A preparation method of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole

Abstract

The present invention provides a preparation method of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole, specifically, 1,1-dibromoformaldehyde oxime and a reaction solvent are added into a reaction vessel, under the condition of 5-30°C, a part of an acid binding agent is added while stirring, and then isobutylene gas is continuously passed below the liquid level in the reaction vessel, and the remaining acid binding agent is added in batches while passing the isobutylene gas to control the pH value of the reaction solution in the reaction vessel within the range of 4-6, and after passing the isobutylene, 5-30°C of insulation reaction is continued to obtain 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole. The preparation method of the present invention is simple to operate, environmentally friendly, has few side reactions, has low equipment investment cost, and is more suitable for industrial-scale production.

Description

Technical Field

[0001] The invention belongs to the field of chemistry and chemical engineering, and specifically relates to a method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole. Background Art

[0002] Pyroxasulfone, whose chemical name is [3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylsulfonyl]-4,5-dihydro-5,5-dimethyloxazole], is a pre-emergence soil treatment agent developed by Kuibo Chemical Industries, Ltd. of Japan that can be used in most crop fields. Its mechanism of action is similar to that of acetochlor and related herbicides, but it is applicable to a wide range of crops and its biological activity is far greater than that of acetochlor and isopropylamine.

[0003] Patent CN113735791A prepares a solution of dibromoformaldehyde oxime and a reaction solvent, dissolves sodium bicarbonate in water, adds the reaction solvent, and introduces isobutylene gas in an ice-water bath, then drips the prepared dibromoformaldehyde oxime solution, removes the ice-water bath after the dripping, and reacts by stirring at room temperature. The yield of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole is 70% to 80% under the preparation process, and the process is relatively time-consuming. The molar amount of isobutylene is twice that of dibromoformaldehyde oxime.

[0004] Patent CN113336716A first adds sodium carbonate to a dichloroethane layer containing dibromoformaldehyde oxime, and then controls the temperature at 40-45°C to introduce isobutylene for cyclization reaction. Under the preparation process, the yield of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole is about 80%.

[0005] The above method has the problem of low yield. Patent CN116102510A reacts dibromoformaldehyde oxime and isobutylene in a high-pressure reactor to improve the yield of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole. Since the high-pressure reactor is expensive and has certain risks, it is not the most suitable method for industrial production. In addition, isobutylene is also added in excess in this method. The utilization rate of isobutylene needs to be further improved to avoid unnecessary waste and environmental impact. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole which can be carried out under normal pressure and has high isobutylene utilization rate, few side reactions, low cost and is environmentally friendly.

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0008] A method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole comprises the following steps: adding 1,1-dibromoformaldehyde oxime and a reaction solvent into a reaction container, adding a portion of an acid-binding agent while stirring at 5-30°C, then continuously passing isobutylene gas below the liquid level in the reaction container, adding the remaining acid-binding agent in batches while passing the isobutylene gas to control the pH value of the reaction liquid in the reaction container within the range of 4-6, and continuing the reaction at 5-30°C after passing the isobutylene gas to obtain the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole.

[0009] Preferably, isobutylene gas is continuously introduced below the liquid level in the reaction container at 15-25°C.

[0010] Further preferably, isobutylene gas is continuously introduced below the liquid level in the reaction container at 20-25°C.

[0011] Preferably, the temperature of the insulation reaction is 15-25°C.

[0012] More preferably, the temperature of the insulation reaction is 20-25°C.

[0013] Preferably, the insulation reaction time is 20 min to 50 min.

[0014] More preferably, the insulation reaction time is 25 min to 35 min.

[0015] Preferably, the acid binding agent is independently one or more of triethylamine, potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate.

[0016] Preferably, the total molar amount of the acid binding agent is 1-1.5 times the molar amount of the 1,1-dibromoformaldehyde oxime.

[0017] More preferably, the total molar amount of the acid binding agent is 1-1.2 times the molar amount of the 1,1-dibromoformaldehyde oxime.

[0018] Preferably, the molar amount of the acid binding agent when added for the first time is 5%-15% of the total molar amount of the acid binding agent.

[0019] Further preferably, the molar amount of the acid binding agent when added for the first time is 8%-10% of the total molar amount of the acid binding agent.

[0020] Preferably, the reaction solvent is one or more of ethyl acetate, chlorobenzene, acetonitrile, butyronitrile, and methyl tert-butyl ether.

[0021] More preferably, the reaction solvent is ethyl acetate or methyl tert-butyl ether.

[0022] Preferably, the amount of the reaction solvent used is 0.5-10 times the mass of the 1,1-dibromoformaldehyde oxime fed.

[0023] Further preferably, the amount of the reaction solvent used is 0.5-5 times the mass of the 1,1-dibromoformaldehyde oxime fed.

[0024] Still more preferably, the amount of the reaction solvent used is 1-3 times the mass of the 1,1-dibromoformaldehyde oxime fed.

[0025] Preferably, the feeding molar ratio of the 1,1-dibromoformaldehyde oxime to the isobutylene gas is 1:(0.9-1.5).

[0026] Further preferably, the feeding molar ratio of the 1,1-dibromoformaldehyde oxime to the isobutylene gas is 1:(0.95-1.1).

[0027] Preferably, the preparation method is always carried out under stirring conditions after the 1,1-dibromoformaldehyde oxime and the reaction solvent are added.

[0028] Preferably, the introduction rate of the isobutylene gas is controlled to be 0.1-0.5 g / min.

[0029] Further preferably, the isobutylene gas introduction rate is controlled to be 0.15-0.3 g / min.

[0030] Still further preferably, the isobutylene gas introduction rate is controlled to be 0.18-0.25 g / min.

[0031] Preferably, the reaction vessel is a normal pressure reaction vessel.

[0032] Preferably, the preparation method further comprises post-treatment, wherein the post-treatment comprises mixing the reaction solution with water or aqueous hydrochloric acid solution, standing to separate the layers, and recovering the solvent under negative pressure from the oil layer. The obtained substance is the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole.

[0033] Due to the implementation of the above technical solution, the present invention has the following advantages compared with the prior art:

[0034] The present invention continuously introduces a certain amount of isobutylene below the liquid surface of a reaction liquid under normal pressure, and accurately controls the pH value of the reaction liquid in the range of 4 to 6 during the reaction process, thereby ensuring that the isobutylene reacts with the intermediate generated by 1,1-dibromoformaldehyde oxime in a timely and efficient manner. The entire reaction process does not require the use of an expensive high-pressure reactor, thereby reducing costs and improving safety. Meanwhile, the utilization rate of isobutylene is improved, the amount of the raw material isobutylene is saved, side reactions are reduced, and the method is relatively environmentally friendly. The reaction yield reaches more than 92%, and the product purity is greater than 96%, which is truly suitable for industrial production. DETAILED DESCRIPTION

[0035] The present invention is further described in detail below in conjunction with specific examples. It should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited by the following examples. The implementation conditions adopted in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in routine experiments.

[0036] In order to solve the problems of low yield or low utilization rate of isobutylene or high equipment cost in the existing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole preparation process, the present invention adjusts the preparation process. Through a large number of studies and experimental verifications, it is found that under normal pressure, a certain amount of isobutylene is continuously introduced below the liquid level of the reaction liquid, and the pH value of the reaction liquid during the reaction is accurately controlled within the range of 4 to 6, so that the isobutylene can react with the intermediate generated by 1,1-dibromoformaldehyde oxime in a timely and efficient manner. Therefore, the utilization rate of isobutylene can be improved without using a high-pressure reactor, and the yield and purity of the target product can be guaranteed. The preparation method of the present invention is simple to operate, environmentally friendly, has few side reactions, has low equipment investment cost, and is more suitable for industrial-scale production.

[0037] The specific reaction formula involved in the present invention is as follows:

[0038]

[0039] The raw material dibromoformaldehyde oxime is a known compound and there are many methods for synthesizing it. For example, Tetrahedron Letters, 1992, 33, 3113 discloses that oxime acetic acid is synthesized from glyoxylic acid and hydroxylamine and then reacted with bromine to obtain white crystalline dibromoformaldehyde oxime. The remaining raw materials can be directly purchased from commercial products.

[0040] Example 1

[0041] 21g 1,1-dibromoformaldehyde oxime (purity 97%) and 42g ethyl acetate were added to a 500mL reaction bottle. The reaction temperature was controlled at 20-25°C. About 1g sodium bicarbonate was added while stirring. Then 5.6g isobutylene was slowly introduced below the liquid level in the reaction bottle by weight. During the introduction of isobutylene, the pH value of the reaction solution was detected by an online pH detector. When the pH value dropped to 4, an appropriate amount of sodium bicarbonate was added until the pH value rose to 5.5. The pH value of the reaction solution was controlled at 4-5 by adding sodium bicarbonate in batches. 5 until all the isobutylene is passed through, the time required for all the isobutylene to be passed through is 25min, the total amount of sodium bicarbonate used is 10g, after the isobutylene is passed through, the temperature is kept at 20-25℃ for 30min, and the liquid phase is controlled. After the control is qualified (1,1-dibromoformaldehyde oxime ≤0.2%), 83.6g of water is added, stirred, and then allowed to stand for stratification. After the oil layer is separated, the solvent is recovered under negative pressure to obtain 17.1g of light yellow 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole with a purity of 96.6% and a yield of 92.8%.

[0042] Example 2

[0043] 21g 1,1-dibromoformaldehyde oxime (purity 97%) and 42g methyl tert-butyl ether were added into a 500mL reaction bottle, the reaction temperature was controlled at 20-25°C, about 0.9g potassium bicarbonate was added while stirring, and then 5.6g isobutylene was slowly introduced below the liquid level in the reaction bottle by weight. During this process, the pH value of the reaction solution was detected by an online pH detector. When the pH value was 4, an appropriate amount of potassium bicarbonate was added until the pH value rose to 6. The pH value of the reaction solution was controlled at 4-6 by adding potassium bicarbonate in batches. The reaction mixture was stirred within the range until all the isobutylene was passed through, and the time required for all the isobutylene to be passed through was 30 minutes. The total amount of potassium bicarbonate used was 11 g. After all the isobutylene was passed through, the reaction was continued at 20-25°C for 30 minutes. The liquid phase was controlled in the middle. After the control was qualified (1,1-dibromoformaldehyde oxime ≤ 0.2%), 42 g of water was added, stirred, and then allowed to stand for stratification. After the oil layer was separated, the solvent was recovered under negative pressure to obtain 17.15 g of light yellow 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole with a purity of 97% and a yield of 93.5%.

[0044] Example 3

[0045] 21 g of 1,1-dibromoformaldehyde oxime (purity 97%) and 42 g of methyl tert-butyl ether were added into a 500 mL reaction bottle, the temperature was controlled at 20-25°C, 1.2 g of triethylamine was added while stirring, and then 5.6 g of isobutylene was slowly introduced below the liquid level in the reaction bottle by gravimetric weighing. During this process, the pH value change of the reaction liquid was detected by an online pH detector. When the pH value was 4, an appropriate amount of triethylamine was added dropwise until the pH value rose to 6. In this way, the pH value of the reaction liquid was controlled within the range of 4-6 by adding triethylamine in batches. The reaction was continued until all the isobutylene was passed through, and the time required for the complete passage of all the isobutylene was 23 minutes. The total amount of triethylamine used was 12.2 g. After the isobutylene was passed through, the reaction was kept warm for 30 minutes and the liquid phase was centrally controlled. After the central control was qualified (1,1-dibromoformaldehyde oxime ≤ 0.2%), 21 g of 10% dilute hydrochloric acid aqueous solution was added and washed twice. The oil layers were combined and the solvent was recovered under negative pressure to obtain 17 g of light yellow 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole with a purity of 97% and a yield of 92.6%.

[0046] Comparative Example 1

[0047] Put 21g into a 500mL reaction bottle. 1,1-dibromoformaldehyde oxime (purity 97%), 42g ethyl acetate, control the reaction temperature at 20-25°C, add 2g potassium bicarbonate while stirring, and then slowly pass 5.6g isobutylene into the reaction bottle below the liquid level by weight. During this process, the pH value of the reaction solution is detected by an online pH detector. When the pH value is 6, add an appropriate amount of potassium bicarbonate until the pH value rises to 8. In this way, the pH of the reaction solution is controlled in the range of 6-8 by adding potassium bicarbonate in batches until the isobutylene is completely passed. The time required for the isobutylene to be completely passed is 25min, and the total amount of potassium bicarbonate is 15g. After the isobutylene is passed, keep the reaction at 20-25°C for 30min, add 84g water, stir, and then stand for stratification. After the oil layer is separated, the solvent is recovered under negative pressure to obtain 15.5g of light yellow 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole with a purity of 94.5% and a yield of 82.3%.

[0048] Comparative Example 2

[0049] 21g 1,1-dibromoformaldehyde oxime (purity 97%) and 42g ethyl acetate were added to a 500mL reaction bottle. The reaction temperature was controlled at 20-25°C. 0.7g triethylamine was added while stirring. Then 5.6g isobutylene was slowly introduced below the liquid level in the reaction bottle by gravimetric weighing. During this process, the pH value of the reaction solution was detected by an online pH detector. When the pH value was 3, an appropriate amount of triethylamine was added dropwise until the pH value rose to 4.5. The pH of the reaction solution was controlled at 3-4 by adding triethylamine in batches. 5 until all the isobutylene is passed through, the time required for all the isobutylene to be passed through is 25 minutes, the total amount of triethylamine used is 10 g, after the isobutylene is passed through, the reaction is kept at 20-25°C for 30 minutes, 10% dilute hydrochloric acid aqueous solution 18 g is added, washed twice, the oil layers obtained are combined and the solvent is recovered under negative pressure, the oil layers are separated and the solvent is recovered under negative pressure to obtain 14.9 g of light yellow 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole, with a purity of 95.1% and a yield of 79.6%.

[0050] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole, characterized in that: 1,1-dibromoformaldehyde oxime and a reaction solvent are added into a reaction container, and part of an acid-binding agent is added while stirring at 5-30° C., and then isobutylene gas is continuously introduced below the liquid level in the reaction container, and the remaining acid-binding agent is added in batches while the isobutylene gas is introduced to control the pH value of the reaction liquid in the reaction container to be within the range of 4-6, and after the isobutylene is introduced, the reaction is continued at 5-30° C. to obtain the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole. The total molar amount of the acid binding agent is 1-1.5 times the molar amount of the 1,1-dibromoformaldehyde oxime, the molar amount of the acid binding agent when added for the first time is 5%-15% of the total molar amount of the acid binding agent, and the acid binding agent is one or more of triethylamine, potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate.

2. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: At 15-25° C., isobutylene gas is continuously introduced below the liquid level in the reaction container; and / or, the temperature of the insulation reaction is 15-25° C.; and / or, the insulation reaction time is 0.5 to 2 hours.

3. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The reaction solvent is one or more of ethyl acetate, chlorobenzene, acetonitrile, butyronitrile, and methyl tert-butyl ether; and / or, the amount of the reaction solvent is 0.5-10 times the mass of the 1,1-dibromoformaldehyde oxime.

4. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The feeding molar ratio of the 1,1-dibromoformaldehyde oxime to the isobutylene gas is 1:(0.9-1.5).

5. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The preparation method is always carried out under stirring conditions after the 1,1-dibromoformaldehyde oxime and the reaction solvent are added.

6. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The introduction rate of the isobutylene gas is controlled to be 0.1-0.5 g / min.

7. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The reaction container is a normal pressure reaction container.

8. The method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole according to claim 1, characterized in that: The preparation method further comprises post-treatment, wherein the post-treatment comprises mixing the reaction solution with water or hydrochloric acid aqueous solution, standing for stratification, and recovering the solvent under negative pressure from the oil layer to obtain the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole.

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