Preparation method of 3, 5-dimethyl-4-nitrophenol
3,5-dimethyl-4-nitrophenol was synthesized through bromination and nitrite coupling reaction using copper salt and ligand catalyst, which solved the problems of low yield and harsh reaction conditions in the existing technology and achieved high yield and low-cost industrial production.
Patent Information
- Application Number
- CN202411120193.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-15
- Publication Date
- 2025-09-05
AI Technical Summary
The synthesis yield of 3,5-dimethyl-4-nitrophenol in the prior art is low and the reaction conditions are harsh, making it difficult to achieve industrial production.
3,5-Dimethyl-4-nitrophenol was synthesized by bromination reaction and nitrite coupling reaction, using copper salt and ligand as catalysts in an inert solvent and alkaline conditions, avoiding the use of oxidants such as nitric acid or hydrogen peroxide.
The method achieves high yield (85-95%) and low-cost preparation of 3,5-dimethyl-4-nitrophenol under mild reaction conditions, suitable for industrial production, with low catalyst usage, less three wastes, and high product purity.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a method for preparing 3,5-dimethyl-4-nitrophenol. Background Art
[0002] 3,5-Dimethyl-4-nitrophenol is an organic compound with a unique structure and properties. It has a wide range of applications in many fields. The following are some of the main aspects of its application:
[0003] In the pesticide field, 3,5-dimethyl-4-nitrophenol can be used as an intermediate or key ingredient in the synthesis of other pesticides. Due to the presence of a nitro group and a phenolic hydroxyl group, it may possess antibacterial, insecticidal, or herbicidal activity. Through further chemical reactions, it can be converted into new pesticides with higher efficacy and greater safety, which can be used to protect crops and increase yields.
[0004] In the dye industry, 3,5-dimethyl-4-nitrophenol is also used in the production of dyes and pigments due to its unique color and stability. By reacting with other compounds, dyes or pigments with specific colors and properties can be synthesized for coloring textiles, plastics, coatings, and other products.
[0005] 3,5-Dimethyl-4-nitrophenol also plays an important role in pharmaceutical synthesis. It can serve as a raw material or intermediate in the synthesis of certain drugs, participating in complex chemical reactions to produce drug molecules with specific pharmacological activities. These drugs may have potential applications in treating various diseases.
[0006] Currently, the synthesis of 3,5-dimethyl-4-nitrophenol primarily uses 3,5-dimethylphenol as a raw material through direct nitration. This synthetic route suffers from a very low yield of approximately 20%, primarily due to the electron-rich benzene ring, which is easily oxidized. Other literature reports suggest using sodium nitrite to first generate the nitroso group, which is then oxidized to the nitro group using hydrogen peroxide. However, this also oxidizes the benzene ring, resulting in a lower yield.
[0007] Therefore, there is an urgent need in the art to develop a preparation method with high yield, low cost, mild reaction conditions, and suitable for industrial production. Summary of the Invention
[0008] The purpose of the present invention is to provide a method for preparing 3,5-dimethyl-4-nitrophenol with mild reaction conditions, low catalyst dosage, high yield and easy industrial production.
[0009] In a first aspect of the present invention, there is provided a method for preparing 3,5-dimethyl-4-nitrophenol, comprising the following steps:
[0010] a) in an inert solvent, the compound of formula III undergoes a bromination reaction with a bromination reagent to prepare a compound of formula II;
[0011] b) coupling reaction of the compound of formula II with a nitrite in an inert solvent in the presence of a catalyst and a base to prepare a compound of formula I;
[0012]
[0013] The catalyst in step b) consists of copper salt and ligand.
[0014] In another preferred embodiment, the bromination reagent in step a) is selected from the group consisting of bromosuccinimide, dibromohydantoin, bromine (Br2), or a combination thereof.
[0015] In another preferred embodiment, the inert solvent in step a) is selected from the group consisting of alcohols, dichloromethane, dichloroethane, toluene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or a combination thereof.
[0016] In another preferred embodiment, the inert solvent in step a) is dichloromethane or acetonitrile.
[0017] In another preferred embodiment, the mass ratio of the inert solvent volume to the compound of formula III in step a) is 1-30 ml: 0.8-1.2 g;
[0018] In another preferred embodiment, the mass ratio of the inert solvent volume to the compound of formula III in step a) is 5-10 ml: 1 g;
[0019] In another preferred embodiment, the amount of the bromination reagent in step a) is 0.5-5 times the molar equivalent of the compound of formula III.
[0020] In another preferred embodiment, the amount of the bromination reagent in step a) is 0.5-1.5 times the molar equivalent of the compound of formula III;
[0021] In another preferred embodiment, the reaction temperature in step a) is -10-80°C, preferably 0-10°C;
[0022] In another preferred embodiment, the reaction time in step a) is 1-24 hours, preferably 8-12 hours.
[0023] In another preferred embodiment, the copper salt is selected from the group consisting of cuprous iodide, cuprous chloride, cuprous bromide, cuprous oxide, or a combination thereof; preferably cuprous iodide.
[0024] In another preferred embodiment, the ligand is selected from one or more of the following groups (L1-L5):
[0025]
[0026] In another preferred embodiment, the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, or a combination thereof; preferably potassium phosphate;
[0027] In another preferred embodiment, the nitrite is selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, calcium nitrite, or a combination thereof; preferably sodium nitrite;
[0028] In another preferred embodiment, the inert solvent is selected from the group consisting of water, alcohol solvents or ether solvents, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or a combination thereof; preferably N,N-dimethylacetamide;
[0029] in,
[0030] The ether solvent includes tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, or a combination thereof.
[0031] In another preferred embodiment, the amount of the copper salt used is 0.1%-50% times the molar equivalent of the compound of formula II.
[0032] In another preferred embodiment, the amount of the copper salt is 0.5-5% times the molar equivalent of the compound of formula II;
[0033] In another preferred embodiment, the amount of the ligand used is 0.1%-50% times the molar equivalent of the compound of formula II.
[0034] In another preferred embodiment, the amount of the ligand used is 0.5-5% molar equivalent of the compound of formula II.
[0035] In another preferred embodiment, the amount of the base used is 1-10 times the molar equivalent of the compound of formula II, preferably 1.0-3.0 times the molar equivalent.
[0036] In another preferred embodiment, the amount of the nitrite is 1-10 times the molar equivalent of the compound of formula II, preferably 1.0-3.0 times the molar equivalent.
[0037] In another preferred embodiment, in the catalyst, the mass ratio of copper salt to ligand is 1:1-1:5, preferably 1:1-1:3.
[0038] In another preferred embodiment, in the catalyst, the mass ratio of copper salt to ligand is 1:1-1:2.
[0039] In another preferred embodiment, the mass ratio of the catalyst to compound II is 1:40-1:80, preferably 1:50-1:60.
[0040] In another preferred embodiment, the reaction temperature of step b) is 60-150°C, preferably 110-130°C.
[0041] In another preferred embodiment, the reaction time of step b) is 2-48 hours, preferably 10-16 hours.
[0042] In another preferred embodiment, the yield of the compound of formula I in the method is 85-95% (calculated based on the compound of formula II).
[0043] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. DETAILED DESCRIPTION
[0044] After extensive and in-depth research, the inventors unexpectedly discovered that 3,5-dimethylphenol, after undergoing bromination, can undergo a coupling reaction with nitrite under a copper catalyst and alkaline conditions to produce 3,5-dimethyl-4-nitrophenol in high yield and purity. The 3,5-dimethyl-4-nitrophenol produced by this method can achieve a yield of 85-95% (calculated based on the compound of Formula II), and the raw materials are inexpensive, the catalyst dosage is low, and the catalytic efficiency is high. Based on this, the inventors completed the present invention.
[0045] the term
[0046] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
[0047] As used herein, the terms "comprise," "include," and "contain" are used interchangeably to include not only closed definitions but also semi-closed and open definitions. In other words, the terms include "consisting of," "consisting essentially of."
[0048] The "compound of formula III" described in the present invention is 3,5-dimethylphenol, and its structural formula is as follows:
[0049]
[0050] The "compound of formula II" described in the present invention is 4-bromo-3,5-dimethylphenol, and its structural formula is as follows:
[0051]
[0052] The "compound of formula I" described in the present invention is 3,5-dimethyl-4-nitrophenol, and its structural formula is as follows:
[0053]
[0054] The "inert solvent" described in the present invention refers to a solvent that does not react with the compounds in the reaction system.
[0055] Method of the present invention
[0056] As used herein, the terms "the method of the present invention", "the preparation method of the present invention", "the industrial preparation method of the present invention", and "the efficient preparation method of the present invention" may be used interchangeably to refer to the method described in the first aspect of the present invention.
[0057] Preparation method of compound of formula II
[0058] The present invention provides a method for preparing a compound of formula II, comprising the following steps:
[0059] In an inert solvent, the compound of formula III, 3,5-dimethylphenol, undergoes a bromination reaction with a bromination reagent to prepare a compound of formula II.
[0060]
[0061] The brominating agent includes but is not limited to bromosuccinimide, dibromohydantoin, bromine (Br2), or a combination thereof.
[0062] Representative inert solvents include, but are not limited to, alcohols, dichloromethane, dichloroethane, toluene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or combinations thereof.
[0063] Preferably, the inert solvent is dichloromethane or acetonitrile.
[0064] The amount of the bromination reagent used in the bromination reaction is 0.5-5 times the molar equivalent of the compound of formula III.
[0065] Preferably, the amount of the bromination reagent used in the bromination reaction is 0.5-1.5 times the molar equivalent of the compound of formula III.
[0066] The mass ratio of the inert solvent volume to the compound of formula III in step a) is 1-30 ml: 0.8-1.2 g.
[0067] Preferably, the mass ratio of the volume of the inert solvent to the compound of formula III in step a) is 5-10 ml:1 g.
[0068] Preferably, the reaction temperature of the bromination reaction is -10-80 degrees, preferably 0-10 degrees.
[0069] Preferably, the reaction time of the bromination reaction is 1-24 hours, preferably 8-12 hours.
[0070] Preparation method of 3,5-dimethyl-4-nitrophenol
[0071] The present invention provides a method for preparing 3,5-dimethyl-4-nitrophenol with cheap raw materials, mild reaction conditions and high yield, comprising the following steps:
[0072] In an inert solvent, in the presence of a catalyst and a base, a compound of formula II undergoes a coupling reaction with a nitrite to prepare a compound of formula I, 3,5-dimethyl-4-nitrophenol;
[0073]
[0074] The catalyst consists of copper salt and ligand.
[0075] The copper salt for the coupling reaction includes, but is not limited to, cuprous iodide, cuprous chloride, cuprous bromide, cuprous oxide, or a combination thereof.
[0076] Preferably, the copper salt in the coupling reaction is cuprous iodide.
[0077] The ligand for the coupling reaction is selected from L1-L5, or a combination thereof.
[0078] The amount of the copper salt used is 0.1%-50% times the molar equivalent of the compound of formula II, preferably 0.5-5%.
[0079] The amount of the ligand used is 0.1%-50% times the molar equivalent of the compound of formula II, preferably 0.5-5%.
[0080] The nitrite includes but is not limited to sodium nitrite, potassium nitrite, lithium nitrite, calcium nitrite, or a combination thereof.
[0081] Preferably, the nitrite is sodium nitrite.
[0082] The base includes, but is not limited to, sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, or a combination thereof.
[0083] Preferably, the base is potassium phosphate.
[0084] The amount of the nitrite used is 1-10 times the molar equivalent of the compound of formula II, preferably 1.0-3.0 times the molar equivalent.
[0085] The amount of the base used is 1-10 times the molar equivalent of the compound of formula II, preferably 1.0-3.0 times the molar equivalent.
[0086] The inert solvent includes, but is not limited to, water, alcohol solvents or ether solvents, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or a combination thereof.
[0087] Preferably, the inert solvent is N,N-dimethylacetamide.
[0088] In the present invention, representative ether solvents include, but are not limited to, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, or a combination thereof.
[0089] In the catalyst, the mass ratio of copper salt to ligand is 1:1-1:5, preferably 1:1-1:3, and most preferably 1:1-1:2.
[0090] The mass ratio of the catalyst to compound II is 1:40-1:80, preferably 1:50-1:60.
[0091] The reaction temperature of the coupling reaction is 60-150°C, preferably 110-130°C.
[0092] The reaction time of the coupling reaction is 2-48 hours, preferably 10-16 hours.
[0093] The yield of the compound of formula I in the method is 85-95% (calculated based on the compound of formula II).
[0094] The main advantages of the present invention are:
[0095] 1. The present invention provides a method for preparing 3,5-dimethyl-4-nitrophenol in high yield. In the first step, 3,5-dimethylphenol is brominated to obtain a compound of Formula II. Subsequently, in the presence of a catalyst and a base, the compound of Formula II is directly coupled with a nitrite to produce 3,5-dimethyl-4-nitrophenol. The method does not require the use of oxidants such as nitric acid or hydrogen peroxide, operates under mild reaction conditions, and can achieve a final product yield of 85-95% (calculated based on the compound of Formula II).
[0096] 2. The raw materials of the present invention are easily available. 3,5-dimethylphenol has mature industrial production and is cheap. The halogenation reagent is also a commonly used bulk raw material. The sodium nitrite used in the nitro coupling is also a common chemical raw material. The operation is simple and has cost advantages.
[0097] 3. The copper-catalyzed coupling technology in the method of the present invention can achieve efficient preparation with only a catalytic amount of copper and ligand. This technology is green and environmentally friendly and has high catalytic efficiency.
[0098] 4. The preparation method of 3,5-dimethyl-4-nitrophenol of the present invention has a novel route, less three wastes, high product purity, less impurities, and is easy to industrialize.
[0099] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which no specific conditions are specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.
[0100] Unless otherwise stated, the following examples were carried out under normal pressure, and room temperature refers to 20-30°C.
[0101] Example 1: Preparation of compound of formula II
[0102] 3,5-Dimethylphenol (10 g, 81.9 mmol) and dichloromethane (100 mL) were added to the reaction flask, and bromosuccinimide (14.5 g, 81.9 mmol) was added in batches at 0-10 degrees. The reaction was heated to room temperature for 10 hours. After the reaction was completed, water was added to quench the reaction, the layers were separated, and the organic phase was washed with water three times and concentrated to dryness to obtain 14.1 g of 4-bromo-3,5-dimethylphenol with a yield of 86%.
[0103] Example 2: Preparation of compound of formula II
[0104] 3,5-Dimethylphenol (10 g, 81.9 mmol) and 100 mL of dichloromethane were added to a three-necked flask, and dibromohydantoin (11.7 g, 41 mmol) was added in batches at 0-10 degrees. The reaction was heated to room temperature for 8 hours. After the reaction was completed, water was added to quench the reaction. The layers were separated, and the organic phase was washed with water 3 times and concentrated to dryness to obtain 14 g of 4-bromo-3,5-dimethylphenol with a yield of 85%.
[0105] Example 3: Preparation of Compounds of Formula I
[0106] 4-Bromo-3,5-dimethylphenol (10 g, 49.7 mmol), cuprous iodide (0.094 g, 1 mol%), ligand L1 (0.14 g, 1 mol%), sodium nitrite (5.14 g, 74.55 mmol, 1.5 eq), potassium phosphate (15.8 g, 74.55 mmol, 1.5 eq) and N,N-dimethylacetamide (80 mL) were added to a reaction flask. Under nitrogen protection, the reaction was carried out at 120 ° C. for 12 hours. After the reaction, the temperature was cooled to room temperature, ethyl acetate and water were added, the layers were separated, and the organic phase was washed with water three times. After concentration to dryness, it was purified by beating with n-heptane to obtain 7.47 g of 3,5-dimethyl-4-nitrophenol solid with a yield of 90%.
[0107] Example 4: Preparation of Compounds of Formula I
[0108] 4-Bromo-3,5-dimethylphenol (10 g, 49.7 mmol), cuprous iodide (0.094 g, 1 mol%), ligand L2 (0.15 g, 1 mol%), sodium nitrite (5.14 g, 74.55 mmol, 1.5 eq), potassium phosphate (15.8 g, 74.55 mmol, 1.5 eq) and N,N-dimethylacetamide (80 mL) were added to a reaction flask. Under nitrogen protection, the reaction was carried out at 120 ° C. for 12 hours. After the reaction, the temperature was cooled to room temperature, ethyl acetate and water were added, the layers were separated, and the organic phase was washed with water three times. After concentration to dryness, it was purified by beating with n-heptane to obtain 7.14 g of 3,5-dimethyl-4-nitrophenol solid with a yield of 86%.
[0109] Example 5: Preparation of the compound of formula I
[0110] 4-Bromo-3,5-dimethylphenol (20 g, 99.5 mmol), cuprous iodide (0.188 g, 1 mol%), ligand L3 (0.27 g, 1 mol%), sodium nitrite (10.3 g, 149.2 mmol, 1.5 eq), potassium phosphate (31.6 g, 149.2 mmol, 1.5 eq) and N,N-dimethylacetamide (80 mL) were added to a reaction flask. Under nitrogen protection, the reaction was carried out at 120 ° C. for 12 hours. After the reaction, the temperature was cooled to room temperature, ethyl acetate and water were added, the layers were separated, and the organic phase was washed with water three times. After concentration and purification with n-heptane, 14.9 g of yellow solid was obtained with a yield of 90%.
[0111] Example 6: Preparation of Compounds of Formula I
[0112] 4-Bromo-3,5-dimethylphenol (20 g, 99.5 mmol), cuprous iodide (0.188 g, 1 mol%), ligand L4 (0.34 g, 1 mol%), sodium nitrite (10.3 g, 149.2 mmol, 1.5 eq), potassium phosphate (31.6 g, 149.2 mmol, 1.5 eq) and N,N-dimethylacetamide (80 mL) were added to a reaction flask. Under nitrogen protection, the reaction was carried out at 120 ° C. for 12 hours. After the reaction, the temperature was cooled to room temperature, ethyl acetate and water were added, the layers were separated, and the organic phase was washed three times with water. After concentration to dryness, it was purified by beating with n-heptane to obtain 14.4 g of 3,5-dimethyl-4-nitrophenol solid with a yield of 87%.
[0113] Example 7: Preparation of the compound of formula I
[0114] 4-Bromo-3,5-dimethylphenol (20 g, 99.5 mmol), cuprous iodide (0.188 g, 1 mol%), ligand L5 (0.28 g, 1 mol%), sodium nitrite (10.3 g, 149.2 mmol, 1.5 eq), potassium phosphate (31.6 g, 149.2 mmol, 1.5 eq) and N,N-dimethylacetamide (80 mL) were added to a reaction flask. Under nitrogen protection, the reaction was carried out at 120 ° C. for 12 hours. After the reaction, the temperature was cooled to room temperature, ethyl acetate and water were added, the layers were separated, and the organic phase was washed three times with water. After concentration to dryness, it was purified by beating with n-heptane to obtain 14.0 g of 3,5-dimethyl-4-nitrophenol solid with a yield of 85%.
[0115] Comparative Example 1
[0116] 2-Bromo-1-toluene or 2-bromo-1-methoxybenzene (2.0 mmol), cuprous iodide (5 mol%), ligand L5 (5 mol%), sodium nitrite (3 mmol), potassium phosphate (3 mmol) and DMSO (2.0 ml) were added to a reaction flask and reacted at 120° C. under nitrogen protection for 24 hours. The reaction still did not proceed.
[0117] discuss:
[0118] The inventors repeated similar experiments in the literature (J.Org.Chem.2024). As described in the comparative example, when a halogenated benzene with a methyl group at the ortho position was used as a raw material, a catalyst composed of ligand L5 was used for a nitro substitution reaction. Even if the amount of L5 was as high as 5 mol%, it was found that the experiment could not be carried out. The present invention also used ligand L5 for experiments and unexpectedly found that when the raw material was 4-bromo-3,5-dimethylphenol (there are two methyl groups at the ortho position of the halogenated benzene), when the dosage of L5 was 1 mol%, 3,5-dimethyl-4-nitrophenol could be successfully prepared with good purity and high yield.
[0119] Secondly, when the ligand L2 described in the present invention is used to carry out the nitro substitution reaction in this document, the yield of the product is only 35%; however, the present invention uses a catalyst composed of ligand L2 and copper salt to carry out experiments, which can achieve the unexpected effect of improving the product yield. The yield of 3,5-dimethyl-4-nitrophenol can reach 85-95% (calculated based on the compound of formula II).
[0120] Compared with the prior art (using the compound of formula III as a raw material for direct nitration or requiring the use of hydrogen peroxide for oxidation reaction), the present invention can be carried out under normal pressure and mild conditions, has low cost, reduces the three wastes, reduces impurities, and is easy to industrialize.
[0121] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.
Claims
1. A method for preparing 3,5-dimethyl-4-nitrophenol, characterized in that: The method comprises the following steps: a) in an inert solvent, the compound of formula III undergoes a bromination reaction with a bromination reagent to obtain a compound of formula II; b) coupling reaction of the compound of formula II with a nitrite in an inert solvent in the presence of a catalyst and a base to prepare a compound of formula I; The catalyst in step b) consists of copper salt and ligand.
2. The preparation method according to claim 1, wherein The brominating agent in step a) is selected from the group consisting of bromosuccinimide, dibromohydantoin, bromine (Br2), or a combination thereof.
3. The preparation method according to claim 1, wherein The inert solvent in step a) is selected from the group consisting of alcohols, dichloromethane, dichloroethane, toluene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or a combination thereof; preferably dichloromethane or acetonitrile.
4. The preparation method according to claim 1, wherein The mass ratio of the inert solvent volume to the compound of formula III in step a) is 1-30 ml:0.8-1.2 g, preferably 5-10 ml:1 g; and / or The amount of the brominating agent in step a) is 0.5-5 times the molar equivalent of the compound of formula III; preferably 0.5-1.5 times the molar equivalent; and / or The reaction temperature in step a) is -10-80°C, preferably 0-10°C; and / or The reaction time in step a) is 1-24 hours, preferably 8-12 hours.
5. The preparation method according to claim 1, wherein The copper salt is selected from the group consisting of cuprous iodide, cuprous chloride, cuprous bromide, cuprous oxide, or a combination thereof; preferably cuprous iodide.
6. The preparation method according to claim 1, wherein The ligand is selected from one or more of the following groups (L1-L5):
7. The preparation method according to claim 1, wherein The base is selected from the group consisting of sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, or a combination thereof; preferably potassium phosphate; and / or The nitrite in step b) is selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, calcium nitrite, or a combination thereof; preferably, sodium nitrite.
8. The preparation method according to claim 1, wherein The inert solvent in step b) is selected from the group consisting of water, alcohol solvents or ether solvents, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or a combination thereof; preferably N,N-dimethylacetamide.
9. The preparation method according to claim 1, wherein The amount of the copper salt is 0.1%-50% times the molar equivalent of the compound of formula II, preferably 0.5-5% times the molar equivalent; and / or The amount of the ligand used is 0.1%-50% times the molar equivalent of the compound of formula II; preferably 0.5-5% times the molar equivalent; and / or The amount of the base is 1-10 times the molar equivalent of the compound of formula II; preferably 1.0-3.0 times the molar equivalent; and / or The amount of the nitrite is 1-10 times the molar equivalent of the compound of formula II, preferably 1.0-3.0 times the molar equivalent; and / or In the catalyst, the mass ratio of copper salt to ligand is 1:1-1:5; preferably 1:1-1:3; most preferably 1:1-1:2; and / or The mass ratio of the catalyst to compound II is 1:40-1:85, preferably 1:50-1:
60.
10. The preparation method according to claim 1, wherein The reaction temperature of step b) is 60-150°C; preferably 110-130°C; and / or The reaction time of step b) is 2-48 hours, preferably 10-16 hours.