Method for preparing 1-(4-chlorphenyl)-3-pyrazole alcohol

Abstract

The invention discloses a method for preparing 1-(4-chlorphenyl)-3-pyrazole alcohol, and belongs to the technical field of organic synthesis and catalysis. According to the method, CeO2-CuO / TiO2 is used for catalyzing oxygen to oxidize 1-(4-chlorphenyl) pyrazolidine-3-ketone to prepare 1-(4-chlorphenyl)-3-pyrazole alcohol, after the reaction time is 2.0-8.0 h under the conditions that the initial pressure of oxygen is 3 MPa and the reaction temperature is 120-180 DEG C, pressure relief is conducted, a catalyst is filtered out and reused, an obtained filtrate is distilled to remove a reaction solvent and byproduct water, then a crude product is obtained, and the 1-(4-chlorphenyl)-3-pyrazole alcohol is obtained. The yield of the product is 94.5%-98.6%, and the purity of the product is 99.2%-99.6%. Compared with the traditional method, the CeO2-CuO / TiO2 catalyst used in the invention realizes efficient catalysis by virtue of the synergistic effect of CeO2 and CuO, can realize high yield of the reaction and high selectivity of the target product under mild reaction conditions, and has good reusability.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and catalysis, specifically to a method for preparing 1-(4-chlorophenyl)pyrazolol by CeO2-CuO / TiO2 catalytic air oxidation of 1-(4-chlorophenyl)pyrazolidine-3-one. Background Technology

[0002] 1-(4-Chlorophenyl)-3-pyrazol is an important intermediate in the synthesis of pyraclostrobin, a broad-spectrum and highly effective fungicide of the methyl methacrylate class containing pyrazolium structure. It exhibits low toxicity and residue, safety to non-target organisms, and environmental friendliness, making it a promising candidate for industrial applications. Traditional preparation methods primarily rely on oxidants (such as hydrogen peroxide and potassium permanganate) or metal salt catalysts (such as potassium ferrocyanide), but these technologies have significant drawbacks. For example, Chinese patent CN111018785A discloses a method for synthesizing the target product using chloroacetaldehyde and ethylene glycol as raw materials through cyanide reaction, hydrolysis, amidation, and cyclization steps. While this method can yield products with a yield of over 90% and a purity of over 96%, it has significant limitations. Potassium ferrocyanide and trimethylsilyl cyanide, among other cyanides, are highly toxic, posing safety risks during storage, transportation, and reaction. This could increase the burden of waste treatment, complicate production steps, prolong the production cycle, and raise industrial production costs. Chinese patent CN105968048B successfully prepared 1-(4-chlorophenyl)-3-pyrazol using p-bromochlorobenzene and hydrazine hydrate as raw materials. While this method improves wastewater discharge, the oxidation step relies on hydrogen peroxide as an oxidant. Hydrogen peroxide easily decomposes under high-temperature reaction conditions, generating oxygen, which may cause pressure fluctuations in the reaction system, posing a safety hazard. Furthermore, its storage requires strict control of temperature and light conditions, increasing process complexity. In addition, the cyclization step uses toluene as a solvent. Toluene is volatile and toxic, posing a health hazard to operators and requiring additional solvent recovery and treatment processes, potentially causing environmental pollution.

[0003] Based on this, the present invention proposes a method for preparing 1-(4-chlorophenyl)-3-pyrazolol, namely, the oxidation of 1-(4-chlorophenyl)pyrazolidine-3-one to 1-(4-chlorophenyl)-3-pyrazolol under mild air conditions using CeO2-CuO / TiO2 catalysis. The CeO2-CuO / TiO2 catalyst exhibits significant advantages in air oxidation reactions, mainly due to the synergistic effect between its components (CeO2, CuO, TiO2) and the resulting excellent performance. Its core advantages include: strong oxygen storage and release capacity (OSC) of CeO2, and CeO2 being able to […]. 3+ and Ce 4+ The reversible conversion between the two can store and release lattice oxygen (O). 2- CuO exhibits excellent oxidation activity, providing the main catalytic active sites (Cu);2+ / Cu + It readily adsorbs and activates gaseous oxygen molecules (O2), converting them into reactive oxygen species (such as O2). - O2 - CeO2 and CuO are in close contact and form a strong interaction (Ce-O-Cu structure). This interface greatly promotes the migration and transfer of oxygen species between CeO2 (oxygen reservoir) and CuO (active sites), enhances the dispersion and stability of CuO species, prevents sintering, exposes more active sites, and improves the overall performance of Cu. 2+ / Cu + The efficiency of the redox cycle is crucial for activating O2 and initiating oxidation reactions, enhancing the overall electron transfer capacity of the catalyst. Simultaneously, TiO2, as a support, possesses a large specific surface area, good mechanical strength, and thermal stability, providing a highly dispersed platform for CeO2 and CuO particles, preventing sintering and growth during the reaction. High dispersion translates to more CeO2-CuO interfaces and exposed Cu active sites, significantly improving the catalyst's specific activity. Furthermore, the surface of the TiO2 support typically contains oxygen vacancies, which also contribute to the catalyst's activity. The catalyst exhibits strong oxygen activation capabilities, with CeO2 promoting O2 activation to drive the oxidation reaction through reactive oxygen species, while CuO provides redox sites to accelerate electron transfer, synergistically enhancing the oxidation capacity with CeO2. The high specific surface area TiO2 support stabilizes and disperses the active phase, promoting substrate adsorption and mass transfer. After the reaction, the resulting filtrate is distilled and recrystallized to obtain 1-(4-chlorophenyl)-3-pyrazolol, with a product purity of 99.2%-99.6% and a yield of 94.5%-98.6%. The catalyst is recovered and recycled through simple filtration (repeated 16 times with a yield still reaching 97.2%). This invention achieves efficient and green synthesis of 1-(4-chlorophenyl)-3-pyrazolol through the functional integration of catalysts. Summary of the Invention

[0004] This invention addresses the shortcomings of traditional processes, such as high safety risks and heavy waste treatment pressure due to reliance on highly toxic cyanides like potassium ferrocyanide, or the difficulty in controlling the reaction, numerous side reactions, and large amounts of waste generated when using hydrogen peroxide as an oxidant. It proposes a method for preparing 1-(4-chlorophenyl)pyrazolol by catalytic oxidation of 1-(4-chlorophenyl)pyrazolidine-3-one with oxygen under mild conditions using a CeO2-CuO / TiO2 catalyst.

[0005] Based on the above, the present invention relates to a method for preparing 1-(4-chlorophenyl)-3-pyrazolol, characterized in that CeO2-CuO / TiO2 is used as a catalyst and oxygen as an oxidant to catalyze the oxidation reaction of 1-(4-chlorophenyl)pyrazolidine-3-one to prepare 1-(4-chlorophenyl)-3-pyrazolol, wherein the mass ratio of CeO2-CuO / TiO2 to 1-(4-chlorophenyl)pyrazolidine-3-one is 1:10-1:50, and 1-(4-chlorophenyl)pyrazolidine-3-one is used. The mass ratio of alkyl-3-one to reaction solvent is 1:5-1:10, the initial oxygen pressure is 3 MPa, the reaction temperature is 120-180℃, and the reaction time is 2.0-8.0 h. After the reaction is completed, the pressure is released, the catalyst is filtered out and reused, and the resulting filtrate is distilled to remove the reaction solvent and by-product water to obtain the crude product. Then, it is recrystallized in a 30%-50% methanol aqueous solution to obtain the product. The yield is 94.5%-98.6%, and the purity is 99.2%-99.6%.

[0006] The invention is characterized in that the TiO2 has a multi-dimensional porous structure with a specific surface area of ​​386-550 m². 2 / g, the mass ratio of CeO2, CuO, and TiO2 is 1:1:80-1:1:10. The filtered catalyst can be directly reused without the need for new catalyst. Even after 16 reuses, the product yield can still reach 97.2% and the purity is 99.4%.

[0007] The present invention is characterized in that the reaction solvent is one of acetone, methyl isobutyl ketone, dioxane, and tetrahydrofuran.

[0008] The present invention is characterized by the following method for preparing TiO2: 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia are mixed at room temperature until homogeneous. 1.6-3.2 g of template agent is added, and the mixture is stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate is slowly added dropwise at room temperature. After the addition is complete, the mixture is stirred for 2.0 h until it becomes a milky white gel. The mixture is then transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After the reaction, the mixture is cooled to room temperature, centrifuged at high speed, and the supernatant is discarded. The white precipitate is washed with deionized water until neutral. The precipitate is placed in a vacuum drying oven and vacuum dried at 60 °C for 6.0 h. The dried sample is then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, thus obtaining porous TiO2 with a specific surface area of ​​386-550 m². 2 / g; the chemical structural formula of the template agent is C m H (2m+1) -N + (CH3)2-C n H 2n -N +(CH3)2-C m H (2m+1) ·2X - Where m is an integer from 6 to 16, n is an integer from 4 to 12, and X is either Br or OH. The specific surface area of ​​the prepared TiO2 can be controlled by the values ​​of m and n and the amount of template agent.

[0009] The present invention is characterized in that the optimal preparation method of the catalyst CeO2-CuO / TiO2 is as follows: take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at a temperature of 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.

[0010] This invention solves this technical problem through the following technical solution:

[0011] CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO, and TiO2 of 1:1:10 (TiO2 has a specific surface area of ​​550 m²) 2 Taking (g) as the catalyst and acetone as the oxidation reaction solvent as an example, the specific technical solution is explained below:

[0012] Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and mix thoroughly at room temperature. Add 3.2 g of template agent (chemical structural formula C). 16 H 33 -N + (CH3)2-C 12 H 24 -N + (CH3)2-C 16 H 33 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​550 m². 2 / g porous TiO2 support.

[0013] Take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.

[0014] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove acetone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 98.6%, and the purity was 99.6%.

[0015] Compared with the prior art, the present invention has the following significant advantages:

[0016] 1. Construct a CeO2-CuO / TiO2 composite system to achieve efficient substrate conversion through the synergistic effect of the three components, reduce excessive oxidation byproducts from the source, and solve the problems of excessive byproducts and high purification costs in traditional processes.

[0017] 2. After the reaction is complete, the CeO2-CuO / TiO2 catalyst can be recovered by simple filtration and reused directly without additional treatment, overcoming the problems of short lifespan, frequent replenishment, and high cost of waste treatment of traditional catalysts.

[0018] 3. The reaction does not require toxic oxidants, the conditions are mild and easy to control, effectively reducing side reactions, lowering safety risks, and the process is green and environmentally friendly. Detailed Implementation

[0019] The method of the present invention will be further described below with reference to embodiments, but this is not intended to limit the present invention.

[0020] Example 1: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 3.2 g of template agent (chemical structural formula C). 16 H 33 -N +(CH3)2-C 12 H 24 -N + (CH3)2-C 16 H 33 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​550 m². 2 / g porous TiO2 support.

[0021] Take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.

[0022] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove acetone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 98.6%, and the purity was 99.6%.

[0023] Comparative Example 1: The difference between this comparative example and the example is that the catalyst used in the comparative example is an unloaded CeO2-CuO composite oxide. The specific steps are as follows: 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone and 0.25g of CeO2-CuO composite oxide as catalyst (the mass ratio of CeO2 to CuO in the catalyst CeO2-CuO is 1:1) are loaded into the reaction vessel. After sealing the reaction vessel, oxygen is introduced to replace it 3 times, and the initial oxygen pressure is adjusted to 3MPa. Stirring is started and the temperature is raised to 160°C and maintained at this temperature for 6.0h. After the reaction is completed, the pressure is released to atmospheric pressure, the filter cake is collected by filtration, and the filtrate is distilled at atmospheric pressure to remove acetone and by-product water, and a pale yellow solid crude product is obtained. The crude product is added to a 40% mass concentration methanol aqueous solution and recrystallized to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield is 68.5% and the purity is 71.3%.

[0024] Comparative Example 2: The difference between this comparative example and the example is that the comparative example uses a specific surface area of ​​550 m². 2 The oxidation reaction was catalyzed by porous TiO2 as a catalyst, and the specific steps were as follows: 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 0.25g of TiO2 catalyst were loaded into a reaction vessel. After sealing the reaction vessel, oxygen was introduced to replace the acetone three times, and the initial oxygen pressure was adjusted to 3MPa. Stirring was started and the temperature was raised to 160℃ and maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove acetone and water by-product, resulting in a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. Then, it was slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain pale yellow crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 54.3% and the purity was 85.0%.

[0025] Comparative Example 3: The difference between this comparative example and the example is that the comparative example uses hydrogen peroxide as an oxidant to directly carry out the oxidation reaction. The specific steps are as follows: 10g of 1-(4-chlorophenyl)pyrazolidine-3-one and 1.5 times the molar amount of hydrogen peroxide of 1-(4-chlorophenyl)pyrazolidine-3-one were loaded into a reaction vessel. After sealing the reaction vessel, nitrogen gas was introduced to purge the mixture three times. The mixture was stirred and heated to 160°C, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, and the reaction solution was distilled at atmospheric pressure to remove acetone, by-product water, and unreacted hydrogen peroxide, resulting in a pale yellow crude solid. The crude product was added to a 40% (w / w) methanol aqueous solution, heated to 60°C and stirred until completely dissolved. Then, it was slowly cooled to room temperature and allowed to stand for crystallization for 4.0h. The crystallization solution was filtered to obtain dark yellow crystals, which were dried under vacuum at 60°C for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 55.8%, and the purity was 78.3%.

[0026] Comparative Example 4: The difference between this comparative example and the example is that the comparative example uses hydrogen peroxide as an oxidant to directly carry out the oxidation reaction. The specific steps are as follows: 10g of 1-(4-chlorophenyl)pyrazolidine-3-one and 1.5 times the molar amount of hydrogen peroxide of 1-(4-chlorophenyl)pyrazolidine-3-one were loaded into a reaction vessel. After sealing the reaction vessel, nitrogen gas was introduced to purge the mixture three times. The mixture was stirred and heated to 80°C, and the reaction was maintained at this temperature for 4.0h. After the reaction was completed, the pressure was released, and the reaction solution was distilled at atmospheric pressure to remove acetone, by-product water, and unreacted hydrogen peroxide, resulting in a pale yellow crude solid. The crude product was added to a 40% (w / w) methanol aqueous solution, heated to 60°C and stirred until completely dissolved. Then, it was slowly cooled to room temperature and allowed to stand for crystallization for 4.0h. The crystallization solution was filtered to obtain yellow crystals, which were dried under vacuum at 60°C for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 82.0%, and the purity was 94.3%.

[0027] Example 2: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 1.6 g of template agent (chemical structural formula C6H). 13 -N + (CH3)2-C4H8-N + (CH3)2-C6H 13 ·2OH - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​468 m². 2 / g porous TiO2 support.

[0028] Take 50g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:50.

[0029] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 50g of methyl isobutyl ketone, and 1g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:10) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 120℃ and maintained at this temperature for 8.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove methyl isobutyl ketone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 30% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. The solution was then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 95.5% and the purity was 99.3%.

[0030] Example 3: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and mix them thoroughly at room temperature. Add 2.4 g of template agent (chemical structural formula C). 10 H 21 -N + (CH3)2-C8H 16 -N + (CH3)2-C 10 H 21 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​386 m². 2 / g porous TiO2 support.

[0031] Take 80g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:80.

[0032] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 100g of dioxane, and 0.2g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:50) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the original oxygen three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 8.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove dioxane and water byproduct, yielding a pale yellow crude solid. The crude solid was added to a 30% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 96.3%, and the purity was 99.3%.

[0033] Example 4: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia water, and stir until homogeneous at room temperature. Add 3.2 g of template agent (chemical structural formula C). 12 H 25 -N + (CH3)2-C8H 16 -N + (CH3)2-C 12 H 25 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​468 m². 2 / g porous TiO2 support.

[0034] Take 80g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:80.

[0035] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of tetrahydrofuran, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the original oxygen three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove tetrahydrofuran and the byproduct water, yielding a pale yellow crude solid. The crude solid was added to a 50% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. The solution was then slowly cooled to room temperature and allowed to stand for crystallization for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 96.5% and the purity was 99.3%.

[0036] Example 5: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 3.2 g of template agent (chemical structural formula C8H). 17 -N + (CH3)2-C6H 12 -N + (CH3)2-C8H 17 ·2OH - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​386 m². 2 / g porous TiO2 support.

[0037] Take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.

[0038] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 100g of acetone, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 180℃ and maintained at this temperature for 2.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove acetone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. The solution was then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 95.8% and the purity was 99.3%.

[0039] Example 6: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 2.4 g of template agent (chemical structural formula C). 12 H 25 -N + (CH3)2-C 10 H 20 -N + (CH3)2-C 12 H 25 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​468 m². 2 / g porous TiO2 support.

[0040] Take 50g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:50.

[0041] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of methyl isobutyl ketone, and 0.2g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:50) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The stirring was started and the temperature was raised to 180℃ and maintained at this temperature for 2.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove methyl isobutyl ketone and water by-product, yielding a pale yellow crude solid. The crude product was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. Then, it was slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 97.3% and the purity was 99.5%.

[0042] Example 7: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 3.2 g of template agent (chemical structural formula C). 14 H 29 -N + (CH3)2-C8H 16 -N + (CH3)2-C 14 H 29 ·2OH - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​550 m². 2 / g porous TiO2 support.

[0043] Take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.

[0044] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of dioxane, and 1g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:10) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove dioxane and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 50% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 97.5%, and the purity was 99.5%.

[0045] Example 8: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 2.4 g of template agent (chemical structural formula C9H). 19 -N + (CH3)2-C5H 10 -N + (CH3)2-C9H 19 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​386 m². 2 / g porous TiO2 support.

[0046] Take 80g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:80.

[0047] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 50g of tetrahydrofuran, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the original oxygen three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 120℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove tetrahydrofuran and the byproduct water, yielding a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 95.1% and the purity was 99.2%.

[0048] Example 9: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and stir until homogeneous at room temperature. Add 2.4 g of template agent (chemical structural formula C). 15 H 31 -N + (CH3)2-C 11 H 22 -N + (CH3)2-C 15 H 31 ·2OH - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​550 m². 2 / g porous TiO2 support.

[0049] Take 80g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:80.

[0050] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 0.25g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:40) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃ and maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released and the mixture was filtered. The filtrate was distilled at atmospheric pressure to remove acetone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 30% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved. The solution was then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 98.0% and the purity was 99.4%.

[0051] Example 10: Take 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia solution, and mix them thoroughly at room temperature. Add 1.6 g of template agent (chemical structural formula C). 11 H 23 -N + (CH3)2-C7H 14 -N + (CH3)2-C 11 H 23 ·2Br - The sample was stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate was slowly added dropwise at room temperature, and stirring continued for 2.0 h after the addition was complete, resulting in a milky white gel. The gel was transferred to a hydrothermal reactor and reacted at 140 °C for 12.0 h. After cooling to room temperature, the sample was centrifuged at high speed, and the supernatant was discarded. The white precipitate was washed with deionized water until neutral and then placed in a vacuum drying oven at 60 °C for 6.0 h. The dried sample was then calcined in a muffle furnace (heating rate 3 °C / min, up to 550 °C) for 6.0 h to remove the template agent, yielding a sample with a specific surface area of ​​468 m². 2 / g porous TiO2 support.

[0052] Take 50g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:50.

[0053] 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 1g of CeO2-CuO / TiO2 catalyst (catalyst to raw material mass ratio 1:10) were loaded into a reactor. After sealing the reactor, oxygen was introduced to replace the catalyst three times, and the initial oxygen pressure was adjusted to 3MPa. The reactor was stirred and heated to 160℃, and the reaction was maintained at this temperature for 6.0h. After the reaction was completed, the pressure was released, the mixture was filtered, and the filtrate was distilled at atmospheric pressure to remove acetone and water by-product, yielding a pale yellow crude solid. The crude solid was added to a 40% (w / w) methanol aqueous solution, heated to 60℃ and stirred until completely dissolved, then slowly cooled to room temperature and allowed to crystallize for 4.0h. The crystallization solution was filtered to obtain white crystals, which were dried under vacuum at 60℃ for 3.0h to obtain the 1-(4-chlorophenyl)-3-pyrazol product. The product yield was 94.5%, and the purity was 99.5%.

[0054] Example 11: 10g of 1-(4-chlorophenyl)pyrazolidine-3-one, 80g of acetone, and 0.25g of CeO2-CuO / TiO2 catalyst recovered by filtration in Example 1 were added to a high-pressure reactor. The initial oxygen pressure was 3MPa, and the reaction was carried out at 160℃ with stirring for 6.0h. After the reaction, the catalyst was recovered by filtration. The filtrate was distilled and recrystallized to obtain the 1-(4-chlorophenyl)-3-pyrazol product with a yield of 98.5% and a purity of 99.5%. Following the above operation, the recovered catalyst was reused 5 times with a yield of 98.3% and a purity of 99.4%; reused 10 times with a yield of 97.8% and a purity of 99.4%; reused 13 times with a yield of 97.3% and a purity of 99.3%; and reused 16 times with a yield of 97.2% and a purity of 99.4%.

[0055] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. However, these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions claimed by the present invention.

Claims

1. A method for preparing 1-(4-chlorophenyl)-3-pyrazolol, characterized in that... 1-(4-chlorophenyl)-3-pyrazolol was prepared by catalyzing the oxidation of 1-(4-chlorophenyl)pyrazolidine-3-one using CeO2-CuO / TiO2 as a catalyst and oxygen as an oxidant. The mass ratio of CeO2-CuO / TiO2 to 1-(4-chlorophenyl)pyrazolidine-3-one was 1:10-1:50, and the mass ratio of 1-(4-chlorophenyl)pyrazolidine-3-one to the reaction solvent was 1:5-1:

10. The initial oxygen pressure was 3 MPa, the reaction temperature was 120-180℃, and the reaction time was 2.0-8.0 h. After the reaction, the pressure was released, the catalyst was filtered out and reused, and the filtrate was distilled to remove the reaction solvent and byproduct water to obtain the crude product. Then, the crude product was recrystallized in a 30%-50% methanol aqueous solution to obtain the product 1-(4-chlorophenyl)-3-pyrazolol.

2. The method according to claim 1, characterized in that, The TiO2 has a multi-dimensional porous structure with a specific surface area of ​​386-550 m². 2 / g, the mass ratio of CeO2, CuO, and TiO2 is 1:1:80-1:1:10, and the filtered catalyst can be directly reused without the need to add new catalyst.

3. The method according to claim 1, characterized in that, The reaction solvent is one of acetone, methyl isobutyl ketone, dioxane, and tetrahydrofuran.

4. The method according to claim 1, characterized in that, The preparation method of TiO2 is as follows: 100 mL of deionized water, 300 mL of anhydrous ethanol, and 1.5 mL of 28 wt% ammonia water are mixed at room temperature until homogeneous. 1.6-3.2 g of template agent is added, and the mixture is stirred at room temperature for 20.0 min until completely dissolved. 25 mL of tetrabutyl titanate is slowly added dropwise at room temperature. After the addition is complete, the mixture is stirred for 2.0 h until it becomes a milky white gel. The mixture is transferred to a hydrothermal reactor and reacted at 140℃ for 12.0 h. After the reaction, the mixture is cooled to room temperature, centrifuged at high speed, and the supernatant is discarded. The white precipitate is washed with deionized water until neutral. The precipitate is placed in a vacuum drying oven and dried under vacuum at 60℃ for 6.0 h. The dried sample is calcined in a muffle furnace (heating rate 3℃ / min, up to 550℃) for 6.0 h to remove the template agent, thus obtaining porous TiO2 with a specific surface area of ​​386-550 m². 2 / g; the chemical structural formula of the template agent is C m H (2m+1) -N + (CH3)2-C n H 2n -N + (CH3)2-C m H (2m+1) ·2X - Where m is an integer from 6 to 16, n is an integer from 4 to 12, and X is either Br or OH. The specific surface area of ​​the prepared TiO2 can be controlled by the values ​​of m and n and the amount of template agent.

5. The method according to claim 1, characterized in that, The optimal preparation method for the catalyst CeO2-CuO / TiO2 is as follows: Take 10g of the TiO2 support prepared above, add 50mL of an aqueous solution containing 2.5g Ce(NO3)3·6H2O and 3.0g Cu(NO3)2·3H2O, ultrasonically impregnate for 2.0h, stir at 60℃ until the water evaporates, vacuum dry at 80℃ for 4.0h, and then calcine in a muffle furnace at 3℃ / min to 450℃ for 4.0h to obtain CeO2-CuO / TiO2 with a mass ratio of CeO2, CuO and TiO2 of 1:1:10.