脱O-甲基：七氯化二铝，是什么？
文摘
科学
2024-10-20 08:02
天津
下面是BMS公司的案例，该脱O-甲基的条件，没有包含在上述链接里。
- 最初工艺采用盐酸吡啶盐酸盐，无溶剂，160度反应，反应完毕，用盐酸稀释体系，然后纯化，分离，结晶，收率：85−90%。
- 问题：温度高，放大设备不理想；产生焦油，处理不理想，反应一致性，不稳定。
三氯化铝和三甲基氯化铵在二氯甲烷中反应，原位可得离子液体试剂[TMAH]Al2Cl7，作为很强的路易斯酸，活性高，容易和氧结合，氯离子进攻甲基活性更强，释放氯甲烷完成脱O-甲基。温度只需40度。- 反应过程，三甲基氯化铵先加到三氯化铝二氯甲烷的悬浊液中，制备离子液体，然后加入反应底物，
- 副产物氯甲烷作为有毒气体，采用氨气的甲醇溶液吸收。
- 规模：375kg，收率85−95%，含量>99.4%
Trimethylammonium chloride (466 kg, mol) was added in portions at ≤25 °C to a previously prepared slurry of aluminum trichloride (1301 kg, mol) in dry CH2Cl2 (1336 kg) over 150min. To trap offgasses, the reaction vessel was connected to an empty vessel, then a scrubber was filled with methanol/25% aq ammonia/water (1:31.7:1.35 v/v/v) and finally a vessel filled with dilute sulfuric acid to trap basic vapors. The mixture was stirred for 1 h at 22 °C. A 32−38 °C solution of 9 (336 kg,mol) in dry CH2Cl2 (445 kg) was added at 22−33 °C over 35min, maintaining 3 bar pressure to account for CH3Cl offgas pressure, followed by a line rinse with CH2Cl2 (87 kg). (CAUTION: CH3Cl is a hazardous gas!). The mixture was heated to 42 °C over 65 min and stirred at this temperature for a total of 5 h 5 min, taking care to maintain P(vessel) at 3 bar pressure throughout the stirring. HPLC analysis indicated nostarting material, and the mixture was degassed with nitrogen through the scrubber, cooled to 22 °C over 40 min, and poured into 2 °C water (3360 kg) at 2−22 °C over 7 h 20 min. The line was rinsed with CH2Cl2 (87 kg), the mixture was cooled to 0 °C over 80 min and stirred at this temperature for 1 h, and collected by centrifuge over 20 h 25 min. The wet cake was washed with water (168 kg). Wet crude 10 was then added to 22 °C water (1680 kg), the slurry was stirred at 22 °C for 1 h and collected by centrifuge over 10 h 50 min. The wet cake was washed with water (672 kg), and the cake was checked for the presence of residual chloride. Additional water washes were added if necessary. The wet product was dried under vacuum at 50 °C for 13 h 20 min to yield 282 kg of solids (89.4% yield, 99.4% HPLC assay). Org. Process Res. Dev. 2014, 18, 89−102
