A method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetate

Abstract

The application discloses a green synthesis method of 2-(5-fluoro-2,4-dinitrophenoxy) acetic acid ester, which comprises the following steps: reacting 1,5-difluoro-2,4-dinitrobenzene, hydroxy acetic acid ester, a catalyst and an acid-binding agent in a solvent; and after the reaction, the reaction liquid is filtered, washed with water and desolventized to obtain 2-(5-fluoro-2,4-dinitrophenoxy) acetic acid ester; the catalyst is an organic base, and the acid-binding agent is an inorganic alkaline compound. The application uses a small amount of catalyst, the generated salt is separated by filtration, and the post-treatment operation is simple; the small amount of catalyst does not need to be recycled, which is favorable for reducing the energy consumption of production; the reaction condition is mild, which is favorable for controlling the side reaction, and a higher yield can be obtained.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester, and more specifically to a green method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester, belonging to the field of pesticide synthesis technology. Background Technology

[0002] Propylenefluthrin is an N-phenylphthalimide herbicide launched in 1993 by Sumitomo Chemical Co., Ltd. of Japan. It is mainly used to control gramineous and broadleaf weeds on crops such as soybeans, sugarcane, and cotton. The synthesis of propynefluthrin often requires the prior synthesis of pesticide intermediates, followed by the synthesis of propynefluthrin itself. 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester is an important intermediate in the synthesis of propynefluthrin.

[0003] Existing methods for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid esters either have low yields leading to high raw material costs, or are cumbersome processes with complex post-processing, resulting in high manufacturing costs. It is difficult to achieve both simultaneously. Specifically: CN101948389 A uses 1,5-difluoro-2,4-dinitrobenzene to react with glycolic acid or esters, using an equimolar amount of triethylamine, achieving a maximum yield of 90%. However, this method has problems: triethylamine is expensive and requires a separate recovery process. Generally, it involves adding alkali to release the triethylamine, followed by distillation / rectification, separation, and drying to obtain triethylamine. The post-processing is cumbersome and increases manufacturing costs.

[0004] CN105837563A uses 1,5-difluoro-2,4-dinitrobenzene and butyl glycolate to react under equimolar amounts of triethylamine to produce a product with a purity of 90.1% and a yield of 89.9%. However, it also suffers from the problems of cumbersome and costly post-processing.

[0005] CN115466249A describes the reaction of 1,5-difluoro-2,4-dinitrobenzene with ethyl hydroxyacetate in a potassium carbonate and DMF system. While the product yield is relatively high, the reaction requires the dropwise addition of ethyl hydroxyacetate to prevent side reactions. This dropwise addition process is cumbersome and time-consuming, making it unsuitable for industrial production. Furthermore, in actual experiments conducted under these conditions, the yield was only around 85%, indicating poor reproducibility.

[0006] CN110627738A describes the reaction of 1,5-difluoro-2,4-dinitrobenzene with isopropyl chloroacetate under potassium hydroxide and DMF conditions to produce the product. This reaction uses isopropyl chloroacetate as the etherifying agent, involves high reaction temperatures, and consumes a lot of energy. Furthermore, in practice, when the experiment was repeated under these conditions, the conversion rate of the raw materials was less than 40%, and the described experimental results could not be replicated.

[0007] In summary, existing synthetic methods for synthesizing 2-(5-fluoro-2,4-dinitrobenzene) acetate using 1,5-difluoro-2,4-dinitrophenoxy acetate as a raw material either require large amounts of triethylamine and involve cumbersome post-processing, or are complex processes with high energy consumption. Therefore, developing a green synthetic process for this intermediate is of great significance and value. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention provides a green synthesis method for 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester. This method is simple, easy to operate, and readily industrialized. Post-processing is straightforward, the reaction conditions are mild, energy consumption is low, and the yield of the obtained product is also high.

[0009] The specific technical solution of this invention is as follows: A green synthesis method for 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester includes the following steps: reacting 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester, catalyst, and acid-binding agent in a solvent; after the reaction, the reaction solution is filtered, washed with water, and solvent-removed to obtain 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester. This process is simple, the post-processing is straightforward, greatly saves process steps, and is environmentally friendly.

[0010] Furthermore, the catalyst is an organic base, such as at least one nitrogen-containing organic base selected from triethylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, and pyridine. Preferably, the catalyst is at least one selected from triethylamine and N,N-diisopropylethylamine.

[0011] Furthermore, the acid-binding agent is an inorganic compound, including at least one of the following inorganic alkaline compounds: potassium carbonate, sodium carbonate, calcium carbonate, calcium hydroxide, calcium oxide, silicon dioxide, and calcium chloride. Preferably, the acid-binding agent is at least one of calcium hydroxide, calcium oxide, and calcium carbonate. More preferably, the acid-binding agent is at least one of calcium hydroxide and calcium oxide.

[0012] This invention employs a combination of organic base catalysts and inorganic acid-binding agents to suppress side reactions, thereby improving product yield and purity. The catalyst dosage is minimal, post-processing is simple, and the process flow and energy consumption are streamlined.

[0013] Preferably, the mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-5%, for example, 1:0.01%, 1:0.02%, 1:0.03%, 1:0.04%, 1:0.05%, 1:0.06%, 1:0.07%, 1:0.08%, 1:0.09%, 1:0.10%, 1:0.11%, 1:0.12%, 1:0.13%, 1:0.14%, 1:0.15%, 1:0.16%, 1:0.17%, 1:0.18%, 1:0.19%, 1:0.01%. 0.20%, 1:0.21%, 1:0.22%, 1:0.23%, 1:0.24%, 1:0.25%, 1:0.26%, 1:0.27%, 1:0.28%, 1:0.29%, 1:0.30%, 1:0.40%, 1:0.50%, 1:0.60%, 1:0.70%, 1:0.80%, 1:0.90%, 1:1.0%, 1:1.5%, 1:2.0%, 1:2.5%, 1:3.0%, 1:3.5%, 1:4.0%, 1:4.5%, 1:5.0%. More preferably, the mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-0.2%. More preferably, the mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-0.05%.

[0014] Preferably, the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to the acid-binding agent is 1:0.4-1.1, for example, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, or 1:1.1. More preferably, the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to the acid-binding agent is 1:0.5-1.0.

[0015] Furthermore, the glycolic acid ester is selected from methyl glycolate, ethyl glycolate, propyl glycolate, and butyl glycolate.

[0016] Furthermore, the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to glycolic acid ester is 1:0.9-1.5, for example 1:0.9, 1:0.95, 1:1.0, 1:1.05, 1:1.10, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, preferably 1:0.95-1.10.

[0017] Furthermore, the solvent of this invention is selected from one, two, or more of ethers, inert haloalkanes, aromatic hydrocarbons, and aprotic solvents, all of which can achieve good reaction yields. Preferably, the solvent is one, two, or more of inert haloalkanes, aromatic hydrocarbons, and aprotic solvents. Inert haloalkanes can be dichloromethane, dichloroethane, etc. Aromatic hydrocarbons can be toluene, etc. Aprotic solvents can be DMF, etc.

[0018] Furthermore, the amount of solvent used can be 1-20 times the mass of 1,5-difluoro-2,4-dinitrobenzene, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 times, preferably 2-10 times.

[0019] Furthermore, the reaction temperature is -30 to 70°C, for example -30°C, -25°C, -20°C, -15°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, preferably -10 to 30°C.

[0020] Furthermore, there are no special requirements for the order in which 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester, catalyst, acid-binding agent, and solvent are added. However, considering the convenience of industrial production, it is preferable to mix 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester, catalyst, and solvent first, and then add the acid-binding agent.

[0021] Furthermore, the acid-binding agent can be added in any manner, such as continuous addition, batch addition, or one-time addition. Since the reaction is exothermic, batch addition is generally used to better control the temperature stability of the system. The total addition time of the acid-binding agent is approximately 0.5 hours or less.

[0022] Furthermore, 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester, and catalyst are first mixed, and then the acid-binding agent is added in batches while maintaining the reaction temperature. After adding the acid-binding agent, the reaction is continued at this temperature until 1% of the raw material remains, at which point the reaction is considered complete and the reaction is terminated. Generally, the reaction time in this invention is in the range of 0.5-2 hours, for example, 0.5 hours, 1.0 hours, 1.5 hours, and 2.0 hours.

[0023] Furthermore, the reaction is preferably carried out under stirring, and the stirring method can be one commonly used in the prior art, such as mechanical stirring, magnetic stirring, or shearing.

[0024] Furthermore, after the reaction, the by-product salts formed are first removed by filtration, then the catalyst is removed by washing with water, and finally the solvent is removed to obtain 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester. This post-treatment process is easy to operate, simple to implement, and has low energy consumption.

[0025] The present invention has the following beneficial effects: (1) The present invention uses a very small amount of catalyst and acid-binding agent in combination. The salt generated by the acid-binding agent can be directly removed by filtration, and the post-treatment operation is simple. The trace amount of catalyst can be removed by washing with water, without the need for recycling, which simplifies the operation process, reduces energy consumption, reduces catalyst consumption, and is beneficial to industrial production.

[0026] (2) The reaction conditions of this invention are mild, and the use of a very small amount of catalyst and acid-binding agent is beneficial to controlling side reactions and improving product yield. Attached Figure Description

[0027] Figure 1 This is a flowchart of the synthesis process of 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester according to the present invention. Detailed Implementation

[0028] The technical solution of the present invention will be described in detail below through specific embodiments, but the scope of protection of the present invention is not limited to the embodiments described.

[0029] In the embodiments of the present invention, the content of 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester, the intermediate of propyne fluroxypyr, was determined by high performance liquid chromatography.

[0030] In the following examples, unless otherwise specified, the concentration of the 1,5-difluoro-2,4-dinitrobenzene solution is 30%, and the calcium hydroxide content is 95%.

[0031] In the following examples and comparative examples, the product yield is the molar yield, calculated using the formula: Molar yield = Product mass × Product content / (Product molecular weight × Number of moles of raw material) × 100%.

[0032] Example 1 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of butyl glycolate, and 0.03 g of triethylamine were added to a 500 mL reaction flask. The mixture was stirred and kept at a certain temperature. 17.2 g (0.22 mol) of calcium hydroxide was added in portions over a period of 0.5 h. After the addition was complete, the reaction was continued at this temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt, washing, and solvent removal.

[0033] The purity and yield of the products obtained at different temperatures were determined by HPLC, as shown in Table 1 below.

[0034] Example 2 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of butyl glycolate, and 0.60 g of triethylamine were added to a 500 mL reaction flask. The mixture was stirred and cooled to 10 °C. 17.2 g (0.22 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product was obtained by filtration to remove salt, washing, and solvent removal, with a purity of 92.4% and a yield of 90.6%.

[0035] Example 3 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of butyl glycolate, and 1.5 g of triethylamine were added to a 500 mL reaction flask. The mixture was stirred and cooled to 10 °C. 17.2 g (0.22 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product was obtained by filtration to remove salt, washing, and solvent removal, with a purity of 92.2% and a yield of 89.3%.

[0036] Example 4 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of butyl glycolate, and 0.15 g of different catalysts were added to a 500 mL reaction flask. The mixture was stirred and cooled to 10 °C. 17.2 g (0.22 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt, washing, and solvent removal.

[0037] The purity and yield of the products obtained under different catalysts were determined by HPLC, as shown in Table 2 below.

[0038] Example 5 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of butyl glycolate, and 0.15 g of triethylamine were added to a 500 mL reaction flask. The mixture was stirred and cooled to 0 °C. Different types of acid-binding agents (0.26 mol) were added in batches over a period of 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt, washing, and solvent removal.

[0039] The purity and yield of the products obtained with different acid-binding agents were determined by HPLC, as shown in Table 3 below.

[0040] Example 6 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene, 55.9 g (0.42 mol) of glycolate, and 0.15 g of triethylamine were added to a 500 mL reaction flask. The mixture was stirred and cooled to 0 °C. 34.3 g (0.44 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid was obtained by filtration to remove salt, washing, and solvent removal.

[0041] The purity and yield of the products obtained from different glycolic acid esters were determined by HPLC, as shown in Table 4 below.

[0042] Example 7 300 g (0.44 mol) of 1,5-difluoro-2,4-dinitrobenzene was added to a 500 mL reaction flask. Then, 210 g of different types of solvent, 55.9 g (0.42 mol) of butyl glycolate, and 0.15 g of triethylamine were added. The mixture was stirred and cooled to 0 °C. 34.3 g (0.44 mol) of calcium hydroxide was added in batches over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt and solvent.

[0043] The purity and yield of the products obtained in different solvents were determined by HPLC, as shown in Table 5 below.

[0044] Comparative Example 1 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene and 55.9 g (0.42 mol) of butyl glycolate were added to a 500 mL reaction flask. After stirring and cooling to 10 °C, 42.8 g (0.42 mol) of triethylamine was added dropwise. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by washing with water and removing solvent, with a purity of 92.0% and a yield of 90.0%.

[0045] Recovery of triethylamine from washing solution: Calcium hydroxide is added to the washing solution to adjust the pH to 11-12, and triethylamine is separated from the system by distillation. The distilled triethylamine and water are separated by layering and dehydration with caustic soda flakes to obtain qualified triethylamine, which is then recovered and reused in the process. The residue from the distillation vessel is filtered and dried to obtain solid calcium fluoride, and the filtrate is used for wastewater treatment.

[0046] Compared to Example 1, Comparative Example 1 uses a large amount of triethylamine, requiring alkali dissociation and distillation of the washing liquid to recover the triethylamine, which increases energy consumption and adds post-processing steps. However, using the triethylamine + calcium hydroxide combination of this invention simplifies post-processing, requires very little triethylamine and no further treatment, and significantly improves product yield.

[0047] Comparative Example 2 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene and 55.9 g (0.42 mol) of butyl glycolate were added to a 500 mL reaction flask. The mixture was stirred and cooled to 10 °C. 17.2 g (0.22 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt and solvent, with a purity of 87.7% and a yield of 86.2%.

[0048] Comparative Example 3 300 g (0.44 mol) of a dichloroethane solution of 1,5-difluoro-2,4-dinitrobenzene and 55.9 g (0.42 mol) of butyl glycolate were added to a 500 mL reaction flask. The mixture was stirred and cooled to 0 °C. 34.3 g (0.44 mol) of calcium hydroxide was added in portions over 0.5 h. After the addition was complete, the reaction was continued at the specified temperature until the raw materials were successfully converted. After the reaction was complete, the product 2-(5-fluoro-2,4-dinitrophenoxy)butyl acetate was obtained by filtration to remove salt and solvent, with a purity of 88.7% and a yield of 86.9%.

[0049] As described above, although the invention has been shown and described with reference to specific preferred embodiments, it should not be construed as limiting the invention itself. Various changes in form and detail may be made without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. A method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester, characterized in that... Includes the following steps: 1,5-Difluoro-2,4-dinitrobenzene, glycolic acid ester, catalyst, and acid-binding agent are reacted in a solvent. After the reaction, the reaction solution is filtered, washed with water, and desolventized to obtain 2-(5-fluoro-2,4-dinitrophenoxy)acetic acid ester. The mass ratio of 1,5-difluoro-2,4-dinitrobenzene to catalyst is 1:0.01%-5%, and the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to acid-binding agent is 1:0.4-1.

1. The catalyst is selected from at least one of triethylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, and pyridine. The acid-binding agent is selected from at least one of potassium carbonate, sodium carbonate, calcium carbonate, calcium hydroxide, calcium oxide, silicon dioxide, and calcium chloride. The solvent is selected from at least one of ether, inert halogenated hydrocarbon, aromatic hydrocarbon, and aprotic solvent.

2. The synthesis method according to claim 1, characterized in that: The catalyst is at least one of triethylamine and N,N-diisopropylethylamine.

3. The synthesis method according to claim 1 or 2, characterized in that: The acid-binding agent is at least one of calcium hydroxide, calcium oxide, and calcium carbonate.

4. The synthesis method according to claim 1 or 2, characterized in that: The mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-0.2%.

5. The synthesis method according to claim 1 or 2, characterized in that: The molar ratio of 1,5-difluoro-2,4-dinitrobenzene to the acid-binding agent is 1:0.50-1.

0.

6. The synthesis method according to claim 1, characterized in that: The glycolic acid ester is selected from methyl glycolate, ethyl glycolate, propyl glycolate, and butyl glycolate.

7. The synthesis method according to claim 1 or 6, characterized in that: The molar ratio of 1,5-difluoro-2,4-dinitrobenzene to glycolic acid ester is 1:0.9-1.

5.

8. The synthesis method according to claim 7, characterized in that: The molar ratio of 1,5-difluoro-2,4-dinitrobenzene to glycolic acid ester is 1:0.95-1.

10.

9. The synthesis method according to claim 1, characterized in that: The reaction temperature is -30 to 70℃.

10. The synthesis method according to claim 9, characterized in that: The reaction temperature is -10 to 30℃.

11. The synthesis method according to claim 1, characterized in that: The solvent is at least one of inert haloalkanes, aromatic hydrocarbons, and aprotic solvents.

12. The synthesis method according to claim 1 or 11, characterized in that: The amount of solvent used is 1-20 times the mass of 1,5-difluoro-2,4-dinitrobenzene.

13. The synthesis method according to claim 12, characterized in that: The amount of solvent used is 2-10 times the mass of 1,5-difluoro-2,4-dinitrobenzene.

14. The synthesis method according to claim 1, characterized in that: The dichloroethane of 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester, catalyst, acid-binding agent and solvent are mixed, and then the temperature is controlled to the reaction temperature to carry out the reaction.

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