SolutionsMalonic and acetoacetic syntheses
Exercise 1
Propose a synthesis of 2-methylpentanoic acid from diethyl malonate, and one of 2-hexanone from ethyl acetoacetate.
2-Methylpentanoic acid: diethyl malonate + NaOEt + 1-bromopropane; again NaOEt + CH3I; then hot H3O+ (hydrolysis and decarboxylation). 2-Hexanone: ethyl acetoacetate + NaOEt + 1-bromopropane; then hydrolysis with acid or dilute base and heat (ketonic cleavage), which loses CO2 and EtOH.
Exercise 2
Which product is obtained by treating diethyl malonate with 2 eq. of NaOEt and 1,3-dibromopropane, and then with hot H3O+?
The first alkylation introduces the 3-bromopropyl chain; the second deprotonation and intramolecular alkylation close a four-membered ring: diethyl cyclobutane-1,1-dicarboxylate. Hydrolysis and decarboxylation give cyclobutanecarboxylic acid.
Exercise 3
Why do substituted malonic acids and β-keto acids decarboxylate on heating, whereas simple carboxylic acids do not?
Because they have a second carbonyl in the β position that accepts the carboxyl proton in a six-membered cyclic transition state: the C–C bond breaks, CO2 leaves and an enol forms, which tautomerizes. A simple acid lacks that carbonyl, and the carbanion that would have to form would not be stabilized.