A kind of preparation method of 5-fluoro-2-nitrophenol

Abstract

The present invention belongs to the field of organic synthesis, and relates to a method for preparing 5-fluoro-2-nitrophenol, using 2,4-difluoronitrobenzene as a raw material, a non-polar organic solvent as a solvent, a solid base as a hydroxylation reagent, and dimethyl sulfoxide as a solid base cosolvent to prepare 5-fluoro-2-nitrophenol. The system uses a non-polar organic solvent, and the reaction rate is controllable; using a solid base, water is prevented from participating in the reaction and the inorganic base has a low solubility in the organic phase, and the generation of side reactions can be effectively controlled, and the selectivity and yield of the target product can be improved. After the product salt is dissolved, before adding hydrochloric acid to adjust the pH, a calcium chloride solution is added to the system, so that fluoride ions react with calcium chloride to generate calcium fluoride, and since the solubility of calcium fluoride in water is very small, in the process of steaming the product and the water mixture at high temperature, the influence of the acidic system on the equipment is greatly reduced. The method of the present invention is compared with the method for preparing 5-fluoro-2-nitrophenol by traditional hydrolysis, and a good technical effect has been achieved.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and specifically provides a method for preparing 5-fluoro-2-nitrophenol. Background Art

[0002] 5-Fluoro-2-nitrophenol is an important intermediate in the synthesis of fine chemicals such as the herbicide fluazifop-propyl. The synthetic routes of this intermediate reported in the literature are mainly as follows:

[0003] m-Fluorophenol nitration method:

[0004]

[0005] Patent WO2009035407 and others reported this method. However, due to the high price of m-diphenol, the large number of side reaction products during nitration, the low yield, and the difficulty in product separation, this method has low industrial value.

[0006] 2,4-Difluoronitrobenzene hydrolysis method:

[0007]

[0008] The method, reported in the literature "Synthesis of a Novel Herbicide Flumioxazin," involves hydrolyzing 2,4-difluoronitrobenzene with strong inorganic bases such as sodium hydroxide and potassium hydroxide, followed by acidification to yield the target product. This method is widely adopted due to its ease of operation and moderate to high yields. However, it inevitably produces 25% byproducts, which prevents maximum conversion of the raw material to product. This results in high raw material costs and a long reaction cycle, making it unsuitable for industrialization.

[0009] To address the long reaction cycle in the aforementioned pure water system, patent CN110627646A describes the reaction of 2,4-difluoronitrobenzene to obtain 5-fluoro-2-nitrophenol in the presence of alkali, water, and an organic solvent. This method, by adding dimethyl sulfoxide (DMSO) as an organic solvent to the reaction system, can accelerate the reaction rate, effectively shorten the reaction time, reduce energy consumption, and facilitate industrial application. However, after pilot testing, the product yield of the reaction was only maintained at 75-78%, which did not achieve the described effect. Therefore, industrial application suffers from obvious drawbacks.

[0010] 2,4-Difluoronitrobenzene is first aminized and then hydrolyzed:

[0011]

[0012] Patent CN107935858A describes this method, which involves first reacting 2,4-difluoronitrobenzene with NH3 to produce 5-fluoro-2-nitroaniline. This 5-fluoro-2-nitroaniline is then reacted with sulfuric acid and sodium nitrite to produce 5-fluoro-2-nitrophenol. However, this method is complex, requiring two steps to produce 5-fluoro-2-nitrophenol. It also produces a large amount of acidic wastewater, which poses significant environmental challenges and hinders its industrial application.

[0013] Therefore, how to overcome the difficulties existing in the above-mentioned various preparation technologies has become one of the technical problems to be solved urgently in this field. Summary of the Invention

[0014] The present invention addresses the gaps in the above-mentioned technology and provides a method for preparing 5-fluoro-2-nitrophenol. To address the low yield and high cost of existing synthesis methods, which are unfavorable for industrial production, the inventors propose the following solutions: 1) Using 2,4-difluoronitrobenzene as the starting material, a non-polar pure organic solvent is selected as the reaction solvent, and a solid base is used as the hydroxylation reagent. The solid base has low solubility in the organic phase and is added in batches to reduce the generation of impurities and improve the selectivity and yield of the target product. Since the solid base has extremely low solubility in the non-polar organic solvent, dimethyl sulfoxide is added as a cosolvent for the solid base to promote the forward reaction. 2) Even if there is residual raw material in the reaction tracking, it does not affect the solvent recovery and reuse, and the residual raw material continues to participate in the reaction after the solvent is recovered and reused; 3) The post-processing is simple and easy to operate. After the reaction is completed, it is directly filtered and the filtrate is directly reused (the unreacted raw material continues to react to avoid raw material waste). After the system is adjusted for pH, the mixture of the directly distilled product and water is allowed to stand for stratification, the separated product is directly quantified, and the cut water (containing 2-3 points of product) is directly reused in the next batch of acid-adjusting water. Combining the above three improvements, the final product yield of the present invention is increased from 75% to 95-98%. The method has many advantages such as good selectivity, small side reactions, high yield, reusable solvents and acid-adjusting water, less waste, direct distillation and concentration without steam distillation, energy saving, equipment investment saving, simple operation, and easy industrialization.

[0015] The specific technical solutions of the present invention are as follows:

[0016] A method for preparing 5-fluoro-2-nitrophenol, using 2,4-difluoronitrobenzene as a raw material, is characterized by: using a non-polar organic solvent as a solvent, a solid base as a hydroxylation reagent, and dimethyl sulfoxide as a solid base cosolvent to prepare 5-fluoro-2-nitrophenol; the solid base is added in batches;

[0017] The post-processing steps are as follows: filtering the reaction system, eluting the solid salt of the filter cake with the non-polar organic solvent; dissolving the solid salt with water, adding a calcium chloride solution, converting fluoride ions in the system into calcium fluoride precipitates, and adjusting the pH of the system to 2-4; finally, distilling off the product and water, maintaining the temperature above the melting point of 5-fluoro-2-nitrophenol, the upper layer is an aqueous phase, the lower layer is an organic phase, and the lower organic phase is separated to obtain the product 5-fluoro-2-nitrophenol.

[0018] The specific reaction process of the above reaction system is as follows:

[0019]

[0020] 2NaF+CaCl2→CaF2↓+2NaCl

[0021] As a specific embodiment: the molar ratio of the solid base to 2,4-difluoronitrobenzene is 2-5:1; the mass of the solid base co-solvent is 2.5%-11% of the mass of the solid base. A more preferred embodiment: the molar ratio of the solid base to 2,4-difluoronitrobenzene is 3-4:1; the mass of the solid base co-solvent is 4%-6% of the mass of the solid base.

[0022] As a specific embodiment: the non-polar organic solvent is one or more of methyl tert-butyl ether, petroleum ether, toluene, acetonitrile, methylcyclohexane, and cyclohexane.

[0023] In a more preferred embodiment, the non-polar organic solvent is toluene.

[0024] As a specific embodiment: the solid base is solid sodium hydroxide or solid potassium hydroxide.

[0025] As a specific embodiment, a method for preparing 5-fluoro-2-nitrophenol comprises the following steps: dissolving 2,4-difluoronitrobenzene in a non-polar organic solvent to prepare a 5-30% by weight 2,4-difluoronitrobenzene solution; adding dimethyl sulfoxide (DMSO) as a solid base cosolvent; slowly heating the temperature to 40-100°C, maintaining the temperature for reaction; and adding solid base to the system in batches; maintaining the temperature until the remaining 2,4-difluoronitrobenzene is ≤2% by weight. As a more preferred embodiment, the solid base is added in three batches, with a 2-hour interval between each batch.

[0026] As a specific embodiment: the insulation reaction temperature is 60° C.-65° C. If the temperature is too low, the reaction is slow, and if the temperature is too high, the impurity content increases.

[0027] As a specific embodiment: the post-processing steps are specifically as follows:

[0028] a) After the tracking is qualified, the reaction system is filtered, and the solid salt of the filter cake is eluted with toluene with a mass ratio of 12-15% of the mass of 2,4-difluoronitrobenzene. The eluent and filtrate are recycled and used as the solvent for the next batch of reaction;

[0029] b) dissolving the solid salt in 4-7 times its mass of water, adding a pre-prepared calcium chloride solution, wherein the molar ratio of calcium chloride to 2,4-difluoronitrobenzene is 0.5-1.2:1; and adding hydrochloric acid dropwise at 25-30° C. to adjust the pH of the system to 2-4;

[0030] c) slowly heating the acid-adjusted system to 120°C-130°C, and removing the product and water by direct distillation; the upper layer is the aqueous phase, and the lower layer is the organic product phase; the temperature is maintained above 35°C, and the two phases are separated to obtain the organic product phase.

[0031] As a specific embodiment: the mass concentration of the calcium chloride solution in the above step c) is 30%.

[0032] As a specific embodiment: in step d), after the organic phase product is separated, the remaining aqueous phase contains the product, and this portion of water is directly recycled and used as the next batch of acid adjustment water.

[0033] After the reaction liquid in step a) is tracked and qualified, the solid salt is directly filtered out, and the filtrate is directly recycled and applied to the next batch of reactions. At this time, the unreacted raw materials and co-solvents remain in the solvent and continue to participate in the next batch of reactions. The solid salt is the product sodium salt.

[0034] In step b) above, a certain amount of calcium chloride solution is added to the system before acid adjustment, so that the sodium fluoride produced by the reaction reacts to produce solid calcium fluoride. Calcium fluoride is minimally soluble in water, thereby reducing the impact of fluoride ions on the equipment in an acidic system. A low molar ratio of calcium chloride prevents complete reaction of sodium fluoride to produce calcium fluoride. A high molar ratio of calcium chloride results in waste of raw materials and increased solid waste. The preferred molar ratio of 2,4-difluoronitrobenzene to calcium chloride is 1:0.7; the mass concentration of the calcium chloride solution is 30%.

[0035] In step c), the product, 5-fluoro-2-nitrophenol, is liquid and insoluble in water at temperatures above 35°C. The two phases can be separated by standing and demixing, resulting in an organic phase content of 93-97%, of which 3-7% is toluene solvent. This residual toluene has no effect on the subsequent etherification reaction in which the product participates. Furthermore, the subsequent etherification post-processing involves negative pressure desolventizing, which distills the toluene away and prevents it from entering the solid etherified product, thus eliminating the need for removal. After separating the organic phase product, the remaining aqueous phase also contains the product, at a concentration of approximately 2-3%. This water, without extraction, is directly recycled and reused as acid-adjusting water for the next batch, simplifying the process and reducing wastewater generation.

[0036] Compared with the prior art, the main advantages of the present invention are:

[0037] (1) A non-polar organic solvent is selected as the reaction solvent, and a solid base is used as the hydroxylation reagent; water is prevented from participating in the reaction; the solubility of the solid base in the organic phase is relatively low, and the solid base is added in batches, which can effectively control the generation of side reactions in the solid-liquid two-phase reaction, thereby improving the selectivity and yield of the reaction product.

[0038] (2) Since the solubility of solid base in non-polar organic solvent is extremely low, dimethyl sulfoxide is added as a co-solvent of the solid base to promote the forward reaction.

[0039] (3) After the reaction tracking is qualified, the filtered organic solvent filtrate can be directly applied to the next batch of reaction solvent without adding the auxiliary solvent dimethyl sulfoxide, thereby reducing the cost loss of the auxiliary solvent.

[0040] (4) After the sodium salt or potassium salt of the product is dissolved in acidified water, calcium chloride solution is added to the system before adding hydrochloric acid to adjust the pH, so that the generated sodium fluoride reacts with calcium chloride to form calcium fluoride. Since the solubility of calcium fluoride in water is very low, the impact of the acidic system on the equipment is greatly reduced during the high-temperature evaporation of the product and water mixture.

[0041] (5) After acid adjustment, steam distillation is not required. Instead, the distillation concentration method is directly used to evaporate the product and water mixture, saving energy and equipment investment.

[0042] (6) After separating the product organic phase from the mixture of the distilled aqueous phase and the product organic phase, the product content in the aqueous phase is 2-3%. This part of the yield does not need to be extracted, and the aqueous phase is directly applied to the next batch of acid adjustment water, which is simple to operate and reduces the generation of wastewater.

[0043] In summary, the preparation method of the present invention is simple to operate, has a high yield, saves equipment and energy, has a reusable solvent, has little environmental pollution, produces little three wastes, and causes little damage to equipment. The product yield is as high as over 95%, far exceeding the traditional method for preparing 5-fluoro-2-nitrophenol by hydrolysis, and has achieved unexpected technical effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 This is the liquid phase spectrum of the raw material 2,4-difluoronitrobenzene used in the present invention,

[0045] Figure 2 This is the reaction tracking liquid phase diagram of the alkali + water + dimethyl sulfoxide mixed system in Comparative Example 1.

[0046] Figure 3 This is the reaction tracking liquid phase spectrum of the tetrahydrofuran pure solvent system in Comparative Example 2.

[0047] Figure 4 This is the reaction tracking liquid phase spectrum of the pure water system in Comparative Example 3,

[0048] Figure 5 This is the reaction tracking liquid phase spectrum of the pure toluene system used in Example 1 of the present invention.

[0049] Figure 6 This is the liquid phase spectrum of 5-fluoro-2-nitrophenol obtained by the present invention. DETAILED DESCRIPTION

[0050] The following is a detailed description of the above content of the present invention through specific implementation methods in the form of examples, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. All technologies realized based on the above content of the present invention fall within the scope of the present invention;

[0051] Example 1

[0052] A method for preparing 5-fluoro-2-nitrophenol, comprising the following steps:

[0053] (1) Prepare 250 g of a 15% mass fraction of 2,4-difluoronitrobenzene toluene solution in a four-necked flask, add 1.8160 g of dimethyl sulfoxide (the mass of dimethyl sulfoxide is 5.5% of the mass of sodium hydroxide solid) to the system, and prepare 33.0189 g of sodium hydroxide powder according to the molar ratio of 2,4-difluoronitrobenzene to sodium hydroxide of 1:3.5. First, add one-third of the sodium hydroxide powder solid to the system;

[0054] (2) The reaction system was slowly heated to 60-65°C, and after 2 hours of heat preservation, another one-third of sodium hydroxide solid was added, and the heat preservation reaction was continued for 2 hours, and the remaining one-third of sodium hydroxide solid was added, and the heat preservation reaction was continued. The liquid phase tracking raw material remained 0.05% (see Figure 5 shown);

[0055] (3) After the reaction solution is qualified, filter it while hot, rinse the filter cake with 5g of toluene, combine the eluent and the filtrate, and detect the remaining raw material in the filtrate;

[0056] (4) Add the filter cake to another four-necked flask, add 225 g of acidified water, and stir until all the solids are dissolved; add 60 g of a pre-prepared 30% calcium chloride solution at a molar ratio of 2,4-difluoronitrobenzene to calcium chloride of 1:0.7, and then add hydrochloric acid at a temperature of 25-30°C to adjust the pH of the system to 3;

[0057] (5) After adjusting the pH, the system was slowly heated. When the temperature reached 120°C, a yellow liquid began to evaporate. When almost no oil layer evaporated, the distillation was stopped. The evaporated water and oil layer were transferred to a separatory funnel. After the interface between the organic phase oil phase and the upper aqueous phase was separated, 35.6 g of the organic phase oil layer was separated into a barrel. The detection content was 95.0%, and the remaining impurity was toluene. The organic phase yield was 93.2%, the aqueous phase yield was 2.2%, and the total yield was 95.4%. The liquid phase spectrum of the product is shown in FIG. Figure 6 .

[0058] Examples 2-4

[0059] Compared with Example 1, other conditions remain unchanged, and the reaction conditions with different amounts of dimethyl sulfoxide added are compared (the amount added in the table represents the mass ratio of dimethyl sulfoxide to sodium hydroxide solid). The results are as follows:

[0060]

[0061] As can be seen from Examples 1-4, when a small amount of dimethyl sulfoxide is added, the reaction speed is relatively slow, resulting in a long reaction time and increased impurities, which affects the yield; increasing the amount of dimethyl sulfoxide increases the reaction speed, but if the addition amount is further increased, the reaction speed does not increase significantly, but the impurities increase; the final dimethyl sulfoxide addition amount is 5.5%.

[0062] Examples 5-8

[0063] Compared with Example 1, other conditions remain unchanged, and the reaction conditions of 2,4-difluoronitrobenzene toluene solutions with different mass fractions are compared (the mass of dimethyl sulfoxide and sodium hydroxide solids changes in the same proportion as the amount of 2,4-difluoronitrobenzene used). The results are as follows:

[0064]

[0065]

[0066] From Example 1 and Examples 5-8, it is known that if the concentration of the 2,4-difluoronitrobenzene toluene solution participating in the reaction is low, the reaction capacity is affected, and if the concentration is high, the sodium salt will stick to the wall during the reaction, affecting the mass transfer and reaction yield (solid sodium salt will agglomerate and cause the raw material to be wrapped inside). Therefore, considering the yield and capacity, the preferred concentration of 2,4-difluoronitrobenzene in this application is 15%.

[0067] Examples 9-12

[0068] Compared with Example 1, other conditions remain unchanged, the reaction of 2,4-difluoronitrobenzene at different holding temperatures and the effect of calcium chloride dosage on post-treatment are compared, and the results are as follows:

[0069]

[0070] Low incubation reaction temperatures result in slow reaction rates and long reaction times, leading to larger impurities. High incubation reaction temperatures lead to larger side reactions, affecting product yields. The optimal reaction temperature for this application is 60-65°C. A low calcium chloride molar ratio prevents complete reaction of sodium fluoride to calcium fluoride. A high calcium chloride molar ratio results in waste of raw materials and increased solid waste. The most preferred 2,4-difluoronitrobenzene:calcium chloride molar ratio for this application is 1:0.7.

[0071] Examples 13-14

[0072] With other conditions remaining unchanged, the mass of sodium hydroxide changes with the molar ratio, and the mass of dimethyl sulfoxide changes with the mass of sodium hydroxide (the mass of dimethyl sulfoxide is always 5.5% of the mass of sodium hydroxide). Comparing the reactions of different molar ratios of 2,4-difluoronitrobenzene:sodium hydroxide, the results are as follows:

[0073]

[0074] When the molar ratio of sodium hydroxide is low, the reaction speed is slow, resulting in a long reaction time and larger impurities; after increasing the molar ratio of sodium hydroxide to 3.5 and continuing to increase the ratio of sodium hydroxide, the reaction speed does not increase significantly, and the impurities become larger. Finally, the ratio of sodium hydroxide is selected to be 1:3.5.

[0075] Example 15

[0076] A method for preparing 5-fluoro-2-nitrophenol, comprising the following steps:

[0077] (1) Prepare 250 g of a 15% mass fraction of 2,4-difluoronitrobenzene toluene solution in a four-necked flask, add 1.8160 g of dimethyl sulfoxide (the mass of dimethyl sulfoxide is 5.5% of the mass of sodium hydroxide solid) to the system, and prepare 33.0189 g of sodium hydroxide powder according to the molar ratio of 2,4-difluoronitrobenzene to sodium hydroxide of 1:3.5. First, add one-third of the sodium hydroxide powder solid to the system;

[0078] (2) slowly heating the reaction system to 60-65°C, keeping the temperature for 2 hours, adding another one-third of sodium hydroxide solid, continuing to keep the temperature for 2 hours, then adding the remaining one-third of sodium hydroxide solid, continuing to keep the temperature for 0.05% of the liquid phase tracking raw material;

[0079] (3) After the reaction solution is qualified, it is filtered while hot, and the filter cake is rinsed with 5g of toluene. The eluent and filtrate are combined, and the remaining raw material in the filtrate is detected. The toluene filtrate containing the raw material is prepared to be used in the next batch of reaction solvent;

[0080] (4) Add the filter cake to another four-necked flask, add 225 g of acid-adjusted water (recycled water containing 5-fluoro-2-nitrophenol, and make up the shortfall with fresh water), and stir until all the solids are dissolved; add 60 g of a pre-prepared 30% calcium chloride solution dropwise to the system at a molar ratio of 2,4-difluoronitrobenzene to calcium chloride of 1:0.7, and then add hydrochloric acid dropwise at a temperature of 25-30°C to adjust the pH of the system to 2-4;

[0081] (5) After adjusting the pH, slowly heat the system until the temperature reaches 120°C and yellow liquid begins to evaporate. When almost no oil layer evaporates, stop distillation and transfer the evaporated water and oil layer to a separatory funnel. After the interface between the organic phase and the oil phase separates from the upper aqueous phase, separate the organic phase into a barrel and test the content, water content and other indicators. The upper aqueous phase is recycled to the next batch of acid adjustment water for use.

[0082] (6) Effect of applying toluene filtrate on the reaction:

[0083]

[0084]

[0085] As the number of times the toluene filtrate is used increases, the water content increases, resulting in an increase in reaction tracking impurities, affecting the yield. After the toluene filtrate is recycled and used three times, if it is to be recycled and used again, the toluene filtrate needs to be dehydrated. The dehydration effect is better by using reflux water dehydration or adding caustic soda to the toluene filtrate.

[0086] (7) Effect of the number of times the water phase is applied on the yield:

[0087]

[0088] After separating the organic phase from the aqueous phase, the separated aqueous phase can be directly applied to the next batch of reactions as acid-adjusting water, and the product yield in the aqueous phase is 2-3%. After recycling and application, the total yield of the product is 95-98%, greatly improving the reaction yield and the utilization rate of raw materials.

[0089] Comparative Example 1

[0090] This comparative example uses a mixed system of alkali, organic solvent and water to prepare 5-fluoro-2-nitrophenol:

[0091] (1) Prepare 196 g of a 30% potassium hydroxide aqueous solution in a 500 ml four-necked flask, add 55.7 g of tetrahydrofuran solvent, and slowly heat the system to 52°C;

[0092] (2) Add 55.7 g of 2,4-difluoronitrobenzene dropwise at 52 °C, maintaining the temperature at 55-58 °C during the addition process. The addition was completed in 0.5 h. After the addition was completed, the reaction was kept warm for 2 h. The remaining 2,4-difluoronitrobenzene in the liquid phase was 0.51%, the main peak was 80.3%, and the impurities were 19.1%. The liquid phase tracking spectrum is shown in FIG. Figure 2 ;

[0093] (3) At a temperature of 35°C, add hydrochloric acid to adjust the system pH to 4 and allow to stand to separate into layers;

[0094] (4) After the tetrahydrofuran solvent was removed from the organic layer under reduced pressure, 48 g of an oily product was obtained, with a detected content of 80.5% and a yield of 71.7%. The yield of the product in the aqueous phase was 5.6%, and the total yield was 77.3%.

[0095] The reaction system of alkali + water + polar organic solvent is used. Although the addition of polar solvent increases the reaction rate and shortens the reaction cycle, while increasing the main reaction rate, the side reaction rate also increases, resulting in larger impurities and affecting the yield; after separation, a large amount of product remains in the aqueous phase, which needs to be recovered. During recovery, a solvent is used for extraction, and then the solvent is removed to obtain the product. The post-processing operation is cumbersome. If the product is not recovered, it will result in waste of product; the wastewater after extraction is acidic and cannot be reused, resulting in the generation of a large amount of wastewater.

[0096] Comparative Example 2

[0097] This comparative example uses a pure organic solvent tetrahydrofuran system to prepare 5-fluoro-2-nitrophenol:

[0098] Add 32g of 2,4-difluoronitrobenzene, 32g of tetrahydrofuran and 23.5g of potassium hydroxide solid into a 250ml three-necked flask, heat to 55°C, react for 2h and take a sample. The remaining 2,4-difluoronitrobenzene is 0.03%, the impurity liquid phase is 15.8% and the product liquid phase is 84.1%. The liquid phase tracking spectrum is shown in FIG. Figure 3 The system was cooled to 35°C, and hydrochloric acid was added dropwise to adjust the pH of the system to 4. After filtering out insoluble inorganic salts and impurities, the organic phase was desolvated under negative pressure to obtain 27.5 g of an oily product. The impurities in the oily product were normalized to 14.7% of the liquid phase, the remaining raw materials were normalized to 2.9%, and the product liquid phase was normalized to 82.3%; the quantitative content of the oily product was 83.1%, and the yield was 80.4%.

[0099] The potassium phenolate generated during the reaction could not be completely dissolved in tetrahydrofuran and agglomerated, resulting in some unreacted raw materials being wrapped inside. As a result, after negative pressure desolventizing, 2.9% of the raw materials remained in the oily product; and the large lumps that appeared were not conducive to stirring.

[0100] The use of polar solvents for the reaction increases the solubility of the inorganic base in the solvent and accelerates the reaction, but also increases the probability of contact between the base and the raw materials, thereby facilitating the hydrolysis and substitution reaction of the fluorine atom connected to the 4# position, thereby generating impurities. At the same time, the solubility of the generated potassium phenolate in polar solvents is also increased, causing the potassium phenolate to further react to form disubstituted impurities, thereby affecting the yield and product quality.

[0101] Comparative Example 3

[0102] This comparative example uses a pure water system to prepare 5-fluoro-2-nitrophenol:

[0103] (1) Weigh 32 g of 2,4-difluoronitrobenzene into a 500 ml four-necked flask, add 256 g of water, and heat and slowly raise the temperature to 60-65°C;

[0104] (2) According to the molar ratio of 2,4-difluoronitrobenzene to sodium hydroxide of 1:2.4, 77.5 g of a 25% sodium hydroxide aqueous solution was added dropwise to the system. After 1 hour of addition, the mixture was kept warm for 6 hours. The raw material liquid phase was sampled and tracked until the remaining trace was 0.43%, the impurities were normalized to 25.0%, and the main peak was 74.5%. The tracking spectrum was shown in FIG. Figure 4 ;

[0105] (3) Cooling the reaction system to 25-30°C, adding 51 g of a pre-prepared 30% calcium chloride solution at a molar ratio of 2,4-difluoronitrobenzene to calcium chloride of 1:0.7, and then adding hydrochloric acid at 25-30°C to adjust the pH of the system to 2;

[0106] (4) After adjusting the pH, the system was slowly heated to 120°C. A yellow liquid began to evaporate and was distilled until almost no oil layer was evaporated. The evaporated water and oil layer were transferred to a separatory funnel. After the interface between the organic phase and the upper aqueous phase separated, 21 g of the organic phase of the oil layer was separated into a cylinder and sent to the test for content and water content.

[0107] (5) The detected content was 96.5%, and the yield was 65.3%; the yield of the product in the aqueous phase was 4.4%, and the total yield was 69.7%.

[0108] The reaction was carried out using a pure water system. In order to avoid the phenomenon of sodium phenolate agglomeration affecting the raw material tracking during the reaction, more water needed to be added, resulting in an increase in the amount of waste liquid. Since 2,4-difluoronitrobenzene is insoluble in water, the reaction is a liquid-liquid two-phase reaction, so the reaction time is long, resulting in larger impurities and low yield.

[0109] The comparative examples above show that the product yields are low when a water-containing system is used for the hydrolysis reaction and when a pure polar solvent system is used for the reaction. The preparation method provided by the present invention is simple to operate, has a high yield, saves equipment and energy, has a reusable solvent, has little environmental pollution, produces little waste, and causes little damage to the equipment. The product yield is as high as over 95%, far exceeding the traditional method for preparing 5-fluoro-2-nitrophenol by hydrolysis, and has achieved excellent technical results.

[0110] Comparative Example 4

[0111] The other steps were the same as in Example 1 except that no dimethyl sulfoxide solid base cosolvent was added.

[0112] A method for preparing 5-fluoro-2-nitrophenol, comprising the following steps:

[0113] (1) Prepare 250 g of a 15% mass fraction 2,4-difluoronitrobenzene toluene solution in a four-necked flask. Prepare 33.0189 g of sodium hydroxide powder according to a 2,4-difluoronitrobenzene: sodium hydroxide molar ratio of 1:3.5. First, add one-third of the sodium hydroxide powder solid into the system;

[0114] (2) slowly heating the reaction system to 60-65°C, keeping the temperature for 2 hours, adding another one-third of sodium hydroxide solid, continuing to keep the temperature for 2 hours, then adding the remaining one-third of sodium hydroxide solid, and continuing to keep the temperature for 15 hours. The liquid phase tracking raw material remains 1.5%;

[0115] (3) After the reaction solution is qualified, filter it while hot, rinse the filter cake with 5g of toluene, combine the eluent and the filtrate, and detect the remaining raw material in the filtrate;

[0116] (4) Add the filter cake to another four-necked flask, add 225 g of acidified water, and stir until all the solids are dissolved; add 60 g of a pre-prepared 30% calcium chloride solution at a molar ratio of 2,4-difluoronitrobenzene to calcium chloride of 1:0.7, and then add hydrochloric acid at a temperature of 25-30°C to adjust the pH of the system to 3;

[0117] (5) After adjusting the pH, the system was slowly heated. When the temperature reached 120°C, a yellow liquid began to evaporate. When almost no oil layer evaporated, the distillation was stopped. The evaporated water and oil layer were transferred to a separatory funnel. After the interface between the organic phase oil phase and the upper aqueous phase was separated, 30.5 g of the organic phase oil layer was separated into a barrel. The detection content was 95.4%, and the remaining impurity was toluene. The organic phase yield was 80.2%, the aqueous phase yield was 2.4%, and the total yield was 82.6%.

[0118] The various technical features of the above-described embodiments can be combined arbitrarily. To make the description concise, not all possible combinations of the various technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should all be considered to be within the scope of this specification. The description of the above implementation cases can be used to help understand the principles and methods of the present invention. However, the above implementation cases are not exclusive and should not be construed as limiting the present invention. At the same time, for those skilled in the art, according to the principles and methods of the present invention, flexible changes can be made in the specific implementation methods and application scopes.

Claims

1. A method for preparing 5-fluoro-2-nitrophenol, using 2,4-difluoronitrobenzene as a raw material, characterized in that: 5-fluoro-2-nitrophenol is prepared by using a non-polar organic solvent as a solvent, a solid base as a hydroxylation agent, and dimethyl sulfoxide as a solid base co-solvent; wherein the solid base is added in batches; the specific steps are as follows: Dissolve 2,4-difluoronitrobenzene in a non-polar organic solvent to prepare a 2,4-difluoronitrobenzene solution with a mass fraction of 5-30%, add dimethyl sulfoxide as a solid base co-solvent, slowly heat to 40-100°C, keep warm for reaction, and add solid base to the system in batches; keep warm and track until the remaining 2,4-difluoronitrobenzene is ≤2wt%; The non-polar organic solvent is toluene; the solid base is solid sodium hydroxide or solid potassium hydroxide; The post-treatment steps are as follows: filtering the reaction system, eluting the filter cake solid salt with the non-polar organic solvent; after eluting, dissolving the solid salt with water, adding a calcium chloride solution, converting the fluoride ions in the system into calcium fluoride precipitation, and adjusting the pH of the system to 2-4; finally distilling out the product and water, maintaining the temperature above the melting point of 5-fluoro-2-nitrophenol, the upper layer is the water phase, the lower layer is the organic phase, and separating the lower organic phase to obtain the product 5-fluoro-2-nitrophenol.

2. The method for preparing 5-fluoro-2-nitrophenol as claimed in claim 1, characterized in that : The molar ratio of the solid base to 2,4-difluoronitrobenzene is 2-5:1; the mass of the solid base co-solvent is 2.5%-11% of the mass of the solid base.

3. The method for preparing 5-fluoro-2-nitrophenol as claimed in claim 1, characterized in that: The insulation reaction temperature is 60°C-65°C.

4. The method for preparing 5-fluoro-2-nitrophenol as claimed in claim 1, wherein The post-processing steps are specifically: a) After the tracking is qualified, the reaction system is filtered, and the solid salt of the filter cake is eluted with toluene with a mass content of 12-15% of 2,4-difluoronitrobenzene. The eluent and filtrate are recycled and used as the next batch of reaction solvents; b) After dissolving the solid salt with 4-7 times the mass of water, add the prepared calcium chloride solution, the molar ratio of calcium chloride to 2,4-difluoronitrobenzene is 0.5-1.2:1; add hydrochloric acid dropwise at 25-30°C to adjust the pH of the system to 2-4; c) Slowly heat the acid-adjusted system to 120°C-130°C, and use direct distillation to evaporate the product and water; the upper layer is the water phase, and the lower layer is the organic product phase. Maintain the temperature above 35°C to separate the two phases to obtain the organic product phase.

5. The method for preparing 5-fluoro-2-nitrophenol as claimed in claim 4, characterized in that: The mass concentration of the calcium chloride solution in the above step b) is 30%.

6. The method for preparing 5-fluoro-2-nitrophenol as claimed in claim 4, characterized in that: The method further comprises step d). In step d), after the organic phase product is separated, the remaining water phase contains the product, and this part of water is directly recovered and used as the next batch of acid adjustment water.

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