Synthesis Of Substituted Isoquinoline-1,3(2H,4H)-Dione Derivatives By Difunctionalization Of Olefin

Direct difunctional reaction of olefins can efficiently provide functional compounds,meanwhile isoquinoline dione derivativesare important organic intermediates.Developing new approaches ofdirect synthesis of isoquinoline dione derivatives by difunctionallization of olefins are very important.On the basis of civil and foreign literatures,several typical difunctional reactions of olefin were reviewed,and the methods of synthesis of isoquinoline derivatives were summarized.Two synthetic methods of isoquinoline-1,3(2H,4H)-dione derivatives by the difunctionalization of activated olefins were developed.1)Isopropanolas a source of free radical:4-(2-Hydroxy-2-methyl-propyl)-2,4-dimethylisoquinoline-1,3(2H,4H)-dionewassynthesized at100?for 12h using N-acryloyl-N-methyl-benzamide as starting material,isopropanol as a radical precursor and solvent,TBPB as oxidant,catalyzed by Cu I.The yield was 79%.Other target products were also prepared by optimized conditions,including 6-CH₃,7-CH₃,8-CH₃,6-F,6-Cl,6-Br,6-SO₂Me,6-t Bu,6-C₂H₅O,5,7-dimethoxy,2-Et,2-Ph and2-Bn isoquinoline dione.The yield ranged in 8%-79%.2)Sodium nitrite as a source of free radical:2,4-Dimethyl-4-(nitromethyl)isoquinoline-1,3(2H,4H)-dionewas synthesized at 120?for 12h using N-acryloyl-N-methyl-benzamide as starting material,sodium nitrite as a radical precursor,ammonium persulfate as oxidant and dioxane as solvent.The yield was 46%.Other target products were also prepared by optimized conditions,including6-CH₃,6-SO₂Me isoquinoline dione.The yield ranged in 36%-46%.3)N-methacryloyl-N-methylbenzamide was prepared using benzoic acidas raw materials by chlorination reaction,ammoniated reaction and coupling reaction.Then a variety of substituted N-methacryloyl-N-methylbenzamides were synthesized by the above reactions.