Method for preparing aromatic amide through heterogeneous reduction amidation of nitro-aromatic hydrocarbon

Abstract

The invention particularly relates to a method for preparing aromatic amide by reducing and amidating nitro-aromatic hydrocarbon through a heterogeneous one-pot method, which comprises the following step: reacting nitro-aromatic hydrocarbon compound, acetic acid and hydrogen in the presence of a heterogeneous monatomic palladium catalyst to obtain the aromatic amide. And carrying out reduction amidation reaction to synthesize the high-added-value aromatic amide product which is widely applied to paracetamol drugs. According to the process, a novel nitrogen-carbon carrier loaded Pd-based monatomic catalyst is adopted, so that the synthesis process of the aromatic amide medicine is simpler, the reaction activity is excellent, the stability is high, and the service life of the catalyst is long under the condition that no additional acid additive or halogen is needed.

Description

Technical Field

[0001] This invention relates to a process for preparing aromatic amides by heterogeneous one-pot reductive amidation of nitroaromatics using a Pd-based single-atom catalyst supported on a nitrogen-carbon support, belonging to the field of heterogeneous catalysis technology. Background Technology

[0002] Aromatic amides are organic compounds with benzene rings and amide (-NHCO-) ​​groups, widely found in agrochemicals, pharmaceuticals, and medical materials. Due to the prevalence of fever caused by various infectious diseases in the past five years, the demand for paracetamol-like drugs has increased significantly, and aromatic amides are the most basic structural unit of these drugs. Acetaminophen, a commonly used product, is an example of this type. Furthermore, aromatic amides possess excellent thermal stability and are used as additives in polymer manufacturing processes to improve the mechanical strength, durability, and chemical lifespan of materials. Therefore, they are also widely used in aerospace and automotive manufacturing.

[0003] In traditional amidation synthesis, amide groups are generated through the acylation condensation of carboxylic acids (derived from amines) and amines in the presence of a stoichiometric coupling agent, producing an equimolar amount of water as a byproduct. Various activators, such as KI, Mn, TMSI, and PPh3, are commonly used to catalyze this process in traditional amidation synthesis, leading to the generation of large amounts of waste liquid requiring recycling. Therefore, this traditional process faces challenges in terms of reaction toxicity and cost, as well as the need to purify and separate additives and auxiliaries from the product system. To improve the traditional amide synthesis method, direct reductive amidation from nitroaromatics to prepare aromatic amides has become an important means of reducing costs and increasing efficiency. This coupled process step can eliminate at least one reaction step. Based on research hotspots, there are two main pathways: ① Combining the reduction of nitroaromatic hydrocarbons catalyzed by metal Pd and bisphosphine ligands with the hydroammoniation carbonylation of alkenes to prepare various organic amides, in which the olefin substrate can be replaced by halogenated hydrocarbons in equal amounts; ② Combining the reduction of nitrobenzene with the amidation of carboxylic acids or esters, using expensive Zn / TMSCl or PhSiH3 additives as efficient reducing agents to couple the two-step reaction.

[0004] It can be seen that almost no reported inventions can directly reduce and amidate nitroaromatics to aromatic amides without the addition of additives. However, considering the advantages of heterogeneous catalysts in catalytic reactions, they can be recovered in the reaction system through simple separation methods, and the cyclic stability of the catalyst can be achieved by constructing various supports. Further development of heterogeneous single-atom catalysts can also enable small amounts of noble metals to achieve high utilization and activity. The preparation of single-atom catalysts mainly includes the following three methods: ① By preparing oxides with atomic defects, other active metals are bonded and inserted to achieve single-atom stability; ② By designing molecular sieves with specific structures, the metal is confined to a specific cage structure through confinement, preventing it from agglomerating into large nanoparticles; ③ By constructing heteroatom supports with N, S, P, or I atoms, the impregnated metal is anchored by atomic bonding, making the single atom stable. Therefore, using heterogeneous single-atom catalysts for the direct reduction and amidation of nitroaromatics to aromatic amides is a good strategy to reduce costs and improve atom economy.

[0005] In summary, the one-pot reductive amidation reaction of nitroaromatics to obtain high-value aromatic amide compounds is of significant research value. Developing low-cost, high-efficiency, green, clean, heterogeneous single-atom catalysts for separation and application in heterogeneous reactions has also been a major research direction in this field in recent years. Combining these two approaches to increase aromatic amide production capacity and achieve cost reduction and efficiency improvement demonstrates significant advantages in both industrial development and process planning. Summary of the Invention

[0006] To address the shortcomings of existing research, the present invention aims to provide a heterogeneous Pd single-atom catalyst that can be easily separated in industry and has excellent reactivity for realizing the one-pot reductive amidation reaction of nitroaromatics.

[0007] Therefore, this invention provides a method for a one-pot reductive amidation reaction of nitroaromatics. The method employs a heterogeneous nitrogen-carbon support loaded with a single-atom Pd catalyst, consisting of an active metal and a carbon support containing nitrogen heteroatoms. The nitrogen heteroatoms in the carbon support anchor the active metal component, thereby ensuring the active metal is highly dispersed and stably present on the carbon support. The method includes conducting a reductive amidation reaction of nitroaromatic compounds, acetic acid, and hydrogen in a reactor in the presence of the prepared catalyst to synthesize aromatic amide compounds with high added value.

[0008] In a preferred embodiment, the aromatic amide mainly includes one or more of nitrobenzene, o-nitrobenzene, m-nitrobenzene, p-nitrobenzene, p-nitrochlorobenzene, p-nitrochlorobenzene, p-nitrophenol, p-nitrobenzoic acid, p-nitrobenzyl alcohol, and methyl p-nitrobenzoate; the solvent used in the reductive amidation reaction mainly includes one or more of tetrahydrofuran, acetone, toluene, dimethylformamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolinone; no additional acid or halogen auxiliaries are required, and the integrated reaction can be carried out with high stability using only the heterogeneous Pd-based catalyst.

[0009] In a preferred embodiment, the reductive amidation reaction of the nitroaromatic compound is carried out at a temperature of 373–473 K and a reaction pressure of 0.2–10.0 MPa.

[0010] In a preferred embodiment, nitroaromatic compounds and acetic acid feedstock are fed into a reactor, wherein the molar ratio of the nitroaromatic feedstock to acetic acid is 1:0.1 to 1:10, the molar ratio of the nitroaromatic feedstock to hydrogen is 1:1 to 1:50, and the molar ratio of the nitroaromatic feedstock to the active metal in the catalyst is 1000:1 to 10000:1.

[0011] In a preferred embodiment, the inert gas is nitrogen.

[0012] In a preferred embodiment, the reductive amidation reaction of the nitroaromatic compounds is carried out in a batch reactor. The resulting liquid product is separated from the heterogeneous Pd catalyst by filtration and further processed by distillation or flash evaporation to obtain a high-purity aromatic amide product.

[0013] In a preferred embodiment, the active metal component accounts for 0.1% to 1% of the total weight of the catalyst; and the nitrogen heteroatom content accounts for 5% to 20% of the total weight of the catalyst.

[0014] This process utilizes a novel Pd-based single-atom catalyst supported on a nitrogen-carbon carrier, simplifying the synthesis of aromatic amide drugs without the need for additional acid promoters or halogens. It exhibits excellent reactivity, high stability, and a long catalyst lifetime. This invention enables the direct production of aromatic amide compounds using cheaper raw materials, significantly reducing the cost of separating raw materials and catalysts, and effectively improving the economic benefits of the direct reductive amidation of nitroaromatics.

[0015] The beneficial effects of this invention include, but are not limited to, the following: Compared with existing technologies, the one-pot reductive amidation reaction technology for nitroaromatics of this invention uses a heterogeneous Pd catalyst to achieve stable production of aromatic amides without the addition of other additives or halogens. It shortens the original reaction process, saving at least one reaction step, simplifies the reaction apparatus, and utilizes a catalyst with good reactivity and a long lifespan, reducing the separation costs of the reactant system and the catalyst. In terms of industrial applications, there are very few reports on the application of heterogeneous catalytic systems in the direct reductive amidation reaction of nitroaromatics. Therefore, this invention can greatly improve the production capacity of aromatic amide compounds, achieving cost reduction and efficiency improvement, and has broad application prospects. Attached Figure Description

[0016] Figure 1 Results of high-resolution transmission electron microscopy and aberration-corrected transmission electron microscopy Detailed Implementation

[0017] To better illustrate the preparation method of the catalyst of the present invention and its application in the one-pot reductive amidation reaction of nitroaromatic compounds, examples of catalyst preparation and its application in the reaction process are listed below, but the present invention is not limited to the following examples.

[0018] Unless otherwise specified, all reagents used in this application are commercially available and have not undergone further processing. All catalyst evaluation results were performed using an Agilent 7890B liquid chromatograph with an FID detector, capillary column, and internal standard method to analyze the liquid phase composition, with isobutanol as the internal standard. In the examples of this application, conversion was calculated based on the molar number of nitroaromatic hydrocarbons, and selectivity was calculated based on the molar number of aromatic amides.

[0019] Example 1

[0020] The preparation steps of the nitrogen-carbon supported catalyst are as follows: ① Dissolve 12.8 g of Zn(NO3)2·6H2O in 500 mL of deionized water, and dissolve 29.2 g of 2-methylimidazole in 500 mL of deionized water. Mix the two and stir for 2 h, then let stand overnight. ② Centrifuge to separate the white product, and wash with water and ethanol successively. Dry the white powder at 80 °C overnight and label it ZIF-8-p. ③ Dissolve 100 g of KCl in 400 mL of deionized water, add ZIF-8-p, and stir for 2 h. The mixture is then rotary evaporated at 80 °C and vacuum dried overnight to obtain KCl-doped ZIF-8-p. Calcine the KCl-doped ZIF-8-p at 700 °C for 5 h under a nitrogen atmosphere. Wash the product successively with 2 M hydrochloric acid, deionized water, and ethanol. Dry the black powder at 80 °C overnight and label it NC. ④ 1 g of NC support was mixed with 16.7 mg of PdCl2 in tetrahydrofuran (THF), sonicated, stirred for 12 h, and dried by rotary evaporation at 80 °C for 4 h to obtain a black solid catalyst, labeled Pd1 / NC-1. The nitrogen content in the catalyst was determined by XPS photoelectron spectroscopy, and the content of the active metal Pd in ​​the catalyst was determined by ICP electron-coupled plasma spectroscopy. The dispersion state of Pd metal in the catalyst was determined by high-resolution transmission electron microscopy and aberration-corrected transmission electron microscopy. Specific characterization results are shown in Table 1 and [Table data missing]. Figure 1 .

[0021] Example 2

[0022] The process and conditions were the same as in Example 1, except that the content of 2-methylimidazole in Example 1 was changed from 29.2 g to 24.3 g to obtain a black solid catalyst, labeled Pd / NC-2. The nitrogen content in the catalyst was determined by XPS photoelectron spectroscopy, and the content of the active metal Pd in ​​the catalyst was determined by ICP electron-coupled plasma spectroscopy.

[0023] Example 3

[0024] The process and conditions were the same as in Example 1, except that the content of 2-methylimidazole in Example 1 was changed from 29.2 g to 19.4 g to obtain a black solid catalyst, labeled Pd / NC-3. The nitrogen content in the catalyst was determined by XPS photoelectron spectroscopy, and the content of the active metal Pd in ​​the catalyst was determined by ICP electron-coupled plasma spectroscopy.

[0025] Example 4

[0026] The process and conditions were the same as in Example 1, except that the PdCl2 content was changed from 16.7 mg to 10.0 mg to obtain a black solid catalyst, labeled Pd / NC-4. The nitrogen atom content in the catalyst was determined by XPS photoelectron spectroscopy, and the active metal Pd content in the catalyst was determined by ICP electron-coupled plasma spectroscopy.

[0027] Example 5

[0028] The process and conditions were the same as in Example 1, except that the PdCl2 content was changed from 16.7 mg to 3.3 mg to obtain a black solid catalyst, labeled Pd / NC-5. The nitrogen atom content in the catalyst was determined by XPS photoelectron spectroscopy, and the active metal Pd content in the catalyst was determined by ICP electron-coupled plasma spectroscopy.

[0029] Example 6

[0030] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor, along with 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa, and the mixture was slowly heated to 423 K for 5 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetaniline, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0031] Example 7

[0032] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 10 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0033] Example 8

[0034] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor, along with 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa, and the mixture was slowly heated to 423 K for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0035] Example 9

[0036] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 20 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0037] Example 10

[0038] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 1 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0039] Example 11

[0040] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 2 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0041] Example 12

[0042] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 4 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0043] Example 13

[0044] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor, along with 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa, and the mixture was slowly heated to 393 K for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0045] Example 14

[0046] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 453 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0047] Example 15

[0048] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 483 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0049] Example 16

[0050] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor, along with 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of toluene solvent. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa, and the mixture was slowly heated to 423 K for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0051] Example 17

[0052] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of dimethylformamide solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetaniline, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 2.

[0053] Example 18

[0054] The catalyst from Example 8 was washed and vacuum dried with N-methylpyrrolidone and tetrahydrofuran, then loaded back into a high-pressure autoclave. 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The autoclave was sealed, purged four times with inert gas (nitrogen), and then purged with H2 until the pressure reached 3 MPa. The mixture was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 3.

[0055] Example 19

[0056] The catalyst from Example 18 was washed and vacuum dried sequentially with N-methylpyrrolidone and tetrahydrofuran, then loaded back into a high-pressure autoclave. 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The autoclave was sealed, purged four times with inert gas (nitrogen), and then purged with H2 until the pressure reached 3 MPa. The mixture was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 3.

[0057] Example 20

[0058] The catalyst from Example 15 was washed and vacuum dried sequentially with N-methylpyrrolidone and tetrahydrofuran, then loaded back into a high-pressure autoclave. 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The autoclave was sealed, purged four times with inert gas (nitrogen), and then purged with H2 until the pressure reached 3 MPa. The mixture was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 3.

[0059] Example 21

[0060] The catalyst from Example 16 was washed and vacuum dried sequentially with N-methylpyrrolidone and tetrahydrofuran, then loaded back into a high-pressure autoclave. 862 mg nitrobenzene (7 mmol), 1680 mg glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The autoclave was sealed, purged four times with inert gas (nitrogen), and then purged with H2 until the pressure reached 3 MPa. The mixture was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 3.

[0061] Example 22

[0062] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 973 mg of o-nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. 2-Methylaniline and 2-methylacetaniline were obtained after the reaction. The reaction evaluation results are shown in Table 4.

[0063] Example 23

[0064] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 973 mg of m-nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. 3-Methylaniline and 3-methylacetaniline were obtained after the reaction. The reaction evaluation results are shown in Table 4.

[0065] Example 24

[0066] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 973 mg of p-nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. Isobutanol was added as an internal standard to the liquid product, which was then analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. 4-Methylaniline and 4-methylacetaniline were obtained after the reaction. The reaction evaluation results are shown in Table 4.

[0067] Example 25

[0068] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 973 mg of p-nitrophenol (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HPLC-1260 liquid chromatograph equipped with a C18 capillary column and a UV detector. 4-Aminophenol and p-acetaminophen were obtained after the reaction. The reaction evaluation results are shown in Table 4.

[0069] Example 26

[0070] 10 mg of the Pd1 / NC-1 catalyst prepared in Example 1 was loaded into a high-pressure autoclave reactor. 1170 mg of p-nitrobenzoic acid (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. Isobutanol was added as an internal standard to the liquid product, which was then analyzed by an Agilent HPLC-1260 liquid chromatograph equipped with a C18 capillary column and a UV detector. 4-Aminobenzoic acid and p-acetaminobenzoic acid were obtained after the reaction. The reaction evaluation results are shown in Table 4.

[0071] Example 27

[0072] 10 mg of the Pd / NC-2 catalyst prepared in Example 2 was loaded into a high-pressure autoclave reactor. 862 mg of nitrobenzene (7 mmol), 1680 mg of glacial acetic acid (28 mmol), and 5 g of N-methylpyrrolidone solvent were added. The reactor was sealed and purged four times with inert gas (nitrogen). H2 gas was then introduced until the pressure reached 3 MPa. The reactor was slowly heated to 423 K and reacted for 15 h. After the reaction, the reactor was cooled to room temperature, the gas was slowly released, and the catalyst was separated by filtration. The liquid product was added to isobutanol as an internal standard and analyzed by an Agilent HP-7890B gas chromatograph equipped with an FFAP capillary column and an FID detector. Aniline, acetanilide, and other semi-reduced products (nitrosobenzene, azobenzene oxide, azobenzene, and diphenylhydrazine) were obtained after the reaction. The reaction evaluation results are shown in Table 5.

[0073] Example 28

[0074] 10 mg of the Pd / NC-3 catalyst prepared in Example 3 was loaded into a high-pressure autoclave reactor, and other reaction conditions were the same as in Example 27. The reaction evaluation results are shown in Table 5.

[0075] Example 29

[0076] 10 mg of the Pd / NC-4 catalyst prepared in Example 4 was loaded into a high-pressure autoclave reactor, and other reaction conditions were the same as in Example 27. The reaction evaluation results are shown in Table 5.

[0077] Example 30

[0078] 10 mg of the Pd / NC-5 catalyst prepared in Example 5 was loaded into a high-pressure autoclave reactor, and other reaction conditions were the same as in Example 27. The reaction evaluation results are shown in Table 5.

[0079] Comparative Example 1

[0080] 10 mg of commercially purchased 1Pd / C catalyst (Pd 1 wt.%) was loaded into a high-pressure autoclave reactor, and other reaction conditions were the same as in Example 27. The reaction evaluation results are shown in Table 5.

[0081] Comparative Example 2

[0082] 10 mg of commercially purchased 5Pd / C catalyst (Pd 5 wt.%) was loaded into a high-pressure autoclave reactor, and other reaction conditions were the same as in Example 27. The reaction evaluation results are shown in Table 5.

[0083] Implementation Result Analysis

[0084] The molar content of nitrogen in the catalyst was determined by XPS photoelectron spectroscopy, and the mass content of the active metal Pd was determined by ICP electron-coupled plasma spectroscopy. Taking Example 1 as an example, no nanoparticle metal was found in the prepared catalyst Pd1 / NC-1 by high-resolution transmission electron microscopy, while aberration-corrected transmission electron microscopy showed that the active metal Pd was uniformly dispersed on the support in the form of single atoms.

[0085] Table 1. Elemental analysis results of XPS photoelectron spectroscopy and ICP electron-coupled plasma.

[0086]

[0087] The experimental evaluation results are as follows:

[0088] Table 2 Evaluation results of reductive amidation under different reaction conditions

[0089]

[0090]

[0091] The results showed that, in the controlled experiments (Examples 6-9), the conversion rate of PhNO2 in the one-pot reductive amidation process of nitrobenzene was 68.5% when the reaction time was 5 hours, while the feedstock was almost completely converted after the reaction time was extended to 10 hours. Comparing Examples 10-12 with Example 8, the conversion rate of PhNO2 in the reductive amidation process was 60.8% at 1 MPa pressure, while the feedstock was almost completely converted after the pressure was increased to 2 MPa. Comparing Examples 13-15 with Example 8, the selectivity of acetanilide in the reductive amidation reaction was 27.9% at 393 K, while the selectivity rapidly increased to 89.9% when the temperature was increased to 423 K. The results of Examples 16 and 17 compared with Example 8 show that the reductive amidation reaction has the highest reactivity in the presence of N-methylpyrrolidone solvent, achieving a conversion rate of nearly 100% and an amide product selectivity of 89.9%. Toluene also shows some activity, but the amide product selectivity is significantly reduced to 30.1%. DMF solvent, on the other hand, has low activity, with only a conversion rate of 40% and a selectivity of 10.8%, and the amidation reaction hardly occurs. This may be determined by the solubility of the solvent for nitrogen-containing substrates, because N-methylpyrrolidone is weakly basic and has a better solvent effect on nitrogen-containing substrates, which is conducive to their adsorption on the catalyst surface.

[0092] Table 3. Experimental evaluation results of the cyclic stability of heterogeneous Pd1 / NC catalysts

[0093]

[0094] The results show that, compared with Example 8, Examples 18-21 demonstrate that Pd1 / NC exhibits good reactivity in the one-pot reductive amidation reaction system of nitrobenzene. Almost all nitrobenzene is completely converted, and the selectivity for acetanilide is above 80.5%, with no detected semi-reduction byproducts. This indicates that the heterogeneous Pd1 / NC catalyst can stably exist in the reductive amidation reaction, demonstrating the strong stability effect of the nitrogen-doped carbon support anchoring Pd constructed in this invention.

[0095] Table 4 Evaluation results of one-pot reductive amidation reactions of different nitroaromatics

[0096]

[0097]

[0098] The results show that Examples 22-26 and 8 demonstrate that the heterogeneous Pd catalyst and process method prepared by this invention exhibit high reactivity in various one-pot reduction amidation reaction systems for nitroaromatics, with selectivity for most amide products exceeding 80%, demonstrating good versatility. The yield of the most common acetaminophen is also as high as 87.8%, providing strong support for the future expansion of aromatic amide production capacity.

[0099] Table 5 Evaluation results of reductive amidation under different reaction conditions

[0100]

[0101] The results showed that, in control experiments with different catalyst designs, Examples 27, 28, and 8 demonstrated that when the N content in the prepared Pd / NC catalyst decreased from 16.5% to 11.5%, the conversion rate of nitrobenzene remained above 90%, without a significant decrease. However, the selectivity of the target amidation product, acetanilide, decreased from ~90% to ~40%. This change was due to the alteration of the Pd-N coordination microenvironment caused by the reduced N content. Examples 29 and 30, compared to Example 8, showed that when the active metal Pd content in the prepared Pd / NC catalyst decreased, the conversion rate of nitrobenzene decreased significantly, from ~100% to 23.5%, while the selectivity of aniline increased. Both the reduction and amidation processes required active Pd for catalysis. The results of Comparative Examples 1, 2, and Example 8 show that although commercial Pd / C catalysts can also exhibit certain nitrobenzene conversion activity, their main product is aniline, not the high-value acetaniline. This result is likely due to the absence of nitrogen heteroatoms in commercial Pd / C catalysts, preventing the formation of stable Pd-N bonds, resulting in the metals being in nanoparticle form and thus failing to exhibit amidation activity. In summary, the Pd1 / NC catalyst prepared in this invention exhibits high selectivity in generating acetaniline during the reductive amidation of nitrobenzene, demonstrating significant fundamental research value and high industrial potential.

[0102] The foregoing is a detailed description of several embodiments of the present invention, but the present invention is not limited to the specific implementations described herein. Those skilled in the art can make other modifications and variations without departing from the technical scope of the present invention. The scope of the present invention is defined by the appended claims.

Claims

1. A method for preparing aromatic amides by one-pot reductive amidation of nitroaromatic hydrocarbons, characterized in that: Aromatic amide compounds are synthesized by reductive amidation of nitroaromatics, acetic acid, and hydrogen in a reactor in the presence of a nitrogen-containing carbon-supported Pd-based single-atom catalyst.

2. The method according to claim 1, characterized in that, The nitroaromatic hydrocarbons mainly include one or more of the following: nitrobenzene, o-nitrobenzene, m-nitrobenzene, p-nitrobenzene, p-nitrochlorobenzene, p-nitrochlorobenzene, p-nitrophenol, p-nitrobenzoic acid, p-nitrobenzyl alcohol, and methyl p-nitrobenzene. The solvents used in the one-pot reductive amidation reaction mainly include one or more of tetrahydrofuran, acetone, toluene, dimethylformamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolinone.

3. The method according to claim 1, characterized in that, The one-pot reduction amidation reaction of the nitroaromatic compounds is carried out at a temperature of 373–473 K (preferably 393–453 K, more preferably 413–433 K) and a reaction pressure of 0.2–10.0 MPa (preferably 0.6–6.0 MPa, more preferably 1–5 MPa).

4. The method according to claim 1, 2, or 3, characterized in that, The molar ratio of the nitroaromatic feedstock to acetic acid in the reaction is 1:0.1 to 1:10 (preferably 1:1 to 1:10, more preferably 1:4 to 1:10), and the molar ratio of the nitroaromatic feedstock to hydrogen is 1:1 to 1:50 (preferably 1:10 to 1:50, more preferably 1:20 to 1:50).

5. The method according to claim 1, 2, or 3, characterized in that, The one-pot reductive amidation reaction of nitroaromatics is carried out in a batch reactor. The generated liquid product is filtered and separated from the catalyst, and then further distilled or flashed to obtain high-purity aromatic amide products.

6. The method according to claim 1, characterized in that, The nitrogen-carbon supported Pd single-atom catalyst consists of an active metal and a carbon support containing nitrogen heteroatoms.

7. The method according to claim 6, characterized in that, The active metal component Pd accounts for 0.1% to 5% of the total weight of the catalyst (preferably 0.5% to 5%, more preferably 1% to 2%); the molar content of nitrogen atoms accounts for 10% to 30% of the catalyst (preferably 15% to 30%, more preferably 15% to 25%).

8. The method according to claim 1, characterized in that, The one-pot reductive amidation reaction does not require the addition of additional acid or halogen auxiliaries; the integrated reaction can be carried out with high stability using only the heterogeneous Pd-based catalyst.

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