SolutionsThe Knoevenagel reaction
Exercise 1
Which product is obtained from the condensation of cyclohexanone with ethyl cyanoacetate catalysed by ammonium acetate and acetic acid? Why is no strong base needed?
Ethyl 2-cyano-2-cyclohexylideneacetate. Cyanoacetate is rather acidic (pKa ≈ 11 in water), and the amine is enough to form a sufficient concentration of its anion; at the same time, the amine converts the ketone into an iminium ion, which is more electrophilic. The final dehydration, favoured by conjugation with the two electron-withdrawing groups, drives the equilibrium.
Exercise 2
Propose a synthesis of (E)-cinnamic acid from benzaldehyde by a Knoevenagel condensation.
Benzaldehyde and malonic acid in pyridine with a little piperidine, on heating (Doebner modification): after condensation, benzylidenemalonic acid decarboxylates spontaneously to give (E)-cinnamic acid. Alternatively, condense with diethyl malonate and then hydrolyse and decarboxylate.