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

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

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

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

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

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

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

19.17 Decarboxylation of Malonic Acid and Related Compounds

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

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

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

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

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

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

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

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

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

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

Mechanism of Decarboxylation of Malonic Acid OH 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

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