WO2023098592A1 - 一种碳负载铁基催化剂的制备方法及其抗癌抑制剂中间体合成应用 - Google Patents

一种碳负载铁基催化剂的制备方法及其抗癌抑制剂中间体合成应用 Download PDF

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WO2023098592A1
WO2023098592A1 PCT/CN2022/134453 CN2022134453W WO2023098592A1 WO 2023098592 A1 WO2023098592 A1 WO 2023098592A1 CN 2022134453 W CN2022134453 W CN 2022134453W WO 2023098592 A1 WO2023098592 A1 WO 2023098592A1
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carbon
based catalyst
catalyst
reaction
iron
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French (fr)
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邱仁华
李定中
李铖汉
阳天宝
路浩
张文胜
尹双凤
神户宣明
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奥锐特药业股份有限公司
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    • C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
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Definitions

  • the invention relates to a new synthesis method of an iron-based carbon-loaded catalyst and its application in the synthesis of anticancer drug intermediates, belonging to the field of pharmaceutical catalytic synthesis.
  • the preparation process of the catalyst is simple and the conditions are mild, and the catalyst is used to reduce the nitro group of the anticancer drug intermediate to an amino compound.
  • Amino compounds are important fine chemical intermediates, which can be widely used in the fields of pesticides, organic functional materials and medicine.
  • the main method of synthesizing organic amine compounds is to reduce nitro compounds to amino compounds.
  • the most widely used method is to reduce nitro compounds to amine compounds: reduction under the conditions of iron and hydrazine.
  • iron and hydrazine For example: system of iron, calcium chloride and hydrazine, system of ferric trichloride and hydrazine, system of iron oxide hydroxide and hydrazine, system of iron oxide hydroxide, polymer and hydrazine, system of nanometer ferric oxide and hydrazine , the system of nano ferric oxide and hydrazine, the system of iron carbon doping and hydrazine.
  • the purpose of one aspect of the present invention is to provide a carbon-supported iron-based catalyst, the carbon-supported iron-based catalyst contains three elements Fe, O, and C, wherein the iron-based catalyst particle FeO(OH) exists in the form of a large number of cluster atoms Accompanied by a small amount of individual FeO(OH) molecular forms, and the iron-based catalyst particles are surrounded by multilayer curly graphitized carbon.
  • the specific surface area of the catalyst is 21.374-796.498 m 2 /g. In some specific embodiments of the present invention, the pore volume of the catalyst is 0.0443-1.133 cm 3 /g. In some specific embodiments of the present invention, the catalyst loading is 2.36-4.38%. .
  • the object of another aspect of the present invention is to provide the preparation method of the above-mentioned carbon-supported iron-based catalyst, the preparation method comprising the following steps:
  • step (2) drying the product of step (1) at 60-400° C. for 12-24 hours to obtain the carbon-supported iron-based catalyst.
  • the molar ratio of ferric chloride hexahydrate to activated carbon is 1:50-150. In some more preferred specific embodiments of the present invention, the molar ratio of ferric chloride hexahydrate to activated carbon is 1:80-120. For example, 1:80, 1:90, 1:100, 1:110, 1:120, etc.
  • the molar ratio of ferric chloride hexahydrate to sodium hydroxide is 1:1-3. In some more preferred embodiments of the present invention, the molar ratio of ferric chloride hexahydrate to sodium hydroxide is 1:2-2.5.
  • the concentration of the aqueous solution of ferric chloride hexahydrate is 5%-50%. In some more preferred specific embodiments of the present invention, the concentration of the aqueous solution of ferric chloride hexahydrate is 10%-30%.
  • the mass concentration of the sodium hydroxide aqueous solution is 40-60%. In some more preferred specific embodiments of the present invention, the mass concentration of the sodium hydroxide aqueous solution is 45-55%.
  • the preparation method of the above-mentioned carbon-supported iron-based catalyst comprises the following steps:
  • Another object of the present invention is to provide the application of the above-mentioned carbon-supported iron-based catalyst in reducing nitrobenzene derivatives to arylamine compounds.
  • the amount of the carbon-supported iron-based catalyst is such that 1 g of the carbon-supported iron-based catalyst can catalyze 90-100 moles of nitrobenzene derivatives through 7-10 cycles.
  • the reduction of nitrobenzene derivatives using the above-mentioned carbon-supported iron-based catalyst comprises the steps of: placing the carbon-supported iron-based catalyst and nitrobenzene derivatives in an alcohol solvent in the presence of a hydrogen source, Reaction at -25-85°C for 2-8 hours to obtain arylamine compounds,
  • nitrobenzene derivative is selected from nitrobenzene derivative I or nitrobenzene derivative III,
  • the arylamine compound is selected from arylamine compound II, IV or phenylhydrazine derivative V,
  • R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, hydroxyl, fluorine, chlorine, bromine, methyl, ethyl, cyano, hydroxyl, amido, tert-butyl, phenyl, etc. functional group.
  • the weight ratio of nitrobenzene derivatives to carbon-supported iron-based catalysts is 1:0.05-0.15, more preferably 1:0.8-0.12, such as 1:0.8, 1:0.9, 1 :1.0, 1:1.2, etc.
  • the hydrogen source is selected from hydrazine hydrate.
  • the molar ratio of nitrobenzene derivatives to hydrazine hydrate is 1:1.5-3, more preferably 1:1.5-2.5.
  • the alcohol is selected from methanol and/or ethanol.
  • the volume molar ratio of the alcohol solvent to the nitrobenzene derivative is 2-3 L/mol.
  • the reaction temperature for reducing the nitrobenzene derivative I to generate the arylamine compound II is 60-70°C. In some preferred specific embodiments of the present invention, the reaction temperature for reducing the nitrobenzene derivative III to generate the arylamine compound IV is 75-85°C. In some preferred specific embodiments of the present invention, the reaction temperature for reducing the nitrobenzene derivative III to generate the arylamine compound V is -25-25°C.
  • nitrobenzene derivatives may be selected from (2-isopropoxy-5-methyl-4-(pyridin-4-yl)nitrobenzene, (S)-N 4 -(3-chloro-4-fluoro Phenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine, N 1 -(2-(dimethylamino)ethyl)-5-methoxy -N 1 -methyl-N 4 -(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine, N- (4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine, 4-methoxy-5- (3-morpholinepropoxy)-2-nitrobenzonitrile, 1-(4-nitrophenyl)cyclopentane-1
  • arylamine compounds may be selected from N 1 -(2-(dimethylamino)ethyl)-5-methoxy-N 1 -methyl-N 4 -(4-(1-methyl-1H -indol-3-yl)pyrimidin-2-yl)benzene-1,2,4-triamine, 2-amino-4-methoxy-5-(3-morpholine propoxy)benzonitrile, N 4- (3-Chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furyl]oxy]-4,6-quinazolinediamine, N-(5-amino -2-methylphenyl)-4-(3-pyridyl)-2-aminopyrimidine, 2-chloro-3-amino-4-methylpyridine, N-(3-chloro-4-fluorophenyl) -7-methoxy-6-aminoquinazolin-4-amine, (2-
  • the purpose of another aspect of the present invention is to provide a preparation method of arylamine compounds, the preparation method comprises using nitrobenzene derivatives as raw materials, using the above-mentioned carbon-supported iron-based catalyst as a catalyst, and using hydrazine hydrate as a hydrogen source , -25 ⁇ 85 ° C under stirring reaction 2-8h, that is, arylamine compounds.
  • the carbon-supported iron-based catalyst is used in an amount of 0.05-0.5 equivalents based on the weight of the substrate.
  • alcohol is the reaction solvent.
  • the iron-based catalyst particle FeO(OH) of the present invention is more evenly distributed in the activated carbon
  • the carbon-supported iron-based structure of the present invention is that the iron-based catalyst particles FeO(OH) exists in the form of a large number of cluster atoms and is accompanied by a small amount of single FeO(OH) molecules, and the surrounding of the iron-based catalyst particles It is multilayer curly graphitized carbon;
  • the catalyst can efficiently catalyze the nitro reduction reaction of aromatic nitro compounds to generate corresponding amine compounds
  • the catalyst uses Fe element beneficial to the human body as the catalyst, which can be widely used in the field of medicine and chemical industry, and there is no problem of harmful heavy metal residues.
  • the carbon-supported iron-based catalyst provided by the present invention is used as a catalyst to reduce nitrobenzene derivatives to synthesize arylamine compounds, which opens up a new low-cost "green” approach, and its advantages are: the yield of target products is high, The reaction conditions are mild and the reaction operation is simple.
  • Figure 1 is a roadmap for the application of the carbon-supported iron-based catalyst of the present invention to the synthesis of key anticancer drug intermediates.
  • Figure 2 is the EDX mapping image of the carbon-supported iron-based catalyst
  • (a) to (f) Figures illustrate that the carbon-supported iron-based catalyst of the present invention contains three elements of Fe, O, and C, and the iron-based catalyst particles are uniformly dispersed in activated carbon.
  • Figure 3 shows the AC-TEM image of the carbon-supported iron-based catalyst, (a) to (c) illustrate that the carbon-supported iron-based catalyst particle FeO(OH) of the present invention exists in the form of a large number of cluster atoms and accompanied by a small amount of individual FeO (OH) molecules, and the iron-based catalyst particles are surrounded by multi-layer curly graphitized carbon.
  • FIG. 4 shows is the specific surface area of different kinds of carbon-loaded iron-based catalysts, and this figure illustrates laboratory level 2-5nm Chinese fir activated carbon loaded iron-based catalyst (a) with the largest specific surface area (about 796.5m 2 /g);
  • the following are industrial-grade Chinese fir activated carbon (inhomogeneous particle size and micron scale) loaded iron-based catalyst (d,), coal slime activated carbon loaded iron-based catalyst (c), 24nm graphene-loaded iron-based catalyst (b), bamboo charcoal Activated carbon-supported iron-based catalyst (f) and coconut shell activated carbon-supported iron-based catalyst (e), this figure illustrates that the laboratory grade 2-5nm fir activated carbon used in the present invention has the largest specific surface area.
  • FIG. 5 shows is the pore volume of the carbon-loaded iron-based catalyst of the present invention, and this figure has illustrated laboratory level 2-5nm fir activated carbon-loaded iron-based catalyst (a) pore volume is the largest (about 1.133cm 3 /g), thereafter
  • the following are industrial-grade fir activated carbon-supported iron-based catalyst (d,), 24nm24nm graphene-supported iron-based catalyst (b), slime activated carbon-supported iron-based catalyst (c), bamboo charcoal activated carbon-supported iron-based catalyst (f) and coconut shell activated carbon Supported iron-based catalyst (e), the figure illustrates that the laboratory grade 2-5nm fir activated carbon used in the present invention has the largest pore volume.
  • Figure 6 shows the XPS elemental analysis of the carbon-supported iron-based catalyst of the present invention, which shows that the iron-based catalyst is successfully loaded on the industrial-grade Chinese fir activated carbon, and the content of the loaded iron-based catalyst is 2.36%.
  • the characteristic peaks of -O-Fe, Fe-OH, OC, Fe2p 1/2 and Fe2p 3/2 confirm that the carbon-supported iron-based catalyst of the present invention contains three elements of Fe, C and O.
  • FIG. 8 shows is the HRTEM characterization diagram of the carbon-supported iron-based catalyst of the present invention, wherein a figure is laboratory level 2-5nm Chinese fir activated carbon HRTEM; b figure is laboratory level 2-5nm Chinese fir activated carbon loaded iron-based catalyst HRTEM, c
  • the picture shows the lab-grade 2-5nm Chinese fir activated carbon HRTEM; the pictures d 1 , d 2 , d 3 and d 4 show the HRTEM of the industrial-based Chinese fir activated carbon supported iron-based catalyst; the pictures e 1 and e 2 show the 24nm graphene HRTEM ;
  • Figures f 1 and f 2 are 24nm graphene-supported iron-based catalyst HRTEM.
  • the 2-5nm fir activated carbon is a disordered carbon structure.
  • the structure of the activated carbon around the iron-based catalyst FeO(OH) becomes an ordered multilayer curly graphitized carbon structure;
  • Industrial-grade fir activated carbon has a disordered carbon structure.
  • the structure of the activated carbon around the catalyst becomes an ordered spherical multilayer curly graphitized carbon structure;
  • 24nm graphene is a spherical multilayer graphitized carbon structure.
  • FIG. 9 shows is the XRD characterization figure of the carbon-supported iron-based catalyst of the present invention under 100-160 °C of different drying temperatures, and this figure illustrates that the structure of the iron catalyst in the Chinese fir activated carbon-supported iron-based catalyst prepared by drying at different temperatures is FeO( OH).
  • Normal temperature in the description of the present invention refers to 0-40°C, such as 0-40°C, 10-35°C, and 20-30°C, which all belong to the normal temperature mentioned in the present invention.
  • concentration unless otherwise specified, generally refers to mass concentration
  • solution unless otherwise specified, generally refers to aqueous solution.
  • the activated carbon used in the present invention can be selected from 2-5nm Chinese fir activated carbon, industrial-grade Chinese fir activated carbon, coconut shell activated carbon, and coal slime activated carbon.
  • iron-based catalyst FeO of the present invention (OH) is successfully loaded to bamboo charcoal activated carbon (loading capacity is 4.38%), coconut shell activated carbon (loading capacity is 3.76%), coal slime activated carbon (loading capacity is 3.15%), 2 -5nm Chinese fir activated carbon (loading capacity is 2.86%), industrial grade Chinese fir activated carbon (loading capacity is 2.36%).
  • the catalyst particle FeO(OH) exists in the form of a large number of cluster atoms and is accompanied by a small amount of single FeO(OH) molecule form, surrounded by multilayer curly graphitized carbon, which will be disordered around the iron oxyhydroxide catalyst
  • the carbon structure of the structure becomes an ordered multilayer curly graphitized carbon structure is crucial to improve the catalytic activity of the catalyst, because the multilayer ordered graphitized structure is beneficial to stabilize electrons and improve electron transfer efficiency.
  • ferric chloride hexahydrate (270g, 1mol) is dissolved in 1000-2000ml water, gac (1200g, 100mol) is added, the temperature is raised to 60-100°C, and 50% sodium hydroxide solution (160-200g, 2 -2.5mol), stirred at 60-100°C for 1-5h, cooled down to room temperature with stirring, stirred overnight, filtered, and washed with water. Dry at 60-400° C. for 12-24 hours to obtain 1300 g of carbon-supported iron-based catalyst.
  • reaction solution is in 60- The reaction was stirred at 70°C and followed by TLC until complete. After the reaction, hot filter, wash with ethanol, and recover the solvent to obtain a white solid aniline derivative 7-aminoindole with a yield of 86% and a purity of more than 99%.
  • the catalyst is dried at 80-200°C overnight for activation and reused.
  • the catalyst should be dried at 80-200°C overnight for activation and reused.
  • the catalyst should be dried at 80-200°C overnight for activation and reused.
  • the catalyst should be dried at 80-200°C overnight for activation and reused.
  • the catalyst is activated by drying at 200°C overnight and can be reused 9 times.

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Abstract

本发明提供一种碳负载铁基催化剂，及其制备方法和用途，所述制备方法包括将氯化铁溶于水后加入活性炭，在60～100℃下加入氢氧化钠，重复反应后，60～400℃干燥12-24h。本发明的碳负载铁基催化剂可应用于抗癌药奥希替尼、吉非替尼、阿法替尼、伊马替尼、AMG510、达可替尼、色瑞替尼、拉帕替尼和阿帕替尼等抗癌药物关键中间体的合成。该合成方法以上述碳负载铁基催化剂为催化剂，水合肼为氢源，在甲醇、乙醇、异丙醇等溶剂中，温和条件下反应以较高产率合成出关键中间体。本发明的碳负载铁基催化剂经过溶剂洗涤、干燥活化后可以重复使用十次左右。该催化剂的制备方法过程简单、绿色、高效、成本低廉、官能团兼容性好和后处理简单，具有工业化生产的潜在价值。

Description

一种碳负载铁基催化剂的制备方法及其抗癌抑制剂中间体合成应用 技术领域
本发明涉及一种铁基碳负载催化剂的合成新方法，及其在抗癌药物中间体合成中的应用，属于医药催化合成领域。该催化剂制备过程简单，条件温和，利用催化剂将抗癌药中间体硝基还原为氨基化合物。
背景技术
氨基类化合物是重要的精细化工中间体，其可以广泛应用于农药、有机功能材料和医药等领域。合成有机胺类化合物的主要方法是将硝基化合物还原为氨基化合物，目前应用最广泛的方法是将硝基化合物还原为胺类化合物：铁和肼的条件下还原。例如：铁、氯化钙和肼体系，三氯化铁和肼的体系，氢氧化氧化铁和肼的体系，氢氧化氧化铁、聚合物和肼的体系，纳米三氧化二铁和肼的体系，纳米四氧化三铁和肼的体系，铁碳掺杂和肼的体系。以上硝化还原的方法存在诸多问题，产生大量的副产物铁黑，且后处理复杂，产率低，反应时间长，官能团容忍性差，对环境污染大，催化剂的制备比较复杂。另外，钯碳加氢还原，该反应过程需要特制的耐高压反应釜，对设备要求高，存在极大的安全隐患。铁是一种绿色、环保、廉价、人体必须的元素，也是地球上含量最高的金属元素之一。以此为背景，我们通过大量文献调研，制备出一种铁基碳负载单原子催化剂的合成新方法，该催化剂制备过程简单，条件温和，并将其应用于若干关键抗癌药物中间体合成，该方法中采用廉价易得的工业木炭作为催化剂原料。研究表明，我们的催化剂能够高收率地将硝基化合物还原为胺类化合物，且催化剂可以通过简单过滤、溶剂洗涤，重新活化后重复使用十次，催化剂的催化活性仍然很高。目前，国内外还没有关于铁掺杂碳硝化还原的单原子催化剂的公开文献和专利申请。
发明内容
本发明一方面的目的在于提供一种碳负载铁基催化剂，所述碳负载铁基催化剂含有Fe、O、C三种元素，其中铁基催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子形式，且所述铁基催化剂颗粒的周围为多层卷曲石墨化碳。
在本发明的一些具体实施例中，所述催化剂的比表面积为21.374～796.498m 2/g。在本发明的一些具体实施例中，所述催化剂的孔体积为0.0443～1.133cm 3/g。在本发明的一些具体实施例中，所述催化剂的负载量为2.36～4.38％。。
本发明另一方面的目的在于提供上述碳负载铁基催化剂的制备方法，所述制备方法包括以下步骤：
(1)向六水氯化铁的水溶液中加入活性炭，升温至60～100℃，滴加氢氧化钠水溶液，60～100℃搅拌1～5h，搅拌降温至室温，搅拌8～15小时，过滤并水洗；
(2)将步骤(1)的产物，在60～400℃干燥12～24h得到所述碳负载铁基催化剂。
在本发明的一些优选具体实施例中，六水氯化铁与活性炭的摩尔比为1:50～150。在本发明的一些更优选具体实施例中，六水氯化铁与活性炭的摩尔比为1：80～120。例如，1:80、1:90、1:100、1:110、1:120等。
在本发明的一些优选具体实施例中，六水氯化铁与氢氧化钠的摩尔比为1:1～3。在本发明的一些更优选具体实施例中，六水氯化铁与氢氧化钠的摩尔比为1:2～2.5。
在本发明的一些优选具体实施例中，六水氯化铁的水溶液的浓度为5％～50％。在本发明的一更些优选具体实施例中，六水氯化铁的水溶液的浓度为10％～30％。
在本发明的一些优选具体实施例中，氢氧化钠水溶液的质量浓度为40～60％。在本发明的一些更优选具体实施例中，氢氧化钠水溶液的质量浓度为45～55％。
在本发明的一些优选具体实施例中，上述碳负载铁基催化剂的制备方法包括以下步骤：
将六水氯化铁270g，1mol溶于1000～2000ml水中，加入活性炭1200g，100mol，升温至60～100℃，缓慢滴加50％氢氧化钠溶液160～200g，2～2.5mol，60～100℃搅拌1～5h，搅拌降温至室温，搅拌过夜，过滤并水洗，60～400℃干燥12～24h得到碳掺杂铁基单原子催化剂1300g。
本发明再一方面的目的在于提供上述碳负载铁基催化剂在将硝基苯衍生物还原为芳基胺类化合物中的应用。
在本发明的一些优选具体实施例中，碳负载铁基催化剂的用量为1g碳负载铁基催化剂通过7～10次循环可催化90～100摩尔的硝基苯衍生物。
在本发明的一些优选具体实施例中，利用上述碳负载铁基催化剂还原硝基苯衍生物包括步骤：将碳负载铁基催化剂和硝基苯衍生物在醇溶剂中，在氢源存在下，在-25～85℃反应2～8h得到芳基胺类化合物，
其中所述硝基苯衍生物选自硝基苯衍生物I或硝基苯衍生物III，
所述芳基胺类化合物选自芳基胺类化合物II、IV或苯肼类衍生物V，
硝基苯衍生物I、III、芳基胺类化合物II、IV和苯肼类衍生物V的结构式如下所示：
Figure PCTCN2022134453-appb-000001
其中R 1、R 2、R 3、R 4、R 5各自独立地为氢、羟基、氟、氯、溴、甲基、乙基、氰基、羟基、酰胺基、叔丁基、苯基等官能团。
在本发明的一些优选具体实施例中，硝基苯衍生物与碳负载铁基催化剂的重量比为1：0.05～0.15，更优选1：0.8～0.12，例如1：0.8、1：0.9、1：1.0、1：1.2等。
在本发明的一些优选具体实施例中，所述氢源选自水合肼。
在本发明的一些优选具体实施例中，硝基苯衍生物与水合肼的摩尔比为1：1.5～3，更优选1：1.5～2.5。
在本发明的一些优选具体实施例中，所述醇选自甲醇和/或乙醇。
在本发明的一些优选具体实施例中，所述醇溶剂与硝基苯衍生物的体积摩尔比为2～3L/mol。
在本发明的一些优选具体实施例中，将硝基苯衍生物I还原生成芳基胺类化合物II的反应温度为60～70℃。在本发明的一些优选具体实施例中，将硝基苯衍生物III还原生成芳基胺类化合物IV的反应温度为75～85℃。在本发明的一些优选具体实施例中，将硝基苯衍生物III还原生成芳基胺类化合物V的反应温度为-25～25℃。
上述硝基苯衍生物可选自(2-异丙氧基-5-甲基-4-(吡啶-4-基)硝基苯、(S)-N 4-(3-氯-4-氟苯基)-6-硝基-7-((四氢呋喃-3-基)氧基)喹唑啉-4-胺、N 1-(2-(二甲氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)-2-硝基苯-1,4-二胺、N-(4-氟-2-甲氧基-5-硝基苯基)-4-(1-甲基-1H-吲哚-3-基)嘧啶-2-胺、4-甲氧基-5-(3-吗啉丙氧基)-2-硝基苯甲腈、1-(4-硝基苯基)环戊烷-1-碳腈、2-氯-4-甲基-3-硝基吡啶、2-氯-1-((3-氟苄基)氧基)-4-硝基苯、N-(3-氯-4-氟苯基)-7-甲氧基-6-硝基喹唑啉-4-胺或N-(2-甲基-5-硝基苯基)-4-(吡啶-3-基)嘧啶-2-胺)。
上述芳基胺类化合物可选自N 1-(2-(二甲基氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)苯-1,2,4-三胺、2-氨基-4-甲氧基-5-(3-吗啉丙氧基)苯腈、N 4-(3-氯-4-氟苯基)-7-[[(3S)-四氢-3-呋喃基]氧基]-4,6-喹唑啉二胺、N-(5-氨基-2-甲基苯基)-4-(3-吡啶基)-2-氨基 嘧啶、2-氯-3-氨基-4-甲基吡啶、N-(3-氯-4-氟苯基)-7-甲氧基-6-氨基喹唑啉-4-胺、(2-异丙氧基-5-甲基-4-(吡啶-4-基)胺基苯、3-氯-4-(3-氟苯甲氧基)苯胺和1-(4-氨基苯基)环戊基甲腈，这些芳基胺类化合物分别是奥希替尼、吉非替尼、阿法替尼、伊马替尼、AMG510、达可替尼、色瑞替尼、拉帕替尼和阿帕替尼的中间体。
本发明再一方面的目的在于提供一种芳基胺类化合物的制备方法，所述制备方法包括以硝基苯衍生物为原料，以上述碳负载铁基催化剂为催化剂，以水合肼为氢源，-25～85℃下搅拌反应2-8h，即得芳基胺类化合物。
在本发明一些优选具体实施例中，碳负载铁基催化剂的用量为底物重量的0.05～0.5当量。在本发明一些优选具体实施例中，醇为反应溶剂。
本发明的碳负载铁基催化剂具有以下特点：
1、本发明的铁基催化剂颗粒FeO(OH)较为均匀地分布在活性炭中；
2、本发明的碳负载铁基催化剂制备过程简单，原材料廉价易得；
3、本发明的碳负载铁基催化剂失活后，可经活化后继续再使用，反应后可简单回收重复使用7～10次；
4、经表征，本发明的碳负载铁基的结构为铁基催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子形式，且所述铁基催化剂颗粒的周围为多层卷曲石墨化碳；
5、催化剂可高效催化芳香硝基化合物的硝基还原反应生成相应的胺类化合物；
6、催化剂采用对人体有益的Fe元素作为催化剂，可广泛应用于医药化工领域，不存在有害重金属残留问题。
本发明所提供的碳负载铁基催化剂用作催化剂还原硝基苯衍生物合成芳基胺类化合物的方法开辟了新的低成本“绿色”途径，其优点在于：目标产物产率均较高，反应条件温和，反应操作简便。
附图说明
图1所示是本发明的碳负载铁基催化剂应用于关键抗癌药物中间体合成的路线图。
图2所示是碳负载铁基催化剂的EDX mapping成像图，(a)～(f)图说明本发明的碳负载铁基催化剂含有Fe、O、C三种元素，且铁基催化剂颗粒均匀分散在活性炭中。
图3所示是碳负载铁基催化剂的AC-TEM成像图，(a)～(c)说明本发明的碳负载铁基催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子，且所述铁基催化剂颗粒的周围为多层卷曲石墨化碳。
图4显示的是不同种类的碳负载铁基催化剂的比表面积，该图说明了实验室级别2-5nm杉木活性炭负载铁基催化剂(a)比表面积最大(约796.5m 2/g)；其后依次为工业级杉木活性 炭(粒径不均一，且是微米级的)负载铁基催化剂(d，)、煤泥活性炭负载铁基催化剂(c)、24nm石墨烯负载铁基催化剂(b)、竹炭活性炭负载铁基催化剂(f)和椰子壳活性炭负载铁基催化剂(e)，该图说明了本发明所用的实验室级别2-5nm杉木活性炭的比表面积最大。
图5显示的是本发明的碳负载铁基催化剂的孔体积，该图说明了实验室级别2-5nm杉木活性炭负载铁基催化剂(a)孔体积最大(约1.133cm 3/g)，其后依次为工业级杉木活性炭负载铁基催化剂(d，)、24nm24nm石墨烯负载铁基催化剂(b)、煤泥活性炭负载铁基催化剂(c)、竹炭活性炭负载铁基催化剂(f)和椰子壳活性炭负载铁基催化剂(e)，该图说明了本发明所用的实验室级别2-5nm杉木活性炭的孔体积最大。
图6显示的是本发明的碳负载铁基催化剂的XPS元素分析，该图说明了铁基催化剂成功地负载到了工业级杉木活性炭上，且负载的铁基催化剂含量为2.36％。
图7中A图、B图、C图分别显示的是本发明的碳负载铁基催化剂的XPS单元素分析，该图说明了该碳负载铁基催化剂存在着C＝O、C-O-C、C-C、Fe-O-Fe、Fe-O-H、O-C、Fe2p 1/2和Fe2p 3/2等特征峰，确定了本发明的碳负载铁基催化剂含有Fe、C、O三种元素成分。
图8显示的是本发明的碳负载铁基催化剂的HRTEM表征图，其中a图为实验室级别2-5nm杉木活性炭HRTEM；b图为实验室级别2-5nm杉木活性炭负载铁基催化剂HRTEM，c图为实验室级别2-5nm杉木活性炭HRTEM；d 1图、d 2图、d 3图、d 4图为工业基杉木活性炭负载铁基催化剂HRTEM，e 1图、e 2图为24nm石墨烯HRTEM；f 1图、f 2图为24nm石墨烯负载铁基催化剂HRTEM。这些图说明了2-5nm杉木活性炭为无序的碳结构，当2-5nm活性炭负载铁催化剂后，铁基催化剂FeO(OH)周围活性炭部分结构变为有序的多层卷曲石墨化碳结构；工业级杉木活性炭为无序的碳结构，当工业级活性炭负载铁催化剂后催化剂周围活性炭部分结构变为有序的球状多层卷曲石墨化碳结构；24nm石墨烯为球状多层石墨化的碳结构，当24nm石墨烯负载铁催化剂后结构与负载之前的石墨烯没有明显区别。从杉木活性炭负载铁基催化剂HRTEM表征可以发现负载的催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子形式，且在该催化剂颗粒周围能够观察到多层折叠石墨化碳结构(如d 4图所示)。由此初步推断铁基催化剂负载到杉木活性炭之后，在羟基氧化铁催化剂周围的无序结构的炭结构变为有序的多层卷曲的石墨化炭结构，这对提高催化剂的催化活性至关重要，因为多层有序石墨化结构有利于稳定电子，提高电子迁移效率。
图9显示的是本发明的碳负载铁基催化剂在100-160℃不同干燥温度下的XRD表征图，该图说明了不同温度干燥制备的杉木活性炭负载铁基催化剂中铁催化剂的结构均为FeO(OH)。
具体实施方式
本发明的描述中“常温”指0～40℃，例如0～40℃，10～35℃，20～30℃，都属于本发明所 说的常温。
本发明的描述中，“浓度”，除非另有说明，一般指质量浓度；“溶液”，除非另有说明，一般指水溶液。
本发明所使用的活性炭可选自2-5nm杉木活性炭、工业级杉木活性炭、椰子壳活性炭、煤泥活性。
XPS元素分析表明本发明铁基催化剂FeO(OH)成功地负载到竹炭活性炭(负载量为4.38％)，椰子壳活性炭(负载量为3.76％)、煤泥活性炭(负载量为3.15％)、2-5nm杉木活性炭(负载量为2.86％)、工业级杉木活性炭(负载量为2.36％)。
本发明的描述中，催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子形式，周围为多层卷曲石墨化碳，这种在羟基氧化铁催化剂周围将无序结构的炭结构变为有序的多层卷曲的石墨化炭结构对提高催化剂的催化活性至关重要，因为多层有序石墨化结构有利于稳定电子，提高电子迁移效率。
本发明将六水氯化铁(270g，1mol)溶于1000-2000ml水中，加入活性炭(1200g，100mol)，升温至60-100℃，缓慢滴加50％氢氧化钠溶液(160-200g，2-2.5mol)，60-100℃搅拌1-5h，搅拌降温至室温，搅拌过夜，过滤，水洗。60-400℃干燥12-24h得到碳负载铁基催化剂1300g。然后将0.1重量当量的该铁基负载催化剂加入到1mol硝基苯衍生物中，用2-3L醇溶液溶解，在氢源存在下，在60-100℃的环境下反应2-8h得到目标苯胺类化合物。
对本发明的碳负载铁基催化剂进行BET比较面积分析，结果如下表1所示：
表1.
Figure PCTCN2022134453-appb-000002
下面结合具体的制备例对本发明做进一步说明。
综合活性炭的比表面、孔体积和负载量，下列实施例中选用工业级杉木活性炭。
实例1
将六水氯化铁(270g，1mol)溶于1000-2000ml水中，加入活性炭(1200g，100mol)，升温至60-100℃，缓慢滴加50％氢氧化钠溶液(160-200g，2-2.5mol)，60-100℃搅拌1-5h，搅拌降温至室温，搅拌过夜，过滤，水洗，60-400℃干燥12-24h得到碳负载铁基催化剂1300g。
实例2-1
在5L反应瓶内加入硝基苯衍生物I(R 2＝乙基，R 1＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为化合物I重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)， 反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝乙基，R 1＝R 3＝R 4＝R 5)，产率为98％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-2
在5L反应瓶内加入硝基苯衍生物I(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)1mol、实例1制备的碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)，产率为95％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-3
在5L反应瓶内加入硝基苯衍生物I(R 1＝甲基，R 2＝R 3＝R 4＝R 5＝H)1mol、实例1制备的碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.12当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(98mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝甲基，R 2＝R 3＝R 4＝R 5＝H)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-4
在5L反应瓶内加入硝基苯衍生物I(R 1＝氯，R 4＝甲基，R 2＝R 3＝R 5＝H)1mol、实例1制备的碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.12当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(110mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝氯，R 4＝甲基，R 2＝R 3＝R 5＝H)，产率为90％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-5
在5L反应瓶内加入硝基苯衍生物I(R 1＝氟，R 2＝甲基，R 3＝R 4＝R 5＝H)1mol、实例1制备的碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(122mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝氟，R 2＝甲基，R 3＝R 4＝R 5＝H)，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-6
在5L反应瓶内加入硝基苯衍生物I(R 1＝氯，R 2＝R 3＝R 4＝R 5＝H)1mol、实例1制备的碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(100mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝氯，R 2＝R 3＝R 4＝R 5＝H)， 产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-7
在5L反应瓶内加入硝基苯衍生物I(R 3＝氯，R 1＝R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(100mL)，反应液在60-70℃下搅拌反应2-8h，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 3＝氯，R 1＝R 2＝R 4＝R 5＝H)，产率为95％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-8
在5L反应瓶内加入硝基苯衍生物I(R 2＝氟，R 1＝R 3＝R 4＝R 5＝H)1mol和碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(110mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝氟，R 1＝R 3＝R 4＝R 5＝H)，产率为94％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-9
在5L反应瓶内加入硝基苯衍生物I(R 1＝溴，R 2＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.09当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(105mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝溴，R 2＝R 3＝R 4＝R 5＝H)，产率为87％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例10
在5L反应瓶内加入硝基苯衍生物I(R 3＝溴，R 1＝R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.08当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(96mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 3＝溴，R 1＝R 2＝R 4＝R 5＝H)，产率为86％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-11
在5L反应瓶内加入硝基苯衍生物I(R 2＝溴，R 4＝三氟甲基，R 1＝R 3＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(98mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝溴，R 4＝三氟甲基，R 1＝R 3＝R 5＝H)，产率为86％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-12
在5L反应瓶内加入硝基苯衍生物I(R 1＝甲基，R 3＝氟，R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(110mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝甲基，R 3＝氟，R 2＝R 4＝R 5＝H)，产率为46％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-13
在5L反应瓶内加入硝基苯衍生物I(R 3＝氨基，R 1＝R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 3＝氨基，R 1＝R 2＝R 4＝R 5＝H)，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-14
在5L反应瓶内加入硝基苯衍生物I(R 2＝氨基，R 1＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.11当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝氨基，R 1＝R 3＝R 4＝R 5＝H)，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-15
在5L反应瓶内加入硝基苯衍生物I(R 2＝乙基醇，R 1＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.12当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(105mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝乙基醇，R 1＝R 3＝R 4＝R 5＝H)，产率为80％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-16
在5L反应瓶内加入硝基苯衍生物I(R 1＝羟基，R 2＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.15当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(115mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 1＝羟基，R 2＝R 3＝R 4＝R 5＝H)，产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-17
在5L反应瓶内加入硝基苯衍生物I(R 3＝酰胺，R 1＝R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.15当量)，2-3L乙醇和质量浓度为80％的水合肼水 溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 3＝酰胺，R 1＝R 2＝R 4＝R 5＝H)，产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-18
在5L反应瓶内加入硝基苯衍生物I(R 2＝甲酸甲酯，R 1＝R 3＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.12当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(115mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 2＝甲酸甲酯，R 1＝R 3＝R 4＝R 5＝H)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-19
在5L反应瓶内加入硝基苯衍生物I(R 3＝乙炔基，R 1＝R 2＝R 4＝R 5＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物I的重量的0.11当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物II(R 3＝乙炔基，R 1＝R 2＝R 4＝R 5＝H)，产率为90％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-20
在5L反应瓶内加入硝基苯衍生物3-硝基-5-氟吡啶1mol、碳负载铁基催化剂14.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物3-氨基-5-氟吡啶，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用8次。
实例2-21
在5L反应瓶内加入硝基苯衍生物2-硝基-3-羟基-5-溴吡啶1mol、碳负载铁基催化剂21.9g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物2-氨基-3-羟基-5-溴吡啶，产率为92％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-22
在5L反应瓶内加入硝基苯衍生物7-氟-6-硝基喹啉-2-(1H)-酮1mol、碳负载铁基催化剂16.3g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物7-氟-6-氨基喹啉-2-(1氢)-酮，产率为81％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-23
在5L反应瓶内加入硝基苯衍生物7-氯-8-硝基喹啉1mol、碳负载铁基催化剂20.9g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物7-氯-8-氨基喹啉，产率为81％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-24
在5L反应瓶内加入硝基苯衍生物5-硝基苯并咪唑1mol、碳负载铁基催化剂16.3g，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物5-氨基苯并咪唑，产率为88％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-25
在5L反应瓶内加入硝基苯衍生物4-硝基吲哚1mol、碳负载铁基催化剂16.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物4-氨基吲哚，产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-26
在5L反应瓶内加入硝基苯衍生物5-硝基吲哚1mol、碳负载铁基催化剂16.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(110mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物5-氨基吲哚，产率为88％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-27
在5L反应瓶内加入硝基苯衍生物7-硝基吲哚1mol、碳负载铁基催化剂16.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物7-氨基吲哚，产率为86％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-28
在5L反应瓶内加入2-异丙氧基-5-甲基-4-(吡啶-4-基)硝基苯1mol、碳负载铁基催化剂27.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(115mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体2-异丙氧基-5-甲基-4-(吡啶-4-基)苯胺，产率为86％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-29
在5L反应瓶内加入(S)-N 4-(3-氯-4-氟苯基)-6-硝基-7-((四氢呋喃-3-基)氧基)喹唑啉-4-胺1mol、碳负载铁基催化剂37.5g，2-3L乙醇和质量浓度为80％的水合肼水溶液(122mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体(S)-N 4-(3-氯-4-氟苯基)-7-((四氢呋喃-3-基)氧基)喹唑啉-4,6-二胺，产率为86％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-30
在5L反应瓶内加入N 1-(2-(二甲氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)-2-硝基苯-1,4-二胺1mol、碳负载铁基催化剂47.5g，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体N 1-(2-(二甲氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)苯-1,2,4-三胺，产率为92％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-31
在5L反应瓶内加入N-(4-氟-2-甲氧基-5-硝基苯基)-4-(1-甲基-1H-吲哚-3-基)嘧啶-2-胺1mol、碳负载铁基催化剂44.6g，2-3L乙醇和质量浓度为80％的水合肼水溶液(100mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体N-(4-氟-2-甲氧基-5-胺基苯基)-4-(1-甲基-1H-吲哚-3-基)嘧啶-2-胺，产率为92％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-32
在5L反应瓶内加入4-甲氧基-5-(3-吗啉丙氧基)-2-硝基苯甲腈1mol、碳负载铁基催化剂32.1g，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体2-氨基-4-甲氧基-5-(3-吗啉丙氧基)苯腈，产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-33
在5L反应瓶内加入1-(4-硝基苯基)环戊烷-1-碳腈1mol、碳负载铁基催化剂21.6g，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体1-(4-氨基苯基)环戊烷-1-碳腈，产率为94％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-34
在5L反应瓶内加入2-氯-4-甲基-3-硝基吡啶1mol、碳负载铁基催化剂17.3g，2-3L乙醇和质量浓度为80％的水合肼水溶液(115mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪 直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体2-氯-4-甲基吡啶-3-胺，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-35
在5L反应瓶内加入2-氯-1-((3-氟苄基)氧基)-4-硝基苯1mol、碳负载铁基催化剂28.2g，2-3L乙醇和质量浓度为80％的水合肼水溶液(98mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体2-氯-1-((3-氟苄基)氧基)-4-苯胺，产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-36
在5L反应瓶内加入N-(3-氯-4-氟苯基)-7-甲氧基-6-硝基喹唑啉-4-胺1mol、碳负载铁基催化剂34.9g，2-3L乙醇和质量浓度为80％的水合肼水溶液(105mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体N-(3-氯-4-氟苯基)-7-甲氧基喹唑啉-4,6-二胺，产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-37
在5L反应瓶内加入N-(2-甲基-5-硝基苯基)-4-(吡啶-3-基)嘧啶-2-胺1mol、碳负载铁基催化剂30.7g，2-3L乙醇和质量浓度为80％的水合肼水溶液(105mL)，反应液在60-70℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体6-甲基-N 1-(4-(吡啶-3-基)嘧啶-2-基)苯-1,3-二胺，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-38
在5L反应瓶内加入硝基苯衍生物III(R 2＝氨基，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 2＝氨基，R 1＝R 3＝R 4＝H)，产率为94％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-39
在5L反应瓶内加入硝基苯衍生物III(R 1＝R 2＝甲基，R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(95mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 1＝R 2＝甲基，R 3＝R 4＝H)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-40
在5L反应瓶内加入硝基苯衍生物III(R 2＝甲基，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(110mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 2＝甲基，R 1＝R 3＝R 4＝H)，产率为97％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-41
在5L反应瓶内加入硝基苯衍生物III(R 2＝甲氧基，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(100mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 2＝甲氧基，R 1＝R 3＝R 4＝H)，产率为90％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-42
在5L反应瓶内加入硝基苯衍生物III(R 2＝羟基，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(90mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 2＝羟基，R 1＝R 3＝R 4＝H)，产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-43
在5L反应瓶内加入硝基苯衍生物III(R 1＝R 2＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(90mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 1＝R 2＝R 3＝R 4＝H)，产率为76％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-44
在5L反应瓶内加入硝基苯衍生物III(R 1＝氨基，R 2＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 1＝氨基，R 2＝R 3＝R 4＝H)，产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-45
在5L反应瓶内加入硝基苯衍生物III(R 1＝溴，R 2＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液 (130mL)，反应液在75-85℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯胺衍生物IV(R 1＝溴，R 2＝R 3＝R 4＝H)，产率为95％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-46
在5L反应瓶内加入硝基苯衍生物III(R 2＝氯，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 2＝氯，R 1＝R 3＝R 4＝H)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-47
在5L反应瓶内加入硝基苯衍生物III(R 1＝氟，R 2＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 1＝氟，R 2＝R 3＝R 4＝H)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-48
在5L反应瓶内加入硝基苯衍生物III(R 1＝氰基，R 2＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.12当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 1＝氰基，R 2＝R 3＝R 4＝H)，产率为90％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-49
在5L反应瓶内加入硝基苯衍生物III(R 2＝氯，R 4＝氟，R 1＝R 3＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 2＝氯，R 4＝氟，R 1＝R 3＝H)，产率为91％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-50
在5L反应瓶内加入硝基苯衍生物III(R 1＝氟，R 2＝氯，R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 1＝氟，R 2＝氯，R 3＝R 4＝H)， 产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-51
在5L反应瓶内加入硝基苯衍生物III(R 2＝溴，R 4＝氟，R 1＝R 3＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.13当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(120mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 2＝溴，R 4＝氟，R 1＝R 3＝H)，产率为89％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-52
在5L反应瓶内加入硝基苯衍生物III(R 2＝溴，R 1＝R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.15当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(125mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 2＝溴，R 1＝R 3＝R 4＝H)，产率为92％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例2-53
在5L反应瓶内加入硝基苯衍生物III(R 1＝R 2＝氟，R 3＝R 4＝H)1mol、碳负载铁基催化剂(用量为硝基苯衍生物III的重量的0.1当量)，2-3L乙醇和质量浓度为80％的水合肼水溶液(130mL)，反应液在-25℃到25℃下搅拌反应，并用TLC跟踪直至反应完全。反应结束后，热过滤，用乙醇洗涤，回收溶剂，得白色固体苯肼衍生物V(R 1＝R 2＝氟，R 3＝R 4＝H)，产率为93％，纯度大于99％，催化剂80-200℃干燥过夜活化，重复使用。
实例3
将六水氯化铁(270g，1mol)溶于2000ml水中，加入活性炭(1440g，120mol)，升温至60-100℃，缓慢滴加40％氢氧化钠溶液(200g)，100℃搅拌2h，搅拌降温至室温，搅拌过夜，过滤，水洗，350℃干燥18h得到碳负载铁基催化剂。该催化剂按照实例2-2的条件和操作方法，对硝基苯衍生物I(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)进行催化还原，得白色固体苯胺衍生物II(R 2＝乙基，R 1＝R 3＝R 4＝R 5)，产率为96％，纯度大于99％，催化剂80-200℃干燥过夜活化，可重复使用10次。
实例4
将六水氯化铁(270g，1mol)溶于1800ml水中，加入活性炭(960g，80mol)，升温至80℃，缓慢滴加60％氢氧化钠溶液(150g)，100℃搅拌2h，搅拌降温至室温，搅拌过夜，过滤，水洗，350℃干燥18h得到碳负载铁基催化剂。该催化剂按照实例2-2的条件和操作方法，对硝基苯衍生物I(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)进行催化还原，得白色固体苯胺衍生物II(R 2＝ 乙基，R 1＝R 3＝R 4＝R 5)，产率为97％，纯度大于99％，催化剂200℃干燥过夜活化，可重复使用9次。
实例5
将六水氯化铁(270g，1mol)溶于1500ml水中，加入活性炭(960g，60mol)，升温至80℃，缓慢滴加50％氢氧化钠溶液(150g)，70℃搅拌3h，搅拌降温至室温，搅拌过夜，过滤，水洗，200℃干燥18h得到碳负载铁基催化剂。该催化剂按照实例2-2的条件和操作方法，对硝基苯衍生物I(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)进行催化还原，得白色固体苯胺衍生物II(R 2＝乙基，R 1＝R 3＝R 4＝R 5)，产率为96％，纯度大于99％，催化剂200℃干燥过夜活化，可重复使用8次。
实例6～12
将六水氯化铁(270g，1mol)溶于1500ml水中，加入活性炭(1200g，100mol)，升温至80℃，缓慢滴加50％氢氧化钠溶液(160g)，80℃搅拌3h，搅拌降温至室温，搅拌过夜，过滤，水洗，分别在100℃、110℃、120℃、130℃、140℃、150℃、160℃干燥18h得到碳负载铁基催化剂。这些催化剂按照实例2-1的条件和操作方法，对硝基苯衍生物I(R 2，R 3＝甲基，R 1＝R 4＝R 5＝H)进行催化还原，均得白色固体苯胺衍生物II(R 2＝乙基，R 1＝R 3＝R 4＝R 5)，产率分别为96％、90％、92％、85％、96％，89％，93％，纯度均大于99％，催化剂干燥过夜活化，可重复使用。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。

Claims (14)

  1. 一种碳负载铁基催化剂，其特征在于，所述碳负载铁基催化剂含有Fe、O、C三种元素，其中铁基催化剂颗粒FeO(OH)以大量团簇原子形式存在同时伴随少量单个FeO(OH)分子形式，且所述铁基催化剂颗粒的周围为多层卷曲石墨化碳。
  2. 根据权利要求1所述的碳负载铁催化剂，其特征在于，所述催化剂的比表面积为21.374～796.498m 2/g，和/或其孔体积为0.0443～1.133cm 3/g，和/或其负载量为2.36～4.38％。
  3. 权利要求1或2所述的碳负载铁基催化剂的制备方法，其特征在于，所述制备方法包括以下步骤：
    (1)向六水氯化铁的水溶液中加入活性炭，升温至60-100℃，滴加氢氧化钠水溶液，60-100℃搅拌1～5h，搅拌降温至室温，搅拌8～15小时，过滤并水洗；
    (2)将步骤(1)的产物，在60～400℃干燥12～24h得到所述碳负载铁基催化剂。
  4. 根据权利要求3所述的制备方法，其特征在于，六水氯化铁与活性炭的摩尔比为1：50～150，
    和/或六水氯化铁与氢氧化钠的摩尔比为1：1～3。
  5. 根据权利要求3所述的制备方法，其特征在于，六水氯化铁的水溶液的浓度为5％～50％，和/或，
    氢氧化钠水溶液的质量浓度为40～60％。
  6. 一种碳负载铁基催化剂的制备方法，其特征在于，所述催化剂的制备方法包括以下步骤：
    将六水氯化铁270g，1mol溶于1000～2000ml水中，加入活性炭1200g，100mol，升温至60～100℃，缓慢滴加50％氢氧化钠溶液160～200g，2～2.5mol，60～100℃搅拌1～5h，搅拌降温至室温，搅拌过夜，过滤并水洗，60～400℃干燥12～24h得到碳掺杂铁基单原子催化剂1300g。
  7. 权利要求1或2所述的碳负载铁基催化剂或权利要求3-7任一项所述的制备方法制备的碳负载铁基催化剂在将硝基苯衍生物还原为芳基胺类化合物中的应用。
  8. 权利要求8所述应用，其特征在于，碳负载铁基催化剂的用量为1g碳负载铁基催化剂通过7～10次循环可催化90～100摩尔的硝基苯衍生物。
  9. 根据权利要求8所述的应用，其特征在于，利用所述碳负载铁基催化剂还原硝基苯衍生物包括步骤：将碳负载铁基催化剂和硝基苯衍生物在醇溶剂中，在氢源存在下，在-25℃～85℃反应2～8h得到芳基胺类化合物，
    其中所述硝基苯衍生物选自硝基苯衍生物I或硝基苯衍生物III，
    所述芳基胺类化合物选自芳基胺类化合物II、IV或苯肼类衍生物V，
    硝基苯衍生物I、III、芳基胺类化合物II、IV和苯肼类衍生物V的结构式分别如下所示：
    Figure PCTCN2022134453-appb-100001
    其中R 1、R 2、R 3、R 4、R 5各自独立地为氢、羟基、氟、氯、溴、甲基、乙基、氰基、羟基、酰胺基、叔丁基或苯基。
  10. 根据权利要求10所述的用途，其特征在于，硝基苯衍生物与碳负载铁基催化剂的重量比为1：0.05～0.15，和/或
    所述氢源选自水合肼，和/或
    硝基苯衍生物与水合肼的摩尔比为1：1.5～3.0，和/或
    所述醇选自甲醇和/或乙醇，和/或
    所述醇溶剂与硝基苯衍生物的体积摩尔比为2～3L/mol。
  11. 根据权利要求10所述的用途，其特征在于，将硝基苯衍生物I还原生成芳基胺类化合物II的反应温度为60～70℃，
    将硝基苯衍生物III还原生成芳基胺类化合物IV的反应温度为75～85℃，
    将硝基苯衍生物III还原生成芳基胺类化合物V的反应温度为-25～25℃。
  12. 根据权利要求10所述的用途，其特征在于，所述硝基苯衍生物选自(2-异丙氧基-5-甲基-4-(吡啶-4-基)硝基苯、(S)-N 4-(3-氯-4-氟苯基)-6-硝基-7-((四氢呋喃-3-基)氧基)喹唑啉-4-胺、N 1-(2-(二甲氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)-2-硝基苯-1,4-二胺、N-(4-氟-2-甲氧基-5-硝基苯基)-4-(1-甲基-1H-吲哚-3-基)嘧啶-2-胺、4-甲氧基-5-(3-吗啉丙氧基)-2-硝基苯甲腈、1-(4-硝基苯基)环戊烷-1-碳腈、2-氯-4-甲基-3-硝基吡啶、2-氯-1-((3-氟苄基)氧基)-4-硝基苯、N-(3-氯-4-氟苯基)-7-甲氧基-6-硝基喹唑啉-4-胺或N-(2-甲基-5-硝基苯基)-4-(吡啶-3-基)嘧啶-2-胺)。
  13. 根据权利要求10所述的用途，其特征在于，所述芳基胺类化合物选自N 1-(2-(二甲基氨基)乙基)-5-甲氧基-N 1-甲基-N 4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)苯-1,2,4-三胺、2-氨基-4-甲氧基-5-(3-吗啉丙氧基)苯腈、N 4-(3-氯-4-氟苯基)-7-[[(3S)-四氢-3-呋喃基]氧基]-4,6-喹唑啉二胺、N-(5-氨基-2-甲基苯基)-4-(3-吡啶基)-2-氨基嘧啶、2-氯-3-氨基-4-甲基吡啶、N-(3-氯-4-氟苯基)-7- 甲氧基-6-氨基喹唑啉-4-胺、(2-异丙氧基-5-甲基-4-(吡啶-4-基)胺基苯、3-氯-4-(3-氟苯甲氧基)苯胺和1-(4-氨基苯基)环戊基甲腈。
  14. 一种芳基胺类化合物的制备方法，其特征在于，所述制备方法包括以硝基苯衍生物为原料，以权利要求1或2所述的碳负载铁基催化剂或权利要求3～7任一项所述的制备方法制备的碳负载铁基催化剂为催化剂，以水合肼为氢源，-25～85℃下搅拌反应2～8h，生成芳基胺类化合物。
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