acetoacetic ester synthesis
/ ASS-eh-toh-ah-SEE-tik /
The acetoacetic ester synthesis is the malonic ester synthesis's twin, but it builds substituted ketones instead of substituted acids. The starting scaffold is ethyl acetoacetate, CH3-CO-CH2-CO2Et, a beta-keto ester whose central CH2 sits between a ketone and an ester. Just as with malonic ester, those two flanking carbonyls make the central proton very acidic (pKa ~11), so a mild base cleanly forms a stabilized enolate.
The play runs the same three acts. First, deprotonate and alkylate the central carbon with an alkyl halide via SN2, attaching an R group (once, or twice for a disubstituted product). Second, hydrolyze the ester to a beta-keto acid. Third, heat: a beta-keto acid decarboxylates readily — the carbonyl beta to the carboxyl lets CO2 slip away — and you are left with a substituted methyl ketone, CH3-CO-CH2-R. The ester end was, once again, only a temporary handle to make the enolate easy, then it was removed.
The difference from malonic ester is just which carbonyl survives. Malonic ester keeps a carboxylic acid (the product is R-CH2-COOH); acetoacetic ester keeps a ketone (the product is CH3-CO-CH2-R, a substituted acetone). Both exploit the same trick: a doubly-activated, easily-formed enolate for the C-C bond-forming alkylation, followed by hydrolysis and decarboxylation to trim away the helper. Knowing both, you can target either a substituted acid or a substituted methyl ketone at will.
To make pentan-2-one, CH3-CO-CH2-CH2-CH3: deprotonate ethyl acetoacetate with NaOEt, alkylate with ethyl bromide, hydrolyze the ester, then heat to decarboxylate. The surviving methyl ketone is the product.
Same three steps as malonic ester, but the product is a substituted methyl ketone.
The product is always a methyl ketone, CH3-CO-CH2-R, because the acetyl (CH3-CO-) group of the starting ester is retained while the ester end is decarboxylated away. The synthesis cannot make ketones that lack that CH3-CO- piece.