L-4-硝基苯丙氨酸的合成研究  

Study on the Synthesis of L-4-Nitrophenylalanine

作　　者：刘金强[1] 钱超[1] 张涛[1] 陈新志[1] 

机构地区：[1]浙江大学化学工程与生物工程学系,浙江杭州310027

出　　处：《高校化学工程学报》2009年第6期1007-1012,共6页Journal of Chemical Engineering of Chinese Universities

基　　金：国家自然科学基金资助项目(20776127);国家科技支撑计划课题资助项目(2007BAI34B07);浙江省自然科学基金(Y4090045;R4090358)

摘　　要：L-4-硝基苯丙氨酸为合成众多药物的中间体。采用釜式反应器,以混酸(浓硫酸与浓硝酸)为硝化试剂对L-苯丙氨酸进行硝化反应,制备得到了目标产物。在浓硫酸与浓硝酸的体积比为2:1,反应温度为0℃,反应时间为3h的工艺条件下,该法制备L-4-硝基苯丙氨酸的收率达到65.2%。该法在反应过程中得到的副产物,经1H-NMR和13C-NMR鉴定了其结构,证明其为两分子间的缩合产物,据此推测了反应可能的机理。为了减少分子间的缩合反应,采用管式反应器对苯丙氨酸的硝化反应进行探索,并用正交实验法对反应条件进行了优化,结果表明,反应温度为50℃,反应时间为5min,混酸中浓硫酸与浓硝酸体积比为2:1,收率可达80.9%。与釜式反应相比,管式反应器能够有效避免分子间缩合的副反应,并能加快反应速率,提高反应效率。L-4-Nitrophenylalanine is an important intermediate in many medicine syntheses. It is commonly synthesized by the nitration of L-phenylalanine with mixed acid nitrate composed of concentrated H2SO4 and concentrated HNO3 in a batch reactor; and the yield of L-4-Nitrophenylalanine can reach 65.2% when the volume ratio of concentrated H2SO4 and concentrated HNO3 of 2：1 is used at reaction temperature of 0℃ with reaction time of 3 h. The structure of by-product was identified with ^1H-NMR and ^13C-NMR, and the by-product was proved to be a condensation product of L-4-nitrophenylalanine and L-2-nitrophenylalanine. Based on the by-product structure found, the possible nitration mechanism was proposed. In order to depress the side reaction, the tubular reactor was used for the nitration of L-phenylalanine. The orthogonal experiments were adopted to optimize the reaction conditions of nitration with tubular reactor, and the results show that, under the found optimized conditions of the volume ratio of concentrated H2SO4 and concentrated HNO3 equal to 2：1, the reaction temperature of 50℃ and reaction time of 5 min, the L-4-nitrophenylalanine yield could reach 80.9%. Compared with the batch nitration, the nitration of L-phenylalanine with tubular reactor is more adoptable for it can free of dimerization of L-4-nitrophenylalanine and L-2-nitrophenylalanine; moreover, it can also get a higher reaction rate and enhance the reaction efficiency.

关 键 词：L-苯丙氨酸 L-4-硝基苯丙氨酸 硝化 管式反应器 

分 类 号：O621.255.4[理学—有机化学] TQ246.1[理学—化学]