含供电基团的吡啶/吡嗪类化合物硝化反应研究

Study of Nitration Process of Pyridine /Pyrazine Compound with Electron-donating Groups

以2,6-二氨基吡啶和2,6-二甲氧基吡嗪为典型底物,研究含供电基团的氮杂环芳烃吡啶/吡嗪类化合物的硝化反应。探讨不同硝化体系对2,6-二氨基吡啶和2,6-二甲氧基吡嗪硝化收率的影响,确定了适合难硝化的吡啶/吡嗪类底物的硝化体系;在此基础上主要对硝化体系中硝酸用量、反应温度、超酸比例等重要因素进行研究,得到了最优工艺条件,硝化反应收率分别提高到65%和90%以上。最后通过量子化学手段进行模拟,从电子云密度和零点能的角度分析硝化反应的难易和氮杂环芳烃活泼性的内在联系。研究结果表明:随着芳环上N原子个数的增加,C原子上的电子云密度呈下降趋势,氮杂环芳烃活泼性减弱,导致硝化反应难以进行;而供电子基团的引入,则能使环上碳原子的电子云密度增大,从而硝化反应容易进行。

The nitration process of nitrogen-containing heterocyclic aromatics with electron-donating groups, taking 2,6-diaminopyridine and 2,6-dimethoxypyrazine as substrates, is studied. The effects of nitration systems on the yields of 2,6-diaminopyridine and 2,6-dimethoxypyrazine are investigated, respectively. The best nitration system that is suitable for those pyridine and pyrazine compounds which are difficult to be nitrated is determined. On the base of that, some important factors, such as the amount of nitric acid, reaction temperature, ratio of super acid, are further studied, and the optimized reaction con- ditions are obtained. Yields of 90% and 65% are reached for 2,6-diaminopyridine and 2,6-dimethoxy- pyrazine, respectively. Finally, the relationship between the difficulty of nitration and the activity of nitrogen-containing heterocyclic aromatics is analyzed through simulated quantum chemistry calculation in the view of electron cloud density and zero point energy. The results show that, with the increase in nitrogen atom number of aromatic, the electron cloud density of carbon atom displays a decreasing trend, the activity of nitrogen-containing heterocyclic aromatics weakens, and then the nitration reaction is restrain- ed. However, as the introduction of electron-donating group, the electron cloud density of carbon atom increases, promoting the nitration reaction.