Synthesis Ortho-(3-Hydroxy-1-Alkynyl)Benz Amide And Ortho-(3-Alkoxy-1-Alkynyl)Benzamide And Their Application In Synthesis Of Isoquinolin-1(2H)-Ones And Benzo[C]azepin-1-Ones

Allenes, featured by the presence of two cumulated C=C double bonds, have shown a variety of unique chemical reactivity. In recent years, much attention has been paid to the reaction based on allene intermediates generated during the reaction. These reactions could avoid of preparation and storage of allene and could take full advantage of its high reactivity and selectivities.Using o-iodobenzoic acid as the starting materials, ortho-(3-hydroxy-1-alkynyl)benzamide and ortho-(3-alkoxy-1-alkynyl)benzamide were prepared in moderate yields through halogenation, ammonolysis and Sonogashira coupling reaction. Then, a series of ortho-(3-hydroxy-1-alkynyl)benzamide and ortho-(3-alkoxy-1-alkynyl)benzamide were used to the synthesis of isoquinolin-1(2H)-one and benzo[c]azepin-1-one derivatives by the DBU-promoted cyclization, and the results were as follows:1. We found that cyclization of ortho-(3-hydroxy-3-aryl-l-propynyl) benzamide could give trans-3,4-Dihydroisoquinolin-1(2H)-ones in moderate yields in THF at45℃(58～85%). The reactions proceed via a propargyl alcohol-enone isomerization/intramolecular Michael addition process. The trans-3,4-Dihydroisoquinolin-1(2H)-one could be further transformed into benzo[c][1,7]naphthyridin-6(5H)-one.2. We developed a method for the synthesis of (E)-4-(1-Alkenyl) isoquinolin-1(2H)-ones via the DBU-promoted cyclization of ortho-(3-hydroxy-3-alkyl-1-propynyl)benzamide.(E)-4-(1-Alkenyl)isoquinolin-1(2H)-ones were obtained using CH3CN as the solvent at75℃in moderate yields(42～86%).3. We found that cyclization of ortho-(3-alkoxy-3-alkyl-1-propynyl) benzamide could afford2,5-dihydro-benzo[c]azepin-l-ones in moderate yields in CH3CN at75℃(50～82%).