1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and preparation method thereof

Abstract

The invention provides 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a preparation method thereof, and belongs to the technical field of chemical synthesis.The preparation method comprises the following steps that S1, 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, potassium hydroxide, acetonitrile and water are taken and stirred to be dissolved, then Freon is introduced into the mixture, heat preservation is conducted, and a mixture A is obtained; standing for layering, taking an oil phase, washing the oil phase, taking an oil phase, and desolventizing the oil phase under reduced pressure to obtain an intermediate 1; and S2, mixing the intermediate 1, methyl chloromethyl ether and a catalyst, carrying out heat preservation, standing for layering, taking an oil phase, carrying out reduced pressure distillation on the oil phase, and collecting fractions, thereby obtaining the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole. According to the technical scheme provided by the invention, the requirements on reaction conditions are reduced, and the cost is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a preparation method thereof. Background Art

[0002] Pyroxasulfone is a pre-emergence herbicide developed by Kuibo Chemical Co., Ltd. and Ibara Chemical Industry Co., Ltd. It is widely used in crops such as wheat, corn, rice and sunflower. Compared with the traditional herbicide acetochlor, pyroxasulfone has a small dosage and a long lasting effect, and has a good market development prospect.

[0003] The patent with publication number CN113831333B and titled "A method for synthesizing sulfonepyrazol" discloses that 1-methyl-3-trifluoromethyl-5-hydroxy-1H-pyrazole is used as a raw material, and in the presence of an organic solvent and an alkali solution, a hydroxymethylation reaction is carried out with formaldehyde to obtain hydroxypyrazole methanol; hydroxypyrazole methanol is subjected to an etherification reaction with difluorochloromethane to obtain etherified pyrazole methanol; then the etherified pyrazole methanol is subjected to a condensation reaction with an isoxazole thiourea salt and a phase transfer catalyst to obtain a sulfide; and the sulfide is subjected to an oxidation reaction with hydrogen peroxide in the presence of a catalyst to obtain sulfonepyrazol.

[0004] The patent with publication number CN117327016A and titled "A method for preparing a sulfonepyrazol intermediate" discloses that 1-methyl-3-trifluoromethyl-1H-pyrazole-5-ol and formaldehyde are subjected to a hydroxymethylation reaction under alkaline conditions to obtain an intermediate hydroxypyrazole methanol, and the intermediate hydroxypyrazole methanol is further subjected to an etherification reaction with sodium difluorochloroacetate to obtain 5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-methanol; wherein the etherification reaction temperature is 40~90°C, and the molar ratio of hydroxypyrazole methanol to sodium difluorochloroacetate is 1:1~3.

[0005] Both of the above technical solutions use the hydroxymethylation reaction commonly used in the prior art, that is, 1-methyl-3-trifluoromethyl-5-hydroxy-1H-pyrazole reacts with formaldehyde, and then the obtained hydroxypyrazole methanol is subjected to etherification reaction to obtain the corresponding intermediate. However, the reaction conditions for using raw materials such as formaldehyde in the above reaction process are high and the cost is high.

[0006] Therefore, it is necessary to provide a 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole to solve the problems existing in the above-mentioned prior art. Summary of the invention

[0007] In view of this, the present invention provides a 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a preparation method thereof, which achieves the requirements for lowering reaction conditions and reducing costs.

[0008] To achieve the above object, the present invention provides a method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, comprising the following steps: S1. Take 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, a base, an organic solvent and water, stir until dissolved, then introduce freon into the mixture for reaction, detect the residual amount of 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, and when the residual amount meets the condition, stand for stratification and take out the oil phase, wash the oil phase and then take out the oil phase, and then decompress the oil phase to obtain intermediate 1; S2, taking the intermediate 1, methyl chloromethyl ether and the catalyst, mixing and keeping warm, detecting the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, and when the content meets the conditions, standing and stratifying, taking the oil phase, distilling the oil phase under reduced pressure, collecting fractions, and obtaining the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

[0009] Optionally, the catalyst is one of zinc chloride, zinc iodide and zinc bromide.

[0010] Optionally, the residual amount is less than a set value of 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, and the residual amount is less than 1%.

[0011] Optionally, the content is greater than a set value of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, and the content is greater than 95%.

[0012] Optionally, when Freon is introduced into S1 for reaction, the temperature is maintained at 20-30° C. and the reaction time is 0.5-1 h.

[0013] Optionally, when the intermediate 1, methyl chloromethyl ether and the catalyst are mixed and insulated in S2, the temperature is maintained at 20-30° C. for 4.5-5.5 hours.

[0014] Optionally, the collected fractions are fractions collected at a temperature range of 80° C. to 138° C. under a pressure of 72 mm Hg.

[0015] In order to achieve the above object, the present invention also provides a 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

[0016] The above technical solution of the present invention includes at least the following beneficial effects: The invention provides a method for preparing a sulfonepyraclostrobin intermediate 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole. In the preparation process of the sulfonepyraclostrobin intermediate, raw materials such as methyl chloromethyl ether are combined with a catalyst to improve the yield. The preparation process is simple and the production can be carried out while maintaining the temperature at 20-30 DEG C, that is, the production can be carried out at room temperature without additional energy consumption to maintain a higher or lower temperature, thereby facilitating the expansion of production. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the HPLC detection chart of step 1 in Example 1 of the present invention; Figure 2 This is the HPLC detection chart of step 2 in Example 1 of the present invention. DETAILED DESCRIPTION

[0018] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the following will be combined with the appended drawings of the embodiments of the present invention. Figure 1~2 , the technical scheme of the embodiment of the present invention is clearly and completely described. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0019] Example 1 Step 1: Take a 1000mL four-necked bottle, add 110g 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, 55g potassium hydroxide, 133g water, 400g acetonitrile, stir until dissolved, then pass 66.7g Freon, keep warm at 20℃~30℃ for 30 minutes, take samples for HPLC detection, until 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol reacts to less than 1% and the reaction is qualified, after the reaction is qualified, stand and separate, discard the lower aqueous phase, wash the oil phase with 50g water, stand and separate, and discard the aqueous phase. The obtained oil phase is desolvated with acetonitrile under reduced pressure until there is no fraction, and finally 101g of intermediate 1 is obtained.

[0020] Step 2: Take another 1000mL four-necked bottle, add the intermediate 1 obtained in the previous step, 202g methyl chloromethyl ether, 5g zinc chloride, keep warm at 20°C~30°C for 4.5 hours, take samples and send to HPLC for detection, the reaction is qualified if the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greater than 95%, and the reaction is qualified. After the reaction is qualified, stand and separate, discard the lower aqueous phase, and distill the oil phase under reduced pressure. Collect the fractions in the temperature range of 80°C~138°C under 72mm mercury pressure to obtain the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole of 133.72g, content of 98.2%, and yield of 81.09%. Figure 1 This is the HPLC detection chart in step 1 of Example 1, Figure 2 This is the HPLC detection chart in step 2.

[0021] Example 2 Step 1: Take a 1000mL four-necked bottle, add 110g 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, 55g potassium hydroxide, 133g water, 400g acetonitrile, stir until dissolved, and then pass 66.7g Freon into it. After passing, keep warm at 20℃~30℃ for 30 minutes, take samples for HPLC detection, until 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol reacts to less than 1%, stand and separate after the reaction is qualified, discard the lower aqueous phase, wash the oil phase with 50g water, stand and separate, and discard the aqueous phase. The obtained oil phase is desolvated with acetonitrile under reduced pressure until there is no fraction, and finally 101g of intermediate 1 is obtained.

[0022] Step 2: Take another 1000mL four-necked bottle, add the intermediate 1 obtained in the previous step, 202g methyl chloromethyl ether, 5g zinc iodide, keep warm between 20°C and 30°C for 5.5 hours, take samples and send to HPLC for detection, the reaction is qualified if the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greater than 95%, and the reaction is qualified. After the reaction is qualified, stand and stratify, discard the lower aqueous phase, and distill the oil phase under reduced pressure. Collect the fractions in the temperature range of 80°C to 138°C under 72mm mercury pressure to obtain the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is 140.47g, with a content of 98.3% and a yield of 85.36%.

[0023] Example 3 Step 1: Take a 1000mL four-necked bottle, add 110g 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, 55g potassium hydroxide, 133g water, 400g acetonitrile, stir until dissolved, and then pass 66.7g Freon into it. After passing, keep warm at 20℃~30℃ for 1h, take samples for HPLC detection, until 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol reacts to less than 1%, stand and separate after the reaction is qualified, discard the lower aqueous phase, wash the oil phase with 50g water, stand and separate, and discard the aqueous phase. The obtained oil phase is desolvated with acetonitrile under reduced pressure until there is no fraction, and finally 101g of intermediate 1 is obtained.

[0024] Step 2: Take another 1000mL four-necked bottle, add the intermediate 1 obtained in the previous step, 202g methyl chloromethyl ether, 5g zinc bromide, keep warm between 20°C and 30°C for 5 hours, take samples and send to HPLC for detection, the reaction is qualified if the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greater than 95%, and the reaction is qualified. After the reaction is qualified, stand and stratify, discard the lower aqueous phase, and distill the oil phase under reduced pressure. Collect the fractions in the temperature range of 80°C to 138°C under 72mm mercury pressure to obtain the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is 147.52g, with a content of 98.7% and a yield of 89.63%.

[0025] Comparative Example 1 Step 1: Take a 1000mL four-necked bottle, add 110g 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, 55g potassium hydroxide, 133g water, 400g acetonitrile, stir until dissolved, and then pass 66.7g Freon into it. After passing, keep warm at 20℃~30℃ for 1h, take samples for HPLC detection, until 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol reacts to less than 1%, stand and separate after the reaction is qualified, discard the lower aqueous phase, wash the oil phase with 50g water, stand and separate, and discard the aqueous phase. The obtained oil phase is desolvated with acetonitrile under reduced pressure until there is no fraction, and finally 101g of intermediate 1 is obtained.

[0026] Step 2: Take another 1000mL four-necked bottle, add the intermediate 1 obtained in the previous step, 75.3g formaldehyde solution, 5g tin tetrachloride, and keep it warm at 20℃~30℃ for 2 hours, then control the temperature at 20℃~30℃ to quickly add 325g hydrochloric acid to the four-necked bottle, keep it warm for 3 hours after the addition, take a sample and send it to HPLC for detection, the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greater than 95%, and the reaction is qualified. After the reaction is qualified, stand and separate, discard the lower aqueous phase, and distill the oil phase under reduced pressure. Collect the fractions in the temperature range of 80℃~138℃ under 72mm mercury pressure to obtain the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is 101.92g, the content is 90.4%, and the yield is 62.15%.

[0027] Comparative Example 2 Compared with Example 1, the only difference is that methyl chloromethyl ether is replaced by chloromethyl ethyl ether of the same amount, i.e., 237.47 g of chloromethyl ethyl ether. The product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is obtained with a mass of 86.03 g, a content of 86.25%, and a yield of 52.46%.

[0028] Comparative Example 3 Compared with Example 1, the only difference is that methyl chloromethyl ether is replaced with an equivalent amount of chloromethyl butyl ether, i.e., 333.18 g of chloromethyl butyl ether. The product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is obtained with a mass of 75.98 g, a content of 76.34%, and a yield of 46.33%.

[0029] Comparative Example 4 Step 1 is the same as Comparative Example 1, and step 2 is to take another 1000mL four-necked bottle, add the intermediate 1 obtained in the previous step, 75.3g formaldehyde solution, 5g tin tetrachloride, and keep it warm between 20°C and 30°C for 4.5 hours, then control the temperature between 20°C and 30°C to quickly add 325g hydrochloric acid to the four-necked bottle, keep it warm for 2 hours after the addition, take a sample and send it to HPLC for detection, the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole no longer increases, and the reaction is completed. After the reaction is completed, stand and separate, discard the lower aqueous phase, and distill the oil phase under reduced pressure. Collect the fractions in the temperature range of 80°C to 138°C under 72mm mercury pressure to obtain about 80g of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, with a content of 92.0% and a yield of 48.61%.

[0030] The product quality, content and yield of Examples 1 to 3 and Comparative Examples 1 to 4 are summarized to obtain Table 1.

[0031] Table 1 Product quality, content and yield of Examples 1 to 3 and Comparative Examples 1 to 4

[0032] From Table 1, it can be seen from the analysis of Examples 1 to 3 and Comparative Example 1 that the only difference is the type of catalyst, and the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole prepared in Examples 1 to 3 has a high product content and a high yield, while the product content in Comparative Example 1 using a tin tetrachloride catalyst is low and the yield is significantly reduced. Therefore, the catalyst used in the present invention improves the yield and product content of the product.

[0033] From Table 1, combined with Example 1 and Comparative Examples 2-3, it can be seen that the difference lies in the different types of raw materials, and the content and yield of the products prepared in Comparative Examples 2-3 are significantly lower than the content and yield of the products prepared in Example 1. It can be seen that the raw materials used in the present invention can increase the yield and content of the product.

[0034] From the analysis of Table 1 in combination with Examples 1 to 3, Comparative Example 1 and Comparative Example 4, it can be seen that the content and yield of the products prepared in Examples 1 to 3 are higher than those in Comparative Example 1, and the content and yield of the product prepared in Comparative Example 1 are higher than those in Comparative Example 4. It can be seen that the catalyst used in the present invention is combined with the raw material methyl chloromethyl ether to increase the yield and product content of the product.

[0035] The above are preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, characterized in that: The following steps are involved: S1. Take 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, a base, an organic solvent and water, stir until dissolved, then introduce freon into the mixture for reaction, detect the residual amount of 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, and when the residual amount is less than a set value, stand for stratification and take out the oil phase, wash the oil phase and then take out the oil phase, and then decompress the oil phase to obtain intermediate 1; S2, taking the intermediate 1, methyl chloromethyl ether and a catalyst, mixing and keeping warm, detecting the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, and when the content is greater than a set value, standing and stratifying, taking the oil phase, distilling the oil phase under reduced pressure, collecting fractions, and obtaining the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

2. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: The catalyst is one of zinc chloride, zinc iodide and zinc bromide.

3. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: The residual amount is less than the set value, and the residual amount of 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol is less than 1%.

4. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: The content is greater than the set value, that is, the content of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greater than 95%.

5. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: When Freon is introduced into S1 for reaction, the temperature is maintained at 20-30°C and the reaction time is 0.5-1h.

6. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: When the intermediate 1, methyl chloromethyl ether and the catalyst are mixed and kept warm in S2, the temperature is maintained at 20-30° C. for 4.5-5.5 hours.

7. The method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to claim 1, characterized in that: The collected fractions are fractions collected at a temperature range of 80° C. to 138° C. under a pressure of 72 mm Hg.

8. 1-Methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole obtained by the method for preparing 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole according to any one of claims 1 to 7.

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