Binaphthol efficient preparation method based on phase transfer catalysis

Abstract

The invention relates to the technical field of binaphthol production, in particular to an efficient binaphthol preparation method based on phase transfer catalysis, which comprises the following steps: by taking alpha-naphthol as a raw material, adding alpha-naphthol, an alkaline reagent, a phase transfer catalyst and an organic solvent into a three-neck flask, and mixing to form a reaction system, the molar ratio of the alpha-naphthol to the alkaline reagent to the phase transfer catalyst is 1: (1.2-2.0): (0.05-0.2). A reaction system is formed by the alpha-naphthol, the alkaline reagent, the phase transfer catalyst and the organic solvent, the binaphthol is prepared based on the phase transfer catalysis method, the reaction condition is milder, the yield of the binaphthol is increased, the production cost is reduced, large-scale industrial production is facilitated, and the method is suitable for industrial production. The method avoids the use of reagents harmful to the environment, such as a strong oxidant, and wastes generated in the reaction process are mainly a small amount of organic waste liquid and inorganic salt, are easy to treat, and meet the development requirements of green chemistry.

Description

Technical Field

[0001] The present invention relates to the technical field of binaphthol production, and particularly relates to a method for efficiently preparing binaphthol based on phase transfer catalysis. Background Art

[0002] Binaphthol and its derivatives are an important class of chiral ligands and catalysts, and have extensive applications in the fields of asymmetric synthesis, materials science, etc. They are usually used for synthesizing a variety of chiral pharmaceutical intermediates and chiral reagents.

[0003] For example, Chinese Patent CN112479827B discloses a method for efficiently preparing binaphthol with the assistance of a liquid ligand. The reaction conditions are mild, the product yield is greater than 78%, and the product purity is higher than 99%.

[0004] Currently, the preparation methods of binaphthol mainly include oxidative coupling method, transition metal-catalyzed coupling method, etc. The oxidative coupling method usually uses strong oxidants, the reaction conditions are relatively harsh, side reactions are likely to occur, resulting in low product purity, and it is not environmentally friendly. Although the transition metal-catalyzed coupling method has high selectivity, the catalyst cost is expensive, and it is difficult to achieve large-scale industrial production. Phase transfer catalysis (Phase Transfer Catalysis, abbreviated as PTC) is a technology in a multiphase reaction system that accelerates the reaction by transferring reactants from one phase to another through a phase transfer catalyst. Phase transfer catalysis has been widely applied in organic synthesis. However, there are few studies on applying phase transfer catalysis technology to the preparation of binaphthol, and a mature industrial production process has not been formed.

[0005] In summary, developing a method for efficiently preparing binaphthol based on phase transfer catalysis is still a key problem that urgently needs to be solved in the technical field of binaphthol production. Summary of the Invention

[0006] Aiming at the problems existing in the prior art, the purpose of the present invention is to provide a method for efficiently preparing binaphthol based on phase transfer catalysis, so as to solve the problems of serious environmental pollution, low yield and purity, high cost, etc. existing in the existing binaphthol preparation methods, and realize the green, efficient and low-cost preparation of binaphthol.

[0007] To achieve the above purpose, the present invention provides the following technical solutions: A method for efficiently preparing binaphthol based on phase transfer catalysis, comprising the following steps: S1. Using α-naphthol as a raw material, adding α-naphthol, a basic reagent, a phase transfer catalyst and an organic solvent into a three-necked flask and mixing them to form a reaction system, wherein the molar ratio of α-naphthol, the basic reagent, and the phase transfer catalyst is 1:(1.2 - 2.0):(0.05 - 0.2); S2. Stir the above reaction system and react for 6 - 12 h under stirring conditions and at a temperature of 40 - 80 °C. During the reaction, the phase transfer catalyst continuously transfers the phenolate from the aqueous phase to the organic phase, causing it to undergo a coupling reaction with α-naphthol to form binaphthol, obtaining a reaction mixture. The overall reaction equation is as follows: ; S3. After the reaction is completed, cool the reaction mixture to room temperature and add an appropriate amount of water for dilution to obtain a reaction solution; S4. Extract the reaction solution with an organic solvent, combine the organic phases, dry with anhydrous sodium sulfate, filter to remove the desiccant, and then remove the organic solvent by vacuum distillation to obtain a crude product; S5. Purify the crude product by column chromatography or recrystallization to obtain high-purity white crystalline binaphthol.

[0008] The present invention is further configured such that: in step S1, the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, dichloromethane, and chloroform, and 5 - 15 mL of the organic solvent corresponds to each millimole of α-naphthol.

[0009] The present invention is further configured such that: in step S1, the basic reagent is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

[0010] The present invention is further configured such that: in step S1, the phase transfer catalyst is selected from quaternary ammonium salt catalysts or crown ether catalysts. The quaternary ammonium salt catalysts are selected from one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, and benzyltriethylammonium chloride, and the crown ether catalysts are selected from one or more of 18-crown-6 and 15-crown-5.

[0011] The present invention is further configured such that: in step S2, during the reaction, the reaction can be assisted by ultrasonic waves under the condition of introducing nitrogen. The ultrasonic power is 100 - 200 W, and the flow rate of the introduced nitrogen is controlled at 80 - 300 ml / min.

[0012] The present invention is further configured such that: in step S4, extracting the reaction solution with an organic solvent and combining the organic phases includes the following steps: A1. Select a suitable separating funnel, use a glass rod to guide the flow, and carefully pour the reaction solution cooled to room temperature and diluted into the separating funnel; A2. Add an appropriate amount of organic solvent to the separating funnel and quickly close the glass stopper at the upper opening of the separating funnel; A3. Press the glass stopper at the upper opening of the separating funnel with the right hand, hold the piston part with the left hand, invert the separating funnel, and shake it vigorously. During the shaking process, the piston needs to be turned to release gas, and the gas release operation is repeated 2 - 3 times; A4. After the shaking is complete, let the separatory funnel stand for a while to allow the mixture to fully separate. During this process, most of the binaphthol will transfer to the organic phase where the organic solvent is located, while the water-soluble impurities will remain in the aqueous phase, forming distinct upper and lower liquid layers. A5. After the layers are completely separated, open the glass stopper on the top of the separatory funnel to allow the air pressure inside and outside the funnel to flow. Slowly unscrew the piston and release the lower layer of liquid from the bottom opening into a clean container. When the lower layer of liquid is almost released, quickly close the piston to obtain the extracted organic phase. A6. Repeat the above extraction operation 2 to 3 times and combine the organic phases obtained from each extraction.

[0013] The present invention is further configured as follows: in step S4, drying is performed using anhydrous sodium sulfate, the desiccant is removed by filtration, and then the organic solvent is removed by reduced pressure distillation to obtain a crude product, comprising the following steps: B1. Transfer the combined organic phases to a clean, dry container and add anhydrous sodium sulfate to the organic phase in batches while gently stirring. Observe the state of the organic phase. Stop adding when the added anhydrous sodium sulfate no longer clumps but appears as a loose powder and flows freely during stirring. B2. After adding an appropriate amount of anhydrous sodium sulfate, seal the container and let it stand at room temperature for 30 to 60 minutes to allow the anhydrous sodium sulfate to fully absorb the moisture in the organic phase; B3. Use a glass rod to drain and carefully pour the dried organic phase into a Buchner funnel; B4. Connect the filtration device to the vacuum pump, turn on the vacuum pump, and perform decompression filtration. After the filtration is completed, the filtrate obtained is the organic phase after the desiccant and moisture are removed; B5. Set up a vacuum distillation apparatus, add an appropriate amount of zeolite or magnet to the distillation flask to prevent violent boiling, transfer the filtered organic phase, connect a vacuum pump, close the safety bottle stopcock to evacuate the air, ensure good airtightness, open the condenser, slowly open the safety bottle stopcock to adjust the vacuum to the appropriate value, and heat in an oil bath, water bath, or electric heating mantle, gradually increasing the temperature to vaporize the organic solvent; B6. During the distillation process, when the thermometer reading drops significantly or stops rising, indicating that most of the organic solvent has evaporated, turn off the heating, wait until the liquid stops boiling, turn off the vacuum pump, slowly open the stopcock of the safety bottle to the atmosphere, remove the receiving bottle to recover the organic solvent, and the residue in the distillation flask is the crude product of 2-naphthol.

[0014] The present invention is further configured as follows: in step S4, the reaction solution is extracted with an organic solvent to obtain an aqueous phase and an organic phase, the aqueous phase is evaporated and concentrated, cooled and crystallized, and filtered to obtain phase transfer catalyst crystals, which can be reused.

[0015] The present invention is further configured such that in step S5, when purifying the crude product by column chromatography or recrystallization, the reaction progress is monitored, and when the HPLC content of binaphthol is monitored by high performance liquid chromatography to be less than 1%, the reaction is terminated.

[0016] Adopting the technical solution provided by the present invention, compared with the known public technology, it has the following beneficial effects: (1) In the present invention, a reaction system is formed with α-naphthol, a basic reagent, a phase transfer catalyst, and an organic solvent, and binaphthol is prepared based on the method of phase transfer catalysis. The reaction temperature is between 40 and 80 °C. Compared with the traditional oxidative coupling method, the reaction conditions are milder, avoiding the use of harsh conditions such as strong oxidants and high temperature and high pressure, reducing the reaction risk, and at the same time reducing the occurrence of side reactions. By reasonably selecting the phase transfer catalyst, basic reagent, and reaction conditions, the coupling reaction of α-naphthol can be effectively promoted, and the yield of binaphthol can reach more than 85%, and the purity can reach more than 98%, which is significantly higher than the prior art.

[0017] (2) In the present invention, the raw materials used, α-naphthol, basic reagent, and phase transfer catalyst, are all common chemical reagents with relatively low prices, and the phase transfer catalyst can be recycled, reducing the production cost and being conducive to realizing large-scale industrial production. The present invention avoids the use of reagents harmful to the environment such as strong oxidants, and the waste generated during the reaction process is less. The waste generated during the reaction process is mainly a small amount of organic waste liquid and inorganic salts, which are easy to treat and meet the development requirements of green chemistry and are environmentally friendly. Description of the Drawings

[0018] Figure 1 It is a flow chart of a high-efficiency preparation method of binaphthol based on phase transfer catalysis. Detailed Embodiments

[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0020] The present invention will be further described below with reference to the embodiments.

[0021] Example 1: Please refer to Figure 1 As shown, a high-efficiency preparation method of binaphthol based on phase transfer catalysis includes the following steps: Step 1: Using α-naphthol as the raw material, add 10 mmol (1.44 g) of α-naphthol, 12 mmol (0.48 g) of sodium hydroxide, 0.5 mmol (0.16 g) of tetrabutylammonium bromide, and 50 mL of toluene into a 250 mL three-necked flask and mix them to form a reaction system. Among them, the molar ratio of α-naphthol, the basic reagent, and the phase transfer catalyst is 1:1.2:0.05; Step 2: Stir the above reaction system and react for 12 h under the stirring condition and at a temperature of 40 °C. During the reaction process, the phase transfer catalyst continuously transfers the phenolate from the aqueous phase to the organic phase, enabling it to undergo a coupling reaction with α-naphthol to generate binaphthol, obtaining a reaction mixture. The overall reaction formula is as follows: ; Step 3: After the reaction is completed, cool the reaction mixture to room temperature and add 50 mL of water for dilution to obtain a reaction solution; Step 4: Extract the reaction solution twice with 50 mL of an organic solvent (dichloromethane), combine the organic phases, dry them with anhydrous sodium sulfate, filter to remove the desiccant, and then remove dichloromethane by vacuum distillation to obtain a crude product; Step 5: Purify the crude product by column chromatography (the eluent is petroleum ether:ethyl acetate = 10:1). When the HPLC content of binaphthol monitored by high-performance liquid chromatography is <1%, end the reaction to obtain 1.22 g of high-purity white crystalline binaphthol.

[0022] In this example, in Step 2, during the reaction process, the reaction can be assisted by ultrasonic waves under the condition of introducing nitrogen. The ultrasonic power is 100 - 200 W, and the flow rate of the introduced nitrogen is controlled at 80 - 300 ml / min.

[0023] In this example, in Step 4, it specifically includes the following steps: 1) Select a suitable separating funnel, use a glass rod to guide the flow, and carefully pour the reaction solution cooled to room temperature and diluted into the separating funnel; 2) Add an appropriate amount of organic solvent to the separating funnel and quickly close the glass stopper at the upper opening of the separating funnel; 3) Press the glass stopper at the upper opening of the separating funnel with the right hand, hold the piston part with the left hand, invert the separating funnel, and shake it vigorously. During the shaking process, it is necessary to turn the piston to release gas, and repeat the gas release operation 2 times; 4) After the shaking is completed, let the separating funnel stand for a period of time to allow the mixed liquid to fully separate into layers. During this process, most of the binaphthol will transfer to the organic phase where the organic solvent is located, while the water-soluble impurities will remain in the aqueous phase, forming two distinct upper and lower layers of liquid, achieving separation from most of the water-soluble impurities; 5) After the layering is complete, open the glass stopper at the upper opening of the separating funnel to make the pressure inside and outside the funnel the same. Slowly turn the piston to drain the lower layer of liquid from the lower opening into a clean container. When the lower layer of liquid is almost drained, quickly close the piston to obtain the extracted aqueous phase and organic phase. After evaporating, concentrating, cooling, crystallizing, and filtering the aqueous phase, phase transfer catalyst crystals can be obtained and reused. 6) Repeat the above extraction operation 2 times and combine the organic phases obtained each time. 7) Transfer the combined organic phase to a clean and dry container. Add anhydrous sodium sulfate to the organic phase in batches while gently stirring. Observe the state of the organic phase. When the added anhydrous sodium sulfate no longer forms lumps but presents a loose powder form and can flow freely during stirring, stop adding. 8) After adding an appropriate amount of anhydrous sodium sulfate, seal the container and let it stand at room temperature for 40 min to allow the anhydrous sodium sulfate to fully absorb the water in the organic phase and avoid the influence of water on subsequent operations and product quality. 9) Use a glass rod to guide the flow and carefully pour the statically dried organic phase into a Buchner funnel. 10) Connect the suction filtration device to the vacuum pump and turn on the vacuum pump for vacuum filtration. During the vacuum filtration process, pay attention to observing the filtration speed and the state of the filter paper. If the filtration speed is too slow, appropriately adjust the pressure of the vacuum pump or replace the filter paper. If it is found that the filter paper is damaged, immediately stop the vacuum filtration, replace the filter paper, and filter again. After the vacuum filtration is completed, the obtained filtrate is the organic phase after removing the desiccant and water. 11) Set up a vacuum distillation device, mainly including a distillation flask, a Claisen distillation head, a thermometer, a condenser, a receiving flask, a safety flask, and a vacuum pump, etc. Ensure that all components are tightly connected to prevent air leakage. Add an appropriate amount of zeolite or magnetic stirrer to the distillation flask to prevent bumping, and transfer the filtered organic phase. The liquid volume generally does not exceed two-thirds of the volume of the distillation flask. Connect the vacuum pump, close the stopcock of the safety flask and evacuate. Observe the reading of the pressure gauge. If the pressure can continuously and steadily drop and reach the expected vacuum degree and remain unchanged for a period of time, it indicates that the airtightness of the device is good. If the pressure cannot reach the expected value or keeps rising, check each connection point, find the air leakage point and seal it. After ensuring good airtightness, turn on the cooling water to ensure smooth water flow and the condenser is filled with cooling water. Slowly open the stopcock of the safety flask to adjust the vacuum degree to an appropriate value, adjust the vacuum degree to an appropriate range, turn on the heating device, adopt an appropriate heating method (such as oil bath, water bath or heating mantle heating), gradually increase the temperature to make the organic solvent slowly boil and vaporize. During the distillation process, closely monitor the reading of the thermometer and the boiling situation of the liquid in the distillation flask, control the heating speed to make the distillation proceed smoothly, and avoid the liquid boiling violently and causing material flushing. As the distillation progresses, gradually increase the temperature to vaporize the organic solvent and let it flow into the receiving flask after being cooled by the condenser. 12) During the distillation process, when the thermometer reading drops significantly or stops rising, it indicates that most of the organic solvent has been distilled off. Turn off the heating. Wait until the liquid stops boiling, then turn off the vacuum pump, slowly open the stopcock of the safety bottle to let in air, remove the receiving flask to recover the organic solvent, and the residue in the distillation flask is the crude product of binaphthol. Vacuum distillation can reduce the boiling point of the organic solvent, avoid side reactions such as decomposition of the product at high temperatures, and at the same time achieve the recycling of the organic solvent.

[0024] Example 2: Please refer to Figure 1 as shown, a high-efficiency preparation method of binaphthol based on phase transfer catalysis, comprising the following steps: Step 1: Using α-naphthol as the raw material, add 10 mmol (1.44 g) of α-naphthol, 15 mmol (1.65 g) of potassium carbonate, 1.0 mmol (0.27 g) of benzyltriethylammonium chloride, and 75 mL of xylene into a 250 mL three-necked flask and mix to form a reaction system. Among them, the molar ratio of α-naphthol, the basic reagent, and the phase transfer catalyst is 1:1.5:0.1; Step 2: Stir the above reaction system and react for 8 h under stirring conditions and at a temperature of 60 °C. During the reaction process, the phase transfer catalyst continuously transfers the phenolate from the aqueous phase to the organic phase, enabling it to undergo a coupling reaction with α-naphthol to generate binaphthol, obtaining a reaction mixture; Step 3: After the reaction is completed, cool the reaction mixture to room temperature, add 75 mL of water for dilution to obtain a reaction solution; Step 4: Extract the reaction solution twice with 75 mL of an organic solvent (chloroform), combine the organic phases, dry with anhydrous sodium sulfate, filter off the desiccant, and then remove the chloroform by vacuum distillation to obtain the crude product. The specific steps are the same as those in Example 1; Step 5: Purify the crude product by recrystallization (using ethanol as the solvent). When the HPLC content of binaphthol monitored by high-performance liquid chromatography is <1%, end the reaction to obtain 1.30 g of high-purity white crystalline binaphthol.

[0025] Example 3: Please refer to Figure 1 as shown, a high-efficiency preparation method of binaphthol based on phase transfer catalysis, comprising the following steps: Step 1: Using α-naphthol as the raw material, add 10 mmol (1.44 g) of α-naphthol, 20 mmol (1.12 g) of potassium hydroxide, 2.0 mmol (0.54 g) of 18-crown-6, and 100 mL of chlorobenzene into a 250 mL three-necked flask and mix to form a reaction system. Among them, the molar ratio of α-naphthol, the basic reagent, and the phase transfer catalyst is 1:2:0.2; Step 2: Stir the above reaction system and react for 6 h under stirring conditions and at a temperature of 80 °C. During the reaction, the phase transfer catalyst continuously transfers the phenolate from the aqueous phase to the organic phase, enabling it to undergo a coupling reaction with α-naphthol to form binaphthol, thereby obtaining a reaction mixture; Step 3: After the reaction is completed, cool the reaction mixture to room temperature and add 100 mL of water for dilution to obtain a reaction solution; Step 4: Extract the reaction solution twice with 100 mL of an organic solvent (dichloromethane), combine the organic phases, dry them using anhydrous sodium sulfate, filter to remove the desiccant, and then remove dichloromethane by vacuum distillation to obtain a crude product. The specific steps are the same as those in Example 1; Step 5: Purify the crude product by column chromatography (the eluent is petroleum ether:ethyl acetate = 8:1). When the HPLC content of binaphthol monitored by high-performance liquid chromatography is <1%, end the reaction to obtain 1.28 g of high-purity white crystalline binaphthol.

[0026] Comparative example: Binaphthol was prepared according to the traditional oxidative coupling method. Using α-naphthol as the raw material, 10 mmol (1.44 g) of α-naphthol, 20 mmol (1.60 g) of ferric chloride, and 50 mL of toluene were added to a 250 mL three-necked flask and mixed to form a reaction system. The reaction was carried out at a temperature of 80 °C for 12 h. After the reaction was completed, it was treated according to the same separation and purification method as in Example 1 to obtain 0.85 g of binaphthol.

[0027] Test experiment: The binaphthol prepared through Examples 1 to 3 was denoted as Example Groups 1 to 3, and the binaphthol prepared through the comparative example was denoted as the Comparative Group. The yields and purity of the binaphthol in Example Groups 1 to 3 and the Comparative Group were calculated and detected respectively, and the relevant data were recorded in Table 1.

[0028] Among them, when performing the purity detection, taking Example 1 as an example, the purity of the product binaphthol was calculated by high-performance liquid chromatography. The specific steps were as follows: Preparation of standard solution: Accurately weigh a certain amount (about 10 mg) of binaphthol standard product into a 10 mL volumetric flask, dissolve it with an appropriate amount of chromatographically pure methanol, and dilute to the mark and shake well to prepare a standard stock solution with a concentration of about 1 mg / mL. Respectively pipette 0.1 mL, 0.2 mL, 0.5 mL, 1.0 mL, and 2.0 mL of the standard stock solution into 10 mL volumetric flasks, dilute to the mark with methanol, and shake well to obtain a series of standard working solutions with concentrations of 10 μg / mL, 20 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL; Sample solution preparation: Weigh an appropriate amount (about 10 mg) of the binaphthol prepared in Example 1 accurately into a 10 mL volumetric flask, dissolve it with methanol and dilute it to the mark, shake well. If the concentration of the sample solution is too high, it can be further diluted to a suitable concentration. After the solution is prepared, filter it through a 0.45 μm microporous filter membrane, and take the filtrate as the sample solution to be detected; Chromatographic condition setting: Select a C18 reversed-phase chromatographic column, use a methanol-water system as the mobile phase. Before use, the mobile phase needs to be filtered and degassed. Set the flow rate to 1.0 mL / min, control the column temperature at 30 °C. According to the ultraviolet absorption characteristics of binaphthol, select the detection wavelength of 280 nm, and set the injection volume to 20 μL; Standard curve drawing: Inject a series of standard working solutions into the high-performance liquid chromatograph in turn, record the chromatographic peak areas of standard solutions with different concentrations. Take the concentration of the standard solution as the abscissa X, and the corresponding chromatographic peak area as the ordinate Y. Use a data processing system to perform linear regression analysis, draw the standard curve, and obtain the linear regression equation Y = aX + b, where a is the slope and b is the intercept, and the correlation coefficient R 2 should be ≥ 0.999 to ensure that the standard curve has a good linear relationship; Sample determination: Inject the prepared sample solution into the high-performance liquid chromatograph, and perform the determination under the same chromatographic conditions, and record the chromatographic peak area of the sample solution; Purity calculation: According to the chromatographic peak area of the sample solution, substitute it into the linear regression equation of the standard curve to calculate the concentration (μg / mL) of binaphthol in the sample solution. Then, according to the weighed mass (g) and the fixed volume (mL) of the sample, calculate the purity (%) of binaphthol according to the formula.

[0029] To sum up, in Example 1, the raw material α-naphthol was 1.44 g, and the actual obtained product binaphthol was 1.22 g, with a yield of about 85% and the purity of the product binaphthol was about 98%; in Example 2, the raw material α-naphthol was 1.44 g, and the actual obtained product binaphthol was 1.30 g, with a yield of about 90% and the purity of the product binaphthol was about 99%; in Example 3, the raw material α-naphthol was 1.44 g, and the actual obtained product binaphthol was 1.28 g, with a yield of about 89% and the purity of the product binaphthol was about 98.5%; in the control group, the raw material α-naphthol was 1.44 g, and the actual obtained product binaphthol was 0.85 g, with a yield of about 59% and the purity of the product binaphthol was about 92%.

[0030]

[0031] According to the above comparative experiments and their result analysis, the influence of process parameters on the experimental results in the present invention.

[0032] 1. Optimization of temperature and time, temperature range (40~80 °C): ①Low temperature (40 °C) can inhibit the side reaction of phenolic oxidation, but the reaction rate is slow (it takes 12 h to reach 85% yield in Example 1); ②Medium temperature (60 °C) balances the rate and selectivity. In Example 2, 90% yield is reached in 8 h, verifying the promoting effect of temperature on the reaction rate in the Arrhenius equation; ③High temperature (80 °C) can accelerate the decomposition of the catalyst (e.g., the stability of crown ether decreases at high temperature). The yield of Example 3 is slightly lower than that of Example 2 (89% vs 90%), verifying the rationality of the upper temperature limit.

[0033] ④Time window (6 - 12 h): It is found by HPLC monitoring that the conversion rate approaches equilibrium after 8 h of reaction (Example 2). Extending the time has limited improvement on the yield, which is in line with the chemical equilibrium theory.

[0034] 2. Reagent ratio ①Dosage of basic reagent (1.2 - 2.0 times molar ratio): Excessive base ensures the complete conversion of α - naphthol to phenolate (pKa is about 9.5, and strong base activation is required). However, excessive excess (> 2.0 times) can cause the self - polymerization of phenolate. The optimal value in the examples is 1.5 times molar ratio (such as in Example 2); ②Dosage of catalyst (5% - 20% molar ratio): A low concentration (5%) can form effective ion pairs (the critical micelle concentration of quaternary ammonium salt is low). In Example 1, 5% molar ratio (tetrabutylammonium bromide) has reached 85% yield. High concentration (20%) increases the cost but has no significant gain.

[0035] 3. Feasibility of the post - treatment process ①Extraction - distillation - recrystallization process: The separation is achieved by utilizing the solubility difference of binaphthol in organic solvents (such as toluene). HPLC monitoring meets the drug synthesis purification requirement with the standard of impurities < 1%; ②Recycling of the catalyst: The quaternary ammonium salt in the aqueous phase can be recovered by acidification - extraction (such as adding hydrochloric acid to convert it into a water - soluble salt and then separating the liquid). The phase - transfer catalyst can usually be reused 5 - 10 times, further reducing the cost.

[0036] Meanwhile, as can be seen from Table 1 above: Among the binaphthols prepared in Example Groups 1 - 3, the yields of the binaphthols prepared in the three groups of examples are all greater than 85%, and the purities of the product binaphthols are all greater than 98%, meeting the requirements of the electronic chemical grade purity. Moreover, the yield of binaphthol obtained by the preparation method of Example 2 reaches 90%, and the purity of the product binaphthol reaches 99%. By comparing the examples and comparative examples, it can be seen that the high - efficiency preparation method of binaphthol based on phase - transfer catalysis provided by the present invention is significantly superior to the traditional oxidative coupling method in terms of both yield and purity; In addition, the main differences among Example 1, Example 3, and Example 2 are as follows: In Example 1, the alkaline reagent is sodium hydroxide, the phase transfer catalyst is tetrabutylammonium bromide, and the organic solvent is toluene; in Example 3, the alkaline reagent is potassium hydroxide, the phase transfer catalyst is 18-crown-6, and the organic solvent is chlorobenzene; while in Example 2, the alkaline reagent is potassium carbonate, the phase transfer catalyst is benzyltriethylammonium chloride, and the organic solvent is xylene. From the experimental results, 1.22 g of binaphthol product was obtained in Example 1 with a yield of 85% and a reaction time of 12 h; 1.28 g of binaphthol product was obtained in Example 3 with a yield of 89% and a reaction time of 6 h; while 1.30 g of binaphthol was obtained in Example 2 with a yield reaching 90%, and the reaction time was shorter, only 8 h, which is more conducive to industrial production. The phase transfer catalysis method of the present invention is comprehensively superior to the traditional oxidative coupling method in core indicators such as yield, purity, cost, and environmental protection. Among them, Example 2 represents the optimal process conditions, providing a practical industrial path for the efficient and green synthesis of binaphthol.

[0037] Specifically, the phase transfer catalyst (such as quaternary ammonium salt, crown ether) transfers the nucleophile (such as α-naphtholate anion) in the aqueous phase to the organic phase through the ion pair effect or complexation, enabling it to undergo a coupling reaction with the α-naphthol molecule in the organic phase. The specific process is as follows: 1. Aqueous phase reaction: α-naphthol reacts with an alkaline reagent (such as NaOH) to form α-naphtholate (ArO⁻Na⁺); 2. Interface transfer: The cation (R4N⁺) of the phase transfer catalyst (taking quaternary ammonium salt R4N⁺X⁻ as an example) combines with ArO⁻ to form an oil-soluble ion pair (R4N⁺・ArO⁻), which enters the organic phase; 3. Organic phase reaction: ArO⁻ undergoes a nucleophilic substitution or coupling reaction with α-naphthol in the organic phase to form binaphthol (Ar-O-Ar), and at the same time, the catalyst cation (R4N⁺) returns to the aqueous phase for recycling.

[0038] The differences in mechanism from the traditional method mainly lie in the following two points: 1. Traditional oxidative coupling method: It relies on strong oxidants (such as FeCl3) to initiate radical reactions, requires high temperatures, has poor selectivity, and is prone to generating polycondensation by-products; 2. The present invention: Achieves ionic directional coupling through phase transfer catalysis, with a more controllable reaction path and fewer side reactions (the selectivity advantage is confirmed by a purity > 98% in the examples).

[0039] Phase transfer catalysis in phenolic coupling reactions has been supported by the literature (such as the cross-phase reaction mechanism of phenolate in "Organic Chemistry"), and the present invention further optimizes the mass transfer efficiency and reaction environment through ultrasonic assistance (enhancing mass transfer) and nitrogen protection (inhibiting oxidation), which conforms to the principles of multiphase catalytic kinetics.

[0040] In the present invention, a reaction system is formed by using α-naphthol, a basic reagent, a phase transfer catalyst, and an organic solvent. Based on the method of phase transfer catalysis, binaphthol is prepared. A multiphase reaction system is constructed through phase transfer catalysis technology. The phase interface mass transfer effect of the catalyst is used to activate the coupling reaction of α-naphthol, avoiding the dependence on strong oxidants or high-temperature and high-pressure conditions in the traditional oxidative coupling method. The reaction temperature is between 40 and 80 °C, which is lower than the commonly used 100 - 150 °C in the traditional method, and there is no need to use a high-pressure reaction kettle, significantly reducing equipment investment and operation risks. Compared with the traditional oxidative coupling method, the reaction conditions are milder, avoiding the use of harsh conditions such as strong oxidants and high-temperature and high-pressure, reducing the reaction risk. The mild deprotonation process of the basic reagent avoids the side reaction of naphthalene ring degradation under acidic conditions, improving the process stability and also reducing the occurrence of side reactions; The phase transfer catalyst forms a lipophilic ion pair, efficiently transferring the α-naphtholate generated in the aqueous phase to the organic reaction phase, enabling the coupling reaction to proceed directionally in the α-naphthol-rich organic phase, significantly increasing the reaction rate and selectivity. By reasonably selecting the phase transfer catalyst, basic reagent, and reaction conditions, the coupling reaction of α-naphthol can be effectively promoted, and the yield of binaphthol can be increased. The yield of binaphthol by the method of the present invention can reach more than 85%, significantly higher than the prior art; The raw materials used in the present invention, α-naphthol, basic reagent, and phase transfer catalyst, are all common chemical reagents with relatively low prices, and the phase transfer catalyst can be recycled, reducing the production cost and being conducive to large-scale industrial production. No heavy metals, strongly corrosive, or persistent organic pollutants are generated during the entire process. The product separation process uses aqueous phase extraction and physical purification (column chromatography / recrystallization), without the need to use strong acids or alkalis for washing. The pH value of the wastewater is maintained at 6 - 8, with low treatment difficulty, meeting the current development trend of green chemical processes. The present invention avoids the use of environmentally harmful reagents such as strong oxidants, generates less waste during the reaction process, and the waste generated during the reaction process is mainly a small amount of organic waste liquid and inorganic salts, which are easy to treat and meet the development requirements of green chemistry, being environmentally friendly.

[0041] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some of the technical features; and these modifications or replacements will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A high-efficiency preparation method of binaphthol based on phase transfer catalysis, characterized in that The following steps are involved: S1. Using α-naphthol as a raw material, α-naphthol, an alkaline reagent, a phase transfer catalyst, and an organic solvent are added into a three-necked flask and mixed to form a reaction system, wherein the molar ratio of α-naphthol, the alkaline reagent, and the phase transfer catalyst is 1:(1.2-2.0):(0.05-0.2); S2. The reaction system is stirred and reacted at a temperature of 40 to 80° C. for 6 to 12 hours. During the reaction, the phase transfer catalyst continuously transfers the phenolate from the aqueous phase to the organic phase, causing it to undergo a coupling reaction with α-naphthol to form binaphthol, thereby obtaining a reaction mixture. The overall reaction formula is as follows: ； S3. After the reaction is completed, the reaction mixture is cooled to room temperature and diluted with an appropriate amount of water to obtain a reaction solution; S4, extracting the reaction solution with an organic solvent, combining the organic phases, drying with anhydrous sodium sulfate, filtering to remove the desiccant, and then removing the organic solvent by distillation under reduced pressure to obtain a crude product; S5. Purify the crude product by column chromatography or recrystallization to obtain high-purity white crystalline binaphthol.

2. The highly efficient preparation method of binaphthol based on phase transfer catalysis according to claim 1, wherein In step S1, the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, dichloromethane, and chloroform, and each millimole of α-naphthol corresponds to 5 to 15 mL of the organic solvent.

3. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, wherein In step S1, the alkaline reagent is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

4. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, wherein In step S1, the phase transfer catalyst is a quaternary ammonium salt catalyst or a crown ether catalyst. The quaternary ammonium salt catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, and benzyltriethylammonium chloride. The crown ether catalyst is one or more of 18-crown-6 and 15-crown-5.

5. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, characterized in that, In step S2, during the reaction process, the reaction can be assisted by ultrasound under the condition of introducing nitrogen, the ultrasonic power is 100-200W, and the flow rate of the introduced nitrogen is controlled at 80-300 ml / min.

6. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, wherein In step S4, the reaction solution is extracted with an organic solvent and the organic phases are combined, which includes the following steps: A1. Select a suitable separatory funnel and use a glass rod to drain the reaction solution. Carefully pour the diluted reaction solution into the separatory funnel after cooling to room temperature. A2. Add an appropriate amount of organic solvent to the separatory funnel and quickly close the glass stopper at the top of the separatory funnel. A3. Press the glass stopper on the top of the separatory funnel with your right hand, hold the piston with your left hand, turn the separatory funnel upside down, and shake it vigorously. During the shaking process, you need to unscrew the piston to release air. Repeat the deflation operation 2 to 3 times. A4. After the shaking is complete, let the separatory funnel stand for a while to allow the mixture to fully separate. During this process, most of the binaphthol will transfer to the organic phase where the organic solvent is located, while the water-soluble impurities will remain in the aqueous phase, forming distinct upper and lower liquid layers. A5. After the layers are completely separated, open the glass stopper on the top of the separatory funnel to allow the air pressure inside and outside the funnel to flow. Slowly unscrew the piston and release the lower layer of liquid from the bottom opening into a clean container. When the lower layer of liquid is almost released, quickly close the piston to obtain the extracted organic phase. A6. Repeat the above extraction operation 2 to 3 times and combine the organic phases obtained from each extraction.

7. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 6, characterized in that In step S4, anhydrous sodium sulfate is used for drying. After filtering off the desiccant, the organic solvent is removed by vacuum distillation to obtain the crude product, which includes the following steps: B1. Transfer the combined organic phase to a clean and dry container. Add anhydrous sodium sulfate to the organic phase in batches, gently stirring while adding, and observe the state of the organic phase. When the added anhydrous sodium sulfate no longer cakes but presents a loose powder form and can flow freely during stirring, stop adding; B2. After adding an appropriate amount of anhydrous sodium sulfate, seal the container and let it stand at room temperature for 30 - 60 min to allow the anhydrous sodium sulfate to fully absorb the water in the organic phase; B3. Use a glass rod to guide the flow and carefully pour the statically dried organic phase into a Buchner funnel; B4. Connect the suction filtration device to the vacuum pump, turn on the vacuum pump, and perform vacuum filtration. After the filtration is completed, the filtrate obtained is the organic phase after removing the desiccant and water; B5. Set up a vacuum distillation device, add an appropriate amount of zeolite or magnetic stirrer to the distillation flask to prevent bumping, and transfer the filtered organic phase. Connect the vacuum pump, close the stopcock of the safety bottle and evacuate. After ensuring good airtightness, turn on the cooling water, slowly open the stopcock of the safety bottle to adjust the vacuum degree to an appropriate value, and use an oil bath, water bath or electric heating mantle to heat, gradually increasing the temperature to vaporize the organic solvent; B6. During the distillation process, when the thermometer reading drops significantly or no longer rises, indicating that most of the organic solvent has been distilled off, turn off the heating. Wait until the liquid stops boiling, turn off the vacuum pump, slowly open the stopcock of the safety bottle to let in air, remove the receiving flask to recover the organic solvent, and the residue in the distillation flask is the crude product of binaphthol.

8. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, wherein, In step S4, the reaction solution is extracted with an organic solvent to obtain an aqueous phase and an organic phase. After evaporation and concentration, cooling crystallization, and filtration of the aqueous phase, a phase transfer catalyst crystal is obtained, which can be reused.

9. The high-efficiency preparation method of binaphthol based on phase transfer catalysis according to claim 1, characterized in that, In step S5, when purifying the crude product by column chromatography or recrystallization, monitor the reaction progress. When the HPLC content of binaphthol monitored by high performance liquid chromatography is <1%, end the reaction.

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