A method for hydroxylation of 1-phenylpyrazoles mediated by boron

Abstract

This invention relates to the field of selective hydroxylation technology for aromatic compounds, specifically to a boron-mediated hydroxylation method for 1-phenylpyrazole compounds, comprising the following steps: under the action of boron trihalide, a base, and an oxidizing agent, the 1-phenylpyrazole compound represented by formula (I) undergoes a C-H bond borination reaction with boron trihalide, followed by an oxidation reaction to obtain the compound represented by formula (II); wherein, R 1 and R 2 Individually selected from hydrogen, C1-C6 alkyl groups, phenoxy groups, N,N-dimethyl groups, halogens, thiophene groups, and C6-C6 groups respectively. 14 Any of the aryl groups. This invention does not use any metal catalysis. By coordinating boron tribromide with the directing group pyrazole, the 1-phenylpyrazole substrate first undergoes a C-H bond borylation reaction, and then, under the action of an oxidant, a series of 1-(2-hydroxy)-1H-pyrazole compounds are obtained. This method is efficient, low-cost, and environmentally friendly.

Description

Technical Field

[0001] This invention relates to the field of selective hydroxylation technology of aromatic compounds, and more specifically to a boron-mediated hydroxylation method for 1-phenylpyrazole compounds. Background Technology

[0002] In the field of organic synthesis, the conversion of CH bonds into C-C and CX bonds (such as CO, CS, CN) is an important class of hydrocarbon functionalization reactions. Phenolic compounds, due to their p-π conjugation and the presence of lone pairs of electrons in their phenolic hydroxyl groups, can undergo a series of chemical transformations, such as coupling reactions, substitution reactions, and photoelectronization reactions, exhibiting multifunctionality in pharmaceuticals, pesticides, dyes, and polymers. Therefore, the construction of phenolic compounds has become a hot topic of research. Traditional methods for constructing phenolic hydroxyl groups mainly include nucleophilic aromatic substitution reactions of activated aryl halogens, Sandmeyer hydroxylation reactions, and condensation or cyclization reactions of unsaturated carbonyl derivatives. However, these methods have several drawbacks, such as low yields, poor site selectivity, harsh reaction conditions, and high energy consumption. In recent years, although significant progress has been made in the hydroxylation of aromatic CH bonds catalyzed by transition metals, the demand for precious metals and the removal of trace metals from the final product remain the main problems facing this type of catalytic reaction. Therefore, the development of mild, convenient and environmentally friendly methods for the hydroxylation of aromatic CH bonds is of great significance in synthetic chemistry.

[0003] The boronization of CH bonds is another strategy for obtaining phenolic compounds. This method involves first constructing a CB bond via boronization, followed by an additional oxidation step to construct a CO bond. Currently, one of the most attractive strategies for constructing CB bonds is through Lewis acid-directed hydroxylation using directing groups such as acyl, pyridine, imidazolide, pyrazine, pyrimidine, imidazole, and imine. However, pyrazole, a structural fragment with strong coordinating ability and present in many active pharmaceutical molecules, has rarely been reported for directed CH bond hydroxylation. In 2021, Tanaka's group established a photoinduced aromatic CH bond boronization reaction using pyrazole as a directing group, through in-situ generation of rhodium(II) complexes, and successfully synthesized phenolic compounds via an additional oxidation reaction. However, this method requires the use of two noble metals and has low yields. To our knowledge, reports of boron-mediated CH bond hydroxylation reactions using pyrazole as a directing group and boron trihalide under metal-free conditions remain rare. Therefore, developing a cost-effective and efficient method for the hydroxylation of aromatic compounds is extremely necessary. Summary of the Invention

[0004] To address the aforementioned technical problems, the present invention aims to provide a boron-mediated hydroxylation method for 1-phenylpyrazole compounds. This method does not utilize any metal catalyst. Under a protective atmosphere, boron tribromide coordinates with the directing pyrazole group, causing the 1-phenylpyrazole substrate to undergo a CH bond borylation reaction. Subsequently, under the action of an oxidant, a series of 1-(2-hydroxy)-1H-pyrazole compounds are obtained. This method overcomes the shortcomings of existing selective hydroxylation methods for aromatic hydrocarbons, such as the use of noble metal catalysts, insufficient site selectivity, low yield, and harsh reaction conditions. It provides a highly efficient, low-cost, and environmentally friendly method for the hydroxylation of 1-phenylpyrazole compounds.

[0005] To achieve the above objectives, embodiments of the present invention provide a boron-mediated hydroxylation method for 1-phenylpyrazole compounds, comprising the following steps:

[0006] In the presence of boron trihalide, alkali and oxidant, the 1-phenylpyrazole compound shown in formula (Ⅰ) is hydroxylated with boron trihalide to obtain the compound shown in formula (Ⅱ);

[0007] The synthesis route is as follows:

[0008]

[0009] The hydroxylation reaction involves first reacting the 1-phenylpyrazole compound shown in formula (Ⅰ) with boron trihalide via a CH bond boration reaction, followed by an oxidation reaction.

[0010] Among them, R 1 and R 2 Individually selected from hydrogen, C1-C6 alkyl groups, phenoxy groups, N,N-dimethyl groups, halogens, thiophene groups, and C6-C6 groups respectively. 14 Any of the aryl groups.

[0011] Furthermore, the boron trihalide is either boron trichloride or boron tribromide.

[0012] Furthermore, the base is any one of triethylamine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, N,N-diisopropylethylamine, and 2,6-dimethylpyridine.

[0013] Furthermore, the hydroxylation reaction is carried out in an organic solvent.

[0014] Furthermore, the organic solvent is either dichloromethane or 1,2-dichloroethane.

[0015] Furthermore, the hydroxylation reaction is carried out under gas protection.

[0016] Furthermore, the gas is nitrogen, argon, or helium.

[0017] Furthermore, the reaction conditions for the hydroxylation reaction are as follows:

[0018] The reaction temperature is 25℃-90℃, and the time is 4h-24h.

[0019] Furthermore, the molar ratio of the 1-phenylpyrazole compound shown in formula (Ⅰ) to boron trihalide, base and oxidant is 0.2:(0.6-1.2):0.2:0.8.

[0020] The beneficial effects of this invention are:

[0021] 1. This invention does not use any metal catalyst. Under an inert gas atmosphere, boron tribromide coordinates with the directing group pyrazole, causing the 1-phenylpyrazole substrate to undergo a CH bond borylation reaction. Subsequently, under the action of an oxidant, a series of 1-(2-hydroxy)-1H-pyrazole compounds are obtained. This method overcomes the shortcomings of existing methods for the selective hydroxylation of aromatics, such as the use of noble metal catalysts, insufficient site selectivity, low yield, and harsh reaction conditions. It provides a highly efficient, low-cost, and environmentally friendly method for the hydroxylation of 1-phenylpyrazole compounds.

[0022] 2. The method of the present invention has the advantages of low cost, simple operation, high yield, wide substrate applicability, easy product separation and less environmental pollution. It is suitable not only for gram-scale reactions, but also for industrial-scale production. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0024] Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Unless otherwise specified, the experimental methods described in the following embodiments of the present invention are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0026] The following embodiments of the present invention provide a boron-mediated hydroxylation method for 1-phenylpyrazole compounds, and the synthetic route is as follows:

[0027]

[0028] The specific preparation method is as follows: 1-phenylpyrazole compound (as shown in formula (I)), base and dry organic solvent are added to a 25 mL Shrek tube. Under argon protection, BBr3 (1M in dichloromethane) solution is slowly added dropwise and the mixture is placed at 25℃-90℃ for 4-24 h to react completely. After the reaction is completed, the reaction solution is evaporated to dryness. Sodium perborate tetrahydrate, tetrahydrofuran and 1M potassium carbonate aqueous solution are added to the bottle. The reaction solution is stirred at room temperature for 4 h and then poured into a separatory funnel containing saturated saline solution. The mixture is extracted with dichloromethane, the organic layer is collected and dried with anhydrous sodium sulfate, concentrated under vacuum, and then purified and separated by silica gel column chromatography to prepare the corresponding 1-(2-hydroxy)-1H-pyrazole compound (the compound shown in formula (II)).

[0029] The 1-phenylpyrazole compound represented by formula (Ⅰ) is selected from one of the following compounds:

[0030]

[0031] Below, we will provide a detailed explanation of the boron-mediated hydroxylation method for the 1-phenylpyrazole compounds shown in formula (Ⅰ).

[0032] Example 1:

[0033] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method includes the following steps:

[0034] Add 0.2 mmol of 3,5-dimethyl-1-phenyl-1H-pyrazole (Ⅰ-1), 0.2 eq of N,N-diisopropylethylamine (1.0 eq, 0.2 mmol), and 1.5 mL of 1,2-dichloroethane to a 25 mL Shrek tube, respectively. Purge with argon gas and, under argon protection, slowly add 1.0 mL dropwise. A BBr3 (1M in dichloromethane) solution was used to react the reaction mixture in an oil bath at 65°C for 24 hours. After the reaction was complete, the reaction mixture was evaporated to dryness. Sodium perborate tetrahydrate (4.0 eq, 0.8 mmol), tetrahydrofuran (1 mL), and 1M potassium carbonate aqueous solution (1 mL) were added to the flask. The reaction mixture was stirred at room temperature for 4 hours and then poured into a separatory funnel containing saturated saline solution. The mixture was extracted with dichloromethane (15 mL × 3), and the organic layer was collected and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1) to give a white solid with a yield of 84%.

[0035] The structural characterization data of the product obtained in Example 1 are shown below:

[0036] 1H NMR (400MHz, CDCl3, ppm): δ9.86 (s, 1H), 7.21-7.18 (m, 2H), 7.09 (d, J = 8.4Hz, 1H), 6.92 (t, J = 7.6Hz, 1H), 6.03 (s, 1H), 2.39 (s, 3H), 2.30 (s, 3H); 13 C NMR (100MHz, CDCl3, ppm): δ150.9,149.3,140.7,128.3,125.9,122.8,119.4,118.4,107.5,13.5,13.1; HRMS (ESI): m / z[M+H] + calcd.for C 11 H 13 N2O: 189.1028; found: 189.1030

[0037] Based on the above data, the structure of the product can be inferred as follows:

[0038] Example 2:

[0039] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0040] Example 3:

[0041] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0042] Example 4:

[0043] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0044] Example 5:

[0045] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0046] Example 6:

[0047] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0048] Example 7:

[0049] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0050] Example 8:

[0051] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0052] Example 9:

[0053] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0054] Example 10:

[0055] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0056] Example 11:

[0057] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0058] Example 12:

[0059] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0060] Example 13:

[0061] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0062] Example 14:

[0063] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0064] Example 15:

[0065] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0066] Example 16:

[0067] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0068] Example 17:

[0069] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0070] Example 18:

[0071] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0072] Example 19:

[0073] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0074] Example 20:

[0075] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0076] Example 21:

[0077] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0078] Example 22:

[0079] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0080] Example 23:

[0081] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0082] Example 24:

[0083] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0084] Example 25:

[0085] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0086] Example 26:

[0087] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0088] Example 27:

[0089] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0090] Example 28:

[0091] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1.

[0092] Example 29:

[0093] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that boron trihalide is boron trifluoride.

[0094] Example 30:

[0095] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that boron trihalide is replaced with boron trichloride.

[0096] Example 31:

[0097] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the base is triethylamine.

[0098] Example 32:

[0099] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the base is 1,8-diazobisspirocyclic [5.4.0]undecyl-7-ene.

[0100] Example 33:

[0101] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the base is 2,6-dimethylpyridine.

[0102] Example 34:

[0103] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the solvent for the borylation reaction is dichloromethane.

[0104] Example 35:

[0105] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the solvent for the borylation reaction is N,N-dimethylformamide.

[0106] Example 36:

[0107] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the solvent for the borylation reaction is tetrahydrofuran.

[0108] Example 37:

[0109] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the reaction temperature is 25°C.

[0110] Example 38:

[0111] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the reaction temperature is 90°C.

[0112] Example 39:

[0113] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the reaction time is 4 hours.

[0114] Example 40:

[0115] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the reaction time is 12 hours.

[0116] Example 41:

[0117] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the amount of BBr3 used is 0.6 mL.

[0118] Example 42:

[0119] A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, wherein the structure of the 1-phenylpyrazole compound is as follows: The specific method is basically the same as that in Example 1, except that the amount of BBr3 used is 1.2 mL.

[0120] The above embodiments of the present invention mainly use 1-phenylpyrazole compounds (1a) to (1ab) as substrates. The 1-phenylpyrazole substrate undergoes a CH bond borylation reaction first, followed by a hydroxylation reaction under the action of an oxidant, through coordination of boron tribromide with the directing pyrazole group. The optimized reaction conditions are shown in Tables 1-3.

[0121] Table 1. Optimization of boron trihalide

[0122]

[0123] As shown in Table 1, through screening boron trihalides including boron tribromide, boron trifluoride, and boron trichloride, we found that boron tribromide had the best reaction yield (84%) when used as the boron source.

[0124] Table 2 Alkali Optimization Status

[0125]

[0126]

[0127] As shown in Table 2, through screening of bases including N,N-diisopropylethylamine, triethylamine, 1,8-diazobisspirocyclic[5.4.0]undec-7-ene, and 2,6-dimethylpyridine, we found that N,N-diisopropylethylamine had the best reaction yield (84%) when used as a base.

[0128] Table 3. Solvent optimization for borylation reaction

[0129]

[0130] As shown in Table 3, through screening reaction solvents including 1,2-dichloroethane, dichloromethane, N,N-dimethylformamide, and tetrahydrofuran, we found that 1,2-dichloroethane had the best reaction yield (84%) when used as the reaction solvent.

[0131] Table 4. Optimization of borination reaction temperature

[0132]

[0133] As shown in Table 4, by screening the reaction temperature (25℃, 65℃, and 90℃), we found that the reaction yield was best at a reaction temperature of 65℃ (yield 84%).

[0134] Table 5. Optimization of borination reaction time

[0135]

[0136]

[0137] As shown in Table 5, by screening the reaction time to include 4h, 12h and 24h, we found that the reaction yield was the best when the reaction time was 24h (yield 84%).

[0138] Table 6. Optimization of Boron Tribromide Dosage

[0139]

[0140] As shown in Table 6, by screening the amount of boron tribromide used (0.6 mL, 1.0 mL, and 1.2 mL), we found that the reaction yield was the best when the amount of boron tribromide used was 1.0 mL (yield 84%).

[0141] The suitability of different boron-mediated hydroxylation methods for 1-phenylpyrazole compounds as substrates is investigated below, and the optimized conditions described above are verified. See Table 7 for details.

[0142] Table 7. Results of substrate suitability assessment

[0143]

[0144]

[0145]

[0146]

[0147]

[0148] As can be seen from the results in Table 7, in Examples 1 to 28 of the present invention, 1-phenylpyrazole compounds (1a) to (1ab) were used as substrates. By coordinating boron tribromide with the directing group pyrazole, the 1-phenylpyrazole substrates first underwent a CH bond borylation reaction. Subsequently, under the action of an oxidant, a series of 1-(2-hydroxy)-1H-pyrazole compounds were obtained in high yields (yields of 52% to 92%).

[0149] The above results demonstrate that the method of the present invention has advantages such as low cost, simple operation, high yield, wide substrate applicability, easy product separation and low environmental pollution. Furthermore, it is suitable not only for gram-scale reactions but also for industrial-scale production.

[0150] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A boron-mediated hydroxylation method for 1-phenylpyrazole compounds, characterized in that, Includes the following steps: In the presence of boron trihalide, alkali and oxidant, the 1-phenylpyrazole compound shown in formula (Ⅰ) is hydroxylated with boron trihalide to obtain the compound shown in formula (Ⅱ); ； The hydroxylation reaction involves first reacting the 1-phenylpyrazole compound shown in formula (Ⅰ) with boron trihalide via a C−H bond boration reaction, followed by an oxidation reaction. Among them, R 1 Selected from methyl or halogen; R 2 Selected from hydrogen, C1-C6 alkyl groups, phenoxy groups, N , N -Dimethyl, halogen, C6-C 14 Any of the aryl groups; The boron trihalide is either boron trichloride or boron tribromide; The base is any one of triethylamine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, N,N-diisopropylethylamine, and 2,6-dimethylpyridine; The hydroxylation reaction is carried out in the organic solvent dichloromethane or 1,2-dichloroethane; The hydroxylation reaction is carried out under the protection of nitrogen, argon or helium gas; The hydroxylation reaction is carried out at a temperature of 65℃-90℃ for a time of 12h-24h. The oxidizing agent for the oxidation reaction is sodium perborate tetrahydrate.

2. The boron-mediated hydroxylation method for 1-phenylpyrazole compounds according to claim 1, characterized in that, The boron trihalide is boron tribromide.

3. The boron-mediated hydroxylation method for 1-phenylpyrazole compounds according to claim 1, characterized in that, The alkali is N , N -Diisopropylethylamine or 2,6-dimethylpyridine.

4. The boron-mediated hydroxylation method for 1-phenylpyrazole compounds according to claim 1, characterized in that, The molar ratio of the 1-phenylpyrazole compound shown in formula (Ⅰ) to boron trihalide, base and oxidant is 0.2:(0.6-1.2):0.2:0.

8.

5. The boron-mediated hydroxylation method for 1-phenylpyrazole compounds according to claim 1, characterized in that, The 1-phenylpyrazole compound represented by formula (Ⅰ) is selected from one of the following compounds: 。

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