摘要
N-芳基胺和N-芳基含氮杂环化合物广泛应用于生化、药物、光电转化材料中。合成这类化合物的铜催化N-芳基化法在最近几年取得的较大的进展,特别是很多新的配体被报道。但仍存在催化剂活性不高、配体实用性差、底物适用范围窄、官能团容忍性差等缺点。因此,研究开发出高效、通用、价廉易得的配体用于铜催化N-芳基化反应仍然是人们追求的目标。
在前人工作基础上,本文设计了5个含有O=PPh_2结构的O,O双齿配体,初步性能测试发现含有酚羟基的配体L2具有最好的催化活性;在此设计基础上,4个邻胺甲基苯酚类N,O双齿配体被合成,催化性能测试发现该系列配体中N-环己基-2-胺甲基苯酚配体L6明显优于配体L2,并有望作为铜催化N-芳基化反应的配体。
受配体L6启发,我们测试了邻氨基苯酚的催化性能,发现邻氨基苯酚具有显著加速其自身同碘苯的N-芳基化反应的自加速效应。通过6个不同取代基的邻氨基苯酚衍生物配体的催化性能测试,发现配体1,2,3,4-四氢喹啉-8-酚具有最好的催化性能。
以环己胺和溴苯的N-芳基化反应为模型反应,经过条件筛选实验,发现在以CuBr为铜盐、Cs_2CO_3为碱、DMSO为溶剂、配体和铜盐配比为2:1的最佳反应条件下80℃反应12h,目标产物N-环己基苯胺的GC收率达到82%。测试了Cu/1,2,3,4-四氢喹啉-8-酚反应体系的底物适用范围和官能团容忍性,发现该催化体系能有效的催化脂肪胺和N-杂环化合物与溴代芳烃的N-芳基化反应,在80-90℃温和条件下得到65-95%分离收率的目标产物并能容忍-Ac,-CN,-OMe,-F,-NH_2,-CHO等官能团。
这样,本文开发了一种温和条件下简单、有效、通用的N-芳基化反应体系,尤其是体系采用的配体简单经济,有望得到广泛地应用。
N-arylamines and N-arylazoles are important compounds widely employed in biochemical,pharmaceutical,and photoelectric conversion material fields.The significant progress was achieved in the past years for the most important method of copper-catalyzed N-arylation reaction.Especially,many new ligands were developed.However,the effectivity of catalyst system,the availability of ligand,.the scope of substrates,and the tolerance of functional groups are still impefect.Thus,it is necessary to design a simple,efficient,and versatile ligand for these coupling reactions under mild conditions.
Base on the keto-enol tautomerism ofβ-diketone,five O,O-bidentate ligands were tested. The primary result indicated that the ligand of L12 containing phenolic hydroxyl group is the most effective ligand.Thus,four 2-(aminomethyl)phenol derivative ligands were developed, the catalytic performation tests indicated that the ligand of L6 is much more effective than L2 and would be developed into an ligand for copper-catalyzed N-arylation reaction.
Inspired by the L6,we tested the catalytic performation of 2-aminophenol,and demestrated that a dramatical accelerative effective exited in the N-arylation reaction of 2-anminophenol with iodobenzene.The catalytic performation tests of six 2-aminophenol derivatives indicated that the 1,2,3,4-tetrahydronquinoline-8-ol was the most effective ligand. After screening the reaction conditions of model reaction of N-arylation of cyclohexamine with iodobenzene,the model reaction gave N-cyclohexylbenzenamine in GC yield of 82%at 80℃in 12 h under the optimized condions(CuBr,Cs_2CO_3,DMSO,Cu:L= 1:2).The available scope of reaction substance and functional group tolerance of CuBr/ 1,2,3, 4-tetrahydronquinoline-8-ol catalyst system were tested.Both alphatic amines and N-azoles performed well with 68-95%isolated yields under mild condition.Furthermore,the system tolerated various aryl bromides containing -CN,-Ac,-F,-OMe and -NH_2 etc.functional groups.
Thus,an effective and versatile copper-catalyzed system for the arylation of nitrogen nucleophiles under relatively mild conditions was developed.Especially,the 2-aminophenol derivative ligand we employed is very simple,economical and even commercially available, thus,it would be wildly applied in industry.
引文
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