CN104804145A - Chiral catalyst loaded amphiphilic random copolymer grafted hair-like polymer microsphere as well as preparation method and application thereof - Google Patents

Abstract

The invention discloses an amphiphilic random copolymer grafted hair-like polymer microsphere loaded with a chiral catalyst, a preparation method and application thereof. The gist of the technical scheme of the present invention is: by surface reversible addition-fragmentation-chain transfer copolymerization of chiral monomers, hydrophilic monomers and hydrophobic monomers on polymer microspheres with RAFT chain transfer groups on the surface Formed, which has the following structure: . The invention also discloses the preparation method of the amphiphilic random copolymer grafted hair-like polymer microsphere loaded with chiral catalyst and its application in catalyzing asymmetric synthesis reaction in water phase. In addition to obtaining chiral products with high yield and high stereoselectivity, the present invention utilizes the amphiphilic random copolymer grafted hair-like polymer microspheres of the loaded chiral catalyst to catalyze the asymmetric reaction in the aqueous phase. The characteristics of easy separation and recyclable use of the catalyst are realized, and the production cost is reduced.

Description

Amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalyst and its preparation method and application

technical field

The invention belongs to the technical field of polymer catalysts and their synthesis, and in particular relates to an amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalysts and a preparation method and application thereof.

Background technique

Organic chiral small molecule catalysts have been widely developed and applied in asymmetric catalytic reactions, but there are still some key problems and challenges that greatly limit their wider application. One of them is how to prepare Chiral catalysts with excellent performance. In order to solve the above problems, people have carried out a lot of research work, and some positive research results have been obtained so far. For example: by the method of supporting catalysts by polymers with hydrophobic and hydrophilic parts (such as block copolymers, stars, dendrimers, etc.), the catalysts assemble in water to form micelles. Because the hydrophobic core part can isolate the organic reaction substrate from the surrounding water system, and bind the catalyst and organic reactants in the hydrophobic cavity, which can be effectively catalyzed, this effect is called "concentration effect". Although the catalyst obtained by the polymer-supported method can be recycled and reused through certain methods (such as sedimentation, freeze-drying, etc.), the synthesis is complicated, the recycling method is not simple, and the efficiency is low. In addition, the method of supporting chiral catalysts through ionic liquids developed in recent years can also effectively improve the miscibility of catalysts and reaction substrates in water and promote reaction efficiency. Although the method of supporting catalysts through ionic liquids solves the problem of catalyst recovery However, the regeneration process of ionic liquids mainly uses volatile traditional organic solvents (such as ether, etc.) for extraction, and the secondary pollution caused by them cannot be ignored. Therefore, while improving the catalytic activity of chiral catalysts in water, the green recovery and recycling of the catalysts are also important issues worth considering.

Contents of the invention

The technical problem solved by the present invention is to provide a kind of amphiphilic random copolymer grafted hair-like polymer microspheres suitable for aqueous solution system and having high catalytic activity, easy separation and reusable load chiral catalyst. The hair-like polymer microspheres grafted with amphiphilic random copolymers loaded with chiral catalysts have a good catalytic effect on asymmetric synthesis reactions in water. In addition, the invention also provides a simple and universally applicable method for preparing the amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalysts.

In order to solve the above-mentioned technical problems, the present invention adopts the following technical scheme as follows: a kind of amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalyst, characterized in that by having a RAFT chain transfer group on the surface It is formed by initiating chiral monomer, hydrophilic monomer and hydrophobic monomer on the polymer microsphere through surface reversible addition-fragmentation-chain transfer polymerization, which has the following structure:

.

The preparation method of the chiral catalyst-loaded amphiphilic random copolymer grafted hair-like polymer microspheres of the present invention is characterized in that it comprises the following steps: (1) polymer microspheres with RAFT chain transfer groups on the surface For the preparation of balls, the functional monomer and the crosslinking agent are fed into the solvent at a molar ratio of 1:4-6, and the initiator and the chain transfer agent are added, wherein the initiator is 1% of the total amount of the functional monomer and the crosslinking agent. %-5%, the molar ratio of initiator to chain transfer agent is 1:2-6, after the above mixture is completely dissolved, pass nitrogen gas for 30 minutes to remove oxygen, seal the reaction vessel and place it in an oil bath at 25-100°C React for 24 hours, filter, fully wash with solvent, dry, and prepare polymer microspheres with different chain transfer group contents by changing the chain transfer agent content; (2) Grafting hair with amphiphilic random copolymer loaded with chiral catalyst In the preparation of polymer microspheres, the mixed monomer composed of hydrophilic monomer, hydrophobic monomer and chiral monomer, initiator and chain transfer agent are fed into the solvent, wherein the mixed monomer, initiator and chain transfer agent The molar ratio of the mixed monomer is 100-600:1:5, the molar ratio of the chiral monomer, the hydrophilic monomer and the hydrophobic monomer in the mixed monomer is 1-5:3:3, 1g of the mixed monomer corresponds to 3mL solvent, and then Add polymer microspheres with RAFT chain transfer groups on the surface, after degassing and deoxygenating three times, put the reaction vessel in an oil bath at 50-120°C for 10-72 hours, then centrifuge and wash the reaction product at 40°C Vacuum-dried for 48 hours to obtain amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalyst.

The functional monomer of the present invention is methacrylic acid, trifluoromethacrylic acid, acrylamide or 4-vinylpyridine, and the crosslinking agent is ethylene glycol dimethacrylate (EGDMA), trimethyl trimethylolpropyl acrylate (TRIM), divinylbenzene (DVB) or N,N'-methylenebisacrylamide, the initiator is azobisisobutyronitrile or benzoyl peroxide, the The chain transfer agent is cumyl dithiobenzoate, the hydrophilic monomer is acrylic acid, methacrylic acid, acrylamide or N-isopropyl propionamide, and the hydrophobic monomer is methyl methyl acrylate or styrene, and the solvent is one or more of acetonitrile, methanol, water, 1,4-dioxane or N,N-dimethylformamide.

The specific synthetic route in the preparation process of the amphiphilic random copolymer grafted hair-like polymer microspheres of the load chiral catalyst of the present invention is:

.

The synthetic method of chiral monomer of the present invention is:

.

The invention relates to the application of the amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalysts in catalyzing asymmetric synthesis reactions in aqueous phase.

The present invention combines controllable "living" free radical polymerization with research on supported chiral catalysts, and uses reversible-fragmentation-chain transfer polymerization (RAFT) to prepare hydrophobic and hydrophilic polymer segments on the surface and load chiral catalysts The hair-like polymer microspheres are assembled in water by introducing hydrophobic and hydrophilic segments on the surface of the polymer microspheres, and the organic reaction substrate and chiral catalyst are bound to react in a restricted environment to achieve The purpose of effectively catalyzing asymmetric synthesis reactions in the medium, and this type of catalyst can be recycled and reused by simple means (centrifugation or filtration). In addition to obtaining chiral products with high yield and high stereoselectivity, the present invention utilizes the amphiphilic random copolymer grafted hair-like polymer microspheres of the loaded chiral catalyst to catalyze the asymmetric reaction in the aqueous phase. The characteristics of easy separation and recyclable use of the catalyst are realized, and the production cost is reduced.

Description of drawings

Fig. 1 is a scanning electron micrograph of polymer microspheres having RAFT chain transfer agent groups on the surface prepared in Example 1 of the present invention, and the average diameter of the microspheres is 2.54 μm.

Fig. 2 is the emission electron microscope image of the amphiphilic random copolymer grafted hair-like polymer microsphere of the loaded chiral catalyst prepared in Example 1 of the present invention. The average diameter of the microspheres is 2.78 μm, and the surface of the microspheres can be clearly seen Cover with a layer of polymer brush.

Detailed ways

The above-mentioned contents of the present invention are described in further detail below through the embodiments, but this should not be interpreted as the scope of the above-mentioned themes of the present invention being limited to the following embodiments, and all technologies realized based on the above-mentioned contents of the present invention all belong to the scope of the present invention.

Example 1

Synthesis of Chiral Monomers

Measure 20mL of trifluoroacetic acid into a 250mL round bottom flask, add 11.82g of (S)-5-(4-hydroxybenzyl)-2,2,3-trimethyl-4-oximidazole under ice-water bath conditions alkane, stir the reaction until completely dissolved, slowly add 9.6mL of methacryloyl chloride dropwise, and react for 3h at 25°C; The yellow substance precipitated, continued to add dropwise until no more precipitate formed; suction filtered, rinsed with ether, rinsed 3-5 times, and dried in a vacuum oven at 30°C for 12 hours to obtain yellow powder (S)-5 -(4-acryloyloxybenzyl)-2,2,3-trimethyl-4-oximidazole hydrochloride.

Weigh 5.8g of (S)-5-(4-acryloyloxybenzyl)-2,2,3-trimethyl-4-oximidazole hydrochloride into a 250mL round bottom flask, add 4.4mL Tris Ethylamine and 100mL of dichloromethane were reacted for 3h. After the reaction, the excess triethylamine was removed by rotary evaporation, extracted three times with dichloromethane, washed with distilled water three times, dried over _MgSO4 , filtered with suction, and concentrated, with a yield of 80%.

¹ H-NMR(CDCl ₃ ):δ=7.19-7.33ppm(d,2H,ArH), 6.95-7.12ppm(d,2H,ArH), 6.32ppm(s,1H,=CH ₂ ) 5.70-5.80ppm (m,1H,=CH ₂ ), 3.73-3.84ppm(m,1H,COCH), 2.98-3.18ppm(dd×dd,2H,PhCH ₂ -), 2.75ppm(s,3H,N-CH ₃ ) , 1.98-2.08ppm (m, 3H, -CH ₃ ), 1.28ppm (s, 3H, CCH ₃ CH ₃ ), 1.19ppm (s, 3H, -CCH ₃ CH ₃ ).

Example 2

(1) Preparation of polymer microspheres with RAFT chain transfer groups on the surface

Methacrylic acid (0.12 g, 1.50 mmol) and ethylene glycol dimethacrylate (EGDMA) (1.13 mL, 6.00 mmol) were added to 150 mL of a mixed solvent of methanol and water at a volume ratio of 1:4, and then Add cumyl dithiobenzoate (132mg, 0.66mmol) and azobisisobutyronitrile (0.33mmol, 54.1mg), and after the above mixture is completely dissolved, pass nitrogen gas for 30 minutes to remove oxygen, and seal the reaction vessel After that, it was placed in an oil bath at 60°C for 24 hours, filtered, fully washed with a solvent, and dried to obtain polymer microspheres with RAFT chain transfer groups on the surface, with a yield of 60%. Elemental analysis results: C 58.74; H 7.03; S 1.24%, calculated to contain 0.19mmol chain transfer groups per 1g of polymer microspheres, the average diameter of polymer microspheres is 2.54μm, calculated by elemental analysis of polymer microspheres The degree of cross-linking is 76%.

(2) RAFT graft copolymerization on the surface of polymer microspheres

Chiral monomer (3.27g, 10.89mmol), N-isopropylpropionamide (0.74g, 6.54mmol), styrene (0.68g, 6.54mmol), initiator azobisisobutyronitrile AIBN (3.3mg , 0.02mmol), cumyl dithiobenzoate (20mg, 0.1mmol) and polymer microspheres (0.70g) with RAFT chain transfer agent groups on the surface were added to 33mL solvent N,N-dimethylformaldehyde In the amide, after degassing and deoxygenating three times, the reaction vessel was placed in an oil bath at 80°C for 72 hours, and the reaction product was washed by centrifugation, and dried under vacuum at 40°C for 48 hours to obtain the amphiphilic random amphiphilic loaded chiral amine Copolymer grafted hair-like polymer microspheres. The average diameter of the hair-like particles after grafting was 2.78 μm, and the elemental analysis results: C 61.36; H 7.21; N 2.24; S 3.11%, calculated to contain 0.80 mmol Macmillan chiral catalyst per 1 g of polymer microspheres.

Example 3

(1) Preparation of polymer microspheres with RAFT chain transfer groups on the surface

Methacrylic acid (0.12 g, 1.50 mmol) and ethylene glycol dimethacrylate (EGDMA) (1.69 mL, 9.00 mmol) were added to 150 mL of a mixed solvent of methanol and water at a volume ratio of 1:4, and then Cumyl dithiobenzoate (132mg, 0.66mmol) and azobisisobutyronitrile (0.33mmol, 54.1mg), after the above mixture was completely dissolved, nitrogen gas was passed for 30 minutes to remove oxygen, and the reaction vessel was sealed Placed in an oil bath at 60°C for 24 hours, filtered, fully washed with a solvent, and dried to obtain polymer microspheres with RAFT chain transfer groups on the surface, with a yield of 60%. Elemental analysis results: C 58.74; H 7.03; S 1.56%, calculated to contain 0.25mmol chain transfer groups per 1g of polymer microspheres, the average diameter of polymer microspheres is 2.57μm, calculated by elemental analysis of polymer microspheres The degree of cross-linking is 82%.

(2) RAFT graft copolymerization on the surface of polymer microspheres

Chiral monomer (0.65g, 2.18mmol), N-isopropylpropionamide (0.74g, 6.54mmol), styrene (0.68g, 6.54mmol), initiator azobisisobutyronitrile AIBN (3.3mg , 0.02mmol), cumyl dithiobenzoate (20mg, 0.1mmol) and polymer microspheres (0.70g) with RAFT chain transfer agent groups on the surface were added to 33mL solvent N,N-dimethylformaldehyde In the amide, after degassing and oxygen removal three times, the reaction vessel was placed in an oil bath at 80°C for 72 hours, and the reaction product was washed by centrifugation, and dried in vacuum at 40°C for 48 hours to obtain amphiphilic random copolymerization of loaded chiral amine grafted hair-like polymer microspheres. The average diameter of the hair-like particles after grafting was 2.78 μm, and the elemental analysis results: C 61.36; H 7.21; N 1.78; S 3.11%, calculated to contain 0.64 mmol Macmillan chiral catalyst per 1 g of polymer microspheres.

Example 4

Add the Macmillan amine-loaded amphiphilic random copolymer grafted hair-like polymer microspheres prepared in Example 3 as a catalyst (0.2 g, 0.875 mmol), 1 mL H ₂ O, trifluoroacetic acid (0.2 g , 1.75mmol), cinnamaldehyde (0.224mL, 1.75mmol) and cyclopentadiene (0.15mL, 1.75mmol), reacted at room temperature for 48 hours. Extracted three times, combined the organic phase, concentrated, separated by column chromatography to obtain a pure addition product (petroleum ether: ethyl acetate = 50:1), weighed to calculate the yield, and confirmed the target product by proton nuclear magnetic resonance. The chiral substance was separated by a neutral column, and the yield was 85% as measured by high performance liquid chromatography, the anti/syn was 1/1.3, and the ee value was 90% (anti).

Example 5

The amphiphilic random copolymer grafted hair-like polymer microspheres of Macmillan amine used in Example 4 is centrifuged, washed, and fully washed with dichloromethane, and then recovered after vacuum drying and repeated Example 5 as a chiral catalyst. The measured yield was 84%, the anti/syn was 1/1.2, and the e.e. value was 86%.

Example 6

The amphiphilic random copolymer grafted hair-like polymer microspheres loaded with Macmillan amine used in Example 5 was centrifuged, washed, and fully washed with methylene chloride, and then recovered after vacuum drying and repeated Example 6 as a chiral catalyst. The measured yield was 78%, the anti/syn was 1/1.1, and the e.e. value was 80%.

The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the industry should understand that the present invention is not limited by the above-mentioned embodiments, and that described in the above-mentioned embodiments and the specification only illustrates the principle of the present invention, and the present invention also has various aspects without departing from the scope of the principle of the present invention. Changes and improvements, these changes and improvements all fall within the protection scope of the present invention.

Claims (5)

1. The amphiphilic random copolymer grafted hair-like polymer microsphere of load chiral catalyst is characterized in that by initiating chiral monomer, hydrophilic Monomers and hydrophobic monomers are formed by surface reversible addition-fragmentation-chain transfer polymerization, which has the following structure: . 2. A method for preparing the amphiphilic random copolymer grafted hair-like polymer microspheres of the loaded chiral catalyst according to claim 1, characterized in that it comprises the following steps: (1) the surface has a RAFT chain transfer group The preparation of the polymer microspheres of agglomerate, the functional monomer and the crosslinking agent are fed into the solvent in a molar ratio of 1:4-6, and the initiator and the chain transfer agent are added, wherein the initiator is the sum of the functional monomer and the crosslinking agent. The amount of the substance is 1%-5%, the molar ratio of the initiator to the chain transfer agent is 1:2-6, after the above mixture is completely dissolved, pass nitrogen gas for 30 minutes to remove oxygen, seal the reaction vessel and place it at 25-100 React in an oil bath at ℃ for 24 hours, filter, fully wash with solvent, and dry, and prepare polymer microspheres with different chain transfer group contents by changing the chain transfer agent content; (2) amphiphilic random catalyst loaded chiral catalyst The preparation of copolymer-grafted hair-like polymer microspheres, feeds mixed monomers composed of hydrophilic monomers, hydrophobic monomers and chiral monomers, initiators and chain transfer agents into a solvent, wherein the mixed monomers, initiators The molar ratio of agent and chain transfer agent is 100-600:1:5, the molar ratio of chiral monomer, hydrophilic monomer and hydrophobic monomer in mixed monomer is 1-5:3:3, 1g mixed monomer Corresponding to 3mL of solvent, then add polymer microspheres with RAFT chain transfer groups on the surface, after three times of degassing and oxygen removal, place the reaction vessel in an oil bath at 50-120°C for 10-72 hours, and the reaction product Centrifugal washing and vacuum drying at 40°C for 48 hours to obtain amphiphilic random copolymer grafted hair-like polymer microspheres loaded with chiral catalysts; the functional monomers are methacrylic acid, trifluoromethacrylic acid, propylene Amide or 4-vinylpyridine, the crosslinking agent is ethylene glycol dimethacrylate, trimethylolpropyl trimethacrylate, divinylbenzene or N,N'-methylenebisacrylamide , the initiator is azobisisobutyronitrile or benzoyl peroxide, the chain transfer agent is cumyl dithiobenzoate, and the hydrophilic monomer is acrylic acid, methacrylic acid , acrylamide or N-isopropylpropionamide, the hydrophobic monomer is methyl methacrylate or styrene, and the solvent is acetonitrile, methanol, water, 1,4-dioxane or N, One or more of N-dimethylformamide. 3. the preparation method of the amphiphilic random copolymer grafted hair-like polymer microsphere of load chiral catalyst according to claim 2, is characterized in that concrete synthetic route is: . 4. the preparation method of the amphiphilic random copolymer grafted hair-like polymer microsphere of load chiral catalyst according to claim 2, is characterized in that the synthetic method of described chiral monomer is: . 5. The application of the amphiphilic random copolymer grafted hair-like polymer microspheres of the loaded chiral catalyst according to claim 1 in catalyzing an asymmetric synthesis reaction in an aqueous phase.