Green synthesis method of 2-(5-fluoro-2, 4-dinitrophenoxy) acetate

Abstract

The invention discloses a green synthesis method of 2-(5-fluoro-2, 4-dinitrophenoxy) acetate, which comprises the following steps: reacting 1, 5-difluoro-2, 4-dinitrobenzene, glycolic acid ester, a catalyst and an acid-binding agent in a solvent; after the reaction, filtering, washing and desolventizing the reaction liquid to obtain 2-(5-fluoro-2, 4-dinitrophenoxy) acetate; the catalyst is organic alkali, and the acid-binding agent is an inorganic alkali compound. A very small amount of catalyst is used, the generated salt is filtered and separated, and the post-treatment operation is simple; a small amount of catalyst does not need to be recycled, so that the production energy consumption is reduced; the reaction conditions are mild, side reactions can be controlled easily, and high yield can be obtained.

Description

Technical Field

[0001] The invention relates to a method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetate, and more specifically to a green method for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetate, belonging to the technical field of pesticide synthesis. Background Art

[0002] Fluamid-pyrifos is an N-phenylphthalimide herbicide launched by Sumitomo Chemical Co., Ltd. in 1993. It is mainly used to control grass weeds and broadleaf weeds on crops such as soybeans, sugarcane, and cotton. When synthesizing fluamid-pyrifos, it is often necessary to synthesize pesticide intermediates first and then synthesize fluamid-pyrifos. 2-(5-fluoro-2,4-dinitrophenoxy)acetate is an important intermediate for the synthesis of fluamid-pyrifos.

[0003] The existing methods for synthesizing 2-(5-fluoro-2,4-dinitrophenoxy)acetate either have low yields, resulting in high raw material costs, or have complicated processes, complicated post-treatments, and high manufacturing costs. It is difficult to have both, as follows: In CN101948389 A, 1,5-difluoro-2,4-dinitrobenzene is reacted with glycolic acid or ester, and an equimolar amount of triethylamine is used for the reaction, with a maximum yield of 90%. However, the problem with this method is that triethylamine is expensive and requires a separate recovery process, which is generally obtained by adding alkali to free it, distilling / rectifying, layering, and drying, and the post-processing process is cumbersome, which increases the manufacturing cost.

[0004] In CN105837563A, 1,5-difluoro-2,4-dinitrobenzene and butyl glycolate are reacted under equimolar amounts of triethylamine to generate a product with a product content of 90.1% and a yield of 89.9%. However, there is also the problem of complicated post-processing and high cost.

[0005] CN115466249A introduces the reaction of 1,5-difluoro-2,4-dinitrobenzene and ethyl hydroxyacetate in a potassium carbonate and DMF system. Although the yield of the reaction product is relatively high, it is necessary to drip ethyl hydroxyacetate to prevent the occurrence of side reactions. The dripping operation is cumbersome and takes a long time, which is not convenient for industrial production. When the experiment under the conditions is actually repeated, the yield is only about 85%, and the repeatability is poor.

[0006] In CN110627738A, 1,5-difluoro-2,4-dinitrobenzene and isopropyl chloroacetate are reacted under potassium hydroxide and DMF to generate products. The reaction uses isopropyl chloroacetate as an etherification reagent, and has high reaction temperature and high energy consumption. In fact, when the experiment under this condition is repeated, the raw material conversion rate is less than 40%, and the experimental effect cannot be repeatedly achieved.

[0007] In summary, the existing synthesis methods, when using 1,5-difluoro-2,4-dinitrobenzene as a raw material to synthesize 2-(5-fluoro-2,4-dinitrobenzene) acetate, either require the use of a large amount of triethylamine, and the post-treatment process is cumbersome, or the process is cumbersome and energy-intensive. Therefore, it is of great significance and value to develop a green synthesis process for this intermediate. Summary of the invention

[0008] In view of the deficiencies in the prior art, the present invention provides a green synthesis method for 2-(5-fluoro-2,4-dinitrophenoxy)acetate, which has the advantages of simple process, convenient operation, easy industrialization, simple post-treatment operation, mild reaction conditions, low energy consumption, and high yield of the obtained product.

[0009] The specific technical solutions of the present invention are as follows: A green synthesis method of 2-(5-fluoro-2,4-dinitrophenoxy)acetate comprises the following steps: reacting 1,5-difluoro-2,4-dinitrobenzene, hydroxyacetic acid ester, a catalyst and an acid-binding agent in a solvent; after the reaction, filtering, washing and desolventizing the reaction solution to obtain 2-(5-fluoro-2,4-dinitrophenoxy)acetate. The process flow is simple, the post-treatment is simple, the process flow is greatly saved, and it is green and environmentally friendly.

[0010] Further, the catalyst is an organic base, which may be at least one of triethylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, pyridine and other nitrogen-containing organic bases. Preferably, the catalyst is at least one of triethylamine and N,N-diisopropylethylamine.

[0011] Further, the acid binding agent is an inorganic compound, which can be exemplified by at least one of inorganic alkaline compounds such as 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] The present invention adopts an organic base catalyst and an inorganic acid-binding agent to inhibit the occurrence of side reactions and improve the yield and purity of the product. The amount of catalyst used is extremely small, the post-treatment is simple, and the process flow and energy consumption are simplified.

[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 .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, such as 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1. 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] Further, the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to hydroxyacetic 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] Further, the solvent of the present invention is selected from one, two or more of ether, inert halogenated hydrocarbon, aromatic hydrocarbon and aprotic solvent, and a good reaction yield can be achieved in these solvents. Preferably, the solvent is one, two or more of inert halogenated hydrocarbon, aromatic hydrocarbon and aprotic solvent. Inert halogenated hydrocarbon can be dichloromethane, dichloroethane, etc. Aromatic hydrocarbon can be toluene, etc. Aprotic solvent can be DMF, etc.

[0018] Furthermore, the amount of the solvent 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, 20 times, preferably 2-10 times.

[0019] Further, 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 is no special requirement for the order of adding 1,5-difluoro-2,4-dinitrobenzene, hydroxyacetic acid ester, catalyst, acid binding agent and solvent. Considering the convenience of industrial production, it is preferred to first mix 1,5-difluoro-2,4-dinitrobenzene, hydroxyacetic acid ester, catalyst and solvent, 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 all-at-once addition. The reaction is an exothermic reaction, and in order to better control the temperature stability of the system, the acid-binding agent is generally added in batches. The entire addition time of the acid-binding agent is approximately less than or equal to 0.5 h.

[0022] Further, 1,5-difluoro-2,4-dinitrobenzene, glycolic acid ester and catalyst are first mixed, and then the temperature is controlled to the reaction temperature and then the acid binding agent is added in batches. After adding the acid binding agent, the heat preservation reaction is continued, and the reaction is considered qualified when the raw material remains 1%, and the reaction is terminated. Generally, the heat preservation reaction time of the present invention is in the range of 0.5-2h, for example 0.5h, 1.0h, 1.5h, 2.0h.

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

[0024] Furthermore, after the reaction, the by-product salt formed by the reaction is first removed by filtering, and then the catalyst is removed by washing with water, and then the solvent is removed to obtain 2-(5-fluoro-2,4-dinitrophenoxy)acetate. This post-treatment process is easy to operate, simple and easy to operate, 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 an acid-binding agent in combination, and the salt generated by the acid-binding agent can be directly removed by filtration, and the post-treatment operation is simple; a trace amount of catalyst can be removed by washing with water, and no recovery operation is required, which simplifies the operation process, reduces energy consumption, reduces catalyst consumption, and is conducive to industrial production.

[0026] (2) The reaction conditions of the present invention are mild, and a very small amount of catalyst and acid binding agent are used, which is conducive to controlling side reactions and improving product yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The present invention is a synthetic process flow chart of 2-(5-fluoro-2,4-dinitrophenoxy)acetate. DETAILED DESCRIPTION

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

[0029] In the examples of the present invention, the content of the intermediate 2-(5-fluoro-2,4-dinitrophenoxy)acetate of fluazifop-propyl is 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 content of calcium hydroxide is 95%.

[0031] In the following examples and comparative examples, the product yield is the molar yield, which is calculated as follows: molar yield = product mass × product content / (product molecular weight × number of moles of raw materials) × 100%.

[0032] Example 1 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of butyl glycolate, and 0.03g of triethylamine to a 500mL reaction bottle, stir and control to a certain temperature, add 17.2g (0.22mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep the reaction at this temperature until the raw material conversion is qualified. After the reaction is completed, filter, remove salt, wash, and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate.

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

[0034] Example 2 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of butyl glycolate, and 0.60g of triethylamine to a 500mL reaction bottle, stir and cool to 10°C, add 17.2g (0.22mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, the product is obtained by filtering, desalting, washing, and desolventizing, with a content of 92.4% and a yield of 90.6%.

[0035] Example 3 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of butyl glycolate, and 1.5g of triethylamine to a 500mL reaction bottle, stir and cool to 10°C, add 17.2g (0.22mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, the product is obtained by filtering, desalting, washing, and desolventizing, with a content of 92.2% and a yield of 89.3%.

[0036] Example 4 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of butyl glycolate, and 0.15g of different catalysts to a 500mL reaction bottle, stir and cool to 10°C, add 17.2g (0.22mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, filter, desalt, wash, and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate.

[0037] The purity and yield of the products obtained with different catalysts are shown in Table 2 below.

[0038] Example 5 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of butyl glycolate, and 0.15g of triethylamine to a 500mL reaction bottle, stir and cool to 0°C, add different types of acid binding agents (0.26mol) in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, filter, desalt, wash, and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate.

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

[0040] Example 6 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane, 55.9g (0.42mol) of hydroxyacetic acid ester, and 0.15g of triethylamine to a 500mL reaction bottle, stir and cool to 0°C, add 34.3g (0.44mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, filter, remove salt, wash, and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) acetate.

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

[0042] Example 7 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene to a 500mL reaction bottle, add 210g of different types of solvents, 55.9g (0.42mol) of butyl glycolate, and 0.15g of triethylamine, stir and cool to 0°C, add 34.3g (0.44mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, filter, remove salt, and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate.

[0043] The purity and yield of the products obtained in different solvents are shown in Table 5 below.

[0044] Comparative Example 1 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane and 55.9g (0.42mol) of butyl glycolate to a 500mL reaction bottle, stir and cool to 10°C, then start to drop 42.8g of triethylamine (0.42mol). After the addition is complete, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, wash with water and desolventize to obtain the product 2-(5-fluoro-2,4-dinitrophenoxy) butyl acetate, with a content of 92.0% and a yield of 90.0%.

[0045] Recovery of triethylamine in water washing liquid: Calcium hydroxide is added to the water washing liquid to adjust the pH value to 11-12, and triethylamine is separated from the system by distillation. The distilled triethylamine and water are separated by stratification and dehydration with caustic soda to obtain qualified triethylamine, which is recovered and used in the process; the distilled kettle residue is filtered and dried to obtain calcium fluoride solid, and the filtrate is treated as wastewater.

[0046] Compared with Example 1, Comparative Example 1 uses a large amount of triethylamine, and the water washing liquid needs to be treated with alkali, distilled, and other operations to recover the triethylamine, which increases energy consumption and increases the post-processing process. However, the use of the triethylamine + calcium hydroxide combination of the present invention has simple post-processing, very little triethylamine is used and no treatment is required, and the product yield is also significantly improved.

[0047] Comparative Example 2 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane and 55.9g (0.42mol) of butyl glycolate to a 500mL reaction bottle, stir and cool to 10°C, add 17.2g (0.22mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, the product 2-(5-fluoro-2,4-dinitrobenzeneoxy) butyl acetate is obtained by filtration, desalting and desolventizing, with a content of 87.7% and a yield of 86.2%.

[0048] Comparative Example 3 Add 300g (0.44mol) of 1,5-difluoro-2,4-dinitrobenzene in dichloroethane and 55.9g (0.42mol) of butyl glycolate to a 500mL reaction bottle, stir and cool to 0°C, add 34.3g (0.44mol) of calcium hydroxide in batches, and add for 0.5h. After the addition is completed, continue to keep warm and react until the raw material conversion is qualified. After the reaction is completed, the product 2-(5-fluoro-2,4-dinitrobenzeneoxy) butyl acetate is obtained by filtration, desalting and desolventizing, with a content of 88.7% and a yield of 86.9%.

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

Claims

1. A green synthesis method of 2-(5-fluoro-2,4-dinitrophenoxy)acetate, characterized in that The following steps are involved: 1,5-difluoro-2,4-dinitrobenzene, hydroxyacetic acid ester, a catalyst and an acid-binding agent are reacted in a solvent; after the reaction, the reaction liquid is filtered, washed with water and desolventized to obtain 2-(5-fluoro-2,4-dinitrobenzeneoxy)acetate; the catalyst is an organic base, and the acid-binding agent is an inorganic alkaline compound; the mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-5%, and the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to the acid-binding agent is 1:0.4-1.

1.

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

3. The green synthesis method according to claim 1 or 2, characterized in that: 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, preferably at least one of calcium hydroxide, calcium oxide, and calcium carbonate.

4. The green synthesis method according to claim 1, 2 or 3, characterized in that: The mass ratio of 1,5-difluoro-2,4-dinitrobenzene to the catalyst is 1:0.01%-0.2%; preferably, the molar ratio of 1,5-difluoro-2,4-dinitrobenzene to the acid binding agent is 1:0.50-1.

0.

5. The green 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.

6. The green synthesis method according to claim 1 or 5, characterized in that: The molar ratio of 1,5-difluoro-2,4-dinitrobenzene to hydroxyacetic acid ester is 1:0.9-1.5, preferably 1:0.95-1.

10.

7. The green synthesis method according to any one of claims 1 to 6, characterized in that: The reaction temperature is -30 to 70°C, preferably -10 to 30°C.

8. The green synthesis method according to claim 1, characterized in that: The solvent is selected from at least one of ethers, inert halogenated hydrocarbons, aromatic hydrocarbons and aprotic solvents, preferably at least one of inert halogenated hydrocarbons, aromatic hydrocarbons and aprotic solvents.

9. The green synthesis method according to claim 1 or 8, characterized in that: The amount of the solvent used is 1-20 times, preferably 2-10 times, the mass of 1,5-difluoro-2,4-dinitrobenzene.

10. The green synthesis method according to any one of claims 1 to 9, characterized in that: The dichloroethane of 1,5-difluoro-2,4-dinitrobenzene, hydroxyacetic acid ester, a catalyst, an acid-binding agent and a solvent are mixed, and then the temperature is controlled to a reaction temperature to react.

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