CN105797769A - (R)-1-(2-hydroxy-1-phenethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst as well as preparation method and application thereof - Google Patents

Abstract

The invention discloses a (R)-1-(2-hydroxyl-1-phenylethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst, a preparation method and an application thereof. In the present invention, sodium molybdate is first reacted with tetrabutylammonium bromide to generate [N(C ₄ H ₉ ) ₄ ] ₄ [α‑Mo ₈ O ₂₆ ], and then reacted with trihydroxyaminomethane and manganese acetate to obtain organic Double side amino modified polyoxometalates; then synthesize (R)‑1‑(2‑hydroxy‑1‑phenylethyl) isothiocyanate, and then (R)‑1‑(2‑hydroxy‑1‑benzene Ethyl) isothiocyanate reacts with organic bilateral amino-modified polyoxometalates to obtain the target heteropolyacid catalyst. The preparation method of the invention has mild reaction conditions and is environmentally friendly; the obtained catalyst is applied to the asymmetric dihydroxylation reaction of olefins, has high catalytic activity and high enantioselectivity, is recyclable, and is suitable for industrial production.

Description

(R)-1-(2-hydroxyl-1-phenylethyl)thiourea-modified Mn-Anderson type heteropolyacid catalyst, preparation method and application thereof

technical field

The invention belongs to the technical field of catalytic chemistry, in particular to asymmetric selective catalysis, specifically a (R)-1-(2-hydroxyl-1-phenylethyl)thiourea-modified Mn-Anderson type heteropolyacid catalyst , preparation method and application thereof.

Background technique

Professor Noyori, a Nobel Prize winner in 2001, pointed out: "Future synthetic chemistry must be economical, safe, environmentally friendly, and resource- and energy-saving chemistry. Chemists need to work hard to achieve 'perfect reaction chemistry', that is, Only the desired product is produced with 100% selectivity and 100% yield and no waste is generated". Chiral catalytic synthesis is one of the important ways to realize "perfect synthetic chemistry". Among them, chiral catalyst is the core scientific problem in the research of chiral catalysis. From the perspective of the reaction principle, chiral organic small molecule catalysis is to reversibly form an active intermediate with an unstable covalent bond with the reaction substrate or activate the reaction substrate through some interactions, such as oxygen bonds, van der Waals forces or ion pairs. things. Homogeneous chiral catalysis is characterized by high efficiency, high enantioselectivity and mild reaction conditions.

Catalysis is the most promising and practical research direction in the application of polyoxometalates. Polyoxometallates combine the excellent properties of acid-base catalysts, redox catalysts, and metal oxide nanocatalysts, and are considered to be green multifunctional catalysts with wide applications. As early as the beginning of the 20th century, people began to study the catalytic performance of polyacids. So far, eight polyacid catalytic industrialization projects have been successfully developed. Catalysis has become an eternal research topic in polyacid chemistry. Since chiral polyoxometalates were successfully synthesized, people began to explore chiral polyacids in the field of asymmetric catalysis. Chiral polyoxometalates combine the excellent properties of polyacids and chiral materials. Its unique soluble mineral-like metal-oxide structure provides an ideal model for the theory of the origin of chiral non-life and the exploration of chiral transfer in inorganic solids; its high electronegativity, adjustable acidity, alkalinity, redox Activity and nanometer size, more multifunctional nonlinear optics, nanomaterials, stereoselective catalysis, and medicine have brought new hope to the design and synthesis of new materials.

Since Zubieta et al. reported in "Nature" in 1993 that the compound (Me ₂ NH ₂ )K ₄ [V ₁₀ O ₁₀ (H ₂ O) ₄ (OH ) ₄ (PO ₄ ) ₇ ]·H ₂ O, people began to explore chiral polyacids in the field of asymmetric catalysis. Professor Luo Sanzhong from the Institute of Chemistry, Chinese Academy of Sciences, and others have done excellent work in the field of using organic amine small molecule catalysts as counter cations and polyacids as catalyst supports (Organic letters, 2007, 9(18): 3675-3678 .). They synthesized a series of secondary amine-tertiary amine proline derivatives, using strongly acidic polyanions [PW ₁₂ O ₄₀ ] ^3- to replace mineral acids in traditional acid-base synergistic catalysis, and synthesized a series of chiral Organic amine-polyacid hybrid materials. These materials show high catalytic activity and chiral selectivity for the direct Aldol reaction of aldehydes and ketones and the asymmetric Michael addition reaction. Small organic amine molecules are used as counter cations to assemble with polyacids through electrostatic interaction, but these materials do not have a clear molecular structure, and the catalytic mechanism cannot be further explored, and the synergistic effect of chiral amines and polyacids cannot be explained. Duan Chunying's research group at the Dalian Institute of Physics and Chemistry used the composition, structure diversity, and adjustable charge of polyoxometalates (POMs) to design and assemble a series of porous POMOFs with catalytic functions, and realized their catalytic performance in heterogeneous catalysis. (Journal of the American Chemical Society, 2013, 135(28): 10186-10189.), but these materials also do not have a clear molecular structure, and the catalytic mechanism cannot be further explored, and the synergy between MOFs and POMs cannot be explained.

As mentioned above, although chiral catalytic synthesis is one of the important ways to realize "perfect synthetic chemistry", chiral organic small molecule catalysts are rarely used in industrial production due to their low activity, high dosage and difficult recycling.

Contents of the invention

For the deficiencies in the prior art, the object of the present invention is to provide a kind of (R)-1-(2-hydroxyl-1-phenylethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst, preparation method and application thereof . The preparation method of the invention is simple, and the obtained heteropolyacid catalyst has high catalyst activity, less consumption and is easy to recycle. The obtained catalyst can be used in the field of asymmetric catalytic synthesis.

Starting from the idea of designing small organic molecule catalysts, the present invention innovatively proposes the use of "acid-base" synergistic catalytic strategy, using chiral small organic molecules with potential catalytic activity as precursors, and through organic modification and other methods, to skillfully make The combination of small organic molecules and high Bronsted acidic vacancy polyanions constructs chiral polyacid materials. The obtained chiral heteropolyacid catalyst not only retains the original structure of polyacids, but also expands the research field of polyacids, making it It has potential application value in catalysis, medicine and functional materials. In addition, polyacids are hydrophilic, and can be catalyzed by green and cheap water as a solvent. After the reaction is completed, organic solvents (ethanol, methanol, etc.) can be added to the system, and polyacids are easily precipitated and can be recycled.

The technical scheme of the present invention is specifically introduced as follows:

The present invention provides a kind of preparation method of (R)-1-(2-hydroxyl-1-phenylethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst (see Figure 1 for structure), the synthetic route is as shown in Figure 2 The specific steps are as follows:

1) Mix sodium molybdate and tetrabutylammonium bromide at a molar ratio of 1:1 to 2:1, and react at room temperature under the action of concentrated hydrochloric acid to obtain the parent [N(C ₄ H ₉ ) ₄ ] ₄ [ α-Mo ₈ O ₂₆ ];

2) Reflux the above-obtained precursor [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ] with trishydroxyaminomethane and manganese acetate in an organic solvent to obtain the Mn-Anderson type poly Oxymetalate;

3) Synthesizing (R)-1-(2-hydroxyl-1-phenylethyl)isothiocyanate with D-phenylglycinol as raw material;

4) (R)-1-(2-hydroxyl-1-phenylethyl) isothiocyanate and Mn-Anderson type polyoxometalate modified with organic bilateral amino groups in a molar ratio of 5:1 to 8:1 Mix and dissolve in the reaction solvent, and react at a temperature of 45-55°C to obtain (R)-1-(2-hydroxyl-1-phenylethyl)thiourea-modified Mn-Anderson heteropolyacid catalyst.

In the present invention, in step 1), the molar ratio of sodium molybdate to concentrated hydrochloric acid is 1:1˜1:2.

In the present invention, in step 2), the molar ratio of [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ] to trihydroxyaminomethane and manganese acetate is 1:(3～4):(1 ~2).

In the present invention, in step 2), the organic solvent is a polar aprotic solvent.

In the present invention, in step 2), the organic solvent is acetonitrile or 1,2-dichloroethane.

In the present invention, in step 3), the specific steps for synthesizing (R)-1-(2-hydroxyl-1-phenylethyl) isothiocyanate with D-phenylglycinol as raw material are as follows: D-benzene Glycinol, CS ₂ and triethylamine are mixed in a molar ratio of 1:(2~4):1, and after stirring at room temperature for 1h~2h, di-tert-butyl dicarbonate and 4-dicarbonate are added under ice bath conditions After the addition of methylaminopyridine, continue to keep stirring under ice bath conditions for 3h to 5h to obtain (R)-1-(2-hydroxyl-1-phenylethyl)isothiocyanate; among them, D-phenylglycerin The molar ratio of aminoalcohol, di-tert-butyl dicarbonate and 4-dimethylaminopyridine is 1:1:(0.02～0.05).

In the present invention, in step 4), the reaction solvent is selected from one or more of DMF, DMSO or NMP.

In the present invention, in step 4), the Mn-Anderson type polyoxometallic acid modified by (R)-1-(2-hydroxyl-1-phenylethyl) isothiocyanate and the organic bilateral amino group obtained in step 2) After the salt reacts in the solvent for 2 to 3 days, if the reaction solution is not clear, it should be treated with a needle filter. After obtaining the clear solution, place it in an ether atmosphere to crystallize. After a few days, crystals can be obtained, that is, (R)-1-(2-hydroxy- 1-phenylethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst.

The present invention also provides a (R)-1-(2-hydroxy-1-phenylethyl)thiourea-modified Mn-Anderson heteropolyacid catalyst prepared by the above-mentioned preparation method.

The present invention further provides an application of the above-mentioned (R)-1-(2-hydroxy-1-phenylethyl)thiourea modified Mn-Anderson heteropolyacid catalyst in the field of asymmetric dihydroxylation reaction of olefins. The application method is as follows: mix olefin and (R)-1-(2-hydroxy-1-phenylethyl)thiourea-modified Mn-Anderson type heteropolyacid catalyst in a mixed solvent composed of water and acetonitrile, and heat at 30°C to React at a temperature of 50°C to obtain an o-diol compound; wherein: the dosage of the Mn-Anderson type heteropolyacid catalyst modified by (R)-1-(2-hydroxyl-1-phenylethyl)thiourea is 0.5mol% to 5mol% of olefins.

Preferably, the molar ratio of water to acetonitrile is 1:1-3:1, hydrogen peroxide is used as the oxygen source, and its usage amount is 1-3 equivalents (taking olefin as a reference).

After the asymmetric dihydroxylation reaction, after adding an organic solvent (ethanol, methanol, etc.) to the system, polyacids are precipitated, filtered, and vacuum-dried, and the recovered polyacids can be used in the asymmetric dihydroxylation reaction of olefins.

Compared with the prior art, the beneficial effect of the present invention is that: the present invention can not only use the covalent modification of chiral organic small molecules to break the high symmetry of polyacids, introduce chirality, and improve its stereoselectivity in catalytic reactions properties, and can also introduce functional properties such as asymmetric catalysis or biomedical activity of organic chiral small molecules into polyacids, and organically combine organic parts and inorganic polyanions into a whole, thereby producing synergistic effects and obtaining more novelties nature. The preparation method of the invention has mild reaction conditions and is environmentally friendly, and the obtained catalyst has the advantages of high efficiency, high enantioselectivity, recyclability and the like, and is suitable for industrial production.

Description of drawings

Figure 1 is a schematic representation of the structure of the target catalyst of the present invention.

Figure 2 is an illustration of the synthetic route of the present invention.

Figure 3 is the NMR spectrum of (R)-1-(2-hydroxyl-1-phenylethyl)isothiocyanate.

Fig. 4 is the infrared spectrum of Mn-Anderson type polyoxometalate modified with double amino groups.

Fig. 5 is the nuclear magnetic spectrum of Mn-Anderson type polyoxometalates modified with double amino groups.

Fig. 6 is a NMR spectrum of (R)-1-(2-hydroxyl-1-phenylethyl)thiourea modified Mn-Anderson type heteropolyacid catalyst.

detailed description

The following examples are used to describe the implementation of the present invention in detail, so as to fully understand and implement the process of how to apply technical means to solve technical problems and achieve technical effects in the present invention.

Example 1

Preparation of Polyacid Precursor [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ]

In a 50 mL flask, dissolve 5.00 g (20.7 mmol) of Na ₂ MoO ₄ ·2H ₂ O in 12 mL of deionized water, add 5.17 mL of 6.0N hydrochloric acid solution, and stir vigorously at room temperature for 1-2 min. Then 3.34 g (10.4 mmol) of tetrabutylammonium bromide was dissolved in 10 ml of deionized water, and added to the flask under vigorous stirring to form a white precipitate immediately. After the mixture was stirred for 10 minutes, the precipitate was collected on a medium porosity filter by suction and washed with 20 mL of water, 20 mL of ethanol, 20 mL of acetone and 20 mL of diethyl ether, respectively. This crude product (4.78g) was dissolved in 35mL of acetonitrile and allowed to stand at -10°C for 24h. Clear, colorless, block-like crystals were collected by suction filtration and dried under vacuum for 12 hours. The clarity of the crystals is lost as they dry. Yield 3.58g (1.66mmol), yield 64%.

Example 2

Preparation of (R)-1-(2-hydroxy-1-phenylethyl)isothiocyanate

Add D-phenylglycinol (0.6859g, 5mmol) into a dry reaction vessel, dissolve it with 20mL of ethanol, then slowly add CS ₂ (0.1142g, 15mmol) and triethylamine (0.506mg, 5mmol) respectively, in After stirring at room temperature for 1 h, di-tert-butyl dicarbonate (Boc ₂ O) (1.091 mg, 5 mmol) and 4-dimethylaminopyridine (DMAP) (18 mg, 0.15 mmol) were added at 0°C, and stirred at room temperature After 2 hours of reaction (gas is generated during the stirring process, attention should be paid to degassing and decompression), 0.7194 g of (R)-1-(2-hydroxyl-1-phenylethyl)isothiocyanate can be obtained.

The NMR spectrum of (R)-1-(2-hydroxy-1-phenylethyl) isothiocyanate is shown in Figure 3, and the specific data are as follows:

¹ H NMR (501MHz, CDCl ₃ ) δ7.39–7.22 (m, 5H), 4.99 (dt, J=52.6, 9.1Hz, 2H), 4.43 (dd, J=8.8, 7.0Hz, 1H), 1.25( dd,J=51.2,35.5Hz,1H).

Example 3

Preparation of Mn-Anderson Polyoxometalates Modified by Bilateral Amino Groups

Take [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ] (8.00g, 3.7mmol), Mn(CH ₃ COO) ₃ ·2H ₂ O (1.49g, 5.6mmol) and (HOCH ₂ ) ₃ CNH ₂ (1.56g, 12.8mmol), in 150mL of acetonitrile solution was refluxed for 16h. The orange solution was cooled to room temperature and filtered to remove a very fine black solid. The filtrate was exposed to ether vapor. After 2 hours, the white precipitate was filtered off. The orange filtrate was again exposed to ether vapor for several days. Plenty of orange crystals were obtained. They were isolated by filtration, washed with acetonitrile and a small amount of ether, and dried under vacuum.

The infrared spectrum of the Mn-Anderson type polyoxometalates modified with double amino groups is shown in Figure 4.

The nuclear magnetic spectrum of the Mn-Anderson type polyoxometalates modified with double amino groups is shown in Figure 5.

Example 4

Preparation of (R)-1-(2-hydroxy-1-phenylethyl)thiourea Modified Mn-Anderson Type Heteropolyacid Catalyst

After dissolving 0.5 g (0.2683 mmol) of the organic double amino modified [N(C ₄ H ₉ ) ₄ ] ₃ [MnMo ₆ O ₁₈ {(OCH ₂ ) ₃ CNH ₂ } ₂ ] in 5 mL of DMF at 50°C, Add 0.3585 g (2 mmol) of (R)-1-(2-hydroxy-1-phenylethyl) isothiocyanate, and maintain stirring at 50°C, the reaction time is 2 to 3 days, and the water red is clarified after the reaction The solution was placed in ether atmosphere to crystallize, and red crystals could be obtained after several days, that is, (R)-1-(2-hydroxy-1-phenylethyl)thiourea-modified Mn-Anderson heteropolyacid catalyst was obtained.

The NMR spectrum of (R)-1-(2-hydroxyl-1-phenylethyl)thiourea modified Mn-Anderson type heteropolyacid catalyst is shown in Figure 6. The specific data are as follows:

¹ H NMR (501MHz, DMSO) δ66.06(s, 12H), δ7.28(s, 10H), 3.12(s, 24H), 1.53(s, 24H), 1.27(s, 24H), 0.89(s ,36H).

Example 5

(R)-1-(2-Hydroxy-1-phenylethyl)thiourea Modified Mn-Anderson Polyacids Catalyzed Asymmetric Dihydroxylation of Alkenes

Add 1.0415g (0.01mol) styrene to a clean reaction bottle, then add 10ml mixed solvent (the molar ratio of water and acetonitrile is 1:1~3:1), and finally add 1.7g 30% hydrogen peroxide and 0.0099g (R)-1-(2-hydroxy-1-phenylethyl) thiourea modified Mn-Anderson type polyacid catalyst, reacted for 24 hours, took 5ml of ethanol and added to the reaction system, centrifuged to make the catalyst settle, then added 3ml of ethanol to separate again The catalyst was filtered to obtain the catalyst and dried in vacuum. The reaction system was extracted three times with ethyl acetate, and the obtained product was desolventized under reduced pressure, and the vicinal diol compound was obtained by column chromatography separation, and 1.36 g of the product was obtained, with a yield of 99%. The enantiomeric excess of the product was measured by chiral high performance liquid chromatography, and the ee value reached 99%. The catalysts can carry out catalytic reactions in different degrees, and have good stereoselectivity. The reaction equations using different olefins and catalysts are shown below, and the experimental results obtained are shown in Table 1.

The catalyst obtained by the above-mentioned recovery is directly used in the next reaction (dihydroxylation reaction of styrene), and the enantiomeric excess value of the product obtained is determined by HPLC (chiral AS-H column, Virahol: normal hexane=3 : 7,254nm, 20°C, 0.5mL/min). The results obtained for catalyst recycling are shown in Table 2.

Table 1 Experimental results of polyacid-catalyzed asymmetric dihydroxylation of alkenes

The experimental result of table 2 catalyst recycling

All the above-mentioned embodiments are not intended to limit other forms of implementing this new product and/or new method. Those skilled in the art will, with this important information, modify the above to achieve a similar implementation. However, all modifications or transformations based on the present invention belong to the rights reserved by the present invention.

The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention to other forms. Any skilled person who is familiar with this profession may use the technical content disclosed above to change or modify the equivalent of equivalent changes. Example. However, any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still belong to the protection scope of the technical solution of the present invention.

Claims (10)

1. a preparation method of the Mn-Anderson type heteropolyacid catalyst modified by (R)-1-(2-hydroxyl-1-phenylethyl) thiourea, is characterized in that, concrete steps are as follows: 1) Mix sodium molybdate and tetrabutylammonium bromide at a molar ratio of 1:1 to 2:1, react at room temperature under the action of concentrated hydrochloric acid, and prepare the precursor [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ]; 2) Reflux the above-obtained precursor [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ] with trishydroxyaminomethane and manganese acetate in an organic solvent to obtain the Mn-Anderson type poly Oxymetalate; 3) Synthesizing (R)-1-(2-hydroxyl-1-phenylethyl)isothiocyanate with D-phenylglycinol as raw material; 4) The Mn-Anderson type polyoxometalates modified by (R)-1-(2-hydroxyl-1-phenylethyl) isothiocyanate and step 2) obtained according to the molar ratio of 5: Mix and dissolve in the reaction solvent at a ratio of 1 to 8:1, and react at a temperature of 45-55°C to obtain (R)-1-(2-hydroxy-1-phenylethyl)thiourea-modified Mn-Anderson heteropolyacid catalyst. 2. The preparation method according to claim 1, characterized in that, in step 1), the molar ratio of sodium molybdate to concentrated hydrochloric acid is 1:1 to 1:2. 3. The preparation method according to claim 1, characterized in that, in step 2), the matrix [N(C ₄ H ₉ ) ₄ ] ₄ [α-Mo ₈ O ₂₆ ] and trishydroxyaminomethane, manganese acetate The molar ratio is 1:(3~4):(1~2). 4. The preparation method according to claim 1, characterized in that, in step 2), the organic solvent is a polar aprotic solvent. 5. The preparation method according to claim 1, characterized in that, in step 2), the organic solvent is acetonitrile or 1,2-dichloroethane. 6. The preparation method according to claim 1, characterized in that, in step 3), using D-phenylglycinol as raw material to synthesize (R)-1-(2-hydroxyl-1-phenylethyl) isosulfur The specific steps of cyanate ester are as follows: mix D-phenylglycine alcohol, CS ₂ and triethylamine in a molar ratio of 1:(2~4):1, stir and react at room temperature for 1h~2h, then cool in ice bath. Add di-tert-butyl dicarbonate and 4-dimethylaminopyridine at low temperature. After the addition is complete, continue to keep stirring under ice bath conditions for 3h to 5h to obtain (R)-1-(2-hydroxyl-1-phenylethyl) Isothiocyanate; wherein, the molar ratio of D-phenylglycinol, di-tert-butyl dicarbonate and 4-dimethylaminopyridine is 1:1:(0.02～0.05). 7. The preparation method according to claim 1, wherein in step 4), the reaction solvent is selected from any one or more of DMF, DMSO or NMP. 8. A (R)-1-(2-hydroxyl-1-phenylethyl)thiourea-modified Mn-Anderson type heteropolyacid catalyst prepared by the preparation method according to any one of claims 1-7. 9. a kind of (R)-1-(2-hydroxyl-1-phenylethyl) thiourea modified Mn-Anderson type heteropolyacid catalyst as claimed in claim 8 is in the asymmetric dihydroxylation reaction field of alkene Applications. 10. application as claimed in claim 9, is characterized in that, application method is as follows: the Mn-Anderson type heteropolyacid of alkene and (R)-1-(2-hydroxyl-1-phenylethyl) thiourea modification The catalyst is mixed in a mixed solvent composed of water and acetonitrile, and reacted at a temperature of 30°C to 50°C to obtain an o-diol compound; wherein: the (R)-1-(2-hydroxyl-1-phenylethyl)thiourea The dosage of the modified Mn-Anderson type heteropolyacid catalyst is 0.5mol%-5mol% of the olefin.