A synthetic method of a spiro fluorene and indole derivative structure
By employing a simplified four-step synthesis route and using inexpensive and readily available raw materials and excipients, the high cost and low purity problems of existing technologies are solved, providing high-purity 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole] for use in organic optoelectronic materials.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- 西安欧得光电材料有限公司
- Filing Date
- 2023-06-05
- Publication Date
- 2026-06-05
AI Technical Summary
Existing methods for synthesizing spirofluorene-indole derivatives use highly corrosive and costly raw materials and catalysts, involve cumbersome synthesis steps, and are difficult to remove impurities, resulting in low product purity and unsuitability for industrial production.
Using 1-indanone and 1,1-diphenylhydrazine hydrochloride as starting materials, intermediate A was synthesized via the Fischer-indole reaction. After oxidation with potassium permanganate, it was reacted with 2-bromo-4'-chlorobiphenyl and n-butyllithium at low temperature, followed by cyclization with methanesulfonic acid to obtain high-purity 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole].
It simplifies the synthesis steps, reduces costs, improves product purity, is suitable for industrial production, and provides high-purity intermediates for organic optoelectronic materials.
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Figure CN116768785B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to a synthetic method for a spirofluorenoid derivative structure, specifically relating to a 2-chloro-5'-phenyl-5'H-spiro[fluoren-9,10'-indo[1,2-b]indole] and its synthetic method. Background Technology
[0002] Spirofluorenoid derivatives have been increasingly used in the development of organic optoelectronic materials in recent years, and organic electroluminescent materials with spirofluorenoid cores have shown good feedback in device evaluation.
[0003] The main methods for synthesizing this compound are as follows:
[0004] The literature [ARKIVOC, 2011, vol. 2011, #5, p76-91] reports a method for preparing the intermediate of this compound. Using indole and 2-iodobenzoyl chloride as starting materials, a Friedel-Crafts reaction is first carried out, followed by cyclization to obtain the intermediate. The reaction route is as follows:
[0005]
[0006] However, in the synthesis methods of the above compounds, the 2-iodobenzoyl chloride used in the first step has a strong odor and is highly corrosive, requiring high-end equipment and is not suitable for large-scale industrial production; the second step uses a palladium catalyst for cyclization, which requires a high temperature (around 140°C) and is therefore costly.
[0007] Current literature reports only on methods for synthesizing intermediates, and only on methods for synthesizing similar products for the target product.
[0008] Patent CN 106187861 B discloses a spirodifluorenindole derivative, its preparation method, and its application. The synthetic route is as follows:
[0009]
[0010] Based on the above synthesis method, the following reaction synthesis route can be obtained. This route has a total of 7 steps. The coupling reaction in the first and second steps will require expensive palladium catalysts (such as Pd(PPh3)4 or Pd(dppf)Cl2, etc.), which will result in relatively high costs. In addition, this route has 7 steps, which leads to a long cycle for synthesizing the product and high energy consumption of the equipment.
[0011]
[0012] Secondly, following the above-mentioned route, the final CN coupling reaction will produce a small amount of self-coupled impurity A. The impurity has a large molecular weight and is difficult to remove, which leads to the difficulty of purification and makes it impossible to obtain a product with particularly high purity.
[0013]
[0014] Therefore, it is necessary to develop a new synthetic method for spirofluorene-indole derivatives. Summary of the Invention
[0015] The purpose of this invention is to overcome the shortcomings of the prior art and provide a synthetic method containing spirofluorene-indole derivative structures.
[0016] To solve the technical problem, the technical solution of the present invention is: a method for synthesizing a spirofluorene-indole derivative structure, comprising the following steps:
[0017] Step 1: Using 1-indanone and 1,1-diphenylhydrazine hydrochloride as starting materials, a Fischer-indole reaction is carried out to synthesize intermediate A. The molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.5–2.0. The structural formula of intermediate A is as follows:
[0018] Step 2: Intermediate A and potassium permanganate undergo an oxidation reaction to obtain intermediate B. The molar ratio of intermediate A to potassium permanganate is 1:2.0–3.0. The structural formula of intermediate B is as follows:
[0019] Step 3: 2-Bromo-4'-chlorobiphenyl reacts with n-butyllithium at -78°C, and then reacts with intermediate B to generate intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.0–1.5:0.5–0.9. The structural formula of intermediate C is as follows:
[0020] Step 4: Intermediate C undergoes a cyclization reaction with methanesulfonic acid to obtain the final product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], wherein the molar ratio of intermediate C to methanesulfonic acid is 1:1.0 to 3.0.
[0021] Preferably, step 1 specifically involves: adding 1-indanone and 1,1-diphenylhydrazine hydrochloride, as well as zinc chloride and glacial acetic acid, to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating is initiated with stirring and the temperature is slowly increased to 90–100°C for reaction. After TLC detection confirms the complete reaction of the 1-indanone, heating is stopped and the temperature is lowered to room temperature. Water is added, the solid is filtered out, and then dried to obtain intermediate A. The molar ratio of 1-indanone to zinc chloride is 2:1, the molar ratio of 1-indanone to glacial acetic acid is 0.1 mol: 65–68 ml, and the molar ratio of 1-indanone to water is 0.1 mol: 65–68 ml.
[0022] Preferably, the molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.7.
[0023] Preferably, step 2 specifically involves: adding intermediate A, acetone, and water into a three-necked flask equipped with a stirrer and thermometer; stirring until completely dissolved; cooling to -10 to 0°C; slowly adding potassium permanganate; allowing the temperature to rise naturally after the addition is complete; and reacting for 20 hours. After TLC detection confirms the complete reaction of intermediate A, sodium bisulfite aqueous solution is slowly added to the reaction solution at 20 to 40°C until the purplish-black color fades. Then, ethyl acetate is added for extraction, and the mixture is washed with water until neutral. After drying with anhydrous sodium sulfate, the mixture is separated by column chromatography with ethyl acetate to obtain intermediate B. The ratio of intermediate A to acetone and water is 0.1 mol: 168-170 ml: 26-30 ml.
[0024] Preferably, the molar ratio of intermediate A to potassium permanganate is 1:2.5.
[0025] Preferably, step 3 specifically involves: adding 2-bromo-4'-chlorobiphenyl and tetrahydrofuran into a three-necked flask equipped with a low-temperature thermometer, a stirrer, and a constant-pressure dropping funnel; cooling to -78 to -90°C under argon protection; then adding n-butyllithium dropwise over 20.0 min; maintaining the reaction temperature for 60 min after the addition is complete; and then adding a tetrahydrofuran solution of intermediate B dropwise over 20.0 min at -78 to -90°C; and allowing the temperature to rise naturally after the addition is complete. After the reaction was complete, the solvent was removed under negative pressure, ethyl acetate was added, and the mixture was washed with water until neutral. Then, column chromatography with ethyl acetate and petroleum ether was performed to obtain intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl to tetrahydrofuran was 0.1 mol: 213-215 ml, the molar ratio of intermediate B to tetrahydrofuran was 0.1 mol: 215-218 ml, and the molar ratio of intermediate B to ethyl acetate was 0.1 mol: 536-540 ml.
[0026] Preferably, the molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.2:0.7.
[0027] Preferably, step 4 specifically involves: adding intermediate C, methanesulfonic acid, and dichloroethane to a three-necked flask equipped with a stirrer and a thermometer, reacting with stirring at 20–40°C, and after TLC detection confirms the complete reaction of intermediate C, washing with water until neutral, drying with anhydrous sodium sulfate, and then separating by column chromatography with ethyl acetate and petroleum ether to obtain the product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole]. The molar ratio of intermediate C to dichloroethane is 0.1 mol: 290–295 ml, and the molar ratio of intermediate C to water is 0.1 mol: 645–650 ml.
[0028] Preferably, the molar ratio of intermediate C to methanesulfonic acid is 1:2.5.
[0029] Preferably, the 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole] is used to prepare organic electroluminescent materials and applied to organic light-emitting devices.
[0030] Compared with the prior art, the advantages of the present invention are as follows:
[0031] (1) This invention discloses a method for synthesizing a spirofluorenoid derivative structure, wherein the spirofluorenoid derivative structure is 2-chloro-5'-phenyl-5'H-spiro[fluoren-9,10'-indo[1,2-b]indole]. The raw materials for this synthesis method are readily available, all four steps of the reaction are easy to operate, the post-processing is simple, there are no dangerous operations such as high temperature and high pressure, and no violent reactions, and it is suitable for large-scale production.
[0032] (2) The main raw materials of this invention are inexpensive and readily available, and the auxiliary materials used are also widely available on the market. The synthesis route and preparation process have fewer side reactions and fewer impurities, which are easy to purify and remove. The final target product, 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], has a purity of LC>99%, which is high.
[0033] (3) The synthesis method of the present invention includes four steps, the synthesis route is relatively short, the cycle required for synthesizing the product is relatively short, the equipment energy consumption is low, and the synthesis method of the present invention does not use expensive palladium catalyst, which greatly reduces the cost;
[0034] (4) The product synthesized in this invention, 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], is a very important intermediate in the field of organic optoelectronic materials. Based on this, a series of spirofluorene-indole-containing terminal derivative compounds can be prepared. Attached Figure Description
[0035] Figure 1 1. The NMR spectrum of intermediate A in Example 1 of this invention;
[0036] Figure 2 1. The NMR spectrum of intermediate B in Example 1 of the present invention;
[0037] Figure 3 1. The NMR spectrum of intermediate C in Example 1 of this invention;
[0038] Figure 4 1. The NMR spectrum of the product of Example 1 of the present invention. Detailed Implementation
[0039] The present invention will be described below with reference to specific embodiments. The raw materials, solvents and catalysts used are all conventional commercial products. The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the present invention.
[0040] This invention discloses a synthetic method for a spirofluorene-indole derivative structure, comprising the following steps:
[0041] Step 1: Using 1-indanone and 1,1-diphenylhydrazine hydrochloride as starting materials, a Fischer-indole reaction is carried out to synthesize intermediate A. The molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.5–2.0. The structural formula of intermediate A is as follows:
[0042] Step 2: Intermediate A and potassium permanganate undergo an oxidation reaction to obtain intermediate B. The molar ratio of intermediate A to potassium permanganate is 1:2.0–3.0. The structural formula of intermediate B is as follows:
[0043] Step 3: 2-Bromo-4'-chlorobiphenyl reacts with n-butyllithium at -78°C, and then reacts with intermediate B to generate intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.0–1.5:0.5–0.9. The structural formula of intermediate C is as follows:
[0044] Step 4: Intermediate C undergoes a cyclization reaction with methanesulfonic acid to obtain the final product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], wherein the molar ratio of intermediate C to methanesulfonic acid is 1:1.0 to 3.0.
[0045] Preferably, step 1 specifically involves: adding 1-indanone and 1,1-diphenylhydrazine hydrochloride, as well as zinc chloride and glacial acetic acid, to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating is initiated with stirring and the temperature is slowly increased to 90–100°C for reaction. After TLC detection confirms the complete reaction of the 1-indanone, heating is stopped and the temperature is lowered to room temperature. Water is added, the solid is filtered out, and then dried to obtain intermediate A. The molar ratio of 1-indanone to zinc chloride is 2:1, the molar ratio of 1-indanone to glacial acetic acid is 0.1 mol: 65–68 ml, and the molar ratio of 1-indanone to water is 0.1 mol: 65–68 ml.
[0046] Preferably, the molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.7.
[0047] Preferably, step 2 specifically involves: adding intermediate A, acetone, and water into a three-necked flask equipped with a stirrer and thermometer; stirring until completely dissolved; cooling to -10 to 0°C; slowly adding potassium permanganate; allowing the temperature to rise naturally after the addition is complete; and reacting for 20 hours. After TLC detection confirms the complete reaction of intermediate A, sodium bisulfite aqueous solution is slowly added to the reaction solution at 20 to 40°C until the purplish-black color fades. Then, ethyl acetate is added for extraction, and the mixture is washed with water until neutral. After drying with anhydrous sodium sulfate, the mixture is separated by column chromatography with ethyl acetate to obtain intermediate B. The ratio of intermediate A to acetone and water is 0.1 mol: 168-170 ml: 26-30 ml.
[0048] Preferably, the molar ratio of intermediate A to potassium permanganate is 1:2.5.
[0049] Preferably, step 3 specifically involves: adding 2-bromo-4'-chlorobiphenyl and tetrahydrofuran into a three-necked flask equipped with a low-temperature thermometer, a stirrer, and a constant-pressure dropping funnel; cooling to -78 to -90°C under argon protection; then adding n-butyllithium dropwise over 20.0 min; maintaining the reaction temperature for 60 min after the addition is complete; and then adding a tetrahydrofuran solution of intermediate B dropwise over 20.0 min at -78 to -90°C; and allowing the temperature to rise naturally after the addition is complete. After the reaction was complete, the solvent was removed under negative pressure, ethyl acetate was added, and the mixture was washed with water until neutral. Then, column chromatography with ethyl acetate and petroleum ether was performed to obtain intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl to tetrahydrofuran was 0.1 mol: 213-215 ml, the molar ratio of intermediate B to tetrahydrofuran was 0.1 mol: 215-218 ml, and the molar ratio of intermediate B to ethyl acetate was 0.1 mol: 536-540 ml.
[0050] Preferably, the molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.2:0.7.
[0051] Preferably, step 4 specifically involves: adding intermediate C, methanesulfonic acid, and dichloroethane to a three-necked flask equipped with a stirrer and a thermometer, reacting with stirring at 20–40°C, and after TLC detection confirms the complete reaction of intermediate C, washing with water until neutral, drying with anhydrous sodium sulfate, and then separating by column chromatography with ethyl acetate and petroleum ether to obtain the product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole]. The molar ratio of intermediate C to dichloroethane is 0.1 mol: 290–295 ml, and the molar ratio of intermediate C to water is 0.1 mol: 645–650 ml.
[0052] Preferably, the molar ratio of intermediate C to methanesulfonic acid is 1:2.5.
[0053] Preferably, the 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole] is used to prepare organic electroluminescent materials and applied to organic light-emitting devices.
[0054] Example 1
[0055] This embodiment provides a method for synthesizing 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], the method comprising the following steps:
[0056] 66.1 g of 1-indanone (molecular weight 132.16, 0.5 mol), 165 g of 1,1-diphenylhydrazine hydrochloride (molecular weight 220.5, 0.75 mol), zinc chloride (molecular weight 136.32, 0.25 mol), and 330 ml of glacial acetic acid were added to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating was started with stirring and the temperature was slowly increased to 90–100 °C for the reaction. After TLC analysis showed that the 1-indanone reaction was complete, heating was stopped and the mixture was cooled to room temperature. Approximately 330 ml of water was added, and the solid was filtered out and dried. After drying, 118 g of intermediate A was obtained, with a purity of LC = 95.6% and a yield of 83.86%.
[0057] like Figure 1 As shown, the NMR spectrum data are consistent with the product structure. 1H NMR (500MHz, DMSO) δ 8.25, 7.94, 7.62, 7.58, 7.50, 7.38, 7.37, 7.35, 7.27, 6.67, 4.16.
[0058] 100g of intermediate A (molecular weight 281.35, 0.355mol), 600ml of acetone, and 100ml of water were added to a three-necked flask equipped with a stirrer and thermometer. The mixture was stirred until completely dissolved. After cooling to -10 to 0℃, 112.34g of potassium permanganate (molecular weight 158.03, 0.711mol) was slowly added. After the addition was complete, the temperature was naturally raised. After the reaction proceeded for about 20 hours, TLC was used to confirm that intermediate A had reacted completely. At 20–40℃, sodium bisulfite aqueous solution was slowly added to the reaction solution until the purple-black color disappeared. Then, ethyl acetate was added for extraction. The mixture was washed with water until neutral, dried over anhydrous sodium sulfate, and separated by column chromatography with ethyl acetate to obtain 65.0g of intermediate B, with an LC ratio of 98.2% and a yield of 61.29%.
[0059] like Figure 2 As shown, the NMR spectrum data are consistent with the product structure. 1H NMR (500MHz, DMSO) δ 8.95, 8.45, 7.96, 7.94, 7.78, 7.72, 7.62, 7.58, 7.50, 7.35.
[0060] 50.0 g of 2-bromo-4'-chlorobiphenyl (molecular weight 267.55, 0.187 mol) and 400 ml of tetrahydrofuran were added to a three-necked flask equipped with a cryostat, stirrer, and constant-pressure dropping funnel. Under argon protection, the mixture was cooled to -78 to -90 °C, and then 112.0 ml of n-butyllithium (2.0 M, 0.224 mol) was added dropwise over 20.0 min. After the addition was complete, the reaction was maintained at this temperature for 60 min, and then the mixture was cooled to -78 to -90 °C. At ℃, a tetrahydrofuran solution (27.60 g / 200 ml) of intermediate B (molecular weight 295.33, 0.093 mol) was added dropwise over 20.0 min. After the addition was complete, the temperature was naturally raised to allow the reaction to proceed. After the reaction was complete, the solvent was removed under negative pressure, and 500 ml of ethyl acetate was added. The mixture was washed with water until neutral, and then separated by column chromatography with ethyl acetate and petroleum ether to obtain 30.0 g of intermediate C, with a purity of LC = 98.4% and a yield of 66.34%.
[0061] like Figure 3 As shown, the NMR spectrum data are consistent with the product structure. 1H NMR (500MHz, DMSO) δ 8.25, 7.94, 7.80, 7.78, 7.66, 7.62, 7.58, 7.50, 7.47, 7.42, 7.35, 7.34, 6.71, 6.67.
[0062] 30.0 g of intermediate C (molecular weight 483.99, 0.062 mol), 11.91 g of methanesulfonic acid (molecular weight 96.11, 0.124 mol), and 180 ml of dichloroethane were added to a three-necked flask equipped with a stirrer and thermometer. The reaction was carried out at 20–40 °C with stirring. After the reaction of intermediate C was complete as detected by TLC, the mixture was washed with 400 ml of water until neutral. After drying with anhydrous sodium sulfate, the product was separated by column chromatography with ethyl acetate and petroleum ether to obtain 25.0 g of 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], with a purity of 99.20% and a yield of 86.56%.
[0063] like Figure 4 As shown, the NMR spectrum data are consistent with the product structure. 1H NMR (500MHz, DMSO) δ 8.25, 7.94, 7.90, 7.84, 7.83, 7.82, 7.62, 7.58, 7.50, 7.48, 7.38, 7.37, 7.35, 7.34, 7.27, 7.24, 6.67.
[0064] Example 2
[0065] This embodiment provides a method for synthesizing 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], the method comprising the following steps:
[0066] 66.1 g of 1-indanone (molecular weight 132.16, 0.5 mol), 187 g of 1,1-diphenylhydrazine hydrochloride (molecular weight 220.5, 0.85 mol), zinc chloride (molecular weight 136.32, 0.25 mol), and 330 ml of glacial acetic acid were added to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating was started with stirring and the temperature was slowly increased to 90–100 °C for the reaction. After TLC analysis showed that the 1-indanone reaction was complete, heating was stopped and the mixture was cooled to room temperature. Approximately 330 ml of water was added, and the solid was filtered out and dried. After drying, 121 g of intermediate A was obtained, with a purity of LC = 94.9% and a yield of 85.99%.
[0067] 100g of intermediate A (molecular weight 281.35, 0.355mol), 600ml of acetone, and 100ml of water were added to a three-necked flask equipped with a stirrer and thermometer. The mixture was stirred until completely dissolved. After cooling to -10 to 0℃, 140.42g of potassium permanganate (molecular weight 158.03, 0.888mol) was slowly added. After the addition was complete, the temperature was naturally raised. After the reaction proceeded for about 20 hours, TLC was used to confirm that intermediate A had reacted completely. At 20–40℃, sodium bisulfite aqueous solution was slowly added to the reaction solution until the purple-black color disappeared. Then, ethyl acetate was added for extraction. The mixture was washed with water until neutral, dried over anhydrous sodium sulfate, and separated by column chromatography with ethyl acetate to obtain 68.0g of intermediate B, with an LC ratio of 98.0% and a yield of 64.78%.
[0068] 50.0 g of 2-bromo-4'-chlorobiphenyl (molecular weight 267.55, 0.187 mol) and 400 ml of tetrahydrofuran were added to a three-necked flask equipped with a cryostat, stirrer, and constant-pressure dropping funnel. Under argon protection, the mixture was cooled to -78 to -90 °C, and then 112.0 ml of n-butyllithium (2.0 M, 0.224 mol) was added dropwise over 20.0 min. After the addition was complete, the reaction was maintained at this temperature for 60 min, and then the mixture was cooled to -78 to -90 °C. At 0℃, a tetrahydrofuran solution (38.6 g / 200 ml) of intermediate B (molecular weight 295.33, 0.131 mol) was added dropwise over 20.0 min. After the addition was complete, the temperature was naturally raised to allow the reaction to proceed. After the reaction was complete, the solvent was removed under negative pressure, and 500 ml of ethyl acetate was added. The mixture was washed with water until neutral, and then separated by column chromatography with ethyl acetate and petroleum ether to obtain 44.0 g of intermediate C, with a purity of LC = 98.1% and a yield of 69.50%.
[0069] 30.0 g of intermediate C (molecular weight 483.99, 0.062 mol), 14.89 g of methanesulfonic acid (molecular weight 96.11, 0.155 mol), and 180 ml of dichloroethane were added to a three-necked flask equipped with a stirrer and thermometer. The reaction was carried out at 20–40 °C with stirring. After the reaction of intermediate C was complete as detected by TLC, the mixture was washed with 400 ml of water until neutral. After drying with anhydrous sodium sulfate, the product was separated by column chromatography with ethyl acetate and petroleum ether to obtain 25.5 g of 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], with a purity of 99.25% and a yield of 88.29%.
[0070] Example 3
[0071] This embodiment provides a method for synthesizing 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], the method comprising the following steps:
[0072] 66.1 g of 1-indanone (molecular weight 132.16, 0.5 mol), 220 g of 1,1-diphenylhydrazine hydrochloride (molecular weight 220.5, 1.0 mol), zinc chloride (molecular weight 136.32, 0.25 mol), and 330 ml of glacial acetic acid were added to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating was started with stirring and the temperature was slowly increased to 90–100 °C for the reaction. After TLC analysis showed that the 1-indanone reaction was complete, heating was stopped and the mixture was cooled to room temperature. Approximately 330 ml of water was added, and the solid was filtered out and dried. After drying, 115 g of intermediate A was obtained, with an LC content of 96.0% and a yield of 81.72%.
[0073] 100g of intermediate A (molecular weight 281.35, 0.355mol), 600ml of acetone, and 100ml of water were added to a three-necked flask equipped with a stirrer and thermometer. The mixture was stirred until completely dissolved. After cooling to -10 to 0℃, 168.50g of potassium permanganate (molecular weight 158.03, 1.07mol) was slowly added. After the addition was complete, the temperature was naturally raised. After the reaction proceeded for about 20 hours, TLC was used to confirm that intermediate A had reacted completely. At 20–40℃, an aqueous solution of sodium bisulfite was slowly added to the reaction solution until the purple-black color disappeared. Then, ethyl acetate was added for extraction. The mixture was washed with water until neutral, dried over anhydrous sodium sulfate, and separated by column chromatography with ethyl acetate to obtain 60.0g of intermediate B, with a purity of LC = 98.1% and a yield of 57.16%.
[0074] 50.0 g of 2-bromo-4'-chlorobiphenyl (molecular weight 267.55, 0.187 mol) and 400 ml of tetrahydrofuran were added to a three-necked flask equipped with a cryostat, stirrer, and constant-pressure dropping funnel. Under argon protection, the mixture was cooled to -78 to -90 °C, and then 112.0 ml of n-butyllithium (2.0 M, 0.224 mol) was added dropwise over 20.0 min. After the addition was complete, the reaction was maintained at this temperature for 60 min, and then the mixture was cooled to -78 to -90 °C. At 0℃, a tetrahydrofuran solution (49.7 g / 250 ml) of intermediate B (molecular weight 295.33, 0.168 mol) was added dropwise over 25.0 min. After the addition was complete, the temperature was naturally raised to allow the reaction to proceed. After the reaction was complete, the solvent was removed under negative pressure, and 500 ml of ethyl acetate was added. The mixture was washed with water until neutral, and then separated by column chromatography with ethyl acetate and petroleum ether to obtain 52.0 g of intermediate C, with a purity of LC = 98.5% and a yield of 63.88%.
[0075] 30.0 g of intermediate C (molecular weight 483.99, 0.062 mol), 17.9 g of methanesulfonic acid (molecular weight 96.11, 0.186 mol), and 180 ml of dichloroethane were added to a three-necked flask equipped with a stirrer and thermometer. The reaction was carried out at 20–40 °C with stirring. After the reaction of intermediate C was complete as detected by TLC, the mixture was washed with 400 ml of water until neutral. After drying with anhydrous sodium sulfate, the product was separated by column chromatography with ethyl acetate and petroleum ether to obtain 23.5 g of 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], with a purity of 99.30% and a yield of 81.36%.
[0076] The reaction principle of this invention is as follows:
[0077]
[0078] This invention discloses a synthetic method for a spirofluorenoid indole derivative structure. Starting with 1-indanone and 1,1-diphenylhydrazine hydrochloride, a Fischer indole reaction is performed to obtain intermediate A. Intermediate A is oxidized with potassium permanganate to obtain intermediate B. 2-Bromo-4'-chlorobiphenyl reacts with n-butyllithium at -78°C, and then reacts with intermediate B to generate intermediate C. Intermediate C undergoes a cyclization reaction with methanesulfonic acid to obtain the final product [2-chloro-5'-phenyl-5'H-spiro[fluoren-9,10'-indo[1,2-b]indole]. The raw materials used in this invention are inexpensive, readily available, odorless, and non-corrosive. The equipment requirements are low, all four reaction steps are easy to operate, post-processing is simple, no expensive catalysts are used, the cost is low, it is suitable for large-scale production, and the product has high purity and good quality.
[0079] This invention discloses a synthetic method for a spirofluorenoid derivative structure, wherein the spirofluorenoid derivative structure is 2-chloro-5'-phenyl-5'H-spiro[fluoren-9,10'-indo[1,2-b]indole]. The raw materials for this synthetic method are readily available, all four steps of the reaction are easy to operate, the post-processing is simple, and there are no dangerous operations such as high temperature and high pressure or violent reactions, making it suitable for large-scale production.
[0080] The main raw materials of this invention are inexpensive and readily available, and the auxiliary materials used are also widely available on the market. The synthesis route and preparation process involve fewer side reactions and fewer impurities, which are easy to purify and remove. The final target product, 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], has a purity LC>99%, indicating high purity.
[0081] The synthesis method of this invention includes four steps, with a shorter synthesis route, a shorter cycle required for synthesizing the product, and lower equipment energy consumption. Furthermore, the synthesis method of this invention does not use expensive palladium catalysts, which greatly reduces costs.
[0082] The product synthesized in this invention, 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole], is a very important intermediate in the field of organic optoelectronic materials. Based on this, a series of spirofluorene-indole-containing terminal derivative compounds can be prepared.
[0083] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.
[0084] Many other changes and modifications can be made without departing from the concept and scope of this invention. It should be understood that this invention is not limited to the specific embodiments, and the scope of this invention is defined by the appended claims.
Claims
1. A method for synthesizing a spirofluorene-indole derivative structure, characterized in that, Includes the following steps: Step 1: Using 1-indanone and 1,1-diphenylhydrazine hydrochloride as starting materials, a Fischer-indole reaction is carried out to synthesize intermediate A. The molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.5~2.
0. The structural formula of intermediate A is as follows: ; Step 1 specifically involves adding 1-indanone and 1,1-diphenylhydrazine hydrochloride, along with zinc chloride and glacial acetic acid, to a three-necked flask equipped with a stirrer, thermometer, and condenser. Heating is initiated with stirring and the temperature is slowly increased to 90-100°C for reaction. After TLC detection confirms the complete reaction of the 1-indanone, heating is stopped and the temperature is lowered to room temperature. Water is added, and the solid is filtered out and dried. After drying, intermediate A is obtained. The molar ratio of 1-indanone to zinc chloride is 2:1, the molar ratio of 1-indanone to glacial acetic acid is 0.1 mol: 65-68 ml, and the molar ratio of 1-indanone to water is 0.1 mol: 65-68 ml. Step 2: Intermediate A and potassium permanganate undergo an oxidation reaction to obtain intermediate B. The molar ratio of intermediate A to potassium permanganate is 1:2.0~3.
0. The structural formula of intermediate B is as follows: ; Step 2 specifically involves: adding intermediate A, acetone, and water into a three-necked flask equipped with a stirrer and thermometer, stirring until completely dissolved, cooling to -10 to 0°C, slowly adding potassium permanganate, allowing the temperature to rise naturally after the addition is complete, and reacting for 20 hours. After TLC detection confirms that intermediate A has reacted completely, sodium bisulfite aqueous solution is slowly added to the reaction solution at 20 to 40°C until the purplish-black color fades, followed by extraction with ethyl acetate, washing with water until neutral, drying with anhydrous sodium sulfate, and then column separation with ethyl acetate to obtain intermediate B. The ratio of intermediate A to acetone and water is 0.1 mol: 168 to 170 ml: 26 to 30 ml. Step 3: 2-Bromo-4'-chlorobiphenyl reacts with n-butyllithium at -78°C, and then reacts with intermediate B to generate intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.0~1.5:0.5~0.
9. The structural formula of intermediate C is as follows: ; Step 4: Intermediate C undergoes a cyclization reaction with methanesulfonic acid to obtain the final product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole]. The molar ratio of intermediate C to methanesulfonic acid is 1:1.0~3.
0. The final product 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole] is a spirofluorene-indole derivative structure, used to prepare organic electroluminescent materials and applied to organic light-emitting devices.
2. The method for synthesizing a spirofluorene-indole derivative structure according to claim 1, characterized in that: The molar ratio of 1-indanone to 1,1-diphenylhydrazine hydrochloride is 1:1.
7.
3. The method for synthesizing a spirofluorene-indole derivative structure according to claim 1, characterized in that: The molar ratio of intermediate A to potassium permanganate is 1:2.
5.
4. The method for synthesizing a spirofluorene-indole derivative structure according to claim 1, characterized in that, Step 3 specifically involves adding 2-bromo-4'-chlorobiphenyl and tetrahydrofuran into a three-necked flask equipped with a low-temperature thermometer, a stirrer, and a constant-pressure dropping funnel. Under argon protection, the temperature is lowered to -78°C, and then n-butyllithium is added dropwise over 20.0 min. After the addition is complete, the reaction is maintained at this temperature for 60 min. Then, at -78°C, a tetrahydrofuran solution of intermediate B is added dropwise over 20.0 min. After the addition is complete, the temperature is naturally raised to allow the reaction to proceed. After the reaction is complete, the solvent is removed under negative pressure, and ethyl acetate is added. After washing with water until neutral, the mixture is separated by column chromatography using ethyl acetate and petroleum ether to obtain intermediate C. The molar ratio of 2-bromo-4'-chlorobiphenyl to tetrahydrofuran is 0.1 mol: 213~215 ml, and the molar ratio of intermediate B to ethyl acetate is 0.1 mol: 536~540 ml.
5. The method for synthesizing a spirofluorene-indole derivative structure according to claim 4, characterized in that: The molar ratio of 2-bromo-4'-chlorobiphenyl, n-butyllithium, and intermediate B is 1:1.2:0.
7.
6. The method for synthesizing a spirofluorene-indole derivative structure according to claim 1, characterized in that, Step 4 specifically involves adding intermediate C, methanesulfonic acid, and dichloroethane to a three-necked flask equipped with a stirrer and thermometer. The mixture is then reacted at 20-40°C with stirring. After TLC detection confirms the complete reaction of intermediate C, it is washed with water until neutral. After drying with anhydrous sodium sulfate, the product is separated by column chromatography using ethyl acetate and petroleum ether to obtain 2-chloro-5'-phenyl-5'H-spiro[fluorene-9,10'-indo[1,2-b]indole]. The molar ratio of intermediate C to dichloroethane is 0.1 mol: 290-295 ml, and the molar ratio of intermediate C to water is 0.1 mol: 645-650 ml.
7. The method for synthesizing a spirofluorene-indole derivative structure according to claim 6, characterized in that: The molar ratio of intermediate C to methanesulfonic acid is 1:2.5.