CN102950025B - Asymmetric hydrogenation catalyst of imine and its use - Google Patents
Asymmetric hydrogenation catalyst of imine and its use Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 38
- 150000002466 imines Chemical class 0.000 title claims abstract description 30
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 title claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 26
- 150000001412 amines Chemical class 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 238000011065 in-situ storage Methods 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 7
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 4
- ORBBTCHHNMWMCP-UHFFFAOYSA-K cycloocta-1,5-diene trichloroiridium Chemical compound [Ir](Cl)(Cl)Cl.C1=CCCC=CCC1 ORBBTCHHNMWMCP-UHFFFAOYSA-K 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 239000000575 pesticide Substances 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 1
- WVQBLGZPHOPPFO-LBPRGKRZSA-N (S)-metolachlor Chemical compound CCC1=CC=CC(C)=C1N([C@@H](C)COC)C(=O)CCl WVQBLGZPHOPPFO-LBPRGKRZSA-N 0.000 abstract 1
- 239000005617 S-Metolachlor Substances 0.000 abstract 1
- GQENPXQJRUSMDY-UHFFFAOYSA-N [Ir+].ClC1=CCCC=CCC1 Chemical group [Ir+].ClC1=CCCC=CCC1 GQENPXQJRUSMDY-UHFFFAOYSA-N 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 239000002994 raw material Substances 0.000 description 11
- 238000004817 gas chromatography Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 7
- 125000001453 quaternary ammonium group Chemical group 0.000 description 7
- 229940107816 ammonium iodide Drugs 0.000 description 6
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 4
- JJVKJJNCIILLRP-UHFFFAOYSA-N 2-ethyl-6-methylaniline Chemical compound CCC1=CC=CC(C)=C1N JJVKJJNCIILLRP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- -1 aldehyde compound Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- CUZLJOLBIRPEFB-UHFFFAOYSA-N 1-methoxypropan-2-one Chemical compound COCC(C)=O CUZLJOLBIRPEFB-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000011982 enantioselective catalyst Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 150000008365 aromatic ketones Chemical class 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical group OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 1
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- IIQIBCQCZQPBFE-UHFFFAOYSA-N [Li]CCCC.CN(C)CCN(C)C Chemical compound [Li]CCCC.CN(C)CCN(C)C IIQIBCQCZQPBFE-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- LRRJQNMXIDXNIM-UHFFFAOYSA-M benzyl(trimethyl)azanium;iodide Chemical compound [I-].C[N+](C)(C)CC1=CC=CC=C1 LRRJQNMXIDXNIM-UHFFFAOYSA-M 0.000 description 1
- 239000012018 catalyst precursor Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910001505 inorganic iodide Inorganic materials 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an asymmetric hydrogenation catalyst of imine. The asymmetric hydrogenation catalyst of imine is an in-situ mixture of a chiral ligand having a structure represented by formula I and a metallic iridium complex, or a complex generated from the chiral ligand of the formula I and the metallic iridium complex, wherein R1 in the formula I is a C1-C5 alkyl group, R2, R3 and R4 in the formula I can be same or different from each other, and are respectively selected from C1-C6 straight-chain or branched-chain alkyl groups, and aryl groups substituted by zero-three C-C6 alkyl groups, and n in the formula I is 1-6; and the metallic iridium complex is chloro-1,5-cyclooctadiene iridium(I) dimer. The asymmetric hydrogenation catalyst of imine has the advantages of easy large-scale preparation of the ligand, simple operation, and realization of continuous operation, is suitable for the large-scale preparation of chiral amine, and is especially suitable for preparing the chiral intermediate of a pesticide S-metolachlor.
Description
Technical Field
The invention belongs to the field of organic synthesis, relates to a bifunctional asymmetric catalyst with a novel structure and application of the catalyst in preparation of a chiral amine pesticide intermediate by imine asymmetric catalytic hydrogenation, and particularly relates to an imine asymmetric hydrogenation catalyst and application thereof.
Technical Field
Asymmetric hydrogenation of prochiral imines is one of the important methods for the synthesis of chiral amines, and many catalysts have been selected (Tang W and Zhang X, chem. rev., 2003, 103, 3029.). The selection and use of asymmetric catalysts are key to the success of the reaction, and at present, the catalysts either only have good enantioselectivity of products and low chemical activity, so that the practical utilization value is lost; or the catalyst has good chemical activity and low enantioselectivity, so that the use value is lost. Asymmetric hydrogenation is particularly difficult to achieve with good enantioselectivity of the product, since the open-chain imine is a mixture of cis and trans geometric isomers during synthesis, but the situation has changed in recent years. Patent (EP0691949B1) discloses the use of { (R) -1- [ (S) -2-diphenylphosphinomethane-based ] } ethyl-bis- (3, 5-dimethyl-phenyl) phosphine as ligand to form a catalyst precursor in situ with an iridium complex, in the presence of an acid and tetrabutylammonium iodide at 50 ℃ and 80 atm hydrogen, to catalyze the asymmetric hydrogenation of linear imines, which is reacted in an autoclave to give chiral amine intermediates up to 76% e.e (enantiomeric excess), meeting the requirements as intermediates for pesticides. However, the existing catalysts require the use of a large amount of quaternary ammonium iodide, which makes the post-treatment cumbersome and increases the cost.
Disclosure of Invention
The invention aims to provide a bifunctional asymmetric catalyst with a novel structure for asymmetric catalytic hydrogenation of imine, which meets the requirement of synthesizing a chiral intermediate of a pesticide by large-scale asymmetric catalytic hydrogenation, and particularly meets the requirement of preparing the chiral intermediate of a pesticide of Gordon.
The technical scheme of the invention is as follows:
an imine asymmetric hydrogenation catalyst is an in-situ mixture or a newly generated complex of a ferrocene-derived quaternary ammonium iodide salt chiral ligand with a diphosphine ligand and a metal iridium complex shown in a formula I:
in the formula: r1Is C1-C5An alkyl group; r2、R3、R4Can be the same or different and are respectively selected from C1-C6Straight or branched chain alkyl, 0-3C1-C6Alkyl-substituted aryl; n is 1-6;
the metal iridium complex is dimeric 1, 5-cyclooctadiene iridium chloride (cyclooctadiene abbreviated as DOC), and is commercially available or prepared according to a known method.
Preferred catalysts of the invention are: in the formula: r1Is C1-C3An alkyl group; r2、R3、R4Can be the same or different and are respectively selected from C1-C4Straight or branched chain alkyl, 0-2C1-C6Alkyl-substituted aryl; n is 1-4;
the preparation method of the catalyst comprises the following steps:
the preparation method of the catalyst is specifically exemplified by:
the method comprises the steps of taking diphosphine compounds such as { (R) -1- [ (S) -2-di-phenyl-phosphino-cyclopentadienyl iron group ] } -ethyl-di- (3, 5-dimethyl-phenyl) phosphine and the like as raw materials, reacting with 2.5 times of hydroborane to prepare a diphosphine-hydroborane compound, reacting with butyl lithium-tetramethyl ethylenediamine as a lithiating agent in situ to obtain a derivative aldehyde compound, reducing the compound in methanol by taking sodium borohydride as a reducing agent to obtain an alcohol compound, converting the alcohol into an iodide in situ, reacting the generated iodide with tributylamine to obtain a new diphosphine compound compounded with the hydroborane, and dissociating a ligand from the diethylamine before using the compound. The other ligands of formula I of the invention can be prepared by changing the raw materials in the same way.
The ligand reacts with dimeric 1, 5-cyclooctadiene iridium chloride and is used for preparing a complex in situ, the complex is directly used as a good asymmetric hydrogenation catalyst in asymmetric hydrogenation reaction, and the good practicability is achieved; the quaternary ammonium iodide salt does not need to be added under certain catalyst concentration. The dosage of the catalyst suitable for the method is 0.0002-0.3 mol% of the raw material imine; further preferably, the amount of the catalyst is 0.0005 to 0.1 mol% based on the starting imine. The catalyst of the invention is used for catalyzing asymmetric hydrogenation reaction of imine, the obtained chiral amine reaches more than 70% e.e and can reach more than 77% e.e, and the requirement of preparing chiral amine products, such as chiral intermediates for synthesizing pesticide Tunduer, is completely met. The inventor uses a new ligand to modify the catalyst structure, and adds a quaternary ammonium iodide salt group on a derivative ligand, namely, the catalyst can partially play a role in phase transfer of the added quaternary ammonium salt, so that the use amount of the quaternary ammonium iodide salt can be removed or reduced, a good catalytic effect is obtained, the production cost is reduced, and the post-treatment procedure is simplified.
The catalyst of the invention is suitable for preparing chiral amine intermediates by asymmetric catalytic hydrogenation as shown in the following:
in the formula: r5Is selected from C1-C6Alkyl, phenyl, naphthyl or heteroaryl; r6、R7Can be the same or different and are respectively selected from C1-C3Alkyl, phenyl or naphthyl, said group may further contain C1-C3Alkyl or phenyl.
The amines used in the in situ synthesis of the imines according to the invention are selected from C1-C6Aliphatic, aniline, naphthylamine or heterocyclic aromatic amines of (a); the ketone for synthesizing imine is selected from symmetric or asymmetric aliphatic ketone or aryl substituted aliphatic ketone, or symmetric or asymmetric aromatic ketone and symmetric or asymmetric aromatic ketone with substituent; the amine and ketone are dehydrated and condensed, and imine obtained by in situ or separation is asymmetrically hydrogenated to synthesize chiral amine under the catalysis of the catalyst under the condition of solvent or no solvent. The reaction conditions are within the skill of the art. In practice, at low reactant/catalyst (s/c, mol/mol) (e.g., s/c less than 14 ten thousand) no iodide or organic iodide salt is required; when the s/c value is high, the reaction is facilitated by adding an iodide salt. When an iodide salt is used, the iodide salt used is an inorganic iodide salt or an organic iodide salt, preferably an organic iodide salt such as benzyltrimethylammonium iodide or tetrabutylammonium iodide. The amount of the iodine salt to be used is in the range of 0.001 to 5.0 mol%, preferably 0.001 to 1.0 mol%, based on the raw material imine. When a solvent is used, an acid (organic acid or inorganic acid) is usually used as the solvent, and an organic acid, particularly acetic acid, is preferred. The amount of solvent used is 1.0-50%, especially 5.0-50%, based on the weight of the starting imine.
The catalyst provided by the invention is preferably used for preparing 2-methyl-6-ethyl-aniline by asymmetric catalytic hydrogenation of imine generated by 2-methyl-6-ethyl-aniline and methoxy acetone:
specific procedures of the present invention are listed below (wherein the ferrocene-derived quaternary ammonium iodonium salt chiral ligand with bisphosphine ligand of formula I is prepared as described above):
1. in an autoclave with a proper volume, under the protection of nitrogen, a catalytic amount of dimeric iridium 1, 5-cyclooctadiene chloride complex and a quaternary ammonium iodide salt chiral ligand of diphosphine ligands such as { (R) -1- [ (S) -2-di-phenyl-phosphino-cyclopentadienyl iron base ] } -ethyl-di- (3, 5-dimethyl-phenyl) phosphine are mixed in organic acid, preferably acetic acid, the amount of the acetic acid is up to 50 percent of the total material weight, for the reaction with a high S/c value, a proper amount of tetrabutyl ammonium iodide needs to be added, and the prepared mixture is used as a catalyst under the protection of nitrogen.
2. Under the protection of nitrogen, imine generated by 2-methyl-6-ethyl-aniline and methoxy acetone is added into the autoclave. Replacing nitrogen with hydrogen, fixing the reaction solution under certain pressure and reacting at room temperature or 50 ℃ until the system can not absorb hydrogen any more. Discharging the residual air, transferring the material into a reduced pressure distillation device, recovering acetic acid and evaporating out a hydrogenation product; the content was analyzed by gas chromatography and the product e.e value (enantiomeric excess) was analyzed by liquid phase (with chiral column).
Experiments show that the catalyst of the invention is used, the imine/catalyst ratio is 100-500000, under 10-100 atmospheric pressure hydrogen, in acetic acid and in the presence or absence of tetrabutyl ammonium iodide, the product is completely converted within 24 hours, and the e.e value of the product is up to more than 77%. Increasing the reaction temperature increases the reaction rate, but the e.e value of the product decreases slightly.
The ligand is easy to obtain, and the preparation method is convenient for mass production; the method is simple and convenient to operate, can realize continuous operation, is suitable for large-scale preparation of chiral amine, has the e.e value of the product higher than the best level (more than 1 percent) in the prior art, and completely meets the requirement of being used as a pesticide intermediate. In the reaction process, the organic iodide derived from the chiral ligand can undoubtedly enable the ligand to play a role in chiral induction, and simultaneously play a role in phase transfer to improve the efficiency of the catalyst; moreover, as the ligand is quaternary ammonium salt and has positive charge, the catalyst can be separated and recovered through a medium or macromolecular anion resin after catalytic reaction, and the operation is simple and easy.
Detailed Description
The examples described below serve to illustrate the invention in further detail. In these examples, unless otherwise specified, the order of addition of the reaction mass can be combined as desired between the masses, the imine used being obtained by dehydro-condensation of 2-methyl-6-ethyl-aniline with methoxyacetone and measured in g (mol), the catalyst being exemplified by a mixture of dimeric 1, 5-cyclooctadieneiridium chloride and { (R) -1- [ (S) -2-di-phenyl-phosphino-1' -methylene-tri-butyl ammoniuodide-cyclopentadienyl ] } -ethyl-bis- (3, 5-dimethyl-phenyl) phosphine (ligand for short), all in mg (mg) (mmol), the acid used being exemplified by acetic acid and measured in mL (mL), tetrabutylammonium iodide being measured in mg (mg) (mmol), the content of hydrogenation products is detected by high performance liquid chromatography analysis, and the conditions are as follows: a chromatographic column: eclipse XDB-C18150 mm X4.6 mm (i.d.), 5-Micron stainless steel column; column temperature: 30 ℃; mobile phase: acetonitrile to water 70: 30 (V/V); flow rate: 0.6 ml/min; detection wavelength: 254 nm; sample introduction amount: 20 mu l of the mixture; or by GC under the following analytical conditions: using Hp-5 gas chromatographic column, initially heating to 60 deg.C (hold 3min), heating to 160 deg.C at 20 deg.C/min, and heating to 220 deg.C (hold 30min) at 5 deg.C/min; e.e values were done by HPLC (Agilent 1200) under the analysis conditions: using an AD-H chiral liquid phase column, wherein the flow rate of a mobile phase n-hexane to isopropanol is 95: 5: v is 1.0 and the detection wavelength λ is 220 nm. E.e value of the hydrogenation product is detected by high performance liquid chromatography analysis, and conditions are as follows: a chromatographic column: CHIRALPAK OD-H250 mm by 4.6mm (i.d.) stainless steel column; column temperature: 30 ℃; mobile phase: n-hexane to isopropanol 99.8 to 0.2 (V/V); flow rate: 0.8 ml/min; detection wavelength: 254 nm; sample introduction amount: 1 mul; s/c is the starting imine/catalyst (mol/mol).
Example 1
Under the protection of nitrogen, ligand 14mg, [ Ir (COD) Cl]25mg and 10mL of acetic acid were charged into a 100mL autoclave, and 44.9g of imine (s/c: 3.0 ten thousand) was added thereto, followed by installation of the autoclave and replacement with 10 atmospheres of hydrogen three times (the same procedure in each example below); introducing 80-atmosphere hydrogen, heating to 50 ℃ under stirring, stopping the reaction after 5 hours, analyzing the conversion rate of the raw materials by using a gas chromatography to be 100%, and distilling under reduced pressure to obtain 41.5g of a product with the yield of 91.5%, and analyzing by using a high performance liquid chromatography to obtain the product with the e.e value of 74.6%.
Example 2
The reaction was stopped by reacting the mixture at room temperature for 24 hours under the same conditions as in example 1, and the conversion of the raw material was 97.6% by gas chromatography, and the product was distilled under reduced pressure to give 41.0g, yield 90.4% by high performance liquid chromatography, and e.e. value was 76.0%.
Example 3
Otherwise, the reaction was stopped after 24 hours by introducing 50 atmospheres of hydrogen gas, and the conversion of the starting material was analyzed by gas chromatography and the e.e value was 73.6% by high performance liquid chromatography as in example 2.
Example 4
Under the protection of nitrogen, ligand 2.6mg, [ Ir (COD) Cl]21mg、Bu4NI 15mg and 10mL of acetic acid were charged in a 100mL autoclave, and after 44.5g of imine (s/c: 14.8 ten thousand) was added, the autoclave was placed, and the reaction was stopped after introducing 80 atm hydrogen gas and reacting at room temperature for 36 hours with stirring, and the conversion of the raw material was 100% by gas chromatography and the e.e value was 73.6%.
Example 5
Under the protection of nitrogen gas, ligand 2.6mg, [ Ir (COD) Cl]21mg and 10mL of acetic acid were charged in a 100mL autoclave, 44.5g of imine (s/c: 14.8 ten thousand) was added, the autoclave was placed, and the reaction was stopped after introducing 80 atm hydrogen gas and reacting at room temperature for 36 hours with stirring, and the reaction was carried out in a gas phaseThe chromatographic analysis showed 78.5% conversion of the starting material and an e.e value of 73.1%.
Example 6
Ligand 126mg, [ Ir (COD) Cl]250mg and 30mL of acetic acid were placed in a 100mL autoclave, and after addition of 44.5g of imine (s/c 0.30 ten thousand), the autoclave was set up, purged with 10 atmospheres of hydrogen, and so on for 3 times; introducing 80-atmosphere hydrogen, reacting at room temperature for 24 hours under stirring, stopping the reaction, and analyzing by gas chromatography, wherein the conversion rate of the raw materials is 100 percent, and the e.e value is 76.8 percent.
Example 7
Otherwise, the reaction was stopped by introducing 40 atmospheres of hydrogen gas and reacting for 24 hours under the same conditions as in example 6, and the conversion of the raw material was analyzed by gas chromatography to be 100% and the e.e value was 75.9% by high performance liquid chromatography.
Example 8
Otherwise, the reaction was stopped after 24 hours by supplying 100 atm hydrogen gas and the conversion of the raw material was analyzed by gas chromatography to be 100% and the e.e value was 77.4% by high performance liquid chromatography, as in example 6.
Comparative example
Otherwise, the catalyst ligand was changed to equimolar { (R) -1- [ (S) -2-bis-phenyl-phosphinotrieneiron base ] } -ethyl-bis- (3, 5-dimethyl-phenyl) phosphine under the same conditions as in example 4, and the reaction was stopped after 36 hours at room temperature, and the conversion of the raw material was 100% by gas chromatography and the e.e value was 76.1%.
Claims (4)
1. An asymmetric hydrogenation catalyst for imine, which is characterized in that: an in situ mixture or a newly formed complex of a chiral ligand of formula I:
in the formula: r1Is C1-C5An alkyl group; r2、R3、R4Can be the same or different, eachIs selected from C1-C6Straight or branched chain alkyl, 0-3C1-C6Alkyl-substituted aryl; n is 1-6;
the metal iridium complex is dimeric 1, 5-cyclooctadiene iridium chloride.
2. The catalyst of claim 1, wherein: r1Is C1-C3An alkyl group; r2、R3、R4Can be the same or different and are respectively selected from C1-C4Straight or branched chain alkyl, 0-2C1-C6Alkyl-substituted aryl; n is 1-4.
3. Use of a catalyst according to claim 1 or 2 for the preparation of a chiral amine intermediate having the structure:
in the formula: r5Is selected from C1-C6Alkyl, phenyl, naphthyl or heteroaryl; r6、R7Can be the same or different and are respectively selected from C1-C3Alkyl, phenyl or naphthyl; said group may further contain C1-C3Alkyl or phenyl;
or,
r5 is selected from phenyl, further containing an ethyl group at the C2 position and a methyl group at the C6 position on the R5; r6 is selected from methyl; r7 is selected from methyl, and R7 further contains methoxy;
or,
r5 is selected from phenyl, further containing an ethyl group at the C2 position and a methyl group at the C6 position on the R5; r6 is selected from methyl, and R6 further contains methoxy; r7 is selected from methyl.
4. Use according to claim 3, characterized in that: the catalyst is used for preparing the compound shown as the following formula,
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| EP0646590A1 (en) * | 1993-10-01 | 1995-04-05 | Ciba-Geigy Ag | Ferrocenyldiphosphines substituted with fluoroalkyl groups as ligands for homogeneous catalysis |
| US5466844A (en) * | 1993-02-26 | 1995-11-14 | Ciba-Geigy Corporation | Ferrocene diphosphines as ligands for homogeneous catalysts |
| CN1139930A (en) * | 1994-02-02 | 1997-01-08 | 希巴-盖吉股份公司 | Hydrogenation catalyst, process for the preparation thereof and hydrogenation process |
| EP0691949B1 (en) * | 1994-02-02 | 1998-10-14 | Novartis AG | Process for the hydrogenation of imines |
| CN101857612A (en) * | 2010-06-11 | 2010-10-13 | 南京工业大学 | Chiral diphosphine ligand, iridium composite catalyst thereof, preparation method and application of chiral diphosphine ligand in asymmetric hydrogenation synthesis of -metolachlor |
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| US5466844A (en) * | 1993-02-26 | 1995-11-14 | Ciba-Geigy Corporation | Ferrocene diphosphines as ligands for homogeneous catalysts |
| EP0646590A1 (en) * | 1993-10-01 | 1995-04-05 | Ciba-Geigy Ag | Ferrocenyldiphosphines substituted with fluoroalkyl groups as ligands for homogeneous catalysis |
| CN1139930A (en) * | 1994-02-02 | 1997-01-08 | 希巴-盖吉股份公司 | Hydrogenation catalyst, process for the preparation thereof and hydrogenation process |
| EP0691949B1 (en) * | 1994-02-02 | 1998-10-14 | Novartis AG | Process for the hydrogenation of imines |
| CN101857612A (en) * | 2010-06-11 | 2010-10-13 | 南京工业大学 | Chiral diphosphine ligand, iridium composite catalyst thereof, preparation method and application of chiral diphosphine ligand in asymmetric hydrogenation synthesis of -metolachlor |
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