Heterocyclic
Advanced
Skraup quinoline synthesis mechanism: aniline and glycerol
Question
Aniline is heated with glycerol, concentrated H₂SO₄, nitrobenzene and FeSO₄. Draw the complete Skraup mechanism, including dehydration of glycerol to acrolein, conjugate addition, ring closure and dehydration to 1,2-dihydroquinoline, and the final oxidation to quinoline. State which steps are reversible, what drives the sequence, and the role of FeSO₄ and nitrobenzene.
Question images
Expert answer
Glycerol → acrolein (⇌): acid-catalysed dehydration through 3-hydroxypropanal. Conc. H₂SO₄ removes the water and pushes it forward.
Conjugate addition (⇌): aniline adds to acrolein, and tautomerisation gives the β-aminoaldehyde.
Ring closure (⇌): the protonated aldehyde is attacked by the ortho carbon, a 6-endo-trig electrophilic aromatic substitution.
Rearomatisation and dehydration (→): loss of H⁺, then loss of water, gives 1,2-dihydroquinoline.
Oxidation (→): PhNO₂ is reduced to PhNO via proposed radical pathways, and aromatisation drives the step. In hot acid the product is the quinolinium salt until work-up.
FeSO₄: it moderates an otherwise violent reaction.