Preparation of 5-Cyano-4,6-dimethyl-2H-pyran-2-one and 3-Cyano-5-methoxy-4-methyl-5H-furan-2-one via a One-Pot, Domino-Knoevenagel Process

Abstract

5-Cyano-4,6-dimethyl-2H-pyran-2-one (1) has been prepared via a simple one-pot domino-Knoevenagel reaction starting from ethyl acetoacetate (2) and cyanoacetone (3). Similarly, a new racemic 3-cyano-5-methoxy-4-methyl-5H-furan-2-one (7) has been prepared from 1,1-dimethoxyacetone (6) and cyanoacetic acid (4). The new alkylidene derivatives (Z/E)-ethyl-4-cyano-3-methylbut-3-enoate (5), (Z/E)-ethyl 5-amino-4-cyano-3-methyl-5-oxopent-3-enoate (9), and (2,2-dimethoxy-1-methylethylidene)malononitrile (11) have been prepared via the Knoevenagel reactions. The easy access to these new compounds in good yields shows that ammonium acetate/acetic acid–catalyzed Knoevenagel reactions and domino-Knoevenagel reactions have a broad scope of application.

Keywords:

• (2,2-Dimethoxy-1-methylethylidene)malononitrile
• (Z/E)-ethyl 5-amino-4-cyano-3-methyl-5-oxopent-3-enoate
• (Z/E)-ethyl 4-cyano-3-methylbut-3-enoate
• NMR spectroscopy

ACKNOWLEDGMENTS

This work was supported by grants from Volkswagen Stiftung (I/79979). We are very thankful to Dr. W. Gaertner (Max Planck-Institute for Bioinorganic Chemistry, Muelheim, Germany) for his valuable suggestion. The authors thank C. Erkelens and F. Lefeber for recording the NMR spectra and H. Peeters (Free University of Amsterdam, The Netherlands) for recording the mass spectra.