Alpha Bromination of Carboxylic Acids

The a bromination of carbonyl compounds by Br2 in acetic acid is limited to aldehydes and ketones because acids, esters, and amides don t enoUze to a suf-hcient extent. Carboxylic acids, however, can be a brominated by a mixture of Br2 and PBra in the Hell-Volhard-Zelinskii (HVZ) reaction. 

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I Alpha Bromination of Carboxylic Acids The Hell-Volhard-Zelinskii Reaction... 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

Alpha-bromination of a carboxylic acid is a critical step in some laboratory syndieses of amino acids. Devise a synthesis of racemic alanine from propionic acid. 

This bromination reaction results exclusively in alpha substitution and therefore is limited to carboxylic acids with a hydrogens. Chlorine with a trace of phosphorus reacts similarily but with less overall specificity, because concurrent free-radical chlorination can occur at all positions along the chain (as in hydrocarbon halogenation see Section 4-6A). 

In the presence of a small amount of phosphorus, aliphatic carboxylic acids react smoothly with chlorine or bromine to yield a compound in which a-hydrogen has been replaced by halogen. This is the Hell-Volhard-Zelinsky reaction. Because of its specificity—only alpha halogenation-- the readiness with which it takes place, it is of considerable importance in synthesis. 

At this point, only an amino (NH2) group need be added, alpha to the carboxyl group to obtain alanine. To do this, first add a halogen, either Br or Cl, to the alpha position. This can be accomplished using the Hell-Volhard-Zelinsky reaction. This reaction results in a-halo acids. The carboxylic acid is reacted with a halogen (bromine or chlorine) in the presence of catalytic amounts of phosphorus trihalide. Hence,... 

Alpha halogenation, as described in the previous section, occurs readily with ketones and aldehydes, but not with carboxylic acids, esters, or amides. This is likely due to the fact that these functional groups are not readily converted to their corresponding enols. Nevertheless, carboxylic acids do undergo alpha halogenation when treated with bromine in the presence of PBt3. 

In the Hell-Volhard-Zelinski reaction, a carboxylic acid undergoes alpha halogenation when treated with bromine in the presence of PBrs. 

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