Process for the preparation of haloalkenylalkoxymethyl ethers and terminal conjugated alkadiene-1-yl acetates and alkadiene-1-ols therefrom

Abstract

The present invention relates to halogenated alkenylalkoxymethyl ether compounds of the following general formula (1): R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1), wherein R 1 represents a hydrogen atom, a n-alkyl group having 1 to 9 carbon atoms, or a phenyl group, X 1 represents a halogen atom, and a represents an integer of 3 to 14. The present invention also relates to a method for producing terminal conjugated alkadien-1-yl acetate compounds of the following general formula (5): CH2=CHCH=CH(CH2) a OAc (5), wherein a is defined as above, and Ac represents an acetyl group, and a method for producing terminal conjugated alkadien-1-ol compounds of the following general formula (6): CH2=CHCH=CH(CH2) a OH (6), wherein a is defined as above.

Description

Technical Field

[0001] This invention relates to haloalkenylalkoxymethyl ether compounds and methods for preparing terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds from them. Background Technology

[0002] Many species of lepidopteran pests utilize acetate compounds with a terminally conjugated diene skeleton (hereinafter referred to as "terminally conjugated diene-1-yl acetate compounds") or alcohol compounds with a terminally conjugated diene skeleton (hereinafter referred to as "terminally conjugated diene-1-ol compounds") as sex pheromones. For example, one of the sex pheromones of the South American apple pest, the South American leafroller moth (Argyrotaenia sphaleropa), is (11Z)-11,13-tetradecadien-1-yl acetate; one of the sex pheromones of the Southeast Asian peanut pest, the peanut moth (Aproaerema modicella), is (7Z)-7,9-decadien-1-yl acetate; and another is (Parasa spp.). The sex pheromone of Lepida is (7Z)-7,9-decadien-1-ol. In recent years, with the increasing environmental awareness, pest control methods that reduce the amount of pesticide spraying have attracted attention, and the use of sex pheromones is expected to be one of them (non-patent literature 1, 2 and 3 listed below).

[0003] For example, methods for preparing the sex pheromones (11Z)-11,13-tetradecadien-1-yl acetate and (11Z)-11,13-tetradecadien-1-ol from the South American leafroller moth have been reported as methods for preparing terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds (Non-Patent Document 2 listed below). Specifically, the hydroxyl group of the starting material 11-bromoundecane-1-ol is acetylated with acetic anhydride to synthesize 11-bromoundecane-1-yl acetate. Next, the 11-bromoundecane-1-yl acetate thus obtained is reacted with triphenylphosphine to prepare a phosphonium salt, then reacted with a base, and then subjected to a Wittig reaction with acrolein at -78°C to prepare (11Z)-11,13-tetradecadien-1-yl acetate. Subsequently, the (11Z)-11,13-tetradecadien-1-yl acetate obtained therefrom was hydrolyzed with potassium hydroxide in the presence of methanol to give (11Z)-11,13-tetradecadien-1-ol (Non-Patent Literature 1 listed below).

[0004] Methods for preparing the sex pheromone (7Z)-7,9-decadien-1-yl acetate of the peanut moth and the sex pheromone (7Z)-7,9-decadien-1-ol of the green tussock moth have been reported as methods for preparing terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds (Non-Patent Literature 2 listed below). Specifically, the starting material 2-(chloromethyl)tetrahydrofuran is reacted with bromopropane in ammonia in the presence of lithium ammonium to open the tetrahydrofuran ring to synthesize 4-octyne-1-ol. Subsequently, the 4-octyne-1-ol thus obtained is subjected to an alkyne zip reaction with 1,3-diaminopropane to synthesize 7-octyne-1-ol, which is then coupled with ethylene bromide in the presence of tetra(triphenylphosphine)palladium and copper iodide, and subjected to a catalytic reduction reaction to synthesize (7Z)-7,9-decadien-1-ol. Subsequently, the hydroxyl groups of the (7Z)-7,9-decadien-1-ol thus obtained are acetylated to prepare (7Z)-7,9-decadien-1-yl acetate (Non-Patent Literature 2 and 3 listed below).

[0005] List of Literature

[0006] [Non-patent literature]

[0007] [Non-patent literature 1] C. Ricard Unelius et al., 2004, Z. Naturforsch. 59c: 708-712.

[0008] [Non-patent literature 2] JSYadav et al., 1995, Synthetic Communications., 25(24): 4035-4043.

[0009] [Non-patent literature 3] S. Wakamura et al., 2007, Appl. Entomol. Zool., 42(3): 347-352.

[0010] The problem to be solved by the present invention

[0011] In Non-Patent Literature 1, the synthesis method uses acrolein, which has a low boiling point, a strong odor, and high polymerizability, making this method difficult to apply in industrial production. Furthermore, the Wittig reaction is carried out at -78°C in the synthesis method, requiring specialized reaction equipment, which makes the method less economically viable. In addition, the overall yield during the synthesis is as low as less than 15%.

[0012] Non-Patent Literature 2 uses 2-(chloromethyl)tetrahydrofuran, a special raw material with a strong odor. Ammonia is also used as a solvent. Ammonia has a strong odor and is therefore designated as an odor substance by odor control laws. Ammonia is toxic to humans and is therefore designated as a harmful gas. These require specialized reaction and post-processing equipment, making the method unsuitable for industrial production. Furthermore, the use of expensive palladium catalysts makes the method less economically viable. Additionally, the hyperhydrogenation of the terminal double bonds occurs in the hydrogenation of enyne compounds with terminal double bonds, which is undesirable in terms of purity.

[0013] The present invention was made under these circumstances and aims to provide an efficient method for preparing terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds. Summary of the Invention

[0014] To overcome the aforementioned problems in the prior art, the inventors, through in-depth research, have discovered that haloalkenylalkoxymethyl ether compounds are useful intermediates for preparing terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds. The inventors have also found that haloalkenylalkoxymethyl ether compounds can be used to prepare terminally conjugated dien-1-yl acetate compounds and terminally conjugated dien-1-ol compounds with high purity and efficiency in a short number of steps. These compounds can have different numbers of carbon atoms, thus completing this invention.

[0015] According to one aspect of the present invention, a method is provided for preparing terminally conjugated diene-1-yl acetate compounds of the following general formula (5):

[0016] CH2=CHCH=CH(CH2) a OAc (5)

[0017] Where 'a' represents an integer from 3 to 14, and 'Ac' represents an acetyl group.

[0018] The method includes:

[0019] Dealkyloxymethylation of haloalkenyl alkoxymethyl ether compounds of general formula (1):

[0020] R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1)

[0021] Where R 1 X represents a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, or a phenyl group. 1 Represents a halogen atom, and a is as specified above.

[0022] To prepare halo-3-chain en-1-ol compounds of the following general formula (2):

[0023] HOCH2CH2CH=CH(CH2) a X 1 (2)

[0024] Where X 1 and 'a' as specified above;

[0025] Acetoxylated halo-3-alken-1-ol compound (2) to prepare hydroxyalkenyl acetate compound of general formula (3):

[0026] HOCH2CH2CH=CH(CH2) a OAc (3)

[0027] Where a and Ac are as defined above;

[0028] Halogenation of hydroxyl-chain alkenyl acetate compound (3) is used to prepare haloalkenyl acetate compounds of the following general formula (4):

[0029] X 2 CH2CH2CH=CH(CH2) a OAc (4)

[0030] Where X 2 Represents a halogen atom, and a and Ac are as defined above; and

[0031] The haloalkenyl acetate compound (4) was subjected to an elimination reaction in the presence of a base to prepare a terminally conjugated diene-1-yl acetate compound (5).

[0032] According to another aspect of the present invention, a method for preparing terminally conjugated dien-1-ol compounds of the following general formula (6) is provided:

[0033] CH2=CHCH=CH(CH2) a OH (6)

[0034] Where a represents an integer from 3 to 14,

[0035] The method includes:

[0036] The method described above for preparing the terminally conjugated diene-1-yl acetate compound (5), and

[0037] The terminally conjugated diene-1-yl acetate compound (5) is deacetylated to prepare the terminally conjugated diene-1-ol compound (6).

[0038] According to another aspect of the invention, in the method for preparing the terminally conjugated diene-1-ol compound (6), the elimination reaction and the deacetylation are carried out in parallel in the presence of a base.

[0039] According to another aspect of the present invention, haloalkenylalkoxymethyl ether compounds of the following general formula (1) are provided:

[0040] R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1)

[0041] Where R 1 X represents a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, or a phenyl group. 1 represents a halogen atom, and a represents an integer from 3 to 14.

[0042] According to the present invention, terminally conjugated diene-1-yl acetate compounds (5) and terminally conjugated diene-1-ol compounds (6) can be prepared in a short number of steps with high purity, and these compounds may have different numbers of carbon atoms. Detailed Implementation

[0043] Halogenated alkenyl alkoxymethyl ether compounds (1)

[0044] First, the haloalkenyl alkoxymethyl ether compounds of the following general formula (1) will be described.

[0045] R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1)

[0046] R 1 The group represents a hydrogen atom, an 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.

[0047] n-alkyl R 1 Examples include straight-chain saturated hydrocarbon groups such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and n-nonyl.

[0048] a represents an integer from 3 to 14, preferably used for preparing pheromones of lepidopteran pests, from 3 to 10, more preferably from 6 to 10, and even more preferably from 6, 7 or 10.

[0049] X 1This refers to halogen atoms such as fluorine, chlorine, bromine, or iodine. Chlorine, bromine, or iodine atoms are preferred, especially chlorine and bromine atoms, to suppress side reactions in the dealkoxymethylation step.

[0050] Specific examples of haloalkenyl alkoxymethyl ether compounds (1) include the following compounds:

[0051] 7-Halo-3-heptenylalkoxymethyl ether compounds (a=3), such as 7-chloro-3-heptenylmethoxymethyl ether, 7-chloro-3-heptenylethoxymethyl ether, 7-bromo-3-heptenylmethoxymethyl ether, 7-bromo-3-heptenylethoxymethyl ether, 7-iodo-3-heptenylmethoxymethyl ether and 7-iodo-3-heptenylethoxymethyl ether;

[0052] 8-Halo-3-octenylalkoxymethyl ether compounds (a=4), such as 8-chloro-3-octenylmethoxymethyl ether, 8-chloro-3-octenylethoxymethyl ether, 8-bromo-3-octenylmethoxymethyl ether, 8-bromo-3-octenylethoxymethyl ether, 8-iodo-3-octenylmethoxymethyl ether and 8-iodo-3-octenylethoxymethyl ether;

[0053] 9-Halo-3-nonenylalkoxymethyl ether compounds (a=5), such as 9-chloro-3-nonenylmethoxymethyl ether, 9-chloro-3-nonenylethoxymethyl ether, 9-bromo-3-nonenylmethoxymethyl ether, 9-bromo-3-nonenylethoxymethyl ether, 9-iodo-3-nonenylmethoxymethyl ether and 9-iodo-3-nonenylethoxymethyl ether;

[0054] 10-Halo-3-decenylalkoxymethyl ether compounds (a=6), such as 10-chloro-3-decenylmethoxymethyl ether, 10-chloro-3-decenylethoxymethyl ether, 10-chloro-3-decenylpropoxymethyl ether, 10-chloro-3-decenylbutoxymethyl ether, 10-chloro-3-decenylpentoxymethyl ether, 10-chloro-3-decenylhexoxymethyl ether, 10-chloro-3-decylheptoxymethyl ether, 1 0-Chloro-3-decenyl octoxymethyl ether, 10-chloro-3-decenyl nonoxymethyl ether, 10-chloro-3-decenyl decoxymethyl ether, 10-chloro-3-decenyl benzyloxymethyl ether, 10-bromo-3-decenyl methoxymethyl ether, 10-bromo-3-decenyl ethoxymethyl ether, 10-bromo-3-decenyl propoxymethyl ether, 10-bromo-3-decenyl butoxymethyl ether, 10-bromo-3-decenyl pentyrooxy 10-Bromo-3-decenylhexyloxymethyl ether, 10-Bromo-3-decenylheptyloxymethyl ether, 10-Bromo-3-decenyloctyloxymethyl ether, 10-Bromo-3-decenylnonoxymethyl ether, 10-Bromo-3-decenyldecoxymethyl ether, 10-Bromo-3-decenylbenzyloxymethyl ether, 10-iodo-3-decenylmethoxymethyl ether, 10-iodo-3-decenylethoxymethyl ether, 10-iodo- 3-Dectenylpropoxymethyl ether, 10-iodine-3-decenylbutoxymethyl ether, 10-iodine-3-decenylpentoxymethyl ether, 10-iodine-3-decenylhexoxymethyl ether, 10-iodine-3-decenylheptoxymethyl ether, 10-iodine-3-decenyloctoxymethyl ether, 10-iodine-3-decenylnonoxymethyl ether, 10-iodine-3-decenyldecoxymethyl ether and 10-iodine-3-decylbenzyloxymethyl ether;

[0055] 11-Halo-3-undecenylalkoxymethyl ether compounds (a=7), such as 11-chloro-3-undecenylmethoxymethyl ether, 11-chloro-3-undecenylethoxymethyl ether, 11-bromo-3-undecenylmethoxymethyl ether, 11-bromo-3-undecenylethoxymethyl ether, 11-iodo-3-undecenylmethoxymethyl ether and 11-iodo-3-undecenylethoxymethyl ether;

[0056] 12-Halo-3-dodecenylalkoxymethyl ether compounds (a=8), such as 12-chloro-3-dodecenylmethoxymethyl ether, 12-chloro-3-dodecenylethoxymethyl ether, 12-bromo-3-dodecenylmethoxymethyl ether, 12-bromo-3-dodecenylethoxymethyl ether, 12-iodo-3-dodecenylmethoxymethyl ether and 12-iodo-3-dodecenylethoxymethyl ether;

[0057] 13-Halo-3-tetracene-enylalkoxymethyl ether compounds (a=9), such as 13-chloro-3-tetracene-enylmethoxymethyl ether, 13-chloro-3-tetracene-enylethoxymethyl ether, 13-bromo-3-tetracene-enylmethoxymethyl ether, 13-bromo-3-tetracene-enylethoxymethyl ether, 13-iodo-3-tetracene-enylmethoxymethyl ether and 13-iodo-3-tetracene-enylethoxymethyl ether;

[0058] 14-Halo-3-tetradecenylalkoxymethyl ether compounds (a=10), such as 14-chloro-3-tetradecenylmethoxymethyl ether, 14-chloro-3-tetradecenylethoxymethyl ether, 14-chloro-3-tetradecenylpropoxymethyl ether, 14-chloro-3-tetradecenylbutoxymethyl ether, 14-chloro-3-tetradecenylpentoxymethyl ether, 14-chloro-3-tetradecenylhexoxymethyl ether, 14-chloro-3-tetradecenylheptoxymethyl ether, 14-Chloro-3-tetradecenyl octoxymethyl ether, 14-chloro-3-tetradecenyl nonoxymethyl ether, 14-chloro-3-tetradecenyl decaoxymethyl ether, 14-chloro-3-tetradecenyl benzyloxymethyl ether, 14-bromo-3-tetradecenyl methoxymethyl ether, 14-bromo-3-tetradecenyl ethoxymethyl ether, 14-bromo-3-tetradecenyl propoxymethyl ether, 14-bromo-3-tetradecenyl butoxymethyl ether, 14-bromo-3-tetradecenyl... 14-Bromo-3-tetradecenylhexoxymethyl ether, 14-Bromo-3-tetradecenylheptoxymethyl ether, 14-Bromo-3-tetradecenyloctoxymethyl ether, 14-Bromo-3-tetradecenylnonoxymethyl ether, 14-Bromo-3-tetradecenyldecoxymethyl ether, 14-Bromo-3-tetradecenylbenzyloxymethyl ether, 14-iodo-3-tetradecenylmethoxymethyl ether, 14-iodo-3-tetradecenylethoxymethyl ether, 14- Iodo-3-tetradecenylpropoxymethyl ether, 14-iodo-3-tetradecenylbutoxymethyl ether, 14-iodo-3-tetradecenylpentoxymethyl ether, 14-iodo-3-tetradecenylhexoxymethyl ether, 14-iodo-3-tetradecenylheptoxymethyl ether, 14-iodo-3-tetradecenyloctoxymethyl ether, 14-iodo-3-tetradecenylnonoxymethyl ether, 14-iodo-3-tetradecenyldecoxymethyl ether and 14-iodo-3-tetradecenylbenzyloxymethyl ether;

[0059] 15-Halo-3-pentadecanenylalkoxymethyl ether compounds (a=11), such as 15-chloro-3-pentadecanenylmethoxymethyl ether, 15-chloro-3-pentadecanenylethoxymethyl ether, 15-bromo-3-pentadecanenylmethoxymethyl ether, 15-bromo-3-pentadecanenylethoxymethyl ether, 15-iodo-3-pentadecanenylmethoxymethyl ether and 15-iodo-3-pentadecanenylethoxymethyl ether;

[0060] 16-Halo-3-hexadecenylalkoxymethyl ether compounds (a=12), such as 16-chloro-3-hexadecenylmethoxymethyl ether, 16-chloro-3-hexadecenylethoxymethyl ether, 16-bromo-3-hexadecenylmethoxymethyl ether, 16-bromo-3-hexadecenylethoxymethyl ether, 16-iodo-3-hexadecenylmethoxymethyl ether and 16-iodo-3-hexadecenylethoxymethyl ether;

[0061] 17-Halo-3-heptadecenylalkoxymethyl ether compounds (a=13), such as 17-chloro-3-heptadecenylmethoxymethyl ether, 17-chloro-3-heptadecenylethoxymethyl ether, 17-bromo-3-heptadecenylmethoxymethyl ether, 17-bromo-3-heptadecenylethoxymethyl ether, 17-iodo-3-heptadecenylmethoxymethyl ether and 17-iodo-3-heptadecenylethoxymethyl ether; and

[0062] 18-Halo-3-Octadecanylalkoxymethyl ether compounds (a=14), such as 18-chloro-3-octadecenylmethoxymethyl ether, 18-chloro-3-octadecenylethoxymethyl ether, 18-bromo-3-octadecenylmethoxymethyl ether, 18-bromo-3-octadecenylethoxymethyl ether, 18-iodo-3-octadecenylmethoxymethyl ether and 18-iodo-3-octadecenylethoxymethyl ether.

[0063] Among these haloalkenylalkoxymethyl ether compounds (1), 10-halo-3-decenylalkoxymethyl ether compound (a=6) and 14-halo-3-tetradecenylalkoxymethyl ether compound (a=10) are preferred for the preparation of the peanut moth sex pheromone (7Z)-7,9-decadien-1-yl acetate and the South American leafroller sex pheromone (11Z)-11,13-tetradecadien-1-yl acetate. 11-halo-3-undecenylalkoxymethyl ether compound (a=7) is preferably a useful intermediate for the preparation of the nettle caterpillar (Setothosea asigna) sex pheromone (9E)-9,11-dodecadienal and the copper-spotted brown tussock moth (Setoranitens) sex pheromone (9Z)-9,11-dodecadienal.

[0064] The haloalkenyl alkoxymethyl ether compound (1) can be synthesized according to the number a in general formula (1) by various synthetic methods shown below. It should be noted that the description of the compounds in the following synthetic methods is not limited to the cases where the compounds are prepared according to the specific synthetic methods shown below, but also applies to the cases where the compounds are prepared according to methods other than the specific synthetic methods described above.

[0065] When a represents an integer from 5 to 14, the haloalkenyl alkoxymethyl ether compound (1) can be synthesized, for example, according to the following reaction scheme comprising at least 5 steps.

[0066]

[0067] First, the alkoxymethyl 3-butynyl ether compound of general formula (8) is reacted with a base, and then with ethylene oxide to increase the number of carbon atoms, thereby obtaining the 6-hydroxy-3-hexynylalkoxymethyl ether compound of general formula (9) (step one). The carbon-carbon triple bond of the obtained 6-hydroxy-3-hexynylalkoxymethyl ether compound (9) is reduced to obtain the 6-hydroxy-3-hexenylalkoxymethyl ether compound of general formula (10) (step two). The hydroxyl group of the obtained 6-hydroxy-3-hexenylalkoxymethyl ether compound (10) is halogenated to obtain the 6-halo-3-hexenylalkoxymethyl ether compound of general formula (11) (step three). The obtained 6-halo-3-hexenylalkoxymethyl ether compound (11) is reacted with a reagent such as magnesium or organolithium in a solvent to obtain the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound of general formula (12) (step four). Then, the obtained nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) is coupled with a dihaloalkanes of general formula (13) to obtain a haloalkenyl alkoxymethyl ether compound (1) with an increased number of carbon atoms (step 5).

[0068] The aforementioned method for preparing haloalkenyl alkoxymethyl ether compounds (1) will be described in more detail below.

[0069] The following will explain alkoxymethyl 3-butynyl ether compound (8).

[0070] R in general formula (8) 1 As defined in general formula (1).

[0071] Specific examples of alkoxymethyl 3-butynyl ether compounds (8) include methoxymethyl 3-butynyl ether, ethoxymethyl 3-butynyl ether, propoxymethyl 3-butynyl ether, butoxymethyl 3-butynyl ether, pentooxymethyl 3-butynyl ether, hexoxymethyl 3-butynyl ether, heptaoxymethyl 3-butynyl ether, octoxymethyl 3-butynyl ether, nonoxymethyl 3-butynyl ether, decaoxymethyl 3-butynyl ether and benzyloxymethyl 3-butynyl ether.

[0072] Examples of bases used in homologation reactions include organometallic reagents such as n-butyllithium, tert-butyllithium, methylmagnesium chloride, methylmagnesium bromide, sodium acetylenide, and potassium acetylenide; and metal hydride reagents such as sodium hydride and potassium hydride. Organometallic reagents are preferred due to their reactivity.

[0073] Considering reactivity, the amount of base used is preferably 1.0 to 5.0 mol, more preferably 1.0 to 2.0 mol, relative to each mol of alkoxymethyl 3-butynyl ether compound (8).

[0074] Considering reactivity, the amount of ethylene oxide is preferably 1.0 to 10.0 mol, more preferably 1.0 to 3.0 mol, relative to each mol of alkoxymethyl 3-butynyl ether compound (8).

[0075] Solvents may be used in the above homologation reactions if necessary.

[0076] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and hexamethylphosphoric triamine; and nitriles, such as acetonitrile and propionitrile. Ethers, such as diethyl ether, tetrahydrofuran, and 4-methyltetrahydropyran, are preferred due to their reactivity.

[0077] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0078] Considering reactivity, the amount of solvent is preferably 50 to 3,000 g, more preferably 100 to 1,200 g, relative to each mol of alkoxymethyl 3-butynyl ether compound (8).

[0079] The following will explain the 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0080] R in general formula (9) 1 As defined in general formula (1).

[0081] Specific examples of 6-hydroxy-3-hexynyl alkoxymethyl ether compounds (9) include 6-hydroxy-3-hexynyl methoxymethyl ether, 6-hydroxy-3-hexynyl ethoxymethyl ether, 6-hydroxy-3-hexynyl propoxymethyl ether, 6-hydroxy-3-hexynyl butyloxymethyl ether, 6-hydroxy-3-hexynyl pentooxymethyl ether, 6-hydroxy-3-hexynyl hexoxymethyl ether, 6-hydroxy-3-hexynyl heptaoxymethyl ether, 6-hydroxy-3-hexynyl octoxymethyl ether, 6-hydroxy-3-hexynyl nonoxymethyl ether, 6-hydroxy-3-hexynyl decaoxymethyl ether and 6-hydroxy-3-hexynyl benzyloxymethyl ether.

[0082] Examples of reductions for the synthesis of 6-hydroxy-3-hexenyl alkoxymethyl ether compound (10) include (i) catalytic hydrogenation, (ii) reduction in an alcohol solvent using a zinc compound, (iii) hydroboration with a dialkylborane followed by protonation, (iv) reduction with potassium hydroxide and N,N-dimethylformamide (DMF) in the presence of a palladium catalyst such as palladium acetate, (v) hydrosilylation to form a vinylsilane followed by desilylation, (vi) hydroalumination, and (vii) Birch reduction. For selectivity and productivity, catalytic hydrogenation (i), reduction with a zinc compound (ii), hydroboration followed by protonation (iii), and hydroalumination (vi) are preferred. Catalytic hydrogenation (i) is preferred if it is desired to form a carbon-carbon double bond in the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (10) in a Z-selective manner. If it is desired to form carbon-carbon double bonds in 6-hydroxy-3-hexenylalkoxymethyl ether compound (10) in an E-selective manner, aluminum hydride (vi) is preferred.

[0083] (i) Catalytic hydrogenation

[0084] Catalytic hydrogenation is carried out by supplying hydrogen in the presence of a metal catalyst.

[0085] Examples of metal catalysts used for catalytic hydrogenation include Lindlar catalysts; nickel catalysts, such as p-2 nickel boride catalysts (Thomas J. Caggiano et al. Encyclopedia of Reagents for Organic Synthesis: 3694-3699) (hereinafter also referred to as "p-2 nickel catalysts"); and palladium catalysts, such as palladium on carbon and Pd-PEI, i.e., palladium on carbon poisoned with polyethyleneimine polymer (PEI). Lindlar catalysts and nickel catalysts are preferred for economic reasons.

[0086] The amount of metal catalyst varies depending on the catalyst used. Considering reactivity, when the catalyst is solid, such as a Lindla catalyst, it is preferably 0.01 to 50 g relative to each mol of 6-hydroxy-3-hexynylalkoxymethyl ether compound (9). When reducing to nickel compounds, the P-2Ni catalyst is preferably used in an amount of 0.001 to 0.50 mol relative to each mol of 6-hydroxy-3-hexynylalkoxymethyl ether compound (9).

[0087] Solid catalysts can be dispersed in solvents.

[0088] When a metal catalyst has high activity, a catalyst poison may be added if necessary.

[0089] Examples of catalyst poisons include amine compounds such as pyridine, quinoline, and ethylenediamine; phosphorus compounds such as triphenylphosphine, thylphosphine, and triethyl phosphite; and sulfur compounds such as benzenethiol, diphenyl sulfide, dimethyl sulfide, and dimethyl sulfoxide.

[0090] The amount of catalyst poison varies greatly depending on the catalyst poison used, and considering the reaction rate and geometric selectivity, it is preferably 0.0001 to 10.0 g per mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0091] Examples of solvents used in 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.

[0092] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0093] When using a Lindela catalyst, considering reactivity, the solvent is preferably a hydrocarbon, such as hexane, heptane, toluene, or xylene. When using a nickel catalyst, considering reactivity, the solvent is preferably an alcohol, such as methanol, ethanol, propanol, butanol, or 2-propanol. When using a palladium catalyst, such as palladium on carbon, considering reactivity, the solvent is preferably an ester, such as methyl acetate or ethyl acetate.

[0094] The amount of solvent used varies depending on the catalyst and / or solvent used, and taking into account reactivity, preferably 0 to 1,000 g per mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0095] The reaction temperature for catalytic hydrogenation varies depending on the catalyst and / or solvent used, and is preferably 0 to 160 °C, more preferably 20 to 100 °C, taking into account geometric selectivity.

[0096] Considering the yield, the reaction time for catalytic hydrogenation is preferably 1 to 100 hours.

[0097] (ii) Reduction of zinc compounds in alcohol solvents

[0098] The reduction is carried out using a zinc compound in an alcohol solvent.

[0099] Alcohols used as solvents preferably have 1 to 10, more preferably 1 to 5, carbon atoms. Examples of alcohols used as solvents include straight-chain alcohols such as methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, and decanol; branched-chain alcohols such as 2-propanol and 2-butanol; and cyclic alcohols such as cyclohexanol. Considering reactivity, alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propanol, butanol, pentanol, and 2-propanol, are preferred.

[0100] Considering reactivity, the amount of alcohol is preferably 46 to 1,000 g relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0101] Zinc compounds refer to metallic zinc or activated zinc, as described below.

[0102] Considering reactivity, the amount of zinc compound is preferably 1.0 to 1,000 mol, more preferably 1.0 to 200 mol, relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0103] Due to the low reactivity of zinc, reduction may take longer. Therefore, an activator for activating zinc can be added, or a pre-activated zinc compound can be used.

[0104] Examples of activators include 1,2-dibromoethane, cuprous chloride, cuprous bromide, cuprous iodide, lithium bromide, iodine, and trimethylchlorosilane.

[0105] Activators can be used alone or in combination if necessary.

[0106] Considering reactivity, the amount of activator is preferably 0.01 to 10.0 mol relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0107] 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 dibromocopper oxide in tetrahydrofuran.

[0108] The reduction reaction temperature varies depending on the solvent used, but is preferably 20 to 120°C, taking into account reactivity.

[0109] To ensure the reaction is complete, the reduction reaction time is preferably 1 to 150 hours.

[0110] (iii) Hydroboration with dialkylborane, followed by protonation

[0111] To achieve reduction, the solution is first hydroborinated in a solvent using dialkylborane.

[0112] The dialkylborane used in hydroboration preferably has 4 to 18, more preferably 6 to 12, carbon atoms.

[0113] Examples of dialkylboranes include dicyclohexylborane, diisopentylborane, diisopentylborane, 9-boronbicyclo[3.3.1]nonane (9-BBN), diisopinocampheylborane, catecholborane, and pinacolborane. Considering reactivity, dicyclohexylborane and diisopentylborane are preferred.

[0114] Considering reactivity, the amount of dialkylborane is preferably 1.0 to 4.0 mol relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0115] Examples of solvents for borohydride treatment include ethers such as tetrahydrofuran, diethyl ether, butyl ether, 4-methyltetrahydropyran, cyclopentylmethyl ether, 1,4-dioxane, and diethylene glycol dimethyl ether; and hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. Tetrahydrofuran, 4-methyltetrahydropyran, and diethylene glycol dimethyl ether are preferred considering reactivity.

[0116] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0117] Considering reactivity, the amount of solvent is preferably 100 to 3,000 g relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (10).

[0118] Considering geometric selectivity, the preferred reaction temperature for the hydroboration reaction is -20 to 50°C.

[0119] The reaction time for hydroboration varies depending on the reaction temperature and / or the reaction scale, and is preferably 1 to 100 hours, taking into account reactivity.

[0120] To achieve reduction, protonation is performed in a solvent using acid after hydroboration.

[0121] Examples of acids used in protonation include carboxylic acids such as acetic acid, propionic acid, butyric acid, valeric acid, neopentanoic acid, heptanoic acid, trifluoroacetic acid, chloroacetic acid, formic acid, and oxalic acid; sulfonic acids such as p-toluenesulfonic acid; and inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid. Considering reactivity, carboxylic acids, such as acetic acid and propionic acid, are preferred.

[0122] Considering reactivity, the amount of acid is preferably 2.0 to 20.0 mol relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0123] The type and amount of solvent are the same as in hydroboration, because protonation subsequently occurs in the hydroboration reaction system.

[0124] The reaction temperature for protonation varies depending on the reagents used, but is preferably between 0 and 150 °C, taking into account the reaction rate.

[0125] The protonation reaction time varies depending on the reaction temperature and / or reaction scale, and is preferably 1 to 70 hours, taking reactivity into account.

[0126] (iv) Reduction using potassium hydroxide and N,N-dimethylformamide (DMF) in the presence of a palladium catalyst (such as palladium acetate).

[0127] 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 to 180 °C for 6 to 100 hours.

[0128] (v) Hydrosilylation to form vinylsilane, followed by desilylation

[0129] Hydrosilylation is carried out using metal catalysts such as Wilkinson or Trost catalysts and trialkylsilanes.

[0130] Considering reactivity, the amount of metal catalyst is preferably 0.0001 to 4.0 mol, more preferably 0.001 to 1.0 mol, relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0131] Hydrosilylation is preferably carried out at 5 to 100°C for 1 to 100 hours.

[0132] The desilylation following hydrosilylation is preferably carried out at 5 to 80°C for 1 to 100 hours using at least one of the following acids: sulfuric acid or hydrochloric acid, hydrogen iodide, acetyl chloride, titanium tetrachloride, and iodine.

[0133] (vi) Aluminum hydride

[0134] Aluminum hydride is performed using lithium aluminum hydride.

[0135] Considering reactivity, the amount of lithium aluminum hydride is preferably 0.25 to 4.0 mol, more preferably 0.35 to 2.0 mol, relative to each mol of 6-hydroxy-3-hexynyl alkoxymethyl ether compound (9).

[0136] Examples of solvents used in aluminum hydride include ethers such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, 1,4-dioxane, and diethylene glycol dimethyl ether; and hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. Ethers, such as tetrahydrofuran, 4-methyltetrahydropyran, and diethylene glycol dimethyl ether, are preferred due to their reactivity.

[0137] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0138] The aluminum hydrogenation is preferably carried out at 20 to 180°C for 1 to 100 hours.

[0139] (vii) Burch Restoration

[0140] Birch reduction is carried out using metals in amines or alcohols.

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

[0142] Examples of amines include ammonia; and lower amines such as methylamine, ethylamine, and propylamine.

[0143] Examples of alcohols include methanol, ethanol, and 2-methylpropanol.

[0144] Birch reduction is preferably carried out at -78 to 20°C for 1 to 100 hours.

[0145] By selecting reduction conditions, the carbon-carbon double bond geometry of 6-hydroxy-3-hexenylalkoxymethyl ether compound (10) can be selectively constructed in E- or Z-configuration.

[0146] The following will explain the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (10).

[0147] R in general formula (10) 1 As defined in general formula (1).

[0148] Specific examples of 6-hydroxy-3-hexenyl alkoxymethyl ether compounds (10) include 6-hydroxy-3-hexenyl methoxymethyl ether, 6-hydroxy-3-hexenyl ethoxymethyl ether, 6-hydroxy-3-hexenyl propoxymethyl ether, 6-hydroxy-3-hexenyl butoxymethyl ether, 6-hydroxy-3-hexenyl pentooxymethyl ether, 6-hydroxy-3-hexenyl hexoxymethyl ether, 6-hydroxy-3-hexenyl heptaoxymethyl ether, 6-hydroxy-3-hexenyl octoxymethyl ether, 6-hydroxy-3-hexenyl nonoxymethyl ether, 6-hydroxy-3-hexenyl decaoxymethyl ether and 6-hydroxy-3-hexenyl benzyloxymethyl ether.

[0149] The halogenation reaction for synthesizing 6-halo-3-hexenylalkoxymethyl ether compound (11) can be carried out, for example, by tosulphonylating the hydroxyl group with p-toluenesulfonyl halide followed by halogenation with lithium halide compound, or by directly halogenating the hydroxyl group with a halogenating agent.

[0150] Examples of halogenating agents include halogen molecules such as chlorine, bromine, and iodine; hydrogen halides 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 halides such as phosphorus trichloride, phosphorus pentachloride, and phosphorus tribromide; carbon tetrahalides such as carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide; and alkylsilyl halides. Halides, such as tetramethylchlorosilane, tetramethylbromosilane, tetramethyliodosilane, triethylchlorosilane, triethylbromosilane, triethyliodosilane, triisopropylchlorosilane, triisopropylbromosilane, triisopropyliodosilane, tert-butyldimethylchlorosilane, tert-butyldimethylbromosilane, and tert-butyldimethyliodosilane; oxalyl halides, such as oxalyl chloride, oxalyl bromide, and oxalyl iodide; and N-halosuccinimide compounds, such as N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Methanesulfonyl halides, benzenesulfonyl halides, and p-toluenesulfonyl halides, especially methanesulfonyl halides, are preferred for the suppression of side reactions.

[0151] Halogenating agents can be used alone or in combination if necessary. Halogenating agents can be commercially available.

[0152] The amount of halogenating agent is preferably 0.8 to 5.0 mol, more preferably 1.0 to 2.5 mol, relative to each mol of 6-hydroxy-3-hexenyl alkoxymethyl ether compound (10).

[0153] If necessary, a base can be added during the halogenation reaction.

[0154] Examples of bases 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, dimethylpyridine, 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 trimethylstyrylphosphine.

[0155] When the halogenating agent is a methanesulfonyl halide, benzenesulfonyl halide, or p-toluenesulfonyl halide, the base is preferably an amine, more preferably a pyridine, such as pyridine, dimethylpyridine, or 4-dimethylaminopyridine.

[0156] Alkali can be used alone or in combination if necessary. Alkali can be commercially available.

[0157] Considering yield and / or economy, the amount of base is preferably 0 to 8.0 mol, more preferably 0 to 3.0 mol, relative to each mol of 6-hydroxy-3-hexenylalkoxymethyl ether compound (10).

[0158] If necessary, metal salts can be added during the halogenation reaction.

[0159] Examples of metal salts 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.

[0160] Metal salts can be used alone or in combination if necessary. Metal salts are commercially available.

[0161] Considering reactivity, the amount of metal salt is preferably 0 to 30.0 mol, more preferably 0 to 5.0 mol, relative to each mol of 6-hydroxy-3-hexenylalkoxymethyl ether compound (10).

[0162] Although metal salts increase the concentration of halide ions in the reaction system, thereby improving reactivity, it is preferable not to add metal salts considering economic and / or environmental protection factors.

[0163] If necessary, a solvent can be added to the halogenation reaction.

[0164] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); nitriles, such as acetonitrile and propionitrile; and esters, such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile are preferred. For safety reasons, γ-butyrolactone and acetonitrile are particularly preferred.

[0165] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0166] The amount of solvent used for the halogenation reaction is preferably 0 to 3,000 g, more preferably 0 to 800 g, relative to each mol of 6-hydroxy-3-hexenyl alkoxymethyl ether compound (10).

[0167] Solvents can occupy part of the reactor space, reducing the space available for starting materials and thus decreasing productivity. Therefore, the reaction can be carried out without solvent or with alkali as the solvent.

[0168] The reaction temperature for halogenation varies depending on the halogenating agent used, and is preferably 5 to 180°C, taking into account reactivity.

[0169] The reaction time for halogenation varies depending on the halogenating agent and / or the scale of the reaction, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0170] The following will explain the 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0171] R in general formula (11) 1 As defined in general formula (1).

[0172] Specific examples of 6-halo-3-hexenyl alkoxymethyl ether compounds (11) include 6-halo-3-hexenyl methoxymethyl ether, 6-halo-3-hexenyl ethoxymethyl ether, 6-halo-3-hexenyl propoxymethyl ether, 6-halo-3-hexenyl butoxymethyl ether, 6-halo-3-hexenyl pentooxymethyl ether, 6-halo-3-hexenyl hexoxymethyl ether, 6-halo-3-hexenyl heptaoxymethyl ether, 6-halo-3-hexenyl octoxymethyl ether, 6-halo-3-hexenyl nonoxymethyl ether, 6-halo-3-hexenyl decaoxymethyl ether and 6-halo-3-hexenyl benzyloxymethyl ether.

[0173] The 6-halo-3-hexenyl alkoxymethyl ether compound (11) is converted into the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12), and then coupled with the dihaloalkane compound (13) to obtain the haloalkenyl alkoxymethyl ether compound (1) with an increased number of carbon atoms.

[0174] An example of a method for synthesizing the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) involves reacting a 6-halo-3-hexenyl alkoxymethyl ether compound (11) with magnesium in a solvent to give the Grignard reagent 6-(alkoxymethoxy)-3-hexenyl magnesium halide compound (12: M = MgZ), as shown in the following chemical reaction formula. This process is referred to below as “conversion with magnesium”.

[0175]

[0176] Considering the completion of the reaction, the amount of magnesium used for conversion with magnesium is preferably 1.0 to 2.0 g atoms relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0177] Examples of solvents used for magnesium conversion include ethers such as tetrahydrofuran, diethyl ether, and 4-methyltetrahydropyran; and hydrocarbons such as toluene, xylene, and hexane. Ethers, particularly tetrahydrofuran, are preferred, considering the reaction rate of Grignard reagent formation.

[0178] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0179] Considering reactivity, the amount of solvent used is preferably 50 to 5,000 g, more preferably 100 to 3,000 g, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0180] The reaction temperature for magnesium conversion varies depending on the solvent used, and considering reactivity, it is preferably 0 to 120°C.

[0181] The reaction time for magnesium conversion varies depending on the solvent used and / or the scale of the reaction, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0182] Another example of a method for synthesizing the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) involves reacting a 6-halo-3-hexenyl alkoxymethyl ether compound (11) in a solvent with an organolithium reagent to give a 6-(alkoxymethoxy)-3-hexenyl lithium compound (12: M = Li), as shown in the following chemical reaction formula. (This process is hereinafter referred to as "conversion with organolithium reagent")

[0183]

[0184] 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. Methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium are preferred for their availability.

[0185] Considering reactivity, the amount of organolithium reagent used is preferably 1.0 to 4.0 mol, more preferably 1.0 to 2.0 mol, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0186] Examples of solvents used in conversions 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, and hexane are preferred due to their reactivity.

[0187] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0188] Considering reactivity, the amount of solvent used is preferably 50 to 5,000 g, more preferably 100 to 3,000 g, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0189] The reaction temperature for conversion with organolithium reagents varies depending on the solvent used, and considering reactivity, it is preferably -78 to 25°C.

[0190] The reaction time for conversion with organolithium reagents varies depending on the solvent used and / or the scale of the reaction, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0191] The nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) will be explained below.

[0192] R in general formula (12) 1 As defined in general formula (1).

[0193] M represents Li or MgZ, where Z represents a halogen atom or 6-(alkoxymethoxy)-3-hexenyl. Examples of halogen atoms Z include chlorine, bromine, and iodine atoms.

[0194] Examples of nucleophilic 6-(alkoxymethoxy)-3-hexenyl compounds (12) include (3E)-6-(alkoxymethoxy)-3-hexenyl compounds of the following general formula (12-E), (3Z)-6-(alkoxymethoxy)-3-hexenyl compounds of the following general formula (12-Z), and mixtures thereof.

[0195]

[0196] Specific examples of nucleophilic (3E)-6-(alkoxymethoxy)-3-hexenyl compounds (12-E) include the following compounds:

[0197] (3E)-6-(alkoxymethoxy)-3-hexenyl lithium compounds, such as (3E)-6-(methoxymethoxy)-3-hexenyl lithium, (3E)-6-(ethoxymethoxy)-3-hexenyl lithium, (3E)-6-(propoxymethoxy)-3-hexenyl lithium, (3E)-6-(butoxymethoxy)-3-hexenyl lithium, (3E)-6-(pentoxymethoxy)-3-hexenyl lithium, (3E)-6-(hexoxymethoxy)-3-hexenyl lithium, (3E)-6-(heptoxymethoxy)-3-hexenyl lithium, (3E)-6-(octoxymethoxy)-3-hexenyl lithium, (3E)-6-(nonoxymethoxy)-3-hexenyl lithium and (3E)-6-(decoxymethoxy)-3-hexenyl lithium;

[0198] (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium chloride compounds, such as (3E)-6-(methoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(ethoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(propoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(butoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(pentoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(hexoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(heptoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(octoxymethoxy)-3-hexenyl magnesium chloride, (3E)-6-(nonoxymethoxy)-3-hexenyl magnesium chloride and (3E)-6-(decoxymethoxy)-3-hexenyl magnesium chloride;

[0199] (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium bromide compounds, such as (3E)-6-(methoxymethoxy)-3-hexenyl magnesium bromide, (3E)-6-(ethoxymethoxy)-3-hexenyl magnesium bromide, (3E)-6-(propoxymethoxy)-3-hexenyl magnesium bromide, (3E)-6-(butoxymethoxy)-3-hexenyl magnesium bromide, (3E)-6-(pentoxy) Magnesium bromide of (3E)-6-(hexyloxymethoxy)-3-hexenyl, magnesium bromide of (3E)-6-(heptyloxymethoxy)-3-hexenyl, magnesium bromide of (3E)-6-(octyloxymethoxy)-3-hexenyl, magnesium bromide of (3E)-6-(nonoxymethoxy)-3-hexenyl and magnesium bromide of (3E)-6-(decyloxymethoxy)-3-hexenyl; and

[0200] (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium iodide compounds, such as (3E)-6-(methoxymethoxy)-3-hexenyl magnesium iodide, (3E)-6-(ethoxymethoxy)-3-hexenyl magnesium iodide, (3E)-6-(propoxymethoxy)-3-hexenyl magnesium iodide, (3E)-6-(butoxymethoxy)-3-hexenyl magnesium iodide, (3E)-6-(pentoxymethoxy)-3-hexenyl magnesium iodide, and (3E)-6-(pentoxymethoxy)-3-hexenyl magnesium iodide. Magnesium iodide of (3E)-6-(hexyloxymethoxy)-3-hexenyl, magnesium iodide of (3E)-6-(heptyloxymethoxy)-3-hexenyl, magnesium iodide of (3E)-6-(octyloxymethoxy)-3-hexenyl, magnesium iodide of (3E)-6-(nonoxymethoxy)-3-hexenyl and magnesium iodide of (3E)-6-(decyloxymethoxy)-3-hexenyl.

[0201] Among these, considering availability, (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium halide compounds are preferred, such as (3E)-6-(alkoxymethoxy)-3-hexenyl magnesium chloride compounds.

[0202] Specific examples of nucleophilic (3Z)-6-(alkoxymethoxy)-3-hexenyl compounds (12-Z) include the following compounds:

[0203] (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-(pentoxymethoxy)-3-hexenyl lithium, (3Z)-6-(hexoxymethoxy)-3-hexenyl lithium, (3Z)-6-(heptoxymethoxy)-3-hexenyl lithium, (3Z)-6-(octoxymethoxy)-3-hexenyl lithium, (3Z)-6-(nonoxymethoxy)-3-hexenyl lithium and (3Z)-6-(decoxymethoxy)-3-hexenyl lithium;

[0204] (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium chloride compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(ethoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(propoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(butoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(pentoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(hexoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(heptoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(octoxymethoxy)-3-hexenyl magnesium chloride, (3Z)-6-(nonoxymethoxy)-3-hexenyl magnesium chloride and (3Z)-6-(decoxymethoxy)-3-hexenyl magnesium chloride;

[0205] (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium bromide compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(ethoxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(propoxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(butoxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(pentoxy) (3Z)-6-(hexyloxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(heptyloxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(octyloxymethoxy)-3-hexenyl magnesium bromide, (3Z)-6-(nonoxymethoxy)-3-hexenyl magnesium bromide and (3Z)-6-(decyloxymethoxy)-3-hexenyl magnesium bromide; and

[0206] (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium iodide compounds, such as (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium iodide, (3Z)-6-(ethoxymethoxy)-3-hexenyl magnesium iodide, (3Z)-6-(propoxymethoxy)-3-hexenyl magnesium iodide, (3Z)-6-(butoxymethoxy)-3-hexenyl magnesium iodide, (3Z)-6-(pentoxymethoxy)-3-hexenyl magnesium iodide, etc. Magnesium iodide of (3Z)-6-(hexyloxymethoxy)-3-hexenyl, magnesium iodide of (3Z)-6-(heptyloxymethoxy)-3-hexenyl, magnesium iodide of (3Z)-6-(octyloxymethoxy)-3-hexenyl, magnesium iodide of (3Z)-6-(nonoxymethoxy)-3-hexenyl and magnesium iodide of (3Z)-6-(decyloxymethoxy)-3-hexenyl.

[0207] Among these, considering availability, (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium halide compounds are preferred, such as (3Z)-6-(alkoxymethoxy)-3-hexenyl magnesium chloride compounds.

[0208] If necessary, the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) can be used alone or in combination.

[0209] The nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) can be commercially available or can be prepared in-house.

[0210] For economic reasons, the amount of the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) used for the coupling reaction is preferably 0.8 to 3.0 mol, more preferably 1.0 to 1.8 mol, relative to each mol of 6-halo-3-hexenyl alkoxymethyl ether compound (11).

[0211] The following will explain dihaloalkanes (13).

[0212] R in general formula (13) 1 As defined by general formula (1), and X 1 and X 4 Halogen atoms can be represented independently of each other, such as fluorine, chlorine, bromine, or iodine atoms.

[0213] In general formula (13), b represents an integer from 3 to 12, preferably from 4 to 8.

[0214] The haloalkenyl alkoxymethyl ether compound (1) with the desired number of carbon atoms can be prepared by selecting the number of carbon atoms, i.e., b, of the dihaloalkane compound (13).

[0215] Considering reactivity, the amount of dihaloalkanes (13) is preferably 0.7 to 5.0 mol, more preferably 0.7 to 2.5 mol, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0216] Specific examples of dihaloalkanes (13) include the following compounds:

[0217] 1,3-Dihalopropane compounds (b=3) such as 1,3-dichloropropane, 1,3-dibromopropane, 1,3-diiodopropane, 1-bromo-3-chloropropane, 1-chloro-3-iodopropane and 1-bromo-3-iodopropane;

[0218] 1,4-Dihalobutane compounds (b=4) such as 1,4-dichlorobutane, 1,4-dibromobutane, 1,4-diiodobutane, 1-bromo-4-chlorobutane, 1-chloro-4-iodobutane and 1-bromo-4-iodobutane;

[0219] 1,5-Dihalopentane compounds (b=5) such as 1,5-dichloropentane, 1,5-dibromopentane, 1,5-diiodopentane, 1-bromo-5-chloropentane, 1-chloro-5-iodopentane and 1-bromo-5-iodopentane;

[0220] 1,6-Dihalohexane compounds (b=6) such as 1,6-dichlorohexane, 1,6-dibromohexane, 1,6-diiodohexane, 1-bromo-6-chlorohexane, 1-chloro-6-iodohexane and 1-chloro-6-iodohexane;

[0221] 1,7-Dihaloheptane compounds (b=7) such as 1,7-dichloroheptane, 1,7-dibromoheptane, 1,7-diiodoheptane, 1-bromo-7-chloroheptane, 1-chloro-7-iodoheptane and 1-bromo-7-iodoheptane;

[0222] 1,8-Dihalooctane compounds (b=8) such as 1,8-dichlorooctane, 1,8-dibromooctane, 1,8-diiodooctane, 1-bromo-8-chlorooctane, 1-chloro-8-iodooctane and 1-bromo-8-iodooctane;

[0223] 1,9-Dihalononane compounds (b=9) such as 1,9-dichlorononane, 1,9-dibromononane, 1,9-diiodononane, 1-bromo-9-chlorononane, 1-chloro-9-iodononane and 1-bromo-9-iodononane;

[0224] 1,10-Dihalodecane compounds (b=10) such as 1,10-dichlorodecane, 1,10-dibromodecane, 1,10-diiododecane, 1-bromo-10-chlorodecane, 1-chloro-10-iododecane and 1-bromo-10-iododecane;

[0225] 1,11-Dihaloundecane compounds (b=11) such as 1,11-dichloroundecane, 1,11-dibromoundecane, 1,11-diiodoundecane, 1-bromo-11-chloroundecane, 1-chloro-11-iodoundecane, and 1-bromo-11-iodoundecane; and

[0226] 1,12-Dihalododecane compounds (b=12) such as 1,12-dichlorododecane, 1,12-dibromododecane, 1,12-diiododecane, 1-bromo-12-chlorododecane, 1-chloro-12-iododecane and 1-bromo-12-iododecane.

[0227] If necessary, dihaloalkanes (13) may be used alone or in combination. Dihaloalkanes (13) may be commercially available or may be prepared in-house.

[0228] If necessary, a solvent can be added to the coupling reaction. Examples of solvents include common solvents such as ethers like diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons like hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents like trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents like dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); and nitriles like acetonitrile and propionitrile. Considering reactivity, toluene, tetrahydrofuran, 4-methyltetrahydropyran, and acetonitrile, especially tetrahydrofuran, are preferred.

[0229] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0230] Considering reactivity, the amount of solvent used is preferably 30 to 5,000 g, more preferably 50 to 3,000 g, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0231] If necessary, a catalyst may be added to the coupling reaction. Examples of catalysts include copper compounds, including cuprous halides such as cuprous chloride, cuprous bromide, and cuprous iodide, and copper halides such as copper chloride, copper bromide, and copper iodide; iron 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 methoxide (IV), titanium ethoxide (IV), titanium isopropoxide (IV), and titanium oxide (IV); palladium(II) compounds such as dichlorobis(triphenylphosphine)palladium and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium; and nickel compounds such as nickel chloride, dichloro[1,2-bis(diphenylphosphine)ethane]nickel(II) and dichlorobis(triphenylphosphine)nickel(II). When the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12) is a Grignard reagent, i.e., 6-(alkoxymethoxy)-3-hexenyl magnesium halide compound (12:M=MgZ), copper compounds are preferred, especially cuprous halides such as cuprous chloride, cuprous bromide and cuprous iodide, taking into account reactivity and / or economy.

[0232] Catalysts can be used alone or in combination if necessary. Catalysts can be commercially available.

[0233] Considering the reaction rate and ease of post-processing, the amount of catalyst used is preferably 0.0003 to 0.300 mol, more preferably 0.003 to 0.100 mol, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0234] When a catalyst is used in a coupling reaction, a co-catalyst may be added if necessary. Examples of co-catalysts include: trialkyl phosphite compounds having 3 to 9 carbon atoms, such as triethyl phosphite; and arylphosphine compounds having 18 to 44 carbon atoms, such as triphenylphosphine, thimerylphosphine, or 2,2'-bis(diphenylphosphine)-1,1'-binaphthyl (BINAP). Trialkyl phosphite compounds, particularly triethyl phosphite, are preferred for their reactivity.

[0235] If necessary, the co-catalyst can be used alone or in combination. The co-catalyst can be commercially available.

[0236] The amount of co-catalyst is preferably 0.0001 to 1.00 mol relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11), more preferably 0.001 to 0.300 mol.

[0237] When organolithium reagents are used in coupling reactions, N,N,N',N'-tetramethylethylenediamine (TMEDA), hexamethylphosphoric triamine (HMPA), or N,N'-dimethylacrylurea (DMPU) may be added if necessary to improve the reaction rate.

[0238] When a catalyst is used in a coupling reaction, lithium halides may be added if necessary. Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide. Lithium chloride is preferred due to its reactivity.

[0239] Considering reactivity, the amount of lithium halide used in the coupling reaction is preferably 0.0001 to 1.00 mol, more preferably 0.001 to 0.300 mol, relative to each mol of 6-halo-3-hexenylalkoxymethyl ether compound (11).

[0240] The reaction temperature of the coupling reaction varies depending on the nucleophile 6-(alkoxymethoxy)-3-hexenyl compound (12), and is preferably -78 to 80 °C, more preferably -25 to 40 °C, taking into account reactivity.

[0241] The reaction time of the coupling reaction varies depending on the solvent and / or the scale of the reaction, and is preferably 0.5 to 100 hours, taking into account reactivity.

[0242] When a represents an integer from 3 to 14, especially from 3 to 4, the haloalkenylalkoxymethyl ether compound (1) can also be synthesized, for example, according to a chemical reaction formula including at least the following two steps.

[0243]

[0244] First, the alkoxymethyl 3-butynedyl ether compound of general formula (8) is deprotonated in the presence of a base, and then reacted with a dihaloalkane compound (13) to increase the number of carbon atoms, producing a halo-3-alkynylalkoxymethyl ether compound of general formula (14). The carbon-carbon triple bond of the resulting halo-3-alkynylalkoxymethyl ether compound (14) is reduced to give a haloalkenylalkoxymethyl ether compound (1). R in general formula (14) 1 As defined in general formula (1).

[0245] Preparation of halo-3-alken-1-ol compound (2)

[0246] The halo-3-alken-1-ol compound (2) can be prepared by dealkyloxymethylation of the haloalkenyl alkoxymethyl ether (1), as shown in the following chemical reaction formula.

[0247]

[0248] In dealkoxymethylation, haloalkenylalkoxymethyl ether compounds may be used alone or in combination if necessary (1).

[0249] For example, (3E)-10-halo-3-decenylmethoxymethyl ether compound (1:R 1 =H;a=6) and (3Z)-10-halo-3-decenylmethoxymethyl ether compounds (1:R 1 A mixture of (3E)-10-halo-3-decen-1-ol (2:a=6) and (3Z)-10-halo-3-decen-1-ol (2:a=6) can yield a mixture of (3E)-10-halo-3-decen-1-ol (2:a=6).

[0250] For example, (3E)-11-halo-3-undecenylmethoxymethyl ether compound (1:R 1 =H;a=7) and (3Z)-11-halo-3-undecenylmethoxymethyl ether compounds (1:R 1 A mixture of (3E)-11-halo-3-undecen-1-ol (2:a=7) and (3Z)-11-halo-3-undecen-1-ol (2:a=7) yields a mixture of (3E)-11-halo-3-undecen-1-ol (2:a=7).

[0251] Furthermore, for example, compounds of (3E)-14-halo-3-tetradecenylmethoxymethyl ether (1:R) 1 =H;a=10) and (3Z)-14-halo-3-tetradecenylmethoxymethyl ether compounds (1:R 1 A mixture of (3E)-14-halo-3-tetradecen-1-ol (2:a=10) and (3Z)-14-halo-3-tetradecen-1-ol (2:a=10) was obtained.

[0252] The optimal conditions for dealkoxymethylation are based on R 1 However, it varies. For example, when R 1 When R is phenyl, dealkoxymethylation can be carried out under Birch reducing conditions, wherein sodium is used in liquid ammonia. 1 When the atom is hydrogen or a n-alkyl group such as methyl, dealkoxymethylation can be carried out using an acid or the following alcohol compound (7).

[0253] Examples of acids 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 trimethylsilane iodochloride and titanium tetrachloride. To suppress side reactions, p-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, and hydrobromic acid are preferred, with hydrochloric acid and hydrobromic acid being particularly preferred.

[0254] The acid preferably contains X in the halogenated alkenyl alkoxymethyl ether compound (1) corresponding to the substrate. 1 The halogen atom. For example, when using a chlorinated alkenylalkoxymethyl ether compound as a substrate, hydrochloric acid is preferred. When using a bromine alkenylalkoxymethyl ether compound as a substrate, hydrobromic acid is preferred.

[0255] Acids can be used alone or in combination if necessary. Acids can be commercially available.

[0256] The amount of acid used is preferably 0.0001 to 10.0 mol relative to each mol of haloalkenylalkoxymethyl ether compound (1), more preferably 0.001 to 1.0 mol.

[0257] Alcohol compounds (7) are represented by the following general formula (7):

[0258] R 2 OH (7)

[0259] Considering price or availability, R 2 This refers to a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 6 carbon atoms. Examples of monovalent hydrocarbon groups include straight-chain saturated hydrocarbon groups such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl; branched-chain saturated hydrocarbon groups such as isopropyl, 2-isobutyl, and 2-methylbutyl; straight-chain unsaturated hydrocarbon groups such as 2-propenyl; branched-chain unsaturated hydrocarbon groups such as 2-methyl-2-propenyl; cyclic saturated hydrocarbon groups such as cyclopropyl; and their isomers. Some of the hydrogen atoms in the hydrocarbon group may be replaced by methyl, ethyl, or hydroxyl groups.

[0260] For ease of operation, the monovalent hydrocarbon group is preferably methyl, ethyl, n-propyl, or n-butyl.

[0261] Examples of alcohol compounds (7) 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-undecylol, n-decithinol, n-tetradecylol, 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. Methanol and ethanol are preferred, with methanol being particularly preferred, considering their reactivity.

[0262] Alcohol compounds may be used alone or in combination if necessary (7).

[0263] The alcohol compound (7) may be commercially available.

[0264] Considering reactivity, the amount of alcohol compound (7) used is preferably 1 to 1,000 mol, more preferably 1 to 100 mol, relative to each mol of haloalkenylalkoxymethyl ether compound (1).

[0265] If necessary, solvents other than alcohol compounds (7) can be used in dealkoxymethylation.

[0266] Examples of solvents include common solvents such as ethers such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents such as dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); nitriles such as acetonitrile and propionitrile; and esters such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate.

[0267] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0268] The amount of solvent used for dealkoxymethylation is preferably 0 to 2,000 g, more preferably 0 to 500 g, relative to each mol of haloalkenylalkoxymethyl ether compound (1).

[0269] Solvents occupy space in the reactor, reducing the space available for starting materials and consequently decreasing productivity. Therefore, dealkoxymethylation can be performed without solvents.

[0270] The reaction temperature for dealkoxymethylation varies depending on the haloalkenylalkoxymethyl ether compound (1) used, and is preferably 5 to 180 °C, taking into account reactivity.

[0271] The reaction time for dealkoxymethylation varies depending on the haloalkenylalkoxymethyl ether compound (1) and / or the reaction scale, and is preferably 1 to 100 hours, taking into account reactivity.

[0272] In dealkoxymethylation, if necessary, alkoxymethoxymethane, which is a byproduct, can be distilled off from the reaction system, thereby shifting the equilibrium toward the product side and reducing the reaction time.

[0273] The following will explain the halo-3-alken-1-ol compound (2).

[0274] X in general formula (2) 1 a is defined by general formula (1).

[0275] Specific examples of halo-3-alken-1-ol compounds (2) include the following compounds:

[0276] 7-Halo-3-hepten-1-ol compounds (a=3) such as (3Z)-7-chloro-3-hepten-1-ol, (3Z)-7-bromo-3-hepten-1-ol, (3Z)-7-iodo-3-hepten-1-ol, (3E)-7-chloro-3-hepten-1-ol, (3E)-7-bromo-3-hepten-1-ol and (3E)-7-iodo-3-hepten-1-ol;

[0277] 8-Halo-3-octen-1-ol compounds (a=4) such as (3Z)-8-chloro-3-octen-1-ol, (3Z)-8-bromo-3-octen-1-ol, (3Z)-8-iodo-3-octen-1-ol, (3E)-8-chloro-3-octen-1-ol, (3E)-8-bromo-3-octen-1-ol and (3E)-8-iodo-3-octen-1-ol;

[0278] 9-Halo-3-nonen-1-ol compounds (a=5) such as (3Z)-9-chloro-3-nonen-1-ol, (3Z)-9-bromo-3-nonen-1-ol, (3Z)-9-iodo-3-nonen-1-ol, (3E)-9-chloro-3-nonen-1-ol, (3E)-9-bromo-3-nonen-1-ol and (3E)-9-iodo-3-nonen-1-ol;

[0279] 10-Halo-3-decen-1-ol compounds (a=6) such as (3Z)-10-chloro-3-decen-1-ol, (3Z)-10-bromo-3-decen-1-ol, (3Z)-10-iodo-3-decen-1-ol, (3E)-10-chloro-3-decen-1-ol, (3E)-10-bromo-3-decen-1-ol and (3E)-10-iodo-3-decen-1-ol;

[0280] 11-Halo-3-undecen-1-ol compounds (a=7) such as (3Z)-11-chloro-3-undecen-1-ol, (3Z)-11-bromo-3-undecen-1-ol, (3Z)-11-iodo-3-undecen-1-ol, (3E)-11-chloro-3-undecen-1-ol, (3E)-11-bromo-3-undecen-1-ol and (3E)-11-iodo-3-undecen-1-ol;

[0281] 12-Halo-3-dodecen-1-ol compounds (a=8) such as (3Z)-12-chloro-3-dodecen-1-ol, (3Z)-12-bromo-3-dodecen-1-ol, (3Z)-12-iodo-3-dodecen-1-ol, (3E)-12-chloro-3-dodecen-1-ol, (3E)-12-bromo-3-dodecen-1-ol and (3E)-12-iodo-3-dodecen-1-ol;

[0282] 13-Halo-3-tetracene-1-ol compounds (a=9) such as (3Z)-13-chloro-3-tetracene-1-ol, (3Z)-13-bromo-3-tetracene-1-ol, (3Z)-13-iodo-3-tetracene-1-ol, (3E)-13-chloro-3-tetracene-1-ol, (3E)-13-bromo-3-tetracene-1-ol and (3E)-13-iodo-3-tetracene-1-ol;

[0283] 14-Halo-3-tetradecen-1-ol compounds (a=10) such as (3Z)-14-chloro-3-tetradecen-1-ol, (3Z)-14-bromo-3-tetradecen-1-ol, (3Z)-14-iodo-3-tetradecen-1-ol, (3E)-14-chloro-3-tetradecen-1-ol, (3E)-14-bromo-3-tetradecen-1-ol and (3E)-14-iodo-3-tetradecen-1-ol;

[0284] 15-Halo-3-pentadecanen-1-ol compounds (a=11) such as (3Z)-15-chloro-3-pentadecanen-1-ol, (3Z)-15-bromo-3-pentadecanen-1-ol, (3Z)-15-iodo-3-pentadecanen-1-ol, (3E)-15-chloro-3-pentadecanen-1-ol, (3E)-15-bromo-3-pentadecanen-1-ol and (3E)-15-iodo-3-pentadecanen-1-ol;

[0285] 16-Halo-3-hexadecen-1-ol compounds (a=12) such as (3Z)-16-chloro-3-hexadecen-1-ol, (3Z)-16-bromo-3-hexadecen-1-ol, (3Z)-16-iodo-3-hexadecen-1-ol, (3E)-16-chloro-3-hexadecen-1-ol, (3E)-16-bromo-3-hexadecen-1-ol and (3E)-16-iodo-3-hexadecen-1-ol;

[0286] 17-Halo-3-heptadecen-1-ol compounds (a=13) such as (3Z)-17-chloro-3-heptadecen-1-ol, (3Z)-17-bromo-3-heptadecen-1-ol, (3Z)-17-iodo-3-heptadecen-1-ol, (3E)-17-chloro-3-heptadecen-1-ol, (3E)-17-bromo-3-heptadecen-1-ol and (3E)-17-iodo-3-heptadecen-1-ol; and

[0287] 18-Halo-3-octadecen-1-ol compounds (a=14) such as (3Z)-18-chloro-3-octadecen-1-ol, (3Z)-18-bromo-3-octadecen-1-ol, (3Z)-18-iodo-3-octadecen-1-ol, (3E)-18-chloro-3-octadecen-1-ol, (3E)-18-bromo-3-octadecen-1-ol and (3E)-18-iodo-3-octadecen-1-ol.

[0288] Preparation of hydroxyl-chain alkenyl acetate compound (3)

[0289] Hydroxy-chain alkenyl acetate compound (3) can be prepared by acetoxylation of halo-3-chain alken-1-ol compound (2), as shown in the following chemical reaction formula.

[0290]

[0291] In acetoxylation, halo-3-alken-1-ol compounds may be used alone or in combination if necessary (2).

[0292] For example, a mixture of (3Z)-10-halo-3-decen-1-ol compound (2:a=6) and (3E)-10-halo-3-decen-1-ol compound (2:a=6) yields a mixture of (7Z)-10-hydroxy-7-decenyl acetate compound (3:a=6) and (7E)-10-hydroxy-7-decenyl acetate compound (3:a=6).

[0293] For example, a mixture of (3Z)-11-halo-3-undecen-1-ol compound (2:a=7) and (3E)-11-halo-3-undecen-1-ol compound (2:a=7) yields a mixture of (8Z)-11-hydroxy-8-undecenyl acetate compound (3:a=7) and (8E)-11-hydroxy-8-undecenyl acetate compound (3:a=7).

[0294] Furthermore, for example, a mixture of (3Z)-14-halo-3-tetradecen-1-ol compound (2:a=10) and (3E)-14-halo-3-tetradecen-1-ol compound (2:a=10) yields a mixture of (11Z)-14-hydroxy-11-tetradecenyl acetate compound (3:a=10) and (11E)-14-hydroxy-11-tetradecenyl acetate compound (3:a=10).

[0295] Acetoxylation can be performed using acetoxylating agents.

[0296] Examples of acetoxylating agents include, for example, alkali metal acetates such as lithium acetate, sodium acetate, and potassium acetate; and alkaline earth metal acetates such as calcium acetate and magnesium acetate. Alkali metal acetates, such as sodium acetate and potassium acetate, are preferred in terms of reactivity.

[0297] Considering reactivity, the amount of acetoxylating agent is preferably 1.0 to 10.0 mol, more preferably 1.0 to 3.0 mol, relative to each mol of halo-3-alken-1-ol compound (2).

[0298] If necessary, halides can be added during the acetoxylation reaction.

[0299] Examples of halides include iodides such as sodium iodide and potassium iodide; and bromides such as sodium bromide and potassium bromide. Iodides such as sodium iodide and potassium iodide are preferred considering reactivity.

[0300] Halides can be used alone or in combination if necessary. Halides are commercially available.

[0301] The amount of halide used is preferably 0.001 to 10.0 mol relative to each mol of halo-3-alken-1-ol compound (2), more preferably 0.01 to 3.0 mol.

[0302] If necessary, a solvent can be added to the acetoxylation reaction.

[0303] Examples of solvents include common solvents such as ethers like tetrahydrofuran, diethyl ether, butyl ether, 4-methyltetrahydropyran, cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; and polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, γ-butyrolactone, acetonitrile, dichloromethane, and chloroform. Considering reactivity, ethers such as tetrahydrofuran and 4-methyltetrahydropyran are preferred; and polar solvents such as acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, and γ-butyrolactone are preferred, with acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, and γ-butyrolactone being even more preferred.

[0304] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0305] Considering reactivity, the amount of solvent is preferably 50 to 5,000 g, more preferably 200 to 2,000 g, relative to each mol of halo-3-alken-1-ol compound (2).

[0306] The following will explain the hydroxyl-chain alkenyl acetate compound (3).

[0307] In general formula (3), Ac represents acetyl group, and a is defined as in general formula (1).

[0308] Specific examples of hydroxyl-chain alkenyl acetate compounds (3) include the following compounds:

[0309] 7-Hydroxy-4-heptenyl acetate compounds (a=3) such as (4Z)-7-hydroxy-4-heptenyl acetate and (4E)-7-hydroxy-4-heptenyl acetate;

[0310] 8-hydroxy-5-octenyl acetate compounds (a=4) such as (5Z)-8-hydroxy-5-octenyl acetate and (5E)-8-hydroxy-5-octenyl acetate;

[0311] 9-Hydroxy-6-nonenyl acetate compounds (a=5) such as (6Z)-9-hydroxy-6-nonenyl acetate and (6E)-9-hydroxy-6-nonenyl acetate;

[0312] 10-hydroxy-7-decenyl acetate compounds (a=6) such as (7Z)-10-hydroxy-7-decenyl acetate and (7E)-10-hydroxy-7-decenyl acetate;

[0313] 11-Hydroxy-8-undecenyl acetate compounds (a=7) such as (8Z)-11-hydroxy-8-undecenyl acetate and (8E)-11-hydroxy-8-undecenyl acetate;

[0314] 12-hydroxy-9-dodecenyl acetate compounds (a=8) such as (9Z)-12-hydroxy-9-dodecenyl acetate and (9E)-12-hydroxy-9-dodecenyl acetate;

[0315] 13-hydroxy-10-tetratenyl acetate compounds (a=9) such as (10Z)-13-hydroxy-10-tetratenyl acetate and (10E)-13-hydroxy-10-tetratenyl acetate;

[0316] 14-hydroxy-11-tetradecenyl acetate compounds (a=10) such as (11Z)-14-hydroxy-11-tetradecenyl acetate and (11E)-14-hydroxy-11-tetradecenyl acetate;

[0317] 15-hydroxy-12-pentadecanenyl acetate compounds (a=11) such as (12Z)-15-hydroxy-12-pentadecanenyl acetate and (12E)-15-hydroxy-12-pentadecanenyl acetate;

[0318] 16-hydroxy-13-hexadecenyl acetate compounds (a=12) such as (13Z)-16-hydroxy-13-hexadecenyl acetate and (13E)-16-hydroxy-13-hexadecenyl acetate;

[0319] 17-hydroxy-14-heptadecenyl acetate compounds (a=13) such as (14Z)-17-hydroxy-14-heptadecenyl acetate and (14E)-17-hydroxy-14-heptadecenyl acetate; and

[0320] 18-hydroxy-15-octadecenyl acetate compounds (a=14) such as (15Z)-18-hydroxy-15-octadecenyl acetate and (15E)-18-hydroxy-15-octadecenyl acetate.

[0321] Preparation of haloalkenyl acetate compound (4)

[0322] The halogenated alkenyl acetate compound (4) can be prepared by halogenating the hydroxyl alkenyl acetate compound (3) as shown in the following chemical reaction formula.

[0323]

[0324] Hydroxy-chain alkenyl acetate compounds may be used alone or in combination if necessary (3).

[0325] For example, a mixture of (7Z)-10-hydroxy-7-decenyl acetate compound (3:a=6) and (7E)-10-hydroxy-7-decenyl acetate compound (3:a=6) yields a mixture of (7Z)-10-halo-7-decenyl acetate compound (4:a=6) and (7E)-10-halo-7-decenyl acetate compound (4:a=6).

[0326] For example, a mixture of (8Z)-11-hydroxy-8-undecenyl acetate compound (3:a=7) and (8E)-11-hydroxy-8-undecenyl acetate compound (3:a=7) yields a mixture of (8Z)-11-halo-8-undecenyl acetate compound (4:a=7) and (8E)-11-halo-8-undecenyl acetate compound (4:a=7).

[0327] Furthermore, for example, a mixture of (11Z)-14-hydroxy-11-tetradecenyl acetate compound (3:a=10) and (11E)-14-hydroxy-11-tetradecenyl acetate compound (3:a=10) is used to obtain a mixture of (11Z)-14-halo-11-tetradecenyl acetate compound (4:a=10) and (11E)-14-halo-11-tetradecenyl acetate compound (4:a=10).

[0328] Halogenation reactions can be carried out, for example, by toluenesulfonating the hydroxyl group with a p-toluenesulfonyl halide followed by halogenation with a lithium halide compound, or by directly halogenating the hydroxyl group with a halogenating agent.

[0329] Examples of halogenating agents include halogen molecules such as chlorine, bromine, and iodine; hydrogen halides 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 halides such as phosphorus trichloride, phosphorus pentachloride, and phosphorus tribromide; carbon tetrahalides such as carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide; and alkylsilyl compounds. Halides such as tetramethylchlorosilane, tetramethylbromosilane, tetramethyliodosilane, triethylchlorosilane, triethylbromosilane, triethyliodosilane, triisopropylchlorosilane, triisopropylbromosilane, triisopropyliodosilane, tert-butyldimethylchlorosilane, tert-butyldimethylbromosilane, and tert-butyldimethyliodosilane; oxalyl halides such as oxalyl chloride, oxalyl bromide, and oxalyl iodide; and N-halosuccinimide compounds such as N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Methanesulfonyl halides, benzenesulfonyl halides, and p-toluenesulfonyl halides are preferred, especially methanesulfonyl halides, considering the suppression of side reactions.

[0330] Halogenating agents can be used alone or in combination if necessary. Halogenating agents can be commercially available.

[0331] The amount of halogenating agent used is preferably 0.8 to 5.0 mol, more preferably 1.0 to 2.5 mol, relative to each mol of hydroxyl alkenyl acetate compound (3).

[0332] If necessary, a base can be added during the halogenation reaction.

[0333] Examples of bases 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; and amines such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU).

[0334] When the halogenating agent is a methanesulfonyl halide, benzenesulfonyl halide, or p-toluenesulfonyl halide, the base is preferably an amine, more preferably a pyridine such as pyridine, dimethylpyridine, or 4-dimethylaminopyridine.

[0335] Alkali can be used alone or in combination if necessary. Alkali can be commercially available.

[0336] Considering yield and / or economy, the amount of base is preferably 0 to 8.0 mol, more preferably 0 to 3.0 mol, relative to each mol of hydroxyl alkenyl acetate compound (3).

[0337] If necessary, metal salts can be added during the halogenation reaction.

[0338] Examples of metal salts 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.

[0339] Metal salts can be used alone or in combination if necessary. Metal salts are commercially available.

[0340] Considering reactivity, the amount of metal salt is preferably 0 to 30.0 mol, more preferably 0 to 5.0 mol, relative to each mol of hydroxyl alkenyl acetate compound (3).

[0341] Although metal salts increase the concentration of halide ions in the reaction system, thereby improving reactivity, it is preferable not to add metal salts considering economic and / or environmental protection factors.

[0342] If necessary, a solvent can be added to the halogenation reaction.

[0343] Examples of solvents include common solvents such as ethers like diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons like hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents like trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents like dimethyl sulfoxide, γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamine (HMPA); nitriles like acetonitrile and propionitrile; and esters like methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile are preferred. For safety reasons, γ-butyrolactone and acetonitrile are particularly preferred.

[0344] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0345] The amount of solvent used for the halogenation reaction is preferably 0 to 3,000 g, more preferably 0 to 800 g, relative to each mol of hydroxyl alkenyl acetate compound (3).

[0346] Solvents can occupy part of the reactor space, reducing the space available for starting materials and thus decreasing productivity. Therefore, the reaction can be carried out without solvent or with alkali as the solvent.

[0347] The reaction temperature for halogenation varies depending on the halogenating agent used, but is preferably between 5 and 180°C, taking into account reactivity.

[0348] The reaction time for halogenation varies depending on the halogenating agent and / or the scale of the reaction, and is preferably 1 to 100 hours, taking into account reactivity.

[0349] The following will explain the haloalkenyl acetate compound (4).

[0350] X in general formula (4) 2 denoted as a halogen atom, such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. 'a' is defined as in general formula (1), and 'Ac' is defined as in general formula (3).

[0351] Specific examples of haloalkenyl acetate compounds (4) include the following compounds:

[0352] 7-Halo-4-heptenyl acetate compounds (a=3), such as (4Z)-7-chloro-4-heptenyl acetate, (4Z)-7-bromo-4-heptenyl acetate, (4Z)-7-iodo-4-heptenyl acetate, (4E)-7-chloro-4-heptenyl acetate, (4E)-7-bromo-4-heptenyl acetate and (4E)-7-iodo-4-heptenyl acetate;

[0353] 8-Halo-5-octenyl acetate compounds (a=4), such as (5Z)-8-chloro-5-octenyl acetate, (5Z)-8-bromo-5-octenyl acetate, (5Z)-8-iodo-5-octenyl acetate, (5E)-8-chloro-5-octenyl acetate, (5E)-8-bromo-5-octenyl acetate and (5E)-8-iodo-5-octenyl acetate;

[0354] 9-Halo-6-nonenyl acetate compounds (a=5), such as (6Z)-9-chloro-6-nonenyl acetate, (6Z)-9-bromo-6-nonenyl acetate, (6Z)-9-iodo-6-nonenyl acetate, (6E)-9-chloro-6-nonenyl acetate, (6E)-9-bromo-6-nonenyl acetate and (6E)-9-iodo-6-nonenyl acetate;

[0355] 10-Halo-7-decenyl acetate compounds (a=6), such as (7Z)-10-chloro-7-decenyl acetate, (7Z)-10-bromo-7-decenyl acetate, (7Z)-10-iodo-7-decenyl acetate, (7E)-10-chloro-7-decenyl acetate, (7E)-10-bromo-7-decenyl acetate and (7E)-10-iodo-7-decenyl acetate;

[0356] 11-Halo-8-undecenyl acetate compounds (a=7), such as (8Z)-11-chloro-8-undecenyl acetate, (8Z)-11-bromo-8-undecenyl acetate, (8Z)-11-iodo-8-undecenyl acetate, (8E)-11-chloro-8-undecenyl acetate, (8E)-11-bromo-8-undecenyl acetate and (8E)-11-iodo-8-undecenyl acetate;

[0357] 12-Halo-9-dodecenyl acetate compounds (a=8), such as (9Z)-12-chloro-9-dodecenyl acetate, (9Z)-12-bromo-9-dodecenyl acetate, (9Z)-12-iodo-9-dodecenyl acetate, (9E)-12-chloro-9-dodecenyl acetate, (9E)-12-bromo-9-dodecenyl acetate and (9E)-12-iodo-9-dodecenyl acetate;

[0358] 13-Halo-10-tetratenyl acetate compounds (a=9), such as (10Z)-13-chloro-10-tetratenyl acetate, (10Z)-13-bromo-10-tetratenyl acetate, (10Z)-13-iodo-10-tetratenyl acetate, (10E)-13-chloro-10-tetratenyl acetate, (10E)-13-bromo-10-tetratenyl acetate and (10E)-13-iodo-10-tetratenyl acetate;

[0359] 14-Halo-11-tetradecenyl acetate compounds (a=10), such as (11Z)-14-chloro-11-tetradecenyl acetate, (11Z)-14-bromo-11-tetradecenyl acetate, (11Z)-14-iodo-11-tetradecenyl acetate, (11E)-14-chloro-11-tetradecenyl acetate, (11E)-14-bromo-11-tetradecenyl acetate and (11E)-14-iodo-11-tetradecenyl acetate;

[0360] 15-Halo-12-pentadecanenyl acetate compounds (a=11), such as (12Z)-15-chloro-12-pentadecanenyl acetate, (12Z)-15-bromo-12-pentadecanenyl acetate, (12Z)-15-iodo-12-pentadecanenyl acetate, (12E)-15-chloro-12-pentadecanenyl acetate, (12E)-15-bromo-12-pentadecanenyl acetate and (12E)-15-iodo-12-pentadecanenyl acetate;

[0361] 16-Halo-13-hexadecenyl acetate compounds (a=12), such as (13Z)-16-chloro-13-hexadecenyl acetate, (13Z)-16-bromo-13-hexadecenyl acetate, (13Z)-16-iodo-13-hexadecenyl acetate, (13E)-16-chloro-13-hexadecenyl acetate, (13E)-16-bromo-13-hexadecenyl acetate and (13E)-16-iodo-13-hexadecenyl acetate;

[0362] 17-Halo-14-heptadecenyl acetate compounds (a=13), such as (14Z)-17-chloro-14-heptadecenyl acetate, (14Z)-17-bromo-14-heptadecenyl acetate, (14Z)-17-iodo-14-heptadecenyl acetate, (14E)-17-chloro-14-heptadecenyl acetate, (14E)-17-bromo-14-heptadecenyl acetate and (14E)-17-iodo-14-heptadecenyl acetate; and

[0363] 18-Halo-15-Octadecanenyl acetate compounds (a=14), such as (15Z)-18-chloro-15-octadecenyl acetate, (15Z)-18-bromo-15-octadecenyl acetate, (15Z)-18-iodo-15-octadecenyl acetate, (15E)-18-chloro-15-octadecenyl acetate, (15E)-18-bromo-15-octadecenyl acetate and (15E)-18-iodo-15-octadecenyl acetate.

[0364] Preparation of terminally conjugated diene-1-yl acetate compound (5)

[0365] The terminally conjugated diene-1-yl acetate compound (5) can be prepared by eliminating the halo-chain alkenyl acetate compound (4) in the presence of a base, as shown in the following chemical reaction formula.

[0366]

[0367] Used to eliminate the elimination group X 2 Examples of bases that can participate in elimination reactions include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-amyloxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amyloxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-amyloxide; and organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride, and sodium dimethyl sulfoxide. Sodium acetylene, sodium acetylene, and potassium acetylene; metal amines, such as sodium amine, lithium amine, lithium diisopropylamine, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium dicyclohexylamine; metal hydride reagents, such as sodium hydride, potassium hydride, and calcium hydride; and amines, such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU).

[0368] Considering the suppression of side reactions and the better yield of the terminally conjugated diene-1-yl acetate compound (5), the preferred bases are N,N-diisopropylethylamine, pyridine, and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0369] Alkali can be used alone or in combination if necessary. Alkali can be commercially available.

[0370] Considering yield and / or economy, the amount of base is preferably 0.8 to 10.0 mol, more preferably 1.0 to 5.0 mol, relative to each mol of haloalkenyl acetate compound (4).

[0371] Solvents can be used in elimination reactions if necessary.

[0372] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran, cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and hexamethylphosphoric triamine; nitriles, such as acetonitrile and propionitrile; and esters, such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, ethers such as 4-methyltetrahydropyran and tetrahydrofuran are preferred; aprotic polar solvents such as γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide; and nitriles such as acetonitrile, more preferably γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide and acetonitrile.

[0373] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0374] Bases can be used as solvents without the use of other solvents.

[0375] The solvent amount is preferably 0 to 8,000 g, more preferably 0 to 3,000 g, relative to each mol of the haloalkenyl acetate compound (4).

[0376] The reaction temperature for the elimination reaction varies depending on the base used, and considering reactivity, it is preferably -40 to 140°C, more preferably -20 to 100°C.

[0377] The reaction time for the elimination reaction varies depending on the base used and / or the scale of the reaction, but is preferably 1 to 100 hours, taking into account reactivity.

[0378] The terminally conjugated diene-1-yl acetate compound (5) will be explained below.

[0379] In general formula (5), a is defined as in general formula (1), and Ac is defined as in general formula (3).

[0380] Specific examples of terminally conjugated diene-1-yl acetate compounds (5) include the following compounds:

[0381] 4,6-Heptadien-1-yl acetate compounds (a=3), such as (4Z)-4,6-heptadien-1-yl acetate and (4E)-4,6-heptadien-1-yl acetate;

[0382] 5,7-octadien-1-yl acetate compounds (a=4), such as (5Z)-5,7-octadien-1-yl acetate and (5E)-5,7-octadien-1-yl acetate;

[0383] 6,8-Nonadien-1-yl acetate compounds (a=5), such as (6Z)-6,8-nonadien-1-yl acetate and (6E)-6,8-nonadien-1-yl acetate;

[0384] 7,9-decadien-1-yl acetate compounds (a=6), such as (7Z)-7,9-decadien-1-yl acetate and (7E)-7,9-decadien-1-yl acetate;

[0385] 8,10-Undecadien-1-yl acetate compounds (a=7), such as (8Z)-8,10-undecadien-1-yl acetate and (8E)-8,10-undecadien-1-yl acetate;

[0386] 9,11-dodecadien-1-yl acetate compounds (a=8), such as (9Z)-9,11-dodecadien-1-yl acetate and (9E)-9,11-dodecadien-1-yl acetate;

[0387] 10,12-tetadecadien-1-yl acetate compounds (a=9), such as (10Z)-10,12-dodecadecadien-1-yl acetate and (10E)-10,12-dodecadecadien-1-yl acetate;

[0388] 11,13-Tetradecadien-1-yl acetate compounds (a=10), such as (11Z)-11,13-tetradecadien-1-yl acetate and (11E)-11,13-tetradecadien-1-yl acetate;

[0389] 12,14-pentadecanediene-1-yl acetate compounds (a=11), such as (12Z)-12,14-pentadecanediene-1-yl acetate and (12E)-12,14-pentadecanediene-1-yl acetate;

[0390] 13,15-hexadecadien-1-yl acetate compounds (a=12), such as (13Z)-13,15-hexadecadien-1-yl acetate and (13E)-13,15-hexadecadien-1-yl acetate;

[0391] 14,16-heptadecadien-1-yl acetate compounds (a=13), such as (14Z)-14,16-heptadecadien-1-yl acetate and (14E)-14,16-heptadecadien-1-yl acetate; and

[0392] 15,17-octadecadien-1-yl acetate compounds (a=14), such as (15Z)-15,17-octadecadien-1-yl acetate and (15E)-15,17-octadecadien-1-yl acetate.

[0393] Preparation of terminally conjugated diene-1-ol compounds (6)

[0394] The terminally conjugated dien-1-ol compound (6) can be prepared by deacetylation of the terminally conjugated dien-1-yl acetate compound (5), as shown in the following chemical reaction formula.

[0395]

[0396] Examples of bases used in deacetylation reactions include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-amyloxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amyloxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-amyloxide; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride, sodium dimethylsulfonyl, sodium acetylenide, and potassium acetylenide; and metal amines such as sodium amino, lithium amino, etc. Lithium diisopropylamino, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium dicyclohexylamino; metal hydride reagents, such as sodium hydride, potassium hydride, and calcium hydride; and amines, such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU).

[0397] Deacetylation is carried out in a non-aqueous system using nucleophilic bases, such as metal alkoxides like sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-pentoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-pentoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-pentoxide. Meanwhile, when using weakly nucleophilic bases, such as hydroxides like sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; and amines like triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), water is used in addition to the aforementioned bases for deacetylation.

[0398] Considering reactivity and / or economy, hydroxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide, are preferred as bases.

[0399] Alkali can be used alone or in combination if necessary. Alkali can be commercially available.

[0400] Considering yield and / or economy, the amount of base is preferably 1.0 to 10.0 mol, more preferably 1.0 to 6.0 mol, relative to each mol of terminally conjugated diene-1-yl acetate compound (5).

[0401] If necessary, a solvent can be added during the deacetylation reaction.

[0402] Examples of solvents include common solvents such as alcohols, such as methanol, ethanol, n-propanol, n-butanol, isopropanol, 2-butanol, 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; and ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran, and cyclopentyl ether. Methyl ethers and 1,4-dioxanes; 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, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and hexamethylphosphoric triamine; nitriles such as acetonitrile and propionitrile; and esters such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. The optimal solvent depends on the base used. When metal alkoxides are used as bases, ethers such as tetrahydrofuran are preferred; aprotic polar solvents such as γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide are preferred. When hydroxides are used as bases, alcohols such as methanol and ethanol are preferred.

[0403] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0404] The amount of solvent used in the deacetylation reaction is preferably 0 to 8,000 g, more preferably 0 to 3,000 g, relative to each mol of terminally conjugated diene-1-yl acetate compound (5).

[0405] The deacetylation reaction temperature varies depending on the base used, and is preferably -40 to 140°C, more preferably -20 to 100°C, taking into account reactivity.

[0406] The deacetylation reaction time varies depending on the base used and / or the scale of the reaction, and is preferably 1 to 100 hours, taking into account reactivity.

[0407] Furthermore, the terminally conjugated diene-1-ol compound (6) can be prepared by deacetylation of the haloalkenyl acetate compound (4) in the presence of a base in parallel with an elimination reaction, as shown in the following chemical reaction formula (see Example 12 below).

[0408]

[0409] Examples of bases used in elimination and deacetylation reactions include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-pentoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-pentoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-pentoxide; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride, sodium dimethylsulfonyl, sodium acetylenide, and potassium acetylenide; and metal amines such as sodium amino, amino... Lithium, lithium diisopropylamino, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium dicyclohexylamino; metal hydride reagents, such as sodium hydride, potassium hydride, and calcium hydride; and amines, such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU).

[0410] Elimination reactions and deacetylation are carried out in non-aqueous systems using nucleophilic bases, such as metal alkoxides like sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-pentoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-pentoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-pentoxide. Meanwhile, when using weakly nucleophilic bases, such as hydroxides like sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; and amines like triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, dimethylpyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), in addition to the aforementioned bases, horizontal lines are used for elimination reactions and deacetylation.

[0411] Considering the suppression of side reactions and the better yield of terminally conjugated diene-1-ol compound (5), metal alkoxides, such as sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide, are preferred as bases.

[0412] Alkali can be used alone or in combination if necessary. Alkali can be commercially available.

[0413] Considering yield and / or economy, the amount of base is preferably 0.8 to 15.0 mol, more preferably 1.0 to 8.0 mol, relative to each mol of haloalkenyl acetate compound (4).

[0414] When elimination and deacetylation reactions proceed in parallel, a solvent may be added to both reactions if necessary.

[0415] Examples of solvents include common solvents such as ethers, such as diethyl ether, butyl ether, 4-methyltetrahydropyran, tetrahydrofuran, cyclopentylmethyl ether, and 1,4-dioxane; hydrocarbons, such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents, such as trichloroethylene, dichloromethane, and chloroform; aprotic polar solvents, such as dimethyl sulfoxide, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and hexamethylphosphoric triamine; nitriles, such as acetonitrile and propionitrile; and esters, such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Considering reactivity, ethers such as 4-methyltetrahydropyran and tetrahydrofuran are preferred; aprotic polar solvents such as γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide; and nitriles such as acetonitrile, more preferably tetrahydrofuran, 4-methyltetrahydropyran, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide and acetonitrile.

[0416] Solvents can be used alone or in combination if necessary. Solvents can be commercially available.

[0417] The amount of solvent used for deacetylation is preferably 0 to 8,000 g, more preferably 0 to 3,000 g, relative to each mol of the haloalkenyl acetate compound (4).

[0418] When the elimination reaction and deacetylation reaction proceed in parallel, the reaction temperature varies depending on the base used, preferably -40 to 140°C, more preferably -20 to 100°C, taking into account reactivity.

[0419] When the elimination reaction and deacetylation reaction are carried out in parallel, the reaction time varies depending on the base used and / or the scale of the reaction, and is preferably 1 to 100 hours, taking into account reactivity.

[0420] The terminally conjugated diene-1-ol compound (6) will be explained below.

[0421] In general formula (6), 'a' is defined as in general formula (1).

[0422] Specific examples of terminally conjugated dien-1-ol compounds (6) include the following compounds:

[0423] 4,6-Heptadien-1-ol compounds (a=3), such as (4Z)-4,6-heptadien-1-ol and (4E)-4,6-heptadien-1-ol;

[0424] 5,7-octadien-1-ol compounds (a=4), such as (5Z)-5,7-octadien-1-ol and (5E)-5,7-octadien-1-ol;

[0425] 6,8-Nonadien-1-ol compounds (a=5), such as (6Z)-6,8-nonadien-1-ol and (6E)-6,8-nonadien-1-ol;

[0426] 7,9-decadien-1-ol compounds (a=6), such as (7Z)-7,9-decadien-1-ol and (7E)-7,9-decadien-1-ol;

[0427] 8,10-Undecadien-1-ol compounds (a=7), such as (8Z)-8,10-Undecadien-1-ol and (8E)-8,10-Undecadien-1-ol;

[0428] 9,11-dodecadien-1-ol compounds (a=8), such as (9Z)-9,11-dodecadien-1-ol and (9E)-9,11-dodecadien-1-ol;

[0429] 10,12-Tetracenedien-1-ol compounds (a=9), such as (10Z)-10,12-tetracenedien-1-ol and (10E)-10,12-tetracenedien-1-ol;

[0430] 11,13-Tetradecadien-1-ol compounds (a=10), such as (11Z)-11,13-tetradecadien-1-ol and (11E)-11,13-tetradecadien-1-ol;

[0431] 12,14-pentadecanadien-1-ol compounds (a=11), such as (12Z)-12,14-pentadecanadien-1-ol and (12E)-12,14-pentadecanadien-1-ol;

[0432] 13,15-Hexadecadien-1-ol compounds (a=12), such as (13Z)-13,15-hexadecadien-1-ol and (13E)-13,15-hexadecadien-1-ol;

[0433] 14,16-Heptadecanedien-1-ol compounds (a=13), such as (14Z)-14,16-Heptadecanedien-1-ol and (14E)-14,16-Heptadecanedien-1-ol; and

[0434] 15,17-Octadecadien-1-ol compounds (a=14), such as (15Z)-15,17-Octadecadien-1-ol and (15E)-15,17-Octadecadien-1-ol.

[0435] Example

[0436] The present invention will be described with reference to the following embodiments. It should be noted that the present invention is not limited to or not construed as limited by these embodiments.

[0437] Unless otherwise stated, the term "purity" as used herein refers to the percentage of area obtained by gas chromatography (GC). The term "yield ratio" refers to the ratio of the percentage of area obtained by GC. The term "yield" is calculated based on the percentage of area determined by GC.

[0438] In the examples, reaction monitoring and yield calculation were performed under the following GC conditions.

[0439] GC conditions: GC: GC-2014 capillary gas chromatograph (Shimadzu Corporation); Column: DB-WAX (sp-2331), 0.25μm×0.25mmφ×30m; Carrier gas: He (1.55mL / min); Detector: FID; Column temperature: 150℃, increased at a rate of 5℃ / min, up to 230℃.

[0440] Taking into account the purity (%GC) of the starting materials and products, the yield is calculated according to the following formula.

[0441] Yield (%) = {[(weight of product × % GC) / molecular weight of product] ÷ [(weight of starting material × % GC) / molecular weight of starting material]} × 100

[0442] THF represents tetrahydrofuran, DMAC represents N,N-dimethylacetamide, DMF represents N,N-dimethylformamide, GBL represents γ-butyrolactone, and DBU represents 1,8-diazabicyclo[5.4.0]-7-undecene. t Bu represents a tert-butyl group, and Ph represents a phenyl group.

[0443] Example 1: Preparation of (3Z)-10-bromo-3-decenylmethoxymethyl ether (1:R 1 =H,X 1 =Br; a=6)

[0444]

[0445] Magnesium (26.73 g, 1.1 g atom) and tetrahydrofuran (300.00 g) were placed in a reactor at room temperature and stirred at 60 to 65 °C for 29 minutes. After stirring, (3Z)-6-chloro-3-hexene methoxymethyl ether (11:R) was added dropwise to the reactor at 60 to 75 °C. 1 =H,X 3 =Cl)(184.15g, 1.00mol, purity 97.02%). After the addition was complete, the reaction mixture was stirred at 75 to 80°C for 2 hours to obtain (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R 1=H, M=MgCl).

[0446] Subsequently, cuprous iodide (1.00 g, 0.0053 mol), triethyl phosphite (1.00 g, 0.0060 mol), tetrahydrofuran (389.20 g), and 1,4-dibromobutane (431.84 g, 2.00 mol) were added to another reactor, and then the (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R) obtained above was added dropwise at -5 to 15 °C. 1 =H, M=MgCl). After the addition was complete, the reaction mixture was stirred at 5 to 15 °C for 3.5 hours. After stirring was complete, an aqueous solution of ammonium chloride (ammonium chloride (21.83 g) and water (455.87 g) were added, followed by the addition of acetic acid (102.56 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-10-bromo-3-decenylmethoxymethyl ether (1:R 1 =H,X 1 =Br;a=6)(230.57g, 0.79mol, purity 95.70%, bp=124.1 to 130.0℃ / 0.40kPa(3.0mmHg)), yield 79.03%.

[0447] The following is the prepared (3Z)-10-bromo-3-decenyl methoxymethyl ether (1:R 1 =H,X 1 Spectral data of (Br; a=6).

[0448] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.27-1.46 (6H, m), 1.84 (2H, quin-like, J = 7.3Hz), 2.05 (2H, dt, J = 6.9Hz, 6.9Hz), 2.33 (2H, dt, J = 6.9Hz, 6.9Hz), 3.35 ( 3H,s),3.39(2H,t,J=6.9Hz),3.52(2H,t,J=6.9Hz),4.62(2H,s),5.38(1H,dtt,J=11.1Hz,6.9Hz,1.5Hz),5.46(1H,dtt,J=10.7Hz,6.9Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=27.14,27.87,27.99,28.32,29.31,32.72,33.90,55.10,67.34,96.31,125.66,131.79.

[0449] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 277 (M + -1),247,216,190,176,162,148,123,109,95,81,67,45.

[0450] Infrared absorption spectrum (D-ATR): νmax=2929,2856,1464,1440,1213,1150,1111,1072,1035,919,727.

[0451] Example 2: Preparation of (3Z)-11-chloro-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1 =Cl; a=7)

[0452]

[0453] Magnesium (53.05 g, 2.18 g atom) and tetrahydrofuran (623.70 g) were placed in a reactor at room temperature and stirred at 60-65 °C for 16 minutes. After stirring, (3Z)-6-chloro-3-hexene methoxymethyl ether (11:R) was added dropwise to the reactor at 60-75 °C. 1 =H,X 3 =Cl)(381.66g, 2.08mol, purity 97.33%). After the addition was complete, the reaction mixture was stirred at 75 to 80°C for 2 hours to obtain (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R 1 =H,M=MgCl).

[0454] Subsequently, cuprous iodide (3.96 g, 0.021 mol), triethyl phosphite (8.29 g, 0.050 mol), tetrahydrofuran (207.90 g), and 1-bromo-5-chloropentane (358.64 g, 1.93 mol) were added to another reactor, and then the (3Z)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R) obtained above was added dropwise at -5 to 15 °C. 1 =H,M=MgCl). After the addition was complete, the reaction mixture was stirred at 5 to 15°C for 4 hours. After stirring was complete, an aqueous solution of acetic acid (acetic acid (259.88 g) and water (779.63 g)) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-11-chloro-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1=Cl;a=7)(465.53g, 1.80mol, purity 96.25%, bp=134.1 to 142.2℃ / 0.40kPa(3.0mmHg)), yield 93.19%.

[0455] The following is the prepared (3Z)-11-chloro-3-undecenylmethoxymethyl ether (1:R) 1 =H,X 1 Spectral data of (=Cl; a=7).

[0456] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.26-1.45 (8H, m), 1.75 (2H, quin-like, J = 7.3Hz), 2.04 (2H, dt, J = 6.9Hz, 6.9Hz), 2.33 (2H, dt, J = 6.9Hz, 6 .9Hz),3.35(3H,s),3.50-3.54(4H,m),4.62(2H,s),5.38(1H,dtt,J=10.7Hz,6.9Hz,1.6Hz),5.46(1H,dtt,J=11.1Hz,7.3Hz,1.6Hz); 13 C-NMR (500MHz, CDCl3): δ=26.79,27.23,27.86,28.72,29.01,29.42,32.56,45.08,55.09,67.35,96.30,125.50,131.96.

[0457] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 247 (M + -1),217,186,165,144,118,95,68,45.

[0458] Infrared absorption spectrum (D-ATR): νmax = 2929, 2856, 1465, 1150, 1111, 1073, 1036, 919, 726, 652.

[0459] Example 3: Preparation of (3E)-11-chloro-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1 =Cl; a=7)

[0460]

[0461] Magnesium (25.52 g, 1.05 g atom) and tetrahydrofuran (300.00 g) were placed in a reactor at room temperature and stirred at 60 to 65 °C for 20 minutes. After stirring, (3E)-6-chloro-3-hexene methoxymethyl ether (11:R) was added dropwise to the reactor at 60 to 75 °C. 1 =H,X 3 =Cl)(183.02g, 1.00mol, purity 97.62%). After the addition was complete, the reaction mixture was stirred at 75 to 80°C for 2 hours to obtain (3E)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R 1 =H,M=MgCl).

[0462] Subsequently, cuprous iodide (1.90 g, 0.010 mol), triethyl phosphite (3.99 g, 0.024 mol), tetrahydrofuran (100.00 g), and 1-bromo-5-chloropentane (172.51 g, 0.93 mol) were added to another reactor, and then the (3E)-6-(methoxymethoxy)-3-hexenyl magnesium chloride (12:R) obtained above was added dropwise at -5 to 15 °C. 1 =H,M=MgCl). After the addition was complete, the reaction mixture was stirred at 5 to 15°C for 4 hours. After stirring was complete, an aqueous solution of acetic acid (acetic acid (125.00 g) and water (375.00 g)) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3E)-11-chloro-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1 =Cl;a=7)(224.30g, 0.88mol, purity 98.11%, bp=139.1 to 145.0℃ / 0.40kPa(3.0mmHg)), yield 95.11%.

[0463] The following is the prepared (3E)-11-chloro-3-undecenylmethoxymethyl ether (1:R) 1 =H,X 1 Spectral data of (=Cl; a=7).

[0464] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ = 1.24-1.46 (8H, m), 1.75 (2H, quin-like, J = 6.9Hz), 1.98 (2H, dt, J = 6.9Hz, 6.9Hz), 2.28 (2H, dd t,J=1.1Hz,6.7Hz,6.7Hz),3.35(3H,s),3.52(4H,q-like,J=6.9Hz),4.61(2H,s),5.35-5.44(1H,m),5.45-5.54(1H,m); 13 C-NMR (500MHz, CDCl3): δ=26.79,28.69,28.89,29.24,32.52,32.58,33.01,45.09,55.08,67.61,96.32,126.26,132.55.

[0465] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 247 (M + -1),217,186,158,144,109,95,82,68,45.

[0466] Infrared absorption spectrum (D-ATR): νmax=2928,2856,1465,1443,1150,1111,1072,1041,968,919,726,652.

[0467] Example 4: Preparation of (3Z)-14-chloro-3-tetradecenylmethoxymethyl ether (1:R 1 =H,X 1 =Cl; a=10)

[0468]

[0469] Magnesium (13.37 g, 0.55 g atom) and tetrahydrofuran (150.00 g) were placed in a reactor at room temperature and stirred at 60-65 °C for 39 minutes. After stirring, (3Z)-11-chloro-3-undecenylmethoxymethyl ether (1:R) was added dropwise to the reactor at 60-75 °C. 1 =H,X 1 =Cl; a=7)(130.82g, 0.50mol, purity 95.09%). After the addition was complete, the reaction mixture was stirred at 75 to 80°C for 2 hours to obtain (8Z)-11-(methoxymethoxy)-8-undecenyl magnesium chloride (12:R 1 =H,M=MgCl).

[0470] Subsequently, cuprous iodide (0.95 g, 0.0050 mol), triethyl phosphite (1.99 g, 0.012 mol), tetrahydrofuran (50.00 g), and 1-bromo-3-chloropropane (73.21 g, 0.47 mol) were added to another reactor, and then the (8Z)-11-(methoxymethoxy)-8-undecenyl magnesium chloride (12:R) obtained above was added dropwise at -5 to 15 °C. 1 =H,M=MgCl). After the addition was complete, the reaction mixture was stirred at 5 to 15 °C for 2.5 hours. After stirring, an aqueous solution of ammonium chloride (ammonium chloride (5.27 g) and water (136.06 g)) was added to the reaction mixture, followed by the addition of acetic acid (51.28 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-14-chloro-3-tetradecenylmethoxymethyl ether (1:R 1 =H,X 1 =Cl; a=10)(122.32g, 0.39mol, purity 92.00%, bp=130.0 to 146.1℃ / 0.40kPa(3.0mmHg)), yield 83.20%.

[0471] The following is the prepared (3Z)-14-chloro-3-tetradecenylmethoxymethyl ether (1:R) 1 =H,X 1 Spectral data of (=Cl; a=10).

[0472] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.23-1.37 (12H, m), 1.37-1.45 (2H, m), 1.76 (2H, quin-like, J = 6.9Hz), 2.04 (2H, dt, J = 6.9Hz, 6.9Hz), 2.34 (2H, dt, J = 7.1H z,7.1Hz),3.35(3H,s),3.52(4H,dt,J=6.9Hz,3.1Hz),4.62(2H,s),5.37(1H,dtt,J=11.1Hz,7.3Hz,1.5Hz),5.47(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=26.85,27.31,27.87,28.85,29.22,29.41,29.44,29.46,29.57,32.62,45.13,55.09,67.39,96.31,125.36,132.14.

[0473] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 289 (M + -1),259,228,214,200,186,172,158,110,96,82,68.

[0474] Infrared absorption spectrum (D-ATR): νmax = 2926, 2854, 1465, 1150, 1111, 1036, 920, 724.

[0475] Example 5: Preparation of (3Z)-11-iodo-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1 =I; a=7)

[0476]

[0477] The (3Z)-11-chloro-3-undecenylmethoxymethyl ether (1:R) obtained in Example 2 1 =H,X 1 =Cl;a=7)(10.00g, 0.038mol, purity 95.09%), sodium iodide (28.45g, 0.19mol), and acetone (191.10g) were placed in a reactor at room temperature and stirred at 55 to 60°C for 23 hours. After stirring, water (200.00g) was added to the reaction mixture, followed by hexane (200.00g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was purified by column chromatography (ethyl acetate / n-hexane = 50 / 1) to obtain (3Z)-11-iodo-3-undecenylmethoxymethyl ether (1:R 1 =H,X 1 =I;a=7)(12.05g, 0.032mol, purity 91.23%), yield 84.52%.

[0478] The following is the prepared (3Z)-11-iodo-3-undecenylmethoxymethyl ether (1:R) 1 =H,X 1 Spectral data of (=I; a=7).

[0479] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ = 1.25-1.44 (8H, m), 1.81 (2H, quin-like, J = 7.3Hz), 2.04 (2H, dt, J = 6.9Hz, 6.9Hz), 2.34 (2H, dt, J = 6.9Hz, 6.9Hz), 3.18 ( 2H,t,J=6.9Hz),3.35(3H,s),3.52(2H,t,J=6.9Hz),4.62(2H,s),5.38(1H,dtt,J=10.7Hz,7.3Hz,1.2Hz),5.46(1H,dtt,J=11.1Hz,7.3Hz,1.6Hz); 13 C-NMR (500MHz, CDCl3): δ=7.19,27.23,27.89,28.38,28.98,29.43,30.41,33.49,55.11,67.38,96.32,125.52,131.96.

[0480] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 339 (M + -1), 309, 278, 252, 196, 180, 95, 69, 45.

[0481] Infrared absorption spectrum (D-ATR): νmax = 2927, 2854, 1464, 1150, 1111, 1035, 919, 722.

[0482] Example 6: Preparation of (3Z)-11-chloro-3-undecenylbutoxymethyl ether (1:R 1 =CH3CH2CH2,X 1 =Cl; a=7)

[0483]

[0484] Zinc chloride (0.038 g, 0.28 mmol) and dibutoxymethane (7.57 g, 0.046 mol, 98.00% purity) were placed in a reactor at room temperature and stirred at 15–25 °C for 12 minutes. After stirring, acetyl chloride (3.30 g, 0.042 mol) was added dropwise at 20–35 °C. After the addition was complete, the reaction mixture was stirred at 35–40 °C for 2 hours to obtain chloromethyl butyl ether.

[0485] Subsequently, (3Z)-11-chloro-3-undecen-1-ol (2:X) was added dropwise to the reactor at 20 to 30°C. 1=Cl;a=7)(6.00 g, 0.028 mol, purity 95.73%) and N,N-diethylaniline (6.27 g, 0.042 mol) were mixed and stirred at 20 to 30 °C for 6 hours. After stirring, a 25% by mass aqueous solution of sodium hydroxide (10.00 g, 0.063 mol as sodium hydroxide) was added to the reaction mixture, followed by the addition of water (15.00 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-11-chloro-3-undecenylbutoxymethyl ether (1:R 1 =CH3CH2CH2,X 1 =Cl; a=7)(7.49g, 0.023mol, purity 89.10%), yield 82.84%.

[0486] The following is the prepared (3Z)-11-chloro-3-undecenylbutoxymethyl ether (1:R) 1 =CH3CH2CH2,X 1 Spectral data of (=Cl; a=7).

[0487] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 0.92 (3H, t, J = 7.3Hz), 1.26-1.46 (10H, m), 1.53-1.60 (2H, m), 1.76 (2H, quin-like, J = 7.3Hz), 2.04 (2H, dt, J = 6.9Hz, 6.9H z),2.33(2H,dt,J=7.1Hz,7.1Hz),3.50-3.55(6H,m),4.66(2H,s),5.38(1 H,dtt,J=11.1Hz,7.3Hz,1.6Hz),5.46(1H,dtt,J)=11.1Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=13.85,19.36,26.81,27.25,27.89,28.74,29.04,29.45,31.79,32.59,45.08,67.33,67.55,95.17,125.57,131.93.

[0488] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 289 (M + -1),217,186,172,158,144,87,57.

[0489] Infrared absorption spectrum (D-ATR): νmax = 2930, 2858, 1464, 1379, 1116, 1074, 1040, 727.

[0490] Example 7: Preparation of (3Z)-11-chloro-3-undecenylbenzyloxymethyl ether (1:R 1 =Ph,X 1 =Cl; a=7)

[0491]

[0492] Sodium hydride (0.90 g, 0.021 mmol, 55% purity), potassium iodide (0.031 g, 0.19 mmol), and tetrahydrofuran (30.00 g) were placed in a reactor at room temperature and stirred at 0 to 5 °C for 10 minutes. After stirring, (3Z)-11-chloro-3-undecen-1-ol (2:X) was added dropwise at 0 to 10 °C. 1 =Cl;a=7)(4.00 g, 0.019 mol, purity 95.73%) and stirred at 45 to 55 °C for 3 hours. Subsequently, water (59.00 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure, and the concentrate was purified by column chromatography (ethyl acetate / n-hexane = 20 / 1) to obtain (3Z)-11-chloro-3-undecenylbenzyloxymethyl ether (1:R 1 =Ph,X 1 =Cl; a=7)(0.78g, 0.0020mol, purity 83.50%), yield 10.72%.

[0493] The following is the prepared (3Z)-11-chloro-3-undecenylbenzyloxymethyl ether (1:R) 1 =Ph,X 1 Spectral data of (=Cl; a=7).

[0494] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ=1.28-1.39(6H,m),1.39-1.47(2H,m),1.73-1.81(2H ,m),2.06(2H,dt,J=6.9Hz,6.9Hz),2.36(2H,q-like,J=6.9Hz),3.53(2H,t,J= 6.9Hz),3.61(2H,t,J=6.9Hz),4.62(2H,s),4.77(2H,s),5.41(1H,dtt,J=10.7 Hz,7.3Hz,1.2Hz),5.49(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz),7.34-7.38(5H,m);13 C-NMR (500MHz, CDCl3): δ=26.80,27.26,27.86,28.74,29.04,29.44,32.57,45.09,67 .58,69.26,94.51,125.52,127.63,127.69,127.85,127.92,128.37,128.40,132.02.

[0495] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 324 (M + ),217,186,137,121,91.

[0496] Infrared absorption spectrum (D-ATR): νmax=2929,2856,1455,1378,1113,1041,1028,735,698,651.

[0497] Example 8: Preparation of (3Z)-10-bromo-3-decen-1-ol (2:X) 1 =Br; a=6)

[0498]

[0499] The (3Z)-10-bromo-3-decenylmethoxymethyl ether (1:R) obtained in Example 1 1 =H,X 1 =Br;a=6)(60.00g, 0.21mol, purity 95.70%), methanol (102.85g, 3.21mol), and 20% by mass hydrobromic acid (21.65g, 0.053mol as hydrogen bromide) were placed in a reactor equipped with a distillation column, and the reaction mixture was heated to 60°C and stirred for 3 hours. After stirring, the internal temperature was raised to 65 to 70°C, and a mixture of dimethoxymethane and methanol, which were generated as byproducts, was distilled off from the distillation column. The reaction mixture was sampled during the reaction process, and when the reaction rate reached 100%, water (300.00g) was added, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-10-bromo-3-decen-1-ol (2:X 1 =Br;a=6)(48.69g, 0.19mol, purity 91.00%, bp=119.0 to 121.1℃ / 0.40kPa(3.0mmHg)), yield 91.57%.

[0500] The following is the prepared (3Z)-10-bromo-3-decen-1-ol (2:X) 1 Spectral data of (Br; a=6).

[0501] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.27-1.47 (6H, m), 1.59 (1H, br.s), 1.84 (2H, quin-like, J = 6.9Hz), 2.06 (2H, dt, J = 6.9Hz, 6.9Hz), 2.32 (2H, dt, J = 6 .9Hz, 6.9Hz), 3.39 (2H, t, J = 6.9Hz), 3.63 (2H), t, J = 6.5Hz), 5.36 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz), 5.53 (1H, dtt, J = 11.1Hz, 7.3Hz, 1.5Hz); 13 C-NMR (500MHz, CDCl3): δ = 27.16, 27.97, 28.32, 29.38, 30.76, 32.70, 33.92, 62.25, 125.22, 133.06.

[0502] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 233 (M + -1),216,190,137,123,109,95,81,67,55,41.

[0503] Infrared absorption spectrum (D-ATR): νmax = 3333, 2930, 2855, 1462, 1437, 1048, 726, 645, 562.

[0504] Example 9: Preparation of (7Z)-10-hydroxy-7-decenyl acetate (3:a=6)

[0505]

[0506] The (3Z)-10-bromo-3-decen-1-ol (2:X) obtained in Example 8 1 =Br;a=6)(29.56 g, 0.11 mol, purity 91.00%), sodium acetate (16.89 g, 0.21 mol), sodium iodide (1.14 g, 0.0076 mol), and DMAC (114.40 g) were placed in a reactor at room temperature and stirred at 125 to 135 °C for 3.5 h. After cooling to 50 to 60 °C, water (150.00 g) was added to the reaction mixture, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate / n-hexane = 5 / 1) to give (7Z)-10-hydroxy-7-decenyl acetate (3:a=6) (19.63 g, 0.086 mol, purity 93.73%), in a yield of 75.06%.

[0507] The following are the spectral data of the prepared (7Z)-10-hydroxy-7-decenyl acetate (3:a=6).

[0508] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.25-1.39 (6H, m), 1.60 (2H, quin-like, J = 6.9Hz), 1.72 (1H, br.s), 2.02 (3H, s), 2.04 (2H, q-like, J = 6.5Hz), 2.30 (2H, q-like,J=6.9Hz),3.61(2H,t,J=6.5Hz),4.03(2H,t,J=6.9Hz),5.35(1H,dtt,J=11.1Hz,7.3Hz,1.5Hz),5.52(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=20.93,25.69,27.15,28.47,28.76,29.42,30.74,62.22,64.52,125.19,133.00,171.23.

[0509] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 196 (M + -18), 124, 107, 95, 81, 67, 54, 43.

[0510] Infrared absorption spectrum (D-ATR): νmax = 3421, 2931, 2857, 1740, 1366, 1242, 1049, 725.

[0511] Example 10: Preparation of (7Z)-10-chloro-7-decenyl acetate (4:X) 2 =Cl; a=6)

[0512]

[0513] The (7Z)-10-hydroxy-7-decenyl acetate (3:a=6) (17.52 g, 0.077 mol, purity 93.73%), pyridine (13.13 g, 0.17 mol), and GBL (55.32 g) obtained in Example 9 were placed in a reactor and stirred at 0 to 10 °C for 26 minutes.

[0514] Subsequently, methanesulfonyl chloride (14.79 g, 0.13 mol) was added dropwise at 0 to 10 °C. After the addition was complete, the temperature was raised to 60 to 65 °C, and the reaction mixture was stirred for 7 hours. After stirring was complete, water (92.22 g) was added, followed by hexane (92.22 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was washed with an aqueous solution of acetic acid (acetic acid (9.22 g) and water (92.22 g)) and then with an aqueous solution of sodium bicarbonate (sodium bicarbonate (4.61 g) and water (92.22 g)). The obtained organic phase was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 5 / 1) to give (7Z)-10-chloro-7-decenyl acetate (4:X). 2 =Cl; a=6)(18.28g, 0.077mol, purity 97.60%), yield 100.00%.

[0515] The following is the prepared (7Z)-10-chloro-7-decenyl acetate (4:X) 2 Spectral data of (=Cl; a=6).

[0516] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.27-1.40 (6H, m), 1.61 (2H, quin-like, J = 6.9Hz), 2.01-2.06 (2H, m), 2.03 (3H, s), 2.50 (2H, q-like, J = 7. 1Hz), 3.49 (2H, t, J = 6.9Hz), 4.04 (2H, t, J = 6.9Hz), 5.36 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz), 5.51 (1H, ddt, J = 10.7Hz, 7.3Hz, 1.5Hz); 13 C-NMR (500MHz, CDCl3): δ = 20.96, 25.75, 27.23, 28.51, 28.79, 29.32, 30.65, 44.17, 64.50, 124.99, 132.97, 171.16.

[0517] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 172 (M + -60), 136, 116, 95, 81, 67, 43.

[0518] Infrared absorption spectrum (D-ATR): νmax = 2932, 2857, 1739, 1366, 1240, 1038, 734.

[0519] Example 11: Preparation of (7Z)-7,9-decadien-1-yl acetate (5:a=6)

[0520]

[0521] The (7Z)-10-chloro-7-decenyl acetate (4:X) obtained in Example 10 2 =Cl;a=6)(4.84g, 0.020mol, purity 97.60%) and DMF(30.00g) were placed in a reactor and stirred at 15 to 25°C for 5 minutes.

[0522] DBU (9.27 g, 0.061 mol) was then added dropwise at 15–25 °C. After the addition was complete, the temperature was raised to 75–85 °C, and the reaction mixture was stirred for 6.5 hours. After stirring was complete, water (100.00 g) was added, followed by hexane (50.00 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 80 / 1) to give (7Z)-7,9-decadien-1-yl acetate (5:a = 6) (3.26 g, 0.016 mol, purity 97.54%), in a yield of 79.82%.

[0523] The following are the spectral data of the prepared (7Z)-7,9-decadien-1-yl acetate (5:a=6).

[0524] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.28-1.44 (6H, m), 1.61 (2H, quin-like, J = 6.9Hz), 2.03 (3H, s), 2.18 (2H, dt, J = 7.3Hz, 7.3Hz), 4.04 (2H, t, J = 6.9Hz), 5.07 (1 H,d,J=9.9Hz),5.17(1H,dd,J=17.0Hz,1.9Hz),5.43(1H,q-like,J=8.1Hz),5.99(1H,dd,J=11.1Hz,11.1Hz),6.62(1H,ddd,J=16.9Hz,10.5Hz,1.2Hz); 13 C-NMR (500MHz, CDCl3): δ=20.95,25.73,27.53,28.51,28.74,29.38,64.51,116.78,129.26,132.20,132.65,171.14.

[0525] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 196 (M + ),136,121,107,93,79,67,54,43.

[0526] Infrared absorption spectrum (D-ATR): νmax = 2932, 2857, 1741, 1366, 1240, 1036, 903, 607.

[0527] Example 12: Preparation of (7Z)-7,9-decadien-1-ol (6:a=6)

[0528]

[0529] Potassium tert-butoxide (13.66 g, 0.12 mol) and tetrahydrofuran (30.44 g) were placed in a reactor and stirred at -5 to 5 °C for 26 minutes.

[0530] Subsequently, (7Z)-10-chloro-7-decenyl acetate (4:X) obtained in Example 10 was added dropwise at 0 to 10°C. 2 =Cl;a=6)(4.84 g, 0.020 mol, purity 97.60%). After the addition was complete, the temperature was raised to 20 to 25 °C, and the reaction mixture was stirred for 5.5 hours. After stirring was complete, water (100.00 g) was added, followed by hexane (70.00 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 20 / 1) to give (7Z)-7,9-decadien-1-ol (6:a=6) (2.27 g, 0.013 mol, purity 87.37%), in a yield of 63.34%.

[0531] The following are the spectral data of the prepared (7Z)-7,9-decadien-1-ol (6:a=6).

[0532] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.29-1.43 (6H, m), 1.55 (2H, quin-like, J = 6.9Hz), 1.66 (1H, br.s), 2.18 (2H, q-like, J = 7.2Hz), 3.62 (2H, t, J = 6.5Hz), 5.07 (1H, d, J=10.0Hz),5.17(1H,dd,J=16.8Hz,1.9Hz),5.44(1H,q-like,J=8.1Hz),5.99(1H,dd,J=11.1Hz,11.1Hz),6.62(1H,dddd,J=16.8Hz,10.5Hz,10.5Hz,1.2Hz); 13C-NMR (500MHz, CDCl3): δ = 25.53, 27.56, 28.91, 29.47, 32.63, 62.86, 116.73, 129.18, 132.23, 132.77.

[0533] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 154 (M + ),136,121,107,93,79,67,54,41.

[0534] Infrared absorption spectrum (D-ATR): νmax=3334,2931,2856,1463,1434,1056,997,902,785,726,656.

[0535] Example 13: Preparation of (7Z)-7,9-decadien-1-ol (6:a=6)

[0536]

[0537] The (7Z)-7,9-decadien-1-yl acetate (5:a=6) (3.00 g, 0.015 mol, purity 97.54%) obtained in Example 11 and methanol (0.45 g) were placed in a reactor and stirred at 20 to 25 °C for 5 minutes.

[0538] Subsequently, a 25% (w / w) aqueous solution of sodium hydroxide (2.53 g, 0.016 mol as sodium hydroxide) was added dropwise at 20–25 °C. After the addition was complete, the temperature was raised to 60–65 °C, and the reaction mixture was stirred for 3 hours. After stirring was complete, water (40.00 g) was added, followed by hexane (40.00 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 20 / 1) to give (7Z)-7,9-decadien-1-ol (6:a = 6) (2.31 g, 0.015 mol, purity 99.55%), in 100.00% yield.

[0539] The polynomial spectra of the prepared (7Z)-7,9-decadien-1-ol (6:a=6) were the same as those obtained in Example 11.

[0540] Example 14: Preparation of (3Z)-14-chloro-3-tetradecenyl-1-ol (2:X) 1 =Cl; a=10)

[0541]

[0542] The (3Z)-14-chloro-3-tetradecenylmethoxymethyl ether (1:R) obtained in Example 41 =H,X 1 =Cl;a=10)(114.44g, 0.36mol, purity 92.00%), methanol (181.00g, 5.65mol) and 20% by mass hydrochloric acid (18.10g, 0.099mol, as hydrogen chloride) were placed in a reactor equipped with a distillation column, and the reaction mixture was heated to 60°C and stirred for 3 hours. After stirring, the internal temperature was raised to 65 to 70°C, and a mixture of dimethoxymethane and methanol generated as byproducts was distilled off from the distillation column. The reaction mixture was sampled during the reaction process, and when the reaction rate reached 100%, water (400.00g) was added, followed by hexane (300.00g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained therefrom was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (3Z)-14-chloro-3-tetradecenyl-1-ol (2:X 1 =Cl; a=10)(91.31g, 0.36mol, purity 97.58%, bp=152.1 to 154.0℃ / 0.40kPa(3.0mmHg)), yield 99.73%.

[0543] The following is the prepared (3Z)-14-chloro-3-tetradecenyl-1-ol (2:X) 1 Spectral data of (=Cl; a=10).

[0544] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ=1.23-1.37(12H,m),1.37-1.45(2H,m),1.55(1H,br.s),1.76(2H,quin-like,J=7.3Hz),2.05(2H,q-like,J=7.1Hz),2.32( 2H,q-like,J=6.9Hz),3.52(2H,t,J=6.9Hz),3.63(2H,t,J=6.5Hz),5.35(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz),5.55(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=26.84,27.32,28.83,29.23,29.39,29.42,29.44,29.64,30.76,32.61,45.14,62.29,124.93,133.45.

[0545] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 245 (M +-1),228,200,186,172,158,144,109,95,82,68,55,41.

[0546] Infrared absorption spectrum (D-ATR): νmax = 3,330, 2,925, 2854, 1465, 1048, 723.

[0547] Example 15: Preparation of (11Z)-14-hydroxy-11-tetradecenyl acetate (3:a=10)

[0548]

[0549] The (3Z)-14-chloro-3-tetradecenyl-1-ol (2:X) obtained in Example 14 1 =Cl;a=10)(70.45 g, 0.28 mol, purity 97.58%), sodium acetate (40.37 g, 0.49 mol), sodium iodide (2.77 g, 0.018 mol), and DMAC (34.92 g) were placed in a reactor at room temperature and stirred at 125 to 135 °C for 5.5 h. After stirring, the reaction mixture was cooled to 50 to 60 °C, and water (171.30 g) was added, followed by phase separation. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (11Z)-14-hydroxy-11-tetradecenyl acetate (3:a=10) (66.20 g, 0.23 mol, purity 93.95%), with a yield of 82.68%.

[0550] The following are the spectral data of the prepared (11Z)-14-hydroxy-11-tetradecenyl acetate (3:a=10).

[0551] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.22-1.37 (14H, m), 1.60 (2H, quin-like, J = 6.9Hz), 1.65 (1H, br.s), 2.03 (3H, s), 2.04 (2H, q-like, J = 7.3Hz), 2.31 (2H, dt,J=6.9Hz,6.9Hz),3.62(2H,t,J=6.5Hz),4.03(2H,t,J=6.9Hz),5.34(1H,dtt,J=10.7Hz,7.3Hz,1.5Hz),5.53(1H,dtt,J=10.7Hz,7.3Hz,1.6Hz); 13C-NMR (500MHz, CDCl3): δ=20.95,25.83,27.30,28.54,29.17,29.20,29.41,29.43,29.62,30.75,62.26,64.62,124.95,133.34,171.24.

[0552] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 252 (M + -18), 180, 166, 152, 138, 124, 110, 96, 82, 67, 43.

[0553] Infrared absorption spectrum (D-ATR): νmax = 3434, 2926, 2854, 1741, 1466, 1366, 1240, 1047, 722.

[0554] Example 16: Preparation of (11Z)-14-chloro-11-tetradecenyl acetate (4:X) 2 =Cl; a=10)

[0555]

[0556] The (11Z)-14-hydroxy-11-tetradecenyl acetate (3:a=10) (16.46 g, 0.057 mol, purity 93.95%) obtained in Example 15, pyridine (8.55 g, 0.11 mol), and GBL (36.02 g) were placed in a reactor and stirred at 0 to 10 °C for 13 minutes.

[0557] Subsequently, methanesulfonyl chloride (9.63 g, 0.084 mol) was added dropwise at 0 to 10 °C. After the addition was complete, the temperature was raised to 60 to 65 °C, and the reaction mixture was stirred for 7 hours. After stirring was complete, water (60.04 g) was added, followed by hexane (60.04 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The obtained organic phase was washed with an aqueous solution of acetic acid (acetic acid (6.00 g) and water (60.04 g)), followed by an aqueous solution of sodium bicarbonate (sodium bicarbonate (3.00 g) and water (60.04 g)). The obtained organic phase was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 5 / 1) to give (11Z)-14-chloro-11-tetradecenyl acetate (4:X). 2 =Cl; a=10)(15.51g, 0.052mol, purity 97.69%), yield 91.71%.

[0558] The following is the prepared (11Z)-14-chloro-11-tetradecenyl acetate (4:X) 2 Spectral data of (=Cl; a=10).

[0559] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.23-1.38 (14H, m), 1.60 (2H, quin-like, J = 6.9Hz), 2.03 (3H, s), 2.03 (2H, q-like, J = 7.0Hz), 2.50 (2H, dt, J = 6. 9Hz, 6.9Hz), 3.49 (2H, t, J = 6.9Hz), 4.04 (2H, t, J = 6.9Hz), 5.36 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz), 5.52 (1H, dtt, J = 10.7Hz, 7.3Hz, 1.5Hz); 13 C-NMR (500MHz, CDCl3): δ=20.97,25.86,27.34,28.56,29.19,29.42,29.45,29.47,30.67,44.20,64.61,124.78,133.24,171.18.

[0560] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 228 (M + -60), 192, 177, 163, 149, 135, 116, 95, 81, 67, 43.

[0561] Infrared absorption spectrum (D-ATR): νmax = 2926, 2854, 1741, 1465, 1365, 1239, 1038, 723.

[0562] Example 17: Preparation of (11Z)-11,13-tetradecadien-1-yl acetate (5:a=10)

[0563]

[0564] The (11Z)-14-chloro-11-tetradecenyl acetate (4:X) obtained in Example 16 2 =Cl;a=10)(5.97g, 0.020mol, purity 97.69%) and DMF (30.00g) were placed in a reactor and stirred at 15 to 25°C for 5 minutes.

[0565] DBU (9.23 g, 0.061 mol) was then added dropwise at 15–25 °C. After the addition was complete, the temperature was raised to 75–85 °C, and the reaction mixture was stirred for 5 hours. After stirring was complete, water (100.00 g) was added, followed by hexane (50.00 g), and then phase separation was performed. The aqueous phase was removed to obtain the organic phase. The organic phase obtained was concentrated under reduced pressure. The residue was subjected to column chromatography (ethyl acetate / n-hexane = 80 / 1) to give (11Z)-11,13-tetradecadien-1-yl acetate (5:a = 10) (4.37 g, 0.017 mol, purity 98.82%), in 84.43% yield.

[0566] The following are the spectral data of the prepared (11Z)-11,13-tetradecadien-1-yl acetate (5:a=10).

[0567] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ = 1.24-1.41 (14H, m), 1.61 (2H, quin-like, J = 6.9Hz), 2.04 (3H, s), 2.17 (2H, ddt, J = 1.5Hz, 7.4Hz, 7.4Hz), 4.04 (2H, t, J = 6.9Hz), 5. 07(1H,d,J=10.4Hz),5.17(1H,dd,J=16.8Hz,1.9Hz),5.44(1H,q-like,J=8.8H z), 5.99 (1H, t, J = 11.1Hz), 6.63 (1H, dddd, J = 16.8Hz, 10.5Hz, 10.5Hz, 1.2Hz); 13 C-NMR (500MHz, CDCl3): δ=20.98,25.87,27.69,28.57,29.15,29.17,29.20,29.41,29.45,29.57,64.62,116.63,129.10,132.31,133.00,171.17.

[0568] Mass spectrometry: EI-mass spectrometry (70 eV): m / z 252 (M + ),192,163,149,135,121,107,95,81,67,55,43.

[0569] Infrared absorption spectrum (D-ATR): νmax = 2926, 2855, 1742, 1365, 1238, 1039, 902, 607.

Claims

1. A method for preparing a terminal conjugated alkadien-1-yl acetate compound of the following general formula (5): wherein a represents an integer of 3 to 14, and Ac represents an acetyl group, the method comprising: dealkoxymethylating a haloalkenylalkoxymethyl ether compound of the following general formula (1): to prepare a halo-3-alken-1-ol compound of the following general formula (2): acetyloxyiating the halo-3-alken-1-ol compound (2) to prepare a hydroxyalkenyl acetate compound of the following general formula (3): wherein a and Ac are defined as above; halogenating the hydroxyalkenyl acetate compound (3) to prepare a haloalkenyl acetate compound of the following general formula (4): and eliminating the haloalkenyl acetate compound (4) in the presence of a base to prepare the terminal conjugated alkadien-1-yl acetate compound (5). CH2=CHCH=CH(CH2) a OAc (5) 2. A method for preparing a terminal conjugated alkadien-1-ol compound of the following general formula (6): wherein a is defined as above, the method comprising: the method for preparing the terminal conjugated alkadien-1-yl acetate compound (5) according to claim 1, and deacetylating the terminal conjugated alkadien-1-yl acetate compound (5) to prepare the terminal conjugated alkadien-1-ol compound (6).

3. The method for preparing the terminal conjugated alkadien-1-ol compound according to claim 2, wherein the elimination reaction and the deacetylation are carried out in parallel in the presence of a base.

4. A haloalkenylalkoxymethyl ether compound of the following general formula (1): R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1) wherein R 1 represents a hydrogen atom, a n-alkyl group having 1 to 9 carbon atoms, or a phenyl group, X 1 represents a halogen atom, and a is as defined above 5. The haloalkenylalkoxymethyl ether compound of the following general formula (1) according to claim 4, wherein a represents an integer of 6 to 10. HOCH2CH2CH=CH(CH2) a X 1 (2) wherein X 1 and a is as defined above; 6. The haloalkenylalkoxymethyl ether compound of the following general formula (1) according to claim 5, wherein a represents an integer of 6, 7 or 10. HOCH2CH2CH=CH(CH2) a OAc (3) ​ ​ X 2 CH2CH2CH=CH(CH2) a OAc (4) wherein X 2 represents a halogen atom, and a and Ac are as defined above; ​ ​ ​ CH2=CHCH=CH(CH2) a OH (6) ​ ​ ​ ​ ​ ​ R 1 CH2OCH2OCH2CH2CH=CH(CH2) a X 1 (1) wherein R 1 represents a hydrogen atom, a n-alkyl group having 1 to 9 carbon atoms, or a phenyl group, X 1 represents a halogen atom, and a represents an integer of 3 to 14. ​ ​

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