NXL-104合成及苯胺衍生物單溴代反應(yīng)的研究
發(fā)布時間：2019-01-18 11:27
【摘要】：本學(xué)位論文共分為兩部分,包括新型β-內(nèi)酰胺酶抑制劑阿維巴坦(NXL-104)的合成和苯胺及其苯環(huán)衍生物的單溴代反應(yīng)。第一部分內(nèi)容為新型β-內(nèi)酰胺酶抑制劑阿維巴坦的合成研究。首先對β-內(nèi)酰胺酶抑制劑的作用、種類和合成方法做了綜述。然后在對國內(nèi)外已有合成路線分析的基礎(chǔ)上,我們設(shè)計了一條合成阿維巴坦的改進路線,以L-焦谷氨酸為起始原料,經(jīng)保護、親核取代開環(huán)、成肟、成環(huán)、加氫、磺化成鹽等十二步反應(yīng)合成了NXL-104。該合成路線提高了關(guān)鍵反應(yīng)的產(chǎn)率、簡化了多步反應(yīng)產(chǎn)物提純的方法,與文獻報道方法相比較,具有總產(chǎn)率高、易實現(xiàn)放大的優(yōu)點。第二部分內(nèi)容為苯胺及其苯環(huán)衍生物的單溴代反應(yīng)的研究。以丙酸、甲基叔丁基醚和三乙胺的緩沖體系為溶劑,在低溫條件下用溴素直接對苯胺及其苯環(huán)衍生物進行溴代,高產(chǎn)率得到單溴代產(chǎn)物,產(chǎn)物結(jié)構(gòu)均由~1H NMR確認無誤。與文獻報道方法相比較,該方法減少了副反應(yīng)的發(fā)生,同時回收一半量的溴原子,避免了對環(huán)境的污染,也避免了浪費。該溴代方法簡單、高效、經(jīng)濟、環(huán)保而且不用金屬催化劑,易實現(xiàn)規(guī)�；a(chǎn)。
[Abstract]:This dissertation is divided into two parts, including the synthesis of new 尾 -lactamase inhibitor Avibactam (NXL-104) and the monobromination of aniline and its benzene-ring derivatives. The first part is about the synthesis of new 尾-lactamase inhibitor Avibactam. Firstly, the effects, types and synthesis methods of 尾-lactamase inhibitors were reviewed. Then, based on the analysis of the existing synthetic routes at home and abroad, we designed an improved route for the synthesis of Avibartan, using L-pyroglutamic acid as the starting material, protected, nucleophilic substitution, ring opening, oxime formation, ring formation, hydrogenation. NXL-104. was synthesized by 12 steps reaction, such as sulfonation and salt formation. The synthetic route improves the yield of the key reaction and simplifies the method of purification of the multi-step reaction product. Compared with the method reported in the literature, it has the advantages of high total yield and easy amplification. The second part deals with the monobromination of aniline and its benzene-ring derivatives. With the buffer system of propionic acid, methyl tert-Ding Ji ether and triethylamine as solvent, bromine was directly brominated on aniline and its benzene-ring derivatives at low temperature. The monobrominated product was obtained in high yield, and the structure of the product was confirmed by ~ 1H NMR. Compared with the reported method, this method reduces the occurrence of side reactions and reclaims half of the bromine atoms, thus avoiding environmental pollution and waste. The bromination method is simple, efficient, economical, environmentally friendly and easy to scale production without metal catalyst.
【學(xué)位授予單位】：煙臺大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：O621.25
，
本文編號：2410665
[Abstract]:This dissertation is divided into two parts, including the synthesis of new 尾 -lactamase inhibitor Avibactam (NXL-104) and the monobromination of aniline and its benzene-ring derivatives. The first part is about the synthesis of new 尾-lactamase inhibitor Avibactam. Firstly, the effects, types and synthesis methods of 尾-lactamase inhibitors were reviewed. Then, based on the analysis of the existing synthetic routes at home and abroad, we designed an improved route for the synthesis of Avibartan, using L-pyroglutamic acid as the starting material, protected, nucleophilic substitution, ring opening, oxime formation, ring formation, hydrogenation. NXL-104. was synthesized by 12 steps reaction, such as sulfonation and salt formation. The synthetic route improves the yield of the key reaction and simplifies the method of purification of the multi-step reaction product. Compared with the method reported in the literature, it has the advantages of high total yield and easy amplification. The second part deals with the monobromination of aniline and its benzene-ring derivatives. With the buffer system of propionic acid, methyl tert-Ding Ji ether and triethylamine as solvent, bromine was directly brominated on aniline and its benzene-ring derivatives at low temperature. The monobrominated product was obtained in high yield, and the structure of the product was confirmed by ~ 1H NMR. Compared with the reported method, this method reduces the occurrence of side reactions and reclaims half of the bromine atoms, thus avoiding environmental pollution and waste. The bromination method is simple, efficient, economical, environmentally friendly and easy to scale production without metal catalyst.
【學(xué)位授予單位】：煙臺大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：O621.25
，
本文編號：2410665
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