The Structure Modification Of Active Substances Containing Imidazoles Structures And Courmarins In Traditional Chinese Medicine By Palladium-N-Heterocyclic Carbene(Pd-NHC) Complexes

Traditional Chinese medicine is a great treasure of the world civilization. The China pharmacopoeia made in 2015 has included more than 2000 kinds of Traditional Chinese medicine(TCM).How to illuminate the active ingredient of Chinese traditional medicine, valid development of Traditional Chinese medicine resources, strengthen the Traditional Chinese medicine(TCM) modernization, make the dream that the traditional Chinese medicine resources with its sustainable development come true, is a basic research work of the development of Traditional Chinese medicine(TCM).Imidazole structure as common nitrogen heterocyclic structure exists in Traditional Chinese Medicine, some structure has biological activity of antibacterial and nerve stimulation.Coumarin is a common natural product, mainly found in incense snake whip chrysanthemum, black beans, orchid. Its biological activity mainly included antitumor, antibacterial, antifungal, anticoagulant effect, fall blood sugar and so on. Imidazole structure is a common nitrogen heterocyclic structure exists in Traditional Chinese medicine active ingredients. The structure modification of coumarin and imidazole structure has important significance for how to realize the redevelopment of Traditional Chinese medicine.C-H bond is a kind of common chemical bonds exist in heterocyclic compounds in great quantities, C-H direct arylation reaction is a quick and easy way to alter the structure of heterocyclic compounds, the same time the Suzuki reaction is also the commonly used means of implementation of compound coupling. Transition metal complexes as catalysts in C-H is widely used in the research of activation and Suzuki reaction, therefore it is feasible method that using transition metal complexes as catalysts in coupling reaction for structure modification of the coumarin and imidazoles structure,s Traditional Chinese medicine active ingredients.In this paper, we synthesized a series of nitrogen heterocyclic carbene palladium complexes, and catalytic the reaction of C-H direct arylation reaction of imidazoles structure,s compounds and Suzuki reaction of coumarin derivatives, provided the feasible method for the structure modification research of coumarin and imidazoles structure,s Traditional Chinese medicine active ingredients.Ⅰ, The purpose of the researchSynthesized and developed some highly efficient and stable nitrogen heterocyclic carbene catalyst, used for catalytic C-H arylation reaction of imidazoles compound,s and Suzuki reaction of coumarin derivatives. To provide a effective study method for the structure modification of imidazoles and coumarins Traditional Chinese medicine active ingredients.Ⅱ,The methods of the researchIn this paper, we designed and synthesized four carbene palladium complexes, synthesis process is mainly divided into three steps: one is the synthesis of ligand; two is the synthesis of carbene salt; Three is the synthesis of carbene synthesis.After four complexes were successfully synthesized, we do this: 1)C-H activation reaction of imidazoles compounds, Screened the optimal conditions, To provide a effective study method for the structure modification of imidazoles; 2)The Suzuki reaction of the coumarins, make sure modification of coumarins.Ⅲ, The results of researchThis paper synthesized four nitrogen heterocyclic carbene and palladium complexes, catalyzed C-H activation reaction by two imidazoles with forth-eight aromatic substrate compounds, catalytic Suzuki reaction by one coumarin substrate with nine substituted, completed structure modification for imidazoles and coumarins of Traditional Chinese Medicine active ingredients.The research illustrated:The conditions screening results showed that the most effective reaction condition were: by using K2CO3 as the base, Piv OH as the acid, solvent were with N,N-dimethylacetamide, the reaction systems were heat to 130℃ for 12 hours under aerobic, catalyst also can be as low as 0.5%mmol. In C-H activation reaction, electron-withdrawing groups active substrates were generally highed than give electronic group substrate. C4 has higher activity of catalyst.The Suzuki reaction of Structures of coumarin, achieved nine kinds of C-C coupling compounds reaction.There has three production rate is over 90%, the overall yield is generally high.Ⅳ, ConclusionsIn this paper, the experimental we used four catalystes in the Suzuki reaction of coumarin or C-H activation reaction of imidazoles Traditional Chinese medicine active ingredients showed good catalytic activity, the success of the catalytic product separation characterization: carbene catalyst C-H activation reaction of imidazoles or Suzuki reaction of coumarin, provided a good method of structure modification for Traditional Chinese medicine active ingredients. Larger space steric C4 has higher activity of catalyst in the two types of reaction. In C-H activation reaction, electron-withdrawing groups active substrates were generally highed than give electronic group substrate.