CN101073779B - Quaternary ammonium salt poly-L-leucine catalyst and its preparation and application - Google Patents
Quaternary ammonium salt poly-L-leucine catalyst and its preparation and application Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 115
- 108010050934 polyleucine Proteins 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 150000003242 quaternary ammonium salts Chemical class 0.000 title abstract description 7
- 238000006735 epoxidation reaction Methods 0.000 claims abstract description 32
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 20
- 150000002576 ketones Chemical class 0.000 claims abstract description 9
- 238000005406 washing Methods 0.000 claims description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 24
- 238000002386 leaching Methods 0.000 claims description 22
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 17
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 11
- 208000035126 Facies Diseases 0.000 claims description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 11
- 230000006837 decompression Effects 0.000 claims description 11
- 239000008367 deionised water Substances 0.000 claims description 11
- 229910021641 deionized water Inorganic materials 0.000 claims description 11
- VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 150000002118 epoxides Chemical class 0.000 claims description 11
- 238000010898 silica gel chromatography Methods 0.000 claims description 11
- 229940045872 sodium percarbonate Drugs 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- 238000000967 suction filtration Methods 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- -1 amino quaternary ammonium salt Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims 2
- 239000004395 L-leucine Substances 0.000 claims 1
- 235000019454 L-leucine Nutrition 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 229960003136 leucine Drugs 0.000 claims 1
- 239000007791 liquid phase Substances 0.000 claims 1
- 238000004809 thin layer chromatography Methods 0.000 claims 1
- 238000006116 polymerization reaction Methods 0.000 abstract description 10
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- 230000000977 initiatory effect Effects 0.000 abstract description 3
- 238000004064 recycling Methods 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 12
- 235000005513 chalcones Nutrition 0.000 description 12
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
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- 150000001788 chalcone derivatives Chemical class 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 208000012839 conversion disease Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229920001308 poly(aminoacid) Polymers 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical class O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- 239000004593 Epoxy Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 150000001413 amino acids Chemical class 0.000 description 1
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- OCBHHZMJRVXXQK-UHFFFAOYSA-M benzyl-dimethyl-tetradecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 OCBHHZMJRVXXQK-UHFFFAOYSA-M 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
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- 239000003814 drug Substances 0.000 description 1
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- 239000000203 mixture Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
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- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- Catalysts (AREA)
Abstract
一种季铵盐多聚-L-亮氨酸催化剂及其制备和应用，属催化剂及其制备和应用的技术领域。该催化剂由带有氨基的季铵盐与多聚-L-亮氨酸连接而成。 以带有氨基的季铵盐引发L-Leu NCA聚合，制得该催化剂。该催化剂特别适用于α，β-不饱和酮的不对称环氧化，具有催化剂用量少、反应速度快、产物及催化剂回收方便、催化剂可多次循环使用、收率和对映选择性ee％值高的特点，具有很好的工业应用前景。A quaternary ammonium salt poly-L-leucine catalyst and its preparation and application belong to the technical field of catalysts and its preparation and application. The catalyst is formed by linking quaternary ammonium salt with amino group and poly-L-leucine. The catalyst was prepared by initiating the polymerization of L-Leu NCA with quaternary ammonium salts with amino groups. The catalyst is especially suitable for the asymmetric epoxidation of α, β-unsaturated ketones. It has the advantages of less catalyst consumption, fast reaction speed, convenient recovery of products and catalysts, multiple recycling of catalysts, high yield and enantioselectivity ee The characteristic of high % value has good industrial application prospect.
Description
Technical field
The present invention relates to a kind of quaternary-ammonium poly-L-leucine catalyst and preparation thereof and application; Application is meant this catalyst alkene asymmetric Epoxidation, exactly, is meant this catalyst α; The alpha, beta-unsaturated ketone asymmetric Epoxidation, the technical field of metal catalyst and preparation thereof and application.
Background technology
The optically active epoxy ketone compounds is the synthetic son of one type of important biological compound, through reactions such as selective opening and functional group's conversions, can synthesize many valuable chipal compounds.α, the asymmetry catalysis epoxidation of alpha, beta-unsaturated ketone are one of most important reactions of such optically active epoxy thing of preparation.And in catalytic reaction; Adopt the catalyst of organic molecule as asymmetric epoxidation reaction; Have not containing metal, pollute less, advantages such as toxicity is little, good stability, reaction condition gentleness, to significant with the security and the chemical process greenization of synthetic drug.Juli á reported first polyamino acid in 1980 can the catalysis chalcone compounds asymmetric epoxidation reaction (Angrew.Ch em.Int.Ed.Engl.1980; 19; 929), the Polyalanine enantioselectivity (e e%) of making catalyst reaction can reach 83%, yield 85%.These amino acid polymers are called as synzyme (syntheticenzyme) or synthase (synzyme).Polyaminoacid has the following advantages as the catalyst of asymmetric organic synthesis for native enzyme: be easy to get, inexpensive, be prone to from reactant mixture, to separate, activity stabilized, product photochemistry purity high, be easy to recycling.After this because its potential theoretical research is worth and the application prospect in industrial synthesizing, and increasing researcher begins it is studied, a large amount of research work constantly are seen in report.The reaction of improved polyamino acid catalysis chalcone compounds can make almost Quantitative yield of substrate, and enantioselectivity ee% value is up to 95% (Tetrahedron Lett.2004,45,5069) simultaneously.Yet traditional polyaminoacid catalyst has 3 its application aspect industrialization of factor restriction at least: (1) catalyst amount is big, is about 200% of substrate weight; (2) reaction speed is very slow, generally needs several days time could accomplish (Tetrahedron1984,40,5207); (3) catalyst is gluey, brings very big difficulty to the recovery of practical operation and catalyst.Geller etc. have reported and in the alkene asymmetric epoxidation reaction system of poly-L-leucine catalysis, have added quaternary ammonium salt as phase transfer catalyst; But fast reaction speed; Reduce catalyst amount, but because catalyst still is gluey, product separates and the catalyst recovery problem does not still solve (Tetrahedron Lett.2004; 45,5069).In order to address these problems, the inventor was once immobilized on silica gel with the scion grafting of poly-L-leucine covalency, made catalyst be Powdered; Be convenient to reclaim; But the problem of catalyst amount big (be about substrate weight 400%) does not still solve, and catalyst enantioselectivity e e% value decline (Tetrahedron Lett., 2005 rapidly when recycling; 46,5665).
Summary of the invention
First technical problem that the present invention will solve is to release a kind of quaternary-ammonium poly-L-leucine catalyst.
For solving the problems of the technologies described above, the present invention adopts following technical scheme, it is characterized in that, described catalyst is formed by connecting having amino quaternary ammonium salt and poly-L-leucine, has molecular structural formula as follows:
Wherein, R
1, R
2, R
3Be C
1-C
16Alkyl, substituted alkyl, alkoxyl, substituted alkoxy, substituted aryl or substituted heterocyclic radical, X
-Be anion F
-, Cl
-, B r
-, I
-, SO
4 2-, BF
4 -Or PF
6 -, n>=1, average chain length m=10～60.
Second technical problem that the present invention will solve provides a kind of preparation method of quaternary-ammonium poly-L-leucine catalyst.
For solving the problems of the technologies described above, the present invention adopts following technical scheme.Cause L-Leu NCA polymerization to have amino quaternary ammonium salt, make quaternary-ammonium poly-L-leucine catalyst, do with the relevant chemical reaction skeleton symbol of preparation
Specify technical scheme of the present invention at present.
A kind of quaternary-ammonium poly-L-leucine alkene Preparation of catalysts method is characterized in that concrete operations: add 100～300g anhydrous tetrahydro furan among the L-Leu NCA of 7.8g, room temperature and nitrogen protection are stirred down, obtain settled solution; To the quaternary ammonium salt of described solution adding 1～6mmol, room temperature and nitrogen protection were stirred 72 hours down; Filter, the ether washing, oven dry, porphyrize get the powdery product quaternary-ammonium poly-L-leucine catalyst, yield 33%～91%, average chain length m=10～60 of product.
The 3rd technical problem that the present invention will solve is to release described quaternary-ammonium poly-L-leucine catalyst to be used for catalysis α, the method for the asymmetric epoxidation reaction of alpha, beta-unsaturated ketone.
For solving above-mentioned technical problem, the present invention adopts following technical scheme:
Described catalyst is used for α; The method of the asymmetric epoxidation reaction of alpha, beta-unsaturated ketone; It is characterized in that; With the quaternary ammonium salt poly-L-leucine catalyst of 0.1～2mmol, the α of 10mmol, beta-unsaturated ketone compound and 80g dimethoxy-ethane drop into 80g water, stir 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 5 minutes～12 hours under the room temperature, it is complete that TLC tracks to raw material reaction; Suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and obtains epoxidation product, and yield is 90%～99%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity ee% value that obtains epoxides was up to 99.4% to isopropyl alcohol, and described catalyst can be recycled.
The catalyst that reclaims can repeatedly recycle, and recycles the catalyst after seven times, and its activity and enantioselectivity e e% value still remain unchanged.
Compare with background technology, the present invention has the following advantages:
1. catalyst amount reduces significantly, is merely α, the 1mol% of alpha, beta-unsaturated ketone consumption.
2. reaction speed is fast, and minimum needs a few minutes, can make α, the complete epoxidation of alpha, beta-unsaturated ketone.
3. catalyst is Powdered, and product separation and catalyst recovery are easy.
4. reaction conversion ratio and enantioselectivity e e% value are high, and reaction conversion ratio is up to 99%, and enantioselectivity e e% value is up to 99.4%.
The specific embodiment
Embodiment 1: cause L-Leu NCA polymerization, average chain length m=10 with chlorination N-aminopropyl-N-methylimidazole salt ([Pamim] Cl).
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.264g [Pamin] Cl to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.4g white powder product [Pamim] Cl-PLL 10 catalyst, yield 73%.[Pamim] Cl-PLL 10 catalyst are one of quaternary-ammonium poly-L-leucine catalysts, the average chain length m=10 of product.
Embodiment 2: cause L-Leu NCA polymerization, average chain length m=30 with chlorination N-aminopropyl-N-methylimidazole salt ([Pamim] Cl).
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.088g [Pamin] Cl to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.2g white powder product [Pamim] Cl-P LL 30 catalyst, yield 63%.[Pamim] Cl-PLL 30 catalyst are one of quaternary-ammonium poly-L-leucine catalysts, the average chain length m=30 of product.
Embodiment 3: cause L-Leu NCA polymerization, average chain length m=60 with chlorination N-aminopropyl-N-methylimidazole salt ([Pamim] Cl).
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.044g [Pamin] Cl to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.1g white powder product [Pamim] Cl-PLL60 catalyst, yield 57%.[Pamim] Cl-PLL60 catalyst is one of quaternary-ammonium poly-L-leucine catalyst, the average chain length m=60 of product.
Embodiment 4: cause L-Leu NCA polymerization, average chain length m=30 with bromination N-aminopropyl-N-methylimidazole salt ([Pamim] Br).
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.22g [Pamin] B r to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.7g white powder product [Pamin] Br-PLL 30 catalyst, yield 91%.[Pamin] Br-PLL 30 catalyst are one of quaternary-ammonium poly-L-leucine catalysts, the average chain length m=30 of product.
Embodiment 5: with N-aminopropyl-N-methylimidazole hexafluorophosphate ([Pamim] PF
6) initiation L-Leu NCA polymerization, average chain length m=30.
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.14g [Pamim] PF to described solution
6, room temperature and nitrogen protection were stirred 11 days down, and filtration, ether washing, oven dry, porphyrize get 0.84g yellow powder powder product [Pamim] PF
6-PLL30 catalyst, yield 33%.[Pamim] PF
6-PLL30 catalyst is one of quaternary-ammonium poly-L-leucine catalyst, the average chain length m=30 of product.
Embodiment 6: with N-aminopropyl-N-methyl imidazolium tetrafluoroborate ([Pamim] B F
4) initiation L-Leu NCA polymerization, average chain length m=30.
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.11g [Pamim] BF to described solution
4, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.14g white powder product [Pamim] BF
4-PLL30 catalyst, yield 43%.[Pamim] BF
4-PLL30 catalyst is one of quaternary-ammonium poly-L-leucine catalyst, the average chain length m=30 of product.
Embodiment 7: cause L-LeuNCA polymerization, average chain length m=30 with sal-ammoniac butyl tributyl ammonium ([TB AA] Cl).
Add 2.5g L-Leu NCA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.15g [TB AA] Cl to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.27g white powder product [TB AA] Cl-PLL30 catalyst, yield 65%.[TB AA] Cl-PLL 30 catalyst are one of quaternary-ammonium poly-L-leucine catalysts, the average chain length m=30 of product.
Embodiment 8: cause L-Leu NCA polymerization, average chain length m=30 with zephiran chloride diethyl amino propyl ammonium ([BD EA] Cl).
Add 2.5g L-Leu N CA in the reaction bulb, the 50g anhydrous tetrahydro furan, room temperature and nitrogen protection are stirred down, obtain settled solution.Add 0.13g [BD EA] Cl to described solution, room temperature and nitrogen protection were stirred 72 hours down, and filtration, ether washing, oven dry, porphyrize get 1.35g white powder product [BD EA] Cl-PLL30 catalyst, yield 70%.[BD EA] Cl-PLL 30 catalyst are one of quaternary-ammonium poly-L-leucine catalysts, the average chain length m=30 of product.
Embodiment 9: [Pamim] Br-PLL30 catalyst chalcone asymmetric Epoxidation.
[Pamim] Br-PLL30 catalyst of 0.1～2mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 15 minutes under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.22g epoxidation product, and yield is 98%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity ee% value that obtains epoxides was 94% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 10: the application of catalyst [Pamim] Br-PLL 30 in the chalcone asymmetric epoxidation reaction.
[Pamim] Br-PLL 30 catalyst of 2mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 1 hour under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.22g epoxidation product, and yield is 98%; Utilize chiral column (chiralpak AD chiral phase) to carry out HP LC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 96% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 11: the application of catalyst [Pamim] Br-PLL 30 in (E)-1-(4-chlorphenyl)-3-phenylpropyl alcohol-2-alkene-1-ketone asymmetric epoxidation reaction.
[Pamim] Br-PLL 30 catalyst of 2mmol, (E)-1-(4-chlorphenyl)-3-phenylpropyl alcohol-2-alkene-1-ketone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 30 minutes under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.27g epoxidation product, and yield is 99%; Utilize chiral column (chiralpakAD chiral phase) to carry out HP L C and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 99.4% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 12: the application of catalyst [Pamim] Br-PLL 30 in (E)-1-(4-methoxyphenyl)-3-phenylpropyl alcohol-2-alkene-1-ketone asymmetric epoxidation reaction.
[Pamim] Br-PLL 30 catalyst of 2mmol, (E)-1-(4-methoxyphenyl)-3-phenylpropyl alcohol-2-alkene-1-ketone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 10 minutes under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.25g epoxidation product, and yield is 94%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity ee% value that obtains epoxides was 96% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 13: the application of catalyst [Pamim] Br-PLL 30 in (E)-3-(4-methoxyphenyl)-1-phenylpropyl alcohol-2-alkene-1-ketone asymmetric epoxidation reaction.
[Pamim] Br-PLL 30 catalyst of 2mmol, (E)-3-(4-methoxyphenyl)-1-phenylpropyl alcohol-2-alkene-1-ketone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 30 minutes under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.25g epoxidation product, and yield is 94%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 95% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 14: the application of catalyst [Pamim] Cl-PLL 30 in the chalcone asymmetric epoxidation reaction.
[Pamim] Cl-PLL 30 catalyst of 0.1mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 12 hours under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.23g epoxidation product, and yield is 94%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 96% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 15: the application of catalyst [Pamim] Cl-P LL 30 in the chalcone asymmetric epoxidation reaction.
[Pamim] Cl-PLL 30 catalyst of 0.5mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are thrown 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 12 hours under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.24g epoxidation product, and yield is 99%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 99.4% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 16: the application of catalyst [Pamim] Cl-P LL30 in the chalcone asymmetric epoxidation reaction.
[Pamim] Cl-PLL 30 catalyst of 1mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 12 hours under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.24g epoxidation product, and yield is 99%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity ee% value that obtains epoxides was 99.4% to isopropyl alcohol.Described catalyst can be recycled.
Embodiment 17: the application of catalyst [Pamim] Cl-PLL 30 in the chalcone asymmetric epoxidation reaction.
[Pamim] Cl-PLL 30 catalyst of 2mmol, chalcone and the 80g dimethoxy-ethane of 10mmol are dropped into 80g water, stirred 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 15 minutes under the room temperature, suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and gets the 0.22g epoxidation product, and yield is 93%; Utilize chiral column (chiralpak AD chiral phase) to carry out HPLC and analyze, flowing phase is n-hexane: (90: 1, v: v), the enantioselectivity e e% value that obtains epoxides was 93.6% to isopropyl alcohol.Described catalyst can be recycled.
Catalyst of the present invention is specially adapted to α; The asymmetric Epoxidation of alpha, beta-unsaturated ketone; Have that catalyst amount is few, reaction speed is fast, product and catalyst recovery is convenient, catalyst can repeatedly recycle, yield and the high characteristics of enantioselectivity e e% value, has better industrial application prospect.
Claims (3)
1. a quaternary-ammonium poly-L-leucine catalyst is characterized in that, described catalyst is formed by connecting having amino quaternary ammonium salt and poly-L-leucine, has molecular structural formula as follows:
Wherein, R
1, R
2, R
3Be C
1-C
16Alkyl, substituted alkyl, alkoxyl, substituted alkoxy, substituted aryl or substituted heterocyclic radical, X
-Be anion F
-, Cl
-, Br
-, I
-, SO
4 2-, BF
4 -Or PF
6 -, n>=1, average chain length m=10～60.
2. the preparation method of the described quaternary-ammonium poly-L-leucine catalyst of claim 1; It is characterized in that; Add 100～300g anhydrous tetrahydro furan in the L-leucine N-carboxy acid anhydride of concrete operations: 7.8g, room temperature and nitrogen protection are stirred down, obtain settled solution; To the amino quaternary ammonium salt that has of described solution adding 1～6mmol, room temperature and nitrogen protection were stirred 72 hours down; Filter, the ether washing, oven dry, porphyrize get the powdery product quaternary-ammonium poly-L-leucine catalyst, yield 33%～91%, average chain length m=10～60 of product.
3. the described quaternary-ammonium poly-L-leucine catalyst of claim 1 is used for α; The method of the asymmetric epoxidation reaction of alpha, beta-unsaturated ketone; It is characterized in that; With the quaternary-ammonium poly-L-leucine catalyst of 0.1～2mmol, the α of 10mmol, alpha, beta-unsaturated ketone compound and 80g dimethoxy-ethane drop in the 80g water, stir 30 minutes under the room temperature; Add the 2.4g SODIUM PERCARBONATE, stirred 5 minutes～12 hours under the room temperature, it is complete that thin-layer chromatography tracks to raw material reaction; Suction filtration, with the abundant washing leaching cake of ethyl acetate, filtrating merges; With the abundant washing leaching cake of deionized water, reclaim catalyst; Organic facies is used saturated common salt water washing, anhydrous sodium sulfate drying; Decompression is solvent evaporated down, and silica gel column chromatography separates, and obtains epoxidation product, and yield is 90%～99%; Utilize chiral column chiralpak AD chiral phase to carry out efficient liquid phase chromatographic analysis; Flowing phase is the solution of n-hexane and isopropyl alcohol; Wherein the volume ratio of n-hexane and isopropyl alcohol is 90: 1; The enantioselectivity e e% value that obtains epoxides is up to 99.4%, and described catalyst can be recycled.
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