作为有机合成中间体,用于合成医药、农药等精细化工产品,包括抗炎症药、2,6-二氯苯腈除草剂、植物生长调节剂、环氧树脂固化剂等。
医药; 农药; 精细化工
合成路线 1(2,6-二氯苯甲酸为原料)
- 步骤: 在0℃及氮气保护下,将2,6-二氯苯甲酸(0.1g,0.52mmol)溶解于二氯甲烷(5mL)中,加入N,N-二甲基甲酰胺(3.83mg,52.35μmol)作为催化剂,随后缓慢加入草酰二氯(0.20g,1.57mmol)。反应混合物在0℃下逐滴加入,并在0至20℃范围内搅拌2小时。通过薄层色谱(TLC,展开剂比例为石油醚:乙酸乙酯=5:1,Rf=0.77)监测反应进程,确认原料完全消耗后,减压除去溶剂,得到2,6-二氯苯甲酰氯(0.11g,0.37mmol,收率70%),产物无需进一步纯化即可用于下一步反应。
- 条件: 溶剂为二氯甲烷,催化剂为N,N-二甲基甲酰胺,反应温度0-20℃,反应时间2小时,氮气保护,TLC监测(石油醚:乙酸乙酯=5:1),收率70%。
- 后续反应: 将28g-int(65mg,0.17mmol,盐酸盐形式)和N,N-二异丙基乙胺(DIEA,87.3mg,0.68mmol)溶解于二氯甲烷(10mL)中,在0℃及氮气保护下,缓慢滴加2,6-二氯苯甲酰氯(88.43mg,0.42mmol)的二氯甲烷(5mL)溶液。反应混合物在0-20℃下搅拌16小时,LCMS分析显示28g-int完全消耗并生成28h-int。减压除去溶剂后,粗产物通过制备型高效液相色谱(HPLC)纯化,得到纯的28h-int。
- HPLC纯化条件: Gilson 281半制备型HPLC系统,流动相A:0.075% TFA水溶液,流动相B:乙腈,梯度洗脱(0分钟20% B,12分钟40% B),色谱柱YMC-Actus Triart C18(150×30mm,5μm),流速20mL/min,检测波长220和254nm。
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