Synthesis of butoxycarbamide

Abstract

The application discloses a synthesis method of buthionine, which is obtained by amidation reaction of N-(2,6-diisopropyl-4-phenoxyphenyl) isothiocyanate and tert-butylamine in an organic solvent; the amidation reaction is carried out in a n-butyl acetate solvent under reflux without adding a catalyst. It is found through a large number of experiments that, the amidation reaction is carried out in the n-butyl acetate solvent under reflux, and the reaction time is short, the reaction yield and product purity are high, and compared with a methyl acetate + lithium hydroxide system, the catalyst lithium hydroxide can be omitted, the production cost is reduced, the post-treatment is simple, distillation and recrystallization are not needed, the treatment cost is reduced, and the method has a greater industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of insecticide synthesis technology, specifically relating to a method for synthesizing butyl urea. Background Technology

[0002] Diethyl urea, also known as acaricide, is a novel thiourea insecticide and acaricide developed and marketed by Syngenta, Switzerland. It possesses a unique chemical structure and a distinctive mechanism of action, making it a precursor to other insecticides. Completely different from existing insecticides and acaricides, it exhibits no cross-resistance. Under ultraviolet light or with the aid of multifunctional oxidases within the insect, diethyl urea decomposes into carbodiimide. This substance inhibits the function of mitochondria in the nerve cells of pests, affecting their respiration and energy conversion, leading to insect death. It is safe for all beneficial adult insects, predatory mites, adult lacewings, and earthworms.

[0003] Diethyl urea, a highly effective, low-toxicity, low-residue, and pollution-free pesticide, features systemic and fumigation action and a long-lasting effect. It is widely used on vegetables, fruit trees, tea, cotton, and ornamental plants, effectively controlling sensitive aphid strains and aphids, leafhoppers, and whiteflies resistant to carbamates, organophosphates, and pyrethroids. It also shows high efficacy against highly resistant diamondback moths, cabbage caterpillars, and noctuid moths, and is very effective against resistant adult mites, nymphs, and eggs of phytophagous mites (Tetranychidae and Tardiidae families).

[0004] The most common method for obtaining butyl ether urea by amination of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate with tert-butylamine is currently [see references US4328247A, US4962126A, CN114702422A, etc.].

[0005] However, most existing techniques for this amination reaction are carried out in toluene solvent at room temperature, which not only results in a long reaction time (more than 12 hours), but also in low reaction yield and product purity.

[0006] As an improvement, Chinese patent document CN121005641A discloses a method for carrying out the amination reaction in an organic solvent of alkyl acetate (mainly methyl acetate and ethyl acetate), under lithium hydroxide catalysis, and at a temperature of 40-75°C, which can shorten the reaction time (as low as 4 hours) and improve the reaction yield and product purity.

[0007] However, the method still has the following shortcomings: (1) It requires the use of lithium hydroxide catalyst, which cannot be recycled and reused, resulting in resource waste and high production costs; (2) The post-processing is more complicated, requiring not only distillation to recover the solvent, but also recrystallization of methanol, resulting in high processing costs. Summary of the Invention

[0008] The purpose of this invention is to solve the above-mentioned problems and provide a method for synthesizing butyl ether urea that not only has a shorter reaction time, higher reaction yield and product purity, but also lower production and processing costs.

[0009] The technical solution to achieve the purpose of this invention is: a method for synthesizing butyl ether urea, which is obtained by amination reaction of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate and tert-butylamine in an organic solvent; wherein the amination reaction is carried out by reflux reaction in n-butyl acetate solvent without the addition of a catalyst.

[0010] The post-treatment after the amination reaction is completed includes cooling, crystallization, filtration, and drying.

[0011] The molar ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to tert-butylamine is 1:1 to 1:1.8.

[0012] The weight ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to n-butyl acetate is 1:5 to 1:10.

[0013] The positive effects of this invention are as follows: Through extensive experiments, this invention has found that using n-butyl acetate as a solvent and carrying out the amination reaction under reflux conditions also has the advantages of short reaction time, high reaction yield and high product purity. Moreover, compared with the methyl acetate + lithium hydroxide system, not only can the lithium hydroxide catalyst be omitted, reducing production costs, but the post-processing is also simple, eliminating the need for distillation and recrystallization, thus reducing processing costs and showing greater industrial application prospects. Detailed Implementation

[0014] (Example 1) The specific method for synthesizing 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) and 200 g of n-butyl acetate 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 reflux 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.

[0015] After the reaction was completed, the temperature was lowered to below 0℃ to induce crystallization. The crystals were then filtered, and the filtrate was directly recycled. The filter cake was dried in a vacuum drying oven at 50℃ to obtain 34.5g of butyl ether urea, a white crystalline solid with a yield of 89.8% and an HPLC purity of 99.4%.

[0016] (Example 2) The specific method for synthesizing 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) and 195 g of the reaction filtrate obtained in Example 1 were added to a 500 mL four-necked reaction flask equipped with a thermometer and mechanical stirrer. Then, 5 g of fresh n-butyl acetate was added, and the mixture was stirred and the temperature was controlled below 40 °C. 8.74 g of tert-butylamine (0.12 mol, 1.2 eq) was added dropwise. After the addition was complete, the temperature was raised to reflux 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.

[0017] After the reaction was completed, the temperature was lowered to below 0℃ to induce crystallization. The crystals were then filtered, and the filtrate was continuously recycled. The filter cake was dried in a vacuum drying oven at 50℃ to obtain 36.8g of butyl ether urea, a white crystalline solid with a yield of 95.8% and an HPLC purity of 98.9%.

[0018] (Examples 3 to 8) Each embodiment is basically the same as Embodiment 2, the only difference being the number of times it is applied, as shown in Table 1.

[0019] Table 1 Example 1 1.4eq / / / 4h 34.5g 89.8% 99.4% White crystals Example 2 1.2eq 1st time 195g 5g 4h 36.8g 95.8% 98.9% White crystals Example 3 1.2eq 2nd time 192g 8g 4h 37.3g 97.1% 98.6% White crystals Example 4 1.2eq 3rd 190g 10g 4.5h 37.2g 96.9% 98.8% White crystals Example 5 1.2eq 4th 190g 10g 4.5h 37.2g 96.9% 98.9% White crystals Example 6 1.2eq 5th 192g 8g 5h 37.4g 97.4% 98.7% White crystals Example 7 1.2eq 6th 189g 11g 5h 37.5g 97.7% 98.6% pale yellow crystals Example 8 1.2eq 7th 188g 12g 5.5h 37.4g 97.4% 98.7% pale yellow crystals .

[0020] 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.

[0021] As can be seen from Table 1, the reuse of mother liquor has little effect on the reaction yield and product content. However, repeated reuse will cause the product color to darken. According to Table 1, it is advisable to reuse the mother liquor 5 times.

[0022] (Example 9) The specific method for synthesizing 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) was added to a 500 mL four-necked reaction flask equipped with a thermometer and mechanical stirrer. Then, 170 g of n-butyl acetate was obtained by vacuum distillation of the reaction filtrate obtained in Example 8, and 30 g of new n-butyl acetate was added. 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 reflux 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.

[0023] After the reaction was completed, the temperature was lowered to below 0℃ to induce crystallization. The crystals were then filtered, and the filtrate was continuously recycled. The filter cake was dried in a vacuum drying oven at 50℃ to obtain 34.2 g of butyl ether urea, a white crystalline solid with a yield of 89.1% and an HPLC purity of 99.6%.

[0024] As can be seen from Example 9, the n-butyl acetate obtained by vacuum distillation after multiple reuses can still be reused without affecting the reaction.

[0025] (Comparative Examples 1 to 4) Each comparative example is basically the same as Example 1, except for the organic solvent, as shown in Table 2.

[0026] Table 2 Example 1 n-Butyl acetate 4h 34.5g 89.8% 99.4% White crystals Comparative Example 1 Methyl acetate 10h 26.1g 68.0% 97.8% White crystals Comparative Example 2 Ethyl acetate 11h 32.5g 84.6% 98.8% White crystals Comparative Example 3 Isopropyl acetate 9h 32.0g 83.3% 98.4% White crystals Comparative Example 4 tert-butyl acetate 8h 31.4g 81.8% 98.2% White crystals .

Claims

1. A method for synthesizing butyl ether urea, comprising an amination reaction of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate with tert-butylamine in an organic solvent; characterized in that: The amination reaction is carried out under reflux in a butyl acetate solvent without the addition of a catalyst.

2. The method for synthesizing butyl ether urea according to claim 1, characterized in that: The weight ratio of N-(2,6-diisopropyl-4-phenoxyphenyl)isothiocyanate to n-butyl acetate is 1:5 to 1:

10.

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

8.

4. The method for preparing butyl ether urea according to any one of claims 1 to 3, characterized in that: The post-treatment of the amination reaction includes cooling, crystallization, filtration, and drying.