Synthesis method of 2-(4-(tert-butyl) naphthalene-2-yl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of 2-(4-(tert-butyl) naphthalene-2-yl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane. The preparation method of the 2-(4-(tert-butyl) naphthalene-2-yl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane comprises the following steps: carrying out a series of reactions on benzaldehyde, piperidine and 1, 1-dimethoxypropyl-2-ketone to obtain a compound 3, a compound 4 and a compound 5, and finally preparing the 2-(4-(tert-butyl) naphthalene-2-yl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane. The whole reaction process is mild, and the method is suitable for industrial amplification and has good industrial value.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Background Art

[0002] With the development of technology and the continuous improvement of product performance, the application of OLED in flat panel displays, lighting and backlighting has attracted more and more attention. At present, it has been gradually widely used in the fields of commerce, communications, computers, electronic products and transportation.

[0003] The advantages of OLED are closely related to the properties of organic optoelectronic materials. Organic materials with excellent performance can not only improve the various properties of OLED, but also simplify the production process and reduce costs.

[0004] In recent years, 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane has attracted extensive attention and research as a key intermediate for synthesizing OLED red light doping materials.

[0005] For example, the Chinese patent document with the announcement number CN115974903A discloses a technical solution for preparing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane using 2-naphthol and pyridine-2-sulfonyl chloride as raw materials through three steps of esterification, tert-butylation, and borylation. However, although the synthetic route is short, the boiling point of the reagent tert-butyl chloride used in the second step is only 52°C, while the reaction temperature is 130°C. The reaction process requires a sealed tank, which places high demands on the reactor equipment and is difficult to achieve industrial production.

[0006] For example, the Chinese patent document with the announcement number CN116969984A discloses another synthesis route that does not use a palladium catalyst. However, the materials used in its synthesis method are not easy to source and involve multiple hazardous chemicals. In addition, the third step reaction not only has relatively harsh reaction conditions, but is also a rearrangement reaction with severe outgassing, and the conditions for achieving industrial production are relatively harsh.

[0007] Therefore, the existing preparation route of 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane is difficult to carry out large-scale industrial production, and it is urgent to explore new synthetic routes. Summary of the invention

[0008] The technical problem to be solved by the present invention is to provide a method for preparing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, so as to solve the defect that the existing preparation route of 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane is difficult to carry out large-scale industrial production.

[0009] In order to solve the above technical problems, the first aspect of the present invention provides a method for synthesizing 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Compound 8), comprising:

[0010]

[0011] Under an inert gas atmosphere, compound 7 was dissolved in an organic solvent, and diboric acid pinacol ester, Pd(dppf)Cl2, and potassium acetate were added to react to obtain compound 8;

[0012]

[0013] In some specific embodiments of the first aspect, the organic solvent is selected from any one of 1,4-dioxane, THF, DMF, DCM, or a mixture thereof.

[0014] In some specific embodiments of the first aspect, the molar amount of compound 7 per 1 L of organic solvent is 280-320 mmol, preferably 301 mmol.

[0015] In some specific embodiments of the first aspect, the molar amount of biboric acid pinacol ester in each 1L of organic solvent is 320-380 mmol, preferably 360 mmol.

[0016] In some specific embodiments of the first aspect, the molar amount of Pd(dppf)Cl2 in each 1L of organic solvent is 2.80-3.20 mmol, preferably 3.0 mmol.

[0017] In some specific embodiments of the first aspect, the molar amount of potassium acetate added per 1 L of organic solvent is 580-620 mmol, preferably 602 mmol.

[0018] In some specific embodiments of the first aspect, the inert atmosphere is nitrogen or argon, or a mixture thereof.

[0019] In some specific embodiments of the first aspect, the synthesis method of compound 7 comprises:

[0020]

[0021] Add triethylamine to the organic solution of compound 6, and dropwise add trifluoromethanesulfonic anhydride to react to obtain compound 7;

[0022]

[0023] In some specific embodiments of the first aspect, the organic solvent is selected from toluene, xylene, dichloromethane, THF, DMF or a mixture thereof.

[0024] In some specific embodiments of the first aspect, the molar amount of compound 6 in each 1 L of organic solvent is 480-530 mmol, preferably 515 mmol.

[0025] In some specific embodiments of the first aspect, the molar amount of triethylamine in each 1 L of organic solvent is 600-640 mmol, preferably 620 mmol.

[0026] In some specific embodiments of the first aspect, the molar amount of trifluoromethanesulfonic anhydride fed per 1 L of organic solvent is 610-630 mmol, preferably 619 mmol.

[0027] In some specific embodiments of the first aspect, the reaction temperature is -5 to 5°C, preferably 0°C.

[0028] In some specific embodiments of the first aspect, the synthesis method of compound 6 comprises:

[0029]

[0030] Step 1: Add InCl3 to the organic solution of compound 2, control the temperature, and add tert-butylmagnesium bromide solution under an inert atmosphere to react to obtain compound 3;

[0031]

[0032] Step 2: dissolving compound 3 in alcohol, controlling the temperature, adding sodium borohydride under an inert atmosphere, and reacting to obtain compound 4;

[0033]

[0034] Step 3: Dissolve compound 4 in an organic solvent, add TiCl4 at 0°C, stir at room temperature for 2 hours, and react to obtain compound 5;

[0035]

[0036] Step 4: Add TMSOTf and NBS to the organic solution of compound 5, and react under inert atmosphere and temperature control to obtain compound 6;

[0037]

[0038] In some specific embodiments of the first aspect, the organic solvent in step 1 is any one of tetrahydrofuran, alcohol, N,N-dimethylamide, acetonitrile or a mixture thereof.

[0039] In some specific embodiments of the first aspect, the inert atmosphere in step 1 is argon, nitrogen, or a mixture thereof.

[0040] In some specific embodiments of the first aspect, in step 1, 450-500 mmol, preferably 484 mmol, of compound 2 is added per 1 L of organic solvent.

[0041] In some specific embodiments of the first aspect, in step 1, 5 to 500 mmol, preferably 24.3 mmol, of InCl3 is added per 1 L of organic solvent.

[0042] In some specific embodiments of the first aspect, the temperature of the temperature control in step 1 is -30°C to -10°C, preferably -20°C.

[0043] In some specific embodiments of the first aspect, the tert-butylmagnesium bromide solution is a tetrahydrofuran solution of tert-butylmagnesium bromide.

[0044] In some specific embodiments of the first aspect, the molar ratio of tert-butylmagnesium bromide to compound 2 is (1-1.5):1, preferably 1.1:1.

[0045] In some specific embodiments of the first aspect, the alcohol in step 2 is methanol, ethanol or a mixture thereof.

[0046] In some specific embodiments of the first aspect, the inert atmosphere in step 2 is argon, nitrogen, or a mixture thereof.

[0047] In some specific embodiments of the first aspect, in step 2, 350-400 mmol, preferably 378 mmol, of compound 3 is added per 1 L of alcohol.

[0048] In some specific embodiments of the first aspect, in step 2, the amount of sodium borohydride added per 1 L of alcohol is 756-1512 mmol, preferably 1135 mmol.

[0049] In some specific embodiments of the first aspect, the temperature of the temperature control in step 1 is -5°C to 5°C, preferably -0°C.

[0050] In some specific embodiments of the first aspect, the organic solvent in step 3 is any one of tetrahydrofuran, ethyl acetate, dichloromethane, acetonitrile or a mixture thereof.

[0051] In some specific embodiments of the first aspect, the inert atmosphere in step 3 is argon, nitrogen, or a mixture thereof.

[0052] In some specific embodiments of the first aspect, in step 1, 350-400 mmol, preferably 375 mmol, of compound 4 is added per 1 L of organic solvent.

[0053] In some specific embodiments of the first aspect, in step 1, 280 to 480 mmol, preferably 375 mmol, of TiCl4 is added to every 1 L of organic solvent.

[0054] In some specific embodiments of the first aspect, the organic solvent used in the organic solution in step 4 is any one of tetrahydrofuran, alcohol, N,N-dimethylamide, acetonitrile or a mixture thereof.

[0055] In some specific embodiments of the first aspect, the inert atmosphere in step 4 is argon, nitrogen, or a mixture thereof.

[0056] In some specific embodiments of the first aspect, in step 4, 450-500 mmol, preferably 492 mmol, of compound 5 is added per 1 L of organic solvent.

[0057] In some specific embodiments of the first aspect, in step 4, 5 to 50 mmol, preferably 24.6 mmol, of TMSOTf is added to every 1 L of organic solvent.

[0058] In some specific embodiments of the first aspect, in step 4, 450 to 750 mmol, preferably 590 mmol, of NBS is added to every 1 L of organic solvent.

[0059] In some specific embodiments of the first aspect, the temperature of step 4 is controlled at 20°C to 40°C, preferably 30°C.

[0060] In some specific embodiments of the first aspect, the synthesis method of compound 2 includes: adding piperidine to an organic solution containing benzaldehyde (compound 1) and 1,1-dimethoxypropane-2-one, controlling the temperature, and reacting to obtain compound 2.

[0061] Preferably, in the synthesis method of compound 2, the organic solvent is any one of tetrahydrofuran, alcohol, N,N-dimethylamide, acetonitrile or a mixture thereof.

[0062] In some specific embodiments of the first aspect, the compound 1 is added in an amount of 900 to 1000 mmol, preferably 942 mmol, per 1 L of organic solvent.

[0063] In some specific embodiments of the first aspect, the amount of 1,1-dimethoxypropan-2-one added to each 1 L of organic solvent is 900 to 3000 mmol, preferably 1884 mmol.

[0064] In some specific embodiments of the first aspect, the amount of piperidine added to each 1 L of organic solvent is 450-2000 mmol, preferably 942 mmol.

[0065] In some specific embodiments of the first aspect, the temperature of the temperature control is 60°C to 80°C, preferably 70°C.

[0066] The beneficial effects of the present invention are:

[0067] 1. The present invention uses low-cost and readily available benzaldehyde, piperidine, and 1,1-dimethoxypropan-2-one as basic raw materials, and obtains compound 3, compound 4, and compound 5 through a series of reactions. The overall reaction process is mild, and as an intermediate capable of synthesizing OLED organic light-emitting materials, it has good industrial value. The preparation method of 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane provided by the present invention has the characteristics of simple operation, high yield, readily available raw materials, low cost, and suitability for industrial scale-up. DETAILED DESCRIPTION

[0068] In order to explain the technical content, achieved objectives and effects of the present invention in detail, the following is an explanation in conjunction with the implementation methods.

[0069]

[0070]

[0071] Example 1

[0072]

[0073] Add benzaldehyde (471.2mmol) and 1,1-dimethoxypropan-2-one (942.4mmol) to methanol (500mL), then add piperidine (471.2mmol), stir and heat to reflux 70℃ for 18 hours. TLC spot plate shows that the raw materials are basically reacted and returned to room temperature. Add water to the reaction solution and extract with dichloromethane. Wash the organic phase with water three times, dry it with anhydrous sodium sulfate, concentrate it to obtain a crude product, and then distill it under reduced pressure to obtain compound 2 (390.8mmol, yield 83%).

[0074] Example 2

[0075]

[0076] Dissolve compound 2 (387.9 mmol) in tetrahydrofuran (800 mL), add InCl3 (19.4 mmol), cool to -20 ° C, and add tert-butylmagnesium bromide (853 mL, 426.7 mmol, 0.5 M in THF) under nitrogen protection. After the addition is complete, slowly return to 0 ° C and stir for 2 hours. TLC spot plate shows that the reaction is complete. Add saturated ammonium chloride aqueous solution to the reaction solution and extract with ethyl acetate. Wash the organic phase three times with water, dry it over anhydrous sodium sulfate, concentrate it, and the crude product is subjected to column chromatography to obtain compound 3 (263.6 mmol, yield 68%).

[0077] Example 3

[0078]

[0079] Compound 3 (189.1 mmol) was dissolved in ethanol (500 mL), cooled to 0°C, sodium borohydride (567.4 mmol) was added in batches under nitrogen protection, and stirred at 0°C for 2 hours. TLC plate showed that the reaction was complete, water was added to the reaction solution, and stirred at room temperature for 2 hours. Ethyl acetate was extracted, and the organic phase was washed three times with water, dried over anhydrous sodium sulfate, concentrated, and the crude product was subjected to column chromatography to obtain compound 4 (170.0 mmol, yield 90%).

[0080] Example 4

[0081]

[0082] Compound 4 (112.6 mmol) was dissolved in dichloromethane (300 mL), TiCl4 (112.6 mmol) was added at 0°C, and the mixture was stirred at room temperature for 2 hours. TLC showed that the reaction was complete, and saturated NaHCO3 aqueous solution was added to the reaction solution for low temperature quenching, and dichloromethane was extracted. The organic phase was then washed three times with water, dried over anhydrous sodium sulfate, concentrated, and the crude product was subjected to column chromatography to obtain compound 5 (73.8 mmol, yield 65%).

[0083] Example 5

[0084]

[0085] Compound 5 (73.8 mmol) was dissolved in acetonitrile (150 mL), TMSOTf (3.69 mmol) and NBS (88.6 mmol) were added, and the mixture was stirred at 30°C for 16 hours under nitrogen protection. TLC showed that the reaction was complete, and water was added to the reaction solution, and ethyl acetate was used for extraction. The organic phase was then washed three times with water, dried over anhydrous sodium sulfate, and concentrated. The crude product was then subjected to column chromatography to obtain compound 6 (61.9 mmol, yield 84%).

[0086] Comparative Example 5-1

[0087] Compound 5 (14.76 mmol) was dissolved in acetonitrile (30 mL), NBS (17.72 mmol) was added, and the mixture was stirred at 30°C for 16 hours under nitrogen protection. TLC plate showed that no product was generated.

[0088] Example 6

[0089]

[0090] Compound 6 (61.9 mmol) was dissolved in dichloromethane (120 mL), triethylamine (74.3 mmol) was added, trifluoromethanesulfonic anhydride (74.3 mmol) was added dropwise at 0°C, and stirred at 0°C for 2 hours after the addition was complete. TLC plate showed that the reaction was complete, water was added to the reaction solution, and dichloromethane was extracted. The organic phase was washed three times with water, dried over anhydrous sodium sulfate, concentrated, and the crude product was subjected to column chromatography to obtain compound 7 (55.1 mmol, yield 89%).

[0091] Example 7

[0092]

[0093] Compound 7 (45.2 mmol) was dissolved in 1,4-dioxane (150 mL), and diboric acid pinacol ester (54.2 mmol), Pd(dppf)Cl2 (0.452 mmol), and potassium acetate (90.4 mmol) were added. The mixture was stirred at 100°C overnight under nitrogen protection. TLC showed that the reaction was complete. Water was added to the reaction solution and extracted with ethyl acetate. The organic phase was washed three times with water, dried over anhydrous sodium sulfate, and concentrated. The crude product was crystallized with a mixed solvent of ethyl acetate and ethanol to obtain compound 8 (39.6 mmol, yield 88%).

[0094] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent transformations made using the contents of the present invention specification, or directly or indirectly applied in related technical fields, are also included in the patent protection scope of the present invention.

[0095] It should be noted that the specific parameters or some commonly used reagents in the above embodiments are specific embodiments or preferred embodiments under the concept of the present invention, rather than limiting thereof; those skilled in the art can make adaptive adjustments within the concept and protection scope of the present invention.

Claims

1. A method for synthesizing 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Compound 8), comprising: Under an inert gas atmosphere, compound 7 was dissolved in an organic solvent, and diboric acid pinacol ester, Pd(dppf)Cl2, and potassium acetate were added to react to obtain compound 8; 2. The method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to claim 1, characterized in that , the organic solvent is selected from any one of 1,4-dioxane, THF, DMF, DCM or a mixture thereof, and / or, the molar amount of compound 7 in each 1L of organic solvent is 280-320mmol, and / or, the molar amount of biboric acid pinacol ester in each 1L of organic solvent is 320-380mmol, and / or, the molar amount of Pd(dppf)Cl2 in each 1L of organic solvent is 2.80-3.20mmol, and / or, the molar amount of potassium acetate in each 1L of organic solvent is 580-620mmol, and / or, the inert atmosphere is one of nitrogen or argon or a mixture thereof.

3. A method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to any one of claims 1 or 2, characterized in that , the synthesis method of compound 7 comprises: Add triethylamine to the organic solution of compound 6, and dropwise add trifluoromethanesulfonic anhydride to react to obtain compound 7; 4. The method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to claim 3, characterized in that: The organic solvent is selected from one of toluene, xylene, dichloromethane, THF, DMF or a mixture thereof, and / or the molar amount of compound 6 per 1L of organic solvent is 480-530mmol, and / or the molar amount of triethylamine per 1L of organic solvent is 600-640mmol, and / or the molar amount of trifluoromethanesulfonic anhydride per 1L of organic solvent is 610-630mmol, and / or the reaction temperature is -5-5°C.

5. The method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to claim 3, characterized in that: The synthesis method of compound 6 comprises: Step 1: Add InCl3 to the organic solution of compound 2, control the temperature, and add tert-butylmagnesium bromide solution under an inert atmosphere to react to obtain compound 3; Step 2: dissolving compound 3 in alcohol, controlling the temperature, adding sodium borohydride under an inert atmosphere, and reacting to obtain compound 4; Step 3: Dissolve compound 4 in an organic solvent, add TiCl4 at 0°C, stir at room temperature for 2 hours, and react to obtain compound 5; Step 4: Add TMSOTf and NBS to the organic solution of compound 5, and react under inert atmosphere and temperature control to obtain compound 6; 6. The method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to claim 5, characterized in that: In the step 1, the organic solvent is any one of tetrahydrofuran, alcohol, N,N-dimethylamide, acetonitrile or a mixture thereof, and / or, the inert atmosphere in the step 1 is any one of argon and nitrogen or a mixture thereof, and / or, in every 1L of organic solvent in the step 1, 450 to 500 mmol of compound 2 is added, and / or, in every 1L of organic solvent in the step 1, 5 to 500 mmol of InCl3 is added, and / or, the temperature of the temperature control in the step 1 is -30°C to -10°C, preferably -20°C, and / or, the tert-butyl magnesium bromide solution is a tetrahydrofuran solution of tert-butyl magnesium bromide, and / or, the molar ratio of the tert-butyl magnesium bromide to compound 2 is (1 to 1.5):

1.

7. The method for synthesizing 2-(4-(tert-butyl)naphthalene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to any one of claims 5 or 6, characterized in that: In the step 2, the alcohol is any one of methanol and ethanol or a mixture thereof, and / or, the inert atmosphere in the step 2 is any one of argon and nitrogen or a mixture thereof, and / or, in the step 2, 350 to 400 mmol of compound 3 is added per 1 L of alcohol, and / or, 756 to 1512 mmol of sodium borohydride is added per 1 L of alcohol in the step 2, and / or, the temperature of the temperature control in the step 1 is -5°C to 5°C.

8. The method for synthesizing 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to any one of claims 5 to 7, characterized in that: In the step 3, the organic solvent is any one of tetrahydrofuran, ethyl acetate, dichloromethane, acetonitrile or a mixture thereof, and / or, the inert atmosphere in the step 3 is any one of argon and nitrogen or a mixture thereof, and / or, in the step 1, 350 to 400 mmol of compound 4 is added per 1 L of organic solvent, and / or, 280 to 480 mmol of TiCl4 is added per 1 L of organic solvent in the step 1.

9. The method for synthesizing 2-(4-(tert-butyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane according to any one of claims 5 to 8, characterized in that: In the step 4, the organic solvent is any one of tetrahydrofuran, alcohol, N,N-dimethylamide, acetonitrile or a mixture thereof, and / or, the inert atmosphere in the step 4 is any one of argon and nitrogen or a mixture thereof, and / or, in the step 4, 450 to 500 mmol of compound 5 is added to every 1 L of organic solvent, and / or, in the step 4, 5 to 50 mmol of TMSOTf is added to every 1 L of organic solvent, and / or, in the step 4, 450 to 750 mmol of NBS is added to every 1 L of organic solvent, and / or, the temperature of the temperature control in the step 4 is 20° C. to 40° C.

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