CN113307978A - Inorganic microsphere modified by cyclodextrin grafted chiral proline metal complex and preparation method and application thereof - Google Patents
Inorganic microsphere modified by cyclodextrin grafted chiral proline metal complex and preparation method and application thereof Download PDFInfo
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- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 69
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 239000004005 microsphere Substances 0.000 title claims abstract description 49
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 title claims abstract description 34
- -1 proline metal complex Chemical class 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 25
- 229910052751 metal Inorganic materials 0.000 claims abstract description 21
- 239000002184 metal Substances 0.000 claims abstract description 21
- 239000000047 product Substances 0.000 claims description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 238000001035 drying Methods 0.000 claims description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 30
- 238000005406 washing Methods 0.000 claims description 29
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 26
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 25
- 239000007787 solid Substances 0.000 claims description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 18
- 229920000768 polyamine Polymers 0.000 claims description 18
- 239000003208 petroleum Substances 0.000 claims description 17
- BENKAPCDIOILGV-RQJHMYQMSA-N (2s,4r)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(O)=O BENKAPCDIOILGV-RQJHMYQMSA-N 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- 238000000926 separation method Methods 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000012043 crude product Substances 0.000 claims description 10
- 239000000284 extract Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 claims description 5
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 claims description 5
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 4
- FRGPKMWIYVTFIQ-UHFFFAOYSA-N triethoxy(3-isocyanatopropyl)silane Chemical compound CCO[Si](OCC)(OCC)CCCN=C=O FRGPKMWIYVTFIQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 2
- 238000006053 organic reaction Methods 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 25
- 238000003786 synthesis reaction Methods 0.000 abstract description 24
- 150000003147 proline derivatives Chemical class 0.000 abstract description 19
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 abstract description 15
- 239000000377 silicon dioxide Substances 0.000 abstract description 12
- 230000003197 catalytic effect Effects 0.000 abstract description 11
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 abstract description 4
- 235000012239 silicon dioxide Nutrition 0.000 abstract description 4
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 3
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002131 composite material Substances 0.000 abstract 3
- 230000004048 modification Effects 0.000 abstract 2
- 238000012986 modification Methods 0.000 abstract 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical class O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 abstract 1
- 125000003277 amino group Chemical group 0.000 abstract 1
- 238000003980 solgel method Methods 0.000 abstract 1
- 229960002429 proline Drugs 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000007821 HATU Substances 0.000 description 11
- 229910052681 coesite Inorganic materials 0.000 description 8
- 229910052906 cristobalite Inorganic materials 0.000 description 8
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 229910052682 stishovite Inorganic materials 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 229910052905 tridymite Inorganic materials 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 5
- 238000005575 aldol reaction Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 229930182821 L-proline Natural products 0.000 description 3
- MMNLHUHQFDVPSQ-UHFFFAOYSA-N N=C=O.CCO[Si](OCC)(OCC)C(C)C Chemical compound N=C=O.CCO[Si](OCC)(OCC)C(C)C MMNLHUHQFDVPSQ-UHFFFAOYSA-N 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- BJDLPDPRMYAOCM-UHFFFAOYSA-N triethoxy(propan-2-yl)silane Chemical compound CCO[Si](OCC)(OCC)C(C)C BJDLPDPRMYAOCM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002444 silanisation Methods 0.000 description 2
- 125000000174 L-prolyl group Chemical class [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 239000006087 Silane Coupling Agent Substances 0.000 description 1
- 229910002808 Si–O–Si Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000003622 immobilized catalyst Substances 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002114 nanocomposite Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/001—Macromolecular compounds containing organic and inorganic sequences, e.g. organic polymers grafted onto silica
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2213—At least two complexing oxygen atoms present in an at least bidentate or bridging ligand
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- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/50—Catalysts, in general, characterised by their form or physical properties characterised by their shape or configuration
- B01J35/51—Spheres
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
- B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
- B01J2231/342—Aldol type reactions, i.e. nucleophilic addition of C-H acidic compounds, their R3Si- or metal complex analogues, to aldehydes or ketones
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Abstract
The invention discloses an inorganic microsphere modified by a cyclodextrin grafted chiral proline metal complex, a preparation method and application thereof, and belongs to the technical field of organic synthesis. The invention firstly prepares inorganic microspheres by a sol-gel method, then carries out surface modification on the inorganic microspheres, grafts proline derivatives, and then carries out modification with 6-amino group modified cyclodextrin (a)α‑CD、βCondensing the derivatives of-CD and gamma-CD) to obtain a product containing inorganic microsphere parent nucleus (silicon dioxide and ferroferric oxide), chiral 4-hydroxyproline derivatives and amino groups with different chain lengthsModified cyclodextrin three-component composite material. Finally, the nano metal is immobilized on the composite material by utilizing an immobilization means, and the inorganic microsphere catalyst modified by the cyclodextrin-grafted chiral proline metal complex is obtained. The composite material prepared by the invention simultaneously contains nano metal, inorganic microspheres, chiral proline and functional cyclodextrin structural units, has the advantages of high catalytic activity, high stereoselectivity, environmental protection and the like, and can be used as a green catalyst.
Description
Technical Field
The invention relates to an inorganic microsphere modified by cyclodextrin grafted chiral proline metal complex, a preparation method and application thereof, belonging to the technical field of organic synthesis.
Background
Proline and its derivatives are used as organic chiral catalysts and widely applied to asymmetric organic synthesis. The catalyst has the advantages of simple structure, abundant sources, high selectivity and the like, but still has the defects of large catalyst consumption, difficult recovery, incapability of recycling and the like. In recent years, with the development of immobilization technology, immobilized proline and its derivatives have attracted much attention, and silanization is one of effective methods for immobilizing L-proline and its derivatives on inorganic nanoparticle carriers, in which a "molecular bridge" is formed between inorganic microspheres and L-proline and its derivatives by using a bifunctional silane coupling agent. The immobilized catalyst prepared by the silanization reaction has higher catalyst immobilization amount, but the catalytic sites are not uniformly distributed, so that the catalytic activity and the selectivity are not ideal, and a stabilizer is required to be added to weaken the aggregation degree of the catalytic sites. The cyclodextrin (alpha-CD, beta-CD, gamma-CD) has a hollow truncated cone structure with relatively hydrophilic outside and relatively hydrophobic inside, and can include proline to form a host-guest embedded catalyst. Cyclodextrin immobilized (4S) -phenoxy- (S) -proline catalysts have been synthesized in one step by a thermal reflux process in ethanol/water. But still has some shortcomings, such as unstable inclusion compound, and the like, so that the development of a high-efficiency, high-stereoselectivity, concise and green nano-catalytic system has important academic significance and application value.
Disclosure of Invention
The invention aims to provide inorganic microspheres modified by cyclodextrin-grafted chiral proline metal complexes, wherein the cyclodextrin comprises alpha-CD, beta-CD and gamma-CD; the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex simultaneously contains nano metal, inorganic microsphere, chiral proline and functional cyclodextrin structural units, has the advantages of easy separation and recovery, high catalytic activity, high stereoselectivity, environmental protection and the like, can be used as a green catalyst, and has a molecular structure general formula as follows:
wherein
n-1 is α -CD; n-2 is β -CD; and n-3 is gamma-CD.
Wherein R groups are each R1、R2、R3、R4In the above-mentioned manner, the first and second substrates are,
the invention also aims to provide a preparation method of the cyclodextrin grafted chiral proline metal complex modified inorganic microsphere, which has the advantages of reasonable process, simple operation and low cost, and comprises the following specific steps:
(1) sequentially adding Boc-L-hydroxyproline, benzyl bromide, potassium carbonate and anhydrous N, N-Dimethylformamide (DMF) into a reactor at 0 ℃ according to the mole ratio of Boc-L-hydroxyproline to benzyl bromide to potassium carbonate of 1 (1.2-1.6) to react for 10-48 hours at 0 ℃ to generate a mixed product A, extracting the mixed product A with ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and then carrying out separation and purification to obtain the Boc-L-hydroxyproline derivative: 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylate.
(2) According to the molar ratio of 1 (1.2-1.6) to 1.8-2.6 of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester, isocyanatopropyltriethoxysilane and triethylamine, sequentially adding 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester, isocyanatopropyltriethoxysilane, triethylamine and anhydrous Tetrahydrofuran (THF) into a reactor, carrying out reflux reaction for 10-48 hours to generate a mixed product B, extracting the mixed product B with ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and then carrying out separation and purification to obtain a product d.
(3) And sequentially adding the product d, the target carbon and the methanol into a reactor according to the molar ratio of the product d to the target carbon to the methanol of 1 (0.2-0.6), reacting for 5-15 hours at 25 ℃ under the condition of hydrogen to generate a mixed product C, filtering, and spin-drying to obtain a product e.
(4) Sequentially adding the product e, the inorganic microspheres, the toluene and the water into a reactor according to the mass ratio of the product e to the inorganic microspheres (1-2) to 1, the solid-liquid ratio of the product e to the toluene to water (mL: microlitre: 1) (55-75) to (35-55), carrying out reflux reaction for 18-48 hours to generate a mixed product D, filtering by using a sand core funnel to obtain a solid D, washing and drying to obtain a product f.
(5) According to the molar ratio of the product f to polyamine cyclodextrin and 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea Hexafluorophosphate (HATU) to N, N-Diisopropylethylamine (DIPEA) being 1:1 (1.6-2.6) to (4-8), firstly adding the product f into anhydrous N, N-Dimethylformamide (DMF), adding DIPEA under the ice bath condition, stirring for 15min, then adding HATU, stirring for 3 h at room temperature, adding polyamine cyclodextrin, reacting for 10-48 h at room temperature to generate a mixed product E, dropwise adding the mixed product E into an acetone solution to obtain a solid E, washing the solid E with acetone and water, and drying to obtain a product g.
(6) Sequentially adding the product g, trifluoroacetic acid and dichloromethane into a reactor according to the ratio of the solid-liquid ratio mol: mL: mL of the product g to the dichloromethane being 1:1 (3-7), reacting at room temperature for 2-5 hours to generate a mixed product F, spin-drying the solvent, neutralizing with potassium carbonate, washing with water, and drying to obtain a product h.
(7) And (3) sequentially adding the product h, the metal and toluene into a reactor according to the molar ratio of the product h to the metal of 1 (0.08-0.2), reacting at room temperature in a dark place for 24-72 hours to generate a mixed product G, filtering, washing with toluene and acetone, and drying to obtain the product i.
Preferably, the washing process of the solid D in the step (4) of the present invention is as follows: respectively washing with polar solvents from large to small, such as methanol, ethyl acetate, dichloromethane, petroleum ether and diethyl ether.
Preferably, in step (5) of the present invention, the polyamine cyclodextrin is one of amino cyclodextrin (α -CD, β -CD, γ -CD), ethylenediamine cyclodextrin (α -CD, β -CD, γ -CD), diethylenetriamine cyclodextrin (α -CD, β -CD, γ -CD), and triethylenetetramine cyclodextrin (α -CD, β -CD, γ -CD).
Preferably, the metal in step (7) of the present invention is a transition metal, such as Cu, Pd, Fe, etc.
The inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex contains nano metal, inorganic microspheres, chiral proline and a functional cyclodextrin structural unit, can be used as a green catalyst to be applied to asymmetric organic reactions (such as Aldol reaction, Michael addition reaction, Mannich reaction and the like), and as the immobilization technology is mature day by day and new carrier materials appear, the immobilized proline and derivatives thereof are believed to have very wide application prospects as efficient green chiral catalysts.
The invention has the beneficial effects that:
(1) the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex simultaneously contains nano metal, inorganic microspheres, chiral proline and functional cyclodextrin structural units, and when cyclodextrin and small organic molecules are simultaneously grafted onto the inorganic microspheres, the water solubility of a catalyst can be well controlled, and a stable environment can be provided for a substrate of a reaction.
(2) The inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex synthesized by the invention has the advantages of high catalytic activity, high stereoselectivity, easy separation and recovery and environmental protection, and promotes the development of the field of green catalysts.
(3) The inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex, which is synthesized by the invention, contains inorganic microspheres, so that the inorganic microsphere has larger specific surface area, good dispersibility, biocompatibility, modifiability and low toxicity, can be designed and provided with a plurality of catalytic sites, and can also be used as a load template; in addition, the silicon dioxide/ferroferric oxide inorganic microspheres are easy to separate, and particularly, the ferroferric oxide can be easily separated from the outside by using a permanent magnet, so that the catalyst can be easily separated;
(4) the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex, which is synthesized by the invention, contains cyclodextrin with a unique structure of external hydrophilicity and internal hydrophobicity, so that the effects of selective molecular recognition, solubilization and stability enhancement on a substrate, effective stabilization of nano metal and the like can be realized;
(5) the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex, which is synthesized by the invention, has high activity and high selectivity of a homogeneous catalyst and high cyclicity of the heterogeneous catalyst due to the fact that the inorganic microsphere contains immobilized chiral L-proline derivatives, and can be used for selectively catalyzing asymmetric organic chemical reactions in a water phase in a circulating and efficient manner.
Drawings
FIG. 1 is a process flow diagram of the present invention;
FIG. 2 g0The structural formula (1);
FIG. 3 g3The structural formula (1);
FIG. 4 i0The structural formula (1);
FIG. 5 i3The structural formula (1);
FIG. 6 SiO2,f,g0,g3An infrared spectrum of (1);
FIG. 7 a, b, c are SiO2、g0、g3A TEM image of (a).
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to the examples.
Example 1
The synthesis of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester specifically comprises the following steps: adding Boc-L-hydroxyproline, benzyl bromide, potassium carbonate and anhydrous DMF (the addition amount of the anhydrous DMF is not limited and can ensure that the raw materials are just dissolved) into a reactor at the temperature of 0 ℃, reacting for 10 hours at room temperature to obtain a mixed product A, extracting the mixed product A with ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and carrying out column chromatography separation and purification, wherein an eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1:4, so as to obtain the Boc-L-hydroxyproline derivative: (2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylate) according to the formula:
the product nuclear magnetic resonance spectrum characterization data are as follows:
1H NMR(600MHz,CDCl3)δ:7.33(5H,brs),5.25-5.05(2H,m),4.50-4.41(1H, m),3.61-3.03(3H,overlap),2.31-2.24(1H,m),2.07-1.98(1H,m),1.43and 1.32(9H, s)。
example 2
The synthesis of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester specifically comprises the following steps: adding Boc-L-hydroxyproline, benzyl bromide, potassium carbonate and anhydrous DMF (the addition amount of the anhydrous DMF is not limited and can ensure that the raw materials are just dissolved) into a reactor according to the mol ratio of Boc-L-hydroxyproline, benzyl bromide and potassium carbonate of 1:1.4:2.2 at the temperature of 1 ℃, reacting for 29 hours at room temperature to obtain a mixed product A, extracting the mixed product A by using ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and carrying out column chromatography separation and purification, wherein an eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1: 4; namely obtaining Boc-L-hydroxyproline derivative (2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic ester) with the reaction formula
The product nuclear magnetic resonance spectrum characterization data are as follows:
1H NMR(600MHz,CDCl3)δ:7.33(5H,brs),5.25-5.05(2H,m),4.50-4.41(1H, m),3.61-3.03(3H,overlap),2.31-2.24(1H,m),2.07-1.98(1H,m),1.43and 1.32(9H, s)。
example 3
Synthesis of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylate: adding Boc-L-hydroxyproline, benzyl bromide, potassium carbonate and anhydrous DMF (the addition amount of the anhydrous DMF is not limited and can ensure that the raw materials are just dissolved) into a reactor according to the mol ratio of Boc-L-hydroxyproline, benzyl bromide and potassium carbonate of 1:1.6:2.6 at the temperature of 0 ℃, reacting for 48 hours at room temperature to obtain a mixed product A, extracting the mixed product A by using ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and then carrying out column chromatography separation and purification, wherein an eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1: 4; namely obtaining Boc-L-hydroxyproline derivative (2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic ester) with the reaction formula
The product nuclear magnetic resonance spectrum characterization data are as follows:
1H NMR(600MHz,CDCl3)δ:7.33(5H,brs),5.25-5.05(2H,m),4.50-4.41(1H, m),3.61-3.03(3H,overlap),2.31-2.24(1H,m),2.07-1.98(1H,m),1.43and 1.32(9H, s)。
example 4
The synthesis of the silanized proline derivative specifically comprises the following steps:
refluxing and reacting the product 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester obtained in example 1,2 or 3 with isopropyltriethoxysilane, triethylamine and anhydrous THF for 10 hours (the addition of anhydrous THF is not limited and the raw materials can be just dissolved) to obtain a mixed product B, extracting the mixed product B with ethyl acetate, combining the extracts, washing and drying, distilling under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain d, wherein the reaction formula is
Wherein, the molar ratio of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester to isopropyltriethoxysilane isocyanate to triethylamine is 1:1.2:1.8, the eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1: 10.
The product nuclear magnetic resonance spectrum characterization data are as follows:1H NMR(600MHz,CDCl3)δ7.38–7.27(5H, m),5.50–4.86(4H,m),4.54–4.20(1H,m),3.81(3H,d),3.75–3.61(4H,m),3.33 –2.86(1H,m),2.53–2.00(2H,m),1.67–1.56(3H,m),1.44(3H,s),1.33(6H,d), 1.22(9H,s),0.75–0.47(2H,m)。
example 5
The synthesis of the silanized proline derivative specifically comprises the following steps:
refluxing and reacting the product 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester obtained in example 1,2 or 3 with isopropyltriethoxysilane, triethylamine and anhydrous THF for 29 hours (the addition of anhydrous THF is not limited and the raw materials can be just dissolved) to obtain a mixed product B, extracting the mixed product B with ethyl acetate, combining the extracts, washing and drying, distilling under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain d, wherein the reaction formula is
Wherein, the molar ratio of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester to isopropyltriethoxysilane isocyanate to triethylamine is 1:1.4:2.2, the eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1: 10.
The product nuclear magnetic resonance spectrum characterization data are as follows:1H NMR(600MHz,CDCl3)δ7.38–7.27(5H, m),5.50–4.86(4H,m),4.54–4.20(1H,m),3.81(3H,d),3.75–3.61(4H,m),3.33 –2.86(1H,m),2.53–2.00(2H,m),1.67–1.56(3H,m),1.44(3H,s),1.33(6H,d), 1.22(9H,s),0.75–0.47(2H,m)。
example 6
The synthesis of the silanized proline derivative specifically comprises the following steps:
refluxing the product 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester obtained in example 1,2 or 3 with isopropyltriethoxysilane, triethylamine and anhydrous THF for 48 h (the addition of anhydrous THF is not limited to make the raw materials just dissolve) to obtain mixed product B, extracting mixed product B with ethyl acetate, mixing the extracts, washing, drying, distilling under reduced pressure to obtain crude product, and purifying by column chromatography to obtain d
Wherein, the molar ratio of 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester to isopropyltriethoxysilane isocyanate to triethylamine is 1:1.6:2.6, the eluent for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1: 10.
The product nuclear magnetic resonance spectrum characterization data are as follows:1H NMR(600MHz,CDCl3)δ7.38–7.27(5H, m),5.50–4.86(4H,m),4.54–4.20(1H,m),3.81(3H,d),3.75–3.61(4H,m),3.33 –2.86(1H,m),2.53–2.00(2H,m),1.67–1.56(3H,m),1.44(3H,s),1.33(6H,d), 1.22(9H,s),0.75–0.47(2H,m)。
example 7
The synthesis of the proline derivative e specifically comprises the following steps:
adding the product d obtained in the example 4 or 5 or 6, target carbon and methanol into a reactor in sequence at 25 ℃ under the condition of hydrogen to react for 5 hours to generate a mixed product C, filtering and spin-drying to obtain e, wherein the reaction formula is
Wherein the molar ratio of the product d to the target carbon is 1: 0.2.
Example 8
The synthesis of the proline derivative e specifically comprises the following steps:
adding the product d obtained in the example 4 or 5 or 6, target carbon and methanol into a reactor in sequence at 25 ℃ under the condition of hydrogen to react for 10 hours to generate a mixed product C, filtering and spin-drying to obtain e, wherein the reaction formula is
Wherein the molar ratio of the product d to the target carbon is 1: 0.4.
Example 9
The synthesis of the proline derivative e specifically comprises the following steps:
adding the product d obtained in the example 4 or 5 or 6, target carbon and methanol into a reactor in sequence at 25 ℃ under the condition of hydrogen to react for 15 hours to generate a mixed product C, filtering and spin-drying to obtain e, wherein the reaction formula is
Wherein the molar ratio of the product d to the target carbon is 1: 0.6.
Example 10
The synthesis of the proline derivative f specifically comprises the following steps:
the product e obtained in the embodiment 7, 8 or 9 reacts with inorganic microspheres, toluene and water under reflux for 18 hours to generate a mixed product D, a sand core funnel is used for filtering to obtain a solid D, the solid D is respectively washed by solvents (methanol, ethyl acetate, dichloromethane, petroleum ether and diethyl ether) with large polarity to small polarity, and the solid D is dried to obtain the product f, wherein the reaction formula is shown in the specification
Wherein the mass ratio of e to the inorganic microspheres is 1: 1; the solid-liquid ratio g, mL and mu L of the e to the toluene and water is 1:55: 35.
Example 11
The synthesis of the proline derivative f specifically comprises the following steps:
the product e obtained in the embodiment 7, 8 or 9 is reacted with inorganic microspheres, toluene and water for 29 hours under reflux to generate a mixed product D, a sand core funnel is used for filtering to obtain a solid D, the solid D is respectively washed by solvents (methanol, ethyl acetate, dichloromethane, petroleum ether and diethyl ether) with large polarity to small polarity, and the solid D is dried to obtain the product f, wherein the reaction formula is shown in the specification
Wherein the mass ratio of e to the inorganic microspheres is 1.5: 1; the solid-liquid ratio g, mL and mu L of the e to the toluene and the water is 1:65: 45.
Example 12
The synthesis of the proline derivative f specifically comprises the following steps:
and (2) carrying out reflux reaction on the product e obtained in the embodiment 7, 8 or 9 with inorganic microspheres, toluene and water for 48 hours to obtain a mixed product D, filtering the mixed product D by using a sand core funnel to obtain a solid D, washing the solid D by using solvents (methanol, ethyl acetate, dichloromethane, petroleum ether and diethyl ether) with large polarity and small polarity respectively in sequence, and drying to obtain a product f, wherein the reaction formula is as follows:
wherein the mass ratio of e to the inorganic microspheres is 2: 1; the solid-liquid ratio g: mL: mu L of the e to toluene and water is 1:75: 55.
Example 13
The synthesis of the proline derivative g specifically comprises the following steps:
reacting the product f obtained in the example 10 or 11 or 12 with polyamine cyclodextrin, HATU, DIPEA and anhydrous DMF at room temperature for 12 hours to generate a mixed product E, dropwise adding the mixed product E into an acetone solution to obtain a solid E, washing the solid E with acetone and water, and drying to obtain g, wherein the reaction formula is as follows:
wherein the molar ratio of f to the polyamine cyclodextrin, HATU and DIPEA is 1:1:1.6: 4.
Wherein, the feeding sequence is as follows: adding f into anhydrous DMF, adding DIPEA under the ice bath condition, stirring for 15min, then adding HATU, stirring for 3 hours at room temperature, adding polyamine cyclodextrin, and reacting at room temperature to generate a mixed product E; wherein the polyamine cyclodextrin is one of amino cyclodextrin, ethylenediamine cyclodextrin, diethylenetriamine cyclodextrin and triethylenetetramine cyclodextrin.
Example 14
The synthesis of the proline derivative g specifically comprises the following steps:
reacting the product f obtained in the example 10, 11 or 12 with polyamine cyclodextrin, HATU, DIPEA and anhydrous DMF at room temperature for 24 hours to generate a mixed product E, dropwise adding the mixed product E into an acetone solution to obtain a solid E, washing the solid E with acetone and water, and drying to obtain g, wherein the reaction formula is as follows:
wherein the molar ratio of f to the polyamine cyclodextrin, HATU and DIPEA is 1:1:2.1: 6.
Wherein, the feeding sequence is as follows: adding f into anhydrous DMF, adding DIPEA under the ice bath condition, stirring for 15min, then adding HATU, stirring for 3 hours at room temperature, adding polyamine cyclodextrin, and reacting at room temperature to generate a mixed product E; wherein the polyamine cyclodextrin is one of amino cyclodextrin, ethylenediamine cyclodextrin, diethylenetriamine cyclodextrin and triethylenetetramine cyclodextrin.
Example 15
The synthesis of the proline derivative g specifically comprises the following steps:
reacting the product f obtained in the example 10, 11 or 12 with polyamine cyclodextrin, HATU, DIPEA and anhydrous DMF at room temperature for 48 hours to generate a mixed product E, dropwise adding the mixed product E into an acetone solution to obtain a solid E, washing the solid E with acetone and water, and drying to obtain g, wherein the reaction formula is as follows:
wherein the molar ratio of f to the polyamine cyclodextrin, HATU and DIPEA is 1:1:2.6: 8.
Wherein, the feeding sequence is as follows: adding f into anhydrous DMF, adding DIPEA under the ice bath condition, stirring for 15min, then adding HATU, stirring for 3 hours at room temperature, adding polyamine cyclodextrin, and reacting at room temperature to generate a mixed product E; wherein the polyamine cyclodextrin is one of amino cyclodextrin, ethylenediamine cyclodextrin, diethylenetriamine cyclodextrin and triethylenetetramine cyclodextrin.
In examples 13 to 15, g is when m is 00The structural formula of (A) is shown in figure 2; when m is equal to 3, g3The structural formula of (A) is shown in figure 3; FIG. 6 is SiO2，f，g0，g3The infrared spectrum of (2) can be seen from the graph at 1095 cm-1The strong absorption peak is attributed to the stretching vibration peak of Si-O-Si, which shows that the material contains SiO2. With SiO2Comparison with g4、g1F in the infrared spectrum of 1530cm-1A new peak appears to the left and right due to the bending vibration of the N-H bond in proline. This result indicates that Boc-L-hydroxyproline has been successfully grafted to SiO2Without the original structure of the inorganic nano-microspheres being destroyed. In FIG. 7, a, b and c are SiO2、g0、g3The TEM image shows that the nano composite material prepared by the invention has better spherical morphology and regular structure. In SiO2After proline and cyclodextrin groups are introduced into the surface of the silicon dioxide film, the overall appearance of the silicon dioxide film is similar to that of SiO alone2In contrast, inorganic nanospheres (g)0、g3) Aggregation occurred, but there was no significant increase in size, g0、g3The average grain diameter of the nano-microspheres is about 200 nm.
Example 16
The synthesis of the proline derivative h specifically comprises the following steps:
g of the product obtained in example 13 or 14 or 15 is reacted with a dichloromethane solution of trifluoroacetic acid for 2 hours at room temperature to form a mixed product F, the solvent is dried by spinning, neutralized with potassium carbonate, washed with water, and dried to obtain h, the reaction formula is as follows:
wherein the solid-liquid ratio of g to trifluoroacetic acid and dichloromethane is 1:1:3, wherein the mol: mL: mL ratio is the solid-liquid ratio of g to trifluoroacetic acid and dichloromethane.
Example 17
The synthesis of the proline derivative h specifically comprises the following steps:
g of the product obtained in example 13 or 14 or 15 is reacted with a dichloromethane solution of trifluoroacetic acid for 4 hours at room temperature to form a mixed product F, the solvent is dried by spinning, neutralized with potassium carbonate, washed with water, and dried to obtain h, the reaction formula is as follows:
wherein the solid-liquid ratio of g to trifluoroacetic acid and dichloromethane is 1:1:5, wherein the mol: mL: mL ratio is 1:1: 5.
Example 18
The synthesis of the proline derivative h specifically comprises the following steps:
g of the product obtained in example 13 or 14 or 15 is reacted with a dichloromethane solution of trifluoroacetic acid at room temperature for 6 hours to give a mixed product F, the solvent is dried by spinning, neutralized with potassium carbonate, washed with water and dried to obtain h, the reaction formula is:
wherein the solid-liquid ratio of g to trifluoroacetic acid and dichloromethane is 1:1:7, wherein the mol: mL: mL ratio is 1:1: 7.
Example 19
The synthesis of the proline derivative i specifically comprises the following steps:
and (2) reacting the product obtained in the example 16, 17 or 18 with metal and toluene at room temperature in a dark place for 24 hours to generate a mixed product G, filtering, washing by using a large amount of toluene and acetone, and drying to obtain the compound I, wherein the reaction formula is as follows:
wherein the molar ratio of h to metal is 1: 0.08.
Example 20
The synthesis of the proline derivative i specifically comprises the following steps:
and (2) reacting the product obtained in the example 16, 17 or 18 with metal and toluene at room temperature in a dark place for 48 hours to generate a mixed product G, filtering, washing by using a large amount of toluene and acetone, and drying to obtain the compound I, wherein the reaction formula is as follows:
wherein the molar ratio of h to metal is 1: 0.14.
Example 21
The synthesis of the proline derivative i specifically comprises the following steps:
and (3) reacting the product h obtained in the example 16, 17 or 18 with metal and toluene at room temperature in a dark place for 72 hours to generate a mixed product G, filtering, washing by using a large amount of toluene and acetone, and drying to obtain the compound I, wherein the reaction formula is as follows:
wherein the molar ratio of h to metal is 1: 0.2.
Example 22
Inorganic microsphere catalyst (i) modified by cyclodextrin grafted chiral proline metal complex0) The method is used for catalyzing asymmetric Aldol reaction in a water phase, and p-nitrobenzaldehyde and cyclohexanone are selected as Aldol reaction raw materials, and the method comprises the following specific steps:
adding p-nitrobenzaldehyde and cyclohexanone to water, then adding catalyst (i)0) Reacting at 80 ℃ for 48 hours to obtain a corresponding product; wherein the molar consumption of the inorganic microsphere catalyst modified by the cyclodextrin grafted chiral proline metal complex is 20 percent of the molar quantity of the p-nitrobenzaldehyde, the yield is more than 90 percent, and the ee value is 80 percent; after the catalyst is filtered and dried, the catalytic experiment is continued, the catalyst is repeatedly recycled for 4 times, and the catalytic efficiency is not reduced.
Example 23
Inorganic microsphere catalyst (i) modified by cyclodextrin grafted chiral proline metal complex3) The method is used for catalyzing asymmetric Aldol reaction in a water phase, and p-nitrobenzaldehyde and cyclohexanone are selected as Aldol reaction raw materials, and the method comprises the following specific steps:
adding p-nitrobenzaldehyde and cyclohexanone to water, then adding catalyst (i)3) Reacting at 80 ℃ for 48 hours to obtain a corresponding product; wherein the molar dosage of the inorganic microsphere catalyst modified by the cyclodextrin grafted chiral proline metal complex is p-nitroThe yield is more than 91 percent and the ee value is 82 percent, wherein the molar weight of the benzaldehyde is 20 percent; after the catalyst is filtered and dried, the catalytic experiment is continued, the catalyst is repeatedly recycled for 4 times, and the catalytic efficiency is not reduced.
Claims (6)
1. An inorganic microsphere modified by cyclodextrin grafted chiral proline metal complex is characterized in that the general formula of the molecular structure is as follows:
wherein
n-1 is α -CD; n-2 is β -CD; n-3 is γ -CD;
wherein R groups are each R1、R2、R3、R4In the above-mentioned manner, the first and second substrates are,
2. the preparation method of the cyclodextrin grafted chiral proline metal complex modified inorganic microsphere as claimed in claim 1, which is characterized by comprising the following steps:
(1) sequentially adding Boc-L-hydroxyproline, benzyl bromide, potassium carbonate and anhydrous N, N-dimethylformamide into a reactor at 0 ℃ according to the mole ratio of Boc-L-hydroxyproline to benzyl bromide to potassium carbonate of 1 (1.2-1.6) to (1.8-2.6) to react for 10-48 hours to generate a mixed product A, extracting the mixed product A by using ethyl acetate, combining extract liquor, washing and drying, distilling under reduced pressure to obtain a crude product, and then separating and purifying to obtain the Boc-L-hydroxyproline derivative: 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylate;
(2) adding 2-benzyl-1- (tert-butyl) (2R,4S) -4-hydroxypyrrolidine-1, 2-dicarboxylic acid ester, isocyanatopropyltriethoxysilane and triethylamine in a molar ratio of 1 (1.2-1.6) to (1.8-2.6) into a reactor in sequence, carrying out reflux reaction for 10-48 hours to generate a mixed product B, extracting the mixed product B with ethyl acetate, combining extract liquor, washing and drying, carrying out reduced pressure distillation to obtain a crude product, and then carrying out separation and purification to obtain a product d;
(3) sequentially adding the product d, the target carbon and the methanol into a reactor according to the molar ratio of the product d to the target carbon to the methanol of 1 (0.2-0.6), reacting for 5-15 hours at 25 ℃ under the condition of hydrogen to generate a mixed product C, filtering, and spin-drying to obtain a product e;
(4) sequentially adding the product e, the inorganic microspheres, toluene and water into a reactor according to the mass ratio of the product e to the inorganic microspheres (1-2) to 1, the solid-liquid ratio of the product e to the toluene to water (mL: microlitre is 1 (55-75)) to (35-55), carrying out reflux reaction for 18-48 hours to generate a mixed product D, filtering by using a sand core funnel to obtain a solid D, washing and drying to obtain a product f;
(5) adding the product f into anhydrous N, N-dimethylformamide according to the molar ratio of the product f to the polyamine cyclodextrin to the 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea hexafluorophosphate to the N, N-diisopropylethylamine being 1:1 (1.6-2.6) to (4-8), adding N, N-diisopropylethylamine for stirring for 15min under an ice bath condition, adding 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea hexafluorophosphate, stirring for 3 hours at room temperature, adding the polyamine cyclodextrin, reacting for 10-48 hours at room temperature to generate a mixed product E, dropwise adding the mixed product E into an acetone solution to obtain a solid E, washing the solid E with acetone and water, drying to obtain a product g;
(6) sequentially adding the product g, trifluoroacetic acid and dichloromethane into a reactor according to the ratio of the solid-liquid ratio mol: mL: mL of the product g to the dichloromethane of 1:1 (3-6), reacting at room temperature for 2-5 hours to generate a mixed product F, spin-drying the solvent, neutralizing with potassium carbonate, washing with water, and drying to obtain a product h;
(7) and (3) sequentially adding the product h, the metal and toluene into a reactor according to the molar ratio of the product h to the metal of 1 (0.08-0.2), reacting at room temperature in a dark place for 24-72 hours to generate a mixed product G, filtering, washing with toluene and acetone, and drying to obtain the product i.
3. The method for preparing the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex according to claim 2, which is characterized in that: the washing process of the solid D in the step (4) comprises the following steps: respectively washing with polar solvents from large to small, such as methanol, ethyl acetate, dichloromethane, petroleum ether and diethyl ether.
4. The method for preparing the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex according to claim 2, which is characterized in that: in the step (5), the polyamine cyclodextrin is one of amino cyclodextrin, ethylenediamine cyclodextrin, diethylenetriamine cyclodextrin and triethylenetetramine cyclodextrin.
5. The method for preparing the inorganic microsphere modified by the cyclodextrin grafted chiral proline metal complex according to claim 2, which is characterized in that: the metal in the step (7) is a transition metal.
6. The cyclodextrin grafted chiral proline metal complex modified inorganic microspheres of claim 1 for use as a catalyst in asymmetric organic reactions.
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| JP2007182419A (en) * | 2005-12-07 | 2007-07-19 | Tokyo Univ Of Science | Proline derivative and optically active anti-selection promoting catalyst |
| CN102909070A (en) * | 2012-10-30 | 2013-02-06 | 河南师范大学 | Load type chiral catalyst and preparation method thereof |
| CN103601823A (en) * | 2013-11-29 | 2014-02-26 | 北京化工大学 | Preparation method for beta-cyclodextrin chiral stationary phase |
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| JP2007182419A (en) * | 2005-12-07 | 2007-07-19 | Tokyo Univ Of Science | Proline derivative and optically active anti-selection promoting catalyst |
| CN102909070A (en) * | 2012-10-30 | 2013-02-06 | 河南师范大学 | Load type chiral catalyst and preparation method thereof |
| CN103601823A (en) * | 2013-11-29 | 2014-02-26 | 北京化工大学 | Preparation method for beta-cyclodextrin chiral stationary phase |
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