Heterocycle synthesis — carbazole via naphthol
Bucherer carbazole synthesis
How the Bucherer carbazole synthesis 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: 2-Naphthol, phenylhydrazine, NaHSO₃ (aq). Conditions: Aqueous bisulfite, 100–150 °C; acid work-up. Bonds formed: C=N (hydrazone); C–C (aryl–C, [3,3]); C–N (ring); aromatic pyrrole; bonds broken: C–OH (via keto form); N–N; C–NH₂; C–SO₃H. Stereochemistry: None (planar aromatic product). Rate and selectivity: [3,3]-shift (Fischer-type) is rate-limiting; loss of NH₃ and bisulfite drives it.
At a glance
Step 1: Keto tautomer, bisulfite adduct, hydrazone
2-Naphthol is in tiny equilibrium with its keto tautomer, and bisulfite adds to it, just as in the standalone Bucherer reaction, giving 2-tetralone-4-sulfonate. The carbonyl then condenses with an arylhydrazine (here phenylhydrazine) to form a hydrazone.
Step 2: Ene-hydrazine and [3,3]-sigmatropic shift
The hydrazone tautomerises to an ene-hydrazine, which undergoes a [3,3]-sigmatropic shift exactly as in the Fischer indole synthesis: a new C–C bond forms to the ortho carbon of the aryl ring while the weak N–N bond breaks. (Drawn on a simplified model; R is the rest of the tetralone ring.)
Step 3: Close the pyrrole ring, lose NH₃, aromatise
The aniline nitrogen re-aromatises its ring, attacks the neighbouring imine carbon and loses NH₃ to close the pyrrole ring. Elimination of bisulfite then re-aromatises the old naphthalene ring, delivering the fully aromatic carbazole (7H-benzo[c]carbazole).
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Bucherer carbazole synthesis | Bischler indole synthesis | Bischler-Napieralski reaction | |
|---|---|---|---|
| Reagents | 2-Naphthol, phenylhydrazine, NaHSO₃ (aq) | Aniline (excess), α-haloketone (PhCOCH₂Br) | β-Arylethylamide, POCl₃ (or P₂O₅, Tf₂O) |
| Conditions | Aqueous bisulfite, 100–150 °C; acid work-up | Step 1: 25–80 °C; step 2: acid (or aniline·HBr), 150–200 °C | Toluene or MeCN, reflux |
| Stereochemistry | None (planar aromatic product) | None | Product is a 3,4-dihydroisoquinoline; none created |
| Rate / selectivity | [3,3]-shift (Fischer-type) is rate-limiting; loss of NH₃ and bisulfite drives it | Cyclisation (high T) is slow; SN2 alkylation is fast | Nitrilium formation then SEAr; electron-rich arenes react best |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Bucherer carbazole synthesis?
2-Naphthol, phenylhydrazine, NaHSO₃ (aq). Conditions: Aqueous bisulfite, 100–150 °C; acid work-up.
Which bonds are formed and which are broken?
Formed: C=N (hydrazone); C–C (aryl–C, [3,3]); C–N (ring); aromatic pyrrole. Broken: C–OH (via keto form); N–N; C–NH₂; C–SO₃H.
What is the stereochemical outcome?
None (planar aromatic product)
What controls the rate or the selectivity?
[3,3]-shift (Fischer-type) is rate-limiting; loss of NH₃ and bisulfite drives it
Study guides that help with this reaction
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go
- How to answer mechanism questions in an exam