Preparation method of tomato leaf miner sex pheromone, intermediate thereof and preparation method thereof

Abstract

The present invention discloses a preparation method of tomato leafminer sex pheromone, an intermediate thereof and a preparation method thereof. Innovatively, the route uses commercially available 5-hexen-1-ol as the starting material to synthesize a new intermediate (E)-8-hydroxy-3-octene acetate that can be used for the preparation of tomato leafminer sex pheromone and the intermediate (E)-8-aldehyde-3-octene acetate obtained by further oxidation. Then, using this as an intermediate raw material, an 8Z-double bond is constructed through the Wittig reaction. The overall route has fewer steps. When the hydroxyl protecting group is selected as acetyl, the total number of steps for preparing the two components of tomato leafminer sex pheromone is only 4 steps. When other protecting groups are selected for the hydroxyl group, by adding a deprotection group and acetylation process with mild reaction conditions, the total number of steps is also only 8 steps. In particular, the raw materials for each step of the synthesis route of the present invention are simple and easily available, the reaction conditions are mild, and the product selectivity is relatively high, which is conducive to large-scale production.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and particularly to carboxylic ester compounds containing carbon-carbon double bonds in acyclic compounds. Specifically, the present invention relates to a preparation method of the sex pheromone of Tuta absoluta, an intermediate thereof, and a preparation method thereof. Background Art

[0002] Tuta absoluta belongs to the family Gelechiidae of the order Lepidoptera and is one of the most destructive and invasive pests in tomatoes and other Solanaceae plants (such as potatoes, tobacco, etc.). At present, the control of Tuta absoluta mainly relies on chemical control, but the effect is not ideal. Since the development of the larvae of this pest mainly occurs inside plants or the soil, general pesticides cannot reach them, so the killing power of pesticides is limited. In addition, the extensive use of pesticides has also caused problems such as pesticide residues, drug resistance, and the killing of its natural enemies. At present, integrated management strategies including the introduction of natural enemies, biological control of insect pathogens, and enhancement of crop resistance are being increasingly adopted, and their effects are relatively better compared with traditional pesticide insecticides. Among them, the control strategy of using the sex pheromone released by female Tuta absoluta to attract the same species of males is considered to be a very promising killing solution.

[0003] In 1995, A. B. Attygalle et al. isolated and identified the main component of the sex pheromone of Tuta absoluta, (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (Tetrahedron Lett., 1995, 36: 5471-5474), and carried out the first artificial synthesis; in 1996, F. C. Griepink et al. isolated and identified the minor component of the sex pheromone of Tuta absoluta, (3E,8Z)-3,8-tetradecadiene acetate (Tetrahedron Lett., 1996, 37: 411-414). It is reported that the large-scale trapping and killing of male adults with these two components in a ratio of 91:9 can significantly reduce the population of Tuta absoluta, and the combined application with insecticides has a better control effect.

[0004] At present, due to different bond-forming positions during synthesis, two different strategies have emerged for the two pheromones. Based on the C5+C5+C4 synthesis route (Route 1), THP (tetrahydropyranyl)-protected 4-pentyn-1-ol is coupled with two different C5 bromo synthons, then reduced, brominated, and then coupled with a nucleophilic C4 alkynyllithium synthon, and then reduced with lithium aluminum hydride and acetylated to obtain the two pheromones. However, the total number of steps in this strategy is as long as 14 steps, and there are also some dangerous processes among them, such as hydrogenation reduction and reduction with lithium aluminum hydride at high temperature.

[0005]

[0006] Based on the synthetic route of C4 + C1 + C9 (Route 2), the MOM (methoxymethyl)-protected 3-butyn-1-ol first reacts with the C1 synthon - triethyl orthoformate to form a C5 intermediate. After reduction, acidification, and acetylation, it is then coupled with the C9 synthon - Grignard reagent to obtain an intermediate with the pheromone C14 skeleton. After deprotection and acetylation, two pheromones are obtained. However, the total number of steps in this strategy is as long as 14 steps, and the preparation conditions of the Grignard reagent are harsh, the steps are cumbersome, there is a lot of acidic wastewater, and the construction and removal of protecting groups also increase the time cost and material cost.

[0007]

[0008] It can be seen that the existing synthetic routes are basically more than 14 steps, and there are problems such as harsh reaction conditions, difficult operation, long time consumption, and relatively high material and labor costs.

[0009] It should be noted that the information disclosed in the above background art section is only used to understand the background of the present application. Therefore, the background section of the present invention may include background information about the problems or environment of the present invention, rather than necessarily describing the prior art. Therefore, the content included in the background art section is not an admission by the applicant of the prior art. Summary of the Invention

[0010] An object of the present invention is to overcome one or more deficiencies in the prior art and provide a new method for preparing the sex pheromone of Tuta absoluta with fewer steps and relatively mild conditions.

[0011] The present invention also provides an intermediate for preparing the above-mentioned sex pheromone of Tuta absoluta and a preparation method thereof.

[0012] To achieve the above object, a technical solution adopted by the present invention is:

[0013] A preparation method of the sex pheromone of Tuta absoluta, the sex pheromone of Tuta absoluta includes (3E,8Z,11Z)-3,8,11-tetradecatriene acetate having the structure shown in formula (SP-1), and the preparation method includes:

[0014] Reaction (1): Reacting the compound shown in formula (I) with the compound shown in formula (II) and / or the compound shown in formula (III) in the presence of a metal catalyst to carry out an olefin cross-metathesis reaction to generate a compound shown in formula (IV);

[0015]

[0016] Reaction (2): Using the compound shown in formula (IV) as a substrate and oxidizing it in the presence of an oxidant to generate a compound shown in formula (V);

[0017]

[0018] Reaction (3): Subject the compound represented by formula (V) to a ylide reaction (Wittig reaction) with the compound represented by formula (VII) to form the compound represented by formula (IX);

[0019]

[0020] Reaction (4): Using the compound represented by formula (IX) as a substrate, under alkaline conditions, react to form the compound represented by formula (XI);

[0021]

[0022] Reaction (5): Subject the compound represented by formula (XI) to an acetylation reaction to form (3E,8Z,11Z)-3,8,11-tetradecatriene acetate of the structure represented by formula (SP-1);

[0023]

[0024] Among them, in formula (II), formula (III), formula (IV), formula (V), and formula (IX), R is a hydroxyl protecting group;

[0025] In formula (VII), R1 is a halogen.

[0026] In some embodiments of the present invention, in the reaction (1), the metal catalyst includes one or more combinations selected from tungsten catalysts, titanium catalysts, molybdenum catalysts, ruthenium catalysts, and cuprous catalysts.

[0027] Further, in the reaction (1), the metal catalyst includes a catalytic combination of a ruthenium catalyst and a cuprous catalyst. In the catalytic combination, the molar ratio of the cuprous catalyst to the ruthenium catalyst is 1:1 - 15, and can be, for example, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:14, etc.

[0028] According to some preferred and specific aspects of the present invention, the cuprous catalyst is one or more combinations selected from CuI, CuCl, and CuBr.

[0029] According to some preferred and specific aspects of the present invention, the ruthenium catalyst is one or more combinations selected from bis(tricyclohexylphosphine)benzylidene ruthenium dichloride, phenylmethylene-[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinyl]-dichloro-(tricyclohexylphosphine)ruthenium, dichloro(o-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium, and (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium.

[0030] In some preferred and specific aspects of the present invention, the molar ratio of the compound represented by formula (II) and / or the compound represented by formula (III) to the cuprous catalyst is 1:0.01 - 0.2, for example, it can be 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.15, 1:0.18, etc.

[0031] In some embodiments of the present invention, in the reaction (1), the olefin cross-metathesis reaction is controlled to be carried out in a protective atmosphere and a first solvent. The protective atmosphere is formed by introducing nitrogen and / or an inert gas, and the first solvent is a combination of one or more selected from dichloromethane, ethyl acetate, tetrahydrofuran, ether, toluene, N,N-dimethylformamide, cyclohexane, and n-hexane.

[0032] In some embodiments of the present invention, in the reaction (1), the molar ratio of the compound represented by formula (II) and / or the compound represented by formula (III) to the compound represented by formula (I) is 1:0.1 - 20. Further, it can be 1:0.1 - 10, 1:0.1 - 5, etc.; According to some specific aspects of the present invention, the molar ratio of the compound represented by formula (II) and / or the compound represented by formula (III) to the compound represented by formula (I) can be 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:2, 1:5, 1:10, 1:15, etc.

[0033] In some embodiments of the present invention, in the reaction (1), the reaction temperature of the olefin cross-metathesis reaction is controlled to be 0 - 120 °C. Further, it can be 5 - 80 °C, 5 - 40 °C, etc.; According to some specific aspects of the present invention, the reaction temperature of the olefin cross-metathesis reaction is controlled to be 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, etc.

[0034] In some embodiments of the present invention, in the reaction (1), the reaction time of the olefin cross-metathesis reaction is controlled to be 1 - 40 h, for example, it can be 2 - 35 h, 5 - 35 h, 5 - 30 h, 8 - 25 h, 10 - 20 h, etc.

[0035] According to some specific aspects of the present invention, the implementation of the reaction (1) includes: under a protective atmosphere, at room temperature, mixing the compound shown in the formula (I), the compound shown in the formula (II) and / or the compound shown in the formula (III), a metal catalyst and a first solvent, heating to a preset reaction temperature (for example, it can be 5-80 °C), and stirring for reaction.

[0036] Further, after the reaction (1) is completed, the solvent is first distilled off under reduced pressure, concentrated, and then purified by silica gel column chromatography to obtain a pale yellow transparent liquid, which is the compound shown in the formula (IV); wherein, the eluent for the silica gel column chromatography is preferably a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 2.5-3.5∶1.

[0037] In some embodiments of the present invention, in the reaction (2), the oxidant is selected from one or more combinations of ruthenium tetroxide (RuO4), manganese dioxide (MnO2), potassium monopersulfate compound salt (Oxone), sodium hypochlorite (NaOCl), lead tetraacetate (Pb(OAc)4), sodium periodate (NaIO4), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), Dess-Martin periodinane (DMP), peroxybenzoic acid (PBA), and pyridinium dichromate (PDC).

[0038] According to a specific aspect of the present invention, in the reaction (2), the oxidant is Dess-Martin periodinane (DMP).

[0039] In some embodiments of the present invention, the reaction (2) is controlled to be carried out at -5~10 °C. According to a specific aspect of the present invention, the reaction (2) is controlled to be carried out under ice bath conditions.

[0040] In some embodiments of the present invention, the reaction (2) is controlled to be carried out in a second solvent, and the second solvent is selected from one or more combinations of dichloromethane, ethyl acetate, tetrahydrofuran, diethyl ether, toluene, N,N-dimethylformamide, cyclohexane, and n-hexane.

[0041] In some embodiments of the present invention, in the reaction (2), the molar ratio of the compound shown in the formula (IV) to the oxidant is 1∶1.0-3.0, for example, it can be 1∶1.05, 1∶1.1, 1∶1.2, 1∶1.3, 1∶1.4, 1∶1.5, 1∶1.55, 1∶1.6, 1∶1.7, 1∶1.8, 1∶1.9, 1∶2.0, 1∶2.1, 1∶2.2, 1∶2.3, 1∶2.4, 1∶2.5, etc.

[0042] In some embodiments of the present invention, after the reaction (2) is completed, it is preferred to add a mixed solution of an excessive amount of saturated sodium thiosulfate solution and saturated sodium bicarbonate to the reaction system, and then stir well. The stirring duration is preferably 2 to 3 h. The resulting mixture is extracted with ethyl acetate to obtain an organic layer, and then the organic layer is dried with anhydrous sodium sulfate and concentrated to obtain a crude product. Then, it is purified by silica gel column chromatography to obtain a pale yellow transparent liquid, which is the compound shown in formula (V); wherein, the eluent for the silica gel column chromatography is preferably a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 8 - 12∶1.

[0043] In some embodiments of the present invention, in the reaction (3), the ylide reaction is controlled to proceed in the presence of a first basic substance, and the first basic substance includes one or more combinations selected from sodium hydroxide (NaOH), potassium carbonate (K2CO3), sodium hydride (NaH), n-butyllithium (n-BuLi), lithium diisopropylamide (LDA), lithium bis(trimethylsilyl)amide (LiHMDS), sodium bis(trimethylsilyl)amide (NaHMDS), potassium bis(trimethylsilyl)amide (NaHMDS), potassium tert-butoxide ((CH3)3COK), sodium methoxide (CH3ONa), and sodium ethoxide (CH3CH2ONa).

[0044] Further, the molar ratio of the compound shown in formula (V) to the first basic substance in the feed is controlled to be 1∶1.5 - 3, for example, it can be 1∶1.6, 1∶1.7, 1∶1.8, 1∶1.9, 1∶2.0, 1∶2.1, 1∶2.2, 1∶2.3, 1∶2.4, 1∶2.5, 1∶2.6, 1∶2.7, 1∶2.8, 1∶2.9, etc.

[0045] In some embodiments of the present invention, in the reaction (3), the molar ratio of the compound shown in formula (V) to the compound shown in formula (VII) in the feed is 1∶1 - 3, for example, it can be 1∶1.1, 1∶1.3, 1∶1.4, 1∶1.5, 1∶1.8, 1∶2, 1∶2.1, 1∶2.2, 1∶2.3, 1∶2.4, 1∶2.5, 1∶2.6, 1∶2.7, 1∶2.8, 1∶2.9, 1∶2.95, etc.

[0046] In some embodiments of the present invention, in the reaction (3), the reaction temperature of the ylide reaction is controlled to be -78~25 °C.

[0047] In some embodiments of the present invention, in the reaction (3), the reaction time of the ylide reaction is controlled to be 1 - 40 h, for example, it can be 2 - 30 h, 2 - 20 h, 2 - 10 h, etc.

[0048] In some embodiments of the present invention, in the reaction (3), the ylide reaction is controlled to be carried out in a protective atmosphere and in a third solvent. The protective atmosphere is formed by introducing nitrogen and / or an inert gas, and the third solvent includes tetrahydrofuran.

[0049] According to some specific aspects of the present invention, the embodiments of the reaction (3) include: in a protective atmosphere and at a temperature of -10 to 10 °C, adding a solution of a first basic substance to the compound represented by the formula (VII) to obtain a mixture, stirring the mixture at -10 to 10 °C, and then adding a solution of the compound represented by the formula (V) to the mixture at -78 to -65 °C, and then stirring and reacting at -60 to -35 °C and 10 - 25 °C in sequence; wherein, the dispersion solvents used for the solution of the first basic substance and the solution of the compound represented by the formula (V) are both the third solvent, and the third solvent includes tetrahydrofuran.

[0050] In some embodiments of the present invention, after the reaction (3) is completed, an excessive amount of saturated ammonium chloride solution is added at room temperature to quench the reaction. When quenching, it is preferred to add the saturated ammonium chloride solution under nitrogen, stir well, and the preferred stirring time is 1 to 1.5 h. The resulting mixture is extracted with ethyl acetate to obtain an organic layer, and then the organic layer is dried with anhydrous sodium sulfate and concentrated to obtain a crude product; then silica gel column chromatography purification is carried out to obtain a pale yellow transparent liquid, and the compound represented by the formula (IX) is obtained; wherein, the eluent for the silica gel column chromatography purification is preferably a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 18 - 22∶1.

[0051] In some embodiments of the present invention, in the reaction (4), the basic condition is formed by adding a second basic substance or an aqueous solution thereof, and the second basic substance is a combination of one or more selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, and tetrabutylammonium fluoride (TBAF).

[0052] In some embodiments of the present invention, the reaction (4) is controlled to be carried out in a fourth solvent, and the fourth solvent is a combination of one or more selected from methanol, ethanol, isopropanol, tetrahydrofuran, and water.

[0053] In some embodiments of the present invention, the reaction temperature of the reaction (4) is controlled to be 0 - 60 °C, for example, it can be 5 - 50 °C, 10 - 40 °C, 15 - 35 °C, etc. According to a specific aspect of the present invention, the reaction temperature of the reaction (4) is controlled to be room temperature.

[0054] In some embodiments of the present invention, the reaction time of the reaction (4) is controlled to be 1 - 40 h, for example, it can be 1 - 30 h, 1 - 20 h, 1 - 10 h, 1 - 5 h, etc.

[0055] According to some specific aspects of the present invention, the embodiment of the reaction (4) includes: mixing the compound shown in the formula (IX) with a fourth solvent, and then adding an aqueous solution of a second basic substance, and stirring for reaction. In some embodiments of the present invention, the aqueous solution of the second basic substance can be an aqueous sodium hydroxide solution with a concentration of 1% - 15%.

[0056] In some embodiments of the present invention, after the reaction (4) ends, the solvent is first rotary evaporated, then water and dichloromethane are added for extraction to obtain an organic layer, and then the organic layer is dried with anhydrous sodium sulfate and concentrated to obtain a crude product; then silica gel column chromatography purification is carried out to obtain a pale yellow transparent liquid, and the compound shown in the formula (XI) is obtained; wherein, the eluent for the silica gel column chromatography purification is preferably a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 4 - 6∶1.

[0057] In some embodiments of the present invention, in the reaction (5), the acetylation reaction is controlled to be carried out in the presence of an organic base, and the organic base includes one or more combinations selected from triethylamine, 4 - dimethylaminopyridine, and pyridine.

[0058] According to some specific aspects of the present invention, the organic base is composed of triethylamine and 4 - dimethylaminopyridine. Further, the molar ratio of the triethylamine to the 4 - dimethylaminopyridine in the feed is 1∶50 - 200, for example, it can be 1∶50 - 150, 1∶50 - 120, 1∶60 - 120, etc.

[0059] In some embodiments of the present invention, in the reaction (5), the acetylation reaction is controlled to be carried out in a fifth solvent, and the fifth solvent is one or more combinations selected from dichloromethane, ethyl acetate, tetrahydrofuran, and pyridine.

[0060] In some embodiments of the present invention, in the reaction (5), the reaction temperature of the acetylation reaction is controlled to be 0 - 100 °C, for example, it can be 0 - 80 °C, 5 - 70 °C, 10 - 60 °C, 15 - 50 °C, 15 - 40 °C, 15 - 35 °C, etc. According to some specific aspects of the present invention, the reaction temperature of the acetylation reaction is room temperature.

[0061] In some embodiments of the present invention, in the reaction (5), the reaction time of the acetylation reaction is controlled to be 1 - 24 h, for example, it can be 1 - 20 h, 1 - 15 h, 1 - 8 h, etc.

[0062] In some embodiments of the present invention, in the reaction (5), the acetylation reaction uses acetic anhydride to react with the compound shown in formula (Ⅺ) to prepare (3E,8Z,11Z)-3,8,11-tetradecatriene acetate with the structure shown in formula (SP-1).

[0063] According to some specific aspects of the present invention, the embodiment of the reaction (5) includes: mixing the compound shown in formula (Ⅺ), an organic base, acetic anhydride and a fifth solvent, and reacting.

[0064] In some embodiments of the present invention, after the reaction (5) ends, the organic phase is washed once with hydrochloric acid and once with a saturated sodium bicarbonate solution, the organic phases are combined, dried over anhydrous sodium sulfate, rotary evaporated to obtain a pale yellow transparent liquid, and concentrated to obtain a crude product; then silica gel column chromatography purification is carried out to obtain a pale yellow transparent liquid, and (3E,8Z,11Z)-3,8,11-tetradecatriene acetate with the structure shown in formula (SP-1) is obtained; wherein, the eluent for the silica gel column chromatography purification is preferably a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 18-22∶1.

[0065] In some embodiments of the present invention, the hydroxy protecting group is an acyl hydroxy protecting group, an alkane hydroxy protecting group, a silyl hydroxy protecting group or an acetal hydroxy protecting group.

[0066] Further, the hydroxy protecting group is acetyl, and when the hydroxy protecting group is acetyl, the reactions (4) and (5) in the preparation method do not exist, and the compound shown in formula (Ⅸ) is (3E,8Z,11Z)-3,8,11-tetradecatriene acetate with the structure shown in formula (SP-1).

[0067] In some embodiments of the present invention, in formula (Ⅶ), R1 is bromine or iodine.

[0068] Another technical solution provided by the present invention: A preparation method of the sex pheromone of Tuta absoluta, the sex pheromone of Tuta absoluta includes (3E,8Z)-3,8-tetradecadiene acetate with the structure shown in formula (SP-2), and the preparation method includes:

[0069] Reaction (a): Reacting the compound shown in formula (Ⅰ) with the compound shown in formula (Ⅱ) and / or the compound shown in formula (Ⅲ) in the presence of a metal catalyst to carry out an olefin cross-metathesis reaction to generate the compound shown in formula (Ⅳ);

[0070]

[0071] Reaction (b): Using the compound represented by the formula (IV) as a substrate, it is oxidized in the presence of an oxidant to form the compound represented by the formula (V);

[0072]

[0073] Reaction (c): The ylide reaction occurs between the compound represented by the formula (V) and the compound represented by the formula (VI) to form the compound represented by the formula (VIII);

[0074]

[0075] Reaction (d): Using the compound represented by the formula (VIII) as a substrate, under alkaline conditions, it reacts to form the compound represented by the formula (X);

[0076]

[0077] Reaction (e): The compound represented by the formula (X) undergoes an acetylation reaction to form (3E,8Z)-3,8-tetradecadienyl acetate with the structure represented by the formula (SP-2);

[0078]

[0079] Among them, in the formula (II), formula (III), formula (IV), formula (V), and formula (VIII), R is a hydroxyl protecting group;

[0080] In the formula (VI), R2 is a halogen.

[0081] In some embodiments of the present invention, the reaction processes of the reaction (a), the reaction (b), the reaction (c), the reaction (d), and the reaction (e) are the same as the aforementioned reactions (1)-(5) respectively.

[0082] In some embodiments of the present invention, R2 is bromine or iodine.

[0083] When the hydroxyl protecting group is an acetyl group, the reaction (d) and the reaction (e) in the preparation method do not exist, and the compound represented by the formula (VIII) is (3E,8Z)-3,8-tetradecadienyl acetate with the structure represented by the formula (SP-2).

[0084] Another technical solution provided by the present invention: An intermediate for preparing the sex pheromone of Tuta absoluta, the intermediate is selected from the compound represented by the formula (IV) and / or the compound represented by the formula (V);

[0085]

[0086] In the formula (IV) and the formula (V), R is a hydroxyl protecting group.

[0087] Another technical solution provided by the present invention: A preparation method of a tomato leafminer sex pheromone intermediate, and the tomato leafminer sex pheromone intermediate has the structure shown in formula (V);

[0088] The preparation method includes: using the compound shown in formula (IV) as a substrate, and oxidizing it in the presence of an oxidant to generate the compound shown in formula (V);

[0089]

[0090] In formula (IV) and formula (V), R is a hydroxyl protecting group.

[0091] Furthermore, the preparation method of the tomato leafminer sex pheromone intermediate further includes:

[0092] Carrying out an olefin cross-metathesis reaction on the compound shown in formula (I) and the compound shown in formula (II) and / or the compound shown in formula (III) in the presence of a metal catalyst to generate the compound shown in formula (IV);

[0093] 。

[0094] Another technical solution provided by the present invention: A preparation method of a tomato leafminer sex pheromone intermediate, and the tomato leafminer sex pheromone intermediate has the structure shown in formula (IX);

[0095] The preparation method includes: carrying out a ylide reaction on the compound shown in formula (V) and the compound shown in formula (VII) to generate the compound shown in formula (IX);

[0096]

[0097] In formula (V) and formula (IX), R is a hydroxyl protecting group other than acetyl; in formula (VII), R1 is a halogen.

[0098] Another technical solution provided by the present invention: A preparation method of a tomato leafminer sex pheromone intermediate, and the tomato leafminer sex pheromone intermediate has the structure shown in formula (VIII);

[0099] The preparation method includes: carrying out a ylide reaction on the compound shown in formula (V) and the compound shown in formula (VI) to generate the compound shown in formula (VIII);

[0100]

[0101] In formula (V) and formula (VIII), R is a hydroxyl protecting group other than acetyl; in formula (VI), R2 is a halogen.

[0102] Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art:

[0103] The present invention provides a new route for preparing the sex pheromone of Tuta absoluta. This route innovatively uses commercially available 5-hexen-1-ol as the starting material to synthesize the new intermediate (E)-8-hydroxy-3-octene acetate which can be used as an intermediate for preparing the sex pheromone of Tuta absoluta and the further oxidized intermediate (E)-8-aldehyde-3-octene acetate. Then, using these as intermediate raw materials, the 8Z-double bond is constructed through the Wittig reaction. The overall route has fewer steps. When the hydroxyl protecting group is selected as acetyl, the total number of steps for preparing the two components of the sex pheromone of Tuta absoluta is only 4 steps. When other protecting groups are selected for the hydroxyl group, by adding a deprotection group and acetylation process with mild reaction conditions, the total number of steps is also only 8 steps. In particular, the raw materials for each step of the synthesis route of the present invention are simple and easily available, the reaction conditions are mild, and the product selectivity is relatively high, which is conducive to large-scale production. Description of the Drawings

[0104] Figure 1 1H NMR spectrum of (E)-8-hydroxy-3-octene acetate (the compound shown in formula (IV)); 1 H NMR spectrum;

[0105] Figure 2 1H NMR spectrum of (E)-8-aldehyde-3-octene acetate (the compound shown in formula (V)); 1 H NMR spectrum;

[0106] Figure 3 1H NMR spectrum of (3E,8Z)-3,8-tetradecadien-1-ol (the compound shown in formula (X)); 1 H NMR spectrum;

[0107] Figure 4 1H NMR spectrum of (3E,8Z,11Z)-3,8,11-tetradecatrien-1-ol (the compound shown in formula (XI)); 1 H NMR spectrum;

[0108] Figure 5 1H NMR spectrum of (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate (SP-1); 1 H NMR spectrum;

[0109] Figure 6 1H NMR spectrum of (3E,8Z)-3,8-tetradecadienyl acetate (SP-2); 1 H NMR spectrum. Detailed Embodiments

[0110] The above solution will be further described below in conjunction with specific embodiments; it should be understood that these embodiments are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited by the scope of the following embodiments; the implementation conditions adopted in the embodiments can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0111] In the following embodiments, unless otherwise specified, all raw materials are commercially available or prepared by conventional methods in the art.

[0112] Example 1: This example provides a preparation method of (3E,8Z,11Z)-3,8,11-tetradecatriene acetate with the structure shown in formula (SP-1) and (3E,8Z)-3,8-tetradecadiene acetate with the structure shown in formula (SP-2).

[0113] Example 1-1: Preparation of (E)-8-hydroxy-3-octene acetate (compound shown in formula (IV))

[0114] In a 25 mL round-bottom flask, under a N2 atmosphere and at room temperature, 5-hexen-1-ol (200 mg, 2 mmol), 3-butenyl acetate (570 mg, 5 mmol), copper(I) iodide (19 mg, 0.1 mmol), Grubbs II catalyst (phenylmethylene-[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinyl]-dichloro-(tricyclohexylphosphine)ruthenium, 336 mg, 0.4 mmol) and 5 mL of diethyl ether were added in sequence. The reaction temperature was raised to 30 °C and stirred for 14 h. The reaction was monitored by thin-layer chromatography; after the reaction was completed, the solvent was concentrated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1, volume ratio) to obtain the product (E)-8-hydroxy-3-octene acetate, a pale yellow transparent liquid, 171 mg, with a yield of 46% and a purity of 98%; the 1 1H NMR spectrum of the prepared product (E)-8-hydroxy-3-octene acetate is shown in Figure 1 as follows, 1 1H NMR (400 MHz, Chloroform- d ) δ 5.51 (d, J J = 9.1Hz, 1H), 5.42 (s, 1H), 4.06 (s, 2H), 3.65 (s, 2H), 2.33 (d, J J = 8.0 Hz, 2H),2.05 (s, 5H), 1.54 (d, J J = 15.2 Hz, 3H), 1.43 (s, 2H). 1313C NMR (101 MHz, Chloroform-d) δ 171.26, 133.06, 125.55, 64.12, 62.74, 32.24, 32.10, 31.93, 25.42, 20.98。

[0115] Example 1-2: Preparation of (E)-8-formyl-3-octenyl acetate (the compound shown in formula (V))

[0116] In a 25 mL round-bottom flask, 10 mL of dichloromethane, (E)-8-hydroxy-3-octenyl acetate (171 mg, 0.92 mmol), and Dess-Martin periodinane (424 mg, 1 mmol) were successively added under an ice bath. The ice bath was maintained for 2 - 4 h, and the reaction was monitored by thin-layer chromatography. After the reaction was completed, a mixed solution of 5 mL of saturated sodium thiosulfate solution and 5 mL of saturated sodium bicarbonate was added to the reaction, and then stirred well for 3 h. The resulting mixture was extracted with ethyl acetate to obtain an organic layer, which was then dried over anhydrous sodium sulfate and concentrated to obtain a crude product. Then, it was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1, v / v) to obtain the product (E)-8-formyl-3-octenyl acetate, a pale yellow transparent liquid, 100 mg, with a yield of 59% and a purity of 98%. The 1H NMR spectrum of the prepared product (E)-8-formyl-3-octenyl acetate is shown in 1 See Figure 2 as follows 1 1H NMR (400 MHz, Chloroform- d ) δ 9.77 (s, 1H), 5.60 – 5.38 (m, 2H), 4.08 (t, J J = 6.8 Hz, 2H), 2.44 (s, 2H), 2.31 (s, 2H), 2.06 (d, J J = 13.8 Hz, 5H), 1.69 (d, J J = 7.3 Hz, 2H). 13 13C NMR (101 MHz, Chloroform-d) δ 202.49, 171.09, 131.98, 126.64, 63.94, 31.90, 21.65, 20.96。

[0117] Example 1-3: Preparation of (3E,8Z)-3,8-tetradecadienyl acetate (the compound shown in formula (VIII))

[0118] In a 50 mL three-necked flask, under a nitrogen atmosphere, hexyltriphenylphosphonium bromide (307 mg, 0.72 mmol) was added. Then, potassium bis(trimethylsilyl)amide (0.72 mL, 0.72 mmol, 1 M solution in tetrahydrofuran) was added under an ice bath. The mixture was stirred for 2 h while maintaining the ice bath. Then, it was transferred to -78 °C, and a 2 mL tetrahydrofuran solution of (E)-8-formyl-3-octene acetate (67 mg, 0.35 mmol) was added. Subsequently, the reaction was heated to -50 °C and stirred for 2 h, then further heated to room temperature and stirred for 2 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, 4 mL of saturated ammonium chloride solution was added, and the resulting mixture was extracted with ethyl acetate to obtain the organic layer. Then, after drying the organic layer with anhydrous sodium sulfate, it was concentrated to obtain the crude product. Subsequently, it was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1, v / v) to obtain the product (3E,8Z)-3,8-tetradecadienyl acetate (the hydroxyl protecting group is acetyl, so this compound is SP-2), a pale yellow transparent liquid, 53 mg, with a yield of 60% and a purity of 99%.

[0119] Example 1-4: Preparation of (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate (the compound shown in formula (IX))

[0120] In a 50 mL three-necked flask, under a nitrogen atmosphere, (Z)-3-hexenyltriphenylphosphonium iodide (253 mg, 0.53 mmol) was added. Then, potassium bis(trimethylsilyl)amide (0.54 mL, 0.54 mmol, 1 M solution in tetrahydrofuran) was added under an ice bath. The mixture was stirred for 2 h while maintaining the ice bath. Then, it was transferred to -78 °C, and a 2 mL tetrahydrofuran solution of (E)-8-formyl-3-octene acetate (50 mg, 0.19 mmol) was added. Subsequently, the reaction was heated to -50 °C and stirred for 2 h, then further heated to room temperature and stirred for 2 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, 4 mL of saturated ammonium chloride solution was added, and the resulting mixture was extracted with ethyl acetate to obtain the organic layer. Then, after drying the organic layer with anhydrous sodium sulfate, it was concentrated to obtain the crude product. Subsequently, it was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1, v / v) to obtain (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate (the hydroxyl protecting group is acetyl, so this compound is SP-1), a pale yellow transparent liquid, 47 mg, with a yield of 70% and a purity of 99%.

[0121] In this example, 3-butenyl acetate is used as the compound shown in formula (II), that is, the hydroxyl protecting group is acetyl. Therefore, the compound shown in formula (VIII) prepared in this example is (3E,8Z)-3,8-tetradecadienyl acetate (SP-2), and the compound shown in formula (IX) is (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate (SP-1). That is, two components of the sex pheromone of Tuta absoluta can be prepared in a total of 4 steps;

[0122] Among them, calculated based on 5-hexen-1-ol, the total yield of (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate (SP-1) is 46%×59%×70% = 18.998%, and the total yield of (3E,8Z)-3,8-tetradecadienyl acetate (SP-2) is 46%×59%×60% = 16.284%.

[0123] The deprotection process and acetylation process of the present invention will be further described below in combination with the above process.

[0124] Examples 1-5: Preparation of (3E,8Z)-3,8-tetradecadien-1-ol (compound shown in formula (X))

[0125] In a 50 mL three-necked flask, add (3E,8Z)-3,8-tetradecadienyl acetate (47 mg, 0.18 mmol) and 10 mL of methanol. Then, at room temperature, add 1.3 mL of 5% aqueous sodium hydroxide solution and stir at room temperature for 2 h. Monitor the reaction by thin-layer chromatography; after the reaction is completed, first evaporate the methanol, then add 20 mL of H2O and 20 mL of DCM (dichloromethane), extract and separate the layers to obtain the organic layer. After drying the organic layer with anhydrous sodium sulfate, concentrate to obtain the crude product; then purify by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1, volume ratio) to obtain (3E,8Z)-3,8-tetradecadien-1-ol (compound shown in formula (X)), a pale yellow transparent liquid, 35 mg, with a yield of 90% and a purity of 99%. The 1H NMR spectrum of the prepared (3E,8Z)-3,8-tetradecadien-1-ol is shown in 1 See Figure 3 as shown.

[0126] Examples 1-6: Preparation of (3E,8Z,11Z)-3,8,11-tetradecatrien-1-ol (compound shown in formula (XI))

[0127] In a 50 mL three-necked flask, (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (47 mg, 0.18 mmol) and 10 mL of methanol were added. Then, 1.3 mL of 5% aqueous sodium hydroxide solution was added at room temperature, and the mixture was stirred at room temperature for 2 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the methanol was first evaporated, then 20 mL of H2O and 20 mL of DCM were added, and the mixture was extracted and separated to obtain the organic layer. After drying the organic layer with anhydrous sodium sulfate, it was concentrated to obtain the crude product. Then, it was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1, volume ratio) to obtain (3E,8Z,11Z)-3,8,11-tetradecatrien-1-ol, a pale yellow transparent liquid, 35 mg, with a yield of 90% and a purity of 99%. The 1 1H NMR spectrum of the prepared (3E,8Z,11Z)-3,8,11-tetradecatrien-1-ol is shown in Figure 4 the following figure.

[0128] Examples 1-7: Preparation of (3E,8Z)-3,8-tetradecadiene acetate (SP-2)

[0129] In a 50 mL round-bottom flask, (3E,8Z)-3,8-tetradecadien-1-ol (61 mg, 0.29 mmol), 4-dimethylaminopyridine (1 mg, 0.008 mmol), triethylamine (88 mg, 0.87 mmol), acetic anhydride (59 mg, 0.58 mmol) and 5 mL of dichloromethane were added in sequence at room temperature, and the reaction was carried out for 2 h. The reaction was monitored by gas chromatography. After the reaction was completed, 10 mL of 1 M hydrochloric acid was added at room temperature to wash the organic phase once, and the organic phase was washed with saturated sodium bicarbonate solution once. The organic phases were combined, dried with anhydrous sodium sulfate, and evaporated to dryness to obtain a pale yellow transparent liquid, and the product (3E,8Z)-3,8-tetradecadiene acetate (SP-2) was obtained, 71 mg, with a yield of 97% and a purity of 99%. The 1 1H NMR spectrum of the prepared (3E,8Z)-3,8-tetradecadiene acetate (SP-2) is shown in Figure 6 the following figure, 1 1H NMR (400 MHz, Chloroform-d) δ 5.53-5.39 (m, 1H), 5.36-5.17 (m, 3H), 3.99 (t, J = 6.9 Hz, 2H), 2.34-2.16 (m, 2H), 1.95 (d, J = 4.5 Hz, 9H), 1.35-1.11 (m, 8H), 0.82 (t, J = 6.8 Hz, 3H). 1313C NMR (101 MHz, CDCl3) δ 170.84, 133.17, 131.51, 130.73, 130.19, 129.78, 129.29, 128.58, 125.29, 77.42, 77.09, 76.78, 64.46, 64.00, 62.52, 32.52, 32.09, 31.93, 31.47, 29.92, 29.38, 29.21, 28.49, 27.14, 26.97, 26.55, 25.51, 22.52, 22.49, 20.81, 13.98。

[0130] Examples 1 - 8: Preparation of (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (SP-1)

[0131] Into a 50 mL round-bottom flask, (3E,8Z,11Z)-3,8,11-tetradecatrien-1-ol (50 mg, 0.24 mmol), 4-dimethylaminopyridine (1 mg, 0.008 mmol), triethylamine (58 mg, 0.57 mmol), acetic anhydride (39 mg, 0.38 mmol) and 5 mL of dichloromethane were successively added at room temperature. The reaction was carried out for 2 h, and the reaction was monitored by gas chromatography. After the reaction was completed, the organic phase was washed once with 10 mL of 1 M hydrochloric acid at room temperature and once with saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous sodium sulfate, and evaporated to dryness to obtain a pale yellow transparent liquid. The product (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (SP-1), 58 mg, with a yield of 97% and a purity of 99% was obtained. The 1H NMR spectrum of the prepared (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (SP-1) 1 is shown in Figure 5 as follows, 1 1H NMR (400 MHz, Chloroform-d) δ 5.47 (dtt, J = 14.5, 6.5, 1.3 Hz, 1H), 5.43 - 5.08 (m, 5H), 4.02 (t, J = 6.9 Hz, 2H), 2.72 (t, J = 6.1 Hz, 2H), 2.27 (qd, J = 6.9, 1.2 Hz, 2H), 2.09 - 1.87 (m, 9H), 1.38 (p, J = 7.5 Hz, 2H), 0.93 (t, J = 7.6 Hz, 3H). 1313C NMR (101 MHz, CDCl3) δ171.04, 133.15, 131.77, 130.26, 129.66, 128.74, 128.34, 127.31, 127.06, 125.72, 125.39, 77.39, 77.07, 76.76, 64.52, 64.07, 32.12, 31.94, 30.30, 29.28, 28.50, 27.02, 26.97, 26.59, 25.51, 20.92, 20.51, 14.24。

[0132] As can be seen from the above process, even if other hydroxyl protecting groups other than acetyl groups are selected in the present invention, the total number of steps for preparing the two components of the sex pheromone of Tuta absoluta in the present invention is only 8 steps.

[0133] Example 2: This example is basically the same as Example 1, except that the preparation process of the compound shown in formula (IV) is different. Specifically, the preparation process of (E)-8-hydroxy-3-octene acetate (the compound shown in formula (IV)) is as follows:

[0134] In a 25 mL round-bottom flask, under a nitrogen atmosphere and at room temperature, 5-hexen-1-ol (100 mg, 1 mmol), 3-butenyl acetate (570 mg, 5 mmol), copper(I) iodide (19 mg, 0.1 mmol), Hoveyda-Grubbs II catalyst (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxybenzylidene)ruthenium, 62 mg, 0.1 mmol) and 5 mL of diethyl ether were added in sequence. The reaction temperature was raised to 30 °C and stirred for 14 h. The reaction was monitored by thin-layer chromatography; after the reaction was completed, the solvent was concentrated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1, volume ratio) to obtain the product (E)-8-hydroxy-3-octene acetate, a pale yellow transparent liquid, 65 mg, with a yield of 35% and a purity of 98%.

[0135] Example 3: This example is basically the same as Example 1, except that the preparation process of the compound shown in formula (V) is different. Specifically, the preparation process of (E)-8-formyl-3-octene acetate (the compound shown in formula (V)) is as follows:

[0136] In a 25 mL round-bottom flask, 10 mL of dichloromethane, (E)-8-hydroxy-3-octene acetate (145 mg, 0.78 mmol), and Dess-Martin periodinane (662 mg, 1.56 mmol) were successively added under an ice bath. The ice bath was maintained for 2 - 4 h, and the reaction was monitored by thin-layer chromatography. After the reaction was completed, a mixed solution of 5 mL of saturated sodium thiosulfate solution and 5 mL of saturated sodium bicarbonate was added to the reaction, and then stirred thoroughly for 3 h. The resulting mixture was extracted with ethyl acetate to obtain an organic layer. After drying the organic layer with anhydrous sodium sulfate, it was concentrated to obtain a crude product. Then, it was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1, v / v) to obtain the product (E)-8-formyl-3-octene acetate, a pale yellow transparent liquid, 123 mg, with a yield of 86% and a purity of 98%.

[0137] In this example, calculated based on 5-hexen-1-ol, the total yield of (3E,8Z,11Z)-3,8,11-tetradecatriene acetate (SP-1) was 46% × 86% × 70% = 27.692%, and the total yield of (3E,8Z)-3,8-tetradecadiene acetate (SP-2) was 46% × 86% × 60% = 23.736%.

[0138] The above embodiments are only for illustrating the technical concept and features of the present invention, and the purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. It should not be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be covered within the protection scope of the present invention.

[0139] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values and individual point values of each range, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

Claims

1. A method for preparing a sex pheromone of a tomato leafminer, wherein the sex pheromone of the tomato leafminer comprises (3E,8Z,11Z)-3,8,11-tetradecatriene acetate having a structure shown in formula (SP-1), characterized in that: The preparation method comprises: Reaction (1): allowing the compound represented by formula (I) to undergo olefin cross-metathesis reaction with the compound represented by formula (II) and / or the compound represented by formula (III) in the presence of a metal catalyst to generate a compound represented by formula (IV); ； Reaction (2): using the compound represented by formula (IV) as a substrate, oxidizing it in the presence of an oxidant to generate a compound represented by formula (V); ； Reaction (3): allowing the compound represented by formula (V) to undergo a ylide reaction with the compound represented by formula (VII) to generate a compound represented by formula (IX); ； Reaction (4): using the compound represented by formula (IX) as a substrate, reacting under alkaline conditions to generate a compound represented by formula (XI); ； Reaction (5): subjecting the compound represented by formula (XI) to an acetylation reaction to generate (3E,8Z,11Z)-3,8,11-tetradecatriene acetate represented by formula (SP-1); ； Among them, in formula (II), formula (III), formula (IV), formula (V), and formula (IX), R is a hydroxyl protecting group; In the formula (VII), R1 is halogen.

2. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (1), the metal catalyst comprises a combination of one or more selected from the group consisting of a tungsten catalyst, a titanium catalyst, a molybdenum catalyst, a ruthenium catalyst and a cuprous catalyst; and / or, in the reaction (1), the olefin cross-metathesis reaction is controlled to be carried out in a protective atmosphere and a first solvent, the protective atmosphere is formed by introducing nitrogen and / or an inert gas, and the first solvent is a combination of one or more selected from the group consisting of dichloromethane, ethyl acetate, tetrahydrofuran, ether, toluene, N,N-dimethylformamide, cyclohexane and n-hexane; and / or, in the reaction (1), the molar ratio of the compound represented by formula (II) and / or the compound represented by formula (III) to the compound represented by formula (I) is 1:0.1-20; and / or, in the reaction (1), the reaction temperature of the olefin cross-metathesis reaction is controlled to be 0-120°C.

3. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (1), the metal catalyst comprises a catalytic combination of a ruthenium catalyst and a cuprous catalyst. In the catalytic combination, the molar ratio of the cuprous catalyst to the ruthenium catalyst is 1:1-15.

4. The method for preparing the sex pheromone of tomato leafminer according to claim 3, characterized in that: The cuprous catalyst is a combination of one or more selected from CuI, CuCl, and CuBr; and / or, the ruthenium catalyst is a combination of one or more selected from di(tricyclohexylphosphine)benzylidene ruthenium dichloride, phenylmethyl-[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinyl]-dichloro-(tricyclohexylphosphino)ruthenium, dichloro(o-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium, and (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinyl)dichloro(o-isopropoxybenzylidene)ruthenium; and / or, the molar ratio of the compound represented by formula (II) and / or the compound represented by formula (III) to the cuprous catalyst is 1:0.01-0.

2.

5. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (2), the oxidant is a combination of one or more selected from ruthenium tetroxide, manganese dioxide, potassium monopersulfate, sodium hypochlorite, lead tetraacetate, sodium periodate, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, Dess-Martin oxidant, perbenzoic acid and pyridinium dichromate; and / or, the reaction (2) is controlled to be carried out at -5 to 10 °C; and / or, the reaction (2) is controlled to be carried out in a second solvent, and the second solvent is a combination of one or more selected from dichloromethane, ethyl acetate, tetrahydrofuran, ether, toluene, N,N-dimethylformamide, cyclohexane and n-hexane; and / or, the molar ratio of the compound represented by formula (IV) to the oxidant is 1:1.0-3.

0.

6. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (3), the ylide reaction is controlled to be carried out in the presence of a first alkaline substance, the first alkaline substance comprises a combination of one or more selected from the group consisting of sodium hydroxide, sodium carbonate, sodium hydride, n-butyl lithium, lithium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, potassium tert-butoxide, sodium methoxide and sodium ethoxide, and the molar ratio of the compound represented by formula (V) to the first alkaline substance is controlled to be 1:1.5-3; and / or, in the reaction (3), the molar ratio of the compound represented by formula (V) to the compound represented by formula (VII) is controlled to be 1:1-3; and / or, in the reaction (3), the reaction temperature of the ylide reaction is controlled to be -78~25°C; and / or, in the reaction (3), the ylide reaction is controlled to be carried out in a protective atmosphere and in a third solvent, the protective atmosphere is formed by introducing nitrogen and / or an inert gas, and the third solvent comprises tetrahydrofuran.

7. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: The implementation method of the reaction (3) comprises: adding a first alkaline substance solution to the compound represented by the formula (VII) under a protective atmosphere at -10 to 10°C to obtain a mixed solution, stirring the mixed solution at -10 to 10°C, then adding the solution of the compound represented by the formula (V) to the mixed solution at -78 to -65°C, and then stirring and reacting at -60 to -35°C and 10 to 25°C in sequence; wherein the first alkaline substance solution is formed by dispersing the first alkaline substance using a third solvent, and the solution of the compound represented by the formula (V) is formed by dispersing the compound represented by the formula (V) using a third solvent, and the third solvent in the first alkaline substance solution and the solution of the compound represented by the formula (V) both comprises tetrahydrofuran.

8. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (4), the alkaline condition is formed by adding a second alkaline substance or an aqueous solution thereof, wherein the second alkaline substance is a combination of one or more selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide and tetrabutylammonium fluoride; and / or, the reaction (4) is controlled to be carried out in a fourth solvent, wherein the fourth solvent is a combination of one or more selected from the group consisting of methanol, ethanol, isopropanol, tetrahydrofuran and water; and / or, the reaction temperature of the reaction (4) is controlled to be 0-60° C.; and / or, the hydroxyl protecting group is an acyl hydroxyl protecting group, an alkane hydroxyl protecting group, a silicon hydroxyl protecting group or an acetal hydroxyl protecting group.

9. The method for preparing the sex pheromone of tomato leafminer according to claim 1, characterized in that: In the reaction (5), the acetylation reaction is controlled to be carried out in the presence of an organic base, and the organic base includes a combination of one or more selected from triethylamine, 4-dimethylaminopyridine, and pyridine; and / or, in the reaction (5), the acetylation reaction is controlled to be carried out in a fifth solvent, and the fifth solvent is a combination of one or more selected from dichloromethane, ethyl acetate, tetrahydrofuran, and pyridine; and / or, in the reaction (5), the reaction temperature of the acetylation reaction is controlled to be 0-100°C; and / or, the hydroxyl protecting group is an acetyl group, and when the hydroxyl protecting group is an acetyl group, the reaction (4) and the reaction (5) in the preparation method do not exist, and the compound represented by formula (IX) is (3E,8Z,11Z)-3,8,11-tetradecatriene acetate having a structure represented by formula (SP-1); and / or, in formula (VII), R1 is bromine or iodine.

10. A method for preparing a sex pheromone of a tomato leafminer, wherein the sex pheromone of the tomato leafminer comprises (3E,8Z)-3,8-tetradecadienyl acetate having a structure shown in formula (SP-2), characterized in that: The preparation method comprises: Reaction (a): allowing the compound represented by formula (I) to undergo olefin cross-metathesis reaction with the compound represented by formula (II) and / or the compound represented by formula (III) in the presence of a metal catalyst to generate a compound represented by formula (IV); ； Reaction (b): using the compound represented by formula (IV) as a substrate, oxidizing it in the presence of an oxidant to generate a compound represented by formula (V); ； Reaction (c): allowing the compound represented by formula (V) to undergo a ylide reaction with the compound represented by formula (VI) to generate a compound represented by formula (VIII); ； Reaction (d): using the compound represented by the formula (VIII) as a substrate, reacting under alkaline conditions to generate the compound represented by the formula (X); ； Reaction (e): subjecting the compound represented by formula (X) to an acetylation reaction to generate (3E,8Z)-3,8-tetradecadienyl acetate represented by formula (SP-2); ； Among them, in formula (II), formula (III), formula (IV), formula (V), and formula (VIII), R is a hydroxyl protecting group; In formula (VI), R2 is halogen.

11. A method for preparing a sex pheromone intermediate of tomato leafminer, characterized in that: The tomato leafminer sex pheromone intermediate has a structure shown in formula (IX); The preparation method comprises: allowing the compound represented by formula (V) to undergo a ylide reaction with the compound represented by formula (VII) to generate a compound represented by formula (IX); ； In formula (V) and formula (IX), R is a hydroxyl protecting group other than acetyl; in formula (VII), R1 is a halogen.

12. A method for preparing a sex pheromone intermediate of tomato leafminer, characterized in that: The tomato leafminer sex pheromone intermediate has a structure shown in formula (VIII); The preparation method comprises: allowing the compound represented by formula (V) to undergo a ylide reaction with the compound represented by formula (VI) to generate a compound represented by formula (VIII); ； In formula (V) and formula (VIII), R is a hydroxyl protecting group other than acetyl; in formula (VI), R2 is a halogen.

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