2-巰基-5-甲氧基-1H-苯并咪唑合成工藝研究

論文編號(hào):HG232  論文字?jǐn)?shù):9627,頁(yè)數(shù):17

摘要：本文主要研究奧美拉唑(Omeprazole)關(guān)鍵中間體2-巰基-5-甲氧基-1H-苯并咪唑的合成，并且對(duì)其合成工藝優(yōu)化改進(jìn)。2-巰基-5-甲氧基-1H-苯并咪唑的合成以撲熱息痛為原料，經(jīng)過(guò)5步化學(xué)反應(yīng)得到。其中關(guān)鍵步驟是2-硝基-4-甲氧基苯胺經(jīng)還原環(huán)合作用得到2-巰基-5-甲氧基-1H-苯并咪唑。
 經(jīng)探索性實(shí)驗(yàn)，選擇反應(yīng)時(shí)間、溫度、2-硝基-4-甲氧基苯胺與鐵粉的摩爾比、2-硝基-4-甲氧基苯胺與二硫化碳摩爾比四因素，對(duì)2-硝基-4-甲氧基苯胺經(jīng)還原環(huán)合作用進(jìn)行正交優(yōu)化實(shí)驗(yàn)，得到最佳工藝條件是反應(yīng)溫度60℃、反應(yīng)時(shí)間8h、2-硝基-4-甲氧基苯胺與鐵粉的摩爾比1:3、2-硝基-4-甲氧基苯胺與二硫化碳摩爾比1:2。
 以撲熱息痛為原料，經(jīng)甲基化，硝化，水解得到2-硝基-4-甲氧基苯胺，以鐵粉-鹽酸來(lái)還原硝基，在二硫化碳作用下環(huán)合得到2-巰基-5-甲氧基-1H-苯并咪唑，收率為60.2%。
關(guān)鍵詞: 撲熱息痛；2-巰基-5-甲氧基-1H-苯并咪唑；中間體；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