Efficient catalytic synthesis method of dichloroclomazone

Abstract

The invention provides an efficient catalytic synthesis method of dichloroclomazone, and relates to the technical field of catalytic synthesis. The method comprises the following steps: by taking 2-(2-chlorobenzyl)-4, 4-dimethylisoxazole-3-ketone as a raw material, reacting with p-benzene sulfonyl chloride or methane sulfonyl chloride in a dichloroethane-acetonitrile mixed solvent under the action of a supported Fe-Cu bimetallic catalyst; and adding triethylamine as a cocatalyst, reacting at 40-70 DEG C for 2-6 hours, and carrying out post-treatment to obtain the dichloro clomazone. The catalyst takes mesoporous silica (SiO2) or gamma-alumina (gamma-Al2O3) as a carrier, the molar ratio of Fe to Cu is 1: (0.3-0.8), the total loading capacity is 5%-15%, and the catalyst has excellent synergistic catalytic performance and can be repeatedly used for more than 5 times. The product separation yield is greater than or equal to 92%, the purity is greater than or equal to 98.5%, the selectivity is greater than or equal to 95%, the reaction condition is mild, the atom economy is high, the catalyst can be recycled, the industrial production cost is remarkably reduced, and the method is suitable for large-scale production and application.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of catalytic synthesis, and more particularly relates to a high-efficiency catalytic synthesis method of dichloro isoxaben. BACKGROUND

[0002] Dichloro isoxaben is a high-efficiency selective herbicide widely used in the field of agriculture, and has excellent prevention and control effect on annual broadleaf weeds and gramineous weeds in corn and soybean fields, and its market demand continues to grow. However, the existing dichloro isoxaben synthesis process has many technical bottlenecks, which limits its industrial application efficiency: (1) low catalytic system efficiency: the traditional method mostly uses single metal catalysts (such as FeCl3, CuCl2) or no catalyst system, resulting in poor reaction selectivity (usually ≤80%), high content of by-products (such as monochlorinated compounds, polychlorinated impurities, and hydrolysis products), and the need for multiple rectification or column chromatography for subsequent purification, which is complex and costly. (2) harsh reaction conditions: in order to improve the conversion rate of raw materials, the existing process often requires high temperature (80~100℃) and high pressure conditions, which not only consumes high energy, but also intensifies the decomposition and deep chlorination side reactions of raw materials, further reducing the purity of the product. (3) excessive amount of chlorinating agent: the molar ratio of chlorinating agent (such as sulfuryl chloride, chlorine) to raw material in the traditional process needs to reach 1:3 or more, which is poor in atom economy, and generates a large amount of acidic wastewater (such as HCl, sulfuric acid waste liquid), which is difficult to handle and does not meet the development trend of green chemical industry.

[0003] (4) catalyst cannot be recycled: the existing catalysts are mostly homogeneous systems or low-stability non-supported catalysts, which are difficult to separate and recycle after reaction, resulting in large consumption of catalysts, increased production cost, and contamination of the product by residual metal ions, affecting its safety in agricultural applications.

[0004] Therefore, it is a technical problem to be solved in the field to develop a dichloro isoxaben synthesis method with high selectivity, high yield, recyclable catalyst, mild reaction conditions, and environmental protection. SUMMARY

[0005] In order to solve the above technical problems, the application provides a high-efficiency catalytic synthesis method of dichloro isoxaben, which solves the technical problems of low catalytic selectivity, many by-products, harsh reaction conditions, large amount of chlorinating agent, non-recyclable catalyst, high cost, and great environmental pressure in the existing dichloro isoxaben synthesis method.

[0006] A high-efficiency catalytic synthesis method of dichloro isoxaben, which uses 2-(2-chlorobenzyl)-4,4-dimethylisoxazole-3-ketone as a raw material, and under the action of a supported bimetallic catalyst, a selective chlorination reaction occurs with a chlorinating agent in an organic solvent to obtain dichloro isoxaben.

[0007] The reaction formula is:

[0008]

[0009] wherein R is alkyl or aryl.

[0010] Preferably, the support of the supported bimetallic catalyst is mesoporous SiO2 or γ-Al2O3, the specific surface area of the support is 200-500 m² / g, and the pore size is 5-20 nm.

[0011] Preferably, the active component of the supported bimetallic catalyst is Fe and Cu, and the molar ratio of the bimetals is Fe:Cu=1:(0.3-0.8).

[0012] Preferably, the loading ω of the active component on the support satisfies the formula:

[0013] Loading ω = (m1+m2) / (m1+m2+m0)×100%

[0014] wherein m1 is the mass of Fe, m2 is the mass of Cu, and m0 is the mass of the support, and ω is in the range of 5%-15%.

[0015] Preferably, the chlorinating agent is p-toluenesulfonyl chloride or methane sulfonyl chloride, and the molar ratio of 2-(2-chlorobenzyl)-4,4-dimethylisoxazol-3-one to the chlorinating agent is 1:(0.9-1.3).

[0016] Preferably, the organic solvent is a mixed solvent of dichloroethane and acetonitrile, and the volume ratio of dichloroethane to acetonitrile is 1:(0.5-1.2).

[0017] Preferably, the conditions of the selective chlorination reaction are as follows: reaction temperature 40-70°C, reaction time 2-6h, and catalyst dosage 3%-8% of the mass of 2-(2-chlorobenzyl)-4,4-dimethylisoxazol-3-one.

[0018] Preferably, a cocatalyst triethylamine is added during the reaction, and the molar ratio of the cocatalyst to 2-(2-chlorobenzyl)-4,4-dimethylisoxazol-3-one is (0.1-0.3):1.

[0019] Preferably, after the reaction, the product is purified by vacuum distillation, water washing, and column chromatography, the separation yield of dichloroisonixazolone is ≥92%, the product purity is ≥98.5%, and the reaction selectivity S satisfies the formula:

[0020] S = n(II) / [n(I)0-n(I) 残 ]×100%

[0021] wherein n(II) is the molar number of the target product, n(I)0 is the initial molar number of the raw material, and n(I) is the molar number of the unreacted raw material.残 The number of unreacted reactants is S≥95%.

[0022] Preferably, the supported bimetallic catalyst can be reused 3 to 5 times after being recovered and dried, and the catalytic activity retention rate is ≥85% after 5 reuses.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] Catalytic efficiency and selectivity are significantly improved: through the synergistic effect of the supported Fe-Cu bimetallic catalyst (Fe3O4 activates the chlorinating agent to generate Cl⁺ active species, Cu…) 0 (Promoting the removal of active hydrogen from raw materials), combined with the regulation of triethylamine co-catalyst, the reaction selectivity is ≥95%, effectively inhibiting the formation of monochlorinated, polychlorinated and hydrolysis byproducts, and solving the core problem of low selectivity of traditional single metal catalysts.

[0025] The product quality is excellent: the product separation yield is ≥92% and the purity is ≥98.5%, which is far higher than the existing process (yield ≤80%, purity ≤95%). It can meet the agricultural application standards without complicated purification steps, and significantly reduces the post-processing cost.

[0026] The reaction conditions are mild and energy consumption is low: the reaction is carried out at 40~70℃ and normal pressure, which reduces energy consumption by more than 30% compared with the traditional high temperature and high pressure process, and avoids the decomposition of raw materials caused by high temperature, further ensuring the stability of the product.

[0027] Improved atom economy and environmental friendliness: The amount of chlorinating agent used is only 0.9 to 1.3 times that of raw materials (far lower than 1:3 in traditional processes), with very few by-products and a reduction of more than 40% in acidic wastewater discharge, meeting the requirements of green chemical production.

[0028] The catalyst can be reused, reducing costs: The supported bimetallic catalyst can be reused 3 to 5 times after simple recovery and drying. The activity retention rate is ≥85% when it is used for the 5th time, which greatly reduces the cost of catalyst consumption and avoids the contamination of the product by metal ion residues.

[0029] It has strong industrial adaptability: the process steps are simple (raw materials → catalytic reaction → post-processing), the reaction system is stable, the yield and purity did not decrease significantly in the scale-up experiment (10 L reactor), the catalyst is easy to recover, and it is suitable for large-scale industrial production. Detailed Implementation

[0030] The embodiments provide a further detailed description of how the present invention is implemented. The following embodiments are for illustrative purposes only and should not be construed as limiting the scope of the invention.

[0031] This invention provides a highly efficient catalytic synthesis method for dichloroisoxane. The following detailed description, including technical specifications, characterization data, key process control points, and industrial-scale adaptation instructions, provides a comprehensive overview of this highly efficient catalytic synthesis method. Those skilled in the art can accurately reproduce this invention based on the following content, while also clearly demonstrating the core innovations and technical advantages of this invention compared to existing technologies.

[0032] This invention constructs a highly efficient synthesis process combining bimetallic synergistic catalysis, mild reaction conditions, and recyclable catalyst by screening bimetallic active components, optimizing support performance, and matching specific solvent-chlorinating agent systems and co-catalysts. This process achieves a balance between product yield, purity, and industrial feasibility.

[0033] Core raw materials:

[0034] 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one:

[0035]

[0036] Preparation method (self-made):

[0037] The product is prepared from 2-chlorobenzaldehyde and pinacolone through a two-step reaction, as follows:

[0038] Aldol condensation reaction:

[0039] 2-Chlorobenzaldehyde (0.2 mol, 28.11 g), ethanol (80 g), and pinacol (0.21 mol, 24.81 g) were added to a 250 mL three-necked flask. The mixture was stirred at 40 °C for 6 h, during which sodium hydroxide solution was slowly added dropwise to maintain the pH of the system at 7.0–7.3, generating 1-(2-chlorophenyl)-4,4-dimethyl-1-penten-3-one.

[0040] Isoxazolone cyclization reaction:

[0041] Add 0.2 mol (13.90 g) of hydroxylamine hydrochloride to the above reaction solution, reflux and stir, and continuously add 50% sodium hydroxide solution to maintain the pH of the solution at about 7. After the addition is completed, continue the reaction for 8 h to generate 2-(2-chlorobenzyl)-4,4-dimethylisoxazol-3-one.

[0042] Purity control:

[0043] The purity was ≥99.0% as determined by HPLC, with a water content ≤0.1% (Kal Fischer method). Impurities were mainly undecarboxylated oxime compounds (≤0.5%). The structure was determined by... 1 HNMR (400MHz, CDCl3) and 13CNMR (100 MHz, CDCl3) confirmed.

[0044] Dichloroisoxane (target product):

[0045]

[0046] Physical properties:

[0047] White needle-like crystals, melting point 78~80℃, boiling point 320~325℃ (normal pressure), solubility: easily soluble in organic solvents such as dichloroethane, acetonitrile, and toluene, sparingly soluble in water (solubility ≤5 mg / L at 25℃).

[0048] Purity requirements:

[0049] For industrial applications, the purity must be ≥98.5%, with monochlorinated impurities ≤0.8%, polychlorinated impurities ≤0.3%, and other organic impurities ≤0.4%.

[0050] Reagent Specifications and Selection:

[0051]

[0052]

[0053] Preparation and characterization of supported bimetallic catalysts:

[0054] Preparation method (taking Fe-Cu / mesoporous SiO2 as an example, with a loading of 10% and Fe:Cu = 1:0.5):

[0055] Carrier pretreatment:

[0056] Take 20.0 g of mesoporous silica powder, place it in a quartz boat, put it in a muffle furnace, and program the temperature rise: room temperature → 200℃ (hold temperature for 1 h to remove physically adsorbed water) → 500℃ (heating rate 5℃ / min, hold temperature for 4 h to remove surface hydroxyl groups and residual organic matter).

[0057] After cooling to room temperature, the pore volume of the carrier was determined to be 0.9 cm³ using liquid nitrogen adsorption-desorption (BET) method. 3 / g (used for subsequent preparation of equal-volume impregnation solution) ensures that the volume of impregnation solution is completely matched with the pore volume, avoiding waste of active components or insufficient adsorption.

[0058] Preparation of mixed solution of active components:

[0059] Calculate the required precursor mass: target loading 10%, carrier mass 20.0 g, Fe:Cu molar ratio 1:0.5, Fe atomic weight 55.85, Cu atomic weight 63.55.

[0060] Let the amount of Fe be x, then the amount of Cu is 0.5x. According to the loading formula ω = (m1+m2) / (m1+m2+m0)×100%, substitute the data:

[0061] 10% = (55.85x + 63.55 × 0.5x) / (55.85x + 63.55 × 0.5x + 20.0) × 100%, solving for x gives x = 0.032 mol.

[0062] Weigh 0.032 mol of ferric nitrate (Fe(NO3)3·9H2O) × 404.0 g / mol = 12.93 g, and 0.016 mol of copper nitrate (Cu(NO3)2·3H2O) × 241.6 g / mol = 3.87 g.

[0063] Add the above precursor to a beaker, and add 18.0 mL of deionized water (carrier pore volume 20.0 g × 0.09 cm). 3 / g = 1.8 cm 3 18.0 mL was added and stirred until completely dissolved to obtain a clear and transparent mixed impregnation solution (total metal ion concentration 1.78 mol / L). The solution was allowed to stand for 30 min to eliminate the effect of heat of dissolution.

[0064] Equal volume impregnation and aging:

[0065] The pretreated mesoporous SiO2 support was slowly added to the impregnation solution and mechanically stirred (300 r / min) for 1 h at room temperature to ensure that the support particles were fully wetted and that there was no dry powder agglomeration.

[0066] After stopping stirring, the mixture was transferred to a sealed container and aged at a constant temperature of 25°C for 12 hours, with gentle agitation every 2 hours to promote the diffusion of metal ions into the pores of the carrier and form a uniform adsorption layer.

[0067] Drying and roasting:

[0068] The aged samples were transferred to a vacuum drying oven, set at 80℃ and -0.08 MPa, and dried for 6 h. The drying rate was controlled to avoid rapid evaporation of moisture, which could lead to aggregation of active components.

[0069] After drying, the sample was transferred to a muffle furnace and calcined using the following program: room temperature → 200℃ (heating rate 5℃ / min, constant temperature for 1 h, to decompose the nitrate precursor) → 450℃ (heating rate 5℃ / min, constant temperature for 3 h, to convert the metal oxide into the active phase).

[0070] During the roasting process, the exhaust gas composition was monitored in real time (NO2 and O2 content were detected by an infrared gas analyzer). When the NO2 emission was below 10 ppm, the roasting was confirmed to be complete. The gas was then naturally cooled to room temperature to obtain a brownish-red Fe-Cu oxide / mesoporous SiO2 catalyst precursor.

[0071] Reduction and activation:

[0072] The catalyst precursor was loaded into a quartz reaction tube (20 mm inner diameter) and placed in a tube furnace. Ar gas (flow rate 50 mL / min) was first introduced to purge the tube for 30 min to remove the air inside.

[0073] Switch to H2 / Ar mixed gas (volume ratio 1:9, total flow rate 80 mL / min), with programmed temperature ramp: room temperature → 150℃ (hold for 1 h to remove surface-adsorbed moisture and CO2) → 300℃ (heating rate 3℃ / min, hold for 2 h to reduce Fe2O3 to Fe3O4 and CuO to Cu). 0 ).

[0074] After reduction, Ar gas was continuously purged (flow rate 50 mL / min), and the mixture was allowed to cool naturally to room temperature to obtain a black supported Fe-Cu bimetallic catalyst. This catalyst was sealed and stored in a desiccator for later use to prevent oxidation and deactivation.

[0075] Catalyst characterization methods and results:

[0076] BET characterization: The specific surface area, pore size and pore volume of the catalyst were determined using a liquid nitrogen adsorption-desorption apparatus.

[0077] The results showed that the specific surface area was 320 m². 2 / g, average pore size 11.5 nm, pore volume 0.85 cm³ 3 / g, compared to the carrier (specific surface area 350 m²) 2 The slight decrease in (g) indicates that the active component was successfully loaded into the pores without causing serious pore blockage.

[0078] XRD characterization: The crystal phase of the catalyst was determined using X-ray diffraction (Cu Kα radiation, λ = 0.154 nm). The results showed that:

[0079] Characteristic diffraction peaks of Fe3O4 appear at 2θ = 30.1°, 35.5°, 57.1°, and 62.7°, while Cu appears at 2θ = 43.3° and 50.4°. 0 The characteristic diffraction peaks showed no obvious FeO, Fe3O4, or CuO peaks, proving that the reduction process was complete and the target active phase was formed.

[0080] XPS characterization: The valence states of elements on the catalyst surface were determined using X-ray photoelectron spectroscopy.

[0081] The results showed that Fe2p 3 / 2 The combined energy is 711.2 eV (corresponding to Fe). 3+ ) and 708.5 eV (corresponding to Fe) 2+ This indicates that Fe exists in the form of Fe3O4; Cu2p 3 / 2 The binding energy is 932.6 eV (corresponding to Cu). 0 ), without Cu 2 The characteristic peak of ⁺ (934.5 eV) verifies the complete reduction of CuO. Simultaneous detection of characteristic peaks for Si 2p and O 1s indicates a stable support structure.

[0082] ICP-OES characterization: The actual loading of Fe and Cu in the catalyst was determined by inductively coupled plasma atomic emission spectrometry. The results showed that the Fe loading was 6.2%, the Cu loading was 3.5%, and the total loading was 9.7%, which was ≤3% of the target loading of 10%, meeting the requirements for industrial production.

[0083] Transmission electron microscopy (TEM) characterization: The microstructure of the catalyst was observed using transmission electron microscopy, and the results showed that:

[0084] Fe3O4 particles (5-8 nm in diameter) and Cu 0 The particles (3-5 nm in diameter) are uniformly dispersed on the surface and within the pores of the mesoporous SiO2 support, with no obvious agglomeration. The distance between the bimetallic particles is ≤10 nm, providing a structural basis for synergistic catalysis.

[0085] Synthesis process and control of dichloroisoxane:

[0086] Reaction equipment and apparatus configuration:

[0087] Reaction vessel: 500 mL four-necked round-bottom flask, equipped with a mechanical stirrer (adjustable speed range 100~500 r / min), a constant pressure dropping funnel (50 mL), a thermometer (accuracy ±0.1℃), a nitrogen inlet tube (with flow meter) and a reflux condenser (equipped with a tail gas absorption device, containing 10% NaOH solution to absorb HCl and SO2).

[0088] Auxiliary equipment: vacuum distillation apparatus (equipped with rotary evaporator and vacuum pump, vacuum degree adjustable to -0.095MPa), high performance liquid chromatograph (for online sampling and detection), centrifuge (for catalyst recovery, speed 8000 r / min), column chromatography apparatus (silica gel column specification φ50 mm×500 mm).

[0089] Synthesis steps:

[0090] Preparation of the reaction system:

[0091] Check the four-necked flask for leaks; add 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one (0.1 mol, 18.3 g, weigh and record the exact mass) and Fe-Cu / mesoporous SiO2 catalyst (0.915 g, 5% of the raw material mass, weighed to 0.001 g) to the flask in sequence.

[0092] Preparation of mixed organic solvent: Measure 75 mL of dichloroethane and 75 mL of acetonitrile in a volume ratio of 1:1, mix them evenly, add them to a flask, turn on the mechanical stirrer (300 r / min), stir for 30 min to fully dissolve the raw materials and form a homogeneous and transparent reaction solution (by sampling observation, no solid particles are suspended).

[0093] Open the nitrogen cylinder, adjust the flow meter to a flow rate of 20 mL / min, and purge the reaction solution with nitrogen for 30 min to remove air from the system (to prevent oxygen from oxidizing the raw materials or catalyst). Keep stirring during this process.

[0094] Addition of chlorinating agent and co-catalyst:

[0095] Weigh p-benzenesulfonyl chloride (0.11 mol, 19.4 g), add it to a constant pressure dropping funnel, and slowly add it dropwise to a reaction flask at a rate of 1 mL / min (to be completed in about 40 min). During the addition process, the system temperature is controlled to not exceed 30℃ by cooling with a water bath (to avoid local overheating and side reactions).

[0096] After the chlorinating agent is added, continue stirring for 15 min to ensure the reaction solution is mixed evenly. Then, add triethylamine (0.02 mol, 2.02 g) to the constant pressure dropping funnel and add it slowly (dropping rate 0.5 mL / min, to be completed in about 4 min). During the addition process, the temperature of the system rises slightly (≤35℃), and no additional cooling is required.

[0097] Reaction process control and monitoring:

[0098] After the addition is complete, remove the water bath and turn on the oil bath to raise the reaction temperature to 55℃ (heating rate 2℃ / min, to avoid excessive temperature rise causing system fluctuations). Maintain a nitrogen atmosphere (flow rate 10 mL / min) and a stirring rate of 300 r / min, and start timing the reaction.

[0099] Samples were taken every 1 hour during the reaction (0.5 mL each time), filtered through a 0.22 μm organic phase filter membrane, and the conversion rate of the raw materials and the selectivity of the products were determined by HPLC.

[0100] Raw material conversion rate = (1 - remaining raw material peak area / initial raw material peak area) × 100%;

[0101] Target product selectivity = (Target product peak area / (Sum of peak areas of all organic products)) × 100%;

[0102] After 4 hours of reaction, sampling and testing showed that the raw material conversion rate was ≥98% and the target product selectivity was ≥97%, at which point the reaction was stopped (if the conversion rate did not meet the requirements, the reaction could be extended by 0.5 to 1 hour until the conversion rate was ≥98%).

[0103] Post-processing and purification:

[0104] Turn off the oil bath and cool the reaction solution to room temperature (about 30 min). Turn on the centrifuge, pour the reaction solution into a centrifuge tube, and centrifuge at 8000 r / min for 10 min to separate the catalyst (the upper layer is a clear organic phase and the lower layer is a black catalyst precipitate).

[0105] The upper organic phase was collected and transferred to a rotary evaporator. The temperature was set to 60℃ and the vacuum degree to -0.09 MPa. The distillation was carried out under reduced pressure for 30 min to remove dichloroethane and acetonitrile (the fraction was recovered by condensation and could be reused), and a brownish-yellow oily residue was obtained.

[0106] Add 50 mL of deionized water to the residue and stir for 10 min (to wash away residual hydrochloric acid, sodium chloride, and triethylamine salt). Allow the mixture to stand for separation (about 15 min) and discard the lower aqueous phase. Repeat the water washing operation 3 times until the pH of the aqueous phase is 6.5~7.0 (without any acidic impurities remaining).

[0107] Take the organic phase, add 5.0 g of anhydrous sodium sulfate, dry for 2 h (until the organic phase is completely clear and free of turbidity), filter to remove the anhydrous sodium sulfate, and obtain a light yellow oily liquid;

[0108] The above liquid was purified by column chromatography: a silica gel G (200-300 mesh) column was packed, and the column was pre-eluted with eluent (petroleum ether / ethyl acetate volume ratio 8:1) for 10 min. The sample was then loaded onto the column and eluted at an eluent flow rate of 5 mL / min. The elution process was monitored by thin-layer chromatography (TLC) (developing solvent was the same as the eluent, and observation was performed under a UV lamp at 254 nm; Rf value = 0.4 to -0.5 was the target product).

[0109] Collect the target product fraction, transfer it to a rotary evaporator, and distill it under reduced pressure at 45℃ and -0.095 MPa for 15 min to remove the eluent, obtaining white needle-like crystals. Dry them under vacuum (50℃, -0.09 MPa) for 2 h, cool them to room temperature, weigh them, and calculate the separation yield.

[0110] Catalyst recovery and reuse processes:

[0111] The catalyst precipitate obtained by centrifugation was washed three times with anhydrous ethanol (20 mL each time), stirred for 5 min, and then centrifuged (8000 r / min, 5 min) to remove the organic matter and impurities adsorbed on the surface.

[0112] The washed catalyst was transferred to a vacuum drying oven and dried at 80℃ and -0.08 MPa for 4 h to restore the pore structure and active sites of the catalyst.

[0113] The dried catalyst does not need to be reduced again and can be used directly in the next round of reaction (due to the Fe3O4 and Cu on the catalyst surface). 0 It will not be deeply oxidized in air in a short time, and the reaction system is a reducing atmosphere, which can maintain its activity.

[0114] If the catalyst activity decreases during repeated use (product yield is below 85%), the catalyst can be reduced twice (300℃, H2 / Ar atmosphere, 1 h) to restore its activity and then it can be used again.

[0115] Product testing and performance evaluation methods:

[0116] Structural characterization:

[0117] 1 HNMR and 13 CNMR characterization:

[0118] Instrument: Bruker AVANCE III 400MHz nuclear magnetic resonance spectrometer;

[0119] Sample preparation: Take about 10 mg of the target product, dissolve it in 0.5 mL of CDCl3 (containing 0.03% TMS internal standard), and transfer it to a 5 mm NMR tube;

[0120] Test parameters: 1 The HNMR spectrum width was 10 ppm, the relaxation delay was 2 s, and the number of scans was 16. 13 CNMR spectrum width 200 ppm, relaxation delay 3 s, 1024 scans;

[0121] Characteristic peaks of the target product:

[0122] 1 HNMRδ: 1.268 (s, 6H), 4.015 (s, 2H), 4.792 (s, 2H), 7.26-7.39 (m, 3H);

[0123] ¹³ CNMRδ: 21.57 (C10, C11), 42.69 (C1), 46.03 (C3), 78.92 (C2), 127.32–134.24 (ArC4, C5, C6, C7, C8, C9), 174.59 (isoxazole ring C).

[0124] GC-MS characterization:

[0125] Instrument: Agilent 7890A-5975C gas chromatography-mass spectrometry (GC-MS);

[0126] Chromatographic conditions: HP-5MS capillary column (30 m × 0.25 mm × 0.25 μm), column temperature program: initial temperature 60℃ (hold for 1 min) → 20℃ / min ramp to 280℃ (hold for 5 min), injection port temperature 250℃, carrier gas He (flow rate 1.0 mL / min), split ratio 10:1, injection volume 1 μL;

[0127] Mass spectrometry conditions: electron impact source (EI), electron energy 70 eV, ion source temperature 230℃, mass scan range m / z = 50-300;

[0128] Target product characteristics: molecular ion peak m / z = 274 (M⁺, C⁻¹) 12 H 13 The molecular weight of Cl2NO2 is 251.14, and the main fragment peaks are m / z = 239 (M⁺-Cl) and 204 (M⁺-2Cl), which are consistent with the standard spectrum.

[0129] Purity and yield testing:

[0130] HPLC purity testing:

[0131] Instrument: Agilent 1260 high performance liquid chromatograph;

[0132] Chromatographic conditions: C18 column (250 mm × 4.6 mm, 5 μm), column temperature 30℃, mobile phase methanol / water (volume ratio 7:3), flow rate 1.0 mL / min, detection wavelength 254 nm, injection volume 20 μL, run time 20 min;

[0133] Standard curve preparation: Accurately weigh 0.05 g, 0.10 g, 0.20 g, 0.40 g, and 0.80 g of dichloroisoxane standard (99.9% purity), dissolve them in 100 mL of methanol respectively, and prepare standard solutions of 0.5 μg / μL, 1.0 μg / μL, 2.0 μg / μL, 4.0 μg / μL, and 8.0 μg / μL. Inject the solutions for analysis, and plot the standard curve against the concentration (X) using peak area (Y). The regression equation obtained is Y = 12568X + 12.3 (R²). 2 = 0.9998);

[0134] Sample testing: Take about 0.1 g of sample, dissolve it in 100 mL of methanol, inject the sample for testing, and calculate the concentration based on the peak area in the regression equation, and then obtain the purity (purity = sample concentration / theoretical concentration × 100%).

[0135] Separation yield calculation:

[0136] Theoretical mass = Amount of raw material × Molar mass of target product = 0.1 mol × 274.14 g / mol = 27.414 g;

[0137] Separation yield = (actual mass of target product / theoretical mass) × 100%;

[0138] Example: In Example 1, 25.82 g of the target product was obtained, and the separation yield = 25.82 / 27.414 × 100% = 94.2%.

[0139] The formula for selective calculation is:

[0140] S=n(II) / [n(I)0-n(I) 残 ]×100%

[0141] In the formula: n(II) is the number of moles of the target product = actual product mass / 274.14 g / mol; n(I)0 is the initial number of moles of raw material = 0.1 mol; n(I) 残 The number of unreacted reactant moles = (initial mass of reactant - mass of remaining reactant) / 115.13 g / mol (molar mass of reactant 115.13 g / mol), and the mass of remaining reactant is calculated using an HPLC standard curve;

[0142] Example: n(I) in Example 1 残= 0.002 mol, n(II) = 25.82 / 27.414 ≈ 0.0946 mol, selectivity S = 0.0946 / (0.1-0.002) × 100% ≈ 96.5% (the deviation from the previous 97.5% is the detection error, which is within the industrial allowable range).

[0143] Examples and Comparative Examples:

[0144] Examples with different process parameters:

[0145]

[0146] Comparison of the impact of key parameters:

[0147]

[0148] Industrial scale-up experimental data (10 L reactor):

[0149] Raw material usage: 1.0 mol (239.7 g) of 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one, 9.15 g (5%) of Fe-Cu / mesoporous SiO2 catalyst, 1.1 mol (193.6 g) of p-benzenesulfonyl chloride, 0.2 mol (20.2 g) of triethylamine, and 1500 mL of mixed solvent (DCE:MeCN=1:1);

[0150] Reaction equipment: 10 L stainless steel reactor, equipped with mechanical stirring (250 r / min), jacket heating (temperature control accuracy ±1℃), online sampling port, and nitrogen protection device;

[0151] Reaction process: The temperature was raised to 55℃, and the reaction was carried out for 4 hours. Samples were taken and the conversion rate of the raw materials was tested to be 98.7%.

[0152] Post-processing results: After vacuum distillation, water washing, and column chromatography purification, 257.3 g of the target product was obtained, with a separation yield of 93.9%, purity of 99.0%, and selectivity of 97.2%.

[0153] Catalyst recovery: Centrifugation yielded 8.7 g of catalyst (recovery rate 95.1%), which was reused 5 times with a yield of 88.6% and an activity retention rate of 94.4%.

[0154] Conclusion: The process of this invention has stable performance after scale-up, with no significant decrease in yield and purity, and meets the requirements for industrial production.

[0155] This invention achieves the following:

[0156] Innovation of bimetallic synergistic catalytic system: through Fe3O4 and Cu 0The synergistic effect of Fe3O4 activating the chlorinating agent to produce Cl + Active species, Cu 0 It promotes the removal of active hydrogen from the raw material molecules, and the two work together to improve the reaction selectivity (≥95%), solving the problem of low selectivity of traditional single metal catalysts;

[0157] Catalyst structure optimization: Mesoporous SiO2 or γ-Al2O3 is selected as the support. The high specific surface area and suitable pore size ensure uniform dispersion of active components. The loading is controlled at 5%~15%, balancing catalytic activity and cost. The catalyst can be reused more than 5 times, reducing industrial production costs.

[0158] The reaction system has strong adaptability: a specific dichloroethane-acetonitrile mixed solvent adjusts the polarity of the system, matches the solubility of the chlorinating agent and the raw materials, and triethylamine co-catalyst neutralizes acidic by-products, inhibits catalyst deactivation and raw material hydrolysis, and further improves reaction efficiency;

[0159] The reaction conditions are mild: the reaction temperature is 40~70℃, the operation is at normal pressure, and the reaction time is 2~6 hours. Compared with the traditional high temperature and high pressure process, the energy consumption is reduced by more than 30%, and the amount of chlorinating agent used is only 0.9~1.3 times that of the raw materials. It has higher atom economy and less environmental pressure.

[0160] The product quality is excellent: the product yield is ≥92% and the purity is ≥98.5%, which is far higher than that of traditional processes (yield ≤80% and purity ≤95%). Furthermore, the by-products are easy to separate and the subsequent purification cost is low, making it suitable for large-scale industrial production.

[0161] The embodiments of the present invention are given for illustrative and descriptive purposes only, and are not intended to be exhaustive or to limit the invention to the forms disclosed. Many modifications and variations will be apparent to those skilled in the art. The embodiments were chosen and described to better illustrate the principles and practical application of the invention, and to enable those skilled in the art to understand the invention and design various embodiments with various modifications suitable for a particular purpose.

Claims

1. A highly efficient catalytic synthesis method for dichloroisoxane, characterized in that: 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one (C 12 H 14 Using ClNO2 as a raw material, a selective chlorination reaction is carried out with a chlorinating agent in an organic solvent under the action of a supported bimetallic catalyst to obtain dichloroisoxane (CNO2). 12 H 14 Cl2NO2), Wherein, R is an alkyl or aryl group.

2. The method according to claim 1, characterized in that, The supported bimetallic catalyst is supported on mesoporous SiO2 or γ-Al2O3, with a specific surface area of ​​200~500 m². 2 / g, with a pore size of 5~20 nm.

3. The method according to claim 1, characterized in that, The active components of the supported bimetallic catalyst are Fe and Cu, with a bimetallic molar ratio of Fe:Cu = 1:(0.3~0.8).

4. The method according to claim 3, characterized in that, The loading amount of the active component on the support satisfies the formula: Load ω = (m1+m2) / (m1+m2+m0)×100% Where m1 is the mass of Fe, m2 is the mass of Cu, m0 is the mass of the carrier, and ω ranges from 5% to 15%.

5. The method according to claim 1, characterized in that, The chlorinating agent is p-benzenesulfonyl chloride or methanesulfonyl chloride, and the molar ratio of 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one to the chlorinating agent is 1:(0.9~1.3).

6. The method according to claim 1, characterized in that, The organic solvent is a mixture of dichloroethane and acetonitrile, with a volume ratio of dichloroethane to acetonitrile of 1:(0.5~1.2).

7. The method according to claim 1, characterized in that, The conditions for the selective chlorination reaction are: reaction temperature 40~70℃, reaction time 2~6 h, and catalyst dosage of 3%~8% of the mass of 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one.

8. The method according to claim 1, characterized in that, The reaction requires the addition of triethylamine as a co-catalyst, with a molar ratio of (0.1~0.3):1 to 2-(2-chlorobenzyl)-4,4-dimethylisozol-3-one.

9. The method according to claim 1, characterized in that, After the reaction, the product was purified by vacuum distillation, water washing, and column chromatography. The yield of dichloroisoxane was ≥92%, the purity was ≥98.5%, and the reaction selectivity S satisfied the formula: S = n(II) / [n(I)0-n(I) 残 ]×100% Wherein, n(II) represents the number of moles of the target product, n(I)0 represents the initial number of moles of the raw material, and n(I) 残 The number of unreacted reactants is S≥95%.

10. The method according to any one of claims 1 to 9, characterized in that, The supported bimetallic catalyst can be reused 3 to 5 times after being recovered and dried, and the catalytic activity retention rate is ≥85% after 5 reuses.

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