摘要
目的对川芎嗪系列衍生物合成中间体:2-溴甲基-3,5,6-三甲基吡嗪(TMP-Br)的合成工艺进行优化。方法 HPLC-MS法对反应物中的主要化学成分进行初步归属;HPLC法考察反应时间、原料比例、光照强度、溶剂用量对TMP-Br产率的影响;最后由正交工艺优化法初步确定中间体的最佳合成工艺。结果以1 g川芎嗪计算,合成TMP-Br的最佳反应条件为:NBS/TMP=0.9,CCl4/TMP=5 mL·g-1,选用4盏85 W节能灯作为引发剂,反应时间为1 h。结论影响川芎嗪溴代反应的4个因素中,NBS和CCl4的用量对单溴代物产率的影响最大;在今后的工艺放大过程中,可优先考察最佳投料比与溶剂用量。
Objective To simplify and optimize the synthetic process of an important intermediate, 2-bromomethy1-3,5,6-trimeth-ylpyrazine （TMP-Br）, which was widely applied for designing various ligustrazine derivatives. Methods We determined the main chem-ical components of reaction liquid with the aid of HPLC-MS, investigated the effects of reaction time, raw materials, light intensity and sol-vent on productivity of TMP-Br, then got the optimum preparation method by the orthogonal process. Results Calculated by 1 g TMP, the optimum reaction conditions were NBS/TMP = 0.9, CC1JTMP = 5 mL · g^-1,4 energy-saving lamps （85 W） being used as the initiators, and reaction time being 1 h. Conclusions Among all the influential factors of ligustrazine brominating reaction,the amount of NBS and solvent impacted end-product＇ yield greatly ;in the future craft enlaxgement, attentions should be focused preferentially on the amotlnt of the brominating agents and solvent.
出处
《安徽医药》
CAS
2013年第9期1467-1470,共4页
Anhui Medical and Pharmaceutical Journal
基金
国家自然科学基金项目(No 81173519)
北京中医药大学创新团队项目(No 2011-CXTD-15)
