Amino Acid Synthesis: HVZ Method: Videos & Practice Problems

The Hell–Volhard–Zelinsky (HvZ) reaction synthesizes amino acids through a two-step process. In the first step, bromine displaces the alpha hydrogen of a carboxylic acid, forming an alpha bromo carboxylic acid using Br₂ and phosphorus tribromide as a catalyst. The second step involves amination, where ammonia attacks the alpha carbon in an SN2 reaction, replacing the bromine with an NH₂ group, resulting in an alpha amino acid. This method highlights the importance of nucleophiles and leaving groups in organic synthesis.

Amino Acid Synthesis: HVZ Method Concept 1

Amino acid synthesis can be effectively achieved through the Hell, Bohard, and Zelinsky (Hvz) method, which involves a two-step process. The first step focuses on the Hvz reaction, where a bromine atom replaces the alpha hydrogen atom of a carboxylic acid. In this reaction, the alpha carbon is crucial, as it is the carbon adjacent to the carboxyl group. The reaction utilizes bromine (Br₂) in the presence of a catalyst, phosphorus tribromide (PBr₃), to facilitate the displacement of the alpha hydrogen, resulting in the formation of alpha-bromo carboxylic acid.

In the second step, known as the amination step, ammonia (NH₃) attacks the alpha carbon through a nucleophilic substitution reaction (S_N2). This process displaces the bromine atom, leading to the formation of an alpha amino acid, characterized by the presence of the amino group (NH₂) at the alpha position. This method highlights a systematic approach to synthesizing amino acids, integrating both the Hvz reaction and subsequent amination to achieve the desired product.

Amino Acid Synthesis: HVZ Method Example 1

In this synthetic route, we begin with ethyl chloride and utilize sodium cyanide (NaCN) in a dimethyl sulfoxide (DMSO) solvent, which is aprotic. The NaCN dissociates into sodium ions (Na⁺) and cyanide ions (CN^-). The nucleophilic cyanide ion attacks the carbon atom of ethyl chloride, displacing the chlorine atom through an SN2 mechanism, resulting in the formation of a nitrile.

Next, we perform acid hydrolysis on the nitrile, converting it into a carboxylic acid. Following this, we apply bromine (Br₂) in the presence of phosphorus tribromide (PBr₃), which facilitates the Hal Bovar Zielinski reaction. This step introduces a bromine atom to the alpha carbon of the carboxylic acid.

Subsequently, we carry out amination using ammonia (NH₃) in water. This process replaces the bromine atom with an amino group (NH₂) through another SN2 reaction. The final product of this synthetic pathway is an amino acid, where the alpha carbon is bonded to an amino group, a carboxylic acid group, and a methyl group as the R group.

Since the R group is a methyl group, the resulting amino acid is identified as alanine. Therefore, the final answer is option B, which corresponds to alanine.

Predict the final product based on the list of reagents given. 

• A.
• B.
• C.
• D.

Answer: (C)

Beginning from propane, select the best reagents provided to synthesize valine via the HVZ method. 

• A.
• B.
• C.
• D.

Answer: (D)

Beginning from benzene, provide the chemical steps needed to prepare phenylalanine via HVZ method. 

• A.
• B.
• C.
• D.

Answer: (C)

Here’s what students ask on this topic:

What is the Hell–Volhard–Zelinsky (HvZ) reaction?

The Hell–Volhard–Zelinsky (HvZ) reaction is a chemical reaction used to halogenate the alpha position of carboxylic acids. In this reaction, bromine (Br₂) and phosphorus tribromide (PBr₃) are used to replace the alpha hydrogen of a carboxylic acid with a bromine atom, forming an alpha bromo carboxylic acid. This reaction is significant in organic synthesis, particularly in the synthesis of alpha amino acids when followed by an amination step.

How does the HvZ reaction contribute to amino acid synthesis?

The HvZ reaction contributes to amino acid synthesis by providing a method to introduce a bromine atom at the alpha position of a carboxylic acid. This alpha bromo carboxylic acid can then undergo an amination step, where ammonia (NH₃) attacks the alpha carbon in an SN2 reaction, replacing the bromine with an amino group (NH₂). This two-step process results in the formation of an alpha amino acid, which is a fundamental building block of proteins.

What reagents are required for the HvZ reaction?

The reagents required for the HvZ reaction are bromine (Br₂) and phosphorus tribromide (PBr₃). Bromine is used to introduce the bromine atom at the alpha position of the carboxylic acid, while phosphorus tribromide acts as a catalyst to facilitate the reaction. Together, these reagents convert the carboxylic acid into an alpha bromo carboxylic acid, which can then be further processed in amino acid synthesis.

What is the role of ammonia in the HvZ method for amino acid synthesis?

In the HvZ method for amino acid synthesis, ammonia (NH₃) plays a crucial role in the amination step. After the alpha hydrogen of the carboxylic acid is replaced by a bromine atom in the HvZ reaction, ammonia attacks the alpha carbon in an SN2 reaction. This nucleophilic substitution replaces the bromine atom with an amino group (NH₂), resulting in the formation of an alpha amino acid. This step is essential for converting the intermediate alpha bromo carboxylic acid into the desired amino acid.

What is the significance of the alpha position in the HvZ reaction?

The alpha position in the HvZ reaction is significant because it is the site where the bromine atom is introduced, replacing the alpha hydrogen of the carboxylic acid. This position is crucial for subsequent reactions, such as the amination step, where ammonia attacks the alpha carbon to form an alpha amino acid. The alpha position's reactivity is key to the success of the HvZ method in synthesizing amino acids and other important organic compounds.