CN111285769B - Method for aqueous phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst - Google Patents
Method for aqueous phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst Download PDFInfo
- Publication number
- CN111285769B CN111285769B CN202010308787.3A CN202010308787A CN111285769B CN 111285769 B CN111285769 B CN 111285769B CN 202010308787 A CN202010308787 A CN 202010308787A CN 111285769 B CN111285769 B CN 111285769B
- Authority
- CN
- China
- Prior art keywords
- amino acid
- liquid type
- catalyst
- henry
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- 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
- B01J31/0284—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 of an aromatic ring, e.g. pyridinium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0213—Complexes without C-metal linkages
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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, carrying out a Henry asymmetric addition reaction on an aldehyde compound and a nitroalkane compound 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 is mainly 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 beneficial to the development of green chemical industry.
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 a novel chiral ligand, but the existing patent rarely uses ionic liquid amino acid directly complexed 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.
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 shown in a general formula (4);
R 5 -CHO formula (2)
R 6 CH 2 NO 2 Formula (3)
In formula (1):
* Represents R configuration or S configuration;
R 1 、R 2 independently selected from hydrogen, alkyl, aryl-substituted alkyl;
R 3 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 of (a);
in the formula (2), R 5 Selected from hydrogen, alkyl, substituted alkyl, phenyl, aryl, heterocyclic-containing groups;
in the formula (3), R 6 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 in the formula (2) 3 Selected from a hydrogen atom or a methyl group; r 4 Selected from methyl, ethyl, phenyl.
Preferably, the nitroalkane compound is nitromethane.
In the formula (3), R 5 One of the following substituents is selected from:
that is, the aldehyde compound is preferably benzaldehyde (formula C) 7 H 6 O); 4-bromobenzaldehyde (formula C) 7 H 5 BrO); 4-chlorobenzaldehyde (formula C) 7 H 5 ClO); 4-methoxybenzaldehyde (formula C) 8 H 8 O 2 ) (ii) a 4-nitrobenzaldehyde (formula C) 7 H 5 NO 3 ) (ii) a 4-cyanobenzaldehyde (formula C) 8 H 5 NO); 2-bromobenzaldehyde (formula C) 7 H 5 BrO); 2-chlorobenzaldehyde (formula C) 7 H 5 ClO); 2-methoxybenzaldehyde (formula C) 8 H 10 O 2 ) (ii) a 2-nitrobenzaldehyde (formula C) 7 H 5 NO 3 ) (ii) a 2-cyanobenzaldehyde (formula C) 8 H 5 NO)。
The beta-nitroalcohol compound is (R) -1-phenyl-2-nitroalcoholSub-formula C 8 H 9 NO 3 ) (ii) a (R) -1- (4-bromophenyl) -2-nitroalcohol (formula C) 8 H 8 BrNO 3 ) (ii) a (R) -1- (4-chlorophenyl) -2-nitroalcohol (formula C) 8 H 8 ClNO 3 ) (ii) a (R) -1- (4-methoxyphenyl) -2-nitroalcohol (formula C) 9 H 11 NO 4 ) (ii) a (R) -1- (4-nitrophenyl) -2-nitroalcohol (formula C) 8 H 8 N 2 O 5 ) (ii) a (R) -1- (4-cyanophenyl) -2-nitroalcohol (formula C) 9 H 8 N 2 O 3 ) (ii) a (R) -1- (2-bromophenyl) -2-nitroalcohol (formula C) 8 H 8 BrNO 3 ) (ii) a (R) -1- (2-chlorophenyl) -2-nitroalcohol (formula C) 8 H 8 ClNO 3 ) (ii) a (R) -1- (2-methoxyphenyl) -2-nitroalcohol (formula C) 9 H 11 NO 4 ) (ii) a (R) -1- (2-nitrophenyl) -2-nitroalcohol (formula C) 8 H 8 N 2 O 5 ) (ii) a (R) -1- (2-cyanophenyl) -2-nitroalcohol (formula C) 9 H 8 N 2 O 3 )。
As a preferable scheme, the asymmetric Henry addition reaction comprises the following 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 1-1.
As a preferable scheme, the asymmetric Henry addition reaction is carried out at the temperature of-50 ℃ for 1-48 h. The reaction temperature is most preferably from 0 ℃ to 20 ℃, and the reaction time is more preferably from 1 to 24 hours.
As a preferred scheme, the polyion liquid type chiral copper amino acid catalyst is prepared by the following method:
(1) By reacting doubly-bound imidazoles with halogensAlkane (R) 1 X) 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) n Having a structure of formula (9); ionic liquid type chiral copper amino acid complex catalyst P (IL-A) n -Cu has the structure of formula (1);
in the above step (1), R 1 Selected from alkyl, aryl substituted alkyl; x is halogen element Br or Cl;
in the formula (6), R 2 A variable group selected from amino acids; * Represents R configuration or S configuration;
R 3 、R 4 each 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 method (RAFT) 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 subjected to controllable polymerization to obtain polymerized ionic liquid type amino acid P (IL-A) n 。
Wherein the carbon thioester has a structure of formula (10);
R 3 、R 4 each independently selected from hydrogen, alkyl, aryl, and aryl-substituted alkyl;
synthesis of polymerized ionic liquid type amino acid P (IL-A) by controlled-broken chain transfer polymerization (RAFT) n The reaction formula (A) is as follows:
in the step (4), the polyion liquid type amino acid polymer P (IL-A) n Dissolving in organic solvent, adding copper salt for coordination, and polymerizing to obtain polymer P (IL-A) n Formation of a metal complex catalyst P (IL-A) by coordination of the metal n -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 invention n The Cu catalyst has the advantages of:
(1) P (IL-A) n the-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 invention n the-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) n the-Cu catalyst can be conveniently recovered and effectively reused through phase transfer.
In addition, the present invention P (IL-A) n the-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 profile (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, R 1 Is ethyl, X is bromineAn 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 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) n Preparation of
Reaction formula 3:
in the above reaction formula 3, R 3 Is benzyl, R 4 Is 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 (5 mmol) prepared above was dissolved in anhydrous methanol, and benzyl thiopropionate (chain transfer agent, 1/6mmol,0.0330 g) and AIBN (chain initiator, 1/30mmol, 0.0052g) were added to the reaction solution. N is a radical of 2 Under 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 polymeric ionic liquid type amino acid P (IL-A) n 。
(4)P(IL-A) n Preparation of-Cu catalyst
Reaction formula 4:
4mmol of the above-prepared P (IL-A) was taken n Dissolved 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 C n -Cu. For P (IL-A) n Characterization of 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 .α 25 D ＝-62.7(C＝0.005g mL- 1 ,CH 2 Cl 2 )。
Example 2
P (IL-A) obtained in example 1 n -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) n Carrying out asymmetric Henry addition reaction under the catalytic action of a-Cu catalyst to obtain the beta-nitroalcohol compound.
The aldehyde compound has a structure of general formula (2); the nitroalkane has a 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 CH 2 NO 2 Formula (3)
In this example R 5 Is phenyl, R 6 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 bottle n -Cu，1mL H 2 O 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 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 to obtain 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 solid, silica gel column chromatography (ethanol: n-hexane =85 (volume ratio)), (98% yield, 99% ee). And (3) product structure characterization: IR (film) 3508,2921,2851,1552,1515,1416,1379,1347,1080,855cm -1 ； 1 H NMR(400MHz,CDCl 3 )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,CH 2 NO 2 ),3.09(d,J＝4.0Hz,OH)； 13 C NMR(100MHz,CDCl 3 ) 148.0,145.0,126.9,124.1,80.6,69.9. The ee value was determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =15 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm, temperature 25 ℃ C.).
P (IL-A) obtained in example 1 n Cu and conventional catalysts for the catalysis of Henry addition reactionsFor comparison, the results are shown in table 1 below:
TABLE 1
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 traditional 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 low. When catalyst P (IL-A) is used n When 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) n Cu 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) n the-Cu has great advantages in yield and ee value, the catalytic effects of different substrates are obviously improved, and the yield of the product beta-nitroalcohol is greatly improved. TheThe polyion liquid type chiral amino acid catalyst can solve the problem of difficult water phase reaction mass transfer in industry.
The characterization data for the partial products are as follows:
(R) -1-phenyl-2-nitroalcohol: colorless oil, silica gel column chromatography (ethanol: dichloromethane =90 (volume ratio)), (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 ； 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) 138.3,129.3,129.2,126.2,81.4,71.2; the ee value was determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =15 (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 (volume ratio)), (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 ； 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, ee value determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =15 (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 (volume ratio)), (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 ； 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-values determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =15 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-nitrophenyl) -2-nitroalcohol: brown crystals were separated by silica gel column chromatography (ethanol: n-hexane =80 (volume ratio)), (95% yield, 99% ee). And (3) product structure characterization: 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,CHOH),4.89(dd,1H,J＝13.9,2.2Hz,CH 2 NO 2 ),4.57(dd,1H,J＝13.9,8.8Hz,CH 2 NO 2 ),3.15(d,1H,4.2Hz,OH)；13C NMR(100MHz,CDCl 3 ) 147.1,134.4,133.9,129.7,128.7,125.0,80.0,66.8, ee values were determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =10 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-chlorophenyl) -2-nitroalcohol: brown crystals, silica gel column chromatography (ethanol: n-hexane =80 (volume ratio)), (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 ； 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,CHOH),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 2 ),3.01(d,1H,4.4Hz,OH)； 13 C NMR(125MHz,CDCl 3 ) 135.4,131.4,129.9,129.7,127.6,127.5,79.2,67.8, ee values determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =3 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm at 25 ℃).
(R) -1- (2-methylphenyl) -2-nitroalcohol: brown crystals were separated by silica gel column chromatography (ethanol: n-hexane =80 (volume ratio)), (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 ； 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 2 ),2.97(s,1H,OH),2.38(s,3H,CH 3 )； 13 C NMR(125MHz,CDCl 3 ) 136.5,134.7,131.1,128.9,127.0,125.8,80.4,68.1; the ee value of 19.1,ee was determined by chiral high performance liquid chromatography (column: daicel chiralpak AD, mobile phase: isopropanol/n-hexane =85 (volume ratio), flow rate: 0.8mL/min, wavelength: 215nm, temperature 25 ℃ C.).
Example 4
Catalyst P (IL-A) n Experiment of-Cu Re-use Properties
And adding n-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 n-hexane, and drying to obtain the recovered catalyst. Recovering catalyst P (IL-A) n The effect of the repeated use of Cu in the next catalytic reaction system 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 fig. 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 should be subject to the appended claims.
Claims (5)
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 CH 2 NO 2 Formula (3)
In formula (1):
* Represents R configuration or S configuration;
R 1 is ethyl;
R 2 is a variable group of an amino acid;
R 3 is benzyl;
R 4 ethyl, isopropyl, isobutyl, tert-butyl;
in the formula (2), the reaction mixture is,
said R is 5 One of the following substituents is selected from:
in the formula (3), R 6 Is hydrogen.
2. The method for water-phase catalysis of Henry asymmetric addition reaction based on 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, obtaining the polyion liquid type chiral amino acid copper complex catalyst through coordination of the polymer under the action of a 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 has a structure of a general formula (8); the polymeric ionic liquid amino acid has a structure of the general formula (9); the ionic liquid type chiral copper amino acid complex catalyst has a structure shown in a general formula (1);
the general formula of the halogenated alkane in the step (1) is R 1 X，R 1 Is ethyl; and X is Br or Cl.
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 1, wherein n in the formula (1) is 20-100.
4. The method for aqueous phase catalysis Henry asymmetric addition reaction based on the polyion liquid type chiral copper amino acid complex catalyst according to claim 1, is characterized in that the asymmetric Henry addition reaction comprises the following specific steps of dissolving the polyion liquid type chiral copper amino acid complex 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 complex catalyst to the aldehyde compound is 1.
5. 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 1, wherein the asymmetric Henry addition reaction is carried out at the temperature of-50 ℃ and the reaction time of 1-48 h.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019109327365 | 2019-09-29 | ||
| CN201910932736.5A CN110551031A (en) | 2019-09-29 | 2019-09-29 | method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111285769A CN111285769A (en) | 2020-06-16 |
| CN111285769B true CN111285769B (en) | 2023-02-24 |
Family
ID=68741956
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910932736.5A Pending CN110551031A (en) | 2019-09-29 | 2019-09-29 | method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst |
| CN202010308787.3A Active CN111285769B (en) | 2019-09-29 | 2020-04-18 | Method for aqueous phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst |
| CN202010308782.0A Active CN111285768B (en) | 2019-09-29 | 2020-04-18 | Polyion liquid type chiral copper amino acid catalyst and preparation method thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910932736.5A Pending CN110551031A (en) | 2019-09-29 | 2019-09-29 | method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010308782.0A Active CN111285768B (en) | 2019-09-29 | 2020-04-18 | Polyion liquid type chiral copper amino acid catalyst and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (3) | CN110551031A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303441B (en) * | 2020-02-17 | 2021-09-03 | 忻州师范学院 | Proline and proline derivative functionalized chiral metal organic framework material and synthesis method thereof |
| CN112044472B (en) * | 2020-09-14 | 2023-03-17 | 哈尔滨工程大学 | Chiral mesoporous amino acid polymer supported transition metal asymmetric catalyst and preparation method thereof |
| CN113717317B (en) * | 2021-08-09 | 2023-06-27 | 浙江理工大学 | Metal ion-loaded single-chiral helical copolymerization substituted polyacetylene and preparation method and application thereof |
| CN114524801A (en) * | 2022-01-21 | 2022-05-24 | 湖北工程学院 | Method for efficiently producing esomeprazole sodium based on mobile phase |
| CN114933666B (en) * | 2022-05-31 | 2023-04-11 | 河南大学 | Metal-doped polyion liquid catalyst for hydrogenation of cyclohexyl acetate and preparation method and application thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101327450B (en) * | 2008-07-10 | 2011-05-25 | 浙江大学 | Aminoacid ion liquid carried Salen metallic catalyst and preparation method |
| CN103497082B (en) * | 2013-09-24 | 2015-12-02 | 台州学院 | A kind of method preparing beta-nitrostyrene and derivative thereof |
| CN106795542B (en) * | 2014-06-12 | 2021-08-31 | 帕西昂奥地利有限两合公司 | (R) -selective cupin-nitroaldol reactions catalyzed by proteins of the cupin superfamily |
| CN105061225B (en) * | 2015-08-07 | 2017-03-08 | 辽宁科技大学 | A kind of both hands alkamine compound and its preparation method and application |
| CN106422410B (en) * | 2016-09-18 | 2018-11-06 | 四川大学 | A kind of preparation method and application of antenna type amino acid pattern immobilization ionic liquid |
| CN107652380B (en) * | 2017-09-03 | 2019-12-06 | 河南师范大学 | Heterogeneous chiral catalyst based on polyionic liquid and preparation method and application thereof |
| CN108586649B (en) * | 2018-05-18 | 2020-07-07 | 中国工程物理研究院化工材料研究所 | Series energetic polyion liquid and preparation method thereof |
-
2019
- 2019-09-29 CN CN201910932736.5A patent/CN110551031A/en active Pending
-
2020
- 2020-04-18 CN CN202010308787.3A patent/CN111285769B/en active Active
- 2020-04-18 CN CN202010308782.0A patent/CN111285768B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN111285768B (en) | 2022-09-27 |
| CN111285769A (en) | 2020-06-16 |
| CN110551031A (en) | 2019-12-10 |
| CN111285768A (en) | 2020-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111285769B (en) | Method for aqueous phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst | |
| Lee et al. | Heterogeneous asymmetric Henry reaction using a chiral bis (oxazoline)-copper complex immobilized on magnetically separable mesocellular mesoporous silica support | |
| CN113402350B (en) | Biaryl compound and preparation method and application thereof | |
| CN109718851B (en) | Chiral quaternary phosphonium salt phase transfer catalyst and preparation method and application thereof | |
| CN113549062A (en) | Chiral quaternary ammonium salt phase transfer catalyst with high steric hindrance derived from cinchona alkaloid and synthesis method thereof | |
| Itsuno et al. | Synthesis of chiral iridium complexes immobilized on amphiphilic polymers and their application to asymmetric catalysis | |
| CN104311424A (en) | Optically pure beta-nitroalcohol derivatives and synthesis method thereof | |
| CN107915653B (en) | Method for preparing amide by catalyzing ester and amine to react | |
| JP2012082155A (en) | Triazolium salt and method for producing the same, and method for producing alkylated oxindol using azide alcohol and asymmetric reaction | |
| CN110508323B (en) | Method for water-phase catalysis Henry asymmetric addition reaction based on temperature-sensitive chiral copper amino acid complex catalyst | |
| CN104945434B (en) | (2 ﹣ bis- substitution phosphines phenyl) -1- alkyl-indols Phosphine ligands and its synthetic method and application | |
| CN105481738A (en) | Method for carrying out catalytic synthesis on arene 2,2,2-trifluoro-ethyl sulfide through copper | |
| CN114524801A (en) | Method for efficiently producing esomeprazole sodium based on mobile phase | |
| CN101712697B (en) | Ferrocene phosphinimine ligand containing imidazole salt group, preparation thereof and application in catalyzing asymmetric allyl substitution reaction | |
| CN110479380A (en) | A kind of temperature sensitive type chiral amino acid copper complex catalyst and preparation method thereof | |
| JP2009023927A (en) | Method for producing optically active cyanohydrin | |
| JP6689750B2 (en) | Solid-phase supported ruthenium-diamine complex and method for producing optically active compound | |
| CN109293575A (en) | A kind of chiral monomer and preparation method thereof | |
| CN110002976B (en) | Method for synthesizing beta-trifluoromethyl-beta-hydroxy-1, 2-diphenyl acetone by copper-catalyzed alkenyl azide | |
| CN112279789B (en) | Method for preparing isonitrile compound | |
| JP2013185150A (en) | Polystyrene supported pyridine bisoxazoline derivative-calcium catalyst | |
| CN109081785B (en) | Synthetic method of fluorine-containing glycine ester derivative | |
| JP2009208027A (en) | Ruthenium catalyst immobilized in macromolecule and use thereof | |
| Xiong et al. | Synthesis of the carboxyl and pyridine functional ionic liquids | |
| CN117447462A (en) | Chiral triazole-oxazoline compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |