Hel-Volhard-Zelinski (HVZ) Reaction

Overview

• Purpose: Alpha substitution of a carboxylic acid.
• Key Reagents:
  • Bromine (Br₂)
  • Phosphorus tribromide (PBr₃)
  • Water (H₂O)
• Key Concept: Substitution of a bromine at the alpha position replacing the hydrogen.

Reaction Steps

Step 1: Formation of Acyl Bromide

• Reagents: Carboxylic acid + PBr₃
• Process:
  • PBr₃ converts carboxylic acid to acyl bromide by replacing OH with Br.
  • The reaction involves acid-catalyzed tautomerization from keto to enol form.

Step 2: Bromination

• Reagents: Acyl bromide enol + Br₂
• Mechanism:
  • Induced dipole on Br₂ allows pi electrons to attack as a nucleophile.
  • Formation of a bromide anion, resulting in an alpha-bromo acyl bromide.
  • Loss of HBr, forming alpha-bromo acyl bromide.

Step 3: Hydrolysis

• Reagents: Alpha-bromo acyl bromide + H₂O
• Mechanism:
  • Water acts as a nucleophile, attacking the electrophilic carbon.
  • Replacement of bromine with OH, resulting in the formation of a carboxylic acid with a bromine at the alpha position.
  • Loss of HBr.

Applications

• Synthesis of Amino Acids:
  • Example: Conversion of propanoic acid to alanine.
  • Process:
    • HVZ reaction creates alpha-bromo carboxylic acid.
    • Use of ammonia to substitute the bromine with an amino group.
    • SN2 mechanism where ammonia acts as a nucleophile.
  • Stereochemistry: Formation of a chiral center, yielding a mixture of enantiomers.

Key Points

• HVZ reaction is useful for substituting the alpha position of carboxylic acids.
• Can be leveraged to synthesize amino acids by following up with ammonia.
• Reaction involves various mechanistic steps, such as tautomerization, nucleophilic attack, and proton transfers.