1,8-萘啶酮类化合物的高效合成  

Study on Efficient Synthesis of 1,8-naphthyridone

作　　者：郭安路 开丽比努尔·艾山 许利清 王栋[1] Guo Anlu;Aishan Kalbinur;Xu Liqing;Wang Dong(Xinjiang University,Urumqi 830017,China)

机构地区：[1]新疆大学,新疆乌鲁木齐830017

出　　处：《广东化工》2024年第13期21-24,共4页Guangdong Chemical Industry

基　　金：新疆维吾尔自治区大学生创新训练计划项目(S202210755040);国家自然科学基金(22261051)。

摘　　要：含氮芳香杂环是非常重要的一类有机化合物,其中1,8-萘啶酮是数个已上市小分子药物的母体结构。目前已报道的合成方法存在步骤冗长,原子效率低的问题。本论文以价廉易得的烟酸甲酯为原料,通过克莱森酯缩合反应,氧化反应,活化剂作用下C-H键胺化反应以及酸催化关环反应合成了1,8-萘啶酮。优化了氧化反应中的氧化剂,并研究了不同活化剂对胺化反应的影响。采用优化后的工艺,实现了该合成路线克级规模的反应,最终通过四步反应,约20%总产率合成了目标产物。Aromatic Nitrogen heterocycles are a very important class of organic compounds,of which 1,8-naphthyridone is the parent structure of several marketed small molecule drugs.The currently reported synthetic methods have problems with lengthy steps and low atom efficiency.Using inexpensive and readily available methyl nicotinate as the starting material,1,8-naphthyridone is prepared through Claisen condensation,oxidation,activating reagent mediated C-H amination and acid catalyzed cyclization.The oxidant has been optimized and the effect of different activating reagents on the amination reaction has been investigated.The optimized process is used to achieve a gram scale reaction of the synthesis route,and the target product is synthesized in a total yield of about 20%through four steps.

关 键 词：1 8-萘啶酮 色酮 电子等排体置换 合成方法 含氮杂环化合物 吡啶氮氧化物 C-H键活化 

分 类 号：TQ[化学工程]