Method for co-production of 2, 4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride

Abstract

The invention discloses a method for co-production of 2, 4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride, and belongs to the technical field of organic chemical industry, 2, 4-dichlorofluorobenzene is used as a raw material, alkylation and reaction with tert-butyl nitrite are performed to generate oxime, and then hydrochloric acid hydrolysis is performed to generate 2, 4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride; according to the method, co-production of the 2, 4-dichloro-5-fluoroacetophenone and the hydroxylamine hydrochloride is innovatively realized, not only are high yield and high purity of the target product 2, 4-dichloro-5-fluoroacetophenone ensured, but also the nitrogen element in the reaction is recycled and converted into the hydroxylamine hydrochloride with high additional value, and the atom economy is remarkably improved; according to the method, the operation process is greatly simplified, the use of dangerous reagents is avoided, and the intrinsic safety and environmental friendliness of the process are improved from the source; the method is simple to operate, safe and environment-friendly, the production cost is effectively reduced, and the market competitiveness of the product is enhanced.

Description

Technical Field

[0001] This application belongs to the field of organic chemical technology, and in particular relates to a method for the co-production of hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone. Background Technology

[0002] 2,4-Dichloro-5-fluoroacetophenone is an important intermediate in the synthesis of ciprofloxacin. The conventional synthetic method involves using 2,4-dichlorofluorobenzene as a starting material and acetyl chloride and acetic anhydride as acylation reagents, and preparing it via a Friedel-Crafts reaction catalyzed by excess aluminum trichloride.

[0003] Patent CN85107015A reports the preparation of 2,4-dichloro-5-fluoroacetophenone using 2,4-dichlorofluorobenzene and acetyl chloride as raw materials, and aluminum trichloride, zinc chloride or ferric chloride as catalysts, at 10-150 °C.

[0004] The paper "Study on Acetylation Process of 2,4-Dichlorofluorobenzene [J], Fine and Specialty Chemicals, 2006, 14, 6" reports the optimal process conditions for the acetylation reaction of 2,4-dichlorofluorobenzene: using acetyl chloride as the acylating agent, aluminum trichloride as the catalyst, and a material ratio of n(2,4-dichlorofluorobenzene): n(acetyl chloride): n(anhydrous aluminum trichloride) = 1: 2.0: 2.5. The reaction was carried out at 110 °C for 1.5 h, followed by a reaction at 120 °C for 1 h. Dichloromethane was used as the extractant, and the product yield was 80.1%, which was quite good. The chlorofluoroacetophenone and unreacted 2,4-dichlorofluorobenzene in the pre-distillate were recovered by vacuum distillation.

[0005] The paper "Synthesis of 2,4-dichloro-5-fluoroacetophenone [J], Tianjin Chemical Industry, 1997, 3, 26" reports the process of adding 2,4-dichlorofluorobenzene, acetyl chloride, and aluminum trichloride to a reactor, heating the mixture to 135-140 °C with stirring, reacting for 1 h, cooling the mixture, thawing the reactants with ice, allowing them to separate into layers, extracting the aqueous phase three times with toluene, merging the toluene layer into the oil phase, drying the oil phase, and distilling the fraction collected at 110-120 °C and 0.67 kPa to obtain the fluorochloroacetophenone product with a yield of 80% and a purity of 95%.

[0006] The paper "Synthesis of Ethyl 2,4-Dichloro-5-fluorobenzoyl acetate [J], China Pharmaceutical Industry Magazine, 1991, 12, 551" reports the process of adding freshly distilled acetyl chloride dropwise to a mixture of fluorochlorobenzene and aluminum trichloride under ice-water cooling, gradually heating to 110 °C with stirring, reacting for 1 h, and then heating to 120 °C for another 1 h. The raw material ratio was fluorochlorobenzene: aluminum trichloride: acetyl chloride = 1: 2.38: 1.67, with a yield of 75%.

[0007] Patent CN102249881A reports the acylation reaction of 2,4-dichlorofluorobenzene with acetyl chloride in the presence of Lewis acids aluminum trichloride, zinc chloride or boron trifluoride, at 10-150 °C, with a molar ratio of 2,4-dichlorofluorobenzene, acetyl chloride and Lewis acid of 1 : (0.5-2.5) : (1-3).

[0008] Hydroxylamine hydrochloride is an important chemical raw material with wide applications in many fields such as pharmaceuticals, pesticides, and chemical fibers. The literature "Synthesis and Production Methods of Hydroxylamine Hydrochloride [J]. Chemical Production and Technology, 2021, 27(6), 12-15" summarizes the following mainstream methods for synthesizing hydroxylamine hydrochloride: 1. Nitromethane Method: The nitromethane method for preparing hydroxylamine hydrochloride was the earliest industrialized method introduced to China. Using nitromethane and hydrochloric acid as raw materials, hydroxylamine hydrochloride and formic acid are obtained under reflux conditions. Excess hydrochloric acid and formic acid are distilled off under reduced pressure, followed by cooling, crystallization, centrifugation, and drying to obtain the final hydroxylamine hydrochloride product. The nitromethane used in this method is prepared from sodium nitrite and dimethyl sulfate, with a yield of approximately 56%. This route involves several hazardous chemicals, making it relatively dangerous and with low atom utilization.

[0009] 2. Nitric oxide method: This process uses ammonia, oxygen, and water as starting materials, and nitric oxide is produced by ammonia oxidation under Pt / Rh catalysis. Then, in hydrochloric acid solution, a mixed gas and hydrogen are reduced to hydroxylamine hydrochloride aqueous solution under Pt catalysis. This process is complex, requires high-end equipment, involves high costs due to precious metal catalysis, and produces many byproducts; therefore, there are currently virtually no industrial-scale production facilities for it.

[0010] 2,4-Dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride are two high-value compounds, and existing technologies produce them separately. However, this application discovers a co-production process route for 2,4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride. Summary of the Invention

[0011] The purpose of this application is to provide a method for the co-production of hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone, which achieves high-yield production of 2,4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride in a one-pot reaction, thus obtaining two high-value products simultaneously.

[0012] To achieve the above objectives, the technical solution adopted in this application is: to provide a method for the co-production of hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone, specifically including the following steps: (a) 2,4-Dichlorofluorobenzene and anhydrous aluminum chloride were added to the reaction vessel, and after replacing the nitrogen gas, ethylene was introduced to carry out the reaction; after the reaction was completed, the mixture was washed with water and 2,4-dichloro-5-fluoroethylbenzene was obtained. (ii) 2,4-Dichloro-5-fluoroethylbenzene, tert-butyl nitrite and solvent are added to the reaction vessel, and the reaction is carried out after nitrogen is replaced; after the reaction is completed, the first material is obtained by processing; hydrochloric acid and acetone are added to the first material to carry out hydrolysis reaction; after the reaction is completed, the material is extracted, and the oil phase is post-treated to obtain 2,4-dichloro-5-fluoroacetophenone, and the aqueous phase is treated to obtain hydroxylamine hydrochloride.

[0013] In one embodiment, In step (i), the molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride is 1:0.1-0.3, and the molar ratio of 2,4-dichlorofluorobenzene to ethylene is 1:1.0-1.2.

[0014] In one embodiment, The reaction temperature in step (1) is 40-80 ℃, and the reaction time is 4-8 h.

[0015] In one embodiment, During the water washing described in step (1), the temperature of the reaction system needs to be reduced to below 50 ℃.

[0016] In one embodiment, The concentration of tert-butyl nitrite in step (ii) is 90%.

[0017] In one embodiment, The solvent in step (ii) is dichloroethane or chloroform; the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite is 1:1.0-1.2, and the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to the solvent is 1:10-20.

[0018] In one embodiment, The reaction temperature in step (ii) is 40-80 ℃, and the reaction time is 8-16 h.

[0019] In one embodiment, In step (ii), the concentration of hydrochloric acid is 5-15%, and the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid is 1:1.5-3.

[0020] In one embodiment, In step (ii), the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone is 1:2-6.

[0021] In one embodiment, The hydrolysis reaction in step (ii) takes 4-6 hours.

[0022] This application provides a method for the co-production of hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone. Using 2,4-dichlorofluorobenzene as a raw material, the method involves alkylation, reaction with tert-butyl nitrite to generate an oxime, and then hydrolysis with hydrochloric acid to produce 2,4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride. This method ensures high-yield production of 2,4-dichloro-5-fluoroacetophenone while simultaneously producing hydroxylamine hydrochloride. This innovative method achieves the co-production of 2,4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride. Using 2,4-dichlorofluorobenzene as a raw material, the method involves alkylation, reaction with tert-butyl nitrite to generate an oxime, and then hydrolysis with hydrochloric acid to produce 2,4-dichloro-5-fluoroacetophenone and hydroxylamine hydrochloride, ensuring high yields of both. The high yield and high purity of the target product, 2,4-dichloro-5-fluoroacetophenone, also convert nitrogen in the reaction into high-value-added hydroxylamine hydrochloride, significantly improving atom economy. Compared to traditional processes, this route greatly simplifies the operation process, avoids the use of hazardous reagents, and improves the inherent safety and environmental friendliness of the process from the source. Furthermore, this method uses tert-butyl nitrite as a raw material to generate hydroxylamine hydrochloride, which is simpler, safer, and more environmentally friendly than traditional processes, effectively reducing production costs and enhancing the product's market competitiveness. It provides a feasible solution with both economic value and environmental benefits for clean production and the circular economy in the fine chemical industry. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this application, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The gas chromatogram of 2,4-dichloro-5-fluoroacetophenone prepared in Example 11; Figure 2 The gas chromatogram of 2,4-dichloro-5-fluoroacetophenone prepared in Example 22 is shown. Detailed Implementation

[0025] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, this application will be further described in detail. It should be understood that the specific embodiments described herein are only for explaining this application and are not intended to limit this application.

[0026] Example 1 165.00 g of 2,4-dichlorofluorobenzene and 13.33 g of anhydrous aluminum chloride (molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride was 1:0.1) were added to a high-pressure reactor. After purging with nitrogen, 30.68 g of ethylene was introduced into the reactor, and the temperature was raised to 60 °C and maintained for 4 h. After the reaction was completed, the reaction system was washed with an equal mass of water at 50 °C. After standing and separation, the organic phase was separated by distillation to obtain 145.89 g of product with a purity of 99.77% and a yield of 75.45%.

[0027] Example 2 In Example 1, the amount of aluminum chloride was changed to 6.67 g (the molar ratio of 2,4-dichlorofluorobenzene to aluminum chloride was 1:0.05), and the rest of the operation was the same, yielding 137.19 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.64% and a yield of 70.81%.

[0028] Example 3 In Example 1, the amount of aluminum chloride was changed to 26.67 g (the molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride was 1:0.2), and the rest of the operation was the same, yielding 160.84 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.58% and a yield of 82.97%.

[0029] Example 4 In Example 1, the amount of aluminum chloride was changed to 40.00 g (the molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride was 1:0.3), and the rest of the operation was the same, yielding 154.10 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.52% and a yield of 79.97%.

[0030] Comparative Examples 1-4: The molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride was 1:0.05-0.30. When the amount of aluminum chloride was less than or greater than 0.20, the yield of 2,4-dichloro-5-fluoroethylbenzene decreased. When the amount of aluminum chloride was 0.20, the yield of 2,4-dichloro-5-fluoroethylbenzene was the highest at 82.97%. Therefore, the preferred molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride was 1:0.20.

[0031] Example 5 In Example 3, the amount of ethylene was changed to 28.05 g (the molar ratio of 2,4-dichlorofluorobenzene to ethylene was 1:1.0), and the rest of the operation was the same, yielding 150.49 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.50% and a yield of 77.57%.

[0032] Example 6 In Example 3, the amount of ethylene was changed to 33.66 g (the molar ratio of 2,4-dichlorofluorobenzene to ethylene was 1:1.2), and the rest of the operation was the same, yielding 158.40 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.57% and a yield of 81.70%.

[0033] Comparative Examples 3, 5, and 6: the molar ratio of 2,4-dichlorofluorobenzene to ethylene was 1:1.0-1.2. Comparing different amounts of ethylene, the highest yield (82.97%) was achieved when the amount of ethylene was 1.1. Therefore, the preferred molar ratio of 2,4-dichlorofluorobenzene to ethylene is 1:1.1.

[0034] Example 7 In Example 3, the reaction temperature was changed to 40 °C, and the rest of the operation was the same, yielding 135.52 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.74% and a yield of 70.02%.

[0035] Example 8 In Example 3, the reaction temperature was changed to 80 °C, and the rest of the operation was the same, yielding 151.88 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.57% and a yield of 78.34%.

[0036] Comparative Examples 3, 7, and 8: The reaction temperature range is 40-80 ℃. The yield decreases when the temperature is below or above 60 ℃. Therefore, the preferred reaction temperature is 60 ℃.

[0037] Example 9 In Example 3, the reaction time was changed to 6 h, and the rest of the operation was the same, yielding 165.49 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.74% and a yield of 85.51%.

[0038] Example 10 In Example 3, the reaction time was changed to 8 h, and the other operations were the same, yielding 166.07 g of 2,4-dichloro-5-fluoroethylbenzene with a purity of 99.64% and a yield of 85.72%.

[0039] Comparative Examples 3, 9, and 10: The reaction time ranges from 4 to 8 hours. When the reaction time is shorter than 6 hours, both the purity and yield decrease. When the reaction time is extended to 8 hours, the purity decreases but the yield does not increase significantly. To measure the overall process energy consumption, the preferred reaction time is 6 hours.

[0040] Example 11 193.04 g of 2,4-dichloro-5-fluoroethylbenzene, 114.58 g of 90% tert-butyl nitrite (molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite was 1:1.0), and 2895.60 g of dichloroethane solvent (mass ratio of 2,4-dichloro-5-fluoroethylbenzene to dichloroethane was 1:15) were added to the reaction flask. After purging with nitrogen, the mixture was heated to 60 °C under 254 nm UV irradiation and reacted for 12 h. After the reaction was complete, the reaction system was distilled under reduced pressure to remove the solvent, yielding a white solid first material. 1460 g of 5% hydrochloric acid (molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid was 1:2.0) and 772.16 g of acetone solvent (mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone was 1:4) were added to the first material. The mixture was then heated to 55 °C. The hydrolysis reaction was carried out under reflux at ℃ for 5 h; after the reaction was completed, acetone was distilled off the system under reduced pressure; then 186.08 g of dichloroethane was added to extract the reaction system; the resulting oil phase was separated into 180.74 g of 2,4-dichloro-5-fluoroacetophenone by distillation, with a purity of 99.69% and a yield of 87.05% (based on 2,4-dichloro-5-fluoroethylbenzene). The gas phase chromatogram of 2,4-dichloro-5-fluoroacetophenone is shown below. Figure 1 As shown; the aqueous phase was evaporated to dryness to obtain 60.47 g of hydroxylamine hydrochloride solid, with a purity of 98.34% and a yield of 85.57% (based on tert-butyl nitrite).

[0041] Example 12 In Example 11, the amount of 90% tert-butyl nitrite was changed to 126.04 g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite was 1:1.1), and the rest of the operation was the same, yielding 188.30 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.77% and a yield of 90.75% (based on 2,4-dichloro-5-fluoroethylbenzene), and 63.50 g of hydroxylamine hydrochloride solid with a purity of 98.19% and a yield of 81.57% (based on tert-butyl nitrite).

[0042] Example 13 In Example 11, the amount of 90% tert-butyl nitrite was changed to 137.49 g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite was 1:1.2), and the rest of the operation was the same, yielding 187.79 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.65% and a yield of 90.40% (based on 2,4-dichloro-5-fluoroethylbenzene), and 61.93 g of hydroxylamine hydrochloride solid with a purity of 98.30% and a yield of 73.01% (based on tert-butyl nitrite).

[0043] Comparative Examples 11-13: When the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite is 1:1.0-1.2, and the molar ratio is 1:1.0-1.1, the yield of 2,4-dichloro-5-fluoroacetophenone is the highest at 90.75% (based on 2,4-dichloro-5-fluoroethylbenzene), corresponding to a yield of hydroxylamine hydrochloride of 81.57% (based on tert-butyl nitrite). Therefore, the preferred molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite is 1:1.1.

[0044] Example 14 In Example 12, the amount of dichloroethane solvent was changed to 1930.40 g (the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to dichloroethane was 1:10), and the other operations were the same, yielding 181.85 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.61% and a yield of 87.51% (based on 2,4-dichloro-5-fluoroethylbenzene) and 59.62 g of hydroxylamine hydrochloride solid with a purity of 98.01% and a yield of 76.45% (based on tert-butyl nitrite).

[0045] Example 15 In Example 12, the amount of dichloroethane solvent was changed to 3860.80 g (the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to dichloroethane was 1:20), and the other operations were the same, yielding 183.26 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.81% and a yield of 88.37% (based on 2,4-dichloro-5-fluoroethylbenzene) and 60.77 g of hydroxylamine hydrochloride solid with a purity of 98.50% and a yield of 78.31% (based on tert-butyl nitrite).

[0046] Comparative Examples 12, 14, and 15: The highest yield of 2,4-dichloro-5-fluoroacetophenone was achieved when the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to dichloroethane was 1:10-20 and the solvent amount was 15. Increasing or decreasing the solvent amount reduced the yield. Therefore, the preferred mass ratio of 2,4-dichloro-5-fluoroethylbenzene to dichloroethane was 1:15.

[0047] Example 16 In Example 12, the reaction temperature was changed to 40 °C, and the other operations were the same, yielding 177.40 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.70% and a yield of 85.45% (based on 2,4-dichloro-5-fluoroethylbenzene) and 58.84 g of hydroxylamine hydrochloride solid with a purity of 98.18% and a yield of 75.58% (based on tert-butyl nitrite).

[0048] Example 17 In Example 12, the reaction temperature was changed to 80 °C, and the other operations were the same, yielding 182.33 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.93% and a yield of 88.02% (based on 2,4-dichloro-5-fluoroethylbenzene) and 61.38 g of hydroxylamine hydrochloride solid with a purity of 98.14% and a yield of 78.80% (based on tert-butyl nitrite).

[0049] Comparative Examples 12, 16, and 17: The reaction temperature range was 40-80 °C. The reaction temperature was higher or lower than 60 °C, and the 2,4-dichloro-5-fluoroacetophenone was reduced. Therefore, the preferred reaction temperature was 60 °C.

[0050] Example 18 In Example 12, the reaction time was changed to 8 h, and the other operations were the same, yielding 178.47 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.61% and a yield of 85.89% (based on 2,4-dichloro-5-fluoroethylbenzene) and 59.54 g of hydroxylamine hydrochloride solid with a purity of 98.20% and a yield of 76.50% (based on tert-butyl nitrite).

[0051] Example 19 In Example 12, the reaction time was changed to 16 h, and the other operations were the same, yielding 186.52 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.91% and a yield of 90.03% (based on 2,4-dichloro-5-fluoroethylbenzene) and 61.83 g of hydroxylamine hydrochloride solid with a purity of 98.29% and a yield of 79.50% (based on tert-butyl nitrite).

[0052] Comparative Examples 12, 18, and 19: The reaction time ranges from 8 to 16 hours. When the reaction time is shorter or longer than 12 hours, the yield of 2,4-dichloro-5-fluoroacetophenone decreases. Therefore, the preferred reaction time is 12 hours.

[0053] Example 20 In Example 12, the amount of 5% hydrochloric acid was changed to 1095 g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid was 1:1.5), and the rest of the operation was the same, yielding 181.82 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.64% and a yield of 87.52% (based on 2,4-dichloro-5-fluoroethylbenzene), and 61.42 g of hydroxylamine hydrochloride solid with a purity of 98.47% and a yield of 79.12% (based on tert-butyl nitrite).

[0054] Example 21 In Example 12, the amount of 5% hydrochloric acid was changed to 2190g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid was 1:3.0), and the rest of the operation was the same, yielding 184.99 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.75% and a yield of 89.15% (based on 2,4-dichloro-5-fluoroethylbenzene), and 61.14 g of hydroxylamine hydrochloride solid with a purity of 98.41% and a yield of 78.71% (based on tert-butyl nitrite).

[0055] Comparative Examples 12, 20, and 21: The molar ratio of 2,4-dichloro-5-fluoroethylbenzene to 5% hydrochloric acid was 1:1.5-3.0. When the amount of hydrochloric acid was greater than or less than 2.0, the yield of 2,4-dichloro-5-fluoroacetophenone decreased. Therefore, the preferred molar ratio of 2,4-dichloro-5-fluoroethylbenzene to 5% hydrochloric acid was 1:2.0.

[0056] Example 22 In Example 12, the hydrochloric acid concentration was changed to 10%, and the amount used was 730 g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid was 1:2.0). The remaining operations were the same, yielding 195.08 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.74% and a yield of 94.00% (based on 2,4-dichloro-5-fluoroethylbenzene). The gas chromatogram of 2,4-dichloro-5-fluoroacetophenone is shown below. Figure 2 As shown, 64.83 g of hydroxylamine hydrochloride solid was titrated and the purity was determined to be 98.27%, with a yield of 83.34% (based on tert-butyl nitrite).

[0057] Example 23 In Example 12, the hydrochloric acid concentration was changed to 15%, and the amount used was 486.67 g (the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid was 1:2.0). The rest of the operation was the same, and 188.94 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.92% and a yield of 91.20% (based on 2,4-dichloro-5-fluoroethylbenzene) and 64.37 g of hydroxylamine hydrochloride solid with a purity of 98.26% and a yield of 82.75% (based on tert-butyl nitrite) were obtained.

[0058] Comparative Examples 12, 22, and 23: The hydrochloric acid concentration ranged from 5% to 15%. Comparing different hydrochloric acid concentrations, when the hydrochloric acid concentration was changed to 10%, the yield of 2,4-dichloro-5-fluoroacetophenone was the highest at 94.00% (based on 2,4-dichloro-5-fluoroethylbenzene), and the corresponding yield of hydroxylamine hydrochloride was 83.34% (based on tert-butyl nitrite). Therefore, the preferred hydrochloric acid concentration was 10%.

[0059] Example 24 In Example 22, the amount of acetone was changed to 386.08 g (the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone was 1:2), and the other operations were the same, yielding 188.83 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.74% and a yield of 90.98% (based on 2,4-dichloro-5-fluoroethylbenzene), and 66.47 g of hydroxylamine hydrochloride solid with a purity of 98.09% and a yield of 85.30% (based on tert-butyl nitrite).

[0060] Example 25 In Example 22, the amount of acetone was changed to 1158.24 g (the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone was 1:6), and the other operations were the same, yielding 176.78 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.85% and a yield of 85.28% (based on 2,4-dichloro-5-fluoroethylbenzene), and 62.53 g of hydroxylamine hydrochloride solid with a purity of 98.20% and a yield of 80.33% (based on tert-butyl nitrite).

[0061] Comparative Examples 22, 24, and 25: The mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone was 1:2-6. When the amount of acetone was greater than or less than 4, the yield of 2,4-dichloro-5-fluoroacetophenone decreased. Therefore, the preferred mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone was 1:4.

[0062] Example 26 In Example 22, the hydrolysis time was changed to 4 h, and the other operations were the same, yielding 190.60 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.91% and a yield of 92.00% (based on 2,4-dichloro-5-fluoroethylbenzene) and 65.19 g of hydroxylamine hydrochloride solid with a purity of 98.27% and a yield of 83.80% (based on tert-butyl nitrite).

[0063] Example 27 In Example 22, the hydrolysis time was changed to 6 h, and the other operations were the same, yielding 186.37 g of 2,4-dichloro-5-fluoroacetophenone with a purity of 99.96% and a yield of 90.00% (based on 2,4-dichloro-5-fluoroethylbenzene) and 65.42 g of hydroxylamine hydrochloride solid with a purity of 98.26% and a yield of 84.10% (based on tert-butyl nitrite).

[0064] Comparative Examples 22, 26, and 27: The hydrolysis time ranges from 4 to 6 hours. The yield of 2,4-dichloro-5-fluoroacetophenone decreases when the hydrolysis time is greater than or less than 5 hours. Therefore, the preferred hydrolysis time is 5 hours.

[0065] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for the co-production of hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone, characterized in that, Specifically, the following steps are included: (a) 2,4-Dichlorofluorobenzene and anhydrous aluminum chloride were added to the reaction vessel, and after replacing the nitrogen gas, ethylene was introduced to carry out the reaction; after the reaction was completed, the mixture was washed with water and 2,4-dichloro-5-fluoroethylbenzene was obtained. (ii) 2,4-Dichloro-5-fluoroethylbenzene, tert-butyl nitrite and solvent are added to the reaction vessel, and the reaction is carried out after nitrogen is replaced; after the reaction is completed, the first material is obtained by processing; hydrochloric acid and acetone are added to the first material to carry out hydrolysis reaction; after the reaction is completed, the material is extracted, and the oil phase is post-treated to obtain 2,4-dichloro-5-fluoroacetophenone, and the aqueous phase is treated to obtain hydroxylamine hydrochloride.

2. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, In step (i), the molar ratio of 2,4-dichlorofluorobenzene to anhydrous aluminum chloride is 1:0.1-0.3, and the molar ratio of 2,4-dichlorofluorobenzene to ethylene is 1:1.0-1.

2.

3. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The reaction temperature in step (1) is 40-80 ℃, and the reaction time is 4-8 h.

4. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, During the water washing described in step (i), the temperature of the reaction system needs to be reduced to below 50 ℃.

5. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The concentration of tert-butyl nitrite in step (ii) is 90%.

6. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The solvent in step (ii) is dichloroethane or chloroform; the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to tert-butyl nitrite is 1:1.0-1.2, and the mass ratio of 2,4-dichloro-5-fluoroethylbenzene to the solvent is 1:10-20.

7. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The reaction temperature in step (ii) is 40-80 ℃, and the reaction time is 8-16 h.

8. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, In step (ii), the concentration of hydrochloric acid is 5-15%, and the molar ratio of 2,4-dichloro-5-fluoroethylbenzene to hydrochloric acid is 1:1.5-3.

9. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The mass ratio of 2,4-dichloro-5-fluoroethylbenzene to acetone in step (ii) is 1:2-6.

10. The method for co-producing hydroxylamine hydrochloride from 2,4-dichloro-5-fluoroacetophenone according to claim 1, characterized in that, The hydrolysis reaction in step (ii) takes 4-6 hours.

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