Method for continuously synthesizing 3, 5-dihalogen bromobenzene by using continuous flow reactor

Abstract

The invention relates to the field of chemistry, and discloses a method for continuously synthesizing 3, 5-dihalogen bromobenzene by using a continuous flow reactor, which is used for continuously synthesizing 3, 5-dihalogen bromobenzene by using the continuous flow reactor for the first time, changes a traditional kettle process into a continuous process, solves a series of problems of long reaction time, high safety risk and the like of batch-type reaction, and improves the yield of 3, 5-dihalogen bromobenzene. According to the present invention, the reaction conditions are mild, the reaction parameters of the 3, 5-dihalogen bromobenzene are optimized, the use of the expensive raw material or solvent is avoided, the raw material is simple and easily available, and the method has advantages of low production cost, simple operation, environmental protection, mild reaction, short reaction time, safe reaction safety compared with the conventional method, high conversion rate, less impurity, simple post-treatment, and industrial production benefiting, and can be used for industrial production of 3, 5-dihalogen bromobenzene. Compared with the prior art, obvious technical progress is achieved.

Description

Technical Field

[0001] The invention relates to the technical field of injection devices, in particular to a method for continuously synthesizing 3,5-dihalobromobenzene by utilizing a continuous flow reactor. Background Art

[0002] 3,5-difluorobromobenzene is an important organic compound, which is widely used in medicine, liquid crystal materials and many other fields. In the field of medicine, it is a key intermediate for the synthesis of certain drugs. Through structural modification, it can prepare drugs with pharmacological activities such as anti-tumor and antibacterial, which has played an important role in promoting the development of the pharmaceutical industry. At the same time, in the field of liquid crystal materials, 3,5-difluorobromobenzene, as an important raw material, helps to improve the performance and stability of liquid crystal materials, and provides strong support for the development of display technology and optical devices. In addition, it can also be used to synthesize organic compounds such as dyes and pesticides, and shows wide application potential in scientific research, biotechnology, environmental testing and chromatographic analysis. With the advancement of science and technology and the expansion of the market, the application field of 3,5-difluorobromobenzene will be more extensive, and its role in promoting human scientific and technological progress and social development will become increasingly prominent, and the market prospects are very broad.

[0003] However, traditional batch reactors face problems such as complex operation, fluctuating reaction conditions, excessive by-product generation and low production efficiency when synthesizing 3,5-dihalobenzene. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for continuously synthesizing 3,5-dihalobromobenzene by using a continuous flow reactor in view of the above-mentioned deficiencies in the prior art.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is: a method for continuously synthesizing 3,5-dihalobromobenzene using a continuous flow reactor, comprising the following steps: Step 1: Pour 7 V of tetrahydrofuran into a 500 ml conical flask, add the raw material 2-bromo-4,6-dichloroaniline or 2-bromo-4,6-difluoroaniline and stir to dissolve; Step 2: Add 11 V water and 3.0 equivalents of isopropanol and stir, then add 5%wt of catalyst; Step 3: Slowly drop 5.0 equivalents of concentrated sulfuric acid under low temperature conditions to obtain a reaction mixture AC (containing 2-bromo-4,6-dichloroaniline) or AF (containing 2-bromo-4,6-difluoroaniline); Step 4: The prepared reaction mixture AC or AF and the sodium nitrite aqueous solution (B) are continuously fed into the continuous flow reactor through two high-pressure feed pumps, and the reaction conditions such as temperature, pressure, flow rate, etc. are controlled to react; Step 5: The collected reaction solution is allowed to stand and separate into layers to obtain a crude target product.

[0006] Preferably, the solution (AC or AF) prepared in step 4 and the sodium nitrite aqueous solution (B) raw material are continuously injected into the continuous flow reactor by a high-pressure plunger pump in an equivalent ratio of 1:1. During the reaction, a high-precision control system is used to ensure precise control of the reaction conditions, the temperature is strictly maintained at 25°C, and the reaction residence time is 2 minutes.

[0007] Preferably, the reaction temperature is adjusted to 50° C., and other conditions remain unchanged, including the reaction residence time of 2 minutes.

[0008] Preferably, the reaction residence time is changed to 3 minutes.

[0009] Preferably, the reaction residence time is up to 4 minutes.

[0010] Preferably, the equivalent ratio of the raw material to sodium nitrite is adjusted to 1:1.1, and other conditions remain unchanged, including the reaction temperature is still 50° C. and the reaction residence time is still 4 minutes.

[0011] The present invention uses a continuous flow reactor to continuously synthesize 3,5-dihalogenobromobenzene for the first time, thereby changing the traditional autoclave process into a continuous process, solving a series of problems of intermittent reaction such as long reaction time and high safety risk, and optimizing the reaction parameters of 3,5-dihalogenobromobenzene, avoiding the use of expensive raw materials or solvents, and the raw materials are simple and easy to obtain, and has the advantages of low production cost, simple operation, environmental friendliness, mild reaction, short reaction time, safer reaction safety than conventional methods, high conversion rate, less impurities, simple post-treatment, and being conducive to industrial production. Compared with the prior art, significant technical progress has been achieved. DETAILED DESCRIPTION

[0012] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0013] The present invention uses a continuous flow reactor to continuously synthesize 3,5-dihalogenobromobenzene for the first time, thereby changing the traditional autoclave process into a continuous process, solving a series of problems of intermittent reaction such as long reaction time and high safety risk, and optimizing the reaction parameters of 3,5-dihalogenobromobenzene, avoiding the use of expensive raw materials or solvents, and the raw materials are simple and easy to obtain, and has the advantages of low production cost, simple operation, environmental friendliness, mild reaction, short reaction time, safer reaction safety than conventional methods, high conversion rate, less impurities, simple post-treatment, and being conducive to industrial production. Compared with the prior art, significant technical progress has been achieved.

[0014] A method for continuously synthesizing 3,5-dihalobromobenzene using a continuous flow reactor, wherein a continuous flow reactor is used for continuous flow reaction, and specifically comprises the following steps:

[0015] Configuration materials: (1) Pour 7 V of tetrahydrofuran into a 500 ml conical flask, add the raw material (2-bromo-4,6-dichloroaniline or 2-bromo-4,6-difluoroaniline) and stir to dissolve; (2) Add 11 V water and 3.0 equivalents of isopropanol, stir, and then add catalyst (5% wt); (3) slowly adding 5.0 equivalents of concentrated sulfuric acid dropwise under low temperature conditions to obtain a reaction mixture AC (containing 2-bromo-4,6-dichloroaniline) or AF (containing 2-bromo-4,6-difluoroaniline); (4) continuously feeding the prepared reaction mixture AC or AF and the sodium nitrite aqueous solution (B) into a continuous flow reactor through two high-pressure feed pumps, and controlling the reaction conditions, such as temperature, pressure, flow rate, etc., to carry out the reaction; The collected reaction solution is allowed to stand and separate into layers to obtain a crude target product.

[0016] Example 1 The pre-configured solution (AC) and sodium nitrite aqueous solution (B) (the equivalent ratio of raw material to sodium nitrite is 1:1) are continuously injected into the continuous flow reactor through high-pressure plunger pumps. During the reaction, a high-precision control system is used to ensure precise control of the reaction conditions, the temperature is strictly maintained at 25°C, and the reaction residence time is 2 minutes. After the reaction, the purity of 3,5-dichlorobromobenzene is 19.46% through central control detection; Example 2 On the basis of maintaining the same experimental apparatus and operation process as Example 1, only the reaction temperature was adjusted to 50°C, and other conditions remained unchanged, including the reaction residence time of 2 minutes. After the reaction was completed, the central control test showed that the purity of 3,5-dichlorobromobenzene was increased to 84.79%; Example 3 Further on the basis of Example 2, only the reaction residence time was changed to 3 minutes, and other conditions remained unchanged, including the reaction temperature of 50° C. After the reaction was completed, the central control test showed that the purity of 3,5-dichlorobromobenzene was further increased to 90.25%; Example 4 Based on Example 3, only the reaction residence time was extended to 4 minutes, and other conditions remained unchanged, including the reaction temperature of 50° C. After the reaction, the central control test showed that the purity of 3,5-dichlorobromobenzene reached 99.67%, which is the best condition at present; Example 5 Based on Example 4, the equivalent ratio of raw materials to sodium nitrite was adjusted to 1:1.1 to explore more optimal reaction conditions. Other conditions remained unchanged, including the reaction temperature of 50°C and the reaction residence time of 4 minutes. After the reaction, the central control test showed that the purity of 3,5-dichlorobromobenzene was 92.23%; Example 6 The pre-configured solution (AF) and sodium nitrite aqueous solution (B) (the equivalent ratio of raw material to sodium nitrite is 1:1) are continuously injected into the continuous flow reactor through high-pressure plunger pumps. During the reaction, a high-precision control system is used to ensure precise control of the reaction conditions, the temperature is strictly maintained at 50°C, and the reaction residence time is 4 minutes. After the reaction, the purity of 3,5-difluorobromobenzene is 99.4% through central control detection.

[0017] The following table is the GC table of 3,5-dichlorobromobenzene of the present invention:

[0018] In summary, the method for continuously synthesizing 3,5-dihalobromobenzene using a continuous flow reactor proposed in the present invention provides solid support and promotion for industrial production due to its many advantages such as high efficiency, safety and environmental friendliness.

Claims

1. A method for continuously synthesizing 3,5-dihalobromobenzene using a continuous flow reactor, characterized in that: The following steps are involved: Step 1: Pour 7 V of tetrahydrofuran into a 500 ml conical flask, add the raw material 2-bromo-4,6-dichloroaniline or 2-bromo-4,6-difluoroaniline, and stir to dissolve; Step 2: Add 11 V water and 3.0 equivalents of isopropanol and stir, then add 5%wt of catalyst; Step 3: Slowly drop 5.0 equivalents of concentrated sulfuric acid under low temperature conditions to obtain a reaction mixture AC (containing 2-bromo-4,6-dichloroaniline) or AF (containing 2-bromo-4,6-difluoroaniline); Step 4: The prepared reaction mixture AC or AF and the sodium nitrite aqueous solution (B) are continuously fed into the continuous flow reactor through two high-pressure feed pumps, and the reaction conditions such as temperature, pressure, flow rate, etc. are controlled to react; Step 5: The collected reaction solution is allowed to stand and separate into layers to obtain a crude target product.

2. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 1, characterized in that: The raw material of step 1 is replaced by 2-bromo-4,6-difluoroaniline.

3. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 1, characterized in that: In step 4, the pre-configured solution (AC or AF) and the sodium nitrite aqueous solution (B) are continuously injected into the continuous flow reactor through a high-pressure plunger pump at an equivalent ratio of 1:1 between the raw material and sodium nitrite. During the reaction, a high-precision control system is used to ensure precise control of the reaction conditions, the temperature is strictly maintained at 25°C, and the reaction residence time is 2 minutes.

4. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 3, characterized in that: The reaction temperature was adjusted to 50°C, and other conditions remained unchanged, including the reaction residence time of 2 minutes.

5. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 4, characterized in that: The reaction residence time was changed to 3 minutes.

6. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 4, characterized in that: The reaction residence time was up to 4 minutes.

7. The method for continuously synthesizing 3,5-dihalobenzene using a continuous flow reactor according to claim 6, characterized in that: The equivalent ratio of raw materials to sodium nitrite was adjusted to 1:1.1, and other conditions remained unchanged, including the reaction temperature of 50°C and the reaction residence time of 4 minutes.

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