1. 19.16 a-Halogenation of Carboxylic Acids: The Hell-Volhard-Zelinsky Reaction

2. a-Halogenation of Carboxylic Acids
R2CCOH O H
R2CCOH O X + X2 + HX
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) 22

3. this combination is called the Hell-Volhard- Zelinsky reaction
But...
R2CCOH O H
R2CCOH O X
P or PX3 + X2 + HX
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 23

4. Example
CH2COH O +
Br2
PCl3
benzene 80°C
CHCOH O Br
(60-62%) 24

5. a-Halogen can be replaced by nucleophilic substitution
Value
CH3CH2CH2COH O
CH3CH2CHCOH O Br
Br2 P
(77%)
a-Halogen can be replaced by nucleophilic substitution 25

6. Value CH3CH2CH2COH O CH3CH2CHCOH O Br Br2 P (77%) K2CO3 H2O heat
(69%) 25

7. Synthesis of a-Amino Acids
(CH3)2CHCHCOH O Br
Br2
(CH3)2CHCH2COH
PCl3
(88%)
NH3 H2O
(CH3)2CHCHCOH O
NH2
(48%) 25

8. 19.17 Decarboxylation of Malonic Acid and Related Compounds

9. Decarboxylation of Carboxylic Acids
Simple carboxylic acids do not decarboxylate readily.
RCOH O RH +
CO2 28

10. Decarboxylation of Carboxylic Acids
Simple carboxylic acids do not decarboxylate readily.
RCOH O RH +
CO2
But malonic acid does.
HOCCH2COH O
CH3COH O
150°C +
CO2 28

11. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO H O HO H 29

12. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO H O HO H C O H OH HO
This compound is the enol form of acetic acid. + 29

13. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO H O HO H
HOCCH3 O C O H OH HO + 29

14. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO H O HO H
These hydrogens play no role.
HOCCH3 O C O H OH HO + 29

15. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO R R' O HO R R' H
Groups other than H may be present.
HOCCHR' O C O R R' OH HO + R 29

16. Decarboxylation is a general reaction for 1,3-dicarboxylic acids
CO2H
CO2H
185°C H
(74%)
CH(CO2H)2
160°C
CH2CO2H
(96-99%) 30

17. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH HO R R' O HO R R' H
This OH group plays no role. C O
HOCCHR' O R R R' OH HO + 29

18. Mechanism of Decarboxylation of Malonic Acid
One carboxyl group assists the loss of the other. O OH
R" R R' O R R' H
R"
Groups other than OH may be present.
R"CCHR' O R C O R' OH +
R" R 29

19. Mechanism of Decarboxylation of Malonic AcidOH
R" R R' a
This kind of compound is called a b-keto acid. b
R"CCHR' O R
Decarboxylation of a b-keto acid gives a ketone. 29

20. Decarboxylation of a b-Keto Acid
CH3C O
CH3
CO2H C
CH3C O
CH3 H
25°C +
CO2 32