Continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate

Abstract

The invention relates to the technical field of fine chemical engineering, in particular to a 2-chloro-4-fluoro-5-methyl nitrobenzoate continuous preparation process which at least comprises the following steps: S1, adding fuming nitric acid into concentrated sulfuric acid to obtain a mixed acid solution; s2, the mixed acid and the 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester sequentially pass through a vortex plate type reactor and a dynamic tubular reactor through a metering pump under the control of the flow speed respectively, and then the mixed acid and the 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester are obtained, the retention time of materials in the vortex plate type reactor and the dynamic tubular reactor is controlled, and the temperatures of the materials in the vortex plate type reactor and the dynamic tubular reactor are controlled through external circulation of the reactors for reaction; s3, a solvent is added into the mixture obtained after the reaction in the step S2, then the mixture is dropwise added into water for quenching, then phase splitting, lower-layer oil phase water washing, neutralizing and solvent recycling are conducted, the 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester product is obtained, conditions are mild, operation is easy and convenient, safety is high, and production efficiency is high.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemicals, and in particular to a continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate. Background Art

[0002] Safensulfuron, a pyrimidine-based protoporphyrinogen oxidase (PPO) inhibitor, is a lethal herbicide that effectively controls a wide range of broadleaf weeds, including those resistant to glyphosate, ALS, and triazines. It exhibits rapid lethality and rapidly degrades soil residues. Safensulfuron can also be mixed with grass herbicides, such as glyphosate, with excellent results. It can be applied to a variety of crop fields and non-arable land, with minimal crop rotation restrictions.

[0003] Methyl 2-chloro-4-fluoro-5-nitrobenzoate is a key intermediate in the preparation of saflufenacil and is currently primarily synthesized via a batch process. For example, U.S. Patent Publication No. US 6689773 provides a method for preparing the herbicide phenylsulfamoylcarboxamide and an intermediate compound useful therein. Specifically, the intermediate methyl 2-chloro-4-fluoro-5-nitrobenzoate is obtained by batch nitration of a mixed acid of concentrated sulfuric acid and fuming nitric acid with methyl 2-chloro-4-fluoro-benzoate in an 85% yield. However, this process route suffers from poor reaction safety and long reaction time, so the authors opted to employ a continuous reaction to address this issue. Summary of the Invention

[0004] In order to solve the above problems, the present invention provides a continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate, which has mild conditions, simple operation, high safety and high production efficiency.

[0005] The present invention provides a continuous preparation process for methyl 2-chloro-4-fluoro-5-nitrobenzoate, which comprises at least the following steps:

[0006] S1: Add fuming nitric acid to concentrated sulfuric acid to obtain a mixed acid solution;

[0007] S2: using metering pumps to control the flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate through the vortex plate reactor and the dynamic tubular reactor respectively, controlling the residence time of the materials in the vortex plate reactor and the dynamic tubular reactor and controlling the temperature of the materials in the vortex plate reactor and the dynamic tubular reactor by external circulation of the reactor to carry out the reaction;

[0008] S3: adding a solvent to the mixture after the reaction in step S2 and dropping it into water for quenching, then performing phase separation, washing the lower oil phase with water, neutralizing, and recovering the solvent to obtain methyl 2-chloro-4-fluoro-5-nitrobenzoate product.

[0009] As a preferred technical solution, the concentration of the fuming nitric acid and concentrated sulfuric acid is ≥98wt%.

[0010] As a preferred technical solution, the molar ratio of the fuming nitric acid, concentrated sulfuric acid, and 2-chloro-4-fluoro-benzoic acid methyl ester is (1.1-1.2): (1-1.5): 1; preferably 1.2:1.2:1.

[0011] As a preferred technical solution, the residence time of the material in the vortex plate reactor is 8 to 15 minutes, preferably 10 to 15 minutes, and most preferably 10 minutes.

[0012] As a preferred technical solution, the residence time of the material in the dynamic tubular reactor is 8 to 15 minutes, preferably 10 to 15 minutes, and most preferably 10 minutes.

[0013] As a preferred technical solution, the material temperature in the vortex plate reactor is -10 to 10°C, preferably 0 to 10°C.

[0014] As a preferred technical solution, the material temperature in the dynamic tubular reactor is 10-30°C, preferably 10-20°C.

[0015] As a preferred technical solution, the static liquid holding capacity of the vortex plate reactor and the dynamic tubular reactor is 1-5L.

[0016] As a preferred technical solution, the flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate is 30-60 mL / min.

[0017] Preferably, the flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate is 40-50 mL / min.

[0018] As a preferred technical solution, the solvent is at least one of dichloroethane, dichloromethane, ethanol, and acetone, preferably dichloroethane.

[0019] According to the current fine chemical industry policy, the nitration reaction needs to be carried out in a continuous manner. The present invention realizes the continuous nitration reaction by optimizing the reaction conditions, so that the reaction is completed in 30 minutes while improving production safety. The inventor found in the process of exploration that by optimizing the molar ratio of the reaction materials, the mixed acid and 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester are first reacted through a vortex plate reactor and then through a dynamic tubular reactor, and the reaction conditions are controlled to ensure the purity and yield of the 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester product. On the one hand, by controlling the molar ratio of fuming nitric acid, concentrated sulfuric acid, and 2-chloro-4-fluoro-benzoic acid methyl ester to (1.1-1.2): (1-1.5): 1, and controlling the flow rate of the mixed acid and 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester, it is ensured that the reaction is fully carried out, while ensuring production efficiency and product yield and purity. On the other hand, the material temperature in the vortex plate reactor is controlled to be 0-10°C, and the residence time is 10-15min. The material temperature in the dynamic tubular reactor is controlled to be 10-20°C, and the residence time is 10-15min to carry out the reaction, so that 2-chloro-4-fluoro-methyl benzoate is fully reacted to generate 2-chloro-4-fluoro-5-nitro-methyl benzoate in a relatively short time, avoiding the generation of by-products such as 2-chloro-3-nitro-4-chloro-methyl benzoate. In addition, the continuous preparation process provided by the present invention directly performs the subsequent hydrogenation step of preparing saflufenacil after quenching, washing, and dehydration, effectively reducing equipment investment costs and facilitating large-scale industrial production and promotion.

[0020] Beneficial effects

[0021] 1. The present invention provides a continuous preparation process for methyl 2-chloro-4-fluoro-5-nitrobenzoate, which has mild conditions, simple operation, high safety and high production efficiency.

[0022] 2. The present invention realizes the continuity of nitration reaction by optimizing reaction conditions, so that the reaction is completed within 30 minutes while improving production safety.

[0023] 3. By optimizing the molar ratio of the reaction materials, the mixed acid and 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester are first reacted through a vortex plate reactor and then through a dynamic tubular reactor, and the reaction conditions are controlled to ensure the purity and yield of the 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester product.

[0024] 4. The present invention ensures that the reaction proceeds fully by controlling the molar ratio of fuming nitric acid, concentrated sulfuric acid, and 2-chloro-4-fluoro-methyl benzoate to (1.1-1.2): (1-1.5): 1, and controlling the flow rates of the mixed acid and 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester, thereby ensuring production efficiency while also ensuring product yield and purity.

[0025] 5. The present invention controls the material temperature in the eddy current plate reactor to be 0-10°C and the residence time to be 10-15min, and cooperates with controlling the material temperature in the dynamic tubular reactor to be 10-20°C and the residence time to be 10-15min for the reaction, so that 2-chloro-4-fluoro-methyl benzoate is fully reacted to generate 2-chloro-4-fluoro-5-nitro-methyl benzoate in a relatively short time, avoiding the generation of by-products such as 2-chloro-3-nitro-4-chloro-methyl benzoate. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a physical diagram of the equipment used in the continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate in Example 1 of the present invention. DETAILED DESCRIPTION

[0027] Example 1

[0028] Example 1 of the present invention provides a continuous preparation process for methyl 2-chloro-4-fluoro-5-nitrobenzoate, comprising the following steps:

[0029] S1: Add fuming nitric acid to concentrated sulfuric acid to obtain a mixed acid solution;

[0030] S2: using metering pumps to control the flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate through the vortex plate reactor and the dynamic tubular reactor respectively, controlling the residence time of the materials in the vortex plate reactor and the dynamic tubular reactor and controlling the temperature of the materials in the vortex plate reactor and the dynamic tubular reactor by external circulation of the reactor to carry out the reaction;

[0031] S3: adding a solvent to the mixture after the reaction in step S2 and dropping it into water for quenching, then performing phase separation, washing the lower oil phase with water, neutralizing, and recovering the solvent to obtain methyl 2-chloro-4-fluoro-5-nitrobenzoate product.

[0032] The concentration of the fuming nitric acid and concentrated sulfuric acid is 98 wt %, and the specific gravity of the mixed acid solution at room temperature (25° C.) is 1.65 g / mL.

[0033] The molar ratio of the fuming nitric acid, concentrated sulfuric acid and 2-chloro-4-fluoro-benzoic acid methyl ester is 1.2:1.2:1.

[0034] The residence time of the material in the vortex plate reactor is 10 min.

[0035] The residence time of the material in the dynamic tubular reactor is 10 min.

[0036] The material temperature in the vortex plate reactor is 5°C.

[0037] The material temperature in the dynamic tubular reactor is 15°C.

[0038] The static liquid holding capacity of the vortex plate reactor and the dynamic tubular reactor is 1L.

[0039] The flow rates of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate were both 45 mL / min.

[0040] The solvent is dichloroethane.

[0041] Example 2

[0042] Example 2 of the present invention provides a continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate, and its specific implementation method is the same as that of Example 1, except that the molar ratio of fuming nitric acid, concentrated sulfuric acid, and methyl 2-chloro-4-fluoro-benzoate is 1.2:1.2:1, the flow rate of the mixed acid is 46 mL / min, and the flow rate of methyl 2-chloro-4-fluoro-5-nitrobenzoate is 45 mL / min.

[0043] Performance Testing

[0044] The oil phases of the outlet materials from the vortex plate reactor and the dynamic tubular reactor of Examples 1 and 2 were respectively subjected to LC analysis to obtain the purity of 2-chloro-4-fluoro-5-nitro-benzoic acid methyl ester; the yield of 2-chloro-4-fluoro-5-nitro-benzoic acid methyl ester was calculated based on 2-chloro-4-fluoro-benzoic acid methyl ester. The results are shown in Table 1.

[0045] Table 1

[0046]

[0047]

Claims

1. A continuous preparation process for methyl 2-chloro-4-fluoro-5-nitrobenzoate, characterized in that: At least the following steps are included: S1: adding fuming nitric acid into concentrated sulfuric acid to obtain a mixed acid solution; S2: using a metering pump to control the flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate to pass through the vortex plate reactor and the dynamic tubular reactor in sequence, controlling the residence time of the materials in the vortex plate reactor and the dynamic tubular reactor and controlling the temperature of the materials in the vortex plate reactor and the dynamic tubular reactor through external circulation of the reactor to react; S3: adding a solvent to the mixture after the reaction in step S2 and then dropping it into water for quenching, then performing phase separation, washing the lower oil phase with water, neutralizing, and recovering the solvent to obtain methyl 2-chloro-4-fluoro-5-nitrobenzoate product.

2. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The molar ratio of the fuming nitric acid, concentrated sulfuric acid and 2-chloro-4-fluoro-benzoic acid methyl ester is (1.1-1.2):(1-1.5):

1.

3. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The residence time of the material in the vortex plate reactor is 8 to 15 minutes.

4. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The residence time of the material in the dynamic tubular reactor is 8 to 15 minutes.

5. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The material temperature in the vortex plate reactor is -10 to 10°C.

6. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The material temperature in the dynamic tubular reactor is 10-30°C.

7. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate is 30-60 mL / min.

8. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 7, characterized in that: The flow rate of the mixed acid and methyl 2-chloro-4-fluoro-5-nitrobenzoate is 40-50 mL / min.

9. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The solvent is at least one of dichloroethane, dichloromethane, ethanol and acetone.

10. The continuous preparation process of methyl 2-chloro-4-fluoro-5-nitrobenzoate according to claim 1, characterized in that: The static liquid holding capacity of the vortex plate reactor and the dynamic tubular reactor is 1-5L.

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