Synthesis Of Highly Substituted Isoquinolones By Base-promoted Cyclization Of Ortho-alkynylbenzamides And Its Structure Confirmation

Highly isoquinolones are the basic building blocks for many naturally occurring products,they also have attracted much attention of chemists due to their unique biological activities and pharmacological activities.Using o-iodobenzoic acid as the raw materials,ortho-alkynylbenzamides were prepared in good yield through halogenation,acylation with a-aminoketone and Sonogashira coupling reactions.Base-selective intramolecular cyclizations of ortho-alkynylbenzamides providing an efficient method for the synthesis of four different 1(2H)-isoquinolones under mild conditions and its structure confirmation was carried out by Nuclear magnetic resonance(1H,13C,2D NMR)?Mass spectrometry and X-ray diffraction.The results of this paper were as follows:1.We developed a method for the synthesis of 3,4-disubstituted isoquinolin-1(2H)-ones via DBU-promoted cyclization of ortho-alkynylbenzamides using CH3CN as the solvent at room temperature.2.We also obtained 4-substituted isoquinolin-1(2H)-ones via t-BuOK promoted cyclization of ortho-alkynylbenzamides using CH3CN as the solvent at 50? for 1 h.3.We found an efficient method for the synthesis of 3,4-dihydroisoquinolin-1(2H)-ones via K2C03-promoted cyclization of ortho-alkynylbenzamides using CH3CN as the solvent at 50 ?.4.By the NaH-promoted cyclization of ortho-alkynylbenzamides ethyl acetate using CH3CN as the solvent at 50 ? for 1h,we get a series of ethyl 4-benzyl-1-oxo-2-phenyl-1,2-dihydroisoquinoline-3-carboxylates.