A preparation method of diphenylamine adamantane-type substituent compound

Abstract

The invention belongs to the technical field of chemical synthesis and specifically discloses a preparation method of a diphenylamine-type adamantane substituent compound. The method comprises the following steps: adding adamantane alcohol and acetanilide to a solvent for reaction to obtain adamantane acetanilide; adding adamantane acetanilide and NBS to the solvent for reaction to obtain bromoadamantanacetanilide; adding bromoadamantanacetanilide, phenylboric acid, a catalyst and an alkali salt to the solvent for reaction to obtain phenyladamantanacetanilide; and adding phenyladamantanacetanilide and hydrochloric acid to the solvent for reaction to obtain adamantane diphenylamine. The method has readily available raw materials and simple operation, has achieved kilogram-level production, and has high product purity, with a liquid phase purity of over 99.9%.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a method for preparing a diphenylamine adamantane-based substituent compound. Background Art

[0002] Due to the unique "sandwich" structure of organic light-emitting diodes (OLEDs) and their excellent performance such as ultra-thinness, light weight, high brightness, full-color emission, low driving voltage, and fast response time, they have rapidly developed into a potential next-generation display and solid-state lighting technology in the past thirty years.

[0003] The development of OLED technology is inextricably linked to the advancement of corresponding functional materials and devices. The research approach for OLED materials and devices typically centers around the luminescent material, then develops other functional materials (such as carrier transport materials, host materials, and electrode materials) that match its energy levels. This maximizes the efficacy of the luminescent material, resulting in high-performance OLED devices. Therefore, the development of luminescent materials is a crucial component of OLED technology development.

[0004] Adamantane aniline compounds are important intermediates in the OLED field. A series of specific organic molecular structures such as electron transport materials and hole blocking materials used by domestic and foreign customers all contain their structural parts. Especially in recent years, as domestic manufacturers seek localization, more different types of materials containing their structures urgently need the industrial production of this intermediate.

[0005] Currently, no synthesis scheme for this compound has been reported. Patents for its related applications are CN 111146349 A and CN 107148408 B. Specific reports on their applications reflect the huge application prospects of this type of compound.

[0006] Therefore, it is necessary to design a method for preparing diphenylamine-type adamantane-based compounds that is economical, suitable for industrial production, and meets market demand and is environmentally friendly. Summary of the Invention

[0007] In view of the above-mentioned shortcomings, the present invention provides a method for preparing a diphenylamine-type adamantane substituent compound. The present invention can solve the problems in the prior art of lacking a synthesis process for adamantane diphenylamine, which cannot be industrialized and cannot meet the increasing demand of the OLED market.

[0008] In order to achieve the above object, the present invention provides a method for preparing a diphenylamine adamantane-based substituent compound, comprising the following steps:

[0009] Step 1: Add adamantane alcohol and acetanilide of the following formula 1 into dichloroethane solvent, stir and dissolve, and then dropwise add concentrated sulfuric acid to react to obtain adamantane acetanilide of formula 2. The reaction process is as follows:

[0010]

[0011] Step 2: Add the adamantane acetanilide of Formula 2 and NBS into dichloroethane solvent, stir and dissolve to obtain 2-bromoadamantane acetanilide of Formula 3. The reaction process is as follows:

[0012]

[0013] Step 3: Add the 2-bromoadamantaneacetanilide of Formula 3, phenylboric acid, catalyst Pd(PPh3)4, and alkali salt K2CO3 into a toluene / water solvent and perform a reflux reaction to obtain 2-phenyladamantaneacetanilide of Formula 4. The reaction process is as follows:

[0014]

[0015] Step 4: Add the 2-phenyladamantane acetanilide of Formula 4 and hydrochloric acid to a mixed solvent of ethanol and water for reflux reaction to obtain 2-phenyladamantane diphenylamine of Formula 5. The reaction process is as follows:

[0016]

[0017] According to one aspect of the present invention, in step 1, the reaction temperature is 0°C.

[0018] According to one aspect of the present invention, in step 1, the molar ratio of the adamantane alcohol to acetanilide is 1:1-1.3; the molar ratio of the adamantane alcohol to concentrated sulfuric acid is 1:1.4-3.

[0019] According to one aspect of the present invention, in step 2, the reaction temperature is 0°C.

[0020] According to one aspect of the present invention, in step 2, the molar ratio of adamantane acetanilide to NBS is 1:1 to 1.5.

[0021] According to one aspect of the present invention, in step 3, the molar ratio of the 2-bromoadamantanacetanilide to phenylboric acid is 1:1.1-1.5; the molar ratio of the 2-bromoadamantanacetanilide to the catalyst Pd(PPh3)4 is 1:0.0005-0.02.

[0022] According to one aspect of the present invention, in step 4, the molar ratio of the 2-phenyladamantanacetanilide to the hydrochloric acid is 1:1.5-3.

[0023] According to one aspect of the present invention, the liquid phase purity of the 2-phenyladamantanediphenylamine is above 99.9%.

[0024] Beneficial effects of the present invention:

[0025] (1) The present invention uses adamantane alcohol to directly react with acetanilide. Compared with the reaction with aniline, the product yield is high. Compared with the intermediate with aniline structure, acetanilide has a stable structure in the subsequent reaction, with fewer side reactions and impurities. Kilogram-level production has been achieved, and the obtained product has a high purity and quality of more than 99.9%;

[0026] (2) The adamantane acetanilide bromination reaction of the present invention cleverly utilizes the acetyl group to passivate the activity of the amino group and utilizes its certain steric hindrance to control the selectivity of the single and double ends, thereby reducing the difficulty of purification and improving the yield. The raw materials in the synthetic route are all basic raw materials, the operation is simple, economical and applicable, meets market demand, is environmentally friendly and suitable for industrial production;

[0027] (3) In the coupling reaction of 2-bromoadamantane acetanilide and phenylboronic acid of the present invention, the catalyst dosage can be optimized to 0.5% to ensure high yield, and the catalyst cost accounts for a low proportion. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 For the adamantane diphenylamine of Example 1 of the present invention 1 H NMR;

[0029] Figure 2 This is the liquid phase spectrum of adamantane diphenylamine according to Example 1 of the present invention. DETAILED DESCRIPTION

[0030] To facilitate understanding of the present invention, the present invention will be described in more comprehensive and detailed form below in conjunction with the accompanying drawings and preferred embodiments. However, the protection scope of the present invention is not limited to the following specific embodiments.

[0031] Unless otherwise defined, all technical terms used hereinafter have the same meanings as those generally understood by those skilled in the art. The technical terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0032] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0033] In order to solve the problem that the prior art lacks a synthesis process for adamantane diphenylamine, cannot be industrialized for production, and cannot meet the increasing demand of the OLED market, the inventors of the present application provide a method for preparing a diphenylamine-type adamantane substituent compound, comprising the following steps:

[0034] Step 1: Add adamantane alcohol and acetanilide of the following formula 1 into dichloroethane solvent, stir and dissolve, and then dropwise add concentrated sulfuric acid to react to obtain adamantane acetanilide of formula 2. The reaction process is as follows:

[0035]

[0036] Step 2: Add the adamantane acetanilide of Formula 2 and NBS into dichloroethane solvent, stir and dissolve to obtain 2-bromoadamantane acetanilide of Formula 3. The reaction process is as follows:

[0037]

[0038] Step 3: Add the 2-bromoadamantaneacetanilide of Formula 3, phenylboric acid, catalyst Pd(PPh3)4, and alkali salt K2CO3 into a toluene / water solvent and perform a reflux reaction to obtain 2-phenyladamantaneacetanilide of Formula 4. The reaction process is as follows:

[0039]

[0040] Step 4: Add the 2-phenyladamantane acetanilide of Formula 4 and hydrochloric acid to a mixed solvent of ethanol and water for reflux reaction to obtain 2-phenyladamantane diphenylamine of Formula 5. The reaction process is as follows:

[0041]

[0042] In the present invention, the synthetic route of adamantane diphenylamine is as follows:

[0043]

[0044] As an optional embodiment, in step 1, the reaction temperature is 0°C.

[0045] As an optional embodiment, in step 1, the molar ratio of the adamantane alcohol to acetanilide is 1:1-1.3; the molar ratio of the adamantane alcohol to concentrated sulfuric acid is 1:1.4-3.

[0046] As an optional embodiment, in step 2, the reaction temperature is 0°C.

[0047] As an optional embodiment, in step 2, the molar ratio of adamantane acetanilide to NBS is 1:1 to 1.5.

[0048] As an optional embodiment, in step 3, the molar ratio of the 2-bromoadamantanacetanilide to phenylboric acid is 1:1.1-1.5; the molar ratio of the 2-bromoadamantanacetanilide to the catalyst Pd(PPh3)4 is 1:0.0005-0.02.

[0049] As an optional embodiment, in step 4, the molar ratio of the 2-phenyladamantane acetanilide to hydrochloric acid is 1:1.5-3.

[0050] As an optional embodiment, the liquid phase purity of the 2-phenyladamantane diphenylamine is above 99.9%.

[0051] The above describes the specific implementation methods of the present application. In order to objectively illustrate the technical effects produced by the present application, the following examples and comparative examples will be used for description.

[0052] Example 1

[0053] A method for preparing a diphenylamine adamantane-based substituent compound comprises the following steps:

[0054] 1) Add 50 g of adamantane alcohol and 500 mL of 1.2-dichloroethane to a 1 L three-necked flask, stir at room temperature, add 53.27 g of acetanilide, and cool to 0°C in an ice-water bath. Then slowly drop 35 mL of concentrated sulfuric acid into the reaction system, maintaining the system temperature at around 0°C. After the addition is complete, continue stirring at 0°C for 30 minutes, raise the reaction temperature to room temperature, and continue the reaction for 18 hours. Stop the reaction after the reaction is complete by liquid phase monitoring. Let it stand for 0.5 hours, separate the layers, remove the concentrated sulfuric acid layer, adjust the pH to neutral or weak alkaline with an alkaline aqueous solution, let it stand and separate the liquids, and separate by column chromatography to obtain 80 g of the product as a white powder solid with a yield of 83.19%. MS (EI): m / z 269.18;

[0055] 2) Add 80 g of adamantane acetanilide and 500 mL of dichloromethane to a 1 L three-necked flask and stir at room temperature until dissolved, leaving a clear, transparent state. Cool to 0°C in an ice-water bath. Add 56 g of NBS in ten portions to the reaction system, maintaining the system temperature around 0°C. After addition, return the mixture to room temperature and react for 30 minutes. After completion of the reaction, monitor the reaction by TLC spot plate. Wash the reaction solution with water and separate it by column chromatography to obtain 85 g of bromoadamantanacetanilide as a white powder in an 88.43% yield. MS (EI): m / z 347.09.

[0056] 3) Add 80 g of bromoadamantanacetanilide, 800 ml of toluene, 95.24 g of potassium carbonate, and 160 ml of water to a 2 L three-necked flask. Replace the atmosphere with nitrogen three times with stirring. Then add 33.6 g of phenylboric acid and 40.53 g of Pd(PPh3). Heat to 85°C under nitrogen and allow to react. After completion of the reaction, monitor the reaction by TLC. The aqueous phase is separated and washed twice with hot water. The organic phase is then concentrated and separated by column chromatography to yield 70 g of phenyladamantanacetanilide as a white powdery solid in an 87.33% yield. MS (EI): m / z 345.21.

[0057] 4) Add 70 g of phenyladamantane acetanilide and 700 ml of ethanol to a 1 L three-necked flask, heat to 80 degrees and reflux, add 15 g of concentrated hydrochloric acid dropwise, and keep warm for reaction. After the reaction is complete, monitor the reaction by TLC plate, add water to precipitate the product, filter and obtain a solid, and purify by column chromatography to obtain 54 g of a white solid with a yield of 87.74%. MS (EI): m / z 303.30. 1 HNMR Figure 1 The liquid phase spectrum of the product is shown in Figure 2 shown.

[0058] Example 2

[0059] 1) Turn on stirring, add 2.5kg of adamantane alcohol and 25L of 1.2-dichloroethane to a 50L glass kettle, stir at room temperature, add 2.67kg of acetanilide, cool to 0°C, and then slowly add 1.75L of concentrated sulfuric acid to the reaction system, maintain the system temperature at about 0°C, and after the addition is complete, continue stirring at 0°C for 30min, raise the reaction temperature to room temperature, and continue the reaction for 18h. Stop the reaction after the reaction is complete by liquid phase monitoring. Let it stand for 0.5h, separate the layers, remove the lower concentrated sulfuric acid layer, adjust the pH value to neutral or weak alkaline with an alkaline aqueous solution, let it stand and separate the liquids, and wash with water twice. Distill 20L of solvent from the organic phase, add 20L of mixed solvent (methanol: water = 1:1) and hot beat, keep warm at 70°C for 1h, hot filter to obtain a yellow-white solid, dry and lose weight to obtain 4kg of crude product, with a yield of 83.17%;

[0060] 2) Add 4 kg of adamantane acetanilide and 20 L of dichloromethane to a 50 L glass kettle, stir and dissolve at room temperature until clear and transparent, then cool to 0°C in an ice-water bath, connect to a tail gas absorber, and then add 28 g of NBS to the reaction system in ten portions, totaling 280 g, maintaining the system temperature at around 0°C. After the addition is complete, return to room temperature for reaction. After monitoring the reaction completion by TLC spot plate, add 10 L of water and wash twice, then concentrate the solvent, add 20 L of a mixed solvent (methanol: water = 1:1) and insulate at 70°C for 1 hour. Filter hot to obtain a yellow solid, and dry to obtain 4.2 kg of crude product, with a yield of 87.39%;

[0061] 3) In a 50 L glass kettle, 4.2 kg of bromoadamantaneacetanilide, 21 L of toluene, 5 kg of potassium carbonate, and 4.2 L of water were added. The atmosphere was replaced with nitrogen three times with stirring. 1 kg of phenylboric acid and 415 g of Pd(PPh3) were added, and the reaction was carried out by heating to 85°C under nitrogen protection. There is an obvious exothermic temperature rise phenomenon. The reaction rate is controlled. After 1 hour, the temperature is lowered to 50 degrees. Under nitrogen protection, 0.38kg of phenylboric acid and 6.5g of Pd(PPh3)4 are continuously added. The temperature is raised to 85 degrees and kept for reaction. After 1 hour, the operation is repeated, 0.38kg of phenylboric acid and 6.5g of Pd(PPh3)4 are added. The temperature is raised to 85 degrees and kept for reaction. After the reaction is complete, the water phase is separated and washed twice with hot water. 15L of the toluene organic phase is separated and evaporated. The temperature is lowered to 50 degrees and 15L of methanol is added. The temperature is raised to 70°C and kept for 1h. The temperature is lowered to 30 degrees and filtered and dried to obtain 3.5kg of the target product as a gray powder solid with a yield of 83.17%.

[0062] 4) 3.5 kg of phenyl-substituted adamantane acetanilide and 15 L of ethanol were added to a 50 L glass kettle, the temperature was raised to 80 degrees and refluxed, 750 g of concentrated hydrochloric acid was added dropwise, and the reaction was kept warm. After the reaction was complete by TLC plate monitoring, 10 L of concentrated ethanol was added to 10 L of water to precipitate the product, and the solid was filtered off to obtain a solid. After drying, 15 L of a mixed solvent (toluene: methanol = 1:2) was added for crystallization to obtain 2.5 kg of a light pink powdery solid with a purity of 99.9% and a yield of 81.24%.

[0063] Comparative Example 1

[0064] This comparative example is to adjust the concentrated sulfuric acid equivalent in step 1) of Example 1 from 2eq to 1.3eq, and the other steps are the same, as follows:

[0065] To a 1L three-necked flask, add 50g of adamantane alcohol and 500mL of 1.2-dichloroethane. Stir at room temperature, add 53.27g of acetanilide, and cool to 0°C in an ice-water bath. Then slowly add 22.75mL of concentrated sulfuric acid dropwise to the reaction system, maintaining the system temperature at around 0°C. After the addition is complete, continue stirring at 0°C for 30min, raise the reaction temperature to room temperature, and continue the reaction for 18h before stopping the reaction. Let stand for 0.5h, separate the layers, remove the concentrated sulfuric acid layer, adjust the pH to neutral or weakly alkaline with an alkaline aqueous solution, let stand and separate the liquids. Separate by column chromatography to obtain 60g of the product as a white powder solid in a yield of 62.39%.

[0066] Comparative Example 2

[0067] In this comparative example, the catalyst Pd(PPh3)4 in step 3) of Example 1 is replaced with Pd(DPPF)2Cl2, and the other steps are the same, as follows:

[0068] To a 2L three-necked flask, add 80g of bromoadamantanacetanilide, 800ml of toluene, 95.24g of potassium carbonate, and 160ml of water. Nitrogen was replaced three times with stirring. Phenylboric acid (33.6g) and Pd(DPPF)2Cl2 (0.34g) were added and the reaction was allowed to proceed at 85°C under nitrogen. After 18 hours of reaction, the reaction was terminated. The aqueous phase was separated and washed twice with hot water. The organic phase was then concentrated and separated by column chromatography to yield 61g of phenyladamantanacetanilide as a white powder in a yield of 76.11%.

[0069] Comparative Example 3

[0070] The phenylboronic acid equivalent in step 3) of Example 1 was replaced by 1 eq from 1.2 eq, and the other steps were the same, as follows:

[0071] To a 2L three-necked flask, add 80g of bromoadamantanacetanilide, 800ml of toluene, 95.24g of potassium carbonate, and 160ml of water. Nitrogen was replaced three times with stirring. Phenylboric acid (28g) and Pd(PPh3) (40.53g) were added and the reaction was allowed to proceed at 85°C under nitrogen. After 18 hours of reaction, the reaction was terminated. The aqueous phase was separated and washed twice with hot water. The organic phase was then concentrated and separated by column chromatography to yield 52g of phenyladamantanacetanilide as a white powder in a yield of 64.87%.

[0072] As can be seen from Example 1 and Comparative Example 1, reducing the concentrated sulfuric acid equivalent from 2 eq to 1.3 eq in step 1) reduces the yield from 83.19% to 62.39%. As can be seen from Example 1 and Comparative Example 2, replacing the catalyst from Pd(PPh3)4 to Pd(DPPF)2Cl2 in step 3) reduces the yield from 87.33% to 76.11%. As can be seen from Example 1 and Comparative Example 3, reducing the phenylboric acid equivalent from 1.2 eq to 1 eq in step 3) reduces the yield from 87.33% to 64.87%. This indicates that to achieve a high yield, the concentrated sulfuric acid, phenylboric acid, and catalyst must be within the scope of this application.

[0073] In summary, by setting different reaction conditions, replacing the catalyst, and changing the proportion of materials, the yield of the intermediate product obtained is the best according to the preferred synthesis scheme in this article. At the same time, this article also carried out industrial production according to this scheme, and obtained a higher yield, low production cost, simple operation and extremely high product quality.

[0074] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A method for preparing a diphenylamine adamantane-based substituent compound, characterized in that: The following steps are involved: Step 1: Add adamantane alcohol and acetanilide of the following formula 1 into dichloroethane solvent, stir and dissolve, and then dropwise add concentrated sulfuric acid to react to obtain adamantane acetanilide of formula 2. The reaction process is as follows: Step 2: Add the adamantane acetanilide of Formula 2 and NBS into dichloroethane solvent, stir and dissolve to obtain 2-bromoadamantane acetanilide of Formula 3. The reaction process is as follows: Step 3: Add the 2-bromoadamantaneacetanilide of Formula 3, phenylboric acid, catalyst Pd(PPh3)4, and alkali salt K2CO3 into a toluene / water solvent and perform a reflux reaction to obtain 2-phenyladamantaneacetanilide of Formula 4. The reaction process is as follows: Step 4: Add the 2-phenyladamantane acetanilide of Formula 4 and hydrochloric acid to a mixed solvent of ethanol and water for reflux reaction to obtain 2-phenyladamantane diphenylamine of Formula 5. The reaction process is as follows:

2. The method for preparing a diphenylamine adamantane-based compound according to claim 1, wherein: In step 1, the reaction temperature is 0°C.

3. The method for preparing a diphenylamine adamantane-substituted compound according to claim 1, wherein: In step 1, the molar ratio of the adamantane alcohol to acetanilide is 1:1-1.3; the molar ratio of the adamantane alcohol to concentrated sulfuric acid is 1:1.4-3.

4. The method for preparing a diphenylamine adamantane-based compound according to claim 1, wherein: In step 2, the reaction temperature is 0°C.

5. The method for preparing a diphenylamine adamantane-based substituent compound according to claim 1, wherein: In step 2, the molar ratio of adamantane acetanilide to NBS is 1:1 to 1.

5.

6. The method for preparing a diphenylamine adamantane-based substituent compound according to claim 1, wherein: In step 3, the molar ratio of the 2-bromoadamantanacetanilide to phenylboric acid is 1:1.1-1.5; the molar ratio of the 2-bromoadamantanacetanilide to the catalyst Pd(PPh3)4 is 1:0.0005-0.

02.

7. The method for preparing a diphenylamine adamantane-based substituent compound according to claim 1, wherein: In step 4, the molar ratio of the 2-phenyladamantane acetanilide to the hydrochloric acid is 1:1.5-3.

8. The method for preparing a diphenylamine adamantane-substituted compound according to any one of claims 1 to 7, characterized in that: The liquid phase purity of the 2-phenyladamantane diphenylamine is above 99.9%.

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