氟哌酸合成工藝優化

制藥工程論文編號:ZY100    論文字數:6477,頁數:18

目  錄
中文摘要 I
英文摘要 II
目錄 III
1. 緒論 1
 1.1 前言 1
 1.2 研究現狀 1
2. 實驗部分 5
 2.1 實驗儀器和試劑 5
 2.1.1 實驗儀器 5
 2.1.2 實驗試劑 5
2.2 實驗操作步驟 5
3. 結果與討論 8
 3.1 正交實驗方案設計 8
3.2 實驗結果數據處理 9
4．總結與展望 12
 4.1 總結 12
 4.2 展望 12
致謝 14
參考文獻 15

摘要：氟哌酸是第三代喹諾酮類抗菌藥物的優秀代表之一, 它的合成路線有很多種，而以形成硼螯合物的方法倍受關注。中間體(1-乙基-6-氟-7-氯-1,4-二氫-4-氧代-喹啉-3-羧酸-O3O4)-二-(乙酸-O)-硼與哌嗪的縮合反應是氟哌酸生產工藝中的關鍵步驟。本論文用正交試驗法對氟哌酸縮哌反應條件進行了優化設計。通過考察縮哌反應的反應溫度、反應時間、反應物的配料比和溶劑的用量等四種因素，用L16(44)正交試驗篩選得出該反應的最佳工藝條件為：反應溫度70℃，反應時間6h，無水哌嗪:螯合物摩爾比=4:1，溶劑使用量甲苯:DMF質量比=50:20。

關鍵詞：氟哌酸；無水哌嗪；縮合；正交設計

Abstract: Norfloxacin is one of the outstanding representatives of the third generation of quinolone antibiotics，and there are a good deal of methods for synthesizing it. Forming boride is the most useful method. Piperazine condensation of intermediate (1-ethyl-6-fluoride-7-chloro-1,4-dihydro-4-oxo-
quinoline-3-carboxylic acid-O3O4)-bis-(acetate-O)-boron is a crucial step in norfloxacin production. Optimizing the best conditions of piperazine condensation by orthogonal test. Reaction temperature, time, reactant mixture ratio and the amount of solvent were discussed. The best condition of piperazine condensation was investigated by L16(44) orthogonal design. At the temperature of 70℃, 6 hours, molar ratio of anhydrous piperazine : chelate complex = 4:1, dosage of solvents toluene : DMF = 50 : 20 by mass ratio are the best conditions.

Key words: Norfloxacin; Anhydrous piperazine; Condensation; Orthogonal design