CN111517931A - Method for synthesizing 2, 4-difluorobenzaldehyde by using microchannel reactor - Google Patents
Method for synthesizing 2, 4-difluorobenzaldehyde by using microchannel reactor Download PDFInfo
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- CN111517931A CN111517931A CN202010520715.5A CN202010520715A CN111517931A CN 111517931 A CN111517931 A CN 111517931A CN 202010520715 A CN202010520715 A CN 202010520715A CN 111517931 A CN111517931 A CN 111517931A
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- difluorobenzaldehyde
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
Abstract
The invention discloses a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, which mainly adopts 2, 4-dinitrobenzaldehyde and potassium fluoride as raw materials, utilizes the microchannel reactor to react for 50-55 seconds at the temperature of 200 plus materials and 210 ℃, and finally carries out rectification and purification on the product to obtain a refined 2, 4-difluorobenzaldehyde product with the purity of more than or equal to 99 percent. The preparation method of the invention realizes the micro-channel continuous synthesis of the 2, 4-difluorobenzaldehyde, reduces the production cost by 10-15% compared with the traditional batch kettle method, improves the yield by 1-2%, and improves the production efficiency and the yield by 30-35%. The method adopts the micro-channel continuous flow reactor, and the micro-channel continuous flow reaction technology has the characteristics of continuous reaction process, good reaction liquid mixing effect, mild reaction conditions, quick reaction time, good product consistency and the like, is particularly suitable for the synthesis and preparation of the 2, 4-difluorobenzaldehyde, and provides powerful technical support for the large-scale low-cost continuous synthesis and production of the 2, 4-difluorobenzaldehyde.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor.
Background
2, 4-difluorobenzaldehyde, DFBA for short, is an organic synthesis intermediate with wide application, and can be used for synthesizing medicines, pesticides, dyes, fluorine-containing functional materials and the like. And is an intermediate for preparing new-generation triazole antifungal drug fluconazole. However, the requirement of the 2, 4-difluorobenzaldehyde in China is imported, the price is high, and the development of various aspects is influenced and limited to a great extent.
The current synthesis process methods reported by 2, 4-difluorobenzaldehyde include the following methods:
(1) synthetic route using 2, 4-dinitrotoluene as raw material
Chenhong biao et al uses easily available 2, 4-dinitrotoluene as raw material, and prepares it through reduction, improved Zeeman reaction fluorination, side chain chlorination and hydrolysis. The specific reaction scheme is as follows:
although the raw materials of the route are easy to obtain and the process is simple, the process steps are complex, the reaction is carried out in multiple steps, a large amount of catalyst and chlorine are needed to be used as reaction catalysts, and the method is difficult to implement in industrial production.
(2) Synthetic route using toluene as raw material
Zhangjinan et al take toluene as a raw material, and prepare 2, 4-difluorobenzaldehyde through multiple reactions such as nitration, oxidation reduction, fluorination and the like in sequence, wherein a specific synthetic route is as follows:
although the raw materials and the catalyst of the process route are easy to obtain, the reaction steps are more, and the concentration of the alkaline solution has a great influence on the total reaction yield, so that the method has certain difficulty in realizing industrial production.
In the production process, the method has more reaction steps, large catalyst consumption, difficult recovery, high reaction temperature, difficult product quality guarantee and harsh reaction conditions, and is difficult to implement industrially. The conventional method for synthesizing the 2, 4-difluorobenzaldehyde at present is a conventional kettle type method, has high production cost, low yield, high impurity content in a product, belongs to batch production, has low production efficiency and cannot meet the market demand. Although researchers at home and abroad carry out extensive research on the synthesis method and process, reports on continuous synthesis of 2, 4-difluorobenzaldehyde by a microchannel continuous flow reaction technology are not seen at present.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, and when the method is applied, a microchannel continuous reaction technology is adopted, 2, 4-dinitrobenzaldehyde is used as a raw material, potassium fluoride is used as a fluorinating agent, and the fluorodenitration reaction can be completed at the temperature of 200-210 ℃, so that the efficient continuous synthesis process of the 2, 4-difluorobenzaldehyde is realized.
The invention is realized by the following technical scheme:
a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor comprises the following steps:
(1) dissolving a certain amount of 2, 4-dinitrobenzaldehyde in a sulfolane solvent under stirring to form a solution A;
(2) dissolving a certain amount of potassium fluoride in sulfolane under stirring to form a solution B;
(3) and (2) adding a proper amount of tetramethylammonium bromide as a phase transfer catalyst into the solution A and the solution B according to a molar ratio of 1:4 by using a peristaltic pump, injecting the mixture into a microchannel reactor to realize intensive mixing of the two solutions, flowing the reaction liquid out of the microchannel reactor, then introducing the reaction liquid into a purification tank by using a guide pipe, rectifying and purifying the mixed liquid of 2, 4-difluorobenzaldehyde and sulfolane in the purification tank, steaming the sulfolane, and returning the mixed liquid to the system for reuse to obtain a 2, 4-difluorobenzaldehyde refined product with the purity of more than or equal to 99%.
Further, a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, wherein the aperture of the microchannel reactor is 0.9-1.2 mm.
Further, a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, wherein the reaction temperature of a jacket cavity of the microchannel reactor is controlled by adopting an oil bath, and the temperature is controlled at 200-210 ℃.
Further, a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, wherein the reaction time in the microchannel reactor is controlled to be 50-55 seconds.
At present, because the traditional method for synthesizing 2, 4-difluorobenzaldehyde is a conventional kettle-type method, the production cost is high, the yield is low, the impurity content in the product is high, the batch-type production is realized, the production efficiency is low, and the market demand cannot be met, the application provides a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, a peristaltic pump is used for injecting a solution A and a solution B into the microchannel reactor according to the molar ratio of 1:4 and adding a proper amount of tetramethylammonium bromide as a phase transfer catalyst to realize the intensive mixing of the two solutions, the reaction time is controlled at 50-55 seconds at the temperature of 200 ℃ and 210 ℃, the reaction liquid flows out of the microchannel reactor and is guided into a purification tank by a guide pipe, the mixed solution of the 2, 4-difluorobenzaldehyde and sulfolane in the purification tank is rectified and purified, the sulfolane is distilled and recycled in the system, obtaining the refined 2, 4-difluorobenzaldehyde product with the purity of more than or equal to 99 percent.
The reaction equation is:
in summary, the following beneficial effects of the invention are:
1. the invention relates to a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, which adopts a microchannel continuous flow reactor, and has the characteristics of continuous reaction process, good reaction liquid mixing effect, mild reaction conditions, quick reaction time, good product consistency and the like, and is particularly suitable for synthesizing and preparing the 2, 4-difluorobenzaldehyde.
2. The synthesis method can realize the continuous synthesis of the 2, 4-difluorobenzaldehyde by the micro-channel, the production cost is reduced by 10-15% compared with the traditional batch kettle method, the yield can be improved by 1-2%, and the production efficiency and the yield are improved by 30-35%.
3. The invention relates to a method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor, which provides powerful technical support for large-scale low-cost continuous synthesis and production of the 2, 4-difluorobenzaldehyde.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
Example 1
A method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor comprises the following steps: dissolving a certain amount of 2, 4-dinitrobenzaldehyde in a sulfolane solvent under stirring to form a solution A; dissolving a certain amount of potassium fluoride in sulfolane under stirring to form a solution B; and (2) adding a proper amount of tetramethylammonium bromide as a phase transfer catalyst into the solution A and the solution B according to a molar ratio of 1:4 by using a peristaltic pump, injecting the mixture into a microchannel reactor to realize intensive mixing of the two solutions, flowing the reaction liquid out of the microchannel reactor, then introducing the reaction liquid into a purification tank by using a guide pipe, rectifying and purifying the mixed liquid of 2, 4-difluorobenzaldehyde and sulfolane in the purification tank, steaming the sulfolane, and returning the mixed liquid to the system for reuse to obtain a 2, 4-difluorobenzaldehyde refined product with the purity of more than or equal to 99%.
Specifically, the aperture of the micro-channel reactor is 0.9-1.2 mm.
Specifically, the reaction temperature of the jacket cavity of the microchannel reactor is controlled by adopting an oil bath, and the temperature is controlled at 200-210 ℃.
Specifically, the reaction time in the microchannel reactor is controlled to be 50-55 seconds.
Example 2
Dissolving 20g of 2, 4-dinitrobenzaldehyde in 300ml of sulfolane solvent under stirring to form a solution A; dissolving 30g of potassium fluoride in 300ml of sulfolane under stirring to form a solution B; and simultaneously injecting the solution A and the solution B by using a peristaltic pump, adding 0.8g of tetramethylammonium bromide as a phase transfer catalyst, injecting the solution A and the solution B into a microchannel reactor to realize strong mixing of the two solutions, keeping the temperature at 200 ℃ and 210 ℃, controlling the reaction time at 50-55 seconds, guiding the reaction liquid flowing out of the microchannel reactor into a purification tank by using a guide pipe, rectifying and purifying the mixed solution of 2, 4-difluorobenzaldehyde and sulfolane in the purification tank, evaporating the sulfolane, and returning the distilled solution to the system for repeated use to obtain the 2, 4-difluorobenzaldehyde refined product with the purity of more than or equal to 99%.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (4)
1. A method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor is characterized by comprising the following steps:
(1) dissolving a certain amount of 2, 4-dinitrobenzaldehyde in a sulfolane solvent under stirring to form a solution A;
(2) dissolving a certain amount of potassium fluoride in sulfolane under stirring to form a solution B;
(3) and (2) adding tetramethylammonium bromide serving as a phase transfer catalyst into the solution A and the solution B according to a molar ratio of 1:4 by using a peristaltic pump, injecting the solution A and the solution B into a microchannel reactor to realize intensive mixing of the two solutions, flowing the reaction liquid out of the microchannel reactor, then introducing the reaction liquid into a purification tank by using a guide pipe, rectifying and purifying the mixed liquid of 2, 4-difluorobenzaldehyde and sulfolane in the purification tank, steaming the sulfolane, and returning the mixed liquid to the system for reuse to obtain a 2, 4-difluorobenzaldehyde refined product with the purity of more than or equal to 99%.
2. The method for synthesizing 2, 4-difluorobenzaldehyde according to claim 1, wherein the pore size of the microchannel reactor is 0.9-1.2 mm.
3. The method for synthesizing 2, 4-difluorobenzaldehyde by using a microchannel reactor as claimed in claim 1, wherein the jacketed cavity in the microchannel reactor is oil bath controlled at 200-210 ℃.
4. The method for synthesizing 2, 4-difluorobenzaldehyde according to claim 1, wherein the reaction time in the microchannel reactor is controlled to 50-55 seconds.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112133553A (en) * | 2020-10-30 | 2020-12-25 | 福州大学 | Continuous preparation method of water-based magnetofluid |
| CN113527020A (en) * | 2021-07-06 | 2021-10-22 | 浙江大学 | Method for continuous fluorination in pipeline by using fluorine salt as fluorine source |
| CN114308023A (en) * | 2021-12-31 | 2022-04-12 | 江苏擎动新能源科技有限公司 | Platinum-carbon catalyst and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5237087A (en) * | 1991-09-21 | 1993-08-17 | Hoechst Aktiengesellschaft | Process for the preparation of chlorinated and fluorinated benzene compounds by selective nucleophilic fluorodenitration |
| CN104496801A (en) * | 2014-11-27 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Preparation method of 2,4-difluorobenzoic acid |
| CN105130744A (en) * | 2015-08-19 | 2015-12-09 | 浙江林江化工股份有限公司 | Method for synthesizing 1,3,5-trichloro-2,4,6-trifluorobenzene from 2,4-difluoro-3,5-dichloronitrobenzene |
| WO2019110710A1 (en) * | 2017-12-06 | 2019-06-13 | Solvay Specialty Polymers Italy S.P.A. | Process for preparing fluorohalogenoethers |
-
2020
- 2020-06-10 CN CN202010520715.5A patent/CN111517931A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5237087A (en) * | 1991-09-21 | 1993-08-17 | Hoechst Aktiengesellschaft | Process for the preparation of chlorinated and fluorinated benzene compounds by selective nucleophilic fluorodenitration |
| CN104496801A (en) * | 2014-11-27 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Preparation method of 2,4-difluorobenzoic acid |
| CN105130744A (en) * | 2015-08-19 | 2015-12-09 | 浙江林江化工股份有限公司 | Method for synthesizing 1,3,5-trichloro-2,4,6-trifluorobenzene from 2,4-difluoro-3,5-dichloronitrobenzene |
| WO2019110710A1 (en) * | 2017-12-06 | 2019-06-13 | Solvay Specialty Polymers Italy S.P.A. | Process for preparing fluorohalogenoethers |
Non-Patent Citations (3)
| Title |
|---|
| THOMAS M.MOORE等: "A rapid microfluidic synthesis of [18F]fluoroarenes from nitroarenes", 《APPLIED RADIATIONANDISOTOPES》 * |
| 张精安等: "氟康唑中间体2,4-二氟苯甲醛的合成", 《中国医药工业杂志》 * |
| 杨光富: "《有机合成 第二版》", 30 August 2016 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112133553A (en) * | 2020-10-30 | 2020-12-25 | 福州大学 | Continuous preparation method of water-based magnetofluid |
| CN112133553B (en) * | 2020-10-30 | 2021-12-21 | 福州大学 | Continuous preparation method of water-based magnetofluid |
| CN113527020A (en) * | 2021-07-06 | 2021-10-22 | 浙江大学 | Method for continuous fluorination in pipeline by using fluorine salt as fluorine source |
| CN113527020B (en) * | 2021-07-06 | 2022-04-08 | 浙江大学 | Method for continuous fluorination in pipeline by using fluorine salt as fluorine source |
| CN114308023A (en) * | 2021-12-31 | 2022-04-12 | 江苏擎动新能源科技有限公司 | Platinum-carbon catalyst and preparation method thereof |
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