What is Hell Volhard Zelinsky Reaction?

What is Hell Volhard Zelinsky Reaction?

The Hell-Volhard-Zelinsky (HVZ) reaction is a chemical reaction named after the German chemists Jacob Volhard, Carl Magnus von Hell, and Nikolay Zelinsky. It is a halogenation reaction that involves the conversion of a carboxylic acid into an α-halogenated carboxylic acid using a halogen, typically bromine or chlorine.

The HVZ reaction was first discovered by Jacob Volhard in 1873, who found that when a carboxylic acid is treated with bromine in the presence of red phosphorus, the α-halogenated carboxylic acid is formed. However, it was later improved by Carl Magnus von Hell and Nikolay Zelinsky, who added a catalytic amount of water to regenerate the red phosphorus catalyst.

The general reaction scheme for the HVZ reaction is as follows:

1. Formation of the α-haloacid: A carboxylic acid (R-COOH) reacts with a halogen (X2), usually bromine (Br2), in the presence of a catalytic amount of red phosphorus (P) and a small amount of water (H2O). This leads to the formation of the corresponding α-haloacid (R-CO-X) and phosphorus acid (H3PO3) as a byproduct.

2. Rearrangement: The α-haloacid undergoes rearrangement in the presence of a base, typically aqueous sodium hydroxide (NaOH) or potassium hydroxide (KOH), to give the final product, which is an α-hydroxyacid (R-CO-OH).

 

Let's now dive deeper into each step of the reaction and explore the mechanisms involved.

Step 1: Formation of the α-haloacid The first step of the HVZ reaction involves the formation of the α-haloacid. The carboxylic acid reacts with the halogen (bromine or chlorine) in the presence of red phosphorus and water.

The reaction proceeds through a free radical mechanism. Red phosphorus serves as a catalyst by generating halogen radicals (Br• or Cl•) from the halogen. This is achieved by the reaction between red phosphorus and the halogen:

P4 + 6X2 → 4PX3

The halogen radicals then abstract a hydrogen atom from the carboxylic acid to form a carboxylic acid radical and a hydrogen halide (H-X):

R-COOH + X• → R-COO• + H-X

The carboxylic acid radical then reacts with the halogen to form the α-haloacid:

R-COO• + X2 → R-CO-X + X•

Simultaneously, the halogen radicals formed in the previous step are regenerated by reacting with water:

X• + H2O → HX + HO•

Overall, this step results in the conversion of the carboxylic acid into the α-haloacid and the formation of phosphorus acid as a byproduct.

 

Step 2: Rearrangement The second step of the HVZ reaction involves the rearrangement of the α-haloacid to give the final product, which is the α-hydroxy acid. This step typically occurs in the presence of a base, such as aqueous sodium hydroxide or potassium hydroxide.

The base deprotonates the α-haloacid to form the carboxylate anion:

R-CO-X + OH- → R-CO-O- + X-

The carboxylate anion then undergoes rearrangement via a nucleophilic acyl substitution mechanism. The nucleophilic oxygen attacks the electrophilic carbon of the carbonyl group, leading to the migration of the halogen atom to the carbonyl carbon and the formation of an acyl-oxygen bond:

R-CO-O- + R'-C=O → R-CO-C=O + R'-OH

The resulting intermediate is an acyl-oxygen-bonded species. Hydrolysis of this intermediate by the hydroxide ion results in the formation of the α-hydroxy acid:

R-CO-C=O + OH- → R-CO-OH

The α-hydroxy acid is the final product of the HVZ reaction.

The Hell-Volhard-Zelinsky reaction has found broad applications in organic synthesis. The selective introduction of a halogen atom at the α-position of a carboxylic acid allows for the subsequent functionalization and synthesis of various organic compounds. The α-haloacids obtained from the HVZ reaction can serve as versatile intermediates for the synthesis of a wide range of organic compounds, including pharmaceuticals, natural products, and materials.

 

In summary, the Hell-Volhard-Zelinsky (HVZ) reaction is a halogenation reaction that involves the conversion of a carboxylic acid into an α-halogenated carboxylic acid. The reaction proceeds through two steps: the formation of the α-haloacid and the rearrangement to yield the α-hydroxyacid. The reaction relies on the use of a halogen (typically bromine or chlorine), red phosphorus as a catalyst, and a small amount of water. The HVZ reaction has found significant applications in organic synthesis, providing a useful method for introducing halogens into carboxylic acids and facilitating further chemical transformations.

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