Multi-core Salen catalyst and preparation method and application thereof

Abstract

The invention discloses a Salen catalyst. The Salen catalyst has a structure as shown in a formula (I-1). The Salen catalyst is a multi-core catalyst, two or more mononuclear catalysts can be connected into the multi-core catalyst through groups containing amido bonds, the catalytic efficiency, the resolution yield, the recovery rate and the activity after recovery of the catalyst can be improved, and the recovered catalyst can be mixed with a fresh multi-core catalyst for use; and the method still has the advantages of high resolution yield and the like, and can be recycled for multiple times. Besides, when the multinuclear catalyst participates in the resolution reaction, excessive water is not needed, the reaction yield can be increased, the time for splitting the terminal epoxy compound can be shortened, the prepared product is high in purity and few in impurity, and the problems that the final product is difficult to purify and the like can be solved. # imgabs0 #

Description

Technical Field

[0001] The present application belongs to the technical field of organic compounds, and specifically relates to a multi-nuclear Salen catalyst and a preparation method and application thereof. Background Art

[0002] Chiral chemistry is the science of studying molecular chirality, that is, the existence of non-superposable mirror image isomers in molecular structures. In medicinal chemistry, different enantiomers of chiral molecules may have completely different biological activities, so the synthesis and separation of chiral compounds have important scientific and industrial significance. Among them, epichlorohydrin is an important organic compound that is widely used in the synthesis of various drugs, pesticides and fine chemicals. Due to the presence of its chiral center, the enantiomers of epichlorohydrin have different biological activities and application values.

[0003] Salen catalyst plays an important role in chiral synthesis due to its structural adjustability and catalytic activity. In particular, for the kinetic resolution of chiral terminal epoxides such as epichlorohydrin, Salen catalyst can efficiently catalyze the generation of products with high optical purity. Summary of the invention

[0004] Although existing Salen catalysts have shown good performance in certain chiral syntheses, they usually have some limitations, such as low catalytic efficiency, long reaction time, and difficult to control catalyst activity, leading to overreaction; the raw materials for preparing the catalyst are not easy to obtain, the reaction conditions are harsh and require nitrogen protection, and strict control of anhydrous and oxygen-free, which is not suitable for industrial production; the catalyst needs to be further activated before recycling, resulting in high costs.

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

[0006] The present application aims to solve at least one of the technical problems existing in the prior art to a certain extent. To this end, the present application provides a multi-nuclear Salen catalyst.

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

[0008] At present, industrial production mostly uses mononuclear catalysts, which have the following problems:

[0009] 1. When using the mononuclear catalyst in the prior art, after the catalytic reaction is completed, the catalyst is recovered. When the catalyst is recovered after use, the filtration resistance is very large, so the recovery rate is not high, only about 60%.

[0010] 2. Using the mononuclear catalyst in the prior art, the yield of S-epichlorohydrin is about 40%, not exceeding 43%.

[0011] 3. The subsequent product "L-carnitine" is prepared from S-epichlorohydrin obtained after splitting by the existing technology. The product contains many by-products and needs to be purified at multiple stages to obtain pure carnitine. The purification route is complicated.

[0012] At present, the binuclear catalysts that have been disclosed also have certain limitations. For example: CN114146731A discloses an oligomeric binuclear MOFs-type epichlorohydrin kinetic splitting catalyst and its synthesis method. During the splitting, 2.824 equivalents of water are added, which easily leads to overreaction and low catalyst recovery rate. CN113856762A discloses a high-polymer Salen trivalent cobalt catalyst, which requires toluene as a solvent and expensive tetrabutylammonium iodide as a catalyst when preparing intermediates, which is not suitable for industrial production; and its splitting yield is less than 43%, which is not superior to the splitting yield of the mononuclear Salen cobalt catalyst; in addition, after the catalyst is used, the cobalt changes from trivalent to divalent, and when it is recycled, it needs to be activated first, and the recovery steps are complicated.

[0013] However, the multi-nuclear catalyst of the present application can shorten the reaction time, improve the catalytic efficiency, improve the splitting yield, the splitting reaction degree is better controlled, the catalyst recovery rate is improved, and the recovered catalyst can be used directly and still maintains a high catalytic activity. In addition, the preparation method of the multi-nuclear catalyst is simple, the reaction conditions are mild, no halogen is required for halogenation reaction, no hazardous reagents and solvents are required, and it is more suitable for industrial production.

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

[0015]

[0016] in, is empty or a chemical bond;

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

[0018] is a chemical bond, -R1-R2- is selected from a group comprising -NH-C(O)-;

[0019] R3 is selected from a group comprising -NH-C(O)-;

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

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

[0022] In this article, no special instructions are required. Empty, representing There is nothing.

[0023] The Salen catalyst ligand of the present application can be used to prepare a multi-nuclear catalyst. The prepared multi-nuclear catalyst can shorten the reaction time of splitting terminal epoxy compounds, improve the catalytic efficiency, improve the splitting yield, and improve the recovery rate of the catalyst and the activity after recovery.

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

[0025]

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

[0027] is empty or a chemical bond;

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

[0029] is a chemical bond, -R1-R2- is selected from a group comprising -NH-C(O)-;

[0030] R3 is selected from a group comprising -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 the present application is a multi-nuclear catalyst, which can shorten the reaction time for splitting terminal epoxy compounds, improve the catalytic efficiency, improve the splitting yield, and improve the recovery rate of the catalyst and the activity after recovery.

[0034] According to an embodiment of the present application, M is selected from Co, Mn, and Cu.

[0035] According to an embodiment of the present 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 an embodiment of the present application, R3 is selected from -NH-C(O)-, or -C(O)-NH-C 1～10 Alkylene-NH-C(O)-.

[0037] According to an embodiment of the present application, R3 is selected from -C(O)-NH-C 1～6 Alkylene-NH-C(O)-.

[0038] According to an embodiment of the present application, R3 is selected from -C(O)-NH-C 1～4 Alkylene-NH-C(O)-.

[0039] According to an embodiment of the present application, R3 is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

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

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

[0042] According to an embodiment of the present application, R4 is selected from isopropyl or tert-butyl.

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

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

[0045] According to an embodiment of the present application, is empty, R1 and R2 are the same or different.

[0046] According to an embodiment of the present application, Empty, R1 and R2 are the same.

[0047] According to an embodiment of the present application, Empty, R1 and R2 are different.

[0048] According to an embodiment of the present application, is a chemical bond, -R1-R2- is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-.

[0049] In this document, unless otherwise specified, "-R1-R2-" refers to the structure in which the R1 group and the R2 group are connected.

[0050] According to an embodiment of the present application, is a chemical bond, -R1-R2- is selected from -C(O)-NH-C 1～6 Alkylene-NH-C(O)-.

[0051] According to an embodiment of the present application, is a chemical bond, and -R1-R2- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

[0052] According to an embodiment of the present application, is a chemical bond, R3 is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-.

[0053] According to an embodiment of the present application, is a chemical bond, R3 is selected from -C(O)-NH-C 2～6 Alkylene-NH-C(O)-.

[0054] According to an embodiment of the present application, It is a chemical bond, -R1-R2- and R3 are the same.

[0055] According to an embodiment of the present application, is a chemical bond, -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 an embodiment of the present application, is a chemical bond, -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 an embodiment of the present application, is a chemical bond, 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 Alkylene -NH-C(O)-, -R1-R2- and R3 are the same.

[0058] According to an embodiment of the present application, is a chemical bond, 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 Alkylene -NH-C(O)-, -R1-R2- and R3 are the same.

[0059] According to an embodiment of the present application, is a chemical bond, when n is 1, -R1-R2- is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-, R3 is selected from -C(O)-NH-C 1～10Alkylene -NH-C(O)-, -R1-R2- and R3 are the same.

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

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

[0062] According to the embodiments of the present 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 are the same or different.

[0063] According to the embodiments of the present 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 are the same or different.

[0064] According to an embodiment of the present 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]

[0066]

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

[0068] According to an embodiment of the present application, the Salen catalyst described in the second aspect has a structure shown in Formula (Ib1), Formula (Ib2), Formula (Ib3) or Formula (Ib4):

[0069]

[0070]

[0071] Wherein m is any integer between 1 and 10.

[0072] According to an embodiment of the present application, in the structure represented by Formula (Ia3) or Formula (Ib3), R1 is H, -NH2 or -COOH, and R2 is H, -COOH or -NH2.

[0073] According to an embodiment of the present application, in the structure represented by formula (Ia3) or formula (Ib3), R1 and R2 are the same.

[0074] According to an embodiment of the present application, in the structure represented by formula (Ia3) or formula (Ib3), R1 and R2 are -COOH.

[0075] According to an embodiment of the present application, in the structure represented by formula (Ia3) or formula (Ib3), R1 and R2 are different.

[0076] According to an embodiment of the present application, in the structure represented by formula (Ia3) or formula (Ib3), R1 is -COOH, and R2 is -NH2.

[0077] According to an embodiment of the present application, the Salen catalyst ligand described in the first aspect has any structure as shown below:

[0078]

[0079]

[0080] According to an embodiment of the present application, the Salen catalyst described in the second aspect has any structure as shown below:

[0081]

[0082]

[0083]

[0084]

[0085]

[0086] When such catalysts are used to split terminal epoxy compounds, the reaction time can be further shortened, the catalytic efficiency can be improved, the splitting yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0087] In the third aspect of the present application, the present application proposes a method for preparing the Salen catalyst ligand described in the first aspect. According to an embodiment of the present application, the method comprises:

[0088] The Salen catalyst ligand is obtained by connecting two or more mononuclear Salen catalyst ligands represented by formula (II) through a group containing -NH-C(O)-;

[0089] The multi-nuclear Salen catalyst ligand is a ring structure or a chain structure;

[0090]

[0091] The preparation method of the present application is simple, and no flammable or explosive reagents or expensive reagents are required during the preparation process, which is more suitable for industrial production. In addition, the prepared Salen catalyst ligand can be used to prepare a Salen catalyst, and the prepared Salen catalyst has high catalytic efficiency, high separation yield, high catalyst recovery rate, and high activity after recovery.

[0092] According to an embodiment of the present application, the method described in the third aspect may further include at least one of the following technical features:

[0093] According to an embodiment of the present application, the group containing -NH-C(O)- is selected from -NH-C(O)-, or -C(O)-NH-C 1～10 Alkylene-NH-C(O)-.

[0094] According to an embodiment of the present application, the multi-nuclear Salen catalyst is a ring structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-C 1～6 Alkylene-NH-C(O)-.

[0095] According to an embodiment of the present application, the multi-nuclear Salen catalyst is a ring structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

[0096] According to an embodiment of the present application, the multi-nuclear Salen catalyst is 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)-.

[0097] According to an embodiment of the present application, the group containing -NH-C(O)- is obtained by subjecting -COOH and -NH2 to an amidation reaction.

[0098] According to an embodiment of the present application, the condensation agent for the amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0099] According to an embodiment of the present application, the catalyst for the amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0100] According to an embodiment of the present application, the organic solvent for the amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0101] According to an embodiment of the present application, the mononuclear Salen catalyst ligand represented by formula (II) is obtained by subjecting the structure represented by formula (IV) and the structure represented by formula (V) to a Schiff base reaction;

[0102]

[0103] According to an embodiment of the present application, the catalyst in the Schiff base reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine.

[0104] According to an embodiment of the present application, the organic solvent in the Schiff base reaction is selected from at least one of methanol and ethanol.

[0105] According to an embodiment of the present application, the reaction temperature of the Schiff base reaction is 60°C to 65°C.

[0106] According to an embodiment of the present application, the reaction time of the Schiff base reaction is 4 h to 6 h.

[0107] According to an embodiment of the present application, in the Schiff base reaction, the molar ratio of the structure represented by formula (IV) to the structure represented by formula (V) is 1.0:(0.5-1.5).

[0108] In the fourth aspect of the present application, the present application proposes a method for preparing the Salen catalyst described in the second aspect. According to an embodiment of the present application, the method comprises: subjecting the Salen catalyst ligand described in the first aspect, or the Salen catalyst ligand prepared according to the method described in the third aspect to a complex reaction to obtain the Salen catalyst. The preparation method of the present application is simple, and no flammable and explosive reagents or costly reagents are required during the preparation process, and is more suitable for industrial production.

[0109] In the fifth aspect of the present application, the present application proposes a method for splitting terminal epoxy compounds. According to an embodiment of the present application, the method comprises: using the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect to perform a splitting reaction to obtain the split epoxy compound.

[0110] In the sixth aspect of the present application, the present application proposes the use of the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, in the splitting of terminal epoxy compounds.

[0111] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through the practice of the present application. DETAILED DESCRIPTION

[0112] The embodiments of the present application are described in detail below. The embodiments described below are exemplary and are only used to explain the present application, and cannot be understood as limiting the present application.

[0113] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. Further, in the description of this application, unless otherwise specified, the meaning of "plurality" is two or more.

[0114] It should be noted that, for the structural formula and chemical formula in the examples or embodiments of the present application, the present application is intended to cover all substitutions, modifications and equivalent technical solutions, which are all within the scope of the present application as defined in the claims. Those skilled in the art should recognize that many methods and materials similar or equivalent to those described in the present application can be used to practice the present application. The present application is by no means limited to the methods and materials described in the present application. In the event that one or more of the combined documents, patents and similar materials are different from or contradictory to the present application (including but not limited to defined terms, term applications, described technologies, etc.), the present application shall prevail.

[0115] It should be further recognized that certain features of the present application, for clarity, are described in multiple independent embodiments or implementations, but may also be provided in combination in a single embodiment or implementation. Conversely, various features of the present application, for brevity, are described in a single embodiment or implementation, but may also be provided separately or in any suitable sub-combination.

[0116] Unless otherwise noted, the technical and scientific terms used in this application have the same meanings as commonly understood by those skilled in the art to which this application belongs. Unless otherwise noted, all patent publications cited in the entire disclosure of this application are incorporated herein by reference in their entirety.

[0117] The following definitions will apply to this application unless otherwise indicated. For the purposes of this application, chemical elements are defined according to the Periodic Table of the Elements, CAS version and Handbook of Chemicals, 75, th Ed, 1994. In addition, 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, and all of the content of this application is incorporated by reference.

[0118] In this document, the terms "include" or "comprising" are open expressions, that is, including the contents specified in the present application but not excluding other contents.

[0119] As used herein, the terms "optionally", "optional" or "optionally" generally mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0120] Herein, the compounds of the present application also include isotopically labeled compounds of the present application, which are identical to those described herein except for the fact that one or more atoms are replaced by atoms having an atomic mass or mass number different from the naturally occurring atomic mass or mass number.

[0121] In this document, the minimum and maximum carbon content of a hydrocarbon group is indicated by a prefix, for example, the prefix C a～b It means containing "a" to "b" carbon atoms. 1～n ” refers to a straight or branched saturated / unsaturated carbon chain containing 1, 2, 3, 4, 5, ... or n carbon atoms; further understand that “C 1～n " shall be interpreted as including any sub-ranges included therein, such as C 2～6 Including C 2～6 , C 2～5 , C 2～4 , C 2～3 , C 3～10 , C 3～6 , C 3～5 , C 3～4 , C 4～6 , C 4～5 .

[0122] As used herein, the term "alkyl" refers to a linear or branched saturated monovalent hydrocarbon group having carbon atoms.

[0123] As used herein, the term "alkylene" refers to a group formed by removing a hydrogen atom from an "alkyl" group.

[0124] As used herein, the term "-NH-C(O)-" or "-NH-C(=O)-" refers to an amide group, the structural formula of which is

[0125] The present application proposes a multi-nuclear Salen catalyst and a preparation method and application thereof, which will be described in detail below.

[0126] Salen catalyst ligand and Salen catalyst

[0127] In the first aspect of the present application, the present application proposes a Salen catalyst ligand. According to an embodiment of the present application, the Salen catalyst ligand has a ligand structure shown in formula (I):

[0128]

[0129] in, is empty or a chemical bond;

[0130] is empty, R1 is H, or -COOH, or -NH2, R2 is H, or -COOH, or -NH2;

[0131] is a chemical bond, -R1-R2- is selected from a group comprising -NH-C(O)-;

[0132] R3 is selected from a group comprising -NH-C(O)-;

[0133] R4 is selected from C 3～6 alkyl;

[0134] n is any integer between 0 and 10.

[0135] The Salen catalyst ligand of the present application can be used to prepare a multi-nuclear catalyst. The prepared multi-nuclear catalyst can shorten the reaction time of splitting terminal epoxy compounds, improve the catalytic efficiency, improve the splitting yield, and improve the recovery rate of the catalyst and the activity after recovery.

[0136] According to an embodiment of the present application, the Salen catalyst ligand has a structure shown in formula (Ia1):

[0137]

[0138] n is any integer between 0 and 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0139] In an optional embodiment of the present 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.

[0140] In an optional embodiment of the present 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.

[0141] In an optional embodiment of the present 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.

[0142] According to an embodiment of the present application, the Salen catalyst ligand has a structure shown in formula (Ia2):

[0143]

[0144] Wherein m is any integer between 1 and 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0145] Therefore, in the structure represented by the above formula (Ib2), the reaction time for splitting the terminal epoxy compound can be further shortened, the catalytic efficiency can be improved, the splitting yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0146] In an optional embodiment of the present 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.

[0147] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia2), R4 is selected from isopropyl or tert-butyl.

[0148] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia2), R4 is selected from isopropyl.

[0149] According to an embodiment of the present application, the Salen catalyst ligand has a structure shown in formula (Ia3):

[0150]

[0151] Wherein m is any integer between 1 and 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0152] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5. 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 are the same or different.

[0153] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5, 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.

[0154] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5. 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.

[0155] In an optional embodiment of the present 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.

[0156] In an optional embodiment of the present 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.

[0157] In an optional embodiment of the present 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.

[0158] According to an embodiment of the present application, the Salen catalyst ligand has a structure shown in formula (Ia4):

[0159]

[0160] Wherein m is any integer between 1 and 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0161] In an optional embodiment of the present 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.

[0162] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia4), R4 is selected from isopropyl.

[0163] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ia4), R4 is selected from tert-butyl.

[0164] In the second aspect of the present application, the present application proposes a Salen catalyst. According to an embodiment of the present application, the Salen catalyst has a structure shown in formula (I-1):

[0165]

[0166] Wherein, M is selected from Co, Mn, or Cu;

[0167] is empty or a chemical bond;

[0168] is empty, R1 is H, -COOH, or -NH2, R2 is H, -COOH, or -NH2;

[0169] is a chemical bond, -R1-R2- is selected from a group comprising -NH-C(O)-;

[0170] R3 is selected from a group comprising -NH-C(O)-;

[0171] R4 is selected from C 3～6 alkyl;

[0172] n is any integer between 0 and 10.

[0173] The Salen catalyst of the present application is a multi-nuclear catalyst. The present application first discovered that two or more mono-nuclear catalysts can be connected into a multi-nuclear catalyst (which can be a ring-shaped multi-nuclear catalyst or a chain-shaped multi-nuclear catalyst) through a group containing an amide bond, which can not only improve the catalytic efficiency, splitting yield, recovery rate and activity of the catalyst in splitting terminal epoxy compounds, but also can be used alone or mixed with fresh multi-nuclear catalysts after recovery, and still has the advantages of high splitting yield, and can be recycled and reused multiple times. In addition, when the multi-nuclear catalyst of the present application participates in the splitting reaction, it does not require excessive water, can improve the reaction yield, and can also shorten the time for splitting terminal epoxy compounds. The prepared product has high purity and few impurities, which can solve the problem of difficulty in purifying the final product.

[0174] The current binuclear catalysts are basically connected by ether structures, which cannot take into account the splitting yield, recovery rate and activity after recovery at the same time. When the splitting yield is high, its recovery rate and activity effect after recovery cannot be guaranteed; when the recovery rate is high, its activity effect after recovery cannot be guaranteed; and the reaction activity is difficult to control, which easily leads to overreaction. However, compared with the above binuclear catalysts, the multinuclear catalyst of the present application can simultaneously meet the advantages of high splitting yield (up to 48% and above), high recovery rate (up to 85% and above), high activity after recovery (the splitting yield after recovery can also reach 48% and above), and high purity of the prepared final product.

[0175] In this article, without special explanation, the bond between N and M (such as Co) in the Salen catalyst is a coordination bond.

[0176] According to an embodiment of the present application, in the Salen catalyst, n is 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between endpoint values.

[0177] According to an embodiment of the present application, the Salen catalyst has a structure shown in formula (Ib1):

[0178]

[0179] n is any integer between 0 and 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0180] Thus, in the structure represented by the above formula (Ib1), the reaction time for resolving the terminal epoxy compound can be further shortened, the catalytic efficiency can be improved, the resolution yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0181] In an optional embodiment of the present 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.

[0182] In an optional embodiment of the present 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.

[0183] In an optional embodiment of the present 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.

[0184] In an optional embodiment of the present application, M is selected from Co.

[0185] In an optional embodiment of the present application, M is selected from Mn.

[0186] In an optional embodiment of the present application, M is selected from Cu.

[0187] According to an embodiment of the present application, the Salen catalyst has a structure shown in formula (Ib2):

[0188]

[0189] Wherein m is any integer between 1 and 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0190] Therefore, in the structure represented by the above formula (Ib2), the reaction time for splitting the terminal epoxy compound can be further shortened, the catalytic efficiency can be improved, the splitting yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0191] In an optional embodiment of the present 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.

[0192] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib2), R4 is selected from isopropyl or tert-butyl.

[0193] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib2), R4 is selected from isopropyl.

[0194] In an optional embodiment of the present application, M is selected from Co.

[0195] In an optional embodiment of the present application, M is selected from Mn.

[0196] In an optional embodiment of the present application, M is selected from Cu.

[0197] According to an embodiment of the present application, the Salen catalyst has a structure shown in formula (Ib3):

[0198]

[0199] Wherein m is any integer between 1 and 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values;

[0200] R1, R2 and R4 are as defined in the first aspect of the invention summary of this application.

[0201] Therefore, in the structure represented by the above formula (Ib3), the reaction time for splitting the terminal epoxy compound can be further shortened, the catalytic efficiency can be improved, the splitting yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0202] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5, 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 are the same or different.

[0203] In an optional embodiment of the present 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.

[0204] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5. 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.

[0205] In an optional embodiment of the present 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.

[0206] In an optional embodiment of the present 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.

[0207] In an optional embodiment of the present 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.

[0208] In an optional embodiment of the present application, M is selected from Co.

[0209] In an optional embodiment of the present application, M is selected from Mn.

[0210] In an optional embodiment of the present application, M is selected from Cu.

[0211] According to an embodiment of the present application, the Salen catalyst has a structure shown in formula (Ib4):

[0212]

[0213] Wherein m is any integer between 1 and 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or any two values ​​therebetween as a range value between the endpoint values.

[0214] Therefore, in the structure represented by the above formula (Ib4), the reaction time for splitting the terminal epoxy compound can be further shortened, the catalytic efficiency can be improved, the splitting yield can be improved, and the recovery rate and activity of the catalyst after recovery can be improved.

[0215] In an optional embodiment of the present application, m is 1, 2, 3, 4 or 5, and in the structure shown in formula (Ib4), R4 is selected from isopropyl or tert-butyl.

[0216] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib4), R4 is selected from isopropyl.

[0217] In an optional embodiment of the present application, m is 1, 2, 3 or 4, and in the structure shown in formula (Ib4), R4 is selected from tert-butyl.

[0218] In an optional embodiment of the present application, M is selected from Co.

[0219] In an optional embodiment of the present application, M is selected from Mn.

[0220] In an optional embodiment of the present application, M is selected from Cu.

[0221] In one aspect of the present application, the present application provides a Salen catalyst composition. According to an embodiment of the present application, the Salen catalyst composition includes one or more of the above-mentioned Salen catalysts.

[0222] According to an embodiment of the present application, the Salen catalyst composition includes multiple structures represented by formula (Ib1).

[0223] In this article, "Salen catalyst composition includes multiple structures represented by formula (Ib1)" means that it simultaneously contains multiple structures represented by formula (Ib1) in which n=0, structure represented by formula (Ib1) in which n=1, structure represented by formula (Ib1) in which n=2, structure represented by formula (Ib1) in which n=3, structure represented by formula (Ib1) in which n=4, structure represented by formula (Ib1) in which n=5, structure represented by formula (Ib1) in which n=6, structure represented by formula (Ib1) in which n=7, structure represented by formula (Ib1) in which n=8, structure represented by formula (Ib1) in which n=9, and structure represented by formula (Ib1) in which n=10.

[0224] Method for preparing Salen catalyst

[0225] In the third aspect of the present application, the present application proposes a method for preparing the Salen catalyst ligand described in the first aspect. According to an embodiment of the present application, the method comprises:

[0226] Two or more mononuclear Salen catalyst ligands represented by formula (II) are connected by a group containing -NH-C(O)- to obtain a polynuclear Salen catalyst ligand;

[0227] The multi-nuclear Salen catalyst ligand is a ring structure or a chain structure;

[0228]

[0229] The preparation method of the present application is simple, and no flammable or explosive reagents or expensive reagents are required during the preparation process, which is more suitable for industrial production. In addition, the prepared Salen catalyst ligand can be used to prepare a Salen catalyst, and the prepared Salen catalyst has high catalytic efficiency, high separation yield, high catalyst recovery rate, and high activity after recovery.

[0230] In this article, "two or more mononuclear Salen catalysts of formula (II) are connected through a group containing -NH-C(O)-, and optionally complexed" means that the connection treatment is first performed to obtain the Salen catalyst of formula (I) described in the first aspect (the specific connection method is not limited and is within the scope of protection of this application). If a Salen catalyst of formula (I-1) is prepared, and then a complex reaction is performed based on the structure of formula (I), the Salen catalyst of formula (I-1) described in the first aspect is obtained.

[0231] In the fourth aspect of the present application, the present application proposes a method for preparing the Salen catalyst described in the second aspect. According to an embodiment of the present application, the method comprises: subjecting the Salen catalyst ligand described in the first aspect, or the Salen catalyst ligand prepared according to the method described in the third aspect, to a complex reaction to obtain the Salen catalyst.

[0232] The inventors of the present application have found that the current binuclear catalysts are all connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, it is difficult to separate the binuclear catalyst and the product due to the principle of like dissolves like. In addition, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0233] However, the Salen catalyst of the present application is connected by an amide-containing group, and no flammable and explosive reagents or expensive reagents are required in the preparation process, and the preparation method is simple and more suitable for industrial production. In addition, the prepared Salen catalyst has the advantages of shortening the reaction time of splitting terminal epoxy compounds, improving catalytic efficiency, improving splitting yield, improving catalyst recovery rate and improving activity after recovery.

[0234] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst ligand. According to an embodiment of the present application, the method comprises:

[0235] Compound I-1 and compound I-2 are subjected to a first amidation reaction to obtain compound I-3;

[0236] Compound I-3 and compound I-4 are subjected to a first condensation reaction to obtain compound I-5;

[0237] The compound I-5 is subjected to a first de-BOC reaction to obtain a compound I-6;

[0238] The compound I-6 and the compound I-3 are subjected to a second condensation reaction to obtain a compound Ia2 (i.e., a Salen catalyst ligand);

[0239]

[0240]

[0241] Wherein, m is any integer between 1 and 10;

[0242] R4 is selected from C 3～6 alkyl.

[0243] The inventors of the present application have found that the current binuclear catalysts are all connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, it is difficult to separate the binuclear catalyst and the product due to the principle of like dissolves like. In addition, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0244] However, the Salen catalyst of the present application is connected by constructing an amide group through a carboxyl group and an amine group, and no flammable and explosive reagents or expensive reagents are required in the preparation process, and the preparation method is simple and more suitable for industrial production. In addition, the prepared Salen catalyst has the advantages of shortening the reaction time of splitting terminal epoxy compounds, improving catalytic efficiency, improving splitting yield, improving catalyst recovery rate and improving activity after recovery.

[0245] It should be noted that the first condensation reaction and / or the second condensation reaction are both Schiff base reactions.

[0246] According to the embodiments of the present application, m and R4 refer to the definitions in the Salen catalyst described in the first aspect.

[0247] According to an embodiment of the present application, the condensation agent of the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0248] According to an embodiment of the present application, the catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0249] According to an embodiment of the present application, the organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0250] According to an embodiment of the present 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.

[0251] According to an embodiment of the present 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.

[0252] According to an embodiment of the present application, the reaction temperature of the first condensation reaction and / or the second condensation reaction is 40°C to 70°C.

[0253] According to an embodiment of the present application, the reaction time of the first condensation reaction and / or the second condensation reaction is 4 hours to 8 hours.

[0254] According to an embodiment of the present application, in the first condensation reaction, the molar ratio of the compound I-3 to the compound I-4 is 1.0:(1.0-1.2).

[0255] According to an embodiment of the present application, in the second condensation reaction, the molar ratio of the compound I-6 to the compound I-3 is (1.0-1.2):1.0.

[0256] According to an embodiment of the present application, the first de-BOC reaction is carried out in an acidic environment.

[0257] According to an embodiment of the present application, the organic solvent of the first de-BOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0258] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst. According to an embodiment of the present application, the method comprises: adding a divalent metal salt to a compound Ia2 to perform a first complexation reaction to obtain a compound Ib2 (i.e., a Salen catalyst);

[0259]

[0260] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0261] M is selected from Co, Mn, or Cu.

[0262] According to an embodiment of the present application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0263] According to an embodiment of the present application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0264] According to an embodiment of the present application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0265] According to an embodiment of the present application, the reaction temperature of the first complexing reaction is 60°C to 65°C.

[0266] According to an embodiment of the present application, the reaction time of the first complexation reaction is 3 h to 5 h.

[0267] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst ligand. According to an embodiment of the present application, the method comprises:

[0268] Compound I-1 and compound I-2 are subjected to a first amidation reaction to obtain compound I-3;

[0269] Compound I-3 and compound I-4 are subjected to a first condensation reaction to obtain compound I-5;

[0270] The compound I-5 is subjected to a first de-BOC reaction to obtain a compound I-6;

[0271] The compound I-6 and the compounds I-R1 and I-R2 are subjected to a second condensation reaction to obtain a compound Ia3 (i.e., a Salen catalyst ligand);

[0272]

[0273]

[0274] Wherein, m is any integer between 1 and 10;

[0275] R4 is selected from C 3～6 alkyl.

[0276] The inventors of the present application have found that the current binuclear catalysts are all connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, it is difficult to separate the binuclear catalyst and the product due to the principle of like dissolves like. In addition, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0277] However, the Salen catalyst of the present application is connected by constructing an amide-containing group through a carboxyl group and an amine group, and no flammable and explosive reagents or expensive reagents are required in the preparation process, and the preparation method is simple and more suitable for industrial production. In addition, the prepared Salen catalyst has the advantages of shortening the reaction time of splitting terminal epoxy compounds, improving catalytic efficiency, improving splitting yield, improving catalyst recovery rate and improving activity after recovery.

[0278] It should be noted that the first condensation reaction and / or the second condensation reaction are both Schiff base reactions.

[0279] According to the embodiments of the present application, R1, R2, R4 and m are defined as in the Salen catalyst described in the first aspect.

[0280] According to an embodiment of the present application, the condensation agent of the first amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0281] According to an embodiment of the present application, the catalyst for the first amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0282] According to an embodiment of the present application, the organic solvent for the first amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0283] According to an embodiment of the present 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.

[0284] According to an embodiment of the present 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.

[0285] According to an embodiment of the present application, the reaction temperature of the first condensation reaction and / or the second condensation reaction is 40°C to 70°C.

[0286] According to an embodiment of the present application, the reaction time of the first condensation reaction and / or the second condensation reaction is 4 hours to 8 hours.

[0287] According to an embodiment of the present application, in the first condensation reaction, the molar ratio of the compound I-3 to the compound I-4 is 1.0:(1.0-1.2).

[0288] According to an embodiment of the present application, in the second condensation reaction, the molar ratio of the compound I-6 and the compounds I-R1 and I-R2 is (1.0-1.2): 1.0:1.0.

[0289] According to an embodiment of the present application, the first de-BOC reaction is carried out in an acidic environment.

[0290] According to an embodiment of the present application, the organic solvent of the first de-BOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0291] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst. According to an embodiment of the present application, the method comprises: cooling compound Ia3, adding a divalent metal salt to the cooling product to perform a first complexation reaction, and obtaining compound Ib3 (i.e., Salen catalyst);

[0292]

[0293] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0294] M is selected from Co, Mn, or Cu.

[0295] According to an embodiment of the present application, the temperature of the cooling treatment is 15-25°C, for example, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C or a range therebetween.

[0296] According to an embodiment of the present application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0297] According to an embodiment of the present application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0298] According to an embodiment of the present application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0299] According to an embodiment of the present application, the reaction temperature of the first complexing reaction is 60°C to 65°C.

[0300] According to an embodiment of the present application, the reaction time of the first complexation reaction is 3 h to 5 h.

[0301] According to an embodiment of the present application, the solvent for the first complexation reaction is N-methylpyrrolidone.

[0302] In another aspect of the present application, the present application proposes a method for preparing a Salen catalyst ligand. According to an embodiment of the present application, the method comprises:

[0303] Compound I-7 and compound I-4 are subjected to a third condensation reaction to obtain compound I-8;

[0304] The compound I-8 is subjected to a second de-BOC reaction to obtain a compound I-9;

[0305] The compound I-9 and the compound I-10 are subjected to a fourth condensation reaction to obtain a compound I-11;

[0306] The compound I-11 is subjected to an acid hydrolysis reaction to obtain a compound I-12;

[0307] The compound I-12 is subjected to a second amidation reaction to obtain compound Ia1 (i.e., Salen catalyst ligand);

[0308]

[0309]

[0310] Wherein, R4 is selected from C 3～6 alkyl;

[0311] n is any integer between 0 and 10.

[0312] The inventors of the present application have found that the current binuclear catalysts are all connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, it is difficult to separate the binuclear catalyst and the product due to the principle of like dissolves like. In addition, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0313] However, the multi-core Salen catalyst of the present application is connected by constructing an amide group through a carboxyl group and an amino group, and no flammable and explosive reagents or expensive reagents are required in the preparation process, and the preparation method is simple and more suitable for industrial production. In addition, the prepared Salen catalyst has the advantages of shortening the reaction time of splitting terminal epoxy compounds, improving catalytic efficiency, improving splitting yield, improving catalyst recovery rate and improving activity after recovery.

[0314] It should be noted that the third condensation reaction and / or the fourth condensation reaction are both Schiff base reactions.

[0315] According to the embodiments of the present application, n and R4 are defined as in the Salen catalyst described in the first aspect.

[0316] According to an embodiment of the present 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.

[0317] According to an embodiment of the present 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.

[0318] According to an embodiment of the present application, the reaction temperature of the third condensation reaction and / or the fourth condensation reaction is 40°C to 70°C.

[0319] According to an embodiment of the present application, the reaction time of the third condensation reaction and / or the fourth condensation reaction is 4 h to 8 h.

[0320] According to an embodiment of the present application, in the third condensation reaction, the molar ratio of the compound I-7 to the compound I-4 is 1.0:(1.0-1.2).

[0321] According to an embodiment of the present application, in the fourth condensation reaction, the molar ratio of the compound I-9 to the compound I-10 is (1.0-1.2):1.0.

[0322] According to an embodiment of the present application, the second de-BOC reaction is carried out in an acidic environment.

[0323] According to an embodiment of the present application, the organic solvent of the second de-BOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0324] According to an embodiment of the present application, the first acid hydrolysis reaction is carried out under concentrated hydrochloric acid conditions.

[0325] According to an embodiment of the present application, the reaction temperature of the first acid hydrolysis reaction is 70°C to 80°C.

[0326] According to an embodiment of the present application, the reaction time of the first acid hydrolysis reaction is 2h to 4h.

[0327] According to an embodiment of the present application, the catalyst for the second amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0328] According to an embodiment of the present application, the organic solvent for the second amidation reaction is selected from at least one of N-methylpyrrolidone, N,N-dimethylformamide, and dichloromethane.

[0329] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst. According to an embodiment of the present application, the method comprises: adding a divalent metal salt to compound Ia1 to perform a second complexation reaction to obtain compound Ib1 (i.e., Salen catalyst);

[0330]

[0331] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0332] M is selected from Co, Mn, or Cu.

[0333] According to an embodiment of the present application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0334] According to an embodiment of the present application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0335] According to an embodiment of the present application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0336] According to an embodiment of the present application, the reaction temperature of the second complexing reaction is 60°C to 65°C.

[0337] According to an embodiment of the present application, the reaction time of the second complex reaction is 3h to 5h.

[0338] In another aspect of the present application, the present application proposes a method for preparing a Salen catalyst ligand. According to an embodiment of the present application, the method comprises:

[0339] Compound I-1 and compound I-2 are subjected to a third amidation reaction to obtain compound I-13;

[0340] Compound I-13 and compound I-4 are subjected to a fifth condensation reaction to obtain compound I-14;

[0341] The compound I-14 is subjected to a third de-BOC reaction to obtain a compound I-15;

[0342] The compound I-15 is subjected to a sixth condensation reaction with the compound I-7 to obtain a compound I-16;

[0343] The compound I-16 is subjected to a third de-Cbz reaction to obtain a compound I-17;

[0344] The compound I-17 is subjected to a second acid hydrolysis reaction to obtain a compound I-18;

[0345] The compound I-18 is subjected to a fourth amidation reaction twice to obtain a compound I-19;

[0346] The compound I-19 is subjected to a fifth amidation reaction to obtain a compound Ia4 (i.e., a Salen catalyst ligand);

[0347]

[0348]

[0349] Wherein, R4 is selected from C 3～6 alkyl;

[0350] m is any integer between 1 and 10.

[0351] The inventors of the present application have found that the current binuclear catalysts are all connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, it is difficult to separate the binuclear catalyst and the product due to the principle of like dissolves like. In addition, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0352] However, the multi-core Salen catalyst of the present application is connected by constructing an amide group through a carboxyl group and an amino group, and no flammable and explosive reagents or expensive reagents are required in the preparation process, and the preparation method is simple and more suitable for industrial production. In addition, the prepared Salen catalyst has the advantages of shortening the reaction time of splitting terminal epoxy compounds, improving catalytic efficiency, improving splitting yield, improving catalyst recovery rate and improving activity after recovery.

[0353] It should be noted that the fifth condensation reaction and / or the sixth condensation reaction are both Schiff base reactions.

[0354] According to the embodiments of the present application, m and R4 refer to the definitions in the Salen catalyst described in the first aspect.

[0355] According to an embodiment of the present application, the condensation agent of the third amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide.

[0356] According to an embodiment of the present application, the catalyst for the third amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0357] According to an embodiment of the present application, the organic solvent for the third amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone, and dichloromethane.

[0358] According to an embodiment of the present 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.

[0359] According to an embodiment of the present 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.

[0360] According to an embodiment of the present application, the reaction temperature of the fifth condensation reaction and / or the sixth condensation reaction is 40°C to 70°C.

[0361] According to an embodiment of the present application, the reaction time of the fifth condensation reaction and / or the sixth condensation reaction is 4 h to 8 h.

[0362] According to an embodiment of the present application, in the fifth condensation reaction, the molar ratio of the compound C3 to the compound I-4 is 1.0:(1.0-1.2).

[0363] According to an embodiment of the present application, in the sixth condensation reaction, the molar ratio of the compound I-15 to the compound I-7 is (1.0-1.2):1.0.

[0364] According to an embodiment of the present application, the third de-BOC reaction is carried out in an acidic environment.

[0365] According to an embodiment of the present application, the organic solvent of the third de-BOC reaction is selected from at least one of methanol, ethanol, ethyl acetate, and dioxane.

[0366] According to an embodiment of the present application, the third de-Cbz reaction is carried out in a hydrobromic acid and acetic acid system.

[0367] According to an embodiment of the present application, the second acid hydrolysis reaction is carried out under concentrated hydrochloric acid conditions.

[0368] According to an embodiment of the present application, the reaction temperature of the second acid hydrolysis reaction is 70°C to 80°C.

[0369] According to an embodiment of the present application, the reaction time of the second acid hydrolysis reaction is 2h to 4h.

[0370] According to an embodiment of the present 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-pyrrolidinopyridine, and 1-hydroxybenzotriazole.

[0371] According to an embodiment of the present application, the organic solvent of the fourth amidation reaction and / or the fifth amidation reaction is selected from at least one of N-methylpyrrolidone, N,N-dimethylformamide, and dichloromethane.

[0372] In one aspect of the present application, the present application proposes a method for preparing a Salen catalyst. According to an embodiment of the present application, the method comprises: adding a divalent metal salt to compound Ia4 to perform a third complexation reaction to obtain compound Ib4 (i.e., Salen catalyst);

[0373]

[0374] Wherein, the divalent metal salt is a divalent cobalt salt, a divalent manganese salt, or a divalent copper salt;

[0375] M is selected from Co, Mn, or Cu.

[0376] According to an embodiment of the present application, the divalent cobalt salt is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt carbonate.

[0377] According to an embodiment of the present application, the divalent manganese salt is selected from at least one of manganese acetate, manganese chloride, manganese sulfate, and manganese carbonate.

[0378] According to an embodiment of the present application, the divalent copper salt is selected from at least one of copper acetate, copper chloride, copper sulfate, and copper carbonate.

[0379] According to an embodiment of the present application, the reaction temperature of the third complexation reaction is 60°C to 65°C.

[0380] According to an embodiment of the present application, the reaction time of the third complexation reaction is 3h to 5h.

[0381] Method for improving the recovery rate, splitting yield, or activity after splitting and recovery of Salen catalyst

[0382] In a fifth aspect of the present application, the present application proposes a method for improving the recovery rate, splitting yield, or post-split activity of a Salen catalyst. According to an embodiment of the present application, the method comprises:

[0383] Two or more mononuclear Salen catalyst ligands represented by formula (II) are connected by a group containing -NH-C(O)-, and then a complex reaction is performed to obtain the multinuclear Salen catalyst;

[0384] The multi-nuclear Salen catalyst is a ring structure or a chain structure;

[0385]

[0386] The inventors of the present application have found that the cores of the binuclear catalysts in the prior art are connected by ether structures. Since the ether structure is similar to the epoxy structure of the product, the binuclear catalyst and the product are difficult to separate due to the principle of like dissolves like. Moreover, ethers are flammable and explosive compounds, which are flammable and explosive in the chemical production process and are not suitable for industrial production.

[0387] Thus, the method of the present application connects two or more mononuclear Salen catalysts represented by formula (II) through a group containing -NH-C(O)-, and the prepared Salen catalyst can improve its recovery rate, splitting yield, or activity after splitting and recovery.

[0388] Method for splitting terminal epoxy compounds

[0389] In the sixth aspect of the present application, the present application proposes a method for splitting terminal epoxy compounds. According to an embodiment of the present application, the method comprises: using the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect to perform a splitting reaction to obtain the split epoxy compound.

[0390] According to an embodiment of the present application, the resolution reaction is quenched by adding vitamin C.

[0391] According to an embodiment of the present application, the terminal epoxy compound is selected from propylene oxide, butylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl butyrate.

[0392] use

[0393] In the seventh aspect of the present application, the present application proposes the use of the Salen catalyst described in the second aspect, or the Salen catalyst prepared according to the method described in the fourth aspect, in the splitting of terminal epoxy compounds.

[0394] According to an embodiment of the present application, the resolution reaction is quenched by adding vitamin C.

[0395] According to an embodiment of the present application, the terminal epoxy compound is selected from propylene oxide, butylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl butyrate.

[0396] The scheme of the present application will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present application and should not be considered as limiting the scope of the present application. If no specific technology or conditions are indicated in the embodiments, the technology or conditions described in the literature in this area or the product specification are carried out. The reagents used or the instruments that do not indicate the manufacturer are all conventional products that can be obtained commercially.

[0397] Example 1: Preparation method of binuclear cyclic Salen cobalt catalyst E

[0398] The synthetic route is as follows:

[0399]

[0400]

[0401]

[0402] Step 1: Into a 1L reaction bottle, 400mL DMF, 60g compound A1 (0.288mol) and 55.24g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide) (i.e. EDCI, 0.288mol) were added in sequence, and stirred at room temperature for 0.5h. Then 14.36g compound B1 (0.14mol) and 1.8g DMAP (0.0147mol) were added in sequence to the reaction solution, and the reaction was carried out at room temperature for 3.5h. After the reaction was completed, the filtrate was filtered and dissolved in 1000mL water, and then extracted with ethyl acetate. The extract was concentrated under reduced pressure and dried at 50°C to obtain 120g compound A (yield 91.60%).

[0403] Step 2: Into a 1L reaction bottle, add 50g of compound A (0.11mol), 48.33g of compound B (0.22mol), 5g of potassium acetate (0.051mol), and 600mL of methanol in sequence, raise the temperature to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 92.82g of compound C (yield 99.61%).

[0404] Step 3: To a 1L reaction bottle, add 80g of compound C (0.0944mol) and 200mL of methanol in sequence, stir and cool to 0°C, then control the temperature to -5~5°C, then add 300mL of 4M hydrochloric acid / methanol solution dropwise, and after the addition, keep the reaction at -5°C~5°C for 3h, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 56.40g of compound D (yield 92.32%).

[0405] Step 4: Add 50 g of compound D (0.0773 mol), 35.13 g of compound A (0.0773 mol), 5 g of potassium acetate (0.051 mol), and 600 mL of methanol to a 1 L reaction bottle in sequence, heat to 63°C and react for 5 h to obtain a reaction solution containing ligand E' and proceed directly to the next step.

[0406] Step 5: Add 27.44 g of cobalt acetate (0.155 mol) to the reaction solution of step 4, carry out the reaction at 63°C for 4 h, cool to 20-30°C and filter, rinse the filter cake with a small amount of methanol, and dry at 50°C to obtain 89.63 g of compound E (yield 98.39%, relative to compound D).

[0407] Ligand E' of compound E: 1H NMR (400MHz, CDCl3): δ=0.99-1.05(m,8H),1.13(d,J=8.0Hz,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.

[0408] Compound E: MALDI-TOF-MS (ESI + ):calcd for Co2C 62 H 77 N8O8[M+H] + 1179.4528, found1179.4536.

[0409] Example 2: Preparation of trinuclear annular Salen cobalt catalyst E2:

[0410] The synthetic route is as follows:

[0411] Step 1: Step 2:

[0412]

[0413] Step 3: Step 4:

[0414]

[0415] Step 5:

[0416]

[0417] Step 6:

[0418]

[0419] Step 7:

[0420]

[0421] Step 8:

[0422]

[0423] Steps 9 and 10:

[0424] Step 1: Into a 1L reaction bottle, 200mL DMF, 30g compound A1 (0.144mol) and 27.62g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (EDCI, 0.144mol) were added in sequence, and the mixture was stirred at room temperature for 0.5h. Then, 36g compound B2 (0.173mol) and 0.9g DMAP (0.007mol) were added in sequence to the reaction solution, and the mixture was reacted at room temperature for 3.5h. After the reaction was completed, the mixture was filtered and the filtrate was dissolved in 600mL water, and then extracted with ethyl acetate. The extract was concentrated under reduced pressure and dried at 50°C to obtain 51.8g compound A2 (yield 90.25%).

[0425] Step 2: Into a 1L reaction bottle, add 50g of compound A2 (0.125mol), 32g of compound B (0.149mol), 15g of potassium acetate (0.153mol) and 600mL of methanol in sequence, raise the temperature to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 74.26g of compound C1 (yield 99.50%).

[0426] Step 3: Add 70 g of compound C1 (0.118 mol) and 200 mL of methanol to a 1 L reaction bottle, stir and cool to 0°C, then control the temperature to -5 to 5°C, then add 300 mL of 4 M hydrochloric acid / methanol solution dropwise, and after the addition, keep the reaction at -5 to 5°C for 3 h, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 55.67 g of compound D1 (yield 95.62%).

[0427] Step 4: Into a 1L reaction bottle, 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 in sequence, raise the temperature to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 65.57g of compound D2 (yield 99.23%).

[0428] Step 5: To a 500 mL reaction bottle, add 60 g of compound D2 (0.084 mol) and 200 mL of acetic acid solution containing 33% hydrobromic acid in sequence, and react with stirring at room temperature for 3 h. After the reaction, concentrate under reduced pressure to remove volatiles, and concentrate to dryness to obtain 48.65 g of solid compound D3 (yield 99.87%).

[0429] Step 6: Add 48 g of compound D3 (0.083 mol) and 250 mL of concentrated hydrochloric acid to a 500 mL reaction bottle, heat to 70-80 °C and react for 3 h. After the reaction is completed, filter directly, rinse the filter cake with appropriate amount of water and dry it at 100 °C to obtain 48.60 g of compound D4 (yield 99.81%).

[0430] Step 7: Add 200 ml NMP, 16 g compound D4 (0.027 mol) and 5.22 g EDCI (0.027 mol) to a 500 ml reaction bottle, stir at room temperature for 0.5 h, then add 16 g compound D4 (0.027 mol) and 0.17 g DMAP (0.0014 mol) to the reaction solution, heat to 50-60 ° C and keep the reaction for 3.5 h. After the reaction is completed, cool to room temperature and filter. The filter cake is used for the next step.

[0431] Step 8: Add 200 mL of NMP and 5.22 g of EDCI (0.027 mol) to the filter cake of 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°C and react for 3.5 h. After the reaction is completed, filter and the filter cake is ready for the next step.

[0432] Step 9: Add 600 mL of NMP to the filter cake in 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 ° C and react for 5 h. After the reaction is completed, filter and use the filter cake for the next step.

[0433] Step 10: Add 200 mL of NMP and 14.34 g of cobalt acetate (0.081 mol) to the filter cake of 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 warm at about 20 ° C for 1-2 h to crystallize, then filter, rinse 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).

[0434] Compound E2: MALDI-TOF-MS (ESI + ):calcdfor Co3C 93 H 115 N 12 O 12 [M+H] + 1768.6725, found1768.6731.

[0435] ICP test results: Anal.Calcd for Co3C 93 H 114 N 12 O 12: Co, 10.00%. Found: Co, 9.98%.

[0436] Example 3: Preparation of Chain Binuclear Salen Cobalt Catalyst F

[0437] Step 1:

[0438]

[0439] Step 2:

[0440]

[0441] Step 3:

[0442]

[0443] Step 4:

[0444]

[0445] Step 5:

[0446]

[0447] Step 1: Into a 1L reaction bottle, 200mL DMF, 58.3g compound A1 (0.28mol) and 55.24g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (EDCI, 0.288mol) were added in sequence, and stirred at room temperature for 0.5h. Then, 10.37g compound B3 (0.14mol) and 0.88g DMAP (0.0072mol) were added in sequence to the reaction solution, and the reaction was carried out at room temperature for 3.5h. After the reaction was completed, the mixture was filtered, and the filter cake was rinsed with a small amount of water and then dried at 50°C to obtain 59.02g compound A3 (yield 92.7%).

[0448] Step 2: Into a 1L reaction bottle, 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 in sequence, raise the temperature to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 99.77g of compound C2 (yield 97.33%).

[0449] Step 3: Add 90 g of compound C2 (0.106 mol) and 400 mL of methanol to a 1 L reaction bottle in sequence, stir and cool to 0°C, then control the temperature to -5 to 5°C, then add 500 mL of 4 M hydrochloric acid / methanol solution dropwise, and after the addition, keep the reaction at -5 to 5°C for 3 hours, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 66.35 g of compound C3 (yield 96.54%).

[0450] Step 4: Into a 1L reaction bottle, 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 in sequence, raise the temperature to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 101.93g of compound C4 (yield 98.75%).

[0451] Step 5: Into a 1L reaction bottle, add 400mL NMP, 80g compound C4 (0.078mol) and 27.62g cobalt acetate (0.156mol), heat to 75-85℃ and react for 5h, then cool to 20-30℃, slowly add 500mL of water, keep warm at about 20℃ for 1-2h to crystallize, then filter, rinse the filter cake with a small amount of methanol, and dry at 50-70℃ to obtain 86.98g of compound F (yield 97.88%).

[0452] Ligand C4 of compound F: 1 H NMR (400MHz, CDCl3): δ = 1.01-1.06 (m, 4H), 1.30 (d, J = 8.0Hz, 24H), 1.52-1.56 (m, 2 H),1.62-1.66(m,4H),1.79-1.81(m,4H),1.83-1.96(m,4H),2.12-2.19(m,4H),3.0 9-3.13(m,4H),3.25-3.33(m,4H),7.90(s,2H),8.1(s,2H),8.21-8.25(m,2H),8.2 7-8.31(m,2H),8.35(s,2H),8.37(s,2H),9.50(s,2H),12.74(s,2H),13.75(s,4H).

[0453] Compound F: MALDI-TOF-MS (ESI + ):calcd for Co2C 59 H 71 N6O 10 [M+H] + 1141.3896, found1141.378.

[0454] Example 4: Preparation of Chain Binuclear Salen Cobalt Catalyst F1:

[0455] The synthetic route is as follows:

[0456]

[0457]

[0458] Step 1: Into a 1L reaction bottle, 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 in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 90.58g of intermediate product compound 3 (yield 98.95%).

[0459] Step 2: Add 80g of intermediate product compound 3 (0.185mol) and 200mL of methanol to a 1L reaction bottle in sequence, stir and cool to 0°C, then control the temperature to -5~5°C or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition, keep the reaction at -5°C~5°C for 3h, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 57.56g of intermediate product compound 4 (yield 93.62%).

[0460] Step 3: Into a 1L reaction bottle, add 50g of intermediate product compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol in sequence, raise the temperature to 63°C and keep the reaction for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 89.05g of intermediate product compound 6 (yield 97.42%).

[0461] Step 4: Add 80 g of intermediate product compound 6 (0.135 mol) and 300 mL of concentrated hydrochloric acid to a 500 mL reaction bottle, heat to 70-80 ° C and react for 3 h. Filter directly after the reaction is completed. Rinse the filter cake with appropriate amount of water and dry it at 100 ° C to obtain 65.34 g of intermediate product compound 7 (yield 96.59%).

[0462] Step 5: Add 50 g of intermediate compound 7 (0.1 mol) and 5 g of DMAP (0.041 mol) to a 500 mL reaction bottle in sequence, and then add 600 ml of NMP. After the addition, heat to 40 ° C and keep warm for 4 hours. After the reaction is completed, filter and the filter cake will be used for the next step.

[0463] Step 6: Add 200 mL of NMP and 17.7 g of cobalt acetate (0.1 mol) to the filter cake of step 5, keep the temperature at 75-85 ° C for 5 h, then cool to 20-30 ° C, slowly add 100 mL of water, keep the temperature at about 20 ° C for 1-2 h to crystallize, then filter, rinse 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%).

[0464] Ligand 8 of chemical F1: 1 H NMR (400MHz, CDCl3): δ=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,1 H),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.

[0465] Chemical F1: MALDI-TOF-MS (ESI + ):calcd for Co2C 54 H 65 N6O7[M+H] + 1027.3655, found 1027.375.

[0466] Example 5: Synthesis of 4-nuclear chain-shaped Salen cobalt catalyst F2:

[0467] Step 5:

[0468]

[0469] Step 6: Step 7:

[0470]

[0471] Step 1: Into a 1L reaction bottle, 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 in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 90.63g of intermediate product compound 3 (yield 99.00%).

[0472] Step 2: Add 80g of intermediate product compound 3 (0.185mol) and 200mL of methanol to a 1L reaction bottle in sequence, stir and cool to 0°C, then control the temperature to -5~5°C or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition, keep the reaction at -5°C~5°C for 3h, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 57.52g of intermediate product compound 4 (yield 93.55%).

[0473] Step 3: Into a 1L reaction bottle, add 50g of intermediate product compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 88.65g of intermediate product compound 6 (yield 96.98%).

[0474] Step 4: Add 80 g of intermediate product compound 6 (0.135 mol) and 300 mL of concentrated hydrochloric acid to a 500 mL reaction bottle, heat to 70-80 ° C and react for 3 h. Filter directly after the reaction is completed. Rinse the filter cake with an appropriate amount of water and dry it at 100 ° C to obtain 66.16 g of intermediate product compound 7 (yield 97.81%).

[0475] Step 5: To a 1L reaction bottle, add 500mlNMP, 30g intermediate compound 7 (0.06mol) and 11.46gEDCI (0.06mol) in sequence, stir at room temperature for 0.5h, then add 30g intermediate compound 7 (0.06mol) and 0.36g DMAP (0.003mol) to the reaction solution in sequence, raise the temperature to 50-60℃ and keep the reaction for 3.5h, cool to room temperature after the reaction, filter and use the filter cake for the next step.

[0476] Step 6: Divide the filter cake from step 5 into two equal parts, add 200 mL of NMP and 5.73 g of EDCI (0.03 mol) to one of the filter cakes, stir at room temperature for 0.5 h, then add another equal part 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 keep the reaction for 3.5 h, cool to room temperature after the reaction is completed, filter, and the filter cake is ready for the next step.

[0477] Step 7: Continue to add 200 mL of NMP and 10.62 g of cobalt acetate (0.06 mol) to the filter cake of step 6, keep warm at 75-85 ° C for 4 hours, then cool to 20-30 ° C, slowly add 100 mL of water, keep warm at about 20 ° C for 1-2 hours to crystallize, then filter, rinse the filter cake with a small amount of methanol, and dry at 50-70 ° C to obtain 49.89 g of chain multi-nuclear catalyst compound F2 (yield 98.65%, n = 2 in the structure of F2).

[0478] F2 compound information: MALDI-TOF-MS (ESI + ):calcd for Co4C 108 H 128 O 13 C1N 12 [M+H] + 2071.6754, found 2071.6757.

[0479] ICP test results: Anal.Calcd for Co4C 108 H 127 O 13 C1N 12: Co,11.37%.Found:Co,11.29%.

[0480] Example 6: Synthesis of 10-nuclear chain Salen cobalt catalyst F3:

[0481] Step 5:

[0482]

[0483] Step 6:

[0484] Step 7:

[0485]

[0486] Step 8:

[0487]

[0488] Step 1: Into a 1L reaction bottle, 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 in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 89.92g of intermediate product compound 3 (yield 98.23%).

[0489] Step 2: Add 80g of intermediate product compound 3 (0.185mol) and 200mL of methanol to a 1L reaction bottle in sequence, stir and cool to 0°C, then control the temperature to -5~5°C or add 300mL of 4M hydrochloric acid / methanol solution dropwise. After the addition, keep the reaction at -5°C~5°C for 3h, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 57.87g of intermediate product compound 4 (yield 94.12%).

[0490] Step 3: Into a 1L reaction bottle, add 50g of intermediate product compound 4 (0.15mol), 41.9g of compound 5 (0.15mol), 10g of potassium acetate (0.102mol), and 600mL of methanol in sequence, raise the temperature to 63°C and keep the reaction for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 88.72g of intermediate product compound 6 (yield 97.06%).

[0491] Step 4: Add 80 g of intermediate product compound 6 (0.135 mol) and 300 mL of concentrated hydrochloric acid to a 500 mL reaction bottle, heat to 70-80 ° C and react for 3 h. Filter directly after the reaction is completed. Rinse the filter cake with appropriate amount of water and dry it at 100 ° C to obtain 66.07 g of intermediate product compound 7 (yield 97.68%).

[0492] Step 5: To a 1L reaction bottle, add 500mlNMP, 24g intermediate compound 7 (0.05mol) and 9.17gEDCI (0.05mol) 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, raise the temperature to 50-60℃ and keep the reaction for 3.5h, cool to room temperature after the reaction, filter and use the filter cake for the next step.

[0493] Step 6: Divide the filter cake from step 5 into two equal parts, add 200 mL of NMP and 4.58 g of EDCI (0.024 mol) to one of the filter cakes, stir at room temperature for 0.5 h, then add another equal part 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 keep the reaction for 3.5 h, cool to room temperature after the reaction is completed, filter, and the filter cake is ready for the next step.

[0494] Step 7: Add 200 mL NMP and 4.58 g EDCI (0.024 mol) to the filter cake of step 6, stir at room temperature for 0.5 h, then add 12 g intermediate compound 7 (0.024 mol) and 0.14 g DMAP (0.001 mol) to the reaction solution, heat to 50-60 ° C and keep warm for 3.5 h, cool to room temperature after the reaction, filter and wait for the next step.

[0495] Step 8: Continue to add 200 mL of NMP and 21.95 g of cobalt acetate (0.124 mol) to the filter cake of step 7, keep warm at 75-85 ° C for 4 hours, then cool to 20-30 ° C, slowly add 100 mL of water, keep warm at about 20 ° C for 1-2 hours to crystallize, then filter, rinse the filter cake with a small amount of methanol, and dry at 50-70 ° C to obtain 50.11 g of chain multi-nuclear catalyst compound F3 (yield 99.07%, n=8 in the structure of F3).

[0496] F3 compound information: MALDI-TOF-MS (ESI + ):calcd for Co 10 C 271 H 317 O 31 C1N 30 [M+H] + 5111.7218, found 5111.717.

[0497] ICP test results: Anal.Calcd for Co 10 C 271 H 316 O 31 C1N 30: Co,11.53%.Found:Co,11.48%.

[0498] Example 7: Synthesis of binuclear chain-like Salen cobalt catalyst F4:

[0499] The synthetic route is as follows:

[0500] Step 1:

[0501] Step 2:

[0502] Step 3:

[0503] Step 4:

[0504] Step 5:

[0505]

[0506] Step 6:

[0507]

[0508] Step 1: Into a 1L reaction bottle, add 53g of compound 1' (0.212mol), 47.62g of compound B (0.222mol), 10g of potassium acetate (0.102mol), and 600mL of methanol in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 91.84g of intermediate product compound 3' (yield 97.12%).

[0509] Step 2: Add 80 g of intermediate product compound 3' (0.18 mol) and 200 mL of methanol to a 1 L reaction bottle, stir and cool to 0°C, then control the temperature to -5 to 5°C or add 300 mL of 4M hydrochloric acid / methanol solution dropwise. After the addition, keep the reaction at -5 to 5°C for 3 hours, then filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 58.99 g of intermediate product compound 4' (yield 95.05%).

[0510] Step 3: Into a 1L reaction bottle, add 54g of intermediate product compound 4' (0.156mol), 44g of compound 5' (0.150mol), 10g of potassium acetate (0.102mol), and 600mL of methanol in sequence, heat to 63°C and react for 5h, then cool to 20°C and filter, rinse the filter cake with a small amount of methanol, and then dry at 50°C to obtain 90.34g of intermediate product compound 6' (yield 96.86%).

[0511] Step 4: Add 80 g of intermediate compound 6' (0.129 mol) and 300 mL of concentrated hydrochloric acid to a 500 mL reaction bottle, heat to 70-80°C and react for 3 h. Filter directly after the reaction is completed. Rinse the filter cake with appropriate amount of water and dry it at 100°C to obtain 70.61 g of intermediate compound 7' (yield 98.33%).

[0512] Step 5: Add 60g of intermediate compound 7' (0.107mol) and 5g of DMAP (0.041mol) to a 500mL reaction bottle in sequence, and then add 600ml of NMP. After the addition, heat to 40°C and keep warm for 4 hours. After the reaction is completed, filter to obtain a filter cake of ligand 8' for the next step.

[0513] Step 6: Add 200 mL of NMP and 19.03 g of cobalt acetate (0.107 mol) to the filter cake of step 5, keep warm at 75-85 ° C for 5 h, then cool to 20-30 ° C, slowly add 100 mL of water, keep warm at about 20 ° C for 1-2 h to crystallize, then filter, rinse 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%).

[0514] Ligand 8' of chemical F4: 1 H NMR (400MHz, CDCl3): δ=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,1 H),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.

[0515] Chemical F4: MALDI-TOF-MS (ESI + ):calcd for Co2C 54 H 77 N6O7[M+H] + 1084.1283, found 1084.1277.

[0516] The mononuclear catalysts in the following Examples 8, 9 and 10 are all prepared using conventional techniques available in the art. The structure of the mononuclear catalyst is as follows:

[0517]

[0518] The NMR data of the prepared mononuclear catalyst (before coordination) are: 1HNMR (400MHz, CDCl3): δ = 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.

[0519] HRMS (ESI) of the prepared mononuclear catalyst + ):calcd for CoC 36 H 55 N2O2[M+H] + 606.3596, found 606.3581.

[0520] Example 8: Preparation of S-epichlorohydrin with fresh catalyst, and then preparation of L-carnitrile with S-epichlorohydrin

[0521] 1. The experimental steps for splitting epichlorohydrin are as follows:

[0522] The eight reaction bottles are numbered 1, 2, 3, 4, 5, 6, 7, and 8, and epichlorohydrin (12 mol) is added in sequence, and then the mononuclear catalyst (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) prepared by the prior art are added respectively, and then glacial acetic acid (126 mmol) is added respectively and stirred, and water is slowly added dropwise under an ice bath, water (6.8 mol) is added dropwise to the reaction bottle No. 1, and water (6.1 mol) is added dropwise to the reaction bottles No. 2-8 respectively, and the addition is completed in about 30 minutes. After the addition is completed, the reaction bottles are transferred to a 25°C water bath and air is slowly blown in while stirring. After a period of reaction (6-22 h), the optical rotation value of the reaction solution is detected. When the optical rotation value is above 33°, the reaction can be stopped (vitamin C can be added for quenching). The reaction liquid is distilled under reduced pressure at -0.09Mpa (-0.1-(-0.05)Mpa is acceptable), and the distillate below 90°C is collected, and the organic phase in the distillate is separated to obtain S-epichlorohydrin. The distillate residue is cooled to room temperature and then filtered, and the filter cake is dried and recovered to obtain the catalyst, and the filtrate is the by-product glycerol chloride.

[0523] The recovered catalyst can be directly put into the next batch of reactions, or it can be mixed with fresh catalyst in a certain proportion and then recycled.

[0524] 2. The experimental steps for preparing L-carnitrile are as follows:

[0525] (1) subjecting 1 mol of each of the eight S-epichlorohydrins prepared in step 1 to an amination reaction with seven equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50° C. to obtain an L-quaternary ammonium salt reaction solution, adding 229 g of a 30% aqueous solution of sodium cyanide (0.7 mol in pure form) to the reaction solution, and subjecting the reaction solution to a cyanation reaction at 30-70° C. to obtain a cyanation reaction solution;

[0526] (2) adding hydrochloric acid to the cyanidation reaction solution obtained in step (1), decolorizing with activated carbon, filtering, concentrating and removing water to a water content of 20-35wt% and an L-carnitrile content of 40-70wt%, filtering while hot, cooling the aqueous filtrate to 0-20°C for crystallization, drying the L-carnitrile obtained by centrifugation to obtain a finished product of L-carnitrile, and detecting the HPLC purity of the L-carnitrile.

[0527] The experimental results are shown in Table 1.

[0528] Table 1

[0529]

[0530]

[0531] a: The ee value of pure product refers to the ee value of pure S-epichlorohydrin obtained by splitting

[0532] Example 9: Recovered catalyst is mixed with fresh catalyst to prepare S-epichlorohydrin, and then S-epichlorohydrin is used to prepare L-carnitrile

[0533] 1. The experimental steps for splitting epichlorohydrin are as follows:

[0534] Epichlorohydrin (6 mol) was added to 8 reaction bottles in sequence, and then the mononuclear catalyst (6 mmol), catalyst E (1.5 mmol), catalyst E2 (1 mmol), catalyst F1 (1.5 mmol), catalyst F1 (1.5 mmol), catalyst F2 (0.75 mmol), catalyst F3 (0.3 mmol) and catalyst F4 (1.5 mmol) prepared by the prior art were added respectively, each catalyst containing 50% of fresh catalyst and 50% of catalyst recovered from Example 8 (for example, the catalyst E used in this example contains 50% of fresh catalyst and 50% of catalyst recovered from Example 8). Glacial acetic acid (63 mmol) was added respectively and stirred, and water was slowly added dropwise under an ice bath (wherein, water (3.4 mol) was added to the reaction bottle containing the catalyst prepared by the prior art, and water (3.05 mol) was added to the other reaction bottles respectively), and the addition was completed in about 30 minutes. After the addition was completed, the reaction bottle was transferred to a 25°C water bath and air was slowly blown in while stirring. After a period of reaction (8-28h), the optical rotation of the reaction liquid is detected. When the optical rotation value is above 33°, the reaction can be stopped (vitamin C can be added for quenching). The reaction liquid is distilled under reduced pressure at -0.09Mpa (-0.1-(-0.05)Mpa). The distillate below 90°C is collected, and the organic phase in the distillate is separated to obtain S-epichlorohydrin. The distillation residue is cooled to room temperature and filtered, and the filter cake is dried and recovered to obtain the catalyst. The filtrate is the by-product glycerol trichloride.

[0535] The recovered catalyst can be directly put into the next batch of reactions, or it can be mixed with fresh catalyst in a certain proportion and then recycled.

[0536] 2. The experimental steps for preparing L-carnitrile are as follows:

[0537] (1) subjecting 1 mol of each of the eight S-epichlorohydrins prepared in step 1 to an amination reaction with six equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50° C. to obtain an L-quaternary ammonium salt reaction solution, adding 229 g of a 30% aqueous solution of sodium cyanide (0.7 mol in pure form) to the reaction solution, and subjecting the reaction solution to a cyanation reaction at 30-70° C. to obtain a cyanation reaction solution;

[0538] (2) adding hydrochloric acid to the cyanidation reaction solution obtained in step (1), decolorizing with activated carbon, filtering, concentrating and removing water to a water content of 20-35wt% and an L-carnitrile content of 40-70wt%, filtering while hot, cooling the aqueous filtrate to 0-20°C for crystallization, drying the L-carnitrile obtained by centrifugation to obtain a finished product of L-carnitrile, and detecting the HPLC purity of the L-carnitrile.

[0539] The experimental results are shown in Table 2.

[0540] Table 2

[0541]

[0542]

[0543] a: The ee value of pure product refers to the ee value of pure S-epichlorohydrin obtained by splitting

[0544] Example 10: Preparation of S-epichlorohydrin using the recovered catalyst, and then preparation of L-carnitrile using S-epichlorohydrin

[0545] 1. The experimental steps for splitting epichlorohydrin are as follows:

[0546] Epichlorohydrin (3 mol) was added to 8 reaction bottles in sequence, and then 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 were added respectively, and then glacial acetic acid (32 mmol) was added respectively and stirred, and water was slowly added dropwise under an ice bath (wherein, water (1.7 mol) was added to the reaction bottle to which the catalyst prepared by the prior art was added, and water (1.53 mol) was added to the other reaction bottles respectively), and the addition was completed in about 30 minutes. After the addition was completed, the reaction bottle was transferred to a 25°C water bath and air was slowly blown in while stirring. After a period of reaction (6-25 h), the optical rotation value of the reaction solution was detected. When the optical rotation value was above 33°, the reaction could be stopped. The reaction liquid is distilled under reduced pressure at -0.09Mpa (-0.1-(-0.05)Mpa is acceptable), and the distillate below 90°C is collected, and the organic phase in the distillate is separated to obtain S-epichlorohydrin. The distillate residue is cooled to room temperature and then filtered, and the filter cake is dried and recovered to obtain the catalyst, and the filtrate is the by-product glycerol chloride.

[0547] The recovered catalyst can be directly put into the next batch of reactions, or it can be mixed with fresh catalyst in a certain proportion and then recycled.

[0548] 2. The experimental steps for preparing L-carnitrile are as follows:

[0549] (1) subjecting 1 mol of each of the eight S-epichlorohydrins prepared in step 1 to an amination reaction with six equal parts of trimethylamine hydrochloride (1.01 mol) at 10-50° C. to obtain an L-quaternary ammonium salt reaction solution, adding 229 g of a 30% aqueous solution of sodium cyanide (0.7 mol in pure form) to the reaction solution, and subjecting the reaction solution to a cyanation reaction at 30-70° C. to obtain a cyanation reaction solution;

[0550] (2) adding hydrochloric acid to the cyanidation reaction solution obtained in step (1), decolorizing with activated carbon, filtering, concentrating and removing water to a water content of 20-35wt% and an L-carnitrile content of 40-70wt%, filtering while hot, cooling the aqueous filtrate to 0-20°C for crystallization, drying the L-carnitrile obtained by centrifugation to obtain a finished product of L-carnitrile, and detecting the HPLC purity of the L-carnitrile.

[0551] The experimental results are shown in Table 3.

[0552] Table 3

[0553]

[0554] a: The ee value of pure product refers to the ee value of pure S-epichlorohydrin obtained by splitting

[0555] Example 11: Preparation of Salen manganese and Salen copper catalysts

[0556] The Salen ligands prepared in Examples 1 to 6 are respectively complexed with metal Cu or Mn to obtain Salen copper or Salen manganese catalysts, whose catalytic effects are substantially the same as those of the Salen cobalt catalysts prepared in Examples 1 to 6.

[0557] This example shows some results, which are as follows:

[0558] 1. Preparation of binuclear cyclic Salen manganese catalyst

[0559] 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. The temperature was then lowered to 20-30° C. and filtered. The filter cake was rinsed with a small amount of methanol and dried at 50° C. to obtain 88.25 g of catalyst E-Mn (yield 97.54%, relative to compound D).

[0560] Compound E: MALDI-TOF-MS (ESI + ):calcd forMn2C 62 H 77 N8O8[M+H] + 1171.4623, found1171.4615.

[0561] 2. Preparation of binuclear chain-like Salen manganese catalyst

[0562] Ligand C4 was prepared according to steps 1-4 in Example 3, and 400 mL of NMP, 80 g of compound C4 (0.078 mol) and 27 g of manganese acetate (0.156 mol) were added to a 1 L reaction bottle in sequence, the temperature was raised to 75-85 ° C for reaction for 5 h, and then the temperature was lowered to 20-30 ° C, 500 mL of water was slowly added, and the temperature was kept at about 20 ° C for 1-2 h for crystallization, and then filtered. The filter cake was rinsed with a small amount of methanol and dried at 50-70 ° C to obtain 85.27 g of catalyst F-Mn (yield 96.54% relative to compound C4).

[0563] Compound F: MALDI-TOF-MS (ESI + ):calcd for Mn2C 59 H 71 N6O 10 [M+H] + 1133.4521, found1133.3958.

[0564] 3. Preparation of S-epichlorohydrin using binuclear cyclic or binuclear chain Salen manganese catalyst

[0565] Two reaction bottles are numbered 1 and 2, and epichlorohydrin (6 mol) is added respectively. Catalyst E-Mn (1.5 mmol) prepared in Example 10 is added to reaction bottle No. 1, and catalyst F-Mn (1.5 mmol) prepared in Example 11 is added to reaction bottle No. 2. Glacial acetic acid (63 mmol) is added and stirred respectively. Water (3.05 mol) is slowly added dropwise under an ice bath. The addition is completed in about 30 minutes. After the addition is completed, the reaction bottles are transferred to a 25°C water bath and air is slowly blown in while stirring. After a period of reaction (6-12 h), the optical rotation value of the reaction solution is detected. When the optical rotation value is above 33°, the reaction can be stopped (vitamin C can be added for quenching). The reaction solution is distilled under reduced pressure under -0.09Mpa (within the range of -0.1-(-0.05)Mpa), and the distillate below 90°C is collected. The organic phase in the distillate is separated to obtain S-epichlorohydrin. The distillation residue is cooled to room temperature and then filtered, and the filter cake is dried and recovered to obtain the catalyst, and the filtrate is the by-product chloroglycerol.

[0566] The recovered catalyst can be directly put into the next batch of reactions, or it can be mixed with fresh catalyst in a certain proportion and then recovered. The experimental results are shown in Table 4.

[0567] Table 4

[0568]

[0569] a: The ee value of pure product refers to the ee value of pure S-epichlorohydrin obtained by splitting

[0570] The results of comprehensive examples 1-7 show that the catalysts and their ligands prepared in this application have mild preparation conditions and are suitable for industrial production. The results of comprehensive examples 8 to 11 show that the reaction time of fresh catalyst E, catalyst E2, catalyst F, catalyst F1, catalyst F2, catalyst F3, catalyst F4, catalyst E-Mn, and catalyst F-Mn in this application is 9 to 11 hours, the split yield is more than 48%, and the catalyst recovery rate is more than 97%. The results of comprehensive examples 8 to 10 show that the catalyst E, catalyst E2, catalyst F, catalyst F1, catalyst F2, catalyst F3, and catalyst F4 recovered in this application do not need to be activated, and can be mixed with fresh catalysts or used alone, and the reaction time is 14 to 20 hours, the split yield is more than 48%, and the catalyst recovery rate is more than 97%.

[0571] Therefore, it can be further explained that the catalyst of the present application has a high recovery rate and excellent activity after recovery, and the catalyst of the present application has a short reaction time in the reaction of splitting terminal epoxide compounds, high catalytic efficiency, and high splitting yield.

[0572] Furthermore, when B1 in Example 1 is replaced with an equal molar amount of methylenediamine, ethylenediamine, 1,4-butylenediamine, 1,5-pentanediamine, 1,6-hexanediamine, 1,7-heptanediamine, 1,8-octanediamine, 1,9-nonanediamine, and 1,10-decanediamine, the catalytic effect of the obtained binuclear annular catalyst is basically the same as that of Catalyst E.

[0573] By controlling the temperature of step 5 in Examples 3 to 5, the amount of solvent, and the speed of adding the substrate, the value of n in the chain structure can be controlled to obtain chain multi-nuclear catalysts with different polymerization degrees, whose catalytic effects are basically the same as those of catalysts F1, F2, and F3.

[0574] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0575] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A Salen catalyst ligand, characterized in that: It has the structure shown in formula (I): Among them, --- is empty or a chemical bond; --- is empty, R1 is H, -COOH, or -NH2, R2 is H, -COOH, or -NH2; --- is a chemical bond, -R1-R2- is selected from a group containing -NH-C(O)-; R3 is selected from a group comprising -NH-C(O)-; R4 is 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 formula (I-1): Wherein, M is selected from Co, Mn, or Cu; ---Empty or chemical bond; --- is empty, R1 is H, -COOH, or -NH2, R2 is H, -COOH, or -NH2; --- is a chemical bond, -R1-R2- is selected from a group containing -NH-C(O)-; R3 is selected from a group comprising -NH-C(O)-; R4 is 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, characterized in that: R3 is selected from -NH-C(O)-, or -C(O)-NH-C 1～10 Alkylene-NH-C(O)-; Optionally, R3 is selected from -NH-C(O)-; Optionally, R3 is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-; Optionally, R3 is selected from -C(O)-NH-C 2～6 Alkylene-NH-C(O)-; Optionally, R3 is selected from -C(O)-NH(CH2)3-NH-C(O)-; Optionally, R4 is selected from isopropyl or tert-butyl; Optionally, n is 0, or n is any integer between 1 and 10.

4. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that: ---Empty, R1 and R2 are the same or different; Optionally, --- is a chemical bond, -R1-R2- is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-; Optionally, --- is a chemical bond, -R1-R2- is selected from -C(O)-NH-C 1～6 Alkylene-NH-C(O)-; Optionally, --- is a chemical bond, and -R1-R2- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

5. The Salen catalyst ligand according to claim 1 or the Salen catalyst according to claim 2, characterized in that: --- is a chemical bond, R3 is selected from -C(O)-NH-C 1～10 Alkylene-NH-C(O)-; and / or, --- is empty, R3 is selected from -NH-C(O)-, or -C(O)-NH-C 1～10 Alkylene-NH-C(O)-.

6. The Salen catalyst ligand according to claim 1, characterized in that The Salen catalyst ligand has a structure shown in formula (Ia1), formula (Ia2), formula (Ia3) or formula (Ia4): Where m is any integer between 1 and 10; Optionally, R1 is H, -NH2 or -COOH, and R2 is H, -COOH or -NH2.

7. The Salen catalyst according to claim 2, characterized in that The Salen catalyst has a structure shown in Formula (Ib1), Formula (Ib2), Formula (Ib3) or Formula (Ib4): Where m is any integer between 1 and 10; Optionally, R1 is H, -NH2 or -COOH, and R2 is H, -COOH or -NH2.

8. The Salen catalyst ligand according to claim 1, characterized in that The Salen catalyst ligand has any of the structures shown below:

9. The Salen catalyst according to claim 2, characterized in that The catalyst has any of the structures shown below:

10. A method for preparing the Salen catalyst ligand according to any one of claims 1, 3 to 6, and 8, characterized in that: include: The Salen catalyst ligand is obtained by connecting two or more mononuclear Salen catalyst ligands represented by formula (II) through a group containing -NH-C(O)-; The Salen catalyst ligand is a ring structure or a chain structure; Optionally, the group containing -NH-C(O)- is selected from -NH-C(O)-, or -C(O)-NH-C 1～10 Alkylene-NH-C(O)-; Optionally, the Salen catalyst ligand is a cyclic structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-C 1～6 Alkylene-NH-C(O)-; Optionally, the Salen catalyst ligand is a cyclic structure, and the group containing -NH-C(O)- is selected from -C(O)-NH-(CH2)3-NH-C(O)-.

11. The method according to claim 10, characterized in that The group containing -NH-C(O)- is obtained by subjecting -COOH and -NH2 to an amidation reaction; Optionally, the condensation agent for the amidation reaction is selected from at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, diisopropylcarbodiimide, and dicyclohexylcarbodiimide; Optionally, the catalyst for the amidation reaction is selected from at least one of 4-N,N-dimethylpyridine, 4-pyrrolidinopyridine, and 1-hydroxybenzotriazole; Optionally, the organic solvent for the amidation reaction is selected from at least one of N,N-dimethylformamide, N-methylpyrrolidone and dichloromethane.

12. The method according to claim 10, characterized in that The mononuclear Salen catalyst ligand represented by formula (II) is obtained by subjecting the structure represented by formula (IV) and the structure represented by formula (V) to a Schiff base reaction; Optionally, the catalyst in the Schiff base reaction is selected from at least one of potassium acetate, potassium carbonate, and triethylamine; Optionally, the organic solvent in the Schiff base reaction is selected from at least one of methanol and ethanol; Optionally, the reaction temperature of the Schiff base reaction is 60°C to 65°C; Optionally, the reaction time of the Schiff base reaction is 4 h to 6 h; Optionally, in the Schiff base reaction, the molar ratio of the structure represented by formula (IV) to the structure represented by formula (V) is 1.0:(0.5-1.5).

13. A method for preparing the Salen catalyst according to any one of claims 2 to 5, 7 and 9, characterized in that: include: The Salen catalyst is obtained by subjecting the Salen catalyst ligand described in any one of claims 1, 3 to 6, and 8, or the Salen catalyst ligand prepared according to the method described in any one of claims 10 to 12 to a complex reaction.

14. A method for splitting a terminal epoxy compound, characterized in that: include: Using the Salen catalyst described in any one of claims 2 to 5, 7, and 9, or the Salen catalyst prepared according to the method of claim 13, to perform a split reaction on a terminal epoxy compound to obtain a split epoxy compound; Optionally, the resolution reaction is quenched by adding vitamin C; Optionally, the terminal epoxy compound is selected from propylene oxide, butylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl n-butyrate.

15. Use of the Salen catalyst according to any one of claims 2 to 5, 7, and 9, or the Salen catalyst prepared according to the method according to claim 13, in the resolution of terminal epoxide compounds; Optionally, the resolution reaction of the terminal epoxy compound is quenched by adding vitamin C; Optionally, the terminal epoxy compound is selected from propylene oxide, butylene oxide, epichlorohydrin, epichlorohydrin, benzyl glycidyl ether, and glycidyl n-butyrate.

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