Carboxylic acid Hell-Volhard-Zelinskii reaction

Reacts with carboxylic acids in the presence of PBr3 to yield a-bromo carboxylic acids (Hell-Volhard-Zelinskii reaction Section 22.4). 

By application of the Hell-Volhard-Zelinskii reaction,an a-hydrogen of a carboxylic acid 1 can be replaced by bromine or chlorine to give an a-bromo-or a-chlorocarboxylic acid 2 respectively. 

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

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins with reaction of the carboxylic acid with PBr3 to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an cr-substitution reaction to give an cv-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the a-bromo carboxylic acid product. 

Amino acids can also be prepared by a two-step sequence that involves Hell— Volhard-Zelinskii reaction of a carboxylic acid followed by treatment with ammonia. Show how you would prepare leucine, (C bCHCl-HClKNPfylCC H, and identify the mechanism of the second step. 

Hell-Volhard-Zelinskii reaction (Section 22.4) the a-bromination of a carboxylic acid by treatment with bromine and phosphorus tribromide. 

The first step in the Hell-Volhard-Zelinskii reaction takes place bet PBra and a carboxylic acid to yield an intermediate acid bromide plus] (Section 21.4). The HBr thus formed catalyzes enolization of the acid I mide, and the resultant enol reacts rapidly with Brg in an a-substittttif reaction. Addition of water results in hydrolysis of the a-bromo acid 1 mide (a nucleophilic acyl substitution reaction) and gives the n-bromo< boxylic acid product. 

Hell-Volhard-Zelinskii reaction The reaction in which a carboxylic acid is treated with Br2 and PBr3 (often formed in situ from red phosphorus and bromine) to give the a-bromocarboxylic acid bromide. 

We have already encountered an important synthesis of amino acids in the sequence of Figure 22.18—a Hell-Volhard-Zelinskii reaction followed by amination of the a-halo acid. There is no multiple substitution of the ammonia because the electron-withdrawing effect of the carboxylic acid makes the amine less nucleophilic. Also, as soon as it is formed, the acid converts to the zwitterionic form. An alternative process uses the Gabriel phthalimide synthesis (Figure 22.19). 

Hell-Volhard-Zelinskii (HVZ) reaction (Section 22.4) The reaction of a carboxylic acid with Br2 and phosphorus to give an -bromo carboxylic acid. 

Carbonyl compounds are in a rapid equilibrium with their cnols, a process called keto-enol tautomerism. Although enol tautomers arc normally present to only a small extent at equilibrium and can t usually be isolated in pure form, they nevertheless contain a highly nucleophilic double bond and react with electrophiles. P or example, aldehydes and ketones are rapidly halogenated at the a position by reaction with CI2 Br2, or I2 in acetic acid solution. Alpha bromination of carboxylic acids can be similarly accomplished by the Hell-Volhard-Zelinskii (HVZ) reaction, in which an acid is treated with Bt2 and PBrThe a--halogenated inoducts can then undergo base-induced E2 elimination to yield a,/3-un.salurated carbonyl compounds. 

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