Preparation method of 2-bromo-1-(3, 5-diisopropyl-[1, 1 '-biphenyl]-4-yl)-1H-benzo [d] imidazole
Through a series of organic synthesis reactions, including NBS and triphenylphosphine bromination reaction, Suzuki coupling reaction and methoxy substitution reaction under the action of phosphorus-containing organic base catalyst, 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole was successfully prepared, solving the problem of lack of effective synthesis methods in the prior art and achieving an efficient and safe process.
Patent Information
- Application Number
- CN202411795573.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-09
- Publication Date
- 2025-03-14
AI Technical Summary
There is a lack of effective synthetic methods in the prior art to prepare 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole, which is an important intermediate in the construction of organic light emitters (OLEDs).
The compound was successfully prepared through a series of organic synthesis reactions, including NBS and triphenylphosphine bromination reaction, Suzuki coupling reaction and methoxy substitution reaction under the action of phosphorus-containing organic base catalyst.
This method improves bromination yield, simplifies the process route, is easy to obtain raw materials, safe and stable process, is suitable for industrial scale expansion, and achieves efficient compound preparation.
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Abstract
Description
Technical Field
[0001] The invention relates to a preparation method of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole, belonging to the technical field of organic synthesis. Background Art
[0002] 2-Bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole, which contains both benzo[d]imidazole and diisopropylbiphenyl structural units, is an important intermediate for constructing organic light-emitting devices (OLEDs). Using benzo[d]imidazole compounds as the main material of the electron transport layer or the light-emitting layer can significantly improve the current efficiency, power efficiency and external quantum efficiency of OLED devices, while extending the device life. Benzo[d]imidazole compounds have broad application prospects in the field of OLEDs.
[0003] There are few methods for synthesizing 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole. In view of its wide application, it is necessary to study its synthesis method and develop a process route suitable for factory production to meet the growing market demand. Summary of the invention
[0004] In order to solve the above technical problems, the present invention provides a preparation method of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole. 1,3-diisopropyl-2-methoxybenzene is used as a raw material, and 5-bromo-1,3-diisopropyl-2-methoxybenzene is generated through a bromination reaction with NBS and triphenylphosphine; then, 3,5-diisopropyl-1-methoxy-1,1'-biphenyl is generated through a Suzuki coupling reaction with phenylboric acid under the action of a palladium catalyst and a base; and then, 2-bromo-1H-benzo[d]imidazole is obtained under the action of a phosphorus-containing organic base catalyst and lithium tert-butoxide. 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole. This route provides an effective new path for the preparation of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole through a direct substitution reaction between the benzimidazole amino group and the benzyloxy group.
[0005] The preparation method of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole of the present invention is represented by the following reaction equation:
[0006]
[0007] The steps include:
[0008] A. Mix 1,3-diisopropyl-2-methoxybenzene, NBS and triphenylphosphine in an organic solvent to generate 5-bromo-1,3-diisopropyl-2-methoxybenzene;
[0009] In a preferred embodiment of the present invention, the organic solvent is selected from dichloromethane, 1,2-dichloroethane or chloroform.
[0010] In a preferred embodiment of the present invention, the molar ratio of 1,3-diisopropyl-2-methoxybenzene, NBS and triphenylphosphine is 1:1-1.1:0.05-0.1.
[0011] B. Mix 5-bromo-1,3-diisopropyl-2-methoxybenzene, phenylboric acid, palladium catalyst and alkali solution in an organic solvent, heat the reaction, and obtain 3,5-diisopropyl-1-methoxy-1,1'-biphenyl after treatment;
[0012] In a preferred embodiment of the present invention, the palladium catalyst is PdCl2dppf or Pd(PPh3)4; the organic solvent is selected from dioxane, DMSO, DMF, and toluene.
[0013] In a preferred embodiment of the present invention, the base is selected from potassium phosphate, potassium carbonate or sodium carbonate.
[0014] In a preferred embodiment of the present invention, the temperature of the reaction is 80-120°C.
[0015] In a preferred embodiment of the present invention, the molar ratio of 5-bromo-1,3-diisopropyl-2-methoxybenzene, phenylboric acid, palladium catalyst and base is 1:1-1.2:0.02-0.05:1.5-3.
[0016] C. Mix 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 2-bromo-1H-benzo[d]imidazole, a phosphorus-containing organic base catalyst and lithium tert-butoxide in dioxane, and react under elevated temperature conditions to obtain 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole.
[0017] In a preferred embodiment of the present invention, the phosphorus-containing organic base catalyst is a phosphazene base P4-t-Bu solution (0.8 M n-hexane solution).
[0018] In a preferred embodiment of the present invention, the temperature of the reaction is 40-45°C.
[0019] In a preferred embodiment of the present invention, the molar ratio of 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 2-bromo-1H-benzo[d]imidazole, phosphorus-containing organic base catalyst and lithium tert-butoxide is 1:1-2:0.05-0.1:1-1.1.
[0020] Beneficial effects of the invention:
[0021] (1) In the first step of the present invention, 1,3-diisopropyl-2-methoxybenzene is used as a raw material to carry out a bromination reaction with NBS under the action of a triphenylphosphine catalyst, thereby greatly improving the bromination yield.
[0022] (2) In the third step of the present invention, 3,5-diisopropyl-1-methoxy-1,1'-biphenyl and 2-bromo-1H-benzo[d]imidazole are directly subjected to a methoxy substitution reaction in the presence of a phosphorus-containing organic base catalyst and lithium tert-butoxide (when no base such as lithium tert-butoxide is added, the conversion rate is less than 10%), and the route is relatively simple. This provides a route reference for the synthesis of such compounds.
[0023] (3) The raw materials for this process are easily available in the market, the process is simple, safe and stable, and is suitable for industrial scale expansion. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 This is the NMR spectrum of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole obtained in Example 4. Specific embodiments
[0025] The present invention will be further described below by specific examples. These embodiments should be understood to be only used to illustrate the present invention and not to limit the scope of protection of the present invention. After reading the content of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.
[0026] Example 1
[0027]
[0028] Under nitrogen protection, 19.2 g (0.1 mol) of 1,3-diisopropyl-2-methoxybenzene, 18.7 g (0.105 mol) of NBS and 1.8 g (0.007 mol) of triphenylphosphine were mixed in 400 mL of dichloromethane, reacted at room temperature for 1 hour, 80 mL of saturated sodium thiosulfate aqueous solution was added, the layers were separated, concentrated, and distilled under reduced pressure to obtain 24.4 g of 5-bromo-1,3-diisopropyl-2-methoxybenzene, with a yield of 90%, HPLC 99.2%. LC-MS [M+H] + =272.1.
[0029] Example 2
[0030]
[0031] Under nitrogen protection, 13.6 g (0.05 mol) of 5-bromo-1,3-diisopropyl-2-methoxybenzene, 6.7 g (0.055 mol) of phenylboronic acid, 41.73 g (1.5 mmol) of Pd(PPh3) and 63 mL of potassium phosphate (2M) were mixed in 200 mL of dioxane, heated to 80-85°C for 6 hours, cooled and filtered, 50 mL of saturated aqueous ammonium chloride solution was added, and then 100 mL of dichloromethane was added for extraction twice, the layers were separated, and then the dichloromethane layer was concentrated and slurried with n-hexane to generate 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 11.1 g, with a yield of 83%, and HPLC 98.8%. LC-MS [M+H] + =269.3.
[0032] Example 3
[0033]
[0034] Under nitrogen protection, 13.6 g (0.05 mol) of 5-bromo-1,3-diisopropyl-2-methoxybenzene, 7.3 g (0.06 mol) of phenylboric acid, 42.3 g (2 mmol) of Pd(PPh3) and 75 mL of sodium carbonate (2M) were mixed in 200 mL of dioxane, heated to 85-90 ° C for reaction for 8 hours, cooled and filtered, 50 mL of saturated aqueous ammonium chloride solution was added, and then 100 mL of dichloromethane was added for extraction twice, the layers were separated, and the dichloromethane layer was concentrated and slurried with n-hexane to generate 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 11.8 g, yield 88%, HPLC 99%.
[0035] Example 4
[0036]
[0037] Under nitrogen protection, 13.4 g (0.05 mol) of 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 14.8 g (0.075 mol) of 2-bromo-1H-benzo[d]imidazole, 3.75 mL of phosphazene base P4-t-Bu solution (0.8 M hexane solution) and 4.2 g (0.053 mol) of lithium tert-butoxide were mixed in 300 mL of dioxane and heated to 40-45 °C. , react for 5 hours, cool to room temperature, slowly add 50mL saturated aqueous ammonium chloride solution, then add 200mL dichloromethane to extract twice, concentrate the organic layer, and purify the crude product by column chromatography, eluent dichloromethane / n-hexane (v / v=1:10), to obtain 17.8g of 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole, yield 82%, HPLC 99.3%. LC-MS[M+H] + =434.4; HNMR spectrum is attached Figure 1 .
[0038] Example 5
[0039]
[0040] Under nitrogen protection, 13.4 g (0.05 mol) of 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 14.8 g (0.075 mol) of 2-bromo-1H-benzo[d]imidazole, 12.5 mL (0.8 M hexane solution) of phosphazene base P4-t-Bu and 5.9 g (0.053 mol) of potassium tert-butoxide were mixed in 300 mL of dioxane and heated to 70-75 °C. The mixture was reacted for 10 hours, cooled to room temperature, 50 mL of saturated aqueous ammonium chloride solution was slowly added, and then 200 mL of dichloromethane was added for extraction twice. The organic layer was concentrated, and the crude product was purified by column chromatography with an eluent of dichloromethane / n-hexane (v / v=1:10) to obtain 15.2 g of the target product 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole with a yield of 70% and an HPLC yield of 99.3%.
[0041] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
Claims
1. A method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, characterized in that: The reaction equation is as follows:
2. The method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl according to claim 1, characterized in that: The steps include: (1) 1,3-diisopropyl-2-methoxybenzene, NBS and triphenylphosphine are mixed in an organic solvent to generate 5-bromo-1,3-diisopropyl-2-methoxybenzene; (2) 5-bromo-1,3-diisopropyl-2-methoxybenzene, phenylboric acid, a palladium catalyst and an alkaline aqueous solution are mixed in an organic solvent, heated to react, and treated to obtain 3,5-diisopropyl-1-methoxy-1,1'-biphenyl.
3. The method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl according to claim 2, characterized in that: In step (1), the organic solvent is selected from dichloromethane, 1,2-dichloroethane or chloroform.
4. The method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl according to claim 2, characterized in that: In step (1), the molar ratio of 1,3-diisopropyl-2-methoxybenzene, NBS and triphenylphosphine is 1:1-1.1:0.05-0.
1.
5. The method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl according to claim 2, characterized in that: In step (2), the palladium catalyst is PdCl2dppf or Pd(PPh3)4; the organic solvent is selected from dioxane, DMSO, DMF, toluene; the base is selected from potassium phosphate, potassium carbonate or sodium carbonate; and the temperature of the reaction is 80-120°C.
6. The method for preparing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl according to claim 2, characterized in that: In step (2), the molar ratio of 5-bromo-1,3-diisopropyl-2-methoxybenzene, phenylboric acid, palladium catalyst and base is 1:1-1.2:0.02-0.05:1.5-3.
7. A method for preparing 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole, characterized in that: The method comprises the following steps: obtaining 3,5-diisopropyl-1-methoxy-1,1'-biphenyl by any one of the methods of claims 1 to 6, and then mixing 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 2-bromo-1H-benzo[d]imidazole, a phosphorus-containing organic base catalyst and lithium tert-butoxide in dioxane and heating the mixture to obtain 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole.
8. The method for preparing 2-bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazole according to claim 7, characterized in that: The phosphorus-containing organic base catalyst is a phosphazene base P4-t-Bu solution; and the temperature-raising reaction condition is 40-45°C.
9. 2-Bromo-1-(3,5-diisopropyl-[1,1'-biphenyl]-4-yl)-1H-benzo [d] A method for preparing imidazole, characterized in that: The molar ratio of the 3,5-diisopropyl-1-methoxy-1,1'-biphenyl, 2-bromo-1H-benzo[d]imidazole, phosphorus-containing organic base catalyst and lithium tert-butoxide is 1:1-2:0.05-0.1:1-1.1.