General Synthesis of Hantzsch Esters in 2,2,2-Trifluoroethanol

Significance

Reported is the standard three-component Hantzsch synthesis of 1,4-dihydropyridines (acetoacetate ester, ammonium acetate and aldehyde) under new conditions - in 2,2,2-trifluoroethanol (TFE) . The reaction proceeds rapidly at 70 ˚C to afford the 1,4-dihydropyridines in very good yields (÷95%). The reaction shows broad scope for aldehydes (aliphatic, aromatic, hetero­aromatic and α,β-unsaturated). An unsymmetrical Hantzsch reaction (cyclic 1,3-diketone, aldehyde, acetoacetate and ammonium acetate) was also realized under the same conditions to afford polyhydroquinolines in good to excellent yields. Further, the synthesis of two 1,8-dioxodecahydro-acridines starting from cyclic 1,3-diketone and ­aromatic aldehydes was described.