Synthesis method of 3-methyl-5-trifluoromethylpyrazole

Abstract

The invention belongs to the technical field of pesticides, and particularly relates to a synthesis method of 3-methyl-5-trifluoromethylpyrazole, which comprises the following steps: by taking trifluoroacetylacetone and hydrazine hydrate as reaction raw materials, synthesizing 3-methyl-5-trifluoromethylpyrazole under reaction conditions (1) or (2); wherein in the reaction condition 1, water is used as a reaction solvent, and quaternary ammonium salt is used as a catalyst; the reaction condition (2) is as follows: an organic solvent immiscible with water is used as a reaction solvent, and protonic acid is used as a catalyst. According to the preparation method, water or an organic solvent insoluble in water is used for replacing alcohols or other water-soluble and high-toxicity solvents, so that the problems that the product 3-methyl-5-trifluoromethylpyrazole is directly crystallized and is difficult to discharge and the like are solved; quaternary ammonium salt or protonic acid is used as the catalyst, so that the synthesis efficiency of the 3-methyl-5-trifluoromethylpyrazole is effectively improved. The method has the advantages of simple reaction conditions, easily available raw materials, yield of more than 95% and purity of more than 92%, and is suitable for industrial production amplification.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and specifically relates to a method for synthesizing 3-methyl-5-trifluoromethylpyrazole. Background Art

[0002] Fluthiapyrrolidone is the first piperidinyl thiazole isoxazoline fungicide developed by DuPont. Fluthiapyrrolidone has a unique site of action on Oomycete pathogens and achieves a fungicide effect by inhibiting oxysterol-binding protein (OSBP). It has excellent preventive effects on downy mildew and blight of potatoes, grapes, vegetables and other specialty crops.

[0003] 3-Methyl-5-trifluoromethylpyrazole is an important intermediate of the fungicide fluthiazolylpyrone. Existing literature reports that when synthesizing 3-methyl-5-trifluoromethylpyrazole, methanol or ethanol is used as a solvent, trifluoroacetylacetone and hydrazine hydrate are used as raw materials, and 3-methyl-5-trifluoromethylpyrazole is generated by cyclization. The above method has obvious disadvantages: 3-methyl-5-trifluoromethylpyrazole is too soluble in alcohol solvents. When alcohol is used as a solvent, direct crystallization is difficult to discharge, and water-soluble impurities cannot be removed by separation, washing or filtration. Some researchers also use chloroform as a solvent, but chloroform is volatile and highly toxic, and is rarely used in production.

[0004] Chinese patent application CN115974785A dissolves trifluoroacetylacetone in tetrahydrofuran and reacts with hydrazine hydrate. The disadvantages of this method are that tetrahydrofuran is expensive and there is also the problem that water-soluble impurities cannot be directly removed. The product must be extracted to remove tetrahydrofuran and water-soluble impurities, and tetrahydrofuran must also be recovered from water, which is cumbersome. Summary of the invention

[0005] Aiming at the technical problems of the existing 3-methyl-5-trifluoromethylpyrazole synthesis method, such as the difficulty in direct crystallization and the difficulty in removing water-soluble impurities, the present invention provides a 3-methyl-5-trifluoromethylpyrazole synthesis method.

[0006] In a first aspect, the present invention provides a method for synthesizing 3-methyl-5-trifluoromethylpyrazole, and the reaction scheme is as follows: ; With trifluoroacetylacetone and hydrazine hydrate as the reaction raw materials and quaternary ammonium salt as the catalyst, 3-methyl-5-trifluoromethylpyrazole is reacted in water.

[0007] Furthermore, the quaternary ammonium salt is selected from one or more of tetrabutylammonium bromide, benzyltriethylammonium chloride, trioctylmethylammonium chloride or dodecyltrimethylammonium chloride.

[0008] Furthermore, the molar ratio of trifluoroacetylacetone to hydrazine hydrate is 1:1-1.5.

[0009] Furthermore, the molar ratio of trifluoroacetylacetone to quaternary ammonium salt is 1:0.01-0.15.

[0010] Furthermore, the reaction temperature is -15 to 45°C, preferably 15 to 35°C.

[0011] Furthermore, after the reaction is completed, the temperature is lowered for crystallization and filtered to obtain 3-methyl-5-trifluoromethylpyrazole. Water is used as a solvent, and the post-treatment process can use a filtration method instead of desolventizing, which is simple to operate, and the wastewater mother liquor basically does not contain the product, which reduces production energy consumption and is conducive to scale-up production.

[0012] In a second aspect, the present invention also provides a method for synthesizing 3-methyl-5-trifluoromethylpyrazole, and the reaction scheme is as follows: ; With trifluoroacetylacetone and hydrazine hydrate as reaction raw materials and protonic acid as catalyst, 3-methyl-5-trifluoromethylpyrazole is reacted in an organic solvent immiscible with water.

[0013] Furthermore, the protonic acid is selected from one or more of sulfuric acid, phosphoric acid, and p-toluenesulfonic acid.

[0014] Furthermore, the low-toxic or non-toxic organic solvent that is immiscible with water is selected from toluene or ethylene dichloride.

[0015] Furthermore, the molar ratio of trifluoroacetylacetone to hydrazine hydrate is 1:1-1.5, preferably 1:1-1.1.

[0016] Furthermore, the molar ratio of trifluoroacetylacetone to the catalyst is 1:0.01-0.15.

[0017] Furthermore, the reaction temperature is 0-110°C, preferably 60-110°C.

[0018] Furthermore, after the reaction is completed, the temperature is lowered and the mixture is washed with water, and the organic phase is desolvated to obtain 3-methyl-5-trifluoromethylpyrazole.

[0019] The beneficial effects of the present invention are: The invention uses water or water-insoluble organic solvents to replace alcohols or other water-soluble and highly toxic solvents, thereby avoiding the problem that the product 3-methyl-5-trifluoromethylpyrazole is difficult to discharge by direct crystallization.

[0020] At the same time, the present invention creatively uses quaternary ammonium salt or protonic acid as a catalyst, which effectively improves the synthesis efficiency of 3-methyl-5-trifluoromethylpyrazole.

[0021] The method of the invention has simple reaction conditions, readily available raw materials, a yield of more than 95%, and a purity of more than 92%, and is suitable for industrial production and expansion. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0023] Figure 1 It is the NMR spectrum of the product of Example 3. DETAILED DESCRIPTION

[0024] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0025] Example 1 Under stirring, add 50mL of water, 15.4g (1eq) of trifluoroacetylacetone, and 0.46g (0.0143eq) of tetrabutylammonium bromide to a 100mL four-necked reaction bottle in sequence, and keep the temperature at 20-25°C. Slowly drop 9.4g (1.5eq) of hydrazine hydrate with a content of 80% into the system, and stir for 5h at 20-25°C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5°C for crystallization, keep it at this temperature for 1h, filter, and dry the filter cake to obtain 15.4g of the product. The HPLC purity is 92.7% and the yield is 95.1%.

[0026] Example 2 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.46 g (0.0143 eq) of tetrabutylammonium bromide to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 8.1 g (1.3 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 6 hours at a temperature of 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep it at this temperature for 1 hour, filter, and dry the filter cake to obtain 15.4 g of the product. The HPLC purity is 95.0%, and the yield is 97.5%.

[0027] Example 3 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.46 g (0.0143 eq) of tetrabutylammonium bromide to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 7 hours at 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep at this temperature for 1 hour, filter, and dry the filter cake to obtain 14.9 g of the product. The HPLC purity is 99.3% and the yield is 98.6%.

[0028] The product was tested by HNMR, and the test data were as follows: 1 H NMR (400MHz, CDCl3): δ 9.90-11.08(br, 1H), 6.34(s, 1H), 2.37(s,3H). Comparative Examples 1-3 show that when the amount of hydrazine hydrate used is 1.1 eq, the reaction result is the best, the purity and yield of the product are the highest, and the reaction time is gradually prolonged as the amount of hydrazine hydrate used decreases.

[0029] Example 4 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.33 g (0.0143 eq) of benzyltriethylammonium chloride to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 7 hours at 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep at this temperature for 1 hour, filter, and dry the filter cake to obtain 14.4 g of the product. The HPLC purity is 98.6% and the yield is 94.6%.

[0030] Example 5 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.58 g (0.0143 eq) of trioctylmethylammonium chloride to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 7 hours at 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep it at this temperature for 1 hour, filter, and dry the filter cake to obtain 14.5 g of the product. The HPLC purity is 98.5%, and the yield is 95.2%.

[0031] Example 6 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.038 g (0.0143 eq) of dodecyltrimethylammonium chloride to a 100 mL four-necked reaction bottle, and keep the temperature at 20-25 ° C. Slowly drop 6.9 g (1.1 eq) of 80% hydrate into the system, and stir for 7 hours at 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep it at this temperature for 1 hour, filter, and dry the filter cake to obtain 14.6 g of the product. The HPLC purity is 99.0%, and the yield is 96.3%.

[0032] Examples 3-6 compare the effects of different quaternary ammonium salt catalyst types on the reaction results. Tetrabutylammonium bromide, benzyltriethylammonium chloride, trioctylmethylammonium chloride or dodecyltrimethylammonium chloride all have good catalytic effects, among which tetrabutylammonium bromide has the best catalytic effect.

[0033] Comparative Example 1 Under stirring, add 50 mL of water, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.23 g (0.00714 eq) of tetrabutylammonium bromide to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 13 hours at 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep at this temperature for 1 hour, filter, and dry the filter cake to obtain 14.5 g of the product. The HPLC purity is 99.1% and the yield is 95.7%.

[0034] Comparative Example 2 Under stirring, add 50 mL of water and 15.4 g (1 eq) of trifluoroacetylacetone to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 20-25 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 7 hours at a temperature of 20-25 ° C. A large amount of solid is generated in the system. Take a small amount of reaction liquid and extract it with ethyl acetate. The gas phase detection shows that the remaining raw material is 16.7%. Continue to keep warm for 3 hours, and the remaining raw material is basically unchanged by gas phase detection. Cool down to 0-5 ° C for crystallization, keep at this temperature for 1 hour, filter, and recrystallize the filter cake with 1 times 50% ethanol. After drying, 8.1 g of the product is obtained. The HPLC purity is 99.0% and the yield is 53.4%. After testing, the loss yield in the filtrate is about 20%.

[0035] After determining the optimal dosage of hydrazine hydrate and the type of quaternary ammonium salt catalyst, the dosage of the quaternary ammonium salt catalyst was studied. According to the reaction results of Example 3 and Comparative Example 1 and Comparative Example 2, when the dosage of the quaternary ammonium salt is too small (<0.01eq) or not used, the conversion rate of the raw material slows down and the reaction time is prolonged, which is not conducive to industrial amplification production, indicating that the quaternary ammonium salt has a positive effect on improving the raw material conversion rate.

[0036] Comparative Example 3 Under stirring, add 50 mL of ethanol, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.46 g (0.0143 eq) of tetrabutylammonium bromide to a 100 mL four-necked reaction bottle in sequence, and keep the temperature at 25-30 ° C. Slowly add 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% to the system, and stir for 6 hours at a temperature of 25-30 ° C. A large amount of solid is generated in the system. Take a small amount of the reaction solution and extract it with ethyl acetate. The gas phase detection shows that the raw material is completely converted. Cool down to 0-5 ° C for crystallization, keep it at this temperature for 1 hour, filter, and dry the filter cake to obtain 15.0 g of the product. The HPLC purity is 98.3% and the yield is 98.2%.

[0037] Example 3 and Comparative Example 3 use different post-treatment processes, which proves that when 3-methyl-5-trifluoromethylpyrazole is prepared using ethanol as a solvent, the reaction solution is not washed with water, and the water-soluble impurity tetrabutylammonium bromide and excess hydrazine hydrate will affect the product content and yield.

[0038] Example 7 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 1.9 g (0.1 eq) of p-toluenesulfonic acid monohydrate were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 °C and refluxed. Water was taken out of the water separator. When the temperature in the reaction bottle reached the boiling point of toluene (the temperature was 110-111 °C at this time), the mixture was refluxed for 2 hours until no water was evaporated from the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.9 g of the product. The HPLC purity was 99.3%, and the yield was 98.6%.

[0039] The product was tested by HNMR, and the test data were as follows: 1H NMR (400MHz, CDCl3): δ9.87-11.07(br, 1H), 6.34(s, 1H), 2.37(s,3H). Example 8 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 1.0 g (0.05 eq) of p-toluenesulfonic acid monohydrate were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 ° C and began to reflux. Water was taken out of the water separator. When the temperature in the reaction bottle rose to the boiling point of toluene (the temperature was 110-111 ° C at this time), the mixture was refluxed for 2 hours until no water was evaporated in the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.8 g of the product. The HPLC purity was 99.8%, and the yield was 98.4%.

[0040] Example 9 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.6 g (0.03 eq) of p-toluenesulfonic acid monohydrate were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.9 g (1.1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 °C and refluxed. Water was taken out of the water separator. When the temperature in the reaction bottle reached the boiling point of toluene (the temperature was 110-111 °C at this time), the mixture was refluxed for 2 hours until no water was evaporated from the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.8 g of the product. The HPLC purity was 99.7%, and the yield was 98.3%.

[0041] According to the test data of Examples 7 to 9, it can be seen that when p-toluenesulfonic acid monohydrate is used as a catalyst and the catalyst dosage is 0.03 to 0.1 eq, the product purity can reach more than 99% and the yield can reach more than 98%.

[0042] Example 10 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.6 g (0.03 eq) of p-toluenesulfonic acid monohydrate were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.6 g (1.06 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 °C and refluxed. Water was taken out of the water separator. When the temperature in the reaction bottle reached the boiling point of toluene (the temperature was 110-111 °C at this time), the mixture was refluxed for 2 hours until no water was evaporated from the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.9 g of the product. The HPLC purity was 99.5%, and the yield was 98.8%.

[0043] Embodiment 11 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.6 g (0.03 eq) of p-toluenesulfonic acid monohydrate were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.3 g (1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 ° C and began to reflux. Water was taken out of the water separator. When the temperature in the reaction bottle rose to the boiling point of toluene (the temperature was 110-111 ° C at this time), the mixture was refluxed for 2 hours until no water was evaporated in the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.9 g of the product. The HPLC purity was 99.6%, and the yield was 98.9%.

[0044] It can be seen from the test data of Examples 9 to 11 that when the hydrazine hydrate ratio is 1 to 1.1 eq, the purity is maintained at more than 99% and the yield is maintained at more than 98%.

[0045] Example 12 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.3 g (0.03 eq) of 98 wt% concentrated sulfuric acid were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.3 g (1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 ° C and began to reflux. Water was taken out of the water separator. When the temperature in the reaction bottle rose to the boiling point of toluene (the temperature was 110-111 ° C at this time), the mixture was refluxed for 2 hours until no water was evaporated in the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.8 g of the product. The HPLC purity was 99.9%, and the yield was 98.5%.

[0046] Embodiment 13 Under stirring, 100 mL of toluene, 15.4 g (1 eq) of trifluoroacetylacetone, and 0.4 g (0.03 eq) of 75 wt% phosphoric acid were added to a 250 mL four-necked reaction bottle equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.3 g (1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 ° C and began to reflux. Water was taken out of the water separator. When the temperature in the reaction bottle rose to the boiling point of toluene (the temperature was 110-111 ° C at this time), the mixture was refluxed for 2 hours until no water was evaporated in the water separator. The gas phase was sampled for detection. The raw material was completely converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. Toluene was evaporated under reduced pressure to obtain 14.8 g of the product. The HPLC purity was 99.5%, and the yield was 98.1%.

[0047] It can be seen from the test data of Examples 11 to 13 that the yield and content of using sulfuric acid or phosphoric acid as a catalyst are basically the same as those of using p-toluenesulfonic acid monohydrate as a catalyst.

[0048] Comparative Example 4 Under stirring, 100 mL of toluene and 15.4 g (1 eq) of trifluoroacetylacetone were added to a 250 mL four-necked reaction flask equipped with a water separator. The mixture was stirred and dissolved at room temperature. After the mixture was completely dissolved, 6.3 g (1 eq) of hydrazine hydrate with a content of 80% was slowly added dropwise. After the addition was completed, the mixture was heated to 84-85 °C and refluxed. Water was taken out of the water separator. When the temperature in the reaction flask rose to the boiling point of toluene (the temperature was 110-111 °C at this time), the mixture was refluxed for 2 hours until no water was evaporated from the water separator. The raw material remained 13% after sampling for gas phase detection. The mixture was refluxed for 6 hours. The raw material was basically not converted. The mixture was cooled to room temperature, 90 mL of water was added for washing, and toluene was separated. The toluene phase was washed with water twice until the pH was neutral. The toluene was evaporated under reduced pressure. The crude product was crystallized with 50% ethanol to obtain 12.7 g of the product. The HPLC purity was 94.3% and the yield was 79.8%.

[0049] It can be seen from the test data of Comparative Example 4 that when no catalyst is added, the raw material conversion is incomplete and the yield content is low.

[0050] Although the present invention has been described in detail with reference to the accompanying drawings and in combination with the preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, a person of ordinary skill in the art may make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions shall be within the scope of the present invention. Any person of ordinary skill in the art may easily think of changes or substitutions within the technical scope disclosed by the present invention, and these shall be within the scope of protection of the present invention.

Claims

1. A method for synthesizing 3-methyl-5-trifluoromethylpyrazole, It is characterized in that The reaction route is as follows: ； With trifluoroacetylacetone and hydrazine hydrate as the reaction raw materials and quaternary ammonium salt as the catalyst, 3-methyl-5-trifluoromethylpyrazole is reacted in water.

2. The synthesis method according to claim 1, It is characterized in that The quaternary ammonium salt is selected from one or more of tetrabutylammonium bromide, benzyltriethylammonium chloride, trioctylmethylammonium chloride or dodecyltrimethylammonium chloride.

3. The synthesis method according to claim 1 or 2, It is characterized in that The molar ratio of trifluoroacetylacetone to hydrazine hydrate is 1:1-1.

5.

4. The synthesis method according to claim 1 or 2, It is characterized in that The molar ratio of trifluoroacetylacetone to quaternary ammonium salt is 1:0.01-0.

15.

5. The synthesis method according to claim 1 or 2, It is characterized in that The reaction temperature is -15~45℃.

6. A method for synthesizing 3-methyl-5-trifluoromethylpyrazole, It is characterized in that The reaction route is as follows: ； With trifluoroacetylacetone and hydrazine hydrate as reaction raw materials and protonic acid as catalyst, 3-methyl-5-trifluoromethylpyrazole is reacted in an organic solvent immiscible with water.

7. The synthesis method according to claim 6, It is characterized in that The protonic acid is selected from one or more of sulfuric acid, phosphoric acid, and p-toluenesulfonic acid.

8. The synthesis method according to claim 6 or 7, It is characterized in that The water-immiscible organic solvent is selected from toluene or ethylene dichloride.

9. The synthesis method according to claim 6 or 7, It is characterized in that The molar ratio of trifluoroacetylacetone to hydrazine hydrate is 1:1-1.5; the molar ratio of trifluoroacetylacetone to catalyst is 1:0.01-0.

15.

10. The synthesis method according to claim 6 or 7, It is characterized in that The reaction temperature is 0~110℃.

Images