Synergetic Study On Mannich Reaction Of Three Components

Three types of effective cooperative catalyst systems were designed and prepared. They are multifunctional organocatalysts, homogeneous and heterogeneous binary acid systems of Br(?)nsted acid and Lewis acid. They all showed high catalytic acitivity in three-component Mannich reactions. The corresponding catalytic mechanisms were proposed by NMR, IR, SEM, XPS and XRD analyses. At the same time, the synergistic effect between catalytic active sites in the catalytic systems was validated by controlled experiments indirectly. In addition, the active intermediates of catalytic systems were acquired to support the corresponding catalytic mechanism strongly. The main contents are included as follows:(1) A water-soluble Br(?)nsted acid,5-sulfo salicylic acid, efficiently catalyzed the direct three-component Mannich reactions of cyclohexanone and 3-pentanone in pure water.5-sulfosalicylic acid as catalyst had many characteristics, such as a wide range of applicability, highly effective reactivity, decent diastereoselectivity and good recycled. 21 Examples of Mannich reactions were presented, which afforded the corresponding β-amino ketones with up to 97% yield. The acid catalyst can be recycled as an aqueous solution for at least six times and the yield of the Mannich product remained over 90%.(2) A new binary acid system featuring an air-stable organometallic precusor, titanocene dichloride and simple Bransted acid/base compound, was developed. The new catalyst system allowed for mild and highly efficient direct three-component Mannich reactions of both aryl ketones and alkyl ketones, particularly acetone and its derivatives with excellent yields. The catalytic system reflected the higher reactivity than other catalytic systems with 65%-96% yields. The intermediates derived from Cp2TiCl2 and p-aminophenol were observed by 1H NMR experiments. The results supported the dramatic synergistic effect of the new binary acid system.(3) A new heterogeneous cooperative catalysis system featuring the synergistic effect of organometallic Lewis acid and Br(?)nsted acid supporter was also developed. The binary catalysis system successfully catalyzed the direct three-component Mannich reaction of both aromatic and aliphatic ketones to form various β-amino ketones in 67～97% yields. Besides, the catalyst can be recycled for at least five times and the yield of the Mannich product remains over 90%. SEM, XRD, FT-IR, XPS analyses of heterogeneous catalysis system elucidate that the poly((o-aminophenol)-supported Cp2TiCl2 is the key catalytic species, which strongly supported a dual activation pathway.