A concise and versatile synthesis of 2-amino-3-cyanopyridine derivatives in 2,2,2-trifluoroethanol

Trifluoroethanol (TFE) is found to be an efficient and recyclable medium in promoting one-pot, four-component coupling reactions of aldehydes, ketones, malononitrile, and ammonium acetate to afford the corresponding 2-amino-3-cyanopyridine derivatives in high yields. The solvent (TFE) can be readily separated from reaction products and recovered in excellent purity for direct reuse.

Graphical abstract2-Amino-3-cyanopyridine derivatives were synthesized in excellent yield in 2,2,2-trifluoroethanol.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► In this study we examine the TFE as a new recyclable medium. ► 2-Amino-3-cyanopyridine were synthesized in trifluoroethanol. ► This method has the ability to tolerate a wide variety of substitutions. ► TFE was easily recovered.