鲁苯哒唑中间体5-(4-氟苯磺酰氧基)-2-乙酰胺基硝基苯的合成

Synthesis of 5-(4-Fluorophenylsulfonyloxy)-2-acetamino-nitrobenzene as the Intermediate of Luxabendazole

5-（4-氟苯磺酰氧基）-2-乙酰胺基硝基苯是合成驱虫新药鲁苯哒唑药物的主要中间体之一。该文以对氨基苯酚为原料,与乙酸酐回流反应3 h,然后缓慢滴加w（HNO3）=98%的硝酸反应1.5 h,再慢慢滴加w（HNO3）=65%的硝酸反应1.5 h,反应温度控制在25℃,制得4-乙酰氧基-2-硝基苯基乙酰胺（Ⅰ）;Ⅰ与NaOH以n（Ⅰ）∶n（NaOH）=1∶0.25的比例在w（CH3CH2OH）=95%的乙醇中回流反应1 h,水解制得4-乙酰胺基-3-硝基苯酚（Ⅱ）;Ⅱ在25～30℃条件下与对氟苯磺酰氯以n（Ⅱ）∶n（对氟苯磺酰氯）=1∶1.1的比例进行缩合,反应4 h,制得5-（4-氟苯磺酰氧基）-2-乙酰胺基硝基苯（Ⅲ）,总收率65%（以对氨基苯酚计算）。用IR、HRMS、^1HNMR对最终产品结构进行了表征。该工作的新颖性,已为江苏省科技查新咨询中心2006年11月17日出具的第200632B2503543号《科技查新报告》所证实。

5-（4-Fluorophenylsulfonyloxy）-2-acetaminonitrobenzene is one of the main raw materials of Luxabendazole as a new anthelmintic. Starting from 4-aminophenol, reacting with acetic anhydride under reflux for 3 h,adding 98% HNO3 dropwise under stirring for 1.5 h,and then adding 65% HNO3 dropwise slowly for 1.5 h（the temperature not exceeding 25 ℃ ） ,4-acetoxy-2-nitroacetanilide（Ⅰ） was prepared. Then Ⅰ and NaOH in mole ratio 1：0. 25 reacted in 95% ethanol under reflux for 1 h to afford 4-acetamino-3-nitrophenol （ Ⅱ ）. Finally, 5-（4-fluorophenylsulfonyloxy） -2-acetaminonitrobenzene （ Ⅲ ） was obtained by condensation of Ⅱ and p-fluorobenzenesulfonyl chloride in mole ratio 1 ： 1.1 for 4 h at 25 - 30 ℃. The total yield of Ⅲ amounted to 65 %. Structures of the products were confirmed by IR, HRMS and ^1HNMR. The novelty of this procedure was confirmed in novelty search innovation report of science and technology offered by Jiangsu New Methods Consultation Center on 17th, November 2006 （ serial number 200632B2503543 ）.