The Study Of Bobbitt's Salt In Cross-dehydrogenative Coupling Reaction And In The Preparation Of Tranexamic Acid

C-C bond forming reaction is one of the most important branches in organic synthetic chemistry,which can build lots of complex molecules from simple precursors efficiently.Among the vast C-H activation strategies,cross dehydrogenative coupling(CDC)reaction offers an elegant pathway for the efficient,cost-effective and atom-economical construction of new C-C bonds,because it does not require tedious prior functionalization of both coupling partners,avoiding unnecessary downstream processing and waste.From the viewpoint of academic and industrial research,CDC reaction has the advantages of being atom-economical and environmental benignity that meet the criteria of sustainable chemistry.Recent decades,a number of CDC reactions at sp3 C-H bonds adjacent to tertiary amines have been developed,because nitrogen heterocycles,especially tetrahydroisoquinoline(THIQ)and quinoline derivatives are present in numerous natural products and biologically active materials.Therefore,developing protocols for efficiently preparing structurally diverse nitrogen heterocycles will be of significant interest.More recently,oxoammonium salts,especially Bobbitt's salt,have emerged as efficient organic oxidants for activating C-H bonds,playing a pivotal role in the construction of C-C bonds.By virtue of the advantages of Bobbitt's salt as oxidant,namely it's metal-free species,easy separation,recyclability and colorimetric reaction which can facilitate oxidation under mild reaction conditions.Moreover,it's reasonable to develop reactions in water for oxoammonium salts' great water-solubility,making the reaction to meet the criteria of green chemistry.In this thesis,investigations are focused on the usage of Bobbitt's salt in cross-dehydrogenation coupling of diverse THIQs to 2-alkylazaarenes and other nucleophiles,as well as in the preparation of Tranexamic acid.The main contents include the following three aspects.(1)Briefly describes the development of the oxoammonium salts,the overview of Bobbitt's salt in organic synthesis as well as its synthetic and recycling methods.(2)Under mild water conditions,using Bobbitt's salt to realize the CDC reactions between N-aryl-THIQs and 2-alkylazaarenes,as well as active methylene compounds.With the safety and easy-storage Bobbitt's salt as oxidant,water as solvent,this metal-free reaction provided an efficient,convenient and eco-friendly route for the preparation of nitrogen heterocycles.Compared with traditional methods,this reaction did not require any metal catalyst or other auxiliary reagent,aqueous media,also,high yields,simple isolation of products and recyclability of the oxidant all make this method fully embodied the concept of green chemistry.Additionally,oxidant used in the reaction could be recycled directly in the reaction system and be reused many times with a high reaction activity.(3)Under mild reaction conditions,using Bobbitt's salt to realize the oxidation reactions of aliphatic secondary alcohol and its application in the total synthesis of Tranexamic acid;moreover,three alternative synthetic processes of Tranexamic acid were desired and optimized.With the cheep and recycable Bobbitt's salt as oxidant,an efficient oxidation reaction of aliphatic secondary alcohol to corresponding ketone was performed smoothly.This ketone could be used in the process of total synthesize Tranexamic acid in 40% overall yield.Additionally,three alternative synthetic processes of Tranexamic acid were desired and optimized,including: 1.With 4-methyl benzoic acid as the starting material,Tranexamic acid was generated in 35% overall yield under four steps.The selective single chlorination reaction performed by TCCA instead of chlorine gas was the key process;2.With dimethyl cyclohexane-1,4-dicarboxylate as the starting material,Tranexamic acid was obtained in 45% overall yield under six steps.The key steps include selective single hydrolysis reaction and hydrogenation of cyano compound;3.With dimethyl terephthalate as the starting material,Tranexamic acid was produced in 59% overall yield under seven steps.The key steps were the same with method 2.As a highly cost-effective antifibrinolytic drug,Tranexamic acid has been included in the WHO list of essencial medicines.Therefore,developing protocols for efficient synthesizing Tranexamic acid has significant application value.