CN110551031A - 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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- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0281—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the nitrogen being a ring member
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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 by a polyion liquid type chiral copper amino acid catalyst. In a water phase, an aldehyde compound and a nitroalkane compound are subjected to a Henry asymmetric addition reaction under the catalytic action of a polyion liquid type chiral copper amino acid catalyst to obtain a chiral beta-nitroalcohol compound; in the reaction process, the polyion liquid type chiral copper amino acid catalyst can effectively perform water phase asymmetric Henry addition reaction, and meanwhile, the catalyst can be effectively recovered and reused 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
The chiral beta-nitroalcohol compound has wide application, and the chiral beta-nitroalcohol compound is obtained by directly carrying out asymmetric Henry addition reaction on nitroalkane and aldehyde substances under the action of a chiral catalyst at present. However, the reaction is mainly carried out in an organic solvent, which is not favorable for the development of green chemical engineering.
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 beta-nitroalcohol compound;
wherein, the polyion liquid type chiral copper amino acid catalyst has a structure of a general formula (1); the aldehyde compound has a structure of general formula (2); the nitroalkane compound has a structure of a general formula (3); the beta-nitroalcohol compound has a structure of a general formula (4);
r 5 -CHO formula (2)
R 6 NO 2 formula (3)
In formula (1):
Represents the R configuration or the S configuration;
r 1 and R 2 are independently selected from hydrogen, alkyl, aryl and aryl-substituted alkyl;
R 3 is selected from a hydrogen atom or an alkyl group;
R 4 is selected from C 1 -C 16 alkyl, isopropyl, isobutyl, tert-butyl, benzyl or substituted aryl;
In formula (2), R 5 is selected from hydrogen, alkyl, substituted alkyl, phenyl, aryl, heterocyclic group containing;
In formula (3), R 6 is selected 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 3 in formula (2) is selected from hydrogen atom or methyl group, and R 4 is selected from methyl, ethyl and phenyl.
Preferably, the nitroalkane compound is nitromethane.
In the formula (3), R 5 is selected from one of the following substituents:
The aldehyde compound is preferably benzaldehyde (molecular formula C 7 H 6 O), 4-bromobenzaldehyde (molecular formula C 7 H 5 BrO), 4-chlorobenzaldehyde (molecular formula C 7 H 5 ClO), 4-methoxybenzaldehyde (molecular formula C 8 H 8 O 2), 4-nitrobenzaldehyde (molecular formula C 7 H 5 NO 3), 4-cyanobenzaldehyde (molecular formula C 8 H 5 NO), 2-bromobenzaldehyde (molecular formula C 7 H 5 BrO), 2-chlorobenzaldehyde (molecular formula C 7 H 5 ClO), 2-methoxybenzaldehyde (molecular formula C 8 H 10 O 2), 2-nitrobenzaldehyde (molecular formula C 7 H 5 NO 3) and 2-cyanobenzaldehyde (molecular formula C 8 H 5 NO).
8 9 3 8 8 3 8 8 3 9 11 4 8 8 2 5 9 8 2 3 8 8 3 8 8 3 9 11 4 8 8 2 5 9 8 2 3the beta-nitroalcohol compound is (R) -1-phenyl-2-nitroalcohol (molecular formula C H NO), (R) -1- (4-bromophenyl) -2-nitroalcohol (molecular formula C H BrNO), (R) -1- (4-chlorophenyl) -2-nitroalcohol (molecular formula C H ClNO), (R) -1- (4-methoxyphenyl) -2-nitroalcohol (molecular formula C H NO), (R) -1- (4-nitrophenyl) -2-nitroalcohol (molecular formula C H N O), (R) -1- (4-cyanophenyl) -2-nitroalcohol (C H N O), (R) -1- (2-bromophenyl) -2-nitroalcohol (molecular formula C H BrNO), (R) -1- (2-chlorophenyl) -2-nitroalcohol (C H ClNO), (R) -1- (2-methoxyphenyl) -2-nitroalcohol (C H NO), (R) -1- (2-nitrophenyl) -2-nitroalcohol (C H NO), (R) -2-cyanophenyl) -2-nitroalcohol (C H ClNO), (R) -1- (2-nitrophenyl) -2-nitroalcohol (C H N) (molecular formula C H ClNO).
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 double-bond imidazole with halogenated alkane (R 1 X), 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 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.
In the step (1), the double-bond imidazole has a structure shown in a general formula (5), the chiral amino acid has a structure shown in a general formula (6), the double-bond ionic liquid has a structure shown in a general formula (7), the double-bond ionic liquid chiral amino acid (IL-A) has a structure shown in a general formula (8), the polymerized ionic liquid amino acid P (IL-A) n has a structure shown in a general formula (9), and the ionic liquid chiral amino acid copper complex catalyst P (IL-A) n -Cu has a structure shown in a general formula (1);
In the step (1), R 1 is selected from alkyl, aryl and aryl-substituted alkyl, X is halogen element Br or Cl;
in formula (6), R 2 is selected from the variable groups of amino acids, and represents R configuration or S configuration;
r 3 and R 4 are independently selected from hydrogen, alkyl, aryl and 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, Azobisisobutyronitrile (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 subjected to controllable polymerization to obtain the polymerized ionic liquid type amino acid P (IL-A) n.
Wherein the carbon thioester has a structure of formula (10);
R 3 and R 4 are independently selected from hydrogen, alkyl, aryl and aryl-substituted alkyl;
The reaction formula for synthesizing the polymerized ionic liquid amino acid P (IL-A) n by a controlled-fragmentation chain transfer polymerization (RAFT) method is as follows:
In the step (4), the polyion liquid amino acid polymer P (IL-A) n is dissolved in an organic solvent, copper salt is added for coordination, and the polymer P (IL-A) n forms a metal complex catalyst P (IL-A) n -Cu under the coordination of metal.
The copper salt is one of copper acetate, copper nitrate, copper chloride and copper sulfate.
Compared with the traditional catalyst with the structure of the general formula (11), the P (IL-A) n -Cu catalyst has the advantages that:
(1) The P (IL-A) n -Cu catalyst adopts cheap and easily-obtained chiral amino acid as a starting material, and has simple synthesis steps and high catalyst yield.
(2) the P (IL-A) n -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, the P (IL-A) n -Cu catalyst can be conveniently recovered and effectively reused by phase transfer by adding an organic solvent.
in addition, the P (IL-A) n -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 is a Transmission Electron Micrograph (TEM) of catalyst P (IL-A) n -Cu in aqueous solution (20 times);
FIG. 2 is a graph of the dynamic light scattering characterization (DLS) of catalyst P (IL-A) n -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 adopted, namely Azobisisobutyronitrile (AIBN), polyion liquid type amino acid polymer (P (IL-A) n) and polyion liquid type chiral copper amino acid catalyst (P (IL-A) n -Cu).
Example 1
A method for preparing P (IL-A) n -Cu, comprising the steps of:
(1) synthesis of ionic liquid compound containing double bond
Reaction formula 1:
In the above reaction formula 1, R 1 is an ethyl group, 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, R 2 is a variable group of an amino acid, specifically represented by benzyl.
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) Preparation of polymerized ionic liquid type amino acid P (IL-A) n
Reaction formula 3:
in the reaction formula 3, R 3 is benzyl, R 4 is ethyl;
the preparation method comprises the following specific operation processes of preparing an ionic liquid type amino acid polymer by adopting a controlled-broken chain transfer radical polymerization (RAFT) method, dissolving the prepared ionic liquid type chiral amino acid (5mmol) in absolute methanol, adding benzyl thiopropionate (chain transfer agent, 1/6mmol,0.0330g) and AIBN (chain initiator, 1/30mmol,0.0052g) into a reaction solution, placing the reaction solution into a Schlenk tube under the protection of N 2, reacting for 24 hours at 60 ℃, concentrating the reaction solution in vacuum to obtain a light yellow solid product after the reaction is finished, and drying in vacuum at 30 ℃ to obtain the polymerized ionic liquid type amino acid P (IL-A) n.
(4) preparation of P (IL-A) n -Cu catalyst
Reaction formula 4:
4mmol of the P (IL-A) n prepared above is taken and dissolved in 30mL of absolute ethyl alcohol/ethyl acetate, 2mmol of copper acetate is added into the solution, the reflux reaction is carried out for 24h, after the reaction is finished, the solvent is dried in a spinning mode, vacuum drying is carried out at the temperature of 30 ℃, P (IL-A) n -Cu. is obtained, and the corresponding characterization is carried out on P (IL-A) n -Cu, FT-IR (KBr): gamma max/cm -1 3427,3060,2963,1725,1616,1551,1452,1391,1335,1270,1172,1134,1101,1046,1013,920,833,670,625,551,512,450cm -1, alpha 25 D ═ 62.7(C ═ 0.005g mL -1 2 Cl 2).
Example 2
The P (IL-A) n -Cu obtained in the example 1 is used for catalyzing Henry asymmetric addition reaction, namely, in an aqueous medium, the aldehyde compound and the nitroalkane are subjected to asymmetric Henry addition reaction under the catalysis of a P (IL-A) n -Cu catalyst to obtain the beta-nitroalcohol compound.
The aldehyde compound has a structure of general formula (2); the nitroalkane has the structure of the general formula (3); the beta-nitroalcohol compound has a structure of a general formula (4).
R 5 -CHO formula (2)
R 6 -NO 2 formula (3)
Reaction formula 5
In this example, R 5 is phenyl, R 6 is methyl, that is, the aldehyde compound is benzaldehyde, the nitroalkane is nitromethane, and the specific catalytic process is that 0.8mmol of catalyst P (IL-a) n -Cu, 1mL of H 2 O is added into a 10mL reaction flask, then 1mmol of benzaldehyde and 3mmol of nitromethane are added thereto, and the reaction is stirred at 25 ℃, thin layer chromatography monitors the reaction in real time, after the reaction is finished, n-hexane is added into the reaction system, a layering phenomenon occurs in the reaction liquid, the catalyst is separated, the aqueous phase is extracted with dichloromethane to obtain a product, and the product is subjected to liquid chromatography to detect the conversion rate and selectivity and the enantioselectivity of the product, and the product is subjected to 8655 to calculate to obtain the yield, nuclear magnetic chromatography to determine the product structure, the characterization data of the obtained product are (R) -2-nitro-1- (4-nitrophenyl) alcohol: white solid, silica gel column chromatography (ethanol: n-hexane: 85: 15 (volume ratio), ee (98% yield, 99% ir: 1- (4H 5: 85H-55 MHz), the product structure of the obtained is characterized by (CH), the flow rate of the H-2H-55H-75H equivalent of the CH-2H-55H flow rate of the CH-2H-55H flow rate of the product (CH-27H-2H-55H flow rate of the 1H-2H flow rate of the 1H-27H-2H-27H flow rate of the 1H-99H-2H-75H flow-99H flow rate of the product), the sample (CH-85H flow rate of the 1H-27H-55H flow rate of the 1H flow rate of the sample), the sample of the sample.
the results of comparing the P (IL-A) n -Cu obtained in example 1 with a conventional catalyst for catalyzing Henry addition reaction 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-Cu | 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.
nAs can be seen from Table 1, the traditional catalyst is difficult to dissolve in water, but the contact between the organic catalyst and an organic substrate is better than that between copper acetate, so that the yield is 35% after 48 hours of reaction, but the enantioselectivity is lower.
example 3
Catalyst P (IL-a) n -Cu and a conventional copper amino acid catalyst were used to catalyze the reaction of other aldehyde compounds and nitroalkanes, the results of which are shown in table 2 below:
TABLE 2
As can be seen from the table, compared with the traditional catalyst, the catalyst P (IL-A) n -Cu has great advantages in yield and ee value after 24h reaction, the catalytic effects of different substrates are obviously improved, and the yield of the product beta-nitroalcohol is greatly improved.
The characterization data for the partial products are as follows:
(R) -1-phenyl-2-nitroalcohol as colorless oil, isolated by silica gel column chromatography (ethanol: dichloromethane: 90: 10 (vol.)), (59% yield, 91% ee.) product structural characterisation IR (film)3542,3033,2920,1688,1555,1494,1454,1418,1379,1288,1201,1066,894,765,700,508cm -1; 1 H NMR (400MHz, CDCl 3)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, CH 2 NO 2),4.43-4.40(dd,1H, J ═ 13.2,2.9Hz, CH 2 NO 2),2.96(d,1H, J ═ 3.9Hz, OH), 13 C NMR (125MHz, CDCl3)138.3,129.3,129.2,126.2,81.4, chiral HPLC (chiral chromatographic column: 15 mL), HPLC temperature (DalH: 85 nm), HPLC temperature: 15 mL), HPLC temperature (DalH: 25 nm).
(R) -1- (4-bromophenyl) -2-nitroalcohol as colorless oil, which was separated by silica gel column chromatography (ethanol: dichloromethane: 90: 10 (vol.))), (72% yield, 89% ee.) the product was characterized by IR (film)3527,2921,1596,1556,1493,1414,1379,1343,1296,1210,1192,1090,1014,896,829,740,661,526cm -1, 1 H NMR (500MHz, CDCl 3)7.38-7.32(m,4H, ArH),5.44-5.41(m,1H, CHOH),4.56(dd,1H, J ═ 13.3,9.5Hz, CH 2 NO 2),4.48(dd,1H, J ═ 13.3,2.9, CH 2 NO 2),3.14(d,1H,4.0Hz, OH), 13 C NMR (125MHz, CDCl 3)136.5,134.7,129.1,127.3,80.9,70.2, the value was determined by chiral liquid chromatography (Chirac: daik: 15 mL), the flow rate of chloroform: 85 nm).
(R) -1- (4-cyanophenyl) -2-nitroalcohol as colorless oil, silica gel column chromatography (ethanol: dichloromethane 90: 10 (vol.)), (83% yield, 95% ee.) the product structure was characterized by IR (film)3527,2921,1597,1555,1496,1416,1377,1342,1294,1013,895,825,743,664,526cm -1, 1 H NMR (500MHz, CDCl 3)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, CH 2 NO 2),3.25(d,1H,4.0Hz, OH), 13 C NMR (125MHz, CDCl 3)143.2,132.3,126.6,118.3,112.4,78.1,70.3, ee value was determined by chiral high performance liquid chromatography (column: I icetralpak, mobile phase: isopropanol/85 (vol.: 85 min), n-hexane/vol.: 25: 8, 25 nm, flow rate: 215 mL, wavelength).
(R) -1- (2-nitrophenyl) -2-nitroalcohol: brown crystals, silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol)), (95% yield, 99% ee.) the product is characterised by IR (film)3541,1548,1532,1410,1365,1354,1093,1071,865cm -1, 1 H NMR (500MHz, CDCl 3)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, CHddOH), 4.89 (1H, J ═ 13.9,2.2Hz, CH 2 NO 2),4.57(dd,1H, J ═ 13.9,8.8, 7.89 (H, J ═ 13.9, 2Hz, CH 2 NO 2),4.57 (ddy, 10H, J ═ 358, 8.8, 7.8, 7H, J ═ 13.35, J ═ 13.9, 13.8, H, J: (60, 35, 60, 35, 60, 15H, 35, 60, 15H, 15H, 60, 15H, 35, 60.
(R) -1- (2-chlorophenyl) -2-nitroalcohol: brown crystals, silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol.)), (76% yield, 92% ee.) the product structure is characterised by IR (film)3531,1556,1493,1414,1379,1296,1210,1090,1014,896,829,740,661,530cm -1; 1 H NMR (500MHz, CDCl 3)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, CHiceH), 4.65(dd,1H, J: 13.7,2.4Hz, CH 2 NO 2),4.43(dd,1H, J: 13.7,9.8Hz, CH 2 NO 5), 3.01(d,1H,4 OH, 4.4838 Hz, 7, 7.8 Hz, CH 2 NO 5, 3.01(d, 8H, 4 OH, 35.35 MHz, 35% HCl, 97: 8% HCl/7, 97: 8% HCl, 97: 7, 2: 97: 7, 35: 7, 3.7, 35.
(R) -1- (2-methylphenyl) -2-nitroalcohol: brown crystals, silica gel column chromatography (ethanol: n-hexane: 80: 20 (vol)), (43% yield, 89% ee.) the product is characterised by IR (film)3522,3444,3033,2911,1688,1550,1483,1461,1411,1378,1286,1208,1069,895,762,730,616cm -1, 1 H NMR (500MHz, CDCl 3)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, CH 2 NO 2),4.43-4.40(dd,1H, J-13.2, 2.4Hz, CH 2 NO 4), 2.97(s,1H, OH), 2.38H, 483, 10.8 MHz, 10% GC-2, 15: 35 mL), HPLC (18: 15: 10: 10.8 MHz, 15: 10.85 ℃ C), HPLC (HPLC), HPLC).
example 4
experiment of reusability of catalyst P (IL-A) n -Cu
Adding normal hexane into the solution after the reaction is finished, separating a water phase and an organic phase, centrifuging the catalyst, washing the normal hexane, and drying to obtain a recovered catalyst, wherein the recovered catalyst P (IL-A) n -Cu is used in the next catalytic reaction system, and the reuse effect is shown in the following table 3:
TABLE 3
from the above data, it can be seen that the catalyst has better reusability. The reaction system is a green and environment-friendly process using water as a reaction solvent, can provide an economic and environment-friendly route for industrially generating the chiral beta-nitroalcohol, and solves the problem of environmental pollution in the industrial production process.
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 the water phase, aldehyde compounds and nitroalkane compounds are subjected to Henry asymmetric addition reaction under the catalysis of the polyion liquid type chiral copper amino acid catalyst to obtain chiral beta-nitroalcohol compounds;
Wherein, the polyion liquid type chiral copper amino acid catalyst has a structure of a general formula (1); the aldehyde compound has a structure of general formula (2); the nitroalkane compound has a structure of a general formula (3); the beta-nitroalcohol compound has a structure of a general formula (4);
R 5 -CHO formula (2)
r 6 NO 2 formula (3)
In formula (1):
Represents the R configuration or the S configuration;
r 1 and R 2 are independently selected from hydrogen, alkyl, aryl and aryl-substituted alkyl;
R 3 is selected from a hydrogen atom or an alkyl group;
R 4 is selected from C 1 -C 16 alkyl, isopropyl, isobutyl, tert-butyl, benzyl or substituted aryl;
In formula (2), R 5 is selected from hydrogen, alkyl, substituted alkyl, phenyl, aryl, heterocyclic group containing;
In formula (3), R 6 is selected 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 1 is selected from alkyl, aryl substituted alkyl;
R 2 is selected from the variable groups of amino acids, representing the R configuration or the S configuration;
R 3 and R 4 are independently selected from hydrogen, alkyl, aryl and aryl-substituted alkyl.
4. 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, wherein the general formula of the halogenated alkane is R 1 X, R 1 is selected from alkyl, aryl and aryl-substituted alkyl, and X is halogen element Br or Cl.
5. The method for water-phase catalysis of Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid complex catalyst as claimed in claim 1, wherein R 5 is selected from one of the following substituents:
6. 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 R 6 is selected 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 1h to 48 h.
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