Historic rearrangement — isomerization
Wöhler synthesis of urea
How the Wöhler synthesis of urea works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Ammonium cyanate (from AgOCN + NH₄Cl). Conditions: Heat in water, evaporation. Bonds formed: C–N σ; N–H; bonds broken: N⁺–H (proton transfer); C=N π (as it adds). Stereochemistry: No stereocentres; planar urea. Rate and selectivity: Thermal isomerization; proceeds via NH₃ + HNCO.
At a glance
Step 1: Ammonium cyanate (ion pair)
Ammonium cyanate, an ionic salt held together by simple electrostatic attraction between NH₄⁺ and OCN⁻, is heated in aqueous solution — famously prepared in 1828 by evaporating a solution made from silver cyanate and ammonium chloride.
Step 2: Proton transfer, then N attacks C
The ammonium ion's proton transfers onto the cyanate nitrogen, and the resulting neutral species undergoes an intramolecular rearrangement — the ammonia nitrogen's lone pair attacks the adjacent, now more electrophilic cyanate carbon directly.
Step 3: Urea
The product is urea, H₂N-C(=O)-NH₂ — chemically identical in molecular formula to the starting ammonium cyanate, just constitutionally rearranged. This unplanned laboratory result, converting a simple inorganic salt into an organic compound previously found only in living organisms, is historically credited with beginning the collapse of vitalism as a scientific idea.
Abbreviations and terms
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Wöhler synthesis of urea | Payne rearrangement | Bamberger rearrangement | |
|---|---|---|---|
| Reagents | Ammonium cyanate (from AgOCN + NH₄Cl) | 2,3-Epoxy alcohol, aqueous NaOH or t-BuOK (catalytic to stoichiometric base) | N-Phenylhydroxylamine, dilute H₂SO₄ (aq) |
| Conditions | Heat in water, evaporation | H₂O/THF or t-BuOH, 0–25 °C | H₂O, 25–60 °C |
| Stereochemistry | No stereocentres; planar urea | Inversion at the attacked carbon (SN2); chirality transferred | None; para-selective |
| Rate / selectivity | Thermal isomerization; proceeds via NH₃ + HNCO | Reversible; position set by epoxide substitution; can be trapped by nucleophiles | Loss of water to give the nitrenium ion is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Wöhler synthesis of urea?
Ammonium cyanate (from AgOCN + NH₄Cl). Conditions: Heat in water, evaporation.
Which bonds are formed and which are broken?
Formed: C–N σ; N–H. Broken: N⁺–H (proton transfer); C=N π (as it adds).
What is the stereochemical outcome?
No stereocentres; planar urea
What controls the rate or the selectivity?
Thermal isomerization; proceeds via NH₃ + HNCO
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti