A method for preparing a 2,7-dichlorofluorene derivative

Abstract

The application discloses a preparation method of 2,7-dichlorofluorene derivatives. The method comprises the following steps: taking a fluorene compound shown in formula (II) as raw material, reacting with chloroagent trichloroisocyanuric acid under the action of a catalyst at a certain temperature in an organic solvent, and separating and purifying the obtained reaction liquid to obtain 2,7-dichlorofluorene derivatives shown in formula (I). In the formula, a substituent R is substituted or not substituted. When the substituent R is substituted, the substituent R is CH3-, C2H5-, Bn-, C6H5-, CH3O-, C2H5O- or C6H5O-. The preparation method has the advantages of cheap and easily available raw material, environmental friendliness, simple process, simple operation, high purity, good yield and the like, conforms to the concept of green pharmacy, and is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmaceutical intermediates, and particularly relates to a preparation method of 2,7-dichlorofluorene derivative. BACKGROUND

[0002] Fluorene derivatives are widely used in various fields such as material science, organic chemistry, medicinal chemistry, and the like. 2,7-dichlorofluorene is an important intermediate of primaquine, an antimalarial drug. There are two main types of drugs for treating malaria, but the drugs for controlling clinical onset, such as quinine, chloroquine and artemisinin, have all shown drug resistance. In order to solve the problem of drug resistance, the World Health Organization advocates combination therapy, and the artemether-primaquine compound preparation is currently the preferred drug for treating malaria. This compound drug has been included in the WHO basic list of antimalarial drugs, and the compound ratio is artemether: primaquine = 1:6. 2,7-dichlorofluorene is an intermediate of the antimalarial drug primaquine.

[0003] At present, the main synthesis methods of 2,7-dichlorofluorene are as follows:

[0004] 1) In 1992, the Institute of Microbiology and Epidemiology of Military Medical Sciences tried to use N-chlorosuccinimide (NCS) as a chlorinating agent (Wang J, Zhong J X, Journal of Military Medical Academy, 1992, (4): 302-303.). This method avoids heating reflux and saves resources, but the reaction time is too long, and the cost is too high due to the high price of raw materials.

[0005]

[0006] 2) In 1992, the Institute of Microbiology and Epidemiology of Military Medical Sciences also tried to use dichloroamine T as a chlorinating agent. In the presence of concentrated H2SO4 as a catalyst, 2,7-dichlorofluorene was obtained by electrophilic substitution reaction, with a yield of only 33%. This method has a low yield, a long cycle, and the most important is that dichloroamine T pollutes the environment and the three wastes are difficult to handle (Wang J, Zhong J X, Journal of Military Medical Academy, 1992, (4): 302-303.).

[0007]

[0008] 3) Chinese patent CN103193588A discloses a method for large-scale production of 2,7-dichlorofluorene using Cl2 as a chlorinating agent. This reaction is a typical electrophilic substitution chlorination reaction of aromatic ring. The use of chlorine gas as a chlorinating agent has the problems of inconvenient gas dosage, multiple by-products, large amount of residual halogen, high requirement for environmental protection equipment, difficulty in green environmental protection process control, and difficulty in three waste treatment.

[0009]

[0010] 4) Chinese patent CN102786399A discloses a method that uses dichlorohydantoin as a chlorinating agent to react under acidic conditions to obtain 2,7-dichlorofluorene with a yield of 54%. This method uses a novel chlorinating agent, dichlorohydantoin, which has good selectivity and a considerable yield. It overcomes the shortcomings of traditional chlorination agents, such as poor selectivity and low chlorination efficiency, but requires an auxiliary reaction step and the reaction time is too long.

[0011] Summary of the Invention

[0012] To address the aforementioned problems in the existing technology, the present invention aims to provide a method for preparing 2,7-dichlorofluorene derivatives from fluorene compounds as starting materials. This method is characterized by its simple process, convenient operation, low cost, environmental friendliness, and high yield.

[0013] To achieve the above objectives, the following technical solution is proposed:

[0014] A method for preparing a 2,7-dichlorofluorene derivative involves using a fluorene compound of formula (II) as a raw material, reacting it with the chlorinated agent trichloroisocyanuric acid in an organic solvent at a certain temperature under the action of a catalyst, and then separating and purifying the resulting reaction solution to obtain the 2,7-dichlorofluorene derivative of formula (I).

[0015]

[0016] In the formula, the substituent R may or may not be substituted. When substituted, the substituent R is CH3-, C2H5-, Bn-, C6H5-, CH3O-, C2H5O-, or C6H5O-.

[0017] Furthermore, the catalyst is a Lewis acid or a protic acid, wherein the protic acid is concentrated hydrochloric acid, concentrated sulfuric acid, H3PO4 or sulfonic acid, and the Lewis acid is anhydrous aluminum chloride, tin tetrachloride, aluminum chloride hexahydrate or ferric nitrate nonahydrate, preferably concentrated hydrochloric acid, concentrated sulfuric acid, anhydrous aluminum chloride or tin tetrachloride.

[0018] Further, the organic solvent is 1,2-dichloroethane, toluene, isopropyl ether, ethyl acetate, dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, ethanol, or dichloromethane.

[0019] Furthermore, the amounts of fluorene compounds, trichloroisocyanuric acid and catalyst shown in formula (II) are in the following molar ratio: fluorene compounds: trichloroisocyanuric acid: catalyst = 1.0: 0.7~2.5: 0.01~0.5.

[0020] Furthermore, the reaction time is 3 to 6 hours.

[0021] Furthermore, the reaction process temperature is controlled at -10~60℃.

[0022] Furthermore, the volume ratio of the organic solvent to the mass ratio of the fluorene compound shown in formula (II) is 3~6:1, with volume in mL and mass in g.

[0023] Further, the specific separation and purification process is as follows: After the reaction is completed, the precipitate is filtered, washed with ethanol, dissolved in ethyl acetate, the insoluble matter is filtered off, the ethyl acetate is recovered by rotary evaporation, and dried to obtain the 2,7-dichlorofluorene derivative as shown in formula (I).

[0024] The beneficial effects of this invention are as follows:

[0025] 1) The preparation method of the present invention is simple to operate, the raw material trichloroisocyanuric acid is cheap and readily available, the reaction can be carried out under mild conditions, the yield is high, and it is suitable for industrial production.

[0026] 2) The preparation method of the present invention is environmentally friendly, avoiding the high requirements for environmental protection equipment when using Cl2 as a chlorinating agent, and only requires a catalytic amount of acid system. Detailed Implementation

[0027] The technical solution of the present invention is illustrated by the following specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0028] Example 1 Synthesis of 2,7-Dichlorofluorene

[0029] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, add fluorene (20 g, 120.32 mmol) and trichloroisocyanuric acid (69.91 g, 300.80 mmol). o Add solvent acetonitrile (80 mL) to C, mechanically stir and cool to 0 °C, slowly add concentrated hydrochloric acid solution (0.61 g, 6.02 mmol) as catalyst. After the addition is complete, stir the reaction at 0 °C for 4 hours. Monitor the reaction progress with HPLC. After the reaction is complete, filter, wash the precipitate with 30 mL of ethanol, dissolve it in 100 mL of ethyl acetate, filter off the insoluble matter, evaporate to dryness to recover ethyl acetate, dry and weigh to obtain 24.73 g of white or pale yellow crystalline solid, yield 87.42%, HPLC purity 98.64%, melting point 126~128 °C.

[0030] 1H NMR (600 MHz, DMSO-d6): δ 7.91 (d, J = 8.2 Hz, 2H), 7.64 (d, J =1.9 Hz, 2H), 7.43 (dd, J = 8.2, 2.0 Hz, 2H), 3.94 (s, 2H).

[0031] Example 2

[0032] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene was added in a molar ratio of fluorene:trichloroisocyanuric acid:Lewis acid catalyst of 1.0:2.0:0.3, with 20 g of fluorene used. The Lewis acid catalyst was tin tetrachloride, and the organic solvent was N,N-dimethylformamide. The volume ratio of N,N-dimethylformamide to fluorene was 5 mL:1 g. The reaction temperature was 0 °C, and the reaction time was 5 hours. Other operations were the same as in Example 1. 25.31 g of 2,7-dichlorofluorene was obtained, with a product yield of 89.47%, HPLC purity of 99.13%, and melting point of 126-128 °C.

[0033] Example 3

[0034] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:2.4:0.15, with 20 g of fluorene used. The protic acid catalyst was concentrated hydrochloric acid, and the organic solvent was N,N-dimethylformamide. The volume ratio of N,N-dimethylformamide to the mass ratio of fluorene was 4 mL:1 g. The reaction temperature was 25 °C, and the reaction time was 4.5 hours. Other operations were the same as in Example 1. 24.57 g of 2,7-dichlorofluorene was obtained, with a product yield of 86.85%, HPLC purity of 99.51%, and melting point of 126-128 °C.

[0035] Example 4

[0036] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:0.8:0.4, with 20 g of fluorene used. The protic acid catalyst was concentrated sulfuric acid, and the organic solvent was N,N-dimethylformamide. The volume ratio of N,N-dimethylformamide to the mass ratio of fluorene was 4 mL:1 g. The reaction temperature was 0 °C, and the reaction time was 4 hours. Other operations were the same as in Example 1. 24.26 g of 2,7-dichlorofluorene was obtained, with a product yield of 85.75%, HPLC purity of 99.53%, and melting point of 126-128 °C.

[0037] Example 5

[0038] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene was added in a molar ratio of fluorene:trichloroisocyanuric acid:Lewis acid catalyst of 1.0:2.0:0.10, with 20 g of fluorene used. The Lewis acid catalyst was anhydrous aluminum trichloride, and the organic solvent was acetonitrile, with a volume ratio of acetonitrile to fluorene of 4 ml:1 g. The reaction temperature was 25 °C, and the reaction time was 5 hours. Other operations were the same as in Example 1. 23.95 g of 2,7-dichlorofluorene was obtained, with a product yield of 84.66%, HPLC purity of 98.55%, and melting point of 126-128 °C.

[0039] Example 6

[0040] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:Lewis acid catalyst was added in a molar ratio of 1.0:1.0:0.10, with 20 g of fluorene used. The Lewis acid catalyst was aluminum trichloride hexahydrate, and the organic solvent was 1,2-dichloroethane, with a volume ratio of 6 mL to 1 g of fluorene. The reaction temperature was 0 °C, and the reaction time was 5 hours. Other operations were the same as in Example 1. 19.66 g of 2,7-dichlorofluorene was obtained, with a product yield of 69.49%, an HPLC purity of 92.04%, and a melting point of 126–128 °C.

[0041] Example 7

[0042] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:0.75:0.25, with 20 g of fluorene used. The protic acid catalyst was concentrated hydrochloric acid, and the organic solvent was acetonitrile. The volume ratio of acetonitrile to fluorene was 4 mL:1 g. The reaction temperature was 60 °C, and the reaction time was 4.5 hours. Other operations were the same as in Example 1. 22.52 g of 2,7-dichlorofluorene was obtained, with a product yield of 79.60%, HPLC purity of 98.65%, and melting point of 126-128 °C.

[0043] Example 8

[0044] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:1.15:0.15, with 20 g of fluorene used. The protic acid catalyst was concentrated hydrochloric acid, and the organic solvent was toluene, with a toluene volume-to-fluorene mass ratio of 6 mL:1 g. The reaction temperature was 60 °C, and the reaction time was 4 hours. Other operations were the same as in Example 1, yielding 21.13 g of 2,7-dichlorofluorene, with a product yield of 74.69%, HPLC purity of 92.42%, and melting point of 126-128 °C.

[0045] Example 9

[0046] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:2.0:0.2, with 20 g of fluorene used. The protic acid catalyst was sulfonic acid, and the organic solvent was N,N-dimethylformamide. The volume ratio of N,N-dimethylformamide to the mass ratio of fluorene was 6 mL:1 g. The reaction temperature was 25 °C, and the reaction time was 4 hours. Other operations were the same as in Example 1. 20.41 g of 2,7-dichlorofluorene was obtained, with a product yield of 72.15%, HPLC purity of 97.65%, and melting point of 126-128 °C.

[0047] Example 10

[0048] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene was added in a molar ratio of fluorene:trichloroisocyanuric acid:Lewis acid catalyst of 1.0:1.75:0.3, with 20 g of fluorene used. The Lewis acid catalyst was tin tetrachloride, and the organic solvent was isopropyl ether, with a volume ratio of 6 ml to 1 g of fluorene. The reaction temperature was 45 °C, and the reaction time was 6 hours. Other operations were the same as in Example 1. 16.02 g of 2,7-dichlorofluorene was obtained, with a product yield of 56.63%, HPLC purity of 94.58%, and melting point of 126-128 °C.

[0049] Example 11

[0050] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:1.0:0.05, with 20 g of fluorene used. The protic acid catalyst was H3PO4, and the organic solvent was N,N-dimethylacetamide. The volume ratio of N,N-dimethylacetamide to the mass ratio of fluorene was 3 mL:1 g. The reaction temperature was -5 °C, and the reaction time was 3 hours. Other operations were the same as in Example 1. 18.45 g of 2,7-dichlorofluorene was obtained, with a product yield of 65.22%, HPLC purity of 99.51%, and melting point of 126-128 °C.

[0051] Example 12

[0052] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:1.25:0.25, with 20 g of fluorene used. The protic acid catalyst was concentrated sulfuric acid, and the organic solvent was anhydrous ethanol. The volume ratio of anhydrous ethanol to fluorene was 4 mL:1 g. The reaction temperature was 0 °C, and the reaction time was 5.5 hours. Other operations were the same as in Example 1. 18.33 g of 2,7-dichlorofluorene was obtained, with a product yield of 64.79%, HPLC purity of 94.88%, and melting point of 126-128 °C.

[0053] Example 13

[0054] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:Lewis acid catalyst was added in a molar ratio of 1.0:1.5:0.02, with 20 g of fluorene used. The Lewis acid catalyst was anhydrous aluminum trichloride, and the organic solvent was ethyl acetate, with a volume ratio of 3 ml to 1 g of fluorene. The reaction temperature was 45 °C, and the reaction time was 5 hours. Other operations were the same as in Example 1. 18.19 g of 2,7-dichlorofluorene was obtained, with a product yield of 64.29%, an HPLC purity of 93.62%, and a melting point of 126-128 °C.

[0055] Example 14

[0056] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene was added in a molar ratio of fluorene:trichloroisocyanuric acid:Lewis acid catalyst of 1.0:1.25:0.05, with 20 g of fluorene used. The Lewis acid catalyst was anhydrous aluminum trichloride, and the organic solvent was dichloromethane, with a volume ratio of dichloromethane to fluorene of 3 ml:1 g. The reaction temperature was 0 °C, and the reaction time was 5 hours. Other operations were the same as in Example 1. 17.78 g of 2,7-dichlorofluorene was obtained, with a product yield of 62.85%, HPLC purity of 99.35%, and melting point of 126-128 °C.

[0057] Example 15

[0058] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, fluorene:trichloroisocyanuric acid:protic acid catalyst was added in a molar ratio of 1.0:1.2:0.2, with 20 g of fluorene used. The protic acid catalyst was concentrated sulfuric acid, and the organic solvent was dimethyl sulfoxide. The volume ratio of dimethyl sulfoxide to fluorene was 5 mL:1 g. The reaction temperature was 25 °C, and the reaction time was 6 hours. Other operations were the same as in Example 1. 15.35 g of 2,7-dichlorofluorene was obtained, with a product yield of 54.26%, HPLC purity of 92.15%, and melting point of 126-128 °C.

[0059] Example 16

[0060] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-methylfluorene (110.96 mmol) and 30.94 g of trichloroisocyanuric acid (133.15 mmol) were added. Acetonitrile (80 mL) was added at 25 °C, and concentrated hydrochloric acid solution (3.37 g, 33.29 mmol) was slowly added dropwise at 25 °C. After the addition was complete, the mixture was stirred at 25 °C for 5 hours. The reaction progress was monitored by HPLC. After the reaction was completed, the mixture was filtered, and the precipitate was washed with 30 mL of ethanol, dissolved in 100 mL of ethyl acetate, filtered to remove the insoluble matter, and the ethyl acetate was recovered by rotary evaporation. The precipitate was dried and weighed to obtain 19.91 g of 2,7-dichloro-9-methyl-9H-fluorene, with a yield of 72.03%, an HPLC purity of 98.15%, and a melting point of 128 °C.

[0061] Example 17

[0062] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-methylfluorene, aluminum trichloride as the Lewis acid catalyst, and N,N-dimethylacetamide as the organic solvent were added. The volume ratio of N,N-dimethylacetamide to the mass ratio of the fluorene compound was 5 mL: 1 g. The reaction temperature was 0 °C, and the reaction time was 3 hours. Other operations were the same as in Example 16. 17.23 g of 2,7-dichloro-9-methyl-9H-fluorene was obtained, with a product yield of 62.34%, HPLC purity of 92.94%, and melting point of 128 °C.

[0063] Example 18

[0064] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-ethylfluorene (102.95 mmol) and 47.85 g of trichloroisocyanuric acid (205.89 mmol) were added. 80 mL of N,N-dimethylformamide (NDM) was added at 0 °C, and the mixture was cooled to 0 °C. A concentrated sulfuric acid solution (1.55 g, 15.44 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the temperature was raised to 45 °C, and the mixture was stirred at 45 °C for 3 hours. The reaction progress was monitored by HPLC. After the reaction was complete, the mixture was filtered. The precipitate was washed with 30 mL of ethanol, dissolved in 100 mL of ethyl acetate, and the insoluble matter was filtered off. The ethyl acetate was recovered by rotary evaporation, dried, and weighed to obtain 18.52 g of 2,7-dichloro-9-ethyl-9H-fluorene, with a yield of 68.36% and an HPLC purity of 98.42%.

[0065] Example 19

[0066] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-ethylfluorene, anhydrous tin tetrachloride, and ethyl acetate were added as the organic solvent. The volume ratio of ethyl acetate to the mass ratio of the fluorene compound was 6 mL: 1 g. The reaction temperature was 25 °C, and the reaction time was 4 hours. Other operations were the same as in Example 18. 14.82 g of 2,7-dichloro-9-ethyl-9H-fluorene was obtained, with a product yield of 54.71% and an HPLC purity of 91.75%.

[0067] Example 20

[0068] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-benzylfluorene and 19.94 g of trichloroisocyanuric acid (85.82 mmol) were added. 80 mL of 1,2-dichloroethane was added at 0 °C, and the mixture was cooled to 0 °C. A concentrated sulfuric acid solution (2.34 g, 23.41 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at 0 °C for 5 hours. The reaction progress was monitored by HPLC. After the reaction was completed, the mixture was filtered. The precipitate was washed with 30 mL of ethanol, dissolved in 100 mL of ethyl acetate, and the insoluble matter was filtered off. The ethyl acetate was recovered by rotary evaporation, dried, and weighed to obtain 15.74 g of 9-benzyl-2,7-dichloro-9H-fluorene, with a yield of 62.04%, an HPLC purity of 96.58%, and a melting point of 110–111 °C.

[0069] Example 21

[0070] In a 250 mL three-necked round-bottom flask equipped with a magnetic stirrer and a thermometer, 20 g of 9-benzylfluorene, anhydrous aluminum trichloride as the Lewis acid catalyst, and N,N-dimethylformamide as the organic solvent were reacted. The volume ratio of N,N-dimethylformamide to the mass ratio of the fluorene compound was 3 mL: 1 g. The reaction temperature was 25 °C, and the reaction time was 4 hours. Other operations were the same as in Example 20. 13.91 g of 9-benzyl-2,7-dichloro-9H-fluorene was obtained, with a product yield of 54.83%, HPLC purity of 94.59%, and melting point of 110-111 °C.

[0071] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for preparing a 2,7-dichlorofluorene derivative, characterized in that... Using the fluorene compound shown in formula (II) as a raw material, under the action of a catalyst, it is reacted with the chlorinated agent trichloroisocyanuric acid in an organic solvent at a certain temperature. The resulting reaction solution is separated and purified to obtain the 2,7-dichlorofluorene derivative shown in formula (I). ， In the formula, R is H, CH3-, C2H5-, Bn-, C6H5-, CH3O-, C2H5O-, or C6H5O-; The catalyst is anhydrous aluminum chloride, tin tetrachloride, aluminum chloride hexahydrate, or ferric nitrate nonahydrate; the organic solvent is 1,2-dichloroethane, toluene, isopropyl ether, ethyl acetate, dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, ethanol, or dichloromethane.

2. The method for preparing a 2,7-dichlorofluorene derivative according to claim 1, characterized in that... The amounts of fluorene compounds, trichloroisocyanuric acid and catalyst shown in formula (II) are in the following molar ratio: fluorene compounds: trichloroisocyanuric acid: catalyst = 1.0: 0.7~2.5: 0.01~0.

5.

3. The method for preparing a 2,7-dichlorofluorene derivative according to claim 1, characterized in that... The reaction time is 3 to 6 hours.

4. The method for preparing a 2,7-dichlorofluorene derivative according to claim 1, characterized in that... The reaction process is controlled at a temperature of -10 to 60℃.

5. The method for preparing a 2,7-dichlorofluorene derivative according to claim 1, characterized in that... The volume ratio of the organic solvent to the mass ratio of the fluorene compound shown in formula (II) is 3~6:1, with volume in mL and mass in g.

6. The method for preparing a 2,7-dichlorofluorene derivative according to claim 1, characterized in that... The specific separation and purification process is as follows: After the reaction is completed, the precipitate is filtered, washed with ethanol, dissolved in ethyl acetate, the insoluble matter is filtered off, the ethyl acetate is recovered by rotary evaporation, and dried to obtain the 2,7-dichlorofluorene derivative as shown in formula (Ⅰ).

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