6-Hydroxy-3-hexenyl alkoxymethyl ether compound and method for preparing 3,13-octadecadien-1-ol therefrom

Abstract

The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1), R 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and also relates to a method for preparing a 3,13-octadecadien-1-ol compound of the following formula (6) from a 6-hydroxy-3-hexenylalkoxymethyl ether compound (1): CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OH(6).

Description

Technical Field

[0001] The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethyl ether compound and a method for preparing a 3,13-octadecadien-1-ol compound using the same. Background Art

[0002] Carmenta chrysophanes is a well-known pest that harms persimmons in Australia. It is reported that the appropriate time to apply traditional insecticides that are effective against this pest is unclear, and the insecticides themselves are not very effective against this pest (Non-Patent Document 1 listed below). The poplar clearwing moth (Paranthrene tabaniformis) is one of the most serious pests that harm poplars in the Northern Hemisphere and is known to be difficult to control. One of the sex pheromones of the poplar clearwing moth is a 3,13-octadecadiene-1-ol compound (Non-Patent Document 2 listed below). Therefore, biological control methods have attracted people's attention, and the use of sex pheromone substances is expected to become one of them.

[0003] 3,13-Octadecadien-1-ol, a compound extracted from adult females of Carmenta foraseminis, which has recently severely damaged cocoa trees in South America (including Peru), is considered a sex pheromone candidate and is expected to be used (Non-Patent Document 3 listed below).

[0004] The method for preparing 3,13-octadecadien-1-ol compounds is described in Patent Document 1 listed below. In this method, the starting material 1-hexyne is subjected to a coupling reaction with 1,8-dibromohexane in tetrahydrofuran and hexamethylphosphoric triamide in the presence of n-butyl lithium to synthesize 14-bromo-5-tetradecyne. Next, the 14-bromo-5-tetradecyne thus obtained is hydrogenated using 5% palladium-barium sulfate as a catalyst and quinoline as a catalyst poison to reduce the carbon-carbon triple bond to a carbon-carbon double bond to synthesize (5Z)-14-bromo-5-tetradecene. Subsequently, 3-butyl-1-ol and lithium are reacted with each other in the presence of ammonia, and then subjected to a coupling reaction with (5Z)-14-bromo-5-tetradecene to synthesize (13Z)-octadecene-3-yn-1-ol. Then, the carbon-carbon triple bond of (13Z)-octadecene-3-yn-1-ol is reduced to a carbon-carbon double bond.

[0005] Another method for preparing 3,13-octadecadien-1-ol compounds is described in non-patent document 5 listed below. In this method, one hydroxyl group of the starting material 1,9-nonanediol is semi-brominated with hydrogen bromide, and the other hydroxyl group is protected with 2,3-dihydropyran to synthesize 2-[(9-bromononyl)oxy]tetrahydro-2H-pyran. Next, the 2-[(9-bromononyl)oxy]tetrahydro-2H-pyran thus obtained is reacted with 1-hexynyl lithium in tetrahydrofuran and hexamethylphosphoric triamide, and then Birch reduction is performed with metallic lithium. Then, the 2-tetrahydropyranyl group is removed to obtain 10-pentadecan-1-ol. Subsequently, the hydroxyl group of the 10-pentadecan-1-ol thus obtained is iodinated with iodine in the presence of triphenylphosphine and imidazole as a base in a mixed solvent of diethyl ether and acetonitrile to synthesize 15-iodo-5-pentadecane. Next, 3-butynyl tetrahydropyranyl ether is reacted with n-butyl lithium in tetrahydrofuran and hexamethylphosphoric triamide, followed by a coupling reaction with 15-iodo-5-pentadecene to synthesize (13E)-13-octadecen-3-yl tetrahydropyranyl ether. Subsequently, the (13E)-13-octadecen-3-yl tetrahydropyranyl ether thus obtained is hydrogenated using 5% palladium-barium sulfate as a catalyst and quinoline as a catalyst poison to reduce the carbon-carbon triple bond at position 3 to a carbon-carbon double bond. Finally, the 2-tetrahydropyranyl group is removed.

[0006] 3,13-Octadecadienyl acetate compounds are also known to be sex pheromones of many openwing insects, such as the peach borer (Synanthedon exitiosa) (Non-Patent Document 4 listed below). 3,13-Octadecadienyl acetate compounds are reportedly prepared by acetylation of 3,13-octadecadien-1-ol compounds (Non-Patent Document 5 listed below).

[0007] Reference List

[0008] [Patent Document]

[0009] [Patent Document 1] KR-A-180056877

[0010] [Non-patent literature]

[0011] [Non-patent document 1] Richard A Vickers et al., 2001, Australian Journal of Entomology, 40: 69-73.

[0012] [Non-patent document 2] Raimondas Mozuraitis et al., 2007, Z. Naturforsch., 62C: 138-142.

[0013] [Non-patent document 3] Abstracts of the 1st Latin American Meeting of Chemical Ecology Colonia del Sacramento, Uruguay October 17-20, 2010

[0014] [Non-patent document 4] DG Nielsen et al., 1975, Environmental entomology, 3(1): 451-454.

[0015] [Non-patent document 5] T. Ando et al., 2006, Biosci. Biotechnol. Biochem., 70(2): 508-516.

[0016] [Non-patent document 6] Thomas J. Caggiano et al. Encyclopedia of Reagents for Organic Synthesis: 3694-3699. Summary of the Invention

[0017] Problems to be solved by the present invention

[0018] The preparation methods described in Patent Document 1 and Non-Patent Document 5 use large amounts of hexamethylphosphoric triamide as a solvent. This solvent is carcinogenic, making the method difficult to apply industrially. Expensive palladium catalysts are used in the hydrogenation process, making the method economically unsuitable. Quinoline, used as a catalyst poison in these methods, has recently been found to have adverse effects on the human body, making it difficult to use industrially. Ammonia used in the coupling reaction and Birch reduction can cause severe symptoms even at low concentrations and is regulated by the Offensive Odor Control Act and the High Pressure Gas Safety Act. This requires specialized equipment, making these methods unsuitable for industrial production. These methods use metallic lithium, which easily ignites when in contact with water, making it unsuitable for industrial application. These methods involve numerous steps. Furthermore, the double bond formed at the 3-position by reduction in the latter stage creates the risk that the double bond formed at the 13-position by reduction in the previous stage will also be hydrogenated, producing the byproduct 3-octadecene-1-ol, thereby reducing purity.

[0019] Summary of the Invention

[0020] The present invention has been made under these circumstances, and an object of the present invention is to provide a method for efficiently preparing a high-purity 3,13-octadecadien-1-ol compound.

[0021] Through intensive research to overcome the aforementioned problems of the prior art, the present inventors have discovered that 6-hydroxy-3-hexenyl alkoxymethyl ether compounds are useful starting materials for preparing 3,13-octadecadien-1-ol compounds. The present inventors have also discovered that 6-hydroxy-3-hexenyl alkoxymethyl ether compounds enable efficient preparation of 3,13-octadecadien-1-ol compounds in a shorter number of steps and with high purity, while simultaneously controlling stereoisomerism at the 3- and 13-positions, thereby completing the present invention.

[0022] According to one aspect of the present invention, a method for preparing a 3,13-octadecadien-1-ol compound of the following formula (6):

[0023] CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OH (6),

[0024] The method comprises:

[0025] Halogenate the 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1):

[0026] HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1)

[0027] where R 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group

[0028] To prepare the following 6-halogeno-3-hexenyl alkoxymethyl ether compound of general formula (2):

[0029] X 1 CH2CH2CH=CHCH2CH2OCH2OCH2R 1 (2)

[0030] where X 1 represents a halogen atom, and R 1 As defined above;

[0031] The 6-halogeno-3-hexenyl alkoxymethyl ether compound (2) is converted into a nucleophile, a 6-(alkoxymethoxy)-3-hexenyl compound of the following general formula (3):

[0032] MCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (3)

[0033] Where M represents Li, Mg, Z 2 、CuZ 2 or CuLiZ 2 , where Z2 represents a halogen atom or a 6-(alkoxymethoxy)-3-hexenyl group, and R 1 As defined above;

[0034] A coupling reaction is performed between a nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) and a 12-halogeno-5-dodecene of the following general formula (4):

[0035] CH3(CH2)3CH=CH(CH2)6X 2 (4)

[0036] where X 2 represents a halogen atom,

[0037] To prepare the following 3,13-octadecadienyl alkoxymethyl ether compound of general formula (5):

[0038] CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OCH2OCH2R 1 (5)

[0039] where R 1 as defined above; and

[0040] The 3,13-octadecadien-1-ol compound (6) is prepared by dealkoxymethylating the 3,13-octadecadien-1-ol compound (6).

[0041] According to another aspect of the present invention, there is provided a method for preparing a 3,13-octadecadienyl acetate compound of the following formula (7):

[0042] CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OAc (7)

[0043] Wherein Ac represents an acetyl group,

[0044] The method comprises:

[0045] The aforementioned method for preparing 3,13-octadecadien-1-ol compound (6), and

[0046] The obtained 3,13-octadecadien-1-ol compound (6) is acetylated to prepare a 3,13-octadecadienyl acetate compound (7).

[0047] According to another aspect of the present invention, a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1) is provided:

[0048] HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1)

[0049] where R 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group.

[0050] According to the present invention, it is possible to prepare 3,13-octadecadien-1-ol compound (6) in a shorter process, in high yield and with high purity. DETAILED DESCRIPTION

[0051] 6-Hydroxy-3-hexenyl alkoxymethyl ether compound (1)

[0052] First, the 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1) will be explained.

[0053] HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1)

[0054] R in the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms (preferably 1 to 5 carbon atoms, more preferably 1 to 2 carbon atoms), or a phenyl group.

[0055] n-alkyl group R 1 Examples include straight-chain saturated hydrocarbon groups such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group and an n-nonyl group.

[0056] Specific examples of the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) include the following compounds:

[0057] (3E)-6-hydroxy-3-hexenyl alkoxymethyl ether compounds, such as (3E)-6-hydroxy-3-hexenyl methoxymethyl ether, (3E)-6-hydroxy-3-hexenyl ethoxymethyl ether, (3E)-6-hydroxy-3-hexenyl propoxymethyl ether, (3E)-6-hydroxy-3-hexenyl butoxymethyl ether, (3E)-6-hydroxy-3-hexenyl pentoxymethyl ether, (3E)-6-hydroxy-3-hexenyl hexyloxymethyl ether, (3E)-6-hydroxy-3-hexenyl heptoxymethyl ether, (3E)-6-hydroxy-3-hexenyl octyloxymethyl ether, (3E)-6-hydroxy-3-hexenyl nonyloxymethyl ether, (3E)-6-hydroxy-3-hexenyl decyloxymethyl ether and (3E)-6-hydroxy-3-hexenyl benzyloxymethyl ether; and

[0058] (3Z)-6-Hydroxy-3-hexenylalkoxymethyl ether compounds, such as (3Z)-6-hydroxy-3-hexenylmethoxymethyl ether, (3Z)-6-hydroxy-3-hexenylethoxymethyl ether, (3Z)-6-hydroxy-3-hexenylpropoxymethyl ether, (3Z)-6-hydroxy-3-hexenylbutoxymethyl ether, (3Z)-6-hydroxy-3-hexenylpentoxymethyl ether, (3Z)-6-hydroxy-3-hexenylhexyloxymethyl ether, (3Z)-6-hydroxy-3-hexenylheptyloxymethyl ether, (3Z)-6-hydroxy-3-hexenyloctyloxymethyl ether, (3Z)-6-hydroxy-3-hexenylnonyloxymethyl ether, (3Z)-6-hydroxy-3-hexenyldecyloxymethyl ether and (3Z)-6-hydroxy-3-hexenylbenzyloxymethyl ether.

[0059] The 6-hydroxy-3-vinylalkoxymethyl ether compound (1) can be synthesized, for example, according to the following two-step chemical reaction formula.

[0060]

[0061] First, an alkoxymethyl 3-butynyl ether compound of the general formula (9) is reacted with a base and then with ethylene oxide to increase the number of carbon atoms, thereby obtaining a 6-hydroxy-3-hexynyl alkoxymethyl ether compound of the general formula (10) (first step). The carbon-carbon triple bond of the thus obtained 6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) is reduced to obtain a 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) (second step).

[0062] The aforementioned process for producing the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) will be explained in more detail below.

[0063] First, the alkoxymethyl 3-butynyl ether compound (9) will be explained below.

[0064] R in the general formula (9) 1 As defined by general formula (1).

[0065] Specific examples of the alkoxymethyl 3-butynyl ether compound (9) include methoxymethyl 3-butynyl ether, ethoxymethyl 3-butynyl ether, propoxymethyl 3-butynyl ether, butoxymethyl 3-butynyl ether, pentoxymethyl 3-butynyl ether, hexyloxymethyl 3-butynyl ether, heptyloxymethyl 3-butynyl ether, octyloxymethyl 3-butynyl ether, nonyloxymethyl 3-butynyl ether, decyloxymethyl 3-butynyl ether and benzyloxymethyl 3-butynyl ether.

[0066] Examples of the base used in the homologation reaction in which the alkoxymethyl 3-butynyl ether compound (9) is reacted with a base and then with ethylene oxide to increase the number of carbon atoms include organometallic reagents such as n-butyllithium, tert-butyllithium, methylmagnesium chloride, methylmagnesium bromide, sodium acetylide, and potassium acetylide; and metal hydride reagents such as sodium hydride and potassium hydride. In view of reactivity, organometallic reagents are preferred.

[0067] The amount of the base to be used is preferably 1.0 to 5.0 mol, more preferably 1.0 to 2.0 mol, per mol of the alkoxymethyl 3-butynyl ether compound (9), in view of reactivity.

[0068] The amount of ethylene oxide to be used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 3.0 mol, per mol of the alkoxymethyl 3-butynyl ether compound (9), in view of reactivity.

[0069] If necessary, a solvent may be used in the above homologation reaction. Examples of solvents include commonly used solvents, for example, ethers such as diethyl ether, dibutyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl 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, N,N-dimethylformamide, N,N-dimethylacetamide, and hexamethylphosphoric triamide; and nitriles such as acetonitrile and propionitrile. In view of reactivity, ethers such as diethyl ether, tetrahydrofuran, and 4-methyltetrahydropyran are preferred.

[0070] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0071] The amount of the solvent is preferably 50 to 3,000 g, more preferably 100 to 1,200 g per mol of the alkoxymethyl 3-butynyl ether compound (9), in view of reactivity.

[0072] Next, the 6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) will be explained.

[0073] R in the general formula (10) 1 As defined by general formula (1).

[0074] Specific examples of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) include 6-hydroxy-3-hexynylmethoxymethyl ether, 6-hydroxy-3-hexynylethoxymethyl ether, 6-hydroxy-3-hexynylpropoxymethyl ether, 6-hydroxy-3-hexynylbutoxymethyl ether, 6-hydroxy-3-hexynylpentoxymethyl ether, 6-hydroxy-3-hexynylhexyloxymethyl ether, 6-hydroxy-3-hexynylheptyloxymethyl ether, 6-hydroxy-3-hexynyloctyloxymethyl ether, 6-hydroxy-3-hexynylnonyloxymethyl ether, 6-hydroxy-3-hexynyldecyloxymethyl ether and 6-hydroxy-3-hexynylbenzyloxymethyl ether.

[0075] Examples of reduction methods for synthesizing 6-hydroxy-3-hexenyl alkoxymethyl ether compounds (1) include (i) catalytic hydrogenation, (ii) reduction using a zinc compound in an alcohol solvent, (iii) hydroboration of dialkylborane followed by protonation, (iv) reduction using potassium hydroxide and N,N-dimethylformamide (DMF) in the presence of a palladium catalyst (e.g., palladium acetate), (v) hydrosilylation to form vinylsilane followed by desilylation, (vi) hydroalumination, and (vii) Birch reduction. In view of selectivity and productivity, catalytic hydrogenation (i), reduction using a zinc compound (ii), hydroboration followed by protonation (iii), and hydroalumination (vi) are preferred. If it is desired to form a carbon-carbon double bond in the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) in a Z-selective manner, catalytic hydrogenation (i) is preferred. If it is desired to form a carbon-carbon double bond in the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1) in an E-selective manner, the hydroalumination reaction (vi) is preferred.

[0076] (i) Catalytic hydrogenation

[0077] Catalytic hydrogenation is carried out by providing hydrogen in the presence of a metal catalyst.

[0078] Examples of metal catalysts used in catalytic hydrogenation include Lindela catalysts; nickel catalysts such as P-2 nickel boride catalyst (Thomas J. Caggiano et al. Encyclopedia of Reagents for Organic Synthesis: 3694-3699) (hereinafter also referred to as "P-2Ni catalyst"); and palladium catalysts such as palladium carbon and Pd-PEI (palladium carbon poisoned by polyethyleneimine polymer (PEI)). In view of economic efficiency, Lindela catalysts and nickel catalysts are preferred.

[0079] The amount of the metal catalyst varies depending on the catalyst used, and when the catalyst is a solid such as Lindela catalyst, it is preferably 0.01 to 50 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in consideration of reactivity. The P-2Ni catalyst is preferably used in an amount of 0.001 to 0.50 mol per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) for reduction to a nickel compound.

[0080] The solid catalyst may be dispersed in a solvent.

[0081] When the metal catalyst has high activity, a catalyst poison may be added if necessary.

[0082] Examples of the catalyst poison include amine compounds such as pyridine, quinoline, and ethylenediamine; phosphorus compounds such as triphenylphosphine, tritolylphosphine, and triethyl phosphite; and sulfur compounds such as benzenethiol, diphenyl sulfide, dimethyl sulfide, and dimethyl sulfoxide.

[0083] The amount of the catalyst poison varies greatly depending on the catalyst poison used, and is preferably 0.0001 to 10.0 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in consideration of the reaction rate and geometric selectivity.

[0084] Examples of the solvent used in the catalytic hydrogenation include hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; nitriles such as acetonitrile and propionitrile; esters such as methyl acetate, ethyl acetate, n-propyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, propanol, butanol, pentanol, hexanol, 2-propanol, 2-butanol and cyclohexanol.

[0085] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0086] When a Lindela catalyst is used, the solvent is preferably a hydrocarbon such as hexane, heptane, toluene, or xylene in view of reactivity. When a nickel catalyst is used, the solvent is preferably an alcohol such as methanol, ethanol, propanol, butanol, or 2-propanol in view of reactivity. When a palladium catalyst such as palladium on carbon is used, the solvent is preferably an ester such as methyl acetate or ethyl acetate in view of reactivity.

[0087] The amount of the solvent used varies depending on the catalyst and / or solvent used, and is preferably 0 to 1,000 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of reactivity.

[0088] The reaction temperature of the catalytic hydrogenation varies depending on the catalyst and / or solvent used, and is preferably 0°C to 160°C, more preferably 20°C to 100°C, in consideration of geometric selectivity.

[0089] The reaction time of the catalytic hydrogenation is preferably 1 to 100 hours in consideration of yield.

[0090] (ii) Reduction using zinc compounds in alcohol solvents

[0091] The reduction is carried out using a zinc compound in an alcohol solvent.

[0092] The alcohol used as a solvent preferably has 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms. Examples of the alcohol used as a solvent include linear alcohol compounds such as methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, and decanol; branched alcohol compounds such as 2-propanol and 2-butanol; and cyclic alcohol compounds such as cyclohexanol. In view of reactivity, alcohol compounds having 1 to 5 carbon atoms, such as methanol, ethanol, propanol, butanol, pentanol, and 2-propanol, are preferred.

[0093] In view of reactivity, the amount of the alcohol is preferably 46 to 1,000 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10).

[0094] The zinc compound refers to metallic zinc or active zinc, as described below.

[0095] The amount of the zinc compound is preferably 1.0 to 1,000 mol, more preferably 1.0 to 200 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10), in view of reactivity.

[0096] Due to the low reactivity of zinc, the reduction may require a longer time.An activator that activates the zinc may then be added or a pre-activated zinc compound may be used.

[0097] Examples of the activating agent include 1,2-dibromoethane, cuprous chloride, cuprous bromide, cuprous iodide, lithium bromide, lithium iodide, and chlorotrimethylsilane.

[0098] If necessary, activators may be used alone or in combination.

[0099] The amount of the activator is preferably 0.01 to 10.0 mol per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of reactivity.

[0100] Activated zinc can be prepared, for example, by treating metallic zinc with an acid such as hydrochloric acid; reducing zinc chloride with metallic lithium in tetrahydrofuran; or reacting metallic zinc with 1,2-dibromoethane and lithium dibromocuprate in tetrahydrofuran.

[0101] The reaction temperature of the reduction varies depending on the solvent used, but is preferably 20° C. to 120° C. in view of reactivity.

[0102] In view of completion of the reaction, the reaction time of the reduction is preferably 1 to 150 hours.

[0103] (iii) Hydroboration with dialkylborane followed by protonation

[0104] For the reduction, hydroboration is first performed using a dialkylborane in a solvent.

[0105] The dialkylborane used in the hydroboration preferably has 4 to 18, more preferably 6 to 12 carbon atoms.

[0106] Examples of dialkylborane include dicyclohexylborane, diisopentylborane, disiamylborane, 9-borabicyclo[3.3.1]nonane (9-BBN), diisopinocampheylborane, catecholborane, and pinacolborane. In view of reactivity, dicyclohexylborane and diisopentylborane are preferred.

[0107] The amount of the dialkylborane is preferably 1.0 to 4.0 mol per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of reactivity.

[0108] Examples of the solvent used in the hydroboration include ethers such as tetrahydrofuran, diethyl ether, butyl ether, 4-methyltetrahydropyran, cyclopentyl methyl ether, 1,4-dioxane, and diethylene glycol dimethyl ether; and hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. In view of reactivity, ethers such as tetrahydrofuran, 4-methyltetrahydropyran, and diethylene glycol dimethyl ether are more preferred.

[0109] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0110] The amount of the solvent is preferably 100 to 3,000 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of reactivity.

[0111] Taking geometric selectivity into consideration, the reaction temperature of the hydroboration is preferably -20°C to 50°C.

[0112] The reaction time of the hydroboration varies depending on the reaction temperature and / or reaction scale, and is preferably 1 to 100 hours in view of reactivity.

[0113] For the reduction, hydroboration is followed by protonation with an acid in a solvent.

[0114] Examples of the acid used in protonation include carboxylic acids such as acetic acid, propionic acid, butyric acid, valeric acid, pivalic acid, heptanoic acid, trifluoroacetic acid, chloroacetic acid, formic acid, and oxalic acid; sulfonic acids such as p-toluenesulfonic acid; and mineral acids such as sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid. In view of reactivity, carboxylic acids such as acetic acid and propionic acid are preferred.

[0115] The amount of the acid is preferably 2.0 to 20.0 mol per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of reactivity.

[0116] The kind and amount of the solvent are the same as those in the hydroboration because protonation is subsequently performed in the hydroboration reaction system.

[0117] The reaction temperature for protonation varies depending on the reagent used, and is preferably 0°C to 150°C in consideration of the reaction rate.

[0118] The reaction time for protonation varies depending on the reaction temperature and / or reaction scale, and is preferably 1 to 70 hours in view of reactivity.

[0119] (iv) Reduction using potassium hydroxide and N,N-dimethylformamide (DMF) in the presence of a palladium catalyst (such as palladium acetate)

[0120] The reduction is carried out using potassium hydroxide and N,N-dimethylformamide (DMF) in the presence of a palladium catalyst (such as palladium acetate), preferably at 100° C. to 180° C. for 6 to 100 hours.

[0121] (v) Hydrosilylation to form vinylsilane followed by desilylation

[0122] The hydrosilylation is carried out using a metal catalyst such as Wilkinson's catalyst or Trost and a trialkylsilane.

[0123] The amount of the metal catalyst is preferably 0.0001 to 4.0 mol, more preferably 0.001 to 1.0 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10), in view of reactivity.

[0124] The hydrosilylation is preferably performed at 5°C to 100°C for 1 to 100 hours.

[0125] The desilylation after the hydrosilylation is preferably carried out using at least one acid such as sulfuric acid or hydrochloric acid, hydrogen iodide, acetyl chloride, titanium tetrachloride and iodine at 5°C to 80°C for 1 to 100 hours.

[0126] (vi) Hydroalumination reaction

[0127] The hydroalumination reaction was carried out using lithium aluminum hydride.

[0128] The amount of lithium aluminum hydride is preferably 0.25 to 4.0 mol, more preferably 0.35 to 2.0 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10), in view of reactivity.

[0129] Examples of solvents used in the hydroalumination reaction include ethers such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl ether, 1,4-dioxane, and diethylene glycol dimethyl ether; and hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. In view of reactivity, ethers such as tetrahydrofuran, 4-methyltetrahydropyran, and diethylene glycol dimethyl ether are preferred.

[0130] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0131] The hydroalumination reaction is preferably carried out at 20°C to 180°C for 1 to 100 hours.

[0132] (vii) Birch reduction

[0133] Birch reduction using metals in amines or alcohols.

[0134] Examples of the metal include alkali metals such as potassium, sodium, and lithium; and alkaline earth metals such as calcium and magnesium.

[0135] Examples of the amine include lower amines such as ammonia, methylamine, ethylamine and propylamine.

[0136] Examples of alcohols include methanol, ethanol, and 2-methylpropanol.

[0137] The Birch reduction is preferably carried out at -78°C to 20°C for 1 to 100 hours.

[0138] The geometric structure of the carbon-carbon double bond of the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) can be selectively constructed in the E- or Z-configuration by selecting the reduction conditions.

[0139] Preparation of 6-halogeno-3-hexenyl alkoxymethyl ether compounds (2) by halogenation

[0140] The 6-halogeno-3-hexenylalkoxymethyl ether compound (2) can be prepared by halogenating the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1), as shown in the following chemical reaction formula.

[0141]

[0142] In the halogenation, one or more of the 6-hydroxy-3-hexenyl alkoxymethyl ether compounds (1) may be used, if necessary.

[0143] For example, a mixture of (3E)-6-hydroxy-3-hexenylalkoxymethyl ether compound (1) and (3Z)-6-hydroxy-3-hexenylalkoxymethyl ether compound (1) will yield a mixture of (3E)-6-halo-3-hexenylalkoxymethyl ether compound (2) and (3Z)-6-halo-3-hexenylalkoxymethyl ether compound (2).

[0144] The halogenation reaction for synthesizing the 6-halogeno-3-hexenylalkoxymethyl ether compound (2) can be carried out, for example, by p-toluenesulfonating the hydroxyl group using p-toluenesulfonyl halide and then halogenating using a lithium halide compound, or by directly halogenating the hydroxyl group using a halogenating agent.

[0145] Examples of the halogenating agent include halogen molecules such as chlorine, bromine and iodine; hydrogen halide compounds such as hydrogen chloride, hydrogen bromide and hydrogen iodide; methanesulfonyl halides such as methanesulfonyl chloride, methanesulfonyl bromide and methanesulfonyl iodide; benzenesulfonyl halides such as benzenesulfonyl chloride, benzenesulfonyl bromide and benzenesulfonyl iodide; p-toluenesulfonyl halides such as p-toluenesulfonyl chloride, p-toluenesulfonyl bromide and p-toluenesulfonyl iodide; phosphorus halide compounds such as phosphorus trichloride, phosphorus pentachloride and phosphorus tribromide; carbon tetrahalide compounds such as carbon tetrachloride, carbon tetrabromide and carbon tetraiodide; alkylsilyl halides such as tetramethylsilyl chloride, tetramethylsilyl chloride and tetramethylsilyl chloride. Methylsilyl bromide, tetramethylsilyl iodide, triethylsilyl chloride, triethylsilyl bromide, triethylsilyl iodide, triisopropylsilyl chloride, triisopropylsilyl bromide, triisopropylsilyl iodide, tert-butyldimethylsilyl chloride, tert-butyldimethylsilyl bromide and tert-butyldimethylsilyl iodide; oxalyl halides such as oxalyl chloride, oxalyl bromide and oxalyl iodide; and N-halogenosuccinimide compounds such as N-chlorosuccinimide, N-bromosuccinimide and N-iodosuccinimide. In view of the suppression of side reactions, methanesulfonyl halides, benzenesulfonyl halides and p-toluenesulfonyl halides are more preferred, particularly methanesulfonyl halides.

[0146] If necessary, a halogenating agent may be used alone or in combination. The halogenating agent may be a commercially available product.

[0147] The amount of the halogenating agent to be used is preferably 0.8 to 5.0 mol, more preferably 1.0 to 2.5 mol, per mol of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1).

[0148] If necessary, a base may be added to the halogenation reaction.

[0149] Examples of the base include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and magnesium hydroxide; carbonates such as sodium carbonate, potassium carbonate, calcium carbonate and magnesium carbonate; amines such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, lutidine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU); and phosphines such as tributylphosphine, triphenylphosphine and tritolylphosphine.

[0150] When the halogenating agent is methanesulfonyl halide, benzenesulfonyl halide or p-toluenesulfonyl halide, the base is preferably an amine, more preferably a pyridine such as pyridine, lutidine or 4-dimethylaminopyridine.

[0151] If necessary, a base may be used alone or in combination. The base may be a commercially available product.

[0152] The amount of the base is preferably 0 to 8.0 mol, more preferably 0 to 3.0 mol, per mol of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1), in view of yield and / or economic efficiency.

[0153] If necessary, a metal salt may be added to the halogenation reaction.

[0154] Examples of the metal salt include lithium salts such as lithium chloride, lithium bromide and lithium iodide; sodium salts such as sodium chloride, sodium bromide and sodium iodide; potassium salts such as potassium chloride, potassium bromide and potassium iodide; calcium salts such as calcium chloride, calcium bromide and calcium iodide; and magnesium salts such as magnesium chloride, magnesium bromide and magnesium iodide.

[0155] If necessary, metal salts may be used alone or in combination. The metal salts may be commercially available products.

[0156] The amount of the metal salt is preferably 0 to 30.0 mol, more preferably 0 to 5.0 mol, per mol of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1), in view of reactivity.

[0157] Although metal salts increase the concentration of halide ions in the reaction system, thereby improving reactivity, it is preferred not to add metal salts in consideration of economical efficiency and / or environmental protection.

[0158] If necessary, a solvent may be added during the halogenation reaction.

[0159] Examples of the solvent include commonly used solvents such as ethers such as diethyl ether, dibutyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl 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 triamide (HMPA); nitriles such as acetonitrile and propionitrile; and esters such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. In view of reactivity, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile are preferred. In view of safety, γ-butyrolactone and acetonitrile are particularly preferred.

[0160] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0161] The amount of the solvent used in the halogenation reaction is preferably 0 to 3,000 g, more preferably 0 to 800 g, per mol of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1).

[0162] The solvent may occupy part of the reactor space, thereby reducing the space for the starting materials and resulting in reduced productivity. Therefore, the reaction can be carried out without a solvent or with a base as a solvent.

[0163] The reaction temperature of the halogenation varies depending on the halogenating agent used, and is preferably 5° C. to 180° C. in view of reactivity.

[0164] The reaction time of the halogenation reaction varies depending on the halogenating agent and / or the reaction scale, and is preferably 0.5 to 100 hours in view of reactivity.

[0165] Next, the 6-halogeno-3-hexenylalkoxymethyl ether compound (2) will be explained.

[0166] X in the general formula (2) 1 R represents a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and in view of storage stability, a chlorine atom, a bromine atom and an iodine atom are preferred, and a chlorine atom and a bromine atom are particularly preferred. 1 As defined by general formula (1).

[0167] Specific examples of the 6-halogeno-3-hexenylalkoxymethyl ether compound (2) include the following compounds:

[0168] (3E)-6-chloro-3-hexenyl alkoxymethyl ether compounds, such as (3E)-6-chloro-3-hexenyl methoxymethyl ether, (3E)-6-chloro-3-hexenyl ethoxymethyl ether, (3E)-6-chloro-3-hexenyl propoxymethyl ether, (3E)-6-chloro-3-hexenyl butoxymethyl ether, (3E)-6-chloro-3-hexenyl pentoxymethyl ether, (3E)-6-chloro-3-hexenyl hexyloxymethyl ether, (3E)-6-chloro-3-hexenyl heptoxymethyl ether, (3E)-6-chloro-3-hexenyl octoxymethyl ether, (3E)-6-chloro-3-hexenyl nonoxymethyl ether, (3E)-6-chloro-3-hexenyl decoxymethyl ether and (3E)-6-chloro-3-hexenyl benzyloxymethyl ether;

[0169] (3E)-6-bromo-3-hexenylalkoxymethyl ether compounds, such as (3E)-6-bromo-3-hexenylmethoxymethyl ether, (3E)-6-bromo-3-hexenylethoxymethyl ether, (3E)-6-bromo-3-hexenylpropyloxymethyl ether, (3E)-6-bromo-3-hexenylbutoxymethyl ether, (3E)-6-bromo-3-hexenylpentoxymethyl ether, (3E)-6-bromo-3-hexenylhexyloxymethyl ether, (3E)-6-bromo-3-hexenylheptyloxymethyl ether, (3E)-6-bromo-3-hexenyloctyloxymethyl ether, (3E)-6-bromo-3-hexenylnonyloxymethyl ether, (3E)-6-bromo-3-hexenyldecyloxymethyl ether and (3E)-6-bromo-3-hexenylbenzyloxymethyl ether;

[0170] (3E)-6-iodo-3-hexenylalkoxymethyl ether compounds, such as (3E)-6-iodo-3-hexenylmethoxymethyl ether, (3E)-6-iodo-3-hexenylethoxymethyl ether, (3E)-6-iodo-3-hexenylpropyloxymethyl ether, (3E)-6-iodo-3-hexenylbutoxymethyl ether, (3E)-6-iodo-3-hexenylpentoxymethyl ether, (3E)-6-iodo-3-hexenylhexyloxymethyl ether, (3E)-6-iodo-3-hexenylheptyloxymethyl ether, (3E)-6-iodo-3-hexenyloctyloxymethyl ether, (3E)-6-iodo-3-hexenylnonyloxymethyl ether, (3E)-6-iodo-3-hexenyldecyloxymethyl ether and (3E)-6-iodo-3-hexenylbenzyloxymethyl ether;

[0171] (3Z)-6-chloro-3-hexenylalkoxymethyl ether compounds, such as (3Z)-6-chloro-3-hexenylmethoxymethyl ether, (3Z)-6-chloro-3-hexenylethoxymethyl ether, (3Z)-6-chloro-3-hexenylpropoxymethyl ether, (3Z)-6-chloro-3-hexenylbutoxymethyl ether, (3Z)-6-chloro-3-hexenylpentoxymethyl ether, (3Z)-6-chloro-3-hexenylhexyloxymethyl ether, (3Z)-6-chloro-3-hexenylheptyloxymethyl ether, (3Z)-6-chloro-3-hexenyloctyloxymethyl ether, (3Z)-6-chloro-3-hexenylnonyloxymethyl ether, (3Z)-6-chloro-3-hexenyldecyloxymethyl ether and (3Z)-6-chloro-3-hexenylbenzyloxymethyl ether;

[0172] (3Z)-6-bromo-3-hexenylalkoxymethyl ether compounds, such as (3Z)-6-bromo-3-hexenylmethoxymethyl ether, (3Z)-6-bromo-3-hexenylethoxymethyl ether, (3Z)-6-bromo-3-hexenylpropyloxymethyl ether, (3Z)-6-bromo-3-hexenylbutoxymethyl ether, (3Z)-6-bromo-3-hexenylpentoxymethyl ether, (3Z)-6-bromo-3-hexenylhexyloxymethyl ether, (3Z)-6-bromo-3-hexenylheptyloxymethyl ether, (3Z)-6-bromo-3-hexenyloctyloxymethyl ether, (3Z)-6-bromo-3-hexenylnonyloxymethyl ether, (3Z)-6-bromo-3-hexenyldecyloxymethyl ether, and (3Z)-6-bromo-3-hexenylbenzyloxymethyl ether; and

[0173] (3Z)-6-iodo-3-hexenylalkoxymethyl ether compounds, such as (3Z)-6-iodo-3-hexenylmethoxymethyl ether, (3Z)-6-iodo-3-hexenylethoxymethyl ether, (3Z)-6-iodo-3-hexenylpropyloxymethyl ether, (3Z)-6-iodo-3-hexenylbutoxymethyl ether, (3Z)-6-iodo-3-hexenylpentoxymethyl ether, (3Z)-6-iodo-3-hexenylhexyloxymethyl ether, (3Z)-6-iodo-3-hexenylheptyloxymethyl ether, (3Z)-6-iodo-3-hexenyloctyloxymethyl ether, (3Z)-6-iodo-3-hexenylnonyloxymethyl ether, (3Z)-6-iodo-3-hexenyldecyloxymethyl ether and (3Z)-6-iodo-3-hexenylbenzyloxymethyl ether.

[0174] As shown in the following chemical reaction formula, a 6-halogeno-3-hexenyl alkoxymethyl ether compound (2) is converted into a nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3), which then undergoes a coupling reaction with a 12-halogeno-5-dodecene (4) to obtain a 3,13-octadecadienyl alkoxymethyl ether compound (5).

[0175]

[0176] Preparation of nucleophilic reagent 6-(alkoxymethoxy)-3-hexenyl compound (3)

[0177] One example of a method for synthesizing a nucleophilic reagent 6-(alkoxymethoxy)-3-hexenyl compound (3) comprises reacting a 6-halogeno-3-hexenylalkoxymethyl ether compound (2) with magnesium in a solvent to obtain a Grignard reagent 6-(alkoxymethoxy)-3-hexenyl magnesium chloride compound (3: M = MgZ 2 ), as shown in the following chemical reaction formula. This method is hereinafter referred to as "conversion with magnesium".

[0178]

[0179] The amount of magnesium used in the conversion with magnesium is preferably 1.0 to 2.0 gram atoms per mol of the 6-halogeno-3-hexenylalkoxymethyl ether compound (2) in view of completion of the reaction.

[0180] Examples of solvents used in the conversion with magnesium include ethers such as tetrahydrofuran, diethyl ether and 4-methyltetrahydropyran; and hydrocarbons such as toluene, xylene and hexane. In view of the reaction rate of the Grignard reagent formation, ethers such as tetrahydrofuran, diethyl ether and 4-methyltetrahydropyran are preferred, and tetrahydrofuran is particularly preferred.

[0181] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0182] The amount of the solvent to be used is preferably 50 to 5,000 g, more preferably 100 g to 3,000 g, per mol of the 6-halogeno-3-hexenylalkoxymethyl ether compound (2), in view of reactivity.

[0183] The reaction temperature for conversion with magnesium varies depending on the solvent used, and is preferably 0°C to 120°C in view of reactivity.

[0184] The reaction time for conversion with magnesium varies depending on the solvent used and / or the reaction scale, and is preferably 0.5 to 100 hours in view of reactivity.

[0185] Another example of a method for synthesizing a nucleophilic reagent 6-(alkoxymethoxy)-3-hexenyl compound (3) includes reacting a 6-halogeno-3-hexenylalkoxymethyl ether compound (2) with an organolithium reagent in a solvent to obtain a 6-(alkoxymethoxy)-3-hexenyl lithium compound (3: M=Li), as shown in the following chemical reaction formula. This method is hereinafter referred to as "conversion with an organolithium reagent."

[0186]

[0187] Examples of organolithium reagents include linear organolithium reagents such as methyllithium, ethyllithium, n-propyllithium, n-butyllithium, and n-pentyllithium; and branched organolithium reagents such as sec-butyllithium and tert-butyllithium. In view of availability, methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium are preferred.

[0188] The amount of the organolithium reagent to be used is preferably 1.0 to 4.0 mol per mol of the 6-halogeno-3-hexenylalkoxymethyl ether compound (2) in view of reactivity.

[0189] Examples of solvents used in the conversion with organolithium reagents include ethers such as tetrahydrofuran, diethyl ether, and 4-methyltetrahydropyran; and hydrocarbons such as toluene, xylene, and hexane. Preferred solvents vary depending on the organolithium reagent used. Generally, tetrahydrofuran, diethyl ether, toluene, or hexane are preferred, taking reactivity into consideration.

[0190] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0191] The amount of the solvent used is preferably 50 to 5,000 g, more preferably 100 to 3,000 g, per mol of the 6-halogeno-3-hexenylalkoxymethyl ether compound (2), in view of reactivity.

[0192] The reaction temperature for conversion with an organolithium reagent varies depending on the solvent used, and is preferably -78°C to 25°C in view of reactivity.

[0193] The reaction time for conversion with an organolithium reagent varies depending on the solvent used and / or the reaction scale, and is preferably 0.5 to 100 hours in view of reactivity.

[0194] Next, the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) will be explained.

[0195] R in the general formula (3) 1 As defined by general formula (1).

[0196] M represents Li or MgZ 2 , where Z 2 represents a halogen atom or a 6-(alkoxymethoxy)-3-hexenyl group. Halogen atom Z 2 Examples of include a chlorine atom, a bromine atom, and an iodine atom.

[0197] Examples of the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) include a nucleophile, a (3E)-6-(alkoxymethoxy)-3-hexenyl compound of the following general formula (3-E), a nucleophile, a (3Z)-6-(alkoxymethoxy)-3-hexenyl compound of the following general formula (3-Z), and mixtures thereof.

[0198]

[0199] Specific examples of the nucleophile (3E)-6-(alkoxymethoxy)-3-hexenyl compound (3-E) include the following compounds:

[0200] (3E)-6-(alkoxymethoxy)-3-hexenyllithium compounds, such as (3E)-6-(methoxymethoxy)-3-hexenyllithium, (3E)-6-(ethoxymethoxy)-3-hexenyllithium, (3E)-6-(propoxymethoxy)-3-hexenyllithium, (3E)-6-(butoxymethoxy)-3-hexenyllithium, (3E)-6-(pentyloxymethoxy)-3-hexenyllithium, (3E)-6-(hexyloxymethoxy)-3-hexenyllithium, (3E)-6-(heptyloxymethoxy)-3-hexenyllithium, (3E)-6-(octyloxymethoxy)-3-hexenyllithium, (3E)-6-(nonyloxymethoxy)-3-hexenyllithium, and (3E)-6-(decyloxymethoxy)-3-hexenyllithium; and

[0201] (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium halide compounds, including

[0202] (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride compounds, such as (3E)-6-(methoxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(propoxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(butoxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(pentyloxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium chloride, (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium chloride, and (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium chloride;

[0203] (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium bromide compounds, such as (3E)-6-(methoxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(propoxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(butoxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(pentoxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(methoxy)-3-hexenylmagnesium bromide, (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium bromide, (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium bromide, and (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium bromide; and

[0204] (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium iodide compounds, such as (3E)-6-(methoxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(propoxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(butoxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(pentoxymethoxy)-3-hexenylmagnesium iodide, Magnesium iodide, (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium iodide, (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium iodide and (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide.

[0205] Among them, (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium halide compounds such as (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium chloride compounds are preferred in view of availability.

[0206] Specific examples of the nucleophile (3Z)-6-(alkoxymethoxy)-3-hexenyl compound (3-Z) include the following compounds: (3Z)-6-(alkoxymethoxy)-3-hexenyl lithium compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenyl lithium, (3Z)-6-(ethoxymethoxy)-3-hexenyl lithium, (3Z)-6-(propoxymethoxy)-3-hexenyl lithium, (3Z)-6-(butoxymethoxy)-3-hexenyl lithium, (3Z)-6-(pentyloxymethoxy)-3-hexenyllithium, (3Z)-6-(hexyloxymethoxy)-3-hexenyllithium, (3Z)-6-(heptyloxymethoxy)-3-hexenyllithium, (3Z)-6-(octyloxymethoxy)-3-hexenyllithium, (3Z)-6-(nonyloxymethoxy)-3-hexenyllithium, and (3Z)-6-(decyloxymethoxy)-3-hexenyllithium; and

[0207] (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium halide compounds, including

[0208] (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(pentyloxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium chloride, (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium chloride, and (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium chloride;

[0209] (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium bromide compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(pentoxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium bromide, (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium bromide, and (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium bromide; and

[0210] (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium iodide compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(pentoxymethoxy)-3-hexenylmagnesium iodide, Magnesium iodide, (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium iodide, (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium iodide and (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide.

[0211] Among them, (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium halide compounds such as (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride compounds are preferred in view of availability.

[0212] If necessary, one or more of the nucleophilic 6-(alkoxymethoxy)-3-hexenyl compounds (3) may be used.

[0213] The nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) may be a commercially available product or may be prepared by itself.

[0214] For example, a mixture of a nucleophile (3E)-6-(alkoxymethoxy)-3-hexenyl compound (3-E) and a nucleophile (3Z)-6-(alkoxymethoxy)-3-hexenyl compound (3-Z) will yield a mixture of a (3E)-3,13-octadecadienylalkoxymethyl ether compound and a (3Z)-3,13-octadecadienylalkoxymethyl ether compound.

[0215] Preparation of 3,13-octadecadienyl alkoxymethyl ether compound (5) by coupling reaction

[0216] A nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) is subjected to a coupling reaction with a 12-halogeno-5-dodecene compound (4) to prepare a 3,13-octadecadienyl alkoxymethyl ether compound (5).

[0217] First, 12-halogeno-5-dodecene (4) will be explained below.

[0218] X in the general formula (4) 2 represents a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. 2 It is preferably a chlorine atom, a bromine atom or an iodine atom, and more preferably a bromine atom or an iodine atom.

[0219] Specific examples of 12-halogeno-5-dodecene (4) include 12-fluoro-5-dodecene, 12-chloro-5-dodecene, 12-bromo-5-dodecene, and 12-iodo-5-dodecene. In view of reactivity, 12-bromo-5-dodecene and 12-iodo-5-dodecene are preferred.

[0220] If necessary, one or more of the 12-halogeno-5-dodecene compounds (4) may be used.

[0221] 12-Halo-5-dodecene (4) can be prepared by itself, for example, by deprotonating the terminal alkyne of 1-hexyne, subjecting the product to a coupling reaction with a 1,6-dihaloalkane to synthesize a 12-halo-5-dodecyne compound, and then reducing the carbon-carbon triple bond to a carbon-carbon double bond. Alternatively, a 1-halo-3-octene compound is converted into an organometallic reagent, i.e., a 3-dodecenyl nucleophile, and then reacting it with a 1,4-dihaloalkane compound to obtain a 12-halo-5-dodecyne compound (4).

[0222] In view of economy, the amount of the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) used in the coupling reaction is preferably 0.8 to 3.0 mol, more preferably 1.0 to 1.8 mol, per mol of 12-halogeno-5-dodecene (4).

[0223] If necessary, a solvent may be added to the coupling reaction. Examples of solvents include commonly used solvents, for example, ethers such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl 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 triamide (HMPA); and nitriles such as acetonitrile and propionitrile. In view of reactivity, toluene, tetrahydrofuran, 4-methyltetrahydropyran, or acetonitrile is preferred, and tetrahydrofuran is particularly preferred.

[0224] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0225] The amount of the solvent to be used is preferably 30 to 5,000 g, more preferably 50 to 3,000 g, per mol of the 12-halogeno-5-dodecene compound (4), in view of reactivity.

[0226] If necessary, a catalyst may be added to the coupling reaction. Examples of the catalyst include copper compounds, including cuprous halides (such as cuprous chloride, cuprous bromide, and cuprous iodide), and cupric halides (such as cupric chloride, cupric bromide, and cupric iodide); ferrous compounds, such as ferrous (II) chloride, ferric (III) chloride, ferrous (II) bromide, ferric (III) bromide, ferrous (II) iodide, ferric (III) iodide, and ferric (III) acetylacetonate; silver compounds, such as silver chloride, silver nitrate, and silver acetate; titanium compounds, such as titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium (IV) ethoxide, titanium (IV) isopropoxide, and titanium (IV) oxide; palladium (II) compounds, such as dichlorobis(triphenylphosphine)palladium and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium; and nickel compounds, such as nickel chloride, dichloro[1,2-bis(diphenylphosphino)ethane]nickel(II), and dichlorobis(triphenylphosphine)nickel(II). When the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) is a Grignard reagent, i.e., a 6-(alkoxymethoxy)-3-hexenyl magnesium halide compound (3: M = MgZ 2 ), in view of reactivity and / or economy, copper compounds are preferred, in particular cuprous halides such as cuprous chloride, cuprous bromide and cuprous iodide.

[0227] If necessary, a catalyst may be used alone or in combination. The catalyst may be a commercially available product.

[0228] The amount of the catalyst to be used is preferably 0.0003 to 0.300 mol, more preferably 0.003 to 0.100 mol, per mol of the 12-halogeno-5-dodecene compound (4), in view of the reaction rate and ease of post-treatment.

[0229] When an organolithium reagent is used in the coupling reaction, N,N,N',N'-tetramethylethylenediamine (TMEDA), hexamethylphosphoric triamide (HMPA), or N,N'-dimethylpropyleneurea (DMPU) may be used to improve the reaction rate, if necessary.

[0230] When a catalyst is used in the coupling reaction, a co-catalyst may be added if necessary. Examples of co-catalysts include trialkylphosphites having 3 to 9 carbon atoms, such as triethylphosphite; and arylphosphine compounds having 18 to 44 carbon atoms, such as triphenylphosphine, tritolylphosphine, or 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). Considering reactivity, trialkylphosphites, particularly triethylphosphite, are preferred.

[0231] If necessary, a co-catalyst may be used alone or in combination. The co-catalyst may be a commercially available product.

[0232] The amount of the co-catalyst to be used is preferably 0.0001 to 1.00 mol, more preferably 0.001 to 0.300 mol, per mol of 12-halogeno-5-dodecene (4).

[0233] When a catalyst is used in the coupling reaction, a lithium halide may be added if necessary. Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide. In view of reactivity, lithium chloride is preferred.

[0234] The amount of the lithium halide used in the coupling reaction is preferably 0.0001 to 1.00 mol, more preferably 0.001 to 0.300 mol, per mol of the 12-halogeno-5-dodecene compound (4), in view of reactivity.

[0235] The reaction temperature of the coupling reaction varies depending on the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3), but is preferably -78°C to 80°C, more preferably -25°C to 40°C, in view of reactivity.

[0236] The reaction time of the coupling reaction varies depending on the solvent and / or reaction scale, and is preferably 0.5 to 100 hours in view of reactivity.

[0237] Next, the 3,13-octadecadienyl alkoxymethyl ether compound (5) will be explained.

[0238] R in general formula (5) 1 As defined by general formula (1).

[0239] Specific examples of the 3,13-octadecadienyl alkoxymethyl ether compound (5) include the following compounds:

[0240] (3Z,13Z)-3,13-octadecadiene alkoxymethyl ether compounds, such as (3Z,13Z)-3,13-octadecadiene methoxymethyl ether, (3Z,13Z)-3,13-octadecadiene ethoxymethyl ether, (3Z,13Z)-3,13-octadecadiene allyloxymethyl ether, (3Z,13Z)-3,13-octadecadiene butoxymethyl ether, (3Z,13Z)-3,13-octadecadiene pentoxymethyl ether ether, (3Z,13Z)-3,13-octadecadienylhexyloxymethyl ether, (3Z,13Z)-3,13-octadecadienylheptyloxymethyl ether, (3Z,13Z)-3,13-octadecadienyloctyloxymethyl ether, (3Z,13Z)-3,13-octadecadienylnonyloxymethyl ether, (3Z,13Z)-3,13-octadecadienyldecyloxymethyl ether, and (3Z,13Z)-3,13-octadecadienylbenzyloxymethyl ether;

[0241] (3Z,13E)-3,13-octadecadienyl alkoxymethyl ether compounds, such as (3Z,13E)-3,13-octadecadienyl methoxymethyl ether, (3Z,13E)-3,13-octadecadienyl ethoxymethyl ether, (3Z,13E)-3,13-octadecadienyl allyloxymethyl ether, (3Z,13E)-3,13-octadecadienyl butoxymethyl ether, (3Z,13E)-3,13-octadecadienyl pentoxymethyl ether ether, (3Z,13E)-3,13-octadecadienylhexyloxymethyl ether, (3Z,13E)-3,13-octadecadienylheptyloxymethyl ether, (3Z,13E)-3,13-octadecadienyloctyloxymethyl ether, (3Z,13E)-3,13-octadecadienylnonyloxymethyl ether, (3Z,13E)-3,13-octadecadienyldecyloxymethyl ether and (3Z,13E)-3,13-octadecadienylbenzyloxymethyl ether;

[0242] (3E,13Z)-3,13-octadecadienyl alkoxymethyl ether compounds, such as (3E,13Z)-3,13-octadecadienyl methoxymethyl ether, (3E,13Z)-3,13-octadecadienyl ethoxymethyl ether, (3E,13Z)-3,13-octadecadienyl allyloxymethyl ether, (3E,13Z)-3,13-octadecadienyl butoxymethyl ether, (3E,13Z)-3,13-octadecadienyl pentoxymethyl ether, (3E,13Z)-3,13-octadecadienylhexyloxymethyl ether, (3E,13Z)-3,13-octadecadienylheptyloxymethyl ether, (3E,13Z)-3,13-octadecadienyloctyloxymethyl ether, (3E,13Z)-3,13-octadecadienylnonyloxymethyl ether, (3E,13Z)-3,13-octadecadienyldecyloxymethyl ether, and (3E,13Z)-3,13-octadecadienylbenzyloxymethyl ether; and

[0243] (3E,13E)-3,13-octadecadienyl alkoxymethyl ether compounds, such as (3E,13E)-3,13-octadecadienyl methoxymethyl ether, (3E,13E)-3,13-octadecadienyl ethoxymethyl ether, (3E,13E)-3,13-octadecadienyloxymethyl ether, (3E,13E)-3,13-octadecadienyloxymethyl ether, (3E,13E)-3,13-octadecadienyloxymethyl ether, ether, (3E,13E)-3,13-octadecadienylhexyloxymethyl ether, (3E,13E)-3,13-octadecadienylheptyloxymethyl ether, (3E,13E)-3,13-octadecadienyloctyloxymethyl ether, (3E,13E)-3,13-octadecadienylnonyloxymethyl ether, (3E,13E)-3,13-octadecadienyldecyloxymethyl ether and (3E,13E)-3,13-octadecadienylbenzyloxymethyl ether.

[0244] Among them, in view of economic efficiency, 3,13-octadecadienyl methoxymethyl ether compound, 3,13-octadecadienyl ethoxymethyl ether compound, 3,13-octadecadienyl butoxymethyl ether compound, and 3,13-octadecadienyl benzyloxymethyl ether compound are preferred.

[0245] Preparation of 3,13-octadecadien-1-ol compound (6) by dealkoxymethylation

[0246] 3,13-Octadecadien-1-ol compound (6) can be prepared by dealkoxymethylating 3,13-octadecadienyl alkoxymethyl ether compound (5), as shown in the following chemical reaction formula.

[0247]

[0248] If necessary, one or more of the 3,13-octadecadienyl alkoxymethyl ether compounds (5) may be used in the dealkoxymethylation reaction.

[0249] For example, a mixture of (3Z,13Z)-3,13-octadecadien-1-ol (5) and (3Z,13E)-3,13-octadecadien-1-ol (6) will yield a mixture of (3Z,13Z)-3,13-octadecadien-1-ol (6) and (3Z,13E)-3,13-octadecadien-1-ol (6).

[0250] The optimal conditions for dealkoxymethylation reaction are based on R 1 For example, when R 1 When R is a phenyl group, dealkoxymethylation can be carried out under Birch reduction conditions using sodium in liquid ammonia. 1 When it is a hydrogen atom or an n-alkyl group (eg, a methyl group), dealkoxymethylation can be carried out using the following acid or alcohol compound (8).

[0251] Examples of the acid include inorganic acids such as hydrochloric acid and hydrobromic acid; sulfonic acids such as p-toluenesulfonic acid and benzenesulfonic acid; organic acids such as trifluoroacetic acid, acetic acid, formic acid, and oxalic acid; and Lewis acids such as iodotrimethylsilane and titanium tetrachloride. In view of suppressing side reactions, p-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, and hydrobromic acid are preferred, and p-toluenesulfonic acid, hydrochloric acid, and hydrobromic acid are particularly preferred.

[0252] If necessary, an acid may be used alone or in combination. The acid may be a commercially available product.

[0253] The amount of the acid to be used is preferably 0.0001 to 10.0 mol, more preferably 0.001 to 1.0 mol, per mol of the 3,13-octadecadienylalkoxymethyl ether compound (5).

[0254] The alcohol compound (8) is represented by the following general formula (8):

[0255] R 2 OH (8)

[0256] Considering price or availability, R 2 " represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 6 carbon atoms. Examples of the monovalent hydrocarbon group include straight-chain saturated hydrocarbon groups such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, and an n-dodecyl group; branched-chain saturated hydrocarbon groups such as an isopropyl group, a 2-isobutyl group, and a 2-methylbutyl group; straight-chain unsaturated hydrocarbon groups such as a 2-propenyl group; branched-chain unsaturated hydrocarbon groups such as a 2-methyl-2-propenyl group; cyclic saturated hydrocarbon groups such as a cyclopropyl group; and isomers thereof. A portion of the hydrogen atoms of the hydrocarbon group may be substituted by a methyl group, an ethyl group, or a hydroxyl group.

[0257] In view of handling, the monovalent hydrocarbon group is preferably a methyl group, an ethyl group, an n-propyl group or an n-butyl group.

[0258] Examples of the alcohol compound (8) include straight-chain alcohols such as methanol, ethanol, n-propanol, n-butanol, n-pentanol, n-hexanol, n-heptanol, n-octanol, n-nonanol, n-decanol, n-undecanol, n-dodecanol, n-tridecanol, n-tetradecanol, and n-pentadecanol; branched-chain alcohols such as isopropanol and 2-butanol; and diols such as ethylene glycol, propylene glycol, 2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 1,2-dimethyl-1,3-propanediol, 1,3-dimethyl-1,3-propanediol, and 2-methyl-1,4-butanediol. In view of reactivity, methanol and ethanol are preferred, and methanol is particularly preferred.

[0259] If necessary, the alcohol compound (8) may be used alone or in combination.

[0260] The alcohol compound (8) may be a commercially available product.

[0261] The amount of the alcohol compound (8) to be used is preferably 1 to 1,000 mol, more preferably 1 to 100 mol, per mol of the 3,13-octadecadienylalkoxymethyl ether compound (5), in view of reactivity.

[0262] If necessary, a solvent other than the alcohol compound (8) may be used in the dealkoxymethylation reaction.

[0263] Examples of the solvent include commonly used solvents, for example, ethers such as diethyl ether, dibutyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl 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 triamide (HMPA); nitriles such as acetonitrile and propionitrile; and esters such as methyl acetate, ethyl acetate, n-propyl acetate and n-butyl acetate.

[0264] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0265] The amount of the solvent used in the dealkoxymethylation reaction is preferably 0 to 2,000 g, more preferably 0 to 500 g, per mol of the 3,13-octadecadienylalkoxymethyl ether compound (5).

[0266] The solvent takes up space in the reactor, thereby reducing the space available for the starting materials, resulting in reduced productivity. Therefore, dealkoxymethylation can be carried out without a solvent.

[0267] The reaction temperature of dealkoxymethylation varies depending on the 3,13-octadecadienylalkoxymethyl ether compound (5) used, but is preferably -5°C to 180°C in view of reactivity.

[0268] The reaction time of dealkoxymethylation varies depending on the 3,13-octadecadienylalkoxymethyl ether compound (5) and / or the reaction scale, but is preferably 0.5 to 100 hours in view of reactivity.

[0269] In the dealkoxymethylation process, if necessary, alkoxymethoxymethane produced as a by-product may be distilled off from the reaction system to shift the equilibrium to the product side to shorten the reaction time.

[0270] Specific examples of the 3,13-octadecadien-1-ol compound (6) include (3Z,13Z)-3,13-octadecadien-1-ol, (3Z,13E)-3,13-octadecadien-1-ol, (3E,13Z)-3,13-octadecadien-1-ol, and (3E,13E)-3,13-octadecadien-1-ol.

[0271] Preparation of 3,13-octadecadienyl acetate compounds by acetylation (7)

[0272] 3,13-Octadecadienyl acetate compound (7) can be prepared by acetylation of 3,13-octadecadien-1-ol compound (6), as shown in the following chemical reaction formula.

[0273]

[0274] If necessary, one or more of the 3,13-octadecadien-1-ol compounds (6) may be used in the acetylation.

[0275] For example, a mixture of (3Z,13Z)-3,13-octadecadien-1-ol (6) and (3Z,13E)-3,13-octadecadien-1-ol (6) will yield a mixture of (3Z,13Z)-3,13-octadecadienyl acetate compound (7) and (3Z,13E)-3,13-octadecadienyl acetate compound (7).

[0276] Acetylation can be performed using an acetylating agent.

[0277] Examples of the acetylating agent include acid anhydrides such as acetic anhydride; acetyl halides such as acetyl chloride, acetyl bromide and acetyl iodide; and acetate ester compounds such as methyl acetate and ethyl acetate. In view of availability, acetic anhydride and acetyl halides are preferred.

[0278] The amount of the acetylating agent used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 5.0 mol, per mol of the 3,13-octadecadien-1-ol compound (6), in view of reactivity and economy.

[0279] If necessary, an acid or a base may be added during the acetylation.

[0280] Examples of the acid 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 dimethanolate, dibutyltin oxide, magnesium chloride, magnesium bromide, titanium tetrachloride, titanium tetrabromide, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) isopropoxide, and titanium(IV) oxide.

[0281] If necessary, acids may be used alone or in combination.

[0282] The amount of the acid to be used is preferably 0.001 to 3.00 mol, more preferably 0.01 to 1.50 mol, per mol of the 3,13-octadecadien-1-ol compound (6), in view of reactivity and economy.

[0283] Examples of the base 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, lutidine, 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-amylate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amylate, potassium methoxide, potassium ethoxide, potassium tert-butoxide and potassium tert-amylate.

[0284] If necessary, a base may be used alone or in combination.

[0285] The amount of the base to be used is preferably 0.010 to 10.0 mol, more preferably 1.0 to 5.0 mol, per mol of the 3,13-octadecadien-1-ol compound (6), in view of reactivity and economy.

[0286] If necessary, a solvent may be added during the acetylation.

[0287] Examples of the solvent include commonly used solvents such as ethers such as diethyl ether, dibutyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentyl methyl 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 triamide (HMPA); nitriles such as acetonitrile and propionitrile; and esters such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. In view of reactivity, hydrocarbons such as toluene and xylene are preferred.

[0288] If necessary, solvents may be used alone or in combination. The solvents may be commercially available products.

[0289] The acetylation can be carried out with or without a solvent as desired.

[0290] The amount of the solvent used in the acetylation is preferably 0 to 2,000 g, more preferably 0 to 500 g, per mol of the 3,13-octadecadien-1-ol compound (6).

[0291] The following will explain the 3,13-octadecadienyl acetate compound (7).

[0292] In formula (7), Ac represents an acetyl group.

[0293] Example

[0294] The present invention will be described with reference to the following examples. It should be understood that the present invention is not limited to or by these examples.

[0295] Unless otherwise specified, the term "purity" used herein refers to the area percentage in gas chromatography (GC). The term "yield ratio" refers to the ratio of area percentages in GC. The term "yield" is calculated by the area percentage determined by GC.

[0296] In the examples, reaction monitoring and yield calculation were performed under the following GC conditions.

[0297] GC conditions: capillary gas chromatograph GC-2014 (Shimadzu Corporation); column: DB-WAX (sp-2331), 0.25 μm × 0.25 mmφ x 30 m; carrier gas: He (1.55 mL / min), detector: FID; column temperature: 150°C, increasing at a rate of 5°C / min to a maximum of 230°C.

[0298] Taking into account the purity (% GC) of the starting material and the product, the yield was calculated according to the following equation.

[0299] Yield (%) = {[(weight of product obtained in the reaction × %GC) / molecular weight of product] ÷ [(weight of starting material in the reaction × %GC) / molecular weight of starting material]} × 100

[0300] THF represents tetrahydrofuran, GBL represents γ-butyrolactone, P-2Ni represents P-2 nickel boride, Ms represents a methanesulfonyl group, Me represents a methyl group, Et represents an ethyl group, Ac represents an acetyl group, and Ph represents a phenyl group.

[0301] Example 1: Preparation of 6-hydroxy-3-hexynyl methoxymethyl ether (10:R 1 =H)

[0302]

[0303] Methylmagnesium chloride (366.84 g, 4.91 mol) and tetrahydrofuran (1530.16 g) were placed in a reactor at room temperature and stirred at 20°C to 25°C for 4 minutes. After the stirring was completed, 3-butynyl methoxymethyl ether (9:R 1=H) (517.25g, 4.50mol, purity 99.30%) was added dropwise to the reactor. After the addition was completed, the reaction mixture was stirred at 60°C to 70°C for 5 hours. Subsequently, ethylene oxide (257.69g, 5.85mol) was added dropwise at 40°C to 60°C. After the addition was completed, the reaction mixture was stirred at 60°C to 65°C for 3.5 hours. Next, a solution of acetic acid (800.00g) in water (1600.00g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain 6-hydroxy-3-hexynyl methoxymethyl ether (10:R 1 =H) (635.95 g, 3.91 mol, purity 97.16%, bp = 105.6°C to 125.1°C / 0.40 kPa (3.0 mmHg)), yield 86.80%.

[0304] The following is the 6-hydroxy-3-hexynyl methoxymethyl ether (10:R 1 =H) spectral data.

[0305] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ=2.37-2.42(2H,m), 2.42-2.47(2H,m), 3.34(3H,s), 3.60(2H,t,J=6.5Hz), 3.64(2H,t,J=6.2Hz), 4.62(2H,s); 13 C-NMR (500MHz, CDCl3): δ=20.16, 23.03, 55.17, 61.10, 66.17, 77.77, 79.03, 96.23.

[0306] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 157 (M + -1),127,109,97,75,45.

[0307] Infrared absorption spectrum (D-ATR): νmax = 3427, 2936, 2885, 1383, 1208, 1150, 1111, 1072, 1040, 918, 849.

[0308] Example 2: Preparation of (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H)

[0309]

[0310] 6-Hydroxy-3-hexynyl methoxymethyl ether (10:R1 =H) (635.95 g, 3.91 mol, purity 97.16%) and P-2Ni catalyst (108.60 g) were placed in a reactor. The reactor was purged with hydrogen at 45° C. to 55° C. for 7.5 hours under stirring. After confirming that the conversion rate was 100%, water (170.94 g) was added to the reaction mixture, and then phase separation was performed. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H) (612.16 g, 3.62 mol, purity 94.74%, bp = 107.2°C to 111.0°C / 0.40 kPa (3.0 mmHg)), yield 92.58%.

[0311] The following is the (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H) spectral data.

[0312] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 2.32 (2H, dt, J = 6.9Hz, 6.9Hz), 2.37 (2H, dt, J = 7.3Hz, 7.3Hz), 3 .33(3H,s),3.54(2H,t,J=6.5Hz),3.61(2H,t,J=6.5Hz),4.59(2H,s),5.46-5.59(2H,m); 13 C-NMR (500MHz, CDCl3): δ=27.82, 30.69, 55.13, 61.84, 66.87, 96.19, 127.83, 129.16.

[0313] Mass spectrum: EI-mass spectrum (70eV): m / z 159 (M + -1),130,111,100,81,68,55,45.

[0314] Infrared absorption spectrum (D-ATR): νmax = 3423, 2932, 2883, 1442, 1404, 1150, 1109, 1035, 919, 725.

[0315] Example 3: Preparation of (3E)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H)

[0316]

[0317] Lithium aluminum hydride (42.50 g, 1.12 mol) and diethylene glycol dimethyl ether (666.24 g) were placed in a reactor at room temperature and stirred at 50°C to 55°C for 15 minutes. After stirring, 6-hydroxy-3-hexynyl methoxymethyl ether (260.85 g, 1.60 mol, 97.03% purity) obtained according to Example 1 was added dropwise at 50°C to 60°C, and stirred at 130°C to 135°C for 20 hours. After cooling to 20°C to 25°C, tetrahydrofuran (2508.78 g), water (42.50 g), an aqueous solution of sodium hydroxide (0.16 mol) (170.03 g), and diatomaceous earth (529.51 g) were added in sequence, and stirred for 12 hours. After stirring, the reaction mixture was filtered to obtain an organic phase. The organic phase thus obtained was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3E)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H) (235.15 g, 1.44 mol, purity 98.13%, bp = 104.3°C to 105.6°C / 0.40 kPa (3.0 mmHg)), yield 90.02%.

[0318] The following is the (3E)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H) spectral data.

[0319] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.89 (1H, br.s), 2.25 (2H, ddt, J = 0.8Hz, 6.5Hz, 6.5Hz), 2.30 (2H, ddt, J = 0.8Hz, 6.9Hz, 6.9Hz), 3.33 (3H, s), 3.54 (2H, t, J = 6.9Hz), 3.60 (2H, t, J = 6.5Hz), 4.59 (2H, s), 5.43-5.58 (2H, m); 13 C-NMR (500MHz, CDCl3): δ=33.02, 35.96, 55.09, 61.77, 67.24, 96.29, 128.27, 129.91.

[0320] Mass spectrum: EI-mass spectrum (70eV): m / z 159 (M + -1),130,100,81,68,55,45.

[0321] Infrared absorption spectrum (D-ATR): νmax = 3410, 2931, 2885, 1442, 1383, 1211, 1150, 1110, 1043, 970, 919.

[0322] Example 4: Preparation of (3Z)-6-hydroxy-3-hexenylbutoxymethyl ether (1:R 1 =CH2CH2CH3).

[0323]

[0324] The steps of Examples 1 and 2 were repeated except that 3-butynyl butoxymethyl ether (9:R 1 =CH2CH2CH3) (276.94 g, 1.52 mol, purity 85.75%) was used as the starting material instead of 3-butynyl methoxymethyl ether to obtain (3Z)-6-hydroxy-3-hexenyl butoxymethyl ether (1:R 1 =CH3CH2CH2) (251.00 g, 1.20 mol, purity 96.42%, bp = 122.0°C to 126.9°C / 0.40 kPa (3.0 mmHg)), yield 78.71%.

[0325] The following is the (3Z)-6-hydroxy-3-hexenyl butoxymethyl ether (1:R 1 =CH3CH2CH2) spectrum data.

[0326] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.91 (3H, t, J = 7.3Hz), 1.31-1.41 (2H, m), 1.51-1.59 (2 H,m),2.17(1H,br.s),2.33(2H,dt,J=6.7Hz,6.7Hz),2.37(2H,dt,J=6.7Hz,6.7Hz ),3.50(2H,t,J=6.5Hz),3.56(2H,t,J=6.5Hz),3.62(2H,t,J=6.1Hz),4.64(2H,s) ,5.50(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz),5.56(1H,dtt,J=11.1Hz,7.3Hz,1.2Hz); 13 C-NMR (500MHz, CDCl3): δ=13.81,19.31,27.85,30.70,31.70,61.87,66.83,67.61,95.08,127.80,129.32.

[0327] Mass spectrometry: EI-mass spectrometry (70eV): m / z 201 (M + -1),185,129,111,99,87,69,57,41,29.

[0328] Infrared absorption spectrum (D-ATR): νmax = 3431, 2957, 2933, 2873, 1465, 1380, 1146, 1115, 1045, 828, 725.

[0329] Example 5: Preparation of (3Z)-6-hydroxy-3-hexenylbenzyloxymethyl ether (1:R 1 =Ph)

[0330]

[0331] The steps of Examples 1 and 2 were repeated except that 3-butynylbenzyloxymethyl ether (9:R 1 =Ph) (190.79 g, 0.95 mol, purity 95.21%) was used as the starting material instead of 3-butynyl methoxymethyl ether to obtain (3Z)-6-hydroxy-3-hexenyl benzyloxymethyl ether (1:R 1 =Ph) (163.56 g, 0.65 mol, purity 94.20%, bp = 160.0°C to 163.7°C / 0.40 kPa (3.0 mmHg)), yield 68.28%.

[0332] The following is the (3Z)-6-hydroxy-3-hexenylbenzyloxymethyl ether (1:R 1 =Ph) spectrum data.

[0333] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 2.06 (1H, br.s), 2.35 (2H, dt, J = 6.6Hz, 6.6Hz), 2.40 (2H, dt, J = 6.6Hz, 6.6Hz), 3.64 (2H, t, J = 6.5Hz), 3.64 (2H ,t,J=6.2Hz),4.60(2H,s),4.76(2H,s),5.52(1H,dtt,J=10.7Hz,7.3Hz,1.6Hz),5.59(1H,J=11.1Hz,7.3Hz,1.1Hz),7.27-7.37(5H,m); 13 C-NMR (500MHz, CDCl3): δ=27.85, 30.73, 61.90, 67.13, 69.39, 94.49, 127.65, 127.85, 127.87, 128.36, 129.28, 137.81.

[0334] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 235 (M + -1),218,206,160,129,108,91,77,65,53,41,29.

[0335] Infrared absorption spectrum (D-ATR): νmax = 3420, 2939, 2877, 1454, 1379, 1164, 1110, 1046, 1027, 737, 698.

[0336] Example 6: Preparation of (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2:R 1 =H,X 1 =Cl)

[0337]

[0338] The (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1:R 1 =H) (541.14 g, 3.20 mol, purity 94.74%), pyridine (455.62 g, 5.76 mol) and GBL (960.00 g) were placed in a reactor and stirred at 0°C to 10°C for 26 minutes.

[0339] Subsequently, methanesulfonyl chloride (513.18g, 4.48mol) was added dropwise at 0 DEG C to 10 DEG C. After completion of the addition, the reaction mixture was heated to 60 DEG C to 65 DEG C and stirred for 5 hours. After completion of the stirring, water (1280.00g) and hexane (1280.00g) were added sequentially in the reaction mixture, and then phase separation was performed. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was washed with acetic acid (160.00g) in water (1280.00g), and then with a solution of sodium bicarbonate (80.00g) in water (1280.00g). The organic phase thus obtained was concentrated under reduced pressure. Concentrate was distilled under reduced pressure to obtain (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2:R 1 =H,X 1 =Cl) (496.72 g, 2.71 mol, purity 97.33%, bp = 80.0°C to 82.9°C / 0.40 kPa (3.0 mmHg)), yield 84.57%.

[0340] The following is the (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2:R 1 =H,X 1 =Cl) spectral data.

[0341] NMR spectroscopy: 1H-NMR (500MHz, CDCl3): δ = 2.36 (2H, dt, J = 6.5Hz, 6.5Hz), 2.53 (2H, dt, J = 7.1Hz, 7.1Hz), 3.35 (3H, s), 3.51 (2H, t, J = 6.9H z), 3.54 (2H, t, J = 6.9Hz), 4.61 (2H, s), 5.49 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz), 5.57 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.6Hz); 13 C-NMR (500MHz, CDCl3): δ=28.03, 30.71, 44.01, 55.12, 66.98, 96.32, 127.08, 128.98.

[0342] Mass spectrum: EI-mass spectrum (70eV): m / z 177 (M + -1),147,129,112,97,75,65,55,45,29.

[0343] Infrared absorption spectrum (D-ATR): νmax = 2951, 2884, 1444, 1381, 1296, 1209, 1148, 1111, 1036, 919, 738, 661.

[0344] Example 7: Preparation of (3Z,13Z)-3,13-octadiene methoxymethyl ether (5:R 1 =H)

[0345]

[0346] Magnesium (15.24 g, 0.63 gram atoms) and tetrahydrofuran (171.00 g) were placed in a reactor at room temperature and stirred at 60° C. to 65° C. for 9 minutes. After the stirring was completed, (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2:R) obtained in Example 6 was added dropwise at 60° C. to 75° C. 1 =H,X 1 =Cl) (109.86 g, 0.60 mol, purity 97.33%). After the dropwise addition was completed, the reaction mixture was stirred at 75°C to 80°C for 2 hours to prepare (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3:R 1 =H, M =MgCl).

[0347] Subsequently, cuprous chloride (0.44 g, 0.010 mol), lithium chloride (6.39 g, 0.038 mol), triethyl phosphite (6.39 g, 0.038 mol), tetrahydrofuran (114.00 g) and (5Z)-12-bromo-5-dodecene (4:X2 =Br) (140.92 g, 0.57 mol, purity 100%) was placed in another reactor, and the (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3:R 1 =H, M = MgCl). After the addition was completed, the reaction mixture was stirred at 15°C to 25°C for 2.5 hours. Next, a solution of ammonium chloride (6.28 g) in water (163.01 g) and hydrochloric acid (11.98 g, 0.066 mol of hydrogen chloride) were added to the reaction mixture in sequence, and then phase separation was performed and the aqueous phase was removed. The organic phase thus obtained was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z, 13Z)-3,13-octadiene methoxymethyl ether (5:R 1 =H) (163.39 g, 0.49 mol, purity 92.36%, bp = 150.5°C to 156.1°C / 0.40 kPa (3.0 mmHg)), yield 85.27%.

[0348] The following is the (3Z,13Z)-3,13-octadiene methoxymethyl ether (5:R 1 =H) spectral data.

[0349] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.89 (3H, t, J = 7.3Hz), 1.24-1.38 (16H, m), 1.96-2.07 (6H, m), 2.34 (2H, q sample, J = 6.9Hz ),3.36(3H,s),3.53(2H,t,J=7.3Hz),4.62(2H,s),5.32-5.41(3H,m),5.47(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=13.97,22.33,26.89,27.16,27.33,27.88,29.27,29. 49,29.59,29.74,31.95,55.10,67.40,96.32,125.34,129.82,129.84,132.19.

[0350] Mass spectrometry: EI-mass spectrometry (70eV): m / z 310 (M + ),278,248,219,151,135,109,81,45,29.

[0351] Infrared absorption spectrum (D-ATR): νmax = 2925, 2854, 1465, 1379, 1151, 1111, 1074, 1037, 920, 723.

[0352] Example 8: Preparation of (3Z,13Z)-3,13-octadecadien-1-ol (6)

[0353]

[0354] The (3Z,13Z)-3,13-octadiene methoxymethyl ether (5:R 1 =H) (157.99 g, 0.47 mol, purity 92.36%), methanol (234.95 g, 7.33 mol), and 20% hydrochloric acid (23.50 g, 0.13 mol of hydrogen chloride) were placed in a reactor equipped with a distillation column, and the reaction mixture was heated to 60°C and stirred for 1 hour. After the stirring was completed, the internal temperature was raised to 65°C to 70°C to distill off a mixture of dimethoxymethane and methanol produced as by-products from the distillation column. The reaction mixture was sampled during the reaction. After confirming that the conversion rate was 100%, water (140.97 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was subjected to reduced pressure distillation to obtain (3Z,13Z)-3,13-octadecadien-1-ol (6) (127.12 g, 0.44 mol, purity 91.56%, bp = 160.0°C to 165.8°C / 0.40 kPa (3.0 mmHg)) with a yield of 92.96%.

[0355] The following is the spectrum data of (3Z,13Z)-3,13-octadecadien-1-ol (6) prepared in this way.

[0356] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ=0.89(3H,t,J=7.3Hz,1.24-1.38(16H,m),1.54(1H,br.s),1.98-2.09(6H,m),2 .32(2H,q sample,J=6.7Hz),3.63(2H,t,J=6.5Hz),5.30-5.40(3H,m),5.55(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=13.96,22.32,26.89,27.16,27.34,29.26,29.47,29.68,29.73,30.77,31.94,62.31,124.91,129.84,133.51.

[0357] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 266 (M + ),248,222,208,194,177,163,149,135,121,109,95,81,55,41.

[0358] Infrared absorption spectrum (D-ATR): νmax = 3333, 2925, 2854, 1465, 1049, 722.

[0359] Example 9: Preparation of (3Z,13Z)-3,13-octadecadienyl acetate (7)

[0360]

[0361] (3Z,13Z)-3,13-octadecadien-1-ol (6) (104.31 g, 0.36 mol, purity 91.56%) obtained in Example 8, toluene (78.56 g), and pyridine (53.86 g, 0.68 mol) were placed in a reactor at room temperature and stirred at 15°C to 25°C for 2 minutes. After stirring, acetic anhydride (153.14 g, 0.54 mol) was added dropwise at 20°C to 40°C, and stirred at 30°C to 35°C for 6.5 hours. Next, water (94.14 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was subjected to reduced pressure distillation to obtain (3Z,13Z)-3,13-octadecadienyl acetate (7) (116.35 g, 0.36 mol, purity 95.03, bp = 136.9°C to 145.1°C / 0.40 kPa (3.0 mmHg)) with a yield of 100%.

[0362] The following is the spectrum data of (3Z,13Z)-3,13-octadecadienyl acetate (7) prepared in this way.

[0363] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.89 (3H, t, J = 7.3Hz), 1.24-1.38 (16H, m), 1.98-2.06 (6H, m), 2.04 (3H, s), 2. 37 (2H, q sample e, J = 7.1Hz), 4.05 (2H, t, J = 6.9Hz), 5.30-5.38 (3H, m), 5.50 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz); 13C-NMR (500MHz, CDCl3): δ=13.96, 20.94, 22.32, 26.79, 26.89, 27.16, 27.28, 29. 25,29.47,29.49,29.57,29.73,31.94,63.96,124.21,129.83,132.97,171.08.

[0364] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 308 (M + ),248,219,191,163,135,109,81,65,43.

[0365] Infrared absorption spectrum (D-ATR): νmax = 2926, 2854, 1745, 1465, 1383, 1363, 1237, 1036, 723.

[0366] Example 10: Preparation of (3Z,13E)-3,13-octadiene methoxymethyl ether (5:R 1 =H)

[0367]

[0368] Magnesium (5.07 g, 0.21 gram atoms) and tetrahydrofuran (59.78 g) were placed in a reactor at room temperature and stirred at 60° C. to 65° C. for 16 minutes. After the stirring was completed, (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2:R) obtained in Example 6 was added dropwise at 60° C. to 75° C. 1 =H,X 1 =Cl) (36.58 g, 0.20 mol, purity 97.33%). After the dropwise addition was completed, the reaction mixture was stirred at 75°C to 80°C for 2 hours to prepare (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3:R 1 =H, M =MgCl).

[0369] Subsequently, cuprous chloride (0.21 g, 0.0021 mol), lithium chloride (0.15 g, 0.035 mol), triethyl phosphite (2.13 g, 0.013 mol), tetrahydrofuran (37.96 g) and (5E)-12-bromo-5-dodecene (4:X 2 =Br) (47.23 g, 0.19 mol, purity 99.37%) was placed in another reactor, and the (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3:R 1=H, M = MgCl). After the addition was completed, the reaction mixture was stirred at 15 ° C to 25 ° C for 3 hours. After the stirring was completed, an aqueous solution of ammonium chloride (2.09 g) in water (54.28 g) and hydrochloric acid (3.99 g, 0.022 mol hydrogen chloride) were added to the reaction mixture in sequence, and then phase separation was performed. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z, 13E) -3,13- octadiene methoxymethyl ether (5: R 1 =H) (59.78 g, 0.18 mol, purity 92.42%, bp = 130.0°C to 145.9°C / 0.40 kPa (3.0 mmHg)), yield 93.75%.

[0370] The following is the (3Z,13E)-3,13-octadiene methoxymethyl ether (5:R 1 =H) spectral data.

[0371] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.88 (3H, t, J = 7.3Hz), 1.23-1.38 (16H, m), 1.93-2.00 (4H, m), 2.04 (2H, dt, J = 7.3Hz, 7.3Hz), 2.34 ( 2H,q sample,J=6.9Hz),3.36(3H,s),3.53(2H,t,J=6.9Hz),4.62(2H,s),5.32-5.43(3H,m),5.47(1H,dtt,J=10.7Hz,7.3Hz,1.6Hz); 13 C-NMR (500MHz, CDCl3): δ=13.94,22.17,27.33,27.88,29.14,29.27,29.46,29.49,29. 59,29.63,31.82,32.27,32.58,55.10,67.40,96.32,125.33,130.29,130.31,132.20.

[0372] Mass spectrometry: EI-mass spectrometry (70eV): m / z 310 (M + ),278,248,221,151,135,109,81,45,29.

[0373] Infrared absorption spectrum (D-ATR): νmax = 2925, 2854, 1465, 1151, 1111, 1037, 967, 920, 724.

[0374] Example 11: Preparation of (3Z,13E)-3,13-octadecadien-1-ol (6)

[0375]

[0376] The (3Z,13E)-3,13-octadiene methoxymethyl ether (5:R 1 =H) (59.54 g, 0.18 mol, purity 92.42%), methanol (88.60 g, 2.77 mol) and 20% hydrochloric acid (8.86 g, 0.045 mol of hydrogen chloride) were placed in a reactor equipped with a distillation column, and the reaction mixture was heated to 60°C and stirred for 1 hour. After the stirring was completed, the internal temperature was raised to 65°C to 70°C to distill off a mixture of dimethoxymethane and methanol produced as by-products from the distillation column. The reaction mixture was sampled during the reaction. After confirming that the conversion rate was 100%, water (53.16 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was subjected to reduced pressure distillation to obtain (3Z,13E)-3,13-octadecadien-1-ol (6) (47.35 g, 0.16 mol, purity 91.11%, bp = 131.2°C to 150.0°C / 0.40 kPa (3.0 mmHg)) with a yield of 91.34%.

[0377] The following is the spectrum data of (3Z,13E)-3,13-octadecadien-1-ol (6) prepared in this way.

[0378] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.88 (3H, t, J = 7.3Hz), 1.22-1.38 (16H, m), 1.54 (1H, br.s), 1.93-2.00 (4H, m), 2.05 (2H, q sample ,J=6.9Hz),2.32(2H,q sample,J=6.9Hz),3.63(2H,t,J=6.5Hz),5.32-5.42(3H,m),5.55(1H,dtt,J=11.1Hz,7.3Hz,1.6Hz); 13 C-NMR (500MHz, CDCl3): δ=13.93,22.16,27.34,29.12,29.27,29.44,29.47 ,29.61,29.67,30.76,31.81,32.26,32.57,62.30,124.89,130.29,133.52.

[0379] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 266 (M +),248,222,208,194,177,163,149,135,121,109,95,81,55,41.

[0380] Infrared absorption spectrum (D-ATR): νmax = 3330, 2924, 2854, 1465, 1049, 967, 723.

[0381] Example 12: Preparation of (3Z,13E)-3,13-octadecadienyl acetate (7)

[0382]

[0383] (3Z,13E)-3,13-octadecadien-1-ol (6) (44.25 g, 0.15 mol, purity 91.11%) obtained in Example 11, toluene (33.16 g), and pyridine (22.74 g, 0.29 mol) were placed in a reactor at room temperature and stirred at 15°C to 25°C for 2 minutes. After stirring, acetic anhydride (23.17 g, 0.23 mol) was added dropwise at 20°C to 40°C, and stirred at 30°C to 35°C for 7 hours. Next, water (39.74 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain an organic phase. The organic phase thus obtained was subjected to reduced pressure distillation to obtain (3Z,13E)-3,13-octadecadienyl acetate (7) (46.68 g, 0.15 mol, purity 95.68, bp = 133.9°C to 141.2°C / 0.40 kPa (3.0 mmHg)) with a yield of 100%.

[0384] The following is the spectrum data of (3Z,13E)-3,13-octadecadienyl acetate (7) prepared in this way.

[0385] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ=0.88(3H,t,J=7.3Hz),1.22-1.38(16H,m),1.93-1.99(4H,m),2.03(2H,q-like,J=6.9Hz),2.04(3H,s),2.37(2H,q -like,J=7.1Hz),4.05(2H,t,J=6.9Hz),5.33(1H,dtt,J=11.1Hz,7.3Hz,1.5Hz),5.36-5.40(2H,m),5.50(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13C-NMR (500MHz, CDCl3): δ=13.93,20.95,22.16,26.78,27.29,29.13,29.25,29.44, 29.49,29.58,29.62,31.81,32.26,32.58,63.96,124.20,130.30,132.98,171.08.

[0386] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 308 (M + ),248,219,191,163,135,109,81,65,43.

[0387] Infrared absorption spectrum (D-ATR): νmax = 2925, 2854, 1745, 1465, 1363, 1237, 1036, 967, 724.

Claims

1. A method for preparing a 3,13-octadecadien-1-ol compound of the following formula (6): CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OH (6), The method comprises: Halogenate the 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1) where R 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group To prepare the following 6-halogeno-3-hexenyl alkoxymethyl ether compound of general formula (2): X 1 CH2CH2CH=CHCH2CH2OCH2OCH2R 1 (2) where X 1 represents a halogen atom, and R 1 As defined above; The 6-halogeno-3-hexenyl alkoxymethyl ether compound (2) is converted into a nucleophile, a 6-(alkoxymethoxy)-3-hexenyl compound of the following general formula (3): MCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (3) Where M represents MgZ 2 、CuZ 2 or CuLiZ 2 , where Z 2 Represents the halogen atom X 1 the same halogen atom or 6-(alkoxymethoxy)-3-hexenyl group, and R 1 As defined above; The nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (3) is subjected to a coupling reaction with 12-halogenated-5-dodecene of the following general formula (4): CH3(CH2)3CH=CH(CH2)6X 2 (4) where X 2 represents a halogen atom, To prepare the following 3,13-octadecadienyl alkoxymethyl ether compound of general formula (5): CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OCH2OCH2R 1 (5) where R 1 as defined above; and The 3,13-octadecadien-1-ol compound (6) is prepared by dealkoxymethylating the 3,13-octadecadien-1-ol compound (6).

2. A method for preparing a 3,13-octadecadienyl acetate compound of the following formula (7): CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OAc (7) Wherein Ac represents an acetyl group, The method comprises: The method for preparing the 3,13-octadecadien-1-ol compound (6) according to claim 1, and The obtained 3,13-octadecadien-1-ol compound (6) is acetylated to prepare the 3,13-octadecadienyl acetate compound (7).

3. A 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH2CH2CH=CHCH2CH2OCH2OCH2R 1 (1) where R 1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group.

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