Kiliani–Fischer synthesis template

Cyanide adds to the aldehyde of D-arabinose and protonation gives the cyanohydrins, epimeric at the new C2; hydrolysis to the aldonic acids, lactonisation and Na(Hg) reduction of the lactones give the two aldohexoses D-glucose and D-mannose, which differ only at C2.

Mechanism step by step

An aldose gains one carbon at C1 through a cyanohydrin: D-arabinose gives D-glucose and D-mannose

1. Cyanide adds – CN⁻ attacks C1 from either face: two configurations at the new stereocentre
2. Protonation – HCN protonates the alkoxide: the cyanohydrins (gluco drawn; the manno epimer forms too)
3. Hydrolysis – Hot water hydrolyses the nitrile to the aldonic acid, D-gluconic acid (summarised)
4. Lactone – The acid closes to the γ-lactone (1,4-lactone), which can be separated from its epimer (summarised)
5. Reduction – Sodium amalgam in weak acid reduces the lactone to the aldose: D-glucose (D-mannose from the other epimer; summarised)

Key points

• The chain grows at C1: the old C1 becomes C2, a new stereocentre, so two C2 epimers form (usually not 1 : 1).
• The old stereocentres are untouched, so a D-aldopentose gives two D-aldohexoses: D-arabinose → D-glucose + D-mannose.
• Fischer used this route to relate the aldoses; the improved version reduces the nitriles directly to imines (H₂, Pd/BaSO₄), which hydrolyse to the aldoses.
• The reverse, removing C1, is the Ruff (or Wohl) degradation.

Drawn with 171 atoms, 10 arrows, 10 shapes – every one editable in MolDraw.

Sources

• Wade, Organic Chemistry, 8th ed., Pearson 2013, ch. 23 Textbook