CN111285769A - Method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst - Google Patents
Method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst Download PDFInfo
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Abstract
The invention relates to the field of asymmetric catalysis, in particular to a method for water-phase catalysis Henry asymmetric addition reaction of a polyion liquid type chiral copper amino acid catalyst, wherein in a water phase, an aldehyde compound and a nitroalkane compound are subjected to the Henry asymmetric addition reaction under the catalysis of the polyion liquid type chiral copper amino acid catalyst to obtain a chiral β -nitroalcohol compound, and in the reaction process, the polyion liquid type chiral copper amino acid catalyst can effectively perform the water-phase asymmetric Henry addition reaction and can realize effective recovery and reuse of the catalyst through simple phase transfer.
Description
Technical Field
The invention relates to the field of asymmetric catalysis, in particular to a method for water-phase catalysis Henry asymmetric addition reaction based on a polyion liquid type chiral copper amino acid catalyst.
Background
Chiral β -nitroalcohol compounds have wide application, and at present, the chiral β -nitroalcohol compounds are obtained mainly by directly carrying out asymmetric Henry addition reaction on nitroalkane and aldehyde substances under the action of a chiral catalyst.
The chiral amino acid is a naturally-occurring chiral ligand, and various metal complex catalysts can be obtained by complexing metal ions and the chiral amino acid. However, such catalysts are difficult to use in aqueous phase catalytic reactions and often result in less than ideal chiral effects due to steric hindrance.
With the continuous development of ionic liquid design, in recent years, some scholars begin to research the introduction of chiral centers into ionic liquids, namely, chiral ionic liquids are prepared, and the chiral ionic liquids can be applied to the fields of chiral asymmetric synthesis, chiral resolution and the like.
At present, a plurality of reports exist in the field of chiral ionic liquid synthesis and application, for example, a series of chiral ionic liquids are synthesized by taking ephedrine as a chiral source. Amino acids as natural chiral sources have also been used to synthesize chiral ionic liquids. Chinese patent CN1383920A published in 2002 discloses an L-amino acid sulfate type chiral ionic liquid, and Chinese patent published in 2016 reports an amino acid ester bromide type chiral ionic liquid and a preparation method thereof.
From the above, chiral ionic liquid is apparently a novel chiral ligand, but the existing patent only needs to complex ionic liquid amino acid directly with metal for chiral catalysis. Because the amino acid ionic liquid has the advantages of low toxicity, easy recovery and the like, the development of a catalyst which utilizes the aqueous phase of the amino acid ionic liquid to catalyze efficiently and is easy to recover has important significance.
Disclosure of Invention
In order to solve the mass transfer problem of the catalyst in the water phase, the invention aims to provide a method for catalyzing Henry asymmetric addition reaction based on the water phase of the polyion liquid type chiral copper amino acid catalyst.
In order to achieve the purpose, the method for water phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral copper amino acid catalyst, which is designed by the invention, is characterized in that in a water phase, an aldehyde compound and a nitroalkane compound are subjected to Henry asymmetric addition reaction under the action of the polyion liquid type chiral copper amino acid catalyst to obtain a chiral β -nitroalcohol compound;
wherein the polyion liquid type chiral copper amino acid catalyst has a structure shown in a general formula (1), the aldehyde compound has a structure shown in a general formula (2), the nitroalkane compound has a structure shown in a general formula (3), and the β -nitroalcohol compound has a structure shown in a general formula (4);
R5-CHO formula (2)
R6NO2Formula (3)
In formula (1):
represents the R configuration or the S configuration;
R1、R2independently selected from hydrogen, alkyl, aryl-substituted alkyl;
R3selected from a hydrogen atom or an alkyl group;
R4is selected from C1～C16Alkyl, isopropyl, isobutyl, tert-butyl, benzyl or substituted aryl of (a);
in the formula (2), R5Selected from hydrogen, alkyl, substituted alkyl, phenyl, aryl, heterocyclic group containing;
in the formula (3), R6Selected from alkyl groups.
The principle of improving the catalytic reaction efficiency of the Henry asymmetric addition reaction in the water phase by utilizing the polyion liquid type chiral copper amino acid catalyst is as follows: the polyion liquid type chiral copper amino acid catalyst can be dissolved in water and can also be dissolved in reaction substrate nitroalkane.
Therefore, in the water phase, the catalyst, the reaction substrate and the water can be mutually dissolved and mutually contained. Further solving the problem that the organic substrate is insoluble in water, thereby increasing the collision frequency, accelerating the reaction rate and efficiently carrying out the Henry asymmetric addition reaction.
Preferably, R in the formula (2)3Selected from a hydrogen atom or a methyl group; r4Selected from methyl, ethyl, phenyl.
Preferably, the nitroalkane compound is nitromethane.
In the formula (3), R5One of the following substituents is selected from:
that is, the aldehyde compound is preferably benzaldehyde (formula C)7H6O); 4-bromobenzaldehyde (formula C)7H5BrO); 4-chlorobenzaldehyde (formula C)7H5ClO); 4-methoxybenzaldehyde (formula C)8H8O2) (ii) a 4-nitrobenzaldehyde (formula C)7H5NO3) (ii) a 4-cyanobenzaldehyde (formula C)8H5NO); 2-bromobenzaldehyde (formula C)7H5BrO); 2-chlorobenzaldehyde (formula C)7H5ClO); 2-methoxybenzaldehyde (formula C)8H10O2) (ii) a 2-nitrobenzaldehyde (formula C)7H5NO3) (ii) a 2-cyanobenzaldehyde (formula C)8H5NO)。
The β -nitroalcohol compound is (R) -1-phenyl-2-nitroalcohol (molecular formula C)8H9NO3) (ii) a (R) -1- (4-bromophenyl) -2-nitroalcohol (formula C)8H8BrNO3) (ii) a (R) -1- (4-chlorophenyl) -2-nitroalcohol (formula C)8H8ClNO3) (ii) a (R) -1- (4-methoxyphenyl) -2-nitroalcohol (formula C)9H11NO4) (ii) a (R) -1- (4-nitrophenyl) -2-nitroalcohol (formula C)8H8N2O5) (ii) a (R) -1- (4-cyanophenyl) -2-nitroalcohol (formula C)9H8N2O3) (ii) a (R) -1- (2-bromophenyl) -2-nitroalcohol (formula C)8H8BrNO3) (ii) a (R) -1- (2-chlorophenyl) -2-nitroalcohol (formula C)8H8ClNO3) (ii) a (R) -1- (2-methoxyphenyl) -2-nitroalcohol (formula C)9H11NO4) (ii) a (R) -1- (2-nitrophenyl) -2-nitroalcohol (formula C)8H8N2O5) (ii) a (R) -1- (2-cyanophenyl) -2-nitroalcohol (formula C)9H8N2O3)。
Preferably, the asymmetric Henry addition reaction comprises the specific steps of dissolving a polyion liquid type chiral copper amino acid catalyst in water, and adding an aldehyde compound and a nitroalkane compound into the aqueous solution, wherein the molar ratio of the polyion liquid type chiral copper amino acid catalyst to the aldehyde compound is 1: 30-1: 1000, and the molar ratio of the nitroalkane compound to the aldehyde compound is 1: 1-10: 1.
Preferably, the asymmetric Henry addition reaction is carried out at the temperature of-50 ℃ to 50 ℃ for 1 to 48 hours. The most preferable scheme is that the reaction temperature is 0-20 ℃, and the reaction time is further preferably 1-24 h.
As a preferred scheme, the polyion liquid type chiral copper amino acid catalyst is prepared by the following method:
(1) reacting a doubly-bound imidazole with a haloalkane (R)1X) reacting, and exchanging through anion resin to obtain double-bond ionic liquid;
(2) reacting the prepared double-bond ionic liquid with chiral amino acid to obtain double-bond ionic liquid type chiral amino acid;
(3) carrying out controllable free radical polymerization on the double-bond ionic liquid type chiral amino acid to obtain polymerized ionic liquid type amino acid;
(4) finally, the polyion liquid type chiral amino acid copper complex catalyst is obtained by the coordination of the polyion liquid type amino acid under the action of the metal copper salt.
The double-bond imidazole in the step (1) has a structure of a general formula (5); the chiral amino acid has a structure of a general formula (6); the double-bond ionic liquid has a structure of a general formula (7); the double-bond ionic liquid type chiral amino acid (IL-A) has a structure of a general formula (8); polymeric ionic liquid type amino acid P (IL-A)nHaving a structure of formula (9); ionic liquid type chiral copper amino acid complex catalyst P (IL-A)n-Cu junction of formula (1)Structuring;
in the above step (1), R1Selected from alkyl, aryl substituted alkyl; x is halogen element Br or Cl;
in the formula (6), R2A variable group selected from amino acids; represents the R configuration or the S configuration;
R3、R4each independently selected from hydrogen, alkyl, aryl-substituted alkyl;
the reaction formula of imidazole with haloalkane is:
in the step (2), the prepared ionic liquid is taken to react with chiral amino acid to obtain the double-bond ionic liquid type chiral amino acid.
In the step (3), a controllable-fragmentation chain transfer polymerization (RAFT) method is adopted, Azodiisobutyronitrile (AIBN) is used as a chain initiator, carbon thioester is used as a molecular weight regulator, and the double-bond ionic liquid type chiral amino acid is controllably polymerized to obtain polymerized ionic liquid type amino acid P (IL-A)n。
Wherein the carbon thioester has a structure of formula (10);
R3、R4each independently selected from hydrogen, alkyl, aryl-substituted alkyl;
synthesis of polymerized ionic liquid type amino acid P (IL-A) by controlled-broken chain transfer polymerization (RAFT)nThe reaction formula (A) is as follows:
in the step (4), the polyion liquid type amino acid polymer P (IL-A)nDissolving in organic solvent, adding copper salt for coordination, and adding polymer P (IL-A)nFormation of a metal complex catalyst P (IL-A) by coordination of the metaln-Cu。
The copper salt is one of copper acetate, copper nitrate, copper chloride and copper sulfate.
The invention has the advantages that: compared with the traditional catalyst with the structure of the general formula (11), the P (IL-A) of the inventionnThe Cu catalyst has the advantages of:
(1) p (IL-A) of the present inventionnthe-Cu catalyst adopts cheap and easily obtained chiral amino acid as a starting material, and has simple synthesis steps and high catalyst yield.
(2) P (IL-A) of the present inventionnthe-Cu catalyst can be used in an asymmetric Henry addition reaction system in a pure water phase, and effectively solves the problems of difficult mass transfer and low catalytic efficiency of the traditional catalyst in the water phase.
(3) After the reaction is finished, adding an organic solvent, P (IL-A)nthe-Cu catalyst can be conveniently recovered and effectively reused through phase transfer.
In addition, the present invention P (IL-A)nthe-Cu catalyst does not damage the active center of chiral amino acid in the preparation process, and has the advantages of wide source of synthetic raw materials, simple preparation method, safe operation, mild process conditions and contribution to large-scale industrial production.
Drawings
FIG. 1 shows catalyst P (IL-A)n-Transmission Electron Microscopy (TEM) image (20 x) of Cu in aqueous solution;
FIG. 2 shows catalyst P (IL-A)n-dynamic light scattering characterization (DLS) plot of Cu in aqueous solution.
Detailed Description
For a better understanding of the present invention, reference will now be made in detail to the present invention, examples of which are illustrated in the accompanying drawings.
The following abbreviations are used: azobisisobutyronitrile (AIBN), polyion liquid type amino acid polymer (P (IL-A)n) Polyion liquid type chiral copper amino acid catalyst (P (IL-A)n-Cu)。
Example 1
P(IL-A)n-a method for the preparation of Cu comprising the steps of:
(1) synthesis of ionic liquid compound containing double bond
Reaction formula 1:
in the above reaction formula 1, R1Is ethyl, and X is a bromine atom.
The specific operation process comprises the steps of adding 20mL of redistilled bromoethane and 20mL of ethyl acetate as a solvent into a 250mL three-neck flask, slowly dripping 20mL of ethyl acetate solution of vinyl imidazole by using a constant pressure dripping hole under the condition of heating reflux, and continuously heating, refluxing and stirring for 8 hours after white milky turbidity appears. After the reaction is finished, the solution is divided into two phases after the stirring is stopped, and the lower colorless viscous liquid is a crude product. Cooling to room temperature to obtain a white solid, carrying out suction filtration on the product, leaching with a small amount of petroleum ether, and finally recrystallizing with 20mL of acetonitrile and 20mL of ethyl acetate to obtain a white crystal product. Exchanging with 201X 7 type anion exchange resin to obtain double bond ionic liquid compound.
(2) Preparation of double-bond ionic liquid type chiral amino acid IL-A
Reaction formula 2:
in the above reaction formula 2, R2Is a variable group of amino acids, embodied as a benzyl group.
Adding 10mmol of the double-bond ionic liquid compound into a 100mL flask, slowly dropwise adding an aqueous solution dissolved with 10mmol of L-phenylalanine into the flask under magnetic stirring, continuously stirring at room temperature for reaction for 15h, and then spin-drying water by using a rotary evaporator to obtain a colorless liquid crude product. Vacuum drying the crude product for 48h, then adding 50mL acetonitrile and 10mL methanol into the system, violently stirring for 2h at room temperature, filtering, spin-drying the solvent, and vacuum drying for 24h at 80 ℃ to obtain the pure product.
(3) Polymeric ionic liquid type amino acid P (IL-A)nPreparation of
Reaction formula 3:
in the above reaction formula 3, R3Is benzyl, R4Is ethyl;
the specific operation process is that the ionic liquid type amino acid polymer is prepared by adopting a controllable-broken chain transfer radical polymerization (RAFT) method. The ionic liquid type chiral amino acid (5mmol) prepared above was dissolved in anhydrous methanol, and benzyl thiopropionate (chain transfer agent, 1/6mmol,0.0330g) and AIBN (chain initiator, 1/30mmol,0.0052g) were added to the reaction solution. N is a radical of2Under protection, the reaction solution is placed in a Schlenk tube to react for 24h at 60 ℃, after the reaction is finished, the reaction solution is concentrated in vacuum to obtain a light yellow solid product, and the light yellow solid product is dried in vacuum at 30 ℃ to obtain the polymerized ionic liquid type amino acid P (IL-A)n。
(4)P(IL-A)nPreparation of-Cu catalyst
Reaction formula 4:
4mmol of the P (IL-A) prepared above are takennDissolved in 30mL of absolute ethanol/ethyl acetate, and 2mmol of copper acetate was added thereto, followed by reaction under reflux for 24 hours. After the reaction is finished, the solvent is dried by spinning, and the P (IL-A) is obtained by vacuum drying at the temperature of 30 DEG Cn-Cu. For P (IL-A)nCharacterization of Cu, FT-IR (KBr): gammamax/cm-13427,3060,2963,1725,1616,1551,1452,1391,1335,1270,1172,1134,1101,1046,1013,920,833,670,625,551,512,450cm-1.α25 D＝-62.7(C＝0.005g mL-1,CH2Cl2)。
Example 2
P (IL-A) obtained in example 1n-Cu is used to catalyze Henry asymmetric addition reactions; that is, in an aqueous medium, the aldehyde compound and the nitroalkane are in P (IL-A)nCarrying out asymmetric Henry addition reaction under the catalytic action of a-Cu catalyst to obtain β -nitroalcohol compound.
The aldehyde compound has a structure shown in a general formula (2), the nitroalkane compound has a structure shown in a general formula (3), and the β -nitroalcohol compound has a structure shown in a general formula (4).
R5-CHO formula (2)
R6-NO2Formula (3)
In this example R5Is phenyl, R6Is methyl, namely the aldehyde compound is benzaldehyde, the nitroalkane is nitromethane, and the specific catalytic process is that 0.8mmol of catalyst P (IL-A) is added into a 10mL reaction bottlen-Cu，1mL H2O dissolves the catalyst, then 1mmol of benzaldehyde and 3mmol of nitromethane are added into the solution, and the reaction is stirred at the temperature of 25 ℃. And (3) monitoring the reaction in real time by using a thin-layer chromatography, and adding n-hexane into the reaction system after the reaction is finished, so that the reaction solution is layered. Separating out the catalyst, extracting the water phase with dichloromethane to obtain a product, performing liquid chromatography on the product to detect the conversion rate and selectivity and the enantiomer selectivity of the product, performing column chromatography and the like on the product, calculating to obtain the yield, and performing nuclear magnetic characterization to determine the structure of the product. Characterization data for the obtained product were: (R) -2-nitro-1- (4-nitrophenyl) alcohol: white solidAnd (4) silica gel column chromatography (ethanol: n-hexane: 85: 15 (vol.)), (98% yield, 99% ee). And (3) product structure characterization: IR (film)3508,2921,2851,1552,1515,1416,1379,1347,1080,855cm-1；1H NMR(400MHz,CDCl3)8.31-8.27(m,2H,ArH),7.65-7.63(m,2H,ArH),5.62(dt,1H,J＝8.0,4.0Hz,CHOH),4.65-4.55(m,2H,CH2NO2),3.09(d,J＝4.0Hz,OH)；13C NMR(100MHz,CDCl3)148.0,145.0,126.9,124.1,80.6,69.9. The ee value is determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane: 15:85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm, temperature 25 ℃ C.).
P (IL-A) obtained in example 1nComparison of Cu and conventional catalysts for catalysis of Henry addition reactions, the results are shown in Table 1 below:
TABLE 1
| Serial number | Catalyst and process for preparing same | Time (h) | Yield (%) | Enantioselectivity (%) |
| 1 | P(IL-A)n- |
15 | 70 | 99 |
| 2 | P(IL-A)n-Cu | 24 | 96 | 99 |
| 3 | Conventional catalyst | 12 | 10 | 35 |
| 4 | Conventional catalyst | 48 | 35 | 35 |
The conventional catalyst in Table 1 has a structure of the general formula (11):
r is methyl, carboxyl, phenyl, long-chain alkyl and other amino acid substituent groups.
As can be seen from Table 1, the conventional catalyst is difficult to dissolve in water, but the organic catalyst is better in contact with an organic substrate than copper acetate, so that the reaction time is 48 hours, the yield is 35%, but the enantioselectivity is lower. When catalyst P (IL-A) is usednWhen the Cu-Cu reaction is carried out, the catalyst has good solubility in water, so that the good contact between an organic substrate and the catalyst can be promoted, the reaction can be finished in 24 hours, the yield is up to 96%, and the enantioselectivity is up to 99%.
Example 3
Catalyst P (IL-A)nCu and a conventional copper amino acid catalyst for catalyzing the reaction of other aldehyde compounds with nitroalkanes, the results of which are shown in table 2 below:
TABLE 2
As can be seen from the table, the reaction time was 24 hours, compared with the conventional catalyst, catalyst P (IL-A)nthe-Cu has great advantages in yield and ee value, the catalytic effects of different substrates are obviously improved, and the yield of the product β -nitroalcohol is greatly improved.
The characterization data for the partial products are as follows:
(R) -1-phenyl-2-nitroalcohol: colorless oil, silica gel column chromatography (ethanol: dichloromethane: 90: 10 (vol.)), (59% yield, 91% ee). And (3) product structure characterization: IR (film)3542,3033,2920,1688,1555,1494,1454,1418,1379,1288,1201,1066,894,765,700,508cm-1；1H NMR(400MHz,CDCl3)7.42-7.35(m,5H,ArH),5.45-5.42(m,1H,CHOH),4.54-4.49(dd,1H,J＝13.2,9.8Hz,CH2NO2),4.43-4.40(dd,1H,J＝13.2,2.9Hz,CH2NO2),2.96(d,1H,J＝3.9Hz,OH)；13C NMR (125MHz, CDCl3)138.3,129.3,129.2,126.2,81.4, 71.2; the ee value is determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane: 15:85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm, temperature 25 ℃ C.).
(R) -1- (4-bromophenyl) -2-nitroalcohol: colorless oil, silica gel column chromatography (ethanol: dichloromethane: 90: 10 (vol.)), (72% yield, 89% ee). And (3) product structure characterization: IR (film)3527,2921,1596,1556,1493,1414,1379,1343,1296,1210,1192,1090,1014,896,829,740,661,526cm-1；1H NMR(500MHz,CDCl3)7.38-7.32(m,4H,ArH),5.44-5.41(m,1H,CHOH),4.56(dd,1H,J＝13.3,9.5Hz,CH2NO2),4.48(dd,1H,J＝13.3,2.9,CH2NO2),3.14(d,1H,4.0Hz,OH)；13C NMR(125MHz,CDCl3)136.5,134.7,129.1,127.3,80.9,70.2, ee value determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane 15:85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (4-cyanophenyl) -2-nitroalcohol: colorless oil, silica gel column chromatography (ethanol: dichloromethane: 90: 10 (vol.)), (83% yield, 95% ee). And (3) product structure characterization: IR (film)3527,2921,1597,1555,1496,1416,1377,1342,1294,1013,895,825,743,664,526cm-1；1H NMR(500MHz,CDCl3)7.38-7.32(m,4H,ArH),5.51-5.55(m,1H,CHOH),4.53-4.56(dd,2H,J＝13.3,9.5Hz,CH2NO2),3.25(d,1H,4.0Hz,OH)；13C NMR(125MHz,CDCl3)143.2,132.3,126.6,118.3,112.4,78.1,70.3, ee value determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane 15:85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-nitrophenyl) -2-nitroalcohol: the brown crystals were isolated by silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol.)), (95% yield, 99% ee). And (3) product structure characterization: IR (film)3541,1548,1532,1410,1365,1354,1093,1071,865cm-1；1H NMR(500MHz,CDCl3)8.11-8.08(m,1H,ArH),7.98-7.96(m,1H,ArH),7.78-7.74(m,1H,ArH),7.59-7.55(m,1H,ArH),6.07(ddd,1H,J＝8.8,4.2,2.2Hz,CHOH),4.89(dd,1H,J＝13.9,2.2Hz,CH2NO2),4.57(dd,1H,J＝13.9,8.8Hz,CH2NO2),3.15(d,1H,4.2Hz,OH)；13C NMR(100MHz,CDCl3)147.1,134.4,133.9,129.7,128.7,125.0,80.0,66.8, ee value determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane ═ 10:90 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-chlorophenyl) -2-nitroalcohol: the brown crystals were isolated by silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol.)), (76% yield, 92% ee). And (3) product structure characterization: IR (film)3531,1556,1493,1414,1379,1296,1210,1090,1014,896,829,740,661,530cm-1；1H NMR(500MHz,CDCl3)7.64(dd,1H J＝8.0,2.0Hz,ArH),7.37-7.32(m,2H,ArH),7.30-7.27(m,1H,ArH),5.84-5.81(m,1H,CHOH),4.65(dd,1H,J＝13.7,2.4Hz,CH2NO2),4.43(dd,1H,J＝13.7,9.8Hz,CH2NO2),3.01(d,1H,4.4Hz,OH)；13C NMR(125MHz,CDCl3)135.4,131.4,129.9,129.7,127.6,127.5,79.2,67.8, ee value determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane 3:97 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-methylphenyl) -2-nitroalcohol: the brown crystals were isolated by silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol.)), (43% yield, 89% ee). And (3) product structure characterization: IR (film)3522,3444,3033,2911,1688,1550,1483,1461,1411,1378,1286,1208,1069,895,762,730,616cm-1；1H NMR(500MHz,CDCl3)7.51-7.49(m,1H,ArH),7.27-7.25(m,2H,ArH),7.19-7.18(m,1H,ArH),5.66-5.64(m,1H,CHOH),4.54-4.49(dd,1H,J＝13.2,9.8Hz,CH2NO2),4.43-4.40(dd,1H,J＝13.2,2.4Hz,CH2NO2),2.97(s,1H,OH),2.38(s,3H,CH3)；13C NMR(125MHz,CDCl3)136.5,134.7,131.1,128.9,127.0,125.8,80.4, 68.1; 19.1, the ee value is determined by chiral high performance liquid chromatography (column: Daicel chiralpak AD, mobile phase: isopropanol/n-hexane ═ 15:85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm, temperature 25 ℃ C.).
Example 4
Catalyst P (IL-A)nExperiment of-Cu reusability
And adding normal hexane into the solution after the reaction is finished, separating out the catalyst, separating a water phase from an organic phase, centrifuging the catalyst, washing the normal hexane, and drying to obtain the recovered catalyst. Recovering catalyst P (IL-A)nThe effect of the repeated use of Cu in the next catalytic reaction system is shown in the following Table 3:
TABLE 3
The reaction system adopts a green and environment-friendly process with water as a reaction solvent, an economic and environment-friendly route can be provided for industrially generating chiral β -nitroalcohol, and the problem of environmental pollution in the industrial production process is solved.
As can be seen from fig. 1 and 2, the catalyst can form nano-spherical particles in water, and the particles are uniform and have a single shape.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (9)
1. A method for water phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst is characterized in that in water phase, aldehyde compound and nitroalkane compound are subjected to Henry asymmetric addition reaction under the catalysis of polyion liquid type chiral copper amino acid catalyst to obtain chiral β -nitroalcohol compound;
wherein the polyion liquid type chiral copper amino acid catalyst has a structure shown in a general formula (1), the aldehyde compound has a structure shown in a general formula (2), the nitroalkane compound has a structure shown in a general formula (3), and the β -nitroalcohol compound has a structure shown in a general formula (4);
R5-CHO formula (2)
R6NO2Formula (3)
In formula (1):
represents the R configuration or the S configuration;
R1、R2independently selected from hydrogen, alkyl, aryl-substituted alkyl;
R3selected from a hydrogen atom or an alkyl group;
R4is selected from C1～C16Alkyl, isopropyl, isobutyl, tert-butyl, benzyl or substituted aryl of (a);
in the formula (2), R5Selected from hydrogen, alkyl, substituted alkyl, phenyl, aryl, heterocyclic group containing;
in the formula (3), R6Selected from alkyl groups.
2. The method for water-phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral copper amino acid catalyst as claimed in claim 1, wherein the polyion liquid type chiral copper amino acid catalyst is prepared by the following method:
(1) reacting double-bond imidazole with halogenated alkane, and exchanging by anion resin to obtain double-bond ionic liquid;
(2) reacting the prepared double-bond ionic liquid with chiral amino acid to obtain double-bond ionic liquid chiral amino acid;
(3) carrying out controllable free radical polymerization on the double-bond ionic liquid type chiral amino acid to obtain polymerized ionic liquid type amino acid;
(4) finally, the polyion liquid type chiral amino acid copper complex catalyst is obtained by the coordination of the polymer under the action of metal copper salt.
3. The method for water-phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral copper amino acid complex catalyst as claimed in claim 2,
the double-bond imidazole in the step (1) has a structure of a general formula (5); the chiral amino acid has a structure of a general formula (6); the double-bond ionic liquid has a structure of a general formula (7); the double-bond ionic liquid type chiral amino acid has a structure of a general formula (8); the polymerized ionic liquid type amino acid has a structure of a general formula (9); the ionic liquid type chiral copper amino acid complex catalyst has a structure shown in a general formula (1);
wherein R is1Selected from alkyl, aryl substituted alkyl;
R2a variable group selected from amino acids; represents the R configuration or the S configuration;
R3、R4independently selected from hydrogen, alkyl, aryl substituted alkyl.
4. The method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid complex catalyst as claimed in claim 2, wherein the general formula of the halogenated alkane is R1X，R1Selected from alkyl, aryl substituted alkyl; x is halogen element Br or Cl.
5. The method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral amino acid copper complex catalyst according to claim 1, wherein R is5One of the following substituents is selected from:
6. the method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral amino acid copper complex catalyst according to claim 1, wherein R is6Selected from methyl.
7. The method for water-phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral copper amino acid complex catalyst as claimed in claim 1, wherein n in the formula (1) is 20-100.
8. The method for water-phase catalysis Henry asymmetric addition reaction based on the polyion liquid chiral copper amino acid complex catalyst as claimed in claim 1, wherein the asymmetric Henry addition reaction is specifically carried out by dissolving the polyion liquid chiral copper amino acid complex catalyst in water, and then adding an aldehyde compound and a nitroalkane compound into the aqueous solution, wherein the molar ratio of the polyion liquid chiral copper amino acid complex catalyst to the aldehyde compound is 1: 30-1: 1000, and the molar ratio of the nitroalkane compound to the aldehyde compound is 1: 1-10: 1.
9. The method for water-phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral amino acid copper complex catalyst according to claim 1, wherein the asymmetric Henry addition reaction is carried out at a temperature of-50 ℃ to 50 ℃ for 1 h to 48 h.
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