Study On Highly Ortho-selective Chlorination Of Anilines Using Organocatalyst

Halogenated anilines are important organic compounds,which are widely used in medicine,pesticides,natural products and dyes,etc.,and can also be used as key intermediates to construct complex molecules.Therefore,it is very important to develop highly selective ortho-halogenation methods for aniline compounds.In this study,with diisopropylamine as catalyst and sulfonyl chloride as chlorine source,the synthesis of ortho chlorinated anilines was achieved under mild conditions with high selectivity.The scheme is environmentally friendly,low cost,mild conditions,easy to operate,the substrate functional group tolerance and regional selectivity is good,the reaction can be scaled up to gram scale.In addition,the scheme can be used for highly selective chlorination of pharmaceutical or biologically active molecules.Therefore,the ortho-halogenation method developed in this study has potential applications in large-scale production and drug development.In the first chapter,the research progress of halogenation reaction at home and abroad is discussed.The ortho-chlorination schemes,such as electrophilic substitution,ortho-lithium,transition metal catalysis,chlorination oxide and organic small molecule catalysis,have been developed successively,and progress has been made in the field of organic synthesis.Through comparison,it can be found that the scheme of organic small molecule catalysis has the advantages of no heavy metal participation,environmental friendliness,cheap and easy to obtain catalyst,simple operation,mild reaction conditions and so on,which has a huge space for improvement.The optimization of ortho-chlorination reaction conditions is discussed in the chapter 2.The optimum reaction conditions of ortho-chlorination were determined by investigating catalyst,chlorine source,temperature,concentration and solvent.The results show that the reactions of N-acyl,N-sulfonyl,N-OAc and N-Cbz protected aniline substrates with different substituents can be carried out smoothly,indicating that the organic o-chlorinated substrates are easy to be expanded.The scale-up study of the reaction shows the feasibility of large-scale production in industry by scaling up to gram scale.The ortho-chlorination scheme of organic catalysis has potential application value in the practical application of drug molecules and bioactive molecules.The reaction mechanism of chlorination reaction was preliminarily explored.The third chapter of this paper discusses the experimental operation and experimental data representation.The fourth chapter of this paper summarizes and prospects,including the understanding of the subject and further research direction.