Continuous production method of saflufenacil intermediate
By adopting continuous production methods and optimizing reaction conditions in the production of phenylazine intermediates, the existing process safety and isomers are solved, and efficient and safe intermediate production is achieved, which is suitable for industrial applications.
Patent Information
- Application Number
- CN202411174764.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-26
- Publication Date
- 2024-12-17
AI Technical Summary
The production process of existing phenylazine intermediates is poor in safety and cannot avoid nitrifying isomers, resulting in increased process complexity and cost.
Using a continuous production method, the nitrating reagent and 2-chloro-4-fluoro-trichloromethylbenzene are reacted through a vortex plate and dynamic tube reactor respectively through a two-stage reaction, combining the optimized reaction conditions and the nitrating reagent are A mixture of nitric acid and smoky sulfuric acid controls the reaction time and molar ratio to achieve efficient production of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene.
It improves production safety and efficiency, reduces isomer content, simplifies the process flow, reduces the cost of raw materials and equipment, and is suitable for large-scale industrial production.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of fine chemicals, and in particular to a continuous production method for a saflufenacil intermediate. Background Art
[0002] Safamiflu has a wide range of crop applicability and an excellent broadleaf weed control spectrum. It is a protoporphyrinogen oxidase (PPO) inhibitor and is easily absorbed by roots, buds and leaves. Once absorbed, it is mainly transmitted upward to various parts of the weeds through the xylem. It has huge weed control market potential in no-till stubble, non-arable land, orchards, beans and wheat crops.
[0003] 2-Chloro-4-fluoro-5-nitro-trichloromethylbenzene is a key intermediate for preparing saflufenacil. Currently, 2-chloro-4-fluorotoluene trichloride is mainly used as a raw material. 2-Chloro-4-fluoro-5-nitro-trichloromethylbenzene intermediate is obtained by intermittent nitration through multiple steps of reactions such as nitration, hydrolysis, and chlorination. For example, a method for synthesizing a key intermediate of saflufenacil provided in a Chinese patent (publication number CN101948390A) has poor safety and cannot avoid the problem of nitrated isomers. Subsequent impurity removal measures are also required, which increases the complexity of the process and the cost of industrial raw materials and equipment. Summary of the invention
[0004] In order to solve the above problems, the present invention provides a continuous production method of a saflufenacil intermediate, which effectively solves the problem that the existing process has poor safety and cannot avoid nitration isomers, and is very suitable for industrial large-scale production.
[0005] The present invention provides a continuous production method of a saflufenacil intermediate, comprising at least the following steps:
[0006] S1: using a metering pump to control the flow rate of the nitrating agent and 2-chloro-4-fluoro-trichloromethylbenzene through two-stage reactors to perform a two-stage reaction, thereby obtaining a crude product of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene;
[0007] S2: Add solvent to the crude 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene, then drop it into water for quenching, then separate the phases, wash the lower oil phase with water, neutralize it, and recover the solvent to obtain the 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene product, and concentrate the aqueous phase as a by-product.
[0008] As a preferred technical solution, the nitrating agent is a mixture of fuming nitric acid and fuming sulfuric acid.
[0009] Preferably, the concentration of the fuming nitric acid is ≥98wt%.
[0010] Preferably, the concentration of the oleum is 120-150 wt %, preferably 120-140 wt %.
[0011] Preferably, the molar ratio of the fuming nitric acid to the fuming sulfuric acid is 1:(1-5), preferably 1:(2-4), and further preferably 1:(3-4).
[0012] As a preferred technical solution, the molar ratio of 2-chloro-4-fluoro-trichloromethylbenzene to fuming nitric acid is (1-3):1, preferably (1.5-2.5):1, and more preferably (1.8-2.2):1.
[0013] As a preferred technical solution, the flow rate of the nitrating agent is ≥1.8 L / h, preferably 2.4-3 L / h.
[0014] As a preferred technical solution, the flow rate of the 2-chloro-4-fluoro-trichloromethylbenzene is ≥1.8 L / h, preferably 2.4-3 L / h.
[0015] As a preferred technical solution, the two-stage reactors are respectively a vortex plate reactor and a dynamic tubular reactor.
[0016] As a preferred technical solution, the temperature of the material in the vortex plate reactor is -10 to 10°C, and the residence time is 8 to 15 minutes.
[0017] Preferably, the temperature of the material in the vortex plate reactor is -5 to 5°C, and the residence time is 10 to 12 minutes.
[0018] As a preferred technical solution, the material temperature in the dynamic tubular reactor is 10-30°C, and the residence time is 8-15 minutes.
[0019] Preferably, the material temperature in the dynamic tubular reactor is 10-20° C., and the residence time is 10-12 min.
[0020] As a preferred technical solution, the static liquid holding capacity of the vortex plate reactor and the dynamic tubular reactor is 1-3L.
[0021] As a preferred technical solution, the solvent is at least one of dichloroethane, dichloromethane, ethanol, and acetone, preferably dichloroethane.
[0022] The present invention realizes the continuous production of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene by optimizing the process design and the reaction conditions, and controls the nitration reaction of 2-chloro-4-fluoro-trichloromethylbenzene to be completed within 30 minutes, has high safety, and complies with the current fine chemical industry policy.
[0023] Specifically, the nitrating agent and 2-chloro-4-fluoro-trichloromethylbenzene are designed to successively pass through a vortex plate reactor and a dynamic tubular reactor for a two-stage reaction, and the molar ratio of each raw material and the reaction conditions are further controlled, so that the raw materials are completely converted and the 2-chloro-3-nitro-4-fluoro-trichloromethylbenzene is controlled within 2%, thereby ensuring the purity and yield of the product.
[0024] Furthermore, by optimizing the nitrating agent to be a mixture of fuming nitric acid and fuming sulfuric acid, especially controlling the concentration of fuming sulfuric acid to be 120-150wt%, the amount of fuming nitric acid used is effectively reduced while ensuring the reaction rate, thereby improving production safety and production efficiency.
[0025] In addition, the 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene obtained in the present application has a content of more than 97 wt% (isomer content <2 wt%), and can be directly used for the next step reaction to prepare saflufenacil without the need for subsequent impurity removal measures, thereby reducing the process complexity and the cost of industrial raw materials and equipment.
[0026] Beneficial Effects
[0027] 1. The present invention provides a continuous production method for a saflufenacil intermediate, which effectively solves the problem that the existing process has poor safety and cannot avoid nitration isomers, and is very suitable for industrial large-scale production.
[0028] 2. The present invention realizes the continuous production of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene by optimizing the process design and the reaction conditions, and controls the nitration reaction of 2-chloro-4-fluoro-trichloromethylbenzene to be completed within 30 minutes, which is highly safe and complies with the current fine chemical industry policy.
[0029] 3. The present invention designs a nitrating agent and 2-chloro-4-fluoro-trichloromethylbenzene to successively pass through a vortex plate reactor and a dynamic tubular reactor for a two-stage reaction, further controlling the molar ratio of each raw material and the reaction conditions, so that the raw materials are completely converted and the 2-chloro-3-nitro-4-fluoro-trichloromethylbenzene is controlled within 2%, thereby ensuring the purity and yield of the product.
[0030] 4. The present invention optimizes the nitrating agent to be a mixture of fuming nitric acid and fuming sulfuric acid, especially controls the concentration of fuming sulfuric acid to be 120-150wt%, effectively reduces the amount of fuming nitric acid used while ensuring the reaction rate, thereby improving production safety and production efficiency.
[0031] 5. The 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene obtained in the present application has a content of more than 97 wt% (isomer content <2 wt%), and can be directly used for the next step reaction to prepare saflufenacil without the need for subsequent impurity removal measures, thereby reducing the process complexity and the cost of industrial raw materials and equipment. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Figure 1 This is a physical picture of the equipment used in the continuous production method of the intermediate of saflufenacil in Example 1 of the present invention. DETAILED DESCRIPTION
[0033] Example 1
[0034] Embodiment 1 of the present invention provides a continuous production method of a saflufenacil intermediate, comprising the following steps:
[0035] S1: using a metering pump to control the flow rate of the nitrating agent and 2-chloro-4-fluoro-trichloromethylbenzene through two-stage reactors to perform a two-stage reaction, thereby obtaining a crude product of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene;
[0036] S2: Add solvent to the crude 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene, then drop it into water for quenching, then separate the phases, wash the lower oil phase with water, neutralize it, and recover the solvent to obtain the 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene product, and concentrate the aqueous phase as a by-product.
[0037] The nitrating agent is a mixture of fuming nitric acid and fuming sulfuric acid.
[0038] The concentration of the fuming nitric acid is 98 wt %.
[0039] The concentration of the oleum is 130 wt %.
[0040] The molar ratio of the fuming nitric acid to the fuming sulfuric acid is 1:3.5.
[0041] The molar ratio of the 2-chloro-4-fluoro-trichloromethylbenzene to the fuming nitric acid is 2:1.
[0042] The flow rate of the nitrating reagent was 2.7 L / h.
[0043] The flow rate of the 2-chloro-4-fluoro-trichloromethylbenzene was 2.7 L / h.
[0044] The two-stage reactors are respectively a vortex plate reactor and a dynamic tubular reactor.
[0045] The temperature of the material in the vortex plate reactor is 0° C., and the residence time is 10 min.
[0046] The material temperature in the dynamic tubular reactor is 10° C. and the residence time is 10 min.
[0047] The static liquid holding capacity of the vortex plate reactor and the dynamic tubular reactor is 1L.
[0048] The solvent is ethylene dichloride.
[0049] Example 2
[0050] Example 2 of the present invention provides a continuous production method for a saflufenacil intermediate, and its specific implementation method is the same as that of Example 1, except that the concentration of the oleum is 120 wt %, and the flow rate of the nitrating agent is 2.76 L / h.
[0051] Performance Testing
[0052] The oil phases of the outlet materials of the vortex plate reactor and the dynamic tubular reactor of Examples 1 and 2 were respectively taken for LC analysis to obtain the purity of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene; the yield of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene was calculated based on 2-chloro-4-fluoro-trichloromethylbenzene. The results are shown in Table 1.
[0053] Table 1
[0054]
[0055]
Claims
1. A continuous production method for a saflufenacil intermediate, characterized in that: At least the following steps are included: S1: using a metering pump to control the flow rate of the nitrating agent and 2-chloro-4-fluoro-trichloromethylbenzene through two-stage reactors to perform a two-stage reaction, thereby obtaining a crude product of 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene; S2: Add solvent to the crude 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene, then drop it into water for quenching, then separate the phases, wash the lower oil phase with water, neutralize it, and recover the solvent to obtain the 2-chloro-4-fluoro-5-nitro-trichloromethylbenzene product, and concentrate the aqueous phase as a by-product.
2. The continuous production method of the saflufenacil intermediate according to claim 1, characterized in that: The nitrating agent is a mixture of fuming nitric acid and fuming sulfuric acid.
3. The continuous production method of the saflufenacil intermediate according to claim 2, characterized in that: The concentration of the oleum is 120-150 wt %.
4. The continuous production method of the saflufenacil intermediate according to claim 2, characterized in that: The molar ratio of the fuming nitric acid to the fuming sulfuric acid is 1:(1-5).
5. The continuous production method of the saflufenacil intermediate according to claim 2, characterized in that: The molar ratio of the 2-chloro-4-fluoro-trichloromethylbenzene to the fuming nitric acid is (1-3):
1.
6. The continuous production method of a saflufenacil intermediate according to claim 1, characterized in that: The flow rate of the nitrating agent is ≥1.8 L / h, and the flow rate of the 2-chloro-4-fluoro-trichloromethylbenzene is ≥1.8 L / h.
7. The continuous production method of a saflufenacil intermediate according to claim 1, characterized in that: The two-stage reactors are respectively a vortex plate reactor and a dynamic tubular reactor.
8. The continuous production method of the saflufenacil intermediate according to claim 7, characterized in that: The temperature of the material in the vortex plate reactor is -10 to 10°C, and the residence time is 8 to 15 minutes.
9. The continuous production method of a saflufenacil intermediate according to claim 7, characterized in that: The material temperature in the dynamic tubular reactor is 10-30° C., and the residence time is 8-15 minutes.
10. The continuous production method of a saflufenacil intermediate according to claim 1, characterized in that: The solvent is at least one of dichloroethane, dichloromethane, ethanol and acetone.