Microwave-Assisted Aqueous Krapcho Decarboxylation

Abstract

The Krapcho decarboxylation of alkyl malonate derivatives has been adapted to aqueous microwave conditions. Various salt additives were examined, and both the cation and the anion impacted the facility of the reaction. A strong correlation was found between the pKa of the anion and the reaction rate, suggesting a straightforward base-catalyzed hydrolysis. Lithium sulfate gave the best results, obviating the need for DMSO co-solvent.

Key words

cleavage - esters - hydrolysis - lithium - solvent effects

• References and Notes

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• 12 Experimental Procedure: To a 2–5 mL microwave vial were added the diethyl alkyl malonate (1.5 mmol), lithium sulfate (166 mg, 1.5 mmol), and deionized H₂O (3.0 mL). The vial was sealed and heated at 210 °C for 30 min (see ref. 13) after which the contents were poured into sat. NaHCO₃ (10 mL) and extracted with EtOAc (2 × 15 mL). The combined organic phases were washed sequentially with NaHCO₃ (15 mL) and brine (15 mL), dried over Na₂SO₄, and concentrated in vacuo to yield a crude oil, which was purified by column chromatography.
• 13 Since carbon dioxide is liberated during the reaction, 3–4 atm of residual pressure remains after the vial is cooled. The manufacturer’s instructions for releasing this pressure should be carefully followed before opening the vial for aqueous workup.