19.16
a-Halogenation of Carboxylic Acids:
The Hell-Volhard-Zelinsky Reaction

analogous to a-halogenation of aldehydes and
ketones
key question: Is enol content of carboxylic
acids high enough to permit reaction to occur
at reasonable rate? (Answer is NO)
a-Halogenation of Carboxylic Acids
+ X2
+ HX
R2CCOH
O
H
R2CCOH
O
X

reaction works well if a small amount of
phosphorus or a phosphorus trihalide is added to
the reaction mixture
this combination is called the Hell-Volhard-
Zelinsky reaction
But...
+ X2
+ HX
R2CCOH
O
H
R2CCOH
O
X
P or PX3

Example
CH2COH
O
PCl3 benzene
80°C
CHCOH
O
Br
(60-62%)
+ Br2

Value
CH3CH2CH2COH
O
Br2
P
CH3CH2CHCOH
O
Br
(77%)
a-Halogen can be replaced by nucleophilic
substitution

Value
CH3CH2CH2COH
O
Br2
P
CH3CH2CHCOH
O
Br
CH3CH2CHCOH
O
OH
(77%)
(69%)
K2CO3
H2O
heat

Synthesis of a-Amino Acids
(CH3)2CHCH2COH
O
Br2
PCl3
(CH3)2CHCHCOH
O
Br
(CH3)2CHCHCOH
O
NH2
(88%)
(48%)
NH3
H2O

19.17
Decarboxylation of Malonic Acid
and Related Compounds

Decarboxylation of Carboxylic Acids
Simple carboxylic acids do not decarboxylate
readily.
RH + CO2
RCOH
O

Decarboxylation of Carboxylic Acids
Simple carboxylic acids do not decarboxylate
readily.
But malonic acid does.
RH + CO2
RCOH
O
150°C
CH3COH
O
+ CO2
HOCCH2COH
O O

Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other.
O O
OH
HO
H H
O
HO O
O
H H
H

Mechanism of Decarboxylation of Malonic Acid
This compound is
the enol form of
acetic acid.
O O
OH
HO
H H
H
H
OH
HO
O
HO O
O
H H
H
+ C
O
O
One carboxyl group assists the loss of the other.

Mechanism of Decarboxylation of Malonic Acid
O O
OH
HO
H H
H
H
OH
HO
O
HO O
O
H H
H
+ C
O
O
One carboxyl group assists the loss of the other.
HOCCH3
O

Mechanism of Decarboxylation of Malonic Acid
O O
OH
HO
H H
H
H
OH
HO
O
HO O
O
H H
H
+ C
O
O
One carboxyl group assists the loss of the other.
HOCCH3
O
These hydrogens play no role.

Mechanism of Decarboxylation of Malonic Acid
O O
OH
HO
R R'
R
R'
OH
HO
O
HO O
O
R R'
H
+ C
O
O
One carboxyl group assists the loss of the other.
HOCCHR'
O
Groups other than H may be present.
R

185°C
Decarboxylation is a general reaction
for 1,3-dicarboxylic acids
160°C
CO2H
CO2H
CO2H
H
(74%)
(96-99%)
CH(CO2H)2 CH2CO2H

Mechanism of Decarboxylation of Malonic Acid
O O
OH
HO
R R'
R
R'
OH
HO
O
HO O
O
R R'
H
+ C
O
O
One carboxyl group assists the loss of the other.
This OH group plays no role.
HOCCHR'
O
R

Mechanism of Decarboxylation of Malonic Acid
O O
OH
R"
R R'
R
C
O
O
One carboxyl group assists the loss of the other.
Groups other than OH may be present.
R"CCHR'
O
R
O
O
O
R R'
H
R"
R'
OH
+
R"

Mechanism of Decarboxylation of Malonic Acid
O O
OH
R"
R R'
This kind of compound
is called a b-keto acid.
a
b
R"CCHR'
O
R
Decarboxylation of a
b-keto acid gives a
ketone.

Decarboxylation of a b-Keto Acid
C
CH3C
O
CH3
CH3
CO2H
25°C
CO2
C
CH3C
O
CH3
CH3
H
+