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Zn-CO2-H2O体系中芳香硝基化合物选择还原制备芳香羟胺

The Selective Reduction of Nitroarenes to N-arylhydroxylamines in Zn-CO2-H2O System

【作者】 刘世娟

【导师】 蒋景阳;

【作者基本信息】 大连理工大学 , 应用化学, 2010, 博士

【摘要】 芳香羟胺和对氨基苯酚均是重要的精细化学品,主要用于药物及其中间体的合成。迄今为止,由芳香硝基化合物选择还原制备芳香羟胺的传统方法仍在沿用,即在氯化铵水溶液中用锌粉还原的方法。该方法需要加入大量的氯化铵,反应后产生含盐废水。对氨基苯酚可以经由苯羟胺在酸性(常用硫酸)介质中发生Bamberger重排而制得。然而,酸是过量的,反应后需加碱中和,产生大量含盐废水。因此,开发一种可以有效地避免使用无机酸、盐的环境友好合成方法是一项既有重要应用价值,又有学术意义的研究课题。CO2-H2O体系是原位酸,可以促进许多酸催化的有机反应。本文提出在CO2-H2O体系中用锌粉选择还原芳香硝基化合物制备芳香羟胺,进一步探讨CO2-H2O体系在Bamberger重排反应中的应用。以硝基苯为底物,系统考察了常压CO2-H2O体系中反应温度、锌粉量、水量、反应时间等反应因素对硝基苯选择还原制备苯羟胺反应的影响。在nNB=10 mmol,n2n/nNB=3,T=25℃,VH2O=20mL,t=1.5 h的优化反应条件下,苯羟胺的产率达88%。反应后水回收使用了20次,苯羟胺的产率基本不变。而且,此法对具有不同取代基的芳香硝基化合物也有较好的反应效果,相应羟胺的产率达86%-98%。然后,在常压Zn-CO2-H2O体系中系统研究了邻硝基甲苯选择还原制备邻甲基苯羟胺反应,但邻甲基苯羟胺的产率在所研究的条件下没有超过70%。发现乙醇能明显提高邻甲基苯羟胺的选择性,在25℃常压Zn-CO2-H2O体系中,加入适量乙醇,邻甲基苯羟胺的选择性由70%增加到90%。为了抑制芳香羟胺进一步还原成芳胺,控制反应停留在羟胺阶段,本文在常压Zn-CO2-H2O体系中引入超声波,研究超声波对反应的影响。发现超声波能有效地促进芳香硝基化合物选择还原反应,缩短了反应时间、减少了锌粉用量、提高了目标产物的选择性,苯羟胺的产率从88%升至95%。最后,本文在加压CO2-H2O体系中研究了锌粉选择还原硝基苯制备苯羟胺,在nNB=10 mmol,nZn/nNB=3,T=40℃,PCO2=0.5 MPa,VH2O=25 mL,t=3 h的优化条件下,苯羟胺的产率达79%。然后,在此体系中进一步探讨了苯羟胺的Bamberger重排反应,在本实验的研究条件下,对氨基苯酚的产率可达80%。为由硝基苯一步生成对氨基苯酚提供了依据。

【Abstract】 Both N-arylhydroxylamines and p-aminophenol are useful fine chemicals, and mostly applied in the synthesis of the pharmaceuticals and important intermediates. To date, the traditional method that N-arylhydroxylamines are prepared from the selective reduction of nitroarenes is still used. Nevertheless, during the reaction a large amount of NH4Cl is consumed and a lot of wastewater is formed.p-Aminophenol can be prepared by the Bamberger rearrangement of N-phenylhydroxylamine in the presence of acid medium (H2SO4 widely used), and alkali needs to be added after the reaction, thus a lot of wastewater is formed. So it is essential to open up an environmentally benign method, which efficiently avoids using inorganic acid and salt, and the subject is quite pertinent value and academic significance.Carbonic acid is formed in situ and it can be served as an acidic promoter for some reactions. We put forward the protocol that nitroarenes are reduced selectively to N-arylhydroxylamines using Zn in CO2-H2O system, and the application of the system is further explored in the Bamberger rearrangement.Firstly, nitrobenzene was selected as a model substrate, and the effects of many reaction factors on the selective reduction of nitrobenzene to N-phenylhydroxylamine, such as the reaction temperature, the molar ratio of Zn to nitrobenzene, the amount of water and the reaction time, were investigated systematically in normal pressure CO2-H2O system. Under the optimal reaction condition of nNB=10 mmol,nZn/nNB=3,T=25℃,VH2O=20mL, t=1.5 h, the yield of N-phenylhydroxylamine was 88%.The yield of N-phenylhydroxylamine was almost constant for 20 times of H2O recovered in the conditions adopted. And good results were also obtained for other nitrobenzenes substituted with other reducible functionaries, and the yields of the corresponding N-arylhydroxylamines were from 86% to 98%.Then the reduction of o-nitrotoluene to N-(o-methylphenyl)hydroxylamine was studied in Zn-CO2-H2O system systematically, and the yield of N-(o-methylphenyl)hydroxylamine was less 70% under the conditions adopted. The promoting effect of ethanol on the selectivity of N-methylphenyl)hydroxylamine in Zn-CO2-H2O system was observed. By adding appropriate amount of ethanol, the selectivity of N-(o-methylphenyl) hydroxylamine increased from 70% to 90% when the reduction was carried out at 25℃under normal pressure of CO2. Secondly, to suppress the further reduction of A N-arylhydroxylamine to aniline, the reaction need stop in the N-arylhydroxylamine stage. Ultrasound was introduced in Zn-CO2-H2O system and the effect of ultrasound on the reaction was studied. The results demonstrated that ultrasound did promote the selective reduction of nitroarenes to N-arylhydroxylamines, the reaction time was shortened, the amount of Zn powder was decreased and the selectivity of N-phenylhydroxylamine was improved. The yield of N-phenylhydroxylamine increased from 88% to 95%.At last, it was investigated that the selective reduction of nitrobenzene to N-phenylhydroxylamines using Zn in pressured CO2-H2O system, Under the optimal condition of nNB=10 mmol, nZn/nNB=3,T=40℃,PCO2=0.5 MPa,VH2O=25mL,t=3h, the yield of N-phenylhydroxylamine was 79%.Then the Bamberger rearrangement of N-phenylhydroxylamines to p-aminophenol was further explored in the system, the yield of p-aminophenol was 80% in the conditions adopted. It provides a basis for the selective reduction of nitrobenzene to p-aminophenol.

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