The Study On Reaction Of N-Alkylation Aromatization And Synthesis Of Antidepressants

Part1:Synthesis of 2,3-dihydro-1H-pyrrolizin-1-one derivativesThe structure of 2,3-dihydro-1H-pyrrolizin-l-one was first found in pyrrolizidine alkaloids, which have physiological activities such as anti-tumor, anti-inflammatory, antipyretic and analgesic and so on. In this paper, the N-alkylation aromatization of P-phenyl acetone with trans-4-hydroxy-L-proline has been developed to prepare 2,3-dihydro-1H-pyrrolizin-1-one derivatives at one step, under condition of acetic acid as solvent and 4A molecular sieves as a dehydrating agent. The raw materials are cheap and readily available with high atom utilization. Operation is simple and no "three wastes" generated. This new method of synthesis of 2,3-dihydro-1H-pyrrolizin-1-one derivatives is suitable for industrial production.Part2:Synthesis of candidate compounds of antidepressantWe tried to synthesize candidate compounds of antidepressant through One-Pot cascade reaction catalyzed by organocatalysts. It was synthesized by using 2-fluorophenylacetic acid as the starting material, via nitration to form 2-(2-fluoro-5-nitrophenyl)acetic acid, followed to synthesize of 1-(2-fluoro-5-nitrophenyl)propan-2-one by the Dakin-West reaction, and then got 1-bromo-l-(2-fluoro-5-nitrophenyl)-propan-2-one by bromination. But in the end, the construction of chiral carbon ring with cinnamaldehyde did not react because of lower activity.Then we considered to construct indole ring first followed by building the carbon ring, using 1-(2-fluoro-5-nitrophenyl)propan-2-one reacted with benzaldehyde to form 3-(2-fluoro-5-nitrophenyl)-4-phenylbut-3-en-2-one, and then constructing indole ring by reductive amination-SNAr cascade reaction with isobutylamine. But it did not react due to the lower activity.