Common names
b
a
O
b
g
O
g-butyrolactone
a
g
O
d
O
d-valerolactone
Ring size is designated by Greek letter
corresponding to oxygenated carbon
A g lactone has a five-membered ring
A d lactone has a six-membered ring
Lactones
Reactions designed to give hydroxy acids often
yield the corresponding lactone, especially if the
resulting ring is 5- or 6-membered.
Example
O
O
CH3CCH2CH2CH2COH
1. NaBH4
2. H2O, H+
O
O
H3C
5-hexanolide (78%)
Example
O
O
CH3CCH2CH2CH2COH
1. NaBH4
2. H2O, H+
via:
OH
O
CH3CHCH2CH2CH2COH
O
O
H3C
5-hexanolide (78%)