A process for the preparation of 4-bromocyclopropylbenzene

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 4-bromocyclopropylbenzene. The method comprises the following steps: in step 1, bromobenzene, a Lewis acid and 3-chloropropionyl chloride are reacted to obtain 4-bromo-3-chloropropiophenone; in step 2, 4-bromo-3-chloropropiophenone and a reducing agent are reacted to obtain 4-bromochloropropylbenzene; and in step 3, 4-bromochloropropylbenzene is reacted under the action of an alkali catalyst to obtain 4-bromocyclopropylbenzene. The method has the advantages that common reagents are used in each step, the cost of raw materials is low, the synthesis process is short, the yield is high, there is no harsh reaction condition, the method is safe, convenient to operate, friendly to the environment, suitable for large-scale industrial production, and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 4-bromocyclopropylbenzene. Background Technology

[0002] 4-Bromocyclopropylbenzene is an important pharmaceutical intermediate used in the synthesis of drugs such as antibacterial quinolones. Therefore, the development of its preparation method is an important research topic.

[0003] In 1961, Levina, R.Ya., et al. used cyclopropylbenzene as a starting material and obtained the target product in a one-step reaction via the route shown in the formula (see By: Levina, R.Ya.; et al Zhurnal Obshchei Khimii (1961), 31, 3480-1). Although this method has fewer process steps, the raw materials are rare and expensive, and the reaction requires ultra-low temperatures of -80 degrees Celsius, making the reaction conditions harsh, difficult to produce, and not easy to synthesize. The reaction formula is as follows:

[0004]

[0005] In 1987, O'Connor, Edward J., et al. used p-bromobenzaldehyde as a starting material and obtained the target product in a one-step reaction using the route shown in the formula (see Journal of the American Chemical Society (1987), 109(12), 3739-47). Although this method has fewer process steps, the two starting materials are not easy to synthesize and are very expensive, making production difficult and generating a large amount of wastewater, which can easily cause environmental pollution.

[0006] The reaction formula is as follows:

[0007]

[0008] In 2016, Pitts, Cody Ross, et al. used p-dibromobenzene and cyclopropylboronic acid as starting materials to obtain the target product in a one-step reaction via the route shown in the formula (see Pitts, Cody Ross; et al Journal of the American Chemical Society (2016), 138(20), 6598-6609). Although this method has fewer process steps, the raw material cost is high, and it uses expensive catalysts, requires harsh reaction conditions, and is difficult to synthesize. The reaction formula is as follows:

[0009]

[0010] In summary, existing methods for preparing 4-bromocyclopropylbenzene suffer from harsh reaction conditions, high costs, and environmental pollution. Therefore, developing new synthetic routes to achieve milder, lower-cost, and more environmentally friendly methods for preparing 4-bromocyclopropylbenzene remains an important research topic in this field. Summary of the Invention

[0011] To address the problems of existing technologies, this invention provides a mild, low-cost, and environmentally friendly method for preparing 4-bromocyclopropylbenzene.

[0012] A method for preparing 4-bromocyclopropylbenzene includes the following steps:

[0013]

[0014] Step 1: Bromobenzene, Lewis acid, and 3-chloropropionyl chloride are reacted to give 4-bromo-3-chlorophenylpropionone;

[0015] Step 2: React 4-bromo-3-chlorophenylacetone with a reducing agent to obtain 4-bromochloropropylbenzene;

[0016] Step 3: 4-Bromochloropropylbenzene is reacted under the action of an alkaline catalyst to obtain 4-bromocyclopropylbenzene.

[0017] Preferably, in step 1, the Lewis acid is selected from aluminum trichloride.

[0018] Preferably, in step 2, the reducing agent is selected from at least one of triethylsilane and boron trifluoride ether.

[0019] Preferably, in step 3, the alkaline catalyst is selected from at least one of hexamethyldisilamide lithium, n-butyllithium, sodium hydride, sodium amide, lithium amide, and diisopropylamide lithium.

[0020] Preferably, in step 1, the reaction temperature is 10-40℃;

[0021] And / or, when adding reaction materials to the reaction vessel, the temperature is controlled at 10-40℃;

[0022] And / or, the molar ratio of bromobenzene, anhydrous aluminum trichloride and 3-chloropropionyl chloride is 1:(1.1-1.3):(1.1-1.3);

[0023] And / or, the reaction medium is selected from at least one of dichloromethane, dichloroethane, chlorobenzene, nitrobenzene, and o-dichlorobenzene;

[0024] And / or, the reaction time is 1-5 hours.

[0025] Preferably, in step 1, the reaction temperature is 25-30℃;

[0026] And / or, when adding reaction materials to the reaction vessel, the temperature is controlled at 10-15℃;

[0027] And / or, the molar ratio of bromobenzene, anhydrous aluminum trichloride, and 3-chloropropionyl chloride is 1:1.3:1.3;

[0028] And / or, the reaction medium is selected from dichloromethane;

[0029] And / or, the reaction time is 1-2 hours.

[0030] Preferably, in step 2, the reaction temperature is 20-30℃;

[0031] And / or, when adding reaction materials into the reaction vessel, the temperature is controlled at 0-30℃;

[0032] And / or, the molar ratio of the 4-bromo-3-chlorophenylacetone, triethylsilane and boron trifluoride diethyl ether is 1:(1.5-2):(1-1.5);

[0033] And / or, the reaction medium is selected from at least one of tetrahydrofuran, acetonitrile, methyl tert-butyl ether, toluene, and 2-methyltetrahydrofuran;

[0034] And / or, the reaction time is 3-10 hours.

[0035] Preferably, in step 2, the reaction temperature is 25-30℃;

[0036] And / or, when adding reaction materials into the reaction vessel, the temperature is controlled at 0-5℃;

[0037] And / or, the molar ratio of the 4-bromo-3-chlorophenylacetone, triethylsilane and boron trifluoride diethyl ether is 1:2:1.5;

[0038] And / or, the reaction medium is selected from tetrahydrofuran;

[0039] And / or, the reaction time is 8-10 hours.

[0040] Preferably, in step 3, the reaction temperature is 20-40℃;

[0041] And / or, when adding reaction materials into the reaction vessel, the temperature is controlled at 0-30℃;

[0042] And / or, the molar ratio of the 4-bromochloropropylbenzene to the base catalyst is 1:(1.1-1.3);

[0043] And / or, the reaction medium is selected from at least one of tetrahydrofuran, toluene, methyl tert-butyl ether, acetonitrile, and 2-methyltetrahydrofuran;

[0044] And / or, the reaction time is 1-6 hours.

[0045] Preferably, in step 3, the reaction temperature is 25-30℃;

[0046] And / or, when adding reaction materials into the reaction vessel, the temperature is controlled at 0-5℃;

[0047] And / or, the molar ratio of the 4-bromochloropropylbenzene to the base catalyst is 1:1.3;

[0048] And / or, the reaction medium is selected from tetrahydrofuran;

[0049] And / or, the reaction time is 1-2 hours.

[0050] This invention provides a novel synthetic route for the synthesis of 4-bromocyclopropylbenzene and optimizes the synthetic conditions for each step. The method for preparing 4-bromocyclopropylbenzene according to this invention is low-cost, uses readily available and inexpensive raw materials, has a simple reaction process, requires no special equipment such as ultra-high temperature equipment, is convenient and safe to operate, has a high overall yield, and is environmentally friendly. Therefore, this invention has excellent application prospects.

[0051] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0052] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0053] Figure 1 4-Bromocyclopropylbenzene prepared in Example 1 1 H NMR spectrum. Detailed Implementation

[0054] In the following examples, reagents and raw materials not specifically described are all commercially available products.

[0055] Example 1

[0056] (1) Preparation of 4-bromo-3-chlorophenylacetone

[0057] 50 g of bromobenzene (1.0 eq) and 500 g of dichloromethane were added to a three-necked flask, followed by 55.2 g of anhydrous aluminum trichloride (1.3 eq). Then, 52.5 g of 3-chloropropionyl chloride (1.3 eq) was added dropwise at 10-15 °C. After the addition was complete, the system was reacted at 25-30 °C for 1 hour. Once the reaction was complete, the mixture was quenched, separated into layers, and concentrated to obtain crude 4-bromo-3-chlorophenylpropanone, yield: 95%.

[0058] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.82(d,2H),7.63(d,2H),3.91(t,2H),3.42(t,2H).

[0059] (2) Preparation of 4-bromochloropropylbenzene

[0060] The above-mentioned 4-bromo-3-chlorophenylacetone (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g), cooled to 0-5 °C, and triethylsilane (47 g, 2.0 eq) was added dropwise to the reaction system. Boron trifluoride diethyl ether (43 g, 1.5 eq) was then slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature and reacted for 8 h. The reaction was quenched, and the system was extracted with methyl tert-butyl ether (500 g). The organic phase was concentrated to dryness to obtain 4-bromo-N-(2-hydroxyphenyl)benzamide, yield: 85%.

[0061] MRI scan: 1 H NMR (400MHz, CDCl3): δ7.82(d,2H), 7.09(d,2H), 3.68(t,2H), 2.63(t,2H), 1.90(t,2H).

[0062] (3) Preparation of 4-bromocyclopropylbenzene

[0063] 4-Bromochloropropylbenzene (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g). The mixture was cooled to 0-5 °C, and hexamethyldisilamide lithium (1 M, 278 mL, 1.3 eq) was slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature. Under nitrogen protection, the system temperature was raised to 25-30 °C, and the reaction was allowed to proceed for 1 hour. After the reactants had reacted completely, the mixture was cooled to room temperature, and the reaction was quenched with water. The organic phase was extracted with methyl tert-butyl ether (500 g), separated, concentrated to dryness, and then distilled to give 4-bromocyclopropylbenzene. Yield: 80%

[0064] MRI scan: 1H NMR (400MHz, CDCl3) δ7.36(d,2H),6.94(d,,2H),1.90-1.81(m,1H),1.10-0.94(m,2H),0.70-0.63(m,2H).

[0065] Example 2

[0066] (1) Preparation of 4-bromo-3-chlorophenylacetone

[0067] 50 g of bromobenzene (1.0 eq) and 500 g of dichloromethane were added to a three-necked flask, followed by 55.2 g of anhydrous aluminum trichloride (1.3 eq). Then, 52.5 g of 3-chloropropionyl chloride (1.3 eq) was added dropwise at 35-40 °C. After the addition was complete, the system was reacted at 35-40 °C for 1 hour. Once the reaction was complete, the mixture was quenched, separated into layers, and concentrated to obtain crude 4-bromo-3-chlorophenylpropanone, yield: 88%.

[0068] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.82(d,2H),7.63(d,2H),3.91(t,2H),3.42(t,2H).

[0069] (2) Preparation of 4-bromochloropropylbenzene

[0070] The above-mentioned 4-bromo-3-chlorophenylacetone (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g), and at room temperature (25-30 °C), triethylsilane (47 g, 2.0 eq) was added dropwise to the reaction system, followed by slow dropwise addition of boron trifluoride diethyl ether (43 g, 1.5 eq). The reaction was carried out at room temperature for 8 h, and the reaction was quenched. The system was then extracted with methyl tert-butyl ether (500 g), and the organic phase was concentrated to dryness to give 4-bromo-N-(2-hydroxyphenyl)benzamide, yield: 81%.

[0071] MRI scan: 1 H NMR (400MHz, CDCl3): δ7.82(d,2H), 7.09(d,2H), 3.68(t,2H), 2.63(t,2H), 1.90(t,2H).

[0072] (3) Preparation of 4-bromocyclopropylbenzene

[0073] 4-Bromochloropropylbenzene (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g). At room temperature (25-30 °C), hexamethyldisilamide lithium (1 M, 278 mL, 1.3 eq) was slowly added dropwise to the reaction system. Under nitrogen protection, the system temperature was raised to 25-30 °C, and the reaction was allowed to proceed for 1 h. After the reactants had reacted completely, the mixture was cooled to room temperature, and the reaction was quenched with water. The organic phase was extracted with methyl tert-butyl ether (500 g), separated, concentrated to dryness, and then distilled to give 4-bromocyclopropylbenzene. Yield: 75%

[0074] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.36(d,2H),6.94(d,,2H),1.90-1.81(m,1H),1.10-0.94(m,2H),0.70-0.63(m,2H).

[0075] Example 3

[0076] (1) Preparation of 4-bromo-3-chlorophenylacetone

[0077] 50 g of bromobenzene (1.0 eq) and 500 g of dichloromethane were added to a three-necked flask, followed by 46.7 g of anhydrous aluminum trichloride (1.1 eq). 3-Chloropropionyl chloride (44.4 g, 1.1 eq) was then added dropwise at 10-15 °C. After the addition was complete, the system was reacted at 25-30 °C for 1 hour. Once the reaction was complete, the mixture was quenched, separated into layers, and concentrated to obtain crude 4-bromo-3-chlorophenylpropanone, yield: 85%.

[0078] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.82(d,2H),7.63(d,2H),3.91(t,2H),3.42(t,2H).

[0079] (2) Preparation of 4-bromochloropropylbenzene

[0080] The above-mentioned 4-bromo-3-chlorophenylacetone (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g), cooled to 0-5 °C, and triethylsilane (35.3 g, 1.5 eq) was added dropwise to the reaction system. Boron trifluoride diethyl ether (28.7 g, 1.0 eq) was slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature and reacted for 8 h. The reaction was quenched, and the system was extracted with methyl tert-butyl ether (500 g). The organic phase was concentrated to dryness to give 4-bromo-N-(2-hydroxyphenyl)benzamide, yield: 76%.

[0081] MRI scan: 1H NMR (400MHz, CDCl3): δ7.82(d,2H), 7.09(d,2H), 3.68(t,2H), 2.63(t,2H), 1.90(t,2H).

[0082] (3) Preparation of 4-bromocyclopropylbenzene

[0083] 4-Bromochloropropylbenzene (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g). The mixture was cooled to 0-5 °C, and hexamethyldisilamide lithium (1 M, 235 ml, 1.1 eq) was slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature. Under nitrogen protection, the system temperature was raised to 25-30 °C, and the reaction was allowed to proceed for 1 h. After the reactants had reacted completely, the mixture was cooled to room temperature, and the reaction was quenched with water. The organic phase was extracted with methyl tert-butyl ether (500 g), separated, concentrated to dryness, and then distilled to give 4-bromocyclopropylbenzene. Yield: 72%

[0084] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.36(d,2H),6.94(d,,2H),1.90-1.81(m,1H),1.10-0.94(m,2H),0.70-0.63(m,2H).

[0085] Example 4

[0086] (1) Preparation of 4-bromo-3-chlorophenylacetone

[0087] 50 g of bromobenzene (1.0 eq) and 500 g of dichloroethane were added to a three-necked flask, followed by 55.2 g of anhydrous aluminum trichloride (1.3 eq). Then, 52.5 g of 3-chloropropionyl chloride (1.3 eq) was added dropwise at 10-15 °C. After the addition was complete, the system was reacted at 25-30 °C for 1 hour. Once the reaction was complete, the mixture was quenched, separated into layers, and concentrated to obtain crude 4-bromo-3-chlorophenylacetone, yield: 92%.

[0088] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.82(d,2H),7.63(d,2H),3.91(t,2H),3.42(t,2H).

[0089] (2) Preparation of 4-bromochloropropylbenzene

[0090] The above-mentioned 4-bromo-3-chlorophenylacetone (50 g, 1.0 eq) was dissolved in acetonitrile (500 g), cooled to 0-5 °C, and triethylsilane (47 g, 2.0 eq) was added dropwise to the reaction system. Boron trifluoride diethyl ether (43 g, 1.5 eq) was then slowly added dropwise to the reaction system. The reaction system was warmed to room temperature and reacted for 8 h. The reaction was quenched, and the system was extracted with methyl tert-butyl ether (500 g). The organic phase was concentrated to dryness to obtain 4-bromo-N-(2-hydroxyphenyl)benzamide, yield: 80%.

[0091] MRI scan: 1 H NMR (400MHz, CDCl3): δ7.82(d,2H), 7.09(d,2H), 3.68(t,2H), 2.63(t,2H), 1.90(t,2H).

[0092] (3) Preparation of 4-bromocyclopropylbenzene

[0093] 4-Bromochloropropylbenzene (50 g, 1.0 eq) was dissolved in toluene (500 g). The mixture was cooled to 0-5 °C, and hexamethyldisilamide lithium (1 M, 278 mL, 1.3 eq) was slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature, and under nitrogen protection, the temperature was raised to 25-30 °C and the reaction was allowed to proceed for 1 hour. After the reactants had reacted completely, the mixture was cooled to room temperature, and the reaction was quenched with water. The organic phase was extracted with methyl tert-butyl ether (500 g), separated, concentrated to dryness, and then distilled to give 4-bromocyclopropylbenzene. Yield: 60%

[0094] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.36(d,2H),6.94(d,,2H),1.90-1.81(m,1H),1.10-0.94(m,2H),0.70-0.63(m,2H).

[0095] Example 5

[0096] (1) Preparation of 4-bromo-3-chlorophenylacetone

[0097] 50 g of bromobenzene (1.0 eq) and 500 g of dichloromethane were added to a three-necked flask, followed by 55.2 g of anhydrous aluminum trichloride (1.3 eq). Then, 52.5 g of 3-chloropropionyl chloride (1.3 eq) was added dropwise at 10-15 °C. After the addition was complete, the system was reacted at 25-30 °C for 5 h. Once the reaction was complete, the mixture was quenched, separated into layers, and concentrated to obtain crude 4-bromo-3-chlorophenylpropanone, yield: 91%.

[0098] MRI scan: 1H NMR (400MHz, CDCl3) δ7.82(d,2H),7.63(d,2H),3.91(t,2H),3.42(t,2H).

[0099] (2) Preparation of 4-bromochloropropylbenzene

[0100] The above-mentioned 4-bromo-3-chlorophenylacetone (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g), cooled to 0-5 °C, and triethylsilane (47 g, 2.0 eq) was added dropwise to the reaction system. Boron trifluoride diethyl ether (43 g, 1.5 eq) was then slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature and reacted for 5 h. The reaction was quenched, and the system was extracted with methyl tert-butyl ether (500 g). The organic phase was concentrated to dryness to give 4-bromo-N-(2-hydroxyphenyl)benzamide, yield: 72%.

[0101] MRI scan: 1 H NMR (400MHz, CDCl3): δ7.82(d,2H), 7.09(d,2H), 3.68(t,2H), 2.63(t,2H), 1.90(t,2H).

[0102] (3) Preparation of 4-bromocyclopropylbenzene

[0103] 4-Bromochloropropylbenzene (50 g, 1.0 eq) was dissolved in tetrahydrofuran (500 g). The mixture was cooled to 0-5 °C, and hexamethyldisilamide lithium (1 M, 278 mL, 1.3 eq) was slowly added dropwise to the reaction system. The reaction system was then cooled to room temperature, and under nitrogen protection, the temperature was raised to 25-30 °C. The reaction was allowed to proceed for 6 hours. After the reactants had reacted completely, the mixture was cooled to room temperature, and water was added to quench the reaction. The organic phase was extracted with methyl tert-butyl ether (500 g), separated, concentrated to dryness, and then distilled to give 4-bromocyclopropylbenzene. Yield: 65%

[0104] MRI scan: 1 H NMR (400MHz, CDCl3) δ7.36(d,2H),6.94(d,,2H),1.90-1.81(m,1H),1.10-0.94(m,2H),0.70-0.63(m,2H).

[0105] The process conditions and yields of each step in Examples 1-5 were compared, and the results are shown in Tables 1-3.

[0106] Table 1. Process conditions and yields in the preparation of 4-bromo-3-chlorophenylacetone

[0107]

[0108] Table 2. Process conditions and yields in the preparation of 4-bromo-3-chlorophenylacetone

[0109]

[0110] Table 3. Process conditions and yields in the preparation of 4-bromocyclopropylbenzene

[0111]

[0112] The comparison data of the above process conditions and yields show that the process conditions used in Example 1 have the best yield.

[0113] In summary, this invention provides a novel method for preparing 4-bromocyclopropylbenzene, and optimizes the process conditions for each reaction step. The method of this invention uses common reagents in each step, has low raw material costs, a short synthesis process, high yield, no harsh reaction conditions, is safe and easy to operate, and is environmentally friendly. It is suitable for large-scale industrial production and has good application prospects.

Claims

1. A process for the preparation of 4-bromocyclopropylbenzene, characterized in that, comprising the steps of: Step 1, reacting bromobenzene, Lewis acid and 3-chloropropionyl chloride to obtain 4-bromo-3-chloropropiophenone; Step 2, reacting 4-bromo-3-chloropropiophenone with a reducing agent to obtain 4-bromochloropropylbenzene; Step 3, reacting 4-bromochloropropylbenzene in the presence of a base catalyst to obtain 4-bromocyclopropylbenzene; The base catalyst is selected from lithium hexamethyldisilazide.

2. The method of claim 1, wherein: In Step 1, the Lewis acid is selected from aluminum trichloride.

3. The method of claim 1, wherein: In Step 2, the reducing agent is selected from at least one of triethylsilane and boron trifluoride etherate.

4. The method of claim 1, wherein: In Step 1, the temperature of the reaction is 10-40℃; And / or, the temperature is controlled to be 10-40℃ when the reaction raw materials are added into the reaction container; And / or, the Lewis acid is selected from aluminum trichloride, and the molar ratio of the bromobenzene, aluminum trichloride and 3-chloropropionyl chloride is 1:(1.1-1.3):(1.1-1.3); And / or, the reaction medium is selected from at least one of dichloromethane, dichloroethane, chlorobenzene, nitrobenzene and o-dichlorobenzene; And / or, the reaction time is 1-5 h.

5. The method of claim 4, wherein: In Step 1, the temperature of the reaction is 25-30℃; And / or, the temperature is controlled to be 10-15℃ when the reaction raw materials are added into the reaction container; And / or, the molar ratio of the bromobenzene, aluminum trichloride and 3-chloropropionyl chloride is 1:1.3:1.3; And / or, the reaction medium is dichloromethane; And / or, the reaction time is 1-2 h.

6. The method of claim 1, wherein: In Step 2, the temperature of the reaction is 20-30℃; And / or, the temperature is controlled to be 0-30℃ when the reaction raw materials are added into the reaction container; And / or, the reducing agent is selected from triethylsilane and boron trifluoride etherate, and the molar ratio of the 4-bromo-3-chloropropiophenone, triethylsilane and boron trifluoride etherate is 1:(1.5-2):(1-1.5); And / or, the reaction medium is selected from at least one of tetrahydrofuran, acetonitrile, methyl tert-butyl ether, toluene and 2-methyltetrahydrofuran; And / or, the reaction time is 3-10 h.

7. The method of claim 6, wherein: In Step 2, the temperature of the reaction is 25-30℃; And / or, the temperature is controlled to be 0-5℃ when the reaction raw materials are added into the reaction container; And / or, the molar ratio of the 4-bromo-3-chloropropiophenone, triethylsilane and boron trifluoride etherate is 1:2:1.5; And / or, the reaction medium is tetrahydrofuran; And / or, the reaction time is 8-10 h.

8. The method of claim 1, wherein: In Step 3, the temperature of the reaction is 20-40℃; And / or, the temperature is controlled to be 0-30℃ when the reaction raw materials are added into the reaction container; And / or, the molar ratio of the 4-bromochloropropylbenzene and the base catalyst is 1:(1.1-1.3); And / or, the reaction medium is selected from at least one of tetrahydrofuran, toluene, methyl tert-butyl ether, acetonitrile and 2-methyltetrahydrofuran; And / or, the reaction time is 1-6 h.

9. The method of claim 8, wherein: In Step 3, the temperature of the reaction is 25-30℃; And / or, the temperature is controlled to be 0-5℃ when the reaction raw materials are added into the reaction container; And / or, the molar ratio of the 4-bromochloropropylbenzene and the base catalyst is 1:1.3; And / or, the reaction medium is tetrahydrofuran; and / or the reaction is carried out for a period of 1-2 h. and / or the reaction is carried out for a period of

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