CN111389468B - Application of sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst in asymmetric hydrogenation reaction - Google Patents

Application of sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst in asymmetric hydrogenation reaction Download PDF

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CN111389468B
CN111389468B CN202010385022.XA CN202010385022A CN111389468B CN 111389468 B CN111389468 B CN 111389468B CN 202010385022 A CN202010385022 A CN 202010385022A CN 111389468 B CN111389468 B CN 111389468B
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binap
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ionic liquid
asymmetric hydrogenation
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金欣
王凡
朱琳
李淑梅
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Qingdao University of Science and Technology
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Abstract

The invention relates to a phosphine ligand and polyether functionalized ionic liquid integrated chiral catalyst and application thereof in asymmetric catalytic hydrogenation reaction, in the asymmetric hydrogenation reaction, the dual functions of the chiral catalyst and solvent ionic liquid can be simultaneously exerted only by a catalytic amount of phosphine ligand and ionic liquid integrated catalyst, so that the recovery and circulation of the chiral catalyst are realized, the additional addition of solvent ionic liquid is not needed, the negative effect of the solvent ionic liquid is reduced to the maximum extent, the efficient, green and economic utilization of the ionic liquid is realized, and the problem that a large amount of solvent ionic liquid is needed for recovering the chiral catalyst in the prior art is solved.

Description

Application of sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst in asymmetric hydrogenation reaction
Technical Field
The invention relates to the technical field of chemistry and chemical engineering, in particular to a method for applying a sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric catalytic hydrogenation.
Background
In the past decades, homogeneous asymmetric catalytic hydrogenation has become one of the most efficient and atomic economic means for obtaining fine chemicals such as chiral drugs, pesticides and fragrances due to its high catalytic activity, good stereoselectivity and mild reaction conditions. However, the problem of difficult separation of chiral noble metal catalysts (mainly chiral phosphine ligand-metal complexes) from hydrogenation products has long limited their large-scale industrial application. Therefore, the development of a recyclable and recyclable chiral catalyst has been the focus of research in the field of homogeneous asymmetric hydrogenation.
In recent years, with the increasing importance of green chemistry and the demand for environmentally friendly solvents, green solvent ionic liquids have attracted great attention. Different from the traditional organic solvent, the ionic liquid has the advantages of extremely low saturated vapor pressure, high thermal and chemical stability, good solubility to the transition metal catalyst, designability of the structure and the like, so that the ionic liquid serving as the catalyst carrier becomes an effective means for separating, recovering and recycling the chiral catalyst. Although ionic liquids have been used successfully for separating chiral catalysts in asymmetric hydrogenation reactions, a problem of difficult blending is also apparent, i.e. in order to inhibit the loss of catalyst, a large amount of solvent ionic liquids is usually used in catalytic reactions to sufficiently dissolve and immobilize chiral catalysts (up to 140-5000 times (mol/mol) as much as metal catalysts, which is equivalent to 15-2100% of substrates, mol%), which neither meets the requirements of green chemistry, nor results in waste of resources. Moreover, the application of a large amount of solvent ionic liquid makes the negative effect (such as poisoning the catalyst) of trace impurities in the ionic liquid, which are difficult to remove, on the metal catalyst more remarkable, and the catalytic efficiency is reduced. Therefore, how to apply the ionic liquid in an environment-friendly and economic way to construct a high-efficiency ionic liquid asymmetric hydrogenation system is a problem which needs to be solved urgently at present.
Disclosure of Invention
The invention relates to a method for applying a sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric catalytic hydrogenation, aiming at the limitations in the prior art, by utilizing the designability and easy functionalization characteristics of ionic liquid, a transition metal complex of a chiral diphosphine ligand BINAP and the polyether functionalized ionic liquid are integrated to obtain the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst, and the integrated catalyst not only has the chiral induction capability of the chiral catalyst, but also is ionic liquid and has the functions of ionic liquid dissolution and carrier. Compared with the traditional chiral catalyst used in the prior art, the integrated catalyst has the advantages that: (1) The chiral catalyst has a low melting point (generally 10-60 ℃ or no melting point), belongs to a class of functionalized ionic liquid, and is not an ionic liquid, but a traditional chiral catalyst has a high melting point (generally higher than 100 ℃); (2) The catalyst has a carrier function, can realize separation, recovery and circulation of the catalyst, and the traditional chiral catalyst does not have the capability; (3) The sulfonated phosphine ligand metal chiral catalyst is easy to dissolve in most polar solvents such as water, methanol, ethanol, isopropanol, acetonitrile, acetone, tetrahydrofuran and dioxane, and also is easy to dissolve in partial weak polar solvents such as chloroform, dichloromethane, benzene, toluene and the like, so that the application range of the sulfonated phosphine ligand metal chiral catalyst is greatly expanded, and the sulfonated phosphine ligand metal chiral catalyst is generally only soluble in water and is suitable for water/organic two-phase hydrogenation reaction.
Based on the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst, the invention creates a green, economic and recyclable asymmetric catalytic hydrogenation system. In the asymmetric catalytic hydrogenation system, the dual functions of the chiral catalyst and the solvent ionic liquid can be simultaneously exerted only by the catalytic amount of the sulfonated BINAP and the polyether functionalized ionic liquid integrated chiral catalyst, so that the recovery and circulation of the chiral catalyst are realized, the solvent ionic liquid is not required to be additionally added, the negative effect of the solvent ionic liquid is reduced to the maximum extent, the green and economic utilization of the ionic liquid is realized, and the problem that a large amount of solvent ionic liquid is required for recovering the chiral catalyst in the prior art is solved.
The high-efficiency asymmetric catalytic hydrogenation system constructed by the invention is characterized in that: the homogeneous asymmetric hydrogenation reaction system consists of a chiral catalyst integrating sulfonated BINAP and polyether functionalized ionic liquid, a substrate and an organic solvent, and the asymmetric hydrogenation reaction is carried out at a certain reaction temperature and under a certain hydrogen pressure, wherein the structural formula of the chiral catalyst integrating sulfonated BINAP and polyether functionalized ionic liquid is as follows:
Figure GDA0002518008080000021
chiral catalyst 7 is M (X) 2 (BINAP-(SO 3 A) k ) Which is a mixture of 3 and 4 in any ratio, 3<k<4；
Chiral catalyst 8 is [ M (X) n (Q)(BINAP-(SO 3 A) k )]Y, which is a mixture of 5 and 6 in any ratio, 3<k<4；
BINAP- (SO) in 1 or 2 3 A) 2 Represents a chiral phosphine ligand, the structural formula of which is shown as follows,
Figure GDA0002518008080000031
3 and 5 BINAP- (SO) 3 A) 4 Represents a chiral phosphine ligand having the formula:
Figure GDA0002518008080000032
BINAP- (SO) in 4 and 6 3 A) 3 Represents a chiral phosphine ligand having the formula:
Figure GDA0002518008080000033
wherein the stereo configuration of the chiral phosphine ligand is S type or R type;
a represents an organic onium salt cation having the following structural formula,
Figure GDA0002518008080000034
wherein m =4-140,R 1 Is C 1 –C 12 Alkyl or phenyl, l =0-140,R 2 Is C 1 –C 12 Alkyl or phenyl; r 3 Is C 1 -C 4 Linear alkyl; r is 4 Is H or C 1 -C 4 Linear alkyl;
in 1, 3, 4 and 7: m is divalent or positive Ru Ⅱ X = Cl, br or I;
in 2, 5, 6 and 8: n =1,M is positive divalent Ru Ⅱ X = Cl, br or I, Q is benzene (C) 6 H 6 ) Ligands or p-cymene (p-MeC) 6 H 4 CHMe 2 ) Ligand, Y = Cl, br or I.
The method for separating, recovering and recycling the catalyst comprises the following steps: after the reaction is finished, removing the organic solvent, extracting the product by using an extraction solvent, dividing a homogeneous reaction system into two phases, wherein the upper layer is an organic phase consisting of the extraction solvent and the product, and the lower layer is a chiral catalyst phase, and realizing the recovery and the recycling of the chiral catalyst by simple phase separation;
the substrate is beta-keto ester with the structural formula shown in the specification,
Figure GDA0002518008080000041
wherein R is 5 Is phenyl, substituted phenyl or C 1 -C 15 The linear alkyl group of (1); r is 6 Is methyl, ethyl, isopropyl or tert-butyl;
the specific catalytic reaction process is as follows: adding chiral catalysts 1, 2, 3, 4, 5, 6, 7 or 8, a substrate and an organic solvent into a reactor, wherein the molar ratio of the substrate to the chiral catalysts is 1-30000; the substrate is beta-keto ester with the structural formula shown in the specification,
Figure GDA0002518008080000042
wherein R is 5 Is phenyl, substituted phenyl or C 1 -C 15 The linear alkyl group of (1); r is 6 Is methyl, ethyl, isopropyl or tert-butyl;
the organic solvent I is any one or a mixture of any more of water, methanol, ethanol, isopropanol, n-butanol, acetonitrile, acetone, tetrahydrofuran, dioxane, ethyl acetate, chloroform, dichloromethane, benzene and toluene; the organic solvent II is diethyl ether, methyl tert-butyl ether, C 6 –C 10 Of an alkane, petroleum ether having a boiling range of 30 to 60 ℃, petroleum ether having a boiling range of 60 to 90 ℃ andany one or a mixture of any several of petroleum ether with a boiling range of 90-120 ℃.
Compared with the prior art, the method for applying the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric catalytic hydrogenation reaction has the advantages and obvious technical progress that:
1. high activity: the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst has high catalytic activity, and can catalyze the asymmetric hydrogenation reaction of beta-keto ester in a methanol solvent, wherein the TOF value is up to nearly 3000h -1 (ii) a While BINAP is only 200h -1 Left and right.
2. High enantioselectivity: the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst has high enantioselectivity to asymmetric hydrogenation reaction of beta-keto ester in most polar solvents (such as water, methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, dioxane, ethyl acetate, dichloromethane, chloroform, benzene and toluene) and weak polar solvents (such as dichloromethane, chloroform, benzene and toluene); the traditional metal BINAP chiral catalyst has higher enantioselectivity only in a few polar solvents (such as methanol and ethanol) and weak polar solvents (such as dichloromethane), and has lower enantioselectivity in most polar solvents and weak polar solvents; sulfonated BINAP is insoluble in most organic solvents and can only be used for aqueous phase hydrogenation.
3. High stability, low run-off and solvent-free ionic liquids: the method for asymmetric catalytic hydrogenation is used for asymmetric hydrogenation of beta-keto ester, the dosage of the chiral catalyst integrating sulfonated BINAP and polyether functionalized ionic liquid is only 0.01-1% (mol/mol) of a substrate, the activity and enantioselectivity are not obviously reduced after 5 times of circulation, and the loss rate of noble metal is only 0.05-0.3%, so that the catalytic reaction and the recovery and circulation of the chiral catalyst can be realized only by the chiral catalyst integrating sulfonated BINAP with polyether functionalized ionic liquid in a catalytic amount, and no solvent ionic liquid is required to be added as a catalyst carrier, so that the ionic liquid is efficiently, greenly and economically utilized in the asymmetric hydrogenation; and the system applying the traditional metal BINAP chiral catalyst can not realize the separation, recovery and cyclic utilization of the catalyst.
Detailed Description
Example 1
Catalyst 1 a-1/methyl acetoacetate/methanol system for asymmetric hydrogenation reaction
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1a-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1:1000, then reacting for 20h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the methanol under reduced pressure after the reaction is finished, adding n-hexane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 98.4%; the TOF value of the initial reaction is 2914h by a pressure drop method -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, and the conversion rate and the ee value are respectively as follows: 100%,98.2% (2); 100%,98.1% (3); 100%,98.0% (4); 100 percent, 95.5 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.3 percent.
Example 2
Catalyst 1 a-2/methyl acetoacetate/methanol system for catalyzing asymmetric hydrogenation reaction
The catalyst 1a-2 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 70 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1a-2, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-2 to the methyl acetoacetate is 1 to 1000, reacting for 20 hours at 60 ℃ under the hydrogen pressure of 4.0MPa, removing the methanol under reduced pressure after the reaction is finished, adding n-heptane for extraction, and allowing an upper organic phase to enter a gas phaseChromatography (lipodex A25 m.times.0.25 mm chiral capillary column), substrate conversion 100%, ee (S) value 98.2%; the TOF value of the initial reaction is 2868h measured by a pressure drop method -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,98.3% (2); 100%,98.1% (3); 100%,97.8 (4); 100 percent, 96.3 (5), and the ruthenium loss rate of each circulation is 0.05 to 0.1 percent.
Example 3
Catalyst 1 a-3/methyl acetoacetate/methanol system for asymmetric hydrogenation reaction
The catalyst 1a-3 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[n-C 12 H 25 (OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝n-C 12 H 25 ,R 2 ＝CH 3 ). Adding catalyst 1a-3, methyl acetoacetate and methanol into an autoclave under argon atmosphere, wherein the molar ratio of the catalyst 1a-3 to the methyl acetoacetate is 1-10000, then reacting for 72h at 80 ℃ and under the hydrogen pressure of 4.0MPa, removing the methanol under reduced pressure after the reaction is finished, adding n-heptane for extraction, and carrying out gas chromatography (lipopex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 95% and the ee (S) value is 96.0%.
Example 4
Catalyst 1 a-4/ethyl acetoacetate/methanol system for asymmetric hydrogenation reaction
Catalyst 1a-4 is Ru (Br) 2 (R-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding the catalyst 1a-4, ethyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-4 to the ethyl acetoacetate is 1 to 1000, then reacting for 20 hours at 60 ℃ under the hydrogen pressure of 4.0MPa, removing the methanol under reduced pressure after the reaction is finished, adding n-heptane for extraction, and carrying out gas chromatography analysis on an upper organic phase (lipodex A25 m multiplied by 0.25mm chiral phase)Capillary column), substrate conversion 100%, ee (R) value 92.2%; the TOF value of the initial reaction is 2682h measured by a pressure drop method -1 (ii) a After two phases of the catalyst phase at the lower layer are separated, ethyl acetoacetate and methanol are continuously supplemented, the next cycle is carried out, and the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,92.4% (2); 100%,92.2% (3); 100%,92.0 (4); 100 percent, 91.8 (5), and the ruthenium loss rate of each circulation is 0.1 to 0.2 percent.
Example 5
Catalyst 2 a-1/methyl acetoacetate/methanol system for catalyzing asymmetric hydrogenation reaction
Catalyst 2a-1 is [ RuI (p-Cymene) (S-BINAP- (SO) 3 A) 2 )]I(A＝[CH 3 (OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝CH 3 ,R 2 ＝CH 3 ). Adding a catalyst 2a-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 2a-1 to the methyl acetoacetate is 1:1000, then reacting for 20h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the methanol under reduced pressure after the reaction is finished, adding n-heptane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 96.0%; the TOF value of the initial reaction determined by a pressure drop method is 1082h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, and the conversion rate and the ee value are respectively as follows: 100%,96.1% (2); 100%,96.0% (3); 100 percent, 95.6 (4), 100 percent and 95.8 percent (5), and the ruthenium loss rate of each cycle is 0.1 to 0.2 percent.
Example 6
Catalyst 2 a-1/methyl acetoacetate/water system for catalyzing asymmetric hydrogenation reaction
The catalyst 2a-1 is [ RuI (p-Cymene) (S-BINAP- (SO) 3 A) 2 )]I(A＝[CH 3 (OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝CH 3 ,R 2 ＝CH 3 ). Under argon atmosphere, at high pressureAdding a catalyst 2a-1, methyl acetoacetate and water into a pressure reaction kettle, wherein the molar ratio of the catalyst 2a-1 to the methyl acetoacetate is 1. Continuously replenishing methyl acetoacetate and water after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, and the conversion rate and the ee value are respectively as follows: 100%,96.3% (2); 100%,96.2% (3); 100%,96.3% (4); 100 percent and 96.0 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.2 percent.
Example 7
Catalyst 1 a-1/beta-keto ester (R) 5 ＝Et，R 6 Catalytic asymmetric hydrogenation reaction under Me/ethanol system
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding catalyst 1a-1, beta-keto ester (R) into a high-pressure reaction kettle under argon atmosphere 5 ＝Et，R 6 Me) and ethanol, catalysts 1a-1 and beta-keto esters (R) 5 ＝Et，R 6 = Me) is 1, then reaction is carried out for 20h at 60 ℃ under the hydrogen pressure of 4.0MPa, ethanol is removed under reduced pressure after the reaction is finished, n-hexane is added for extraction, the upper organic phase is subjected to gas chromatography (lipodex A25 m × 0.25mm chiral capillary column), the substrate conversion rate is 100%, and the ee (S) value is 99.0%. (ii) a The TOF value of the initial reaction is 2496h when measured by a pressure drop method -1 (ii) a The catalyst phase at the lower layer is continuously supplemented with beta-keto ester (R) after two-phase separation 5 ＝Et，R 6 Me) and ethanol, the conversion rate and the ee value are not obviously reduced after 5 times of circulation, and the conversion rate and the ee value are respectively as follows: 100%,98.6% (2); 100%,98.5% (3); 100%,98.1 (4); 100 percent and 97.8 (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.2 percent.
Example 8
Catalyst 1 a-5/. Beta-ketoesters (R) 5 ＝Ph，R 6 Catalytic asymmetric hydrogenation reaction in an Et)/methanol system
The catalyst 1a-5 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[CH 3 (OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝CH 3 ,R 2 ＝CH 3 ). Adding catalyst 1a-5, beta-keto ester (R) into a high-pressure reaction kettle under argon atmosphere 5 ＝Ph，R 6 = Et) and methanol, catalysts 1a-5 and beta-keto ester (R) 5 ＝Ph，R 6 = Et) is 1, then reaction is carried out at 60 ℃, under hydrogen pressure of 4.0MPa for 30h, after the reaction is finished, methanol is removed under reduced pressure, n-heptane is added for extraction, the upper organic phase is subjected to gas chromatography (lipodex a 25m × 0.25mm chiral capillary column), substrate conversion is 99%, ee value is 83.0%.
Example 9
Catalyst 1 a-1/beta-ketoester (R) 5 ＝n-C 15 H 31 ，R 6 Catalytic asymmetric hydrogenation reaction under Me/acetonitrile system
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding catalyst 1a-1, beta-keto ester (R) into a high-pressure reaction kettle under argon atmosphere 5 ＝n-C 15 H 31 ，R 6 = Me) and acetonitrile, catalysts 1a-1 and beta-keto ester (R) 5 ＝n-C 15 H 31 ，R 6 = Me) was 1000, then the reaction was carried out at 60 ℃ under hydrogen pressure 4.0MPa for 40h, after the reaction was complete acetonitrile was removed under reduced pressure, methyl tert-butyl ether was added and extraction was carried out, and the upper organic phase was subjected to gas chromatography (lipodex A25 m.times.0.25 mm chiral capillary column), substrate conversion was 99%, ee (S) value was 97.0%.
Example 10
Catalyst 1 a-1/methyl acetoacetate/1, 4-dioxane system for asymmetric hydrogenation
The catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1a-1, methyl acetoacetate and 1, 4-dioxane into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1: 100%,98.8% (2); 100%,98.5% (3); 99%,98.2% (4); 98 percent and 97.6 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.2 percent.
Example 15
Catalyst 1 a-1/methyl acetoacetate/tetrahydrofuran system for asymmetric hydrogenation
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Under argon atmosphere, adding a catalyst 1a-1, methyl acetoacetate and tetrahydrofuran into a high-pressure reaction kettle, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1.
Example 16
Catalyst 1 a-1/methyl acetoacetate/ethyl acetate system for catalyzing asymmetric hydrogenation reaction
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1a-1, methyl acetoacetate and ethyl acetate into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1:1000, then reacting for 40h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the ethyl acetate under reduced pressure after the reaction is finished, adding n-hexane for extraction, carrying out gas chromatography analysis (lipodex A25 m × 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 97.1%, continuously supplementing the methyl acetoacetate and the ethyl acetate after two-phase separation of a lower catalyst phase, and carrying out next circulation, wherein the conversion rate and the ee value are not obviously reduced after 5 times of circulation, and are respectively: 100%,97.2% (2); 100%,97.0% (3); 99%,96.9% (4); 99 percent and 96.6 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.2 percent.
Example 17
Catalyst 1 a-1/methyl acetoacetate/dichloromethane system for asymmetric hydrogenation
The catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1a-1, methyl acetoacetate and dichloromethane into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1:1000, then reacting for 40h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the dichloromethane under reduced pressure after the reaction is finished, adding n-hexane for extraction, carrying out gas chromatography (lipodex A25 m × 0.25mm chiral capillary column) on an upper layer of an organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 98.6%, continuously supplementing the methyl acetoacetate and the dichloromethane after two-phase separation of a lower layer of the catalyst phase, and carrying out next circulation, wherein the conversion rate and the ee value are not obviously reduced after 5 times of circulation, and the steps are as follows: 100%,98.5% (2); 100%,98.4% (3); 100%,97.9% (4); 99 percent and 97.8 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.2 percent.
Example 18
Catalyst 1 a-1/methyl acetoacetate/toluene system for asymmetric hydrogenation reaction
Catalyst 1a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Under argon atmosphere, adding catalyst 1a-1, methyl acetoacetate and toluene into a high-pressure reaction kettle, wherein the molar ratio of the catalyst 1a-1 to the methyl acetoacetate is 1.
Example 19
Catalyst 1 b-1/methyl acetoacetate/methanol system for asymmetric hydrogenation
Catalyst 1b-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[(N-(CH 2 CH 2 O) 16 Ph)Py] + ,m＝16,R 1 Ph). Adding a catalyst 1b-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1b-1 to the methyl acetoacetate is 1:1000, then reacting at 60 ℃ under the hydrogen pressure of 4.0MPa for 20h, removing the methanol under reduced pressure after the reaction is finished, adding n-hexane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 98.1%; the TOF value of the initial reaction determined by a pressure drop method is 2861h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,98.0% (2); 100%,97.9% (3); 100%,97.6% (4); 100 percent, 96.9 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.3 percent.
Example 20
Catalyst 1 c-1/methyl acetoacetate/methanol system for catalyzing asymmetric hydrogenation reaction
Catalyst 1c-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 NEt 3 ] + ,m＝16,R 1 ＝Ph,R 3 = Et). Adding a catalyst 1c-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1c-1 to the methyl acetoacetate is 1:1000, then reacting for 20h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the methanol under reduced pressure after the reaction is finished, adding n-hexane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 97.5%; the TOF value of the initial reaction determined by a pressure drop method is 2637h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,97.5% (2); 100%,97.2% (3); 100%,96.6% (4); 100 percent and 96.0 percent (5), and the ruthenium loss rate of each circulation is 0.1 to 0.2 percent.
Example 21
Catalyst 1 d-1/methyl acetoacetate/methanol system for asymmetric hydrogenation reaction
Catalyst 1d-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 PEt 3 ] + ,m＝16,R 1 ＝Ph,R 3 = Et). Adding a catalyst 1d-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1d-1 to the methyl acetoacetate is 1; the TOF value of the initial reaction determined by a pressure drop method is 2755h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,97.6% (2); 100%,97.4% (3); 100%,96.8% (4); 100 percent and 96.2 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.3 percent.
Example 22
Catalyst 1 e-1/methyl acetoacetate/methanol system for catalyzing asymmetric hydrogenation reaction
Catalyst 1e-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[Ph(OCH 2 CH 2 ) 16 TMG] + ,m＝16,R 1 ＝Ph,R 4 = H). Adding a catalyst 1e-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1e-1 to the methyl acetoacetate is 1; the TOF value of the initial reaction determined by a pressure drop method is 2980h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,98.3% (2); 100%,97.8% (3); 100%,97.6% (4); 100 percent and 96.5 percent (5), and the ruthenium loss rate of each circulation is 0.1 to 0.3 percent.
Example 23
Asymmetric hydrogenation reaction catalyzed by catalyst 1 f-1/methyl acetoacetate/methanol system
Catalyst 1f-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[(N-(CH 2 CH 2 O) 16 Ph)(N-CH 3 )Pi] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1f-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1f-1 to the methyl acetoacetate is 1; the TOF value of the initial reaction determined by a pressure drop method is 2726h -1 (ii) a Continuously adding methyl acetoacetate and methyl after the catalyst phase at the lower layer is subjected to two-phase separationAnd (3) carrying out the next circulation on the alcohol, wherein the conversion rate and the ee value are not obviously reduced after 5 times of circulation, and the conversion rate and the ee value are respectively as follows: 100%,96.3% (2); 100%,96.0% (3); 100%,95.6% (4); 100 percent and 94.6 percent (5), and the ruthenium loss rate of each circulation is 0.1 to 0.3 percent.
Example 24
Catalyst 1 g-1/methyl acetoacetate/methanol system for catalyzing asymmetric hydrogenation reaction
Catalyst 1g-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[(N-(CH 2 CH 2 O) 16 Ph)(N-CH 3 )Mor] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Under argon atmosphere, adding 1g-1 of catalyst, methyl acetoacetate and methanol into a high-pressure reaction kettle, wherein the molar ratio of the 1g-1 of catalyst to the methyl acetoacetate is 1; the TOF value of the initial reaction determined by a pressure drop method is 2693h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,97.1% (2); 100%,96.9% (3); 100%,96.6% (4); 100 percent, 95.4 percent (5), and the ruthenium loss rate of each circulation is 0.1 to 0.3 percent.
Example 25
Catalyst for catalyzing asymmetric hydrogenation reaction under 1 h-1/methyl acetoacetate/methanol system
Catalyst 1h-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 2 )(A＝[(N-(CH 2 CH 2 O) 16 Ph)(N-CH 3 )Pyrr] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 1h-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 1h-1 to the methyl acetoacetate is 1-1000, then reacting for 20h at 60 ℃ under the hydrogen pressure of 4.0MPa, and decompressing and removing pressure after the reaction is finishedRemoving methanol, adding n-hexane for extraction, and subjecting the upper layer organic phase to gas chromatography (lipodex A25 m × 0.25mm chiral capillary column), wherein the substrate conversion rate is 100% and the ee (S) value is 97.5%; the TOF value of the initial reaction determined by a pressure drop method is 2576h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,97.5% (2); 100%,97.0% (3); 100%,97.0% (4); 100 percent and 96.4 percent (5), and the ruthenium loss rate of each circulation is 0.1 to 0.3 percent.
Example 26
Catalyst 7 a-1/methyl acetoacetate/methanol system for asymmetric hydrogenation
Catalyst 7a-1 is Ru (Br) 2 (S-BINAP-(SO 3 A) 3.5 )(k＝3.5，A＝[Ph(OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝Ph,R 2 ＝CH 3 ). Adding a catalyst 7a-1, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 7a-1 to the methyl acetoacetate is 1:1000, then reacting for 20h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the methanol under reduced pressure after the reaction is finished, adding n-hexane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 96.1%; the TOF value of the initial reaction is 3032h measured by a pressure drop method -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,96.0% (2); 100%,96.0% (3); 100%,95.8% (4); 100 percent, 95.1 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.3 percent.
Example 27
Catalyst 7 a-2/methyl acetoacetate/methanol system for asymmetric hydrogenation
Catalyst 7a-2 is Ru (Br) 2 (S-BINAP-(SO 3 A) 3.5 )(k＝3.5，A＝[CH 3 (OCH 2 CH 2 ) 16 IMCH 3 ] + ,m＝16,l＝0,R 1 ＝CH 3 ,R 2 ＝CH 3 ). Adding a catalyst 7a-2, methyl acetoacetate and methanol into a high-pressure reaction kettle under argon atmosphere, wherein the molar ratio of the catalyst 7a-2 to the methyl acetoacetate is 1:1000, then reacting for 20h under the hydrogen pressure of 4.0MPa at 60 ℃, removing the methanol under reduced pressure after the reaction is finished, adding n-hexane for extraction, and carrying out gas chromatography (lipodex A25 m multiplied by 0.25mm chiral capillary column) on an upper organic phase, wherein the substrate conversion rate is 100% and the ee (S) value is 97.2%; the TOF value of the initial reaction determined by a pressure drop method is 1674h -1 (ii) a Continuously replenishing methyl acetoacetate and methanol after the catalyst phase at the lower layer is subjected to two-phase separation, and performing the next cycle, wherein the conversion rate and the ee value are not obviously reduced after 5 cycles, which are respectively: 100%,97.1% (2); 100%,97.0% (3); 100%,96.5% (4); 100 percent and 96.1 percent (5), and the loss rate of ruthenium in each circulation is 0.1 to 0.3 percent.
Example 28
Comparative experiment-1: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/methanol system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl acetoacetate and methanol, ru (Br) 2 The molar ratio of (S-BINAP) to methyl acetoacetate was 1, the reaction was carried out at 60 ℃ under a hydrogen pressure of 4.0MPa for 20h, methanol was removed under reduced pressure after the end of the reaction, the organic phase was subjected to gas chromatography (lipodex A25 m.times.0.25 mm chiral capillary column), the substrate conversion was 100%, and the ee (S) value was 98.4%. (ii) a The TOF value of the initial reaction determined by a pressure drop method is 207h -1 . The catalyst cannot be separated, recovered and recycled.
Example 29
Comparative experiment-2: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/acetonitrile system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl acetoacetate and acetonitrile, ru (Br) 2 (S-BINAP) and methyl acetoacetate were mixed at a molar ratio of 1Acetonitrile, organic phase by gas chromatography (lipodex A25 m.times.0.25 mm chiral capillary column), substrate conversion 100%, ee (S) value 83.0%. The catalyst cannot be separated, recovered and recycled.
Example 30
Comparative experiment-3: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/tetrahydrofuran system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl acetoacetate and tetrahydrofuran, ru (Br) 2 (S-BINAP) and methyl acetoacetate at a molar ratio of 1:1000, followed by reaction at 60 ℃ under a hydrogen pressure of 4.0MPa for 40h, removal of tetrahydrofuran under reduced pressure after the end of the reaction, and chromatography of the organic phase on a gas chromatograph (lipodex A25 m.times.0.25 mm chiral capillary column) with 100% conversion of the substrate and 56.0% ee (S) value. The catalyst cannot be separated, recovered and recycled.
Example 31
Comparative experiment-4: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/ethyl acetate system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl and ethyl acetoacetate, ru (Br) 2 (S-BINAP) and methyl acetoacetate at a molar ratio of 1.1000, followed by reaction at 60 ℃ under a hydrogen pressure of 4.0MPa for 40 hours, removal of ethyl acetate under reduced pressure after the end of the reaction, gas chromatography analysis (lipodex A25 m.times.0.25 mm chiral capillary column) of the organic phase, conversion of substrate of 100%, ee (S) value of 48.8%. The catalyst cannot be separated, recovered and recycled.
Example 32
Comparative experiment-5: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/dichloromethane system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl acetoacetate and dichloromethane, ru (Br) 2 (S-BINAP) and methyl acetoacetate were mixed at a molar ratio of 1:1000, and the mixture was reacted at 60 ℃ under a hydrogen pressure of 4.0MPa for 40 hours, after the reaction was completed, the methylene chloride was removed under reduced pressureThe alkane, the organic phase, was subjected to gas chromatography (lipodex A25 m.times.0.25 mm chiral capillary column), with a substrate conversion of 100% and an ee (S) value of 99.0%. The catalyst cannot be separated, recovered and recycled.
Example 33
Comparative experiment-6: ru (Br) 2 Asymmetric hydrogenation reaction under (S-BINAP)/methyl acetoacetate/toluene system
Adding catalyst Ru (Br) into a high-pressure reaction kettle under argon atmosphere 2 (S-BINAP), methyl acetoacetate and toluene, ru (Br) 2 The molar ratio of (S-BINAP) to methyl acetoacetate was 1, the reaction was carried out at 60 ℃ under a hydrogen pressure of 4.0MPa for 40h, the toluene was removed under reduced pressure after the end of the reaction, and the organic phase was subjected to gas chromatography (lipodex A25 m.times.0.25 mm chiral capillary column), with a substrate conversion of 100% and an ee (S) value of 30.2%. The catalyst cannot be separated, recovered and recycled.

Claims (3)

1. A method for applying a sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric hydrogenation reaction is characterized by comprising the following steps: the homogeneous asymmetric hydrogenation reaction system consists of a chiral catalyst integrating sulfonated BINAP and polyether functionalized ionic liquid, a substrate and an organic solvent, and the asymmetric hydrogenation reaction is carried out at a certain reaction temperature and under a certain hydrogen pressure, wherein the structural formula of the chiral catalyst integrating sulfonated BINAP and polyether functionalized ionic liquid is as follows:
Figure DEST_PATH_IMAGE002AAA
Figure 758511DEST_PATH_IMAGE003
chiral catalyst 7 is M (X) 2 (BINAP-(SO 3 A) k ) Which is a mixture of 3 and 4 in any ratio, 3< k < 4；
Chiral catalyst 8 is [ M (X) n (Q)(BINAP-(SO 3 A) k )]Y, which is a mixture of 5 and 6 in any ratio, 3< k < 4；
BINAP- (SO) in 1 or 2 3 A) 2 Represents a chiral phosphine ligand having the following structural formula:
Figure 958548DEST_PATH_IMAGE004
3 and 5 BINAP- (SO) 3 A) 4 Represents a chiral phosphine ligand having the formula:
Figure 597252DEST_PATH_IMAGE005
BINAP- (SO) in 4 and 6 3 A) 3 Represents a chiral phosphine ligand having the formula:
Figure 554844DEST_PATH_IMAGE006
wherein the stereo configuration of the chiral phosphine ligand is S type or R type;
a represents an organic onium salt cation having the following structural formula:
Figure 557435DEST_PATH_IMAGE007
wherein the content of the first and second substances,m = 4–140，R 1 is C 1 –C 12 An alkyl group or a phenyl group, or a substituted or unsubstituted alkyl group,l = 0–140，R 2 is C 1 –C 12 Alkyl or phenyl; r is 3 Is C 1 -C 4 A linear alkyl group; r is 4 Is H or C 1 -C 4 Linear alkyl;
in 1, 3, 4 and 7: m is divalent or positive Ru Ⅱ X = Cl, br or I;
in 2, 5, 6 and 8:n=1,M is a divalent or positive Ru Ⅱ X = Cl, br or I, Q is benzene（C 6 H 6 ) Ligand or p-cymene (B)p-MeC 6 H 4 CHMe 2 ) Ligand, Y = Cl, br or I;
the substrate isβ-ketoesters, of formula:
Figure 487345DEST_PATH_IMAGE008
wherein R is 5 Is phenyl, substituted phenyl or C 1 -C 15 The linear alkyl group of (1); r 6 Is methyl, ethyl, isopropyl or tert-butyl.
2. A method for applying the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric hydrogenation reaction according to claim 1, which is characterized in that: after the asymmetric hydrogenation reaction is finished, removing the organic solvent, extracting the product by using the extraction solvent, dividing a homogeneous reaction system into two phases, wherein the upper layer is an organic phase consisting of the extraction solvent and the product, and the lower layer is a chiral catalyst phase, and realizing the recovery and the recycling of the chiral catalyst by simple phase separation.
3. A method for applying the sulfonated BINAP and polyether functionalized ionic liquid integrated chiral catalyst to asymmetric hydrogenation reaction according to claim 1, which is characterized in that: adding chiral catalysts 1, 2, 3, 4, 5, 6, 7 or 8, a substrate and an organic solvent into a reactor, wherein the molar ratio of the substrate to the chiral catalysts is 1-30000; the substrate isβ-ketoesters, of formula:
Figure 120451DEST_PATH_IMAGE009
wherein R is 5 Is phenyl, substituted phenyl or C 1 -C 15 The linear alkyl group of (1); r 6 Is methyl, ethyl, isopropyl or tert-butyl;
the organic solvent is any one or a mixture of any more of methanol, ethanol, isopropanol, n-butanol, acetonitrile, acetone, tetrahydrofuran, dioxane, ethyl acetate, chloroform, dichloromethane, benzene and toluene; the extraction solvent is diethyl ether, methyl tert-butyl ether, C 6 –C 10 Any one or a mixture of any several of alkane, petroleum ether with a boiling range of 30-60 ℃, petroleum ether with a boiling range of 60-90 ℃ and petroleum ether with a boiling range of 90-120 ℃.
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CN103483381A (en) * 2013-08-22 2014-01-01 青岛科技大学 Preparation method of first-class phosphorus functionalized ionic liquid and application of ionic liquid in hydroformylation
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