Pictet-Spengler Condensation Reactions Catalyzed By A Recyclable H~+-montmorillonite As A Heterogeneous Brφnsted Acid

A series of metal cation-exchanged montmorillonite and H+-montmorillonite catalysts have been prepared by its intrinsic cation-exchangeable property in the interlayer, using Na-montmorillonite as the initial material. The catalytic activities of the synthesized montmorillonite-based acid catalysts on the Pictet-Spengler reaction ofβ-phenylethylamine and benzaldehyde have been investigated under the condition of solvent-free or in water. The results showed that the best reaction yield can be obtained usingβ-phenylethylamines and benzaldehyde (1:1.2) as the substrates at 120℃under solvent-free conditions for 18h with H+-montmorillonite as the catalyst.Under the optimum reaction conditions, a number of tetrahydroisoquinoline alkaloid derivatives with extensive biological activities have been synthesized by this protocol. The scope and limitation of the condensation reaction of P-phenylethylamines and benzaldehydes have been investigated. H+-mont is effective for the Pictet-Spengler cyclization reaction ofβ-arylethyl-amines with various aldehydes. The higher yield was obtained with electron-rich aryl ethylamine as a substrate rather than electron neutral phenylethylamine. Phenylethylamine carbamates, which were expected to form reactive iminium ion intermediates, were found to be good substrates. In addition, aliphatic aldehydes also gave the corresponding tetrahydro-isoquinolines with better yields.The H+-montmorillonite-catalyzed Pictet-Spengler reaction of tryptamine derivatives with aldehydes in water have been investigated in this paper. An efficient and clean synthetic method of tetrahydroisoquinolines have been developed. Condensation of tryptamine derivatives with aromatic aldehydes bearing the electron-donating group furnished cyclized products in moderate yields. Aryl aldehydes having either electron-neutral or electron-withdrawing groups successfully underwent the Pictet-Spengler reaction in good yields. Aliphatic aldehydes also gave the corresponding tetrahydrocarbolines in moderate to good yields.Finally, the reusability of the H+-montmotillonite catalyst used in the free-solvent Pictet-Spengler reaction were tested. The study exhibited that the H+-montmotillonite can be recycled up to five times with maintenance of high catalytic activity (the yield is 86%).