CN101972676B - Chiral oxidation catalyst and preparation method thereof - Google Patents

Abstract

A chiral oxidation catalyst and a preparation method thereof belong to the technical field of catalyst synthesis. The general formula of chemical composition is: [M ²⁺ _1-x M ³⁺ _x (OH) ₂ ] ^x+ [(Glu ^a- ) _b (CO ₃ ^2- ) _c ]·mH ₂ O. The preparation steps are as follows: preparing a hydrotalcite precursor with interlayer anions being NO ₃ ^- , layer divalent and trivalent cation molar ratios M ²⁺ /M ³⁺ = 2-4; using lye to adjust the pH value of the amino acid to 8 ~12, prepare a negatively charged amino acid anion solution with a concentration of 0.005mol/L~0.30mol/L, add a hydrotalcite precursor whose interlayer anion is NO ₃ ^- , and react at 20~60°C under N ₂ protection and stirring for 12 ~48h, the product was washed with CO2 _- free water, fully washed with absolute ethanol water, centrifuged, and the solid product was recovered, dried in vacuum at 30~50°C, and the prepared intercalated amino acid hydrotalcite was added to 1~4ml of dichloromethane solution In, and then add the compound of vanadium, stir at 10-40 ℃ for 1-5h, that is the chiral oxidation catalyst. The advantage is that the selectivity of reaction products is improved while maintaining a relatively high yield.

Description

A kind of chiral oxidation catalyst and preparation method thereof

technical field

The invention belongs to the technical field of catalyst synthesis, and in particular provides a chiral oxidation catalyst and a preparation method thereof.

Background technique

Asymmetric catalysis has made remarkable achievements in the past few decades, so the 2001 Nobel Prize in Chemistry was awarded to Knowles, Noyori and Sharpless, who were engaged in the synthesis of asymmetric catalysis, in recognition of their outstanding achievements in this field contribute. Many opportunities and challenges in this field come from the research of drugs, and now people are more and more aware of the importance of single enantiomers, the wrong use of enantiomers in racemic drugs is a serious drug contamination, which may cause Unpredictable toxic side effects such as reaction stop has R, S two configurations, wherein the R-isomer is an effective sedative, but the S-configuration is a strong teratogenic agent. Single enantiomeric chiral compounds can be obtained by chiral resolution and asymmetric synthesis, so asymmetric catalytic synthesis by chiral catalysts is the most effective way to obtain optically pure chiral compounds, that is, by using catalyst-scale Chiral starting materials are used to stereoselectively produce a large number of chiral compounds.

At present, the research hotspots of chiral catalysts are mainly concentrated in the two fields of small organic molecules and metal complexes. Small organic molecules mainly include cinchona bases, amino acids and their derivatives, etc.; Derivatives, etc. Among them, metal amino acids and their derivatives have many advantages, such as their structures are easy to design, different metals can catalyze different types of reactions, and amino acid ligands are naturally cheap and easy to obtain, optically active, and easy to derivatize. The polarity, acidity and alkalinity, and the size of the space are easy to adjust, and different electrical properties are displayed at different pHs. Therefore, the research on metal amino acids and their derivatives is relatively sufficient, and good results have been achieved.

The asymmetric catalytic oxidation of double bonds plays an important role in the synthesis of chiral drugs and is an important intermediate in drug synthesis. Therefore, the synthesis of optically pure epoxidized products is of great significance. In 1980, Sharpless reported the oxidation of allyl alcohol with chiral titanate and peroxy tert-butanol, and successfully realized the process of asymmetric epoxidation, and the e.e. of the product was greater than 90%. Vanadium compounds are good oxidants and have important applications in the epoxidation of double bonds. H.Yamamoto et al. have achieved remarkable results by covalently modifying amino acids and complexing vanadium to catalyze asymmetric epoxidation

Double metal composite hydroxides, also known as Layered Double Hydroxides (LDHs for short), are a new type of multifunctional layered material. LDHs have unique composition and structural properties such as two-dimensional order, and their chemical stability Good and the metal ions of the LDHs laminates can be adjusted, and the interlayer anions are exchangeable, and a variety of functional anions can enter the interlayer through ion exchange to generate various functional composite materials. Metal complexes with catalytic properties are introduced into the interlayer of LDHs by ion exchange method, which avoids the tedious steps of covalently modifying ligands, and the two-dimensional ordered cationic rigid layer not only improves the catalytic activity of the material, but also Helps to improve selectivity.

Contents of the invention

The object of the present invention is to provide a chiral oxidation catalyst and a preparation method thereof. The L-amino acid was introduced into the interlayer of two-dimensional ordered LDHs by electrostatic means, and the prepared material was complexed with vanadium compounds to catalyze the epoxidation of different allyl alcohols.

The chiral oxidation catalyst of the present invention is prepared by the hydrotalcite precursor whose interlayer anion is NO ₃ ^- , and the hydrotalcite precursor has the following composition: [M ²⁺ _1-x M ³⁺ _x (OH ) ₂ ] ^X+ NO ₃ ^- _X mH ₂ O, wherein M ²⁺ represents a divalent metal cation selected from Mg ²⁺ , Ni ²⁺ , Co ²⁺ , Zn ²⁺ , Fe ²⁺ and Cu ²⁺ One or more of; M ³⁺ represents a trivalent metal cation, selected from one or more of Al ³⁺ , Cr ³⁺ , Fe ³⁺ , Ga ³⁺ , In ³⁺ , preferably Al ³⁺ . m represents the amount of crystal water, 0.1≤m≤0.8; 0.2≤x≤0.33,

The molecular composition of the chiral oxidation catalyst is [M ²⁺ _1-x M ³⁺ _x (OH) ₂ ] ^x+ [(AA ^a- ) _b (CO ₃ ^2- ) _c ]·mH ₂ O, where M ²⁺ represents di Valence metal cations, which can be selected from one or more of Mg ²⁺ , Ni ²⁺ , Co ²⁺ , Zn ²⁺ , Fe ²⁺ and Cu ²⁺ , preferably Mg ²⁺ , Zn ²⁺ and Ni ² One or more of ⁺ ; trivalent metal cations can be selected from one or more of Al ³⁺ , Cr ³⁺ , Fe ³⁺ , Ga ³⁺ , In ³⁺ , preferably Al ³⁺ . x is M ²⁺ /(M ³⁺ +M ²⁺ ), 0.2≤x≤0.33, a is the charge number of amino acid, AA is amino acid, a=1, 2, b is the number of intercalated amino acid in hydrotalcite , c is the number of ionic carbonates coexisting between the hydrotalcite layers, m is the number of crystallization water, 0.1≤m≤0.8.

In the chiral oxidation catalyst, the hydrotalcite main layer plate selects divalent metal cations Mg ²⁺ , Zn ²⁺ and Ni ²⁺ and trivalent metal cations Al ³⁺ . When divalent metals and trivalent metal cations are selected for the main layer of hydrotalcite, the molar ratio of divalent and trivalent metals is 2 to 4, and amino acid anion ligands account for 10 to 100% of the total number of moles of anions in the interlayer. The material layer spacing is adjustable within the range of 0.70-1.30nm.

The chiral oxidation catalyst of the present invention uses the intercalability of hydrotalcite to insert the titanium tartrate complex into the interlayer of hydrotalcite by ion exchange, and the steps are as follows:

a. Preparation of a hydrotalcite precursor whose interlayer anion is NO ₃ ^- ;

b. Adjust the pH value of the amino acid to 8-12 with lye to prepare a negatively charged amino acid anion solution with a concentration of 0.005mol/L-0.30mol/L;

c. Add the hydrotalcite precursor whose interlayer anion is NO ₃ ^- prepared in a to the amino acid anion solution b, the mass ratio of the hydrotalcite precursor to the amino acid is 1-7, and protect under N ₂ at 20-60°C React under stirring for 12-48 hours, wash the product with CO _{2 -free} water, fully wash with absolute ethanol water, centrifuge, recover the solid product, and vacuum-dry at 30-50°C to obtain amino acid intercalated hydrotalcite, and then store it under dry conditions;

d. Add the vanadium compound to dichloromethane to obtain a solution with a concentration of 0.01mol/L to 0.5mol/L, and then add amino acid intercalated hydrotalcite, wherein the ratio of the vanadium to the intercalated amino acid is 1 to 10 , stirred at 10-40°C for 1-5h, it is a chiral oxidation catalyst.

The amino acid intercalated hydrotalcite was subjected to XRD, IR and elemental analysis. XRD shows that the amino acid intercalated hydrotalcite d(003) matches the molecular size of the amino acid plus the ^thickness of the laminate. It shows that amino acid intercalation is successful. And the value of the unit cell parameter a remains basically unchanged before and after intercalation, and the product has a complete layered structure.

Under the same conditions as the homogeneous reaction, the chiral oxidation catalyst improves the enantioselectivity of the reaction product while maintaining a relatively high yield, and has the characteristics of easy separation and reuse of the catalyst.

Description of drawings

Figure 1 XRD pattern of amino acid intercalated hydrotalcite. Where (a) Zn-Al-CO ₃ -LDHs (b) Zn-Al-NO ₃ -LDHs (c) Zn-Al-Glu-LDHs;

Fig. 2 is an XRD pattern enlarged 50 times from Fig. 1 from 25-65°.

Detailed ways:

The following implementation examples, Steps A.B., are routine in the art.

Example 1

A. Add 0.01mol zinc nitrate hexahydrate, 0.005mol aluminum nitrate nonahydrate and 0.035mol urea into 320ml deionized water, dissolve and transfer to a 500ml three-necked flask, stir and heat to reflux for 24 hours. After the reaction, the product was suction filtered, washed with deionized water until the pH was 7, then washed once with ethanol to disperse the product evenly, and the filter cake was dried in an oven at 60°C to obtain a solid powder, namely Zn-Al-CO ₃ -LDHs

B. Add 0.4 g of Zn-Al-CO ₃ LDHs into NaNO ₃ solution with 1.5 mol/L, then add 0.002 mol concentrated HNO ₃ , protect with N ₂ , stir and crystallize at room temperature for 24 hours, after the reaction, The product was suction filtered, washed with deionized water until the pH was 7, and then washed once with ethanol to disperse the product evenly. The filter cake was dried in an oven at 25°C to obtain a solid powder, which was the Zn-Al-NO ₃ -LDHs precursor.

C. Adjust the pH value of L-glutamic acid to 8 with concentrated ammonia water to prepare a negatively charged L-glutamic acid anion solution with a concentration of 0.005mol/L, add 0.15g of hydrotalcite precursor, and heat Under N ₂ protection and stirring, the reaction was carried out for 24 hours. The product was washed with CO _{2 -free} water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then under dry conditions save.

D. Add 2.5 μl VO(Oi-Pr) ₃ in 1ml dichloromethane to obtain a solution with a concentration of 0.01mol/L, then add the L-glutamic acid intercalation hydrotalcite prepared by C in the above solution, and Stir at 10°C for 5 hours, and it becomes a chiral oxidation catalyst with a ratio of vanadium and amino acid ligands of 1:2.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1: 2 eluent to isolate the pure product with a yield of 87%, and the ee value of the product detected by HPLC was 92%.

Example 2

A. Adopt a method similar to step A in Example 1 to obtain Zn-Al-CO ₃ -LDHs.

B. Obtain Zn-Al-NO ₃ -LDHs precursor by the method similar to step B in Example 1

C. the pH value of L-glutamic acid is adjusted to 12 with the NaOH solution of 2mol/l, and preparation concentration is the negatively charged L-glutamic acid anion solution of 0.086mol/l, adds hydrotalcite precursor 0.15g, in React at 60°C for 12h under _N2 protected stirring. The product was washed with CO2 _-free water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then Store in dry conditions.

D. Add 50 μl VO(Oi-Pr) ₃ in 1ml dichloromethane to obtain a solution with a concentration of 0.5mol/L, and then add the L-glutamic acid intercalation hydrotalcite prepared by C to the above solution, at 40 Stirring at ℃ for 1 h, it becomes a chiral oxidation catalyst with a ratio of vanadium and amino acid ligands of 10:1.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1: 2 eluent to isolate the pure product with a yield of 86%, and the ee value of the product detected by HPLC was 92%.

Example 3

A. Adopt a method similar to step A in Example 1 to obtain Zn-Al-CO ₃ -LDHs.

B. Obtain Zn-Al-NO ₃ -LDHs precursor by the method similar to step B in Example 1

C. Adjust the pH value of L-glutamic acid to 10 with concentrated ammonia water, and prepare a negatively charged L-glutamic acid anion solution with a concentration of 0.3mol/l, add 0.15g of hydrotalcite precursor, and put it under N at 20°C ₂ React under protection stirring for 48h, the product was washed with CO _{2 -free} water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then stored under dry conditions .

D. Add 25 μl VO(Oi-Pr) ₃ in 1ml dichloromethane to obtain a solution with a concentration of 0.1mol/L, then add the L-glutamic acid intercalation hydrotalcite prepared by C in the above solution, and in 10 Stirring at ℃ for 5 hours, it becomes a chiral oxidation catalyst with a ratio of vanadium and amino acid ligands of 5:1.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1: 2 eluent to isolate the pure product with a yield of 85%, and the ee value of the product detected by HPLC was 94%.

Example 4

A. Adopt a method similar to step A in Example 1 to obtain Zn-Al-CO ₃ -LDHs.

B. Obtain Zn-Al-NO ₃ -LDHs precursor by the method similar to step B in Example 1

C. the pH value of L-glutamic acid is adjusted to 10 with the NaOH solution of 2mol/l, and preparation concentration is the negatively charged L-glutamic acid anion solution of 0.086mol/L, adds hydrotalcite precursor 0.15g, in React for 48 hours at 20°C under _N2 protected stirring, the product was washed with CO2 _-free water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then in Store in dry conditions.

D. Add 25 μl VO(Oi-Pr) ₃ in 1ml dichloromethane to obtain a solution with a concentration of 0.1mol/L, then add the L-glutamic acid intercalation hydrotalcite prepared by C in the above solution, and in 10 Stirring at ℃ for 5 hours, it becomes a chiral oxidation catalyst with a ratio of vanadium and amino acid ligands of 5:1.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1:2 eluent to isolate the pure product with a yield of 86%, and the ee value of the product detected by HPLC was 95%.

Example 5

A. Add 0.01mol zinc nitrate hexahydrate, 0.005mol aluminum nitrate nonahydrate and 0.035mol urea into 320ml deionized water, stir and dissolve at room temperature, then transfer the mixture solution to a Teflon sealed self-generating pressure reactor, at 120°C After static crystallization for 24 hours, the precipitate was centrifuged, washed with deionized water until neutral, washed once with absolute ethanol, and dried in a vacuum oven at room temperature for later use to obtain Zn-Al-CO ₃ -LDHs.

B. Add 0.4 g of Zn-Al-CO ₃ -LDHs to NaNO ₃ solution with 1.5 mol/L, then add 0.002 mol concentrated HNO ₃ , protect with N ₂ , stir and crystallize at room temperature for 24 hours, after the reaction , the product was suction filtered, washed with deionized water until the pH was 7, then washed once with ethanol to disperse the product evenly, and the filter cake was dried in an oven at 25°C to obtain a solid powder, which was the Zn-Al-NO ₃ -LDHs precursor.

C. Adjust the pH value of L-glutamic acid to 8 with concentrated ammonia water to prepare a negatively charged L-glutamic acid anion solution with a concentration of 0.005mol/L, add 0.15g of hydrotalcite precursor, and heat Under N ₂ protection and stirring, the reaction was carried out for 24 hours. The product was washed with CO _{2 -free} water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then under dry conditions save.

D. Add 3.2 mg VOSO ₄ into 1 ml of dichloromethane to obtain a solution with a concentration of 0.01 mol/L, then add the L-glutamic acid intercalated hydrotalcite prepared in C to the above solution, and stir at 10°C for 5 h. That is, the ratio of vanadium and amino acid ligands is 1:2 chiral oxidation catalyst.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1:2 eluent to isolate the pure product with a yield of 87%, and the ee value of the product detected by HPLC was 93%.

Example 6

A. Adopt a method similar to step A in Example 5 to obtain Zn-Al-CO ₃ -LDHs.

B. obtain Zn-Al-NO ₃ -LDHs precursor by the method similar to step B in embodiment 5

C. the pH value of L-glutamic acid is adjusted to 10 with the NaOH solution of 2mol/l, and preparation concentration is the negatively charged L-glutamic acid anion solution of 0.086mol/L, adds hydrotalcite precursor 0.15g, in React for 48 hours at 20°C under _N2 protected stirring, the product was washed with CO2 _-free water, fully washed with absolute ethanol water, centrifuged, and vacuum-dried at 25°C to obtain intercalated L-glutamic acid intercalated hydrotalcite, and then in Store in dry conditions.

D. Add 5.3 mg VO(acac) ₂ into 1 ml of dichloromethane to obtain a solution with a concentration of 0.1 mol/L, then add the L-glutamic acid intercalation hydrotalcite prepared in C to the above solution, at 10°C After stirring for 5 hours, it becomes a chiral oxidation catalyst with a ratio of vanadium and amino acid ligands of 5:1.

Add 0.60ml TBHP dichloromethane solution and 1.05mmol 2-methylcinnamyl alcohol to the prepared chiral oxidation catalyst, stir at room temperature for 24h, stop the reaction with saturated NaSO ₃ , extract with ether, dry with anhydrous NaSO ₄ , ethyl acetate/n-hexane = 1: 2 eluent to isolate the pure product with a yield of 85%, and the ee value of the product detected by HPLC was 94%.

Claims (1)

1. chiral oxidization Preparation of catalysts method is characterized in that:

A. 0.01mol zinc nitrate hexahydrate, 0.005mol ANN aluminium nitrate nonahydrate and 0.035mol urea are added in the 320ml deionized water, change the 500ml there-necked flask after the dissolving over to, agitating heating backflow 24h; After reaction finishes, the product suction filtration, spend deionised water to pH be 7, with washing with alcohol product is evenly disperseed then, filter cake gets pressed powder in 60 ℃ of oven dryings, is Zn-Al-CO ₃-LDHs;

B. will obtain Zn-Al-CO ₃-LDHs0.4g joins the NaNO that is dissolved with 1.5mol/L ₃In the solution, the back adds the dense HNO of 0.002mol ₃, N ₂Crystallization 24h is stirred in protection under the room temperature, after reaction finishes, the product suction filtration, spend deionised water to pH be 7, with washing with alcohol product is evenly disperseed then, filter cake gets pressed powder in 25 ℃ of oven dryings, is Zn-Al-NO ₃-LDHs precursor;

C. with concentrated ammonia liquor the pH value of L-glutamic acid is transferred to 8, preparing concentration is the electronegative L-glutamic acid anion solutions of 0.005mol/L, adds Zn-Al-NO ₃-LDHs precursor 0.15g, at 30 ℃ in N ₂Reaction 24h is down stirred in protection, and product spends CO ₂Water washing, fully wash with absolute ethyl alcohol, centrifugal, in 25 ℃ of vacuum drying, obtain intercalation L-glutamic acid intercalated houghite, under drying condition, preserve then;

D. with 2.5 μ l VO (O-i-Pr) ₃Add in the 1ml carrene, obtain the solution that concentration is 0.01mol/L, add the prepared L-glutamic acid intercalated houghite of C then in above-mentioned solution, stir 5h down at 10 ℃, being vanadium and amino acid ligand proportioning is 1: 2 chiral oxidization catalyst.