Method for synthesizing 2, 4-dichloro-5-fluorine (trichloromethyl) benzene by using dynamic tubular reactor
By using a supported ionic liquid catalyst in a dynamic tubular reactor, the synthesis of 2,4-dichloro-5-fluoro(trichloromethyl)benzene is solved, and the raw material consumption and environmental protection problems in traditional methods are achieved. Safe and green continuous production and industrial applicability.
Patent Information
- Application Number
- CN202411601470.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-11
- Publication Date
- 2025-02-14
AI Technical Summary
In the prior art, when synthesizing 2,4-dichloro-5-fluorobenzoyl chloride, CCl4 is used as the raw material, resulting in the production of corrosive gas hydrogen chloride during the production process, causing corrosion damage to the equipment, and the catalyst preparation process is complex and environmental protection problems are prominent.
Using a dynamic tubular reactor, azo-based initiator is supported by a catalyst, trichloromethane is reacted with 2,4-dichlorofluorobenzene through the Fuker reaction to produce 2,4-dichloro-5- Fluorine (trichloromethyl)benzene achieves green continuous production.
This method not only realizes green continuous production, the production process is safe and controllable, suitable for industrial production, and the catalyst is recyclable, and the by-product is only hydrogen, which avoids the problems of large amounts of aluminum-containing acid-containing wastewater and corrosive gases in traditional methods. friendly.
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Figure BDA0005128432790000021
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene by adopting a dynamic tubular reactor. Background Art
[0002] Quinolones are synthetic antibacterial drugs with 4-quinolone as the basic structure. Since the advent of norfloxacin in the late 1970s, the research and development of the third generation of quinolones - fluoroquinolones has caused a revolution in antibacterial drugs, and many new drugs with clinical value have emerged, such as ofloxacin, ciprofloxacin, romioxacin, fleroxacin, etc., which have become one of the main clinical anti-infective drugs, second only to cephalosporins and penicillins. With the continuous expansion of the demand for quinolones, the demand for its key intermediate 2,4-dichloro-5-fluorobenzoyl chloride is also increasing.
[0003] 2,4-dichlorofluorobenzene is used as the starting material, and reacts with CCl4 to generate 2,4-dichloro-5-fluoro-(trichloromethyl)benzene, which is then hydrolyzed and chlorinated to obtain the target product 2,4-dichloro-5-fluorobenzoyl chloride. This process uses CCl4 as a raw material, which is cheap and easy to obtain, and can consume a large amount of CCl4 that will damage the ozone layer. The traditional process usually uses aluminum trichloride as a catalyst for intermittent production, which produces a large amount of aluminum-containing and acid-containing wastewater, and the environmental protection problem is prominent. There are also patent reports that use solid acid or molecular sieve as a catalyst to catalyze the Friedel-Crafts reaction, but the catalyst preparation process is complicated. However, the methods currently reported all use CCl4 as a raw material, and while obtaining the target product, an equimolar amount of corrosive gas hydrogen chloride will be produced, which will cause great corrosion damage to the equipment. Therefore, there is an urgent need for a green catalytic process to achieve the conversion of this type of reaction. Summary of the invention
[0004] In order to overcome the defects of the above-mentioned prior art, the present invention provides a safe, green and continuous method for producing 2,4-dichloro-5-fluoro(trichloromethyl)benzene. The method uses an ionic liquid-loaded azo initiator as a catalyst, uses chloroform as a raw material, generates trichloromethyl free radicals by initiation, and then uses a dynamic tubular reactor to carry out Friedel-Crafts reaction, which can not only realize green continuous production, but also be safe and controllable during the production process, and is suitable for future industrial production.
[0005] The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor provided by the present invention is as follows: 2,4-dichlorofluorobenzene, trichloromethane and a supported ionic liquid are mixed in a dynamic tubular reactor, and a Friedel-Crafts alkylation reaction is performed. After the reaction is completed, the upper supported ionic liquid is recovered, and the lower organic phase is subjected to reduced pressure distillation to obtain 2,4-dichloro-5-fluoro(trichloromethyl)benzene. The reaction equation is as follows:
[0006]
[0007] The above-mentioned loaded ionic liquid uses an imidazolium salt as a carrier to load an azo initiator, wherein the imidazolium salt is selected from any one of 1-butyl-3-methylimidazolium chloride, 1-hexyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium proline salt, 1,3-di(1-adamantane)imidazolium tetrafluoroborate, 1-ethyl-3-methylimidazolium tetrafluoroborate, and 1,3-di-tert-butylimidazolium tetrafluoroborate, and the azo initiator is selected from any one of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate; based on the mass of the loaded ionic liquid being 100%, the loading amount of the azo initiator is 10% to 30%. The loaded ionic liquid is prepared by stirring the imidazolium salt and the azo initiator at 100 to 130° C. for 7 to 10 hours under a nitrogen atmosphere.
[0008] In the above method, preferably, the mass ratio of the 2,4-dichlorofluorobenzene, chloroform and supported ionic liquid is 1:3-10:1-8.
[0009] In the above method, the 2,4-dichlorofluorobenzene, chloroform and supported ionic liquid are all fed as liquids, and the liquid flow rate is the ratio of the liquid holding capacity V of the dynamic tubular reactor to the reaction residence time t; wherein the reaction residence time t is 1 to 25 min, and the liquid holding capacity V of the dynamic tubular reactor is 100 to 1000 mL.
[0010] In the above method, the diameter of the channel inside the dynamic tubular reactor is 8 to 50 mm.
[0011] In the above method, the set temperature of the dynamic tubular reactor is 60-150° C., and the pressure in the dynamic tubular reactor is 0.1-10 MPa. Preferably, the set temperature of the dynamic tubular reactor is 90-130° C., and the pressure in the dynamic tubular reactor is 0.5-5.0 MPa.
[0012] Compared with the prior art, the present invention has the following beneficial effects:
[0013] 1. The present invention utilizes a dynamic tubular reactor to carry out Friedel-Crafts reaction, which can accurately control the reaction temperature and time, avoids repeated meaningless operations of batch reaction feeding, reduces personnel allocation, and greatly reduces the frequency and time of personnel's contact with toxic and harmful raw materials, has a higher safety factor, and is more suitable for industrial continuous production.
[0014] 2. The present invention uses supported ionic liquid and chloroform as catalyst and raw material respectively, and uses a dynamic tubular reactor to react. By strengthening three transfers and one reaction (momentum transfer, heat transfer, mass transfer and chemical reaction), the reaction time is shortened, the amount of catalyst is reduced, and the production cost and operation cost are greatly reduced. The product selectivity is greater than 98%, and the raw material conversion rate is greater than 99%. In addition, the catalyst can be recycled and reused, and the only by-product is hydrogen, which avoids the problem of a large amount of aluminum-containing acid wastewater and by-product hydrogen chloride produced by aluminum chloride as a catalyst. It is environmentally friendly and in line with relevant national policies. DETAILED DESCRIPTION
[0015] The technical solution of the present invention is further described in detail below through examples, but the protection scope of the present invention is not limited to these examples.
[0016] The supported ionic liquids ① to ⑦ used in the following examples were prepared by the following method:
[0017] 50 g of 1-butyl-3-methylimidazolium chloride and 10 g of azobisisobutyronitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ①.
[0018] 50 g of 1-butyl-3-methylimidazolium chloride and 21 g of azobisisobutyronitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ②.
[0019] 50 g of 1-hexyl-3-methylimidazolium chloride and 12 g of azobisisoheptanenitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ③.
[0020] 50 g of 1-butyl-3-methylimidazolium proline salt and 12 g of dimethyl azobisisobutyrate were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ④.
[0021] 50 g of 1,3-bis(1-adamantane)imidazolium tetrafluoroborate and 12 g of azobisisoheptanenitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ⑤.
[0022] 50 g of 1-ethyl-3-methylimidazolium tetrafluoroborate and 12 g of azobisisoheptanenitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ⑥.
[0023] 50 g of 1,3-di-tert-butylimidazole tetrafluoroborate and 12 g of azobisisoheptanenitrile were added to a 100 mL round-bottom flask, and the mixture was stirred at 120° C. for 8 h under a nitrogen atmosphere to obtain a supported ionic liquid ⑦.
[0024] Example 1
[0025] The reaction temperature of the dynamic tubular reactor was set to 90°C, the pressure was set to 0.5MPa, the reaction residence time was set to 3min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ① were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:10:2 by a metering pump. The liquid holding volume V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 93%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 97%.
[0026] Example 2
[0027] The reaction temperature of the dynamic tubular reactor system was set to 100°C, the pressure was set to 0.4MPa, the reaction residence time was 5min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ② were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:4:8 by a metering pump. The liquid holding capacity V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 99%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 96%.
[0028] Example 3
[0029] The reaction temperature of the dynamic tubular reactor system was set to 120°C, the pressure was set to 1.6MPa, the reaction residence time was 15min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ③ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:6:3 by a metering pump. The liquid holding capacity V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 97%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 98%.
[0030] Example 4
[0031] The reaction temperature of the dynamic tubular reactor system was set to 130°C, the pressure was set to 0.6MPa, the reaction residence time was 9min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ④ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:4:6 by a metering pump. The liquid holding capacity V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 93%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 97%.
[0032] Example 5
[0033] The reaction temperature of the dynamic tubular reactor system was set to 150°C, the pressure was set to 2MPa, the reaction residence time was 12min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ⑤ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:10:1 by a metering pump. The liquid holding capacity V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 94%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 91%.
[0034] Example 6
[0035] The reaction temperature of the dynamic tubular reactor system was set to 90°C, the pressure was set to 8MPa, the reaction residence time was 14min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ⑥ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:4:3 by a metering pump. The liquid holding volume V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 98%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 92%.
[0036] Example 7
[0037] The reaction temperature of the dynamic tubular reactor system was set to 100°C, the pressure was set to 0.15MPa, the reaction residence time was 4min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid⑦ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:4:3 by a metering pump. The liquid holding capacity V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 93%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 93%.
[0038] Example 8
[0039] The reaction temperature of the dynamic tubular reactor system was set to 110°C, the pressure was set to 0.2MPa, the reaction residence time was 25min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid⑦ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:3:4 by a metering pump. The liquid holding volume V of the dynamic tubular reactor was 300mL, and the channel diameter inside the reactor was 20mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 94%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 96%.
[0040] Example 9
[0041] The reaction temperature of the dynamic tubular reactor system was set to 120°C, the pressure was set to 5.0 MPa, the reaction residence time was 15 min, and 2,4-dichlorofluorobenzene, trichloromethane and supported ionic liquid ③ were respectively pumped into the dynamic tubular reactor at a mass ratio of 1:3:3 by a metering pump. The liquid holding volume V of the dynamic tubular reactor was 300 mL, and the channel diameter inside the reactor was 20 mm. After the reaction was completed, the product flowed out from the outlet of the reactor, wherein the conversion rate of 2,4-dichlorofluorobenzene was 99%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 90%.
[0042] Comparative Example 1
[0043] A microchannel reactor was used, the reaction temperature of the microchannel reactor was set to 120°C, the pressure was set to 5.0 MPa, the reaction residence time was 15 min, and 2,4-dichlorofluorobenzene, trichloromethane and loaded ionic liquid ③ were respectively pumped into the microchannel reactor in a mass ratio of 1:3:3 through a metering pump, with a total of 2 reaction modules. After the reaction was completed, the product flowed out from the outlet of the reactor, among which the conversion rate of 2,4-dichlorofluorobenzene was 96%, and the selectivity of 2,4-dichloro-5-fluoro(trichloromethyl)benzene was 83%.
[0044] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent changes made to the above embodiments based on the technical essence of the present invention still fall within the protection scope of the technical solution of the present invention.
Claims
1. A method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor, characterized in that: 2,4-dichlorofluorobenzene, trichloromethane and a supported ionic liquid are mixed in a dynamic tubular reactor and subjected to Friedel-Crafts alkylation reaction. After the reaction is completed, the upper supported ionic liquid is recovered and the lower organic phase is subjected to reduced pressure distillation to obtain 2,4-dichloro-5-fluoro(trichloromethyl)benzene; The loaded ionic liquid uses an imidazolium salt as a carrier to load an azo initiator, wherein the imidazolium salt is selected from any one of 1-butyl-3-methylimidazolium chloride, 1-hexyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium proline salt, 1,3-di(1-adamantane)imidazolium tetrafluoroborate, 1-ethyl-3-methylimidazolium tetrafluoroborate, and 1,3-di-tert-butylimidazolium tetrafluoroborate; the azo initiator is selected from any one of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate; and based on the mass of the loaded ionic liquid being 100%, the loading amount of the azo initiator is 10% to 30%.
2. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to claim 1, characterized in that: The mass ratio of the 2,4-dichlorofluorobenzene, chloroform and the supported ionic liquid is 1:3-10:1-8.
3. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to claim 1, characterized in that: The 2,4-dichlorofluorobenzene, chloroform and supported ionic liquid are all fed as liquids, and the liquid flow rate is the ratio of the liquid holding capacity V of the dynamic tubular reactor to the reaction residence time t; wherein the reaction residence time t is 1 to 25 minutes, and the liquid holding capacity V of the dynamic tubular reactor is 100 to 1000 mL.
4. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to claim 1, characterized in that: The diameter of the channel inside the dynamic tubular reactor is 8 to 50 mm.
5. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to claim 1, characterized in that: The set temperature of the dynamic tubular reactor is 60-150° C., and the pressure inside the dynamic tubular reactor is 0.1-10 MPa.
6. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to claim 5, characterized in that: The set temperature of the dynamic tubular reactor is 90-130° C., and the pressure inside the dynamic tubular reactor is 0.5-5.0 MPa.
7. The method for synthesizing 2,4-dichloro-5-fluoro(trichloromethyl)benzene using a dynamic tubular reactor according to any one of claims 1 to 6, characterized in that: The supported ionic liquid is prepared by stirring an imidazolium salt and an azo initiator at 100 to 130° C. for 7 to 10 hours in a nitrogen atmosphere.