Bromination Hell-Volhard-Zelinsky

Chloroacetic acid is readily converted into glycine by treatment with concentrated aqueous ammonia solution, but in general an a-bromocarboxylic acid is preferred. This can usually be prepared in good yield by a Hell-Volhard-Zelinsky bromination (Section 5.14.1, p. 720) of the corresponding carboxylic acid if the carboxylic acid is not readily available it can usually be obtained by the synthesis and bromination of the appropriate alkylmalonic, acid (see Expt 5.166). 

Two variants of the Hell-Volhard-Zelinsky brominations are commonly conducted. According to the first procedure, carboxylic acids A are reacted with one equivalent of bromine and a catalytic amount of phosphorus tribromide to form oc-bromocarboxylic acids (Formula B... 

The mechanism in Figure 12.7 implies that the stoichiometric use of phosphorus tribromide in the second variant of the Hell-Volhard-Zelinsky bromination leads to the selective formation of the a-bromocarboxylic acid bromide (Formula B in Figure 12.8). Often these compounds are hydrolyzed to give the bromocarboxylic acids C. More importantly, a-bromocarboxylic acid bromides B can also undergo alcoholysis and in this way provide access to a-brominated esters D. 

Bromoacetic acid can be prepared by the bromination of acetic acid in the presence of acetic anhydride and a trace of pyridine (55), by the Hell-Volhard-Zelinsky bromination catalyzed by phosphorus, and by direct bromination of acetic acid at high temperatures or with hydrogen chloride as catalyst. Other methods of preparation include treatment of chloroacetic acid with hydrobromic acid at elevated temperatures (56), oxidation of ethylene bromide with fuming nitric acid, hydrolysis of dibromovinyl ether, and air oxidation of bromoacetylene in ethanol. 

Hell-Volhard-Zelinsky Bromination Followed by Amination (Section 26-2)... 

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 ... 

This method of a bromination of carboxylic acids is called the Hell-Volhard-Zelinsky reaction This reaction is sometimes carried out by using a small amount of phosphorus instead of phosphorus trichloride Phosphorus reacts with bromine to yield phosphorus tribromide as the active catalyst under these conditions... 

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 ... 

Although in the present case the amount of phosphorus used is small, equivalent amounts are often employed, particularly for the introduction of bromine, the acid bromide being produced and then substituted in the a-position. As a result, the reaction product is the bromide of the a-brominated acid which must be treated with water to convert it into the latter. Esters of the acid are often prepared from the acid bromide by the action of alcohols. (Hell-Volhard-Zelinsky process.)... 

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. 

Alternatively, bromoacetic acid could be converted to the corresponding acyl chloride, then treated with ethanol. It would be incorrect to try to brominate ethyl acetate the Hell-Volhard-Zelinsky method requires an acid as starting material, not an ester. 

To convert 3-methylbutanoic acid to valine, a leaving group must be introduced at the a carbon prior to displacement by ammonia. This is best accomplished by bromination under the conditions of the Hell-Volhard-Zelinsky reaction. 

The reaction of aliphatic carboxylic acids with bromine in the presence of phosphorous produces a halo acids. This reaction is the Hell-Volhard-Zelinski reaction. 

According to Figure 12.6, the bromination of alkylated malonic acids A initially furnishes oc-brominated alkyl malonic acids B. Upon heating they decarboxylate to form the a-bromo-carboxylic acids C. This two-step approach to C can be managed without using the expensive phosphorus tribromide, which would be required in the alternative single-step Hell-Volhard-Zelinsky synthesis of this compound (Figures 12.7, 12.8). 

Fig. 12.7. Bromination of carboxylic acids in the presence of catalytic amounts of phosphorus tribromide ("Hell-Volhard-Zelinsky reaction I") the reaction product is an a-bromocarboxylic acid.

Fig. 12.8. Bromination of carboxylic acids in the presence of stoichiometric amounts of phosphorus tribromide ("Hell-Volhard-Zelinsky reaction II"). The actual reaction product is an a-bromocarboxylic acid bromide (B), which often undergoes further in situ reaction to afford an a-bromocarboxylic acid (C) or an a-bromocarboxylic acid ester (D).

The bromine is introduced onto the a-carbon by treating the carboxylic acid with Br2 and a catalytic amount of PBr, in a process known as the Hell-Volhard-Zelinsky reaction. This reaction proceeds through an enol intermediate. Because carboxylic acids form enols only with difficulty, a catalytic amount of PBr3 is added to form a small amount of the acyl bromide, which enolizes more readily than the acid. Addition of bromine to the enol produces an a-bromoacyl bromide (see Section 20.2). This reacts with a molecule of the carboxylic acid in a process that exchanges the Br and OH groups to form the... 

The Hell-Volhard-Zelinsky (HVZ) reaction replaces a hydrogen atom with a bromine atom on the a carbon of a carboxylic acid. The carboxylic acid is treated with bromine and phosphorus tribromide, followed by water to hydrolyze the intermediate a-bromo acyl bromide. 

The Hell-Volhard-Zelinsky reaction (Section 22-6) is an effective method for introducing bromine at the a position of a carboxylic acid. The racemic a-bromo acid is converted to a racemic a-amino acid by direct amination, using a large excess of ammonia. 

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. 

Hell-Volhard-Zelinsky reaction. e-Benzoylaminocaproic acid is converted into the a-bromo derivative by stirring a mixture of the acid with red phosphorus in a flask cooled in an ice bath, adding bromine dropwise, gradually increasing the temperature, and stirring on the steam bath until practical disappearance of bromine... 

The bromination of aliphatic carbonic adds, which is not only of great importance in preparation work, but also as a means for determining constitution, is also conducted with the addition of red phosphorus (Hell-Volhard-Zelinsky Method).1... 

COBrj is reported to be a catalyst for the cu-bromination of saturated carboxylic acids, in a modified Hell-Volhard-Zelinsky reaction [e.g. 1320b]. Thus, treatment of octadecanoic acid with bromine in the presence of catalytic amounts of COBrj gave a 99.5% yield of 2-bromooctadecanoic acid [2029]. 

Carboxylic acids can be brominated at the a-position by reaction with bromine and phosphorus tribromide (PBr3) in the Hell-Volhard-Zelinsky reaction. The reaction, which proceeds via an acid bromide, leads to the substitution of an a-hydrogen atom by a bromine atom. 

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