Preparation method of 2, 6-dimethyl-2, 3-dihydro-1-indanone

Abstract

The invention discloses a preparation method of 2, 6-dimethyl-2, 3-dihydro-1-indanone, which comprises the following steps: carrying out a heck reaction on p-bromotoluene and methacrylic acid under the action of a catalyst to generate 2-methyl-3-(4-methylphenyl)-2-acrylic acid, and then carrying out hydrogenation, acylating chlorination and Friedel-Crafts acylation cyclization to synthesize the 2, 6-dimethyl-2, 3-dihydro-1-indanone. The method is mild in reaction condition, high in total yield, clean and environment-friendly in whole route, small in environmental pollution and suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of compound synthesis, and particularly relates to a preparation method of 2,6-dimethyl-2,3-dihydro-1-indanone. BACKGROUND

[0002] 2,6-dimethyl-1-indanone is an important raw material of triazine indanil. Triazine indanil, chemical name N-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-[(1RS)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine, is a triazine herbicide developed by Bayer Company in Germany, which is mainly used for preventing annual weeds (such as crabgrass, Chinese milk vetch, bluegrass, etc.) and 65 other weeds and broadleaf weeds in lawns, flowers and vegetation, and has the advantages of broad-spectrum weed resistance, long drug effect time, low dosage, environmental protection and the like.

[0003] The currently reported synthesis methods of indanone compounds mainly include: 1. A synthesis method using benzaldehyde as a raw material: Substituted benzaldehyde is used as a raw material, and after condensation and decarboxylation reaction with substituted malonate, 3-substituted phenyl-2-substituted propenoic acid is obtained, and then after hydrogenation, acyl chlorination, aluminum trichloride or polyphosphoric acid catalysis, indanone compounds are synthesized (Organometallics 2006, 25, 1217-1229).

[0004] Substituted benzaldehyde is used as a raw material, and after perkin reaction with anhydride, hydrogenation, acyl chlorination, Friedel-Crafts cyclization with aluminum trichloride, indanone compounds are synthesized (European Journal of Medicinal Chemistry, 2013, 62, 632-648).

[0005] 2. Using substituted aromatic hydrocarbon as a raw material: Substituted aromatic hydrocarbon is used as a raw material, and after reaction with 2-substituted propionyl chloride under the catalysis of aluminum trichloride, substituted phenylethyl ketone is generated, and then after bromination, cyclization under the catalysis of aluminum trichloride, hydrolysis, indanone compounds are obtained (US2002077507).

[0006] 3. Using substituted halogenated benzyl as a raw material: Substituted halogenated benzyl such as benzyl chloride is used as a raw material, and the halogenated benzyl reacts with substituted malonate to generate substituted benzyl propionic acid compound, and then after acyl chlorination, aluminum trichloride or phosphorus-containing acidic compound catalysis, indanone compounds are further synthesized (US2007 / 0135595 A1).

[0007] The prior art has high cost of raw materials, complex reaction operation, low purity and low yield of 2,6-dimethyl-2,3-dihydro-1-indenone, incomplete reaction of reactants, and waste of raw materials. SUMMARY

[0008] In view of the above disadvantages in the prior art, the present application provides a new preparation method of 2,6-dimethyl-2,3-dihydro-1-indenone, which adopts a new synthesis route, has mild reaction conditions, a unique double bond position, and no rearrangement, and improves the yield and purity of the obtained product.

[0009] The present application uses p-bromotoluene and olefin as raw materials, generates 2-methyl-3-(4-methylphenyl)-2-propenoic acid through Heck reaction, and then generates 2,6-dimethyl-2,3-dihydro-1-indenone through hydrogenation, acyl chloride, and Friedel-Crafts acylation, and the structural formula of the 2,6-dimethyl-2,3-dihydro-1-indenone is as follows: .

[0010] The specific technical scheme of the present application is as follows: A preparation method of 2,6-dimethyl-2,3-dihydro-1-indenone, comprising the following steps: (A) Heck reaction: p-bromotoluene represented by formula (I) and methacrylic acid represented by formula (II) undergo Heck reaction under the action of a catalyst to obtain an intermediate represented by formula (III); (B) Hydrogenation reaction: the intermediate represented by formula (III) and hydrogen undergo hydrogenation reaction under the action of a catalyst to obtain an intermediate represented by formula (IV); (C) Acylation reaction: the intermediate represented by formula (IV) and an acylation reagent undergo acylation reaction to obtain an intermediate represented by formula (V); (D) Friedel-Crafts acylation reaction: the intermediate represented by formula (V) undergoes Friedel-Crafts acylation reaction under the action of a Lewis acid to generate 2,6-dimethyl-2,3-dihydro-1-indenone product; .

[0011] Further, in step (A), the molar ratio of the p-bromotoluene to the methacrylic acid is 1:1.03-2.0, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0.

[0012] Further, in step (A), the catalyst is at least one of a palladium salt and a ligand, wherein the palladium salt includes at least one of Pd(OAc)2, Pd(dppf)Cl2, PdCl2, [1,1'-bis (di-tert-butylphosphino) ferrocene]dichloropalladium, palladium on carbon (Pd / C), and the ligand includes at least one of BINAP, tri (o-methylphenyl) phosphine, and triphenylphosphine.

[0013] Further, in step (A), the molar ratio of the palladium salt to the p-bromotoluene of formula (I) is 0.005-0.01:1, for example, 0.005:1, 0.006:1, 0.007:1, 0.008:1, 0.009:1, 0.01:1.

[0014] Further, in step (A), the molar ratio of the ligand to the p-bromotoluene of formula (I) is 0.01-0.02:1.

[0015] Further, in step (A), the Heck reaction is carried out in the presence of an acid- trapping agent, which is at least one of an organic base and an inorganic base. The organic base includes, but is not limited to, at least one of triethylamine, pyridine, diisopropylethylamine, morpholine, pyrrolidine, and the like. The inorganic base includes, but is not limited to, at least one of potassium carbonate, sodium carbonate, and the like.

[0016] Further, in step (A), the molar ratio of the acid-trapping agent to the p-bromotoluene of formula (I) is 1.5-2:1, for example, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1.

[0017] Further, in step (A), the Heck reaction is carried out in a solvent. The solvent includes, but is not limited to, at least one of a benzene solvent, an alcohol solvent, an ether solvent, a nitrile solvent, an amide solvent, a sulfone solvent, and the like. For example, the solvent can be at least one of toluene, xylene, methanol, ethanol, THF, acetonitrile, DMF, DMAc, DMSO, and the like. The amount of the solvent used as a reaction medium can be adjusted according to actual needs.

[0018] Further, in step (A), the raw materials and the solvent can be mixed in any order, all the raw materials and the solvent can be mixed together, the solvent can be mixed with part of the raw materials first and then other raw materials can be added, or the raw materials can be mixed with the solvent respectively, and then the solutions of the raw materials can be mixed.

[0019] Further, in step (A), the reaction is carried out under gas protection; the gas is nitrogen, argon or other inert gas.

[0020] Further, in step (A), the reaction temperature is 80-110℃, for example 80℃, 85℃, 90℃, 95℃, 100℃, 105℃, 110℃. The reaction is considered to be completed when the content of p-bromotoluene is <1%, and under this reaction temperature, the reaction time is generally 4-5h.

[0021] Further, in step (A), after the reaction is completed, the reaction liquid is treated to obtain the intermediate represented by formula (III), the treatment steps include: the reaction liquid is concentrated to remove most of the solvent, then water is added to crystallize, and the solid is filtered to obtain a solid, which is dissolved in ethyl acetate, then sodium hydroxide solution is added, stirred thoroughly, and then the water phase is separated, hydrochloric acid is added to the water phase to adjust the pH to 2-3, at this time a large amount of solid is precipitated, after complete crystallization, the solid is filtered, washed and dried to obtain the intermediate represented by formula (III).

[0022] Further, in step (B), the intermediate represented by formula (III) is hydrogenated with hydrogen in the presence of a catalyst to obtain the intermediate represented by formula (IV). The catalyst is commonly used in the field of catalytic hydrogenation, including but not limited to palladium on carbon, platinum on carbon, Raney nickel, etc. The amount of catalyst is 6-10% of the mass of the intermediate represented by formula III.

[0023] Further, in step (B), the reaction is carried out in a solvent, which includes but is not limited to at least one of alcohol solvents, benzene solvents, ether solvents, etc. For example, the solvent is at least one of methanol, ethanol, toluene, tetrahydrofuran, dioxane, etc. The amount of solvent as a reaction medium can be adjusted according to actual needs.

[0024] Further, in step (B), the reaction is carried out in a high-pressure reaction kettle, and the pressure of hydrogen in the system is 0.2-0.5MPa, for example 0.2MPa, 0.3MPa, 0.4MPa, 0.5MPa.

[0025] Further, in step (B), the reaction is carried out at 20-30℃, for example 20℃, 25℃, 30℃. The reaction time is generally 8-10h, for example 8h, 9h, 10h.

[0026] Further, in step (B), after the reaction, the catalyst is recovered by filtration, and then the solvent is recovered to obtain the intermediate shown as formula (IV). The solvent can be recovered by distillation, vacuum distillation, etc.

[0027] Further, in step (C), the acylating agent is selected from the group consisting of dichlorosulfoxide or oxalyl chloride; the molar ratio of the intermediate shown as formula (IV) to the acylating agent is 1:1.03-2.0, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0.

[0028] Further, in step (C), the reaction can be carried out in the presence of a solvent or without a solvent, and the solvent is selected from organic solvents, including but not limited to at least one of halogenated hydrocarbon solvents, benzene solvents, etc. For example, the solvent is at least one of dichloromethane, dichloroethane, toluene, etc. The amount of the solvent as a reaction medium can be adjusted according to actual needs.

[0029] Further, in step (C), there is no special requirement for the order of addition of raw materials. The reaction is carried out at 20-30°C, for example, 20°C, 25°C, 30°C. The reaction time is generally 3-5h.

[0030] Further, in step (C), after the reaction, the excess chlorinating agent is removed to obtain the intermediate shown as formula V in the form of a solid crude product or a reaction liquid containing the intermediate shown as formula V and a solvent, and the crude product or the reaction liquid is used for the next Friedel-Crafts acylation ring-closing reaction.

[0031] Further, in step (D), the Friedel-Crafts acylation ring-closing reaction is carried out in the presence of a Lewis acid, and the Lewis acid is selected from one or a combination of at least one of aluminum chloride, zinc chloride, iron trichloride, tin tetrachloride, aluminum tribromide, etc. The molar ratio of the intermediate shown as formula (V) to the Lewis acid is 1:1.03-2.0, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0.

[0032] Further, in step (D), the reaction is carried out in the presence of a solvent selected from organic solvents including, but not limited to, at least one of halogenated hydrocarbon solvents, benzene solvents, and the like. Illustratively, the solvent is one or a combination of dichloromethane, dichloroethane, toluene, and the like. The solvent is used as a reaction medium, and its amount can be adjusted according to actual needs.

[0033] Further, in step (D), the mixing order of the raw materials is not particularly limited, and all the raw materials can be mixed with the solvent, or the raw materials can be first dissolved in a solution and then mixed. Preferably, the mixture of the intermediate represented by formula V and the solvent is dropped into the mixture of the Lewis acid and the solvent.

[0034] Further, in step (D), the mixing temperature of the raw materials and the reaction temperature are both -5-20℃, such as -5℃, 0℃, 5℃, 10℃, 15℃, and 20℃. The reaction time is generally 2-5h, such as 2h, 3h, 4h, and 5h.

[0035] Further, in step (D), after the reaction is completed, the reaction solution is extracted with water, the organic phase is separated, and the organic phase is subjected to solvent removal to obtain 2,6-dimethyl-2,3-dihydro-1-indenone.

[0036] Compared with the prior art, the present application has the following advantages: 1. The present application provides a novel method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indenone, which avoids high-temperature conditions of perkin reaction, has mild reaction conditions, and is simple to prepare.

[0037] 2. The present application first uses Heck reaction to synthesize intermediate (III), which has the advantages of high yield, unique double bond position, and no rearrangement, thereby improving the reaction yield.

[0038] 3. When aluminum chloride is used as the Lewis acid in the present application, the aluminum-containing wastewater generated during the reaction can be used to make a flocculant, the overall route is clean and environmentally friendly, has little environmental pollution, and is suitable for industrial production.

[0039] 4. The present application improves the yield and purity of the product, and has good industrial practical value. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1 The hydrogen spectrum of 2,6-dimethyl-2,3-dihydro-1-indenone synthesized in Example 1 is shown in the figure.

[0041] Figure 2 The carbon spectrum of 2,6-dimethyl-2,3-dihydro-1-indenone synthesized in Example 1 is shown in the figure. DETAILED DESCRIPTION

[0042] The application will be further described in connection with the following specific examples. The following description is only exemplary and does not limit the scope of protection. Other embodiments obtained by those skilled in the art without creative effort based on the inventive concept of the application are also within the scope of protection.

[0043] In the following examples, the raw materials used are commercially available products unless otherwise specified.

[0044] In the following examples, the concentrations are mass percentages unless otherwise specified.

[0045] In the following examples, the yield = actual mass of product x purity / theoretical mass of product.

[0046] Example 1 Heck reaction: Pd(OAc)20.2 g (content 98%, 0.00087 mol), tris (o-methylphenyl) phosphine 0.54 g (content 98%, 0.0017 mol), p-bromotoluene 30 g (content 99%, 0.1737 mol), methacrylic acid 18.12 g (content 99%, 0.2084 mol), N, N-diisopropyl ethylamine 45.34 g (content 99%, 0.3473 mol), DMF 250 g were added in a four-necked flask at room temperature, replaced with nitrogen for 3 times, protected with nitrogen, stirred at 110°C for 5 h, detected by HPLC, the content of p-bromotoluene was <1% and qualified, concentrated to 100 g under vacuum, added with 250 g of water to precipitate, filtered to obtain a solid, the solid was dissolved in 250 g of ethyl acetate, added with 138.92 g (0.3473 mol) of 10% NaOH aqueous solution, stirred for 3 h, separated into water and organic phases, added with hydrochloric acid in the water phase to adjust the pH to 2-3, at this time a large amount of white solid was precipitated, filtered, added with 30 g of water to wash the filter cake, and dried to obtain a white solid, which was compound III 32.15 g, content (HPLC) 83.0%, yield 87.2% based on p-bromotoluene.

[0047] Hydrogenation reaction: compound III 20 g (0.0942 mol), methanol 200.0 g, and palladium-carbon 2 g were added into an autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at 20-25°C for 10 h. After the reaction, the reaction mixture was filtered, and then the methanol was recovered by vacuum concentration to obtain compound IV crude product 19.86 g, content (HPLC) 82.5%, yield 97.6% based on compound III.

[0048] Acyl chloride-cyclization reaction: In a four-necked flask, add compound IV 20 g (0.0926 mol), dichloro sulfoxide 22.25 g (content 99%, 0.185 mol), stir the reaction at room temperature for 3 h, after the reaction is qualified, remove the excess dichloro sulfoxide. Get compound V crude product. Compound V crude product is dissolved in 20 g dichloromethane, slowly drop into 20 g dichloromethane containing 18.70 g (content 99%, 0.1389 mol) AlCl3 at -5-0 ℃, after the drop is completed, warm to room temperature, stir for 2 h, after the HPLC detection is qualified, add 80 g water to extract, separate, the water phase is washed with dichloromethane twice, combine the organic phase, the organic phase is concentrated under vacuum to get 2,6-dimethyl-2,3-dihydro-1-indenone 15.11 g, content (HPLC) 91.3%, yield is 93% based on compound IV, four-step yield is 79.15% based on p-bromotoluene.

[0049] The structural formula of the synthesized product 2,6-dimethyl-2,3-dihydro-1-indenone is as follows: The hydrogen spectrum and carbon spectrum of 2,6-dimethyl-2,3-dihydro-1-indenone are shown in Figure 1 and Figure 2 The nuclear magnetic resonance information is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.49 (m 1H), 7.40 – 7.34 (m, 1H),7.32 – 7.26 (m, 1H), 3.37 – 3.26 (m, 1H), 2.71 – 2.59 (m, 2H), 2.38 – 2.34(m, 3H), 1.30 – 1.22 (m, 3H) 13 C NMR (101 MHz, CDCl3) δ 209.5, 150.8, 137.3, 136.5, 136.0, 126.2,42.3, 34.6, 21.1, 16.4. Example 2 Prepare 2,6-dimethyl-2,3-dihydro-1-indenone according to the method of Example 1, except that the pd catalyst of the Heck reaction is replaced by 0.31 g (content 98%, 0.00174 mol) PdCl2, and the ligand is replaced by 0.93 g (content 98%, 0.0035 mol) triphenylphosphine. The final separation of the Heck reaction gets white solid compound III 31.00 g, content (HPLC) 84.71%, yield is 85.8% based on p-bromotoluene. Four-step yield is 77.88% based on p-bromotoluene.

[0050] Example 3 2,6 dimethyl-2,3-dihydro-l-indenone was prepared according to the method of example 1, except that the pd catalyst of the Heck reaction was replaced by 0.65 g (content 98%, 0.00087 mol) Pd(dppf)Cl2 and the ligand was replaced by 1.10 g (content 98%, 0.0017 mol) BINAP. The final isolation of the Heck reaction gave compound III 31.25 g as a white solid, content (HPLC) 84.3%, yield 86.1% based on p-bromotoluene. The four steps yield was 78.15% based on p-bromotoluene.

[0051] Example 4 2,6 dimethyl-2,3-dihydro-l-indenone was prepared according to the method of example 1, except that the solvent of the Heck reaction was replaced by an equal mass of acetonitrile and the reaction was stirred at 80°C for 5 h. The final isolation of the Heck reaction gave compound III 28.78 g as a white solid, content (HPLC) 87.3%, yield 82.11% based on p-bromotoluene. The four steps yield was 74.53% based on p-bromotoluene.

[0052] Example 5 2,6 dimethyl-2,3-dihydro-l-indenone was prepared according to the method of example 1, except that the acid binding agent of the Heck reaction was triethylamine and 35.5 g (content 99%, 0.3473 mol) of triethylamine was added. The isolation gave compound III 30.89 g as a white solid, content (HPLC) 85.1%, yield 85.9% based on p-bromotoluene. The four steps yield was 77.97% based on p-bromotoluene.

[0053] Example 6 2,6 dimethyl-2,3-dihydro-l-indenone was prepared according to the method of example 1, except that the acid binding agent of the Heck reaction was pyridine and 27.75 g (content 99%, 0.3473 mol) of pyridine was added. The isolation gave compound III 31.14 g as a white solid, content (HPLC) 85.3%, yield 86.8% based on p-bromotoluene. The four steps yield was 78.79% based on p-bromotoluene.

[0054] Example 7 2,6 dimethyl-2,3-dihydro-l-indenone was prepared according to the method of example 1, except that the catalyst of the hydrogenation reaction was replaced by platinum carbon and 2 g of platinum carbon was added. The reaction gave compound IV 19.25 g, content (HPLC) 82.5%, yield 94.6% based on compound III, four steps yield 76.72% based on p-bromotoluene.

[0055] Example 8 Example 1, except that the hydrogenation catalyst was replaced with Raney nickel, 2 g of Raney nickel was added, and the reaction resulted in 19.03 g of compound IV, 82.5% by HPLC, 93.5% yield based on compound III, 75.82% yield based on p-bromotoluene over four steps.

[0056] Example 9 Example 1, except that the hydrogenation solvent was replaced with an equal mass of THF, and the reaction resulted in 19.97 g of compound IV, 82.8% by HPLC, 98.5% yield based on compound III, 79.88% yield based on p-bromotoluene over four steps.

Claims

1. A method for preparing 2,6-dimethyl-2,3-dihydro-1-indanone, characterized in that, Includes the following steps: (A) p-bromotoluene of formula (I) and methacrylic acid of formula (II) react with a catalyst via the Heck reaction to obtain the intermediate of formula (III); (B) The intermediate shown in formula (III) undergoes a hydrogenation reaction with hydrogen in the presence of a catalyst to obtain the intermediate shown in formula (IV); (C) The intermediate shown in formula (IV) undergoes an acylation reaction with an acylation reagent to obtain the intermediate shown in formula (V); (D) The intermediate shown in formula (V) undergoes Friedel-Crafts acylation under the action of a Lewis acid to give 2,6-dimethyl-2,3-dihydro-1-indanone; 。 2. The preparation method according to claim 1, characterized in that, In step (A), the molar ratio of p-bromotoluene to methacrylic acid is 1:1.03 to 2.

0.

3. The preparation method according to claim 1 or 2, characterized in that, In step (A), the catalyst is a palladium salt and a ligand. The palladium salt includes at least one of Pd(OAc)2, Pd(dppf)Cl2, PdCl2, [1,1'-bis(di-tert-butylphosphine)ferrocene]palladium dichloride, and palladium on carbon. The ligand includes at least one of BINAP, tris(o-methylphenyl)phosphine, and triphenylphosphine.

4. The preparation method according to claim 3, characterized in that, In step (A), the molar ratio of palladium salt to p-bromotoluene shown in formula (I) is 0.005 to 0.01:1; the molar ratio of ligand to p-bromotoluene shown in formula (I) is 0.01 to 0.02:

1.

5. The preparation method according to any one of claims 1-4, characterized in that, In step (A), the reaction is carried out in the presence of an acid-binding agent, which is at least one of an organic base and an inorganic base; preferably, the organic base includes at least one of triethylamine, pyridine, diisopropylethylamine, morpholine, and pyrrolidine, and the inorganic base includes at least one of potassium carbonate and sodium carbonate; preferably, the molar ratio of the acid-binding agent to p-bromotoluene shown in formula (I) is 1.5 to 2:

1.

6. The preparation method according to claim 1, characterized in that, In step (B), the catalyst comprises palladium on carbon, platinum on carbon, or Raney nickel; preferably, the amount of catalyst used is 6-10% of the mass of the intermediate shown in Formula III.

7. The preparation method according to claim 1, characterized in that, In step (C), the molar ratio of the intermediate shown in formula (IV) to the acylation reagent is 1:1.03 to 2.0; preferably, the acylation reagent is selected from thionyl chloride or oxalyl chloride.

8. The preparation method according to claim 1, characterized in that, In step (D), the molar ratio of the intermediate shown in Formula V to the Lewis acid is 1:1.03 to 2.0; preferably, the Lewis acid is selected from at least one of aluminum trichloride, zinc chloride, ferric chloride, tin tetrachloride, and aluminum tribromide.

9. The preparation method according to any one of claims 1-8, characterized in that, In step (A), the reaction is carried out under gas protection; Preferably, in step (A), the reaction temperature is 80-110℃; Preferably, in step (B), the hydrogenation reaction conditions are: temperature 20-30℃, hydrogen pressure 0.2-0.5MPa, and time 8-10h. Preferably, in step (C), the reaction temperature is 20-30℃. Preferably, in step (D), the mixing temperature of the raw materials and the reaction temperature are both -5 to 20°C.

10. The preparation method according to any one of claims 1-9, characterized in that, In step (A), the reaction is carried out in the presence of a solvent, which includes at least one of benzene solvents, alcohol solvents, ether solvents, nitrile solvents, amide solvents, and sulfone solvents; Preferably, in step (B), the reaction is carried out in a solvent, which includes at least one of alcohol solvents, benzene solvents, and ether solvents; Preferably, in step (C), the reaction is carried out in the presence of a solvent, which includes at least one of a haloalkane solvent and a benzene solvent; Preferably, in step (D), the reaction is carried out in the presence of a solvent, which is at least one of a haloalkane solvent and a benzene solvent.

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