Synthesis Of Organocatalysis And The Catalytic Michael/Mannich Reaction

In recent years, due to the high efficiency and environmental friendliness, small molecule organic catalysis attracts more and more chemists’ attention. Small molecule organic catalysis has become an important means to build biologically active chiral macromolecules.To active the substrates and get the target of catalyzing asymmetric organic reactions, intermolecular hydrogen bonds were formed between(thio)urea and substrates. Small organic molecules have been widely used in catalytic asymmetric Michael addition reaction, Mannich reaction, et al. But the research on Michael and Mannich reaction catalyzed by semicarbazide was rarely reported. The main contents of this paper include the following aspects:First, we synthesized a series of semicarbazide and the secondary amine compounds. amino acids were selected as the starting material. By this method the urea derivatives was synthesized through three-step reaction. We had prepared an ester-protection of amino acid and isocyanate group via successively modifying the two functional groups of phenylalanine, to synthesize urea derivatives based on amino acid scaffold. In addition, schiff base were given by condensation reaction between diaminocyclohexane and ketone; Then the secondary amine were producted by reacting with sodium borohydride.Second, the reaction between chalcone and diethyl malonate was selected as a model. Then, we investigated the effect of the type of catalyst, the amount of catalyst, temperature, the reaction substrate ratio through a series of single factor experiments. In addition, we synthesized 20 compounds under the optimal reaction conditions.Finally, we also reported the one pot three-component Mannich reaction of aldehydes, ketones, and amines catalyzed by urea. We selected the Mannich reaction of benzaldehyde, acetophenone, and aniline as an example. The results of single factor experiments told us that only adding 20 mol% catalyst 1c, reacting in water at 40 ℃ for four hours, can the best yield of product be given. All the new products were characterized by 1H NMR, 13 C NMR, MS, etc.