摘要:噁唑杂环化合物是一类常见的含有氧、氮等杂原子环状化合物，广泛应用于医药，材料和有机合成的各个领域。在有机化合物中引入氟原子可以极大的改变化合物的物理化学性质及在生物体内的生理活性。因而在杂环化合物中引入氟原子的研究引起了国内外化学工作者的广泛兴趣。
随着抗生素的大量使用甚至是滥用，使细菌的耐药性问题口益严重。噁唑烷酮类化合物作为一类新型的抗菌剂，其对革兰氏阳性菌的抗菌谱非常广，抗菌活性强，且与其他抗菌药物无交叉耐药现象。为此本课题设计合成了以利奈唑胺为母体,在噁唑环上引入氟烷基合成一种新型噁唑烷酮化合物即4-氟烷基-噁唑烷酮，并且摸索出了一条合成路线，本论文主要研究了碱性条件下N-环合法合成4-氟烷基-噁唑烷酮，以相应的芳基胺为原料，通过与氯甲酸烯丙基酯反应得到相应的芳基氨基甲酸烯丙基酯，氟烷基碘与芳基氨基甲酸烯丙基酯发生自由基加成反应，得到相应的加成产物，加成产物发生分子内的N-环合反应，得到终产物4-氟烷基-2-噁唑烷酮。实验中得到的关键中间体和最终目标产物通过了核磁以及高分辩率质谱的确认,通过工艺条件对照实验，本文优化了这几步反应的实验过程，增强了各步反应的稳定性和重复性，提高了产物收率和纯度，降低了实验成本。10555
关键词： 2-噁唑烷酮；氟烷基化；合成; N-环合法
Design and synthesis of novel double oxazolidinone compounds
Abstract : Oxazole heterocyclic compounds is a common type of cyclic compounds containing oxygen, nitrogen and other heteroatoms, widely used in medicine, materials and organic synthesis. The introduction of fluorine atom into organic compounds may greatly change their biological activities and the physical and chemical properties of the compound. Thus, the introduction of fluorine atoms to the oxazole heterocyclic compounds caused chemists wide interest.
With the widely use of antibiotics and even abuse, make the drug resistance problem increasingly serious. Oxazolidinone derivatives as a new class of antibacterial agents, the Gram-positive bacteria is very wide antimicrobial spectrum, strong antibacterial activity, and no cross resistance with other antibacterial drugs phenomenon.This dissertation make linezolid as matrix, the on the introduction the fluoroalkyl on the oxazole ring designed and synthesized a novel oxazolidinone compound which is 4- fluorine alkyl - oxazolidinone, and explored a synthetic route, This paper is focused on the synthesis of 4-fluoroalkyl-2-oxazolidinones by N-cyclization under alkaline conditions,The aromatic amine reacted with chloroformate allyl ester to give allyl arylcarbamates.Then the allyl arylcarbamates reacted with fluoroalkyl iodide initiated to give the corresponding adducts. The intramolecular N-cyclization of adducts was carried out to obtain the final product 4-fluoralkyoxazolidin-2-one.The key intermediates obtained in the experiment and the final product were confirmed by NMR and the high resolution mass spectrometry, Through the contrast experiment, we optimize experiment condition, enhance stability and reproducibility of each reaction, improve the productivity and purity of product, reduce production cost .
Keywords : 2-Oxazolidone ;Fluorine alkylation; Synthesis ; N-cyclization
目录
1 前言 1
1.1 抗菌药的概况 1
1.2 噁唑烷酮 2
1.2.1 噁唑烷酮类抗菌药概述2
1.2.2 2-噁唑烷酮化合物3
1.3 利奈唑胺 4
1.3.1 利奈唑胺概述 4 新型双噁唑烷酮类化合物的设计与合成:http://www.751com.cn/yixue/lunwen_9649.html