A method for synthesizing 2-amino-3,5-dibromobenzaldehyde

Abstract

This invention discloses a method for synthesizing 2-amino-3,5-dibromobenzaldehyde, belonging to the field of pharmaceutical intermediate synthesis technology. The method uses o-nitrobenzaldehyde as the starting material. First, it reacts with sodium bisulfite in water to form a water-soluble adduct. Then, sodium hydrosulfite is added in batches at 85-90°C for reduction, generating o-aminobenzaldehyde sulfite intermediate. After cooling, crystallization, and filtration purification, the filtrate undergoes selective bromination with liquid bromine at low temperature. Finally, the pH is adjusted to 10-12, and the product precipitates at 0-5°C. The crude product is obtained after post-treatment and recrystallized from acetone and anhydrous ethanol to obtain high-purity 2-amino-3,5-dibromobenzaldehyde. This invention uses water as the sole reaction solvent, achieving a continuous aqueous-phase synthesis involving multiple steps such as reduction, bromination, and precipitation. The process is simple, the conditions are mild, the cost is low, the product yield is high, the purity is high, and there is minimal waste.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 2-amino-3,5-dibromobenzaldehyde, belonging to the field of pharmaceutical intermediate synthesis technology. Background Technology

[0002] The information disclosed in this background section is intended only to enhance some understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art.

[0003] 2-Amino-3,5-dibromobenzaldehyde has wide applications in drug synthesis, especially as an important intermediate in the synthesis of the expectorant ambroxol. In addition, 2-amino-3,5-dibromobenzaldehyde can also be used as a biochemical reagent in life science research.

[0004] Currently, 2-amino-3,5-dibromobenzaldehyde can be synthesized through multiple pathways, mainly including the following: (1) The target product is obtained from methyl anthranilate via bromination, hydrazine hydrate reaction, and oxidation. (2) The target product is synthesized from anthranilic acid via carboxyl reduction, bromination, and oxidation. (3) The target product is obtained from anthranilaldehyde via nitro reduction and bromination. These methods generally suffer from problems such as complex reaction solvents and high costs.

[0005] Currently, there are very few synthetic methods that use o-nitrobenzaldehyde sulfite adduct as the starting material and water as the solvent. Summary of the Invention

[0006] In view of the prior art, the present invention provides a method for synthesizing 2-amino-3,5-dibromobenzaldehyde. This method uses water as a continuous reaction medium and o-nitrobenzaldehyde as a starting material. By forming its water-soluble sodium bisulfite adduct, it ingeniously integrates multiple key steps such as reduction, bromination, and salt desalting into the same aqueous system.

[0007] The technical solution adopted in this invention is as follows: This invention provides a method for synthesizing 2-amino-3,5-dibromobenzaldehyde, the method comprising the following steps: Water and sodium bisulfite were added to a reaction vessel and stirred until dissolved. o-nitrobenzaldehyde was then added to react and the reaction was carried out to obtain the o-nitrobenzaldehyde sodium bisulfite adduct. When the reaction system is heated to 85-90℃, a portion of the sodium hydrosulfite is added to the sodium bisulfite adduct of o-nitrobenzaldehyde. After the foam subsides, the remaining sodium hydrosulfite is added. After the addition is complete, the reaction is carried out at 95-100℃ for 30-45 minutes, and the reaction is monitored by HPLC. The temperature is then lowered to 0-10℃, and crystals are allowed to precipitate for 1-2 hours. The mixture is then filtered, the filter cake is washed with water, and the filtrates are combined for later use. Sulfur dioxide was removed from the filtrate by blowing air. When the temperature reached -10 to -5℃, liquid bromine was added. The temperature was controlled at 10℃ or below, and the reaction was carried out for 30 to 45 minutes. The reaction was monitored by HPLC. Control the temperature to -10~0℃ and below, add sodium hydroxide solution, adjust the pH of the system to 10~12, crystallize at 0~5℃ for 90~120 min, filter, rinse the filter cake with water, collect the filter cake, dry, and obtain the crude product.

[0008] Preferably, the feeding ratio of water, sodium bisulfite and o-nitrobenzaldehyde is 5-8 : 1.2-1.5 : 1.

[0009] Preferably, the step of 'adding o-nitrobenzaldehyde to carry out the reaction' is carried out at 0~10°C for 90~120 minutes.

[0010] In one or more embodiments of the present invention, the molar ratio of sodium hydrosulfite (calculated as active ingredient Na2S2O4), sodium bisulfite adduct of o-nitrobenzaldehyde (calculated as o-nitrobenzaldehyde contained therein) and liquid bromine is 2.2-2.8 : 1 : 2.0-2.2.

[0011] In one or more embodiments of the present invention, a portion of the sodium hydrosulfite is 1 / 3 to 1 / 2 of the sodium hydrosulfite mass.

[0012] In one or more embodiments of the present invention, the product is dried at 50-60°C to obtain a crude product.

[0013] In one or more embodiments of the present invention, the crude product is recrystallized.

[0014] Preferably, the recrystallization step includes: adding the crude product and acetone to a crystallization vessel, deheating until dissolved and clear, adding activated carbon for decolorization, filtering the activated carbon, and rinsing with acetone; collecting the filtrate, cooling to -10°C to precipitate crystals, filtering, rinsing with acetone, collecting the filter cake, and drying for later use; Recrystallization with anhydrous ethanol yields 2-amino-3,5-dibromobenzaldehyde, a bright yellow powder.

[0015] In this invention, sodium hydrosulfite (Na2S2O4) is used as a reducing agent, and its molar ratio (2.2-2.8:1) directly affects the completeness of nitro reduction. If the ratio is too low, incomplete reduction occurs, leading to intermediate residues and a decreased yield; if the ratio is too high, side reactions may occur. Adding it in batches prevents material loss and spillage caused by intense exothermic reactions and excessive foaming, which is crucial for ensuring a stable reaction and improving the yield.

[0016] Temperature (95~100℃) and time (30~45min) must be strictly controlled. If the temperature is too low or the time is too short, the reaction will be incomplete; if the temperature is too high or the time is too long, it will lead to product decomposition or excessive reduction and other side reactions, affecting purity and yield.

[0017] When adding liquid bromine, the temperature must be controlled at 10°C or below, and should be started at a low temperature of -10 to -5°C. Low temperature can inhibit further bromination of dibromo products (such as the formation of tribromo products) and side reactions such as oxidation of amino groups by bromine, which is the key to ensuring the selectivity of 3,5-dibromo and improving the purity of the product.

[0018] The pH was adjusted to 10-12 using sodium hydroxide, and crystals were precipitated at low temperature (0-5°C). pH control ensured complete dissociation of o-aminobenzaldehyde sulfite, releasing free 2-aminobenzaldehyde intermediates for bromination. Simultaneously, the low temperature facilitated the precipitation of the product in solid form, reducing solubility loss in water and increasing yield.

[0019] The ratio of water, sodium bisulfite, and o-nitrobenzaldehyde (5-8:1.2-1.5:1) affects the formation efficiency and solubility of the adduct. Insufficient sodium bisulfite leads to incomplete salt formation; the amount of water affects the solution concentration and subsequent operations. The salt formation temperature (0-10℃) favors the forward direction of the sodium bisulfite addition reaction, ensuring the stability of the starting material.

[0020] The choice of recrystallization solvent (acetone, anhydrous ethanol), decolorization, and cooling crystallization temperature (-10℃) directly affect the purity and crystal form of the final product.

[0021] Compared with the related technologies known to the inventors, one of the technical solutions of the present invention has the following beneficial effects: (1) This invention uses water as a continuous reaction medium and ingeniously integrates multiple key steps such as reduction, bromination, and salting out into the same aqueous system by forming a water-soluble sodium bisulfite adduct of o-nitrobenzaldehyde. The steps are seamlessly connected, and efficient conversion can be achieved through simple temperature control and solid-liquid separation, avoiding the complicated solvent changes, intermediate extraction, and high-temperature distillation operations in traditional processes, thus greatly simplifying the process flow.

[0022] (2) The entire synthesis process uses water as the sole solvent, completely eliminating the large amount of organic solvents (such as DMF, glacial acetic acid, alcohols, etc.) used in traditional methods, thus reducing the generation of highly polluting and difficult-to-treat wastes from the source, which is in line with the development direction of green chemistry. At the same time, the selected raw materials (sodium bisulfite, sodium hydrosulfite) are inexpensive and readily available, which significantly reduces production costs and is particularly suitable for large-scale industrial production.

[0023] (3) By controlling the low-temperature bromination (temperature controlled at 10℃ and below) and specific alkaline crystallization conditions (pH=10~12), side reactions such as excessive bromination and oxidation were effectively suppressed, ensuring the selectivity of 3,5-dibromo. With the optimized recrystallization process, the HPLC purity of the finally obtained 2-amino-3,5-dibromobenzaldehyde was stable at over 99.4%, and the total yield based on o-nitrobenzaldehyde reached over 71.5%. The product quality and reaction efficiency were both superior to the control method mentioned in the background art.

[0024] (4) The use of sodium hydrosulfite aqueous solution reduction instead of high-pressure hydrogenation or iron powder / acid reduction system avoids the high-pressure danger and equipment requirements of using hydrogen, and also eliminates the problem of generating a large amount of iron sludge waste. The bromination reaction is carried out at low temperature and excess sulfur dioxide is removed by air purging, which improves the safety and controllability of the production process. Detailed Implementation

[0025] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0026] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments of the present invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, and / or combinations thereof.

[0027] In a typical embodiment of the present invention, o-nitrobenzaldehyde is used as the starting material. It first forms an o-nitrobenzaldehyde sodium bisulfite adduct with sodium bisulfite. Then, under the action of sodium hydrosulfite, the nitro group is reduced to an amino group to generate an o-aminobenzaldehyde sulfite intermediate, which dissolves in the aqueous phase. After removing SO2, it undergoes an electrophilic bromination reaction with liquid bromine at low temperature. Finally, alkali is added to precipitate 2-amino-3,5-dibromobenzaldehyde.

[0028] The synthesis route is as follows: To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0029] Example 1 Add 500 mL of water and 138 g (1.32 mol) of sodium bisulfite to the reaction vessel and stir until dissolved. Add 151 g (1.0 mol) of o-nitrobenzaldehyde to form a salt and set the salt at 10 °C for 2 hours.

[0030] Heat the mixture to 90℃ and add 240g of total sodium hydrosulfite (containing approximately 1.38mol Na2S2O4) in two batches. Yellow foam will be produced, and the reaction will be vigorous. Be careful not to spray the mixture. Wait for the foam to subside before adding half of the sodium hydrosulfite in the next batch.

[0031] After the addition is complete, react at 95-100℃ for half an hour. Monitor the reaction completion by HPLC (sm < 0.5%). Cool down to 0-10℃, and a large amount of solid will precipitate. Crystallize at 5℃ for 1.5 hours. The precipitated solid is mostly unreacted impurities or byproducts. Filter, rinse the filter cake with a small amount of water, and combine the filtrates for later use.

[0032] Blow air to remove as much sulfur dioxide as possible from the solution, and test the emitted gas with moistened potassium iodide-starch test paper until the paper no longer turns blue. Continue cooling to -10℃, and begin adding liquid bromine (320g of liquid bromine, approximately 2.0mol). Maintain the temperature below 10℃.

[0033] After the addition was complete, the temperature was controlled for 30 minutes, and the reaction was monitored by HPLC until it was complete (sm < 0.5%).

[0034] Control the temperature below -10 to 0℃, slowly add 10w / w% sodium hydroxide solution, adjust the pH of the system to 10~12, and a large amount of yellow solid will precipitate.

[0035] Crystallize at 0-5℃ for two hours, filter, rinse the filter cake with an appropriate amount of water, collect the filter cake, and dry at 50-60℃ to obtain the crude product.

[0036] Recrystallization: Add the crude product and acetone to a crystallization vessel, heat until dissolved and clear, add activated carbon for decolorization for 1 hour, filter the activated carbon, and rinse with a small amount of acetone. Collect the filtrate, cool to -10℃ to crystallize for 2 hours, filter, rinse with acetone, collect the filter cake, and dry for later use.

[0037] The product was recrystallized again with anhydrous ethanol to obtain pure 2-amino-3,5-dibromobenzaldehyde (HPLC purity ≥99.5%), a bright yellow powder solid, with an overall yield of 74.8% based on o-nitrobenzaldehyde.

[0038] Example 2 Add 500 mL of water and 138 g (1.32 mol) of sodium bisulfite to the reaction vessel and stir until dissolved. Add 151 g (1.0 mol) of o-nitrobenzaldehyde to form a salt and set the salt at 5 °C for 1.5 hours.

[0039] Heat the mixture to 85℃ and add 220g of total sodium hydrosulfite (containing approximately 1.26mol Na2S2O4) in two batches. Yellow foam will be produced, and the reaction will be vigorous. Be careful not to spray the mixture. Wait for the foam to subside before adding half of the sodium hydrosulfite in the next batch.

[0040] After the addition is complete, react at 85-90℃ for 45 min. Monitor the reaction completion by HPLC (sm < 0.5%). Cool down to 0-10℃, and a large amount of solid will precipitate. Crystallize at 8℃ for 1.5 h. The precipitated solid is mostly unreacted impurities or byproducts. Filter, rinse the filter cake with a small amount of water, and combine the filtrates for later use.

[0041] Blow air to remove as much sulfur dioxide as possible from the solution, and test the emitted gas with moistened potassium iodide-starch test paper until the paper no longer turns blue. Continue cooling to -10°C, and begin adding 300g of liquid bromine (approximately 1.875 mol). Maintain the temperature below 10°C.

[0042] After the addition was complete, the temperature was controlled for 45 minutes, and the reaction was monitored by HPLC (sm < 0.5%).

[0043] Control the temperature below -10 to 0℃, slowly add 10w / w% sodium hydroxide solution, adjust the pH of the system to 10, and a large amount of yellow solid will precipitate.

[0044] Crystallize at 0-5℃ for two hours, filter, rinse the filter cake with an appropriate amount of water, collect the filter cake, and dry at 50-60℃ to obtain the crude product.

[0045] Recrystallization: Add the crude product and acetone to a crystallization vessel, heat until dissolved and clear, add activated carbon for decolorization for 1 hour, filter the activated carbon, and rinse with a small amount of acetone. Collect the filtrate, cool to -10℃ to crystallize for 2 hours, filter, rinse with acetone, collect the filter cake, and dry for later use.

[0046] The product was recrystallized again with anhydrous ethanol to obtain pure 2-amino-3,5-dibromobenzaldehyde (HPLC purity ≥99.4%), a bright yellow powder. The total yield was 71.5% based on o-nitrobenzaldehyde.

[0047] Example 3 Add 500 mL of water and 145 g (1.39 mol) of sodium bisulfite to the reaction vessel and stir until dissolved. Add 151 g (1.0 mol) of o-nitrobenzaldehyde to form a salt and allow it to form a salt at 0 °C for 2 hours.

[0048] Heat the temperature to 90℃, and then add 250g of total sodium hydrosulfite (containing approximately 1.44mol Na2S2O4) in two batches. Yellow foam will be produced, and the reaction will be violent. Be careful not to spray the material. Wait for the foam to subside before adding half of the sodium hydrosulfite in the next batch.

[0049] After the addition is complete, react at 98-100℃ for 30 min. Monitor the reaction completion by HPLC (sm < 0.5%). Cool down to 0-10℃, and a large amount of solid will precipitate. Crystallize at 5℃ for 2 h. The precipitated solid is unreacted impurities or byproducts. Filter, rinse the filter cake with a small amount of water, and combine the filtrates for later use.

[0050] Blow air to remove as much sulfur dioxide as possible from the solution, and test the emitted gas with moistened potassium iodide-starch test paper until the paper no longer turns blue. Continue cooling to -10°C, and begin adding 330g of liquid bromine (approximately 2.06 mol). Maintain the temperature below 10°C.

[0051] After the addition was complete, the temperature was controlled for 30 minutes, and the reaction was monitored by HPLC until it was complete (sm < 0.5%).

[0052] Control the temperature below -10 to 0℃, slowly add 10w / w% sodium hydroxide solution, adjust the pH of the system to 12, and a large amount of yellow solid will precipitate.

[0053] Crystallize at 0-5℃ for two hours, filter, rinse the filter cake with an appropriate amount of water, collect the filter cake, and dry at 50-60℃ to obtain the crude product.

[0054] Recrystallization: Add the crude product and acetone to a crystallization vessel, heat until dissolved and clear, add activated carbon for decolorization for 1 hour, filter the activated carbon, and rinse with a small amount of acetone. Collect the filtrate, cool to -10℃ to crystallize for 2 hours, filter, rinse with acetone, collect the filter cake, and dry for later use.

[0055] The product was recrystallized again with anhydrous ethanol to obtain pure 2-amino-3,5-dibromobenzaldehyde (HPLC purity ≥99.6%), a bright yellow powder solid, with an overall yield of 75.9% based on o-nitrobenzaldehyde.

[0056] Comparative Example 1 Referring to Example 1, the phrase "using water as a solvent" was replaced with "using 500 mL of N,N-dimethylformamide (DMF) as a solvent." The specific steps were as follows: 151 g (1.0 mol) of o-nitrobenzaldehyde was dissolved in 500 mL of DMF, and the temperature was raised to 90°C. 240 g of sodium hydrosulfite (containing approximately 1.38 mol of Na₂S₂O₄) was added in two batches for reduction. After the reaction was complete, the reaction solution was cooled and poured into 2 L of ice water to precipitate the solid. The solid was then filtered to obtain the reduction intermediate. Subsequent bromination and alkaline precipitation steps were performed as in Example 1, but the intermediate was redispersed in water. After bromination, the product was subjected to alkaline precipitation, filtration, and drying to obtain the crude product, which was then recrystallized using the same steps.

[0057] Results: 2-Amino-3,5-dibromobenzaldehyde was finally obtained with an HPLC purity of 98.8% and an overall yield of 68.3% based on o-nitrobenzaldehyde. The reaction process used a large amount of high-boiling-point, difficult-to-recover DMF solvent, resulting in complex and costly post-treatment and the generation of wastewater containing organic solvents.

[0058] Comparative Example 2 Sodium bisulfite adduct was not prepared. 151 g (1.0 mol) of o-nitrobenzaldehyde, 500 mL of water, 200 mL of ethanol, and 280 g (5.0 mol) of reduced iron powder were added to a reaction vessel. 200 mL of 10 w / w% dilute hydrochloric acid was slowly added dropwise with stirring, maintaining the temperature below 50 °C. After the addition was complete, the reaction was stirred at 80 °C for 4 hours (monitored by TLC). After the reaction was complete, the mixture was filtered while hot, and the residue was washed with hot water. The filtrate and washings were combined to obtain an o-aminobenzaldehyde solution. This solution was cooled to -10 °C, and then subjected to bromination, alkaline precipitation, and post-treatment as described in Example 1.

[0059] Results: The reaction generated a large amount of iron-containing waste residue, which was difficult to filter and resulted in significant material loss. The final product had an HPLC purity of 97.5% and a yield of only 58.7%. Furthermore, the process was lengthy and generated a lot of waste, failing to meet the requirements of green chemistry.

[0060] Comparative Example 3 (1) Bromination: Dissolve 151 g (1.0 mol) of o-nitrobenzaldehyde in 500 mL of glacial acetic acid and cool to 0 °C. Slowly add 336 g (2.1 mol) of liquid bromine, keeping the temperature below 5 °C. After addition, stir the mixture at room temperature (25 °C) overnight. Pour the reaction mixture into ice water, precipitate the solid, filter, wash with water, and dry to obtain a brownish-yellow solid (a mixture of various bromonitrobenzaldehydes).

[0061] (2) Reduction: Take 150g of the mixed solid obtained in the previous step (assuming it contains the target intermediate 3,5-dibromo-2-nitrobenzaldehyde), add 500 mL of ethanol and 300 mL of water, and heat to 70℃. Add excess sodium hydrosulfite (300g) in batches for reduction. After the reaction is complete, cool to crystallize, filter, and obtain the crude product.

[0062] Results: HPLC analysis of the first-step bromination product showed that the content of 3,5-dibromo-2-nitrobenzaldehyde was only about 65%, accompanied by about 25% of isomers such as 2,5-dibromo and 3-bromo, and about 10% of tribromo derivatives. After the second-step reduction, a dark solid was finally obtained with an HPLC purity of only 92.1%, and it was difficult to purify to acceptable standards by conventional recrystallization. This route is cumbersome and has an extremely low overall yield (<40%), demonstrating the fundamental defects of the pre-bromination route in terms of regioselectivity and yield.

[0063] Comparative Example 4 Refer to Example 1, up to the bromination step. Modify "Continue cooling to -10°C, begin adding liquid bromine dropwise. Control the temperature below 10°C" to "Cool the filtrate to room temperature (approximately 25°C), begin adding 320g (2.0 mol) of liquid bromine dropwise, allowing the temperature to rise naturally during the dropwise addition process, controlling the final temperature not to exceed 35°C." The remaining steps are exactly the same as in Example 1.

[0064] Results: The reaction system rapidly turned dark brown. The final product was a dark yellow solid, and after recrystallization using the same steps, its HPLC purity was 98.0%, a significant decrease compared to Example 1 (99.5%). The product yield also slightly decreased to 69.2%. This indicates that higher bromination temperatures may have led to over-bromination (such as the formation of tribromo derivatives), resulting in impurities. This demonstrates the necessity of maintaining a temperature of 10°C or below for ensuring high purity.

[0065] Comparative Example 5 Following Example 1, but omitting the salt formation step, 151 g (1.0 mol) of o-nitrobenzaldehyde was directly mixed with 500 mL of water, forming a suspension under vigorous stirring. The temperature was raised to 90°C, and 240 g of sodium hydrosulfite was added in two batches. Because the raw material is insoluble in water, the reduction reaction occurred at the interface between the two phases, resulting in extremely low efficiency and unevenness. HPLC monitoring showed that even after reacting at 95-100°C for 2 hours, more than 20% of the raw material remained. Subsequent effective bromination was impossible, and the experiment failed.

[0066] Results: This comparative example demonstrates that without converting o-nitrobenzaldehyde into a water-soluble sodium bisulfite adduct, an efficient and uniform reduction reaction cannot be achieved in the aqueous phase, thus rendering the entire aqueous process impossible. This highlights the core value of this invention in making the sodium bisulfite addition reaction the first step in the process.

[0067] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing 2-amino-3,5-dibromobenzaldehyde, characterized in that, The method includes the following steps: Water and sodium bisulfite were added to a reaction vessel and stirred until dissolved. o-nitrobenzaldehyde was then added to react and the reaction was carried out to obtain the o-nitrobenzaldehyde sodium bisulfite adduct. When the reaction system is heated to 85-90℃, a portion of the sodium hydrosulfite is added to the sodium bisulfite adduct of o-nitrobenzaldehyde. After the foam subsides, the remaining sodium hydrosulfite is added. After the addition is complete, the reaction is carried out at 95-100℃ for 30-45 minutes, and the reaction is monitored by HPLC. The temperature is then lowered to 0-10℃, and crystals are allowed to precipitate for 1-2 hours. The mixture is then filtered, the filter cake is washed with water, and the filtrates are combined for later use. Sulfur dioxide was removed from the filtrate by blowing air. When the temperature reached -10 to -5℃, liquid bromine was added. The temperature was controlled at 10℃ or below, and the reaction was carried out for 30 to 45 minutes. The reaction was monitored by HPLC. Control the temperature to -10~0℃ and below, add sodium hydroxide solution, adjust the pH of the system to 10~12, crystallize at 0~5℃ for 90~120 min, filter, rinse the filter cake with water, collect the filter cake, dry, and obtain the crude product.

2. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, The feeding ratio of water, sodium bisulfite, and o-nitrobenzaldehyde is 5-8:1.2-1.5:

1.

3. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, The step of adding o-nitrobenzaldehyde to carry out the reaction is carried out at 0~10°C for 90~120 minutes.

4. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, The molar ratio of sodium hydrosulfite (calculated as active ingredient Na2S2O4), sodium bisulfite adduct of o-nitrobenzaldehyde (calculated as o-nitrobenzaldehyde contained therein), and liquid bromine is 2.2-2.8:1:2.0-2.

2.

5. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, Some sodium hydrosulfite is 1 / 3 to 1 / 2 of the mass of sodium hydrosulfite.

6. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, Dry at 50-60℃ to obtain crude product.

7. The method for synthesizing 2-amino-3,5-dibromobenzaldehyde as described in claim 1, characterized in that, The crude product is recrystallized. The recrystallization steps include: adding the crude product and acetone to a crystallization vessel, deheating until dissolved and clear, adding activated carbon for decolorization, filtering the activated carbon, and rinsing with acetone; collecting the filtrate, cooling to -10℃ to precipitate crystals, filtering, rinsing with acetone, collecting the filter cake, and drying for later use. Recrystallization with anhydrous ethanol yields 2-amino-3,5-dibromobenzaldehyde.

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