2-巯基-5-甲氧基-1H-苯并咪唑合成工艺研究

论文编号:HG232  论文字数:9627,页数:17

摘要：本文主要研究奥美拉唑(Omeprazole)关键中间体2-巯基-5-甲氧基-1H-苯并咪唑的合成，并且对其合成工艺优化改进。2-巯基-5-甲氧基-1H-苯并咪唑的合成以扑热息痛为原料，经过5步化学反应得到。其中关键步骤是2-硝基-4-甲氧基苯胺经还原环合作用得到2-巯基-5-甲氧基-1H-苯并咪唑。
 经探索性实验，选择反应时间、温度、2-硝基-4-甲氧基苯胺与铁粉的摩尔比、2-硝基-4-甲氧基苯胺与二硫化碳摩尔比四因素，对2-硝基-4-甲氧基苯胺经还原环合作用进行正交优化实验，得到最佳工艺条件是反应温度60℃、反应时间8h、2-硝基-4-甲氧基苯胺与铁粉的摩尔比1:3、2-硝基-4-甲氧基苯胺与二硫化碳摩尔比1:2。
 以扑热息痛为原料，经甲基化，硝化，水解得到2-硝基-4-甲氧基苯胺，以铁粉-盐酸来还原硝基，在二硫化碳作用下环合得到2-巯基-5-甲氧基-1H-苯并咪唑，收率为60.2%。
关键词: 扑热息痛；2-巯基-5-甲氧基-1H-苯并咪唑；中间体；合成
Abstract:The dissertation mainly discusses the preparation of the key intermediate of Omeprazole——2-mercapto-5-methoxy-1H-enzimidazole and the reaction conditions were optimized.
 In summary, 2-mercapto-5-methoxy-1H- benzimidazole is prepared in five reaction steps  from commercially available raw materials paracetamol. The key step is for 2-nitro-4-methoxy - aniline by reducing and cyclization. After experiment, we obtain the optimum reaction condition: ratio of N-(2-nitro-4-methoxy)-phenyldiamine and Fe is 1:3, the reaction temperature is 60℃, the reaction time is for 8 hours, ratio of N-(2-nitro-4-methoxy)-phenyldiamine and CS2 is 1:2.
 Take paracetamol as raw materials, after methylation, nitration, hydrolysis ,obtains   2-nitro-4-methoxy – aniline, iron-hydrochloric acid as a reducing agent , through carbon disulfide completed cyclization, finally gains 2-mercapto-5-methoxy-1H – benzimidazole, total yield is 60.2%.
 Keywords: Paracetamol;2-mercapto-5-methoxy-1H-enzimidazole; Intermediate; Synthesis

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