A high-purity p-fluorobenzoyl chloride photochlorination synthesis method

Abstract

The present invention discloses a high-purity photochlorination synthesis method of p-fluorobenzoyl chloride, wherein an aromatic nitro compound or its salt is selected to form an inhibition system with triethanolamine, which not only inhibits side reactions, but also inhibits the photochlorination process to inhibit fluorotoluene, the self-luminous defluorination of p-fluorotrichlorobenzyl, and the high-temperature defluorination of p-fluorobenzoyl chloride in the distillation process, thereby further improving the purity of the synthesized p-fluorobenzoyl chloride to above 99.5. The aromatic nitro compound or its salt is specifically any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite, preferably potassium nitrite; the dosage is 0.1‰ to 1‰ of the mass of p-fluorotoluene, and the addition amount and time are strictly controlled to ensure that the effect of inhibiting the defluorination is achieved while ensuring the safety of the reaction process and the product, and has good practical value and important economic value.

Description

Technical Field

[0001] The invention belongs to the technical field of high molecular polymer synthesis, and particularly relates to a method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination. Background Art

[0002] p-Fluorobenzoyl chloride (i.e. 4-fluorobenzoyl chloride), its chemical structure is as follows Figure 1 As shown. 4-Fluorobenzoyl chloride is an important organic synthesis intermediate. According to research reports, 4-Fluorobenzoyl chloride is a key intermediate in the synthesis of anti-tumor, antibacterial, antiviral and other drugs. At the same time, 4-Fluorobenzoyl chloride is also an important raw material for the synthesis of PEK, PEEK, PEKK, as well as optical, electronic, liquid crystal and other materials. Therefore, its purity not only has an important influence on the purity, therapeutic effect and safety of synthetic drugs, but also has a significant relationship with the performance and stability of materials, which profoundly affects the application of drugs and materials in various fields.

[0003] Existing synthesis methods of p-fluorobenzoyl chloride include thionyl chloride chlorination, photochlorination, solid triphosgene chlorination, two-step method, etc. Among them, the photochlorination is to use p-fluorotoluene as raw material, under the action of light and catalyst, p-fluorotoluene reacts with chlorine to synthesize p-fluorotrichlorotoluene, which is further hydrolyzed into p-fluorobenzoyl chloride, and the product is obtained by distillation; because of its advantages such as low reaction temperature, few side reactions and high product purity, it is an ideal choice for synthesizing p-fluorobenzoyl chloride. It is reported that the product purity of p-fluorobenzoyl chloride synthesized by photochlorination can usually reach 98.0%, however, for the fields of medicine, aerospace, electronics and electricity, even a trace amount of impurities may have a significant negative impact on the performance of the final product, especially in the application of medicine and precision instrument manufacturing.

[0004] Analysis found that the reasons for the existence of impurities in the p-fluorobenzoyl chloride products synthesized by existing photochlorination mainly include the insufficient purity of the raw material p-fluorotoluene, the occurrence of side reactions, insufficient separation and purification, and the use of inhibitors. Among them, in the photochlorination process, the use of side reaction inhibitors is the key, which can improve the selectivity and efficiency of the reaction. However, if the addition ratio and type of the inhibitor are improperly controlled, new impurities will be introduced, which will not only lead to unsatisfactory side reaction control effects, but also cause subsequent purification difficulties, reducing the purity of the final product. In addition, it is worth noting that in actual production, after p-fluorotoluene and p-fluorobenzyl chloride are excited by light, spontaneous luminescence will occur, resulting in the rupture of the CF bond, thereby producing a defluorination phenomenon, which not only destroys the structure of p-fluorotoluene and p-fluorobenzyl chloride, but also causes the selectivity of the product to be reduced, affecting the yield of the final product, and the generated fluorine-containing organic matter and impurities are difficult to purify and separate, posing risks to the environment and human health, while also further reducing the purity of the product. In addition, the inventors also found that the boiling point of p-fluorobenzoyl chloride is 193°C. In the prior art, in order to avoid product decomposition or loss caused by excessive heating, vacuum distillation is generally used, that is, the boiling point is reduced by reducing the pressure, so that p-fluorobenzoyl chloride evaporates at a lower temperature, thereby achieving purification; however, in actual production, the distillation tower configured in the distillation link is very high, and its height can reach more than ten meters, and the pressure and temperature in the tower are difficult to maintain at the set value; especially in the later stage of distillation, as the material decreases, the temperature in the tower can reach more than 200°C, and the high temperature will cause the CF bond of p-fluorobenzoyl chloride to break, causing p-fluorobenzoyl chloride to lose fluorine and form benzoyl chloride, which has a boiling point of 197.2°C, which is very close to p-fluorobenzoyl chloride, and it is difficult to separate it from p-fluorobenzoyl chloride in the distillation link, resulting in an increase in the impurity content in the fraction, which in turn leads to the difficulty in improving the purity of p-fluorobenzoyl chloride synthesized by the chlorination method.

[0005] Therefore, how to overcome the problem of spontaneous luminescent defluorination of p-fluorotoluene and p-fluorobenzyltrichloride and fluorine loss in the distillation stage of the synthesized p-fluorobenzoyl chloride may further improve the purity of p-fluorobenzoyl chloride synthesized by photochlorination. Summary of the invention

[0006] In view of the above-mentioned problems of spontaneous luminescence defluorination of p-fluorotoluene and p-fluorobenzyl chloride and fluorine loss in the distillation stage of the synthesized p-fluorobenzoyl chloride, and in order to achieve the above-mentioned purpose of improving the purity of p-fluorobenzoyl chloride synthesized by photochlorination, the present invention provides a high-purity p-fluorobenzoyl chloride photochlorination synthesis method, and inhibitors are added in both the photochlorination link and the distillation link to inhibit the spontaneous luminescence defluorination of fluorotoluene and p-fluorobenzyl chloride, and inhibit the high-temperature fluorine loss of p-fluorobenzoyl chloride, so as to further improve the purity of the synthesized p-fluorobenzoyl chloride. The specific technical scheme is as follows: A high-purity p-fluorobenzoyl chloride photochlorination synthesis method comprises the following steps: 1) Photochlorination reaction: add p-fluorotoluene and a chlorination catalyst into a reaction kettle, turn on an ultraviolet lamp, control the temperature, introduce chlorine, start to add a first inhibitor in batches, and add a chlorination catalyst; when the p-fluorobenzyl chloride content increases slowly, add a second inhibitor, and stop introducing chlorine until the p-fluorobenzyl chloride content stops increasing, turn off the ultraviolet lamp, cool, and obtain an intermediate product p-fluorobenzyl chloride; the chlorination catalyst is dibenzoyl peroxide; the first inhibitor is an aromatic nitro compound or a salt thereof; the second inhibitor is triethanolamine; 2) Hydrolysis reaction: introducing the p-fluorobenzyl chloride obtained by the photochlorination reaction into a hydrolysis reactor, controlling the reaction temperature and adding a hydrolysis catalyst dropwise to completely convert the p-fluorobenzyl chloride into p-fluorobenzoyl chloride; the hydrolysis catalyst is an aqueous solution of ferric chloride; 3) Distillation and purification: The hydrolysis reaction material is input into a distillation kettle, the temperature and pressure are controlled, vacuum distillation is performed, and a third inhibitor is added in batches, and the target fraction is collected to obtain high-purity p-fluorobenzoyl chloride, the purity of which is not less than 99.5%; the third inhibitor is an aromatic nitro compound or a salt thereof.

[0007] In the above-mentioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the first inhibitor and the third inhibitor are any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite.

[0008] Preferably, in the aforementioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the first inhibitor and the third inhibitor are both potassium nitrite.

[0009] Preferably, in the aforementioned method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination, the total amount of the first inhibitor and the third inhibitor used is 0.1‰ to 1‰ of the mass of p-fluorotoluene, and the mass ratio of the two is 1:4.

[0010] Further preferably, in the aforementioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the amount of the first inhibitor used is 0.1‰ of the mass of p-fluorotoluene, and the amount of the third inhibitor used is 0.4‰ of the mass of p-fluorotoluene.

[0011] In the above-mentioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the total amount of dibenzoyl peroxide is used in a molar ratio of 0.015:2.5 to p-fluorotoluene; the amount of triethanolamine is used in a molar ratio of 0.8:1000 to p-fluorotoluene; the mass concentration of the ferric chloride aqueous solution is 3%, and the molar ratio of its amount to p-fluorobenzyl chloride is 0.02:1.

[0012] As a preferred technical solution, the above-mentioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the specific process of the photochlorination reaction described in step 1) is as follows: 1-1) The first inhibitor is divided into ten equal parts, and the chlorination catalyst is divided into three equal parts for standby use; 1-2) Add p-fluorotoluene and two chlorination catalysts into the reactor, turn on the UV lamp, control the temperature to 80-90°C, start to introduce chlorine gas, and control the chlorine flow rate to 5-10m 3 / h; 1-3) Add the first portion of the first inhibitor, start bubbling, mix the materials, and start the water cooling circulation system, maintain the reaction temperature at 80-90°C, and react for 3 hours; during this period, add one portion of the first inhibitor every half an hour, and add a total of six portions; 1-4) Raise the reaction temperature in the reactor to 130-135°C, continue to introduce chlorine gas, and control the chlorine flow rate to 3-8m 3 / h, adding the remaining portion of chlorination catalyst; 1-5) After half an hour of reaction, add the seventh portion of the first inhibitor, and then add a portion of the first inhibitor every half an hour until the first inhibitor is completely added; 1-6) Half an hour after the first inhibitor is completely added, the GC is used to track the content of 4-fluorobenzyl chloride. When the content of 4-fluorobenzyl chloride increases slowly, the second inhibitor is added until the content of 4-fluorobenzyl chloride stops increasing. Then, the introduction of chlorine is stopped, the UV lamp is turned off, and the mixture is cooled to obtain the intermediate product 4-fluorobenzyl chloride.

[0013] As a preferred technical solution, the above-mentioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the specific process of the hydrolysis reaction described in step 2) is as follows: 2-1) introducing the 4-fluorobenzyl chloride obtained in step 1) into a hydrolysis kettle, and starting to drip a hydrolysis catalyst when the temperature rises to 80-85°C, with the dripping speed controlled at 10 kg / h; 2-2) Start the water cooling circulation system, maintain the reaction temperature at 80-85°C, and start the external circulation system, using the shear force of the pump to fully mix the water and the chlorinated liquid to promote the conversion of 4-fluorobenzyl chloride into 4-fluorobenzoyl; 2-3) After the hydrolysis catalyst is added, the temperature is raised to 120-125°C and kept warm for 1-2 hours. During this period, GC tracking is performed to detect whether the p-fluorobenzyl chloride in the material is completely converted into p-fluorobenzoyl chloride. If not, the hydrolysis catalyst is added until the p-fluorobenzyl chloride is completely converted.

[0014] As a preferred technical solution, the above-mentioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the specific process of distillation purification in step 1) is as follows: 3-1) Divide the third inhibitor into four equal parts for later use; 3-2) The hydrolyzed material obtained in step 2) is fed into a distillation kettle, and a vacuum pump is turned on to allow the kettle to reach a set vacuum degree; 3-3) Turn on the heating to make the material in the kettle boil, and the steam rises into the distillation tower. Open the receiving system and collect the front fraction; 3-4) When the temperature in the kettle is close to the boiling point of the target fraction, add the first portion of the third inhibitor and collect the target fraction; 3-5) monitoring the yield of the target fraction, and when the yield of the target fraction reaches 60%, adding the second portion of the third inhibitor; 3-6) continuously collecting the target fraction and monitoring the yield of the target fraction, and when the yield of the target fraction reaches 80%, adding the third portion of the third inhibitor; 3-7) continuing to collect the target fraction and monitoring the yield of the target fraction, and when the yield of the target fraction reaches 90%, adding the fourth portion of the third inhibitor; 3-8) Continuously monitor the target fraction yield. When the target fraction yield reaches 95%, replace the collection barrel and closely monitor the distillation temperature. When the temperature exceeds the boiling point of the target fraction by 1 to 2°C, stop collecting the target fraction.

[0015] As a further preferred technical solution, in the aforementioned high-purity p-fluorobenzoyl chloride photochlorination synthesis method, the vacuum degree of the distillation purification is set to 720 mmHg, and the collection temperature of the target fraction is 153°C.

[0016] Beneficial effects of the present invention: 1) The method of the present invention adds an aromatic nitro compound or its salt as an inhibitor in the photochlorination step and the distillation step for the first time, and utilizes the strong electron-withdrawing and nucleophilic substitution characteristics of the nitro group to affect the electron distribution on the benzene ring of p-fluorotoluene and p-fluorobenzoyl chloride, so as to achieve the purpose of inhibiting the loss of fluorine from p-fluorotoluene, p-fluorobenzyl trichloride and p-fluorobenzoyl chloride, thereby improving the purity of the synthesized p-fluorobenzoyl chloride.

[0017] 2) The method of the present invention optimizes the inhibitor and adds aromatic nitro compounds or salts thereof, which not only inhibits the occurrence of side reactions, but also inhibits the spontaneous light-emitting defluorination of the raw material fluorotoluene and the generated p-fluorotrichlorobenzyl in the photochlorination process, and inhibits the high-temperature defluorination of p-fluorobenzoyl chloride in the distillation process, thereby forming a multi-action inhibition system and further improving the purity of the synthesized p-fluorobenzoyl chloride.

[0018] 3) The method of the present invention selects any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite as inhibitors in the photochlorination step and the distillation step, and strictly controls the dosage and addition process, fully inhibits the loss of fluorine from p-fluorotoluene, p-fluorobenzyl trichloride and p-fluorobenzoyl chloride, guides the positive direction of the photochlorination reaction, and prevents the generation of fluorine-containing organic matter; at the same time, p-fluorobenzoyl chloride is prevented from losing fluorine to generate benzoyl chloride, thereby improving the purity of the target product p-fluorobenzoyl chloride.

[0019] 4) The inhibitor in the photochlorination step and the distillation step of the method of the present invention is preferably potassium nitrite, which has a higher boiling point than nitrobenzene, dinitrobenzene, etc., is easy to separate from p-fluorobenzoyl chloride in the distillation stage, and is non-toxic, ensuring that the product is not only suitable for the fields of aerospace, electronics and electricity, but also can be used as a pharmaceutical intermediate.

[0020] 5) In the photochlorination stage of the method of the present invention, the inhibitor is added in ten portions, and the amount and time of addition are strictly controlled. This is because studies have found that compared with p-fluorotoluene, p-fluorobenzyl trichloride will undergo a self-luminescent decomposition reaction after being excited by light, and the trifluoromethyl group is activated under the conditions of photoexcitation and is more likely to remove fluorine. Therefore, potassium nitrite is added in small amounts and multiple times to protect the raw material p-fluorotoluene while better protecting the product p-fluorobenzyl trichloride.

[0021] 6) In the distillation stage of the method of the present invention, the inhibitor is added when the temperature approaches the boiling point of the target fraction separation. This is mainly because the reduced pressure distillation is used. For every 0.133 kPa (1 mmHg) difference in pressure, the boiling point rises by about 1°C. The distillation tower in the distillation stage is more than ten meters high, and the pressure in the tower is also different from that in the reactor. This is to prevent the CF bond of p-fluorobenzoyl chloride from breaking easily at high temperatures. The inhibitor is added when the temperature approaches the boiling point of the target fraction separation to fully ensure that the CF of p-fluorobenzoyl chloride is not broken. In addition, the remaining inhibitor is added later according to the yield of p-fluorobenzoyl chloride to avoid the loss of fluorine in the remaining p-fluorobenzoyl chloride due to the reduction of materials in the distillation kettle and the increase in pressure and temperature, thereby fully ensuring the purity of the collected target fraction.

[0022] 7) In the distillation stage of the method of the present invention, the temperature of the target fraction is controlled at 153° C. to more effectively separate the impurities in p-fluorobenzoyl chloride because the boiling points of different components differ more greatly, thereby improving the purity of the product.

[0023] In general: the present invention selects aromatic nitro compounds or their salts and triethanolamine to form an inhibition system, which not only inhibits side reactions, but also inhibits the photochlorination process to inhibit fluorotoluene, the spontaneous luminescent defluorination of fluorotrichlorobenzyl, and the high-temperature defluorination of fluorobenzoyl chloride in the distillation process, further improving the purity of the synthesized fluorobenzoyl chloride to above 99.5. The aromatic nitro compound or its salt is specifically any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite, preferably potassium nitrite; the dosage is 0.1‰ to 1‰ of the mass of fluorotoluene, and the addition amount and time are strictly controlled to ensure that the effect of inhibiting the defluorination is achieved while ensuring the safety of the reaction process and the product, and has good practical value and economic value. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is the chemical structure of p-fluorobenzoyl chloride; Figure 2The liquid chromatography test result of p-fluorobenzoyl chloride synthesized by the method of the present invention; Figure 3 The infrared spectrum of p-fluorobenzoyl chloride synthesized by the present invention; Figure 4 This is the infrared spectrum of p-fluorobenzoyl chloride synthesized in comparative example. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solution and advantages of the present invention more clear, the technical solution of the present invention will be clearly and completely described below in conjunction with embodiments.

[0026] Example 1 This embodiment is a method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination, comprising the following steps: 1) Photochlorination reaction: Take 1000 kg of p-fluorotoluene, 162 kg of dibenzoyl peroxide, 100 g of potassium nitrite, and 10.83 kg of triethanolamine; wherein, the dibenzoyl peroxide is divided into three equal portions, each of which is 54 kg, and the potassium nitrite is divided into ten equal portions, each of which is 10 g.

[0027] First, add p-fluorotoluene and 108 kg of chlorination catalyst into the reactor, turn on the UV lamp, raise the temperature to 85 °C, and start to introduce chlorine gas, controlling the chlorine gas flow rate to 6 m 3 / h, and add a portion of potassium nitrite 10g, start bubbling, mix the materials, and start the water cooling circulation system at the same time, maintain the reaction temperature at 85°C, and react for 3 hours; during this period, add a portion of potassium nitrite every half an hour, and add a total of six portions.

[0028] Then, the reaction temperature in the reactor was raised to 132°C, and chlorine was continued to be introduced, with the chlorine flow rate controlled at 5m 3 / h, add the remaining portion of dibenzoyl peroxide 54kg, bubble and mix the materials; after reacting for half an hour, add the seventh portion of potassium nitrite, and then add a portion of potassium nitrite every half an hour until the potassium nitrite is completely added.

[0029] After the last portion of potassium nitrite was added, the reaction was continued for half an hour. The content of p-fluorobenzyl chloride in the material was tracked by GC. When the content of p-fluorobenzyl chloride increased slowly, triethanolamine was added until the content of p-fluorobenzyl chloride stopped increasing. The introduction of chlorine was stopped, the UV lamp was turned off, and the product was cooled to obtain 1922.4 kg of the intermediate p-fluorobenzyl chloride with a yield of 99.2% and a purity of 99.6%.

[0030] 2) Hydrolysis reaction: Take 30 kg of ferric chloride and prepare a ferric chloride aqueous solution with a mass volume concentration of 3%, and set aside.

[0031] All the p-fluorobenzyl chloride obtained by the photochlorination reaction was introduced into the hydrolysis kettle, and when the temperature reached 82°C, the ferric chloride aqueous solution was added dropwise, and the dropping speed was controlled to be 10kg ferric chloride / h. The water cooling circulation system was turned on to maintain the reaction temperature at 82°C, and the external circulation system was turned on to fully mix the water and the chlorinated liquid by the shear force of the pump, so as to promote the conversion of p-fluorobenzyl chloride into p-fluorobenzoyl, improve the reaction effect, and reduce the entrained materials in the exhaust gas.

[0032] After 3 hours, after the addition of the ferric chloride aqueous solution was completed, the temperature was raised to 122°C and kept warm for 1.5 hours. During this period, GC tracking was performed to detect whether the p-fluorobenzyl chloride in the chlorinated solution was completely converted into p-fluorobenzoyl chloride. If not, some more ferric chloride aqueous solution could be added until the p-fluorobenzyl chloride was completely converted.

[0033] 3) Distillation and purification: Weigh 400 g of potassium nitrite and divide it into four equal portions, 100 g each for later use.

[0034] The material of the hydrolysis reaction is input into the distillation kettle, and the vacuum pump is turned on to make the vacuum degree in the kettle reach 720 mmHg; the heating is turned on to make the material in the kettle boil, and the steam rises into the distillation tower, and the receiving system is turned on to collect the front fraction; when the temperature in the kettle reaches 152°C, the first portion of potassium nitrite is added, and the target fraction p-fluorobenzoyl chloride is collected; Monitor the yield of p-fluorobenzoyl chloride, and add 100 g of the second portion of potassium nitrite when the yield reaches 60%; continue to collect the target fraction, and add the third portion of potassium nitrite when the p-fluorobenzoyl chloride reaches 80%; continue to collect the target fraction and monitor the yield of the target fraction, and add the last portion of potassium nitrite when the yield of the target fraction reaches 90%; continue to monitor the yield of the target fraction, and replace the collection barrel when the yield of the target fraction reaches 95%, and closely monitor the distillation temperature. When the temperature reaches 154°C, stop collecting the target fraction, and obtain 1546 kg of p-fluorobenzoyl chloride, with a yield of 97.8% and a purity of 99.589%. Figure 2 shown.

[0035] Comparative Example This embodiment is also a method for synthesizing p-fluorobenzoyl chloride by photochlorination, which is different from the first embodiment in that potassium nitrite is not used. The method comprises the following steps: 1) Photochlorination reaction: Take 1000 kg of p-fluorotoluene, 162 kg of dibenzoyl peroxide, and 10.83 kg of triethanolamine; wherein, the dibenzoyl peroxide is divided into three portions, each of which has a weight of 54 kg, for later use.

[0036] First, add p-fluorotoluene and 108 kg of chlorination catalyst into the reactor, turn on the UV lamp, raise the temperature to 85 °C, and start to introduce chlorine gas, controlling the chlorine gas flow rate to 6 m 3 / h, start bubbling, mix the materials, and start the water cooling circulation system at the same time, maintain the reaction temperature at 85℃, and react for 3 hours.

[0037] Then, the reaction temperature in the reactor was raised to 132°C, and chlorine was continued to be introduced, with the chlorine flow rate controlled at 5m 3 / h, add the remaining 54kg of dibenzoyl peroxide, bubble and mix the materials; react for 3 hours, track the content of 4-fluorobenzyl chloride in the materials by GC, when the content of 4-fluorobenzyl chloride increases slowly, add triethanolamine until the content of 4-fluorobenzyl chloride stops increasing, stop passing chlorine, turn off the ultraviolet lamp, cool and obtain 1886kg of intermediate 4-fluorobenzyl chloride, with a yield of 97.3% and a purity of 99.1%.

[0038] 2) Hydrolysis reaction: Take 30 kg of ferric chloride and prepare a ferric chloride aqueous solution with a mass volume concentration of 3%, and set aside.

[0039] All the p-fluorobenzyl chloride obtained by the photochlorination reaction was introduced into the hydrolysis kettle, and when the temperature reached 82°C, the ferric chloride aqueous solution was added dropwise, and the dropping speed was controlled to be 10kg ferric chloride / h. The water cooling circulation system was turned on to maintain the reaction temperature at 82°C, and the external circulation system was turned on to fully mix the water and the chlorinated liquid by the shear force of the pump, so as to promote the conversion of p-fluorobenzyl chloride into p-fluorobenzoyl, improve the reaction effect, and reduce the entrained materials in the exhaust gas.

[0040] After 3 hours, after the addition of the ferric chloride aqueous solution was completed, the temperature was raised to 122°C and kept warm for 1.5 hours. During this period, GC tracking was performed to detect whether the p-fluorobenzyl chloride in the chlorinated solution was completely converted into p-fluorobenzoyl chloride. If not, some more ferric chloride aqueous solution could be added until the p-fluorobenzyl chloride was completely converted.

[0041] 3) Distillation and purification: The material of the hydrolysis reaction is input into the distillation kettle, and the vacuum pump is turned on to make the vacuum degree in the kettle reach 720 mmHg; the heating is turned on to make the material in the kettle boil, and the steam rises into the distillation tower, and the receiving system is opened to collect the front fraction; when the temperature in the kettle reaches 153°C, the target fraction p-fluorobenzoyl chloride is collected; the distillation temperature is closely monitored, and when the temperature reaches 154°C, the collection of the target fraction is stopped, and 1516 kg of the product p-fluorobenzoyl chloride is obtained, with a yield of 97.8% and a purity of 98%.

[0042] The p-fluorobenzoyl chloride (product 1) prepared in Example 1 and the p-fluorobenzoyl chloride (product 2) prepared in the comparative example were subjected to infrared spectroscopy analysis. The results are as follows: Figure 3 and Figure 4As shown, it can be seen that the characteristic peaks of the infrared spectrum of p-fluorobenzoyl chloride (product 1) prepared by the method of the present invention are significantly reduced compared with the characteristic peaks of the infrared spectrum of p-fluorobenzoyl chloride (product 2) prepared in the comparative example, indicating that the content of impurities in p-fluorobenzoyl chloride (product 1) prepared by the method of the present invention is significantly reduced compared with that in p-fluorobenzoyl chloride (product 2) prepared in the comparative example, which fully proves that the preparation method of the present invention can improve the product purity of p-fluorobenzoyl chloride.

[0043] In summary, the present invention selects aromatic nitro compounds or their salts to form an inhibition system with triethanolamine, which not only inhibits side reactions, but also inhibits the photochlorination process to inhibit fluorotoluene, the spontaneous luminescent defluorination of fluorotrichlorobenzyl, and the high-temperature defluorination of fluorobenzoyl chloride in the distillation process, further improving the purity of the synthesized fluorobenzoyl chloride to above 99.5. The aromatic nitro compound or its salt is specifically any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite, preferably potassium nitrite; the dosage is 0.1‰ to 1‰ of the mass of fluorotoluene, and the addition amount and time are strictly controlled to ensure that the effect of inhibiting the defluorination is achieved while ensuring the safety of the reaction process and the product, and has good practical value and economic value.

[0044] It is obvious to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be regarded as exemplary and non-restrictive from any point of view. In addition, it should be understood that although this specification is described in accordance with the implementation mode, it does not include only one technical solution. This narrative mode of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in the embodiments can also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A high-purity p-fluorobenzoyl chloride photochlorination synthesis method, characterized in that: The steps include: 1) Photochlorination reaction: add p-fluorotoluene and a chlorination catalyst into a reaction kettle, turn on an ultraviolet lamp, control the temperature, introduce chlorine, start to add the first inhibitor in batches, and add the chlorination catalyst; when the p-fluorobenzyl chloride content increases slowly, add the second inhibitor until the p-fluorobenzyl chloride content stops increasing, stop introducing chlorine, turn off the ultraviolet lamp, cool, and obtain the intermediate p-fluorobenzyl chloride; the chlorination catalyst is dibenzoyl peroxide; the first inhibitor is an aromatic nitro compound or a salt thereof; The second inhibitor is triethanolamine; 2) Hydrolysis reaction: introducing the intermediate 4-fluorobenzyl chloride obtained by the photochlorination reaction into a hydrolysis reactor, controlling the reaction temperature and adding a hydrolysis catalyst dropwise to completely convert 4-fluorobenzyl chloride into 4-fluorobenzoyl chloride; the hydrolysis catalyst is an aqueous solution of ferric chloride; 3) Distillation and purification: The hydrolysis reaction material is input into a distillation kettle, the temperature and pressure are controlled, vacuum distillation is performed, and a third inhibitor is added in batches, and the target fraction is collected to obtain high-purity p-fluorobenzoyl chloride, the purity of which is not less than 99.5%; the third inhibitor is an aromatic nitro compound or a salt thereof.

2. The method for synthesizing high-purity p-fluorobenzoyl chloride according to claim 1, wherein: The first inhibitor and the third inhibitor are any one or two of nitrobenzene, dinitrobenzene, nitrotoluene, sodium nitrite or potassium nitrite.

3. The method for synthesizing high-purity p-fluorobenzoyl chloride according to claim 2, characterized in that: The first inhibitor and the third inhibitor are both potassium nitrite.

4. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to claim 3, wherein: The total amount of the first inhibitor and the third inhibitor used is 0.1‰ to 1‰ of the mass of p-fluorotoluene, and the mass ratio of the first inhibitor and the third inhibitor is 1:

4.

5. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to claim 4, characterized in that: The dosage of the first inhibitor is 0.1‰ of the mass of p-fluorotoluene, and the dosage of the third inhibitor is 0.4‰ of the mass of p-fluorotoluene.

6. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to claim 1, characterized in that: The total amount of dibenzoyl peroxide used is in a molar ratio of 0.015:2.5 to p-fluorotoluene; The molar ratio of triethanolamine to p-fluorotoluene is 0.8:1000; The mass concentration of the ferric chloride aqueous solution is 3%, and the molar ratio of the ferric chloride aqueous solution to 4-fluorobenzyl chloride is 0.02:

1.

7. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to any one of claims 1 to 6, characterized in that: The specific process of the photochlorination reaction described in step 1) is as follows: 1-1) The first inhibitor is divided into ten equal parts, and the chlorination catalyst is divided into three equal parts for standby use; 1-2) Add p-fluorotoluene and two chlorination catalysts into the reactor, turn on the UV lamp, control the temperature to 80-90°C, start to introduce chlorine gas, and control the chlorine flow rate to 5-10m 3 / h; 1-3) Add the first portion of the first inhibitor, start bubbling, mix the materials, and start the water cooling circulation system, maintain the reaction temperature at 80-90°C, and react for 3 hours; during this period, add one portion of the first inhibitor every half an hour, and add a total of six portions; 1-4) Raise the reaction temperature in the reactor to 130-135°C, continue to introduce chlorine gas, and control the chlorine flow rate to 3-8m 3 / h, adding the remaining portion of chlorination catalyst; 1-5) After half an hour of reaction, add the seventh portion of the first inhibitor, and then add a portion of the first inhibitor every half an hour until the first inhibitor is completely added; 1-6) Half an hour after the first inhibitor is completely added, the GC is used to track the content of 4-fluorobenzyl chloride. When the content of 4-fluorobenzyl chloride increases slowly, the second inhibitor is added until the content of 4-fluorobenzyl chloride stops increasing. Then, the chlorine gas is stopped, the UV lamp is turned off, and the mixture is cooled to obtain the intermediate 4-fluorobenzyl chloride.

8. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to any one of claims 1 to 6, characterized in that: The specific process of the hydrolysis reaction in step 2) is as follows: 2-1) The intermediate 4-fluorobenzyl chloride obtained in step 1) is introduced into a hydrolysis reactor, and when the temperature is raised to 80-85°C, a hydrolysis catalyst is added dropwise at a rate of 10 kg / h; 2-2) Start the water cooling circulation system, maintain the reaction temperature at 80-85°C, and start the external circulation system, using the shear force of the pump to fully mix water and para-fluorobenzyl chloride to promote the conversion of para-fluorobenzyl chloride into para-fluorobenzoyl; 2-3) After the hydrolysis catalyst is added, the temperature is raised to 120-125°C and kept warm for 1-2 hours. During this period, GC tracking is performed to detect whether the p-fluorobenzyl chloride in the material is completely converted into p-fluorobenzoyl chloride. If not, the hydrolysis catalyst is added until the p-fluorobenzyl chloride is completely converted.

9. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to any one of claims 1 to 6, characterized in that: The specific process of distillation and purification in step 1) is as follows: 3-1) Divide the third inhibitor into four equal parts for later use; 3-2) The hydrolyzed material obtained in step 2) is fed into a distillation kettle, and a vacuum pump is turned on to allow the kettle to reach a set vacuum degree; 3-3) Turn on the heating to make the material in the kettle boil, and the steam rises into the distillation tower. Open the receiving system and collect the front fraction; 3-4) When the temperature in the kettle is close to the boiling point of the target fraction, add the first portion of the third inhibitor and collect the target fraction; 3-5) monitoring the yield of the target fraction, and when the yield of the target fraction reaches 60%, adding the second portion of the third inhibitor; 3-6) continuously collecting the target fraction and monitoring the yield of the target fraction, and when the yield of the target fraction reaches 80%, adding the third portion of the third inhibitor; 3-7) continuing to collect the target fraction and monitoring the yield of the target fraction, and when the yield of the target fraction reaches 90%, adding the fourth portion of the third inhibitor; 3-8) Continuously monitor the target fraction yield. When the target fraction yield reaches 95%, replace the collection barrel and closely monitor the distillation temperature. When the temperature exceeds the boiling point of the target fraction by 1 to 2°C, stop collecting the target fraction.

10. The method for synthesizing high-purity p-fluorobenzoyl chloride by photochlorination according to claim 9, characterized in that: The vacuum degree of the distillation purification was set to 720 mmHg, and the collection temperature of the target fraction was 153°C.

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