Résumé
@#An analytical liquid-liquid extraction-gas chromatography–mass spectrometry (LLE-GC-MS) method was established for the determination of genotoxic impurities including methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and isopropyl methanesulfonate (IMS) in methanesulfonic acid. An Agilent HP-1MS capillary column (30 m × 0.32 m, 1 μm) was used for separating the analytes by programmed heating with the inlet temperature of 220 °C. Mass spectrometry was operated in positive ion mode, and selective ion monitors were set at m/z 80 for MMS, m/z 79 for EMS, m/z 123 for IMS and m/z 56 for internal standard butyl methanesulfonate (BMS). Results showed that the baseline separation of MMS, EMS and IMS was achieved, and the blank extraction solution had no interference; good linearity was achieved in the range of 37-1 480 ng/mL for three alkyl methanesulfonates; The mean recoveries of MMS, EMS, IMS were 104.99%, 107.26%,108.85%, respectively, with RSD ≤ 4.54%. The established method has the characteristics of specific, sensitive, accurate, stable and good versatility, and has been used for the detection and control of alkyl methanesulfonate impurities in methanesulfonic acid from a variety of manufacturers.
Résumé
Objective To improve the synthetic condition of 6‐methoxyisatin .Methods The starting material 3‐me‐thoxyaniline was firstly converted into the intermediate 1‐oximino‐N‐ (3‐methoxyphenyl) acetamide through Sandmeyer reac‐tion ,then 6‐methoxyisatin was conducted with methanesulfonic acid as catalyst in the following ring closure reaction .Results In the second step of the cyclization reaction ,methanesulfonic acid was used to replace the concentrated sulfuric acid which is widely used in literature .The temperature was 80℃ ,the reaction time was 30 min ,and the yield was 81.24% .Conclusion This study provided a synthesis process of 6‐methoxyisatin with simple operation ,mild reaction condition and high yield ,which is suitable for large scale preparation of the compound .