(6z,9z)-6,9-dodecadien-1-yne and a process for its preparation

Abstract

The present invention provides (6Z,9Z)-6,9-dodecadien-1-yne of the following formula (1). Furthermore, the present invention provides a process for preparing (6Z,9Z)-6,9-dodecadien-1-yne (1) comprising reacting a (3Z,6Z)-10-halogeno-3,6-decadiene compound of the following general formula (2), wherein X represents a halogen atom, with a metal acetylide of the following general formula (3), wherein M represents Na, Li, K, Ag, Cu(I), MgZ, CaZ or Cu(II)Z, wherein Z represents a halogen atom or an ethynyl group, to form (6Z,9Z)-6,9-dodecadien-1-yne (1).

Description

Technical Field

[0001] This invention relates to (6Z,9Z)-6,9-dodecadiene-1-yne and its preparation method. Background Technology

[0002] The tomato leafminer (Tuta absoluta) is one of the most serious tomato pests originating in South America. It invaded Spain in 2006 and quickly spread to other parts of Europe, including Spain, Italy, and France; Africa, including Morocco, Tunisia, and Nigeria; the Middle East, including Turkey, Israel, and Iran; and Asia, including India, Nepal, China, and Japan. It is estimated that 20% of the world's tomato production is lost due to this pest. Therefore, controlling this pest is crucial to preventing severe damage. Depending on the temperature of its habitat, the tomato leafminer has a short lifespan, with 10 or more generations per year, making it highly susceptible to developing pesticide resistance. Consequently, pesticides often lose their effectiveness against this pest within a few years of initial application, making pesticide control difficult. Therefore, biological control methods that prevent the development of resistance have gained attention. As one such method, the use of sex pheromones for mating disruption is increasingly being used worldwide to control this species.

[0003] According to reports, the sex pheromone composition of the tomato leafminer moth is a 90:10 mixture of (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate and (3E,8Z)-3,8-tetradecanediene acetate (Non-Patent Literature 1 listed below).

[0004] However, an industrial preparation method for the main component (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate has not yet been established, which hinders the widespread use of mating interference methods to control tomato leafminer (Non-Patent Literature 2 listed below).

[0005] A method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetrien acetate is described in Non-Patent Document 3 listed below. In this method, 2-(3-butyn-1-yloxy)tetrahydro-2H-pyran is reacted with n-butyllithium in THF, followed by a coupling reaction with (3Z,6Z)-10-bromo-3,6-decadiene in a mixed solvent of THF and N,N'-dimethylpropenylurea (DMPU) to form tetrahydro-2-[(8Z,11Z)-8,11-tetradecanedien-3-yn-1-yloxy]-2H-pyran. Next, the tetrahydropyranyl (THP) group of the tetrahydro-2-[(8Z,11Z)-8,11-tetradecadien-3-yn-1-yloxy]-2H-pyran obtained therefrom was removed in methanol in the presence of Dowex (trademark) 50W-X8 to form (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol. Subsequently, the (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol prepared therefrom was reduced with lithium aluminum hydride to form (3E,8Z,11Z)-3,8,11-tetradectrien-1-ol, and the hydroxyl group of the (3E,8Z,11Z)-3,8,11-tetradectrien-1-ol prepared therefrom was acetylated with acetic anhydride.

[0006] Another method for preparing (3E,8Z,11Z)-3,8,11-tetradecadiene acetate is described in Non-Patent Document 4 listed below. In this method, 2-(3-butyn-1-yloxy)tetrahydro-2H-pyran is reacted with n-butyllithium in THF, followed by a coupling reaction with (3Z,6Z)-10-bromo-3,6-decadiene in a mixed solvent of THF and hexamethylphosphoric triamine (HMPA) to form tetrahydro-2-[(8Z,11Z)-8,11-tetradecadiene-3-yn-1-yloxy]-2H-pyran. Next, the tetrahydro-2-[(8Z,11Z)-8,11-tetradecadien-3-yn-1-yloxy]-2H-pyran prepared therefrom underwent Birch reduction to form tetrahydro-2-[(3E,8Z,11Z)-3,8,11-tetradecadienyloxy]-2H-pyran. Subsequently, the tetrahydropyranyl (THP) group of the tetrahydro-2-[(3E,8Z,11Z)-3,8,11-tetradecadienyloxy]-2H-pyran obtained therefrom was removed in methanol in the presence of an acid catalyst to form (3E,8Z,11Z)-3,8,11-tetradecadien-1-ol. Then, the hydroxyl group of the (3E,8Z,11Z)-3,8,11-tetradecadien-1-ol prepared therefrom was acetylated with acetic anhydride.

[0007] List of Literature

[0008] [Non-patent literature]

[0009] [Non-Patent Literature 1] Athula B. Attygalle et al., 1996, J. Chem. Ecol., 22(4):787-800

[0010] [Non-Patent Literature 2] Peter Witzgall et al., 2010, J.Chem.Ecol., 36(1): 80-100

[0011] [Non-Patent Literature 3] Athula B. Attygalle et al., 1995, Tetrahedron Letters., 36(31): 5471-5474

[0012] [Non-Patent Literature 4] Angel Guerrero et al., 2015, Synthesis, 47(07): 961-968 Summary of the Invention

[0013] The problem to be solved by this invention

[0014] However, in the two preparation methods described in Non-Patent Literatures 3 and 4, the extremely expensive 2-(3-butyn-1-yloxy)tetrahydro-2H-pyran is used as the starting material. Although 2-(3-butyn-1-yloxy)tetrahydro-2H-pyran can be prepared by reacting 3-butyn-1-ol with dihydropyran (DHP) in the presence of an acid catalyst, both 3-butyn-1-ol and DHP are difficult to purchase commercially at low cost. Therefore, these preparation methods are not suitable for industrial production. As described in Non-Patent Literature 1, in the coupling reaction of 2-(3-butyn-1-yloxy)tetrahydro-2H-pyran, 2-hydroxytetrahydropyran is likely to be eliminated, leaving (8Z,11Z)-1,8,11-tetradecanetrien-3-yne as a byproduct, which is undesirable considering purity. Furthermore, the preparation method described in Non-Patent Literature 3 uses the expensive Dowex (trademark), making the method economically disadvantageous. In the preparation method described in Non-Patent Literature 4, carcinogenic hexamethylphosphoric triamine and n-butyllithium (difficult to handle due to their sensitivity to air or water and their flammability when exposed to air) are used extensively as solvents. Therefore, this method is difficult to carry out on an industrial scale. As mentioned above, the preparation methods described in Non-Patent Literatures 3 and 4 both present problems in the industrial production of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol, an intermediate used in the preparation of (3E,8Z,11Z)-3,8,11-tetradectrien acetate (a sex pheromone component of the tomato leafminer moth).

[0015] The present invention was prepared under these conditions with the aim of providing a compound that is a precursor for the industrial preparation of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol. The present invention also aims to provide a method for preparing this compound.

[0016] In order to overcome the aforementioned problems of the prior art, in-depth research was conducted, and as a result, the inventors have successfully prepared (6Z,9Z)-6,9-dodecadien-1-yne, and found that this compound is a useful intermediate for the preparation of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol. The inventors also found that (3E,8Z,11Z)-3,8,11-tetradecanetrien acetate (a sex pheromone component of the tomato leafminer moth) can be prepared from (6Z,9Z)-6,9-dodecadien-1-yne in fewer steps using inexpensive starting materials, thus completing the present invention.

[0017] According to one aspect of the invention, the invention provides (6Z,9Z)-6,9-dodecadien-1-yne of the following formula (1):

[0018]

[0019] According to another aspect of the present invention, the present invention provides a method for preparing (6Z,9Z)-6,9-dodecadien-1-yne of formula (1):

[0020]

[0021] The method includes:

[0022] Make the following (3Z,6Z)-10-halo-3,6-decadiene compounds of general formula (2):

[0023]

[0024] Where X represents a halogen atom

[0025] Reaction with metal acetylenides of the following general formula (3):

[0026] MC≡CH(3)

[0027] Where M represents Na, Li, K, Ag, Cu(I), MgZ, CaZ, or Cu(II)Z, and Z represents a halogen atom or an acetylene group.

[0028] To form (6Z,9Z)-6,9-dodecadiene-1-yne (1).

[0029] According to another aspect of the present invention, the present invention provides a method for preparing (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol of formula (4):

[0030]

[0031] The method includes:

[0032] React (6Z,9Z)-6,9-dodecadien-1-yne (1) with a base; and

[0033] The resulting reaction mixture was homogenized with ethylene oxide to form (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4).

[0034] According to another aspect of the present invention, the present invention provides a method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol of formula (5):

[0035]

[0036] The method includes:

[0037] The aforementioned method for preparing (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4); and

[0038] (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) was reduced to form (3E,8Z,11Z)-3,8,11-tetradectrien-1-ol (5).

[0039] According to another aspect of the present invention, the present invention provides a method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate of formula (6):

[0040]

[0041] Where Ac represents the acetyl group.

[0042] The method includes:

[0043] The aforementioned method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5); and

[0044] Acetylation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) forms (3E,8Z,11Z)-3,8,11-tetradecanetrien acetate (6).

[0045] According to the present invention, (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) and (3E,8Z,11Z)-3,8,11-tetradectrien acetate (6) can be prepared industrially in fewer steps without the use of expensive raw materials. According to the present invention, useful synthetic intermediates for the preparation of these two compounds can also be provided. Detailed Implementation

[0046] A.(6Z,9Z)-6,9-dodecadien-1-yne(1)

[0047] Preparation of (6Z,9Z)-6,9-dodecadien-1-yne (1)

[0048] The (6Z,9Z)-6,9-dodecadien-1-yne of formula (1) can be prepared by reacting the (3Z,6Z)-10-halo-3,6-decadien compound of formula (2) with the metal acetylenide of formula (3). This reaction is a nucleophilic substitution reaction between the (3Z,6Z)-10-halo-3,6-decadien compound (2) and the metal acetylenide (3).

[0049]

[0050] Where X represents a halogen atom and M represents a metal.

[0051] (3Z,6Z)-10-halo-3,6-decadiene compounds (2)

[0052] First, the (3Z,6Z)-10-halo-3,6-decadiene compound of the following general formula (2) will be described.

[0053]

[0054] X represents a halogen atom. Specifically, the halogen atom X is a chlorine atom, a bromine atom, or an iodine atom, with bromine or iodine atom being preferred in consideration of reactivity.

[0055] Specific examples of (3Z,6Z)-10-halo-3,6-decadiene compounds (2) include the following compounds:

[0056] (3Z,6Z)-10-chloro-3,6-decadiene, (3Z,6Z)-10-bromo-3,6-decadiene, and (3Z,6Z)-10-iodo-3,6-decadiene.

[0057] If necessary, (3Z,6Z)-10-halo-3,6-decadiene compound (2) may be used alone or in combination with other compounds.

[0058] (3Z,6Z)-10-halo-3,6-decadiene compound (2) can be commercially available or can be prepared internally, for example by halogenating (4Z,7Z)-4,7-decadien-1-ol.

[0059] Metal acetylene compounds (3)

[0060] Next, the metal acetylene compounds of the following general formula (3) will be described.

[0061] MC≡CH (3)

[0062] M represents Na, Li, K, Ag, Cu(I), MgZ, CaZ, or Cu(II)Z, where Z represents a halogen atom or an acetylene group. Examples of halogen atoms include chlorine, bromine, and iodine atoms. Considering reactivity, bromine or iodine atoms are preferred as halogen atoms.

[0063] Considering reactivity, M is preferably Na, Li, Cu(I) or Cu(II)Z.

[0064] Specific examples of metal acetylenides (3) include the following compounds: sodium acetylenide, lithium acetylenide, potassium acetylenide, magnesium acetylenide, calcium acetylenide, copper acetylenide, and silver acetylenide. Considering reactivity, sodium acetylenide, lithium acetylenide, or copper acetylenide are preferred for metal acetylenide (3).

[0065] Metal acetylene compounds (3) can be prepared internally, for example, by reacting heated sodium or magnesium with acetylene, or by reacting n-butyllithium with acetylene.

[0066] Nucleophilic substitution reaction

[0067] If necessary, the metal acetylene compound (3) may be used alone or in combination with other products. The metal acetylene compound (3) may be a commercially available product.

[0068] Considering reactivity, the amount of metal acetylene compound (3) used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 3.0 mol, relative to each mole of (3Z,6Z)-10-halo-3,6-decadiene compound (2).

[0069] If necessary, a solvent may be added to the nucleophilic substitution reaction.

[0070] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); nitriles, such as acetonitrile and propionitrile; and esters, such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, the preferred solvents are ethers, such as 4-methyltetrahydropyran, tetrahydrofuran, or 2-methyltetrahydrofuran (2-MeTHF); hydrocarbons, such as toluene or xylene; or aprotic polar solvents, such as N,N-dimethylformamide or N,N-dimethylacetamide, more preferably hydrocarbons or aprotic polar solvents.

[0071] Solvents may be used alone or in combination, if necessary. Solvents may be commercially available.

[0072] The amount of solvent used in the nucleophilic substitution reaction is preferably 0 to 7000 g, more preferably 0 to 3000 g, relative to each mole of (3Z,6Z)-10-halo-3,6-decadiene compound (2).

[0073] The reaction temperature in the nucleophilic substitution reaction varies with the metal acetylene compound (3) and / or solvent used, and is preferably -20°C to 180°C, more preferably 0°C to 100°C, taking into account reactivity.

[0074] The reaction time of the nucleophilic substitution reaction varies depending on the metal acetylene compound (3) to be used, the solvent and / or the production scale, and is preferably 0.5 to 100 hours considering reactivity.

[0075] Therefore, (6Z,9Z)-6,9-dodecadien-1-yne (1) can be prepared from (3Z,6Z)-10-halo-3,6-decadien compound (2), and metal acetylenide (3) can be prepared from acetylene and metal (such as sodium), both of which are inexpensive industrial starting materials.

[0076] B. Preparation of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4)

[0077] The (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol of formula (4) can be prepared by reacting (6Z,9Z)-6,9-dodecadien-1-yne (1) with a base, followed by homogenization with ethylene oxide.

[0078]

[0079] Examples of bases added in homologation reactions include organolithium reagents such as n-butyllithium, tert-butyllithium, methyllithium, and phenyllithium; Grignard reagents such as methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, ethylmagnesium chloride, n-propylmagnesium chloride, n-butylmagnesium chloride, isopropylmagnesium chloride, and phenylmagnesium chloride; metal acetylenides such as sodium acetylenide, lithium acetylenide, potassium acetylenide, magnesium acetylenide, calcium acetylenide, copper acetylenide, silver acetylenide, and aluminum acetylenide; and metal hydride reagents such as sodium hydride and potassium hydride. For safety reasons, organolithium reagents, Grignard reagents, or metal acetylenides are preferred; for usability reasons, Grignard reagents are more preferred.

[0080] Considering reactivity, the amount of base used is preferably 1.0 to 10.0 moles, more preferably 1.0 to 3.0 moles, relative to each mole of (6Z,9Z)-6,9-dodecadien-1-yne (1).

[0081] Considering reactivity, the amount of ethylene oxide used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 5.0 mol, relative to each mole of (6Z,9Z)-6,9-dodecadien-1-yne (1).

[0082] Solvents may be used in homogenization reactions if necessary. Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); and nitriles, such as acetonitrile and propionitrile. Considering reactivity, ethers, such as diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, or 4-methyltetrahydropyran; or hydrocarbons, such as toluene or xylene, are preferred solvents.

[0083] Solvents may be used alone or in combination, if necessary. Solvents may be commercially available.

[0084] Considering reactivity, the amount of solvent used is preferably 20 to 7000 g, more preferably 50 to 3000 g, relative to each mole of (6Z,9Z)-6,9-dodecadien-1-yne (1).

[0085] The reaction temperature in the homogenization reaction varies depending on the base and / or solvent to be used, and is preferably -40°C to 180°C, more preferably -10°C to 100°C, taking into account reactivity.

[0086] The reaction time for the homogenization reaction varies depending on the base, solvent, and / or production scale used, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0087] Therefore, (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4) (an important intermediate for the preparation of sex pheromones of the tomato leafminer moth) can be prepared from (6Z,9Z)-6,9-dodecadien-1-yne (1), inexpensive bases and ethylene oxide as raw materials.

[0088] C. Preparation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5)

[0089] The (3E,8Z,11Z)-3,8,11-tetradecadien-1-ol of formula (5) can be prepared by reducing (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4). The reduction reaction results in the conversion of the carbon-carbon triple bond in (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) into a double bond.

[0090]

[0091] Examples of reduction reactions for the preparation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) include (i) reduction with organoaluminum compounds, (ii) Birch reduction, (iii) ammonia-free Birch reduction and (iv) Benkeser reduction.

[0092] (i) Reduction with organoaluminum compounds

[0093] Reduction with organoaluminum compounds involves hydralumination with organoaluminum compounds in a solvent, followed by hydrolysis.

[0094]

[0095] Examples of organoaluminum compounds used in aluminum hydride include lithium aluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al), and diisobutylaluminum hydride (DIBAL).

[0096] Considering reactivity, the amount of organoaluminum compound used in aluminum hydride is preferably 0.25 to 100 moles, more preferably 0.50 to 20 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0097] Examples of solvents used in aluminum hydride include ethers such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), cyclopentylmethyl ether, 1,4-dioxane, and diethylene glycol dimethyl ether; and hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. Considering reactivity, ethers such as tetrahydrofuran, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, or diethylene glycol dimethyl ether are preferred solvents; or hydrocarbons such as hexane or toluene.

[0098] Solvents may be used alone or in combination, if necessary. Solvents may be commercially available.

[0099] Considering reactivity, the amount of solvent used is preferably 20 to 20,000 g, more preferably 50 to 9,000 g, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0100] The reaction temperature in aluminum hydride varies depending on the organoaluminum compound and / or solvent used, and is preferably from 0°C to 250°C, more preferably from 60°C to 150°C, taking into account reactivity.

[0101] The reaction time for aluminum hydration varies depending on the organoaluminum compound to be used, the solvent, and / or the production scale, and is preferably 0.1 to 100 hours, more preferably 0.1 to 5 hours, taking into account reactivity.

[0102] After aluminum is hydrogenated, it is hydrolyzed in a solvent using acid or alkali.

[0103] Examples of acids used in the hydrolysis following aluminum hydride include carboxylic acids such as acetic acid, propionic acid, butyric acid, valeric acid, neopentanoic acid, heptanoic acid, trifluoroacetic acid, chloroacetic acid, formic acid, and oxalic acid; sulfonic acids such as p-toluenesulfonic acid; and inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid. Considering reactivity, the acid is preferably a carboxylic acid (such as acetic acid) or an inorganic acid (such as hydrochloric acid).

[0104] Considering reactivity, the amount of acid used is preferably 0.00010 to 100.0 mol relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0105] Examples of bases used in the hydrolysis of aluminum after hydration include sodium hydroxide, potassium hydroxide, and calcium hydroxide.

[0106] Considering reactivity, the amount of base used is preferably 0.00010 to 100.0 moles relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0107] The solvent and its amount used in hydrolysis can be the same as those used in aluminum hydride, since hydrolysis is carried out in the aluminum hydride reaction system.

[0108] The reaction temperature of hydrolysis varies depending on the reagent used, and is preferably between 0°C and 80°C, taking into account the reaction rate.

[0109] The reaction time for hydrolysis varies with the reaction temperature and / or the scale of the reaction, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0110] (ii) Burch Restoration

[0111] Burch reduction of ammonia using metals.

[0112]

[0113] Considering reactivity, the amount of ammonia used is preferably 1.0 to 10,000 moles, more preferably 10 to 3,000 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0114] Examples of metals include alkali metals such as potassium, sodium, and lithium; and alkaline earth metals such as calcium and magnesium.

[0115] Metals may be used alone or in combination if necessary.

[0116] Considering reactivity, the amount of metal used is preferably 1.0 to 1000 moles, more preferably 1.0 to 100 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0117] In Birch reduction, in addition to ammonia, a proton source is preferably added. Examples of proton sources include alcohols such as methanol, ethanol, n-propanol, 2-propanol, and 2-methyl-2-propanol; as well as tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF).

[0118] If necessary, proton sources can be used alone or in combination. Proton sources can be commercially available products.

[0119] Considering reactivity, the amount of proton source used is preferably 1.0 to 10,000 moles, more preferably 1.0 to 3,000 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0120] Considering reactivity, the reaction temperature in the Birch reduction is preferably -78°C to 0°C, more preferably -78°C to -33°C.

[0121] The reaction time for Birch reduction varies with production scale, but is preferably 0.5 to 100 hours, taking into account reactivity.

[0122] (iii) Ammonia-free Birch reduction

[0123] Ammonia-free Birch reduction is performed using metals in crown ethers.

[0124]

[0125] Examples of crown ethers include 12-crown ether-4, 15-crown ether-5, 18-crown ether-6, dibenzo-18-crown ether-6, and diaza-18-crown ether-6.

[0126] Crown ethers can be used alone or in combination if necessary. Crown ethers are commercially available products.

[0127] Considering reactivity, the amount of crown ether used is preferably 1.0 to 100.0 mol, more preferably 1.0 to 20.0 mol, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4).

[0128] Examples of metals include alkali metals such as potassium, sodium, and lithium; and alkaline earth metals such as calcium and magnesium.

[0129] Metals may be used alone or in combination if necessary.

[0130] Considering reactivity, the amount of metal used is preferably 1.0 to 100.0 mol, more preferably 1.0 to 20.0 mol, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0131] In ammonia-free Birch reduction, in addition to crown ethers, a proton source is preferably added. Examples of proton sources include alcohols such as methanol, ethanol, n-propanol, 2-propanol, and 2-methyl-2-propanol; as well as tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF).

[0132] If necessary, proton sources can be used alone or in combination. Proton sources can be commercially available products.

[0133] Considering reactivity, the amount of proton source used is preferably 1.0 to 100.0 mol, more preferably 1.0 to 20.0 mol, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0134] The reaction temperature in ammonia-free Birch reduction varies depending on the metal and / or crown ether used, and is preferably -78°C to 100°C, more preferably -40°C to 40°C, taking into account reactivity.

[0135] The reaction time for ammonia-free Birch reduction varies depending on the metal to be used and / or crown ether and / or production scale, and is preferably 0.1 to 100 hours, more preferably 0.1 to 5 hours, taking into account reactivity.

[0136] (iv) Benkeser restoration

[0137] Benkeser reduction of alkylamines using metals.

[0138]

[0139] Examples of alkylamines include lower amines such as methylamine, ethylamine, propylamine, and 1,3-propanediamine.

[0140] Considering reactivity, the amount of alkylamine used is preferably 1.0 to 5000 moles, more preferably 1.0 to 1000 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0141] Examples of metals include alkali metals such as potassium, sodium, and lithium; and alkaline earth metals such as calcium and magnesium.

[0142] Metals may be used alone or in combination if necessary.

[0143] Considering reactivity, the amount of metal used is preferably 1.0 to 1000 moles, more preferably 1.0 to 100 moles, relative to each mole of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4).

[0144] Considering reactivity, the reaction temperature in the Benkeser reduction is preferably -78°C to 100°C, more preferably -78°C to 60°C.

[0145] The reaction time for Benkeser reduction varies with production scale, but is preferably 0.5 to 100 hours, taking into account reactivity.

[0146] D. Preparation of (3E,8Z,11Z)-3,8,11-tetradecanetrienyl acetate (6)

[0147] The (3E,8Z,11Z)-3,8,11-tetradecanetrien acetate of formula (6) can be prepared by acetylation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5).

[0148]

[0149] Acetylation can be performed using acetylation agents.

[0150] Examples of acetylation agents include acid anhydrides, such as acetic anhydride; acetylated halide compounds, such as acetyl chloride, acetyl bromide, and acetyl iodide; and acetate compounds, such as methyl acetate and ethyl acetate. For availability, acetylated agents are preferably acetic anhydride or acetylated halide compounds.

[0151] Considering reactivity and economy, the amount of acetylation agent used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 5.0 mol, relative to each mole of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5).

[0152] If necessary, an acid or base may be added during acetylation.

[0153] Examples of acids include inorganic acids such as hydrochloric acid, sulfuric acid, and nitric acid; aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, magnesium chloride, magnesium bromide, titanium tetrachloride, titanium tetrabromide, titanium methoxide (IV), titanium ethoxide (IV), titanium isopropoxide (IV), and titanium oxide (IV).

[0154] If necessary, acids may be used alone or in combination.

[0155] Considering reactivity and economy, the amount of acid used is preferably 0.001 to 3.00 mol, more preferably 0.01 to 1.50 mol, relative to each mole of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5).

[0156] Examples of bases include trialkylamine compounds such as trimethylamine, triethylamine, and N,N-diisopropylethylamine; cyclic amine compounds such as piperidine, pyrrolidine, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU); aromatic amine compounds such as pyridine, dimethylpyridine, N,N-dimethylaniline, N,N-diethylaniline, N,N-dibutylaniline, and 4-dimethylaminopyridine; and metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-amyloxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amyloxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-amyloxide.

[0157] If necessary, alkalis can be used alone or in combination with other substances.

[0158] Considering reactivity and economy, the amount of base used is preferably 0.010 to 10.0 mol, more preferably 1.0 to 5.0 mol, relative to each mole of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5).

[0159] If necessary, a solvent may be added during acetylation.

[0160] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); nitriles, such as acetonitrile and propionitrile; and esters, such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, hydrocarbons, such as toluene or xylene, are preferred solvents.

[0161] Solvents may be used alone or in combination, if necessary. Solvents may be commercially available.

[0162] If necessary, acetylation can be carried out in a solvent or without a solvent.

[0163] The amount of solvent used in acetylation is preferably 0 to 5000 g, more preferably 0 to 2000 g, relative to each mole of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5).

[0164] Therefore, (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate (6) can be prepared from the intermediate (6Z,9Z)-6,9-dodecanediene-1-yne (1) in fewer steps.

[0165] Example

[0166] The present invention will be described with reference to the following embodiments. It should be understood that the present invention is not limited to or not restricted by these embodiments.

[0167] Unless otherwise specified, the term "purity" as used herein refers to the percentage of area obtained by gas chromatography (GC). The term "production ratio" refers to the ratio of the percentage of area obtained by GC. The term "yield" is calculated from the percentage of area determined by GC.

[0168] In the examples, reaction monitoring and yield calculation were performed under the following GC conditions.

[0169] GC conditions: GC-2014 capillary gas chromatograph (Shimadzu Corporation); column: DB-WAX, 0.25μm×0.25mmφ×30m; carrier gas: He (1.55mL / min); detector: FID; column temperature: 150℃, increased at a rate of 5℃ / min, up to 230℃.

[0170] Taking into account the purity (%GC) of the starting materials and products, the yield is calculated according to the following equation.

[0171] Yield (%) = {[(mass of product × % GC) / molecular weight of product] ÷ [(mass of starting material × % GC) / molecular weight of starting material]} × 100

[0172] THF stands for tetrahydrofuran, and DMF stands for N,N-dimethylformamide.

[0173] Example 1: Preparation of (6Z,9Z)-6,9-dodecadien-1-yne (1)

[0174]

[0175] A solution (125.09 g) of sodium acetylene (3:M=Na) (0.60 mol) in xylene and DMF (122.80 g) was placed in a reactor at room temperature and stirred at 38°C to 42°C for 32 minutes. After stirring, (3Z,6Z)-10-bromo-3,6-decadiene (2:X=Br) (119.18 g, 0.46 mol, purity 83.48%) was added dropwise at 38°C to 42°C. After the addition was complete, the mixture was stirred at 38°C to 42°C for 17 hours. Subsequently, water (137.31 g) was added to the reaction mixture, and the reaction mixture was subjected to phase separation. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure. The concentrate was obtained by vacuum distillation to obtain (6Z,9Z)-6,9-dodecadien-1-yne (1) (71.15 g, 0.35 mol, purity 80.53%, bp = 95.2 °C to 99.0 °C / 1.87 kPa (14.0 mmHg)), with a yield of 77.05%.

[0176] The following are the spectral data of (6Z,9Z)-6,9-dodecadiene-1-yne (1) prepared therefrom.

[0177] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ = 0.97 (3H, t, J = 7.7Hz), 1.60 (2H, dt, J = 7.3Hz, 7.3Hz), 1.95 (1H, t, J = 2.7Hz), 2.08 (2H,quin-like,J=7.3Hz),2.16-2.23(4H,m),2.80(2H,dd,J=6.9Hz, 6.9Hz),5.27-5.45(4H,m); 13 C-NMR (500MHz, CDCl3): δ=14.27, 17.84, 20.52, 25.51, 26.10, 28.34, 68.32, 84.35, 127.15, 128.61, 129.22, 131.88.

[0178] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 161 (M + -1),147,133,119,105,91, 79,67,55,41.

[0179] Infrared absorption spectrum (D-ATR): ν = 3309, 3010, 2963, 2934, 1456, 1274, 718, 632.

[0180] Example 2: Preparation of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4)

[0181]

[0182] A solution (58.79 g) of methylmagnesium chloride (0.15 mol) in THF was placed in a reactor at room temperature, and (6Z,9Z)-6,9-dodecadien-1-yne (1) (22.51 g, 0.11 mol, purity 80.53%) obtained in Example 1 was added dropwise at 25°C to 60°C. After the addition was complete, the mixture was stirred at 60°C to 65°C for 3.5 hours. Subsequently, ethylene oxide (7.56 g, 0.17 mol) was added dropwise at 50°C to 60°C. After the addition was complete, the mixture was stirred at 50°C to 60°C for 3 hours. After confirming a conversion of 100% by GC, an aqueous solution of acetic acid (acetic acid (23.48 g) and water (44.03 g)) was added to the reaction mixture. The reaction mixture was subjected to phase separation, and the aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure. The concentrate was obtained by vacuum distillation to obtain (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) (26.52 g, 0.11 mol, purity 84.01%, bp = 111.7 °C to 120.2 °C / 0.40 kPa (3.0 mmHg)), with a yield of 96.66%.

[0183] The following are the spectral data of (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4) prepared therefrom.

[0184] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.97 (3H, t, J = 7.3Hz), 1.55 (2H, dt, J = 7.3Hz, 7.3Hz), 1.89 (1H, br.s), 2.07 (2H, quin-like,J=7.5Hz),2.15(2H,t,J=6.5Hz),2.17(2H,ddt,J=2.3Hz, 2.3Hz,7.3Hz),2.42(2H,ddt,J=2.3Hz,2.3Hz,6.5Hz),2.78(2H,dd, J=6.5Hz, 6.5Hz), 3.67 (2H, t, J=6.5Hz), 5.26-5.41 (4H, m); 13 C-NMR (500MHz, CDCl3): δ=14.24, 18.19, 20.50, 23.13, 25.48, 26.24, 28.79, 61.33, 76.55, 82.31, 127.17, 128.80, 129.02, 131.87.

[0185] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 205 (M + -1),175,159,145,119,105, 91,67,41.

[0186] Infrared absorption spectrum (D-ATR): ν = 3336, 2962, 2933, 1455, 1434, 1337, 1045, 849, 718.

[0187] Example 3: Preparation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5)

[0188]

[0189] Lithium aluminum hydride (7.73 g, 0.20 mol) and diethylene glycol dimethyl ether (210.83 g) were placed in a reactor at room temperature and stirred at 15°C to 20°C for 24 hours. Subsequently, (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) (15.02 g, 0.061 mol, purity 84.01%) obtained in Example 2 was added dropwise at 25°C to 50°C. After the addition was complete, the mixture was stirred at 120°C to 125°C for 3 hours and then cooled to 50°C. THF (532.23 g), water (34.05 g), an aqueous solution of sodium hydroxide (0.029 mol) (4.65 g), and diatomaceous earth (96.31 g) were added. The mixture was filtered, and phase separation was performed to remove the aqueous phase to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure. The concentrate was obtained by vacuum distillation to obtain (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) (10.70 g, 0.37 mol, purity 72.01%, bp = 111.7 °C to 114.1 °C / 0.40 kPa (3.0 mmHg)), in a yield of 60.49%.

[0190] The following are the spectral data of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) prepared therefrom.

[0191] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.97 (3H, t, J = 7.7Hz), 1.43 (2H, tt, J = 7.3Hz, 7.3Hz), 1.54 (1H, t-like, J = 5.4Hz), 1.98-2.11(6H,m),2.26(2H,q-like,J=6.7Hz),2.76(2H,t-like,J=6.5Hz),3.61(2H,q-like,J=6.1Hz),5.29(1H,dtt,J=10.7Hz,7.3Hz, 1.6Hz),5.32-5.43(4H,m),5.55(1H,dtt,J=15.3Hz,6.9Hz,1.2Hz); 13 C-NMR (500MHz, CDCl3): δ=14.25, 20.50, 25.48, 26.63, 29.33, 32.18, 35.95, 61.99, 126.06, 127.25, 128.32, 129.63, 131.78, 133.82.

[0192] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 208 (M + ),190,163,149,135,121,107, 93,79,67,55,41.

[0193] Infrared absorption spectrum (D-ATR): ν = 3336, 2962, 2929, 1455, 1398, 1048, 968, 914, 718.

[0194] Example 4: Preparation of (3E,8Z,11Z)-3,8,11-tetradecanetrienyl acetate (6)

[0195]

[0196] (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) (119.16 g, 0.46 mol, 80.08% purity), pyridine (39.85 g, 0.50 mol), and toluene (120.00 g) were placed in a reactor at room temperature and stirred at 15°C to 25°C for 10 minutes. After stirring, acetic anhydride (Ac₂O) (65.71 g, 0.64 mol) was added dropwise at 20°C to 40°C, and the mixture was stirred at 30°C to 35°C for 2 hours. Next, water (138.54 g) was added to the reaction mixture, followed by phase separation and removal of the aqueous phase to obtain the organic phase. The obtained organic phase was washed with an aqueous solution of sodium bicarbonate (sodium bicarbonate (5.22 g) and water (104.15 g)). The organic phase was concentrated under reduced pressure. The concentrate was distilled under reduced pressure to obtain (3E,8Z,11Z)-3,8,11-tetradecanetrienyl acetate (6) (125.85 g, 0.44 mol, purity 86.60, bp = 134.0 °C to 141.1 °C / 0.40 kPa (3.0 mmHg)), in 95.04% yield.

[0197] The following are the spectral data of (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate (6) prepared therefrom.

[0198] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.97 (3H, t, J = 7.3Hz), 1.41 (2H, tt, J = 7.3Hz, 7.3Hz), 1.98-2.10 (6H, m), 2.03 (3H, s),2.31(2H,dq,J=1.2Hz,6.9Hz),2.76(2H,dd,J=6.5Hz,6.5Hz), 4.06(2H,t,J=6.9Hz),5.28(1H,dtt,J=10.7Hz,6.9Hz,1.5Hz), 5.32-5.41(4H,m),5.51(1H,dtt,J=15.3Hz,6.9Hz,1.5Hz); 13C-NMR (500MHz, CDCl3): δ=14.25,20.50,20.95,25.49,26.58, 29.26,31.91,32.11,64.07,125.34,127.27,128.30,129.65,131.78, 133.14,171.08.

[0199] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 250 (M + ),190,161,147,122,108,93, 79,65,43.

[0200] Infrared absorption spectrum (D-ATR): ν = 2962, 2931, 1743, 1456, 1364, 1237, 1035, 969, 720.

Claims

1. (6Z,9Z)-6,9-dodecadien-1-yne of formula (1):

2. A method for preparing (6Z,9Z)-6,9-dodecadien-1-yne of formula (1): The method includes: Make the following (3Z,6Z)-10-halo-3,6-decadiene compounds of general formula (2): Where X represents a halogen atom Reaction with metal acetylenides of the following general formula (3): MC≡CH (3) Where M represents Na, Li, K, Ag, Cu(I), MgZ, CaZ, or Cu(II)Z, and Z represents a halogen atom or an acetylene group. To form (6Z,9Z)-6,9-dodecadiene-1-yne (1).

3. A method for preparing (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol of formula (4): The method includes: React (6Z,9Z)-6,9-dodecadien-1-yne (1) with a base; and The resulting reaction mixture was subjected to a homologation reaction with ethylene oxide to form (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4).

4. A method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol of formula (5): The method includes: The method for preparing (8Z,11Z)-8,11-tetradecadien-3-yne-1-ol (4) according to claim 3; and (8Z,11Z)-8,11-tetradecadien-3-yn-1-ol (4) was reduced to form (3E,8Z,11Z)-3,8,11-tetradectrien-1-ol (5).

5. A method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetriene acetate of formula (6): Where Ac represents the acetyl group. The method includes: The method for preparing (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) according to claim 4; and Acetylation of (3E,8Z,11Z)-3,8,11-tetradecanetrien-1-ol (5) forms (3E,8Z,11Z)-3,8,11-tetradecanetrien acetate (6).

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