麝香草酚中杂质5-甲基-2-(2,4,4,7-四甲基苯并二氢吡喃基)苯酚的合成

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英文篇名：Synthesis of 5-methyl-2-(2,4,4,7-tetramethylchroman-2-yl) phenol as an impurity in thymol 作者：杨谣谣 ; 于凯 ; 王永广 ; 禹玉洪 英文作者：YANG Yaoyao;YU Kai;WANG Yongguang;YU Yuhong;Department of Pharmaceutics,School of Pharmacy,Shanxi Medical University;Beijing Xinkaiyuan Pharmaceutical Technology Co.,Ltd.; 关键词：麝香草酚 ; 高效液相 ; ~1H-NMR 英文关键词：thymol;;high performance liquid phase;;~1H-NMR 中文刊名：SXYX 英文刊名：Journal of Shanxi Medical University 机构：山西医科大学药学院药剂教研室;北京鑫开元医药科技有限公司; 出版日期：2018-10-17 13:25 出版单位：山西医科大学学报 年：2018 期：v.49;No.312 语种：中文; 页：SXYX201810011 页数：5 CN：10 ISSN：14-1216/R 分类号：57-61

摘要

目的优化5-甲基-2-(2,4,4,7-四甲基苯并二氢吡喃基)苯酚(杂质C)的制备工艺以及该杂质的液相测定方法,为麝香草酚工艺研究和分析有关物质方法建立及质量控制提供重要依据。方法以4,7-二甲基香豆素为起始原料,在氢氧化钾的作用下水解得到物质Ⅱ5-甲基-2-(1-丙烯-2-基)苯酚,纯化后在盐酸作用下后处理得到淡黄色固体,经过高效液相方法检测得到高纯度的主峰,对其进行~1H-NMR测定及谱图进行解谱分析,其结构为杂质C。结果方法优化之后使得到杂质C合成路线操作简单,且得到杂质C纯度高,所得杂质C经1H-NMR谱图分析,为化合物5-甲基-2-(2,4,4,7-四甲基苯并二氢吡喃基)苯酚,同时开发了其液相检测方法。结论所优化的方法实验条件易控制,纯度高,为麝香草酚药学质量控制中有关物质的研究提供了质量保证。
        Objective To optimize the preparation process of 5-methyl-2-( 2,4,4,7-tetramethylchromanyl) phenol( impurity C) and the liquid phase determination method of the impurity,and to provide a basis for the establishment of material methods and quality control of thymol. Methods The 4,7-dimethylcoumarin as the starting material was hydrolyzed by potassium hydroxide to obtain the substance Ⅱ 5-methyl-2-( propan-1-en-2-yl) phenol,and then purified and treated with hydrochloric acid to obtain a pale yellow solid. The high-purity main peak was obtained by high-performance liquid phase method,and it was identified as impurity C by ~1H-NMR measurement and spectrum analysis. Results After optimizing the method,the synthesis route to the impurity C was simple,and the purity of impurity C was high. The obtained impurity C was confirmed by ~1H-NMR to be a compound 5-methyl-2-( 2,4,4,7-tetramethylchromanyl) phenol. The liquid phase detection method was successfully established to identify the compound. Conclusion The optimized method is easy to control and the impurity C has high purity,which provides quality assurance for the study of related substances in thymol quality control.

引文

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