水相中单质镍介导的1,4-二氢吡啶类化合物脱氢芳构化反应

Dehydrogenating Aromatization of 1,4-Dihydropyridines Mediated by Nickel Element in Aqueous Media

目的研究1,4-二氢吡啶类化合物脱氢芳构化反应的原理,确定反应底物的适用性,优化反应条件。方法采用HPLC,以苯磺酸氨氯地平为主要研究化合物,按外标法计算脱氢芳构化物转化量,考察氢离子浓度、介质含氧量、有机溶剂与表面活性剂、酸的种类、反应时间以及单质镍用量对反应的影响。结果反应所需酸性水溶液中的氢离子浓度应大于10^(-5) mol·L^(-1);在介质中通入氧气可以提高反应速率,而通入氮气或其他气体会抑制反应;反应速率与单质镍的纯度与投料量成正比;有机溶剂与表面活性剂会抑制反应速率;可采用无机酸或有机酸配制酸性水溶液;反应4 h即可到达最大转化率。结论 1,4-二氢吡啶类化合物在酸性水溶液中,在镍单质存在的条件下,以介质中的溶氧为氧化剂来源,在常温常压下即可发生脱氢芳构化反应。该反应是一类新型的1,4-二氢吡啶类化合物脱氢芳构化反应,操作简便,转化率高,绿色环保。

OBJECTIVE To study the principle of dehydroaromatization of such 1,4-dihydropyridines,determine the applicability of the reaction substrate,and optimize the reation conditions.METHODS HPLC method was used with amlodipine besylate as the main research compound.The amount of dehydroaromatic compounds was calculated according to the external standard method.The hydrogen ion concentration,the oxygen content of the medium,the organic solvent and surfactant,the acid species,the reaction time,and the amount of nickel on the effects of the reaction were observed.RESULTS The concentration of hydrogen ions in the acidic aqueous solution required for the reaction should be greater than 10-5 mol·L-1.Oxygen in the medium could increase the reaction rate,while nitrogen or other gases could inhibit the reaction.The reaction rate was proportional to the purity of the elemental nickel and the amount of the feed.The organic solvents and surfactants would inhibit the reaction rate,and the inorganic acids or organic acids could be used to prepare acidic aqueous solutions.The reaction could acquire the maximum conversion rate after 4 h.CONCLUSION 1,4-Dihydropyridine compounds can be dehydroaromatized in acidic aquous solution at normal temperature and pressure in the presence of nickel elemental and dissolved oxygen in the medium as the oxidant.The reaction is a new type of 1,4-dihydropyridine dehydroaromatization reaction,which is simple in operation,high in conversion rate,and environmentally friendly.