CN114917953B - Microgel catalyst and synthesis method and application thereof - Google Patents

Microgel catalyst and synthesis method and application thereof Download PDF

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CN114917953B
CN114917953B CN202210557703.9A CN202210557703A CN114917953B CN 114917953 B CN114917953 B CN 114917953B CN 202210557703 A CN202210557703 A CN 202210557703A CN 114917953 B CN114917953 B CN 114917953B
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熊非
马超
朱依仁
陈璐
张艳军
孙宸
张帅军
何一扬
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University of Shanghai for Science and Technology
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
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    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
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Abstract

The invention provides a microgel catalyst and a synthesis method and application thereof, wherein the microgel catalyst is a temperature-sensitive microgel catalyst with a chloramine chiral framework structure, namely, the microgel catalyst can be swelled (dissolved in a solvent) or collapsed (precipitated in the solvent) under different temperature conditions, has the advantages of homogeneous catalysis (high solubility, high reaction activity and selectivity) and heterogeneous catalysis (stability, recovery and reuse), and has good industrial application prospect when the microgel catalyst is used for asymmetric catalytic synthesis, the shrinkage, aggregation and precipitation of the microgel catalyst can be promoted by simply increasing the temperature of a reaction mixture, the catalyst can be separated and recovered from a reaction system conveniently, and the microgel catalyst has the technical advantages of simple experimental operation steps, recoverable catalyst and the like.

Description

Microgel catalyst and synthesis method and application thereof
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a microgel catalyst and a synthesis method and application thereof.
Background
Because of the ease of preparation of meso cyclic anhydrides, enantioselective ring opening reactions to cyclic anhydride intermediates are certainly an important type of asymmetric synthesis reaction. The alcohol nucleophilic reagent which is cheap and easy to obtain is used for carrying out asymmetric alcoholysis ring opening on the reaction substrate anhydride, can be used for preparing important chiral synthesis intermediates (half-esters or thioesters) in organic synthesis, and has wide application prospect in asymmetric synthesis of natural products.
There have been numerous literature reports on the studies of asymmetric catalytic alcoholysis reactions of cyclic anhydrides, with advantages and disadvantages between different catalytic systems. For example: the traditional homogeneous chiral micromolecular catalyst has the advantages of high catalytic reaction activity, good product enantioselectivity and the like, but the catalyst has long synthesis steps, and can be separated from the product only by post-treatment after the reaction is finished, so that the further industrial application of the catalyst is limited. Although the heterogeneous catalyst solves the defect that the homogeneous catalyst is not easy to separate from a product by using an immobilization method, the catalytic activity of the immobilized catalyst is reduced to a certain extent compared with that of a small molecular homogeneous catalyst. Therefore, a novel catalyst with the advantages of homogeneous phase and heterogeneous phase catalysis is required to be designed, and is used for the ring opening reaction of the asymmetric alcoholysis of the cyclic anhydride, so that the high catalytic activity under the homogeneous phase reaction condition and the rapid separation from the product under the heterogeneous phase reaction condition can be realized conveniently.
Disclosure of Invention
In order to solve the technical problems, the invention provides a microgel catalyst, a synthesis method and application thereof, wherein the microgel catalyst has strong temperature responsiveness, and the state of the microgel catalyst can be reversibly switched into a soluble or precipitated form by adjusting the temperature of a reaction solution. The reversible switching behavior (soluble/insoluble) combines the technical advantages of high reaction activity of homogeneous catalysis and easy separation of heterogeneous catalysis, can efficiently catalyze the asymmetric alcoholysis ring-opening reaction of the cyclic anhydride, and is expected to realize industrial application.
The invention provides a microgel catalyst, which comprises an intermediate A, an intermediate B and an intermediate C, wherein the intermediate A, the intermediate B and the intermediate C are synthesized into the microgel catalyst through polymerization under the action of a free radical initiator, and the usage amount of the intermediate A is 95-99 mol%; the usage amount of the intermediate B is 1 mol percent to 5 mol percent, the usage amount of the intermediate C is 3 mol percent, the intermediate A is ethyl acrylate, and the intermediate C isN, N' methylene bisacrylamide, the structural formula of the intermediate B is represented by:
；
wherein R is an aryl (silyl) alkyl substituent
Further, the aryl (silyl) substituent is trityl or tert-butyldiphenylsilyl.
Further, when the aryl (silyl) substituent is trityl, the intermediate B is intermediate D, and the intermediate a, intermediate D and intermediate C synthesize a microgel catalyst by polymerization under the action of a radical initiator; wherein the use amount of the intermediate A is 96 mol%; the use amount of the intermediate B is 4 mol%, and the free radical initiator is 2,2' -azobis (2-methylpropionamide) dihydrochloride.
Further, the intermediate D is chemically synthesized by taking clotrimide as a chiral starting material, and the structural formula of the intermediate D is as follows:
。
further, the specific steps of synthesizing the microgel catalyst through polymerization reaction of the intermediate A, the intermediate D and the intermediate C are as follows:
s1: under the protection of nitrogen, 4 mol% of intermediate D is dissolved in 96 mol% of intermediate A, and then 1 mol% of cetyltrimethylammonium bromide, 3 mol% of intermediate C and water are added to obtain a reaction mixture;
s2: carrying out ultrasonic treatment on the reaction mixture for 15min, and then heating the ultrasonic treated reaction mixture to 70 ℃ under continuous stirring;
s3: adding 1 mol% of an aqueous solution of which the free radical initiator is 2,2' -azo bis (2-methylpropyl-mi) dihydrochloride into the heated reaction mixture, stirring the reaction mixture for reaction 6h, and cooling the reaction mixture to room temperature to obtain a polymer;
s4: and filling the polymer into a dialysis bag, and dialyzing the polymer for 5 days by using distilled water to obtain the microgel catalyst.
Further, the microgel catalyst has temperature sensitivity.
Further, the microgel catalyst is applied to cyclic anhydride alcoholysis ring opening.
Further, the cyclic anhydride alcoholysis ring opening is a cyclic anhydride asymmetric alcoholysis ring opening.
Compared with the prior art, the invention has the beneficial effects that:
the catalyst provided by the invention has the characteristic of sensitivity to temperature, can be reversibly switched into a soluble or precipitation form by adjusting the temperature of the reaction liquid, simultaneously realizes high catalytic activity under homogeneous reaction conditions and rapid separation from products under heterogeneous reaction conditions, has simple experimental operation and post-treatment processes, has high optical purity and separation yield of the products, has little environmental pollution, and has good industrial application prospect.
The synthesis of the microgel catalyst provided by the invention adopts the byproduct chloromycylamine generated in industrial production of chloramphenicol as a chiral starting material for chemical synthesis, and the microgel catalyst prepared by simple reaction with the cheap and easily available chiral source has the technical advantages of high efficiency, practicality and low cost.
Drawings
FIG. 1 is a TEM profile of a microgel catalyst of the invention dispersed in an isopropanol solution at 5℃and 40℃C (b);
FIG. 2 is a graph of temperature versus hydrodynamic radius of microgel particles for a microgel catalyst of the present invention;
FIG. 3 is a graph of temperature versus settling velocity of microgel particles for a microgel catalyst of the present invention;
FIG. 4 is a chart showing the hydrogen nuclear magnetic resonance spectrum of intermediate D of the present invention;
FIG. 5 is a chart of nuclear magnetic resonance carbon spectrum of intermediate D of the present invention;
FIG. 6 is a high resolution mass spectrum of intermediate D of the present invention.
Detailed Description
The synthesis and use of a temperature-sensitive chiral microgel catalyst according to the present invention will be described in more detail with reference to the accompanying schematic drawings, in which preferred embodiments of the present invention are shown, it being understood that the present invention described herein may be modified by those skilled in the art while still achieving the advantageous effects of the present invention, and thus the following description should be construed as broadly known to those skilled in the art and not as limiting the present invention.
The synthesis method of the microgel catalyst comprises the steps of synthesizing the microgel catalyst by polymerization reaction under the action of a free radical initiator, wherein the usage amount of the intermediate A is 95-99 mol%; the usage amount of the intermediate B is 1 mol percent to 5 mol percent, the usage amount of the intermediate C is 3 mol percent, the intermediate A is ethyl acrylate, and the intermediate C isN, N' methylene bisacrylamide, intermediate B has the structural formula:
；
wherein R is an aryl (silyl) substituent, and further wherein the aryl (silyl) substituent is trityl or tert-butyldiphenylsilyl.
The structural formula of the intermediate A is expressed as follows:
；
the structural formula of intermediate C is shown as follows:
。
the method for synthesizing a microgel catalyst according to claim 1, wherein the aryl (silyl) substituent is trityl or t-butyldiphenylsilyl.
Example 1:
when the aryl (silyl) substituent is trityl, the usage amount of the intermediate A is 96 mol%, the usage amount of the intermediate B is 4 mol%, the free radical initiator is 2,2' -azobis (2-methylpropionamide) dihydrochloride, the intermediate B is the intermediate D, the hydroxyl protection form of the structural formula shown in the intermediate B is the structural formula shown in the intermediate D, and the structural formula is as follows:
。
the specific steps for synthesizing the intermediate D are as follows:
；
the synthesis of intermediate G takes the byproduct clomazone E produced by industrial production of chloramphenicol as chiral starting material, and can be carried out according to the literature report methodOrg. Lett., 2002, 4, 3451; Angew. Chem. Int. Ed., 2003, 43, 216)。
Then, at room temperature, (1)S, 2S)-2-(N, N-dimethylamino) -3-tritoxy-1- (p-nitrophenyl) -propan-1-ol (intermediate G, 10 mmol) and Ph 3 P (12.5 mmol) was placed in a three-necked flask, and anhydrous tetrahydrofuran (20 mL) was added for dissolution, and the reaction apparatus was sealed and used with N 2 Purging for three times to remove air in the reaction system, and cooling the three-neck flask to 0 in ice water bath o C. After stirring for a further 10 min, a solution of diisopropyl azodicarboxylate (12.5 mmol) and diphenylphosphorylazide (12.5 mmol) in anhydrous THF (10 mL) was added dropwise. The mixture was then warmed to room temperature and the reaction was stirred10 h, maintaining TLC detection in the reaction process, and heating the mixture to 50 ℃ after the raw materials are completely reacted o C remains heated 2 h. Adding Ph again 3 P (12.5 mmol) and reaction 2 h was stirred continuously. The reaction mixture was cooled to room temperature and H was added 2 O (1 mL) was stirred further for 2 h to quench the reaction. After completion of the reaction, methylene chloride (50 mL) was added, and the resultant reaction solution was washed 3 times with water (3×20 mL), and then the organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product as a reddish brown oil. The crude product was dissolved in absolute ethanol, a suitable amount of anhydrous zinc chloride (20 mmol) was added and stirring was continued for 30 min until a light brown precipitate appeared in the solution, filtered and the filtrate was concentrated under reduced pressure to give a red solid. The crude product was purified by column chromatography (CH 2 Cl 2 :Et 3 N=100:1) to give intermediate H in 59% yield.
Finally, the mixture was added to a round-bottomed flask in this order at room temperature (1R, 2R)-2-(N, N-dimethylamino) -1- (p-nitrophenyl) -3-tritoxy-1, 2-propanediamine (intermediate H, 2 mmol), triethylamine (8 mmol) and dichloromethane (20 mL), and the reaction solution was cooled to 0 in an ice-water bath o C was stirred for 10 min, then 4-vinylbenzenesulfonyl chloride (3 mmol, preparation method can be referred to literature:Bull. Chem. Soc. Jpn., 1983, 56, 762). The reaction mixture was warmed to room temperature naturally and stirred continuously for 2 h, TLC was maintained during the reaction, and after the reaction was completed, the crude product was washed sequentially with water (2X 20 mL), saturated NaCl solution (2X 20 mL), and dried over anhydrous Na 2 SO 4 Drying, filtering and concentrating the filtrate under reduced pressure to give a yellow solid product. The crude product was purified by column chromatography (PE: ea=2:1) to give intermediate D in 70% yield. 188.5-189.5 o C; [α] D 25 = +73.6 (c 0.05, CHCl 3 )。
FIG. 4 is a chart showing nuclear magnetic resonance hydrogen spectra of intermediate D, and the specific structure is characterized as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.96-7.76 (m, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.24-6.97 (m, 17H), 6.68 (dd, J = 17.6, 10.9 Hz, 1H), 5.83 (d, J = 17.6 Hz, 1H), 5.42 (d, J = 10.9 Hz, 1H), 3.93 (d, J = 10.6 Hz, 1H), 3.08 (dd, J = 10.6, 6.1 Hz, 1H), 2.93 (dd, J = 10.6, 3.4 Hz, 1H), 2.70 (ddd, J=9.9, 6.1, 3.3 Hz, 1H), 2.25 (s, 6H.) fig. 5 is a nuclear magnetic resonance spectrum of intermediate D, specifically characterized by the following structure: 13 C NMR (100 MHz, CDCl 3 ): δ143.14, 135.25, 129.15, 128.53, 127.82, 127.26, 126.39, 123.44, 117.73, 87.66, 68.03, 58.05, 56.51, 40.95. Fig. 6 is a high resolution mass spectrum of intermediate D, characterized by the following structure: HRMS (ESI) M/z: [ M+H ]] + calculated for C 38 H 37 N 3 O 5 S648.25140, found 648.25140. The chemical structure of intermediate D was confirmed by combining the spectral analyses of fig. 4, 5 and 6.
The procedure for synthesizing the microgel catalyst was as follows:
under the protection of nitrogen, a certain amount ofN-((1R, 2R) -2- (dimethylamino) -1- (4-nitrophenyl) -3- (trityloxy) propyl) -4-vinylbenzenesulfonamide (intermediate D, 4 mol%) was dissolved in ethyl acrylate (intermediate a, 96 mol%). Cetyl trimethylammonium bromide (CTAB, 1 mol%) and crosslinker were then addedN, N' -methylenebisacrylamide (intermediate C, 3 mol%) and water. The resulting reaction mixture was sonicated for 15min, then the flask was warmed to 70 f with continuous stirring o C. Then adding an aqueous solution of an initiator 2,2' -azobis (2-methylpropionamide) dihydrochloride (AIBA, 1 mol%) into the reaction solution, stirring the reaction solution for reaction 6h, cooling the reaction solution to room temperature, putting the obtained polymer into a dialysis bag, and dialyzing the polymer with distilled water for 5 days to obtain the microgel catalyst with the yield of 65%.
Example 2
In this example, the microgel catalyst of example 1 and the intermediate D of structural formula D were subjected to sulfur element analysis by a high-temperature combustion method, respectively, and the test results further show that the microgel catalyst of example 1 is a copolymerization product of the intermediate D and the intermediates a and C.
Analysis value of organic element content
Entry Sample N(%) C(%) H(%) S(%)
1 Microgel catalyst 1.94 61.07 6.974 0.907
2 Microgel catalyst 2.06 61.31 7.046 1.012
3 Intermediate D 6.49 70.48 5.73 4.89
4 Intermediate D 6.46 70.6 5.68 4.93
5 a Intermediate D 6.48 70.4 5.7 4.94
a Theoretical values of organic element content (C, H, N and S) of intermediate D.
In addition, three analysis methods of Transmission Electron Microscopy (TEM), dynamic Light Scattering (DLS) and sedimentation analysis (lumiffuge) were used, and studies were made on thermal response characteristics and swelling/slump behavior of microgels in a solution state. The morphology, the particle size, the sedimentation velocity and the like of the microgel are studied at different temperatures, so that the linear or nonlinear relation between the thermal response characteristic and the temperature is examined.
And respectively placing isopropanol solutions of microgel catalysts with the same quality in temperature environments of 5 ℃ and 40 ℃, stirring the solutions at constant temperature to enable the microgel systems to be more uniformly dispersed, respectively taking trace solutions from the two dispersion systems, dripping the trace solutions on a copper mesh, respectively performing constant temperature drying at the temperature, and observing the appearance of a transmission electron microscope. As shown in fig. 1, the microgel catalyst at 5 ℃ has good dispersibility, particles are uniformly spread on a copper mesh, and the microgel catalyst has good swelling property in a solvent at low temperature; 40. the microgel at the temperature shows a lumpy aggregation morphology, the particle size is obviously enlarged, the solvent has deswellability at high temperature, and spiral-spherical transition occurs along with the reduction of the solvation degree, so that the microgel catalyst is contracted, aggregated and precipitated.
To further characterize the temperature sensitivity of the microgel catalyst, the microgel catalyst of example 1 was subjected to dynamic light scattering and particle settling velocity studies. As shown in fig. 2, the hydrodynamic radius of the microgel particles decreases with increasing temperature: when the temperature is lower than 20 ℃, the microgel particles are in a swelling state, the hydrodynamic radius is larger and kept between 540 and 555 and nm; when the temperature is higher than 30 ℃, the microgel particles collapse and aggregate and precipitate among particles, the hydrodynamic radius is the lowest, and the fluid dynamic radius is between 480 and 495 nm. Dynamic Light Scattering (DLS) test data indicate that 25 ℃ is the critical transition temperature for the swelling and collapse properties of the microgel. The test results in the sedimentation analysis (lumiffuge) are fully consistent with the data for DLS, as shown in fig. 3, the sedimentation rate of microgel particles increases with increasing temperature: at below 20 ℃, the settling velocity of the microgel particles is low and kept between 1400 and 1600 μm/s; when the temperature is above 40 ℃, the sedimentation velocity tends to be slow, and is between 2100 and 2200 mu m/s. The sedimentation velocity in fig. 3 refers to the median migration velocity of the colloidal particles, not the actual particle sedimentation velocity. Detailed particle sedimentation velocity data are shown in the following table, wherein particle migration velocity at each temperature point was tested 2 times. By analysis of the data in the tables, it can be seen that the velocity profile of the colloidal particles is not concentrated, about 10% or less of the particles have a sedimentation velocity between 530.2 and 835.6 μm/s, 16% or less of the particles have a sedimentation velocity between 677.9 and 1193 μm/s, 50% or less of the particles have a sedimentation velocity between 1406 and 2351 μm/s, 84% or less of the particles have a sedimentation velocity between 2500 and 3367 μm/s, and 90% or less of the particles have a sedimentation velocity between 2772 and 3740 μm/s.
Actual particle sedimentation velocity and distribution data
Sample Name Median in nm Harmonic Mean in nm Std.Dev. in nm Span (x90 x10)/x50 Mean RCA in g 10% ≤ in nm 16% ≤ in nm 50% ≤ in nm 84% ≤ in nm 90% ≤ in nm
10℃-1 1406 1036 842.3 1.594 532.5 530.2 677.9 1406 2500 2772
10℃-2 1449 792.9 1038 1.873 531.3 532.3 680.0 1518 2857 3059
20℃-1 1518 1052 1022 1.679 531.3 532.3 680.0 1518 2857 3082
20℃-2 1594 1292 981.5 1.648 530.4 676.2 793.2 1594 2969 3303
25℃-1 1705 1264 1039 1.597 528.7 771.3 910.3 1705 3000 3496
25℃-2 1767 1325 981.8 1.418 530.0 735.2 897.4 1767 2913 3241
30℃-1 1910 1439 1225 1.717 529.2 765.5 926.6 1910 3644 4044
30℃-2 1971 1431 1150 1.581 529.5 638.5 1020 1971 3348 3754
40℃-1 2123 1415 951.1 1.200 531.9 748.7 1066 2123 3030 3296
40℃-2 2128 1557 934.1 1.196 531.7 772.0 1149 2128 2964 3317
50℃-1 2245 1672 1167 1.391 531.1 835.6 1091 2245 3649 3958
50℃-2 2351 1703 1065 1.237 530.9 831.8 1193 2351 3367 3740
The above test data indicate that microgel polymers exhibit a high sensitivity to solution temperature, they swell at low temperatures to form stable homogeneous-like catalytic systems, but shrink when the solution is heated, which in turn produces aggregated precipitates to form heterogeneous-like catalytic systems. The temperature sensitivity behavior can make the microgel catalyst have the characteristic of high catalytic activity in a homogeneous catalysis state and the characteristic of being convenient to separate from products in a heterogeneous catalysis state, and the temperature of the reaction liquid becomes the switch for controlling and switching two different catalysis modes of the microgel catalyst.
Example 3
This example shows the catalytic activity of the microgel catalyst of example 1 in the ring opening reaction of the asymmetric alcoholysis of cyclic anhydride, and is specifically shown as follows: cis-1, 2, 3, 6-tetrahydrophthalic anhydride (0.5 mmol) was dissolved in methyl tert-butyl ether (10 mL) and the microgel of example 1 was added to the catalystThe catalyst (0.05 mmol) was stirred for 10 min at 20℃and trans-cinnamic alcohol (2.5 mmol) was slowly added dropwise to the reaction system and stirred for reaction 12 h. After the reaction was completed, the resulting reaction mixture was warmed to 40-50 ℃, and after volume shrinkage, aggregation and precipitation of the microgel catalyst were observed, the supernatant and the microgel catalyst were separated by centrifugation. The recovered microgel catalyst is subjected to swelling-sedimentation-centrifugation by pure methyl tertiary butyl ether, and is used for removing the product and reactant residues on the surface of the catalyst, and the treated microgel catalyst can be used as the catalyst for recycling. Combining the washing solution with the supernatant, concentrating under reduced pressure to obtain the corresponding ring-opened product (1)S, 6R) -6- ((cinnamyloxy) carbonyl) cyclohex-3-enecarboxylic acid in 96% yield and 90% ee. 1 H NMR (400 MHz, CDCl 3 ): δ 7.42-7.29 (m, 5H), 6.64 (d, J = 3.2 Hz, 2H), 6.41-6.36 (m, 1H), 5.73 (s, 2H), 4.34-4.33 (m, 2H), 3.14-3.09 (m, 2H), 2.66-2.62 (m, 2H), 2.43-2.39 (m, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ): δ 177.7, 173.2, 136.7, 131.0, 128.5, 127.6, 126.4, 125.1, 123.1, 65.3, 63.4, 39.7, 39.6, 25.8, 25.6 ppm。
Example 4
When the aryl (silyl) substituent is trityl, the usage amount of the intermediate A is 99 mol percent, the usage amount of the intermediate B is 1 mol percent, the usage amount of the intermediate C is 3 mol percent, and the free radical initiator is%N, NWhen the' -diethyl) azo diisobutylamidine hydrochloride is adopted, the intermediate B is the intermediate D, and the steps for synthesizing the microgel catalyst are as follows:
under the protection of nitrogen, a certain amount ofN-((1R, 2R) -2- (dimethylamino) -1- (4-nitrophenyl) -3- (trityloxy) propyl) -4-vinylbenzenesulfonamide (intermediate D, 1 mol%) was dissolved in ethyl acrylate (intermediate a, 99 mol%). Cetyl trimethylammonium bromide (CTAB, 1 mol%) and crosslinker were then addedN, N' -methylenebisacrylamide (intermediate C, 3 mol%) and water. The resulting reaction mixture was sonicated for 15min, and the flask was then placed under continuous stirringHeating to 70 DEG C o C. Then adding initiatorN, NAn aqueous solution of' -diethyl) azo diisobutylamidine hydrochloride (EAIBA, 1 mol%) was added to the reaction solution, the reaction solution was cooled to room temperature after stirring for reaction 6h, and the obtained polymer was put into a dialysis bag and dialyzed with distilled water for 5 days to obtain a microgel catalyst with a yield of 68%.
The microgel catalyst synthesized in this example was subjected to elemental sulfur analysis by high temperature combustion, and the test results further showed that the microgel catalyst of example 4 was a copolymerization product of intermediate D and intermediates a and C.
Analysis value of organic element content
Entry Sample N(%) C(%) H(%) S(%)
1 Microgel catalyst 1.22 59.73 7.253 0.285
2 Microgel catalyst 1.14 59.48 7.174 0.196
The catalytic activity of the microgel catalyst synthesized in the embodiment in the ring opening reaction of the asymmetric alcoholysis of the cyclic anhydride is studied, and the specific experiment is as follows: cis-1, 2, 3, 6-tetrahydrophthalic anhydride (0.5 mmol) was dissolved in methyl tert-butyl ether (10 mL), the microgel catalyst (0.05 mmol) of example 4 was added and the reaction temperature was controlled at 20℃and stirring was continued for 10 min, and trans-cinnamic alcohol (2.5 mmol) was slowly added dropwise to the reaction system and stirring was continued for reaction 12 h when the catalyst was observed to be in a swollen state in the solvent. After the reaction was completed, the resulting reaction mixture was warmed to 40-50 ℃, and after volume shrinkage, aggregation and precipitation of the microgel catalyst were observed, the supernatant and the microgel catalyst were separated by centrifugation. The recovered microgel catalyst is subjected to swelling-sedimentation-centrifugation by pure methyl tertiary butyl ether, and is used for removing the product and reactant residues on the surface of the catalyst, and the treated microgel catalyst can be used as the catalyst for recycling. Combining the washing solution with the supernatant, concentrating under reduced pressure to obtain the corresponding ring-opened product (1)S, 6R) -6- ((cinnamyloxy) carbonyl) cyclohex-3-enecarboxylic acid in 97% yield, ee value 88%.
Example 5
When the aryl (silyl) substituent is tert-butyldiphenylsilyl, the amount of intermediate A is 97 mol%, the amount of intermediate B is 3 mol%, the amount of intermediate C is 3 mol%, and the free radical initiator is ammonium persulfate, intermediate B is intermediate I, the hydroxyl-protected form of the structural formula shown in intermediate B is the structural formula shown in intermediate I, and the structural formula is:
。
the synthesis of intermediate I using clotrimide E as chiral starting material can be performed by reference to the method of example 1 for synthesizing intermediate D, except that tert-butyldiphenylchlorosilane (TBDPSCl) is used instead of triphenylchloromethane (TrCl), and the molar amount of TBDPSCl is identical to TrCl. The synthetic route is as follows:
；
the procedure for synthesizing the microgel catalyst was as follows:
under the protection of nitrogen, a certain amount ofN-((1R, 2R) -2- (dimethylamino) -1- (4-nitrophenyl) -3- (tert-butyldiphenylsiloxy) propyl) -4-vinylbenzenesulfonamide (intermediate I, 3 mol%) was dissolved in ethyl acrylate (intermediate a, 97 mol%). Cetyl trimethylammonium bromide (CTAB, 1 mol%) and crosslinker were then addedN, N' -methylenebisacrylamide (intermediate C, 3 mol%) and water. The resulting reaction mixture was sonicated for 15min, then the flask was warmed to 70 f with continuous stirring o C. And adding an aqueous solution of an initiator ammonium persulfate (APS, 1 mol%) into the reaction solution, stirring for reaction 6h, cooling the reaction solution to room temperature, putting the obtained polymer into a dialysis bag, and dialyzing with distilled water for 5 days to obtain the microgel catalyst with the yield of 66%.
The microgel catalyst synthesized in this example was subjected to elemental sulfur analysis by high temperature combustion, and the test results further showed that the microgel catalyst of example 5 was a copolymerization product of intermediate I and intermediates a and C.
Analysis value of organic element content
Entry Sample N(%) C(%) H(%) S(%)
1 Microgel catalyst 1.728 61.289 7.728 0.788
2 Microgel catalyst 1.730 61.199 7.756 0.803
The catalytic activity of the microgel catalyst synthesized in the embodiment in the ring opening reaction of the asymmetric alcoholysis of the cyclic anhydride is studied, and the specific experiment is as follows: cis-1, 2, 3, 6-tetrahydrophthalic anhydride (0.5 mmol) was dissolved in methyl tert-butyl ether (10 mL), the microgel catalyst (0.05 mmol) of example 5 was added and the reaction temperature was controlled at 20℃and stirring was continued for 10 min, and trans-cinnamic alcohol (2.5 mmol) was slowly added dropwise to the reaction system and stirring was continued for reaction 12 h when the catalyst was observed to be in a swollen state in the solvent. After the reaction was completed, the resulting reaction mixture was warmed to 40-50 ℃, and after volume shrinkage, aggregation and precipitation of the microgel catalyst were observed, the supernatant and the microgel catalyst were separated by centrifugation. The recovered microgel catalyst is subjected to swelling-sedimentation-centrifugation by pure methyl tertiary butyl ether, is used for removing the product and reactant residues on the surface of the catalyst, and can be used as the catalyst for recycling after treatment. Combining the washing solution with the supernatant, concentrating under reduced pressure to obtain the corresponding ring-opened product (1)S, 6R) -6- ((cinnamyloxy) carbonyl) cyclohex-3-enecarboxylic acid in 97% yield, ee value 88%.
The foregoing is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any person skilled in the art will make any equivalent substitution or modification to the technical solution and technical content disclosed in the invention without departing from the scope of the technical solution of the invention, and the technical solution of the invention is not departing from the scope of the invention.

Claims (6)

1. The synthesis method of the microgel catalyst is characterized by comprising an intermediate A, an intermediate B and an intermediate C, wherein the intermediate A, the intermediate B and the intermediate C are synthesized into the microgel catalyst through polymerization under the action of a free radical initiator, and the usage amount of the intermediate A is 95% -99%; the usage amount of the intermediate B is 1% -5%, wherein the usage amounts of the intermediate A and the intermediate B are based on the total substance amount of the intermediate A and the intermediate B;
the usage amount of the intermediate C is 3%, the intermediate A is ethyl acrylate, the intermediate C is N, N' -methylene bisacrylamide, and the structural formula of the intermediate B is expressed as follows:
；
wherein R is an aralkyl substituent or an arylsilane substituent;
the aryl alkyl substituent is trityl, and the aryl silyl substituent is tert-butyl diphenyl silyl;
when the aralkyl substituent is trityl, the intermediate B is an intermediate D, and the intermediate A, the intermediate D and the intermediate C are synthesized into the microgel catalyst through polymerization under the action of a free radical initiator; wherein, based on the total substance amount of the intermediate A and the intermediate D, the using amount of the intermediate A is 96 percent, and the using amount of the intermediate D is 4 percent; the free radical initiator is 2,2' -azo bis (2-methylpropyl-mi) dihydrochloride;
the microgel catalyst has temperature sensitivity.
2. The method for synthesizing the microgel catalyst according to claim 1, wherein the intermediate D is chemically synthesized by using clotrimide as a chiral starting material, and the structural formula of the intermediate D is as follows:
。
3. the method for synthesizing the microgel catalyst according to claim 2, wherein the specific steps of synthesizing the microgel catalyst by polymerization reaction of the intermediate a, the intermediate D and the intermediate C are as follows:
s1: under the protection of nitrogen, 4% of intermediate D is dissolved in 96% of intermediate A, and then cetyltrimethylammonium bromide with the use amount of 1% and intermediate C with the use amount of 3% are added to obtain a reaction mixture, wherein the use amounts of the intermediate A and the intermediate D are based on the total substance amount of the intermediate A and the intermediate D;
s2: carrying out ultrasonic treatment on the reaction mixture for 15min, and then heating the ultrasonic treated reaction mixture to 70 ℃ under continuous stirring;
s3: adding 1% of aqueous solution of 2,2' -azobis (2-methylpropionamide) dihydrochloride serving as the free radical initiator into the heated reaction mixture, stirring and reacting for 6 hours, and cooling the reaction mixture to room temperature to obtain a polymer;
s4: and filling the polymer into a dialysis bag, and dialyzing the polymer for 5 days by using distilled water to obtain the microgel catalyst.
4. A microgel catalyst synthesized using the synthesis method of the microgel catalyst according to any one of claims 1 to 3.
5. The microgel catalyst according to claim 4, wherein the microgel catalyst is applied to cyclic anhydride alcoholysis ring opening.
6. The microgel catalyst according to claim 5, wherein the cyclic anhydride alcoholysis ring opening is a cyclic anhydride asymmetric alcoholysis ring opening.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4791081A (en) * 1986-02-25 1988-12-13 The Dow Chemical Company Supported fluorocarbonsulfonic acid polymers and an improved method for their preparation
CN101724124A (en) * 2009-12-11 2010-06-09 天津工业大学 Temperature-sensitive microgel containing chiral side group and preparation method thereof
CN105131170A (en) * 2015-10-08 2015-12-09 河南师范大学 Nanogel modified by ionic liquid and loaded with chiral catalyst and preparing method and application thereof
CN109225324A (en) * 2018-08-15 2019-01-18 太原理工大学 Immobilized L-PROLINE temperature-responsive nucleocapsid microgel and its preparation and application

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4791081A (en) * 1986-02-25 1988-12-13 The Dow Chemical Company Supported fluorocarbonsulfonic acid polymers and an improved method for their preparation
CN101724124A (en) * 2009-12-11 2010-06-09 天津工业大学 Temperature-sensitive microgel containing chiral side group and preparation method thereof
CN105131170A (en) * 2015-10-08 2015-12-09 河南师范大学 Nanogel modified by ionic liquid and loaded with chiral catalyst and preparing method and application thereof
CN109225324A (en) * 2018-08-15 2019-01-18 太原理工大学 Immobilized L-PROLINE temperature-responsive nucleocapsid microgel and its preparation and application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
《双功能氢键催化剂催化的不对称有机反应研究》;杨鸿均;中国博士学位论文全文数据库 工程科技I辑(第02期);72、81-84 *
《氯霉胺类催化剂在有机反应中的应用研究进展》;徐蒙蒙;徐嘉琪;张奇;尹祥健;杨鸿均;冯豫川;曾碧涛;;化学试剂;40(第01期);31-39 *
氯霉胺类催化剂在有机反应中的应用研究进展;徐蒙蒙;徐嘉琪;张奇;尹祥健;杨鸿均;冯豫川;曾碧涛;;化学试剂(第01期) *

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