藁本内酯二聚体的合成工艺研究

Research on Synthesis Technology of Ligustilide Dipolymer

目的:研究藁本内酯二聚体(化合物Ⅰ)的全合成工艺。方法:以邻苯二甲酸酐(化合物Ⅱ)为原料,经硼氢化钠还原得到苯酞(化合物Ⅲ)后经4步反应得到藁本内酯二聚体,经质谱、核磁共振氢谱(1H-NMR)和核磁共振碳谱(13C-NMR)进行表征。以催化剂、反应温度、反应时间为因素,收率为指标,采用正交试验优化第5步合成工艺,并进行验证。结果:第5步的最优合成工艺为在2%三氯化铝的催化下以温度150℃反应5 h。成功合成目标产物,验证试验平均收率为56.16%(RSD=1.23%,n=3);总的反应产率为24.4%,得到目标产物的纯度为99.4%。结论:成功合成藁本内酯二聚体,且本合成工艺稳定、质量可控。

OBJECTIVE：To study the synthesis technology of Ligustilide dipolymer （compound Ⅰ）. METHODS：Using phthalic anhydride（compoundⅡ）as raw materials,sodium borohydride was reduced to phthalide（compound Ⅲ）,and then syn-thesize ligustilide dipolymer after 4 steps. Ligustilide dipolymer was characterized by 1H-NMR and 13C-NMR. The synthesis technol-ogy of fifth step was optimized by orthogonal test with catalyzer,reaction temperature and reaction time as factors using yield as in-dex. The validation test was conducted. RESULTS：The optimal synthesis technology of fifth step was as follows as aluminium mu-riate of catalyzer,reaction temperature of 150 ℃,reaction time of 5 h. The average yield of validation test was 56.16%（RSD=1.23%,n=3）. Total reaction yield was 24.4%,and the purity of target product was 99.4%. CONCLUSIONS：Ligustilide dipoly-mer is synthesized successfully;synthetic process is stable,and its quality is controllable.