2973-78-6 3-溴-4-羟基苯甲醛

危险性质：否

化学合成

化学合成

路线1：

• 产率：90%
• 合成条件：With oxygen; cobalt(II) diacetate tetrahydrate; sodium hydroxide In ethylene glycol at 80℃; for 8 h;
• 实验步骤：一般步骤：将底物1a（1mmol），钴盐（n1mol％）和NaOH（n2当量）在EG（5mL）中的混合物与O 2（1atm）一起搅拌，在80℃下鼓泡8小时。将盐酸（10mL，2％）和甲基叔丁基醚（MTBE，10mL）依次加入到反应混合物中。分离有机层，并将水相用MTBE（10mL×2）进一步萃取。合并的有机相用无水硫酸钠干燥并浓缩，得到残余物，将其通过硅胶柱色谱纯化（洗脱剂：石油醚/乙酸乙酯，10/1），得到所需产物2a。
• 参考文献： [1] Tetrahedron Letters, 2014, vol. 55, # 8, p. 1406 - 1411 [2] Green Chemistry, 2014, vol. 16, # 5, p. 2807 - 2814 [3] Green Chemistry, 2014, vol. 16, # 3, p. 1248 - 1254 [4] Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3855 - 3863 [5] Journal of Molecular Catalysis A: Chemical, 2016, vol. 420, p. 45 - 49 [6] Molecular Catalysis, 2018, vol. 453, p. 121 - 131

路线2：

• 产率：100%
• 合成条件：With bromine In chloroform at 20℃; for 2 h;
• 实验步骤：实施例8：（E）-5- [2-（1H-吲唑-3-基）乙烯基] -2-（2-吗啉代乙氧基）苯甲酰胺（化合物8）步骤1 4-羟基苯甲醛溶液（10.0g，81.9mmol）在氯仿（100mL）中加入溴（4.30mL，83.5mmol），然后在室温下搅拌2小时。向反应混合物中加入水（100mL），减压蒸发有机层的溶剂，得到3-溴-4-羟基苯甲醛，为淡黄色固体（定量收率）。1H-NMR（270MHz，CDCl3）δ6.27（s，1H），7.15（d，J = 8.4Hz，1H），7.78（dd，J = 1.9,8.4Hz，1H），8.04（d，J = 1.9Hz，1H），9.83（s，1H）。ESI-MS（m / z）; 199,201 [M-H] -
• 参考文献： [1] Patent: EP1652842, 2006, A1. Location in patent: Page/Page column 31 [2] Patent: EP1650194, 2006, A1. Location in patent: Page/Page column 32 [3] Tetrahedron Letters, 2005, vol. 46, # 51, p. 8959 - 8963 [4] Journal of the Chilean Chemical Society, 2011, vol. 56, # 4, p. 863 - 865 [5] Tetrahedron Letters, 1980, vol. 21, p. 4931 - 4934 [6] Patent: CN107118087, 2017, A. Location in patent: Paragraph 0015; 0030; 0034; 0038; 0042; 0046 [7] Tetrahedron Letters, 1997, vol. 38, # 27, p. 4865 - 4868 [8] Tetrahedron, 2005, vol. 61, # 30, p. 7144 - 7152 [9] European Journal of Medicinal Chemistry, 2018, vol. 146, p. 668 - 677 [10] Chinese Chemical Letters, 2011, vol. 22, # 10, p. 1135 - 1138 [11] Journal of Organic Chemistry, 2013, vol. 78, # 17, p. 8680 - 8688 [12] European Journal of Organic Chemistry, 2015, vol. 2015, # 17, p. 3760 - 3766 [13] Patent: WO2010/127212, 2010, A1. Location in patent: Page/Page column 37 [14] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2016, vol. 46, # 6, p. 832 - 837 [15] Patent: US2004/19016, 2004, A1. Location in patent: Page/Page column 39 [16] Journal of Organometallic Chemistry, 2003, vol. 668, # 1-2, p. 101 - 122 [17] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 5, p. 1549 - 1553 [18] Archiv der Pharmazie (Weinheim, Germany), 1989, vol. 322, p. 477 - 482 [19] Asian Journal of Chemistry, 2018, vol. 30, # 8, p. 1892 - 1896 [20] Organic Letters, 2002, vol. 4, # 16, p. 2675 - 2678 [21] Journal of Medicinal Chemistry, 2003, vol. 46, # 15, p. 3193 - 3196 [22] Patent: US2004/19016, 2004, A1. Location in patent: Page/Page column 48 [23] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 7, p. 2464 - 2473 [24] Patent: US6632963, 2003, B1. Location in patent: Page/Page column 13 [25] Tetrahedron Letters, 1993, vol. 34, # 46, p. 7401 - 7404 [26] Journal of the Indian Chemical Society, 1988, vol. 65, # 3, p. 187 - 191 [27] Journal of the Chemical Society, Chemical Communications, 1987, # 14, p. 1102 - 1104 [28] Russian Journal of Organic Chemistry, 1993, vol. 29, # 11.2, p. 1868 - 1870 [29] Zhurnal Organicheskoi Khimii, 1993, vol. 29, # 11, p. 2251 - 2254 [30] South African Journal of Chemistry, 2006, vol. 59, p. 125 - 128 [31] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3540 - 3560 [32] Journal of Labelled Compounds and Radiopharmaceuticals, 2009, vol. 52, # 13, p. 563 - 565 [33] Journal of Medicinal Chemistry, 2012, vol. 55, # 20, p. 8969 - 8973 [34] Green Chemistry, 2012, vol. 14, # 6, p. 1673 - 1679

路线3：

• 产率：87%
• 合成条件：With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper diacetate In water; acetonitrile at 20℃; for 4 h; Green chemistry
• 实验步骤：一般步骤：将醇（5.0mmol），Cu（OAc）2（9.1mg，0.05mmol）和TEMPO（7.8mg，0.05mmol）在CH 3 CN / H 2 O（5 / 10mL）中的混合物在室温下搅拌指定时间。在反应完成后（通过TLC监测，洗脱液：石油醚/乙酸乙酯= 4/1），将二氯甲烷（10mL）加入到所得混合物中。分离二氯甲烷相，水相进一步用二氯甲烷（10mL×2）萃取。合并的有机层用无水硫酸钠干燥并浓缩，得到残余物，将其通过柱色谱（洗脱剂：石油醚/乙酸乙酯= 10/1）纯化，得到所需产物。
• 参考文献： [1] Tetrahedron Letters, 2014, vol. 55, # 10, p. 1677 - 1681