β-Ketoacids are Easily Decarboxylated
CO2 from the carboxyl group of an acid.
Decarboxylation is the loss of ____
Most carboxylic acids are quite resistant to moderate heat. Exceptions
are carboxylic acids that have a carbonyl group __
β to the carbonyl.
These carboxylic acids are derived from Claisen condensations
(following ester hydrolysis).
O
O
warm
O
+
H
CO2
O
3-oxobutanoic acid
keto-enol
tautomerization
O
H
O
O
a cyclic 6-membered TS≠
O
O
H
+
C
O
Alkylation of β-Dicarboxylic Esters
(Malonic Ester Synthesis)
Other synthetic plans take advantage of the ease at which decarboxylation
occurs when a carbonyl group is in the β position relative to the carboxylic
acid. Here is a general synthetic route to carboxylic acids.
O
O
O
1) CH3CH2O (deprotonation)
O
O
malonic ester
2) R–Br (alkylation)
3) H / H2O / heat (hydrolysis
& decarboxylation)
RCH2 COH
heat
–CO2
O
1)
O
HO
O
O
O
O
OH
R
O
2)
O
O
O
R
hydrolysis
Alkylation of β-Ketoesters
(Acetoacetic Ester Synthesis)
Here is a general synthetic route to methyl ketones.
O
O
O
1) EtO Na
OEt 2)
acetoacetic ester
O
OEt
Br
3) NaOH / H2O
4) HCl / H2O
O
The product of
acetoacetic ester
synthesis is a
substituted acetone.
O
+
CO2
heat
O
OH