5-溴-2-(4-甲基哌啶-1-基)嘧啶的晶体结构及密度泛函理论研究  

Crystal Structure and Density Functional Theory of 5-Bromo-2-(4-Methylpiperidin-1-yl)Pyrimidine

作　　者：叶文君 陈玉梅 陈冬梅 郭倩 周志旭[1,2] YE Wenjun;CHEN Yumei;CHEN Dongmei;GUO Qian;ZHOU Zhixu(School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China;Guizhou Engineering Laboratory for Synthetic Drugs, Guiyang 550025, China)

机构地区：[1]贵州大学药学院,贵阳550025 [2]贵州省合成药物工程实验室,贵阳550025

出　　处：《人工晶体学报》2021年第11期2116-2122,共7页Journal of Synthetic Crystals

基　　金：贵州省科技计划(黔科合基础[2020]1Y393)。

摘　　要：嘧啶类衍生物在医药、化工和功能材料等领域有着重要应用。在药物研发,特别是抗癌药物研发领域中,5-溴-2-(4-甲基哌啶-1-基)嘧啶是一种含嘧啶环的重要中间体。本文通过一步芳香亲核取代反应合成了5-溴-2-(4-甲基哌啶-1-基)嘧啶,经溶液结晶法获得其单晶体,并进行了晶体学分析(晶系:正交晶系,空间群:P2_(1)2_(1)2_(1),晶胞:a=10.18142(6)nm,b=17.6200(8)nm,c=10.17902(5)nm,Z=4,ρ_(c)=1.478 g·cm^(-3),R=0.0566,wR=0.1688)。标题化合物的最优结构和前线轨道能量在B3LYP/6-311G(d,p)模式下使用密度泛函理论(DFT)计算得到,经DFT优化的结果与实验确定的数据相近。此外,为进一步揭示标题化合物的物理化学性质,通过DFT进一步研究了分子的静电式和前线分子轨道。Pyrimidine derivatives have important applications in the fields of medicine,chemical industry and functional materials.In drug discovery,especially in the research and development of anticancer drugs,5-bromo-2-(4-methylpiperidin-1-yl)pyrimidine is a significant intermediate containing a pyrimidine ring.In this paper,5-bromo-2-(4-methylpiperidin-1-yl)pyrimidine was prepared by one-step aromatic nucleophilic substitution reaction,and its single crystal was obtained by solution crystallization,and crystallographic analysis was carried out(crystal system:orthorhombic,space group:P2_(1)2_(1)2_(1),unit cell:a=10.18142(6)nm,b=17.6200(8)nm,c=10.17902(5)nm,Z=4,ρ_(c)=1.478 g·cm^(-3),R=0.0566,wR=0.1688).By the way,the crystal structure shows that the intramolecular hydrogen bonds and the van der Waals forces jointly maintain the stable arrangement of molecules space,and hydrogen bonds are one of the key factors for crystal stability.In B3LYP/6-311G(d,p)mode,density functional theory(DFT)was used to calculate the optimal structure and frontier orbit energy,and the result of DFT optimization is similar to the experimentally determined data.The structure and the results are basically the same.In addition,in order to further reveal the physicochemical properties of the title compound,the molecular electrostatic formula and frontier molecular orbital were further investigated by DFT.

关 键 词：5-溴-2-(4-甲基哌啶-1-基)嘧啶 一步法 溶液结晶法 晶体结构 密度泛函理论 合成 

分 类 号：O626[理学—有机化学]