Process for the preparation of chiral epoxides, chiral beta-lactones and polyhydroxyalkanoates

Abstract

This invention provides a method for preparing chiral epoxy compounds, chiral β-lactones, and polyhydroxyalkanoates. The method involves three steps: chiral resolution of the epoxy compound, carbonylation of the chiral epoxy compound to prepare a chiral β-lactone, and ring-opening polymerization of the β-lactone. Using this method, polyhydroxyalkanoates with good tensile strength and toughness, as well as a wide processing window, can be prepared. This invention has advantages such as simple steps, low raw material costs, and no need to introduce a second monomer, making it easy to scale up production.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis and relates to methods for preparing chiral epoxy compounds, chiral β-lactones and polyhydroxy fatty acid esters. Background Technology

[0002] Polyhydroxyalkanoate (PHA) materials are a class of biodegradable plastics that can be synthesized in living organisms. PHA is an ideal biodegradable plastic, capable of completely degrading into water and CO2 under natural conditions. It possesses unique advantages in many aspects, including biocompatibility, optical activity, piezoelectric effect, low permeability, UV resistance, and anticoagulant properties, making it highly sought after and promising for applications in packaging materials, medical materials, textile fibers, and electrical materials. Currently, PHA is mainly obtained through biological methods, which suffer from complex processes, long production cycles, and difficulties in strain modification. This results in small-scale production, low capacity (less than 100,000 tons / year globally), and high prices (40,000-70,000 RMB / ton), limiting its application development.

[0003] Poly(3-hydroxybutyrate) (PHB) is the earliest developed and most widely used PHA product, characterized by its regular structure and high crystallinity, and is used in packaging materials and artificial bone screws. However, PHB products have two problems that limit the application of this material: (1) poor thermodynamic stability, with a relatively low thermodynamic decomposition temperature and a very narrow heat processing window (melting point and decomposition temperature are very close); (2) very poor toughness and very low elongation at break (εb). Currently, this problem is mainly solved by copolymerizing with a second monomer to form copolymers (such as 3-hydroxybutyric acid and 3-hydroxyvalerate copolyester (PHBV), 3-hydroxybutyric acid and 4-hydroxybutyric acid copolyester (P34HB), etc.), but the introduction of the second monomer increases the raw material cost and the synthesis is more difficult, resulting in higher production costs. There are also reports of achieving this through monomer modification, but monomer modification is also very difficult. For example, Eugene Y.X. Chen et al. (Science, 2023, 380, 64-69) reported a method to improve material properties through monomer modification. By introducing two methyl groups onto the polymerizable monomer of PHB, novel polyhydroxyalkanoate products with high thermal stability, good toughness, and chemical recyclability can be prepared. However, monomer modification is difficult and costly, making it difficult to apply in practice. Coates et al. (Nat. Chem., 2023, 15, 856-861) started with 2-butene and prepared novel PHA products with better mechanical and processing properties through an epoxidation-carbonylation-ring-opening polymerization route. However, they also suffered from high raw material costs and limited room for product performance adjustment.

[0004] In summary, PHB products currently suffer from poor toughness and a narrow processing window. Copolymerization and monomer modification can improve their performance, but these methods are technically challenging and costly. Summary of the Invention

[0005] This invention provides a simple method for preparing chiral epoxy compounds and chiral β-lactones, as well as a chemical synthesis method for poly-3-hydroxybutyrate (PHB) with tunable properties. This invention enables the adjustment of the melting point and mechanical properties of PHB products, addressing the current problems of narrow processing windows and poor toughness in PHB products, while offering advantages such as simple steps, low production costs, and no need to introduce a second monomer. This invention allows for convenient control of the ee value of the prepared chiral epoxy compounds and chiral β-lactones by adjusting the amount of chiral resolving catalyst and water added, thereby enabling the preparation of PHB products with different performance indicators as needed.

[0006] Specifically, the first aspect of the present invention provides a method for preparing a chiral epoxy compound, the method comprising:

[0007] Chiral resolution of epoxides: Racemic epoxides undergo a resolution reaction in the presence of water under the catalysis of a chiral resolution catalyst to obtain chiral epoxides.

[0008] In one or more embodiments, the epoxy compound has the structure shown in Formula I or Formula II:

[0009]

[0010] In Equations I and II, R 1 and R 2 They are C1-C10 alkyl groups or C1-C10 alkyl groups substituted with one or more of the following substituents: halogen, C2-C10 alkenyl and aromatic.

[0011] In one or more embodiments, the halogen used as a substituent is selected from F, Cl, Br, and I;

[0012] In one or more embodiments, the C2-C10 alkenyl group as a substituent is a C2-C4 alkenyl group.

[0013] In one or more embodiments, the aromatic group as a substituent is selected from phenyl, naphthyl, anthracene, etc. The compounds are: yl, peryl, benzo[a]pyrene, furanyl, pyrroleyl, thiophene, thiazolyl, imidazole, pyrazolyl, oxazolyl, pyridinyl, pyranyl, pyridazinyl, pyrimidinyl, indolyl, purine, quinolinyl, and isoquinolinyl.

[0014] In one or more embodiments, the epoxy compound is selected from the following compounds:

[0015]

[0016] In one or more embodiments, the chiral resolving catalyst has the structure shown in Formula III or Formula IV:

[0017]

[0018] In Equations III and IV, R 3 and R 5 They are methyl, isopropyl, or isobutyl, respectively; R 4 and R 6 They are acetyl, p-toluenesulfonyl, trifluoromethanesulfonyl, or methanesulfonyl, respectively.

[0019] In one or more embodiments, the chiral resolution catalyst is selected from compounds Cat-1 to Cat-12:

[0020]

[0021] In one or more embodiments, the ee value of the prepared chiral epoxy compound is ≥60% and ≤90%.

[0022] In one or more embodiments, the resulting chiral epoxy compound has an ee value ≥70% and ≤90%.

[0023] In one or more embodiments, the molar ratio of the epoxy compound to the chiral resolving catalyst is (100 to 10000):1.

[0024] In one or more embodiments, the molar ratio of water to the epoxy compound is (0.35 to 0.48):1.

[0025] In one or more embodiments, the molar ratio of water to the epoxy compound is (0.4 to 0.48):1.

[0026] In one or more embodiments, water is gradually added to the reaction system during the chiral resolution of the epoxide.

[0027] In one or more embodiments, during the chiral resolution of the epoxide, water is added to the reaction system at a rate of 0.05 to 500 kg / h, preferably 0.05 to 10 kg / h.

[0028] In one or more embodiments, the reaction pressure for the chiral resolution of the epoxy compound is atmospheric pressure.

[0029] In one or more embodiments, the reaction temperature for the chiral resolution of the epoxy compound is 0–50°C.

[0030] In one or more embodiments, the reaction time for the chiral resolution of the epoxy compound is 0.1 to 120 h.

[0031] A second aspect of the present invention provides a method for preparing a chiral β-lactone, the method comprising:

[0032] (1) Perform chiral resolution of the epoxy compound as described in any embodiment of this document to obtain a chiral epoxy compound;

[0033] (2) Carbonylation reaction of chiral epoxy compounds: Under the catalysis of a carbonylation catalyst, and under reaction conditions with or without solvent, the chiral epoxy compound and carbon monoxide undergo a carbonylation reaction to obtain a chiral β-lactone.

[0034] In one or more embodiments, the ee value of the chiral epoxy compound is ≥60% and ≤90%.

[0035] In one or more embodiments, the ee value of the chiral epoxy compound is ≥70% and ≤90%.

[0036] In one or more embodiments, the chiral β-lactone prepared has an ee value ≥60% and ≤90%.

[0037] In one or more embodiments, the chiral β-lactone prepared has an ee value ≥70% and ≤90%.

[0038] In one or more embodiments, the carbonylation catalyst is a bimetallic catalyst composed of a cationic Lewis acid and a cobalt carbonyl anion; preferably, the cationic Lewis acid is a cationic polydentate ligand metal complex; preferably, the polydentate ligand in the cationic polydentate ligand metal complex has a porphyrin structure or a Salen structure; preferably, the metal atom in the cationic polydentate ligand metal complex is one or more selected from Group IIIA elements, Group IIIB elements, lanthanides, and actinides in the periodic table; preferably, the charge of the cationic polydentate ligand metal complex is +1 or +2; preferably, the cobalt carbonyl anion is Co(CO)4. - .

[0039] In one or more embodiments, the molar ratio of the chiral epoxy compound to the carbonylation catalyst is 1 to 100,000:1.

[0040] In one or more embodiments, the carbon monoxide pressure is 1 to 10 MPa during the carbonylation reaction of the chiral epoxide.

[0041] In one or more embodiments, the reaction temperature for the carbonylation reaction of the chiral epoxy compound is 0–150 °C.

[0042] In one or more embodiments, the reaction time for the carbonylation reaction of the chiral epoxy compound is 0.1 to 1000 h.

[0043] In one or more embodiments, the solvent for the carbonylation reaction of the chiral epoxide is selected from one or more of aromatic solvents and ether solvents, wherein the aromatic solvent is preferably selected from one or two of toluene and benzene, and the ether solvent is preferably selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether and tert-butyl methyl ether.

[0044] In one or more embodiments, the carbonylation catalyst is prepared by pre-reaction of a neutral Lewis acid precursor and a cobalt carbonyl compound, or by in-situ generation of a neutral Lewis acid precursor and a cobalt carbonyl compound in the reaction system.

[0045] In one or more embodiments, the Lewis acid precursor comprises a cationic polydentate ligand metal complex and a coordinating anion; preferably, the polydentate ligand in the cationic polydentate ligand metal complex has a porphyrin or Salen structure; preferably, the metal atom in the cationic polydentate ligand metal complex is one or more selected from Group IIIA, Group IIIB, lanthanides, and actinides of the periodic table; preferably, the charge of the cationic polydentate ligand metal complex is +1 or +2; preferably, the coordinating anion is one or more selected from chloride, bromide, iodide, carboxylate, and sulfonate ions.

[0046] In one or more embodiments, the cobalt carbonyl compound is selected from Co2(CO)8, NaCo(CO)4, KCo(CO)4, and Co4(CO). 12 One or more of them.

[0047] In one or more embodiments, the carbonylation catalyst is prepared by pre-reaction of a cobalt carbonyl compound and a Lewis acid precursor in a molar ratio of 0.1 to 100:1 or generated in-situ in the reaction system.

[0048] A third aspect of the present invention provides a method for preparing a polyhydroxyalkanoate, the method comprising:

[0049] (1) Perform chiral resolution of the epoxy compound as described in any embodiment of this document to obtain a chiral epoxy compound;

[0050] (2) Perform the carbonylation reaction of the chiral epoxy compound as described in any embodiment of this article to obtain a chiral β-lactone;

[0051] (3) The chiral β-lactone is subjected to ring-opening polymerization under the action of a polymerization catalyst to prepare the polyhydroxy fatty acid ester.

[0052] In one or more embodiments, the ee value of the chiral epoxy compound is ≥60% and ≤90%.

[0053] In one or more embodiments, the ee value of the chiral epoxy compound is ≥70% and ≤90%.

[0054] In one or more embodiments, the ee value of the chiral β-lactone is ≥60% and ≤90%.

[0055] In one or more embodiments, the ee value of the chiral β-lactone is ≥70% and ≤90%.

[0056] In one or more embodiments, the polymerization catalyst may be selected from one or more of tin salts, titanium salts, magnesium salts, aluminum salts, calcium salts, iron salts, manganese salts, zinc salts, organotin compounds, organotitanium compounds, organomagnesium compounds, organoaluminum compounds, organocalcium compounds, organoiron compounds, organomanganese compounds, and organozinc compounds.

[0057] In one or more embodiments, the mass of the polymerization catalyst is 0.001% to 3% of the total mass of the polymerization monomers.

[0058] In one or more embodiments, the reaction pressure of the ring-opening polymerization reaction is 0.1 to 10 MPa.

[0059] In one or more embodiments, the reaction temperature of the ring-opening polymerization reaction is 25–150°C.

[0060] In one or more embodiments, the reaction time of the ring-opening polymerization reaction is 0.1 to 120 h.

[0061] In one or more embodiments, the ring-opening polymerization reaction is carried out in a protective atmosphere.

[0062] In one or more embodiments, the polyhydroxyalkanoate has one or more of the following characteristics:

[0063] Melting temperature ≤160℃, preferably ≤150℃;

[0064] Tensile strength ≥5MPa, preferably ≥10MPa;

[0065] Elongation at break ≥2%, preferably ≥5%. Detailed Implementation

[0066] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0067] The theories or mechanisms described and disclosed herein, whether right or wrong, should not in any way limit the scope of the invention, that is, the contents of the invention can be implemented without being limited by any particular theory or mechanism.

[0068] In this document, the terms “contains,” “includes,” “containing,” and similar terms encompass the meanings of “basically composed of” and “composed of.” For example, when this document discloses “A contains B and C,” “A is basically composed of B and C” and “A is composed of B and C” should be considered as having been disclosed in this document.

[0069] In this document, all features defined by numerical ranges or percentage ranges, such as numerical values, quantities, contents, and concentrations, are for the sake of brevity and convenience only. Accordingly, descriptions of numerical ranges or percentage ranges should be considered as covering and specifically disclosing all possible sub-ranges and individual numerical values ​​(including integers and fractions) within those ranges.

[0070] Unless otherwise specified, percentages refer to mass percentages and proportions refer to mass ratios in this article.

[0071] In this document, when describing embodiments or examples, it should be understood that it is not intended to limit the invention to those embodiments or examples. Rather, all alternatives, modifications, and equivalents of the methods and materials described herein are covered within the scope defined by the claims.

[0072] For the sake of brevity, not all possible combinations of the technical features in each implementation scheme or embodiment are described herein. Therefore, as long as there is no contradiction in the combination of these technical features, the technical features in each implementation scheme or embodiment can be combined arbitrarily, and all possible combinations should be considered within the scope of this specification.

[0073] In this paper, enantiomeric excess (ee) is defined as the percentage of the total amount of substance in an enantiomeric mixture where one isomer is more abundant than another. It is used to represent the optical purity of a chiral compound. The higher the ee value, the higher the optical purity. The formula for calculating the ee value is: ee = |[R] - [S]| / ([R] + [S]) * 100%, where [R] represents the amount of substance of the R-type isomer, [S] represents the amount of substance of the S-type isomer, and |[R] - [S]| represents the absolute value of the difference between the amounts of the R-type and S-type isomers.

[0074] This invention utilizes a chiral resolution catalyst to induce a resolution reaction of racemic epoxides in the presence of water, thereby preparing chiral epoxides. The optical purity of the chiral epoxides can be adjusted by regulating the amount of water added. It is understood that, in this text, the resolution reaction is a hydrolytic kinetic resolution, specifically, the chiral resolution catalyst catalyzes the reaction of the racemic epoxide with water to obtain an epoxide enriched with a certain configurational isomer and a diol. Unless otherwise specified, the chiral epoxide and chiral β-lactone are enantiomers with an ee value > 0, rather than a single isomer of a certain configuration. Preferably, the chiral epoxides obtained by this invention have an ee value ≥ 60% and ≤ 90%, more preferably an ee value ≥ 70% and ≤ 90%.

[0075] The epoxy compounds applicable to this invention have the structure shown in Formula I or Formula II:

[0076]

[0077] In Equations I and II, R 1 and R 2 They are C1-C10 alkyl groups or C1-C10 alkyl groups substituted with one or more of the following substituents: halogen, C2-C10 alkenyl and aromatic.

[0078] In this invention, the halogen used as a substituent can be selected from F, Cl, Br, and I. In some embodiments, the halogen used as a substituent is Cl.

[0079] In this invention, the C2-C10 alkenyl group used as a substituent can be a C2-C4 alkenyl group, such as a vinyl group.

[0080] In this invention, the aromatic group used as a substituent can be selected from phenyl, naphthyl, anthracene, etc. The aryl group can be phenyl, peryl, benzo[a]pyrene, furanyl, pyrroleyl, thiophene, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, pyridinyl, pyranyl, pyridazinyl, pyrimidinyl, indolyl, purine, quinolinyl, or isoquinolinyl. In some embodiments, the aromatic group used as a substituent is phenyl.

[0081] In some implementation schemes, R 1 and R 2 They are C1-C8 alkyl groups or C1-C8 alkyl groups substituted with one or more substituents selected from the foregoing. In some embodiments, R 1 and R 2 They are C1-C6 alkyl groups or C1-C6 alkyl groups substituted with one or more substituents selected from the foregoing. In some embodiments, R 2 It is a C1-C4 alkyl group or a C1-C4 alkyl group substituted with one or more substituents selected from the foregoing.

[0082] In some embodiments, the epoxy compounds suitable for use in this invention are selected from the following compounds:

[0083]

[0084] The chiral resolution catalyst suitable for this invention has the structure shown in Formula III or Formula IV:

[0085]

[0086] In Equations III and IV, R 3 and R 5 These are methyl, isopropyl (tPr), or isobutyl (tBu), respectively; R 4 and R 6 They are acetyl (Ac), p-toluenesulfonyl (Ts), trifluoromethanesulfonyl (Tf), or methanesulfonyl (Ms), respectively.

[0087] In some embodiments, the chiral resolution catalyst suitable for use in this invention is selected from the following compounds: Cat-1 to Cat-12:

[0088]

[0089] In this invention, during the chiral resolution of epoxy compounds, the molar ratio of epoxy compounds to chiral resolution catalysts can be (100 to 10000):1, for example, 200:1, 500:1, 800:1, 1000:1, 1200:1, 1500:1, 2000:1, or 5000:1.

[0090] In this invention, during the chiral resolution of the epoxide compound, the molar ratio of water to the epoxide compound can be (0.35–0.48):1, for example, 0.36:1, 0.37:1, 0.38:1, 0.39:1, 0.4:1, 0.41:1, 0.42:1, 0.43:1, 0.44:1, 0.45:1, 0.46:1, and 0.47:1. In this invention, deionized water is preferred. By controlling the molar ratio of water to epoxy compound within the range of (0.33 to 0.48):1, chiral epoxy compounds with an ee value ≥60% and ≤90%, preferably ≥70% and ≤90%, can be prepared. After epoxy carbonylation, chiral β-lactones with an ee value ≥60% and ≤90%, preferably ≥70% and ≤90%, can be obtained. These can then be polymerized to obtain polyhydroxy fatty acid esters that have both good tensile strength and toughness, as well as a wide processing window.

[0091] In some preferred embodiments, the chiral resolution of the epoxy compound includes: adding a chiral resolution catalyst and the epoxy compound to a reactor, and adding water at a certain rate to carry out the resolution reaction. The water addition rate is preferably 0.05–500 kg / h, for example, 0.08 kg / h, 0.1 kg / h, 0.12 kg / h, 0.15 kg / h, 0.2 kg / h, 0.5 kg / h, 1 kg / h, 5 kg / h, 10 kg / h, 50 kg / h, 100 kg / h, or 200 kg / h. In some preferred embodiments, the water addition rate is 0.05–10 kg / h, preferably 0.05–1 kg / h, for example, 0.05–0.5 kg / h. Controlling the water addition rate within the aforementioned range is beneficial for obtaining chiral epoxy compounds with an ee value ≥60% and ≤90%, preferably ≥70% and ≤90%.

[0092] The reaction pressure for the chiral resolution of epoxides can be atmospheric pressure.

[0093] The reaction temperature for the chiral resolution of epoxy compounds can be 0 to 50°C, for example, 5°C, 10°C, 20°C, 25°C, 30°C, and 40°C.

[0094] The reaction time for the chiral resolution of epoxy compounds can be 0.1 to 120 h, for example 0.5 h, 1 h, 5 h, 6 h, 7 h, 8 h, 10 h, 50 h, and 100 h.

[0095] After the chiral resolution reaction of the epoxy compound is completed, the chiral epoxy compound can be obtained by distillation.

[0096] Furthermore, in this invention, a chiral epoxide and carbon monoxide can undergo an epoxide carbonylation reaction under the action of a carbonylation catalyst to prepare a chiral β-lactone.

[0097] In some preferred embodiments, a chiral epoxide with an ee value ≥60% and ≤90%, preferably ≥70% and ≤90%, and carbon monoxide undergo an epoxy carbonylation reaction in the presence of a carbonylation catalyst to prepare a chiral β-lactone with an ee value ≥60% and ≤90%, preferably ≥70% and ≤90%.

[0098] In this invention, the carbonylation reaction of the chiral epoxide includes: under the catalysis of a carbonylation catalyst, and under reaction conditions with or without solvent, a chiral epoxide and carbon monoxide undergo a carbonylation reaction to generate a chiral β-lactone. After the reaction is complete, the chiral β-lactone can be obtained by vacuum distillation.

[0099] The carbonylation catalyst suitable for this invention can be a bimetallic catalyst composed of a cation Lewis acid and a carbonyl cobalt anion.

[0100] The cationic Lewis acid is preferably a cationic polydentate ligand metal complex. The cationic polydentate ligand metal complex comprises a polydentate ligand and a metal atom. The polydentate ligand in the cationic polydentate ligand metal complex preferably has a porphyrin or Salen structure. The metal atom in the cationic polydentate ligand metal complex is selected from one or more elements of Group IIIA, Group IIIB, lanthanides, and actinides in the periodic table, preferably one or more selected from Al, Cr, and Ga. The charge of the cationic polydentate ligand metal complex is preferably +1 or +2.

[0101] The preferred carbonyl cobalt anion is Co(CO)4. - .

[0102] In some embodiments, the carbonylation catalyst is prepared in advance and then added to the carbonylation reaction; preferably, the carbonylation catalyst is formed by reacting a neutral Lewis acid precursor with a cobalt carbonyl compound. In some embodiments, the carbonylation catalyst is generated in-situ in the reaction system from a neutral Lewis acid precursor and a cobalt carbonyl compound.

[0103] The Lewis acid precursor preferably comprises a cationic polydentate ligand metal complex and a coordinating anion. The cationic polydentate ligand metal complex comprises a polydentate ligand and a metal atom. The polydentate ligand in the cationic polydentate ligand metal complex preferably has a porphyrin or Salen structure. The metal atom in the cationic polydentate ligand metal complex is selected from one or more elements chosen from Group IIIA, Group IIIB, lanthanides, and actinides of the periodic table, preferably one or more selected from Al, Cr, and Ga. The charge of the cationic polydentate ligand metal complex is preferably +1 or +2.

[0104] The coordinating anion is preferably selected from one or more of chloride ions, bromide ions, iodide ions, carboxylate ions, and sulfonate ions.

[0105] In some implementations, the Lewis acid precursor is tetraphenylporphyrin aluminum chloride.

[0106] The cobalt carbonyl compound is preferably selected from Co2(CO)8, NaCo(CO)4, KCo(CO)4, and Co4(CO). 12 One or more of them.

[0107] In a preferred embodiment, the carbonylation catalyst is prepared by pre-reaction of a cobalt carbonyl compound and a Lewis acid precursor in a molar ratio of 0.1 to 100:1, preferably 0.5 to 10:1, for example 1:1, 1.5:1, 2:1, or 5:1, or generated in-situ in the reaction system.

[0108] In this invention, the molar ratio of the chiral epoxy compound to the carbonylation catalyst in the carbonylation reaction of the chiral epoxy compound can be 1 to 100,000:1, for example 10:1, 100:1, 1000:1, 2000:1, 4000:1, 5000:1, 6000:1, 8000:1, 10000:1.

[0109] In this invention, the carbon monoxide pressure in the carbonylation reaction of the chiral epoxide can be 1 to 10 MPa, for example 2 MPa, 3 MPa, 4 MPa, 5 MPa, or 8 MPa.

[0110] In this invention, the reaction temperature for the carbonylation reaction of chiral epoxy compounds can be 0 to 150°C, for example 20°C, 40°C, 60°C, 70°C, 80°C, 90°C, 100°C, and 120°C.

[0111] In this invention, the reaction time for the carbonylation reaction of chiral epoxides can be 0.1 to 1000 h, for example 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 20 h, 50 h, 100 h, 200 h, and 500 h.

[0112] In this invention, the carbonylation reaction of chiral epoxides can be carried out with or without a solvent. The solvent for the carbonylation reaction of chiral epoxides is preferably selected from one or more of aromatic solvents and ether solvents. Aromatic solvents are preferably selected from one or both of toluene and benzene. Ether solvents are preferably selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, and tert-butyl methyl ether.

[0113] Furthermore, in this invention, chiral β-lactones can undergo ring-opening polymerization under the action of a polymerization catalyst to prepare polyhydroxyalkanoates. By using chiral β-lactones with different ee values ​​for polymerization, the melting point and toughness of the polyhydroxyalkanoates can be adjusted.

[0114] The ring-opening polymerization of chiral β-lactones can be bulk polymerization, meaning the reaction can be carried out under solvent-free conditions.

[0115] The polymerization catalyst suitable for this invention can be a known ring-opening polymerization catalyst for β-lactones, such as one or more selected from tin salts, titanium salts, magnesium salts, aluminum salts, calcium salts, iron salts, manganese salts, zinc salts, organotin compounds, organotitanium compounds, organomagnesium compounds, organoaluminum compounds, organocalcium compounds, organoiron compounds, organomanganese compounds, and organozinc compounds. In some embodiments, the polymerization catalyst is cycloalkoxide tin, for example... Cycloalkoxide tin can be purchased commercially or synthesized using known methods.

[0116] In this invention, the mass of the polymerization catalyst can be 0.001% to 3% of the total mass of the monomers, preferably 0.1% to 2%, for example 0.2%, 0.5%, 1%, or 1.5%.

[0117] In this invention, the reaction pressure of the ring-opening polymerization reaction can be 0.1 to 10 MPa, for example 0.2 MPa, 0.5 MPa, 0.8 MPa, 1 MPa, 1.2 MPa, 1.5 MPa, 2 MPa, and 5 MPa.

[0118] In this invention, the reaction temperature of the ring-opening polymerization reaction can be 25 to 150°C, preferably 80 to 120°C, for example 85°C, 90°C, 95°C, 100°C, or 110°C.

[0119] In this invention, the reaction time of the ring-opening polymerization reaction can be 0.1 to 120 h, preferably 1 to 24 h, for example 2 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h.

[0120] In this invention, the ring-opening polymerization reaction can be carried out in a protective atmosphere, such as nitrogen.

[0121] In some embodiments, the present invention prepares polyhydroxy fatty acid esters (e.g., PHB) through three steps: chiral resolution of the aforementioned epoxy compound, carbonylation reaction of the chiral epoxy compound to prepare chiral β-lactone, and ring-opening polymerization of β-lactone.

[0122] To address the issues of poor toughness and narrow processing window of PHB, existing technologies mostly employ copolymerization of 3-hydroxybutyric acid with a second monomer, which increases raw material and production costs and is technically challenging. This invention provides a chemical synthesis method for poly-3-hydroxybutyrate with tunable properties, offering advantages such as simple steps, low production costs, and no need to introduce a second monomer. Specifically, this invention obtains polymeric monomers with specific optical activities through chiral resolution. In the chiral resolution step of the epoxide (e.g., propylene oxide) hydrolysis, the optical purity of the chiral epoxide (e.g., chiral propylene oxide) is adjusted by regulating the amount of water added as a resolving agent, thereby adjusting the optical purity of the β-lactone (e.g., β-butyrolactone), ultimately achieving control over the mechanical properties of the polyhydroxy fatty acid ester (e.g., PHB). This invention offers advantages such as simple steps, low raw material costs, and no need to introduce a second monomer, making it easy to scale up production.

[0123] The beneficial technical effect of this invention is that it enables the convenient preparation of polyhydroxy fatty acid ester products that meet various performance requirements by adjusting the ee value of chiral epoxy compounds and chiral β-lactones according to different performance requirements by controlling the conditions of the chiral resolution reaction (e.g., the amount of water added).

[0124] The method of this invention can be used to prepare polyhydroxyalkanoates that possess both good tensile strength and toughness, as well as a wide processing window. In a preferred embodiment, the polyhydroxyalkanoates prepared by this invention meet one or more or all of the following performance requirements:

[0125] The melting temperature is ≤160℃, preferably ≤150℃, more preferably ≤145℃, for example ≤141℃;

[0126] Tensile strength ≥5MPa, preferably ≥10MPa, more preferably ≥12MPa, for example ≥14MPa, ≥20MPa;

[0127] The elongation at break is ≥2%, preferably ≥5%, for example ≥6% or ≥6.7%.

[0128] The present invention will be described below by way of specific embodiments. It should be understood that these embodiments are merely illustrative and are not intended to limit the scope of the invention. The methods, reagents, and materials used in the embodiments are conventional methods, reagents, and materials in the art, unless otherwise stated. The raw material compounds in the embodiments are all commercially available.

[0129] Example 1

[0130]

[0131] Example 1: PHB was prepared by the following steps:

[0132] (1) Chiral resolution: The catalyst (R)-Salen-Co(III)-OAc (compound Cat-1, 13.27 g, 20 mmol) was weighed and added to the reaction flask. The catalyst was dissolved in 1.16 kg of racemic propylene oxide (20 mol), and deionized water (170 g, 9.5 mol) was added at a rate of 0.1 kg / h with stirring, while maintaining the temperature of the reaction solution at 10-25 °C. After the addition was complete, the reaction was stirred for 5 h. After the reaction was completed, the product chiral propylene oxide was separated by distillation under normal pressure, and the fraction at 36-38 °C was collected to obtain 545 g of chiral propylene oxide (main component is (R)-propylene oxide), with a separation yield of 47% and an ee of 89.5%.

[0133] (2) Epoxy carbonylation: Tetraphenylporphyrin aluminum chloride (TPPAlCl, 1 mmol, 680 mg), Co2(CO)8 (1.5 mmol, 513 mg), the chiral propylene oxide prepared in step (1) (5 mol, 290 g), and the reaction solvent tetrahydrofuran (500 mL) were added sequentially to a 2 L autoclave. The autoclave was closed, purged three times with 1.0 MPa N2, then purged three times with 1.0 MPa CO, and then purged with carbon monoxide to 4.0 MPa. The stirring was turned on, and the electric heating was turned on to raise the temperature of the reaction system to 80 °C and maintain it for 5 h. During this period, CO was added through the gas inlet pipe to keep the system pressure constant at 4.0 MPa. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was analyzed by GC, and the raw materials were completely converted. The selectivity of β-butyrolactone was 95%, the selectivity of the isomerization byproduct acetone was 3%, and the rest were high-boiling substances. After removing tetrahydrofuran from the reaction solution, the product chiral β-butyrolactone was separated by vacuum distillation. The fraction collected at 40-42℃@0.5kPa yielded 388g of chiral β-butyrolactone (the main component is (R)-β-butyrolactone), with a separation yield of 90% and an ee of 89.1%.

[0134] (3) Ring-opening polymerization: Under N2 protection, 100g of the chiral β-butyrolactone monomer prepared in step (2) was added to a 300mL polymerization reactor, and the catalyst cycloalkoxide tin (structural formula: The catalyst was used at a rate of 0.3 wt% of the total monomer mass. The polymerization reactor was closed, N2 was introduced to 1.0 MPa, and the reaction was carried out at 90 °C for 12 h to obtain the polymer product PHB-1.

[0135] Example 2

[0136] The difference between Example 2 and Example 1 is that the amount of deionized water added was changed to 160g (8.9mol), while other conditions remained unchanged. The chiral propylene oxide ee was 81.2% (the main component is (R)-propylene oxide), the carbonylation reaction yielded chiral β-butyrolactone ee of 80.6% (the main component is (R)-β-butyrolactone), and the polymerization reaction yielded PHB-2.

[0137] Example 3

[0138] The difference between Example 3 and Example 1 is that the amount of deionized water added was changed to 148g (8.2mol), while other conditions remained unchanged. The chiral propylene oxide ee was 70.8% (the main component is (R)-propylene oxide), the carbonylation reaction yielded chiral β-butyrolactone ee of 70.3% (the main component is (R)-β-butyrolactone), and the polymerization reaction yielded PHB-3.

[0139] Comparative Example 1

[0140] The difference between Comparative Example 1 and Example 1 is that the amount of deionized water added was changed to 120g (6.7mol), while other conditions remained unchanged. The chiral propylene oxide ee was 51.4% (the main component is (R)-propylene oxide), the carbonylation reaction yielded chiral β-butyrolactone ee of 50.9% (the main component is (R)-β-butyrolactone), and the polymerization reaction yielded PHB-4.

[0141] Comparative Example 2

[0142] The difference between Comparative Example 2 and Example 1 is that the amount of deionized water added was changed to 83g (4.6mol), while other conditions remained unchanged. The chiral propylene oxide ee was 29.8% (the main component is (R)-propylene oxide), the carbonylation reaction yielded chiral β-butyrolactone ee of 29.4% (the main component is (R)-β-butyrolactone), and the polymerization reaction yielded PHB-5.

[0143] Comparative Example 3

[0144] The difference between Comparative Example 3 and Example 1 is that the amount of deionized water added was changed to 198.5 g (11 mol), while other conditions remained unchanged. Chiral propylene oxide ee>99% (the main component is (R)-propylene oxide) was obtained, the carbonylation reaction yielded chiral β-butyrolactone ee>99% (the main component is (R)-β-butyrolactone), and the polymerization reaction yielded PHB-6.

[0145] Comparative Example 4

[0146] The polymerization reaction was carried out using racemic β-butyrolactone under the same conditions as step (3) in Example 1, to obtain PHB-7. In particular, this comparative product is not suitable for injection molding, so the test strips were obtained by compression molding and cutting.

[0147] Comparative Example 5

[0148] The difference between Comparative Example 5 and Example 1 is that the water was added all at once, while other conditions remained the same. The yield of chiral propylene oxide was 36%, the ee of chiral propylene oxide was 35.4% (the main component was (R)-propylene oxide), the carbonylation reaction yielded chiral β-butyrolactone with an ee of 34.8% (the main component was (R)-β-butyrolactone), and the polymerization reaction yielded PHB-8.

[0149] The product performance of Examples 1-3 and Comparative Examples 1-5 is shown in Table 1. The performance testing methods are as follows:

[0150] (1) Enantiomer excess (ee): The ee value is calculated based on the content of different configuration substances. The content of different configuration substances is obtained by gas chromatography after separation by a chiral chromatographic column.

[0151] (2) Melting temperature (Tm): DSC test was performed in accordance with the national standard GB / T19466 "Differential Scanning Calorimetry (DSC) for Plastics". The heating / cooling rate was 10K / min, and the test temperature range was -60℃ to 180℃. The melting temperature Tm was read from the test curve.

[0152] (3) Tensile strength and elongation at break: Test specimens were prepared in accordance with the national standard GB / T 17037 "Preparation of injection molded specimens of thermoplastic materials", and tensile tests were conducted in accordance with GB / T 1040 "Test method for tensile properties of plastics" at a tensile speed of 2 mm / min.

[0153] Table 1: Product performance of Examples 1-3 and Comparative Examples 1-5

[0154]

[0155]

[0156] As can be seen from Table 1, the PHBs prepared by the method of the present invention in Examples 1-3 have a lower melting temperature, indicating that they have a wider processing window. They also have good tensile strength and toughness, and have good application prospects.

Claims

1. A method for producing a polyhydroxyalkanoate, characterized by, The preparation method comprises: (1) chiral resolution of an epoxy compound: resolving a racemic epoxy compound in the presence of water under catalysis of a chiral resolution catalyst to obtain a chiral epoxy compound; wherein the molar ratio of water to the epoxy compound is (0.35-0.48):1, and the water is gradually added into the reaction system when the chiral resolution of the epoxy compound is performed; the ee value of the obtained chiral epoxy compound is ≥60% and ≤90%; (2) carbonylation reaction of the chiral epoxy compound: under catalysis of a carbonylation catalyst, the chiral epoxy compound and carbon monoxide are subjected to a carbonylation reaction under solvent or solvent-free reaction conditions to obtain a chiral β-lactone; (3) ring-opening polymerization of the chiral β-lactone under the action of a polymerization catalyst to obtain the polyhydroxyalkanoate; wherein the chiral resolution catalyst has a structure shown in formula III or formula IV: ， ， In formula III and IV, R 3 and R 5 are each methyl, isopropyl or isobutyl; R 4 and R 6 are each acetyl, p-toluenesulfonyl, trifluoromethanesulfonyl or methanesulfonyl; or the chiral resolution catalyst is selected from the following compounds Cat-1, compounds Cat-3 to Cat-7 and compounds Cat-9 to Cat-12: 。 2. The method of claim 1, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. the epoxy compound has a structure shown in formula I or formula II: ， ； In formula I and formula II, R 1 and R 2 are each C1-C10 alkyl or C1-C10 alkyl substituted by one or more substituents selected from the group consisting of halogen, C2-C10 alkenyl and aryl.

3. The method of claim 2, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 5 in the formula I and formula II, the halogen as a substituent is selected from F, Cl, Br and I.

4. The method of claim 2, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 5 in the formula I and formula II, the C2-C10 alkenyl as a substituent is C2-C4 alkenyl.

5. The method of claim 2, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 5 in the formula I and formula II, the aromatic group as a substituent is selected from phenyl, naphthyl, anthryl, chrysenyl, perylenyl, benzopyrenyl, furanyl, pyrrolyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, pyridyl, pyrylyl, pyridazinyl, pyrimidinyl, indolyl, purinyl, quinolinyl and isoquinolinyl.

6. The method of claim 1, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. the epoxy compound is selected from the following compounds: 。 7. The method for preparing polyhydroxyalkanoate as described in claim 1, characterized in that, the chiral resolution catalyst is selected from the following compounds Cat-2 and Cat-8: ， 。 8. The method of claim 1, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. the preparation method has one or more of the following characteristics: ​ the molar ratio of water to the epoxy compound is (0.4-0.48):1; the ee value of the obtained chiral epoxy compound is ≥70% and ≤90%; the molar ratio of the epoxy compound to the chiral resolution catalyst is (100-10000):1; when the chiral resolution of the epoxy compound is performed, the water is added into the reaction system at a rate of 0.05-500 kg / h; the reaction pressure of the chiral resolution of the epoxy compound is normal pressure; the reaction temperature of the chiral resolution of the epoxy compound is 0-50℃; the reaction time of the chiral resolution of the epoxy compound is 0.1-120 h.

9. The method for preparing polyhydroxyalkanoate as described in claim 8, characterized in that, when the chiral resolution of the epoxy compound is performed, the water is added into the reaction system at a rate of 0.05-10 kg / h.

10. The method of claim 1, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. the preparation method has one or more of the following characteristics: the ee value of the obtained chiral β-lactone is ≥60% and ≤90%; the carbonylation catalyst is a bimetallic catalyst composed of a cationic Lewis acid and a carbonyl cobalt anion; the molar ratio of the chiral epoxy compound to the carbonylation catalyst is 1-100000:1; in the carbonylation reaction of the chiral epoxy compound, the pressure of carbon monoxide is 1-10 MPa; The reaction temperature of the chiral epoxide carbonylation reaction is 0-150℃. The reaction time of the chiral epoxide carbonylation reaction is 0.1-1000h. The solvent of the chiral epoxide carbonylation reaction is selected from one or more of aromatic hydrocarbon solvents and ether solvents.

11. The method of claim 10, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 0 The ee value of the prepared chiral β-lactone is ≥70% and ≤90%.

12. The method of claim 10, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 0 The cationic Lewis acid is a cationic polydentate ligand metal complex.

13. The method for preparing polyhydroxyalkanoate as described in claim 12, characterized in that, The polydentate ligand in the cationic polydentate ligand metal complex has a porphyrin structure or a Salen structure.

14. The method for preparing polyhydroxyalkanoate as described in claim 12, characterized in that, The metal atom in the cationic polydentate ligand metal complex is selected from one or more of group IIIA elements, group IIIB elements, lanthanide series elements and actinide series elements in the periodic system.

15. The method of claim 12, wherein the polyhydroxyalkanoate is produced in the presence of a metal salt. 15 The charge of the cationic polydentate ligand metal complex is +1 or +2.

16. The method for preparing polyhydroxyalkanoate as described in claim 10, characterized in that, The cobalt carbonyl anion is Co(CO)4 - .

17. The method of claim 10, wherein the polyhydroxyalkanoate is produced in a bioreactor. 0 The aromatic hydrocarbon solvent is selected from one or both of toluene and benzene.

18. The method of claim 10, wherein the polyhydroxyalkanoate is produced in a bioreactor. 0 The ether solvent is selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether and tert-butyl methyl ether.

19. The method for preparing polyhydroxyalkanoate as described in claim 10, characterized in that, The carbonylation catalyst is pre-reacted from a neutral Lewis acid precursor and a cobalt carbonyl compound, or is generated in situ in the reaction system from a neutral Lewis acid precursor and a cobalt carbonyl compound.

20. The method of making polyhydroxyalkanoates according to claim 19, wherein, The Lewis acid precursor comprises a cationic polydentate ligand metal complex and a coordinating anion.

21. The method of making polyhydroxyalkanoates according to claim 20, wherein, The polydentate ligand in the cationic polydentate ligand metal complex has a porphyrin structure or a Salen structure.

22. The method of making polyhydroxyalkanoates according to claim 20, wherein, The metal atom in the cationic polydentate ligand metal complex is selected from one or more of group IIIA elements, group IIIB elements, lanthanide series elements and actinide series elements in the periodic system.

23. The method of making polyhydroxyalkanoates according to claim 20, wherein, The charge of the cationic polydentate ligand metal complex is +1 or +2.

24. The method of making polyhydroxyalkanoates according to claim 20, wherein, The coordinating anion is selected from one or more of chloride ions, bromide ions, iodide ions, carboxylate ions and sulfonate ions.

25. The method of making polyhydroxyalkanoates according to claim 19, wherein, The cobalt carbonyl compound is selected from the group consisting of Co2(CO)8, NaCo(CO)4, KCo(CO)4, and Co4(CO) 12 one or more of Co2(CO)8, NaCo(CO)4, KCo(CO)4, and Co4(CO)12.

26. The method of making polyhydroxyalkanoates according to claim 19, wherein, The carbonylation catalyst is pre-reacted from a cobalt carbonyl compound and a Lewis acid precursor in a molar ratio of 0.1-100:1 or is generated in situ in the reaction system.

27. The method of making polyhydroxyalkanoates according to claim 1, wherein, The preparation method has one or more of the following characteristics: The polymerization catalyst can be selected from one or more of tin salts, titanium salts, magnesium salts, aluminum salts, calcium salts, iron salts, manganese salts, zinc salts, organic tin compounds, organic titanium compounds, organic magnesium compounds, organic aluminum compounds, organic calcium compounds, organic iron compounds, organic manganese compounds and organic zinc compounds; The mass of the polymerization catalyst is 0.001%-3% of the total mass of the polymerized monomers; The reaction pressure of the ring-opening polymerization reaction is 0.1-10 MPa; The reaction temperature of the ring-opening polymerization reaction is 25-150℃; The reaction time of the ring-opening polymerization reaction is 0.1-120h; The ring-opening polymerization reaction is carried out in a protective atmosphere.

28. The method of making polyhydroxyalkanoates according to claim 1, wherein, The polyhydroxyalkanoate has one or more of the following characteristics: The melting temperature is ≤160℃; The tensile strength is ≥5 MPa; The elongation at break is ≥2%.

29. The method of making polyhydroxyalkanoates according to claim 28, wherein, The melting temperature is ≤150℃.

30. The method of making polyhydroxyalkanoates according to claim 28, wherein, The tensile strength is ≥10 MPa.

31. The method of making polyhydroxyalkanoates according to claim 28, wherein, The elongation at break is ≥5%.

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