论文编号:ZY038论文字数:8362,页数:27
摘 要：N-(4-氯苯基)-2,2-二甲基丙酰胺是合成艾滋病病毒非转录酶抑制剂依法韦伦的重要中间体。本文以对氯苯胺为原料，与2,2-二甲基丙酰氯反应得到N-(4-氯苯基)-2,2-二甲基丙酰胺。研究了反应时间、溶剂、敷酸剂和原料的投料比对反应收率的影响，结果表明以甲苯为溶剂，2,2-二甲基丙酰氯与对氯苯胺的投料比为1.15：1，反应时间为3.5h，氢氧化钠为敷酸剂，反应的收率为93%，通过在乙酸乙酯中重结晶的纯化方式，采用液相色谱对产品的纯度进行分析，流动相为乙腈：水：磷酸= 40：60：0.1，检测波长为245nm色谱柱为Alltima C-8，产物纯度高达99.8%。同时对N-(4-氯苯基)-2,2-二甲基丙酰胺的合成进行了初探。
关键词：对氯苯胺；依法韦伦；纯化；N-(4-氯苯基)-2,2-二甲基丙酰胺
Abstract: N-(4-Chlorophenyl)-2,2-dimethylpropanamide is an important intermediate for the synthesis of an HIV-1 Reverse Transcriptase Inhibitor. This study start with 4-chloroaniline, with reaction of 2,2-dimethylpropanoyl chloride. With the study of the material, the ratio of material, the reation time and the solvent, the best result is that: with the 30% aqueous sodium hydroxide, the ratio of 4-chloroaniline and 2,2-dimethyl- propanoyl chloride is 1:1.15, react at 3.5 hours, with the yield. of N-(4-Chlorophenyl)-2,2-dimethylpropanamide. 93% is got By recrystallization in ethyl acetate purification methods, HPLC was used to analyze the purity of products, mobile phase of acetonitrile: water: phosphoric acid = 40:60:0.1, detection wavelength of 245nm for C-8, a product of purity as high as 99.8%. At the same time, a preliminary study of 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone is done.
Keywords: Efavirenz; 4-chloroaniline; purification; N-(4-Chlorophenyl)-2,2- dimethylpropanamide
目 录
中文摘要I
英文摘要II
目录III
1. 绪论1
1.1 前言1
1.2 依法韦伦的合成路线3
1.3 N-(4-氯苯基)-2,2-二甲基丙酰胺的合成6
2. 实验部分9
2.1 实验仪器和试剂9
2.2 实验步骤10
3. 结果与讨论12
3.1 最佳反应时间的选取12
3.2 最佳溶剂的选取13
3.3 最佳敷酸剂的选取14
3.4 2,2-二甲基丙酰氯投料量的研究14
3.5 4-氯-2-三氟乙酰基苯胺合成的初探16
4．总结与展望17
4.1 总结17
4.2 展望17
致谢19
参考文献20
附录22
N-(4-氯苯基)-2,2-二甲基丙酰胺的合成和纯化......