Halogenation of Carboxylic Acids The Hell-Volhard-Zelinsky Reaction

Reactions that are expected to produce hydroxy acids often yield the derived lactones instead if a five- or six-membered ring can be formed. 

SAMPLE SOLUTION (a) The ring oxygen of the lactone is derived from the hydroxyl group of the hydroxy acid, whereas the carbonyl group corresponds to that of the carboxyl function. To identify the hydroxy acid, disconnect the O—C(0) bond of the ester. 

Lactones whose rings are three or four membered (a-lactones and (3-lactones) are very reactive, making their isolation difficult. Special methods are normally required for the laboratory synthesis of small-ring lactones as well as those that contain rings larger than six membered. 

16 a HALOGENATION OF CARBOXYLIC ACIDS THE HELL-VOLHARD-ZELINSKY REACTION 

Esterification of carboxylic acids involves nucleophilic addition to the carbonyl group as a key step. In this respect the carbonyl group of a carboxylic acid resembles that of an aldehyde or a ketone. Do carboxylic acids resemble aldehydes and ketones in other ways Do they, for example, form enols, and can they be halogenated at their a-carbon atom via an enol in the way that aldehydes and ketones can  

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Halogenation of the a-Carbon of Carboxylic Acids The Hell-Volhard-Zelinski Reaction... 

Halogenation of the a-carbon of carboxylic acids the Hell-Volhard-Zelinski reaction (Section 19.5). 

The conversion of an aliphatic carboxylic acid into the a-bromo- (or a-chloro ) acid by treatment with bromine (or chlorine) in the presence of a catal3rtic amount of phosphorus tribromide (or trichloride) or of red phosphorus is known as the Hell-Volhard-Zelinsky reaction. The procedure probably involves the intermediate formation of the acyl halide, since it is known that halogens react more rapidly with acyl haUdes than with the acids themselves ... 

Section 19.16 Halogenation at the a-carbon atom of carboxylic acids can be accomplished by the Hell-Volhard-Zelinsky reaction. An acid is treated with chlorine or bromine in the presence of a catalytic quantity of phosphorus or a phosphorus trihalide ... 

Nucleophilic substitution by ammonia on a-halo acids (Section 19.16) The a-halo acids obtained by halogenation of carboxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reactive substrates in nucleophilic substitution processes. A standard method for the preparation of a-amino acids is displacement of halide from a-halo acids by nucleophilic substitution using excess aqueous ammonia. 

Reversing the order of steps is not appropriate. It must be the carboxylic acid that is subjected to halogenation because the Hell-Volhard-Zelinsky reaction is a reaction of carboxylic acids, not esters. 

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,... 

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

Carboxylic acids cannot undergo substitution reactions at the a-carbon, because a base will remove a proton from the OH group instead of from the a-carbon, since the OH group is more acidic. If, however, a carboxylic acid is treated with PBr3 and Bt2, the a-carbon can be brominated. This halogenation reaction is called the Hell-Volhard-Zelinski reaction or, more simply, the HVZ reaction. (Red phosphoms can be used in place of PBr3 since P and excess Br2 react to form PBr3.)... 

Because the enol content of carboxylic acids is much lower than that of aldehydes and ketones, carboxylic acids do not react with halogens to give a-halo carboxylic acids. However, bromination does occur in the presence of a catalytic amount of PBt3. The reaction also occurs in the presence of a small amount of phosphorus, which reacts with bromine to generate PBr3 under the reaction conditions. Either variation of the method is called the Hell—Volhard—Zelinsky reaction. 

The oldest method of synthesizing a-amino acids is nucleophihc substitution of the halogen of an a-halocarboxylic acid by ammonia. The a-halocarboxylic acid is prepared by treating a carboxylic acid with Br and PBr. This reaction, which we considered earlier, is named after its inventors, the Hell-Volhard-Zelinsky reaction. It produces a carboxylic acid with a bromine atom at the a position. The a-bromo compound reacts with ammonia by an Sj 2 mechanism to give an a-amino acid. 

Hell-Volhard-Zelinsky reaction (Section 19.16) The phosphorus trihalide-catalyzed a halogenation of a carboxylic acid ... 

Carboxylic acids having an a-hydrogen are halogenated at the a-position on treatment with chlorine or bromine in the presence of small amount of red phosphorus to give a-halocarboxylic acids. The reaction is known as Hell-Volhard-Zelinsky reaction. 

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