Preparation method of diafenthiuron

Abstract

The invention discloses a preparation method of diafenthiuron, and the diafenthiuron is obtained by reacting N-(2, 6-diisopropyl-4-phenoxy phenyl) isothiocyanate with tert-butylamine in an organic solvent, the reaction is carried out in the presence of a catalyst lithium hydroxide; the organic solvent is alkyl acetate. A large number of experiments show that methyl acetate and other alkyl acetate are adopted as the organic solvent, and lithium hydroxide is adopted as the catalyst, so that the reaction time of N-(2, 6-diisopropyl-4-phenoxyphenyl) isothiocyanate and tert-butylamine can be effectively shortened, the reaction yield and the product purity can be effectively improved, and the method is suitable for industrial production. The potential industrial application prospect is realized.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of insecticide preparation, and particularly relates to a preparation method of diafenthiuron. BACKGROUND

[0002] Diafenthiuron, also known as buprofezin, chlorobuprofezin and buprofezin, is a new type of thiourea insecticide and acaricide with a novel chemical structure, which is developed by Syngenta and put on the market. Diafenthiuron has a unique action mechanism and can be regarded as a pioneer of insecticides, which is completely different from existing insecticides and acaricides and has no cross-resistance. Diafenthiuron is decomposed into a carbodiimide under ultraviolet irradiation or with the help of multifunctional oxidase in the insect body. The carbodiimide can hinder the function of mitochondria in the nervous system of the insect, affect the respiration and energy conversion of the insect, and make the insect dead. Diafenthiuron is safe to all adult beneficial insects, predatory mites, adult common green lacewings and earthworms.

[0003] As a high-efficiency, low-toxicity, low-residue and non-polluting pesticide, diafenthiuron has the characteristics of systemic action, fumigation, long persistence and the like. Diafenthiuron is widely used in vegetables, fruit trees, tea, cotton and ornamental plants, and can effectively control sensitive strains of aphids, aphids, leafhoppers and whiteflies that have developed resistance to carbamates, organophosphates and pyrethroid insecticides. Diafenthiuron has high control efficiency on small cabbage moths, cabbage worms and noctuidae pests that have developed high resistance, and has good effects on adult mites, nymphs and mite eggs of phytophagous mites (Tetranychidae and Tarsonemidae).

[0004] The existing diafenthiuron synthesis methods mainly include the following three categories: I. Trimeric phosgene method.

[0005] 2,6-diisopropyl-4-phenoxy aniline is first reacted with trimeric phosgene to obtain N-(2,6-diisopropyl-4-phenoxyphenyl) isocyanate, which is then reacted with tert-butylamine to obtain 3-(2,6-diisopropyl-4-phenoxyphenyl)-1-tert-butyl urea, and finally reacted with phosphorus pentasulfide to obtain diafenthiuron

see documents CN102993075A, CN113024428A and the like

[0006] The disadvantage of this method is that the reaction steps are more, the yield is lower, and it has no industrial value.

[0007] II. Thio-phosgene method.

[0008] 2,6-diisopropyl-4-phenoxy aniline is first reacted with thio-phosgene to obtain N-(2,6-diisopropyl-4-phenoxyphenyl) isothiocyanate, which is then reacted with tert-butylamine to obtain diafenthiuron

see documents US4328247A, US4962126A and the like

[0009] The drawback of this method is that thiophosgene is not only expensive but also highly toxic, making it unsuitable for large-scale industrial production.

[0010] III. Sodium thiocyanate method.

[0011] 2,6-Diisopropyl-4-phenoxyaniline is first reacted with sodium thiocyanate to give N-(2,6-diisopropyl-4-phenoxyphenyl)thiourea, which is then thermally decomposed to give N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate, and finally reacted with tert-butylamine to give butyl ether urea [see references US4997967A, CN114702422A, etc.].

[0012] Sodium thiocyanate method is currently the mainstream process for the industrial production of butyl ether urea. However, the final step, the reaction between N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate and tert-butylamine, is mainly carried out in toluene solvent, which has disadvantages such as long reaction time, low reaction yield and low product purity. Summary of the Invention

[0013] The purpose of this invention is to solve the above problems and provide a method for preparing butyl ether urea with a shorter reaction time, higher reaction yield, and higher product purity.

[0014] The technical solution to achieve the objective of this invention is: a method for preparing butyl ether urea, which is obtained by reacting N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate with tert-butylamine in an organic solvent; the reaction is carried out in the presence of lithium hydroxide catalyst; the organic solvent is an alkyl acetate.

[0015] The alkyl acetate is preferably methyl acetate or ethyl acetate, more preferably methyl acetate.

[0016] The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to tert-butylamine is 1:1 to 1:2, preferably 1:1.2 to 1:1.6, and more preferably 1:1.4 to 1:1.6.

[0017] The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to lithium hydroxide is 1:0.01 to 1:0.2, preferably 1:0.025 to 1:0.1, and more preferably 1:0.05 to 1:0.1.

[0018] The reaction temperature is 40–75°C, preferably 50–60°C.

[0019] The positive effects of this invention are as follows: Through extensive experiments, this invention has found that using alkyl acetates such as methyl acetate as organic solvents and lithium hydroxide as catalyst can not only effectively shorten the reaction time of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate with tert-butylamine, but also effectively improve the reaction yield and product purity, showing potential for industrial application. Detailed Implementation

[0020] (Example 1) The specific preparation method of butyl ether urea in this embodiment is as follows: Under nitrogen protection, 31.1 g of N-(2,6-diisopropyl-4-phenoxyphenyl) isothiocyanate (0.1 mol), 200 mL of methyl acetate, and 0.12 g of lithium hydroxide (0.005 mol, 0.05 eq) were added to a 500 mL four-necked reaction flask equipped with a thermometer and mechanical stirrer. The mixture was stirred and the temperature was controlled below 40 °C. 10.2 g of tert-butylamine (0.14 mol, 1.4 eq) was added dropwise. After the addition was complete, the temperature was raised to 50–60 °C and the reaction was maintained at this temperature for 4 h. The reaction was considered complete when the content of the starting material N-(2,6-diisopropyl-4-phenoxyphenyl) isothiocyanate was <0.5% as monitored by HPLC.

[0021] After the reaction was completed, methyl acetate was recovered by atmospheric distillation until the internal temperature reached 70-80℃, at which point almost no fraction was distilled off, and the concentration was finished. The concentrate was cooled to about 50℃, and 80g of 50% methanol aqueous solution was added. The solution was heated to dissolve the solid, cooled to allow crystals to precipitate, filtered, and dried in a vacuum drying oven at 50℃ to obtain 37.0g of butyl ether urea, a white crystalline solid, with a yield of 96.4% and an HPLC purity of 98.8%.

[0022] (Examples 2 to 8) Each embodiment is basically the same as Embodiment 1, and the differences are shown in Table 1.

[0023] Table 1 Lithium hydroxide Tert-butylamine Reaction time Butyl ether urea Yield Purity Example 1 0.05 eq 1.4 eq 4h 37.0g 96.4% 98.8% Example 2 0.025 eq 1.4 eq 10h 34.5g 89.8% 98.4% Example 3 0.075 eq 1.4 eq 4h 37.4g 97.4% 98.6% Example 4 0.1 eq 1.4 eq 3h 37.2g 96.9% 98.3% Example 5 0.05 eq 1.2 eq 12h 33.0g 85.9% 98.8% Example 6 0.05 eq 1.3 eq 8h 34.9g 90.9% 98.6% Example 7 0.05 eq 1.5 eq 4h 37.2g 96.9% 98.9% Example 8 0.05 eq 1.6 eq 4h 37.3g 97.1% 98.6%

[0024] Note: The reaction times in Table 1 (and Table 2) are the reaction end times when the content of the raw material N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate is <0.5% as monitored by HPLC.

[0025] (Examples 9 to 11) Examples 9 to 11 are basically the same as Example 1 (reaction temperature 50-60℃, tert-butylamine 1.4 eq, lithium hydroxide 0.05 eq), and the differences are shown in Table 2.

[0026] (Comparative Examples 1 to 2) Comparative Examples 1 and 2 were basically the same as Example 1 (reaction temperature 50-60°C, tert-butylamine 1.4 eq, lithium hydroxide 0.05 eq), with the differences shown in Table 2.

[0027] (Comparative Examples 3 to 10) Comparative Examples 3 to 10 were basically the same as Example 1 (reaction temperature 50-60°C, tert-butylamine 1.4 eq), with differences shown in Table 2.

[0028] Table 2 Catalyst Organic solvent Reaction time Butyl ether urea Yield Purity Example 1 Lithium hydroxide 0.05 eq Methyl acetate 4h 37.0g 96.4% 98.8% Example 9 Lithium hydroxide 0.05 eq Ethyl acetate 6h 32.6g 84.9% 98.2% Example 10 Lithium hydroxide 0.05 eq Isopropyl acetate 10h 29.8g 77.6% 98.3% Example 11 Lithium hydroxide 0.05 eq Tert-butyl acetate 9h 30.0g 78.1% 98.4% Comparative Example 1 Lithium hydroxide 0.05 eq Toluene 10h 29.8g 77.6% 98.2% Comparative Example 2 Lithium hydroxide 0.05 eq Tetrahydrofuran ＞16h 21.5g 56.0% 97.4% Comparative Example 3 / Methyl acetate 10h 29.9g 77.9% 98.2% Comparative Example 4 / Ethyl acetate 14h 24.9g 64.8% 97.8% Comparative Example 5 / Toluene 12h 28.8g 75.0% 98.6% Comparative Example 6 / Tetrahydrofuran ＞24h 18.4g 47.9% 95.6% Comparative Example 7 Potassium hydroxide 0.05 eq Methyl acetate 8h 30.7g 79.9% 98.8% Comparative Example 8 Potassium hydroxide 0.05 eq Ethyl acetate 10h 26.1g 68.0% 97.6% Comparative Example 9 Potassium hydroxide 0.05 eq Toluene 10h 29.9g 77.9% 98.3% Comparative Example 10 Potassium hydroxide 0.05 eq Tetrahydrofuran ＞24h 19.2g 50.0% 96.5%

[0029] As shown in Table 2, without a catalyst, toluene and methyl acetate have similar effects, but the yield is only about 75%. When potassium hydroxide is used as a catalyst, toluene and methyl acetate also have similar effects, and the yield is only slightly improved compared to the effect without a catalyst. When lithium hydroxide is used as a catalyst, the effect of toluene is basically the same as that of potassium hydroxide, while the effect of methyl acetate is significantly improved.

Claims

1. A method for preparing butyl ether urea, comprising reacting N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate with tert-butylamine in an organic solvent; characterized in that: The reaction was carried out in the presence of lithium hydroxide as a catalyst; the organic solvent was an alkyl acetate.

2. The method for preparing butyl ether urea according to claim 1, characterized in that: The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to lithium hydroxide is 1:0.01 to 1:0.

2.

3. The method for preparing butyl ether urea according to claim 2, characterized in that: The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to lithium hydroxide is 1:0.025 to 1:0.

1.

4. The method for preparing butyl ether urea according to claim 3, characterized in that: The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to lithium hydroxide is 1:0.05 to 1:0.

1.

5. The method for preparing butyl ether urea according to any one of claims 1 to 4, characterized in that: The alkyl acetate is methyl acetate or ethyl acetate.

6. The method for preparing butyl ether urea according to claim 5, characterized in that: The alkyl acetate is methyl acetate.

7. The method for preparing butyl ether urea according to claim 5, characterized in that: The reaction temperature is 40–75°C.

8. The method for preparing butyl ether urea according to any one of claims 1 to 4, characterized in that: The reaction temperature is 40–75°C.

9. The method for preparing butyl ether urea according to any one of claims 1 to 4, characterized in that: The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to tert-butylamine is 1:1.2 to 1:1.

6.

10. The method for preparing butyl ether urea according to claim 5, characterized in that: The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to tert-butylamine is 1:1.2 to 1:1.6.