CN103008006A - Immobilized chiral phosphoric acid catalyst and preparation method thereof - Google Patents

Abstract

The invention discloses an immobilized chiral phosphoric acid catalyst and a preparation method thereof. A structural formula of the catalyst is as Formula I as shown in the specification; a carrier PS (polystyrene) is aminomethylated polystyrene. HCl, 1%DVB, and an amido substitution value is 1.0mmol/g, and the catalyst is in a chiral binaphthol structure, i.e. BINOL (binaphthol) can be in an R configuration or an S configuration. The preparation method of the catalyst comprises the following steps of a) synthesizing aminomethylated polystyrene immobilized chiral binaphthol, and b) allowing immobilized chiral binaphthol to react with POCl3 when Et3N exists, and obtaining polystyrene immobilized chiral phosphoric acid (Formula I). The heterogeneous catalyst can be prepared easily, the treatment operation after reaction is simple, the catalyst (Formula I) is applied to an asymmetric Friedel-Crafts alkylation reaction, the chemical yield of a product can reach 85%, and the enantiomeric selectivity ee value can reach 91%.

Description

A kind of immobilized chiral phosphoric acid Catalysts and its preparation method

Technical field

The present invention relates to a kind of chiral phosphoric acid Catalysts and its preparation method, particularly relate to a kind of immobilized chiral phosphoric acid Catalysts and its preparation method.

Background technology

In the last few years, people were huge and be the trend of cumulative year after year to the demand of single enantiomer chipal compounds, and this demand is mainly reflected in the fields such as medicine, agricultural chemicals and fine chemicals.The global marketing volume of chiral drug in 2000 is 1,330 hundred million dollars, and with annual 8% speed increase.Since two thousand, the asymmetric organic micromolecule catalyst take proline, chiral phosphoric acid etc. as representative has obtained development at full speed, becomes the important asymmetric catalysis agent of the 3rd class after transition-metal catalyst and biological enzyme agent.With traditional transition-metal catalyst with biological enzyme agent compare, that organic micromolecule catalyst has is simple in structure, preparation easily, reaction condition is gentle and without the characteristics significantly such as metallic pollution.

Product and catalyst are not easily separated, product is difficult for purifying because the homogeneous phase chiral catalyst generally all exists, catalyst is stable not and catalyst is difficult to the shortcomings such as recovery, and its commercial Application still is subject to certain restrictions.

Comparatively speaking, Heterogeneous asymmetric catalysis not only has outside the advantages such as product separates easily with catalyst, the easy purifying of product, but also possess the advantage that catalyst can recycling, therefore heterogeneousization of catalyst causes various countries scientist's attention gradually in recent years.Patent of invention CN101940947B discloses a kind of preparation method who utilizes the immobilized chirality Salen-Co of polystyrene resin (III) catalyst, the method is the solid supported to traditional transition-metal catalyst, and the form by covalent chemical bond between carrier and the catalytic activity unit is connected.Patent of invention CN101306383B discloses chiral organic micromolecule catalyst of a kind of loaded by heteropoly acid and preparation method thereof and application, the method is utilized the acidity of heteropoly acid, form acid ion alkali ion pair with some chiral organic micromolecule that contains alkaline amido by chemical reaction, namely the form with ionic bond loads on the heteropoly acid POM.The chiral organic micromolecule catalyst of this loaded by heteropoly acid is directly obtaining reasonable enantioselectivity and product yield in the Aldol reaction, but the chiral organic micromolecule catalyst that utilizes loaded by heteropoly acid has certain limitation, need the chiral organic micromolecule of institute's load to have alkalescence, in recent years other one large class development uses also simultaneously rapidly very widely that the chiral phosphoric acid catalyst then is difficult to load on above the heteropoly acid.

Summary of the invention

The purpose of this invention is to provide a kind of immobilized chiral phosphoric acid Catalysts and its preparation method.

For achieving the above object, immobilized chiral phosphoric acid catalyst provided by the invention, its structural formula following (formula I):

Formula I

Carrier PS contains amino polystyrene resin (Aminomethylated polystyrene.HCl, 1%DVB, amido substitution value are 1.0mmol/g), available from Nankai University with become technology ﹠ development Co..The chiral binaphthol structure, namely BINOL can be R configuration or S configuration.

The method of the above-mentioned catalyst of preparation provided by the invention the steps include:

A) contain the synthetic of the immobilized chiral binaphthol (formula II) of amino polystyrene resin, can list of references method (Xiao-WuYang, Jian-Heng Sheng, Chao-Shan Da etc.J.Org.Chem., 2000,65 (2), 295-296) obtain, the supported quantity of chiral binaphthol is 0.4mmol/g;

B) the immobilized chiral phosphoric acid (formula I) of polystyrene resin is synthetic: with compound (formula II) at Et ₃N exists lower, with 2 equivalent POCl ₃, at room temperature stirring reaction 3-8 hour, system is chilled to 0 ℃, slowly add entry, returned to stirring at room 3 hours, suction filtration with 1N HCl solution washing, obtains the immobilized chiral phosphoric acid of target product polystyrene resin (formula I)

Formula II formula I

Compared with prior art, the present invention has the following advantages:

1. this method provides immobilized chiral phosphoric acid catalyst (formula I) of a kind of polystyrene resin and preparation method thereof, this heterogeneous catalyst prepares easily, post-reaction treatment is simple to operate, only needs the simple suction filtration can separating catalyst and product, and also relatively easier purifying of product.

2. this immobilized chiral phosphoric acid catalyst (formula I) is applied to asymmetric Friedel-Crafts reaction, and the product chemical yield reaches 85%, and enantioselectivity ee value reaches 91%; And do not have immobilized homogeneous catalyst (formula III) to be applied to asymmetric Friedel-Crafts reaction, only obtained the product of racemization.

Formula III

3. this immobilized chiral phosphoric acid catalyst shows higher stability, is recycling conversion ratio and the enantioselectivity that still can keep relative stability for 6 times.And homogeneous catalyst often can only use once.

The specific embodiment

Synthesizing of the chiral phosphoric acid (formula I) that first's polystyrene resin is immobilized

Embodiment 1 contains the synthetic of the immobilized chiral binaphthol (formula II) of amino polystyrene resin

The list of references method (Xiao-Wu Yang, Jian-Heng Sheng, Chao-Shan Da etc.J.Org.Chem., 2000,65 (2), 295-296) obtain.The infrared spectrum IR (KBr) of compound (formula II): 3344,2827,1644,1626,1570,1308,1270,1245cm ^-1The chiral binaphthol that we are connected Compound C, polystyrene resin and resin (formula II) has carried out respectively infrared spectrum measurement, finds out by contrast, and after resin and Compound C condensation, carboxyl peak 3589,1672cm ^-1, and resin amido peak 3535cm ^-1Disappear, and 3344,1644,1570,1245cm ^-1The characteristic absorption peak of acid amides appears in the place, and 1308 and 1270cm ^-1Show the existence of phenolic hydroxyl group, prove BINOL bonding be connected on the resin.Calculating the supported quantity of chiral binaphthol on polystyrene resin is 0.4mmol/g.

Synthesizing of the chiral phosphoric acid (formula I) that embodiment 2 polystyrene resins are immobilized

Get the dry three-necked bottle of a 50mL, under the argon shield, add immobilized chiral binaphthol (formula II) and the 20mL CH of 6 gram polystyrene resins ₂Cl ₂, be chilled to 0 ℃, drip successively POCl ₃(3.6mL, 39.2mmol), Et ₃N (8.2mL, 58.8mmol), after dropwising, stirring at room 4-6 hour.System is chilled to 0 ℃, slowly drips water (1mL), the solid suction filtration is used DMF, CH successively ₂Cl ₂, the 1N HCl aqueous solution and methanol wash 2 times, vacuum drying obtains the immobilized chiral phosphoric acid of target product polystyrene resin (formula I) to constant weight, and quality is 6.15 grams, and calculating the supported quantity of chiral phosphoric acid on polystyrene resin is 0.4mmol/g.

The infrared spectrum IR (KBr) of compound (formula I): 3397,3344,2827,1735,1644,1626,1570,1308,1270,1245,1099,1075,1007cm ^-1The chiral binaphthol (formula II) that the immobilized chiral phosphoric acid (formula I) of our p-poly-phenyl vinyl is connected with resin has carried out respectively infrared spectrum measurement, finds out by contrast, after compound (formula II) phosphorylation, at 1099,1075cm ^-1The characteristic absorption peak of phosphoryl appears in the place, proves that BINOL all is phosphorylated.

The application of chiral phosphoric acid (formula I) in asymmetric Friedel-Crafts reaction that the second portion polystyrene resin is immobilized

The asymmetric Friedel-Crafts reaction of chiral phosphoric acid (formula III) catalyzing indole that embodiment 3 (Comparative Examples) is not immobilized and sulfimide

Get the dry three-necked bottle of a 50mL; under the argon shield; imines E (2.5mmo1) and not immobilized chiral phosphoric acid catalyst (formula III) (0.25mmo1) are dissolved in the toluene (10mL); stirred 30 minutes under the room temperature; then be chilled to-50 ℃ of lower stirrings 10 minutes, at-50 ℃ of lower indoles D (12.5mmo1) that add.TLC adds 10%NaHCO after following the tracks of the disappearance of imines E raw material ₃The aqueous solution (30mL) cancellation reaction, ethyl acetate (50mL) extraction, organic layer is water (30mL) and saturated aqueous common salt (30mL) washing respectively, anhydrous Na ₂SO ₄Drying, removal of solvent under reduced pressure, column chromatography (AcOEt: PE=1: 3) obtain target product F, be white solid, productive rate 81%, the ee value equals zero. ¹H?NMR(300MHz，CDCl ₃)δ2.34(s，3H)，5.24(d，J＝7.2Hz，1H)，5.82(d，J＝6.9Hz，1H)，6.61(d，J＝2.4Hz，1H)，6.97(t，J＝7.8Hz，1H)，7.06(d，J＝7.8Hz，2H)，7.11-7.27(m，8H)，7.53(d，J＝8.4Hz，2H)，8.02(br，1H)； ¹³C?NMR(75MHz，DMSO-d ₆)δ20.8，54.4，111.4，115.7，118.8，118.9，121.2，123.7，125.4，126.4，126.6，127.0，127.8，128.9，136.3，138.8，141.7，141.8。

The asymmetric Friedel-Crafts reaction of chiral phosphoric acid (formula I) catalyzing indole that embodiment 4 polystyrene resins are immobilized and sulfimide

Identical with the method for embodiment 3, chiral phosphoric acid catalyst (formula III) that just will be not immobilized is (0.25mmo1) with the immobilized chiral phosphoric acid catalyst (formula I) of polystyrene resin (0.625 gram, 0.25mmo1) replace, adding 10%NaHCO in addition ₃After the aqueous solution (30mL) the cancellation reaction, suction filtration is removed the immobilized chiral phosphoric acid of polystyrene resin (formula I), and water, and the ethyl acetate washing obtains target product F, productive rate 85%, 91%ee at last; [α] _D ²⁰=+14.9 ° of (c=0.52, Acetone), The enantiomeric ratio was determined by Daicel Chiralcel OD-H (25cm), Hexanes/IPA=70/30,0.6mL/min, λ=254nm, t (major)=16.92min, t (minor)=32.54min.

Embodiment 5 recycles the performance example

Identical with the method for embodiment 4, just remove in the immobilized chiral phosphoric acid of polystyrene resin (formula I) step at suction filtration, use successively DMF, CH ₂Cl ₂, the 1N HCl aqueous solution and methanol wash 2 times, vacuum drying is to constant weight, and is used further to the next time asymmetric Friedel-Crafts reaction of catalyzing indole and sulfimide, the results are shown in Table 1.Can see immobilized chiral phosphoric acid catalyst (formula I) and still keep higher ee value even use 6 times.

The chiral phosphoric acid catalyst (formula I) that table 1. polystyrene resin is immobilized recycle performance

Catalyst (formula I)	Reaction time (h)	Conversion ratio (%)	Enantioselectivity (%)
				For the first time	6	85	91
For the second time	6	90	90
				For the third time	6	87	88
The 4th time	6	85	88
				The 5th time	6	82	87
The 6th time	6	85	88

Claims (2)

1. immobilized chiral phosphoric acid catalyst, its structural formula following (formula I):

Formula I

Carrier PS contains amino polystyrene resin (Aminomethylated polystyrene.HCl, 1%DVB, amido substitution value are 1.0mmol/g), the chiral binaphthol structure, and namely BINOL can be R configuration or S configuration.

2. method for preparing immobilized chiral phosphoric acid catalyst claimed in claim 1, its key step is:

A) contain the synthetic of the immobilized chiral binaphthol (formula II) of amino polystyrene resin, can list of references method (Xiao-WuYang, Jian-Heng Sheng, Chao-Shan Da etc.J.Org.Chem., 2000,65 (2), 295-296) obtain, the supported quantity of chiral binaphthol is 0.4mmol/g;

B) the immobilized chiral phosphoric acid (formula I) of polystyrene resin is synthetic: with compound (formula II) at Et ₃N exists lower, with 2 equivalent POCl ₃, at room temperature stirring reaction 3-8 hour, system is chilled to 0 ℃, slowly add entry, returned to stirring at room 3 hours, suction filtration with 1N HCl solution washing, obtains the immobilized chiral phosphoric acid of target product polystyrene resin (formula I)

Formula II formula I