四步法合成2-乙基-4-甲氧基苯胺

以氯霉素的副产物邻硝基乙苯为原料,经Bamberger反应、乙酰化反应、o-甲基化反应和水解反应4步合成了可作为5-甲氧基吲哚合成原料的2-乙基-4-甲氧基苯胺;对该工艺路线的关键步骤Bamberger反应进行了工艺条件优化。实验结果表明,邻硝基乙苯经4步反应后,2-乙基-4-甲氧基苯胺的总收率为55%左右;Bamberger反应的优化条件为:以硫酸溶液为介质,H+]为4.42mol/L,Pt/C催化剂质量分数为1.84%(基于邻硝基乙苯的质量),在此条件下,Bamberger反应产物3-乙基-4-氨基苯酚的收率可达81.7%;硫酸中加入磷钼酸不利于羟基苯胺中间体的稳定存在。同时还对各步反应产物进行了红外光谱和核磁共振表征,确定了各步反应的产物结构。

Synthesis of 2-Ethyl-4-Methoxy Aniline Via Four-Step Process

2-Ethyl-4-methoxy aniline was synthesized from o-nitroethylbenzene,a byproduct from chloramphenicol industry,through a four-step process including Bamberger reaction,acetylation,o-methylation and hydrolysis.Product 2-ethyl-4-methoxy aniline is considered as a promising raw material with big potential for producing 5-methoxy indole,an important fine chemical used in synthesis of indole derivatives.Total yield of 2-ethyl-4-methoxy aniline at the end of four step process is about 55%.The Bamberger reaction is the key step.The optimal conditions for the key step are as follows: sulfuric acid as reaction medium, 4.42 mol/L and mass fraction of Pt/C catalyst 1.84%(based on o-nitroethylbenzene).Yield of this key step product-3-ethyl-4-amino phenol is 81.7%.Addition of phosphomolybdic acid to H2SO4 is not favorable to stability of intermediate hydroxylamine.Structures of product and all intermediates were identified and confirmed by means of IR and NMR.