Schmidt reaction template

In concentrated H₂SO₄, HN₃ adds to the protonated ketone; loss of water gives an iminodiazonium ion, and the group anti to N₂⁺ migrates to nitrogen as N₂ leaves. Water traps the nitrilium ion and tautomerisation gives the amide. Carboxylic acids react the same way to give amines with loss of CO₂.

Mechanism step by step

Hydrazoic acid inserts NH next to a carbonyl: ketone → amide, acid → amine

1. Protonation – The acid activates the carbonyl
2. HN₃ adds – Azide N attacks C (HN₃ drawn as H–N⁻–N⁺≡N)
3. Dehydration – Acid-catalysed loss of water: the iminodiazonium ion
4. Migration – The phenyl anti to N₂⁺ moves to N as N₂ leaves
5. Water adds – Attack on the nitrilium carbon
6. Tautomerisation – Proton transfers give the amide
7. Carboxylic acids – Acylium ion + HN₃, R migrates (isocyanate), water: the amine and CO₂

Key points

• The group anti to the N₂⁺ leaving group migrates (as in the Beckmann rearrangement); for aryl alkyl ketones that is usually the aryl group.
• Cyclic ketones give lactams (cyclohexanone → ε-caprolactam), the same products as the Beckmann route.
• RCOOH → RNH₂ + CO₂ in one pot, with retention at a migrating stereocentre (compare Curtius and Hofmann).
• HN₃ is made in situ from NaN₃ and H₂SO₄; it is very toxic and explosive.

Drawn with 181 atoms, 17 arrows, 11 shapes – every one editable in MolDraw.

Sources

• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005, Schmidt reaction Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 18 Textbook