在微波辐照条件下,以甲基咪唑、氯乙醇和四氟硼酸钠为原料制备了含羟基功能化离子液体1-(2-羟乙基)-3-甲基咪唑四氟硼酸盐([2-hydemim][BF4]),并以其为液态载体,首先与乙酰乙酸乙酯反应,得到的中间体再分别和Meldrum酸、醋酸铵以及各种芳香醛反应,最后在温和的条件下用甲醇钠进行切割反应,得到了一系列产率和纯度较高的3,4-二氢吡啶酮衍生物,目标化合物不需要进一步的色谱纯化处理,纯度为95%~98%,产率为83%~93%.回收得到的功能化离子液体可以重复套用至少6次也不影响其活性.表明该方法是一种高效的3,4-二氢吡啶酮衍生物的组合化学合成方法.
Hydroxyl functionalized ionic liquid 1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ([2-hydemim][BF4]) was prepared under microwave irradiation via methylimidazolium, chlorohydrin and sodium tetrafluoroborate as materials. A microwave-assisted solution phase parallel synthesis of 3,4-dihydropyridones was developed using hydroxyl functionalized ionic liquid (IL) as soluble support. Firstly, the [2-hydemim][BF4] was reacted with ethyl acetoacetate to obtained IL-bound acetoacetate, then this intermediate was reacted with Meldrum acid, ammonium acetate and aromatic aldehyde. Finally 3,4-dihydropyridone derivatives were obtained in good yields and high purities without chromatographic purification after mild cleavage with sodium methoxide in methanol at room temperature, the purity of the target compounds was 95%-98%, and the yield was 83%-93%. The recovered functionalized ionic liquid could be recycled at least six times without losing its activity. It was clear that the solution-phase synthesis using functionalized ionic liquid as supports could be used in the combinatorial chemistry synthesis of 3,4-dihydropyridones derivatives in high efficiency.