Amino Acid Synthesis: HVZ Method - Online Tutor, Practice Problems & Exam Prep

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

Hey, everyone. So in this video, we're going to talk about amino acid synthesis using the Hvz method. Now Hvz stands for the Hell, Volhard, Zelinsky reaction. We've seen this in previous chapters. Now, in order to make the amino acid, we're going to have this reaction plus amination.

Now, this process takes place in 2 steps. We're going to say step 1 deals with the Hvz reaction. And in it, we're going to say that a bromine atom displaces the alpha hydrogen atom of a carboxylic acid. So here we have our alpha carbon and here's our alpha hydrogen. We're going to utilize Br₂ over our catalyst in the form of phosphorus tribromide.

This would displace the alpha hydrogen with the bromine creating an alpha-bromo carboxylic acid. Then we would say that in step 2, the amination step, ammonia attacks the alpha carbon in an SN2 reaction. This would kick out the Br and leave us with an NH₂ here. And we can see this as being an alpha amino acid. So again, this is just one way we can synthesize an amino acid, part of it dealing with the reaction we saw previously in the form of the Halvor Zielinski reaction.

Amino Acid Synthesis: HVZ Method Example 1

Hey, everyone. So here in this reaction, it says, identify the amino acid formed from the following synthetic route. So here we're starting out with our ethyl chloride molecule and in the first step we're doing NaCN over DMSO, which is our aprotic solvent. Now, here we're going to say that NaCN is really Na⁺ and CN^-. The CN^- would attack this carbon, kicking out the chlorine by an SN2 mechanism.

This is going to give us a nitrile now. Now remember, under acid hydrolysis, we can change a nitrile into a carboxylic acid. Then we say, okay, we have a carboxylic acid, and we're going to use Br₂ with our catalyst in the form of Phosphorus Tribromide. Remember, this is the Hal Bovar Zielinski reaction. So we're going to add a bromine to the alpha carbon.

So here goes our Br. And then we follow with amination, which is just NH₃ over water. This would replace the bromine by an SN2 reaction, and we get NH₂ here at the end. This would create this amino acid as our final product. And remember, our amino acids here, our alpha carbon is here, and our R-group is this methyl group.

Remember, when your R-group is a methyl group, that means our amino acid is alanine. So here, the answer would be option B.

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

• A.
• B.
• C.
• D.

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

• A.
• B.
• C.
• D.

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

• A.
• B.
• C.
• D.

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.