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过程工程学报 ›› 2020, Vol. 20 ›› Issue (2): 205-212.DOI: 10.12034/j.issn.1009-606X.219204

• 过程与工艺 • 上一篇    下一篇

醋酸可的松合成中碘化反应工艺优化

刘欢1,马政生1,刘庆芬2*   

  1. 1. 西北大学化工学院，陕西 西安 710069 2. 中国科学院过程工程研究所绿色过程与工程重点实验室，北京 100190
  • 收稿日期:2019-05-16 修回日期:2019-06-03 出版日期:2020-02-22 发布日期:2020-02-19
  • 通讯作者: 刘庆芬 qfliu@ipe.ac.cn
  • 基金资助:
    水体污染控制与治理科技重大专项;国家自然科学基金资助项目

Optimization of iodination reaction for the synthesis of cortisone acetate

Huan LIU1, Zhengsheng MA1, Qingfen LIU2*   

  1. 1. School of Chemical Engineering, Northwest University, Xi?an, Shaanxi 710069, China 2. Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
  • Received:2019-05-16 Revised:2019-06-03 Online:2020-02-22 Published:2020-02-19
  • Contact: Qing-Fen LIU qfliu@ipe.ac.cn

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摘要： 以21-脱氧可的松(SSC)为原料、溴碘液为碘化剂，研究了SSC转化为一碘化物及一碘化物与二碘化物相互转化的反应过程，考察了摩尔比SSC/I2 (溴碘液)、溴碘液滴加速度、反应时间、反应温度等因素对C-21位碘化反应的影响，以获得一碘化物为目标优化了反应工艺，采用高效液相色谱检测反应体系中一碘化物、二碘化物及SCC的浓度变化。结果表明，SSC转化为一碘化物与一碘化物转化成二碘化物为竞争反应，在溴碘液滴加结束的后续反应过程中二碘化物可以转化为一碘化物。生成一碘化物最多的最佳工艺条件为SSC/I2 (溴碘液)摩尔比1:0.62、溴碘液滴加速度0.33 mL/min (SSC 20 g)、后续保温反应时间120 min、反应温度?3℃。该条件下醋酸可的松的平均摩尔收率为87.67%，比文献提高了14.93%。

关键词: 醋酸可的松, 碘化反应, 工艺优化, 一碘化物, 二碘化物

Abstract: Cortisone acetate is a steroidal drug and an important raw material for the synthesis of steroidal drugs such as prednisone. The preparation of cortisone acetate can be carried out in two steps: iodization and substitution reaction. Iodination reaction is the key step. The maximum molar yield of cortisone acetate was 72.74% in the literature. In this work, the iodization reaction at C-21 position by using 21-deoxycortisone (SSC) as starting raw material and bromine iodine solution as iodinating agent was explored. The conversion of SSC to monoiodide and the exchange between monoiodide and diiodide were studied. The effects of molar ratio of SSC to I2 (bromine iodine solution), feeding rate of bromine iodine solution, extended reaction time and reaction temperature on iodination reaction were investigated. The process was optimized in order to increase the yield of monoiodide. The changes of monoiodide, diiodide and SSC were detected by HPLC. The results showed that there were competition between the conversion of SSC to monoiodide and the continued conversion of monoiodide to diiodide. When the contents of monoiodide and iodinating agent reached certain values, following continuous addition of iodinating agent, the conversion of monoiodide to diiodide became the main reaction, which led to the increase of SSC in the reaction solution. It was also observed that diiodide could be converted to monoiodide during extended reaction process, therefore the yield of monoiodide could be improved. All the studied factors had significant effects on the iodination reaction. The optimized conditions for the synthesis of monoiodide were as follows: molar ratio of SSC to I2 (bromine iodine solution) 1:0.62, feeding rate of bromine iodine solution 0.33 mL/min (SSC 20 g), extended reaction time 120 min, reaction temperature ?3℃. Under these optimal conditions, the molar yield of cortisone acetate reached 87.67%, which was 14.93% higher than the yield of literature reported. This optimized process could provide better economic benefits.

Key words: cortisone acetate, iodination reaction, technological optimization, monoiodide, diiodide