A process for the preparation of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol

Abstract

The application belongs to the technical field of organic synthesis and particularly relates to a preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, which comprises the following steps: (1) adding acid into a reaction container, adding 40% methylhydrazine aqueous solution and stirring uniformly; (2) adding trifluoroacetyl acetic acid ethyl ester dropwise into the reaction system of step (1), heating after dropwise addition is completed, performing heat preservation reaction and monitoring the reaction by TLC; (3) after the reaction is completed, adding water into the reaction system of step (2) to perform crystallization, performing suction filtration after cooling, washing the filter cake with water and drying to obtain 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, and purifying to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol. The application has the beneficial effect that by controlling the feeding sequence, the acid amount and the reaction temperature, the methylhydrazine addition amount is reduced, methylhydrazine is avoided from being left in waste water, and thus the treatment difficulty of waste water is reduced.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol. BACKGROUND

[0002] Metrafenone, also known as Roket, belongs to a new type of pyrazole selective herbicide, is a new type of pre-emergence herbicide, can interfere with the elongation of C18 chain, inhibit the synthesis of very long chain fatty acids (VLCFA), mainly absorbed into target plants through plant roots or apical meristem, and is mainly effective on annual grass weeds and some broadleaf weeds.

[0003] 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is an important intermediate for synthesizing metrafenone, and the existing preparation method uses ethyl trifluoroacetylacetate and methyl hydrazine as raw materials to perform condensation and cyclization reactions. A large excess of methyl hydrazine is usually required in the reaction process, however, methyl hydrazine has high toxicity, a large amount of methyl hydrazine remains in wastewater, which increases the difficulty of wastewater treatment and also causes harm to the environment; in addition, the reaction time of ethyl trifluoroacetylacetate and methyl hydrazine is long, the reaction yield is low, the selectivity of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is low, and there are many isomer impurities, resulting in low product purity. SUMMARY

[0004] The application provides a preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol.

[0005] The application relates to a preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol.

[0006] (1) adding acid into a reaction container, then adding 40% methyl hydrazine aqueous solution, and stirring uniformly;

[0007] (2) adding ethyl trifluoroacetylacetate dropwise into the reaction system in step (1), after the dropwise addition is completed, heating, then performing heat preservation reaction, and monitoring the reaction through TLC;

[0008] (3) after the reaction is completed, adding water into the reaction system in step (2) to perform crystallization, after cooling, performing suction filtration, washing the filter cake with water, and drying to obtain 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, then performing purification to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol;

[0009] The synthesis route is as follows:

[0010] .

[0011] As preferred, in the step (1), the molar ratio of methylhydrazine to acid is 1:0.4-0.6; the acid is at least one of glacial acetic acid, sulfuric acid, formic acid, phosphoric acid and hydrochloric acid.

[0012] As preferred, in the steps (1) and (2), the molar ratio of ethyl trifluoroacetylacetate to methylhydrazine is 1:1-1.05.

[0013] As preferred, in the step (2), the temperature is controlled at 40-60°C during the dropwise addition of ethyl trifluoroacetylacetate.

[0014] As preferred, in the step (2), the temperature is first raised to 60-90°C; and the reaction is kept at 60-90°C for 1-3 hours.

[0015] As preferred, in the step (3), the water used for crystallization has a mass of 0.5-1.5 times the mass of ethyl trifluoroacetylacetate in the step (2).

[0016] As preferred, in the step (3), the purification method is as follows:

[0017] The crude 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol and water are added to a reaction vessel, and then an inorganic base is added under stirring until completely dissolved. The organic solvent is extracted 1-3 times, and the organic phase is recycled. The water phase is combined and then an inorganic acid is added to adjust the pH value. Filtration is performed, the filter cake is washed with water, and the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is obtained by drying.

[0018] As preferred, the mass of the crude 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is measured in grams, the volume of water added is measured in milliliters, and the volume of water added is 1.6-2.0 times the mass of the crude 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol. The volume ratio of the organic solvent to water used in extraction is 1:1. The molar ratio of the crude 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, the inorganic base and the inorganic acid is 1:1:1.

[0019] The organic solvent is one of dichloromethane, ethyl acetate and methyl tert-butyl ether. The inorganic base is one of sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate. The inorganic acid is one of hydrochloric acid and sulfuric acid.

[0020] As preferred, in the step (3), the purification method is as follows:

[0021] The reaction vessel is added with 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, then added with an organic solvent, stirred at room temperature for 40-80 min, filtered, and the filter cake is washed with the organic solvent and dried to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol.

[0022] Preferably, the mass of the 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product is measured in grams, the volume of the added organic solvent is measured in milliliters, and the volume of the added organic solvent is 1.6-2.0 times the mass of the 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product.

[0023] Preferably, the organic solvent is one of dichloromethane and dichloroethane.

[0024] Compared with the prior art, the present application has the following advantages and positive effects:

[0025] (1) The preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol avoids a large amount of methylhydrazine remaining in the wastewater, thereby reducing the difficulty of wastewater treatment and reducing the harm of methylhydrazine to the environment.

[0026] (2) The preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol has a short reaction time, high reaction yield, and high product purity, thereby reducing the time cost and raw material cost and facilitating large-scale industrial production.

[0027] (3) The preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol has mild reaction conditions, thereby making the reaction process easier to control, improving the safety of large-scale production, and reducing the influence of scaling up to industrial production on the reaction performance. DETAILED DESCRIPTION

[0028] In order to more clearly understand the above-mentioned purposes, features and advantages of the present application, the present application will be further described below in conjunction with examples.

[0029] In the following description, a large number of specific details are set forth in order to provide a thorough understanding of the present application, however, the present application can also be implemented in other ways different from those described herein, and therefore, the present application is not limited to the specific examples disclosed in the following description.

[0030] Example 1

[0031] A preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, characterized by comprising the following steps: A preparation method of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, characterized by comprising the following steps:

[0032] (1) Add 31 g (0.516 mol) of glacial acetic acid to a reaction bottle, then add 84 g (1.048 mol) of 40% methylhydrazine aqueous solution, and start stirring.

[0033] (2) Control the temperature at 40°C, and add 184 g (0.999 mol) of ethyl trifluoroacetylacetate to the reaction system of step (1) dropwise, complete the dropwise addition within 1 h, increase the temperature to 80°C, and perform incubation reaction at 80°C for 2 h, and monitor the reaction by TLC.

[0034] (3) After the reaction is completed, 100 ml of water is added to the reaction system of step (2) and stirred for 0.5 h, cooled to 25°C, and then filtered, the filter cake is washed with 100 ml of water slurry twice, and dried to obtain 158.96 g (0.957 mol) of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, with a yield of 95.8% and a purity of 99.3%; and after purification, the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is obtained.

[0035] Purification method: 158.96 g (0.957 mol) of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product and 300 ml of water are added to a reaction bottle, 38.28 g (0.957 mol) of sodium hydroxide is added under stirring, and after stirring until completely dissolved, 300 ml of dichloromethane is added for extraction twice, the dichloromethane phase is recycled, and the water phase is combined and then 34.89 g (0.957 mol) of hydrochloric acid is added, and after the solid is precipitated, filtration is performed, the filter cake is washed with water, and dried to obtain 157.69 g of the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, with a purity of 99.9%.

[0036] Example 2

[0037] The difference between this embodiment and example 1 is that:

[0038] Purification method: 158.96 g (0.957 mol) of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product and 300 ml of dichloroethane are added to a reaction bottle, stirred at room temperature for 60 min, filtered, the filter cake is washed with dichloroethane, and then dried to obtain 157.37 g of the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, with a purity of 99.8%.

[0039] Example 3

[0040] A method for preparing 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, characterized in that it comprises the following steps:

[0041] (1) Add 21.88 g (0.6 mol) of hydrochloric acid into a reaction bottle, then add 80.15 g (1 mol) of 40% methylhydrazine aqueous solution, and start stirring.

[0042] (2) Control the temperature at 55°C, and add 184.11 g (1 mol) of ethyl trifluoroacetylacetate into the reaction system of step (1) dropwise, complete the dropwise addition within 1 h, increase the temperature to 90°C, and perform incubation reaction at 90°C for 1.5 h, and monitor the reaction by TLC.

[0043] (3) After the reaction is completed, add 100 ml of water into the reaction system of step (2) and stir for 0.5 h, cool to 25°C, and then perform suction filtration, wash the filter cake with 100 ml of water slurry twice, and dry to obtain 159.62 g (0.96 mol) of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, with a yield of 96.1% and a purity of 99.5%; and after purification, the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol is obtained.

[0044] Purification method: add 159.62 g (0.96 mol) of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product and 300 ml of water into a reaction bottle, add 53.9 g (0.96 mol) of potassium hydroxide under stirring, stir until completely dissolved, extract twice with 300 ml of ethyl acetate, recycle the ethyl acetate phase, combine the water phases, add 94.2 g (0.96 mol) of sulfuric acid, and then perform suction filtration after the solid is precipitated, wash the filter cake with water, and dry to obtain 159.14 g of the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, with a purity of 99.8%.

[0045] The above description is only the preferred embodiment of the present application, and is not intended to limit the present application in other forms. Any person skilled in the art can modify or change the above disclosed technical content to equivalent embodiments applied to other fields, but any simple modification, equivalent change, or application in other fields based on the technical essence of the present application to the above embodiments, which does not deviate from the technical solution content of the present application, still belongs to the protection scope of the technical solution of the present application.

Claims

1. A process for the preparation of 1-methyl-3-(trifluoromethyl)-1 H-pyrazol-5-ol, characterized in that, The method comprises the following steps: (1) adding acid into a reaction container, then adding 40% methylhydrazine aqueous solution, and stirring uniformly; (2) adding ethyl trifluoroacetylacetate into the reaction system of step (1) dropwise, heating after dropwise addition is completed, then carrying out heat preservation reaction, and monitoring the reaction by TLC; (3) after the reaction is completed, adding water into the reaction system of step (2) to crystallize, carrying out suction filtration after cooling, washing the filter cake with water, and drying to obtain 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, then carrying out purification to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol; The synthesis route is as follows: ； In the step (1), the molar ratio of methylhydrazine to acid is 1:0.4-0.6; the acid is at least one of glacial acetic acid, sulfuric acid, formic acid, phosphoric acid and hydrochloric acid; In the steps (1) and (2), the molar ratio of ethyl trifluoroacetylacetate to methylhydrazine is 1:1-1.05; In the step (2), the temperature is first increased to 60-90 ℃; the heat preservation reaction is carried out at 60-90 ℃ for 1-3 h.

2. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 1, characterized in that, In the step (2), the temperature is controlled at 40-60 ℃ during the process of adding ethyl trifluoroacetylacetate dropwise.

3. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 1, characterized in that, In the step (3), the mass of water used for crystallization is 0.5-1.5 times the mass of ethyl trifluoroacetylacetate in step (2).

4. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 1, characterized in that, In the step (3), the method for purification is as follows: adding 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product and water into a reaction container, then adding inorganic base under stirring, dissolving completely, adding organic solvent for extraction 1-3 times, recycling the organic phase, combining the water phase, adding inorganic acid to adjust the pH value, carrying out suction filtration, washing the filter cake with water, and drying to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol.

5. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 4, characterized in that, The mass of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product is measured in grams, the volume of water added is measured in milliliters, and the volume of water added is 1.6-2.0 times the mass of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product; the volume ratio of organic solvent to water added during extraction is 1:1; the molar ratio of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product, inorganic base and inorganic acid is 1:1:1; The organic solvent is one of dichloromethane, ethyl acetate and methyl tert-butyl ether; the inorganic base is one of sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate; and the inorganic acid is one of hydrochloric acid and sulfuric acid.

6. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 1, characterized in that, In the step (3), the method for purification is as follows: adding 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product into a reaction container, then adding organic solvent, stirring at room temperature for 40-80 min, carrying out suction filtration, washing the filter cake with organic solvent, and drying to obtain the final product 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol.

7. The process for the preparation of l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-ol according to claim 6, characterized in that, The mass of the 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product is in grams, the volume of the organic solvent added is in milliliters, and the volume of the organic solvent added is 1.6-2.0 times the mass of the 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol crude product; The organic solvent is one of dichloromethane and dichloroethane.

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