Preparation method and application of 4-nitro-1, 3-bis (2-chloro-4-(trifluoromethyl) phenoxy) benzene

Abstract

The invention discloses a preparation method of 4-nitro-1, 3-bis (2-chloro-4-(trifluoromethyl) phenoxy) benzene, which comprises the following steps: S1, adding a solvent into a reaction kettle, adding nitrobenzene and carbonate, starting a stirrer, heating and mixing; s2, the pressure in the reaction kettle is adjusted, the temperature is increased to 85-95 DEG C, fluorophenol is dropwise added, and an ultrasonic reactor is connected; s3, after the fluorophenol is dropwise added, carrying out heat preservation reaction for 1-5 hours; and S4, cooling to room temperature, removing the solvent, washing, and separating to obtain the 4-nitro-1, 3-bis (2-chloro-4-(trifluoromethyl) phenoxy) benzene. According to the invention, the reaction can reach balance in a shorter time, so that the reaction yield is improved. According to the invention, the reaction energy consumption is reduced, the reaction cost is reduced, and dangerous chemical reactions are avoided.

Description

Technical Field

[0001] The present invention relates to the field of synthesis of acyclic or carbocyclic compounds, and in particular to a preparation method and application of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene. Background Art

[0002] 4-Nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene is an important intermediate for the synthesis of the herbicide oxyfluorfen. The traditional synthesis method is to obtain 1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene by nitration and reaction with 2,4-difluoronitrobenzene (or 2,4-dichloronitrobenzene) and 2-chloro-4-trifluoromethylfluorophenol. The reaction pressure is high, the reaction temperature is high, and the reaction conditions are harsh. Therefore, there are problems such as long reaction time, dangerous production reaction, and low yield of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene. Therefore, it is very important to develop a preparation method with mild reaction conditions, high yield and high purity of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0003] Chinese invention patent CN103980127A discloses a method for preparing oxyfluorfen, which includes putting 3-chlorophenol and a suitable solvent into a reaction vessel, adding a catalyst, and dripping nitric acid at a suitable temperature to carry out a nitration reaction. After the reaction is completed, the solvent is removed to obtain the intermediate 3-chloro-4-nitrophenol, which improves the safety of the operation, reduces the production cost, increases the product yield, and reduces the pollution to the environment. However, nitration is required to prepare a solid-supported catalyst, and the preparation steps are cumbersome. Chinese invention patent CN1363548A discloses a new method for synthesizing oxyfluorfen, which uses 3,4-dichlorotrifluorotoluene and resorcinol as raw materials, and obtains the product through three steps of condensation, nitration, and etherification. It has the advantages of simple process, high yield, high content of original drug, and good product quality. However, the reaction temperature is high, the reaction energy consumption is high, and the reaction is dangerous. Summary of the invention

[0004] In order to develop a preparation method of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene with mild reaction conditions, high yield and high purity, the first aspect of the present invention provides a preparation method of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene, comprising the following steps:

[0005] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0006] S2 adjusts the pressure in the reactor, raises the temperature to 85-95°C, drops fluorophenol, and simultaneously performs ultrasound;

[0007] After S3 is finished adding fluorophenol, keep warm and maintain ultrasonic reaction for 1-5h;

[0008] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0009] As a preferred embodiment, the molar ratio of nitrobenzene to carbonate is 1:(1-3).

[0010] As a preferred embodiment, the molar ratio of nitrobenzene to carbonate is 1:(2-3).

[0011] As a preferred embodiment, the molar ratio of nitrobenzene to carbonate is 1:2.75.

[0012] As a preferred embodiment, the reaction temperature in step S1 is 50-70°C.

[0013] As a preferred embodiment, the reaction temperature in step S1 is 60°C.

[0014] As a preferred embodiment, the pressure in the reactor in step S2 is -0.08 to -0.1 MPa.

[0015] As a preferred embodiment, the pressure in the reactor in step S2 is -0.085 to -0.095 MPa.

[0016] As a preferred embodiment, the frequency of the ultrasound in step S2 is 15.10-24.75 kHz.

[0017] As a preferred embodiment, the frequency of the ultrasound in step S2 is 19.75-20.10 kHz.

[0018] As a preferred embodiment, the frequency of the ultrasound in step S2 is 19.95 kHz.

[0019] As a preferred implementation, the amplitude of the ultrasound in step S2 is 50%-90%.

[0020] As a preferred implementation, the amplitude of the ultrasound in step S2 is 70-80%.

[0021] As a preferred implementation, the amplitude of the ultrasound in step S2 is 75%.

[0022] As a preferred embodiment, the molar ratio of nitrobenzene to fluorophenol in step S2 is 1:(1-3).

[0023] As a preferred embodiment, the molar ratio of nitrobenzene to fluorophenol in step S2 is 1:(2-3).

[0024] As a preferred embodiment, the molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.05.

[0025] As a preferred embodiment, the nitrobenzene is chlorine-containing nitrobenzene, and the chlorine-containing nitrobenzene is selected from at least one of m-nitrochlorobenzene, p-nitrochlorobenzene, dichloronitrobenzene and polychloronitrobenzene.

[0026] As a preferred embodiment, the chlorine-containing nitrobenzene is dichloronitrobenzene, and the dichloronitrobenzene is selected from at least one of 2,4-dichloronitrobenzene and 3,5-dichloronitrobenzene. Preferably, the dichloronitrobenzene is 2,4-dichloronitrobenzene.

[0027] As a preferred embodiment, the insulation reaction time in step S3 is 3-4h.

[0028] As a preferred embodiment, the insulation reaction time in step S3 is 3 hours.

[0029] As a preferred embodiment, the carbonate is selected from at least one of sodium carbonate and potassium carbonate. Preferably, the carbonate is potassium carbonate.

[0030] As a preferred embodiment, the solvent is selected from at least one of dimethyl sulfoxide, N,N-dimethylformamide, and tetrahydrofuran. Preferably, the solvent is dimethyl sulfoxide.

[0031] As a preferred embodiment, the molar ratio of the solvent to nitrobenzene is (10-15):1.

[0032] As a preferred embodiment, the molar ratio of the solvent to nitrobenzene is (13-15):1.

[0033] As a preferred embodiment, the molar ratio of the solvent to nitrobenzene is 13.6:1.

[0034] During the experiment, the inventors found that in the process of preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene, under ultrasonic conditions, controlling the pressure of the reactor to -0.085 to -0.09 MPa and maintaining the reaction temperature at 90°C can obtain a higher yield and product purity. It is speculated that the possible reason is that under ultrasonic conditions, the chemical reaction generates a strong shock wave through the cavitation effect of the ultrasonic wave, and can produce short-term high temperature and high pressure reaction conditions, stimulate the occurrence of the chemical reaction, accelerate the reaction efficiency, and enable the chemical reaction to reach reaction equilibrium in a short time, thereby improving the reaction efficiency.

[0035] The inventors further discovered that under ultrasonic conditions, the reactor can be controlled to complete the reaction at a lower reaction temperature and reaction pressure, thereby reducing reaction energy consumption, reducing reaction costs, and avoiding the occurrence of dangerous chemical reactions.

[0036] The second aspect of the present invention provides an application of a method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene, and the prepared 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene is used in the synthesis of oxyfluorfen.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] (1) The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene of the present invention can achieve equilibrium in a shorter time by connecting an ultrasonic reactor during the reaction process, thereby improving the reaction yield.

[0039] (2) In the method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene of the present invention, the ultrasonic reactor adopts a frequency of 15.10-24.75 kHz and an amplitude of 50%-90%, so that micro-areas and extremely short-term high temperature and high pressure appear in the solution, which reduces the reaction energy consumption, reduces the reaction cost, and avoids the occurrence of dangerous chemical reactions.

[0040] (3) The preparation method of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene of the present invention reduces the generation and emission of pollutants and is more in line with the requirements of green chemistry. The use of ultrasonic technology in the synthesis of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene helps to reduce the generation and emission of harmful substances and reduce pollution to the environment.

[0041] (4) The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene of the present invention can promote sufficient mixing and contact between reactants, thereby improving the uniformity and completeness of the reaction, and helping to improve the quality and purity of the synthesized oxyfluorfen.

[0042] (5) The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene of the present invention can reduce the use of dangerous operating conditions such as high temperature and high pressure, thereby improving the safety of the production process. DETAILED DESCRIPTION

[0043] Example 1

[0044] A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene comprises the following steps:

[0045] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0046] S2 adjusts the pressure in the reactor, raises the temperature to 90°C, drops fluorophenol, and simultaneously performs ultrasound;

[0047] After adding fluorophenol, S3 was kept warm and ultrasonic reaction was maintained for 3 h;

[0048] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0049] The molar ratio of nitrobenzene to carbonate is 1:2.75.

[0050] The nitrobenzene is 2,4-dichloronitrobenzene, and the carbonate is potassium carbonate.

[0051] The reaction temperature in step S1 is 60°C.

[0052] The pressure in the reactor in step S2 is -0.085 to -0.095 MPa.

[0053] The frequency of the ultrasound in step S2 is 19.90 kHz.

[0054] The amplitude of the ultrasound in step S2 is 75%.

[0055] The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.1.

[0056] The solvent is dimethyl sulfoxide.

[0057] The molar ratio of the solvent to nitrobenzene is 13.6:1.

[0058] Example 2

[0059] A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene comprises the following steps:

[0060] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0061] S2 adjusts the pressure in the reactor, raises the temperature to 90°C, drops fluorophenol, and simultaneously performs ultrasound;

[0062] After adding fluorophenol, S3 was kept warm and ultrasonic reaction was maintained for 3 h;

[0063] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0064] The molar ratio of nitrobenzene to carbonate is 1:2.75.

[0065] The nitrobenzene is 2,4-dichloronitrobenzene, and the carbonate is potassium carbonate.

[0066] The reaction temperature in step S1 is 60°C.

[0067] The pressure in the reactor in step S2 is -0.09 to -0.095 MPa.

[0068] The frequency of the ultrasound in step S2 is 19.90 kHz.

[0069] The amplitude of the ultrasound in step S2 is 75%.

[0070] The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.1.

[0071] The solvent is dimethyl sulfoxide.

[0072] The molar ratio of the solvent to nitrobenzene is 13.6:1.

[0073] Example 3

[0074] A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene comprises the following steps:

[0075] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0076] S2 adjusts the pressure in the reactor, raises the temperature to 90°C, drops fluorophenol, and simultaneously performs ultrasound;

[0077] After adding fluorophenol, S3 was kept warm and ultrasonic reaction was maintained for 3 h;

[0078] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0079] The molar ratio of nitrobenzene to carbonate is 1:2.75.

[0080] The nitrobenzene is 2,4-dichloronitrobenzene, and the carbonate is potassium carbonate.

[0081] The reaction temperature in step S1 is 60°C.

[0082] The pressure in the reactor in step S2 is -0.085 to -0.90 MPa.

[0083] The frequency of the ultrasound in step S2 is 19.95 kHz.

[0084] The amplitude of the ultrasound in step S2 is 75%.

[0085] The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.1.

[0086] The solvent is dimethyl sulfoxide.

[0087] The molar ratio of the solvent to nitrobenzene is 13.6:1.

[0088] Comparative Example 1

[0089] A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene comprises the following steps:

[0090] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0091] S2 adjusts the pressure in the reactor, raises the temperature to 90°C, and drops fluorophenol;

[0092] After S3 was added dropwise with fluorophenol, the reaction was kept warm for 5 h;

[0093] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0094] The molar ratio of nitrobenzene to carbonate is 1:2.75.

[0095] The nitrobenzene is 2,4-dichloronitrobenzene, and the carbonate is potassium carbonate.

[0096] The reaction temperature in step S1 is 60°C.

[0097] The pressure in the reactor in step S2 is -0.09 to -0.095 MPa.

[0098] The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.1.

[0099] The solvent is dimethyl sulfoxide.

[0100] The molar ratio of the solvent to nitrobenzene is 13.6:1.

[0101] Comparative Example 2

[0102] A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene comprises the following steps:

[0103] S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up;

[0104] S2 adjusts the pressure in the reactor, raises the temperature to 90°C, drops fluorophenol, and controls the reaction temperature to 95°C;

[0105] After S3 was added dropwise with fluorophenol, the reaction was kept warm for 8 hours;

[0106] S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

[0107] The molar ratio of nitrobenzene to carbonate is 1:2.75.

[0108] The nitrobenzene is 2,4-dichloronitrobenzene, and the carbonate is potassium carbonate.

[0109] The reaction temperature in step S1 is 60°C.

[0110] The pressure in the reactor in step S2 is -0.09 to -0.095 MPa.

[0111] The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:2.1.

[0112] The solvent is dimethyl sulfoxide.

[0113] The molar ratio of the solvent to nitrobenzene is 13.6:1.

[0114] Performance Testing

[0115] 1. Purity: The purity of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene in the product was detected by gas chromatography.

[0116] 2. Yield: The content of the product 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene was detected by gas phase internal standard method, and the yield was calculated.

[0117] The test results are shown in Table 1.

[0118] Table 1

[0119] purity / % Yield / % Example 1 90.2 85.9 Example 2 88.5 84.7 Example 3 90.8 87.5 Comparative Example 1 84.8 76.3 Comparative Example 2 88.5 83.9

[0120] It can be seen from the data in Table 1 that by introducing an ultrasonic generator during the reaction, the reaction rate is significantly accelerated, and the reaction reaches equilibrium in a shorter time, thereby increasing the yield and reducing the generation of by-products, and realizing the efficient and environmentally friendly production of 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene. Compared with the prior art, the present invention has significant technical advantages and economic value, and is expected to promote the further development of oxyfluorfen synthesis technology.

Claims

1. A method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene, characterized in that: The following steps are involved: S1 adds the solvent into the reaction kettle, adds nitrobenzene and carbonate, stirs, and heats up; S2 adjusts the pressure in the reactor, raises the temperature to 85-95°C, drops fluorophenol, and simultaneously performs ultrasound; After S3 is finished adding fluorophenol, keep warm and maintain ultrasonic reaction for 1-5h; S4 is cooled to room temperature, the solvent is removed, washed, and separated to obtain 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene.

2. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The molar ratio of nitrobenzene to carbonate is 1:(1-3).

3. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The reaction temperature in step S1 is 50-70°C.

4. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The pressure in the reactor in step S2 is -0.08 to -0.1 MPa.

5. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The frequency of the ultrasound in step S2 is 15.10-24.75 kHz.

6. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The amplitude of the ultrasound in step S2 is 50%-90%.

7. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The molar ratio of nitrobenzene to fluorophenol in step S2 is 1:(1-3).

8. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The nitrobenzene is chlorine-containing nitrobenzene, and the chlorine-containing nitrobenzene is selected from at least one of m-nitrochlorobenzene, p-nitrochlorobenzene, dichloronitrobenzene and polychloronitrobenzene.

9. The method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to claim 1, characterized in that: The insulation reaction time in step S3 is 3-4 hours.

10. An application of the method for preparing 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene according to any one of claims 1 to 9, characterized in that: The prepared 4-nitro-1,3-bis(2-chloro-4-(trifluoromethyl)phenoxy)benzene is used in the synthesis of oxyfluorfen.