Hell-Volhard-Zelinsky reaction, amino acid

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. 

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. 

Chemists do not have to rely on nature to produce amino acids they can synthesize them in the laboratory, using a variety of methods. One of the oldest methods replaces an a-hydrogen of a carboxylic acid with a bromine in a Hell-Volhard-Zelinski reaction (Section 19.5). The resulting a-bromocarboxylic acid then undergoes an Sn2 reaction with ammonia to form the amino acid (Section 10.4). 

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,... 

The Hell-Volhard-Zelinsky reaction has been used to prepare the amino acid valine from 3-methylbutanoic acid by the following procedure. 

An a-bromo acid is prepared by reaction of the acid with bromine and phosphorus tribromide (this is known as the Hell-Volhard-Zelinsky reaction). This reaction was named for the work of C. Hell, Nikolai D. Zelinsky (Russia 1861-1953), and J. Volhard. If 3-phenylpropanoic acid (97) is treated with these reagents, 91 is formed. If 98 is subsequently heated with ammonia (see Section 27.1.1) and the product is neutralized, amino acid 57 is formed (phenylalanine). This route was used as early as 1858, when glycine (52) was prepared by the reaction of chloroacetic acid (99) and ammonia. Amino acids formed this way are racemic. 

Identify the reagents necessary to make each of the following amino acids using a Hell-Volhard-Zelinski 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. 

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