Arndt–Eistert homologation and Wolff rearrangement template

Diazomethane acylates on carbon; a second equivalent removes the proton (and ends up as CH₃Cl and N₂), giving the α-diazoketone. Silver(I), heat or light then triggers the Wolff rearrangement: N₂ leaves as the phenyl group moves to the neighbouring carbon, giving a ketene that water traps as phenylacetic acid.

Mechanism step by step

Acid chloride → diazoketone → ketene → acid with one more CH₂

1. Acylation – Diazomethane carbon attacks the acid chloride
2. Chloride leaves – The tetrahedral intermediate collapses
3. Deprotonation – A second CH₂N₂ removes the acidic α-H: the diazoketone
4. HCl is scavenged – Chloride displaces N₂ (SN2), so no chloromethyl ketone forms
5. Wolff rearrangement – N₂ leaves as phenyl shifts (Ag₂O, heat or hν): a ketene
6. Water adds – Attack on the ketene C=O carbon
7. Tautomerisation – Proton transfers give the homologated acid

Key points

• RCOOH → RCH₂COOH: one CH₂ is added (via RCOCl); an alcohol or amine instead of water gives the ester or amide.
• The migrating group keeps its configuration, so α-amino acids give β-amino acids.
• Two equivalents of CH₂N₂ (or Et₃N, Newman–Beal) are needed; otherwise HCl gives the chloromethyl ketone.
• Diazomethane is toxic and explosive; TMS-diazomethane is the safer substitute. Cyclic diazoketones undergo Wolff ring contraction.

Drawn with 166 atoms, 22 arrows, 12 shapes – every one editable in MolDraw.

Sources

• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005, Arndt–Eistert homologation; Wolff rearrangement Textbook
• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 38 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 18 Textbook