1,4,7,10-四氮杂环十二烷及其N-选择性取代衍生物的合成工艺研究

发布时间：2018-05-02 19:23

本文选题：cyclen + 对称四氮杂化合物　；参考：《华东师范大学》2017年硕士论文

【摘要】：氮杂大环化合物及其N-取代衍生物,因具有易与金属阳离子络合的性质而备受关注。四氮杂环的选择性N-官能化,可通过调节配位亚基的性质来允许微调其络合物性质。此前多是研究各种不对称氮杂大环化合物的合成(受氮杂环和烷基化试剂影响较大),但对称四氮杂化合物的合成研究较少。另吡啶基三氮杂化合物 PCTA(Pyridine Containing Tri Aza-macrocyclic)因增加了热力学稳定性和具有7个可能的供体位点,通过N-烷基化,来获得大量的配合物。然而合成四氮杂化合物才是以上研究最关键的步骤。基于此本论文对适合工业化生产的cyclen的合成、对称四氮杂化合物的合成以及PCTA的合成进行研究。cyclen的两种合成方法:(1)以二乙烯三胺(DIEN)、二乙醇胺为原料,分别经过磺酰化、合环反应,最后在98%H2SO4作用下脱保护得到cyclen;(2)以三乙烯四胺(TETA)为原料,先与乙二醛缩合成双咪唑环化合物,在碱催化下与双亲核试剂1,2-二溴乙烷合环成四环化合物,最后用溴素或盐酸羟胺开环得到cyclen。两类cyclen衍生物的合成:(1)cyclen经草酸二乙酯保护两个相邻N原子,然后与烷基化试剂:苄氯、BrCH2COOC(CH3)3发生SN2反应,脱保护得到对称的1N,4N-二烷基化cyclen;(2)2,6-二氯甲基吡啶与3Ts-保护的二乙烯三胺通过SN2反应合环,98%H2S04脱保护得到PCTA。本论文在文献方法的基础上,结合每一步反应机理,经原料选择、反应条件筛选(包括催化剂、溶剂、反应时间和温度、破坏性探索等)、后处理优化等方面的探索得到了高收率、高纯度且操作简单的合成路线。
[Abstract]:Nitrogen heterocyclic compounds and their N-substituted derivatives have attracted much attention for their easy complexation with metal cations. The selective N-functionalization of tetraazo rings allows fine tuning of their complex properties by adjusting the properties of the coordination subunits. Most of the previous studies were on the synthesis of asymmetric heterocyclic compounds (mainly influenced by heterocyclic nitrogen and alkylation reagents), but less on the synthesis of symmetric tetraazides. In addition, the pyridyl triazo compound PCTA(Pyridine Containing Tri Aza-macrocyclichas increased thermodynamic stability and has seven possible donor sites to obtain a large number of complexes by N-alkylation. However, the synthesis of tetraazides is the most important step in the above research. In this paper, the synthesis of cyclen suitable for industrial production, the synthesis of symmetric tetraazides and the synthesis of PCTA were studied. The two synthetic methods of PCTA were as follows: diethyltriamine, diethanolamine and diethanolamine, respectively, were sulfonated, respectively, using diethylenetriamine, diethanolamine, diethanolamine and diethanolamine as raw materials. Cyclization reaction, finally deprotection under the action of 98%H2SO4, gave cyclenyl 2) from triethylenetetramine (TETAA) as raw material, condensation with Glyoxal to form diimidazole ring compound, and then formed a tetracyclic compound with amphiphilic reagents 1h2- dibromoethane under alkali catalysis. Finally, cyclenes were obtained by ring opening with bromine or hydroxylamine hydrochloride. Synthesis of two kinds of cyclen Derivatives: two adjacent N atoms were protected by diethyl oxalate, and then SN2 reaction took place with alkylation reagent: benzyl chloride BrCH2COOCU CH3H3. The symmetrical 1N- 4N- dichloromethyl pyridine and the 3Ts- protected diethylenetriamine were obtained by deprotection of 1Nb4N- dialkylated cyclenyl pyridine and 3Ts- protected diethylenetriamine through SN2 reaction and cyclization 98% H2S04. In this paper, based on the methods of literature, combined with the reaction mechanism of each step, the reaction conditions (including catalyst, solvent, reaction time and temperature) were selected by the selection of raw materials and reaction conditions. High yield, high purity and simple operation were obtained from the exploration of destructive exploration and post-treatment optimization.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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