The Application Of Metal-free Claisen-Schmidt Condensation And Photocatalytic Dehalogenation In The Synthesis Of Pharmaceutical Intermediates

?,?-unsaturated ketone structure unit is a type of important pharmacophores that exists in many products widely,which is a significant basic skeleton of chalcone ketones compound.Synthesis of a,?-unsaturated ketone is of potential application value for drug research and development.Claisen-Schmidt condensation reaction is one of the main methods of synthesising a,?-unsaturated ketones,but alkali and acid catalysts are used in present technologies,which is not applicable for the substrate containing acid or alkali sensitive groups.Moreover,both acid and Alkalien are likely to cause corrosion of industrial equipment.Therefore,developing a mild,general method for the synthesis of a,?-unsaturated ketones is of important application value in industrial production.On the other hand,recently,photocatalytic organic synthesis has aroused the interests of scientists greatly.Using the inexhaustible solar energy as energy source to replace the traditional high temperature condition,clean and environmental protection is an important direction of the future industrial development.This method is also expected to be applied in pharmaceutical field.However,the present photocatalysis employs metal catalysts,which are not only expensive,but also may cause metal residue.Therefore,developing the matel-free photocatalyst and applying it into the field of pharmaceutical synthesis are of profound meanings.The main results and conclusions in this paper are summarized as following three parts:1.Synthesis of a series of a,?-unsaturated ketone compounds through Claisen-Schmidt condensation,using L-proline as catalyst,secondary amine as addtive,and ethanol as the green solvent.In addition,the structure of the compounds was identified by NMR,IR and mass spectrometry.Compared with existing methods,this method is mild which can be used for the synthesis of substrates with the groups ensitive to acid or base.It has also been applied in the Knoevenagel condensation reaction,to prepare a series of ?,?-unsaturated nitrile compounds.2.Developing a polymer-supported proline catalyst and applying it into claisen-schmidt to synthesize a series of ?,?-unsaturated ketones compounds.This method could generally improve the product yields.Meanwhile,because the polymer catalyst can be recycled for at least 10 times without deactivation,this method is more suitable to be applied in industrial application.3.Designing and synthesising new carbazole organic molecular photosensitizers.Compared with traditional metal pyridine complex photocatalyst,this kind of catalyst has more advantages such as low price stability,easy synthesis,easy operation and modification.Besides,this catalyst has very good photocatalytic activity,which can be used to take off functional groups(such as dehalogenation,decarboxylation reaction),and be further applied in carbon-hydrogen bond activation(reaction)to form carbon-carbon bonds.We successfully used this kind of photosensitizer to photocatalyze synthesis a series of pyrrole compounds.In addition,the correctness of the structure of the compound was identified by NMR,IR.