A catalyst for synthesizing difluoropyrazole acid and a preparation method thereof

Abstract

The present invention relates to the field of catalytic technology, and specifically to a catalyst for synthesizing difluoropyrazole acid and a preparation method thereof, which includes a core body and a shell. The core body is CS2CO3, and the shell is a poly(4-vinylpyridine)-transition metal complex. The catalyst of the present invention can directly catalyze the formation of difluoropyrazole acid without going through a bromination reaction, reducing the generation of toxic waste liquid. Moreover, the reaction yield and product purity are relatively high, having certain prospects for industrial application. It also makes full use of CO2, contributing to reducing CO2 emissions and alleviating the greenhouse effect.

Description

Technical Field

[0001] The invention relates to the technical field of catalysis, in particular to a catalyst for synthesizing difluoropyrazole acid and a preparation method thereof. Background Art

[0002] Difluoropyrazole acid, i.e. 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid, is an important chemical raw material and is widely used in the fields of medicine, pesticides, dyes, etc. It can be used to synthesize a variety of drugs, such as antimalarial drugs, antitumor drugs, anti-inflammatory drugs, etc. In the field of pesticides, difluoropyrazole acid can be used to synthesize a variety of insecticides, fungicides, herbicides, etc. In addition, difluoropyrazole acid can also be used to synthesize dyes and pigments. Therefore, difluoropyrazole acid has a wide range of uses and a broad market prospect.

[0003] One of the synthetic routes of difluoropyrazole acid disclosed in the prior art is to use dichloroacetyl chloride, vinyl ether compounds and methylhydrazine as raw materials to synthesize 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid through a five-step reaction. Although this route has certain advantages in cost control, the reaction conditions are relatively harsh. The intermediate product 3-difluoromethyl-1-methylpyrazole must be brominated first and then catalytically pressurized to form a carboxyl group. This not only causes serious pollution and high operating requirements, but also by-products are difficult to separate, and the prospects for industrial application are limited. Summary of the invention

[0004] Purpose of the invention: In view of the above technical problems, the present invention provides a catalyst for the synthesis of difluoropyrazole acid and a preparation method thereof.

[0005] The technical solutions adopted are as follows:

[0006] A catalyst for synthesizing difluoropyrazole acid comprises a core body and a shell body, wherein the core body is Cs2CO3 and the shell body is a poly-4-vinylpyridine-transition metal complex.

[0007] Furthermore, the transition metal is any one of Cu, Zn, Fe, Ni and Co or a combination of any two thereof.

[0008] Furthermore, the transition metal is Ni.

[0009] Furthermore, the preparation method of the 4-vinylpyridine-transition metal complex is as follows:

[0010] A transition metal salt and 4-vinylpyridine are added to anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B are mixed under stirring, and allowed to stand to allow complete complexation. The precipitate is collected, washed, and vacuum dried.

[0011] Furthermore, the molar ratio of the transition metal salt to 4-vinylpyridine is 1:4.

[0012] The present invention also provides a method for preparing a catalyst for synthesizing difluoropyrazole acid, which is as follows:

[0013] Disperse Cs2CO3 in an organic solvent, add 4-vinylpyridine-transition metal complex and free radical initiator, heat to 90-110°C for 1-10 hours, then return to room temperature, collect the product, wash and dry.

[0014] Furthermore, the mass ratio of the Cs2CO3 and 4-vinylpyridine-transition metal complex is 1:0.1-1.

[0015] Furthermore, the organic solvent is benzene, toluene or xylene.

[0016] Furthermore, the free radical initiator is azobisisobutyronitrile and / or azobisisoheptanenitrile.

[0017] Beneficial effects of the present invention:

[0018] The invention provides a catalyst for synthesizing difluoropyrazole acid. Although there are reports on the preparation of aromatic acids by carboxylation of aromatic compounds with CO2, it is rarely used in pyrazole. How to efficiently and selectively realize the carboxylation of carbon-hydrogen bonds in pyrazole is a more difficult problem. In the present application, Cs2CO3 can destroy the carbon-hydrogen bonds in the substrate, i.e., 3-difluoromethyl-1-methylpyrazole, to form carbon anions, which in turn act as nucleophiles to attack weakly electrophilic CO2 to form carbon-carbon single bonds to realize carboxylation. The nitrogen atom of the pyridine ring in the poly-4-vinylpyridine-transition metal complex coordinates with the transition metal center through lone pairs of electrons to form coordination bonds. In this process, the metal center acts as an electron pair. The acceptor directly exhibits Lewis acidity, can activate CO2 and promote the formation of carboxyl groups in the reaction process, and this process can only realize the direct carboxylation reaction of aromatic substrates with strong carbon-hydrogen bond acidity, such as pyrazole, but cannot complete the direct carboxylation reaction for pyridine. It is found through testing that a single poly 4-vinylpyridine-transition metal complex does not have catalytic activity. The catalyst of the present invention can directly catalyze the formation of difluoropyrazole acid without the need for bromination reaction, thereby reducing the generation of toxic waste liquid, and the reaction yield and product purity are relatively high, having certain industrial application prospects, and making full use of CO2, thus contributing to reducing CO2 emissions and alleviating the greenhouse effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The synthetic route of difluoropyrazole acid disclosed in the prior art;

[0020] Figure 2 The synthetic route of difluoropyrazole acid in Example 1 is shown in FIG. DETAILED DESCRIPTION

[0021] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or the conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially. The techniques not mentioned in the present invention are all referenced to the prior art. Unless otherwise specified, the following examples and comparative examples are parallel experiments, using the same processing steps and parameters.

[0022] Embodiment 1:

[0023] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0024] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0025] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 1 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 °C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0026] The synthesis method of difluoropyrazole acid is as follows:

[0027] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was kept warm for 5 hours. After the reaction was completed, the reaction was cooled to room temperature, and the CO2 gas in the reactor was emptied. The reaction liquid was filtered, and deionized water was added to the collected filtrate. After being fully mixed, the mixture was allowed to stand for stratification, and the aqueous phase was separated. The pH of the aqueous phase was adjusted to 1 to allow crystallization, and the mixture was filtered again. The precipitated product was collected, washed with deionized water, and then dried in vacuo. See Figure 2 , reaction yield 73.4%, content 98.2% (HPLC).

[0028] Embodiment 2:

[0029] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0030] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0031] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 2 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 °C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0032] The synthesis method of difluoropyrazole acid is as follows:

[0033] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was vented. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was fully mixed and allowed to stand for stratification, and the aqueous phase was separated. The pH of the aqueous phase was adjusted to 1 to allow crystallization, and the mixture was filtered again. The precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 73.6%, and the content was 98.5% (HPLC).

[0034] Embodiment 3:

[0035] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0036] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0037] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 3 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 °C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0038] The synthesis method of difluoropyrazole acid is as follows:

[0039] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification, and the aqueous phase was separated. The pH of the aqueous phase was adjusted to 1 to allow crystallization, and the mixture was filtered again. The precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 75.1%, and the content was 98.9% (HPLC).

[0040] Embodiment 4:

[0041] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0042] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0043] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 4 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 ° C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0044] The synthesis method of difluoropyrazole acid is as follows:

[0045] 13.21g of 3-difluoromethyl-1-methylpyrazole and 1.5g of the above catalyst were added to a high-pressure reactor, and 100ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5MPa. The pressure was maintained and the temperature was raised to 180℃ and then the reaction was kept warm for 5h. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was fully mixed and allowed to stand for stratification, and the aqueous phase was separated. The pH of the aqueous phase was adjusted to 1 to allow crystallization, and the mixture was filtered again. The precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 75.3% and the content was 99.1% (HPLC).

[0046] Embodiment 5:

[0047] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0048] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0049] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 5 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 °C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0050] The synthesis method of difluoropyrazole acid is as follows:

[0051] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification. The aqueous phase was separated, and the pH of the aqueous phase was adjusted to 1 to allow crystallization. The product was filtered again, the precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 76.1%, and the content was 99.2% (HPLC).

[0052] Embodiment 6:

[0053] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0054] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0055] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 6 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 ° C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0056] The synthesis method of difluoropyrazole acid is as follows:

[0057] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification. The aqueous phase was separated, and the pH of the aqueous phase was adjusted to 1 to allow crystallization. The product was filtered again, and the precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 76.2%, and the content was 99.2% (HPLC).

[0058] Embodiment 7:

[0059] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0060] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0061] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 7 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 ° C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0062] The synthesis method of difluoropyrazole acid is as follows:

[0063] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification. The aqueous phase was separated, and the pH of the aqueous phase was adjusted to 1 to allow crystallization. The product was filtered again, and the precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 75.5%, and the content was 98.4% (HPLC).

[0064] Embodiment 8:

[0065] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0066] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0067] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 8 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 ° C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0068] The synthesis method of difluoropyrazole acid is as follows:

[0069] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was fully mixed and allowed to stand for stratification, and the aqueous phase was separated. The pH of the aqueous phase was adjusted to 1 to allow crystallization, and the mixture was filtered again. The precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 75.2%, and the content was 98.3% (HPLC).

[0070] Embodiment 9:

[0071] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0072] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0073] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 9 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 °C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0074] The synthesis method of difluoropyrazole acid is as follows:

[0075] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification. The aqueous phase was separated, and the pH of the aqueous phase was adjusted to 1 to allow crystallization. The product was filtered again, the precipitated product was collected, washed with deionized water, and then dried in vacuo. The reaction yield was 75.0%, and the content was 97.2% (HPLC).

[0076] Embodiment 10:

[0077] A catalyst for synthesizing difluoropyrazole acid, comprising a core and a shell, wherein the core is Cs2CO3 and the shell is a poly-4-vinylpyridine-nickel complex;

[0078] The preparation method of the above-mentioned difluoropyrazole acid synthesis catalyst is as follows:

[0079] 10 mmol and 40 mmol of nickel chloride hexahydrate and 4-vinylpyridine were added to 50 ml of anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B were mixed under stirring and allowed to stand at room temperature for 5 h to complete the complexation. The precipitate was collected by filtration, washed with anhydrous ethanol and then dried in vacuum to obtain 4-vinylpyridine-nickel complex. 10 g of Cs2CO3 was dispersed in 100 ml of xylene, and 10 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile were added. The mixture was heated to 100 ° C for reaction for 5 h and then returned to room temperature. The product was collected, washed with anhydrous ethanol and then dried in vacuum.

[0080] The synthesis method of difluoropyrazole acid is as follows:

[0081] 13.21 g of 3-difluoromethyl-1-methylpyrazole and 1.5 g of the above catalyst were added to a high-pressure reactor, and 100 ml of xylene was used as the reaction medium. The high-pressure reactor was sealed and CO2 gas was introduced to make the pressure in the reactor 1.5 MPa. The pressure was maintained and the temperature was raised to 180°C and then the reaction was maintained for 5 hours. After the reaction was completed, it was cooled to room temperature, and the CO2 gas in the reactor was evacuated. The reaction liquid was filtered, deionized water was added to the collected filtrate, and the mixture was mixed thoroughly and allowed to stand for stratification. The aqueous phase was separated, and the pH of the aqueous phase was adjusted to 1 to allow crystallization. The product was filtered again, and the precipitated product was collected, washed with deionized water, and dried in vacuo. The reaction yield was 75.0%, and the content was 97.1% (HPLC).

[0082] Comparative Example 1:

[0083] The method is substantially the same as Example 1, except that 1.5 g of Cs2CO3 is added as a catalyst;

[0084] The synthesis method of difluoropyrazole acid was the same as that of Example 1, with a reaction yield of 37.5% and a content of 94.9% (HPLC).

[0085] Comparative Example 2:

[0086] The process is substantially the same as Example 1, except that 1.5 g of poly-4-vinylpyridine-nickel complex is added as a catalyst.

[0087] The preparation method of poly 4-vinylpyridine-nickel complex is as follows:

[0088] Add 10 g of 4-vinylpyridine-nickel complex and 0.01 g of azobisisobutyronitrile into 100 ml of xylene, heat to 100°C and react for 5 hours, then return to room temperature. Collect the product, wash with anhydrous ethanol and dry in vacuum.

[0089] The synthesis method of difluoropyrazole acid was the same as in Example 1, but no reaction occurred and no product was detected.

[0090] By comparing Examples 1-10, it can be seen that changing the mass ratio of Cs2CO3 to 4-vinylpyridine-nickel complex will affect the reaction yield and product purity. When the mass ratio of Cs2CO3 to 4-vinylpyridine-nickel complex is 1:0.6, the reaction yield and product purity are the highest.

[0091] By comparing Example 1 with Comparative Example 1, it can be seen that the reaction yield and product purity of using Cs2CO3 alone as a catalyst are far inferior to those of the catalyst prepared in Example 1 of the present invention;

[0092] By comparing Example 1 with Comparative Example 1, it can be seen that the carboxylation reaction cannot occur when the poly-4-vinylpyridine-nickel complex is used alone as a catalyst.

[0093] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A catalyst for the synthesis of difluoropyrazole acid, characterized in that: The invention comprises a core body and a shell body, wherein the core body is Cs2CO3 and the shell body is a poly-4-vinylpyridine-transition metal complex.

2. The catalyst for synthesis of difluoropyrazole acid as claimed in claim 1, characterized in that The transition metal is any one of Cu, Zn, Fe, Ni and Co or a combination of any two thereof.

3. The catalyst for synthesis of difluoropyrazole acid as claimed in claim 2, characterized in that The transition metal is Ni.

4. The catalyst for synthesis of difluoropyrazole acid as claimed in claim 1, characterized in that The preparation method of the 4-vinylpyridine-transition metal complex is as follows: A transition metal salt and 4-vinylpyridine are added to anhydrous ethanol to obtain solution A and solution B respectively. Solution A and solution B are mixed under stirring, and allowed to stand to allow complete complexation. The precipitate is collected, washed, and vacuum dried.

5. The catalyst for synthesis of difluoropyrazole acid as claimed in claim 4, characterized in that The molar ratio of the transition metal salt to 4-vinylpyridine is 1:

4.

6. A method for preparing a catalyst for synthesizing difluoropyrazole acid as claimed in any one of claims 1 to 5, characterized in that: The details are as follows: Disperse Cs2CO3 in an organic solvent, add 4-vinylpyridine-transition metal complex and free radical initiator, heat to 90-110°C for 1-10 hours, then return to room temperature, collect the product, wash and dry.

7. The method for preparing a catalyst for synthesizing difluoropyrazole acid as claimed in claim 6, characterized in that: The mass ratio of the Cs2CO3 and 4-vinylpyridine-transition metal complex is 1:0.1-1.

8. The method for preparing a catalyst for synthesizing difluoropyrazole acid as claimed in claim 6, characterized in that: The organic solvent is benzene, toluene or xylene.

9. The method for preparing a catalyst for synthesizing difluoropyrazole acid as claimed in claim 6, characterized in that: The free radical initiator is azobisisobutyronitrile and / or azobisisoheptanenitrile.

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