Synlett 2013; 24(11): 1391-1394
DOI: 10.1055/s-0033-1338701
letter
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Aqueous Krapcho Decarboxylation

Jeremy D. Mason
Department of Chemistry, Allegheny College, Meadville, PA 16335, USA   Fax: +1(814)3322789   Email: smurphre@allegheny.edu
,
S. Shaun Murphree
Department of Chemistry, Allegheny College, Meadville, PA 16335, USA   Fax: +1(814)3322789   Email: smurphre@allegheny.edu
› Author Affiliations
Further Information

Publication History

Received: 24 March 2013

Accepted after revision: 11 April 2013

Publication Date:
08 May 2013 (online)


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.

Supporting Information

 
  • References and Notes

  • 1 Krapcho AP, Glynn GA, Grenon BJ. Tetrahedron Lett. 1967; 215
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  • 11 Rathke MW, Cowan PJ. J. Org. Chem. 1985; 50: 2622
  • 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.