Synthesis method of 2, 5-dibromobenzoquinone

Abstract

The invention relates to the technical field of organic synthesis, in particular to a synthetic method of 2, 5-dibromobenzoquinone, which takes hydroquinone as an initial raw material and comprises the following two steps: step 1, adding 0.5-2% (based on the mass of hydroquinone) of a phase transfer catalyst (such as tetrabutylammonium bromide) into a glacial acetic acid solvent, reacting with bromine at 10-15 DEG C to generate 2, 5-dibromohydroquinone, and reacting for 2-4 hours at the temperature of 10-15 DEG C to obtain 2, 5-dibromohydroquinone; after the reaction, stably storing an intermediate under the protection of inert gas; 2, oxidizing the 2, 5-dibromohydroquinone into 2, 5-dibromobenzoquinone at the temperature of 45-50 DEG C by taking acetonitrile as a solvent and adopting a tert-butyl hydroperoxide (TBHP)-sodium nitrite composite oxidant (the molar ratio is (10: 1)-(15: 1)); meanwhile, glacial acetic acid and acetonitrile mother liquor generated in the reaction process are subjected to vacuum rectification recovery (the acetonitrile recovery rate is greater than or equal to 90%, and the glacial acetic acid recovery rate is greater than or equal to 88%) for recycling. The invention solves the problems of more brominated byproducts, low oxidation efficiency, solvent waste and unstable intermediate in the prior art.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically a method for synthesizing 2,5-dibromobenzoquinone. Background Technology

[0002] 2,5-Dibromobenzoquinone is an important halogenated quinone organic intermediate. Its molecular structure contains both a highly reactive bromine atom and a conjugated quinone group, exhibiting both electron transport capability and electrophilic properties. It has irreplaceable application value in pharmaceuticals, pesticides, and polymer materials. In the pharmaceutical field, 2,5-dibromobenzoquinone can be used as an intermediate for antibacterial drugs, synthesizing novel antibiotics against Gram-positive bacteria. In the pesticide field, it can serve as a herbicide precursor, enhancing the targeted inhibition of weeds by modifying the quinone group. Especially in the field of polymer materials, 2,5-dibromobenzoquinone acts as a crosslinking agent and modifier, forming stable covalent bonds with polymer chains, significantly improving the material's heat resistance (heat distortion temperature increased by 20-30℃), flame retardancy (oxygen index increased to over 28), and mechanical strength (tensile strength increased by 15-20%), making it one of the key raw materials for preparing high-end engineering plastics.

[0003] With the continued growth in demand from the fine chemical industry for high-purity, low-cost 2,5-dibromobenzoquinone, the technological bottlenecks of existing synthesis processes are becoming increasingly prominent, mainly due to the following problems: Bromination reactions have poor selectivity and produce many byproducts: Current technology uses hydroquinone as a raw material to directly react with bromine in glacial acetic acid to generate 2,5-dibromohydroquinone. However, the hydroxyl group of hydroquinone has a strong activating effect, which easily leads to over-substitution of bromine, generating byproducts such as 2,3,5-tribromohydroquinone and 2,5-dibromo-3-hydroxybenzoquinone (the content is usually 3-5%). This not only reduces the yield of intermediates (the current yield is about 62.5%), but also requires purification by complex separation methods such as column chromatography, which increases production costs. The oxidation reaction is inefficient and energy-intensive: the existing oxidation process uses ammonium cerium nitrate (CAN) as a catalyst and requires the reaction to be carried out at boiling acetonitrile (100°C). The high temperature not only increases energy consumption but also poses safety risks due to solvent evaporation. In addition, the CAN catalytic system has a slow reaction rate and requires a holding time of more than 3 hours, resulting in low production efficiency. Furthermore, CAN is expensive (about 80 yuan / 100g), and the residual cerium metal will lead to a decrease in product purity (the purity of the current product is about 98%), which is difficult to meet the needs of high-end materials. The current process results in serious solvent waste and significant environmental pollution: solvents such as glacial acetic acid and acetonitrile are mostly directly discharged or simply recovered by distillation. Due to the lack of optimized distillation parameters, the solvent recovery rate is less than 60%. The loss of a large amount of organic solvents not only wastes resources (acetonitrile costs about 12 yuan / L and glacial acetic acid costs about 3 yuan / L), but also generates volatile organic pollutants (VOCs), which does not meet the national environmental protection requirements. The intermediate has poor storage stability and high storage costs: the phenolic hydroxyl group in the 2,5-dibromohydroquinone molecule is easily oxidized by oxygen in the air. In the existing technology, the intermediate needs to be stored in a sealed container at a low temperature below -5°C, which results in high storage energy consumption. Moreover, after storage for more than one month, the content of oxidized impurities will rise to more than 2%, which will lead to a further decrease in the purity of the product in subsequent oxidation reactions, affecting continuous industrial production. Poor process adaptability and difficulty in flexible adjustment: Existing technologies use the CAN-acetonitrile system and cannot replace the oxidant or solvent according to different production scenarios (such as environmental requirements and cost budgets). When faced with a shortage of CAN supply or tightening of environmental policies, production is prone to stagnation.

[0004] In summary, the existing synthesis process for 2,5-dibromobenzoquinone has significant shortcomings in terms of selectivity, efficiency, environmental friendliness, and stability. There is an urgent need to develop a synthesis method that is highly selective, efficient, energy-saving, and environmentally friendly to promote its industrial application. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention aims to solve the following core technical problems: improve the selectivity of bromination reactions, reduce polybrominated byproducts, and increase the yield and purity of 2,5-dibromohydroquinone; replace the expensive cerium ammonium nitrate catalyst, lower the oxidation reaction temperature, improve reaction efficiency, and avoid metal residues; achieve efficient recovery and recycling of solvents, reduce environmental pollution, and lower raw material costs; improve the storage stability of 2,5-dibromohydroquinone, extend its shelf life, and adapt to the needs of continuous industrial production; provide flexible process alternatives to adapt to different production conditions (such as oxidant and solvent replacement), and enhance process adaptability. This invention provides a method for synthesizing 2,5-dibromobenzoquinone.

[0006] The technical solution adopted by this invention to solve its technical problem is: a method for synthesizing 2,5-dibromobenzoquinone, comprising the following steps: (1) Synthesis of 2,5-dibromohydroquinone: Hydroquinone and glacial acetic acid were added to the reaction vessel, stirred and heated to 30-35℃ to completely dissolve the hydroquinone. 0.5-2% of the mass of hydroquinone was added as a phase transfer catalyst (selected from tetrabutylammonium bromide or hexadecyltrimethylammonium bromide). The temperature was slowly lowered to 10-15℃, and then bromine diluted with glacial acetic acid was added dropwise (the molar ratio of bromine to hydroquinone was 2.05:1-2.1:1). After the addition was completed, the reaction was kept at the temperature for 2 hours. The reaction was stopped when no raw material was detected by TLC (developing solvent EA:PE=1:4). The reaction solution was filtered, and the mother liquor was concentrated under reduced pressure at 60℃ and -0.09MPa until no solvent dripped out. The temperature was lowered to 5-10℃ and filtered again. The two filter cakes were combined and dried under the protection of an inert gas (nitrogen or argon) to obtain 2,5-dibromohydroquinone. (2) Synthesis of 2,5-dibromobenzoquinone: 2,5-dibromohydroquinone and acetonitrile obtained in step (1) were added to another reaction vessel and heated to 45-50℃ to completely dissolve the intermediate. Sodium nitrite (molar ratio of TBHP to TBHP was 1:10-1:15) was added, and then 70% tert-butanol peroxide aqueous solution (molar ratio of TBHP to 2,5-dibromohydroquinone was 1.5:1-1.8:1) was slowly added dropwise. The system temperature was maintained at 40-45℃ during the dropwise addition. After the dropwise addition was completed, the temperature was raised to 45-50℃ and kept at the temperature for 1-1.5h. The reaction was stopped after TLC detection showed no raw material. The system was cooled to 10-15℃ and filtered. The filter cake was washed with a small amount of methanol and dried under vacuum. It was then dried at 35℃ to obtain 2,5-dibromobenzoquinone. (3) Solvent recovery: Collect the glacial acetic acid mother liquor from step (1) and the acetonitrile mother liquor from step (2), and perform vacuum distillation respectively. Glacial acetic acid is recovered by distillation at 110-115℃ and -0.09MPa (purity ≥98%), and acetonitrile is recovered by distillation at 60-65℃ and -0.095MPa (purity ≥99%). The recovered solvent is used for subsequent batch reactions.

[0007] Specifically, the phase transfer catalyst in step (1) is tetrabutylammonium bromide, and the amount used is 1% of the mass of hydroquinone.

[0008] Specifically, in step (1), the dilution ratio of bromine is bromine: glacial acetic acid = 7.256:1 (mass ratio).

[0009] Specifically, in step (2), the molar ratio of TBHP to sodium nitrite is 12:1.

[0010] Specifically, the heat preservation reaction time in step (2) is 1.5h.

[0011] Specifically, in step (1), the inert gas is nitrogen. After the intermediate is dried, it is stored at 0-5℃ under nitrogen-sealed conditions, and the storage period is ≥6 months.

[0012] Specifically, in step (3), the recovery rate of acetonitrile is ≥90% and the recovery rate of glacial acetic acid is ≥88%.

[0013] Specifically, in step (2), the solvent can be replaced with an ethanol-water mixed solvent (ethanol:water = 9:1, volume ratio), at which point the amount of TBHP increases by 10%.

[0014] Specifically, in step (2), tert-butanol peroxide can be replaced with a 30% aqueous solution of hydrogen peroxide, and 1 mol / L sulfuric acid is added as a co-catalyst (the molar ratio of sulfuric acid to 2,5-dibromohydroquinone is 0.05:1).

[0015] Specifically, the prepared 2,5-dibromobenzoquinone product has a purity of ≥99.2%, a polybrominated byproduct content of ≤0.8%, and a melting point of 195-197℃.

[0016] The beneficial effects of this invention are: (1) The method for synthesizing 2,5-dibromobenzoquinone described in this invention introduces a phase transfer catalyst into the bromination reaction, and combines precise reaction temperature control and bromine drop acceleration adjustment to guide the bromination reaction to generate the target intermediate 2,5-dibromohydroquinone, effectively inhibiting the generation of polybrominated byproducts; at the same time, the step-by-step post-treatment with inert gas protection and drying through two filtrations not only improves the purity of the intermediate, but also solves the problem of easy oxidation of the intermediate in the traditional process, extends its shelf life, avoids interference from impurities in subsequent oxidation reactions, and provides a guarantee for the preparation of high-purity final products.

[0017] (2) The method for synthesizing 2,5-dibromobenzoquinone described in this invention replaces the traditional high-cost and metal-residue-prone cerium ammonium nitrate catalyst with TBHP-sodium nitrite composite oxidant. This reduces raw material costs, lowers oxidation reaction temperature, shortens reaction time, and improves oxidation reaction efficiency, while avoiding the impact of metal ion residues on product purity. At the same time, a targeted solvent vacuum distillation recovery system is constructed to achieve efficient recycling of glacial acetic acid and acetonitrile, reducing organic solvent waste and volatile organic pollutant emissions, thus balancing economic efficiency and environmental protection. In addition, alternative solutions for solvents and oxidants are provided, which can be flexibly adjusted according to the cost and environmental protection requirements of the production scenario, enhancing process adaptability and making it easier to meet the needs of continuous industrial production. Detailed Implementation

[0018] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0019] The method for synthesizing 2,5-dibromobenzoquinone according to the present invention specifically includes the following steps: (1) Synthesis of 2,5-dibromohydroquinone (bromination stage) Raw material ratio: 250g hydroquinone (2.27mol), 2.4L glacial acetic acid (solvent), 2.5g phase transfer catalyst (tetrabutylammonium bromide, TBA-Br) (1% of the mass of hydroquinone), 725.6g bromine (4.54mol, molar ratio of hydroquinone to hydroquinone 2.05:1), the bromine is diluted with 0.1L glacial acetic acid (to reduce local concentration and avoid over-bromination).

[0020] Reaction Procedure: Hydroquinone and glacial acetic acid are added sequentially to a 5L four-necked reaction flask. Stirring and oil bath heating are started, and the temperature is raised to 30-35℃. After the hydroquinone is completely dissolved (the solution is colorless and transparent), tetrabutylammonium bromide is added, and the mixture is stirred for 10 minutes to ensure uniform catalyst dispersion. The oil bath is then turned off, and the temperature is slowly lowered to 10-15℃ using an ice-water bath (the cooling rate is controlled at 1-2℃ / min to avoid localized overcooling that could cause precipitation of the raw materials). Then, diluted bromine is added dropwise through a constant-pressure dropping funnel at a rate of 1-2 drops / second. (Approximately 1.5 hours) During the dropwise addition, the system first changes from colorless to a brownish-yellow suspension, then turns into a brown solution when half is added, and then returns to a light brownish-yellow suspension after further addition (indicating that the reaction proceeds smoothly without excessive bromination). After the addition is complete, maintain the reaction at 10-15℃ for 2 hours, and take samples every 30 minutes for TLC analysis (developing solvent: ethyl acetate (EA): petroleum ether (PE) = 1:4, Rf value: hydroquinone approximately 0.3, 2,5-dibromohydroquinone approximately 0.6) until the starting material spot disappears, at which point the reaction is stopped.

[0021] Post-treatment and stabilization: The reaction solution was directly filtered, and the filter cake (initial product) was collected. The filter cake was washed twice with a small amount of glacial acetic acid (about 20 mL) and dried under vacuum. The filtrate (containing the unprecipitated intermediate and glacial acetic acid) was transferred to a rotary evaporator and concentrated under reduced pressure at 60 °C and -0.09 MPa until no solvent dripped out (about 2 h). After cooling to 5-10 °C, it was filtered again, and the second filter cake was collected. The two filter cakes were combined and placed in a nitrogen-protected desiccator to dry (to avoid oxidation by oxygen in the air) to obtain a grayish-white solid of 2,5-dibromohydroquinone. The intermediate was transferred to a nitrogen-sealed polyethylene storage tank and stored at 0-5 °C, which can extend the shelf life to more than 6 months.

[0022] (2) Synthesis of 2,5-dibromobenzoquinone (oxidation stage) Raw material ratio: 360g (1.21mol) of 2,5-dibromohydroquinone obtained in step (1), 2.88L of acetonitrile (solvent), 343.17g (1.82mol, molar ratio with intermediate 1.5:1) of 70% tert-butanol peroxide (TBHP) aqueous solution, and 3.2g (0.046mol, molar ratio with TBHP 1:12, as a co-oxidant) of sodium nitrite.

[0023] Reaction Procedure: Add 2,5-dibromohydroquinone and acetonitrile to a 10L four-necked reaction flask. Turn on the stirrer and heat in an oil bath to 45-50℃. After the intermediate is completely dissolved (the solution is colorless and transparent), add sodium nitrite and stir for 5 minutes to dissolve the oxidizing agent. Maintain the temperature at 45-50℃ and slowly add 70% TBHP aqueous solution dropwise through a constant pressure dropping funnel at a rate of 2-3 drops / second (dropping time is about 2 hours). During the dropwise addition, the temperature of the system will drop to 40-42℃ due to the slight endothermic effect of TBHP. No additional heating is required; maintain the temperature naturally (to avoid side reactions caused by temperature fluctuations). After the dropwise addition is complete, raise the temperature to 45-50℃ and maintain the reaction for 1.5 hours. Take samples every 30 minutes for TLC analysis (developing solvent as above, Rf value: 2,5-dibromohydroquinone about 0.6, 2,5-dibromobenzoquinone about 0.8) until the intermediate spot disappears, then stop the reaction.

[0024] Post-processing: Turn off the oil bath and cool the system to 10-15℃ using an ice-water bath (cooling rate 2-3℃ / min). At this point, a pale yellow solid precipitates out. Filter and collect the filter cake. Rinse the filter cake three times with a small amount of methanol (about 30 mL) (to remove residual TBHP and sodium nitrite), and dry it under vacuum. Transfer the filter cake to a vacuum drying oven and dry it at 35℃ and -0.09 MPa for 4 hours to obtain a pale yellow 2,5-dibromobenzoquinone solid.

[0025] (3) Solvent recovery and recycling Glacial acetic acid recovery: Collect the bromination mother liquor (containing unreacted glacial acetic acid and a small amount of intermediates) from step (1), transfer it to a distillation column (packed with glass springs, column height 1.5m), turn on the vacuum system, control the vacuum degree to -0.09MPa, heat the distillation column bottom to 110-115℃, collect the top distillate (temperature about 105℃), which is the recovered glacial acetic acid. The purity is ≥98% and the recovery rate is ≥88% as detected by gas chromatography (GC). It can be directly used for subsequent bromination reactions (only a small amount of new glacial acetic acid needs to be added to 2.4L).

[0026] Acetonitrile recovery: Collect the oxidation mother liquor (containing unreacted acetonitrile and a small amount of TBHP decomposition products) from step (2), transfer it to the same distillation column, adjust the vacuum to -0.095MPa, heat the column bottom to 60-65℃, and collect the top distillate (temperature about 55℃), which is the recovered acetonitrile. GC detection shows a purity of ≥99% and a recovery rate of ≥90%, which can be directly used for subsequent oxidation reactions (only a small amount of new acetonitrile needs to be added to 2.88L).

[0027] Example 1: Synthesis of 2,5-dibromobenzoquinone based on TBHP-sodium nitrite composite oxidant 1. Experimental materials and equipment Raw materials: hydroquinone (analytical grade, 99%), glacial acetic acid (analytical grade, 99.5%), tetrabutylammonium bromide (analytical grade, 98%), bromine (analytical grade, 99.5%), 70% tert-butanol peroxide aqueous solution (industrial grade, 99%), sodium nitrite (analytical grade, 99%), acetonitrile (analytical grade, 99.9%), methanol (analytical grade, 99.9%), nitrogen (purity 99.99%).

[0028] Equipment: 5L four-necked reaction flask (with stirrer, thermometer, constant pressure dropping funnel, reflux condenser), 10L four-necked reaction flask (same as 5L), rotary evaporator, vacuum drying oven, distillation column (1.5m, glass spring packing), gas chromatograph, high performance liquid chromatograph, melting point apparatus.

[0029] 2. Experimental Procedure (1) Synthesis of 2,5-dibromohydroquinone Add 250g hydroquinone and 2.4L glacial acetic acid sequentially to a 5L four-necked reaction flask. Turn on the stirrer (300rpm) and heat in an oil bath at 40℃. When the system temperature reaches 30-35℃, the hydroquinone will completely dissolve, and the solution will be colorless and transparent. Add 2.5g tetrabutylammonium bromide (1% of the mass of hydroquinone) and stir for 10min until the catalyst is completely dissolved. Turn off the oil bath, place an ice-water bath on top, and slowly cool to 10-15℃ (cooling rate 1.5℃ / min). During this process, a small amount of white solid will precipitate (this is due to hydroquinone supersaturation and does not affect the reaction). Add 725.6g bromine (prepared with 0.1L glacial acetic acid) dropwise through a constant-pressure dropping funnel. (Dilution), the dropping rate was controlled at 1.5 drops / second. In the initial stage of dropping, the system turned into a brownish-yellow suspension. When 360g of bromine was added (about 45 minutes), the suspension completely dissolved and the solution turned brown. The remaining bromine was added dropwise. When 600g was added (about 1 hour), a light brownish-yellow suspension reappeared in the system, indicating that the reaction was directed to produce 2,5-dibromohydroquinone. After the addition was completed (total time 1.5 hours), the reaction was maintained at 10-15℃ for 2 hours. Samples were taken every 30 minutes for TLC detection (developing solvent EA:PE = 1:4). At the 2nd hour, the TLC showed that the starting material spot (Rf = 0.3) had completely disappeared, leaving only the intermediate spot (Rf = 0.6), and the reaction was stopped.

[0030] Turn on the vacuum pump and filter the reaction solution using a Buchner funnel with filter paper pore size of 1-3 μm. Collect the filter cake (initial product, grayish-white). Wash the filter cake twice with 20 mL of glacial acetic acid and dry it until no liquid drips out. Transfer the filtrate to a rotary evaporator, set the temperature to 60℃ and the vacuum degree to -0.09 MPa, and concentrate it under reduced pressure for 2 h until no solvent drips out of the condenser, resulting in a viscous liquid. Transfer the viscous liquid to a beaker, cool it to 5-10℃ in an ice-water bath, and let it stand for 30 min. A large amount of grayish-white solid precipitates out. Filter it again and collect the second filter cake. Combine the two filter cakes and place them in a desiccator under nitrogen protection (nitrogen gas flow rate 100 mL / min). Air dry at room temperature for 4 h to obtain 405 g of 2,5-dibromohydroquinone solid.

[0031] (2) Storage stability test of 2,5-dibromohydroquinone The intermediates were divided into two groups: one group was placed in a nitrogen-sealed storage tank and refrigerated at 0-5℃; the other group was placed in an open beaker and exposed to air at room temperature (25℃). Samples were taken after 1 month, 3 months, and 6 months, and the impurity content was determined by HPLC: the impurity content of the refrigerated group was 0.3% after 1 month, 0.5% after 3 months, and 0.8% after 6 months; the impurity content of the open beaker group was 2.1% after 1 month, 4.5% after 3 months, and 8.2% after 6 months. The results show that nitrogen protection combined with low-temperature storage can significantly improve the stability of the intermediates.

[0032] (3) Synthesis of 2,5-dibromobenzoquinone Add 360g of the above-mentioned 2,5-dibromohydroquinone and 2.88L of acetonitrile to a 10L four-necked reaction flask. Turn on the stirring (250rpm) and oil bath heating, setting the oil bath temperature to 55℃. When the system temperature rises to 45-50℃, the intermediate completely dissolves, and the solution becomes colorless and transparent. Add 3.2g of sodium nitrite and stir for 5min to completely dissolve the oxidizing agent. Maintain the oil bath temperature at 55℃ and slowly add 343.17g of 70% TBHP aqueous solution through a constant pressure dropping funnel at a dropping rate of 2.5 drops / second. During the dropping process, the system temperature drops to 42℃ due to endothermic reaction, and the oil bath temperature is maintained naturally without adjustment. After the dropping is completed (total time 2h), raise the temperature to 45-50℃ and maintain the reaction for 1.5h. Take samples every 30min for TLC detection. At 1.5h, the TLC shows that the intermediate spot (Rf=0.6) has completely disappeared, leaving only the product spot (Rf=0.8), and the reaction is stopped.

[0033] Turn off the oil bath, cover with an ice-water bath, and cool the system to 10-15℃ (cooling rate 2.5℃ / min). Let it stand for 30 min, and a pale yellow solid will precipitate. Collect the filter cake by vacuum filtration, and wash the filter cake three times with 30 mL of methanol (to remove residual TBHP and sodium nitrite). Dry the filter cake until no liquid drips out. Transfer the filter cake to a vacuum drying oven, set the temperature to 35℃ and the vacuum degree to -0.09 MPa, and dry for 4 h to obtain 162 g of pale yellow 2,5-dibromobenzoquinone solid.

[0034] (4) Solvent recovery and recycling The brominated mother liquor (approximately 2.2 L) from step (1) was collected and transferred to a 1.5 m distillation column. The vacuum system was turned on, and the vacuum degree was controlled at -0.09 MPa. The column bottom was heated to 112 °C. When the temperature at the top of the column stabilized at 105 °C, the distillate was collected. The collection continued for 1.8 h, yielding 1.95 L of recovered glacial acetic acid. The purity of the recovered glacial acetic acid was determined by GC: the main peak area accounted for 98.5%, and the impurities were a small amount of brominated products (1.2%) and water (0.3%), with a recovery rate of 88.6%.

[0035] The oxidation mother liquor (approximately 2.7 L) from step (3) was collected and transferred to the same distillation column. The vacuum was adjusted to -0.095 MPa, and the column bottom was heated to 62°C. When the temperature at the top of the column stabilized at 55°C, the distillate was collected and collected continuously for 2 hours to obtain 2.45 L of recovered acetonitrile. The purity of the recovered acetonitrile was determined by GC: the main peak area accounted for 99.3%, and the impurities were a small amount of tert-butanol (0.5%) and water (0.2%), with a recovery rate of 89.8%.

[0036] 3. Product Testing and Results Appearance: Pale yellow needle-like crystals; Melting point: Measured with a melting point apparatus at a heating rate of 1℃ / min, the melting point is 195.5-196.8℃ (consistent with the standard value of 196℃). Purity: Detected by HPLC (C18 column, mobile phase: methanol:water = 7:3, flow rate 1 mL / min, detection wavelength 254 nm), the main peak area accounted for 99.5%, and the impurities were a small amount of unoxidized intermediates (0.3%) and polybrominated compounds (0.2%). Yield: Based on hydroquinone, the overall yield was 45.0% (compared to approximately 39.5% in the prior art), representing an improvement of 14%.

[0037] Example 2 Synthesis of 2,5-dibromobenzoquinone based on hydrogen peroxide-sulfuric acid co-catalysis (oxidant alternative) 1. Experimental Objective Verify the feasibility of using hydrogen peroxide (H2O2) to replace TBHP as an oxidant, thereby reducing raw material costs (approximately 2 yuan / L for 30% H2O2 and approximately 15 yuan / L for 70% TBHP).

[0038] 2. Experimental Procedure (1) Synthesis of 2,5-dibromohydroquinone Following the same procedure as in Example 1 (1), 402g of 2,5-dibromohydroquinone was obtained (yield 67.3%, purity 99.0%).

[0039] (2) Synthesis of 2,5-dibromobenzoquinone Add 360g of 2,5-dibromohydroquinone and 2.88L of acetonitrile to a 10L four-necked reaction flask, and heat to 45-50℃ to completely dissolve the intermediate. Add 36mL of 1mol / L sulfuric acid (molar ratio of 0.05:1 to the intermediate, as a co-catalyst to promote the decomposition of H2O2 to generate hydroxyl radicals), and stir for 5min. Slowly add 480g of 30% H2O2 aqueous solution (molar ratio of 1.8:1 to the intermediate; since the activity of H2O2 is lower than that of TBHP, the amount needs to be increased appropriately) at a dropping rate of 2 drops / second. During the dropping process, the system temperature drops to 41℃. After the dropping is completed, raise the temperature to 45-50℃ and keep the reaction at this temperature for 1.8h. After TLC detection shows that the intermediate has completely reacted, cool to 10-15℃, filter, wash with methanol, and dry at 35℃ to obtain 158g of 2,5-dibromobenzoquinone solid.

[0040] (3) Solvent recovery Following the same procedure as in Example 1, step (4), 2.4 L of acetonitrile (99.1% purity, 87.5% recovery rate) and 1.9 L of glacial acetic acid (98.2% purity, 86.4% recovery rate) were recovered.

[0041] 3. Product Testing and Results Appearance: Pale yellow powder; Melting point: 195.2-196.5℃; Purity: 99.3% as determined by HPLC (0.7% impurities); Yield: 43.9% (slightly lower than the TBHP system, but with a 60% cost reduction), indicating that the H2O2 alternative is feasible and suitable for cost-sensitive production scenarios.

[0042] Example 3 Synthesis of 2,5-dibromobenzoquinone based on ethanol-water solvent (solvent substitution) 1. Experimental Objective To verify the feasibility of using an ethanol-water mixed solvent to replace acetonitrile and reduce solvent toxicity (ethanol is far less toxic than acetonitrile and is a low-VOCs solvent).

[0043] 2. Experimental Procedure (1) Synthesis of 2,5-dibromohydroquinone Following the same procedure as in Example 1 (1), 403g of 2,5-dibromohydroquinone was obtained (yield 67.5%, purity 99.1%).

[0044] (2) Synthesis of 2,5-dibromobenzoquinone Add 360g of 2,5-dibromohydroquinone and 2.88L of ethanol-water mixed solvent (ethanol:water = 9:1, volume ratio) to a 10L four-necked reaction flask, and heat to 45-50℃ until the intermediate is completely dissolved (the solubility of the ethanol-water system is slightly lower than that of acetonitrile, so stirring for 15min is required); add 3.2g of sodium nitrite and stir for 5min; add 377.5g of 70% TBHP aqueous solution dropwise (the amount is increased by 10% because the ethanol-water system has low solubility for TBHP), at a dropping rate of 2 drops / second, during which the system temperature drops to 40℃, and after the addition is complete, raise the temperature to 45-50℃ and keep the reaction at this temperature for 1.6h; after the reaction is complete as detected by TLC, cool to 10-15℃ and filter (the product precipitation is more uniform in the ethanol-water system), wash with ethanol, and dry at 35℃ to obtain 159g of 2,5-dibromobenzoquinone solid.

[0045] (3) Solvent recovery The mother liquor from oxidation was transferred to a distillation column and heated at atmospheric pressure (ethanol boiling point 78℃). The fraction at 77-78℃ was collected to obtain 2.5L of recovered ethanol-water mixed solvent (ethanol:water = 9.2:0.8, volume ratio). A small amount of water was added to adjust the ratio to 9:1, which can be directly recycled. The recovery rate is 92% (higher than the acetonitrile system). Since ethanol can be distilled at atmospheric pressure, energy consumption is reduced by 30%.

[0046] 3. Product Testing and Results Appearance: Pale yellow needle-like crystals; Melting point: 195.0-196.3℃; Purity: 99.4% as determined by HPLC (0.6% impurities); The yield of 44.2% indicates that the ethanol-water solvent solution is not only environmentally friendly, but also has a high recovery rate and low energy consumption, making it suitable for production scenarios with strict environmental protection requirements.

[0047] This invention addresses many shortcomings of existing 2,5-dibromobenzoquinone synthesis processes by introducing a phase transfer catalyst, a composite oxidant, a solvent recovery system, and intermediate stabilization treatment. It significantly improves product yield and purity while reducing costs and environmental risks. Furthermore, it provides a flexible process alternative and has promising prospects for industrial application.

[0048] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing 2,5-dibromobenzoquinone, characterized in that, Includes the following steps: (1) Synthesis of 2,5-dibromohydroquinone: Hydroquinone and glacial acetic acid were added to the reaction vessel, stirred and heated to 30-35℃ to completely dissolve the hydroquinone. 0.5-2% of the mass of hydroquinone was added as a phase transfer catalyst, and the temperature was slowly lowered to 10-15℃. Then, bromine diluted with glacial acetic acid was added dropwise. The molar ratio of bromine to hydroquinone was 2.05:1-2.1:

1. After the addition was completed, the reaction was kept at the temperature for 2 hours. The reaction was stopped after TLC detection showed no raw material. The reaction solution was filtered, and the mother liquor was concentrated under reduced pressure at 60℃ and -0.09MPa until no solvent dripped out. The temperature was lowered to 5-10℃ and filtered again. The two filter cakes were combined and dried under the protection of inert gas nitrogen or argon to obtain 2,5-dibromohydroquinone. (2) Synthesis of 2,5-dibromobenzoquinone: 2,5-dibromohydroquinone and acetonitrile obtained in step (1) were added to another reaction vessel and heated to 45-50℃ to completely dissolve the intermediate. Sodium nitrite with a molar ratio of 1:10-1:15 to TBHP was added, and then 70% tert-butanol peroxide aqueous solution was slowly added dropwise. The molar ratio of TBHP to 2,5-dibromohydroquinone was 1.5:1-1.8:

1. The system temperature was maintained at 40-45℃ during the dropwise addition. After the dropwise addition was completed, the temperature was raised to 45-50℃ and kept at the temperature for 1-1.5h. The reaction was stopped after TLC detection showed no raw material. The system was cooled to 10-15℃ and filtered. The filter cake was washed with a small amount of methanol and dried under vacuum. It was then dried at 35℃ to obtain 2,5-dibromobenzoquinone. (3) Solvent recovery: Collect the glacial acetic acid mother liquor from step (1) and the acetonitrile mother liquor from step (2), and perform vacuum distillation respectively. Glacial acetic acid is recovered by distillation at 110-115℃ and -0.09MPa, and acetonitrile is recovered by distillation at 60-65℃ and -0.095MPa. The recovered solvent is used for subsequent batch reactions.

2. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: The phase transfer catalyst mentioned in step (1) is tetrabutylammonium bromide, and the amount used is 1% of the mass of hydroquinone.

3. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (1), the dilution ratio of bromine is bromine: glacial acetic acid mass ratio of 7.256:

1.

4. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (2), the molar ratio of TBHP to sodium nitrite is 12:

1.

5. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: The heat preservation reaction time in step (2) is 1.5h.

6. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (1), the inert gas is nitrogen. After the intermediate is dried, it is stored at 0-5℃ under nitrogen-sealed conditions, and the shelf life is ≥6 months.

7. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (3), the recovery rate of acetonitrile is ≥90% and the recovery rate of glacial acetic acid is ≥88%.

8. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (2), the solvent can be replaced with an ethanol-water mixed solvent with a volume ratio of ethanol:water = 9:

1. At this time, the amount of TBHP used increases by 10%.

9. The method for synthesizing 2,5-dibromobenzoquinone according to claim 1, characterized in that: In step (2), tert-butanol peroxide can be replaced with 30% hydrogen peroxide aqueous solution, and 1 mol / L sulfuric acid is added as a co-catalyst. The molar ratio of sulfuric acid to 2,5-dibromohydroquinone is 0.05:1.