Preparation method of optically active beta-butyrolactone

Abstract

The invention provides a preparation method of optically active beta-butyrolactone, which is characterized in that in the presence of a catalytic system, butyric acid is used as a cocatalyst, and diketene is subjected to asymmetric hydrogenation reaction to prepare the optically active beta-butyrolactone. The butyric acid is introduced into a catalytic system, so that the catalytic stability of the asymmetric hydrogenation optical activity transition metal catalyst for homogeneous catalysis can be remarkably improved, and a higher cumulative conversion number is realized.

Description

Technical Field

[0001] The present invention belongs to the technical field of asymmetric catalytic hydrogenation reaction, and particularly relates to a method for preparing optically active β-butyrolactone. Background Art

[0002] As a material with very broad application prospects, biodegradable materials have been widely studied at present. Among them, PHAs materials have very obvious advantages in terms of degradation performance and mechanical properties compared with similar materials.

[0003] Existing industrial technologies for preparing PHAs are all prepared by biological methods. Although chemical methods for PHAs have been studied and explored for a long time, no industrial application has been seen yet. The main reason is that its monomer β-butyrolactone is difficult to be efficiently prepared.

[0004] At present, the technical route of β-butyrolactone has problems such as low catalytic activity, poor corresponding selectivity, and high cost, which limit its industrial application.

[0005] J.CHEM.SOC.,CHEM.COMMUN.,1992,1725-1726 describes a catalytic system for preparing optically active β-butyrolactone, and the cumulative turnover number of its catalyst for the substrate is only 500-1000, without application prospects.

[0006] Therefore, it is necessary to find a method for preparing optically active β-butyrolactone, improve the activity of the catalyst, achieve a high cumulative turnover number, thereby reducing the catalyst cost and bringing good economic benefits. Summary of the Invention

[0007] In view of this, the object of the present invention is to provide a method for preparing optically active β-butyrolactone. By introducing butyric acid into the catalytic system for asymmetric hydrogenation of diketene to prepare optically active β-butyrolactone, the catalytic stability of the transition metal catalyst can be significantly improved, thereby achieving higher catalyst activity and lifespan.

[0008] In the experiment of asymmetric hydrogenation of diketene to prepare optically active β-butyrolactone, the inventors of the present application unexpectedly found that introducing butyric acid into the catalytic system can significantly improve the catalytic activity and lifespan of the catalyst, which is reflected in that the catalyst of the present invention has a higher cumulative turnover number.

[0009] The cumulative conversion number is a common term for evaluating the performance of a catalyst and is an evaluation index reflecting the activity and lifespan of the catalyst. Usually, the activity index focuses on the level of high or low, while the cumulative conversion number more emphasizes reflecting the lifespan of the catalyst, indicating the total amount of substrate that the catalyst can catalyze the reaction from the initial use until deactivation. For the activity of a recyclable catalyst, the amount of substrate catalyzed by the catalyst in a single use is represented by the turnover number (TON), and the cumulative conversion number is the sum of the turnover numbers of the catalyst in a single use; among them, the turnover number (TON) is also a common term for evaluating the performance of the catalyst, and the turnover number = the molar amount of the product obtained in a single reaction / the molar amount of the active component in the catalyst used.

[0010] To achieve its objectives, the present invention provides the following technical solutions:

[0011] A method for preparing an optically active β-butyrolactone, which is to prepare the optically active β-butyrolactone by an asymmetric hydrogenation reaction of diketene in the presence of a catalytic system with butyric acid as a co-catalyst.

[0012] In the present invention, the mass concentration of the butyric acid in the reaction system is 10 - 6000 ppm, such as 10, 50, 100, 300, 500, 800, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000 ppm, preferably 30 - 3000 ppm.

[0013] In the present invention, the catalytic system is a transition metal catalytic precursor and a chiral ligand composition, or a complex formed by a transition metal and a ligand;

[0014] Preferably, the transition metal catalyst precursor is selected from at least one of compounds containing ruthenium, rhodium, and iridium, and more preferably Ir(COD) 2 BF 4 、[RuI 2 (cymene)] 2 、Rh(COD) 2 BF 4 、Rh 2 (CO) 4 Cl 2 、[RuCl 2 (cymene)] 2 and at least one of them;

[0015] Preferably, the chiral ligand is selected from at least one of chiral bidentate phosphine ligands, and more preferably at least one of Segphos, Binap, Synphos, BIPHEP, etc.;

[0016] Preferably, the complex formed by the transition metal and the ligand is selected from at least one of the complexes formed by ruthenium, rhodium, iridium and phosphine ligands, more preferably at least one of ruthenium-phosphine complexes and iridium-phosphine complexes, and further preferably at least one of RuCl(p-cymene)((S)-binap)]Cl, [RuI(p-cymene)((S)-3,5-TMS-synphos)]I, [Rh(COD)((R,R)-Me-Duphos)]BF 4 , and at least one of [RuI(p-cymene)((S)-segphos)]I;

[0017] Preferably, in the transition metal catalyst precursor and chiral ligand composition, the molar ratio of the transition metal catalyst precursor to the chiral ligand in terms of the molar amount of the transition metal therein is 1:(1-5), such as 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 5:1, and preferably 1:(1-2.5).

[0018] In the present invention, the addition amount of the catalyst system is 1:10000-200000 in terms of the molar amount of the transition metal therein to the molar amount of diketene, such as 1:10000, 1:50000, 1:100000, 1:150000, 1:200000.

[0019] In the present invention, there is no particular requirement for the source of the butyric acid, and an appropriate amount of butyric acid raw material can be directly added to the reaction system;

[0020] The inventors of the present application also found during the experiment that when a specific catalyst system is selected, under the reaction conditions of the present invention, a trace amount of butyric acid can be generated in-situ, and the amount of butyric acid generated is within the range of 10-6000 ppm by mass concentration in the reaction system. Therefore, butyric acid can also be catalytically generated in-situ in the reaction system by screening a specific catalyst. Both of the above two ways of introducing butyric acid can improve the catalytic activity and will not introduce new impurities; when butyric acid is catalytically generated in-situ in the reaction system by screening a specific catalyst, the catalyst is selected from [RuI(p-cymene)((S)-3,5-TMS-synphos)]I and [RuI(p-cymene)((S)-segphos)]I in the complex formed by the transition metal and the ligand.

[0021] In the present invention, for the asymmetric hydrogenation reaction, the reaction pressure is controlled to be 0.1-10 MPaA by the hydrogen input amount, such as 0.1, 1, 3, 5, 7, 9, 10 MPaA, and preferably 4-8 MPaA.

[0022] In the present invention, the asymmetric hydrogenation reaction is carried out in a solvent environment, and the solvent is selected from at least one of ketone compounds, preferably acetone and / or methyl ethyl ketone;

[0023] Preferably, the mass ratio of the amount of the solvent to the mass of diketene is 4-7:1, such as 4:1, 5:1, 6:1, 7:1.

[0024] In the present invention, for the asymmetric hydrogenation reaction, the reaction temperature is 30-90 °C, such as 30, 40, 50, 60, 70, 80, 90 °C, preferably 40-80 °C, and the time is 1-20 h, such as 1, 3, 5, 8, 10, 13, 15, 18, 20 h, preferably 2-10 h;

[0025] Preferably, before the start of the asymmetric hydrogenation reaction, the air in the system is replaced with nitrogen.

[0026] In the preparation method of the optically active β-butyrolactone of the present invention, the conversion rate can reach up to more than 99%, and the cumulative turnover number can be as high as 80,000.

[0027] The optical purity of the optically active β-butyrolactone product of the present invention can reach up to more than 95 ee%.

[0028] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0029] By introducing the cocatalyst butyric acid, the catalytic activity of the catalyst is significantly improved, so that the cumulative turnover number of the catalyst can be increased to more than 80,000, enabling the asymmetric catalysis of diketene to be applied industrially. Detailed Embodiments

[0030] In order to better understand the technical solution of the present invention, the content of the present invention will be further described below in conjunction with embodiments, but the content of the present invention is not limited to the following embodiments only.

[0031] The performance test parameters and corresponding test methods used in the embodiments of the present invention are as follows:

[0032] Gas chromatograph: Agilent 7890, chromatographic column DB-5 (for conversion rate determination), chromatographic column Supelco β-DEXTM 225 (for optical purity determination), inlet temperature: 300 °C; split ratio 50:1; carrier gas flow rate: 52.8 ml / min; temperature programming: hold at 95 °C for 40 min, increase to 180 °C at a rate of 10 °C / min, hold for 40 min, detector temperature: 280 °C.

[0033] Optical purity:

[0034] Optical purity ee% = (R-butyrolactone peak area in gas chromatography - S-butyrolactone peak area in gas chromatography) / (R-butyrolactone peak area in gas chromatography + S-butyrolactone peak area in gas chromatography).

[0035] Conversion rate:

[0036] Conversion rate = 100% - (diketene peak area in gas chromatography + geranyl aldehyde peak area in gas chromatography) * 100% / total peak area in gas chromatography (excluding solvent).

[0037] Cumulative conversion number: the sum of the single catalyst use turnover number (TON);

[0038] Turnover number (TON) = molar amount of β-butyrolactone obtained in a single reaction / molar amount of transition metal in the catalyst used.

[0039] The sources of the main raw materials in the examples and comparative examples of the present invention are as follows. Other sources are obtained from common commercial channels unless otherwise specified:

[0040] Diethylene ketone: Deyi Chemical Co., Ltd.;

[0041] Acetone: Beijing Inokai Co., Ltd.;

[0042] Butyric acid: Shanghai Aladdin Co., Ltd.;

[0043] Hydrogen: Yantai Mingju Gas Co., Ltd.;

[0044] (S)-Synphos: (S)-(-)-[(5,6),(5',6')-bis(ethylenedioxy)biphenyl-2,2'-yl]diphenylphosphine, Shanghai Haohong Biopharmaceutical Technology Co., Ltd.;

[0045] (S)-Binap: S-(-)-1,1'-binaphthyl-2,2'-bis(diphenylphosphine): Shanghai Haohong Biopharmaceutical Technology Co., Ltd.;

[0046] (S)-Segphos: (S)-(-)-5,5'-bis(diphenylphosphine)-4,4'-di-1,3-benzodioxy, Shanghai Haohong Biopharmaceutical Technology Co., Ltd.;

[0047] [RuI 2 (cymene)] 2 :Shanghai BiDe Pharmaceutical Technology Co., Ltd.;

[0048] Ir(COD) 2 BF 4 : Beijing Inokai Co., Ltd.;

[0049] [RuCl 2 (cymene)] 2: Beijing InnoChem Co., Ltd.;

[0050] ((S)-3,5-TMS-synphos: Shanghai Bide Pharmatech Co., Ltd.;

[0051] (R,R)-Me-Duphos: Shanghai Bide Pharmatech Co., Ltd.;

[0052] Rh(COD) 2 BF 4 : Shanghai Haohong Biopharmaceutical Technology Co., Ltd.;

[0053] Rh 2 (CO) 4 Cl 2 : Shanghai Haohong Biopharmaceutical Technology Co., Ltd.

[0054] Preparation Example of Catalysis System:

[0055] [RuI(p-cymene)((S)-3,5-TMS-synphos)]I Preparation: Prepared according to the method disclosed in J. Org. Chem. 2019, 84, 3201 - 3213. Specifically, take [RuI 2 (cymene)] 2 (10 mmol), (S)-3,5-TMS-synphos (10 mmol), dissolve in 20 ml of methanol, react at 60 °C for 5 h. After the reaction is completed, dry the reaction solution by suction, dissolve it with dichloromethane, and remove dichloromethane under vacuum by filtration. The obtained solid is the product [RuI(p-cymene)((S)-3,5-TMS-synphos)]I. Characterized by 31P NMR spectrum in CDCl3: δ = 23 ppm (d), δ = 40 ppm (d).

[0056] [Rh(COD)((R,R)-Me-Duphos)]BF 4 Preparation: Prepared according to the method disclosed in Org Lett, 1999, 1:167. Specifically, take Rh(COD)2BF 4 (10 mmol), (R,R)-Me-Duphos (10 mmol), dissolve in 20 ml of methanol, react at room temperature for 1 h. After the reaction is completed, dry the reaction solution by suction. The obtained solid is the product [[Rh(COD)((R,R)-Duphos)]BF 4 . Characterized by 31P NMR spectrum in CDCl3: δ = 5 ppm (s).

[0057] The pressures involved in the following examples are all absolute pressures.

[0058] Example 1

[0059] To prepare optically active β-butyrolactone, the steps are as follows:

[0060] Under a nitrogen atmosphere, 200 g of diketene (2.38 mol), 12 mg of Ir(COD) 2 BF 4 (0.03 mmol), and 28.5 mg of (S)-synphos (0.04 mmol) are dissolved in 1000 g of acetone, and then butyric acid with a mass concentration of 500 ppm is added to the system.

[0061] The above materials are added to a reaction kettle, and then the reaction pressure is adjusted to 8 MPaA by injecting hydrogen, and the temperature is raised to 60 °C for an asymmetric hydrogenation reaction. After reacting for 8 h, a sample is taken.

[0062] The conversion rate is measured to be 97.6% by gas chromatography, the optical purity is 93.1 ee%, and the cumulative turnover number is 78640.

[0063] Examples 2 - 5

[0064] To prepare optically active β-butyrolactone, the steps are carried out according to the method of Example 1, except for the selection of the types of transition metal catalyst precursors, chiral phosphine ligands, the addition amount of butyric acid, reaction temperature, reaction pressure, and reaction time. See Table 1 for details.

[0065] Table 1 Examples 2 - 5

[0066]

[0067]

[0068] Example 6

[0069] To prepare optically active β-butyrolactone (in-situ generation of butyric acid), the steps are as follows:

[0070] Under a nitrogen atmosphere, 200 g of diketene (2.38 mol), [RuI(p-cymene)((S)-3,5-TMS-synphos)]I (0.03 mmol), are dissolved in 1400 g of acetone.

[0071] The above materials are added to a reaction kettle, and then the reaction pressure is adjusted to 8 MPaA by injecting hydrogen, and the temperature is raised to 60 °C. After reacting for 8 h, a sample is taken.

[0072] The butyric acid content is measured to be 700 ppm by gas chromatography, the conversion rate is 90.5%, the optical purity is 93.1 ee%, and the cumulative turnover number is 72914.

[0073] Example 7

[0074] To prepare optically active β-butyrolactone, the steps are as follows:

[0075] Under a nitrogen atmosphere, 200 g of diketene (2.38 mol) and [Rh(COD)((R,R)-Duphos)]BF 4 (0.03 mmol) are dissolved in 800 g of acetone, and then butyric acid with a mass concentration of 50 ppm is added to the system.

[0076] The above materials are added to a reaction kettle, and then the reaction pressure is adjusted to 6 MPaA by injecting hydrogen. After heating to 60 °C and reacting for 2 h, a sample is taken.

[0077] The conversion rate is measured to be 96.9% by gas chromatography, the optical purity is 95.1 ee%, and the cumulative turnover number is 78071.

[0078] Comparative Example 1

[0079] Referring to the method of Example 1, the only difference is that butyric acid is not introduced into the system. After reacting for 8 h under the same other operations and conditions, a sample is taken and the conversion rate is measured to be 19.9% by gas chromatography, the optical purity is 93.1 ee%, and the cumulative turnover number is 16003.

[0080] Comparative Example 2

[0081] Referring to the method of Example 1, the only difference is that butyric acid in the system is replaced by acetic acid. After reacting under the same other operations and conditions and taking a sample, the conversion rate is measured to be 15.6% by gas chromatography, the optical purity is 93.5 ee%, and the cumulative turnover number is 12569.

[0082] Comparative Example 3

[0083] Referring to the method of Example 7, the only difference is that butyric acid is not introduced into the system. After reacting under the same other operations and conditions and taking a sample, the conversion rate is measured to be 11.6% by gas chromatography, the optical purity is 92.9 ee%, and the cumulative turnover number is 9346.

Claims

1. A method for preparing an optically active β-butyrolactone, characterized in that, the method is to use butyric acid as a cocatalyst in the presence of a catalytic system, and optically active β-butyrolactone is prepared by the asymmetric hydrogenation reaction of diketene.

2. The preparation method according to claim 1, characterized in that, the mass concentration of the butyric acid in the reaction system is 10 - 6000 ppm, preferably 30 - 3000 ppm.

3. The preparation method according to claim 1, characterized in that, the catalytic system is a transition metal catalytic precursor and a chiral ligand composition, or a complex formed by a transition metal and a ligand.

4. The preparation method according to claim 3, characterized in that, The transition metal catalyst precursor is selected from at least one of compounds containing ruthenium, rhodium, and iridium, and more preferably is Ir(COD) 2 BF 4 , [RuI 2 (cymene)] 2 , Rh(COD) 2 BF 4 , Rh 2 (CO) 4 Cl 2 , [RuCl 2 (cymene)] 2 ; and at least one of the following preferably, the chiral ligand is selected from at least one of chiral bidentate phosphine ligands, more preferably at least one of Segphos, Binap, Synphos, BIPHEP; preferably, in the transition metal catalytic precursor and chiral ligand composition, the molar ratio of the transition metal catalyst precursor to the chiral ligand in terms of the molar amount of the transition metal therein is 1:(1 - 5), preferably 1:(1 - 2.5).

5. The preparation method according to claim 3, characterized in that, the complex formed by the transition metal and the ligand is selected from at least one of the complexes formed by ruthenium, rhodium, iridium and phosphine ligands, more preferably at least one of ruthenium-phosphine complexes and iridium-phosphine complexes, and further preferably at least one of RuCl(p-cymene)((S)-binap)]Cl, [RuI(p-cymene)((S)-3,5-TMS-synphos)]I, [RuI(p-cymene)((S)-segphos)].

6. The preparation method according to claim 1, characterized in that, the addition amount of the catalytic system in terms of the molar amount of the transition metal therein is a molar ratio of diketene of 1:10000 - 200000.

7. The preparation method according to claim 1, characterized in that, for the asymmetric hydrogenation reaction, the reaction pressure is controlled by the hydrogen input amount to be 0.1 - 10 MPaA, preferably 4 - 8 MPaA.

8. The preparation method according to claim 1, characterized in that, the asymmetric hydrogenation reaction is carried out in a solvent environment, and the solvent is selected from at least one of ketone compounds, preferably acetone and / or butanone.

9. The preparation method according to claim 1, characterized in that, the mass ratio of the solvent dosage to diketene is 4 - 7:

1.

10. The preparation method according to claim 1, characterized in that, for the asymmetric hydrogenation reaction, the reaction temperature is 30 - 90 °C, preferably 40 - 80 °C, and the time is 1 - 20 h, preferably 2 - 10 h.

Images