A process for the co-production of trifluoromethoxybenzene and ortho-trifluoromethyl dichloromethylbenzene
The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene utilizes o-trifluoromethyldichloromethylbenzene as a solvent and recycles it, solving the problem of unsuitable solvent selection in existing technologies, realizing an efficient and environmentally friendly production process, improving product yield and reducing costs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NINGXIA ZHONGTONG BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-03-31
- Publication Date
- 2026-06-26
AI Technical Summary
Existing methods for preparing trifluoromethoxybenzene suffer from problems such as numerous side reactions of benzene ring chlorination due to unsuitable solvent selection, low yield, and environmentally unfriendly solvents, making it difficult to achieve efficient and environmentally friendly co-production of trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene.
Using anisole and o-xylene as raw materials, trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene are co-produced through chlorination and fluorination reactions. o-trifluoromethyldichloromethylbenzene is used as a solvent and recycled. With appropriate initiators and catalysts, the reaction conditions are controlled to reduce side reactions, and pure products are obtained by separation.
This improved the yield of trifluoromethoxybenzene, reduced solvent consumption, lowered production costs, achieved efficient resource utilization and an environmentally friendly production process, and reduced costs.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of fine chemical technology, and more specifically, it is a method for the co-production of trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene. Background Technology
[0002] Trifluoromethoxybenzene is an important intermediate in the synthesis of pharmaceuticals, pesticides, dyes, and liquid crystal materials, among other electronic chemicals. Pharmaceuticals synthesized using fluorinated organic compounds as raw materials offer many advantages: they can enhance drug efficacy, improve therapeutic effects, have no side effects, and possess long-lasting and good oral administration properties. In recent years, this organic compound has been widely used.
[0003] o-Trifluoromethyldichloromethylbenzene is an important raw material for the synthesis of o-trifluoromethylbenzaldehyde and other fine chemical intermediates. o-Trifluoromethylbenzaldehyde is used in the synthesis of various organic compounds and is a key intermediate in the fields of pharmaceuticals, pesticides, and materials. The trifluoromethyl group in its molecular structure can be introduced into target molecules to improve physical properties or enhance reactivity. It serves as a core component in the synthesis of pesticides and chemical drugs, used to construct the active molecular skeleton. For example, its derivatives may be used in the development of insecticides, fungicides, or novel drugs.
[0004] Because the methyl chlorination of anisole differs from that of toluene compounds, the methyl chlorination of anisole readily leads to the chlorination of the benzene ring, resulting in cross-linking and the formation of tar. Therefore, a solvent must be added to control the chlorination of the benzene ring. The literature with publication number CN1390820A describes the use of carbon tetrachloride as a solvent, which effectively controls the chlorination of the benzene ring. However, carbon tetrachloride is an ozone-depleting substance and is one of the substances restricted in production and use under the Montreal Protocol on Substances that Deplete the Ozone Layer. Developed countries were required to completely phase it out by 1996, and developing countries were required to cease all use by 2010.
[0005] Patent USO05773668A clearly describes how unsuitable solvents can cause chlorination side reactions on the benzene ring, and the absence of a solvent will also lead to chlorination side reactions on the ring. To reduce benzene ring chlorination side reactions and increase the yield of the intermediate trichloromethoxybenzene, thereby increasing the yield of the target product trifluoromethoxybenzene, a suitable solvent is needed.
[0006] Various solvents have been publicly reported for the chlorination reaction in the preparation of trichloromethoxybenzene, such as carbon tetrachloride, glacial acetic acid, trifluorotoluene, o-chlorotrifluorotoluene, m-chlorotrifluorotoluene, p-chlorotrifluorotoluene, 1,2-dichlorotrifluoroethane, and trichlorotoluene. For example, patent publication number US5773668A uses trifluorotoluene and p-chlorotrifluorotoluene as solvents for chlorination. These two solvents are very effective for the chlorination of anisole; however, they may have adverse effects on subsequent reactions. For instance, trichloromethoxybenzene, after fluorination, yields trifluoromethoxybenzene with a boiling point of 102°C, the same as trifluorotoluene, making separation impossible. Furthermore, p-chlorotrifluorotoluene has a chlorine atom on its benzene ring; if a hydrogenation reaction occurs in the subsequent process, a dechlorination reaction will occur, producing impurities.
[0007] Patent CN103553884A discloses a method for producing trifluoromethoxybenzene. The reaction uses p-dimethylbenzene as a solvent and anisole or a mixture of anisole and p-dimethylbenzene as raw materials. Chlorination is initiated by passing chlorine gas to obtain trichloromethoxybenzene and p-di(trichloromethylbenzene). After chlorination, the solvent is removed, and trichloromethoxybenzene and p-di(trichloromethyl)benzene undergo a fluorination reaction with anhydrous hydrogen fluoride under perfluorosulfonyl fluoride catalyst conditions to obtain trifluoromethoxybenzene and p-di(trifluoromethyl)benzene. The byproduct p-di(trifluoromethyl)benzene is recycled. However, the uses of the byproduct p-di(trifluoromethyl)benzene are limited.
[0008] Pentachloro-o-xylene, also known as Inaba Blue (CAS 2741-57-3), is a polychlorinated aromatic hydrocarbon compound, mainly synthesized via the chlorination reaction of o-xylene. Patent CN111825520A discloses a synthesis of 1,2-bis(dichloromethylbenzene), which requires strict control of the chlorine gas flow rate; otherwise, it is difficult to stop at the 1,2-bis(dichloromethylbenzene) stage, producing 2-trichloromethyl-1-dichloromethylbenzene as a byproduct. The formation of 1,2-bis(trichloromethylbenzene) requires a higher reaction temperature. Summary of the Invention
[0009] To address the aforementioned deficiencies in existing methods for preparing trifluoromethoxybenzene, this invention discloses a method for the co-production of trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene. The byproducts can be used as a solvent in the reaction. Finally, trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene are obtained through distillation. A portion of the o-trifluoromethyldichloromethylbenzene is used as a product to synthesize o-trifluoromethylbenzaldehyde, while the other portion is returned to the reaction system as a solvent. This is a recyclable production method that achieves the same yield as existing methods while simultaneously producing another product. The core advantages of simultaneously producing two or more products using the same chlorination and fluorination system lie in improved resource utilization, reduced costs and energy consumption, and improved environmental safety.
[0010] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for the co-production of trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene, comprising the following steps: Step 1: Using anisole and p-dimethylbenzene as raw materials, chlorine gas is passed through an organic solvent to induce a chlorination reaction, yielding intermediates A and B. The chemical reaction formula is as follows:
[0011] Furthermore, in the above technical solution, the organic solvent is o-trifluoromethyldichloromethylbenzene, and the initiator is any one, two or more of phosphorus trichloride, azobisisobutyronitrile, and benzoyl peroxide, with a mass ratio of 1:1 or 1:1:1. By selecting a suitable initiator, photo-initiation can be omitted, saving production conditions. By selecting a suitable half-life, the amount of initiator used can be effectively reduced. After being diluted with solvent together with the raw materials, it is continuously added to the reactor to reduce the activation on the benzene ring, reduce the chlorination on the benzene ring, and improve the yield of trifluoromethoxybenzene.
[0012] This formulation ensures a complete reaction without wasting any materials. The solvent is completely added to the reactor, while o-xylene, used as a diluent, is continuously added to the reactor along with the anisole / initiator mixture.
[0013] Furthermore, in the above technical solution, the chlorine gas introduction rate is 120-150 g / h; this rate ensures that the amount of chlorine gas reaches the amount required for the reaction.
[0014] Furthermore, in the above technical solution, the chlorination reaction temperature is 100-150℃, and the chlorination reaction time is 12-18h.
[0015] Step 2: Intermediates A and B react with anhydrous hydrogen fluoride in the presence of a perfluorosulfonyl fluoride catalyst to undergo a fluorination reaction, yielding trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene, which are then separated by distillation. The chemical reaction formula is as follows:
[0016] Furthermore, in the above technical solution, the mass ratio of intermediate A and intermediate B to anhydrous hydrogen fluoride is 1:3-8; the mass ratio of intermediate B to catalyst is 1:0.001-0.01. This ratio ensures a complete fluorination reaction, and the excess anhydrous hydrogen fluoride also acts as a solvent in the reaction system. The excess portion can be recovered and reused, thus avoiding waste of raw materials.
[0017] Furthermore, in the above technical solution, the fluorination reaction temperature is 80-150℃, the reaction pressure is 0.5-5.0MPa, and the reaction time is 6-8h.
[0018] Furthermore, in the above technical solution, the perfluorosulfonyl fluoride catalyst is selected from any one, two or more of perfluoropropylsulfonyl fluoride, perfluorobutylsulfonyl fluoride, perfluoropentylsulfonyl fluoride, perfluoroheptylsulfonyl fluoride, and perfluorooctylsulfonyl fluoride.
[0019] Furthermore, in the above technical solution, the method for separating trifluoromethoxybenzene in the fluorination reaction is as follows: after the reaction is completed, excess anhydrous hydrogen fluoride is removed by nitrogen purging, and potassium carbonate aqueous solution, sodium carbonate aqueous solution or sodium hydroxide aqueous solution are added. The pH value of the mixture obtained after the reaction is adjusted to 6-7. After the mixture is allowed to stand and separate into layers, the organic layer is collected and distilled to obtain pure trifluoromethoxybenzene and pure o-trifluoromethyldichloromethylbenzene.
[0020] Furthermore, in the above technical solution, the o-trifluoromethyldichloromethylbenzene undergoes a hydrolysis reaction under Lewis acid catalysis to obtain o-trifluoromethylbenzaldehyde, and / or is added to the first step reaction for recycling.
[0021] This invention uses a mixture of anisole and o-dimethylbenzene as raw materials. A portion of the resulting byproduct (o-trifluoromethyldichloromethylbenzene) can be reused as a solvent in the first-step reaction, while the remainder is used as the final product to synthesize o-trifluoromethylbenzaldehyde. Compared to existing preparation methods, this invention reduces solvent consumption, allows for recyclable production, effectively recovers and utilizes the byproducts, saves resources, reduces production costs, and simultaneously yields a valuable raw material. This method demonstrates high resource efficiency, environmental friendliness, and significant economic benefits.
[0022] o-Trifluoromethyldichloromethylbenzene was used as the solvent for the chlorination reaction of anisole, replacing the traditional solvent carbon tetrachloride. This solved the problems of high toxicity and ozone layer depletion caused by carbon tetrachloride. Since the boiling point of o-trifluoromethyldichloromethylbenzene is 194.3℃, which is significantly different from that of trifluoromethoxybenzene (102℃), the trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene can be easily separated after fluorination.
[0023] Compared with existing technologies, this invention uses a mixture of anisole and o-dimethylbenzene as starting materials and o-trifluoromethyldichloromethylbenzene as a solvent. The initiator does not require light exposure. The entire reaction system undergoes chlorination followed by fluorination to obtain trifluoromethoxy compounds and trifluoromethyl compounds. The anisole and initiator are diluted with o-dimethylbenzene and continuously added to the reactor after mixing, ensuring uniform material concentration and stable temperature control within the reaction system. This facilitates side-chain substitution and inhibits benzene ring substitution, effectively reducing chlorination side reactions on the benzene ring and thus increasing the yield of the product trifluoromethoxybenzene. Furthermore, the byproduct o-trifluoromethyldichloromethylbenzene serves as a valuable raw material, achieving the goal of co-production and making the entire production process green and environmentally friendly. Detailed Implementation
[0024] The present invention will be further illustrated below through examples, but the scope of protection of the present invention is not limited thereto. All raw materials used in this embodiment are commercially available products. Gas chromatography was used to analyze the reaction process. The chemical reaction formula for this embodiment is as follows: Example 1
[0025] Chlorination reaction: Add 150g of o-trifluoromethyldichloromethylbenzene solvent to a reactor equipped with a mechanical stirrer, condenser, thermometer, bottom vent pipe, and dropper. Start stirring and heat to 139-140℃. Begin purging chlorine gas at a rate of 120g / h. After purging chlorine for 10 minutes, begin dropwise adding a mixed solution of 200g anisole, 200g o-xylene solvent, 10g azobisisobutyronitrile, and 10g phosphorus trichloride. Pour the solution at 139-140℃ for 12 hours. After the addition is complete, take a sample for analysis. Stop the reaction when the dichloromethoxybenzene content is below 0.3%. Otherwise, continue purging chlorine until the standard is reached, then cool down.
[0026] Fluorination reaction: 1134.5g of the mixed solution obtained from the chlorination reaction was added to an autoclave, followed by 333.3g of hydrogen fluoride and 1g of perfluoropropylsulfonyl fluoride. Stirring was started, and the temperature was raised to 95℃ / 2.8MPa and maintained for 4-6 hours. The reaction was then stopped, and samples were taken for analysis.
[0027] 3. Product separation: The fluorination reactor was purged with nitrogen for 30 minutes, the product was washed with potassium carbonate solution, the pH of the mixture was adjusted to 6-7 to separate into layers, the lower oil phase was taken and distilled at -0.095 MPa to -0.1 MPa / 90℃ to obtain 580 g of o-trifluoromethyldichloromethylbenzene with a purity of 98.13%; and 286.38 g of trifluoromethoxybenzene with a purity of 99.95%, yielding 95.41%.
[0028] Example 2
[0029] 1. Chlorination reaction: Add 150g of o-trifluoromethyldichloromethylbenzene solvent from Example 1 to a reactor equipped with a mechanical stirrer, condenser, thermometer, bottom vent pipe, and dropper. Start stirring and heat to 139-140℃. Begin purging chlorine gas at a rate of 120g / h. After purging chlorine for 10 minutes, begin dropwise adding a mixed solution of 200g anisole, 200g o-xylene solvent, 10g azobisisobutyronitrile, and 10g phosphorus trichloride. Pour the solution at 139-140℃ for 12 hours. After the addition is complete, take a sample for analysis. If the dichloromethoxybenzene content is below 0.3%, stop the reaction; otherwise, continue purging chlorine until the standard is reached, then cool down.
[0030] 2. Fluorination reaction: Add 1134.5g of the mixed solution obtained from the chlorination reaction to a high-pressure reactor, then add 333.3g of hydrogen fluoride and 1g of perfluoropropylsulfonyl fluoride. Start stirring and heat to 95℃ / 2.8MPa pressure, maintaining the temperature for 4-6 hours. Stop the reaction and take samples for analysis.
[0031] 3. Product separation: The fluorination reactor was purged with nitrogen for 30 minutes, the product was washed with potassium carbonate solution, the pH of the mixture was adjusted to 6-7 to separate into layers, and the lower oil phase was distilled at -0.095 MPa to -0.1 MPa / 90℃ to obtain 575 g of o-trifluoromethyldichloromethylbenzene with a purity of 97.82%; and 285.42 g of trifluoromethoxybenzene with a purity of 99.75%, with a trifluoromethoxybenzene yield of 94.9%. Example 3
[0032] 1. Chlorination reaction: 1100g of o-trifluoromethyldichloromethylbenzene solvent obtained in Examples 1 and 2 (total less than 1200g for Examples 1 and 2) was added to a reactor equipped with a mechanical stirrer, condenser, thermometer, bottom vent pipe, and dropper. Stirring was started, and the temperature was raised to 120-125℃. Chlorine gas was introduced. After chlorination for 10 minutes, a mixed solution of 1600g anisole, 1600g o-xylene solvent, 80g benzoyl peroxide, and 80g phosphorus trichloride was added dropwise. The addition was carried out at 120-125℃ for 15 hours. After the addition was completed, a sample was taken for analysis. When the dichloromethoxybenzene content was below 0.3%, the reaction was stopped. Otherwise, chlorine was introduced until the standard was reached, and then the temperature was lowered.
[0033] 2. Fluorination reaction: Add 8433.31g of the mixed solution obtained from the chlorination reaction to a high-pressure reactor, followed by 1600g of hydrogen fluoride and 5g of perfluorooctyl sulfonyl fluoride. Start stirring and heat to 100℃ / 2.8MPa pressure, maintaining the temperature for 4-5 hours. Stop the reaction and take samples for analysis.
[0034] 3. Product recovery: The fluorination reactor was purged with nitrogen for 30 minutes. The product was washed with sodium carbonate aqueous solution. The pH of the mixture was adjusted to 6-7 to separate the layers. The lower oily liquid was collected and distilled at -0.095 MPa to -0.1 MPa / 100℃ to obtain 5300 g of o-trifluoromethyldichloromethylbenzene with a purity of 99.21%; 2285.97 g of trifluoromethoxybenzene with a purity of 99.87% was obtained, and the yield of trifluoromethoxybenzene was 95.12%. Example 4
[0035] 1. Chlorination reaction: Add 300g of o-trifluoromethyldichloromethylbenzene solvent (Example 3) to a reactor equipped with a mechanical stirrer, condenser, thermometer, bottom vent pipe, and dropper. Start stirring and heat to 140-145℃. After purging with chlorine gas for 10 minutes, start adding a mixed solution of 200g anisole, 300g o-xylene solvent, 15g azobisisobutyronitrile, and 15g phosphorus trichloride. Add the solution dropwise at 140-145℃ for 10 hours. After the addition is complete, take a sample for analysis. When the dichloromethoxybenzene content is below 0.3%, stop the reaction and cool down.
[0036] 2. Fluorination reaction: Add 1178g of the mixed solution obtained from the chlorination reaction to a high-pressure reactor, followed by 150g of hydrogen fluoride, 1g of perfluorooctyl sulfonyl fluoride, and 1g of perfluorobutyl sulfonyl fluoride. Start stirring and heat to 130℃ / 3.0MPa pressure, maintaining the temperature for 3-4 hours. Stop the reaction and take samples for analysis.
[0037] 3. Product separation: The fluorination reactor was purged with nitrogen for 30 minutes. The product was washed with sodium bicarbonate aqueous solution. The pH of the mixture was adjusted to 6-7 to separate the layers. The lower oil phase was collected and distilled at -0.095 MPa to -0.1 MPa / 90℃ to obtain 948 g of o-trifluoromethyldichloromethylbenzene with a purity of 99.2%; and 284.98 g of trifluoromethoxybenzene with a purity of 99.88%. The yield of trifluoromethoxybenzene was 94.88%.
[0038] The above description is only one of the preferred technical solutions of the present invention and is not intended to limit the present invention. Any modifications made within the technical solution of the present invention embody the principle of the present invention and should be included within the protection scope of the present invention.
Claims
1. A method for the co-production of trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene, characterized in that, The method includes the following steps: ； Step 1: Using anisole and p-dimethylbenzene as raw materials, chlorine gas is passed into an organic solvent to produce a chlorination reaction, yielding intermediate A and intermediate B; Step 2: Intermediate A and intermediate B react with anhydrous hydrogen fluoride in the presence of a perfluorosulfonyl fluoride catalyst to produce trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene, which are then separated by distillation.
2. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: The first step is that the organic solvent is o-trifluoromethyldichloromethylbenzene; the initiator is selected from at least one of phosphorus trichloride, azobisisobutyronitrile, and benzoyl peroxide; when there are two or more, the mass ratio of each component is 1:1 or 1:1:
1.
3. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: In the first step, the mass ratio of anisole, o-xylene, and o-trifluoromethyldichloromethylbenzene is 1:1-5:1-2; the mass ratio of anisole to chlorine is 1:9.5-12.8; and the mass ratio of anisole to initiator is 1:0.005-0.
2.
4. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: The first step involves introducing chlorine gas at a rate of 120-150 g / h, with a reaction temperature of 100-150℃ and a reaction time of 12-18 h.
5. The process for the co-production of trifluoromethoxybenzene and ortho- trifluoromethyl dichloromethylbenzene according to claim 1, characterized in that: In the second step, the mass ratio of intermediate A and intermediate B to anhydrous hydrogen fluoride is 1:3-8; the mass ratio of intermediate B to catalyst is 1:0.001-0.
01.
6. The process for the co-production of trifluoromethoxybenzene and ortho- trifluoromethyl dichloromethylbenzene according to claim 1, characterized in that: In the second step, the fluorination reaction temperature is 80-150℃, the reaction pressure is 0.5-5.0MPa, and the reaction time is 6-8h.
7. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: The second step involves selecting one, two, or more of the following perfluorosulfonyl fluoride catalysts: perfluoropropylsulfonyl fluoride, perfluorobutylsulfonyl fluoride, perfluoropentylsulfonyl fluoride, perfluoroheptylsulfonyl fluoride, and perfluorooctylsulfonyl fluoride.
8. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: The second step, the method for separating trifluoromethoxybenzene in the fluorination reaction, is as follows: after the reaction is completed, excess anhydrous hydrogen fluoride is removed by nitrogen purging, and potassium carbonate aqueous solution, sodium carbonate aqueous solution or sodium hydroxide aqueous solution are added. The pH value of the mixture obtained after the reaction is adjusted to 6-7. After the mixture is allowed to stand and separate into layers, the organic layer is collected and distilled to obtain pure trifluoromethoxybenzene and pure o-trifluoromethyldichloromethylbenzene.
9. The method for co-producing trifluoromethoxybenzene and o-trifluoromethyldichloromethylbenzene according to claim 1, characterized in that: In the second step, the o-trifluoromethyldichloromethylbenzene is then hydrolyzed under Lewis acid catalysis to obtain o-trifluoromethylbenzaldehyde, and / or added to the first step reaction for recycling.