THE CONCEPT
'Hofmann Hops' — the R group hops from C to N, and the carbonyl carbon leaves
RCONH₂ + Br₂ + 4 NaOH → RNH₂ + Na₂CO₃ + 2 NaBr + 2 H₂O. Picture the R group hopping off the carbonyl carbon onto the nitrogen. Once it hops, that old carbonyl carbon is stranded as an isocyanate (R–N=C=O), and water plus base strip it away as CO₂ (carbonate). Count carbons: the product always has ONE FEWER carbon than the amide you started with.
1
N-Bromination
Hydroxide removes an N–H proton from the primary amide, and the resulting anion attacks Br₂ to give an N-bromoamide (RCONHBr).
2
Second deprotonation
The remaining N–H of the N-bromoamide is now more acidic; hydroxide removes it to form the N-bromoamide anion.
3
Rearrangement to isocyanate
The R group migrates from carbon to nitrogen as bromide leaves, producing an isocyanate, R–N=C=O. The migration happens with RETENTION of configuration at the migrating carbon.
Textbooks sometimes draw this through a nitrene; either way, the key intermediate you must recognize is the isocyanate.
4
Hydrolysis and loss of CO₂
Water adds to the isocyanate to give a carbamic acid (RNHCOOH), which decarboxylates to the primary amine RNH₂; under the basic conditions the CO₂ ends up as carbonate.
🧪 Lab Application
You need benzylamine (PhCH₂NH₂) and have phenylacetamide (PhCH₂CONH₂) available. Show how the Hofmann rearrangement gets you there.
STEP 1
Count carbons — benzylamine has 7 carbons; phenylacetamide has 8 — exactly one extra carbon, the carbonyl carbon, so a Hofmann rearrangement fits.
STEP 2
Choose reagents — treat phenylacetamide with Br₂ and aqueous NaOH (then warm).
STEP 3
Follow the intermediates — N-bromoamide → anion → benzyl group migrates to N → benzyl isocyanate (PhCH₂N=C=O) → carbamic acid → loses CO₂.
CONCLUDE
The product is benzylamine, PhCH₂NH₂ — a clean primary amine with no over-alkylation, which is a big advantage over making amines by SN2 alkylation of ammonia.
📌 Exam Application
Exams test three things: recognizing the reagents (Br₂/NaOH on a primary amide), predicting a product one carbon shorter, and identifying the isocyanate intermediate. Watch for stereochemistry questions — a chiral migrating carbon keeps its configuration.
⚠️ Most Common Hofmann Rearrangement Mistakes
Don't confuse the Hofmann REARRANGEMENT (amide → amine, lose one carbon) with Hofmann ELIMINATION (quaternary ammonium hydroxide + heat → least-substituted alkene). Also note the Curtius rearrangement reaches the same isocyanate from an acyl azide and heat.
✓ Quick Self-Test
1) What reagents perform a Hofmann rearrangement? 2) How many carbons does the product lose, and which carbon is it? 3) What is the key intermediate? 4) What happens to the configuration of the migrating carbon? 5) How does this reaction differ from Hofmann elimination?