[Objectives] 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 an important basis for the est...[Objectives] 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 an important 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-(1-propylene-2-yl) phenol, and then purified and treated with hydrochloric acid to obtain a pale yellow solid. 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 the method was optimized, 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. [Conclusions] The optimized method is easy to control and the impurity C has high purity and it is expected to provide quality assurance for the study of related substances in the quality control of thymol.展开更多
文摘[Objectives] 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 an important 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-(1-propylene-2-yl) phenol, and then purified and treated with hydrochloric acid to obtain a pale yellow solid. 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 the method was optimized, 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. [Conclusions] The optimized method is easy to control and the impurity C has high purity and it is expected to provide quality assurance for the study of related substances in the quality control of thymol.
