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SolutionsAldol condensation: importance and mechanism

Exercise 1

Which products can form when a mixture of propanal and butanal is treated with aqueous NaOH? How would you selectively prepare the product in which butanal provides the enolate and propanal the carbonyl?

Four aldols (and their dehydration products): the two self-condensation products (propanal + propanal and butanal + butanal) and the two crossed ones, depending on which acts as the nucleophile. To obtain only the desired crossed product, the butanal enolate must be preformed quantitatively (LDA, THF, −78 °C) and propanal added afterwards; at that temperature addition is faster than proton exchange. In practice, with aldehydes, more stable enolate equivalents are often used, such as silyl enol ethers (Mukaiyama reaction) or metalated imines.

Exercise 2

Diacetone alcohol decomposes into acetone when heated with a base. Explain this fact and why, by contrast, the condensation of butanal with hot NaOH gives 2-ethylhex-2-enal in good yield.

The aldol addition is reversible. With ketones the equilibrium lies towards the reactants (the aldol is a hindered tertiary alcohol), and the base catalyses the retro-aldol reaction. With aldehydes the addition equilibrium is more favourable and, above all, the aldol has an α hydrogen and dehydrates on heating (E1cB) to the conjugated aldehyde, practically irreversibly, which pulls the equilibrium.

Exercise 3

Propose a synthesis of (E)-4-phenylbut-3-en-2-one (benzylideneacetone) and explain why the reaction is clean even though it is carried out under equilibrium conditions.

Claisen–Schmidt condensation: benzaldehyde with excess acetone and aqueous-ethanolic NaOH. Benzaldehyde has no α hydrogens and can act only as the electrophile, and it is more electrophilic than acetone, so the acetone enolate attacks the aldehyde preferentially. Dehydration to the system conjugated with the ring drives the equilibrium; the excess of acetone prevents the second condensation, which would give dibenzylideneacetone. The more stable E isomer is formed.