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.