中间体2-溴甲基-3,5,6-三甲基吡嗪的合成工艺优化 |
| |
引用本文: | 绪扩,王鹏龙,徐昕,韩秋俊,汪林,李强,雷海民.中间体2-溴甲基-3,5,6-三甲基吡嗪的合成工艺优化[J].安徽医药,2013,17(9):1467-1470. |
| |
作者姓名: | 绪扩 王鹏龙 徐昕 韩秋俊 汪林 李强 雷海民 |
| |
作者单位: | 北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102;北京中医药大学中药学院,北京,100102 |
| |
基金项目: | 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) |
| |
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.
|
关 键 词: | 川芎嗪衍生物 中间体 2-溴甲基-3 5 6-三甲基吡嗪 合成工艺优化 |
Synthetic process optimization of the intermediate 2-bromomethyl-3,5,6-trimethylpyrazine |
| |
Institution: | XU Kuo, WANG Peng-long, XU Xin, et al ( School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China) |
| |
Abstract: | 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. |
| |
Keywords: | ligustrazine derivatives intermediate 2-bromomethy1-3 5 6-trimethylpyrazine synthetic process optimization |
本文献已被 维普 万方数据 等数据库收录! |
|