Preparation method of 1-bromo-4-(tert-butyl) naphthalene
By mixing compound 3 with an organic solvent and reacting under controlled temperature, bromination is performed to generate compound 4, which is then deaminated, ultimately yielding high-purity 1-bromo-4-(tert-butyl)naphthalene. This solves the problem that existing technologies have few synthetic methods and are not suitable for industrial application, and realizes a highly efficient, selective, green and environmentally friendly synthetic route.
Patent Information
- Application Number
- CN202511046943.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-29
- Publication Date
- 2025-11-07
Smart Images
Figure CN120904008A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of chemical organic synthesis, and specifically discloses a synthesis method of 1-bromo-4-(tert-butyl)naphthalene. BACKGROUND
[0002] 1-bromo-4-(tert-butyl)naphthalene, as an important organic chemical intermediate, has wide application prospects in the fields of medicine, pesticide and photochemical functional materials, for example, 1-bromo-4-(tert-butyl)naphthalene can be used for synthesizing organic phosphor doping materials, and the organic phosphor doping materials can be used as OLED light emitting parts, and the OLED light emitting materials can be divided into red, blue and green, CN119528991A proposes a series of iridium metal heterocyclic complex materials for manufacturing high-performance red light materials, for example, I-463,
[0003] The compound can reduce the driving voltage of an organic electroluminescent device, improve the luminous efficiency, and prolong the service life of the light emitting device: the compound I-463 can be synthesized from 1-bromo-4-(tert-butyl)naphthalene as a starting material through multiple steps: ; However, there are not many synthesis methods of the initial substrate 1-bromo-4-(tert-butyl)naphthalene in the prior art, so it is of great research value and practical significance to develop a high-efficiency, high-selectivity, green and environmentally friendly and industrialized production method for synthesizing 1-bromo-4-(tert-butyl)naphthalene. SUMMARY
[0004] In view of the problems in the prior art, the first aspect of the present application provides a synthesis method of 1-bromo-4-(tert-butyl)naphthalene, comprising , The compound 3 is mixed with an organic solvent, temperature control is performed, a halogenation reagent is added, and compound 4 is obtained by reaction; and the compound 4 is used as a substrate to obtain 1-bromo-4-(tert-butyl)naphthalene through one or more steps.
[0005] In some specific embodiments of the synthesis method for preparing 1-bromo-4-(tert-butyl)naphthalene in the first aspect, the organic solvent is selected from one or more of dichloromethane (DCM), ethyl acetate, tetrahydrofuran, diethyl ether and dimethylbenzene in the process of synthesizing compound 4 from compound 3.
[0006] In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3. In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3. In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3. In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3.
[0007] In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3. , In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3.
[0008] In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3. In some embodiments of the first aspect, the compound 3 is prepared by the method comprising the steps of: mixing the compound 2 with an acid, controlling the temperature, and reacting to obtain the compound 3.
[0009] In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2.
[0010] In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2. , In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2.
[0011] In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2. In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2. In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2. In some embodiments of the first aspect, the compound 2 is prepared by the method comprising the steps of: mixing the compound 1 with an organic solvent under the protection of an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling the temperature, adding water, and separating the organic phase to obtain a mixture comprising the compound 2. In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the BINAP in each 1L of the organic solvent is 5-20 mmol, and in some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the BINAP in each 1L of the organic solvent is optionally 7 mmol, 9 mmol, 11 mmol, 13 mmol, 15 mmol, 17 mmol, or 19 mmol. In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the base in each 1L of the organic solvent is 1.5-2.0 mol, and in some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the base in each 1L of the organic solvent is optionally 1.6 mol, 1.7 mol, 1.8 mol, or 1.9 mol. In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the catalyst in each 1L of the organic solvent is 3-10 mmol, and in some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the molar amount of the catalyst in each 1L of the organic solvent is optionally 4 mmol, 5 mmol, 6 mmol, 7 mmol, 8 mmol, or 9 mmol. In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the catalyst is selected from Pd2(dba)3. In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the temperature of the temperature-controlled reaction is 100-140°C, and in some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 2 from compound 1, the temperature of the temperature-controlled reaction is optionally 110°C, 120°C, or 130°C.
[0012] In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 5 from compound 4, the compound 4 is mixed with a first acid, a second acid, and water, sodium nitrite is added under first temperature control, a third acid is added under second temperature control, and then the mixture is reacted to obtain compound 5. , In some embodiments of the first aspect, the method for synthesizing 1-bromo-4- (tert-butyl) naphthalene, in the process of synthesizing compound 5 from compound 4, the compound 4 is mixed with a first acid, a second acid, and water, sodium nitrite is added under first temperature control, a third acid is added under second temperature control, and then the mixture is reacted to obtain compound 5. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the molar amount of compound 4 in 1 L of water during the synthesis of compound 5 is 800-1200 mmol. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the molar amount of compound 4 in 1 L of water during the synthesis of compound 5 is optionally 850 mmol, 900 mmol, 950 mmol, 1000 mmol, 1050 mmol, 1100 mmol, 1150 mmol. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the first acid in 1 L of water during the synthesis of compound 5 is 0.5-2 L. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the first acid in 1 L of water during the synthesis of compound 5 is optionally 0.7 L, 0.9 L, 1.1 L, 1.3 L, 1.5 L, 1.7 L, 1.9 L.
[0013] In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the second acid in 1 L of water during the synthesis of compound 5 is 0.2-0.5 L. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the second acid in 1 L of water during the synthesis of compound 5 is optionally 0.3 L, 0.4 L.
[0014] In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the molar amount of sodium nitrite in 1 L of water during the synthesis of compound 5 is 1000-1500 mmol. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the molar amount of sodium nitrite in 1 L of water during the synthesis of compound 5 is optionally 1100 mmol, 1200 mmol, 1300 mmol, 1400 mmol.
[0015] In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the third acid in 1 L of water during the synthesis of compound 5 is 1-1.5 L. In some embodiments of the method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to the first aspect, the volume of the third acid in 1 L of water during the synthesis of compound 5 is optionally 1.1 L, 1.2 L, 1.3 L, 1.4 L.
[0016] In some embodiments of the first aspect, the second temperature-controlled reaction time is 5-30 hours, in some embodiments of the first aspect, the second temperature-controlled reaction time is 9 hours, 13 hours, 17 hours, 21 hours, 25 hours, or 29 hours.
[0017] The reagents used in the present application are purchased from open legal market and are not further purified.
[0018] Explanation of terms: In the present application, NCS is N-chlorosuccinimide; and NBS is N-bromosuccinimide.
[0019] In some embodiments, the room temperature is 5-45℃, in some embodiments, the room temperature is 10-30℃, in some embodiments, the room temperature is 15-25℃, and in some embodiments, the room temperature is 25℃.
[0020] Advantages of the present application: The prior art has certain requirements for the purity and components of the reaction substrate. In the technical solution of the present application, after the coupling of compound 1 to obtain a mixed solution comprising compound 2, the mixed solution comprising compound 2 can be directly used as a raw material to synthesize compound 3 without refining compound 2. The components in the mixed solution do not interfere with the synthesis of compound 3. The present application uses a continuous feeding method to avoid the loss of intermediate compound 2, thereby improving the yield.
[0021] In the process of synthesizing compound 4 from compound 3, no isomer is found to be generated during the bromination process by pre-occupying the tert-butyl group. The yield of the target product compound 4 is high. Finally, compound 5 can be obtained by deaminating compound 4 and simple distillation. BRIEF DESCRIPTION OF DRAWINGS
[0022] Figure 1 HPLC chromatogram of compound 5 is shown in the following figure: Figure 2 TLC spot plate diagram of Comparative Example 1 is shown in the following figure: DETAILED DESCRIPTION
[0023] In order to enable those skilled in the art to better understand the technical solutions of the present application, some non-limiting embodiments are further disclosed below to further illustrate the present application in detail.
[0024] A synthesis path of 1-bromo-4-(tert-butyl)naphthalene: The present application is divided into four steps, the first two steps are carried out by continuous injection, the mixed solution including compound 2 can be directly used as the reaction substrate of compound 3 in the second step synthesis, the reaction is clean and the yield is high, in the process of bromination of compound 3 to obtain compound 4, no isomer is found to be generated, and compound 4 is easy to purify, finally, compound 4 is subjected to deamination and diazotization reaction to obtain compound 5, the overall reaction is clean, and high-purity product can be obtained by distillation.
[0025] Example 1
[0026] Compound 1 (914.39 mmol) was added to a three-neck flask, dimethylbenzene (1.6 L) was added to stir and dissolve, then benzophenone imine (1097.27 mmol), BINAP (18.29 mmol), sodium tert-butoxide (2743.18 mmol) were added, nitrogen was replaced for 3 times, under the protection of nitrogen, the catalyst Pd2(dba)3 (9.14 mmol) was added to the reaction system, then the reaction system was heated to 120 ℃ and reacted for 12 h. TLC point plate reaction was complete. The reaction liquid was added with H2O (1000 mL) to separate the organic phase, and 5 L of mixed solution including compound 2 was obtained and directly used in example 2.
[0027] Example 2
[0028] The 5 L mixed solution obtained in example 1 was poured into a 10 L reaction kettle, concentrated HCl (12 mol / L, 500 ml) was added, and the temperature was raised to 60 ℃ and reacted for 12 h. After monitoring that the raw material was completely reacted, the solid product was obtained by filtration, the product was dissolved in H2O (1 L), EA (1.5 L) was added, the pH was adjusted to 8-9, and the product was extracted and separated to obtain compound 3 (yellow solid, two-step yield of compound 1 was 94%).
[0029] 1 H NMR (400 MHz, DMSO-d6) δ 10.49 (s, 2H), 8.51 – 8.42 (m, 1H), 7.99(dd, J = 7.8, 1.8 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.60 – 7.49 (m, 3H),1.57 (s, 9H)。
[0030] Comparative Example 1
[0031] Compound 1 (914.39 mmol) was added to a three-necked flask, and then stirred and dissolved in xylene (1.6 L), and then diphenyl ketimine (1097.27 mmol), sodium tert-butoxide (2743.18 mmol) were added, and the reaction system was replaced with nitrogen for 3 times, and then a catalyst Xphos-Pd-G2 (9.14 mmol) was added to the reaction system under nitrogen protection, and then the reaction system was heated to 120 °C for reaction for 12 h. TLC point plate reaction was completed, and the reaction liquid was added with H2O (1000 mL) to separate the organic phase to obtain a mixed liquid containing compound 2, and the mixed liquid prepared by preparing the comparative example 1 was directly used for the comparative example 2.
[0032] Comparative example 2
[0033] The 5 L mixed liquid prepared by preparing the comparative example 1 was poured into a 10 L reaction kettle, and concentrated HCl (12 mol / L, 500 ml) was added, and the temperature was increased to 60 °C for reaction for 12 h. After monitoring that the raw material was completely reacted, the solid product was filtered to obtain a solid product, and the product was dissolved in H2O (1 L), and then EA (1.5 L) was added, and the pH was adjusted to 8-9, and then extraction separation was performed, and compound 3 (yellow solid, two-step yield of 57% based on compound 1) was obtained by desolventizing.
[0034] 1 H NMR (400 MHz, DMSO-d6) δ 10.49 (s, 2H), 8.51 – 8.42 (m, 1H), 7.99(dd, J = 7.8, 1.8 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.60 – 7.49 (m, 3H),1.57 (s, 9H)。
[0035] Example 3
[0036] Compound 3 (0.75 mol) was weighed into a three-necked flask, DCM (1500 ml) was added, and the temperature was decreased to -20 °C, and then NBS (0.90 mol) was added in batches, and the reaction was continued at the temperature for 12 h. After monitoring that the raw material was completely reacted, H2O (1500 ml) was added for extraction separation, and the organic phase was rotary evaporated to obtain compound 4 (yellow solid, yield 90 %).
[0037] 1H NMR (400 MHz, DMSO-d6) δ 8.30 - 8.21 (m, 1H), 7.95 (dd, J = 8.5, 1.3 Hz, 1H), 7.44 (dddd, J = 8.2, 6.8, 4.3, 1.1 Hz, 1H), 7.28 - 7.18 (m, 2H), 5.67 (s, 2H), 1.53 (s, 9H).
[0038] Example 4
[0039] Compound 4 (647.03 mmol) was weighed into a three-necked flask, acetic acid (1000 mL), concentrated hydrochloric acid (200 ml), H20 (600.0 ml), an aqueous solution of sodium nitrite (750.56 mmol) was added at 0 °C, stirred for 15 min, controlled temperature 5 °C, dropwise addition of hypophosphorous acid (700 ml), controlled temperature 5 °C, reacted overnight. TLC point plate raw material basically reacted, after treatment, petroleum ether (1500 mL) was added, extracted, the organic phase was rotary evaporated, petroleum ether was dissolved and brushed silica gel column, the filtrate was concentrated, and the product compound 5 was distilled at 160 °C under reduced pressure (yield 88.09%).
[0040] 1 H NMR (400 MHz, DMSO-d6) δ 8.53 - 8.48 (m, 1H), 8.26 - 8.18 (m, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.67 - 7.61 (m, 2H), 7.39 (d, J = 8.1 Hz, 1H), 1.56 (s, 9H).
[0041] Comparative Example 3:
[0042] 2-naphthylamine (5.02 mmol), NBS (5.27 mmol) were dissolved in DCM (10 mL), stirred at -30 °C for 2 h, TLC point plate was used for product control, as shown in the following figure, the upper point was the target product point, and the lower point was the disubstituted product by-product 1 or by-product 2. Quenching with water, DCM extraction, separation, concentration of organic phase, 1.5 times silica gel sample, purified by column chromatography, pure petroleum ether flushing, product was obtained, white solid, yield 30%, by-product 1, yield 20%, by-product 2, yield 15%.
[0043] The above merely provides the preferred embodiment of the present application, and is not used to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims
1. A method for synthesizing 1-bromo-4-(tert-butyl)naphthalene, comprising ， mixing the compound 3 with an organic solvent, controlling temperature, adding a halogenating reagent, and reacting to obtain compound 4; subjecting the compound 4 to one or more steps of reaction as a substrate to obtain 1-bromo-4-(tert-butyl)naphthalene.
2. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to claim 1, characterized in that, The molar amount of the compound 3 in each 1L of the organic solvent is 0.3mol-0.7mol; and / or, the halogenating reagent is any one or combination of NBS, NCS, and bromine water; and / or, the molar amount of NBS in each 1L of the organic solvent is 0.3-0.8mol; and / or, the temperature of the temperature control is-30--10℃; and / or, the organic solvent is selected from one or more of dichloromethane, ethyl acetate, tetrahydrofuran, diethyl ether, and xylene. 3.The method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to any one of claims 1 or 2, characterized in that ； mixing the compound 2 with an acid, controlling temperature, and obtaining compound 3.
4. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to claim 3, characterized in that, The acid is selected from any one of hydrochloric acid, sulfuric acid, and nitric acid; and / or, the temperature of the temperature control is controlled to 50-70℃. 5.The method for synthesizing 1-bromo-4-(tert-butyl)naphthalene according to any one of claims 3 or 4, characterized in that ； mixing the compound 1 with an organic solvent under an inert atmosphere, adding benzophenone imine, BINAP, a base, a catalyst, controlling temperature, adding water, and separating the organic phase to obtain a mixture comprising compound 2.
6. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to claim 5, characterized in that, The organic solvent is selected from one or more of toluene, xylene, ethanol, dichloromethane, and tetrahydrofuran; and / or, the molar amount of the compound 1 in each 1L of the organic solvent is 400-800mmol; and / or, the molar amount of benzophenone imine in each 1L of the organic solvent is 500-1000mmol.
7. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to any one of claims 5 or 6, characterized in that, The inert atmosphere is any one or more of nitrogen atmosphere, argon atmosphere, and helium atmosphere; and / or, the molar amount of BINAP in each 1L of the organic solvent is 5-20mmol; and / or, the molar amount of the base in each 1L of the organic solvent is 1500-2000mmol; and / or, the molar amount of the catalyst in each 1L of the organic solvent is 3-10mmol; and / or, the catalyst is selected from Pd2(dba)3; and / or, the temperature of the temperature control reaction is 100-140℃.
8. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to any one of claims 1 to 6, characterized in that, mixing the compound 4 with a first acid, a second acid, and water, adding sodium nitrite under first temperature control, adding a third acid under second temperature control, and reacting to obtain compound 5; 。 9. The process for the synthesis of 1-bromo-4-(tert-butyl)naphthalene according to any one of claims 1 to 8, characterized in that, The volume of the first acid mixed in each 1L of water is 0.5-2L; and / or, the volume of the second acid mixed in each 1L of water is 0.2-0.5L; and / or, the molar amount of sodium nitrite in each 1L of water is 1000-1500mmol; and / or, the volume of the third acid mixed in each 1L of water is 0.5-1.5L; the second temperature control reaction time is 5-30 hours; and / or, the first acid, the second acid, and the third acid are each independently sulfuric acid, nitric acid, and hydrochloric acid.