Synthesis Of The Active Ingredients Containing Thiophenes And Aromatic Amines Structures In Traditional Chinese Medicine By Bulky Phosphine-free Palladium Complexes

Modernization of traditional Chinese medicine(TCM)is the development trend of traditional Chinese medicine,and it is also recognized by the whole world.Because of its complex factors and slow effect and other factors,the traditional Chinese herbal medicine in the application of modern medicine has been greatly limited.In order to seek a breakthrough,countless scientific research workers are committed to the study of effective ingredients in Chinese herbal medicine,and actively develop safe and effective new drugs,and the effective active ingredients of traditional Chinese medicine from the initial extraction of plants from the chemical synthesis and biological synthesis and other directions to meet the needs of the basic research needs of drug pharmacodynamic material basis.Modifying the structural of the active ingredients of TCM to obtain a more stable,less toxic side effects of derivatives for the follow-up drug research,which is one of the hot spots of TCM research.As active substances,aromatic compounds and thiophenes,are/were widely found in natural products and their derivatives.It is a very important synthesis method to introduce a group capable of improving the properties by coupling reaction.In this paper,the C-N bond and C-C bond were constructed in the catalytic system with transition metal palladium as the core,and the catalytic activity of the system and the applicability of the substrate were investigated.(1)Design and synthesis of four kinds of large hindered amine complexes C1-C4 palladium catalyzed C-H arylation directly,to achieve the purpose of the thiophene compounds of structural modification.In this paper,the hydrogen spectrum and carbon spectra of C1-C4 were characterized by screening of catalytic activity and reaction conditions,and the optimum catalytic system was determined.Thiophene compounds(2 mmol)and bromoarene(1 mmol)as the substrate,potassium carbonate(1.5 mmol)as alkali,pivalidine(30 mol%)as additive,0.3 mol% C3 as catalyst,DMAc as solvent,110 ° C for 12 h.In the catalytic system was successfully synthesized 42 kinds of thiophene derivatives,and coumarin 3-bromo-thiophene and various compounds as raw materials obtained nine kinds of coumarin derivatives were characterized NMR.(2)In order to modify the structure of the aromatic amine compounds,coupling reaction were designed by/with three kinds of macroporous nitrogen heterocyclic carbene palladium complexes A1-A3 catalyzed C-N.In this paper,A1-A3 was characterized by 1H NMR and 13 C NMR.The optimum catalytic system was determined by screening the catalytic activity and reaction conditions.Aromatic amine compounds(1.2mol)and Chlorinated aromatic hydrocarbons(1 mmol)was used as base,potassium tert-butoxide(1.5 mmol)as alkali,0.1 mol% A1 as catalyst,1,4-dioxane as solvent and reacted at 100 ° C for 2 h.In the study of the substrate,it was found that both the presence of passivated aniline groups or the substrate with large steric hindrance had a high catalytic activity in the catalytic system and showed good substrate suitability and reaction selectivity.