Synthesis Of Tetrahydroisoquinoline And Functionalized

Tetrahydroisoquinoline and its derivatives are widely existed in various natural products,and they have good properties and high biological activity,and have been widely studied in new drug research and pharmaceutical production.In recent years,there have been a lot of reports and research trends on the synthesis of isoquinoline and its related derivatives.The reaction conditions are relatively harsh,the reaction process is complicated,and the yield is not high,and using more expensive catalyst,so the development of the synthesis of isoquinoline ring method is simple and effective and its derivatives became the hot point of research.In this paper,tetrahydroisoquinoline derivatives were synthesized on the basis of literature and tetrahydroisoquinoline was used as the substrate.The reaction conditions were optimized,and the related synthesis mechanism was studied.In the first part,2-benzyl-1-?3-indole?-tetrahydroisoquinoline and its derivatives were prepared by one pot method with tetrahydroisoquinoline,indole and Benzaldehyde,The optimum reaction conditions were obtained as follows:tetrahydroisoquinoline:benzaldehyde:indole=1.1:1:1.1,CuBr as catalyst,PPh₃ as ligand,AcOH medium,toluene as solvent,reaction temperature was 100?.Under the optimized conditions,26 new small molecule compounds were developed,and their structures were characterized by 1H NMR,13C NMR and high resolution mass spectrometry.The yield of the product ranged from 67%-96%.The experimental results show that the yield of electron withdrawing group substituent is higher than that of electron donating group.The related reaction mechanism is speculated,which provides a good data reference for the later researchers.In the second part,2-Benzyl-3,4-dihydro-2H-isoquinolin-1-one and its derivatives were synthesized by one-step reaction with four hydrogen isoquinoline,benzyl azide and benzaldehyde as raw materials.The optimum reaction conditions were as follows:tetrahydroisoquinoline:benzaldehyde:Benzyl azide=1.4:1.4:1,CuCl₂ as catalyst,AcOH as medium,toluene as solvent,reaction temperature 100,reaction time 3H.Under the optimized conditions,12 kinds of small molecule compounds were synthesized,and the structures of the products were characteri.zed by 1H NMR,13C NMR and high-resolution mass spectrometry.The yield of the products ranged from 52%-62%.The related reaction mechanism was also speculated.