Insect pheromone derivative, and preparation method therefor and use thereof

Abstract

The present invention provides an insect pheromone derivative, which is an imidate derivative having a structure represented by formula (I), or a stereoisomer thereof. The present invention further provides a preparation method for, use of and release method for the insect pheromone derivative. The insect pheromone derivative provided by the present invention has stable properties, is not prone to volatilization and deterioration, is convenient to transport and store, can slowly release ester insect pheromones under certain conditions, involves a simple and convenient preparation process, uses raw materials that are widely available and inexpensive, involves mild and easily-controllable synthesis and release processes, and has high operability. Therefore, the insect pheromone derivative has good industrial applicability and is suitable for large-scale production and application.

Description

An insect pheromone derivative, its preparation method and uses Technical Field

[0001] This invention relates to the field of insect pheromone pesticides, specifically to an insect pheromone derivative, its preparation method, and its uses. Background Technology

[0002] Pheromones are a collective term for compounds that play a role in chemical communication between organisms. They are compounds used by insects to express various information such as gathering, foraging, mating, and alarm. In other words, they are the chemical molecular language of insect communication. Common pheromones include: altruistic pheromones, egoistic pheromones, synergistic pheromones, aggregation pheromones, tracking pheromones, alarm pheromones, dispersal pheromones, and sex pheromones.

[0003] In recent years, the overuse of pesticides has posed a serious threat to the environment, agricultural product safety, and human health. The increasing resistance of pests to pesticides has also presented new challenges to their control. With the improvement of people's environmental and ecological awareness, new pest control technologies that use sex pheromones to interfere with mating, such as sex mating techniques, to reduce the reproduction rate of pest populations and control pest damage are receiving more and more attention.

[0004] Insect sex pheromones are compounds that regulate the attraction behavior of male and female insects. They are both sensitive and specific, with a long range of action and strong attraction. Sex pheromones are biomimetic high-tech products that mimic natural insect sex pheromones and are released into the field through a releaser to lure and kill pests of the opposite sex. This technology kills pests without contacting plants or agricultural products, eliminating concerns about pesticide residues, and is one of the preferred methods for ecological pest control in modern agriculture.

[0005] Typically, insect sex pheromones used for pest monitoring and control are processed into slow-release formulations using physical methods. The carrier materials are often synthetic materials such as rubber, polyethylene, and polyvinyl chloride. These carriers are not easily degraded in the environment, easily becoming agricultural waste and causing farmland pollution. In recent years, researchers have also developed chemical methods to process insect sex pheromones. However, products obtained through chemical processing generally require light exposure for pheromone release, limiting their application.

[0006] For ester-based insect pheromones (whose molecular structure contains ester groups), they are usually highly volatile and prone to deterioration. Therefore, there is an urgent need to develop an insect pheromone derivative that is stable, easy to process, has low application requirements, and can slowly release ester-based insect pheromones. Summary of the Invention

[0007] To overcome the shortcomings of existing technologies, one objective of this invention is to provide an insect pheromone derivative that, under certain conditions, can achieve sustained and controlled release of ester-based insect pheromones, thereby expanding the range of insect pheromones, improving their ease of application, and possessing the potential to serve as an insect trapping and control product.

[0008] Another object of the present invention is to provide a method for preparing, using, and releasing the insect pheromone derivative.

[0009] The first aspect of the present invention provides an insect pheromone derivative, which is an imine ester derivative or a stereoisomer thereof with the structure shown in formula (I).

[0010] Wherein, R represents the residues in the carrier compound with the structure shown in formula (II) after removing x -NH-C(O)-R' groups;

[0011] R' represents a C1 to C6 alkyl group (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.);

[0012] a represents an integer from 1 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0013] b represents an integer from 0 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0014] c represents an integer from 0 to 2 (for example, it can be any integer of 0, 1 or 2);

[0015] d represents an integer from 0 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0016] x represents an integer that is at least 1.

[0017] The insect pheromone derivative provided by this invention belongs to the imine ester derivative category. Compared with common insect pheromones (such as those containing aldehyde or alcohol groups in their molecular structure), it is more stable, less prone to volatility and deterioration, and easier to transport and store. This imine ester derivative can undergo controlled, slow hydrolysis under certain conditions, thereby releasing ester-based insect pheromones. The reaction route is shown below:

[0018] Depending on the number of -NH-C(O)-R' groups involved in the reaction, the carrier compound of the same molecule can contain more than one imine ester structure, forming a "keychain"-like structure. This allows for the release of different quantities and types of insect pheromones, and also enables better control of their release rate, thus achieving the combined application of insect pheromones.

[0019] The insect pheromone derivative provided by this invention can release ester-based insect pheromones of all kinds commonly found in the art, and the different values ​​represented by a, b, c, and d can cover all kinds commonly found in the art. In some preferred embodiments, in formula (I), a can represent an integer from 1 to 12; b can represent an integer from 1 to 12; c can represent an integer from 0 or 1; d can represent an integer from 0 to 8; and x can represent an integer from 1 to 10 (i.e., one molecule of insect pheromone derivative can release 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ester-based insect pheromones). In some more preferred embodiments, in formula (I), a can represent an integer from 6 to 10; b can represent an integer from 1 to 6; c can represent an integer from 0 or 1; d can represent an integer from 0 to 6; and x can represent an integer from 1 to 4. In some most preferred embodiments, the ester-based insect pheromones released by the insect pheromone derivative of this invention can be pheromones with the following structure:

[0020] R' can represent groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.

[0021] The insect pheromone derivatives provided by this invention can be formed using any carrier compound commonly found in the chemical field, as long as their structure contains at least one reactive -NH-C(O)-R' group. The carrier compound is preferably a substance that is easily degradable under natural conditions, causes minimal pollution, and is inexpensive and readily available. It can be a small molecule or a large molecule such as a polymer, polypeptide, or protein.

[0022] In the insect pheromone derivative provided by this invention, in formula (I), R can represent C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C0-C8 alkylene-C3-C20 cycloalkyl, C0-C8 alkylene-3-20 heterocyclic, C0-C8 alkylene-C6-C20 aryl, or C0-C8 alkylene-5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more atoms selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, etc. The alkylene group is substituted with one or more of the following substituents: halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, carboxyl, -C(O)NH-C1-C6 alkyl, -NHC(O)-C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, C6-C12 aryl, or 5-12 membered heteroaryl, wherein one or more of the -CH2- groups in the alkylene group are optionally replaced with one or more of -C(O)NH-, -NHC(O)-, -C(O)-, -NH-, -O-, -S-, -S(O)-, or -S(O)2, wherein the heterocyclic group or heteroaryl group contains 1 to 3 heteroatoms selected from N, O, and S.

[0023] The insect pheromone derivatives provided by this invention can be imine ester derivatives or their stereoisomers with the structure shown in formula (Ⅰ-1).

[0024] In formula (Ⅰ-1), A represents a C3-C8 cycloalkyl, a 3-8 membered heterocyclic group, a C6-C12 aryl group, or a 5-12 membered heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, carboxyl, -C(O)NH-C1-C6 alkyl, -NHC(O)-C1-C6 alkyl, C3-C8 cycloalkyl, a 3-8 membered heterocyclic group, a C6-C12 aryl group, or a 5-12 membered heteroaryl group, wherein the heterocyclic or heteroaryl group contains 1 to 3 heteroatoms selected from N, O, and S;

[0025] L represents a C0-C6 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, C6-C12 aryl, 5-12 membered heteroaryl, wherein the heterocyclic group or heteroaryl contains 1 to 3 heteroatoms selected from N, O, and S;

[0026] a, b, c, and d are each independently defined as in any of the aforementioned technical solutions.

[0027] In some preferred embodiments, in formula (Ⅰ-1), A represents a 5- to 12-membered bicyclic fused ring, which is a fused ring of a monocyclic aryl group and a monocyclic saturated carbide ring, a fused ring of a monocyclic heteroaryl group and a monocyclic saturated carbide ring, or a fused ring of a monocyclic aryl group and a monocyclic heteroaryl group, wherein the monocyclic aryl group, the monocyclic saturated carbide ring, or the monocyclic heteroaryl group is optionally substituted by one or more substituents selected from halogens, C1-C6 alkyl groups, halogenated C1-C6 alkyl groups, C1-C6 alkoxy groups, and halogenated C1-C6 alkoxy groups;

[0028] L represents a C0-C4 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, phenyl, or naphthyl groups;

[0029] a, b, c, and d are each independently defined as in any of the aforementioned technical solutions.

[0030] In some more preferred embodiments, in formula (I-1), A represents a fused ring of phenyl with a C3-C6 monocyclic saturated carbide ring or a fused ring of 5-6 membered heteroaryl with a C3-C6 monocyclic saturated carbide ring, wherein the phenyl, monocyclic saturated carbide ring or heteroaryl is optionally substituted by one or more substituents selected from halogens, C1-C6 alkyl groups, halogenated C1-C6 alkyl groups, C1-C6 alkoxy groups, and halogenated C1-C6 alkoxy groups;

[0031] L represents a C0-C4 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, phenyl, or naphthyl groups;

[0032] a, b, c, and d are each independently defined as in any of the aforementioned technical solutions.

[0033] In some preferred embodiments, in formula (I-1), A represents phenyl, biphenyl, naphthyl, thiophene, pyrazolyl or pyridyl, wherein the phenyl, biphenyl, naphthyl, thiophene, pyrazolyl or pyridyl is optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy;

[0034] L represents a C0-C4 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, phenyl, or naphthyl groups;

[0035] a, b, c, and d are each independently defined as in any of the aforementioned technical solutions.

[0036] The insect pheromone derivatives provided by this invention include, but are not limited to, the carrier compounds with the structure shown in formula (II):

[0037] A second aspect of the present invention provides a method for preparing the insect pheromone derivative as described in any of the above-described technical solutions, the method comprising the following steps:

[0038] S1: The carrier compound reacts with a halogenating reagent to obtain a halogenated product with the structure shown in formula (III); and

[0039] S2: The halogenated product is reacted with an alcoholic insect pheromone with the structure shown in formula (Ⅳ) to obtain the insect pheromone derivative; HO-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3

[0040] Formula (Ⅳ)

[0041] Wherein, R, R', a, b, c, d, and x are each independently defined as in any of the above technical solutions;

[0042] Y represents halogen, preferably chlorine.

[0043] In the preparation method provided by the present invention, the reaction can be carried out in different reaction media (e.g., water, organic solvent or the reaction raw materials themselves) according to the different carrier compounds and other reagents selected, in order to prepare the imine ester derivative. The reaction temperature and reaction time can also be adjusted by those skilled in the art according to different reaction media and in combination with the actual reaction conditions. As needed, the reaction system may also include necessary auxiliaries, such as acid-binding agents, hydrogen-removing agents, etc.

[0044] In the preparation method provided by the present invention, step S1 may further include: in the presence of a first acid-binding agent, the carrier compound and the halogenated reagent are reacted in a first solvent at -10 to 30°C to obtain the halogenated product.

[0045] In the preparation method provided by the present invention, the reaction temperature in step S1 can be about -10°C, about -5°C, about 0°C, about 5°C, about 10°C, about 15°C, about 20°C, about 25°C, about 30°C, or any temperature range. In some preferred embodiments, the reaction temperature can be -5°C to 5°C.

[0046] In the preparation method provided by this invention, the halogenating reagent can be of a type commonly found in the art, capable of forming a halogenated product with the structure shown in formula (III). In some preferred embodiments, the halogenating reagent is a chlorinating reagent, including but not limited to oxaloyl chloride, thionyl chloride, phosgene, triphosgene, etc.

[0047] In the preparation method provided by this invention, the molar ratio of the support compound to the halogenated reagent can be 1:1 to 5, for example, about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, about 1:2.5, about 1:3, about 1:3.5, about 1:4, about 1:4.5, about 1:5, or any molar ratio range. In some preferred embodiments, the molar ratio of the support compound to the halogenated reagent can be 1:1 to 2, for example, 1:1 to 1.2.

[0048] In the preparation method provided by the present invention, the first acid-binding agent can be of a type commonly used in the art, including but not limited to 2,6-dimethylpyridine, pyridine, triethylamine, N,N-diisopropylethylamine, etc.

[0049] In the preparation method provided by this invention, the molar ratio of the carrier compound to the first acid-binding agent can be 1:1 to 5, for example, about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, about 1:2.5, about 1:3, about 1:3.5, about 1:4, about 1:4.5, about 1:5, or any molar ratio range. In some preferred embodiments, the molar ratio of the carrier compound to the first acid-binding agent can be 1:1 to 2, for example, 1:1 to 1.2.

[0050] In the preparation method provided by the present invention, step S2 may further include: in the presence of a dehydrogenating agent and a second acid-binding agent, the halogenated product and the alcoholic insect pheromone are reacted in a second solvent at 10-150°C to obtain the insect pheromone derivative.

[0051] In the preparation method provided by this invention, the reaction temperature in step S2 can be about 10°C, about 20°C, about 30°C, about 40°C, about 50°C, about 60°C, about 70°C, about 80°C, about 90°C, about 100°C, about 110°C, about 120°C, about 130°C, about 140°C, about 150°C, or any temperature range. In some preferred embodiments, the reaction temperature can be 10–60°C.

[0052] In the preparation method provided by this invention, the alcohol-based insect pheromone can be of a type commonly found in the art, including but not limited to the alcohol-based insect pheromone with the following structure (i.e., Z-8-dodecenol):

[0053] In the preparation method provided by the present invention, the molar ratio of the carrier compound to the alcohol insect pheromone can be determined according to the number of -NH-C(O)-R' groups in the carrier compound. One mole of -NH-C(O)-R' group corresponds to one mole of alcohol insect pheromone and an appropriate excess is maintained.

[0054] In the preparation method provided by the present invention, the second acid-binding agent can be of a type commonly used in the art, including but not limited to 2,6-dimethylpyridine, pyridine, triethylamine, N,N-diisopropylethylamine, etc.

[0055] In the preparation method provided by the present invention, the molar ratio of the carrier compound to the second acid-binding agent can be 1:0.05 to 2, for example, it can be about 1:0.05, about 1:0.1, about 1:0.15, about 1:0.2, about 1:0.25, about 1:0.3, about 1:0.45, about 1:0.5, about 1:0.55, about 1:0.6, about 1:0.65, about 1:0.7, about 1:0.75, about 1:0.8, about 1:0.85, about 1:0.9, about 1:0.95, about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, or any molar ratio range. In some preferred embodiments, the molar ratio of the carrier compound to the second acid-binding agent can be 1:0.1 to 1, for example, 1:0.1 to 0.5.

[0056] In the preparation method provided by the present invention, the dehydrogenating reagent can be of a type commonly used in the art, including but not limited to sodium hydride, sodium methoxide, sodium ethoxide, etc.

[0057] In the preparation method provided by this invention, the molar ratio of the alcohol-based insect pheromone to the dehydrogenating agent can be 1:1 to 5, for example, about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, about 1:2.5, about 1:3, about 1:3.5, about 1:4, about 1:4.5, or any molar ratio range. In some preferred embodiments, the molar ratio of the alcohol-based insect pheromone to the dehydrogenating agent can be 1:2 to 4.

[0058] In the preparation method provided by this invention, depending on the different reactants, both the first solvent and the second solvent can be common solvents in the art, such as aliphatic hydrocarbons (e.g., n-pentane, n-hexane), alicyclic hydrocarbons (e.g., cyclopentane, cyclohexane), aromatic hydrocarbons (e.g., benzene, toluene, xylene), heterocyclic hydrocarbons (e.g., tetrahydrofuran, methyltetrahydrofuran, 1,4-dioxane), halogenated aliphatic hydrocarbons (e.g., dichloromethane, trichloromethane, dichloroethane), halogenated aromatic hydrocarbons (e.g., chlorobenzene, bromobenzene, chlorotoluene, bromotoluene), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, n-butanol), ketones (e.g., acetone, butanone), esters (e.g., methyl acetate, ethyl acetate), ethers (e.g., diethyl ether, diethyl ether), nitriles (e.g., acetonitrile), alkyl sulfoxides (e.g., dimethyl sulfoxide), and alkyl amides (e.g., dimethylimide). In some preferred embodiments, the first solvent can be dichloromethane, n-heptane, tetrahydrofuran, etc. In some other preferred embodiments, the second solvent may be cyclohexane, n-hexane, toluene, etc.

[0059] In the preparation method provided by the present invention, depending on the different reaction raw materials, the weight of the first solvent and the second solvent can be 1 to 100 times the weight of the carrier compound, for example, about 2 times, about 5 times, about 8 times, about 10 times, about 12 times, about 15 times, about 18 times, about 20 times, about 22 times, about 25 times, about 28 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, about 100 times, or any multiple range.

[0060] A third aspect of the present invention provides the use of any of the above-described technical solutions of the insect pheromone derivative in the preparation of sustained-release and / or controlled-release formulations of ester-based insect pheromones with the structure shown in formula (V).

[0061] Among them, R', a, b, c, and d are each independently defined as in any of the above technical solutions.

[0062] As mentioned above, the insect pheromone derivatives provided by this invention have good stability and can slowly and controllably release ester-based insect pheromones through the hydrolysis of imine esters. Therefore, the insect pheromone derivatives provided by this invention are very suitable for preparing sustained-release and controlled-release formulations of insect pheromones or other insect pheromone products with similar functions.

[0063] A fourth aspect of the present invention provides a method for releasing an insect pheromone derivative as described in any of the above technical solutions, the method comprising: mixing the insect pheromone derivative with an acidic aqueous solution for hydrolysis to release an ester-type insect pheromone with the structure shown in formula (V).

[0064] Among them, R', a, b, c, and d are each independently defined as in any of the above technical solutions.

[0065] In the release method provided by the present invention, the acidic aqueous solution can be an organic acid aqueous solution with a mass percentage concentration of 1 to 20%, for example, it can be about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 12%, about 15%, about 18%, about 20%, or any mass percentage concentration range.

[0066] In the release method provided by the present invention, the organic acid can be a common weak organic acid in the art, including but not limited to citric acid, acetic acid, strawberry acid, lactic acid, mandelic acid, etc.

[0067] In the release method provided by the present invention, the insect pheromone derivative can be dissolved in an acidic aqueous solution for hydrolysis, or it can be mixed with an acidic aqueous solution to form a mixture (insoluble or partially dissolved) for hydrolysis.

[0068] A fifth aspect of the present invention provides a method for releasing an insect pheromone derivative as described in any of the above technical solutions, the method comprising: mixing the insect pheromone derivative with a solid organic acid and hydrolyzing it in air to release an ester-type insect pheromone with the structure shown in formula (V).

[0069] Among them, R', a, b, c, and d are each independently defined as in any of the above technical solutions.

[0070] In the release method provided by the present invention, the solid organic acid can be a common solid weak organic acid in the art, including but not limited to citric acid, strawberry acid, mandelic acid, etc.

[0071] In the release method provided by this invention, the mass ratio of the insect pheromone derivative to the solid organic acid can be from 1:0.1 to 10, for example, it can be about 1:0.1, about 1:0.2, about 1:0.5, about 1:0.8, about 1:1, about 1:1.2, about 1:1.5, about 1:1.8, about 1:2, about 1:2.5, about 1:3, about 1:3.5, about 1:4, about 1:4.5, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or any volume ratio range. In some preferred embodiments, the mass ratio of the insect pheromone derivative to the solid organic acid can be from 1:0.5 to 2.

[0072] In the release method provided by the present invention, the release rate and release amount of ester insect pheromones can also be adjusted by various means such as adjusting the concentration of acidic aqueous solution, the concentration of insect pheromone derivatives in acidic aqueous solution, the amount of solid organic acid used, and the humidity of the air.

[0073] In the release method provided by this invention, the released ester-based insect pheromones preferably have the following structure:

[0074] The technical solution provided by this invention has the following advantages:

[0075] (1) The insect pheromone derivative provided by the present invention forms a novel imine ester derivative through a chemical reaction. It is stable, not easily volatilized or deteriorated, and easy to transport and store. Under certain conditions, it can release ester insect pheromones, thereby realizing the slow release and controlled release of insect pheromones.

[0076] (2) The insect pheromone derivatives provided by the present invention use alcohol-based insect pheromones and carrier compounds as raw materials. They are widely available, have many choices, are convenient and economical, and the remaining substances after the pheromone is released are easily degraded in the environment, making them green and environmentally friendly.

[0077] (3) The insect pheromone derivatives provided by the present invention can also achieve the combined release of multiple pheromones and regulate the release rate and amount of different pheromones, thereby enabling the control of multiple insects in multiple scenarios.

[0078] (4) The insect pheromone derivatives provided by the present invention are simple to prepare, low in cost, and the synthesis and release processes are mild and easy to control, and highly operable. Therefore, they have good industrial applicability and are suitable for large-scale production and application. Attached Figure Description

[0079] Figure 1 is a graph showing the hydrolysis results of Example 14.

[0080] Figure 2 is a graph showing the hydrolysis results of Example 15.

[0081] Figure 3 is a graph showing the hydrolysis results of Example 16.

[0082] Figure 4 is a graph showing the hydrolysis results of Example 17.

[0083] Figure 5 is a graph showing the hydrolysis results of Example 18.

[0084] Figure 6 is a graph showing the hydrolysis results of Example 19.

[0085] Figure 7 is a graph showing the hydrolysis results of Example 20.

[0086] Figures 8-10 are graphs showing the hydrolysis results obtained in Example 21 based on hydrolysis schemes one, two, and three, respectively.

[0087] Figures 11-13 are graphs showing the hydrolysis results obtained in Example 22 based on hydrolysis schemes one, two, and three, respectively.

[0088] Figure 14 is a graph showing the hydrolysis results of Example 23.

[0089] Figure 15 is a graph showing the hydrolysis results of Example 24.

[0090] Figure 16 is a graph showing the hydrolysis results of Example 25.

[0091] Figure 17 is a graph showing the hydrolysis results of Example 26. Detailed Implementation

[0092] the term

[0093] Unless otherwise defined, the terminology used in this invention should be considered to have the ordinary meaning that can be understood by those skilled in the art. Some common terms are introduced and explained below:

[0094] The singular forms used in this article, such as “a,” “an,” “the,” “the,” “the above,” etc., contain both singular and plural referents.

[0095] The use of "include" or "include" in this document is open-ended rather than restrictive, meaning that it does not exclude unlisted types, elements, or methods or steps.

[0096] As used herein, "one embodiment" specifically refers to the particular feature, structure, or property of the described subject when the phrase appears. Therefore, "one embodiment" appearing in different places herein does not necessarily refer to the same embodiment. On the other hand, some specific embodiments may include some features of other embodiments but not all features of other embodiments. In such cases, combinations of embodiments with different features, although not listed herein, should be assumed to be included in the claims and statements herein.

[0097] As used herein, "C1-Cn" includes C1-C2, C1-C3, ..., C1-Cn. For example, the term "C1-C16" refers to a group having 1 to 16 carbon atoms, meaning the group contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 carbon atoms. Therefore, for example, "C1-C16 alkyl" refers to an alkyl group containing 1 to 16 carbon atoms.

[0098] The term "alkyl" as used alone or in combination herein refers to a saturated aliphatic hydrocarbon with optional substituted straight or optional substituted branched chains. Preferably, it may have 1 to 16 carbon atoms, or 1 to 8 carbon atoms, or 1 to 6 carbon atoms. Non-limiting examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, etc.

[0099] As used alone or in combination herein, the term "alkylene" refers to an optionally substituted saturated straight-chain or branched aliphatic hydrocarbon group having two residues derived from the removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkane, preferably C1-C8 alkylene, more preferably C1-C6 alkylene. Non-limiting examples of alkylene include, but are not limited to, methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, 1,3-propylene, 1,4-butylene, etc. Furthermore, when alkylene is "C0", it means that alkylene is absent.

[0100] As used alone or in combination herein, the term "alkenyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond. It can be straight-chain or branched, preferably C2-C8 alkenyl, more preferably C2-C6 alkenyl. Non-limiting examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl. wait.

[0101] The term "alkynyl" as used alone or in combination herein refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon triple bond. It can be straight-chain or branched, preferably C2-C8 alkynyl, and more preferably C2-C6 alkynyl. Non-limiting examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-, 2-, or 3-butynyl.

[0102] The term "cycloalkyl" as used alone or in combination herein refers to an optionally substituted non-aromatic saturated carbocyclic ring, which may include a monocyclic (having one ring), a bicyclic (having two rings), or a polycyclic (having more than two rings), and the ring type includes fused rings, bridged rings, and spirocyclic rings. Preferably, the cycloalkyl group may have 3 to 10 cyclic carbon atoms, for example, 3 to 6 cyclic carbon atoms. Non-limiting examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

[0103] The term "heterocyclic group" as used alone or in combination herein refers to a non-aromatic, 5- to 20-membered monocyclic, bicyclic, or polycyclic ring, including fused rings, bridged rings, and spirocyclic rings, wherein the cyclic atoms may comprise 1 to 4 (e.g., 1, 2, 3, or 4) atoms selected from nitrogen, oxygen, and / or sulfur. Preferably, the heterocyclic group may have 5 to 12 cyclic atoms, for example, 5 to 10 cyclic atoms, or 5 to 8 cyclic atoms, or 5 to 6 cyclic atoms. Non-limiting examples of heterocyclic groups include, but are not limited to, morpholino, oxobutyryl, thiomorpholino, tetrahydrofurano, tetrahydropyrano, 1,1-dioxo-thiomorpholino, piperidino, 2-oxo-piperidino, pyrrolyl, 2-oxo-pyrrolyl, piperazine-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazine, hexahydropyrimidine, etc.

[0104] As used alone or in combination herein, the term "aryl" refers to an optionally substituted aromatic hydrocarbon group having 6 to 20, such as 6 to 12 or 6 to 10 cyclic carbon atoms, which can be monocyclic, bicyclic, or polycyclic. Bicyclic or more cyclic aryl groups can be a monocyclic aryl group fused with other independent rings, such as alicyclic rings (e.g., saturated carbocyclic rings with 3 to 10, 3 to 8, or 3 to 6 cyclic carbon atoms), or aromatic rings. Non-limiting examples of monocyclic aryl groups include, but are not limited to, phenyl; non-limiting examples of bicyclic aryl groups include naphthyl; non-limiting examples of polycyclic aryl groups include, but are not limited to, phenanthryl, anthracene, fluorenyl, azulel, etc.

[0105] The term "heteroaryl" as used alone or in combination herein refers to an optionally substituted aromatic 5- to 20-membered monocyclic, bicyclic, or polycyclic ring, including fused rings, bridged rings, and spirocyclic rings, wherein the cyclic atoms may comprise 1 to 4 (e.g., 1, 2, 3, or 4) atoms selected from nitrogen, oxygen, and / or sulfur. Preferably, the heteroaryl group may have 5 to 12 cyclic atoms, for example, 5 to 10 cyclic atoms, 5 to 8 cyclic atoms, or 5 to 6 cyclic atoms. Non-limiting examples of heteroaryl groups include, but are not limited to, furanyl, pyridyl, 2-oxo-1,2-dihydropyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiopheneyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrroleyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzo[m]dioxacyclopentenyl, benzo[thiophene], benzimidazolyl, indoleyl, isoyindolyl, 1,3-dioxo-isoindolyl, quinolinyl, inzolyl, benzo[isothiazolyl], benzo[oxazolyl], benzo[isothiazolyl], isothiazolyl, 1H-1,2,4-triazolyl, 4H-1,2,4 - Triazolyl, pyridyl, pyrimidinyl, pyrazin-2(1H)-keto, pyrimidin-4(3H)-keto, pyridazin-3(2H)-keto, 1H-indolyl, 1H-benzo[d]imidazolyl, 1H-pyrrolo[2,3-c]pyridyl, 3H-imidazo[4,5-c]pyridyl, isoquinolinyl, quinazolinyl, 2H-isoindolyl, furan[3,2-b]pyridyl, furan[2,3-c]pyridyl, thieno[2,3-c]pyridyl, benzofuranyl, benzo[b]thienoyl, 1H-pyrrolo[3,2-b]pyridyl, 2H-pyrrolo[3,4-c]pyridyl, etc.

[0106] The term "alkoxy" as used alone or in combination herein refers to an "alkyl-O-" group. Alkyl groups are defined herein. Non-limiting examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, etc.

[0107] The term "nitro" as used alone or in combination in this article refers to the -NO2 group.

[0108] The term "hydroxyl group" as used alone or in combination in this article refers to the -OH group.

[0109] The term “halogen” as used alone or in combination in this article refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0110] The term "amino" as used alone or in combination in this article refers to -NH2.

[0111] The term "cyano" as used alone or in combination in this article refers to -CN.

[0112] The term "carboxyl group" as used alone or in combination in this article refers to -COOH.

[0113] The term "stereoisomer" as used alone or in combination herein includes all isomeric forms, such as R and S configurations arising from one or more asymmetric centers, (Z) and (E) double bond isomers (geometric isomers), (Z) and (E) conformational isomers, trans-restricted isomers, etc. Similarly, the invention can also exist as a mixture of two or more structurally different forms in rapid equilibrium (commonly referred to as tautomers), representative examples of which include keto-enol tautomers, phenol-keto tautomers, nitroso-oxime tautomers, imine-enamine tautomers, etc. It is contemplated that the scope of this invention covers all such isomers or mixtures thereof in any proportion.

[0114] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0115] Unless otherwise specified, all raw materials or reagents used in the embodiments of the present invention are commercially available products, and all percentages used are mass percentages unless otherwise specified.

[0116] In the embodiments of the present invention, room temperature (or normal temperature) refers to 25±5℃.

[0117] In the embodiments of the present invention, the hydrolysis of imine esters was detected by HPLC.

[0118] General synthesis process flow:

[0119] Step 1:

[0120] After N2 replacement, 1.0 eq. of the substrate (i.e., the support), 1.05 eq. of the first acid-binding agent (based on the substrate, such as 2,6-dimethylpyridine), and 15 times the weight of the first solvent (based on the substrate, such as DCM) were added to the jacketed reactor. A mixed solution of 1.05 eq. of oxalyl chloride (based on the substrate) and 5 times the weight of the first solvent (based on oxalyl chloride) was added dropwise at 0°C. The dropwise addition was completed within 10-20 min, and the reaction was continued at 0°C for 1 h under N2 atmosphere with stirring.

[0121] The reaction solution was allowed to return to room temperature naturally. Then, the first solvent was removed by rotary evaporation under reduced pressure at 35°C and N2 protection. 24 times the weight of the second solvent (based on the weight of the residue, such as cyclohexane) was added to the residue. The mixture was stirred at room temperature for 30 minutes and allowed to stand to allow the hydrochloride salt of the first acid-binding agent to precipitate. The supernatant containing the imine chloride in the second solvent was then collected.

[0122] Step 2:

[0123] Add 0.25 eq. of Z-8-dodecenol (based on the substrate), 5 times the weight of the second solvent (based on Z-8-dodecenol), and 3 eq. of the dehydrogenating agent (based on Z-8-dodecenol, such as sodium hydride) to a reaction tube. Stir at 25°C for 30 min, let stand, transfer the supernatant of sodium Z-8-dodecenol to a flat-bottomed flask, add 0.4 eq. of the second acid-binding agent (based on the substrate, such as triethylamine), and then rapidly add the supernatant of the second solvent of imine chloride to the above mixed solution at 25°C. Continue stirring at 25°C for 30 min.

[0124] Step 3:

[0125] The reaction solution obtained in step 2 was subjected to rotary evaporation under reduced pressure at 35°C. One weight of n-heptane (based on the weight of the residue) was added to the residue in the reactor. The mixture was allowed to stand for 30 minutes. The supernatant was then concentrated by rotary evaporation to obtain the imine ester derivative.

[0126] Example 1: Preparation of imine ester derivatives using N-acetanilide as a carrier

[0127] Following the standard process flow, the yield is approximately 82%. 1 H NMR (400MHz, CDCl3) δ7.29-7.22(m,2H),7.04-6.98(m,1H),6.77-6.72(m,2H),5.42-5.31(m,2H),4.15(t,J =6.8Hz,2H),2.05-1.97(m,4H),1.81(s,3H),1.75-1.66(m,2H),1.40-1.30(m,10H),0.90(t,J=7.4Hz,3H).

[0128] Example 2: Preparation of imine ester derivatives using N-(4-methoxyphenyl)acetamide as a carrier

[0129] Following the standard process flow, the yield is approximately 78%. 1 H NMR (400MHz, CDCl3) δ7.38(d,J=8.9Hz,2H),6.84(d,J=8.9Hz,2H),5.43-5.31(m,2H),4.25(t,J=6 .8Hz,2H),3.78(s,3H),2.08(s,3H),2.05-1.98(m,4H),1.44-1.31(m,12H),0.90(t,J=7.4Hz,3H).

[0130] Example 3: Preparation of imine derivatives using N-(4-methylphenyl)acetamide as a carrier

[0131] Following the standard process flow, the yield is approximately 77%. 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.3Hz,2H),7.10(d,J=8.2Hz,2H),5.42-5.31(m,2H),4.15(t,J=6.8Hz,2H) ,2.30(s,3H),2.05-1.97(m,4H),1.81(s,3H),1.75-1.66(m,2H),1.40-1.30(m,10H),0.90(t,J=7.4Hz,3H).

[0132] Example 4: Preparation of imine derivatives using N-(2-methoxyphenyl)acetamide as a carrier

[0133] Following the standard process flow, the yield is approximately 80%. 1 H NMR (400MHz, CDCl3) δ8.35(d,J=7.9Hz,1H),7.03(t,J=7.7Hz,1H),6.95(t,J=7.7Hz,1H),6.87(d,J=8.0Hz,1H),5.43-5. 31(m,2H),4.25(t,J=6.8Hz,2H),3.76(s,3H),2.08(s,3H),2.05-1.98(m,4H),1.44-1.31(m,12H),0.90(t,J=7.4Hz,3H).

[0134] Example 5: Preparation of imine derivatives using N-(1-phenylethyl)acetamide as a carrier

[0135] Following the standard process flow, the yield is approximately 69%. 1 H NMR (400MHz, CDCl3) δ7.36-7.29(m,4H),7.28-7.24(m,1H),6.77-6.72(m,2H),5.42-5.31(m,2H),4.15(t,J=6.8Hz,2H),5.16-5 .09(m,1H),2.05-1.97(m,4H),1.81(s,3H),1.75-1.66(m,2H),1.49(d,J=6.9Hz,1H),1.40-1.30(m,10H),0.90(t,J=7.4Hz,3H).

[0136] Example 6: Preparation of imine ester derivatives using N-(3-thienyl)acetamide as a support

[0137] Following the standard process flow, the yield is approximately 76%. 1 H NMR (400MHz, DMSO-d6) δ77.51-7.47(m,1H),7.40(dd,J=5.1,3.3Hz,1H),7.04(d,J=5.1Hz,1H),5.42-5.31(m,2H),4 .15(t,J=6.8Hz,2H),2.05-1.97(m,4H),1.81(s,3H),1.75-1.66(m,2H),1.40-1.30(m,10H),0.90(t,J=7.4Hz,3H).

[0138] Example 7: Preparation of imine ester derivatives using N-(2,6-dimethylphenyl)acetamide as a carrier

[0139] Following the standard process flow, the yield is approximately 98%. 1 H NMR (400MHz, CDCl3) δ7.00(d,J=7.4Hz,2H),6.85(t,J=7.5Hz,1H),5.41-5.32(m,2H),4.24(t,J=6.8H z,2H),2.09-1.95(m,10H),1.80-1.70(m,2H),1.65(s,3H),1.43-1.30(m,10H),0.90(t,J=7.5Hz,3H).

[0140] Example 8: Preparation of imine ester derivatives using N-(2,6-dimethoxyphenyl)acetamide as a carrier

[0141] Following the standard process flow, the yield is approximately 92%. 1 H NMR (400MHz, CDCl3) δ6.96(t,J=8.3Hz,1H),6.58(d,J=8.3Hz,2H),5.41-5.32(m,2H),4.26(t,J=6.9H z,2H),3.78(s,6H),2.06-1.98(m,4H),1.78-1.70(m,5H),1.43-1.32(m,10H),0.90(t,J=7.4Hz,3H).

[0142] Example 9: Preparation of imine ester derivatives using N-(2-methoxy-6-methylphenyl)acetamide as a support

[0143] Following the standard process flow, the yield is approximately 96%. 1H NMR (400MHz, CDCl3) δ6.90(t,J=7.8Hz,1H),6.79(d,J=7.5Hz,1H),6.73(d,J=8.1Hz,1H),5.43-5.31(m,2H),4.25(t ,J=6.8Hz,2H),3.76(s,3H),2.08(s,3H),2.05-1.98(m,4H),1.68(s,3H),1.44-1.31(m,12H),0.90(t,J=7.4Hz,3H).

[0144] Example 10: Preparation of imine ester derivatives using N-(2-methylnaphthyl)acetamide as a support

[0145] Following the standard process flow, the yield is approximately 98%. 1 H NMR (400MHz, CDCl3) δ7.80-7.74(m,1H),7.73-7.68(m,1H),7.46(d,J=8.3Hz,1H),7.42-7.34(m,2H),7.30(d,J=8.3Hz,1H),5.42-5.32( m,2H),4.39(t,J=6.8Hz,2H),2.23(s,3H),2.08-1.99(m,4H),1.87-1.77(m,2H),1.63(s,3H),1.44-1.30(m,10H),0.90(t,J=7.4Hz,3H).

[0146] Example 11: Preparation of imine ester derivatives using N-(1,3,5-trimethyl-1H-pyrazole-4-)acetamide as a carrier

[0147] Following the standard process flow, the yield is approximately 68%. 1 H NMR (400MHz, CDCl3) δ5.41-5.31(m,2H),4.18(t,J=6.8Hz,2H),3.69(s,3H),2.05-1.9 8(m,10H),1.77(s,3H),1.75-1.67(m,2H),1.43-1.32(m,10H),0.90(t,J=7.4Hz,3H).

[0148] Example 12: Preparation of imine ester derivatives using N-(2-biphenyl)acetamide as a carrier

[0149] Following the standard process flow, the yield is approximately 86%. 1H NMR (400MHz, CDCl3) δ7.43-7.38(m,2H),7.35-7.30(m,3H),7.28-7.22(m,2H),7.10(td,J=7.5,1.1Hz,1H),6.78(dd,J=7.8,0.9H z,1H),5.41-5.32(m,2H),4.05(t,J=6.7Hz,2H),2.06-1.99(m,5H),1.62-1.57(m,4H),1.41-1.26(m,10H),0.90(t,J=7.4Hz,3H).

[0150] Example 13: Preparation of imine ester derivatives using (R)-1,1,3-trimethyl-2,3-dihydro-1H-indene-4-acetamide as a support

[0151] Following the standard process flow, the yield is approximately 86%. 1 H NMR (400MHz, CDCl3) δ7.10(t,J=7.6Hz,1H),6.81(d,J=7.4Hz,1H),6.45(d,J=7.6Hz,1H),5.41-5.30(m,2H),4.23-4.12(m,2 H),2.14(dd,J=12.6,8.2Hz,1H),2.06-1.97(m,4H),1.79(s,3H),1.77-1.68(m,2H),1.43-1.18(m,10H),0.91-0.85(m,12H).

[0152] General hydrolysis process flow:

[0153] Option 1: Add 10 mg of imine ester sample and 150 μL of 1%–10% citric acid solution to the sample vial, let it stand open at 30°C, and test at regular intervals.

[0154] Option 2: Disperse the imine ester sample at a mass concentration of 1 mg / mL in a 1% citric acid aqueous solution, let it stand in an open container at 30°C, and test it at regular intervals.

[0155] Option 3: Mix the imine ester sample with solid citric acid at a mass ratio of 1:1 and place the mixture in a sample vial. Let it stand open at 30°C and perform periodic testing.

[0156] The structure of the target ester pheromone is as follows:

[0157] Example 14: Hydrolysis of imine esters using N-acetanilide as a carrier

[0158] Implemented according to Scheme 1 in the general process flow, the concentration of citric acid water is 10%, and the rate of hydrolysis of imine ester into target ester pheromone at 30℃ is about 70% / 15 days. That is, about 70% of the imine ester was hydrolyzed in 15 days, and correspondingly, about 70% of the theoretical amount of target ester pheromone was released. The hydrolysis results are shown in Figure 1.

[0159] Example 15: Hydrolysis of imine esters supported on N-(4-methoxyphenyl)acetamide

[0160] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 83% / 15 days, and the hydrolysis results are shown in Figure 2.

[0161] Example 16: Hydrolysis of imine esters supported on N-(4-methylphenyl)acetamide

[0162] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 77% / 15 days. The hydrolysis results are shown in Figure 3.

[0163] Example 17: Hydrolysis of imine esters supported on N-(2-methoxyphenyl)acetamide

[0164] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 79% / 15 days. The hydrolysis results are shown in Figure 4.

[0165] Example 18: Hydrolysis of imine esters supported on N-(1-phenylethyl)acetamide

[0166] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 93% / 15 days, and the hydrolysis results are shown in Figure 5.

[0167] Example 19: Hydrolysis of imine esters supported on N-(3-thienyl)acetamide

[0168] Implemented according to Scheme 1 in the general process flow, the concentration of citric acid in water is 10%, and the rate of hydrolysis of imine ester into target ester pheromones at 30℃ is about 90% / 15 days. The hydrolysis results are shown in Figure 6.

[0169] Example 20: Hydrolysis of imine esters supported on N-(2,6-dimethylphenyl)acetamide

[0170] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 47% / 15 days. The hydrolysis results are shown in Figure 7.

[0171] Example 21: Hydrolysis of imine esters using N-(2,6-dimethoxyphenyl)acetamide as a support

[0172] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 56% / 15 days. The hydrolysis results are shown in Figure 8.

[0173] Implemented according to Scheme 2 in the general process flow, the rate of hydrolysis of imine ester into target ester pheromones at 30℃ is approximately 42% / 15 days, and the hydrolysis results are shown in Figure 9.

[0174] Implemented according to Scheme 3 in the general process flow, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 38% / 15 days, and the hydrolysis results are shown in Figure 10.

[0175] Example 22: Hydrolysis of imine esters supported on N-(2-methoxy-6-methylphenyl)acetamide

[0176] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30°C is approximately 52% / 15 days. The hydrolysis results are shown in Figure 11.

[0177] Implemented according to Scheme 2 in the general process flow, the rate of hydrolysis of imine ester into target ester pheromones at 30℃ is approximately 26% / 15 days, and the hydrolysis results are shown in Figure 12.

[0178] Implemented according to Scheme 3 in the general process flow, the rate of hydrolysis of imine ester into target ester pheromones at 30℃ is approximately 30% / 15 days, and the hydrolysis results are shown in Figure 13.

[0179] Example 23: Hydrolysis of imine esters supported on N-(2-methylnaphthyl)acetamide

[0180] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30°C is approximately 53% / 15 days. The hydrolysis results are shown in Figure 14.

[0181] Example 24: Hydrolysis of imine esters supported on N-(1,3,5-trimethyl-1H-pyrazole-4-)acetamide

[0182] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30℃ is approximately 73% / 15 days. The hydrolysis results are shown in Figure 15.

[0183] Example 25: Hydrolysis of imine esters supported on N-(2-biphenyl)acetamide

[0184] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30°C is approximately 57% / 15 days. The hydrolysis results are shown in Figure 16.

[0185] Example 26: Hydrolysis of imine esters supported on (R)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-acetamide

[0186] Implemented according to Scheme 1 in the general process flow, with a citric acid concentration of 10%, the rate of hydrolysis of imine esters into target ester pheromones at 30°C was approximately 47% / 15 days. The hydrolysis results are shown in Figure 17.

[0187] As can be seen from the above embodiments, the imine ester derivative provided by the present invention is prepared from alcohol-based insect pheromones and carrier compounds containing acetyl groups. The imine ester derivative can be hydrolyzed under specific conditions to slowly release ester-based insect pheromones at different rates. Therefore, it has great potential as a sustained-release and controlled-release formulation of insect pheromones. Moreover, the imine ester derivative provided by the present invention has a wide range of raw material sources, is economical, and the residue after pheromone release is easily degraded, thus being environmentally friendly.

[0188] Unless otherwise specified, the terms used in this invention have the meanings commonly understood by those skilled in the art.

[0189] The embodiments described in this invention are for illustrative purposes only and are not intended to limit the scope of protection of this invention. Those skilled in the art can make various other substitutions, changes and improvements within the scope of this invention. Therefore, this invention is not limited to the above embodiments, but is only defined by the claims.

Claims

1. An insect pheromone derivative, characterized in that, It is an imine ester derivative or its stereoisomer with the structure shown in formula (Ⅰ). Wherein, R represents the residues in the carrier compound with the structure shown in formula (II) after removing x -NH-C(O)-R' groups; R' represents a C1-C6 alkyl group; a represents an integer from 1 to 20; b represents an integer from 0 to 20; c represents an integer from 0 to 2; d represents an integer from 0 to 20; x represents an integer that is at least 1.

2. The insect pheromone derivative according to claim 1, characterized in that, In the formula (Ⅰ), a represents an integer from 1 to 12; b represents an integer from 1 to 12; c represents an integer of 0 or 1; d represents an integer from 0 to 8; and x represents an integer from 1 to 10. Preferably, in formula (Ⅰ), a represents an integer from 6 to 10; b represents an integer from 1 to 6; c represents an integer of 0 or 1; d represents an integer from 0 to 6; and x represents an integer from 1 to 4.

3. The insect pheromone derivative according to claim 1 or 2, characterized in that, In formula (I), R represents C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C0-C8 alkylene-C3-C20 cycloalkyl, C0-C8 alkylene-3-20 heterocyclic, C0-C8 alkylene-C6-C20 aryl, or C0-C8 alkylene-5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more elements selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, or halogenated C1-C6 alkoxy. The alkylene group is substituted with one or more of the following substituents: alkyl, cyano, amino, nitro, hydroxyl, carboxyl, -C(O)NH-C1~C6 alkyl, -NHC(O)-C1~C6 alkyl, C3~C8 cycloalkyl, 3~8-membered heterocyclic group, C6~C12 aryl or 5~12-membered heteroaryl, wherein one or more of the -CH2- in the alkylene group are optionally replaced with one or more of -C(O)NH-, -NHC(O)-, -C(O)-, -NH-, -O-, -S-, -S(O)-, -S(O)2, wherein the heterocyclic group or heteroaryl group contains 1 to 3 heteroatoms selected from N, O, and S.

4. The insect pheromone derivative according to any one of claims 1-3, characterized in that, The insect pheromone derivative is an imine ester derivative or its stereoisomer as shown in formula (Ⅰ-1). In formula (Ⅰ-1), A represents a C3-C8 cycloalkyl, a 3-8 membered heterocyclic group, a C6-C12 aryl group, or a 5-12 membered heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, carboxyl, -C(O)NH-C1-C6 alkyl, -NHC(O)-C1-C6 alkyl, C3-C8 cycloalkyl, a 3-8 membered heterocyclic group, a C6-C12 aryl group, or a 5-12 membered heteroaryl group, wherein the heterocyclic or heteroaryl group contains 1 to 3 heteroatoms selected from N, O, and S; L represents a C0-C6 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, C6-C12 aryl, 5-12 membered heteroaryl, wherein the heterocyclic group or heteroaryl contains 1 to 3 heteroatoms selected from N, O, and S; Preferably, A represents a 5- to 12-membered bicyclic fused ring, which is a fused ring of a monocyclic aryl group and a monocyclic saturated carbide ring, a fused ring of a monocyclic heteroaryl group and a monocyclic saturated carbide ring, or a fused ring of a monocyclic aryl group and a monocyclic heteroaryl group, wherein the monocyclic aryl group, monocyclic saturated carbide ring, or monocyclic heteroaryl group is optionally substituted by one or more substituents selected from halogens, C1-C6 alkyl groups, halogenated C1-C6 alkyl groups, C1-C6 alkoxy groups, and halogenated C1-C6 alkoxy groups; Preferably, A represents phenyl, biphenyl, naphthyl, thiophene, pyrazolyl or pyridyl, wherein the phenyl, biphenyl, naphthyl, thiophene, pyrazolyl or pyridyl is optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy; Preferably, L represents a C0-C4 alkylene group, wherein the alkylene group is optionally substituted by one or more substituents selected from C1-C6 alkyl, phenyl, or naphthyl groups; a, b, c, and d are each independently defined as in any one of claims 1-3.

5. The insect pheromone derivative according to any one of claims 1-4, characterized in that, The carrier compound with the structure shown in Formula (II) is selected from one of the following compounds:

6. The method for preparing the insect pheromone derivative according to any one of claims 1-5, characterized in that, Includes the following steps: S1: The carrier compound reacts with a halogenating agent to obtain a halogenated product with the structure shown in formula (Ⅲ); as well as S2: The halogenated product is reacted with an alcoholic insect pheromone with the structure shown in formula (Ⅳ) to obtain the insect pheromone derivative; HO-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3 Formula (Ⅳ) Wherein, R, R', a, b, c, d, and x are each independently defined as in any one of claims 1-5; Y represents halogen, preferably chlorine.

7. The preparation method according to claim 6, characterized in that, Step S1 further includes: in the presence of a first acid-binding agent, the carrier compound and the halogenated reagent are reacted in a first solvent at -10 to 30°C to obtain the halogenated product; Preferably, the halogenated reagent is one or more selected from oxaloyl chloride, sulfoxide, phosgene, and triphosgene; The first acid-binding agent is one or more of 2,6-dimethylpyridine, triethylamine, and N,N-diisopropylethylamine; The first solvent is one or more of the following: aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, heterocyclic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, alcohols, ketones, esters, ethers, nitriles, alkyl sulfoxides, and alkyl amides; preferably one or more of dichloromethane, 1,2-dichloroethane, and tetrahydrofuran.

8. The preparation method according to claim 6 or 7, characterized in that, Step S2 further includes: in the presence of a dehydrogenating agent and a second acid-binding agent, the halogenated product and the alcoholic insect pheromone are reacted in a second solvent at 10-150°C to obtain the insect pheromone derivative; Preferably, the second acid-binding agent is one or more selected from pyridine, triethylamine, and N,N-diisopropylacetamide; The dehydrogenation reagent is one or more of sodium hydride, sodium methoxide, and sodium ethoxide; The second solvent is one or more of the following: aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, heterocyclic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, alcohols, ketones, esters, ethers, nitriles, alkyl sulfoxides, and alkyl amides; preferably one or more of cyclohexane, dichloromethane, n-heptane, and cyclohexane.

9. Use of the insect pheromone derivative according to any one of claims 1-5 in the preparation of sustained-release and / or controlled-release formulations of ester-based insect pheromones with the structure shown in formula (V), in, R', a, b, c, and d are each independently defined as described in any one of claims 1-5.

10. The method for releasing the insect pheromone derivative according to any one of claims 1-5, characterized in that, The insect pheromone derivative is mixed with an acidic aqueous solution and hydrolyzed to release an ester-based insect pheromone with the structure shown in formula (V). Wherein, R', a, b, c, and d are each independently defined as in any one of claims 1-5; Preferably, the acidic aqueous solution is an aqueous solution of an organic acid with a mass percentage concentration of 1-20%; More preferably, the organic acid is one or more of citric acid, acetic acid, strawberry acid, lactic acid, and mandelic acid.

11. The method for releasing the insect pheromone derivative according to any one of claims 1-5, characterized in that, The insect pheromone derivative is mixed with a solid organic acid and hydrolyzed in air to release an ester-type insect pheromone with the structure shown in formula (V). Wherein, R', a, b, c, and d are each independently defined as in any one of claims 1-5; Preferably, the solid organic acid is one or more selected from citric acid, strawberry acid, and mandelic acid; More preferably, the mass ratio of the insect pheromone derivative to the solid organic acid is 1:0.1 to 10.

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