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Catalytic Asymmetric Henry and Aza-Henry Reaction
Author: WeiYu
Tutor: HeZuo
School: Fourth Military Medical University
Course: Pharmaceutical Analysis
Keywords: Henry Reaction Aza-Henry reaction Schiff base ligands Copper Complexes Phase transfer catalyst Cinchona alkaloid
CLC: O643.32
Type: Master's thesis
Year: 2011
Downloads: 55
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Abstract
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The catalytic asymmetric reaction is an economical and efficient method of synthesis of chiral drugs and chiral drug intermediates. Catalytic Asymmetric Henry and Aza-Henry reaction is one of the two important methods to build a new carbon-carbon bond. They are the product of a chiral β-nitro-alcohol β-denitration amine compound can be provided according to the synthesis of needs, be easily converted to the corresponding chiral aldehydes, ketones, carboxylic acids, α-amino alcohols, α-amino acids, alpha, beta-two monoamines such as a series of the synthesis of organic intermediates. The topics for these two types of catalytic asymmetric reactions were carried out in-depth study. The catalyst used in catalytic asymmetric synthesis metal complex catalysts and Organocatalyst two categories, they are in a variety of catalytic asymmetric reaction has a very wide range of applications. \Mainly include the following: 1. Cinchona alkaloid derivatives and hydroxy substituted benzaldehyde synthesis of novel chiral Schiff base ligand with Cu (OAc) 2 ligand investigated the catalytic aldehyde with saltpeter alkane asymmetric Henry reaction. The results show that under optimum reaction conditions in the screened out 75a of Cu (II) / Schiff base complexes could efficiently catalyze various aldehyde substrates include aromatic, isobutyl aromatic and aliphatic aldehydes and nitromethane (or nitro ethane) asymmetric Henry reaction and get up to 99% enantioselectivity, 75:25 stereoselectivity, and 84% yield. This reaction, we have done a preliminary study of the mechanism of a variety of methods by single-crystal X-diffraction, NMR and infrared spectroscopy confirmed the structural characterization of the catalyst and the corresponding ligand coordination mode, and the possible catalytic The transition state a reasonable estimate. 2, with the synthesis of cinchona alkaloid with 2 - (chloromethyl) benzimidazole or 1 - (chloromethyl) benzotriazole 10 kinds of the corresponding quaternary ammonium salt catalyst. These 10 kinds of quaternary ammonium salt phase transfer catalyst is used for catalytic benzene sulfinic acid group-substituted amino compound 90a-u and the asymmetric aza-Henry reaction of nitroalkanes. Experimental results show that the phase transfer catalyst 82a in the aqueous phase under the reaction conditions, it is possible to efficiently catalyze a variety of asymmetric reactions of the aroma, isobutyl aromatic and aliphatic substituents imine up to 94% chemical yield, 99% ee The optical yield. When the amount of catalyst is reduced to 2 mol%, the enantioselectivity of the product yet see reduced. When the extended the nitroalkane substrate by nitromethane nitroethane, still obtain a chemical yield of 78%, greater than 99:1 stereoselectivity and the enantioselectivity 99% ee. The study results show that: we designed and synthesized these two types of cinchona alkaloid derived chiral catalyst energy efficient, high enantioselective catalytic asymmetric Henry and aza-Henry reaction. Two reaction reactant, catalyst synthesis is simple, low cost, low consumption, the product of a very important practical value. The subject for the development of catalytic asymmetric the Henry and aza-Hnery, reaction provides practical catalytic system has broad application prospects.
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CLC: > Mathematical sciences and chemical > Chemistry > Physical Chemistry ( theoretical chemistry ),chemical physics > Chemical kinetics,catalysis > Catalytic > Catalytic reaction
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