A method for preparing aromatic amine compounds by in-situ generating iridium catalyst to reduce nitro group

Abstract

The application discloses a method for preparing aromatic amine compounds by in-situ generating iridium catalyst to reduce nitro, and belongs to the technical field of chemical synthesis. The method is that aromatic nitro compounds, soluble iridium salt precursors and a solvent are placed in a reaction container, hydrogen is replaced after stirring reaction under the conditions of 60 atm hydrogen pressure and 25-50 DEG C for 24-48 hours, and the aromatic amine compounds are separated after reaction is completed; the molar ratio of iridium element in the soluble iridium salt precursors to the aromatic nitro compounds is 1:1000-100000. The method adopts a one-pot feeding method, generates high-activity heterogeneous iridium particle catalyst in-situ in the reaction system by using the soluble iridium salt precursors, and simultaneously completes hydrogenation reduction of the nitro. The method simplifies the process, reduces the cost, optimizes the post-treatment mode, and the in-situ generated catalyst has high activity, good selectivity, can be used repeatedly, and the noble metal catalyst is convenient to recycle.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for preparing aromatic amine compounds by in-situ generation of iridium catalyst to reduce nitro groups. Background Technology

[0002] Aromatic amines are a common and important class of organic intermediates, often in high demand and with diverse applications in the chemical industry. The production and application of aromatic amines, especially aniline, are important indicators of a country's or region's industrialization level. Large-scale production of aromatic amines is often obtained by reducing nitro aromatic compounds. The synthesis and production of these compounds often involve the nitration of readily available petrochemical products. Existing reduction methods often involve large-scale production and byproduct processing. Therefore, how to achieve efficient, safe, economical, highly selective, high-yield, and environmentally friendly large-scale production has always been a core technical problem that those skilled in the art are committed to solving.

[0003] As drug development advances towards more complex structures and more diverse functions, the requirements for chemoselectivity in nitro reduction have significantly increased. Researchers not only want to efficiently and directionally reduce nitro groups to amino groups under mild conditions, but also must avoid reduction or hydrogenolysis of other sensitive functional groups such as halogens, alkenes, alkynes, nitriles, and aldehydes and ketones. Maintaining high reaction efficiency while ensuring selectivity has become one of the key challenges in the synthesis of complex molecules.

[0004] The chemical practice of nitro reduction began in the 19th century when the Russian chemist Nikolay Zinin described the process of converting nitrobenzene to aniline using sodium sulfide (Na₂S) as a reducing agent. Subsequently, the iron powder-hydrochloric acid reduction method, commonly known as the Béchamp reduction, was also developed. Both methods have a long history of application. However, these methods still have significant problems: they suffer from extremely poor atom economy, often requiring 3-4 times the equivalent of metal or sulfur-containing reducing agents, generating large amounts of difficult-to-treat wastewater, complex post-treatment processes, and immense environmental pressure. Although some processes still use these methods today, they are gradually being replaced by cleaner processes as environmental regulations become increasingly stringent.

[0005] Catalytic hydrogenation is currently the mainstream technology for large-scale industrial production of aromatic amines, accounting for over 85% of global capacity. It typically uses hydrogen as a reducing agent and proceeds under the action of a metal catalyst (most commonly palladium / carbon Pd / C, with other options including Raney Ni, Pt, and Ruthenium Ru). This method boasts near 100% atom economy, with water as the only byproduct. Post-treatment usually only requires simple filtration to remove the catalyst, yielding a relatively pure product. It is relatively simple and economical to operate in large-scale production.

[0006] However, the chemoselectivity of nitro reduction is often insufficient when using noble metal catalysis, which is the fundamental reason why catalytic hydrogenation is limited in the synthesis of complex drug molecules. The highly active surfaces of catalysts such as Pd and Pt, while reducing nitro groups, readily exert excessive effects on other functional groups within the molecule. Especially when using metals such as Pd and Rh, this can lead to halogen hydrogenolysis: for halonitroaromatics, the CX bond (X = Cl, Br, I) readily undergoes hydrogenolysis, generating dehalogenated aromatic byproducts, which is devastating for synthetic routes that require halogens as subsequent coupling reaction sites. Furthermore, unsaturated bonds such as alkenes, alkynes, carbonyl groups, imines, and cyano groups are generally more easily reduced than nitro groups.

[0007] Currently, catalysts used for nitro hydrogenation mainly include noble metal catalysts (such as Pd / C, Pt / C, Ru / C) and non-noble metal catalysts (such as Ni, Cu). Among them, iridium (Ir)-based catalysts have attracted much attention due to their excellent selectivity and high activity for nitro reduction. However, existing iridium-based heterogeneous catalysts usually require pre-preparation. Common preparation methods include impregnation and precipitation methods, which involve multiple steps such as loading, reduction, and activation, making the process complex. Furthermore, the preparation conditions have a significant impact on the particle size, dispersion, and activity of the catalyst. In addition, pre-prepared catalysts may experience activity reduction or agglomeration during storage and transportation.

[0008] US2006 / 183938 discloses a supported palladium-iridium bimetallic catalyst for the hydrogenation of nitro compounds, but it requires the prior preparation of a Pd / Ir / Al2O3 catalyst, which is cumbersome, and the reaction needs to be carried out at a high temperature of 190°C. New J. Chem. Patent 2015, 39, 5360-5365 discloses a catalytic transfer hydrogenation method using iridium coordinated with o-phenanthroline, but it suffers from drawbacks such as difficulty in separating and recovering homogeneous catalysts, high cost, and high reaction temperature. Therefore, developing a new nitro hydrogenation method that is simple in process, has high catalyst activity, and is easy to separate and recover has significant practical application value. Summary of the Invention

[0009] To address the above problems, the purpose of this invention is to provide a method for preparing aromatic amine compounds by in-situ generation of iridium catalyst to reduce nitro groups.

[0010] The objective of this invention is achieved by providing an in-situ method for preparing aromatic amine compounds by reducing nitro groups with an iridium catalyst. This method involves placing the aromatic nitro compound, a soluble iridium salt precursor, and a solvent in a reaction vessel, purging with hydrogen gas, and then reacting the mixture at a hydrogen pressure of 60 A. tmThe reaction was stirred at 50°C for 24-48 hours. After the reaction, the target aromatic amine compound was separated. The molar ratio of iridium to aromatic nitro compound in the soluble iridium salt precursor was 1:1000-100000. The reaction formula is as follows: .

[0011] The beneficial effects of this invention are as follows: 1. Extremely simplified process (one-pot method): The entire catalytic system is not sensitive to air and water. From raw material weighing and feeding to pre-reaction preparation, everything can be completed in a normal air atmosphere. There is no need to prepare, reduce and activate heterogeneous catalysts in advance. Catalyst generation and catalytic reaction are combined into one step, which greatly simplifies the operation process, lowers the equipment and operation threshold, and has good industrial application convenience.

[0012] 2. High catalyst activity: The iridium particles generated by in-situ reduction are small in size, highly dispersed, have a large specific surface area, are clean, and have abundant active sites, exhibiting higher intrinsic catalytic activity than many pre-prepared catalysts. Catalyst recyclability: After the reaction, the generated iridium particles exist in solid form and can be recovered through simple solid-liquid separation and directly used in the next round of reaction, demonstrating the advantages of heterogeneous catalysis. Good selectivity and broad substrate applicability: Under optimized conditions, it exhibits high selectivity for nitro reduction without affecting other sensitive functional groups in the substrate molecule (such as C=C double bonds, C≡C triple bonds, carbonyl groups, etc.), demonstrating good substrate versatility.

[0013] 3. Green economy: High atom economy, with only water as a byproduct; low catalyst usage (low iridium loading) and recyclability, meeting the requirements of green chemistry and sustainable development.

[0014] 4. The method for one-pot hydrogenation of heterogeneous iridium-catalyzed nitrobenzene compounds to prepare aniline compounds provided by this invention employs a one-pot feeding method, utilizing a soluble iridium salt precursor to generate a highly active heterogeneous iridium particle catalyst in situ within the reaction system, simultaneously completing the hydrogenation reduction of the nitro group. This method simplifies the process, reduces costs, optimizes post-processing, and the in-situ generated catalyst exhibits high activity, good selectivity, and can be reused multiple times, facilitating the recovery of the precious metal catalyst. Attached Figure Description

[0015] Figure 1 This is the GCMS chromatogram of the reaction product of Example 1; Figure 2 This is the GCMS mass spectrum of the reaction product in Example 1; Figure 3 Here is a SEM image of the nano-iridium particles from Example 1; Figure 4 This is a graph showing the recycling results of the nano-iridium catalyst in Example 1; Figure 5 This is the H-NMR spectrum of the aromatic amine compound prepared in Example 1; Figure 6 This is the C-NMR spectrum of the aromatic amine compound prepared in Example 1; Figure 7 This is the H-NMR spectrum of the aromatic amine compound prepared in Example 2; Figure 8 This is the C-NMR spectrum of the aromatic amine compound prepared in Example 2; Figure 9 This is the H-NMR spectrum of the aromatic amine compound prepared in Example 3; Figure 10 This is the C-NMR spectrum of the aromatic amine compound prepared in Example 3; Figure 11 This is the H-NMR spectrum of the aromatic amine compound prepared in Example 4; Figure 12 This is the C-NMR spectrum of the aromatic amine compound prepared in Example 4; Figure 13 This is the H-NMR spectrum of the aromatic amine compound prepared in Example 5; Figure 14 This is the C-NMR spectrum of the aromatic amine compound prepared in Example 5. Detailed Implementation

[0016] The present invention will be further described below with reference to embodiments, but this is not intended to limit the present invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0017] This invention discloses an in-situ method for preparing aromatic amine compounds by reducing nitro groups with an iridium catalyst. The method involves placing an aromatic nitro compound, a soluble iridium salt precursor, and a solvent in a reaction vessel, purging with hydrogen, and then stirring the mixture at a hydrogen pressure of 60 atm and a temperature of 25-50°C for 24-48 hours. After the reaction is complete, the target aromatic amine compound is obtained by separation. The molar ratio of iridium to aromatic nitro compound in the soluble iridium salt precursor is 1:1000-100000.

[0018] The soluble iridium salt precursor is selected from one or more of iridium trichloride, (1,5-cyclooctadiene)iridium chloride dimer, iridium chloroacid, sodium iridium chloroacidate, iridium acetylacetone, and iridium acetate.

[0019] The general structural formula of the aromatic nitro compounds is shown in formula (I): ; Wherein, the substituent R is one or more identical or different groups, and the substituent R is located at any substituted position on the ring, selected from hydrogen, C1-C12 alkyl, C1-C12 alkoxy, halogen, hydroxyl, amino, alkylamino, polyfluoroalkyl, cyano, borate, sulfonyl, sulfonate, sulfonamide, ester or amide. When R is an alkyl group, the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or isobutyl. When R is an alkoxy group, the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, or isobutoxy. When R is a halogen, the halogen is fluorine, chlorine, bromine or iodine.

[0020] When R is an ester group, the ester group is methyl ester, ethyl ester, isopropyl ester or tert-butyl ester.

[0021] Ar is selected from naphthyl, anthracene, biphenyl, pyridyl, pyrrole, furanyl, indolyl, thiophene, and quinolinyl.

[0022] The solvent is one or more of alcohol solvents, water, ethyl acetate, and tetrahydrofuran.

[0023] Example 1 Under air atmosphere, 0.002 mmol of (1,5-cyclooctadiene)iridium chloride dimer, 100 mmol of nitrobenzene, and 30 mL of methanol were added sequentially to a high-pressure reactor equipped with a glass hydrogenation reaction inner tube. The reactor was sealed, and to ensure safety during hydrogen purging, the gas inside the reactor was replaced with nitrogen. Then, hydrogen was used to purge and the reactor was purged to 60 atm. The reaction was stirred at 25°C for 48 hours until no pressure drop occurred. After the hydrogenation reaction was complete, hydrogen was released, and the reactor was opened. Suspended black nano-iridium was observed in the colorless solution. The solution was filtered using a Buchner funnel and evaporated under reduced pressure to obtain the target product, aniline, with a yield of 99%. The reaction products were systematically analyzed by gas chromatography-mass spectrometry (GC-MS), such as... Figure 1 (Gas chromatogram) and Figure 2 As shown in the mass spectrum, only the characteristic chromatographic peak of the target product aniline was observed in the product, and no obvious byproduct signals (such as byproducts of excessive reduction, hydrogenolysis, or coupling) were detected. This indicates that the method of the present invention has excellent chemoselectivity under mild conditions, the amount of byproduct formation is below the detection limit (<0.1%), the reaction is highly clean, the product separation is simple, and the purity reaches over 99%. Further nuclear magnetic resonance spectroscopy characterization of the obtained aniline product is shown in the following data: 1 H NMR (400 MHz, CDCl3) δ 7.49-7.34 (m, 2H), 7.03 (m,1H), 6.92-6.75 (m, 2H), 3.76 (brs, 2H); 13C NMR (101 MHz, CDCl3) δ 147.00, 129.62, 118.63, 115.43, consistent with the structure of the target product aniline.

[0024] In this reaction, after a one-pot feeding process, the soluble iridium salt precursor in the system spontaneously transforms into heterogeneous nano-iridium particles after an induction period. Transmission electron microscopy (TEM) characterization revealed that the nanoparticles have an average particle size of 5–30 nm and exhibit a highly dispersed state. Figure 3 Left). From the enlarged SEM image ( Figure 3 (Right) It can be clearly seen that the surface of the iridium nanoparticles is composed of different concave and convex crystal planes. The iridium nanoparticles are polycrystalline and have high crystal plane energy, so the iridium nanoparticles have higher catalytic activity.

[0025] After the reaction is complete, the catalyst can be separated from the reaction system by filtration or centrifugation. The resulting black solid is a high-iridium-content nano-iridium catalyst, which requires no additional reduction or heat treatment activation steps. After washing three times with methanol and vacuum drying at 60°C for 4 hours, it can be directly used in the next round of reaction. Under the same conditions, this catalyst can be recycled at least 5 times, and the aniline separation yield remains above 95%. Figure 4 The catalytic activity showed no significant decline.

[0026] The recovered black solid was washed with ethyl acetate and saturated brine, and the organic phase was separated by liquid-liquid extraction. After removing the solvent by rotary evaporation under reduced pressure, a higher purity nano-iridium catalyst was obtained.

[0027] Example 2 Under air atmosphere, 0.0005 mmol of (1,5-cyclooctadiene)iridium chloride dimer, 5 mmol of 4-nitrobenzoate, and 2 mL of methanol were added sequentially to a high-pressure reactor equipped with a glass hydrogenation reaction inner tube. The reactor was sealed, and to ensure safety during hydrogen purging, the gas inside the reactor was replaced with nitrogen. Then, hydrogen was used to purge and the reactor was purged to 60 atm. The reaction was stirred at 50°C for 24 hours until no pressure drop occurred. After the hydrogenation reaction was completed, hydrogen was released, and the reactor was opened. A black iridium precipitate or a suspension containing nano-iridium was observed in the colorless solution. The product was obtained by filtration using a Buchner funnel and rotary evaporation under reduced pressure. For further purification, the crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1 to 5:1), yielding pure benzocaine in 96% yield. 1 H NMR (400 MHz, CDCl3) δ 7.92-7.77 (m, 2H), 6.66- 6.58 (m,2H), 4.31 (q, J = 7.1Hz, 2H), 4.19 (s, 2H), 1.35 (t,J =7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.88, 151.08, 131.56, 119.72, 113.76, 60.37, 14.45.

[0028] Example 3 Under air atmosphere, 0.001 mmol of (1,5-cyclooctadiene)iridium chloride dimer, 5 mmol of 1-iodo-4-nitrobenzene, and 2 mL of methanol were added sequentially to a high-pressure reactor equipped with a glass hydrogenation reaction inner tube. The reactor was sealed, and to ensure safety during hydrogen purging, the gas inside the reactor was replaced with nitrogen. Then, hydrogen was used to purge and the reactor was purged to 60 atm. The reaction was stirred at 50°C for 24 hours until no pressure drop occurred. After the hydrogenation reaction was completed, hydrogen was released, and the reactor was opened. A black iridium precipitate or a suspension containing nano-iridium was observed in the colorless solution. The solution was filtered using a Buchner funnel and evaporated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1 to 5:1) to obtain pure 4-iodoaniline in 94% yield. 1 H NMR (400 MHz, CDCl3) δ7.37-7.29 (m,2H), 6.43-6.36 (m, 2H), 3.57 (s, 2H). 13 C NMR (101MHz, CDCl3) δ 146.14, 137.92, 117.38, 79.42.

[0029] Example 4 Under air atmosphere, 0.001 mmol of (1,5-cyclooctadiene)iridium chloride dimer, 5 mmol of 4-nitrophenylboronic acid pinacol ester, and 2 mL of methanol were added sequentially to a high-pressure reactor equipped with a glass hydrogenation reaction inner tube. The reactor was sealed, and to ensure safety during hydrogen purging, the gas inside the reactor was replaced with nitrogen. Then, hydrogen was used to purge and the reactor was purged to 60 atm. The reaction was stirred at 50°C for 48 hours until no pressure drop occurred. After the hydrogenation reaction was completed, hydrogen was released, and the reactor was opened. A black iridium precipitate or a suspension containing nano-iridium was observed in the colorless solution. The solution was filtered using a Buchner funnel and evaporated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1 to 5:1) to obtain pure 4-aminophenylboronic acid pinacol ester in 94% yield. 1 H NMR (400MHz, CDCl3) δ 7.62 (d, J=8.4Hz, 2H), 6.65 (d, J=8.4Hz, 2H), 3.84 (brs, 2H), 1.32 (s, 12H).13 C NMR (101MHz, CDCl3) δ149.3, 136.4,114.1, 83.3, 24.9.

[0030] Example 5 Under air atmosphere, 0.001 mmol of (1,5-cyclooctadiene)iridium chloride dimer, 5 mmol of 4-nitrobenzenesulfonate, and 2 mL of methanol were added sequentially to a high-pressure reactor equipped with a glass hydrogenation reaction inner tube. The reactor was sealed, and to ensure safety during hydrogen purging, the gas inside the reactor was replaced with nitrogen. Then, hydrogen was used to purge the reactor to 60 atm, and the reaction was stirred at 50°C for 48 hours until no pressure drop occurred. After the hydrogenation reaction was completed, hydrogen was released, and the reactor was opened. A black iridium precipitate or a suspension containing nano-iridium was observed in the colorless solution. The solution was filtered using a Buchner funnel and evaporated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1 to 5:1) to obtain pure 4-iodoaniline in 94% yield. 1 H NMR (400 MHz, DMSO-d6) δ 7.42 (d, J=8.7 Hz, 2H), 7.37 (t, J=7.8 Hz, 2H), 7.28 (t, J=7.4 Hz, 1H), 6.99 (d, J=7.8 Hz, 2H), 6.63 (d, J=8.8Hz, 2H), 6.41(s, 2H). 13 C NMR (101MHz, DMSO-d6) δ 155.1, 149.9, 130.9, 130.2, 127.5, 122.7, 118.2, 113.2.

[0031] The above embodiments fully demonstrate the effectiveness, high activity, high selectivity, and simplicity of the "one-pot in-situ generation of heterogeneous iridium catalyst for nitro hydrogenation" method described in this invention.

[0032] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing aromatic amine compounds by in-situ reduction of nitro groups using an iridium catalyst, characterized in that, An aromatic nitro compound, a soluble iridium salt precursor, and a solvent were placed in a reaction vessel. After purging with hydrogen, the reaction proceeded at a hydrogen pressure of 60 A. tm The reaction was stirred at 50°C for 24-48 hours, and the target aromatic amine compound was obtained after the reaction was completed. The molar ratio of iridium to aromatic nitro compound in the soluble iridium salt precursor was 1:1000-100000.

2. The method for preparing aromatic amine compounds by in-situ generation of iridium catalyst to reduce nitro groups according to claim 1, characterized in that, The soluble iridium salt precursor is selected from one or more of iridium trichloride, (1,5-cyclooctadiene)iridium chloride dimer, iridium chloroacid, sodium iridium chloroacidate, iridium acetylacetone, and iridium acetate.

3. The method for preparing aromatic amine compounds by in-situ generation of iridium catalyst to reduce nitro groups according to claim 1, characterized in that, The general structural formula of the aromatic nitro compounds is shown in formula (I): ； Wherein, the substituent R is one or more identical or different groups, and the substituent R is located at any substituted position on the ring, selected from hydrogen, C1-C12 alkyl, C1-C12 alkoxy, halogen, hydroxyl, amino, alkylamino, polyfluoroalkyl, cyano, borate, sulfonyl, sulfonate, sulfonamide, ester or amide. Ar is selected from naphthyl, anthracene, biphenyl, pyridyl, pyrrole, furanyl, indolyl, thiophene, and quinolinyl.

4. The method for preparing aromatic amine compounds by in-situ generation of iridium catalyst to reduce nitro groups according to claim 1, characterized in that, The solvent is one or more of alcohol solvents, water, ethyl acetate, and tetrahydrofuran.

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