A catalyst for producing flumioxazin intermediate in fixed bed atmospheric hydrogenation and its preparation method and application

Abstract

The application belongs to the field of organic synthesis and particularly relates to a preparation method of a catalyst for producing a propynyl flurochloridone intermediate in a fixed bed atmospheric hydrogenation and a catalytic process, the intermediate is 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-ketone, the catalyst is composed of an alumina carrier, a non-noble metal component and an active noble metal component; the catalyst has the advantages of good activity, high selectivity and long service life; 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate is used as a raw material, and 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-ketone is selectively generated through fixed bed catalytic hydrogenation reaction under the action of the catalyst; compared with a traditional kettle type high-pressure hydrogenation process, the process has the unique advantages of continuous production, high production efficiency, atmospheric hydrogenation and low safety hidden danger.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and specifically relates to a catalyst for the production of propyne fluroxypyr intermediate, namely 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one, by fixed-bed atmospheric pressure hydrogenation, as well as its preparation method and application. Background Technology

[0002] 7-Fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one (hereinafter referred to as propyzoxyl intermediate) is an important intermediate widely used in herbicides and pharmaceuticals. For example, important products among other PPO inhibitor herbicides include propyzoxyl and thiamethoxam. Propylezoxyl is a broad-spectrum, highly effective, promising, and high-growth herbicide for dryland crops, mainly used on soybeans, sugarcane, cotton, corn, cereals, peanuts, fruits, and vegetables to control gramineous and broadleaf weeds. It is applied before planting or pre-emergence, with an active ingredient dosage of 50–100 g / hm². 2 The intermediate of propyne fluroxypyr has broad application prospects, and it is essential to vigorously develop and explore its synthetic process routes.

[0003] The traditional synthetic route for propyzamide intermediates mainly involves four steps. For example, using 2,4,5-trichloronitrobenzene as the starting material, DMF is added as a fluorinating agent for selective fluorination to obtain 2,4-difluoro-5-chloro-nitrobenzene. Then, methyl glycolate is added for etherification to obtain 2-(5-fluoro-4-chloro-2-nitrobenzoxy)acetate. Next, sodium amide is added for amination to obtain 2-(5-fluoro-4-amino-2-nitrobenzoxy)acetate. Finally, hydrogen is introduced for reduction to obtain the propyzamide intermediate (see patent CN109503506A). This route uses readily available raw materials, has high conversion rates, and is simple to operate. However, the synthetic route is complex, the formation of the intermediate selective product is difficult, the reaction yield is low, a large amount of byproducts are generated, resulting in wasted raw materials, high costs, and low economic efficiency.

[0004] In recent years, a strategy has been developed to prepare propyzamide intermediates via catalytic hydrogenation reduction cyclization using 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate as a raw material. Supported noble metals (ruthenium, rhodium, palladium, osmium, iridium, platinum) are used as catalysts, and the reaction is carried out under atmospheric or pressurized conditions. The reaction temperature is typically in the range of room temperature to 200°C, and the target product is obtained in the presence of additives. Although the batch-type catalytic hydrogenation method has good product selectivity, it is a batch operation, complex, cumbersome, labor-intensive, and costly, and requires pressurized hydrogen, posing safety risks. Furthermore, the yield of propyzamide intermediates in existing processes needs further improvement. (See: Patents JP2018135315A; JP2020011976A; CN105837563A; CN107629018A; CN107663181A). In addition, due to the high controllability of continuous flow tubular reactors, a method for producing propyne fluroxypyr intermediates through continuous hydrolysis and nitration in microchannels has emerged. For example, Wu Hao et al. used a microchannel reactor with 2,4-difluoronitrobenzene as raw material for continuous hydrolysis and nitration, followed by cyclization with ethyl chloroacetate as solvent, platinum carbon as catalyst, and iodide and DMAP as co-catalysts to prepare propyne fluroxypyr intermediates. The final product purity reached 98%, and the total yield was over 85%. (See: World Pesticides 2023, 45(09):25-29; Patent: CN116655554A). In fact, the above process has high hydrolysis selectivity and low waste, but it is highly dangerous due to the need for nitration, requires the addition of additives, has high costs, and the reaction is relatively complex. Furthermore, due to the structural characteristics of microchannel reactors, channel blockage and pulsating flow generated by mechanical pump-driven fluid can easily cause instability of the fluid within the microreactor, making industrial-scale production quite complex.

[0005] Therefore, developing a catalyst that minimizes side reactions and product impurities during the hydrogenation reduction ring-closing process, and that facilitates product purification with simple and controllable equipment, is crucial for its industrial production. Thus, developing a highly selective and efficient fixed-bed atmospheric-pressure hydrogenation catalyst and process is of great significance in the production of propyne fluroxypyr intermediates. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a catalyst for the production of propyne fluroxypyr intermediate via fixed-bed atmospheric pressure hydrogenation. The intermediate is 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one. The catalyst is composed of an alumina support, a non-precious metal component, and an active precious metal component. The catalyst exhibits advantages such as high activity, high selectivity, and long lifespan. Using 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate as a raw material, 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one can be selectively generated via fixed-bed catalytic hydrogenation under the action of the above catalyst. Compared to traditional batch-type high-pressure hydrogenation processes, this process offers unique advantages such as continuous production, high production efficiency, atmospheric pressure hydrogenation, and low safety risks.

[0007] The specific technical solution adopted in this invention is as follows:

[0008] A catalyst for the production of propyne fluroxypyr intermediate, namely 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one, by fixed-bed atmospheric pressure hydrogenation is a supported catalyst. The support is alumina, and the supported active components consist of noble metal active components and non-noble metal active components. The non-noble metal active components are any one or more of Ce, Zr, Zn, Mn, Cr, and La, and the noble metal active components are one of Pd or Pt. The molar ratio of non-noble metal to noble metal is 0.5:1 to 10:1.

[0009] The noble metal active component accounts for 0.3-2% of the total mass of the catalyst.

[0010] The noble metal active component in the catalyst is derived from palladium chloride or chloroplatinate.

[0011] The non-precious metal active component in the catalyst is derived from any one or more of cerium nitrate, zirconium nitrate, zinc nitrate, manganese nitrate, chromium nitrate, and lanthanum nitrate.

[0012] Preferably, the proportion of the noble metal active component to the total mass of the catalyst is 0.8-1.6%.

[0013] Preferably, the noble metal active component accounts for 1.0% of the total mass of the catalyst.

[0014] Preferably, the non-precious metal active component in the catalyst is Ce, and the molar ratio of Ce to the precious metal active component is 2:1.

[0015] Furthermore, the carrier is spherical γ-Al₂O₃ with a diameter of 1-5 mm and a specific surface area of ​​100-300 m². 2 / g, with an average pore size of 5-20nm and a water absorption rate of 40-80%.

[0016] Using the aforementioned support can improve its dispersion, reduce the amount of precious metals used, and provide an effective surface and suitable pore structure, thus greatly reducing the sintering and aggregation of active components. Spherical γ-Al₂O₃ is chosen as the support because, compared to other supports, it has advantages such as a high melting point, good thermal stability, and the simultaneous presence of acidic and basic centers on its surface, exhibiting a variety of catalytic properties, diverse crystal phases and pore structures, and broad selectivity.

[0017] The method for preparing the catalyst according to the present invention includes the following steps:

[0018] (1) Prepare an aqueous solution of nitrate containing non-precious metal active components with a concentration range of 0.1-1.0 mol / L; after drying the spherical γ-Al2O3 support, place it into the above solution, stir intermittently, soak for 24 h and then dry at 120 °C, and calcine the obtained sample at 500-800 °C.

[0019] (2) Weigh the sample obtained in (1), prepare a palladium chloride or chloroplatinate solution of the noble metal active component, and immerse the sample obtained in (1) in the above solution for 12 hours according to the dosage ratio. After immersion, dry at 120°C and calcine the obtained sample at 400-700°C to fully impregnate the active component.

[0020] (3) Reduce the sample obtained in (2) with hydrogen gas, with a hydrogen space velocity of 0.5-50 h⁻¹. -1 The target catalyst can be obtained by heating at a rate of 2-5℃ / min and calcining at a temperature of 200-600℃.

[0021] Compared to other supported catalysts, the preparation method is simple and suitable for industrial production. The above catalyst preparation method uses H2 reduction calcination to reduce metal ions to elemental form and fully impregnates the active component. Compared with the two-step deposition method of direct calcination in the prior art, the preparation steps are simpler and easier to mass-produce and industrialize. Moreover, the full impregnation makes the active site more active, fully utilizes the drug, reduces costs, and is more economical.

[0022] In addition, the inventors also provided a specific application of the above catalyst in the production of 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one. This application uses 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid butyl ester (Formula 1) as a starting material, and performs a one-step hydrogenation reduction cyclization to generate the propyne fluroxypyr intermediate (Formula 2). The reaction equation is as follows:

[0023]

[0024] Specifically, the following steps are included:

[0025] (1) The catalyst is loaded layer by layer into the substrate as follows: Figure 1In the fixed-bed reactor shown, the catalyst loading height to diameter ratio is 5-50; hydrogen gas is introduced into the fixed-bed reactor to achieve a fixed-bed gas pressure of 1 bar and a hydrogen space velocity of 5-50 h⁻¹. -1 The catalyst is heated to 100-180°C at a heating rate of 2-5°C / min and then held at that temperature.

[0026] (2) The temperature of the vaporizer is kept consistent with the temperature of the reaction bed. Preheated 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate solution and hydrogen are continuously introduced into the fixed-bed reactor; the hydrogen space velocity is 5-50 h⁻¹. -1 ;

[0027] (3) with 0.1-5h -1 A 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate solution is continuously fed into a fixed-bed reactor at a feed rate of 0.05-1 g / mL, wherein the concentration of the 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate solution is 0.05-1 g / mL, and the solvent is DMAC or other organic polar solvents.

[0028] The above feed rate is the amount of solution that can be processed per unit mass of catalyst per unit time;

[0029] (4) The reaction liquid product obtained in step (3) is quantitatively analyzed by gas chromatography.

[0030] Preferably, the above-mentioned fixed-bed reactor adopts a hydrogen addition process at atmospheric pressure, eliminating the safety hazards associated with high-pressure hydrogenation processes. The fixed-bed reaction tube is installed vertically and can be controlled by electric heating or jacket heating. A preheating device is required at the front end of the reaction tube. The ratio of the inner diameter of the reaction tube to the catalyst particle size is greater than 8, effectively avoiding channel blockage.

[0031] Preferably, the fixed-bed reactor employs an atmospheric pressure hydrogenation process, eliminating the safety hazards associated with high-pressure hydrogenation. The fixed-bed reaction tube is installed vertically and can be controlled by electric heating or jacket heating. A preheating device is required at the front end of the reaction tube. The ratio of the inner diameter of the reaction tube to the catalyst particle size is greater than 8, effectively preventing channel blockage.

[0032] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0033] (1) The present invention adopts a fixed-bed atmospheric pressure hydrogenation process, which can generate 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one by one-step atmospheric pressure hydrogenation under the action of a catalyst.

[0034] (2) The catalyst provided by the present invention has excellent catalytic activity, selectivity and stability, and can efficiently and continuously prepare 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one with a molar conversion of raw material greater than 99% and a selectivity of 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one greater than 90%. The catalysts and conditions involved in the prior art are shown in Table 1.

[0035] Table 1. Comparison with existing catalyst technologies

[0036]

[0037] As can be seen from the table above, the catalyst provided by this invention has unique advantages in the one-step preparation of 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one by fixed-bed atmospheric pressure hydrogenation of 2-(5-fluoro-2,4-dinitrophenoxy)acetate, including continuous production, high production efficiency, and elimination of safety hazards associated with high-pressure hydrogenation. Attached Figure Description

[0038] Figure 1 This is a schematic diagram of the fixed-bed reactor structure used in this invention;

[0039] Figure 2 The NMR spectrum of the separated product in Example 1 1 H spectrum;

[0040] Figure 3 The NMR spectrum of the separated product in Example 1 13 C spectrum;

[0041] Figure 4 Mass spectrometry of the separated product from Example 1;

[0042] The product, as illustrated in the above figures, is 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one. Detailed Implementation

[0043] The following detailed description, in conjunction with specific embodiments, further illustrates the above-mentioned content of the present invention. However, it should not be construed as limiting the scope of the subject matter of the present invention to the following examples. All technologies implemented based on the above-mentioned content of the present invention fall within the scope of the present invention. Unless otherwise specified, the raw materials used in the following embodiments are all commercially available products.

[0044] Catalyst Example 1

[0045] A catalyst for the production of propyne fluroxypyr intermediate, namely 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one, by fixed-bed atmospheric pressure hydrogenation is described below:

[0046] (1) Active γ-Al2O3 spheres purchased from Shanghai Maclean Biochemical Technology Co., Ltd. were selected as the carrier, with a diameter of 1-5 mm and a specific surface area of ​​100-300 m². 2 / g, with an average pore size of 5-20nm and a water absorption rate of 60%.

[0047] (2) Prepare a cerium nitrate aqueous solution with a concentration of 1 mol / L, place the carrier from (1) into the solution, stir intermittently, soak for 24 h and dry at 120 °C, and calcine the obtained sample at 600 °C.

[0048] (3) Weigh the sample obtained in (2) quantitatively, prepare an aqueous solution of palladium chloride, immerse the sample obtained in (2) in the solution for 12 hours, dry it at 120°C after immersion, and calcine the obtained sample at 500°C to ensure that the components are fully impregnated.

[0049] (4) Reduce the sample obtained in (3) with hydrogen gas at a hydrogen space velocity of 10 h⁻¹. -1 The catalyst, denoted as S1, is obtained by heating at a rate of 3℃ / min and reducing at a temperature of 500℃.

[0050] In the final catalyst S1, Pd accounts for 1% of the total catalyst mass, and the molar ratio of cerium to Pd is 2:1.

[0051] Catalyst Example 2

[0052] Ce was replaced with an equimolar amount of Zr, and everything else was the same as in Example 1. The preparation method was the same as in Example 1, and the resulting catalyst was denoted as S2.

[0053] Catalyst Example 3

[0054] Ce was replaced with an equimolar amount of Zn, and everything else was the same as in Example 1. The preparation method was the same as in Example 1, and the resulting catalyst was denoted as S3.

[0055] Catalyst Example 4

[0056] Ce was replaced with an equimolar amount of Mn, and everything else was the same as in Example 1. The preparation method was the same as in Example 1, and the resulting catalyst was denoted as S4.

[0057] Catalyst Example 5

[0058] Ce was replaced with an equimolar amount of Cr, and everything else was the same as in Example 1. The preparation method was the same as in Example 1, and the resulting catalyst was designated as S5.

[0059] Catalyst Example 6

[0060] Ce was replaced with an equimolar amount of La, and everything else was the same as in Example 1. The preparation method was the same as in Example 1, and the resulting catalyst was designated as S6.

[0061] Catalyst Example 7

[0062] Metallic Pd was replaced with an equal mass of metallic Pt. During preparation, chloroplatinate solution was used instead of palladium chloride solution. Other aspects were the same as in Example 1. The preparation method was the same as in Example 1. The resulting catalyst was designated as S7.

[0063] Catalyst Comparative Example 1

[0064] The catalyst sample D1 was prepared without any non-precious metal components and otherwise identical to that in Example 1. The preparation method did not contain any non-precious metal components and the preparation steps were otherwise identical to those in Example 1.

[0065] Catalyst Comparative Example 2

[0066] The catalyst sample D2 was prepared without any precious metal components and otherwise identical to that in Example 1. The preparation method did not include step (2).

[0067] Application Example 1

[0068] The catalyst prepared above is used to produce propyne fluroxypyr intermediate, namely 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one. The production process specifically includes the following steps:

[0069] (1) The catalyst is loaded layer by layer into a fixed-bed reactor (see Appendix for the structure of the fixed-bed reactor). Figure 1 The catalyst loading height-to-diameter ratio is 10. Hydrogen gas is introduced into the fixed-bed reactor to achieve a fixed-bed gas pressure of 1 bar and a hydrogen space velocity of 25 h⁻¹. -1 The catalyst was heated to 120°C at a heating rate of 3°C / min and then held at that temperature.

[0070] (2) The temperature of the vaporizer is kept consistent with the temperature of the reaction bed. Preheated 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate solution and hydrogen are continuously introduced into the fixed-bed reactor; the hydrogen space velocity is 25 h⁻¹. -1 ;

[0071] (3) with 3.5h -1 The feed rate (the amount of solution that can be processed per unit mass of catalyst per unit time) is introduced into the solution; wherein, the concentration of the 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate solution is 1 g / mL, and the solvent is DMAC;

[0072] (4) After separating the reaction liquid product obtained in step (3) by column chromatography, the product is analyzed by nuclear magnetic resonance (see Appendix). Figure 2 ,3) and mass spectrometry (see Appendix) Figure 4 Qualitative analysis was performed to identify the product as 7-fluoro-6-amino-2H-1,4-benzoxazine-3(4H)-one, followed by quantitative analysis by gas chromatography.

[0073] The catalysts provided in Examples 1-7 and Comparative Examples 1 and 2 were used in the production of propyne fluroxypyr intermediates according to the above application steps. The conversion rate of 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate, the selectivity of propyne fluroxypyr intermediates, and the yield are shown in Table 2.

[0074] Table 2. Reaction conditions and results

[0075]

[0076] As shown in Table 2, the catalyst of the present invention has high catalytic activity and selectivity. The conversion rate of the raw material 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid butyl ester can reach up to 99.5%, and the selectivity of the product propyne fluroxypyr intermediate can reach up to 96.8%, which is significantly better than the prior art.

[0077] For those skilled in the art, the specific embodiments are merely illustrative descriptions of the present invention. Obviously, the specific implementation of the present invention is not limited to the above-described manner. Any non-substantial improvements made using the inventive concept and technical solution of the present invention, or the direct application of the inventive concept and technical solution to other situations without modification, are all within the protection scope of the present invention.

Claims

1. Use of a catalyst in the production of an intermediate for flumioxazin, said intermediate being 7-fluoro-6-amino-2H-l,4-benzoxazin-3(4H)-one, in a fixed bed atmospheric hydrogenation, characterized in that: The catalyst carrier is spherical γ-Al2O3, the loaded active component is composed of a noble metal active component and a non-noble metal active component, wherein the non-noble metal active component is any one or several of Ce, Zr, Zn, Mn, Cr and La, the noble metal active component is one of Pd or Pt, the molar ratio of the non-noble metal to the noble metal is 0.5:1-10:1, and the proportion of the noble metal active component in the entire catalyst is 0.3-2%.

2. Use according to claim 1, characterized in that: The noble metal active component is derived from palladium chloride or chloroplatinic acid salt; the non-noble metal active component is derived from any one or several of cerium nitrate, zirconium nitrate, zinc nitrate, manganese nitrate, chromium nitrate, lanthanum nitrate, the diameter of the spherical γ-Al2O3 is 1-5 mm, the specific surface area is 100-300 m 2 / g, the average pore size is 5-20 nm, and the water absorption rate is 40-80%.

3. Use according to claim 1 or 2, characterized in that: The proportion of the noble metal active component in the entire catalyst is 0.8-1.6%.

4. Use according to claim 3, characterized in that: The proportion of the noble metal active component in the entire catalyst is 1.0%.

5. Use according to claim 1 or 2, characterized in that: The non-noble metal active component in the catalyst is Ce, and the molar ratio of Ce to the noble metal active component is 2:

1.

6. Use according to claim 1 or 2, characterized in that, The preparation method of the catalyst comprises the following steps: (1) preparing an aqueous nitrate solution of the non-noble metal active component, the concentration of which is 0.1-1.0 mol / L; placing the dried spherical γ-Al2O3 carrier into the solution, intermittently stirring, drying at 120 ℃ after 24 h of impregnation, and calcining the obtained sample at 500-800 ℃; (2) weighing the sample obtained in (1), preparing a palladium chloride or chloroplatinate solution of the noble metal active component, placing the sample obtained in (1) into the solution according to the proportion of the amount, impregnating for 12 h, drying at 120 ℃ after impregnation, and calcining the obtained sample at 400-700 ℃ to fully impregnate the active component; (3) reducing the sample obtained in (2) with hydrogen gas at a hydrogen gas space velocity of 0.5-50 h -1 at a temperature increase rate of 2-5 ℃ / min and at a calcination temperature of 200-600 ℃, to obtain the target catalyst.

7. Use according to claim 1 or 2, characterized in that, Butyl 2-(5-fluoro-2,4-dinitrophenoxy)acetate shown in formula 1 is used as a raw material, and a propargyl flurochlorisate intermediate shown in formula 2 is generated by one-step hydrogenation reduction to close a ring, and the reaction equation is as follows: 。 8. Use according to claim 7, characterized in that: Specifically comprising the following steps: (1) The catalyst is loaded layer by layer in a fixed bed reactor, and the ratio of the catalyst loading height to the diameter is 5-50; hydrogen is introduced into the fixed bed reactor, so that the gas pressure of the fixed bed is 1 bar, the hydrogen space velocity is 5-50 h -1 After the catalyst is warmed up to 100-180 °C at a warming rate of 2-5 °C / min, it is kept warm; (2) The temperature of the vaporization furnace is consistent with the temperature of the reaction bed, and the preheated butyl 2-(5-fluoro-2,4-dinitrophenoxy)acetate solution and hydrogen are continuously introduced into the fixed bed reactor; the hydrogen space velocity is 5-50 h -1 ; (3) continuously feeding a solution of 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate into a fixed bed reactor at a feed rate of 0.1 to 5 h -1 the amount of solution that can be treated per unit of time per unit of catalyst mass; (4) the reaction liquid product obtained in step (3) is quantitatively analyzed by gas chromatography to obtain the target product 7-fluoro-6-amino-2H-1,4-benzoxazin-3(4H)-one.

9. Use according to claim 8, characterized in that: The concentration of the butyl 2-(5-fluoro-2,4-dinitrophenoxy)acetate solution is 0.05-1 g / mL, and the solvent of the butyl 2-(5-fluoro-2,4-dinitrophenoxy)acetate solution is DMAC or other organic polar solvents.

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