5000-66-8 2-溴-2'-氯苯乙酮

运输信息：冰袋运输。危险描述：危险品运输编号UN 2922 8/PG 2，危险等级8，包装类别II，海关编码29143900，存储类别6.1A - 可燃，急性毒性物质（类别1和类别2）剧毒的危险物质，危险性类别皮肤腐蚀类别1B，Hazard Note:Corrosive/Lachrymatory/Keep Cold，WGK Germany:3。

化学合成

化学合成

路线1：氧化溴化法

• 步骤：搅拌1.2g苯乙酮1a（10mmol）和0.121g Cu(NO₃)₂·3H₂O（0.5mmol）的混合物，连接氧气球（约0.5-1L）；滴加8mol/L氢溴酸水溶液（1.5mL，12mmol）；70℃搅拌3.5h（TLC或GC监测）；反应完成后用CH₂Cl₂萃取，有机相依次用5％亚硫酸钠、饱和碳酸氢钠溶液、水洗涤，无水硫酸镁干燥；真空除溶剂，残余物经柱色谱（硅胶，石油醚/二氯甲烷3：1）纯化得产物α-溴苯乙酮（2a）
• 条件：70℃，3.5h，氧气氛围
• 产率：91％
• 参考文献：[1] Synthetic Communications, 2016, vol. 46, # 2, p. 165 - 168 [2] Patent: US2004/44057, 2004, A1 [3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 2, p. 692 - 702 [4] Tetrahedron, 1998, vol. 54, # 43, p. 13059 - 13072 [5] Tetrahedron Letters, 2012, vol. 53, # 2, p. 191 - 195 [6] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2481 - 2486 [7] Angewandte Chemie - International Edition, 2013, vol. 52, # 29, p. 7509 - 7513 [8] Angew. Chem., 2013, vol. 125, # 29, p. 7657 - 7661,5 [9] Chemical and Pharmaceutical Bulletin, 1992, vol. 40, # 5, p. 1170 - 1176 [10] Collection of Czechoslovak Chemical Communications, 1991, vol. 56, # 11.1, p. 2430 - 2435 [11] Journal of Medicinal Chemistry, 1992, vol. 35, # 16, p. 3045 - 3049 [12] Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 3, p. 601 - 621 [13] Journal of agricultural and food chemistry, 2002, vol. 50, # 12, p. 3486 - 3490 [14] Synthetic Communications, 2007, vol. 37, # 2, p. 199 - 207 [15] Bioscience, Biotechnology and Biochemistry, 2005, vol. 69, # 1, p. 79 - 86 [16] Patent: US2003/207900, 2003, A1. Location in patent: Page/Page column 13-14 [17] Patent: WO2005/26137, 2005, A2. Location in patent: Page/Page column 234-235 [18] Patent: WO2005/75435, 2005, A1. Location in patent: Page/Page column 128 [19] Patent: WO2007/21982, 2007, A2. Location in patent: Page/Page column 24; 45-46 [20] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7273 - 7276 [21] Patent: WO2012/27965, 2012, A1. Location in patent: Page/Page column 18 [22] European Journal of Medicinal Chemistry, 2012, vol. 52, p. 70 - 81 [23] Synlett, 2012, vol. 23, # 12, p. 1797 - 1800 [24] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 403 - 412 [25] Journal of Medicinal Chemistry, 2013, vol. 56, # 1, p. 84 - 96 [26] Journal of Organic Chemistry, 2013, vol. 78, # 12, p. 6276 - 6280 [27] Angewandte Chemie - International Edition, 2013, vol. 52, # 44, p. 11632 - 11636 [28] Angew. Chem., 2013, vol. 125, # 44, p. 11846 - 11850,5 [29] Chemical and Pharmaceutical Bulletin, 2014, vol. 62, # 1, p. 16 - 24 [30] Drug Design, Development and Therapy, 2016, vol. 10, p. 1807 - 1815 [31] MedChemComm, 2016, vol. 7, # 7, p. 1441 - 1448 [32] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 8, p. 1166 - 1173 [33] Patent: CN105315279, 2016, A. Location in patent: Paragraph 0148 [34] Journal of Medicinal Chemistry, 2017, vol. 60, # 4, p. 1591 - 1597 [35] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 16, p. 3726 - 3732 [36] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1986 - 1995 [37] Patent: WO2018/167677, 2018, A1. Location in patent: Page/Page column 64 [38] Patent: WO2008/118455, 2008, A1. Location in patent: Page/Page column 49

路线2：卤代炔水解法

• 步骤：将卤代炔（0.5mmol）、AgF（5mol％）和水（1当量）在TFA（1mL）中混合；40℃搅拌6小时；蒸馏回收TFA；残余物经柱色谱分离得纯样品
• 条件：40℃，6h
• 产率：84％
• 参考文献：[1] Tetrahedron Letters, 2014, vol. 55, # 7, p. 1373 - 1375 [2] Tetrahedron, 2016, vol. 72, # 27-28, p. 3818 - 3822 [3] Tetrahedron Letters, 2016, vol. 57, # 45, p. 4983 - 4986

路线3：邻氯苯乙酮溴化法

• 步骤：将苯和邻氯苯乙酮加入反应锅；室温搅拌下加入部分溴素，待褪色后继续滴加溴，反应时适当加热；滴完后搅拌1h；加入冰水搅拌，静置分层；苯层用碳酸钠溶液洗涤，再水洗；回收苯得α-溴代邻氯苯乙酮