3958-60-9 2-硝基苄溴

运输信息：常温运输。危险描述：危险品运输编号UN 3261 8/PG 2，WGK Germany:3，F:4.8-19-21，危险等级8，包装类别II，海关编码29049085，存储类别8A - 可燃，腐蚀性物质，危险性类别：严重眼损伤 类别1，皮肤腐蚀 类别1B。

有机合成中间体，用于生产祛痰剂溴已胺盐酸盐（溴己胺盐酸盐）

医药

路线1：邻硝基甲苯氢溴酸-过氧化氢溴化法

• 产率：98.5%
• 合成条件：Stage #1: With 2,2'-azobis(isobutyronitrile) In 1,2-dichloro-ethane for 0.33 h; Stage #2: With hydrogen bromide; dihydrogen peroxide In 1,2-dichloro-ethane at 72 - 75℃; for 2 h;
• 实验步骤：在5000L溴化反应器中，依次加入300kg二氯乙烷，226kg邻硝基甲苯和27kg偶氮二异丁腈。搅拌20分钟后，将溶液泵入高槽中备用;并再次放入溴化反应器。将300千克二氯乙烷和226千克邻硝基甲苯充分混合，加入889.03千克40％氢溴酸，并将混合物在72至75℃的温度下搅拌。在上部槽中将混合溶液和448.26kg的30％过氧化氢以1：4的加速度缓慢滴加到溴化反应器中。在添加结束时，反应持续2小时。反应完成后，将温度降至室温，并对反应液进行HPLC分析。原料的转化率大于99.0％，并且没有产生诸如二溴化产物的副产物。反应中原料，40％氢溴酸和30％过氧化氢的摩尔比为1：1.2：1.2。使溶液静置分层，分离上层水层;用600L水洗涤下层有机相后，减压蒸馏除去溶剂，用冷二氯乙烷冲洗，得到白色邻硝基苄基溴固体产物。它是98.5％。
• 参考文献：
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路线2：N-溴代琥珀酰亚胺/三苯基膦溴化法

• 产率：78%
• 合成条件：With N-Bromosuccinimide; triphenylphosphine In acetonitrile at 20℃; for 12 h; Cooling with ice
• 实验步骤：通用方法：向Ph3P（OAc）2溶液中加入3-苯基丙醇（1mmol，0.137mL）。通过TLC监测反应进程（表3，条目2）。反应完成后（0.3小时），过滤反应混合物以除去沉淀的NH4Br，然后蒸发溶剂。使用正己烷/EtOAc（3：1）作为洗脱剂，在硅胶上对粗混合物进行柱色谱，得到3-苯基丙基乙酸酯，收率为90％（0.159g）。
• 参考文献：
• [1] Tetrahedron Letters, 2013, vol. 54, # 14, p. 1813 - 1816

路线3：溴素直接溴化法

• 合成条件：将四氯化碳、邻硝基甲苯及偶氮二异丁腈的水溶液加入反应罐中,搅拌加热,滴加溴的四氯化碳溶液,保持回流至滴加完毕,继续回流5~6h
• 实验步骤：溴化生成邻硝基苄基溴