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第 36 卷第 2 期 精 细 化 工 Vol.36, No.2
201 9 年 2 月 FINE CHEMICALS Feb. 2019

医药与日化原料
非均相氧化法制备利福霉素 S

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于丽君，陈 葵 ，朱家文
（华东理工大学 化学工程研究所，上海 200237）

摘要：利福霉素 S（简称 S）是合成利福平的主要原料，可通过氧化利福霉素 SV（简称 SV）制得。针对 S 生
产工艺中副反应多、反应介质产生设备腐蚀等问题，开发了以有机溶剂/水的非均相体系代替传统水基体系的氧
化新工艺。选定乙酸丁酯/水两相体系为反应溶剂，通过分析比较 5 种氧化剂的氧化效果及作用机理，确定 NaClO
为非均相反应体系的氧化剂。并考察了 NaClO 浓度、NaClO 与 SV 物质的量比、温度、反应时间及 pH 对反应
传质过程及氧化效果的影响。结果表明：在 c(NaClO)=0.3206 mol/L、NaClO 与 SV 物质的量比为 1.4∶1.0、反
应温度 30 ℃、反应时间 12 min、pH=12.3 时，利福霉素 S 粗品收率及选择性最高，分别为 89.02%、92.42%。
与相同条件下的传统工艺相比，收率及选择性分别提高 3.61%、6.74%，并且空时收率由原工艺的 16.75 g/(Lh)
增加至 139.60 g/(Lh)。
关键词：利福霉素 S；利福霉素 SV；非均相氧化；两相体系；选择性；医药原料
中图分类号：TQ465.5 文献标识码：A 文章编号：1003-5214 (2019) 02-0288-07

Preparation of Rifamycin S by Heterogeneous Oxidation

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YU Li-jun, CHEN Kui , ZHU Jia-wen
（Chemical Engineering Research Center, East China University of Science & Technology, Shanghai 200237, China）

Abstract: Rifamycin S (abbreviated as S) is the main material for the synthesis of Rifampicin, which can
be made by oxidation of Rifamycin SV (abbreviated as SV). To solve the problems of side reactions and
equipment corrosion in the production of S, a new oxidation technology was developed with organic
solvent/water heterogeneous system instead of traditional water-based system. Butyl acetate/water
two-phase system was chosen as the reaction solvent. By analyzing and comparing the oxidation effects and
mechanisms of five oxidants, sodium hypochlorite (NaClO) was selected as the oxidant in the
heterogeneous system. Besides, the factors affecting the mass transfer-reaction process and oxidation effects,
such as NaClO concentration, NaClO/SV molar ratio, reaction temperature, reaction time and pH were
investigated. The results showed that under the conditions of NaClO concentration 0.3206 mol/L,
NaClO/SV molar ratio 1.4∶1.0, reaction temperature 30 ℃, reaction time 12 min and pH=12.3, the
highest yield (89.02%) and selectivity (92.42%) to product S were obtained. Compared with the traditional
technology under the same conditions, the yield and selectivity were increased by 3.61% and 6.74%
respectively, and the space-time-yield increased from 16.75 g/(L·h) to 139.60 g/(L·h).
Key words: Rifamycin S; Rifamycin SV; heterogeneous oxidation; two-phase system; selectivity; drug
materials

利福霉素 S（Rifamycin S，简称 S，醌式结构） （Rifamycin SV，简称 SV，酚式结构）氧化法是制
[1]
是利福平、利福布汀等利福类药物的前体物质 。 备 S（反应路线如下所示）的主要方法，其反应实
该类药物广泛应用于结核病及麻风病的治疗中，具 质为分子中氢醌结构向醌式结构的转变，但利福霉
有活性高、普适性强的特点 [2-4] 。 利福霉素 SV 素分子整体结构复杂，氧化过程中易引起 C==C、

收稿日期：2018-08-31; 定用日期：2018-11-09; DOI: 10.13550/j.jxhg.20180643
作者简介：于丽君（1993—），女，硕士生，E-mail：lijun_yu1993@163.com。联系人：陈 葵（1965—），女，副教授，E-mail：
chenkui@ecust.edu.cn。