A multi-component reaction to 5-cyanouracils: Synthesis and mechanistic study

Acetonitrile as a solvent, excess of primary amines as general bases, and a reflux condition make the multi-component reactions of (2-cyanoacetyl) carbamate 1, ethyl orthoformate, and primary amines form 5-cyanouracils 4a-c feasibly. Mechanistic studies of the multi-component reaction were carried out by proton NMR spectrometer. Acetonitrile as a solvent makes the reaction of 1 with ethyl orthoformate produce E-ethyl (2-cyano-3-ethoxyacryloyl) carbamate E-2 without a catalyst of acetic anhydride. The reactions of E-2 with primary amines produce the corresponding Z-3a-c as the only stable isomers eventually in CDCl3 or CD3CN. General-base-catalyzed intramolecular cyclizations of Z-3a-c at a reflux condition in CD3CN generated the corresponding 5-cyanouracils 4a-c. (c) 2006 Elsevier Ltd. All rights reserved.