Preparation method of nickel-based catalyst and chiral beta-butyrolactone

Abstract

The invention provides a method for synthesizing chiral beta-butyrolactone. The method comprises the step of catalyzing asymmetric hydrogenation of diketene by using a catalyst prepared from a diphosphine ligand and a nickel metal precursor in situ in the presence of a weakly alkaline additive to prepare the chiral beta-butyrolactone. The method solves the problem of low catalyst activity caused by byproducts of diketene asymmetric hydrogenation reaction, and is relatively mild in reaction condition, simple to operate, low in catalyst cost, wide in substrate application range and high in enantioselectivity.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for synthesizing chiral beta-butyrolactone through an asymmetric hydrogenation reaction with high stereoselectivity. Background Art

[0002] As a degradable plastic, polyhydroxyalkanoate (PHA) is superior to the current mainstream PLA and PBAT in terms of degradation performance. PHA is currently mainly produced by fermentation and is relatively expensive (40,000-60,000 yuan / ton), which limits its promotion and application. The development of a low-cost chemical synthesis method for PHA can significantly reduce the cost of PHA (20,000 yuan / ton) and promote its promotion and application. In addition, the chemical synthesis of PHA has the advantages of strong controllability and stable process. This process route has important economic and ecological value and can broaden the layout of PHA in the field of degradable plastics (J.Am.Chem.Soc, 2001, 123:3229-3238).

[0003] The monomer with the largest amount used in chemical PHA is β-butyrolactone, and its optical purity is a key factor affecting the performance of the material (J.Am.Chem.Soc.2002,124,15239-15248). Literature reports on the asymmetric hydrogenation of diethylene ketone (J.Chem.Soc.Chem.Commun.1992,23,1725-1727; US005981771A; US0060433 80A) use a noble metal ruthenium metal precursor and a diphosphorus ligand as catalysts, but there is currently a problem of low catalyst activity, resulting in a high catalyst dosage (S / C=3000) and a high asymmetric hydrogenation cost, which ultimately results in the polymer product PHA having no cost advantage over the biofermentation method.

[0004] Therefore, in order to achieve the development and promotion of low-cost biodegradable plastics, it is of great significance to develop an efficient and inexpensive asymmetric hydrogenation catalytic system for diketene. Summary of the invention

[0005] The purpose of the present invention is to develop a new diketene asymmetric hydrogenation catalytic system and provide a cheap nickel-based catalyst. The nickel-based catalyst of the present invention catalyzes the asymmetric hydrogenation of diketene to synthesize chiral β-butyrolactone, has high activity and low cost, and has very high chemical selectivity and stereoselectivity, which can greatly reduce the production cost of chiral β-butyrolactone.

[0006] The technical solution provided by the present invention is as follows:

[0007] A nickel-based catalyst comprising a diphosphine ligand and a metallic nickel precursor;

[0008] In the present invention, the structure of the diphosphine ligand is as follows:

[0009]

[0010] Wherein, the R groups are C1-C40 straight chain or branched alkyl (preferably C1-C5 straight chain or branched alkyl), C1-C40 alkoxy (preferably C1-C5 alkoxy), cycloalkyl with 3-12 carbon atoms or substituted cycloalkyl with 3-12 carbon atoms, phenyl and substituted phenyl, benzyl and substituted benzyl;

[0011] The substituted phenyl or substituted benzyl, the substituent on the benzene ring is selected from C1-C40 straight chain or branched alkyl (preferably C1-C5 straight chain or branched alkyl), C1-C40 alkoxy (preferably C1-C5 alkoxy), halogen (fluorine, chlorine, bromine, iodine), nitro, ester group, or cyano group, preferably methyl, methoxy, tert-butyl; the number of substituents on the phenyl or benzyl is 1-5 (for example, 2, 3);

[0012] The substituent on the cycloalkyl group is a C1-C40 straight or branched chain alkyl group;

[0013] The R group is preferably an aryl group, such as a phenyl group or a substituted phenyl group;

[0014] n is 0-3, for example, 0 (representing a five-membered ring), 1, 2.

[0015] As an embodiment, the synthesis route of the above-mentioned bisphosphine ligand is as follows:

[0016]

[0017] The synthesis process is divided into three steps:

[0018] 1) reacting a chiral cyclic diol compound with about 2 equivalents of trifluoromethanesulfonic anhydride under pyridine conditions to obtain an intermediate protected by a corresponding group;

[0019] 2) The above intermediate is coupled with a phosphine oxide compound under the catalysis of palladium acetate to obtain a phosphonyl compound;

[0020] 3) The phosphono compound is reduced to the target ligand via trichlorosilane.

[0021] In the present invention, the metal nickel precursor is a nickel salt selected from Ni[N(SiHMe 2 ) 2 ]、Ni[N(SiMe 3 ) 2 ] and Ni[NTf 2 ], preferably Ni[N(SiHMe 2 ) 2 ].

[0022] As an example, a preferred method for synthesizing a nickel precursor is as follows: one equivalent of nickel chloride is added to a tetrahydrofuran solution of bis(dimethylsilyl)imide, and the mixture is stirred at 70° C. for 24 hours; after the reaction is completed, the solvent is removed under reduced pressure, and the mixture is stirred at 0° C. in acetone and water (V 丙酮 / V 水 =9 / 1) mixed solvent to obtain Ni[N(SiHMe 2 ) 2 ]crystal.

[0023] The present invention also provides the application of the nickel-based catalyst, wherein the diphosphine ligand and the metal nickel precursor are in situ prepared into a homogeneous catalyst for preparing chiral β-butyrolactone by hydrogenation of diketene.

[0024] In a specific embodiment, the method comprises: under nitrogen protection, adding diketene, a weakly alkaline additive, a metal nickel precursor, a bisphosphine ligand and a solvent into a reaction kettle, stirring at room temperature, and introducing hydrogen to carry out a hydrogenation reaction to prepare chiral β-butyrolactone;

[0025]

[0026] The weak alkaline additive of the present invention is selected from calcium hydroxide or calcium oxide, preferably calcium oxide; the addition amount is 1-5wt% of the reaction raw material diketene, preferably 2wt%.

[0027] The molar ratio of the diphosphine ligand to the metal nickel precursor of the present invention is preferably 1:1 to 1.2:1.

[0028] The molar ratio (S / C) of diketene to the metallic nickel precursor of the present invention is 10,000-120,000, preferably 80,000.

[0029] The solvent of the present invention is preferably one or more of dichloromethane, acetone, 1,2-dichloroethane, dioxane, tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether, toluene, xylene, and n-hexane.

[0030] The hydrogenation reaction temperature of the present invention is preferably 40-100°C.

[0031] The hydrogen pressure of the reaction of the present invention is preferably 0.8-10 MPa, preferably 3-6 MPa.

[0032] The reaction time of the present invention is 1-12 hours, preferably 4-6 hours.

[0033] Compared with the prior art, the present invention has the following positive effects:

[0034] 1) Compared with the asymmetric hydrogenation of diketene catalyzed by metal ruthenium catalyst, the addition of weak alkaline additives effectively inhibits the occurrence of side reactions, the reaction conditions are mild, and the operation is simple;

[0035] 2) The yield can reach up to 98%, and the ee value of the product β-butyrolactone can reach up to 96%;

[0036] 3) The substrate to catalyst (S / C) ratio is up to 120,000:1, and the catalyst activity is high. DETAILED DESCRIPTION

[0037] In order to facilitate the understanding of the present invention, the present invention will be further described below in conjunction with examples. It should be understood that the following examples are only for a better understanding of the present invention and do not mean that the present invention is limited to the following examples.

[0038] Main raw material sources

[0039] Diethylene ketone: 98%, Deyi Chemical;

[0040] Nickel chloride: from Inokay;

[0041] Bis(dimethylsilyl)imine: Reference "Trivalent Rare-Earth Metal Amide Complexes as Catalysts for the Hydrosilylation of Benzophenone Derivatives with HN(SiHMe 2 ) 2 by Amine-Exchange Reaction” method;

[0042] The bisphosphine ligands were prepared in-house using chiral cyclodiols as starting materials.

[0043] Main test methods

[0044] The catalyst activity of the asymmetric hydrogenation reaction was determined by qualitative and quantitative analysis of the components in the reaction solution. The conditions of the GC analysis instrument used were as follows:

[0045] Instrument model: Shimadzu GC2010

[0046] Chromatographic column: DB-5 (30m 0.25mm 0.25μm)

[0047] Column temperature program: first maintain at 35°C for 10 min, then increase to 250°C at a rate of 10°C / min, and maintain at this temperature for 10 min.

[0048] Detector temperature: 300°C

[0049] Carrier gas: 1 bar

[0050] Air: 0.3 bar

[0051] Gas (H2): 0.3 bar

[0052] Sample quality analysis is performed using the internal standard method.

[0053]

[0054] Where m1 is the mass of a product, m is the mass of the internal standard, a1 is the peak area of ​​the product detected in the gas chromatograph, and a is the peak area of ​​the internal standard. k is a correction factor related to the substance being measured and the detection conditions.

[0055] Example 1

[0056] L1 preparation process:

[0057]

[0058] Dissolve commercially available (R,S)-1,2-cyclohexanediol in degassed dichloromethane, cool to 0°C in an ice-water bath, add 0.1 equivalent of pyridine, then slowly drop 2.1 equivalent of trifluoromethanesulfonic anhydride, slowly warm to room temperature and stir for 10 hours. After the reaction is completed, wash three times with water, dry the organic phase with anhydrous sodium sulfate, and remove the solvent under reduced pressure before proceeding to the next step;

[0059] The above product was dissolved in DMSO, and 2 equivalents of diphenylphosphine oxide, 0.05 equivalents of palladium acetate, 0.05 equivalents of DPPB and 0.2 equivalents of DIEA (N, N-diisopropylethylamine) were added in sequence under nitrogen protection, and then heated to 120°C for 14 hours. After the reaction, the product was washed with water and dried, and the concentrate was recrystallized in n-hexane to obtain an intermediate product;

[0060] Under nitrogen protection, the above intermediate was dissolved in degassed toluene and 3 equivalents of triethylamine were added. After the system was cooled to 0°C, 6 equivalents of trichlorosilane were slowly added dropwise. After the addition was completed, the mixture was sealed and heated under reflux for 12 hours. After the reaction was completed, a saturated aqueous solution of sodium bicarbonate was used to quench the reaction, the filter cake was quickly filtered and washed with n-hexane, and the organic phases were combined, dried and concentrated. The concentrate was separated by column chromatography to obtain L1, with a total yield of 56% in three steps. 1 H NMR (400 MHz, CDCl 3 )δ7.45-7.38(m,20H),1.60-1.58(m,2H),1.53-1.50(m,2H),1.43-1.30(m,6H).

[0061] Hydrogenation reaction process:

[0062]

[0063] In a glove box, Ni[N(SiHMe 2 )2 ](0.03mmol) and ligand L1(0.03mmol) were dissolved in 2ml acetone and coordinated for 1 hour under magnetic stirring. Under nitrogen protection, diketene (79g, 0.94mol), the above coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml acetone were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 4MPa, and the heating was turned on at 50℃. The reaction was continued for 6h. The raw material diketene was basically reacted completely, and the yield of the product chiral β-butyrolactone was 96%, the ee value was 92%, and S / C was 31333.

[0064] Example 2

[0065] In a glove box, Ni[N(SiHMe 2 ) 2 ](0.0078mmol) and ligand L1(0.0078mmol) were dissolved in 2ml acetone and coordinated for 1 hour under magnetic stirring. Under nitrogen protection, diketene (79g, 0.94mol), the above coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml acetone were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 6MPa, and the heating was turned on at 40℃. The reaction was continued for 6h. The raw material diketene was basically reacted completely, and the yield of the product chiral β-butyrolactone was 93%, the ee value was 92%, and S / C was 120000.

[0066] Example 3

[0067] In a glove box, Ni[N(SiHMe 2 ) 2 ](0.0118mmol) and ligand L1(0.0118mmol) were dissolved in 2ml acetone and coordinated for 1 hour under magnetic stirring. Under nitrogen protection, diketene (79g, 0.94mol), the above coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml acetone were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 5MPa, and the heating was turned on at 40℃. The reaction was continued for 6h. The raw material diketene was basically reacted completely, and the yield of the product chiral β-butyrolactone was 98%, the ee value was 92%, and S / C was 80000.

[0068] Example 4

[0069] Synthesis of ligand L2:

[0070]

[0071] Compared with the synthesis method of L1, the difference is that the diphenylphosphine oxide compound is replaced by a diarylphosphine oxide, wherein the aryl structure is:

[0072] The total yield of L2 in three steps was 52%. 1 H NMR (400 MHz, CDCl 3 )δ7.49-7.36(m,8H),3.83(s,12H)1.60-1.58(m,2H),1.53-1.50(m,2H),1.43-1.30(m,6H),1.35(s,72H).

[0073] Hydrogenation reaction process:

[0074]

[0075] In a glove box, Ni[N(SiHMe 2 ) 2 ](0.03mmol) and ligand L2(0.03mmol) were dissolved in 2ml toluene and coordinated with magnetic stirring for 1 hour. Under nitrogen protection, diketene (79g, 0.94mol), the above coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml toluene were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 4MPa, and the heating was turned on at 40℃. The reaction was continued for 6h. The raw material diketene was basically reacted completely, and the yield of the product chiral β-butyrolactone was 96%, the ee value was 90%, and S / C was 31333.

[0076] Example 5

[0077] In a glove box, Ni[N(SiHMe 2 ) 2 ](0.0118mmol) and ligand L2(0.0118mmol) were dissolved in 2ml of dichloromethane and coordinated for 1 hour under magnetic stirring. Under nitrogen protection, diketene (79g, 0.94mol), the above-coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml of dichloromethane were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 6MPa, and the heating was turned on at 60℃. The reaction was continued for 6h. The raw material diketene was basically reacted, and the yield of the product chiral β-butyrolactone was 97%, the ee value was 91%, and S / C was 80000.

[0078] Example 6

[0079] In a glove box, Ni[N(SiMe 3 ) 2](0.0078mmol) and ligand L2(0.0078mmol) were dissolved in 2 ml of acetone and coordinated with magnetic stirring for 1 hour. Under nitrogen protection, diketene (79g, 0.94mol), the above-coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80 ml of acetone were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 6MPa, and the heating was turned on at 40℃. The reaction was carried out for 8h. The raw material diketene was basically reacted completely, and the yield of the product chiral β-butyrolactone was 89%, the ee value was 90%, and S / C was 120000.

[0080] Example 7

[0081] Synthesis of ligand L3:

[0082]

[0083] Compared with the synthesis method of L1, the difference is that the diphenylphosphine oxide compound is replaced by a diarylphosphine oxide, wherein the aryl structure is:

[0084] The total yield of L3 in three steps was 60%. 1 H NMR (400 MHz, CDCl 3 )δ7.48-7.40(m,12H),2.34(s,12H)1.61-1.57(m,2H),1.54-1.51(m,2H),1.43-1.29(m,6H).

[0085] Hydrogenation reaction process:

[0086]

[0087] In a glove box, Ni[N(SiHMe 2 ) 2 ](0.03mmol) and ligand L3(0.03mmol) were dissolved in 2ml acetone and coordinated for 1 hour under magnetic stirring. Under nitrogen protection, diketene (79g, 0.94mol), the above coordinated catalyst, calcium oxide (2wt%, 1.6g) and 80ml acetone were added into the reactor. After replacing hydrogen 5 times, the hydrogen pressure was increased to 4MPa, and the heating was turned on at 40℃. The reaction was continued for 6h. The raw material diketene was basically reacted, and the yield of the product chiral β-butyrolactone was 94%, the ee value was 93%, and S / C was 31333.

[0088] It is easy to understand that the above embodiments are only examples for clear explanation and do not mean that the present invention is limited thereto. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from this are still within the protection scope of the present invention.

Claims

1. A nickel-based catalyst comprising a diphosphine ligand and a metallic nickel precursor; in, The structure of the bisphosphine ligand is shown below: Wherein, the R groups are C1-C40 straight chain or branched alkyl (preferably C1-C5 straight chain or branched alkyl), C1-C40 alkoxy (preferably C1-C5 alkoxy), cycloalkyl with 3-12 carbon atoms or substituted cycloalkyl with 3-12 carbon atoms, phenyl and substituted phenyl, benzyl and substituted benzyl; The substituted phenyl or substituted benzyl, the substituent on the benzene ring is selected from C1-C40 straight chain or branched alkyl (preferably C1-C5 straight chain or branched alkyl), C1-C40 alkoxy (preferably C1-C5 alkoxy), halogen (fluorine, chlorine, bromine, iodine), nitro, ester group, or cyano group, preferably methyl, methoxy, tert-butyl; the number of substituents on the phenyl or benzyl is 1-5; The substituent on the cycloalkyl group is a C1-C40 straight or branched chain alkyl group; The R group is preferably an aryl group; n is 0-3.

2. The nickel-based catalyst according to claim 1, wherein The metal nickel precursor is a nickel salt, selected from at least one of Ni[N(SiHMe2)2], Ni[N(SiMe3)2] and Ni[NTf2].

3. Use of the nickel-based catalyst according to claim 1 or 2 for preparing chiral β-butyrolactone by hydrogenation of diketene.

4. The use according to claim 3, wherein the preparation method comprises: Under nitrogen protection, diketene, weak alkaline additive, metal nickel precursor, diphosphine ligand and solvent are added into a reaction kettle, stirred at room temperature, and hydrogen is introduced for hydrogenation reaction to prepare chiral β-butyrolactone.

5. The use according to claim 4, wherein the weakly alkaline additive is selected from calcium hydroxide or calcium oxide, preferably calcium oxide.

6. The use according to claim 5, wherein the amount of the weakly alkaline additive added is 1-5 wt%, preferably 2 wt%, of the reaction raw material diketene.

7. The use according to claim 4, wherein the molar ratio of the bisphosphine ligand to the metallic nickel precursor is 1:1 to 1.2:

1.

8. The use according to any one of claims 4 to 7, wherein the molar ratio of diketene to the metallic nickel precursor is 10,000-120,000.

9. The use according to claim 4, wherein the hydrogenation reaction temperature is 40-100°C.

10. The use according to claim 4, wherein the reaction hydrogen pressure is 0.8-10 MPa, preferably 3-6 MPa.

Images