摘要：本课题的内容就是关于(R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)的制备。并对反应条件进行优化研究，选择出最佳的工艺条件。本毕业论文由D-叔亮氨酸经过四步反应后得到(R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)。研究了在不同反应条件下得到不同的产率。在第一步反应中，D-叔亮氨酸与硼氢化钠和碘的摩尔比为1:2.5:1，得到D-叔亮氨醇，其产率为83.1%，反应第二步，二甲基丙二酸与二氯亚砜和二甲基甲酰胺的摩尔比为1:5:0.09，得到二甲基丙二酰氯，产率为85.7%。反应第三步，D-叔亮氨醇与二甲基丙二酰氯和三乙胺的摩尔比为1:0.5:2.5，得到二甲基丙二酰基叔亮氨酸醇，产率为92.2%。反应第四步，二甲基丙二酰基叔亮氨酸醇与七钼酸铵摩尔比为1:0.2，得到(R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)，产率为90.1%。该路线的总收率为58.6%。
关键词：(R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)；D-叔亮氨酸；合成；西司他丁；21180
Preparation of (R,R)-(+)-2,2'-Isopropylidenebis(4-tert-butyl-2-oxazoline)
Abstract： The contents of the subject is preparing (R,R)-(+)-2,2'-Isopropylidenebis(4-tert-butyl-2-oxazoline). And research the response of condition, selecting the best process conditions. We can get (R,R)-(+)-2,2'-Isopropylidenebis(4-tert-butyl-2-oxazoline) by D-tert-Leucine through four-steps reactions. Studied at different reaction condition can get different yield. The first reaction shows that the highest yield rate is under the mole ratio of D-tert-Leucine with Sodium borohydride and iodine is 1:2.5:1, yield of this step is 83.1%. The second step shows that the highest yield rate is under mole ratio of dimethyl-Propanedioic acid with thionylchloride and DMF is 1:5:0.09, yield of this step is 85.7%. The third reaction shows that the highest yield rate is under mole ratio of (R)-tert-leucinol with dimethymalonyldichloride and N,N-Diethylethanamine is 1:0.5:2.5, yield of this step is 92.2%. The fourth reaction shows that the highest yield rate is under mole ratio of dimethylmalonamidyl-tert-Leucinoldimethyl-1-butan with Ammoinum heptamolybdate is 1:0.2, yield of this step is 90.1%. The total yield of this three-step reaction is 58.6%.
Key words: (R,R)-(+)-2,2'-Isopropylidenebis(4-tert-butyl-2-oxazoline); D-tert-Leucine; synthesis; Cilastatin
目 录
1 绪论 4
1.1 西司他丁国内外研究现状概述 5
1.2 (S)-(+)-2,2二甲基环丙烷甲酰胺的合成路线 6
1.3 (R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)的介绍 10
2 (R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)的合成实验 11
2.1 使用的材料试剂、仪器设备 11
2.1.1 使用的材料试剂 11
2.1.2 仪器设备 12
2.2 (R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)的合成 13
2.2.1 (R,R)-(+)-2,2′-异亚丙基双(4-叔丁基-2-噁唑啉)的合成路线概述 13
2.2.2 实验前的预处理 13
2.2.3 第一步反应 13
2.2.4 第二步的反应 14
2.2.5 第三步的反应 14
2.2.6第四步的反应 14
3 实验结果与讨论 15
3.1 反应第一步条件的优化 15
3.1.1反应物投料比对反应产率的影响 15
3.1.2反应时间对反应产率的影响 16
实验小结 16
3.2合成二甲基丙二酰氯条件的优化 16
3.2.1反应物投料比对反应产率的影响 17
3.2.2 实验原料的选择 17 (R,R)-(+)-2,2'-异亚丙基双(4-叔丁基-2-恶唑啉)的制备:http://www.youerw.com/huaxue/lunwen_13268.html