Synthesis of 5-methyl-2-(2,4,4,7-tetramethylchroman-2-yl) Phenol as an Impurity in Thymol
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摘要
[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.
[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.
[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.
引文
[1]QIU KL,MAO HF,OU WH,et al. Study on the synthesis of Thymol[J]. Flavour Fragrance Cosmetics,2008,4(2):28-32.(in Chinese).
[2]MULLER-RIEBAU F,BERGER B,YEGE O. Chemical composition and fungitoxic properties to phytopathogenic fungi of essential oils of selected aromatic plants growing wild in Turkey[J]. Journal of Agricultural and Food Chemistry,1995,43:2262-2266.
[3]GU T,CAO H. The clinical application of crystal thymol in caries and incidental perforation[J]. Heilongjiang Medical Journal,1994,37(5):25.(in Chinese).
[4]LIAO F,YANG ZD,HUANG QH,et al. In vitro antibacterial effects of Thymol and carvacrol on dysentery bacteria and common bacteria causing enteritis[J]. Herald of Medicine,2005,24(10):868-870.(in Chinese).
[5]DIVAKAR KJ,DHEKNE VV,KULKAMI BD,et al. A novel route to thymol from m-Cresol[J]. Organic Preparations and Procedures International,2000,32:92-94.
[6]KAMAT VP,ASOLKAR RN,KIRTANY JK. Synthesis of flavans:onepotsythesis of flavans from 4-methyl coumarins[J]. Synthetic Communications,1998,28(24):4581-4587.
[2]MULLER-RIEBAU F,BERGER B,YEGE O. Chemical composition and fungitoxic properties to phytopathogenic fungi of essential oils of selected aromatic plants growing wild in Turkey[J]. Journal of Agricultural and Food Chemistry,1995,43:2262-2266.
[3]GU T,CAO H. The clinical application of crystal thymol in caries and incidental perforation[J]. Heilongjiang Medical Journal,1994,37(5):25.(in Chinese).
[4]LIAO F,YANG ZD,HUANG QH,et al. In vitro antibacterial effects of Thymol and carvacrol on dysentery bacteria and common bacteria causing enteritis[J]. Herald of Medicine,2005,24(10):868-870.(in Chinese).
[5]DIVAKAR KJ,DHEKNE VV,KULKAMI BD,et al. A novel route to thymol from m-Cresol[J]. Organic Preparations and Procedures International,2000,32:92-94.
[6]KAMAT VP,ASOLKAR RN,KIRTANY JK. Synthesis of flavans:onepotsythesis of flavans from 4-methyl coumarins[J]. Synthetic Communications,1998,28(24):4581-4587.