关键词: 2, 3, 4-三甲氧基苯甲醛, 新型苯并-?-吡喃酮类, Knoevenagel反应, 设计, 合成, 药物

Abstract: Three novel derivatives of 2H-1-benzopyran-2-one were designed and synthesized from 2,3,4-trimethoxybenzaldehyde by methoxy reduction，Knoevenagel，nitro reduction and acylation reaction. Its structure was confirmed by 1H-NMR，13C-NMR，IR analysis. Experiments based upon orthogonal design with four factors and three levels were carried out for the optimization of Knoevenagel reaction condition. The experimental results show that the optimal condition is found as follows：using toluene and cyclohexane[V(toluene)∶V(cyclohexane)=7∶3] as solvent and piperidine as catalyst，n(2-hydroxy-3,4 dimethoxybenzaldehyde)∶n(methyl nitroacetate)∶n(catalyst) =1∶1.2∶0.20，the reaction temperature of 98℃±2℃ and reaction time of 6h. Under this optimal condition，the average yield can reach 87.2%，higher than the values in literature. Target compounds are novel coumarin derivatives，with potential anticancer activity.

Key words: 2,3,4-trimethoxybenzaldehyde, novel derivatives of 2H-1-benzopyran-2-one, Knoevenagel reaction, design, synthesis, pharmaceuticals