CN114588844B - Application of Liangmianshen Hollow Fiber Membrane Reactor in Suzuki-Miyaura Reaction and Its Membrane Reactor - Google Patents

Abstract

The invention discloses the application of the double-faced hollow fiber membrane reactor in the Suzuki-Miyaura reaction and the membrane reactor thereof, including: (1) using alcohol reagents to fully infiltrate the hydrophobic hollow fiber membrane; (2) preparing a polyphenol compound deposition solution, sending the deposition solution into the inner cavity of the membrane through a peristaltic pump, and circulating the deposition for 1 to 10 hours; (3) washing with deionized water after the deposition is completed, and vacuum drying. It is used as a membrane reactor to participate in the Suzuki-Miyaura reaction, and the reaction and separation functions are integrated; the product biphenyl of the Suzuki reaction is more hydrophobic than the substrate, so that the product can be transported across the membrane in one direction; at the same time, the separation of the product biphenyl can break the chemical balance of the reaction and move the reaction forward, thereby increasing the conversion rate of the reaction.

Description

Application of Liangmianshen hollow fiber membrane reactor in Suzuki-Miyaura reaction and its its membrane reactor

technical field

The invention relates to the field of membrane science and technology, in particular to the application of a double-faced hollow fiber membrane reactor in Suzuki-Miyaura reaction and the membrane reactor.

Background technique

The Suzuki-Miyaura reaction is also called the Suzuki reaction or the Suzuki-Miyaura reaction. It generally refers to the cross-coupling of aryl or alkenyl boronic acid or boronate with chlorine, bromine, iodoarenes or alkenes under the catalysis of zero-valent palladium complexes to generate biphenyl and its derivatives. The Suzuki reaction is one of the most classical and important palladium-catalyzed cross-coupling reactions. Compared with the Herk reaction and the Negishi reaction, the Suzuki reaction has milder reaction conditions, and the organoboron reagent can not only exist stably in air and water, but also the functional groups carried by the substrate have strong applicability in the reaction, resulting in fewer reaction by-products. These advantages make it widely used in many aspects such as organic synthesis, pharmaceuticals and organic optoelectronic materials. At the same time, the environmental pollution caused by a large amount of organic solvents in the reaction has also become a major problem. Therefore, in order to make the Suzuki reaction more green, many researchers use water as a solvent instead of organic solvents for the Suzuki reaction. Water solvents not only have the advantages of being environmentally friendly, non-toxic and harmless, and low cost, but also can improve the reaction speed and selectivity of chemical reactions. At present, the Suzuki reaction using water as a solvent has been developed by leaps and bounds. Although the Suzuki reaction in water achieves zero addition of organic solvents in the reaction stage, it cannot be reacted in batches, and the formation and separation of reactants cannot be carried out continuously, and organic solvents are still required for extraction and distillation when separating products.

Due to the advantages of low energy consumption, high continuity and no pollution, membrane separation technology has been widely concerned in separation applications. As a new type of membrane material, the two sides of the membrane have asymmetric properties. Compared with the traditional separation membrane with uniform properties, it can use the synergistic force on both sides of the membrane to realize the one-way transmembrane transport of the target substance. The common structures of double membranes are mainly flat membrane and hollow fiber membrane. The flat membrane has strong anti-pollution performance and is easy to clean, but the flat membrane membrane module occupies a large area; the hollow fiber membrane occupies a small area and has a large filtration flux. The cross-flow filtration method can improve batch processing efficiency. Therefore, the present invention proposes to prepare an asymmetric wettable double-faced hollow fiber membrane, and use it as a membrane reactor to integrate the reaction and separation functions to realize the continuous formation and separation of the reactants of the aqueous Suzuki reaction; the product biphenyl of the Suzuki reaction is more hydrophobic than the substrate, and one-way transmembrane transport can occur; at the same time, with the formation of the product biphenyl accompanied by timely product separation, the chemical balance of the reaction can be broken, and the reaction moves forward, thereby improving the reaction conversion rate.

Contents of the invention

The first object of the present invention is to provide a Janus Hollow Fiber Membrane Reactor for the deficiencies of the prior art.

The invention provides the following technical solutions:

The membrane module using the Liangmianshin hollow fiber membrane reactor includes the Liangmianshin hollow fiber membrane, wherein the inner side of the hollow is a hydrophilic modified layer, and the outer side is a hydrophobic layer;

The double-faced hollow fiber membrane is prepared by the following steps:

(1), using alcohol reagents to fully infiltrate the hydrophobic hollow fiber membrane;

Preferably, in step (1), the hydrophobic hollow fiber membrane is polypropylene microfiltration/ultrafiltration membrane, polyvinylidene fluoride microfiltration/ultrafiltration membrane, polytetrafluoroethylene microfiltration/ultrafiltration membrane, polyvinyl chloride microfiltration/ultrafiltration membrane or polycarbonate microfiltration/ultrafiltration membrane.

As preferably, in step (1), the alcoholic reagent is absolute ethanol;

Preferably, in step (1), the soaking time is 5-20 minutes.

(2) Prepare a polyphenolic compound deposition solution, and send the polyphenolic compound deposition solution into the inner cavity of the hydrophobic hollow fiber membrane after the treatment in step (1) through a peristaltic pump, and circulate the deposition for 1 to 10 hours;

Preferably, the preparation method of the polyphenolic compound deposition solution is: dissolving the polyphenolic compound and additives in a solvent according to a specific ratio.

The polyphenolic compound is catechol, dopamine, tannic acid or levodopa; the concentration of the polyphenolic compound is 0.01-10 mg/mL.

The solvent in the polyphenol compound deposition solution is a Tris-HCl buffer solution with pH=8.5;

The additive is polyethyleneimine;

More preferably, the Tris-HCl buffer solution concentration in the polyphenolic compound deposition solution is 50 mmol/L, and the polyethyleneimine concentration is 1-50 mg/mL.

In step (2), as the circulation time of the polyphenol compound deposition solution in the cavity of the hollow fiber base membrane increases, the hydrophilic modification layer in the cavity of the membrane will gradually thicken. The self-oxidation and self-polymerization process of polyphenolic compounds is slow and prone to self-agglomeration. Polyethyleneimine can accelerate the formation of polyphenols from polyphenols, and at the same time covalently cross-link with it to prevent polyphenols from agglomerating.

(3) After the deposition in step (2) is completed, use deionized water to circulate and wash the inner cavity of the hydrophobic hollow fiber membrane treated in step (2) to remove the remaining deposition liquid; vacuum dry in an oven to obtain the final product.

Preferably, the drying temperature is 25-100°C.

The second object of the present invention is to provide the application of the double-faced hollow fiber membrane reactor in the Suzuki-Miyaura reaction in water, specifically:

The Suzuki-Miyaura reaction solution is sent into the inner cavity of the Liangmian hollow fiber membrane in the membrane reactor through a peristaltic pump, and the flow rate of the reaction solution is controlled at 0.1-10mL/min. The hydrophilic modification layer can prevent the oil phase product from spreading in the hydrophobic layer, and the hydrophobic layer is attractive to the oil phase product, so that it spontaneously transports across the membrane from the inner surface to the outer surface in one direction, thereby realizing the separation of oil-soluble products. Accelerate the reaction rate, increase the reaction conversion rate, realize the continuous operation of synthesis and separation, and effectively solve the problem of environmental pollution caused by organic reagents.

Significant advantage of the present invention is:

The double-faced hollow fiber membrane reactor of the present invention enables continuous generation and separation of Suzuki-Miyaura reaction products in water, and improves product conversion rate and time efficiency.

The invention prepares the double-faced hollow fiber membrane with hydrophilic modification on the inner surface, uses it as a membrane reactor to carry out Suzuki-Miyaura reaction, and at the same time separates products to promote the forward movement of the reaction and improve the reaction conversion rate.

The preparation method of the present invention has simple experimental operation and mild conditions, and the prepared double-faced hollow fiber membrane reactor can carry out Suzuki-Miyaura reaction in water and simultaneously separate the generated oil-soluble products.

The present invention utilizes the difference in water solubility of the Suzuki-Miyaura reaction substance in water and the asymmetric transmission performance of the double-faced hollow fiber membrane. When the oil phase product passes through the inner cavity of the hydrophilically modified membrane, it will permeate and be discharged to the outer surface, that is, to achieve the purpose of separation; the reduction of the product in the system will make the reaction move forward, thereby increasing the conversion rate. At the same time, the double-faced hollow fiber membrane can make the reactant formation and separation of the entire reaction proceed simultaneously, thereby improving production efficiency.

Description of drawings

Figure 1 is a schematic diagram of the device structure of the double-faced hollow fiber membrane reactor module;

Fig. 2 is the SEM morphology characterization diagram before and after the hydrophilic modification of the inner surface of the hollow fiber membrane in the embodiment. Compared with the inner and outer surfaces of the original hollow fiber membrane (a, c), the inner and outer surfaces of the hollow fiber membrane deposited for 4 hours (b, d) have no pore plugging phenomenon, and the surface morphology basically does not change.

Detailed ways

As mentioned above, in view of the deficiencies in the prior art, the inventor of this case proposed the technical solution of the present invention after long-term research and a large amount of practice, which mainly includes: (1) the present invention prepares the double-faced hollow fiber membrane with hydrophilic modification on the inner surface, uses it as a membrane reactor, conducts Suzuki-Miyaura reaction, and at the same time, separates the product to promote the forward movement of the reaction and increase the reaction conversion rate. (2) The present invention utilizes the difference in water solubility of the Suzuki-Miyaura reaction substance in water and the asymmetric transmission performance of the double-faced hollow fiber membrane. When the oil phase product passes through the inner cavity of the hydrophilically modified membrane, it will permeate to the outer surface and be discharged, that is, to achieve the purpose of separation; the reduction of the product in the system will make the reaction move forward, thereby increasing the conversion rate. At the same time, the double-faced hollow fiber membrane can make the reactant formation and separation of the entire reaction proceed simultaneously, thereby improving production efficiency.

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not constitute a conflict with each other.

On the one hand, the membrane module of the Liangmianshin hollow fiber membrane reactor of the present invention includes the Liangmianshin hollow fiber membrane, wherein the inner side of the hollow is a hydrophilic modified layer, and the outer side is a hydrophobic layer;

The double-faced hollow fiber membrane is prepared by the following steps:

(3), using alcohol reagents to fully infiltrate the hydrophobic hollow fiber membrane;

Preferably, in step (1), the hydrophobic hollow fiber membrane is polypropylene microfiltration/ultrafiltration membrane, polyvinylidene fluoride microfiltration/ultrafiltration membrane, polytetrafluoroethylene microfiltration/ultrafiltration membrane, polyvinyl chloride microfiltration/ultrafiltration membrane or polycarbonate microfiltration/ultrafiltration membrane.

As preferably, in step (1), the alcoholic reagent is absolute ethanol;

Preferably, in step (1), the soaking time is 5-20 minutes.

(4) Prepare a polyphenolic compound deposition solution, send the polyphenolic compound deposition solution into the inner cavity of the hydrophobic hollow fiber membrane after the treatment in step (1) through a peristaltic pump, and circulate the deposition for 1 to 10 hours;

Preferably, the preparation method of the polyphenolic compound deposition solution is: dissolving the polyphenolic compound and additives in a solvent according to a specific ratio.

The polyphenolic compound is catechol, dopamine, tannic acid or levodopa; the concentration of the polyphenolic compound is 0.01-10 mg/mL.

The solvent in the polyphenol compound deposition solution is a Tris-HCl buffer solution with pH=8.5;

The additive is polyethyleneimine;

More preferably, the Tris-HCl buffer solution concentration in the polyphenolic compound deposition solution is 50 mmol/L, and the polyethyleneimine concentration is 1-50 mg/mL.

In step (2), as the circulation time of the polyphenol compound deposition solution in the cavity of the hollow fiber base membrane increases, the hydrophilic modification layer in the cavity of the membrane will gradually thicken. The self-oxidation and self-polymerization process of polyphenolic compounds is slow and prone to self-agglomeration. Polyethyleneimine can accelerate the formation of polyphenols from polyphenols, and at the same time covalently cross-link with it to prevent polyphenols from agglomerating.

(3) After the deposition in step (2) is completed, use deionized water to circulate and wash the inner cavity of the hydrophobic hollow fiber membrane treated in step (2) to remove the remaining deposition liquid; vacuum dry in an oven to obtain the final product.

Preferably, the drying temperature is 25-100°C.

On the other hand, the application of the Two Faces hollow fiber membrane reactor in the Suzuki-Miyaura reaction in water, specifically:

The Suzuki-Miyaura reaction solution is sent into the inner cavity of the Liangmian hollow fiber membrane in the membrane reactor through a peristaltic pump, and the flow rate of the reaction solution is controlled at 0.1-10mL/min. The hydrophilic modification layer can prevent the oil phase product from spreading in the hydrophobic layer, and the hydrophobic layer is attractive to the oil phase product, so that it spontaneously transports across the membrane from the inner surface to the outer surface in one direction, thereby realizing the separation of oil-soluble products. Accelerate the reaction rate, increase the reaction conversion rate, realize the continuous operation of synthesis and separation, and effectively solve the problem of environmental pollution caused by organic reagents.

The technical solution of the present invention will be further explained below in conjunction with several preferred embodiments, but the experimental conditions and set parameters therein should not be regarded as limitations on the basic technical solution of the present invention. And the protection scope of the present invention is not limited to the following examples.

The double-faced hollow fiber membrane reactor in the present invention is prepared by sending the polyphenol deposition liquid into the inner cavity of the hollow fiber membrane through a peristaltic pump for cyclic deposition, and various means are used to characterize its appearance and performance; after it is prepared, it is used as a membrane reactor, composed of membrane modules and a peristaltic pump to build a circulating flow device, and carries out the Suzuki-Miyaura reaction in water.

In the examples, the following data should be measured to evaluate the membrane separation efficiency of the prepared double-faced membrane: water contact angle (WCA), underwater oil contact angle (UOCA), membrane flux and rejection rate.

1)WCA

The wettability of the hydrophobic film surface will change after hydrophilic modification, and the contact angle before and after the film modification is generally measured by an optical contact angle meter. First, stick the film surface to be tested on the glass slide flatly, and use a capillary needle to drop about 3.0 μL of water droplets on the surface of the film. After the contact angle is stable, use the camera in the software to take pictures of the droplet contact surface and measure the contact angle. Take the average value of three times or more as the value of the water contact angle on the side of the film.

2) UOCA

Characterize the lipophilic properties of the underwater oil phase on the membrane surface. The contact angles of oil droplets before and after film modification were measured by optical contact angle measuring instrument. First, stick the film to be tested on the glass slide with the surface to be tested facing up, put the glass slide into a transparent glass tank filled with water, and put the transparent glass tank on the test platform, use a capillary needle to drip 3.0 μL oil droplets on the surface of the film, and use the camera in the software to take real-time pictures of the oil drop contact surface, then measure the contact angle, and take the average value of three times or more as the underwater oil contact angle value on the film surface.

3) Oil flux and retention rate

The oil flux is defined as:

In the formula, V represents the volume of oil collected during the membrane separation process per unit time, A represents the effective area of the separation membrane, and Δt represents the separation time.

The rejection rate is defined as:

where C _F and C _P represent the oil content in feedstock and filtrate, respectively.

The oil phase in the test example is the product corresponding to the Suzuki-Miyaura reaction. After the flux is stable, the filtrate volume of the oil phase can be measured within a certain period of time to calculate the oil flux, and then the water content in the filtrate can be tested to calculate the rejection rate of the membrane for hydrophilic ionic liquids.

Comparative Example 1: Batch type water phase Suzuki-Miyaura reaction operation steps:

1. Catalyst preparation: L-3,4-dihydroxy-phenylalanine (L-DOPA, 200 mg, 1 mmol) was dissolved in Tris buffer (40 ml, 20 mM), and N ₂ was bubbled for 30 minutes to degas. FeCl ₃ (987 mg, 6 mmol) was dissolved in Tris buffer and added to the L-DOPA solution. Stir vigorously under N ₂ for 18 h. The obtained black precipitate was washed with deionized water to remove the remaining iron salt and unreacted L-DOPA, and freeze-dried to obtain eumelanin powder. Eumelanin powder (10 mg) was dispersed in deionized water (5.5 mL), and Na ₂ PdCl ₄ (3.5 mL, 0.03 mmol) was added and stirred for 30 min. In order to reduce the palladium ions adsorbed on eumelanin, excess ascorbic acid (103 mg, 1.36 mmol) was added to the above solution. Washing with deionized water and lyophilization gave the final product.

2. Reaction and product extraction operation: Add 1.6mmol potassium hydroxide, 0.4mmol p-bromotoluene, 0.48mmol phenylboronic acid and 10mL deionized water into the round bottom flask, heat the water bath to 80°C to dissolve the reactants, and then add 0.001mmol Pd catalyst. After reacting for 2 hours, pour the reaction solution into a separatory funnel after the temperature dropped to room temperature, add diethyl ether to extract and separate the liquid, and finally evaporate the diethyl ether by a rotary distiller to obtain the final product. The product was characterized by gas chromatography-mass spectrometry, and the reaction conversion rate was calculated. The reaction was run batchwise and product separation, and after 2 h the conversion reached 90%.

Example 1: Application of Double Faces Hollow Fiber Membrane Reactor in Suzuki-Miyaura Reaction:

1. Select the polypropylene hollow fiber microfiltration membrane with an average pore size of 0.2-0.3 μm as the base, cut it into 15-30 cm long membrane filaments, assemble it into a membrane module, and circulate anhydrous ethanol to the membrane module through a peristaltic pump to pre-soak for 10 minutes;

2. Preparation of deposition solution: prepare 50 mg/mL Tris solution and 1 mol/L HCl solution respectively, and prepare Tris-HCl buffer solution with pH=8.5 at 25° C. for future use. Take 2mg/mL dopamine hydrochloride and polyethyleneimine respectively, and add 50mL Tris-HCl buffer solution to obtain the deposition solution.

3. Send the deposition liquid into the tube side of the hollow fiber membrane module, and circulate and deposit for 1 hour.

4. After the deposition is completed, wash the hollow fiber membrane with deionized water for 3 to 4 hours, and place it in an oven at 60°C for vacuum drying overnight to obtain the asymmetric wettability double-faced hollow fiber membrane.

5. Build a circulating flow device with the above-mentioned double-faced hollow fiber membrane module and peristaltic pump. Add 1.6mmol potassium hydroxide, 0.4mmol p-bromotoluene, 0.48mmol phenylboronic acid and 0.001mmol Pd catalyst to the raw material tank in sequence, and react at 80°C. The reaction solution was sent into the membrane module through a peristaltic pump at a flow rate of 2 mL/min, as shown in Figure 1.

Embodiment 2～6

In Examples 2 to 6, the circulation time of the deposition liquid in the tube side of the hollow fiber membrane was adjusted to 2, 3, 4, 5 and 6 hours respectively, and other conditions were the same as in Example 1.

Performance tests were performed on the double-faced hollow fiber membranes prepared in Example 1 and Examples 2-6, and the test results are shown in Table 1.

Table 1 Performance test results of the double-faced hollow fiber membranes prepared in Example 1 and Examples 2-6

From the test data in Table 1, it can be seen that with the increase of deposition time, the hydrophilicity of the inner wall of the hollow fiber membrane increases, while the oil flux and rejection rate gradually decrease, while the water retention rate and oil purity remain basically unchanged.

Examples 7-10

In Examples 7-10, the delivery rate of the peristaltic pump was adjusted to 4, 6, 8 and 10 mL/min respectively, and other conditions were the same as in Example 1. Two-faced hollow fiber membranes were tested for performance, and the test results are shown in Table 1.

Table 2 Performance Test Results of Surface Hydrophilic Modified Hollow Fiber Membranes Prepared in Examples 7-11

It can be seen from the test data in Table 2 that, other conditions remain unchanged, when the flow rate increases, the oil flux will gradually decrease. This is because the flow rate is too fast, the shear force becomes larger, and the residence time of the oil phase product on the membrane surface is shortened, resulting in the product being carried away with the reaction solution before it can be transported across the membrane.

The above-described embodiments have described the technical solutions and beneficial effects of the present invention in detail. It should be understood that the above-described are only specific embodiments of the present invention, and are not intended to limit the present invention. Any amendments, supplements and equivalent replacements made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims (8)

1. The application of a Liangmianshin hollow fiber membrane reactor in the continuous operation of the Suzuki-Miyaura reaction in water. The membrane reactor module includes the Liangmianshin hollow fiber membrane, and the inner side of the hollow is a hydrophilic modified layer, and the outer side is a hydrophobic layer; The double-faced hollow fiber membrane is prepared by the following steps: (1) Use alcohol reagents to fully infiltrate the hydrophobic hollow fiber membrane; (2) Prepare the polyphenolic compound deposition solution, and send the polyphenolic compound deposition solution into the inner cavity of the hydrophobic hollow fiber membrane after the treatment in step (1) through a peristaltic pump, and circulate the deposition for 1 to 10 h; (3), step (2) After the deposition is completed, use deionized water to circulate and wash the inner cavity of the hydrophobic hollow fiber membrane after step (2) to remove the residual deposition liquid; vacuum dry in an oven to obtain the product; It is characterized in that the Suzuki-Miyaura reaction solution is sent into the inner cavity of the Liangmianshen hollow fiber membrane in the membrane reactor through a peristaltic pump, and the flow rate of the reaction solution is controlled at 0.1-10 mL/min. The hydrophilic modification layer can prevent the oil phase product from spreading in the hydrophobic layer, and the hydrophobic layer is attractive to the oil phase product, so that it spontaneously transports across the membrane in one direction from the inner surface to the outer surface, thereby realizing the separation of oil-soluble products. Carry out in the direction of reduction, speed up the reaction rate, increase the reaction conversion rate, and realize the continuous operation of synthesis and separation; The polyphenolic compound is catechol, dopamine, tannic acid or levodopa. 2. The application according to claim 1, wherein in step (1), the hydrophobic hollow fiber membrane is a microfiltration membrane or an ultrafiltration membrane, and the material is one of polypropylene, polyvinylidene fluoride, polytetrafluoroethylene, polyvinyl chloride, and polycarbonate. 3. The application according to claim 1, characterized in that in step (1), the alcohol reagent is absolute ethanol. 4. The application according to claim 1, characterized in that in step (1), the soaking time is 5-20 min. 5. The application according to claim 1, characterized in that the preparation method of the polyphenolic compound deposition liquid is: dissolving the polyphenolic compound and additives in a solvent; the additive is polyethyleneimine. 6. The application according to claim 5, wherein the concentration of the polyphenolic compound is 0.01 to 10 mg/mL; the concentration of the Tris-HCl buffer solution in the deposition solution of the polyphenolic compound is 50 mmol/L, and the concentration of polyethyleneimine is 1 to 50 mg/mL. 7. The application according to claim 5, characterized in that the solvent in the polyphenol compound deposition solution is a Tris-HCl buffer solution with pH=8.5. 8. The application according to claim 1, characterized in that the drying temperature is 25-100°C.