Silica Sulfuric Acid: An Efficient,Reusable, Heterogeneous Catalyst for the One-Pot,Five-Component Synthesis of Highly Functionalized Piperidine Derivatives

A series of highly functionalized piperidine derivatives was synthesized through one-pot, five-component reaction of aldehydes, amines, and β-ketoesters. Silica sulfuric acid efficiently catalyzes the reaction to afford the corresponding piperidine derivatives in good yields. As a representative example, heating of 4-methylaninle, 4-fluorobezaldehyde, and methyl-acetoacetate in methanol in the presence of silica sulfuric acid furnished the corresponding ethyl 2,6-bis(4-fluorophenyl)-1-p-tolyl-4-(p-tolylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate in excellent yield (85%). Most of the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Most of compounds showed significant antibacterial activity.