A process for the synthesis of 5,5-dimethyl-2-isoxazoline

Abstract

The application discloses a synthesis method of 5,5-dimethyl 2-isoxazoline. First, isoamyl aldehyde is added with hydrogen chloride to generate chloroisoamyl aldehyde, then under alkaline conditions, the chloroisoamyl aldehyde generated in step one is added with hydroxylamine salt to generate chloroisoamyl aldehyde oxime, finally under alkaline conditions, the chloroisoamyl aldehyde oxime generated in step two is cyclized to generate 5,5-dimethyl 2-isoxazoline, the yield is high, the process is simple and suitable for industrial production; compared with the traditional method, the synthesis method has the characteristics of mild reaction condition, green environmental protection and low cost.

Description

Technical Field

[0001] This invention relates to the preparation of pesticide intermediate compounds, specifically to a method for synthesizing 5,5-dimethyl-2-isooxazoline. Background Technology

[0002] 5,5-Dimethyl-2-isooxazoline is an important intermediate in the preparation of active agrochemical compounds and can be used to synthesize sulfopyrazine. The structural formula of 5,5-dimethyl-2-isooxazoline is as follows:

[0003] Chinese patent CN102666502A discloses a reaction using isopentenal and acetone oxime compounds as raw materials in the presence of an acid catalyst or an acid-base catalyst. However, the reaction has problems such as long reaction time and low yield. At the same time, the reaction system uses trifluoroacetic acid or trifluoroacetate as a catalyst, resulting in high production costs.

[0004] Chinese patent CN120682162 discloses the reaction of isopentenal and acetone oxime with a series of boron trifluoride catalysts to obtain 5,5-dimethyl 2-isooxazoline. However, the catalyst is expensive, the reaction product is not extracted, and the production process is not easy to control.

[0005] Chinese patent CN 118373783 discloses a process that uses acrolein and hydroxylamine hydrochloride to form a ring under hydrochloric acid gas catalysis, followed by chlorination to form 3-chloro-4,5-dihydroisoxazole (isoxazoline). This process failed to produce a single intermediate, and repeating the process with isopentenal did not achieve a good yield.

[0006] Therefore, it is necessary to develop a method that uses readily available and inexpensive raw materials and has a simple process that is easy to scale up for production, in order to effectively synthesize 5,5-dimethyl-2-isooxazoline. Summary of the Invention

[0007] In view of the problems existing in the prior art, the purpose of this invention is to provide a method for synthesizing 5,5-dimethyl-2-isooxazoline that is mild in reaction conditions, environmentally friendly, and low in cost.

[0008] To achieve the above objectives, the technical solution of the present invention is as follows: A method for synthesizing 5,5-dimethyl-2-isooxazoline includes the following steps: Step 1: First, isopentenal is reacted with hydrogen chloride to produce chloroisopental; Step 2: Then, under alkaline conditions, the chloroisovaleraldehyde obtained in Step 1 is reacted with hydroxylamine salt to generate chloroisovaleraldehyde oxime. Step 3: Finally, under alkaline conditions, the chloroisovaleraldehyde oxime ring obtained in Step 2 is synthesized into 5,5-dimethyl 2-isooxazoline. The synthetic route is shown below: .

[0009] Furthermore, in step one, the molar ratio of isopentenal to hydrogen chloride is 1:1-3; and the hydrogen chloride in step one is anhydrous gaseous hydrogen chloride.

[0010] Furthermore, the molar ratio of isopentenal to hydrogen chloride in step one is 1:1.5; the solvent used in step one is carbon tetrachloride, dichloroethane, or dichloromethane.

[0011] Furthermore, in step two, the molar ratio of chloroisovaleraldehyde to hydroxylamine salt is 1:1-2; and the molar ratio of chloroisovaleraldehyde to base is 1:2-4.

[0012] Furthermore, in step two, the base is an organic or inorganic base; the hydroxylamine salt is hydroxylamine hydrochloride or hydroxylamine sulfate.

[0013] Furthermore, the organic base is triethylamine, sodium formate, sodium acetate, or pyridine; the inorganic base is sodium hydroxide, potassium oxide, or sodium carbonate.

[0014] Furthermore, the oximation reaction between chloroisovaleraldehyde and hydroxylamine salt in step two is carried out in water or an organic solvent; the oximation temperature is -5 to 50°C.

[0015] Furthermore, the cyclization reaction in step three is carried out in water or an organic solvent, wherein the organic solvent is DMF, acetonitrile, or DMSO.

[0016] Furthermore, the reaction temperature in step three is 10-120℃.

[0017] Furthermore, the reaction temperature in step three is 10-20℃, and the cyclization reaction in step three is carried out with the participation of a catalyst, wherein the catalyst is KI. Compared with the prior art, the beneficial effects of the present invention are as follows: 1) In this invention, isopentenal is added to hydrogen chloride to generate chloroisopental. Then, under alkaline conditions, the chloroisopental obtained in step one is reacted with hydroxylamine salt to generate chloroisopental oxime. Finally, under alkaline conditions, the chloroisopental oxime ring obtained in step two is synthesized into 5,5-dimethyl 2-isooxazoline. The yield is high, the process is simple and suitable for industrial production. 2) Compared with traditional methods, the synthesis method of the present invention has the characteristics of mild reaction conditions, green and environmentally friendly, and low cost. Attached Figure Description

[0018] Figure 1 The gas phase diagram of isovaleraldehyde; Figure 2 This is the mass spectrum of chloroisovaleraldehyde; Figure 3 Here is the liquid phase diagram of isovaleraldehyde oxime; Figure 4 Mass spectrum of isovaleraldehyde oxime Figure 5 Liquid phase diagram of 5,5-dimethyl-2-isooxazoline; Figure 6 NMR image of 2-isooxazoline, which is 5,5-dimethyl. Detailed Implementation

[0019] The present invention will be further described below with reference to the accompanying drawings and embodiments, but the scope of protection of the present invention is not limited to the scope described.

[0020] Example 1

[0021] Add 84 g (1 mol) of isopentenal and 300 g of dichloroethane to a 500 ml four-necked flask. Cool to -5 °C, stir slowly, and begin bubbling with hydrogen chloride gas for 2 hours. After HPLC detection indicates the reaction is complete, concentrate under reduced pressure to remove dichloroethane, yielding a pale yellow liquid of 109.5 g, with a yield of 91.2% and m / z 121.0416 ([M+H)). + ).

[0022] Example 2

[0023] Add 84g (1mol) isopentenal and 300g carbon tetrachloride to a 500ml four-necked flask, cool to 5℃, stir slowly, and start to introduce hydrogen chloride gas. After 2 hours, HPLC detection showed that the reaction of the raw materials was complete. Then, concentrate under reduced pressure to remove dichloroethane to obtain a pale yellow liquid, yielding 107.5g, with a yield of 90.4%.

[0024] The gas phase results for chloroisovaleraldehyde are shown below: .

[0025] Example 3

[0026] 72 g (0.60 mol) of chloroisovaleraldehyde obtained in Example 1, 94.3 g (0.72 mol) of hydroxylamine sulfate, 59.0 g (0.72 mol) of sodium acetate, 300 mL of toluene, and 100 g of water were added to a four-necked flask. The mixture was stirred at room temperature for 3 hours, and a sample was taken for testing. The reaction was continued for another two hours, and a sample was taken for testing. 300 mL of water was added to the reaction mixture, followed by dropwise addition of a 30% sodium hydroxide aqueous solution. The aqueous phase was separated, and the solvent was removed by rotary evaporation of the organic phase, yielding 73.4 g of the product. The yield was 90.6%, m / z 136.0517 ([M+H)). + ).

[0027] Example 4

[0028] 72 g (0.60 mol) of chloroisovaleraldehyde obtained in Example 2, 49.25 g (0.72 mol) of hydroxylamine hydrochloride, 300 ml of dichloroethane, and 100 g of water were added to a four-necked flask. The mixture was stirred at room temperature for 3 hours, and sodium hydroxide solution was slowly added dropwise until the pH reached 8. Sampling was carried out to control the detection. 300 mL of water was added to the reaction mixture to separate the aqueous phase. The solvent was removed by rotary evaporation of the organic phase to obtain 74.6 g of chloroisovaleraldehyde oxime, with a yield of 92.1%.

[0029] Figure 3 The analysis results are shown below: .

[0030] Example 5 67.5 g (0.50 mol) of chloroisovalerate oxime obtained in Example 3, 85 g (1.0 mol) of sodium bicarbonate, and 300 ml of toluene were added to a four-necked flask. The temperature was raised to 80 degrees Celsius, and the reaction was carried out for 4 hours. Samples were taken for testing. After passing the test, the sample was concentrated and recrystallized from methanol to obtain 40.1 g of 5,5-dimethyl-2-isooxazoline and 39.6 g of 2-isooxazoline, with a yield of 80.0%. ¹H NMR (CDCI3): 1.39 (s, 6H), 2.73 (d, 2H), 7.04 (br s, 1H).

[0031] Example 6 67.5 g (0.50 mol) of chloroisovaleraldehyde oxime obtained in Example 4, 138 g (1.0 mol) of potassium carbonate, and 300 ml of DMF were added to a four-necked flask. The temperature was raised to 100 degrees Celsius, and the reaction was carried out for 4 hours. Samples were taken for testing. After passing the test, the product was concentrated and recrystallized from methanol to obtain 40.1 g of 5,5-dimethyl-2-isooxazoline and 42.1 g of 2-isooxazoline, with a yield of 85.1%.

[0032] Example 7

[0033] In Example 2, 60 g (0.50 mol) of chloroisovaleraldehyde, 41.04 g (0.6 mol) of hydroxylamine hydrochloride, and 300 ml of toluene were stirred at room temperature while sodium bicarbonate solid was added in batches. The mixture was stirred until the raw material disappeared, then 85 g of sodium bicarbonate and 1 g of potassium iodide were added. The temperature was raised to 70 degrees Celsius, and the reaction was carried out for 4 hours. Samples were taken for testing. After passing the test, the mixture was concentrated and recrystallized from methanol to obtain 39.1 g of 5,5-dimethyl-2-isooxazoline, with a yield of 78.9%.

[0034] Figure 5 The analysis results are as follows: .

Claims

1. A method for synthesizing 5,5-dimethyl-2-isooxazoline, characterized in that... Includes the following steps: Step 1: First, isopentenal is reacted with hydrogen chloride to produce chloroisopental; Step 2: Then, under alkaline conditions, the chloroisovaleraldehyde obtained in Step 1 is reacted with hydroxylamine salt to generate chloroisovaleraldehyde oxime. Step 3: Finally, under alkaline conditions, the chloroisovaleraldehyde oxime ring obtained in Step 2 is synthesized into 5,5-dimethyl 2-isooxazoline. The synthetic route is shown below: 。 2. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... In step one, the molar ratio of isopentenal to hydrogen chloride is 1:1-3; the hydrogen chloride in step one is anhydrous gaseous hydrogen chloride.

3. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 2, characterized in that... The molar ratio of isopentenal to hydrogen chloride in step one is 1:1.5; the solvent used in step one is carbon tetrachloride, dichloroethane, or dichloromethane.

4. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... In step two, the molar ratio of chloroisovaleraldehyde to hydroxylamine salt is 1:1-2; the molar ratio of chloroisovaleraldehyde to base is 1:2-4.

5. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... In step two, the alkali can be an organic or inorganic alkali; the hydroxylamine salt is hydroxylamine hydrochloride or hydroxylamine sulfate.

6. The method for synthesizing a 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... The organic base is triethylamine, sodium formate, sodium acetate, or pyridine; the inorganic base is sodium hydroxide, potassium oxide, or sodium carbonate.

7. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... In step two, the oximation reaction between chloroisovaleraldehyde and hydroxylamine salt is carried out in water or an organic solvent; the oximation temperature is -5 to 50°C.

8. The method for synthesizing 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... The cyclization reaction in step three is carried out in water or an organic solvent, wherein the organic solvent is DMF, acetonitrile or DMSO.

9. The method for synthesizing a 5,5-dimethyl-2-isooxazoline according to claim 1, characterized in that... The reaction temperature in step three is 10-120℃.

10. The method for synthesizing a 5,5-dimethyl-2-isooxazoline according to claim 9, characterized in that... The reaction temperature in step three is 10-20℃.

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