Chemistry Reference
In-Depth Information
Cyclic esters (
lactones
) are formed when the
carboxyl and hydroxyl groups are in the same
molecule, and are most favoured when this results
in the generation of strain-free five- or six-membered
rings. Thus, 4-hydroxybutyric acid may form a five-
membered
β
α
γ
β
α
H
+
4
5
HOCH
2
CH
2
CH
2
CO
2
H
3
1
γ
2
O
2
4
4-hydroxybutyric acid
γ-hydroxybutyric acid
3
1
O
2-oxacyclopentanone
γ
-lactone
-lactone,
its name coming from the alternative nomenclature
γ
lactone,
which
is
termed
a
γ
β
-hydroxybutyric
acid
for
the
acyclic
compound.
γ
γ
5
Similarly,
-
lactones. It is generally easier to use the fully
systematic -oxa- nomenclature (see Section 1.4) for
the oxygen heterocycle in more complex lactones.
This approach considers nomenclature as if we had a
carbocyclic ring, and uses an -oxa- syllable to indicate
replacement of a carbon with the oxygen heteroatom.
Lactonization, like esterification, is an equilibrium
process.
six-membered
lactones
are
termed
δ
H
+
α
δ
β
α
4
6
HOCH
2
CH
2
CH
2
CH
2
CO
2
H
5
1
3
2
δ
2
4
5-hydroxypentanoic acid
3
1
O O
2-oxacyclohexanone
δ
-lactone
though other substituents, if they are present, also
affect the equilibrium proportions.
Larger lactones do not exist to any appreciable
extent in equilibrium with the free hydroxy acids, but
they may be prepared under appropriate conditions.
These may include removal of water to disturb the
equilibrium, and carrying out the reaction at quite
high dilutions in order to minimize intermolecular
esterification.
-lactones are so readily
formed that the carboxylic acid itself can provide
the required acidic catalyst, and substantial amounts
of the lactone are typically present in solutions of
4- or 5-hydroxy acids respectively (Table 7.3). Inter-
estingly, the proportion of lactone is usually higher
for five-membered rings than for six-membered rings,
γ
-Lactones and
δ
Table 7.3
Hydroxyacid-lactone equilibria
Hydroxyacid
Lactone
Ring size
Equilibrium composition (%)
Hydroxyacid
Lactone
CO
2
H
O
HO
4
100
0
O
HO
CO
2
H
5
27
73
O
O
CO
2
H
HO
6
91
9
O
O
HO
CO
2
H
7
100
0
O
O
Box 7.14
Large ring lactones: erythromycin and amphotericin
Very large ring lactones are called
macrolides
, and are found in the natural
macrolide antibiotics
. Typically,
these may have 12-, 14-, or 16-membered lactone rings, though other sizes are encountered.
Erythromycin
is a
