Schmidt Rearrangement

Schmidt Rearrangement converts carboxylic acids, ketones, or aldehydes into amines and amides using hydrazoic acid.

• The Schmidt rearrangement is a chemical reaction involving the reaction of hydrazoic acid (HN₃) with carbonyl compounds (like carboxylic acids, ketones, or aldehydes) in the presence of acid to yield amines, amides, or nitriles, depending on the substrate.

Overview of Schmidt Rearrangement:

• The Schmidt rearrangement involves the reaction of:
• Carboxylic acids,
• Aldehydes, or
• Ketones
  • with hydrazoic acid (HN₃) in the presence of acid, leading to formation of amines, amides, or nitriles, depending on the substrate.

General Reactions:

1. Carboxylic acid + HN₃ → primary amide + N₂

   • R–COOH  +  HN₃  →  R–CONH₂  +  N₂

2. Aldehyde + HN₃ → nitrile

   • R–CHO  +  HN₃  →  R–C≡N  +  H₂O  +  N₂

3. Ketone + HN₃ → N-substituted amide

   • R1–CO–R2  +  HN₃  →  R1–CONH–R2  +  N₂

Reagents:

• • Hydrazoic acid (HN₃)
  • Strong acid catalyst: H₂SO₄ or HCl

Caution: HN₃ is highly toxic and explosive – often generated in situ.

Mechanism (Ketone as example):

• Step 1: Protonation

  • The ketone is protonated by the acid → activates carbonyl.

• Step 2: Nucleophilic Attack

  • HN₃ attacks the carbonyl carbon → forms a tetrahedral intermediate.

• Step 3: Rearrangement (1,2-Shift)

  • One alkyl/aryl group migrates from carbon to nitrogen, expelling N₂ gas and forming a nitrilium ion.

• Step 4: Hydrolysis

  • Water hydrolyzes the nitrilium ion → gives the amide.

Key Features:

• Loss of N₂ gas drives the reaction forward.
• Useful for introducing nitrogen functionality.
• Carboxylic acids → amides
• Aldehydes → nitriles
• Ketones → amides

Thank you for reading from Firsthope's notes, don't forget to check YouTube videos!