非均相氧化法制备利福霉素S

Preparation of Rifamycin S by Heterogeneous Oxidation

摘要:

利福霉素S是合成利福平的主要原料，可通过氧化利福霉素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H2O2、NaClO等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、pH、反应时间等工艺条件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1.41：1，θ=30 ℃，pH=12.3，反应12 min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)。

Abstract:

Rifamycin S (S), which can be made by oxidation of rifamycin SV (SV), is the main material of rifampicin. 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. In this research, butyl acetate/water two-phase system was chosen as the reaction solvent. Through analyzing and comparing the oxidation effects and mechanisms of different oxidants, sodium hypochlorite (NaClO) was conformed as the oxidant in the heterogeneous system. Besides, the impacts of various factors, such as NaClO concentration, NaClO/SV molar ratio, temperature, pH and reaction time, on the mass transfer - reaction process and oxidation effects were investigated. The results showed that under the conditions of NaClO concentration 0.3206 mol/L, NaClO/SV molar ratio 1.41：1, reaction temperature 30 ℃, pH 12.3 and reaction time 12 min, the yield and selectivity of S were the highest, which were 89.02% and 92.42% respectively. Compared with the traditional technology, the yield and selectivity increased by 3.61% and 6.74% respectively under the same conditions, and the space-time-yield increased from 16.75 g/(L•h) to 139.60 g/(L•h).