钯催化芳基烯烃与烷基胺的请胺羰基化反应研究

发布时间：2018-12-13 13:59

【摘要】：酰胺是一类重要的结构单元,广泛存在于医药、农药、天然产物和功能材料中。其中,支链酰胺作为酰胺的一种,具有广泛的生理活性,如敌草胺,卡草胺,萘丙胺和氟他胺等药物分子中均含有支链酰胺结构单元。因此,如何快速高效地合成支链酰胺对于药物的发现具有至关重要的作用。近几十年中,人们发展了很多从简单原料出发构建酰胺的方法。在这些方法中,烯烃和胺的氢胺羰基化反应是合成酰胺最直接和原子利用率最高的方法。到目前为止,已经有很多关于烯烃的氢胺羰基化反应的报道,但是大部分都是使用芳基胺作为底物,而且钯催化烯烃的氢胺羰基化制备支链酰胺仍具有很大的挑战性。其中主要的难点在于,空间位阻较大的二级烷基钯物种很难形成,并且由于烷基胺的强碱性会抑制重要的活性中间体钯氢物种的产生。本文我们以5mol%的Pd(t-Bu_3P)_2为催化剂,5 mol%盐酸羟胺作为共催化剂,在20 atm的CO和120 oC的条件下,以最高95%的产率获得支链酰胺,区域选择性也可高达20:1(B:L20:1)。该反应底物适用性好,反应条件也比前人报道的条件温和,具有较好的应用前景。利用乙烯基萘醚和苯胺为原料,在CO的气氛下,以93%的产率和近乎完美的区域选择性成功制备了除草剂——萘丙胺。
[Abstract]:Amide is an important class of structural units, widely found in medicine, pesticides, natural products and functional materials. Among them, branched amide, as one of the amides, has a wide range of physiological activities, such as diachlor, carbochlor, naphthalenepropylamine and flutamide, and other drug molecules contain branched chain amide structural units. Therefore, the rapid and efficient synthesis of branched amides plays an important role in drug discovery. In recent decades, many methods of constructing amides from simple raw materials have been developed. Among these methods, hydroamine carbonylation of olefin and amine is the most direct and atomic efficient method for the synthesis of amides. Up to now, there have been many reports on hydroamine carbonylation of olefins, but most of them are based on aryl amines, and palladium catalyzed hydroamine carbonylation of olefins to branched amides is still challenging. The main difficulty is that the secondary alkyl palladium species with large steric hindrance are difficult to form and the alkylamine can inhibit the generation of important active intermediates palladium hydrogen species because of the strong alkylamine. In this paper, we use 5 mol% Pd (t-Bu_3P) _ 2 as catalyst, 5 mol% hydroxylamine hydrochloride as co-catalyst, under the condition of 20 atm CO and 120 oC, we obtain branched chain amide in the highest yield of 95%. Regional selectivity can also be as high as 20:1 (B:L20:1). The reaction substrate has good applicability and the reaction conditions are more mild than those reported by previous reports, so it has a good prospect of application. Using vinyl naphthalene ether and aniline as raw materials, a herbicide, naphthalene propane amine, was successfully prepared with 93% yield and almost perfect regioselectivity in the atmosphere of CO.
【学位授予单位】：浙江工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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