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.
Zhuang
Bo-Ren
BR
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan, ROC.
Hsu
Gien-Jow
GJ
Sung
Kuangsen
K
D000097:Acetonitriles / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D005561:Formates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000097:Acetonitriles; D000588:Amines; D002219:Carbamates; D005561:Formates; D012997:Solvents; C056431:5-cyanouracil; D014498:Uracil; C032159:acetonitrile