A polynuclear salen catalyst and its preparation method and application

Abstract

The application discloses a Salen catalyst which has a structure shown in formula (I-1). The Salen catalyst is a polynuclear catalyst, two or more mononuclear catalysts can be connected into the polynuclear catalyst through a group containing an amide bond, the catalytic efficiency, the resolution yield, the recovery rate and the activity after recovery of the catalyst can be improved, the polynuclear catalyst after recovery can be mixed with a fresh polynuclear catalyst for use, and the resolution yield is high, and the polynuclear catalyst can be recycled and reused for multiple times. In addition, when the polynuclear catalyst participates in a resolution reaction, an excessive amount of water is not needed, the reaction yield can be improved, the time for resolving an end epoxy compound can be shortened, the prepared product has high purity and few impurities, and the problem of difficult purification of a final product can be solved.

Description

Technical Field

[0001] This application belongs to the field of organic compound technology, specifically relating to a polynuclear Salen catalyst, its preparation method, and its application. Background Technology

[0002] Chiral chemistry is the science that studies the chirality of molecules, that is, the existence of non-hyperposable mirror isomers in molecular structures. In medicinal chemistry, different enantiomers of chiral molecules can possess completely different biological activities, thus the synthesis and resolution of chiral compounds have significant scientific and industrial implications. Epichlorohydrin is an important organic compound widely used in the synthesis of various drugs, pesticides, and fine chemicals. Due to the presence of its chiral center, the enantiomers of epichlorohydrin exhibit different biological activities and applications.

[0003] Salen catalysts play a crucial role in chiral synthesis due to their tunable structure and catalytic activity. In particular, for the kinetic resolution of chiral terminal epoxides such as epichlorohydrin, Salen catalysts can efficiently catalyze the production of products with high optical purity. Summary of the Invention

[0004] Although existing Salen catalysts have shown good performance in some chiral synthesis, they generally have some limitations, such as low catalytic efficiency, long reaction time, difficulty in controlling catalyst activity leading to over-reaction; the raw materials for catalyst preparation are not readily available, the reaction conditions are harsh and require nitrogen protection and strict control of anhydrous and oxygen-free conditions, making them unsuitable for industrial production; and the catalysts need further activation before recycling, resulting in high costs.

[0005] Therefore, there is an urgent need to develop a new type of Salen catalyst.

[0006] This application aims to address at least one of the technical problems existing in the prior art to a certain extent. To this end, this application provides a multinuclear Salen catalyst.

[0007] This application is based on the following discoveries of the inventors:

[0008] Currently, mononuclear catalysts are widely used in industrial production, but they have the following problems:

[0009] 1. Using the mononuclear catalyst in the existing technology, the catalyst is recovered after the catalytic reaction is completed. However, the filtration resistance is very high when recovering the catalyst after use, so the recovery rate is not high, only about 60%.

[0010] 2. Using existing mononuclear catalysts, the yield of S-epoxychloropropane is about 40%, not exceeding 43%.

[0011] 3. The preparation of the subsequent product "L-carnitine" from S-epoxychloropropane obtained by existing technology results in a large number of byproducts, requiring multi-stage purification to obtain pure carnitine, making the purification route complex.

[0012] Currently, publicly disclosed binuclear catalysts also have certain limitations. For example, CN114146731A discloses an oligomeric binuclear MOF-based epichlorohydrin kinetic resolution catalyst and its synthesis method. During resolution, 2.824 equivalents of water are added, which easily leads to over-reaction, and the catalyst recovery rate is low. CN113856762A discloses a high-polymerized Salen trivalent cobalt catalyst, which requires toluene as a solvent and expensive tetrabutylammonium iodide as a catalyst during intermediate preparation, making it unsuitable for industrial production. Furthermore, its resolution yield is below 43%, which is not advantageous compared to mononuclear Salen cobalt catalysts. Additionally, after catalyst use, cobalt changes from trivalent to divalent, requiring activation treatment for recycling, making the recovery process complex.

[0013] However, the multinuclear catalyst of this application can shorten the reaction time, improve catalytic efficiency, increase the resolution yield, better control the degree of resolution reaction, improve catalyst recovery rate, and the recovered catalyst can be used directly while still maintaining high catalytic activity. In addition, the preparation method of this multinuclear catalyst is simple, the reaction conditions are mild, it does not require the use of halogens for halogenation reactions, and it does not require the use of hazardous reagents and solvents, making it more suitable for industrial production.

[0014] In a first aspect, this application proposes a Salen catalyst ligand. According to an embodiment of this application, the Salen catalyst ligand has the structure shown in formula (I):

[0015] (I);

[0016] in, Empty or chemical bond;

[0017] If empty, R1 is H, -COOH, or -NH2, and R2 is H, -COOH, or -NH2;

[0018] For chemical bonds, -R1-R2- are selected from groups containing -NH-C(O)-;

[0019] R3 is selected from groups containing -NH-C(O)-;

[0020] R4 is selected from C 3~6 alkyl;

[0021] n is any integer between 0 and 10.

[0022] Unless otherwise specified in this article, Empty means There was nothing there.

[0023] The Salen catalyst ligand of this application can be used to prepare polynuclear catalysts. The prepared polynuclear catalysts can shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate, and enhance the activity after recovery.

[0024] In a second aspect, this application proposes a Salen catalyst. According to embodiments of this application, the Salen catalyst has the structure shown in formula (I-1):

[0025] (I-1),

[0026] Where M is selected from Co, Mn, or Cu;

[0027] Empty or chemical bond;

[0028] If empty, R1 is H, -COOH, or -NH2, and R2 is H, -COOH, or -NH2;

[0029] For chemical bonds, -R1-R2- are selected from groups containing -NH-C(O)-;

[0030] R3 is selected from groups containing -NH-C(O)-;

[0031] R4 is selected from C 3~6 alkyl;

[0032] n is any integer between 0 and 10.

[0033] The Salen catalyst of this application is a multinuclear catalyst, which can shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate, and enhance the activity after recovery.

[0034] According to embodiments of this application, M is selected from Co, Mn, and Cu.

[0035] According to embodiments of this application, the Salen catalyst ligand described in the first aspect and the Salen catalyst described in the second aspect may further include the following technical features:

[0036] According to embodiments of this application, R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0037] According to embodiments of this application, R3 is selected from -C(O)-NH-C 1~6 Alkylene-NH-C(O)-.

[0038] According to embodiments of this application, R3 is selected from -C(O)-NH-C 1~4 Alkylene-NH-C(O)-.

[0039] According to embodiments of this application, R3 is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

[0040] According to an embodiment of this application, R3 is selected from -NH-C(O)-.

[0041] According to an embodiment of this application, R4 is selected from C. 3~6 alkyl.

[0042] According to embodiments of this application, R4 is selected from isopropyl or tert-butyl.

[0043] According to an embodiment of this application, n is 0.

[0044] According to an embodiment of this application, n is any integer between 1 and 10.

[0045] According to the embodiments of this application, If empty, R1 and R2 are the same or different.

[0046] According to the embodiments of this application, If empty, R1 and R2 are the same.

[0047] According to the embodiments of this application, If empty, R1 and R2 are different.

[0048] According to the embodiments of this application, For chemical bonds, -R1-R2- are selected from -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0049] Unless otherwise specified in this article, "-R1-R2-" refers to the structure after the R1 group and the R2 group are connected.

[0050] According to the embodiments of this application, For chemical bonds, -R1-R2- are selected from -C(O)-NH-C 1~6 Alkylene-NH-C(O)-.

[0051] According to the embodiments of this application, For chemical bonds, -R1-R2- are selected from -C(O)-NH-(CH2)3-NH-C(O)-.

[0052] According to the embodiments of this application, It is a chemical bond, and R3 is selected from -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0053] According to the embodiments of this application, It is a chemical bond, and R3 is selected from -C(O)-NH-C 2~6 Alkylene-NH-C(O)-.

[0054] According to the embodiments of this application, These are chemical bonds, and -R1-R2- and R3 are the same.

[0055] According to the embodiments of this application, For chemical bonds, -R1-R2- is selected from -C(O)-NH-C 1~10 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 Alkylene -NH-C(O)-, wherein -R1-R2- and R3 are the same or different.

[0056] According to the embodiments of this application, For chemical bonds, -R1-R2- is selected from -C(O)-NH-C 1~6 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~6 Alkylene -NH-C(O)-, wherein -R1-R2- and R3 are the same.

[0057] According to the embodiments of this application, For chemical bonds, when n is 0 or 1, -R1-R2- is selected from -C(O)-NH-C 1~10 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 The alkylene groups -NH-C(O)-, -R1-R2- and R3 are the same.

[0058] According to the embodiments of this application, For chemical bonds, when n is 0, -R1-R2- is selected from -C(O)-NH-C 1~10 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 The alkylene groups -NH-C(O)-, -R1-R2- and R3 are the same.

[0059] According to the embodiments of this application, For chemical bonds, when n is 1, -R1-R2- is selected from -C(O)-NH-C 1~10alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 The alkylene groups -NH-C(O)-, -R1-R2- and R3 are the same.

[0060] According to the embodiments of this application, If empty, R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0061] According to the embodiments of this application, If empty, R3 is selected from -NH-C(O)- or -C(O)-NH-C 2~10 Alkylene-NH-C(O)-.

[0062] According to an embodiment of this application, when n is 0, R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-, R1 and R2 may be the same or different.

[0063] According to embodiments of this application, when n is any integer between 1 and 10, R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-, R1 and R2 may be the same or different.

[0064] According to embodiments of this application, the Salen catalyst ligand described in the first aspect has a structure shown in formula (Ia1), formula (Ia2), formula (Ia3), or formula (Ia4):

[0065] (Ia1),

[0066] (Ia2), (Ia3), (Ia4),

[0067] Where m is any integer between 1 and 10.

[0068] According to embodiments of this application, the Salen catalyst described in the second aspect has a structure shown in formula (Ib1), formula (Ib2), formula (Ib3), or formula (Ib4):

[0069] (Ib1),

[0070] (Ib2), (Ib3),

[0071] (Ib4),

[0072] Where m is any integer between 1 and 10.

[0073] According to embodiments of this application, in the structure shown in formula (Ia3) or formula (Ib3), R1 is H, -NH2 or -COOH, and R2 is H, -COOH or -NH2.

[0074] According to embodiments of this application, in the structures shown in formula (Ia3) or formula (Ib3), R1 and R2 are the same.

[0075] According to embodiments of this application, in the structure shown in formula (Ia3) or formula (Ib3), R1 and R2 are -COOH.

[0076] According to embodiments of this application, in the structures shown in formula (Ia3) or formula (Ib3), R1 and R2 are different.

[0077] According to embodiments of this application, in the structure shown in formula (Ia3) or formula (Ib3), R1 is -COOH and R2 is -NH2.

[0078] According to embodiments of this application, the Salen catalyst ligand described in the first aspect has any of the following structures:

[0079] , ,

[0080] ,

[0081] ,

[0082] , ,

[0083] ,

[0084] ,

[0085] , , , .

[0086] According to embodiments of this application, the Salen catalyst described in the second aspect has any of the following structures:

[0087] , ,

[0088] ,

[0089] ,

[0090] , ,

[0091] ,

[0092] ,

[0093] , , , ;

[0094] , ,

[0095] ,

[0096] ,

[0097] , ,

[0098] ,

[0099] ,

[0100] , , , ; , ,

[0101] ,

[0102] ,

[0103] , ,

[0104] ,

[0105] ,

[0106] , , , .

[0107] Such catalysts can further shorten reaction time, improve catalytic efficiency, increase resolution yield, improve catalyst recovery rate, and enhance post-recovery activity when resolving terminal epoxides.

[0108] In a third aspect of this application, a method for preparing the Salen catalyst ligand described in the first aspect is provided. According to embodiments of this application, the method includes:

[0109] The Salen catalyst ligand is obtained by linking two or more mononuclear Salen catalyst ligands of formula (II) with a group containing -NH-C(O)-.

[0110] The multinuclear Salen catalyst ligand has a cyclic or chain structure;

[0111] (II).

[0112] The preparation method described in this application is simple, requiring no flammable or explosive reagents or expensive reagents, making it more suitable for industrial production. Furthermore, the prepared Salen catalyst ligand can be used to prepare Salen catalysts, which exhibit high catalytic efficiency, high resolution yield, high catalyst recovery rate, and high activity after recovery.

[0113] According to embodiments of this application, the method described in the third aspect above may further include at least one of the following technical features:

[0114] According to embodiments of this application, the group containing -NH-C(O)- is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0115] According to embodiments of this application, the multinuclear Salen catalyst has a cyclic structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-C 1~6 Alkylene-NH-C(O)-.

[0116] According to embodiments of this application, the multinuclear Salen catalyst has a cyclic structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

[0117] According to embodiments of this application, the multinuclear Salen catalyst has a chain structure, and the group containing -NH-C(O)- is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-.

[0118] According to embodiments of this application, the group containing -NH-C(O)- is obtained by amidation reaction of -COOH and -NH2.

[0119] According to embodiments of this application, the condensing agent for the amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0120] According to embodiments of this application, the catalyst for the amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0121] According to embodiments of this application, the organic solvent for the amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0122] According to an embodiment of this application, the mononuclear Salen catalyst ligand represented by formula (II) is obtained by reacting the structures represented by formula (IV) and formula (V) with a Schiff base reaction.

[0123] (IV) (V).

[0124] According to embodiments of this application, the catalyst in the Schiff base reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0125] According to embodiments of this application, the organic solvent in the Schiff base reaction is selected from at least one of methanol and ethanol.

[0126] According to the embodiments of this application, the reaction temperature of the Schiff base reaction is 60°C to 65°C.

[0127] According to the embodiments of this application, the reaction time of the Schiff base reaction is 4h to 6h.

[0128] According to an embodiment of this application, in the Schiff base reaction, the molar ratio of the structure shown in formula (IV) to the structure shown in formula (V) is 1.0:(0.5~1.5).

[0129] In a fourth aspect of this application, a method for preparing the Salen catalyst described in the second aspect is provided. According to embodiments of this application, the method includes: performing a complexation reaction on the Salen catalyst ligand described in the first aspect, or on the Salen catalyst ligand prepared according to the method described in the third aspect, to obtain the Salen catalyst. The preparation method of this application is simple, and does not require the use of flammable or explosive reagents or expensive reagents during the preparation process, making it more suitable for industrial production.

[0130] In a fifth aspect of this application, a method for resolving terminal epoxide compounds is provided. According to embodiments of this application, the method includes: performing a resolution reaction using the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, to obtain the resolved epoxide compound.

[0131] In a sixth aspect of this application, the application of the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, is proposed for the resolution of terminal epoxides.

[0132] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Detailed Implementation

[0133] The embodiments of this application are described in detail below. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0134] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this application, unless otherwise stated, "multiple" means two or more.

[0135] It should be noted that the structural and chemical formula descriptions in the embodiments or implementations of this application are intended to cover all alternatives, modifications, and equivalent technical solutions, all of which are within the scope of this application as defined in the claims. Those skilled in the art will recognize that many similar or equivalent methods and materials can be used to practice this application. This application is by no means limited to the methods and materials described herein. In the event that one or more of the cited documents, patents, and similar materials differ from or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, etc.), this application shall prevail.

[0136] It should be further appreciated that some features of this application, for clarity, have been described in multiple independent embodiments or implementations, but may also be provided in combination in a single embodiment or implementation. Conversely, various features of this application, for the sake of brevity, have been described in a single embodiment or implementation, but may also be provided individually or in any suitable sub-combination.

[0137] Unless otherwise stated, the technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains, and unless otherwise stated, all patent publications cited in the entirety of this application are incorporated herein by reference.

[0138] This application will apply the following definitions unless otherwise indicated. For the purposes of this application, chemical elements are defined according to the periodic table, CAS version, and Chemical Handbook, 75, 1994. Furthermore, general principles of organic chemistry are found in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007; therefore, all contents of this application incorporate the references.

[0139] In this document, the terms “comprising” or “including” are open-ended expressions, meaning that they include the contents specified in this application but do not exclude other contents.

[0140] In this document, the terms “optionally,” “optionally,” or “optionally” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0141] In this document, the compounds of this application also include isotopically labeled compounds of this application that are identical to those compounds described herein except that one or more atoms are replaced by atoms with atomic masses or mass numbers different from those of naturally common atomic masses or mass numbers.

[0142] In this paper, the minimum and maximum carbon atom content in hydrocarbon groups are indicated by prefixes, for example, prefix C. a~b This refers to a carbon atom, which is "a" to "b". For example, "C 1~n "C" refers to a saturated / unsaturated carbon chain, either straight or branched, containing 1, 2, 3, 4, 5, ..., or n carbon atoms; further understanding, "C" 1~n "Should be interpreted as any subranges included, such as C" 2~6 In, containing C 2~6 C 2~5 C 2~4 C 2~3 C 3~6 C3~5 C 3~4 C 4~6 C 4~5 .

[0143] In this document, the term "alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group having a carbon atom.

[0144] In this article, the term "alkylene" refers to a group formed by removing one more hydrogen atom from an "alkyl" group.

[0145] In this paper, the term "-NH-C(O)-" or "-NH-C(=O)-" refers to an amide group, with the structural formula as follows: .

[0146] This application proposes a multinuclear Salen catalyst, its preparation method, and its applications, which will be described in detail below.

[0147] Salen catalyst ligands and Salen catalysts

[0148] In a first aspect, this application proposes a Salen catalyst ligand. According to an embodiment of this application, the Salen catalyst ligand has a ligand structure shown in formula (I):

[0149] (I);

[0150] in, Empty or chemical bond;

[0151] If empty, R1 is H, -COOH, or -NH2, and R2 is H, -COOH, or -NH2;

[0152] For chemical bonds, -R1-R2- are selected from groups containing -NH-C(O)-;

[0153] R3 is selected from groups containing -NH-C(O)-;

[0154] R4 is selected from C 3~6 alkyl;

[0155] n is any integer between 0 and 10.

[0156] The Salen catalyst ligand of this application can be used to prepare polynuclear catalysts. The prepared polynuclear catalysts can shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate, and enhance the activity after recovery.

[0157] According to embodiments of this application, the Salen catalyst ligand has the structure shown in formula (Ia1):

[0158] (Ia1),

[0159] n is any integer between 0 and 10, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two values ​​between them as the range of endpoint values.

[0160] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ia1), R4 is selected from isopropyl or tert-butyl.

[0161] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ia1), R4 is selected from isopropyl.

[0162] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ia1), R4 is selected from tert-butyl.

[0163] According to embodiments of this application, the Salen catalyst ligand has the structure shown in formula (Ia2):

[0164] (Ia2),

[0165] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two of them as a range of values ​​between endpoints.

[0166] Therefore, the structure shown in formula (Ib2) above can further shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate and the activity after recovery.

[0167] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ia2), R4 is selected from isopropyl or tert-butyl.

[0168] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia2), R4 is selected from isopropyl or tert-butyl.

[0169] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia2), R4 is selected from isopropyl.

[0170] According to embodiments of this application, the Salen catalyst ligand has the structure shown in formula (Ia3):

[0171] (Ia3),

[0172] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two of them as a range of values ​​between endpoints.

[0173] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ia3), R4 is selected from isopropyl or tert-butyl, R1 is empty, -COOH or -NH2, R2 is empty, -COOH or -NH2, and R1 and R2 may be the same or different.

[0174] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ia3), R4 is selected from isopropyl or tert-butyl, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R1 and R2 are different.

[0175] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ia3), R4 is selected from isopropyl or tert-butyl, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R1 and R2 are the same.

[0176] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia3), R4 is selected from isopropyl or tert-butyl, and R1 and R2 are -COOH.

[0177] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia3), R4 is selected from isopropyl, and R1 and R2 are -COOH.

[0178] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia3), R4 is selected from tert-butyl, and R1 and R2 are -COOH.

[0179] According to embodiments of this application, the Salen catalyst ligand has the structure shown in formula (Ia4):

[0180] (Ia4),

[0181] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two of them as a range of values ​​between endpoints.

[0182] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ia4), R4 is selected from isopropyl or tert-butyl.

[0183] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown by formula (Ia4), R4 is selected from isopropyl.

[0184] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia4), R4 is selected from tert-butyl.

[0185] In a second aspect, this application proposes a Salen catalyst. According to embodiments of this application, the Salen catalyst has the structure shown in formula (I-1):

[0186] (I-1),

[0187] Where M is selected from Co, Mn, or Cu;

[0188] Empty or chemical bond;

[0189] If empty, R1 is H, -COOH, or -NH2, and R2 is H, -COOH, or -NH2;

[0190] For chemical bonds, -R1-R2- are selected from groups containing -NH-C(O)-;

[0191] R3 is selected from groups containing -NH-C(O)-;

[0192] R4 is selected from C 3~6 alkyl;

[0193] n is any integer between 0 and 10.

[0194] The Salen catalyst of this application is a polynuclear catalyst. This application is the first to discover that two or more mononuclear catalysts can be linked into a polynuclear catalyst (which can be a cyclic polynuclear catalyst or a chain polynuclear catalyst) through groups containing amide bonds. This not only improves the catalytic efficiency, resolution yield, recovery rate, and activity of the catalyst in resolving terminal epoxides, but also allows for reuse alone or in combination with fresh polynuclear catalysts, while still maintaining high resolution yields. Furthermore, the polynuclear catalyst of this application does not require excess water in the resolution reaction, which can improve the reaction yield and shorten the time for resolving terminal epoxides. The resulting product has high purity and few impurities, solving problems such as difficulties in purifying the final product.

[0195] Current binuclear catalysts are mostly linked by ether structures, which cannot simultaneously achieve high resolution yield, high recovery rate, and high post-recovery activity. When the resolution yield is high, the recovery rate and post-recovery activity cannot be guaranteed; conversely, when the recovery rate is high, the post-recovery activity cannot be guaranteed. Furthermore, the reaction activity is difficult to control, easily leading to over-reaction. However, compared to the aforementioned binuclear catalysts, the multi-nuclear catalyst of this application simultaneously satisfies the advantages of high resolution yield (up to 48% or higher), high recovery rate (up to 85% or higher), high post-recovery activity (the resolution yield after recovery can also reach 48% or higher), and high purity of the final product.

[0196] Unless otherwise specified in this article, the bond between N and M (e.g., Co) in Salen catalysts is a coordinate bond.

[0197] According to an embodiment of this application, in the Salen catalyst, n is 0~10, for example 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range between endpoint values.

[0198] According to embodiments of this application, the Salen catalyst has the structure shown in formula (Ib1):

[0199] (Ib1),

[0200] n is any integer between 0 and 10, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two values ​​between them as the range of endpoint values.

[0201] Therefore, the structure shown in formula (Ib1) above can further shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate and the activity after recovery.

[0202] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ib1), R4 is selected from isopropyl or tert-butyl.

[0203] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ib1), R4 is selected from isopropyl.

[0204] In an optional embodiment of this application, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and in the structure shown in formula (Ib1), R4 is selected from tert-butyl.

[0205] In one alternative embodiment of this application, M is selected from Co.

[0206] In one alternative embodiment of this application, M is selected from Mn.

[0207] In one alternative embodiment of this application, M is selected from Cu.

[0208] According to embodiments of this application, the Salen catalyst has the structure shown in formula (Ib2):

[0209] (Ib2),

[0210] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two of them as a range of values ​​between endpoints.

[0211] Therefore, the structure shown in formula (Ib2) above can further shorten the reaction time for resolving terminal epoxides, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate and the activity after recovery.

[0212] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ib2), R4 is selected from isopropyl or tert-butyl.

[0213] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib2), R4 is selected from isopropyl or tert-butyl.

[0214] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib2), R4 is selected from isopropyl.

[0215] In one alternative embodiment of this application, M is selected from Co.

[0216] In one alternative embodiment of this application, M is selected from Mn.

[0217] In one alternative embodiment of this application, M is selected from Cu.

[0218] According to embodiments of this application, the Salen catalyst has the structure shown in formula (Ib3):

[0219] (Ib3),

[0220] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two values ​​between them as the range between the endpoint values;

[0221] R1, R2 and R4 are as defined in the first aspect of the invention description of this application.

[0222] Therefore, the structure shown in formula (Ib3) above can further shorten the reaction time for resolving terminal epoxide compounds, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate and the activity after recovery.

[0223] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ib3), R4 is selected from isopropyl or tert-butyl, R1 is empty, -COOH or -NH2, R2 is empty, -COOH or -NH2, and R1 and R2 may be the same or different.

[0224] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ib3), R4 is selected from isopropyl or tert-butyl, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R1 and R2 are different.

[0225] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ib3), R4 is selected from isopropyl or tert-butyl, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R1 and R2 are the same.

[0226] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib3), R4 is selected from isopropyl or tert-butyl, and R1 and R2 are -COOH.

[0227] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib3), R4 is selected from isopropyl, and R1 and R2 are -COOH.

[0228] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib3), R4 is selected from tert-butyl, and R1 and R2 are -COOH.

[0229] In one alternative embodiment of this application, M is selected from Co.

[0230] In one alternative embodiment of this application, M is selected from Mn.

[0231] In one alternative embodiment of this application, M is selected from Cu.

[0232] According to embodiments of this application, the Salen catalyst has the structure shown in formula (Ib4):

[0233] (Ib4),

[0234] Where m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any two of them as a range of values ​​between endpoints.

[0235] Therefore, the structure shown in formula (Ib4) above can further shorten the reaction time for resolving terminal epoxide compounds, improve catalytic efficiency, increase the resolving yield, improve the catalyst recovery rate and the activity after recovery.

[0236] In an optional embodiment of this application, m is 1, 2, 3, 4 or 5, and in the structure shown by formula (Ib4), R4 is selected from isopropyl or tert-butyl.

[0237] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown by formula (Ib4), R4 is selected from isopropyl.

[0238] In an optional embodiment of this application, m is 1, 2, 3 or 4, and in the structure shown by formula (Ib4), R4 is selected from tert-butyl.

[0239] In one alternative embodiment of this application, M is selected from Co.

[0240] In one alternative embodiment of this application, M is selected from Mn.

[0241] In one alternative embodiment of this application, M is selected from Cu.

[0242] In one aspect of this application, a Salen catalyst composition is provided. According to embodiments of this application, the Salen catalyst composition comprises one or more of the Salen catalysts described above.

[0243] According to embodiments of this application, the Salen catalyst composition comprises a variety of structures shown in formula (Ib1).

[0244] In this document, "Salen catalyst composition comprising multiple structures shown in formula (Ib1)" means simultaneously comprising multiple structures shown in formula (Ib1) with n=0, n=1, n=2, n=3, n=4, n=5, n=6, n=7, n=8, n=9, and n=10.

[0245] Methods for preparing Salen catalysts

[0246] In a third aspect of this application, a method for preparing the Salen catalyst ligand described in the first aspect is provided. According to embodiments of this application, the method includes:

[0247] Multinuclear Salen catalyst ligands are obtained by linking two or more mononuclear Salen catalyst ligands shown in formula (II) with a group containing -NH-C(O)-.

[0248] The multinuclear Salen catalyst ligand has a cyclic or chain structure;

[0249] (II).

[0250] The preparation method described in this application is simple, requiring no flammable or explosive reagents or expensive reagents, making it more suitable for industrial production. Furthermore, the prepared Salen catalyst ligand can be used to prepare Salen catalysts, which exhibit high catalytic efficiency, high resolution yield, high catalyst recovery rate, and high activity after recovery.

[0251] In this document, "linking two or more mononuclear Salen catalysts of formula (II) by means of a group containing -NH-C(O)- and optionally performing a complexation reaction" means first performing a linking treatment to obtain the Salen catalyst of formula (I) as described in the first aspect (the specific linking method is not limited and is within the scope of protection of this application). If the Salen catalyst of formula (I-1) is prepared, and then a complexation reaction is performed based on the structure of formula (I), the Salen catalyst of formula (I-1) as described in the first aspect is obtained.

[0252] In a fourth aspect of this application, a method for preparing the Salen catalyst described in the second aspect is provided. According to embodiments of this application, the method includes: performing a complexation reaction on the Salen catalyst ligand described in the first aspect, or on a Salen catalyst ligand prepared according to the method described in the third aspect, to obtain the Salen catalyst.

[0253] The inventors of this application have discovered that current binuclear catalysts are all linked by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0254] However, the Salen catalyst of this application is linked by amide-containing groups, which eliminates the need for flammable, explosive, or costly reagents during preparation, making the preparation method simple and more suitable for industrial production. Furthermore, the prepared Salen catalyst offers advantages such as shortening the reaction time for resolving terminal epoxides, improving catalytic efficiency, increasing resolving yield, improving catalyst recovery rate, and enhancing the activity after recovery.

[0255] In one aspect of this application, a method for preparing Salen catalyst ligands is provided. According to embodiments of this application, the method includes:

[0256] Compound I-1 and compound I-2 were subjected to a first amidation reaction to obtain compound I-3;

[0257] Compound I-3 and compound I-4 were subjected to a first condensation reaction to obtain compound I-5;

[0258] Compound I-5 was subjected to a first deBOC reaction to obtain compound I-6;

[0259] Compound I-6 and compound I-3 were subjected to a second condensation reaction to obtain compound Ia2 (i.e., Salen catalyst ligand).

[0260] (I-1) (I-2) (I-3) (I-4) (I-5) (I-6) (Ia2);

[0261] Where m is any integer between 1 and 10;

[0262] R4 is selected from C 3~6 alkyl.

[0263] The inventors of this application have discovered that current binuclear catalysts are all linked by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0264] However, the Salen catalyst of this application is linked by amide groups constructed from carboxyl and amine groups. Its preparation process does not require flammable or explosive reagents or expensive reagents, making it simpler and more suitable for industrial production. Furthermore, the prepared Salen catalyst has advantages such as shortening the reaction time for resolving terminal epoxides, improving catalytic efficiency, increasing resolving yield, improving catalyst recovery rate, and enhancing the activity after recovery.

[0265] It should be noted that the first condensation reaction and / or the second condensation reaction mentioned above are both Schiff base reactions.

[0266] According to embodiments of this application, m and R4 are defined as in the Salen catalyst described in the first aspect.

[0267] According to embodiments of this application, the condensing agent for the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0268] According to embodiments of this application, the catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0269] According to embodiments of this application, the organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0270] According to embodiments of this application, the catalyst in the first condensation reaction and / or the second condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0271] According to embodiments of this application, the organic solvent in the first condensation reaction and / or the second condensation reaction is selected from at least one of methanol and ethanol.

[0272] According to embodiments of this application, the reaction temperature of the first condensation reaction and / or the second condensation reaction is 40°C to 70°C.

[0273] According to an embodiment of this application, the reaction time of the first condensation reaction and / or the second condensation reaction is 4h to 8h.

[0274] According to an embodiment of this application, in the first condensation reaction, the molar ratio of compound I-3 to compound I-4 is 1.0:(1.0~1.2).

[0275] According to an embodiment of this application, in the second condensation reaction, the molar ratio of compound I-6 to compound I-3 is (1.0~1.2):1.0.

[0276] According to an embodiment of this application, the first BOC removal reaction is carried out in an acidic environment.

[0277] According to embodiments of this application, the organic solvent for the first BOC removal reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0278] In one aspect of this application, a method for preparing a Salen catalyst is provided. According to an embodiment of this application, the method includes: adding a divalent metal salt to compound Ia2 to perform a first complexation reaction to obtain compound Ib2 (i.e., the Salen catalyst);

[0279] (Ib2);

[0280] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0281] M is selected from Co, Mn, or Cu.

[0282] According to embodiments of this application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0283] According to embodiments of this application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0284] According to embodiments of this application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0285] According to an embodiment of this application, the reaction temperature of the first complexation reaction is 60°C to 65°C.

[0286] According to an embodiment of this application, the reaction time of the first complexation reaction is 3h to 5h.

[0287] In one aspect of this application, a method for preparing Salen catalyst ligands is provided. According to embodiments of this application, the method includes:

[0288] Compound I-1 and compound I-2 were subjected to a first amidation reaction to obtain compound I-3;

[0289] Compound I-3 and compound I-4 were subjected to a first condensation reaction to obtain compound I-5;

[0290] Compound I-5 was subjected to a first deBOC reaction to obtain compound I-6;

[0291] The compound I-6 and compounds I-R1 and I-R2 were subjected to a second condensation reaction to obtain compound Ia3 (i.e., Salen catalyst ligand).

[0292] (I-1) (I-2) (I-R1) (I-R2) (I-3) (I-4) (I-5) (I-6) (Ia3);

[0293] Where m is any integer between 1 and 10;

[0294] R4 is selected from C 3~6 alkyl.

[0295] The inventors of this application have discovered that current binuclear catalysts are all linked by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0296] However, the Salen catalyst of this application is linked by amide groups constructed from carboxyl and amine groups. Its preparation process does not require flammable or explosive reagents or expensive reagents, making it simpler and more suitable for industrial production. Furthermore, the prepared Salen catalyst has advantages such as shortening the reaction time for resolving terminal epoxides, improving catalytic efficiency, increasing resolving yield, improving catalyst recovery rate, and enhancing the activity after recovery.

[0297] It should be noted that the first condensation reaction and / or the second condensation reaction mentioned above are both Schiff base reactions.

[0298] According to embodiments of this application, R1, R2, R4 and m refer to the definitions in the Salen catalyst described in the first aspect.

[0299] According to embodiments of this application, the condensing agent for the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0300] According to embodiments of this application, the catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0301] According to embodiments of this application, the organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0302] According to embodiments of this application, the catalyst in the first condensation reaction and / or the second condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0303] According to embodiments of this application, the organic solvent in the first condensation reaction and / or the second condensation reaction is selected from at least one of methanol and ethanol.

[0304] According to embodiments of this application, the reaction temperature of the first condensation reaction and / or the second condensation reaction is 40°C to 70°C.

[0305] According to an embodiment of this application, the reaction time of the first condensation reaction and / or the second condensation reaction is 4h to 8h.

[0306] According to an embodiment of this application, in the first condensation reaction, the molar ratio of compound I-3 to compound I-4 is 1.0:(1.0~1.2).

[0307] According to an embodiment of this application, in the second condensation reaction, the molar ratio of compound I-6 to compounds I-R1 and I-R2 is (1.0~1.2):1.0:1.0.

[0308] According to an embodiment of this application, the first BOC removal reaction is carried out in an acidic environment.

[0309] According to embodiments of this application, the organic solvent for the first BOC removal reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0310] In one aspect of this application, a method for preparing a Salen catalyst is provided. According to an embodiment of this application, the method includes: cooling compound Ia3, adding a divalent metal salt to the cooled product to carry out a first complexation reaction, and obtaining compound Ib3 (i.e., the Salen catalyst);

[0311] (Ib3);

[0312] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0313] M is selected from Co, Mn, or Cu.

[0314] According to an embodiment of this application, the temperature of the cooling process is 15~25℃, for example 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃ or a range thereof.

[0315] According to embodiments of this application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0316] According to embodiments of this application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0317] According to embodiments of this application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0318] According to an embodiment of this application, the reaction temperature of the first complexation reaction is 60°C to 65°C.

[0319] According to an embodiment of this application, the reaction time of the first complexation reaction is 3h to 5h.

[0320] According to an embodiment of this application, the solvent for the first complexation reaction is N-methylpyrrolidone.

[0321] In another aspect of this application, a method for preparing Salen catalyst ligands is provided. According to embodiments of this application, the method includes:

[0322] Compound I-7 and compound I-4 were subjected to a third condensation reaction to obtain compound I-8;

[0323] Compound I-8 was subjected to a second deBOC reaction to obtain compound I-9;

[0324] Compound I-9 and compound I-10 were subjected to a fourth condensation reaction to obtain compound I-11;

[0325] Compound I-11 was subjected to acid hydrolysis to obtain compound I-12;

[0326] The compound I-12 was subjected to a second amidation reaction to obtain compound Ia1 (i.e., Salen catalyst ligand).

[0327] (I-7) (I-4) (I-8) (I-9) (I-10) (I-11) (I-12) (Ia1);

[0328] Among them, R4 is selected from C 3~6 alkyl;

[0329] n is any integer between 0 and 10.

[0330] The inventors of this application have discovered that current binuclear catalysts are all linked by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0331] However, the multinuclear Salen catalyst of this application is linked by amide groups constructed from carboxyl and amino groups. Its preparation process does not require flammable or explosive reagents or expensive reagents, making the preparation method simple and more suitable for industrial production. Furthermore, the prepared Salen catalyst has advantages such as shortening the reaction time for resolving terminal epoxides, improving catalytic efficiency, increasing resolving yield, improving catalyst recovery rate, and enhancing the activity after recovery.

[0332] It should be noted that the third and / or fourth condensation reactions mentioned above are both Schiff base reactions.

[0333] According to embodiments of this application, n and R4 are defined as in the Salen catalyst described in the first aspect.

[0334] According to embodiments of this application, the catalyst in the third condensation reaction and / or the fourth condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0335] According to embodiments of this application, the organic solvent in the third condensation reaction and / or the fourth condensation reaction is selected from at least one of methanol and ethanol.

[0336] According to embodiments of this application, the reaction temperature of the third condensation reaction and / or the fourth condensation reaction is 40°C to 70°C.

[0337] According to an embodiment of this application, the reaction time of the third condensation reaction and / or the fourth condensation reaction is 4h to 8h.

[0338] According to an embodiment of this application, in the third condensation reaction, the molar ratio of compound I-7 to compound I-4 is 1.0:(1.0~1.2).

[0339] According to an embodiment of this application, in the fourth condensation reaction, the molar ratio of compound I-9 to compound I-10 is (1.0~1.2):1.0.

[0340] According to an embodiment of this application, the second BOC removal reaction is carried out in an acidic environment.

[0341] According to embodiments of this application, the organic solvent for the second deBOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0342] According to an embodiment of this application, the first acidolysis reaction is carried out under concentrated hydrochloric acid conditions.

[0343] According to an embodiment of this application, the reaction temperature of the first acidolysis reaction is 70°C to 80°C.

[0344] According to an embodiment of this application, the reaction time of the first acidolysis reaction is 2h to 4h.

[0345] According to embodiments of this application, the catalyst for the second amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0346] According to embodiments of this application, the organic solvent for the second amidation reaction is selected from at least one of N-methylpyrrolidone, N,N-dimethylformamide, and dichloromethane.

[0347] In one aspect of this application, a method for preparing a Salen catalyst is provided. According to an embodiment of this application, the method includes: adding a divalent metal salt to compound Ia1 to carry out a second complexation reaction to obtain compound Ib1 (i.e., the Salen catalyst);

[0348] (Ib1);

[0349] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0350] M is selected from Co, Mn, or Cu.

[0351] According to embodiments of this application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0352] According to embodiments of this application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0353] According to embodiments of this application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0354] According to an embodiment of this application, the reaction temperature of the second complexation reaction is 60°C to 65°C.

[0355] According to an embodiment of this application, the reaction time of the second complexation reaction is 3h to 5h.

[0356] In another aspect of this application, a method for preparing Salen catalyst ligands is provided. According to embodiments of this application, the method includes:

[0357] Compound I-1 and compound I-2 were subjected to a third amidation reaction to obtain compound I-13;

[0358] Compound I-13 and compound I-4 were subjected to a fifth condensation reaction to obtain compound I-14;

[0359] Compound I-14 was subjected to a third deBOC reaction to obtain compound I-15;

[0360] Compound I-15 was subjected to a sixth condensation reaction with compound I-7 to obtain compound I-16;

[0361] Compound I-16 was subjected to a third Cbz removal reaction to obtain compound I-17;

[0362] Compound I-17 was subjected to a second acid hydrolysis reaction to obtain compound I-18;

[0363] Compound I-18 was subjected to two fourth amidation reactions to obtain compound I-19;

[0364] Compound I-19 was subjected to a fifth amidation reaction to obtain compound Ia4 (i.e., Salen catalyst ligand).

[0365] (I-1) (I-2) (I-13) (I-4) (I-14) (I-15) (I-7) (I-16) (I-17) (I-18) (I-19) (Ia4);

[0366] Among them, R4 is selected from C 3~6 alkyl;

[0367] m is any integer between 1 and 10.

[0368] The inventors of this application have discovered that current binuclear catalysts are all linked by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0369] However, the multinuclear Salen catalyst of this application is linked by amide groups constructed from carboxyl and amino groups. Its preparation process does not require flammable or explosive reagents or expensive reagents, making the preparation method simple and more suitable for industrial production. Furthermore, the prepared Salen catalyst has advantages such as shortening the reaction time for resolving terminal epoxides, improving catalytic efficiency, increasing resolving yield, improving catalyst recovery rate, and enhancing the activity after recovery.

[0370] It should be noted that the fifth condensation reaction and / or the sixth condensation reaction mentioned above are both Schiff base reactions.

[0371] According to embodiments of this application, m and R4 are defined as in the Salen catalyst described in the first aspect.

[0372] According to embodiments of this application, the condensing agent for the third amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0373] According to embodiments of this application, the catalyst for the third amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0374] According to embodiments of this application, the organic solvent for the third amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0375] According to embodiments of this application, the catalyst in the fifth condensation reaction and / or the sixth condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0376] According to embodiments of this application, the organic solvent in the fifth condensation reaction and / or the sixth condensation reaction is selected from at least one of methanol and ethanol.

[0377] According to embodiments of this application, the reaction temperature of the fifth condensation reaction and / or the sixth condensation reaction is 40°C to 70°C.

[0378] According to embodiments of this application, the reaction time for the fifth condensation reaction and / or the sixth condensation reaction is 4h to 8h.

[0379] According to an embodiment of this application, in the fifth condensation reaction, the molar ratio of compound C3 to compound I-4 is 1.0:(1.0~1.2).

[0380] According to an embodiment of this application, in the sixth condensation reaction, the molar ratio of compound I-15 to compound I-7 is (1.0~1.2):1.0.

[0381] According to an embodiment of this application, the third BOC removal reaction is carried out in an acidic environment.

[0382] According to embodiments of this application, the organic solvent for the third deBOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0383] According to an embodiment of this application, the third Cbz removal reaction is carried out in a hydrobromic acid and acetic acid system.

[0384] According to an embodiment of this application, the second acidolysis reaction is carried out under concentrated hydrochloric acid conditions.

[0385] According to an embodiment of this application, the reaction temperature of the second acidolysis reaction is 70°C to 80°C.

[0386] According to an embodiment of this application, the reaction time of the second acidolysis reaction is 2h to 4h.

[0387] According to embodiments of this application, the catalyst for the fourth amidation reaction and / or the fifth amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

[0388] According to embodiments of this application, the organic solvent for the fourth amidation reaction and / or the fifth amidation reaction is selected from at least one of N-methylpyrrolidone, N,N-dimethylformamide, and dichloromethane.

[0389] In one aspect of this application, a method for preparing a Salen catalyst is provided. According to an embodiment of this application, the method includes: adding a divalent metal salt to compound Ia4 to carry out a third complexation reaction to obtain compound Ib4 (i.e., the Salen catalyst);

[0390] (Ib4);

[0391] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0392] M is selected from Co, Mn, or Cu.

[0393] According to embodiments of this application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0394] According to embodiments of this application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0395] According to embodiments of this application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0396] According to an embodiment of this application, the reaction temperature of the third complexation reaction is 60°C to 65°C.

[0397] According to an embodiment of this application, the reaction time of the third complexation reaction is 3h to 5h.

[0398] Methods to improve the recovery rate, separation yield, or activity of Salen catalysts after separation and recovery.

[0399] In a fifth aspect of this application, a method is proposed to improve the recovery rate, resolution yield, or post-resolution activity of a Salen catalyst. According to embodiments of this application, the method includes:

[0400] The polynuclear Salen catalyst is obtained by linking two or more mononuclear Salen catalyst ligands of formula (II) with a group containing -NH-C(O)- and then performing a complexation reaction.

[0401] The multinuclear Salen catalyst has a cyclic or chain structure;

[0402] (II).

[0403] The inventors of this application have discovered that in existing binuclear catalysts, the cores are connected by ether structures. Because the ether structure is similar to the epoxy structure of the product, and due to the principle of "like dissolves like," the binuclear catalyst and the product are difficult to separate. Furthermore, ethers are flammable and explosive compounds, making them unsuitable for industrial production.

[0404] Therefore, the method of this application links two or more mononuclear Salen catalysts represented by formula (II) by means of a group containing -NH-C(O)-, and the Salen catalyst prepared can improve its recovery rate, resolution yield, or activity after resolution and recovery.

[0405] Methods for resolving terminal epoxides

[0406] In a sixth aspect of this application, a method for resolving terminal epoxide compounds is provided. According to embodiments of this application, the method includes: performing a resolution reaction using the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, to obtain the resolved epoxide compound.

[0407] According to an embodiment of this application, the splitting reaction is quenched by adding vitamin C.

[0408] According to embodiments of this application, the terminal epoxy compound is selected from propylene oxide, epibutylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl butyrate.

[0409] use

[0410] In a seventh aspect of this application, the application of the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, is proposed for the resolution of terminal epoxides.

[0411] According to an embodiment of this application, the splitting reaction is quenched by adding vitamin C.

[0412] According to embodiments of this application, the terminal epoxy compound is selected from propylene oxide, epibutylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl butyrate.

[0413] The following will explain the solution of this application with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of this application. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the art or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0414] Example 1: Preparation method of binuclear cyclic Salen cobalt catalyst E

[0415] The synthesis route is as follows:

[0416]

[0417]

[0418]

[0419]

[0420]

[0421] Step 1: Add 400 mL of DMF, 60 g of compound A1 (0.288 mol), and 55.24 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (i.e., EDCI, 0.288 mol) to a 1 L reaction flask in sequence. Stir at room temperature for 0.5 h. Then add 14.36 g of compound B1 (0.14 mol) and 1.8 g of DMAP (0.0147 mol) to the reaction solution in sequence. React at room temperature for 3.5 h. After the reaction is completed, filter the solution. Dissolve the filtrate in 1000 mL of water and extract with ethyl acetate. Concentrate the extract under reduced pressure and dry at 50 °C to obtain 120 g of compound A (yield 91.60%).

[0422] Step 2: Add 50g of compound A (0.11mol), 48.33g of compound B (0.22mol), 5g of potassium acetate (0.051mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 92.82g of compound C (yield 99.61%).

[0423] Step 3: Add 80g of compound C (0.0944mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃, and then add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and then dry at 50℃ to obtain 56.40g of compound D (yield 92.32%).

[0424] Step 4: Add 50g of compound D (0.0773mol), 35.13g of compound A (0.0773mol), 5g of potassium acetate (0.051mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat the mixture to 63℃ and keep it at that temperature for 5 hours to obtain a reaction solution containing ligand E'. Proceed directly to the next step.

[0425] Step 5: Add 27.44 g of cobalt acetate (0.155 mol) to the reaction solution in Step 4, and carry out the reaction at 63 °C for 4 h. After cooling to 20-30 °C, filter the solution, rinse the filter cake with a small amount of methanol, and dry it at 50 °C to obtain 89.63 g of compound E (yield 98.39%, relative to compound D).

[0426] Ligand E' of compound E: 1 H NMR (400 MHz, CDCl3): d = 0.99-1.05 (m, 8H), 1.13 (d, J= 8.0 Hz, 24H), 1.23-1.27 (m, 4H), 1.56-1.58 (m, 4H), 1.64-1.66 (m, 4H), 1.92-1.99 (m, 4H), 2.16-2.23 (m, 4H), 3.03-3.05 (m, 4H), 3.08-3.12(m, 4H),7.03 (s, 4H), 7.35 (s, 4H), 8.25 (s, 4H), 9.52 (s, 4H), 13.67 (s, 4H) ppm.

[0427] Compound E: MALDI-TOF-MS (ESI) + ): calcd for Co2C 62 H 77 N8O8[M+H] + 1179.4528, found 1179.4536.

[0428] Example 2: Preparation method of trinuclear cyclic Salen cobalt catalyst E2:

[0429] The synthesis route is as follows:

[0430] Step 1:

[0431] Step 2:

[0432] Step 3:

[0433] Step 4:

[0434] Step 5:

[0435] Step 6:

[0436] Step 7:

[0437] Step 8:

[0438] Steps 9 and 10:

[0439] Step 1: Add 200 mL of DMF, 30 g of compound A1 (0.144 mol), and 27.62 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.144 mol) to a 1 L reaction flask in sequence. Stir at room temperature for 0.5 h. Then add 36 g of compound B2 (0.173 mol) and 0.9 g of DMAP (0.007 mol) to the reaction solution in sequence. React at room temperature for 3.5 h. After the reaction is completed, filter the solution. Dissolve the filtrate in 600 mL of water and extract with ethyl acetate. Concentrate the extract under reduced pressure and dry at 50 °C to obtain 51.8 g of compound A2 (yield 90.25%).

[0440] Step 2: Add 50g of compound A2 (0.125mol), 32g of compound B (0.149mol), 15g of potassium acetate (0.153mol) and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 74.26g of compound C1 (yield 99.50%).

[0441] Step 3: Add 70g of compound C1 (0.118mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃, and then add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and then dry at 50℃ to obtain 55.67g of compound D1 (yield 95.62%).

[0442] Step 4: Add 55g of compound D1 (0.085mol), 20.1g of compound 1 (0.085mol), 9.1g of potassium acetate (0.093mol) and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 65.57g of compound D2 (yield 99.23%).

[0443] Step 5: Add 60g of compound D2 (0.084mol) and 200mL of acetic acid solution containing 33% hydrobromic acid to a 500mL reaction flask. Keep the mixture warm and stir at room temperature for 3h. After the reaction is complete, concentrate under reduced pressure to remove volatiles and concentrate to dryness to obtain 48.65g of solid compound D3 (yield 99.87%).

[0444] Step 6: Add 48g of compound D3 (0.083mol) to a 500mL reaction flask, then add 250mL of concentrated hydrochloric acid, heat to 70~80℃ and keep the temperature for 3h. After the reaction is complete, filter directly, rinse the filter cake with an appropriate amount of water and dry it at 100℃ to obtain 48.60g of compound D4 (yield 99.81%).

[0445] Step 7: Add 200ml NMP, 16g compound D4 (0.027mol), and 5.22g EDCI (0.027mol) to a 500mL reaction flask in sequence, stir at room temperature for 0.5h, then add 16g compound D4 (0.027mol) and 0.17g DMAP (0.0014mol) to the reaction solution in sequence, heat to 50~60℃ and keep the temperature for 3.5h, after the reaction is completed, cool to room temperature, filter, and the filter cake is ready for the next step.

[0446] Step 8: Add 200 mL of NMP and 5.22 g of EDCI (0.027 mol) to the filter cake from Step 7, stir at room temperature for 0.5 h, then add 16 g of compound D4 (0.027 mol) and 0.17 g of DMAP (0.0014 mol) to the reaction solution in sequence, heat to 50~60℃ and react for 3.5 h. After the reaction is completed, filter the mixture, and the filter cake is ready for the next step.

[0447] Step 9: Add 600 mL of NMP to the filter cake from Step 8, then add 5.22 g of EDCI (0.027 mol), stir at room temperature for 0.5 h, then add 0.17 g of DMAP (0.0014 mol), heat to 30~40℃ and keep the temperature for 5 h. After the reaction is complete, filter the filter cake for the next step.

[0448] Step 10: Add 200 mL of NMP and 14.34 g of cobalt acetate (0.081 mol) to the filter cake from Step 9, heat to 75-85 °C and react for 5 h, then cool to 20-30 °C, slowly add 300 mL of water, keep at around 20 °C for 1-2 h to crystallize, then filter, wash the filter cake with a small amount of methanol, and dry at 50-70 °C to obtain 47.04 g of compound E2 (yield 98.56%, relative to compound D4).

[0449] Compound E2: MALDI-TOF-MS (ESI) + ): calcd for Co3C 93 H 115 N 12 O 12 [M+H] + 1768.6725, found 1768.6731.

[0450] ICP test result: Anal. Calcd for Co3C 93 H 114 N 12 O 12: Co, 10.00%. Found: Co, 9.98%.

[0451] Example 3: Preparation method of chain-like binuclear Salen cobalt catalyst F

[0452] Step 1:

[0453] Step 2:

[0454] Step 3:

[0455] Step 4:

[0456] Step 5:

[0457] Step 1: Add 200 mL of DMF, 58.3 g of compound A1 (0.28 mol), and 55.24 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.288 mol) to a 1 L reaction flask in sequence. Stir at room temperature for 0.5 h. Then add 10.37 g of compound B3 (0.14 mol) and 0.88 g of DMAP (0.0072 mol) to the reaction solution in sequence. React at room temperature for 3.5 h. After the reaction is completed, filter the solution. Rinse the filter cake with a small amount of water and dry it at 50 °C to obtain 59.02 g of compound A3 (yield 92.7%).

[0458] Step 2: Add 55g of compound A3 (0.121mol), 62.24g of compound B (0.29mol), 14.25g of potassium acetate (0.145mol) and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 99.77g of compound C2 (yield 97.33%).

[0459] Step 3: Add 90g of compound C2 (0.106mol) and 400mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃, and then add 500mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and then dry at 50℃ to obtain 66.35g of compound C3 (yield 96.54%).

[0460] Step 4: Add 65g of compound C3 (0.1mol), 41.6g of compound A1 (0.2mol), 9.86g of potassium acetate (0.1mol) and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 101.93g of compound C4 (yield 98.75%).

[0461] Step 5: Add 400 mL of NMP, 80 g of compound C4 (0.078 mol), and 27.62 g of cobalt acetate (0.156 mol) sequentially to a 1 L reaction flask. Heat to 75-85 °C and react for 5 h. Then cool to 20-30 °C and slowly add 500 mL of water. Keep the mixture at around 20 °C for 1-2 h to allow crystals to precipitate. Filter the mixture, wash the filter cake with a small amount of methanol, and dry it at 50-70 °C to obtain 86.98 g of compound F (yield 97.88%).

[0462] Ligand C4 of compound F: 1 H NMR (400 MHz, CDCl3): d = 1.01-1.06 (m, 4H), 1.30 (d, J = 8.0 Hz, 24H), 1.52-1.56(m, 2H), 1.62-1.66(m, 4H), 1.79-1.81(m,4H), 1.83-1.96(m, 4H), 2.12-2.19 (m, 4H), 3.09-3.13(m, 4H), 3.25-3.33(m, 4H), 7.90(s,2H), 8.1(s, 2H), 8.21-8.25(m, 2H), 8.27-8.31(m, 2H), 8.35(s, 2H), 8.37(s,2H), 9.50(s, 2H), 12.74(s, 2H), 13.75(s, 4H).

[0463] Compound F: MALDI-TOF-MS (ESI) + ): calcd for Co2C 59 H 71 N6O 10 [M+H] + 1141.3896, found 1141.378.

[0464] Example 4: Preparation method of chain-like binuclear Salen cobalt catalyst F1:

[0465] The synthesis route is as follows:

[0466]

[0467]

[0468]

[0469]

[0470] Step 1: Add 50.00g of compound 1 (0.212mol), 47.62g of compound B (0.222mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 90.58g of intermediate product compound 3 (yield 98.95%).

[0471] Step 2: Add 80g of intermediate compound 3 (0.185mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃ or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and dry at 50℃ to obtain 57.56g of intermediate compound 4 (yield 93.62%).

[0472] Step 3: Add 50g of intermediate compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 89.05g of intermediate compound 6 (yield 97.42%).

[0473] Step 4: Add 80g of intermediate compound 6 (0.135mol) to a 500mL reaction flask, then add 300mL of concentrated hydrochloric acid, heat to 70~80℃ and keep the temperature for 3h. After the reaction is completed, filter directly, rinse the filter cake with an appropriate amount of water and dry it at 100℃ to obtain 65.34g of intermediate compound 7 (yield 96.59%).

[0474] Step 5: Add 50g of intermediate compound 7 (0.1mol) and 5g of DMAP (0.041mol) to a 500mL reaction flask, then add 600mL of NMP. After the addition is complete, heat to 40℃ and maintain the temperature for 4 hours. After the reaction is complete, filter the mixture and use the filter cake for the next step.

[0475] Step 6: Add 200 mL of NMP and 17.7 g of cobalt acetate (0.1 mol) to the filter cake from Step 5, keep warm at 75-85 °C for 5 h, then cool down to 20-30 °C, slowly add 100 mL of water, keep warm at around 20 °C for 1-2 h to crystallize, then filter, wash the filter cake with a small amount of methanol, and dry at 50-70 °C to obtain 50.04 g of compound F1 (yield 98.94%).

[0476] Ligand 8 of chemical F1: 1 H NMR (400 MHz, CDCl3): d = 1.14-1.54(m, 24H), 1.54-1.58 (m, 4H), 1.62-1.66 (m, 4H), 1.90-1.96 (m, 4H), 2.19-2.24(m, 4H), 3.03-3.06 (m, 4H), 3.08-3.15 (m, 4H), 6.61(s, 1H), 6.80(s, 1H), 7.26(s, 2H), 7.59(s, 1H), 7.78(s, 1H), 8.09(s, 1H), 8.20(s, 4H), 8.22(s, 1H), 8.27(s, 1H),8.40(s, 1H), 10.32(s, 1H), 12.74(s, 1H), 13.64(s, 4H) ppm.

[0477] Chemical F1: MALDI-TOF-MS (ESI) + ): calcd for Co2C 54 H 65 N6O7[M+H] + 1027.3655, found 1027.375.

[0478] Example 5: Synthesis method of 4-core chain-like Salen cobalt catalyst F2:

[0479] Step 5:

[0480]

[0481] Step 6:

[0482] Step 7:

[0483] Step 1: Add 50.00g of compound 1 (0.212mol), 47.62g of compound B (0.222mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 90.63g of intermediate product compound 3 (yield 99.00%).

[0484] Step 2: Add 80g of intermediate compound 3 (0.185mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃ or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and dry at 50℃ to obtain 57.52g of intermediate compound 4 (yield 93.55%).

[0485] Step 3: Add 50g of intermediate compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 88.65g of intermediate compound 6 (yield 96.98%).

[0486] Step 4: Add 80g of intermediate compound 6 (0.135mol) to a 500mL reaction flask, then add 300mL of concentrated hydrochloric acid, heat to 70~80℃ and keep the temperature for 3h. After the reaction is completed, filter directly, rinse the filter cake with an appropriate amount of water and dry it at 100℃ to obtain 66.16g of intermediate compound 7 (yield 97.81%).

[0487] Step 5: Add 500 mL of NMP, 30 g of intermediate compound 7 (0.06 mol), and 11.46 g of EDCI (0.06 mol) to a 1 L reaction flask in sequence, stir at room temperature for 0.5 h, then add 30 g of intermediate compound 7 (0.06 mol) and 0.36 g of DMAP (0.003 mol) to the reaction solution in sequence, heat to 50~60℃ and keep the temperature for 3.5 h, after the reaction is completed, cool to room temperature, filter, and the filter cake is ready for the next step.

[0488] Step 6: Divide the filter cake from Step 5 into two equal portions. Add 200 mL of NMP and 5.73 g of EDCI (0.03 mol) to one portion of the filter cake and stir at room temperature for 0.5 h. Then add the other equal portion of the filter cake from Step 5 and 0.18 g of DMAP (0.0015 mol) to the reaction solution. Heat to 50-60 °C and maintain the temperature for 3.5 h. After the reaction is complete, cool to room temperature and filter. The filter cake is ready for the next step.

[0489] Step 7: Continue to add 200 mL of NMP and 10.62 g of cobalt acetate (0.06 mol) to the filter cake from Step 6, keep it at 75-85 °C for 4 h, then cool it down to 20-30 °C, slowly add 100 mL of water, keep it at around 20 °C for 1-2 h to crystallize, then filter, wash the filter cake with a small amount of methanol, and dry it at 50-70 °C to obtain 49.89 g of chain polynuclear catalyst compound F2 (yield 98.65%, n=2 in the structure of F2).

[0490] F2 compound information: MALDI-TOF-MS (ESI) + ): calcd for Co4C 108 H 128 O 13 ClN 12 [M+H] + 2071.6754, found 2071.6757.

[0491] ICP test result: Anal. Calcd for Co4C 108 H 127 O 13 ClN 12: Co, 11.37%. Found: Co, 11.29%.

[0492] Example 6: Synthesis method of 10-core chain-like Salen cobalt catalyst F3:

[0493] Step 5:

[0494] Step 6:

[0495] Step 7:

[0496] Step 8:

[0497] Step 1: Add 50.00g of compound 1 (0.212mol), 47.62g of compound B (0.222mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 89.92g of intermediate compound 3 (yield 98.23%).

[0498] Step 2: Add 80g of intermediate compound 3 (0.185mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃ or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and dry at 50℃ to obtain 57.87g of intermediate compound 4 (yield 94.12%).

[0499] Step 3: Add 50g of intermediate compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and keep the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 88.72g of intermediate compound 6 (yield 97.06%).

[0500] Step 4: Add 80g of intermediate compound 6 (0.135mol) to a 500mL reaction flask, then add 300mL of concentrated hydrochloric acid, heat to 70~80℃ and keep the temperature for 3h. After the reaction is complete, filter directly. Rinse the filter cake with an appropriate amount of water and dry it at 100℃ to obtain 66.07g of intermediate compound 7 (yield 97.68%).

[0501] Step 5: Add 500ml NMP, 24g intermediate compound 7 (0.05mol), and 9.17g EDCI (0.05mol) to a 1L reaction flask in sequence, stir at room temperature for 0.5h, then add 24g intermediate compound 7 (0.05mol) and 0.29g DMAP (0.0024mol) to the reaction solution in sequence, heat to 50~60℃ and keep the temperature for 3.5h, after the reaction is completed, cool to room temperature, filter, and the filter cake is ready for the next step.

[0502] Step 6: Divide the filter cake from Step 5 into two equal portions. Add 200 mL of NMP and 4.58 g of EDCI (0.024 mol) to one portion of the filter cake and stir at room temperature for 0.5 h. Then add the other equal portion of the filter cake from Step 5 and 0.14 g of DMAP (0.001 mol) to the reaction solution. Heat to 50-60 °C and maintain the temperature for 3.5 h. After the reaction is complete, cool to room temperature and filter. The filter cake is ready for the next step.

[0503] Step 7: Add 200 mL of NMP and 4.58 g of EDCI (0.024 mol) to the filter cake from Step 6, stir at room temperature for 0.5 h, then add 12 g of intermediate compound 7 (0.024 mol) and 0.14 g of DMAP (0.001 mol) to the reaction solution, heat to 50-60 °C and maintain the temperature for 3.5 h. After the reaction is complete, cool to room temperature and filter. The filter cake is ready for the next step.

[0504] Step 8: Continue to add 200 mL of NMP and 21.95 g of cobalt acetate (0.124 mol) to the filter cake from Step 7, keep warm at 75-85℃ for 4 h, then cool down to 20-30℃, slowly add 100 mL of water, keep warm at around 20℃ for 1-2 h to precipitate crystals, then filter, wash the filter cake with a small amount of methanol, and dry at 50-70℃ to obtain 50.11 g of chain polynuclear catalyst compound F3 (yield 99.07%, n=8 in the structure of F3).

[0505] F3 compound information: MALDI-TOF-MS (ESI) + ): calcd for Co 10 C 271 H 317 O 31 ClN 30 [M+H] + 5111.7218, found 5111.717.

[0506] ICP test result: Anal. Calcd for Co 10 C 271 H 316 O 31 ClN 30: Co, 11.53%. Found: Co, 11.48%.

[0507] Example 7: Synthesis method of binuclear chain-like Salen cobalt catalyst F4:

[0508] The synthesis route is as follows:

[0509] Step 1:

[0510] Step 2:

[0511] Step 3:

[0512] Step 4:

[0513] Step 5:

[0514] Step 6:

[0515] Step 1: Add 53g of compound 1' (0.212mol), 47.62g of compound B (0.222mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 91.84g of intermediate compound 3' (yield 97.12%).

[0516] Step 2: Add 80g of intermediate compound 3' (0.18mol) and 200mL of methanol to a 1L reaction flask, stir and cool to 0℃, then control the temperature to -5~5℃ or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition is complete, keep the reaction at -5℃~5℃ for 3h, then filter, wash the filter cake with a small amount of methanol, and dry at 50℃ to obtain 58.99g of intermediate compound 4' (yield 95.05%).

[0517] Step 3: Add 54g of intermediate compound 4' (0.156mol), 44g of compound 5' (0.150mol), 10g of potassium acetate (0.102mol), and 600mL of methanol to a 1L reaction flask in sequence. Heat to 63℃ and maintain the temperature for 5h. Then cool to 20℃ and filter. Wash the filter cake with a small amount of methanol and dry at 50℃ to obtain 90.34g of intermediate compound 6' (yield 96.86%).

[0518] Step 4: Add 80g of intermediate compound 6' (0.129mol) to a 500mL reaction flask, then add 300mL of concentrated hydrochloric acid, heat to 70~80℃ and keep the temperature for 3h. After the reaction is completed, filter directly, rinse the filter cake with an appropriate amount of water and dry it at 100℃ to obtain 70.61g of intermediate compound 7' (yield 98.33%).

[0519] Step 5: Add 60g of intermediate compound 7' (0.107mol) and 5g of DMAP (0.041mol) to a 500mL reaction flask, then add 600mL of NMP. After the addition is complete, heat to 40℃ and maintain the temperature for 4 hours. After the reaction is complete, filter the mixture to obtain the filter cake of ligand 8' for the next step.

[0520] Step 6: Add 200 mL of NMP and 19.03 g of cobalt acetate (0.107 mol) to the filter cake from Step 5, keep warm at 75-85 °C for 5 h, then cool down to 20-30 °C, slowly add 100 mL of water, keep warm at around 20 °C for 1-2 h to crystallize, then filter, wash the filter cake with a small amount of methanol, and dry at 50-70 °C to obtain 56.78 g of compound F4 (yield 97.54%).

[0521] Ligand 8' of chemical F4: 1 H NMR (400 MHz, CDCl3): d = 1.12-1.50(m, 36H), 1.54-1.58 (m, 4H), 1.62-1.66 (m, 4H), 1.90-1.96 (m, 4H), 2.19-2.24(m, 4H), 3.03-3.06 (m, 4H), 3.08-3.15 (m, 4H), 6.61(s, 1H), 6.80(s, 1H), 7.26(s, 2H), 7.59(s, 1H), 7.78(s, 1H), 8.09(s, 1H), 8.20(s, 4H), 8.22(s, 1H), 8.27(s, 1H),8.40(s, 1H), 10.32(s, 1H), 12.74(s, 1H), 13.64(s, 4H) ppm.

[0522] Chemical F4: MALDI-TOF-MS (ESI) + ): calcd for Co2C 54 H 77 N6O7[M+H] + 1084.1283, found 1084.1277.

[0523] The mononuclear catalysts in Examples 8, 9, and 10 below were all prepared using conventional techniques existing in the art, and the structures of these mononuclear catalysts are as follows:

[0524]

[0525] The NMR data of the prepared mononuclear catalyst (before coordination) are as follows: 1 H NMR (400 MHz, CDCl3): d =1.30(s, 18H), 1.48-1.58 (m, 20H), 1.79 (d, J=4.0Hz , 2H), 1.93 (d, J=8.0Hz , 2H),2.01(d, J=12.0Hz , 2H), 3.34-3.38 (m, 2H), 7.03 (s, 2H), 7.35(s, 2H), 8.35(s, 2H), 13.75(s, 2H) ppm.

[0526] The prepared mononuclear catalyst HRMS (ESI) + ): calcd for CoC 36 H 55 N₂O₂[M+H] + 606.3596, found 606.3581.

[0527] Example 8: Preparation of S-epimylochloropropane from fresh catalyst, followed by preparation of L-cannellonitrile from S-epimylochloropropane.

[0528] 1. The experimental steps for resolving epichlorohydrin are as follows:

[0529] Eight reaction flasks were numbered 1, 2, 3, 4, 5, 6, 7, and 8. Epichlorohydrin (12 mol) was added sequentially, followed by mononuclear catalysts prepared using existing technology (12 mmol), catalyst E (3 mmol), catalyst E2 (2 mmol), catalyst F (3 mmol), catalyst F1 (3 mmol), F2 (1.5 mmol), catalyst F3 (0.6 mmol), and catalyst F4 (3 mmol). Glacial acetic acid (126 mmol) was then added to each flask, and the mixture was stirred. Water was slowly added dropwise under ice bath conditions. Water (6.8 mol) was added to reaction flask 1, and water (6.1 mol) was added to flasks 2-8 respectively. The addition was completed over approximately 30 minutes. After the addition was complete, the reaction flasks were transferred to a 25°C water bath, and air was slowly bubbled in while stirring. After a reaction period (6-22 hours), the optical rotation of the reaction solution was measured. The reaction was stopped when the optical rotation was above 33° (vitamin C can be added to quench the reaction). The reaction solution was distilled under reduced pressure at -0.09 MPa (within the range of -0.1 to -0.05 MPa), and the distillate below 90°C was collected. The organic phase in the distillate was separated to obtain S-epoxychloropropane. The distillation residue was cooled to room temperature and filtered. The filter cake was dried and recovered to obtain the catalyst, and the filtrate was the byproduct chloroglycerol.

[0530] The recovered catalyst can be directly added to the next batch of reaction, or it can be mixed with fresh catalyst in a certain proportion before being recovered.

[0531] 2. The experimental steps for preparing L-carnitine are as follows:

[0532] (1) 1 mol of each of the eight S-epoxychloropropanes prepared in step 1 was reacted with eight equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50℃ to obtain an L-quaternary ammonium salt reaction solution. 229 g of 30% sodium cyanide (0.7 mol pure) aqueous solution was added to the reaction solution and cyanidation was carried out at 30-70℃ to obtain a cyanide reaction solution.

[0533] (2) Add hydrochloric acid to the cyanide reaction solution obtained in step (1), perform activated carbon decolorization, filter, concentrate to remove water until the water content is 20-35wt% and the L-canonitrile content is 40-70wt%, filter while hot, cool the aqueous filtrate to 0-20℃ to crystallize, dry the L-canonitrile obtained by centrifugation to obtain the finished L-canonitrile, and test the HPLC purity of L-canonitrile.

[0534] The experimental results are shown in Table 1.

[0535] Table 1

[0536]

[0537] a: The ee value of pure S-epimercury propane refers to the ee value of the pure S-epimercury propane obtained from the fractionation.

[0538] Example 9: The recovered catalyst was mixed with fresh catalyst to prepare S-epimyl chloride, and then L-cannellonitrile was prepared from S-epimyl chloride.

[0539] 1. The experimental steps for resolving epichlorohydrin are as follows:

[0540] Epichlorohydrin (6 mol) was added sequentially to eight reaction flasks, followed by mononuclear catalysts prepared using existing techniques (6 mmol), catalyst E (1.5 mmol), catalyst E2 (1 mmol), catalyst F1 (1.5 mmol), catalyst F2 (0.75 mmol), catalyst F3 (0.3 mmol), and catalyst F4 (1.5 mmol), respectively. Each catalyst contained 50% fresh catalyst and 50% catalyst recovered from Example 8 (for example, catalyst E used in this example contained 50% fresh catalyst and 50% catalyst recovered from Example 8). Glacial acetic acid (63 mmol) was then added and stirred. Water was slowly added dropwise under an ice bath (3.4 mol of water was added to the reaction flask containing the catalyst prepared using existing techniques, and 3.05 mol of water was added to the other reaction flasks), with the addition completed over approximately 30 minutes. After the addition was complete, the reaction flasks were transferred to a 25°C water bath and air was slowly bubbled in while stirring. After reacting for a period of time (8-28 hours), the optical rotation of the reaction solution is measured. The reaction can be stopped when the optical rotation is above 33° (vitamin C can be added for quenching). The reaction solution is then distilled under reduced pressure at -0.09 MPa (within the range of -0.1 to -0.05 MPa), and the distillate below 90°C is collected. The organic phase in the distillate is separated to obtain S-epoxychloropropane. The distillate residue is cooled to room temperature and filtered. The filter cake is dried and recovered to obtain the catalyst, and the filtrate is the byproduct chloroglycerol.

[0541] The recovered catalyst can be directly added to the next batch of reaction, or it can be mixed with fresh catalyst in a certain proportion before being recovered.

[0542] 2. The experimental steps for preparing L-carnitine are as follows:

[0543] (1) 1 mol of each of the eight S-epoxychloropropanes prepared in step 1 was reacted with eight equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50℃ to obtain an L-quaternary ammonium salt reaction solution. 229 g of 30% sodium cyanide (0.7 mol pure) aqueous solution was added to the reaction solution and cyanidation was carried out at 30-70℃ to obtain a cyanide reaction solution.

[0544] (2) Add hydrochloric acid to the cyanide reaction solution obtained in step (1), perform activated carbon decolorization, filter, concentrate to remove water until the water content is 20-35wt% and the L-canonitrile content is 40-70wt%, filter while hot, cool the aqueous filtrate to 0-20℃ to crystallize, dry the L-canonitrile obtained by centrifugation to obtain the finished L-canonitrile, and test the HPLC purity of L-canonitrile.

[0545] The experimental results are shown in Table 2.

[0546] Table 2

[0547]

[0548] a: The ee value of pure S-epimercury propane refers to the ee value of the pure S-epimercury propane obtained from the fractionation.

[0549] Example 10: Preparation of S-epimylochloropropane using the recovered catalyst, followed by preparation of L-cannellonitrile from S-epimylochloropropane.

[0550] 1. The experimental steps for resolving epichlorohydrin are as follows:

[0551] Epichlorohydrin (3 mol) was added sequentially to eight reaction flasks, followed by the mononuclear catalyst (3 mmol), catalyst E (0.75 mmol), catalyst E2 (0.5 mmol), catalyst F (0.75 mmol), catalyst F1 (0.75 mmol), catalyst F2 (0.375 mmol), catalyst F3 (0.15 mmol), and catalyst F4 (0.75 mmol) recovered from Example 7, respectively. Glacial acetic acid (32 mmol) was then added to each flask, and the mixture was stirred. Water was slowly added dropwise over an ice bath (1.7 mol of water was added to the flask containing the catalyst prepared using existing techniques, and 1.53 mol of water was added to the other flasks), with the addition completed over approximately 30 minutes. After the addition was complete, the reaction flasks were transferred to a 25°C water bath, and air was slowly bubbled in while stirring. After a reaction period (6-25 h), the optical rotation of the reaction solution was measured. The reaction was stopped when the optical rotation was above 33°. The reaction solution was distilled under reduced pressure at -0.09 MPa (within the range of -0.1 to -0.05 MPa), and the distillate below 90°C was collected. The organic phase in the distillate was separated to obtain S-epoxychloropropane. The distillation residue was cooled to room temperature and filtered. The filter cake was dried and recovered to obtain the catalyst, and the filtrate was the byproduct chloroglycerol.

[0552] The recovered catalyst can be directly added to the next batch of reaction, or it can be mixed with fresh catalyst in a certain proportion before being recovered.

[0553] 2. The experimental steps for preparing L-carnitine are as follows:

[0554] (1) 1 mol of each of the eight S-epoxychloropropanes prepared in step 1 was reacted with eight equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50℃ to obtain an L-quaternary ammonium salt reaction solution. 229 g of 30% sodium cyanide (0.7 mol pure) aqueous solution was added to the reaction solution and cyanidation was carried out at 30-70℃ to obtain a cyanide reaction solution.

[0555] (2) Add hydrochloric acid to the cyanide reaction solution obtained in step (1), perform activated carbon decolorization, filter, concentrate to remove water until the water content is 20-35wt% and the L-canonitrile content is 40-70wt%, filter while hot, cool the aqueous filtrate to 0-20℃ to crystallize, dry the L-canonitrile obtained by centrifugation to obtain the finished L-canonitrile, and test the HPLC purity of L-canonitrile.

[0556] The experimental results are shown in Table 3.

[0557] Table 3

[0558]

[0559] a: The ee value of pure S-epimercury propane refers to the ee value of the pure S-epimercury propane obtained from the fractionation.

[0560] Example 11: Preparation of Salen manganese and Salen copper catalysts

[0561] The Salen ligands prepared in Examples 1-6 were complexed with metal Cu or Mn, respectively, to obtain Salen copper or Salen manganese catalysts, whose catalytic effects were basically the same as those of the Salen cobalt catalysts prepared in Examples 1-6.

[0562] This embodiment demonstrates some results as an example, as follows:

[0563] 1. Preparation of binuclear cyclic Salen manganese catalyst

[0564] A reaction solution containing ligand E' was prepared according to steps 1-4 in Example 1. 26.82 g of manganese acetate (0.155 mol) was added to the reaction solution, and the reaction was carried out at 63 °C for 4 h. After cooling to 20-30 °C, the mixture was filtered, the filter cake was washed with a small amount of methanol, and then dried at 50 °C to obtain 88.25 g of catalyst E-Mn (yield 97.54%, relative to compound D).

[0565] Compound E: MALDI-TOF-MS (ESI) + ): calcd forMn2C 62 H 77 N8O8[M+H] + 1171.4623, found 1171.4615.

[0566] 2. Preparation of binuclear chain-like Salen manganese catalyst

[0567] Ligand C4 was prepared according to steps 1-4 in Example 3. 400 mL of NMP, 80 g of compound C4 (0.078 mol), and 27 g of manganese acetate (0.156 mol) were added sequentially to a 1 L reaction flask. The mixture was heated to 75-85 °C and reacted for 5 h. Then, the temperature was lowered to 20-30 °C, and 500 mL of water was slowly added. The mixture was kept at around 20 °C for 1-2 h to allow crystallization. The mixture was then filtered, and the filter cake was washed with a small amount of methanol. The mixture was dried at 50-70 °C to obtain 85.27 g of catalyst F-Mn (yield 96.54%, relative to compound C4).

[0568] Compound F: MALDI-TOF-MS (ESI) + ): calcd for Mn2C 59 H 71 N6O 10 [M+H] + 1133.4521, found 1133.3958.

[0569] 3. Preparation of S-epoxychloropropane using binuclear cyclic or binuclear chain manganese Salen catalysts

[0570] Two reaction flasks, numbered 1 and 2, were filled with epichlorohydrin (6 mol) in each flask. Catalyst E-Mn (1.5 mmol) prepared in Example 10 was added to flask 1, and catalyst F-Mn (1.5 mmol) prepared in Example 11 was added to flask 2. Glacial acetic acid (63 mmol) was then added to each flask, and the mixture was stirred. Water (3.05 mol) was slowly added dropwise over an ice bath, completing the addition in approximately 30 minutes. After the addition was complete, the reaction flasks were transferred to a 25°C water bath, and air was slowly bubbled in while stirring. After a reaction period (6-12 h), the optical rotation of the reaction solution was measured. The reaction was stopped when the optical rotation was above 33° (vitamin C could be added to quench the reaction). The reaction solution was then distilled under reduced pressure at -0.09 MPa (within the range of -0.1 to -0.05 MPa). The distillate below 90°C was collected, and the organic phase in the distillate was separated to obtain S-epicochlorohydrin. The distillation residue was cooled to room temperature and filtered. The filter cake was dried and recovered to obtain the catalyst, and the filtrate was the byproduct chloroglycerol.

[0571] The recovered catalyst can be directly added to the next batch of reaction, or it can be mixed with fresh catalyst in a certain proportion before being recovered. The experimental results are shown in Table 4.

[0572] Table 4

[0573]

[0574] a: The ee value of pure S-epimercury propane refers to the ee value of the pure S-epimercury propane obtained from the fractionation.

[0575] The results of Examples 1-7 show that the catalysts and ligands prepared in this application are prepared under mild conditions and are suitable for industrial production. The results of Examples 8-11 show that the reaction time for fresh catalysts E, E2, F, F1, F2, F3, F4, E-Mn, and F-Mn in this application is 9-11 hours, with a resolution yield of over 48% and a catalyst recovery rate of over 97%. The results of Examples 8-10 show that the recovered catalysts E, E2, F, F1, F2, F3, and F4 in this application do not require activation treatment and can be used in combination with fresh catalysts or alone, with a reaction time of 14-20 hours, a resolution yield of over 48%, and a catalyst recovery rate of over 97%.

[0576] Therefore, it can be further explained that the catalyst of this application has a high recovery rate and excellent activity after recovery. Furthermore, the catalyst of this application has a short reaction time, high catalytic efficiency, and high separation yield in the reaction of resolving terminal epoxides.

[0577] Furthermore, by replacing B1 in Example 1 with equimolar amounts of methyldiamine, ethylenediamine, 1,4-butanediamine, 1,5-pentanediamine, 1,6-hexanediamine, 1,7-heptanediamine, 1,8-octanediamine, 1,9-nonanediamine, and 1,10-decanediamine, the resulting binuclear cyclic catalyst exhibits essentially the same catalytic effect as catalyst E.

[0578] By controlling the temperature, amount of solvent, and rate of substrate addition in step 5 of Examples 3-5, the value of n in the chain structure can be controlled, resulting in chain polynuclear catalysts with different degrees of polymerization. Their catalytic effects are basically the same as those of catalysts F1, F2, and F3.

[0579] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0580] Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of this application.

Claims

1. A Salen catalyst ligand, characterized in that, It has the structure shown in equation (I): (I)； in, Empty or chemical bond; If empty, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-; For chemical bonds, -R1-R2- are selected from -C(O)-NH-C 1~10 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 Alkylene-NH-C(O)-; R4is selected from C 3~6 alkyl; n is any integer between 0 and 10.

2. A Salen catalyst, characterized in that, It has the structure shown in equation (I-1): (I-1)， Where M is selected from Co, Mn, or Cu; Empty or chemical bond; If empty, R1 is -COOH or -NH2, R2 is -COOH or -NH2, and R3 is selected from -NH-C(O)- or -C(O)-NH-C 1~10 Alkylene-NH-C(O)-; For chemical bonds, -R1-R2- are selected from -C(O)-NH-C 1~10 alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1~10 Alkylene-NH-C(O)-; R4is selected from C 3~6 alkyl; n is any integer between 0 and 10.

3. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, If empty, R3 is selected from -NH-C(O)-.

4. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, wherein R3 is selected from -C(O)-NH-C 2~6 Alkylene-NH-C(O)-.

5. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, wherein R3 is selected from -C(O)-NH(CH2)3-NH-C(O)-.

6. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, wherein R4 is selected from isopropyl or tert-butyl.

7. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, wherein n is 0, or n is any integer between 1 and 10.

8. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that, If empty, R1 and R2 are the same.

9. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that, If empty, R1 and R2 are different.

10. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that, For chemical bonds, -R1-R2- are selected from -C(O)-NH-C 1~6 Alkylene-NH-C(O)-.

11. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that, For chemical bonds, -R1-R2- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

12. The Salen catalyst ligand according to claim 1, characterized in that, The Salen catalyst ligand has the structure shown in formula (Ia1), formula (Ia2), formula (Ia3), or formula (Ia4): (Ia1), (Ia2) (Ia3) (Ia4), Where m is any integer between 1 and 10.

13. The Salen catalyst according to claim 2, characterized in that, The Salen catalyst has the structure shown in formula (Ib1), formula (Ib2), formula (Ib3), or formula (Ib4): (Ib1), (Ib2) (Ib3) (Ib4), Where m is any integer between 1 and 10.

14. The Salen catalyst ligand according to claim 1, characterized in that, The Salen catalyst ligand has any of the following structures: ， ， ， ， ， ， ， ， ， ， ， 。 15. The Salen catalyst according to claim 2, characterized in that, The catalyst has any of the following structures: ， ， ， ， ， ， ， ， ， ， ， ； ， ， ， ， ， ， ， ， ， ， ， ； ， ， ， ， ， ， ， ， ， ， ， 。 16. A method for preparing Salen catalyst ligands, characterized in that, include: Compound I-1 and compound I-2 were subjected to a first amidation reaction to obtain compound I-3; Compound I-3 and compound I-4 were subjected to a first condensation reaction to obtain compound I-5; Compound I-5 was subjected to a first deBOC reaction to obtain compound I-6; The compounds I-6 and I-3 were subjected to a second condensation reaction to obtain Salen catalyst ligand Ia2. (I-1)、 (I-2)、 (I-3)、 (I-4)、 (I-5)、 (I-6)、 (Ia2); Where m is any integer between 1 and 10; R4 is selected from C 3~6 alkyl.

17. The method according to claim 16, characterized in that, The condensing agent for the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

18. The method according to claim 16, characterized in that, The catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

19. The method according to claim 16, characterized in that, The organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

20. The method according to claim 16, characterized in that, The catalyst in the first condensation reaction and / or the second condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

21. The method according to claim 16, characterized in that, The organic solvent in the first condensation reaction and / or the second condensation reaction is selected from at least one of methanol and ethanol.

22. The method according to claim 16, characterized in that, The reaction temperature of the first condensation reaction and / or the second condensation reaction is 40℃~70℃.

23. The method according to claim 16, characterized in that, The reaction time for the first condensation reaction and / or the second condensation reaction is 4h to 8h.

24. The method according to claim 16, characterized in that, In the first condensation reaction, the molar ratio of compound I-3 to compound I-4 is 1.0:(1.0~1.2).

25. The method according to claim 16, characterized in that, In the second condensation reaction, the molar ratio of compound I-6 to compound I-3 is (1.0~1.2):1.

0.

26. The method according to claim 16, characterized in that, The first BOC removal reaction is carried out in an acidic environment.

27. The method according to claim 16, characterized in that, The organic solvent for the first BOC removal reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

28. A method for preparing Salen catalyst ligands, characterized in that, include: Compound I-1 and compound I-2 were subjected to a first amidation reaction to obtain compound I-3; Compound I-3 and compound I-4 were subjected to a first condensation reaction to obtain compound I-5; Compound I-5 was subjected to a first deBOC reaction to obtain compound I-6; The compound I-6 and compounds I-R1 and I-R2 were subjected to a second condensation reaction to obtain Salen catalyst ligand Ia3; (I-1)、 (I-2)、 (I-R1)、 (I-R2)、 (I-3)、 (I-4)、 (I-5)、 (I-6)、 (Ia3); Where m is any integer between 1 and 10; R1 is -COOH or -NH2, and R2 is -COOH or -NH2; R4 is selected from C 3~6 alkyl.

29. The method according to claim 28, characterized in that, The condensing agent for the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

30. The method according to claim 28, characterized in that, The catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinylpyridine, and 1-hydroxybenzotriazole.

31. The method according to claim 28, characterized in that, The organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

32. The method according to claim 28, characterized in that, The catalyst in the first condensation reaction and / or the second condensation reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

33. The method according to claim 28, characterized in that, The organic solvent in the first condensation reaction and / or the second condensation reaction is selected from at least one of methanol and ethanol.

34. The method according to claim 28, characterized in that, The reaction temperature of the first condensation reaction and / or the second condensation reaction is 40℃~70℃.

35. The method according to claim 28, characterized in that, The reaction time for the first condensation reaction and / or the second condensation reaction is 4h to 8h.

36. The method according to claim 28, characterized in that, In the first condensation reaction, the molar ratio of compound I-3 to compound I-4 is 1.0:(1.0~1.2).

37. The method according to claim 28, characterized in that, In the second condensation reaction, the molar ratio of compound I-6 to compounds I-R1 and I-R2 is (1.0~1.2):1.0:1.

0.

38. The method according to claim 28, characterized in that, The first BOC removal reaction is carried out in an acidic environment.

39. The method according to claim 28, characterized in that, The organic solvent for the first BOC removal reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

40. A method for preparing the Salen catalyst according to any one of claims 2 to 11, 13, and 15, characterized in that, include: The Salen catalyst ligand according to any one of claims 1, 3 to 12, 14 is subjected to a complexation reaction to obtain the Salen catalyst.

41. A method for resolving terminal epoxide compounds, characterized in that, include: The terminal epoxide compound is resolved by using the Salen catalyst according to any one of claims 2 to 11, 13, and 15 to obtain the resolved epoxide compound; The terminal epoxy compound is selected from propylene oxide, butane oxide, epichlorohydrin, chlorobutylene oxide, benzyl glycidyl ether, and glycidyl butyrate.

42. The method according to claim 41, characterized in that, The splitting reaction was quenched by the addition of vitamin C.

43. The use of the Salen catalyst according to any one of claims 2 to 11, 13, and 15 in the resolution of terminal epoxides; The terminal epoxy compound is selected from propylene oxide, butane oxide, epichlorohydrin, chlorobutylene oxide, benzyl glycidyl ether, and glycidyl butyrate.

44. The application according to claim 43, characterized in that, The resolution reaction of the terminal epoxide compound is quenched by adding vitamin C.

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