Method for producing α-farnesenes and 3-methyl-1,3-butadiene compound having substituent in fourth position and having related structure, and synthetic intermediate compound thereof

Abstract

To provide an efficient method for producing α-farnesenes and their related derivatives, which can avoid problems of synthesizing methods that yield complex mixtures and accompany considerable difficulty in isolation and purification of pure compounds from those mixtures.SOLUTION: A method for producing a 3-methyl-1,3-butadiene compound (A) having a substituent in the fourth position includes at least a step of obtaining a halide compound represented by the following general formula (B) by a reductive removal reaction of an arene sulfonyl group W of a primary allyl sulfone compound represented by the following general formula (D) (where R represents a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally having an unsaturated bond, X represents a halogen atom, and W represents an arene sulfonyl group), and a step of obtaining a 3-methyl-1,3-butadiene compound having a substituent in the fourth position represented by the following general formula (A) by an elimination reaction of hydrogen halide HX of the obtained halide compound represented by the general formula (B).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing α-farnesenes, which are sesquiterpenes useful as fragrances or bioactive substances against insects and the like, and 3-methyl-1,3-butadiene compounds having substituents at the 4-position with related structures, and also to useful synthetic intermediate compounds.

Background Art

[0002] Among the well-known terpene compounds, farnesenes, there are α-type and β-type with different double bond positions. α-Farnesene has four geometric isomers of trisubstituted double bonds present at the 3- and 6-positions, and β-farnesene has two geometric isomers of trisubstituted double bonds present at the 6-position.

[0003]

Chemical Formula

[0004] Among farnesenes, α-farnesene has been identified in many plants such as apples, pears, chrysanthemums ( Chrysanthemum ), perilla ( Perilla ), and chickweeds ( Achillea ). (3E,6E)-α-Farnesene is abundant in the skin of apple fruits (serving as a natural source of this compound) and gives a green apple odor. (3Z,6E)-α-Farnesene is contained in the essential oils of plants such as perilla ( Perilla ) and gardenias ( Gardenia ). α-Farnesene is also contained in extracts of many insects including multiple ants and cotton seed bugs ( Oxycarenus hyalinipennis ), and various biological activities have been reported. For example, the red imported fire ant of the order Hymenoptera ( Solenopsis invictaIt includes trail pheromone of ants, alarm pheromone of termites (Isoptera), aggregation pheromone of Caribbean fruit fly and Mediterranean fruit fly (Diptera), attractant of codling moth (Lepidoptera), etc. In addition, β-farnesene is a component of essential oils of various plants and is known to have alarm pheromone activity against aphids (Hemiptera: Aphididae). These naturally derived and synthetic farnesenes are also used as fragrances (fragrance or flavor) for applications of biological activity to human olfaction.

[0005] α-Farnesenes are characterized by a 4-substituted 3-methyl-1,3-butadiene structure having a substituent at the 4-position shown in the following general formula.

[0006]

Chemical formula

[0007] α-Farnesenes correspond to the case where the substituent R in the above general formula is the (E)- or (Z)-3,7-dimethyl-2,6-octadienyl group. Also, other important related compounds having this characteristic structure are known. As related compounds, for example, the corresponding monoterpenes, α-ocimene and β-ocimene, are known, and these correspond to the cases where the substituent R in the above general formula is the 3-methyl-3-butenyl group and the 3-methyl-2-butenyl group, respectively. There are two geometric isomers of the trisubstituted double bond in α- and β-ocimene, respectively. Ocimenes are found in various plants and fruits, and in nature, they often exist in the form of an isomeric mixture. Both single isomers and mixtures are oily substances with a pleasant smell to humans and are used as fragrances, for example, in perfumes and the like.

[0008] [Chemical formula] [Prior art documents] [Non-patent documents]

[0009] [Non-patent document 1] R.K. Vander Meer et al, Tetrahedron Lett., 1981, 22, 1651 [Non-patent document 2] D.W. Knight et al, J. Chem. Ecol., 1984, 10, 641 [Non-patent document 3] E.F. Anet et al, Aust. J. Chem., 1970, 23, 2101 [Non-patent document 4] G. Brieger et al, J. Org. Chem., 1969, 34, 3789 [Non-patent document 5] H. Yamamoto et al, J. Am. Chem. Soc., 1975, 97, 3252 [Non-patent document 6] E.D.Morgan et al, J.Chem.Soc.Perkin Trans.1, 1985, 399

Non-Patent Document 7

Non-Patent Document 8

Summary of the Invention

Problems to be Solved by the Invention

[0010] For basic research, applied research, and practical use of these farnesenes and their related derivatives, etc., it is necessary to synthesize and manufacture them economically. Although isomers that exist in large quantities in nature may be sold at low cost in some cases, non-natural isomers that do not exist in nature are supplied by synthesis. Also, it is possible to obtain various other isomers by isomerization of natural products, but they usually exist as complex mixtures of isomers and involve great difficulties in isolating specific isomers and improving purity. For example, for basic research such as comparative studies of the activities of isomers and structure-activity relationship studies of derivatives with partially modified structures, etc., it is desired to selectively synthesize isomers such as the position of double bonds and geometric isomers, and the high degree of freedom applicable to the synthesis of derivatives with substituents replaced by others. For applications and practical use such as predicting the occurrence of organisms such as insects using pheromone activity and pest control, and applications to fragrances using fragrance activity for humans, etc., large-scale synthesis is required, and an efficient synthesis suitable for industrial scale-up is desired. In applications and practical use, it is not always necessary to use pure isomers, and in some cases, it may be economically advantageous to use an active mixture of isomers. For such purposes, an efficient manufacturing method for farnesenes and their related derivatives applicable to both basic and applied aspects has been strongly desired.

[0011] Various methods are known as methods for synthesizing α-farnesenes. However, many known methods give complex mixtures, and the isolation and purification of pure compounds from them involve great difficulties. For example, in Non-Patent Document 1, a dehydration reaction of nerolidol gave a mixture of α- and β-farnesene isomers, and the isomers were separated by florisil chromatography. In the syntheses using nerolidol or farnesol as starting materials in Non-Patent Documents 2 and 3, a mixture of farnesene isomers was obtained together with isomeric products including cyclization and triterpenes by polymerization (dimerization), and gas chromatography was used for the isolation of the isomers. Non-Patent Document 2 describes a method of removing by converting to a Diels-Alder adduct with maleic anhydride for isomer separation. The rhodium catalyzed isomerization reaction of β-farnesene in Non-Patent Document 4 also gives a complex mixture. Non-Patent Document 5 reports a synthesis via 3-en-1,2-diol from farnesol. Non-Patent Document 6 reports the synthesis of (Z,E)- and (Z,Z)-farnesenes using the Wittig reaction and separation by silver nitrate-silica gel-column chromatography. Non-Patent Document 7 has a synthesis example by elimination of diphenylphosphinic acid with a base through the formation of a skeleton by Horner-type Wittig and separation of the resulting diastereomers by high performance liquid chromatography (HPLC), and a method of removing the coexisting (E,E)-isomer by converting it to a Diels-Alder adduct with tetracyanoethylene for the synthesis of pure (E,Z)-α-farnesene is described.In addition, Non-Patent Document 8 reports that (E,E)-α-farnesene extracted from apples was photo-isomerized to obtain a mixture of (Z,E)- and (E,E)-α-farnesene, and the (E,E)-isomer was reduced by a method of converting it into the above Diels-Alder adduct to obtain (Z,E)-α-farnesene [(Z,E):(E,E) = 91:9], which was used for disrupting the trail pheromone of red imported fire ants. At this time, it was reported that 115 mg of the (Z,E)-α-farnesene precursor was obtained from 60 kg of apples. However, among these syntheses, in the syntheses using raw materials having a conjugated diene structure that is thermally unstable and unstable in the presence of an acid, or in the syntheses constructing a conjugated diene structure at the intermediate stage in the early stage of synthesis, the stability of the intermediate becomes a major problem in industrial-scale production. In addition, syntheses starting from natural products are limited to specific ones from which the raw materials are available, and are difficult to apply to the synthesis of various derivatives with modified structures. In particular, syntheses starting from natural products such as farnesol in which the carbon framework (the number of carbons and the way they are connected) is already complete cannot be applied to the synthesis of various derivatives with modified structures.

[0012] As described above, there are many problems in the known synthesis methods of α-farnesene, and there has been a strong demand for an efficient production method of α-farnesenes and their related derivatives that can avoid these problems.

Means for Solving the Problems

[0013] As a result of repeated studies in consideration of the above circumstances, a primary allyl sulfone compound described below was designed as a reasonable synthetic intermediate, and it was found that α-farnesene and a 3-methyl-1,3-butadiene compound having a substituent at the 4-position related thereto can be selectively and efficiently produced by a synthetic route applying this, and the present invention was completed. In addition, the production method according to the present invention can be industrially advantageous.

[0014] According to one aspect of the present invention, the following general formula (D)

Chemical formula

Chemical formula

Chemical formula

[0015] According to another aspect of the present invention, the following general formula (D)

Chemical formula

[0016] According to another aspect of the present invention, the following general formula (E)

Chemical formula

Chemical formula

[0017] According to another aspect of the present invention, the following general formula (E)

Chemical formula

[0018] According to another aspect of the present invention, the following general formula (B’)

Chemical formula

Advantages of the Invention

[0019] According to the present invention, a 3-methyl-1,3-butadiene compound having a substituent at the 4-position and having an α-farnesene and related structures can be selectively and efficiently produced.

BEST MODE FOR CARRYING OUT THE INVENTION

[0020] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited thereto.

[0021] In the chemical formulas of intermediates, reagents, and target substances in this specification, when stereoisomers such as enantiomers (enantiomeric isomers) or diastereomers (diastereomeric isomers) may exist structurally, unless otherwise specified, each chemical formula represents all of these isomers in any case. Also, these isomers may be used alone or as a mixture in any ratio. In a mixture of enantiomers, when the enantiomers are present in a ratio of 50:50, it is a racemic mixture, or when either enantiomer is present in an excess ratio, it is a scalemic mixture, and either may be used.

[0022] The present inventors considered the following synthetic plan as a method for producing α-farnesene and the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position related thereto.

[0023] [Chemical formula] [In the formula, the open arrow is a transform in retrosynthetic analysis, R is a linear, branched or cyclic hydrocarbon group which may contain one or more unsaturated bonds, X and Y are each independently a halogen atom, and W represents an arenesulfonyl group.]

[0024] In the above synthetic plan, the one in which the hydrocarbon group R as the substituent at the 4-position is a 3,7-dimethyl-2,6-octadienyl group corresponds to α-farnesene.

[0025] As a key important synthetic intermediate, a primary allyl sulfone compound (D) (a 3-arenesulfonylmethyl-1-halo-3-butene compound having a substituent at the 4-position) was designed. By reductive removal (desulfonation) of the arenesulfonyl group W at the allyl position of the primary allyl sulfone compound (D), a halide compound (B) is obtained, and by elimination of hydrogen halide HX of the halide compound (B), a 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position is obtained. Or, by changing the order of functional group conversion, by elimination of hydrogen halide HX from the primary allyl sulfone compound (D), a primary allyl sulfone diene compound (C) is obtained, and by reductive removal (desulfonation) of the arenesulfonyl group W of the primary allyl sulfone diene compound (C), a 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position is obtained. The primary allyl sulfone compound (D) may be synthesized by allyl rearrangement of the arenesulfonyl group, which is a key reaction, from a secondary allyl sulfone compound (E) (1-halo-4-arenesulfonyl-3-methylenebutane having a substituent at the 4-position). The secondary allyl sulfone compound (E) can be synthesized by alkylation of the anion at the α-position of the sulfone of the allyl sulfone compound (F), and further the allyl sulfone compound (F) can be synthesized from a dihalide compound (G) having an exo-methylene. Many of the intermediates (such as sulfone intermediates having an exo-double bond) in the above synthetic plan are novel compounds and there are no reports of their synthetic examples or reaction examples. However, based on the above synthetic plan, intensive studies were carried out.

[0026] As a result of repeated studies based on the above considerations, the present inventors succeeded in realizing the target reaction and synthesizing an α-farnesene with high efficiency and a 3-methyl-1,3-butadiene compound having a substituent at the 4-position and having a related structure. Hereinafter, embodiments of the present invention will be described in detail step by step.

[0027] <The 3-methyl-1,3-butadiene compound having a substituent at the 4-position, which is the target product of the present invention>

[0028] The α-farnesenes, which are the objects of the present invention, and 3-methyl-1,3-butadiene compounds having a substituent at the 4-position and related structures will be described. The 3-methyl-1,3-butadiene compound having a substituent at the 4-position is represented by the following general formula (A). [Chemical formula] (In the formula, the substituent R is a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and may contain one or more unsaturated bonds. The wavy line represents a bond that does not specify geometric isomerism.) It is represented by.

[0029] The wavy line in the formula is a bond that does not specify geometric isomerism, and the above general formula (A) represents either or both of two geometric isomers, namely E-(A), which is the (E)-isomer, and Z-(A), which is the (Z)-isomer.

[0030] [Chemical formula] (In the formula, R is the same as above.)

[0031] The hydrocarbon group R is a hydrocarbon group having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms, more preferably 5 to 15 carbon atoms, and includes a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, an n-dodecyl group, an n-tridecyl group, an n-tetradecyl group, an n-pentadecyl group, an n-hexadecyl group, an n-heptadecyl group, an n-octadecyl group, an n-nonadecyl group, an n-icosyl group, etc., linear alkyl groups, isopropyl group, isobutyl group, sec-butyl group, tert-butyl group, isopentyl group, branched alkyl groups such as alkyl groups in which 1 to 6 hydrogen atoms of the above linear alkyl groups are substituted with a methyl group or an ethyl group, cyclic alkyl groups containing a cyclic structure such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, benzene, etc. in the structure. Examples of the unsaturated bond contained in the hydrocarbon group R include a double bond and a triple bond, preferably a double bond. The preferred number of unsaturated bonds contained is 1 to 5. For example, R is a 3,7-dimethyl-2,6-octadienyl group, a 3-methyl-2-butenyl group, a 3-methyl-3-butenyl group, a 3-phenyl-2-propenyl group, and the 3,7-dimethyl-2,6-octadienyl group includes at least one of (E)- and (Z)-3,7-dimethyl-2,6-octadienyl groups.

[0032] <Synthesis of starting material allyl sulfone compound (F)>

[0033]

Chemical formula

[0034] The method for synthesizing the allyl sulfone compound (F) which is the starting material of the present invention is not particularly limited. For example, it can be obtained by mixing an arenesulfinate with a dihalide compound (G) having exo-methylene and heating in a solvent to substitute the halogen atom Y at the allyl position with an arenesulfonyl group W.

[0035] [Chemical formula] (wherein, WM 1 is a sulfonating agent, M 1 represents a metal atom. W, X, and Y are the same as above.)

[0036] X and Y of the dihalide compound (G) may be the same or different and are halogen atoms, preferably a chlorine atom, a bromine atom, or an iodine atom, and more preferably a chlorine atom or a bromine atom. X is most preferably a chlorine atom from the viewpoint of stability in subsequent steps. Preferred specific examples of the compound (G) include 4-chloro-2-chloromethyl-1-butene, 2-bromomethyl-4-chloro-1-butene, 4-bromo-2-chloromethyl-1-butene, and 4-bromo-2-bromomethyl-1-butene. Instead of the halogen atoms X and Y, a phosphoryloxy group such as a dimethylphosphoryloxy group, a diethylphosphoryloxy group, or a diphenylphosphoryloxy group, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a nonafluorobutanesulfonyloxy group, a benzenesulfonyloxy group, a p-toluenesulfonyloxy group, or other sulfonyloxy groups, which are pseudo-halogen groups that function as leaving groups in the alkylation of the α-anion (carbon-carbon bond formation reaction) and the de-HX reaction for olefin formation described later, can also be used and are collectively referred to as halogen atoms in this specification (hereinafter the same). W in the allyl sulfone compound (F) is an arenesulfonyl group. The corresponding metal salt of arenesulfinic acid WM used as a reaction reagent 1Since benzenesulfinate and p-toluenesulfinate are commercially available and industrially easy to obtain, as the arylsulfonyl group W, a benzenesulfonyl group and a p-toluenesulfonyl group can be preferably exemplified. As M1, an alkali metal such as sodium, lithium, or potassium, or an alkaline earth metal such as magnesium or barium is preferable. The regioselectivity of this reaction is high, and the halogen atom Y at the allyl position reacts preferentially to the halogen atom X at the homoallyl position, and an allyl sulfone compound (F) can be obtained in good yield. Strictly speaking, W in WM 1 is an arylsulfenyl group Ar―S(=O)-O-, and it is a compound in which the oxygen atom O is bonded to the metal atom M 1 whereas W in the sulfone compound (F) is an arylsulfonyl group Ar―S(=O)2-, and it is a compound in which the sulfur atom S is bonded to the carbon atom C.

[0037] <Alkylation Step from Allyl Sulfone Compound (F) to Secondary Allyl Sulfone Compound (E)>

[0038]

Chemical Formula

[0039] This step is an alkylation reaction at the α-position of the sulfone. The reaction is usually carried out by generating an α-anion of the sulfone compound with a base in a solvent and alkylating the generated anion with an electrophile.

[0040]

Chemical Formula

[0041] The base used for anion generation is not particularly limited as long as it can generate an anion at the α-position of the sulfone compound. Examples include inorganic bases such as sodium hydride, potassium hydride, calcium hydride, sodium amide, potassium amide, sodium hydroxide, and potassium hydroxide; organic bases such as triethylamine, tributylamine, diisopropylethylamine, 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU); alkoxides such as sodium methoxide, sodium ethoxide, lithium tert-butoxide, and potassium tert-butoxide; alkyllithiums such as methyllithium, ethyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium; Grignard reagents such as methylmagnesium halide (including chloride, bromide, iodide, and the same hereinafter), ethylmagnesium halide, and phenylmagnesium halide; alkyl metal compounds such as dimethyldiethylzinc, diethyldiethylzinc, trimethylaluminum, triethylaluminum, and methylaluminum dichloride; metal amides such as lithium diethylamide, lithium diisopropylamide, lithium isopropylcyclohexylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, and halomagnesium hexamethyldisilazide. These can be used alone or in combination. Halide salts such as lithium chloride may be added. Particularly preferred bases are alkyllithiums, Grignard reagents, and metal amides.

[0042] The electrophile RX used for alkylation 1 has a leaving group X that functions to introduce the hydrocarbon group R. 1 X 1It is not particularly limited as long as it functions as a leaving group, and examples thereof include a halogen atom (halo group), a phosphoryloxy group such as a dimethylphosphoryloxy group, a diethylphosphoryloxy group, and a diphenylphosphoryloxy group, a sulfonyloxy group such as a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a nonafluorobutanesulfonyloxy group, a benzenesulfonyloxy group, and a p-toluenesulfonyloxy group. From the viewpoints of economy and availability, a halogen atom is desirable. Among the halogen atoms, a chlorine atom, a bromine atom, and an iodine atom are particularly desirable.

[0043] As the solvent, ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, 4-methyltetrahydropyran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric triamide, either alone or as a mixture of two or more thereof can be mentioned. The reaction temperature can be appropriately selected depending on the type of base used and the reaction conditions, but generally, a temperature from -50°C to the boiling point of the solvent is preferable, and a temperature from -20°C to room temperature (5°C to 35°C, the same hereinafter) is more preferable. The reaction time can be arbitrarily set, but the conversion rate and the isomer ratio can be optimized by monitoring with gas chromatography (GC) or thin-layer chromatography (TLC). Usually, 5 minutes to 240 hours is preferable.

[0044] When the secondary allyl sulfone compound (E) obtained in the above alkylation step or the halogen exchange step described later has sufficient purity and isomer ratio, it may be used in the next step as a crude product, but it can be purified and the isomers can be separated by appropriately selecting from the usual purification methods and isomer separation methods in organic synthesis such as distillation and various chromatographies.

[0045] <Isomerization step by allyl rearrangement of the arenesulfonyl group from the secondary allyl sulfone compound (E) to the primary allyl sulfone compound (D)>

[0046]

Chemical formula

[0047] This isomerization step is an isomerization step from the secondary allyl sulfone compound (E) having an exo-methylene structure to the primary allyl sulfone compound (D) having a thermodynamically more stable trisubstituted double bond. It has been found that this step proceeds in the presence of a transition metal compound, and the synthesis of the important intermediate primary allyl sulfone compound (D) has been realized. The isomerization step usually proceeds by heating the secondary allyl sulfone compound (E) together with the transition metal compound in a solvent.

[0048] As the secondary allyl sulfone compound (E) which is the reaction substrate of this isomerization step, a chloride compound (when X = Cl), a bromide compound (when X = Br), and an iodide compound (when X = I) can be applied. They can be synthesized, for example, in the <halogen exchange step in the intermediate> described later.

[0049] Examples of the transition metal compound used in the isomerization step include transition metal compounds such as nickel, rhodium, palladium, ruthenium, iridium, etc., and particularly palladium compounds are preferred. Specific examples of the palladium compound include zero-valent palladium compounds such as tetrakis(triphenylphosphine)palladium(0), bis(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)dipalladium(0), tris(dibenzylideneacetone)(chloroform)dipalladium(0), bis(tri-tert-butylphosphine)palladium(0), etc.; divalent palladium compounds such as bis(acetylacetonato)palladium(II), dichlorobis(allyl)palladium(II), bis(acetonitrile)dichloropalladium(II), palladium(II) trifluoroacetate, palladium(II) acetate, dichlorobis(tricyclohexylphosphine)palladium(II), dichlorobis(triphenylphosphine)palladium(II), dichlorobis(tri-o-tolylphosphine)palladium(II), dichlorobis[di-t-butyl(p-dimethylaminophenyl)phosphine]palladium(II), 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II), 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II)·dichloromethane, tetrakis(acetonitrile)palladium(II)=tetrafluoroborate, palladium(II) bromide, palladium(II) chloride, dichloro[1,3-bis(diphenylphosphino)propane]palladium(II), dichloro[1,2-bis(diphenylphosphino)ethane]palladium(II), etc. A phosphorus compound may be used as a ligand together with these palladium compounds.Examples of the phosphorus compound used as a ligand include phosphines such as trimethylphosphine, tri-tert-butylphosphine, trioctylphosphine, tricyclohexylphosphine, tri(o-tolyl)phosphine, dimethylphenylphosphine, tri(2-furyl)phosphine, diphenyl-2-pyridylphosphine, tris(hydroxymethyl)phosphine, 1,2-bis(dimethylphosphino)ethane, bis(diphenylphosphino)methane, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,2-bis(dicyclohexylphosphino)ethane, 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, and phosphites such as trimethyl phosphite, triethyl phosphite, and triphenyl phosphite. These transition metal compounds and ligands may be used alone or in any combination. Among the palladium compounds, a zero-valent palladium compound or a combination of a divalent palladium compound and a bidentate phosphine is preferred. An organometallic compound or a metal hydride compound may be used to activate the catalytic activity of the transition metal compound. The amount of the transition metal compound used is 0.000001 to 10 moles, preferably 0.00001 to 0.1 mole, per mole of the secondary allyl sulfone compound (E). The phosphorus compound used as a ligand is 0.1 to 1000 moles, preferably 1 to 100 moles, per mole of the palladium compound.Examples of the solvent used in the isomerization step include ethers such as diethyl ether, dibutyl ether, t-butyl methyl ether, cyclopentyl methyl ether, tetrahydrofuran, 4-methyltetrahydropyran, 1,4-dioxane; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, tert-butyl alcohol, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, cumene; carboxylic acids such as formic acid, acetic acid, propionic acid, benzoic acid; nitriles such as acetonitrile, propionitrile; ketones such as acetone, 2-butanone; esters such as ethyl acetate, butyl acetate; aprotic polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide, N,N-dimethylpropionamide, 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide (HMPA). These can be used alone or in combination. Among the reaction solvents, ethers, hydrocarbons alone or as a mixed solvent are preferred, and a mixed solvent obtained by mixing alcohols or carboxylic acids as a proton source with these is also preferred. The reaction temperature in the isomerization step is preferably from -78°C to the boiling point temperature of the solvent, more preferably from -10°C to 100°C. The reaction time can be arbitrarily set, but it is advisable to optimize by tracking the progress of the reaction using gas chromatography (GC) or thin layer chromatography (TLC). Usually, 5 minutes to 240 hours are preferred. From various viewpoints such as the reaction rate, the presence or absence of by-product formation, and the geometric isomer ratio of the target primary allyl sulfone compound (D), it is possible to select and optimize the reaction conditions of the isomerization step, such as an appropriate transition metal catalyst, solvent, reaction concentration, and reaction temperature.

[0050] When the primary allyl sulfone compound (D) obtained in the above isomerization step has sufficient purity, it may be used in the next step as a crude product, but it can be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation and various chromatographies. Depending on the structure of the substituent R at the 4-position, even if the isomerization reaction does not proceed completely and the starting secondary allyl sulfone compound (E) remains in the target primary allyl sulfone compound (D), they can be separated.

[0051] Also, depending on the structure of the substituent R at the 4-position, it has been found that in some cases, the geometric isomers E-(D) and Z-(D) of the primary allyl sulfone compound (D) can be separated from each other.

[0052]

Chemical formula

[0053] The two geometric isomers of the primary allyl sulfone compound (D) can be stereospecifically led to the geometric isomers of the target 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position, as described later. That is, compound E-(D) can be led to diene compound Z-(A), and compound Z-(D) can be led to diene compound E-(A). Therefore, the ability to separate geometric isomers is very important for obtaining a 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position with high geometric isomer purity. As a separation method for these isomers, separation methods such as chromatography utilizing the difference in polarity can be exemplified, and particularly silica gel column chromatography can be preferably exemplified.

[0054]

Chemical formula

[0055] A mixture of the secondary allyl sulfone compound (E) of the raw material and geometric isomers E-(D) and Z-(D) of the primary allyl sulfone compound of the product in any ratio can be used again as the substrate of this isomerization step to carry out re-isomerization. For the purpose of producing a specific geometric isomer, the ability to re-isomerize and recycle the unnecessary isomer is of great industrial significance.

[0056] [Chemical formula] (In the formula, R, W, and X are the same as above.)

[0057] When the primary allyl sulfone compound (D) obtained in the above isomerization step or the <halogen exchange step in the intermediate> described later has sufficient purity and isomer ratio, it may be used in the next step as a crude product, but it can be purified and the isomers can be separated by appropriately selecting from ordinary purification methods and isomer separation methods in organic synthesis such as distillation and various chromatographies.

[0058] Next, as synthetic routes from the obtained primary allyl sulfone compound (D) to the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position, the following two methods can be considered.

[0059] (I) A method via a halide compound (B), that is, (I)-(1) By reductive cleavage or reductive removal (desulfonation) of the arenesulfonyl group W at the allyl position of the primary allyl sulfone compound (D) to obtain a halide compound (B), (I)-(2) A method of obtaining the target 4-alkyl-3-methyl-1,3-butadiene compound (A) by elimination of hydrogen halide HX from the halide compound (B).

[0060] [Chemical formula] (In the formula, R, W, and X are the same as above.)

[0061] (II) Method via a primary allyl sulfone dienic compound (C), that is, (II)-(1) Obtaining a primary allyl sulfone dienic compound (C) by elimination of hydrogen halide HX from a primary allyl sulfone compound (D), and (II)-(2) Obtaining the target 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position by reductive elimination (desulfonation) of the arenesulfonyl group W of the primary allyl sulfone dienic compound (C).

[0062] [Chemical formula] (In the formula, R, W, and X are the same as above.)

[0063] Synthetic routes (I) and (II) will be described in order, and their applications will be described later.

[0064] (I)-(1) <Reductive elimination step of the arenesulfonyl group W at the allyl position from the primary allyl sulfone compound (D) to the halide compound (B)>

[0065] [Chemical formula] (In the formula, R, W, and X are the same as above.)

[0066] This reductive elimination (desulfonation) step is a step of substituting the arenesulfonyl group W with a hydrogen atom H.

[0067] As the primary allyl sulfone compound (D) which is the reaction substrate of the reductive elimination step, a chloride compound (when X = Cl), a bromide compound (when X = Br), or an iodide compound (when X = I) can be applied. They can be synthesized, for example, in the <halogen exchange step in the intermediate> described later. However, as the substrate of this reductive elimination step, a chloride compound is preferred in terms of suppressing side reactions.

[0068] As the reduction removal reaction, known methods can be applied and are not particularly limited. Examples include direct electron reduction reactions using metals or metal salts, nucleophilic substitution reduction reactions using hydride (H - ) nucleophilic reagents, and radical substitution reduction reactions using hydrogen radical (H · ) reagents.

[0069] As reagents used in the direct electron reduction reaction with metals or metal salts, combinations of protic solvents such as alkali metals like sodium and lithium, other metals like magnesium, zinc, and tin, lower amines such as ammonia, methylamine, ethylamine, and propylamine, lower alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol, carboxylic acids such as formic acid, acetic acid, and propionic acid, and various metal amalgams and metal salts such as samarium diiodide are used. Preferred specific examples of metal-protic solvents include lithium-ammonia, sodium-ammonia, sodium-lower amine, lithium-lower amine, magnesium-methanol, and zinc-acetic acid. It is also preferable to use sodium naphthalenide and Raney-nickel in a solvent. Examples of amalgams include sodium amalgam and aluminum amalgam. Among these, lithium-ammonia, sodium-ammonia, sodium-lower amine, lithium-lower amine, and magnesium-methanol are preferable in terms of ease of industrial implementation. The hydride (H -)As nucleophilic reagents, borane compounds such as borane, alkylborane, dialkylborane, bis(3-methyl-2-butyl)borane, silane compounds such as dialkylsilane, trialkylsilane, alane compounds such as alkylaluminum, dialkylaluminum (such as diisobutylaluminum hydride), metal hydrides (metal hydride) such as sodium hydride, lithium hydride, potassium hydride, calcium hydride, sodium borohydride, lithium borohydride, potassium borohydride, calcium borohydride, sodium aluminum hydride, lithium aluminum hydride, sodium trimethoxyborohydride, lithium trimethoxyaluminum hydride, lithium diethoxyaluminum hydride, lithium tri-tert-butoxyaluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride, lithium triethylborohydride and other complex hydrides and their alkoxy or alkyl derivatives can be exemplified. These complex hydrides can also be combined with formic acid to serve as a hydride source. For the nucleophilic reduction reaction, a transition metal catalyst may be used. Examples thereof include transition metal compounds such as nickel, rhodium, palladium, ruthenium, iridium, etc., and particularly palladium compounds are preferred. Preferred palladium compounds include zero-valent palladium compounds and divalent palladium compounds similar to those described in the isomerization step of the allyl rearrangement of the arenesulfonyl group from the above secondary allyl sulfone compound (E) to the primary allyl sulfone compound (D). Also, a phosphorus compound similar to the above may be used as a ligand together with these palladium compounds. Among these, the combination of complex hydrides and palladium compounds is preferred. Furthermore, the combination of lithium triethylborohydride and a transition metal catalyst, the combination of lithium borohydride, formic acid and a transition metal catalyst has high regioselectivity (in this case, S without allyl rearrangement) N2. Substitution reaction of the mechanism) can be realized, so it is particularly preferred. The palladium compound used at this time is preferably a zero-valent one. However, since the divalent metal compound is reduced to zero valence in the reaction system under reducing conditions, the divalent palladium compound is also preferred. The hydrogen radical (H · ) As a reagent, tributyltin hydride (TBTH) etc. can be exemplified. For the radical reduction reaction, azo compounds such as 2,2'-azobisisobutyronitrile, dimethyl 2,2'-azobis(isobutyrate), 1,1'-azobis(cyclohexanecarbonitrile), di-tert-butyl peroxide, tert-butyl hydroperoxide, benzoyl peroxide and other organic peroxides and other radical initiators may be used in combination.

[0070] As the solvent used in the reductive removal step, in addition to the above-mentioned protic solvents, for example, hydrocarbons such as water, hexane, heptane, benzene, toluene, xylene, cumene, etc., ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, 1,4-dioxane, 4-methyltetrahydropyran, etc., alcohols such as methanol, ethanol, 1-propanol, 2-propanol, t-butyl alcohol, benzyl alcohol, methoxyethanol, ethoxyethanol, etc., ketones such as acetone, 2-butanone, etc., nitriles such as acetonitrile, propionitrile, etc., esters such as ethyl acetate, butyl acetate, etc., aprotic polar solvents such as N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide (HMPA), etc. can be mentioned. An appropriate one can be selected according to the type of reagent used and used alone or in combination. The reaction temperature in the reductive removal step varies depending on the reagent and solvent used, but is preferably from -78°C to 50°C, more preferably from -70°C to 20°C. The reaction time can be arbitrarily set, but it is desirable from the viewpoint of yield to follow the reaction by gas chromatography (GC) or silica gel thin layer chromatography (TLC) and complete the reaction. Usually, 5 minutes to 240 hours is preferable.

[0071] In the above-mentioned reductive removal step, as a side reaction, not only the arenesulfonyl group W but also the halogen atom (halo group) X may be reductively removed and replaced with a hydrogen atom. Therefore, excessive reagents and severe reaction conditions should be avoided. By selecting an appropriate type of reagent and reaction conditions, the selectivity (reductively removing the arenesulfone group W while retaining the halo group X) is good, and it has been found that the selectivity is particularly good when X is a chlorine atom.

[0072] By selecting the conditions of the reductive removal step, it is also possible to directly obtain the halide compound (B) using the secondary allyl sulfone compound (E) in the previous step as a reaction substrate. For example, S with an allyl rearrangement as shown belowN It is a reductive elimination reaction by a substitution reaction of the 2'-mechanism. In this case, usually, an S without rearrangement N 2-mechanism and an S with rearrangement N Since the 2'-mechanism competes, it is effective when a mixture of isomers is desired as the target product. However, for the purpose of selective synthesis of individual isomers, it is better to use the primary allyl sulfone compound (D) as the reaction substrate.

[0073] [Chemical formula] (In the formula, R, W, and X are the same as above.)

[0074] When the halide compound (B) obtained in the above reductive elimination step or the halogen exchange step described later has sufficient purity and isomer ratio, it may be used in the next step as a crude product. However, purification and separation of isomers can be appropriately selected from purification methods and isomer separation methods in ordinary organic synthesis such as distillation and various chromatographies.

[0075] (I)-(2) <Desorption step of hydrogen halide HX from the halide compound (B) to the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position>

[0076] [Chemical formula] (In the formula, R and X are the same as above.)

[0077] This desorption step can usually be carried out by heating or cooling as necessary in the presence of a base in a solvent or without a solvent to desorb HX.

[0078] As the halide compound (B) which is the reaction substrate of this desorption step, a chloride compound (when X = Cl), a bromide compound (when X = Br), and an iodide compound (when X = I) can be applied. They can be synthesized, for example, in the <halogen exchange step in the intermediate> described later.

[0079] Examples of bases used in the elimination process include alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide, sodium t-amyloxide, lithium methoxide, lithium ethoxide, lithium t-butoxide, lithium t-amyloxide, potassium methoxide, potassium ethoxide, potassium t-butoxide, potassium t-amyloxide; hydrides such as lithium hydride, sodium hydride, potassium hydride, calcium hydride; hydroxide salts such as sodium hydroxide, lithium hydroxide, potassium hydroxide, barium hydroxide; carbonate salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride; metal amides such as lithium amide, sodium amide, lithium diisopropylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, lithium dicyclohexylamide; and organic bases such as ammonia, methylamine, ethylamine, propylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine, quinoline, pyrrolidine, piperidine, collidine, lutidine, morpholine, piperazine, 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]-7-undecene (DBU). These bases can be used alone or in combination, and can be selected considering the type, reactivity, and selectivity of the substrate. Among these bases, preferred examples include carbonate salts such as potassium carbonate, alkoxides such as potassium t-butoxide, and organic bases such as 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]-7-undecene (DBU).The amount of the base used is 0.01 to 100 moles, preferably 0.1 to 10 moles, per 1 mole of the halide compound (B) as the substrate. As the solvent used in the elimination step, hydrocarbons such as water, hexane, heptane, benzene, toluene, xylene, cumene, ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, 1,4-dioxane, 4-methyltetrahydropyran, alcohols such as methanol, ethanol, 1-propanol, 2-propanol, t-butyl alcohol, benzyl alcohol, methoxyethanol, ethoxyethanol, ketones such as acetone, 2-butanone, nitriles such as acetonitrile, propionitrile, esters such as ethyl acetate, butyl acetate, aprotic polar solvents such as N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide (HMPA), etc. can be mentioned. An appropriate one can be selected according to the type of the reagent used and used alone or as a mixture. The reaction temperature in the elimination step varies depending on the reagent and solvent used, but is preferably from -78°C to 200°C, more preferably from 0°C to 100°C. The reaction time can be arbitrarily set, but it is desirable from the viewpoint of yield to complete the reaction by tracking the reaction by gas chromatography (GC) or silica gel thin layer chromatography (TLC), and usually 5 minutes to 240 hours is preferable. Note that since the target 3-methyl-1,3-butadiene compound (A) contains a thermally unstable diene structure, a reaction at high temperature for a long time should be avoided, and it is preferable to select mild conditions of low temperature and short time for the reaction to proceed.

[0080] Next, the synthesis route (II) will be described. The synthesis route (II) is (II)-(1) <Elimination step of hydrogen halide HX from the primary allyl sulfone compound (D) to the primary allyl sulfone diene compound (C)>

Chemical formula

[0081] Step (II)-(1) can be carried out by eliminating HX in the same manner as the above-mentioned (I)-(2) <Elimination step of hydrogen halide HX from the halide compound (B) to the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position>. Step (II)-(2) can be carried out by reductively removing the arenesulfonyl group W at the allyl position in the same manner as (I)-(1) <Reductive removal step of the arenesulfonyl group W at the allyl position from the primary allyl sulfone compound (D) to the halide compound (B)>.

[0082] However, as a result of various studies, the elimination reaction of HX from the primary allyl sulfone compound (D) having the arenesulfonyl group W proceeds less readily than that from the halide compound (B) without the arenesulfonyl group W. In order to promote the reaction, by heating for a long time or the like, side reactions such as isomerization due to allyl rearrangement, polyene formation due to elimination of the arenesulfonyl group W, thermal decomposition, and dimerization of the product are found to occur concurrently. Details will be described later as Comparative Synthesis Examples.

[0083] From the above, from the viewpoints such as the cleanness of the reaction, stereospecificity, yield, and the ability to construct a conjugated diene structure that is thermally and acid-labile in the final step, as a synthetic route from the primary allyl sulfone compound (D) to the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position, the synthetic route (I) via the halide compound (B) is found to be more suitable than the synthetic route (II) via the primary allyl sulfone diene compound (C).

[0084] <Halogen Exchange Step in Intermediate>

[0085] In the secondary allyl sulfone compound (E), primary allyl sulfone compound (D), and halide compound (B) having a halogen atom (halo group) X in the intermediate of this production method, three types of chloride compounds, bromide compounds, and iodide compounds can be considered depending on the type of halogen atom X. One of these halide compounds can be used as a raw material to synthesize another type of halide compound (halogen conversion reaction) and applied to the process. For the purpose of improving reactivity, conversion to a more reactive halide compound, for example, conversion from a chloride compound to a bromide compound, from a chloride compound to an iodide compound, or from a bromide compound to an iodide compound, is preferred. These can be selected in terms of yield, reactivity, stability of the intermediate, etc. The halogen exchange reaction involves reacting a starting halide compound (e.g., a chloride compound or a bromide compound) with a halide ion X of the halogen present in the target compound having another halogen atom (e.g., a bromide compound or an iodide compound). - (e.g., Br - or I - ) can be carried out by known methods such as heating with a halogen source such as a halide salt having the same in a solvent. Also, the halogen exchange reaction may be carried out within the system of the process ( in situ ). Note that the halogen exchange reaction can be carried out with any of the intermediates of the secondary allyl sulfone compound (E), primary allyl sulfone compound (D), and halide compound (B), but in order to avoid unwanted side reactions (e.g., side reactions such as the halogen atom being reduced during the reductive removal step of the arenesulfonyl group W), it is preferably carried out with an appropriate intermediate. As an appropriate intermediate, the primary allyl sulfone compound (D) or the halide compound (B) is preferred, and the halide compound (B) is particularly preferred.

[0086] Listing the advantages of the production method of the present invention described above, for example, (1) The process and storage stability of the synthetic intermediate are high because an unstable conjugated diene structure is constructed at the final stage of synthesis or at a stage one step before that. (2) In the case where the substituents R and W are achiral in the synthetic intermediate, since there is no asymmetric carbon or there is only one asymmetric carbon (no plurality of asymmetric carbon atoms) in the molecule, diastereomers derived from the asymmetric carbon do not occur, and the purification and analysis of the intermediate are easier than the synthesis using a mixture of diastereomers as the intermediate. (3) By selecting reagents and reaction conditions with good selectivity, the target product can be synthesized with high isomer purity. (4) It can be applied to the synthesis of various derivatives having the characteristic substituted butadiene structure of farnesenes. (5) For the purpose of utilizing biological activity, a mixture of isomers can also be used as it is. In that case, even if the selectivity is low, an economical synthesis method may be advantageous. (6) The obtained target product has high stability. It can be stored at room temperature. It can be purified by distillation or silica gel chromatography, which are common purification methods for organic compounds. etc. can be mentioned.

Example

[0087] Hereinafter, examples are shown to more specifically explain the present invention, but the present invention is not limited thereto.

[0088] Note that when using the values obtained by gas chromatography (GC) analysis as the purity of raw materials, products, and intermediates, it is denoted as %GC, and when using the values obtained by proton nuclear magnetic resonance ( 1 1H-NMR) analysis, it is denoted as %NMR. The isomer ratio of the product and the intermediate uses the ratio of GC analysis or 1 1H-NMR analysis. GC conditions: GC: Shimadzu GC-14A, Column: 5%Ph-Me silicone 0.25mmφx25m, Carrier gas: He, Detector: FID.

[0089] The yield is the value of the converted yield based on %GC or %NMR. Since the raw materials used in the reaction and the products obtained from the reaction are not necessarily 100% pure, the converted yield (%) = {[(weight of the product obtained by the reaction × %GC) / molecular weight of the product] ÷ [(weight of the starting material in the reaction × %GC) / molecular weight of the starting material]} × 100. Note that since the detection sensitivity of gas chromatography varies depending on the compound, especially when the raw material or product is a crude product, the converted yield may exceed 100%.

[0090] Samples for spectral measurement of the compound were purified as necessary and used for the measurement.

[0091] Synthesis Example <Synthesis of allyl sulfone compound represented by the following general formula (F)>

[0092]

Chemical formula

[0093] Synthesis Example 1 Synthesis of 4-chloro-2-methylenebutyl = p-tolyl = sulfone [when W = Ts = p-toluenesulfonyl group and X = Cl in the general formula (F)]

[0094]

Chemical formula

[0095] Under a nitrogen atmosphere, 12.51 g of 4-chloro-2-chloromethyl-1-butene was added dropwise to a mixture of 22.60 g of sodium p-toluenesulphinate·tetrahydrate and 120 ml of dimethylformamide (DMF) while cooling in an ice-water bath and stirring at 25°C or lower. After stirring at room temperature for 17 hours, 5.05 g of sodium p-toluenesulphinate·tetrahydrate was added and stirring was continued for another 3 days. Water was added to the mixture and extraction was performed with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, 23.85 g of 4-chloro-2-methylenebutyl p-tolyl sulfone (96.7 - 89% NMR, containing 3.3 - 11% DMF, quantitative yield) was obtained. A part of this was subjected to spectral measurement after removing DMF under vacuum.

[0096] 4-chloro-2-methylenebutyl p-tolyl sulfone [Chemical formula]

[0097] C 12 H 15 ClO2S Colorless crystal Melting point [inflection point of the endothermic peak of DSC (differential scanning calorimeter), the same hereinafter]: 61.7°C IR (D-ATR): ν = 2985, 2946, 2929, 1647, 1598, 1494, 1448, 1418, 1405, 1381, 1315, 1308, 1298, 1274, 1237, 1206, 1170, 1147, 1121, 1086, 1034, 1020, 938, 920, 816, 804, 780, 709, 650, 637, 611, 516, 454 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 2.44 (3H, s), 2.68 (2H, t, J = 6.7 Hz), 3.64 (2H, t, J = 6.7 Hz), 3.78 (2H, s), 4.89 (1H, br.s), 5.15 (1H, br.s), 7.34 (2H, d-like, J = ~8 Hz), 7.74 (2H, d-like, J = ~8 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 21.61, 37.91, 42.07, 62.57, 122.44, 128.44, 129.67, 133.60, 135.12, 144.84 ppm. GC-MS (EI, 70 eV): 27, 41, 67 (base peak), 91, 105, 131, 155, 179, 194, 223, 241, 258 (M + ).

[0098] Synthesis Example 2 Synthesis of 4-chloro-2-methylenebutyl phenyl sulfone [when W = benzene sulfonyl group and X = Cl in General Formula (F)]

[0099] [Chemical formula] (In the formula, Ph represents a phenyl group. The same applies hereinafter.)

[0100] Under a nitrogen atmosphere, a mixture of 71.0 g of sodium benzenesulfinate dihydrate, 2.00 g of tetrabutylammonium chloride (TBAC), and 500 ml of acetonitrile was stirred at 50 °C, and 41.2 g of 4-chloro-2-chloromethyl-1-butene was added dropwise over 35 minutes. The mixture was heated to reflux at 80 - 95 °C for 6 hours and further stirred at room temperature for 2 days. Water was added to the mixture, and it was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, a crude product was obtained. This crude product was recrystallized from ethyl acetate - n-hexane to obtain 63.54 g of 4-chloro-2-methylenebutyl phenyl sulfone (including 2.3% TBAC by NMR, yield 89.4%). A part of this product was purified by silica gel column chromatography and used for spectral measurement.

[0101] 4-chloro-2-methylenebutyl phenyl sulfone

Chemical formula

[0102] C 11 H 13 ClO2S Colorless crystals Melting point: 45.1 °C IR (D-ATR): ν = 3086, 2970, 2927, 1649, 1585, 1479, 1447, 1409, 1317, 1294, 1273, 1237, 1203, 1168, 1145, 1118, 1084, 1029, 999, 939, 922, 888, 797, 784, 757, 712, 690, 651, 615, 531 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 2.70 (2H, t, J = 6.7 Hz), 3.65 (2H, t, J = 6.7 Hz), 3.81 (2H, s), 4.90 (1H, br.s), 5.16 (1H, br.s), 7.54 - 7.59 (2H, m), 7.64 - 7.68 (1H, m), 7.86 - 7.90 (2H, m) ppm. 1313C-NMR(125 MHz, CDCl3): δ = 37.92, 42.06, 62.55, 122.62, 128.48, 129.09, 133.49, 133.85, 138.07 ppm. GC-MS (EI, 70 eV): 51, 77, 91, 117 (base peak), 141, 164, 178, 193, 221, 258 (M + ).

[0103] Example <Synthesis of secondary allyl sulfone compound represented by the following general formula (E)>

[0104]

Chemical formula

[0105] Example 1 Synthesis of (E)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl phenyl sulfone [when R = (E)-3,7-dimethyl-2,6-octadienyl group, W = benzenesulfonyl group, X = Cl in the general formula (E)]

[0106]

Chemical formula

[0107] Under a nitrogen atmosphere, a mixture of 43.21 g (≥99% NMR) of 4-chloro-2-methylenebutyl phenyl sulfone synthesized in Synthesis Example 2 above and 500 ml of tetrahydrofuran (THF) was cooled to -65 °C or lower and stirred while dropping 70.0 ml of a 2.80 M n-butyllithium-n-hexane solution. After stirring at this temperature for 1 hour, 42.6 g of geranyl bromide was added dropwise over 30 minutes. The reaction mixture was gradually raised to room temperature and stirred for 30 hours. The reaction mixture was ice-cooled, an aqueous ammonium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, and then purification by silica gel column chromatography, 36.4 g (yield 54%) of (E)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl phenyl sulfone was obtained.

[0108] (E)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl phenyl sulfone

Chem.

[0109] C 21 H 29 ClO2S Yellowish oil IR (D-ATR): ν = 2965, 2918, 2856, 1644, 1585, 1447, 1377, 1305, 1205, 1146, 1084, 923, 823, 755, 721, 670, 615, 546 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.54 (3H, br.s), 1.56 (3H, br.s), 1.65 (3H, br.s), 1.89 - 2.03 (4H, m), 2.43 - 2.59 (3H, m), 2.75 - 2.81 (1H, m), 3.47 - 3.59 (3H, m), 4.90 - 4.95 (1H, m), 4.98 - 5.03 (1H, m), 5.10 (1H, s-like), 5.22 (1H, s-like), 7.52 - 7.57 (2H, m), 7.63 - 7.67 (1H, m), 7.84 - 7.88 (2H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 16.20, 17.64, 25.65, 26.21, 26.38, 38.29, 39.52, 41.79, 70.56, 118.08, 120.42, 123.81, 128.87, 129.27, 131.63, 133.72, 137.08, 137.29, 139.06 ppm。

[0110] Example 2 Synthesis of (Z)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl p-tolyl sulfone [when in the general formula (E), R = (Z)-3,7-dimethyl-2,6-octadienyl group, W = p-toluenesulfonyl group, X = Cl]

[0111]

Chem.

[0112] Under a nitrogen atmosphere, a mixture of 17.1 g (96.0% NMR) of 4-chloro-2-methylenebutyl p-tolyl sulfone synthesized in Synthesis Example 1 above and 250 ml of tetrahydrofuran was cooled to -60 °C or lower and stirred while 28.5 ml of a 2.80 M n-butyllithium-n-hexane solution was added dropwise. After stirring at this temperature for 30 minutes, 14.60 g (Z95.1% NMR) of neryl bromide was added dropwise over 10 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 15 hours. The reaction mixture was ice-cooled, an aqueous ammonium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, followed by purification by silica gel column chromatography, 19.1 g (yield 76%) of (Z)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl p-tolyl sulfone was obtained.

[0113] (Z)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl p-tolyl sulfone

Chem.

[0114] C 22 H 31 ClO2S Colorless oil IR (D-ATR): ν = 2965, 2923, 2858, 1643, 1597, 1448, 1377, 1315, 1301, 1290, 1145, 1085, 922, 816, 735, 667, 593 cm -1 。 1H-NMR (500 MHz, CDCl3): δ = 1.59 (3H, br.s), 1.63 (3H, d, J = ~1.3 Hz), 1.67 (3H, br.s), 1.87 - 2.03 (4H, m), 2.41 - 2.58 (3H, m), 2.45 (3H, s), 2.74 - 2.81 (1H, m), 3.43 - 3.60 (3H, m), 4.93 (1H, t-like, J = ~8 Hz), 4.99 - 5.03 (1H, m), 5.11 (1H, s-like), 5.23 (1H, s-like), 7.33 (2H, dd-like, J = ~8.5, ~0.6 Hz), 7.72 (2H, dt-like, J = ~8.5, ~2 Hz) ppm. 13 C-NMR (125 MHz, CDCl3): δ = 17.63, 21.63, 23.28, 25.73, 26.15, 26.25, 31.95, 38.56, 41.81, 70.72, 118.94, 120.28, 123.78, 129.28, 129.49, 131.94, 134.41, 137.12, 139.04, 144.69 ppm.

[0115] Example 3 Synthesis of 1-chloro-7-methyl-3-methylene-6-octen-4-yl = p-tolyl = sulfone [when R = 3-methyl-2-butenyl group, W = p-toluenesulfonyl group, X = Cl in general formula (E)]

[0116]

Chemical formula

[0117] Under a nitrogen atmosphere, a mixture of 5.00 g of 4-chloro-2-methylenebutyl = p-tolyl = sulfone (96.7% NMR) synthesized in Synthesis Example 2 above and 80 ml of tetrahydrofuran was cooled to -60 °C or lower and stirred while dropping 7.35 ml of a 2.80 M n-butyllithium-n-hexane solution. After stirring at this temperature for 40 minutes, 3.35 g of prenyl bromide (1-bromo-3-methyl-2-butene) was dropped in over 5 minutes. The reaction mixture was gradually raised to room temperature and stirred for 16 hours. The reaction mixture was ice-cooled, an aqueous ammonium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, followed by purification by silica gel column chromatography, 5.35 g of 1-chloro-7-methyl-3-methylene-6-octen-4-yl = p-tolyl = sulfone [97.4 - 98.7% GC (When the purity is described in a range, it indicates that the purities of the obtained multiple fractions were within that range. The same applies to %GC and %NMR of the following purity descriptions.), containing 1.1 - 2.2% of the corresponding bromide, 1-bromo-7-methyl-3-methylene-6-octen-4-yl = p-tolyl = sulfone, yield 88%] was obtained.

[0118] 1-chloro-7-methyl-3-methylene-6-octen-4-yl = p-tolyl = sulfone

Chemical formula

[0119] C 17 H 23 ClO2S Yellowish oil IR (D-ATR): ν = 2967, 2917, 1643, 1597, 1450, 1378, 1315, 130, 1289, 1144, 1086, 923, 816, 709, 667, 593 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 1.55 (3H, br.s), 1.63 (3H, d-like, J = ~1.2 Hz), 2.42 - 2.57 (3H, m), 2.44 (3H, s), 2.73 - 2.79 (1H, m), 3.47 - 3.52 (2H, m), 3.53 - 3.58 (1H, m), 4.88 - 4.93 (1H, m), 5.08 (1H, s-like), 5.21 (1H, s-like), 7.32 (2H, dd-like, J = ~8, ~1 Hz), 7.72 (2H, dt-like, J = ~8, ~2 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.85, 21.62, 25.63, 38.26, 38.38, 41.83, 70.49, 118.36, 120.25, 129.27, 129.48, 134.32, 135.32, 137.23, 144.69 ppm.

[0120] 1-Bromo-7-methyl-3-methylene-6-octen-4-yl = p-tolyl = sulfone

Chemical formula

[0121] C 17 H 23 BrO2S GC-MS (EI, 70 eV): 41, 79, 107 (base peak), 135, 170, 215, 217. GC-MS (CI, isobutane): 157, 215, 371, 373 (M + H + , base peak).

[0122] Example 4 Synthesis of 1-chloro-7-methyl-3-methylene-6-octen-4-yl = phenyl = sulfone [when R = 3-methyl-2-butenyl group, W = benzenesulfonyl group, X = Cl in general formula (E)]

[0123]

Chemical formula

[0124] Under a nitrogen atmosphere, a mixture of 91.4 g (96% NMR) of 4-chloro-2-methylenebutyl=phenyl=sulfone synthesized in the same manner as in Synthesis Example 2 above and 800 ml of tetrahydrofuran was cooled to -60 °C or lower and stirred while adding dropwise 150 ml of a 2.76 M n-butyllithium-n-hexane solution over 20 minutes. After stirring at this temperature for 35 minutes, 67.0 g of prenyl bromide (1-bromo-3-methyl-2-butene) was added dropwise over 20 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 16.5 hours. The reaction mixture was ice-cooled, an aqueous ammonium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, 116.29 g (yield 99%) of 1-chloro-7-methyl-3-methylene-6-octen-4-yl=phenyl=sulfone was obtained.

[0125] 1-chloro-7-methyl-3-methylene-6-octen-4-yl=phenyl=sulfone

Chemical Structure

[0126] C 16 H 21 ClO2S Yellowish oil IR (D-ATR): ν = 3064, 2965, 2916, 1673, 1643, 1585, 1447, 1377, 1304, 1244, 1146, 1085, 923, 755, 720, 690, 615 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.54 (3H, br.s), 1.63 (3H, d-like, J = ~1 Hz), 2.42 - 2.58 (3H, m), 2.73 - 2.82 (1H, m), 3.47 - 3.59 (3H, m), 4.88 - 4.93 (1H, m), 5.10 (1H, s-like), 5.22 (1H, s-like), 7.52 - 7.58 (2H, m), 7.62 - 7.67 (1H, m), 7.83 - 7.89 (2H, m) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 17.84, 25.64, 26.35, 38.33, 41.78, 70.49, 118.24, 120.41, 128.86, 129.25, 133.71, 135.47, 137.09, 137.32 ppm.

[0127] Example 5 Synthesis of 8-chloro-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone [wherein in general formula (E), R = 3-methyl-3-butenyl group, W = benzene sulfonyl group, X = Cl]

[0128]

Chemical formula

[0129] Under a nitrogen atmosphere, a mixture of 16.9 g (˜100% NMR) of 4-chloro-2-methylenebutyl phenyl sulfone synthesized in the same manner as in Synthesis Example 2 above and 160 ml of tetrahydrofuran was cooled to -60° C. or lower and stirred while dropping 28.8 ml of a 2.64 M n-butyllithium-n-hexane solution over 10 minutes. After stirring at this temperature for 45 minutes, 12.35 g of 4-bromo-2-methyl-2-butene was dropped over 5 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 30 hours. The reaction mixture was ice-cooled, ammonium chloride aqueous solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, and then purification by silica gel column chromatography, 9.38 g of 8-chloro-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone [59.1-96.0% GC (including 0-4.3% of the corresponding bromide: 8-bromo-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone), yield 40%] was obtained.

[0130] 8-chloro-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone

Chemical formula

[0131] C 16 H 21 ClO2S Yellowish oil IR (D-ATR): ν = 3071, 2965, 1648, 1585, 1447, 1376, 1305, 1196, 1146, 1085, 895, 756, 721, 690, 612 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, s-like), 1.86 - 1.98 (2H, m), 2.05 - 2.12 (1H, m), 2.21 - 2.28 (1H, m), 2.47 - 2.55 (1H, m), 2.59 - 2.66 (1H, m), 3.52 - 3.67 (3H, m), 4.63 (1H, br.s), 4.74 (1H, br.s), 5.04 (1H, s-like), 5.24 (1H, t-like, J = 1.4 Hz), 7.52 - 7.58 (2H, m), 7.62 - 7.67 (1H, m), 7.82 - 7.88 (2H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 21.99, 24.89, 34.03, 37.86, 41.80, 69.97, 111.54, 120.28, 128.87, 129.29, 133.75, 136.91, 137.09, 143.52 ppm。 GC-MS (EI, 70 eV): 39, 55, 77, 93, 109, 129, 155, 171 (base peak)。

[0132] 8-Bromo-2-methyl-6-methylene-1-octen-5-yl = phenyl = sulfone C 16 H 21 BrO2S

Chem.

[0133] GC-MS (EI, 70 eV): 55, 77 (base peak), 93, 107, 135, 155, 173, 197, 215, 217。

[0134] Example 6 Synthesis of (E)-7-chloro-5-methylene-1-phenyl-1-hepten-4-yl p-tolyl sulfone [when R = 3-phenyl-2-propenyl group, W = p-toluenesulfonyl group, X = Cl in the general formula (E)]

[0135] [Chemical formula]

[0136] Under a nitrogen atmosphere, a mixture of 17.4 g (97% NMR) of 4-chloro-2-methylenebutyl p-tolyl sulfone synthesized in Synthesis Example 1 above and 150 ml of tetrahydrofuran was cooled to -60 °C or lower and stirred while 26.4 ml of a 2.80 M n-butyllithium-n-hexane solution was added dropwise over 15 minutes. After stirring at this temperature for 1 hour, 14.6 g of cinnamyl bromide was added dropwise over 15 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 16 hours. The reaction mixture was ice-cooled, ammonium chloride aqueous solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, 26.03 g (quantitative yield) of crude (E)-7-chloro-5-methylene-1-phenyl-1-hepten-4-yl p-tolyl sulfone was obtained. This had sufficient purity and was used as a raw material for the next step as the crude product.

[0137] 7-chloro-5-methylene-1-phenyl-1-hepten-4-yl p-tolyl sulfone [Chemical formula]

[0138] C 21 H 23 ClO2S colorless oil IR (D-ATR): ν = 3026, 2959, 2923, 2869, 1643, 1597, 1494, 1447, 1313, 1302, 1290, 1144, 1085, 967, 923, 816, 743, 708, 693, 669, 606, 588 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 2.45 (3H, s), 2.48 - 2.62 (2H, m), 2.68 - 2.76 (1H, m), 2.96 - 3.02 (1H, m), 3.51 - 3.61 (2H, m), 3.66 (1H, dd, J = 4.0, 11.4 Hz), 5.14 (1H, s), 5.27 (1H, s-like), 5.99 (1H, dt, J = 15.7, 7.2 Hz), 6.42 (1H, dt-like, J = 15.7, ~1.2 Hz), 7.18 - 7.22 (1H, m), 7.26 - 7.29 (4H, m), 7.34 (2H, d-like, J = ~8.5, ~0.6 Hz), 7.75 (2H, dt-like, J = ~8.5, ~1.9 Hz) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 21.65, 31.32, 38.32, 41.84, 70.37, 120.67, 124.06, 126.14, 127.54, 128.52, 129.37, 129.58, 133.53, 134.02, 136.69, 136.89, 144.93 ppm。

[0139] Example 7 Synthesis of 1-chloro-3-methylenedodecan-4-yl = p-tolyl = sulfone [when R = n-octyl group, W = p-toluenesulfonyl group, X = Cl in the general formula (E)]

[0140]

Chemical Structure

[0141] Under a nitrogen atmosphere, a mixture of 41.58 g of 4-chloro-2-methylenebutyl = p-tolyl = sulfone (~97% NMR) synthesized in the same manner as in Synthesis Example 1 above and 500 ml of tetrahydrofuran was cooled to -60 °C or lower and stirred while 65.5 ml of a 2.76 M n-butyllithium - n-hexane solution was added dropwise over 30 minutes. After stirring at this temperature for 40 minutes, 34.8 g of 1-bromooctane was added dropwise over 10 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 16 hours. The reaction mixture was ice-cooled, an aqueous ammonium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying, and concentration from the ethyl acetate solution, and then purification by silica gel column chromatography, 51.1 g (yield 86%) of 1-chloro-3-methylenedodecan-4-yl = p-tolyl = sulfone was obtained.

[0142] 1-chloro-3-methylenedodecan-4-yl = p-tolyl = sulfone

Chemical formula

[0143] C 20 H 31 ClO2S Colorless solid Melting point: 52.5 °C IR (D-ATR): ν = 2954, 2925, 2855, 1642, 1597, 1494, 1456, 1379, 1313, 1302, 1289, 1145, 1086, 1019, 923, 815, 708, 667 cm -1 。 11H-NMR (500 MHz, CDCl3): δ = 0.86 (3H, t, J = 7.0 Hz), 1.13 - 1.37 (12H, m), 1.72 - 1.82 (1H, m), 1.98 - 2.08 (1H, m), 2.44 (3H, s), 2.45 - 2.53 (1H, m), 2.56 - 2.66 (1H, m), 3.50 (1H, dd, J = 11.7, 3.5 Hz), 3.56 (1H, dt-like, J = 11.7, 3.5 Hz), 3.61 (1H, ddd, J = 11.0, 7.5, 6.3 Hz), 5.01 (1H, s), 5.19 (1H, t-like, J = ~1.4 Hz), 7.32 (2H, dd-like, J = 0.6, 8.6), 7.70 (2H, dt-like, J = 8.2, ~2 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 14.07, 21.64, 22.59, 26.49, 27.12, 29.09, 29.15, 29.19, 31.74, 37.83, 41.90, 71.04, 119.92, 129.29, 129.46, 134.18, 137.33, 144.66 ppm.

[0144] Example <Synthesis of primary allyl sulfone compounds represented by the following general formula (D)>

[0145] [Chemical formula]

[0146] Example 8 Synthesis of (3Z,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone [where in general formula (D), R = (E)-3,7-dimethyl-2,6-octadienyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (3E,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone [where in general formula (D), R = (E)-3,7-dimethyl-2,6-octadienyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0147] [Chemical formula]

[0148] Under a nitrogen atmosphere, while stirring a mixture of 18.10 g of (E)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl phenyl sulfone (≈100% NMR) synthesized in Example 1 above, 1.86 g of triphenylphosphine, 125 ml of tetrahydrofuran and 125 ml of methanol at room temperature, 2.03 g of tetrakis(triphenylphosphine)palladium(0) [Pd(tpp)₄] was added, and the mixture was stirred at room temperature for 30 minutes and then at 70 °C for 1.5 hours. After cooling the reaction mixture, it was filtered through celite and eluted with diethyl ether. After concentrating the diethyl ether solution, it was separated and purified by silica gel column chromatography to obtain the following fractions containing the target compounds (3Z,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl phenyl sulfone and (3E,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl phenyl sulfone: 4.80 g (≈100% GC, ZE:EE = 100:0), 5.09 g (≈100% GC, ZE:EE = 42:57), 2.86 g (≈100% GC, ZE:EE = 12.3:87.7), 3.84 g (≈100% GC, ZE:EE = 2.3:97.7).

[0149] It was shown by Example 8 and the following examples that the isomerization from the secondary sulfone compound to the primary sulfone compound proceeded, the two generated primary sulfone compounds could be easily separated, and the important intermediate for α-farnesene synthesis could be obtained with high purity.

[0150] (3Z,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl phenyl sulfone [Chemical formula]

[0151] C 21 H 29 ClO2S Colorless oil IR (D-ATR): ν = 2967, 2918, 2855, 1669, 1585, 1447, 1376, 1317, 1308, 1243, 1147, 1113, 1085, 902, 837, 746, 723, 689, 656, 614, 532 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.48 (3H, br.s), 1.59 (3H, br.s), 1.67 (3H, br.s), 1.87 - 1.95 (2H, m), 1.98 - 2.04 (2H, m), 2.30 (2H, t, J = 7.0 Hz), 2.67 (2H, dt, J = 1.0, 6.7 Hz), 3.63 (2H, t, J = 6.7 Hz), 3.89 (2H, s), 4.74 - 4.80 (1H, m), 5.01 - 5.07 (1H, m), 5.53 (1H, t, J = 7.4 Hz), 7.53 - 7.59 (2H, m), 7.63 - 7.69 (1H, m), 7.86 - 7.92 (2H, m) ppm。

[0152] 2D-NOESY: Correlations of NOE (Nuclear Overhauser Effect) were observed between the signals of the hydrogen atoms bonded to the carbon atoms at the positions indicated by the double-sided arrows in the following chemical formula.

[0153]

Chem.

[0154] The above 1 chemical shifts of the signals in 1H-NMR and 1 1H- 1 1H coupling constant J, and the correlations in the 2D-NOESY spectrum confirmed the stereochemistry (geometric isomerism of double bonds) of the target compound.

[0155] 13C-NMR (125 MHz, CDCl3): δ = 16.05, 17.66, 25.67, 26.50, 26.93, 39.01, 39.45, 42.82, 57.30, 120.53, 123.03, 123.99, 128.50, 129.21, 131.51, 133.82, 136.79, 136.92, 138.70 ppm.

[0156] (3E,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone

Chem.

[0157] C 21 H 29 ClO2S Colorless oil IR (D-ATR): ν = 2967, 2918, 2855, 1668, 1586, 1447, 1377, 1316, 1307, 1252, 1142, 1086, 887, 839, 742, 689, 657, 621, 531 cm -1 . 1 H-NMR (500 MHz, CDCl3): δ = 1.55 (3H, br.s), 1.60 (3H, br.s), 1.68 (3H, br.s), 1.90 - 1.97 (2H, m), 1.99 - 2.06 (2H, m), 2.69 (2H, t, J = 7.1 Hz), 2.73 (2H, t, J = 7.0 Hz), 3.61 (2H, t, J = 6.9 Hz), 3.78 (2H, s), 4.80 - 4.86 (1H, m), 5.03 - 5.09 (1H, m), 5.19 (1H, t, J = 7.4 Hz), 7.52 - 7.58 (2H, m), 7.62 - 7.67 (1H, m), 7.82 - 7.87 (2H, m) ppm.

[0158] 2D-NOESY: The correlation of NOE (Nuclear Overhauser Effect) was observed between the signals of the hydrogen atoms bonded to the carbon atoms at the positions indicated by the double-sided arrows in the following chemical formula.

[0159] [ka]

[0160] the above 1 Chemical shifts of H-NMR signals and 1 H- 1 The stereochemistry of the target compound (geometric isomerism of the double bond) was confirmed from the geometry including the H-coupling constant J and correlation in the 2D-NOESY spectrum.

[0161] 13 C-NMR (125MHz, CDCl3): δ=16.11,17.69,25.69,26.56,27.29,32.62,39.56,42.42,63.3 5,120.40,123.50,123.98,128.56,128.98,131.60,133.63,136.69,138.05,138.94ppm.

[0162] Example 9 Synthesis of (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone [general formula (D) where R = (Z)-3,7-dimethyl-2,6-octadienyl, W = p-toluenesulfonyl, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl phenyl sulfone [general formula (D) where R = (Z)-3,7-dimethyl-2,6-octadienyl, W = p-toluenesulfonyl, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0163] [ka]

[0164] Under a nitrogen atmosphere, while stirring a mixture of 1.07 g of (Z)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl p-tolyl sulfone (~100% NMR), 0.10 g of triphenylphosphine, 10 ml of tetrahydrofuran and 10 ml of methanol at room temperature, 0.15 g of tetrakis(triphenylphosphine)palladium(0) was added, and the mixture was stirred at 70 - 75 °C for 2.1 hours and then at room temperature for 14 hours. After cooling the reaction mixture, it was eluted with water and diethyl ether. The crude product obtained by concentrating the diethyl ether solution was a mixture of starting material (Z)-1-chloro-7,11-dimethyl-3-methylene-6,10-dodecadien-4-yl p-tolyl sulfone: the ZZ-isomer of the target product (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone: the EZ-isomer of the target product (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone = 2.0:42.4:55.6( 1 H-NMR). These were separated and purified by silica gel column chromatography to obtain the target product (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone and (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone as 0.34 g (89.5% NMR, ZZ:EZ = 100:0 GC), 0.22 g (~100% NMR, ZZ:EZ = 42.2:57.8 GC - 43.2:56.8 NMR), 0.21 g (~100% NMR, ZZ:EZ = 9.5:90.5 GC - 9.5:90.5 NMR), 0.19 g (~100% NMR, ZZ:EZ = 0:100 NMR) (total isomer yield 96%).

[0165] (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl p-tolyl sulfone

Chemical Structure

[0166] C 22 H 31 ClO2S Colorless oil IR (D-ATR): ν = 3030, 2965, 2925, 2856, 1597, 1495, 1449, 1407, 1377, 1317, 1303, 1292, 1242, 1147, 1115, 1087, 951, 901, 816, 729, 671 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, br.s), 1.62 (3H, q-like, J = ~1.2 Hz), 1.69 (3H, q-like, J = ~1.2 Hz), 1.89 (2H, t-like, J = ~8 Hz), 1.99 (2H, q-like, J = ~7.3 Hz), 2.28 (2H, t, J = 7.0 Hz), 2.45 (3H, s), 2.67 (2H, dt-like, J = ~1, ~7 Hz), 3.62 (2H, t, J = 6.8 Hz), 3.86 (2H, s), 4.73 (1H, t-like, J = ~7 Hz), 5.01 - 5.08 (1H, m), 5.50 (1H, t, J = 7.3 Hz), 7.32 - 7.38 (2H, m), 7.74 - 7.89 (2H, m) ppm。

[0167] 2D-NOESY: Correlations of NOE (Nuclear Overhauser Effect) were observed between the signals of the hydrogen atoms bonded to the carbon atoms at the positions indicated by the double-sided arrows in the following chemical formula, and the stereochemistry (double bond geometric isomerism) was determined.

[0168]

Chemical formula

[0169] The above 1 The chemical shift of the signal in 1H-NMR and 1 1H- 1The stereochemistry (geometric isomerism of double bonds) of the target compound was confirmed from the shape including the H coupling constant J and the correlations in the 2D-NOESY spectrum.

[0170] 13 C-NMR (125 MHz, CDCl3): δ = 17.67, 21.62, 23.24, 25.73, 26.33, 26.84, 31.82, 39.07, 42.82, 57.35, 121.42, 123.24, 123.92, 128.55, 129.82, 131.79, 135.80, 136.79 (2C overlapped), 144.83 ppm.

[0171] (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone

Chemical Structure

[0172] C 22 H 31 ClO2S colorless oil IR (D-ATR): ν = 3032, 2965, 2924, 2856, 1597, 1495, 1447, 1404, 1377, 1315, 1302, 1255, 1184, 1145, 1116, 1087, 1039, 1019, 886, 816, 731, 673 cm -1 。 11H-NMR (500 MHz, CDCl3): δ = 1.59 (3H, br.s), 1.66 (3H, q-like, J = ~1.3 Hz), 1.67 (3H, q-like, J = ~0.8 Hz), 1.92 - 2.05 (4H, m), 2.44 (3H, s), 2.67 (2H, br.t, J = ~7 Hz), 2.71 (2H, t, J = 6.9 Hz), 3.60 (2H, t, J = 7.0 Hz), 3.74 (2H, s), 4.81 (1H, t-like, J = ~7 Hz), 5.02 - 5.09 (1H, m), 5.14 (1H, t, J = 7.4 Hz), 7.32 (2H, d, J = 8.2 Hz), 7.69 (2H, dt, J = 8.2, 1.9 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.63, 21.60, 23.27, 25.69, 26.37, 27.14, 31.91, 32.58, 42.45, 63.42, 121.31, 123.60, 123.88, 128.60, 129.58, 131.84, 135.09, 136.65, 138.83, 144.56 ppm.

[0173] Example 10 Synthesis of (3Z,6E)-(1-bromo-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone [where in general formula (D), R = (E)-3,7-dimethyl-2,6-octadienyl group, W = benzenesulfonyl group, X = Br, and the geometric isomerism of the double bond at the 3-position is Z]

[0174]

Chemical formula

[0175] Under a nitrogen atmosphere, a mixture of 2.24 g of (3Z,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone synthesized in Example 8 above (~100% NMR, ZE:EE = 100:0), 5.00 g of bromoethane, 0.200 g of sodium bromide and 20 ml of N-methyl-2-pyrrolidone was stirred at 60 - 72 °C for 11 hours. After cooling the reaction mixture, water was added and the mixture was extracted with ethyl acetate. After the usual post-treatment operations of washing, drying and concentration from the ethyl acetate solution, and then purification by silica gel column chromatography, 1.84 g of the target product (3Z,6E)-(1-bromo-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone (including a trace amount of the starting material chloride, ~93% NMR, yield 81%) was obtained.

[0176] (3Z,6E)-(1-bromo-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone

Chemical Structure

[0177] C 21 H 29 BrO2S Yellowish oil IR(D-ATR): ν = 3061, 2967, 2917, 2855, 1585, 1447, 1376, 1317, 1307, 1145, 1109, 1085, 746, 723, 688, 611, 590, 532 cm -1 。 11H-NMR (500 MHz, CDCl3): δ = 1.48 (3H, br.s), 1.58 (3H, br.s), 1.67 (3H, q-like, J = ~1 Hz), 1.87 - 1.95 (2H, m), 1.98 - 2.04 (2H, m), 2.30 (2H, t, J = 7.1 Hz), 2.67 (2H, dt-like, J = ~1, 7.0 Hz), 3.48 (2H, t, J = 7.0 Hz), 3.89 (2H, s), 4.74 - 4.81 (1H, m), 5.01 - 5.07 (1H, m), 5.53 (1H, t, J = 7.3 Hz), 7.53 - 7.59 (2H, m), 7.63 - 7.69 (1H, m), 7.87 - 7.92 (2H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 16.06, 17.66, 25.67, 26.50, 26.92, 31.08, 39.14, 39.45, 57.14, 120.49, 123.74, 123.99, 128.49, 129.21, 131.49, 133.83, 136.82, 136.87, 138.70 ppm. GC-MS (EI, 70 eV): 41, 69, 105 (base peak), 133, 175, 213, 239, 282.

[0178] Example 11 Synthesis of (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl p-tolyl sulfone [where in general formula (D), R = 3-methyl-2-butenyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (E)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl p-tolyl sulfone [where in general formula (D), R = 3-methyl-2-butenyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0179]

Chemical formula

[0180] Under a nitrogen atmosphere, while stirring a mixture of 2.70 g of 1-chloro-7-methyl-3-methylene-6-octen-4-yl p-tolyl sulfone (≥~95% NMR) synthesized in Example 3 above, 30 ml of tetrahydrofuran and 8 ml of methanol at room temperature, 0.500 g of tetrakis(triphenylphosphine)palladium(0) was added. The reaction mixture was stirred at 50 °C for 25 minutes and then under reflux at 70 °C. Diethyl ether was added, and the mixture was filtered through celite, concentrated, and then separated and purified by silica gel column chromatography to obtain the Z-isomer (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl p-tolyl sulfone and the E-isomer (E)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl p-tolyl sulfone of the target product, 0.740 g (~90.5% GC, Z:E = 100:0), 0.120 g (83.0% GC, Z:E = 34.6:65.4), 0.96 g (86.7% GC, Z:E = 0:100) (total isomer yield 67%).

[0181] (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl p-tolyl sulfone

Chem.

[0182] C 17 H 23 ClO2S Colorless oil IR(D-ATR): ν = 3031, 2968, 2924, 2875, 1597, 1494, 1407, 1377, 1316, 1303, 1292, 1244, 1146, 1117, 1087, 1019, 816, 728, 672, 518 cm -1 。 1H-NMR(500 MHz, CDCl3): δ = 1.48 (3H, br.s), 1.61 (3H, q-like, J =~1 Hz), 2.29 (2H, t, J = 7.2 Hz), 2.44 (3H, s), 2.66 (2H, tq-like, J = 6.7, 1.2 Hz), 3.62 (2H, t, J = 6.9 Hz), 3.86 (2H, s), 4.70 - 4.77 (1H, m), 5.50 (1H, t, J = 7.4 Hz), 7.33 - 7.37 (2H, m), 7.73 - 7.78 (2H, m) ppm. 13 C-NMR(125 MHz, CDCl3): δ = 17.60, 21.60, 25.50, 27.02, 39.00, 42.82, 57.33, 120.79, 123.19, 128.49, 129.79, 133.01, 135.74, 136.66, 144.83 ppm. GC-MS(EI, 70 eV): 41, 65, 91 (base peak), 107, 122, 129, 145, 155, 170.

[0183] (E)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl = p-tolyl = sulfone

Chem.

[0184] C 17 H 23 ClO2S colorless oil IR(D-ATR): ν = 3031, 2970, 2924, 2877, 1597, 1494, 1448, 1405, 1377, 1314, 1302, 1253, 1141, 1118, 1087, 1019, 816, 730, 673, 517 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 1.54 (3H, br.s), 1.65 (3H, q-like, J = ~1 Hz), 2.43 (3H, s), 2.66 (2H, t, J = 7.2 Hz), 2.71 (2H, t, J = 7.0 Hz), 3.59 (2H, t, J = 7.0 Hz), 3.74 (2H, s), 4.78 - 4.83 (1H, m), 5.16 (1H, t, J = 7.6 Hz), 7.30 - 7.34 (2H, m), 7.67 - 7.72 (2H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.66, 21.57, 25.54, 27.34, 32.58, 42.42, 63.35, 120.66, 123.51, 128.54, 129.54, 132.85, 135.04, 138.67, 144.55 ppm. GC-MS (EI, 70 eV): 41, 65, 91, 107, 122, 129, 155, 171 (base peak).

[0185] Example 12 Synthesis of (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl=phenyl=sulfone [where in general formula (D), R = 3-methyl-2-butenyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (E)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl=phenyl=sulfone [where in general formula (D), R = 3-methyl-2-butenyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0186]

Chemical formula

[0187] Under a nitrogen atmosphere, while stirring a mixture of 100.0 g (≈100% GC) of 7-methyl-3-methylene-6-octen-4-yl phenyl sulfone synthesized in Example 4 above, 500 ml of tetrahydrofuran and 125 ml of methanol at room temperature, 18.0 g of tetrakis(triphenylphosphine)palladium(0) was added. The reaction mixture was stirred under reflux at 70 °C for 3.5 hours and then at room temperature for 19 hours. Diethyl ether was added, and the mixture was filtered through celite, concentrated, and then separated and purified by silica gel column chromatography to obtain 14.85 g (Z:E = 100:0 - 95.7:4.3), 32.55 g (Z:E = 70.6:29.4 - 32.3:67.7), and 16.15 g (Z:E = 10.9:89.1 - 0:100) (total isomer yield 66%) of the target Z-isomer (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl) methyl phenyl sulfone and the target E-isomer (E)-(1-chloro-7-methyl-3,6-octadien-3-yl) methyl phenyl sulfone.

[0188] (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl) methyl phenyl sulfone

Chemical Structure

[0189] C 16 H 21 ClO2S Colorless waxy solid. Melting point: 36.4 °C (DSC) IR (D-ATR): ν = 3063, 2966, 2927, 2873, 1585, 1479, 1447, 1317, 1308, 1147, 1085, 903, 745, 722, 689, 655, 614, 533 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 1.49 (3H, br.s), 1.62 (3H, s-like), 2.30 (2H, t, J = 7.1 Hz), 2.67 (2H, tq―like, J = 6.9, ~1 Hz), 3.62 (2H, t, J = 6.9 Hz), 3.89 (2H, s), 4.73 - 4.78 (1H, m), 5.53 (1H, t, J = 7.3 Hz), 7.52 - 7.59 (2H, m), 7.63 - 7.69 (1H, m), 7.86 - 7.91 (2H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.70, 25.51, 27.05, 39.03, 42.81, 57.32, 120.70, 123.04, 128.49, 129.22, 133.15, 133.82, 136.86, 138.73 ppm.

[0190] (E)-(1-Chloro-7-methyl-3,6-octadien-3-yl) methyl = phenyl = sulfone

Chem.

[0191] C 16 H 21 ClO2S Colorless oil. IR (D-ATR): ν = 3062, 2970, 2916, 1712, 1585, 1479, 1447, 1406, 1377, 1307, 1142, 1085, 743, 689, 655, 620, 531 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.55 (3H, br.s), 1.65 (3H, s-like), 2.66 (2H, t, J = 7.1 Hz), 2.72 (2H, t, J = 6.9 Hz), 3.60 (2H, t, J = 7.0 Hz), 3.77 (2H, s), 4.78 - 4.84 (1H, m), 5.17 (1H, t, J = 7.5 Hz), 7.51 - 7.58 (2H, m), 7.61 - 7.67 (1H, m), 7.81 - 7.85 (2H, m) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 17.71, 25.56, 27.38, 32.58, 42.42, 63.32, 120.58, 123.39,128.55, 128.96, 132.96, 133.60, 138.02, 138.89 ppm.

[0192] Example 13 Synthesis of (Z)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl=phenyl=sulfone [wherein in general formula (D), R = 3-methyl-3-butenyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (E)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl=phenyl=sulfone [wherein in general formula (D), R = 3-methyl-3-butenyl group, W = benzenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0193] [Chemical formula]

[0194] Under a nitrogen atmosphere, while stirring a mixture of 4.58 g of 8-chloro-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone synthesized in Example 5 above (96.0% GC, containing 4.3% of the corresponding bromide: 8-bromo-2-methyl-6-methylene-1-octen-5-yl phenyl sulfone), 60 ml of tetrahydrofuran and 16 ml of methanol at room temperature, 0.840 g of tetrakis(triphenylphosphine)palladium(0) was added. The reaction mixture was stirred under reflux at 70 °C for 3 hours and further at room temperature for 18 hours. Diethyl ether was added, and the mixture was filtered through celite, concentrated, and then separated and purified by silica gel column chromatography to obtain 1.67 g (84.2 - 94.3% GC, Z:E = 100:0 - 96.4:3.6), 1.51 g (95.6% GC, Z:E = 32.9:67.1), and 1.22 g (93.0% GC, Z:E = 0:100) of the target Z-isomer (Z)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl phenyl sulfone and the target E-isomer (E)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl phenyl sulfone (total isomer yield 90%).

[0195] (Z)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl phenyl sulfone

Chem.

[0196] C 16 H 21 ClO2S Colorless oil. IR(D-ATR): ν = 3070, 2967, 2934, 1649, 1585, 1478, 1447, 1317, 1307, 1147, 1085, 891, 744, 725, 689, 655, 614, 532 cm -1 . 1H-NMR (500 MHz, CDCl3): δ = 1.61 (3H, br.s), 1.71 - 1.77 (2H, m), 1.79 - 1.84 (2H, m), 2.67 (2H, dt, J = 1.0, 6.7 Hz), 3.62 (2H, t, J = 6.7 Hz), 3.88 (2H, s), 4.51 - 4.53 (1H, m), 4.66 - 4.68 (1H, m), 5.57 (1H, t, J = 7.0 Hz), 7.54 - 7.58 (2H, m), 7.64 - 7.68 (1H, m), 7.87 - 7.91 (2H, m) ppm. 13 C-NMR (125 MHz, CDCl3): δ = 22.34, 26.11, 36.59, 39.00, 42.86, 57.35, 110.42, 123.33, 128.49, 129.20, 133.82, 137.53, 138.68, 144.45 ppm. GC-MS (EI, 70 eV): 39, 55, 77 (base peak), 93, 109, 129, 155, 171.

[0197] (E)-8-chloro-2-methyl-1,5-octadien-6-yl)methyl=phenyl=sulfone

Chemical Structure

[0198] C 16 H 21 ClO2S Colorless oil. IR (D-ATR): ν = 3070, 2968, 2932, 1735, 1649, 1586, 1479, 1447, 1406, 1375, 1307, 1254, 1142, 1085, 889, 742, 689, 656, 621, 532 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 1.66 (3H, br.s), 1.85 - 1.90 (2H, m), 2.11 - 2.17 (2H, m), 2.72 (2H, t, J = 6.9 Hz), 3.62 (2H, t, J = 6.9 Hz), 3.78 (2H, d, J = 0.6 Hz), 4.55 - 4.48 (1H, m), 4.67 - 4.70 (1H, m), 5.25 (1H, t, J = ~7.2 Hz), 7.53 - 7.58 (2H, m), 7.64 - 7.68 (1H, m), 7.83 - 7.87 (2H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 22.34, 26.40, 32.59, 36.72, 42.40, 63.28, 110.52, 123.79, 128.49, 129.03, 133.68, 138.19, 139.61, 144.45 ppm. GC-MS (EI, 70 eV): 39, 55, 77 (base peak), 107, 129, 155, 171.

[0199] Example 14 Synthesis of (3Z,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone [where in general formula (D), R = (E)-cinnamyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (3E,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone [where in general formula (D), R = (E)-cinnamyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0200]

Chemical formula

[0201] Under a nitrogen atmosphere, while stirring a mixture of 22.2 g of the crude (E)-7-chloro-5-methylene-1-phenyl-1-hepten-4-yl = p-tolyl = sulfone synthesized in Example 6 above, 2.33 g of triphenylphosphine, 300 ml of tetrahydrofuran and 100 ml of methanol at room temperature, 3.42 g of tetrakis(triphenylphosphine)palladium(0) was added. The reaction mixture was stirred under reflux at 70 °C for 12 hours. The reaction mixture was filtered through Celite, concentrated, and then separated and purified by silica gel column chromatography to obtain the Z-isomer (3Z,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone of the target product and the E-isomer (3E,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone of the target product in amounts of 6.17 g (Z:E = 95.6:4.4), 4.76 g (Z:E = ~40:60), 4.68 g (Z:E = 0:100), (total isomer yield 74%).

[0202] (3Z,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone

Chemical Structure

[0203] C 21 H 23 ClO2S Colorless oil. IR(D-ATR): ν = 3026, 2961, 2923, 1597, 1494, 1448, 1315, 1302, 1145, 1118, 1086, 967, 816, 735, 694, 671, 635, 603, 516 cm -1 . 1H-NMR(500 MHz, CDCl3): δ = 2.40 (3H, s), 2.62 (2H, br.t, J = ~6.8 Hz), 2.73 (2H, dt-like, J = 1.0, 6.7 Hz), 3.67 (2H, t, J = 6.7 Hz), 3.91 (2H, s), 5.69 (1H, t, J = 7.4 Hz), 5.88 (1H, dt, J = ~15.8, 6.3 Hz), 6.24 (1H, dt-like, J = 16.1, ~1.6 Hz), 7.18 - 7.23 (1H, m), 7.25 - 7.32 (4H, m), 7.35 (2H, d-like, J = ~8.5 Hz), 7.78 (2H, dt-like, J = 8.2, ~1.8 Hz) ppm. 13 C-NMR(125 MHz, CDCl3): δ = 21.61, 31.34, 39.07, 42.78, 57.15, 124.73, 125.97, 126.63, 127.21, 128.45, 128.49, 129.87, 131.02, 134.85, 135.77, 137.13, 144.93 ppm.

[0204] (3E,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone

[0205]

Chem.

[0206] C 21 H 23 ClO2S Yellow solid. IR(D-ATR): ν = 3026, 2993, 2969, 2953, 2925, 1596, 1493, 1444, 1405, 1312, 1301, 1251, 1217, 1177, 1139, 1111, 1084, 962, 815, 744, 725, 694, 657, 631, 532, 510 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 2.33 (3H, s), 2.78 (2H, br.t, J = ~6.8 Hz), 2.92 (2H, dt-like, J = 1.3, 7.1 Hz), 3.65 (2H, t, J = 6.8 Hz), 3.81 (2H, s-like), 5.33 (1H, t, J = 7.5 Hz), 5.94 (1H, dt, J = 15.9, 6.7 Hz), 6.24 (1H, dt-like, J = 15.9, 1.5 Hz), 7.20 - 7.38 (7H, m), 7.71 (2H, dt-like, J = 8.2, ~1.9 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 21.52, 31.68, 32.53, 42.47, 63.31, 125.06, 125.99, 126.65, 127.27, 128.54, 128.56, 129.66, 131.03, 135.00, 136.98, 137.18, 144.73 ppm.

[0207] Example 15 Synthesis of (Z)-(1-chloro-3-dodecen-3-yl)methyl = p-tolyl = sulfone [where in general formula (D), R = n-octyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z] and (E)-(1-chloro-3-dodecen-3-yl)methyl = p-tolyl = sulfone [where in general formula (D), R = n-octyl group, W = p-toluenesulfonyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E]

[0208]

Chemical formula

[0209] Under a nitrogen atmosphere, while stirring a mixture of 7.720 g of 1-chloro-3-methylenedodecan-4-yl p-tolyl sulfone synthesized in Example 7 above, 0.820 g of triphenylphosphine, 80 ml of tetrahydrofuran and 20 ml of methanol at room temperature, 1.20 g of tetrakis(triphenylphosphine)palladium(0) was added. The reaction mixture was stirred under reflux at 70 °C for 5 hours. Diethyl ether was added to the reaction mixture, and the mixture was filtered through celite, concentrated, and then separated and purified by silica gel column chromatography to obtain 2.40 g (Z:E = 100:0), 1.30 g (Z:E = 30.2:69.8), 2.83 g (Z:E = 0:100) of the Z-isomer (Z)-(1-chloro-3-dodecen-3-yl)methyl p-tolyl sulfone of the target product and the E-isomer (E)-(1-chloro-3-dodecen-3-yl)methyl p-tolyl sulfone of the target product, (total yield of isomers 86%).

[0210] (Z)-(1-chloro-3-dodecen-3-yl)methyl p-tolyl sulfone [Chemical formula]

[0211] C 20 H 31 ClO2S Colorless waxy solid. Melting point: 50.7 °C (DSC) IR (D-ATR): ν = 3067, 3045, 2962, 2919, 2849, 1599, 1494, 1468, 1451, 1435, 1413, 1386, 1311, 1302, 1292, 1256, 1245, 1175, 1149, 1131, 1087, 1020, 945, 918, 893, 812, 738, 705, 654, 640, 609, 550, 522, 511 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 0.88 (3H, t, J = 6.8 Hz), 1.05 - 1.32 (12H, m), 1.56 - 1.62 (2H, m), 2.45 (3H, s), 2.66 (2H, dt, J = 1.0, 6.8 Hz), 3.62 (2H, t, J = 6.7 Hz), 3.84 (2H, s), 5.55 (1H, t, J = 7.3 Hz), 7.34 (2H, d-like, J = ~8 Hz), 7.75 (2H, dt, J = ~8, 1.9 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 14.09, 21.63, 22.63, 28.14, 28.92, 29.17, 29.20, 29.34, 31.82, 38.99, 42.93, 57.28, 122.97, 128.51, 129.74, 135.78, 138.33, 144.76 ppm. GC-MS (EI, 70 eV): 41, 69, 77, 91, 109, 130, 157, 178, 214 (base peak), 249, 277, 327, 355.

[0212] (E)-(1-Chloro-3-dodecen-3-yl)methyl = p-tolyl = sulfone

Chemical Structure

[0213] C 20 H 31 ClO2S Colorless waxy solid. Melting point: 37.3 °C (DSC) IR (D-ATR): ν = 2987, 2954, 2921, 2871, 2851, 1598, 1494, 1469, 1449, 1431, 1406, 1384, 1309, 1301, 1260, 1246, 1177, 1144, 1125, 1087, 1020, 946, 920, 881, 815, 775, 720, 704, 656, 632, 620, 540, 510 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 0.88 (3H, t, J = 7.1 Hz), 1.12 - 1.32 (12H, m), 1.94 - 2.02 (2H, m), 2.44 (3H, s), 2.69 (2H, t, J = 7.1 Hz), 3.59 (2H, t, J = 7.1 Hz), 3.75 (2H, s), 5.25 (1H, t, J = 7.3 Hz), 7.33 (2H, d-like, J = ~8 Hz), 7.71 (2H, dt, J = 8.4, 1.9 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 14.10, 21.62, 22.66, 28.32, 29.00, 29.17, 29.19, 29.40, 31.86, 32.56, 42.51, 63.45, 123.49, 128.52, 129.61, 135.26, 140.36, 144.59 ppm. GC-MS (EI, 70 eV): 41, 69, 77, 91, 109, 139, 157, 178, 214 (base peak), 249, 277, 303, 341.

[0214] Example <Synthesis of Halide Compounds Represented by the Following General Formula (B)>

[0215]

Chemical Structure

[0216] Example 16 Synthesis of (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene [when R = (E)-3,7-dimethyl-2,6-octadienyl group, X = Cl, and the geometric isomerism of the double bond at the 9th position is E in the general formula (B)]

[0217]

Chemical Structure

[0218] Under a nitrogen atmosphere, while stirring a mixture of 2.50 g (100% ZE) of (3Z,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone synthesized in Example 8 above, 0.195 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride and 70 ml of tetrahydrofuran, 6.95 ml of a 1.7 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After stirring the reaction mixture under ice-cooling for 65 minutes, 42 g of a 12.5% aqueous sodium hydroxide solution and then 4.73 g of 35% aqueous hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and extraction was carried out with n-hexane. A crude product was obtained by post-treatment operations such as ordinary washing, drying and concentration from the n-hexane solution.

[0219] This product was a 79.5:20.5 mixture of the target product (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene and the E-β-isomer (E)-(12-chloro-2,6-dimethyl-10-methylene-2,6-dodecadiene) resulting from a desulfonation reaction accompanied by allyl rearrangement.

[0220] The crude product was separated and purified by silica gel column chromatography to obtain 0.610 g (97.7% GC, EE-α:E-β = 72.8:27.2 GC) of the target product (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene and 0.550 g (97.3% GC, target product:E-β-isomer = 87.8:12.2 GC) (total isomer yield 73%). Thus, the isomer purity of the target product can be improved by purification means such as chromatography.

[0221] (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical formula

[0222] C 15 H 25 Cl Colorless oil IR (D-ATR): ν = 2967, 2916, 2856, 1670, 1450, 1382, 1325, 1294, 1246, 1151, 1108, 984, 935, 888, 834, 727, 661 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s), 1.62 (3H, q-like, J = ~1 Hz), 1.65 (3H, q-like, J = ~1 Hz), 1.68 (3H, q-like, J = ~1 Hz), 1.95 - 2.01 (2H, m), 2.03 - 2.11 (2H, m), 2.44 (2H, t-like, J = 7 Hz), 2.71 (2H, t-like, J = ~7 Hz), 3.57 (2H, t, J = 7.4 Hz), 5.07 - 5.12 (2H, m), 5.19 - 5.24 (1H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 15.78, 16.06, 17.68, 25.69, 26.66, 26.95, 39.64, 42.63, 43.20, 122.51, 124.25, 126.70, 130.90, 131.38, 135.43 ppm。 GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107, 123 (base peak), 135, 157, 171, 183, 197, 211, 225, 240 (M + )。

[0223] Comparative Example: Separately synthesized E-β-isomer: (E)-12-Chloro-2,6-dimethyl-10-methylene-2,6-dodecadiene

[0224]

Chem.

[0225] C 15 H 25 Cl Colorless oil IR (D-ATR): ν = 2965, 2925, 2855, 1646, 1448, 1377, 1325, 1300, 1242, 1152, 1108, 984, 895, 834, 739, 661 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.61 (6H, br.s), 1.68 (3H, br.s.), 1.67 (3H, s), 1.96 - 2.01 (2H, m), 2.03 - 2.11 (4H, m), 2.12 - 2.17 (2H, m), 2.50 (2H, t, J = 7.5 Hz), 3.61 (1H, t, J = 7.5 Hz), 4.82 (1H, br.s), 4.88 (1H, br.s), 5.07 - 5.15 (2H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 16.02, 17.67, 25.67, 26.17, 26.65, 35.82, 39.16, 39.65, 42.80, 111.67, 123.54, 124.26, 131.32, 135.55, 145.55 ppm。 GC-MS (EI, 70 eV): 27, 41, 55, 69 (base peak), 81, 93, 109, 121, 136, 169, 197, 240 (M + )。

[0226] Example 17 Synthesis of (6E,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene [where R = (E)-3,7-dimethyl-2,6-octadienyl group, X = Cl, and the geometric isomerism of the double bond at the 9th position is Z in the general formula (B)]

[0227]

Chemical formula

[0228] Under a nitrogen atmosphere, while stirring a mixture of 2.75 g of (3E,6E)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone synthesized in Example 8 above (87.7% GC, 97.7% ZE), 0.210 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 80 ml of tetrahydrofuran, 8.00 ml of a 1.7 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes while stirring under ice-cooling. After stirring the reaction mixture under ice-cooling for 50 minutes, 48.0 g of a 12.5% aqueous sodium hydroxide solution and then 5.40 g of 35% aqueous hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and the mixture was extracted with diethyl ether. After the usual post-treatment operations of washing, drying, and concentration from the diethyl ether solution, and then purification by silica gel column chromatography, the target product (6E,9Z)-(12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene 1.53 g (84.7 - 95.8% GC) (yield 86%) was obtained.

[0229] (6E,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical Structure

[0230] C 15 H 25 Cl Colorless oil IR (D-ATR): ν = 2967, 2915, 2856, 1650, 1445, 1378, 1318, 1297, 1242, 1152, 1134, 1108, 1023, 984, 934, 886, 833, 725, 659 cm -1 . 11H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s), 1.63 (3H, q-like, J = ~1 Hz), 1.68 (3H, q-like, J = ~1.5 Hz), 1.72 (3H, q, J = 1.3 Hz), 1.95 - 2.01 (2H, m), 2.03 - 2.11 (2H, m), 2.53 (2H, t, J = 7.6 Hz), 2.71 (2H, t, J = 7.3 Hz), 3.54 (2H, t, J = 7.7 Hz), 5.05 - 5.12 (2H, m), 5.28 (1H, t-like, J = ~7.4 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 16.08, 17.68, 23.16, 25.68, 26.64, 26.90, 35.23, 39.65, 42.64, 122.53, 124.24, 127.34, 130.87, 131.41, 135.44 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107, 123 (base peak), 135, 157, 171, 183, 197, 211, 225, 240 (M + ).

[0231] Example 18 Synthesis of (6Z,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene [wherein in general formula (B), R = (Z)-3,7-dimethyl-2,6-octadienyl group, X = Cl, and the geometric isomerism of the double bond at the 9th position is E]

[0232]

Chemical formula

[0233] Under a nitrogen atmosphere, a mixture of 6.0 g (100% ZE) of (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone synthesized in the same manner as in Example 9 above, 0.400 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 160 ml of tetrahydrofuran was stirred under ice-cooling, and 27.4 ml of a 1.0 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After the reaction mixture was stirred under ice-cooling for 3 hours, 96 g of a 12.5% aqueous sodium hydroxide solution and then 10.4 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture, and the organic layer was separated. A crude product was obtained by performing post-treatment operations such as normal washing, drying, and concentration from the organic layer.

[0234] This product was a mixture of the target product (6Z,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene and the Z-β-isomer (Z)-12-chloro-2,6-dimethyl-10-methylene-2,6-dodecadiene resulting from a desulfonation reaction accompanied by allylic rearrangement in a ratio of 80.7:19.3.

[0235] The crude product was separated and purified by silica gel column chromatography to obtain 1.01 g (99.1% GC, target product:Z-β-isomer = 65.3:32.9 GC) and 2.50 g (97.8% GC, 84.7:13.1) (total isomer yield 82%) of the target product (6Z,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene. Thus, the isomer purity of the target product can be improved by purification means such as chromatography.

[0236] (6Z,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical formula

[0237] C 15 H 25 Cl Colorless oil IR (D-ATR): ν = 2965, 2916, 2856, 1648, 1449, 1376, 1324, 1294, 1246, 1151, 1108, 1087, 984, 888, 831, 727, 660 cm -1 。 1 ¹H-NMR (500 MHz, CDCl₃): δ = 1.61 (3H, q-like, J = ~1 Hz), 1.65 (3H, q-like, J = ~1 Hz), 1.68 - 1.70 (3H, m), 1.70 (3H, q, J = 1.3 Hz), 2.02 - 2.10 (4H, m), 2.43 (2H, t, J = 7.5 Hz), 2.71 (2H, t, J = 7.3 Hz), 3.57 (2H, t, J = 7.5 Hz), 5.07 - 5.15 (2H, m), 5.20 (1H, tq, J = 7.1, 1.3 Hz) ppm。 13 ¹³C-NMR (125 MHz, CDCl₃): δ = 15.77, 17.63, 23.37, 25.71, 26.54, 26.83, 31.97, 42.64, 43.17, 123.28, 124.21, 126.78, 130.87, 131.63, 135.63 ppm。 GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107 (base peak), 121, 144, 158, 171, 183, 197, 211, 225, 240 (M + )。

[0238] Comparative Example: Separately synthesized Z-β-isomer: (Z)-12-chloro-2,6-dimethyl-10-methylene-2,6-dodecadiene

[0239]

Chemical Structure

[0240] C 15 H 25 Cl Colorless oil IR (D-ATR): ν = 2964, 2927, 2856, 1646, 1449, 1376, 1325, 1242, 1152, 1109, 984, 895, 831, 738, 661 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, br.s), 1.69 (6H, s-like), 1.97 - 2.10 (6H, m), 2.10 - 2.17 (2H, m), 2.49 (2H, t, J = 7.5 Hz), 3.61 (2H, t, J = 7.5 Hz), 4.82 (1H, br.s), 4.87 (1H, br.s), 5.09 - 5.15 (2H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 17.62, 23.34, 25.71, 26.08, 26.54, 31.98, 36.10, 39.19, 42.78, 111.63, 124.21, 124.33, 131.63, 135.74, 145.57 ppm。 GC-MS (EI, 70 eV): 27, 41, 53, 69 (base peak), 81, 93, 109, 129, 156, 169, 197, 240 (M + )。

[0241] Example 19 Synthesis of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene [where in general formula (B), R = (Z)-3,7-dimethyl-2,6-octadienyl group, X = Cl, and the geometric isomerism of the double bond at the 9th position is Z]

[0242]

Chemical formula

[0243] Under a nitrogen atmosphere, a mixture of 1.50 g of (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone (86.4% GC, 92.5% EZ) synthesized in the same manner as in Example 9 above, 0.10 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 40 ml of tetrahydrofuran was stirred under ice-cooling, and 4.00 ml of a 1.0 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After the reaction mixture was stirred under ice-cooling for 70 minutes, 7.0 g of a 12.5% aqueous sodium hydroxide solution and then 1.50 g of 35% aqueous hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 0.140 g (97.6% GC) and 0.550 g (94.1% GC) of the target product (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene (yield 83%) were obtained.

[0244] (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene

Chem.

[0245] C 15 H 25 Cl Colorless oil IR(D-ATR): ν = 2966, 2928, 2856, 1660, 1446, 1377, 1318, 1297, 1241, 1145, 1108, 1084, 984, 934, 830, 725, 659 cm -1 。 11H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, q-like, J = ~1 Hz), 1.68 - 1.72 (6H, m), 1.72 (3H, q, J = 1.3 Hz), 2.03 - 2.09 (4H, m), 2.52 (2H, t, J = 7.5 Hz), 2.71 (2H, t, J = 7.3 Hz), 3.54 (2H, t, J = 7.5 Hz), 5.08 (1H, tq-like, J = 7.3, ~1.3 Hz), 5.10 - 5.16 (1H, m), 5.26 (1H, tq, J = 7.3, ~0.8 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.64, 23.15, 23.36, 25.71, 26.53, 26.76, 31.97, 35.20, 42.61, 123.31, 124.18, 127.48, 130.82, 131.67, 135.71 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107 (base peak), 121, 144, 157, 171, 183, 197, 211, 225, 240 (M + ).

[0246] Example 20 Synthesis of (6E,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene [when R = (E)-3,7-dimethyl-2,6-octadienyl group, X = Br, and the geometric isomerism of the double bond at the 9th position is E in general formula (B)]

[0247]

Chemical formula

[0248] Under a nitrogen atmosphere, a mixture of 1.200 g (81.7% EE-α) of (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 16 above, 10.0 g of bromoethane, 0.250 g of sodium bromide and 20 ml of N-methyl-2-pyrrolidone was stirred at 60 - 75 °C for 15.5 hours. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying and concentration from the n-hexane solution, followed by purification by silica gel column chromatography, 1.30 g (92.0% GC, 80.9% EE-α, yield 81%) of the target product (6E,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene was obtained.

[0249] (6E,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical Structure

[0250] C 15 H 25 Br Colorless oil IR (D-ATR): ν = 2968, 2915, 2856, 1698, 1647, 1447, 1382, 1311, 1266, 1210, 1137, 1108, 1084, 984, 934, 888, 833, 656 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s-like), 1.62 (3H, q-like, J = ~1.1 Hz), 1.65 (3H, q-like, J = 1.1 Hz), 1.68 (3H, q-like, J = 1.1 Hz), 1.95 - 2.02 (2H, m), 2.02 - 2.12 (2H, m), 2.53 (2H, t-like, J = ~7.5 Hz), 2.71 (2H, t-like, J = ~7 Hz), 3.43 (2H, t, J = 7.5 Hz), 5.05 - 5.15 (2H, m), 5.21 (1H, tq, J = 7.3, ~1.3 Hz) ppm. 1313C-NMR(125 MHz, CDCl3): δ = 15.63, 16.07, 17.68, 25.70, 26.65, 26.95, 31.67, 39.64, 42.90, 122.45, 124.24, 126.68, 131.38, 131.71, 135.47 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107, 123 (base peak), 149, 173, 187, 201, 215, 241, 269, 284 (M + )

[0251] Example 21 Synthesis of (6E,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene [wherein in general formula (B), R = (E)-3,7-dimethyl-2,6-octadienyl group, X = Br, and the geometric isomerism of the double bond at the 9th position is Z]

[0252]

Chemical formula

[0253] Under a nitrogen atmosphere, a mixture of 1.60 g (91.5% GC) of (6E,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 17 above, 8.00 g of bromoethane, 0.170 g of sodium bromide, and 30 ml of N-methyl-2-pyrrolidone was heated to 80 - 95 °C and stirred for 15 hours while refluxing. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 1.27 g of the target product (6E,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene (~98.3% GC, 82.0% EZ, yield 73%) was obtained.

[0254] (6E,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical formula

[0255] C 15 H 25 Br Colorless oil IR (D-ATR): ν = 2968, 2927, 2856, 1649, 1445, 1377, 1307, 1268, 1210, 1152, 1126, 1108, 1021, 984, 933, 887, 832, 652 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s-like), 1.63 (3H, q-like, J =~1 Hz), 1.67 - 1.74 (6H, m), 1.95 - 2.02 (2H, m), 2.03 - 2.11 (2H, m), 2.62 (2H, t, J = 7.8 Hz), 2.71 (2H, t, J = 7.3 Hz), 3.40 (2H, t, J = 7.7 Hz), 5.05 - 5.14 (2H, m), 5.28 (1H, t-like, J =~7.4 Hz) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 16.10, 17.68, 22.96, 25.69, 26.63, 26.90, 30.81, 35.50, 39.64, 122.46, 124.22, 127.24, 131.41, 131.72, 135.46 ppm。 GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107, 123 (base peak), 135, 149, 157, 173, 187, 201, 215, 241, 255, 269, 284 (M + )。

[0256] Example 22 Synthesis of (6Z,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene [where R = (Z)-3,7-dimethyl-2,6-octadienyl group, X = Br, and the geometric isomerism of the double bond at the 9th position is E in general formula (B)]

[0257]

Chemical formula

[0258] Under a nitrogen atmosphere, a mixture of 1.00 g of (6Z,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene (97.8% GC, 84.7% ZE) synthesized in the same manner as in Example 18 above, 5.00 g of bromoethane, 0.110 g of sodium bromide and 20 ml of N-methyl-2-pyrrolidone was heated to reflux at 80 °C for 18 hours, and then an additional 5.00 g of bromoethane was added and stirred for 4 hours. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 1.27 g of the target product (6Z,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene (~98.3% GC, 82.0% ZE, yield 73%) was obtained.

[0259] (6Z,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical formula

[0260] C 15 H 25 Br Colorless oil IR(D-ATR): ν = 2966, 2915, 2856, 1648, 1447, 1376, 1311, 1266, 1210, 1137, 1108, 1083, 984, 934, 888, 831, 656 cm -1 . 1 1H-NMR(500 MHz, CDCl3): δ = 1.61(3H, q-like, J = ~1 Hz), 1.65(3H, q-like, J = ~1 Hz), 1.67 - 1.71(6H, m), 1.98 - 2.14(4H, m), 2.53(2H, t-like, J = 7.5 Hz), 2.71(2H, t, J = 7.2 Hz), 3.42(2H, t, J = 7.5 Hz), 5.07 - 5.15(2H, m), 5.19(1H, tq, J = 7.1, 1.3 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 15.63, 17.63, 23.37, 25.71, 26.54, 26.83, 31.60, 31.97, 42.91, 123.22, 124.20, 126.76, 131.63, 131.68, 135.66 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107 (base peak), 121, 135, 149, 163, 177, 201, 215, 241, 255, 269, 284 (M + )

[0261] Example 23 Synthesis of (6Z,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene [where R = (Z)-3,7-dimethyl-2,6-octadienyl group, X = Br, and the geometric isomerism of the double bond at the 9th position is Z in general formula (B)]

[0262]

Chemical formula

[0263] Under a nitrogen atmosphere, a mixture of 2.40 g of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene (99.1% GC, 94.6% ZZ) synthesized in the same manner as in Example 19 above, 10.0 g of bromoethane, 0.300 g of sodium bromide, and 40 ml of N-methyl-2-pyrrolidone was heated to reflux at 70 °C for 10 hours, and then an additional 5.00 g of bromoethane was added and stirred for 12 hours. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 2.66 g of the target product (6Z,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene (81.0 - 88.3% GC, ~88.1% ZZ, yield 85%) was obtained.

[0264] (6Z,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical formula

[0265] C 15 H 25 Br Colorless oil IR (D-ATR): ν = 2967, 2927, 2856, 1672, 1446, 1377, 1308, 1268, 1210, 1124, 1108, 1022, 985, 934, 830, 652 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, q-like, J = ~1 Hz), 1.68 - 1.71 (6H, m), 1.72 (3H, q, J = 1.3 Hz), 2.05 - 2.10 (4H, m), 2.62 (2H, t, J = 7.8 Hz), 2.70 (2H, t, J = 7.3 Hz), 3.40 (2H, t, J = 7.8 Hz), 5.05 - 5.17 (2H, m), 5.26 (1H, tq-like, J = 7.3, ~0.6 Hz) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 17.65, 22.95, 23.36, 25.72, 26.52, 26.76, 30.77, 31.97, 35.46, 123.25, 124.16, 127.38, 131.65, 131.68, 135.73 ppm。 GC-MS (EI, 70 eV): 41, 55, 69, 81, 93, 107 (base peak), 121, 135, 149, 163, 177, 201, 215, 241, 255, 269, 284 (M + )。

[0266] Example 24 Synthesis of (6E,9E)-12-Iodo-2,6,10-trimethyl-2,6,9-dodecatriene [when R = (E)-3,7-dimethyl-2,6-octadienyl group, X = I, and the geometric isomerism of the double bond at the 9th position is E in general formula (B)]

[0267]

Chemical formula

[0268] Under a nitrogen atmosphere, a mixture of 40 mg (97.3% GC, 87.8% EE) of (6E,9E)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 16 above, 2.00 g of bromoethane, 50 mg of sodium iodide, 10 g of acetone and 4.0 g of N-methyl-2-pyrrolidone was stirred for 19 hours while heating and refluxing at 70 to 85 °C. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 39 mg (92.4 - 97.2% GC, 47.4 - 89.0% EE, yield 71%) of the target product (6E,9E)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene was obtained.

[0269] (6E,9E)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene

Chemical Structure

[0270] C 15 H 25 I Colorless oil IR (D-ATR): ν = 2966, 2923, 2854, 1647, 1444, 1382, 1328, 1304, 1243, 1169, 1131, 1108, 984, 935, 888, 833, 622 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s-like), 1.62 (3H, q, J = 1.2 Hz), 1.64 (3H, q, J = 1.2 Hz), 1.68 (3H, q, J = 1.2 Hz), 1.95 - 2.01 (2H, m), 2.02 - 2.11 (2H, m), 2.53 (2H, t-like, J = ~8 Hz), 2.69 (2H, t-like, J = ~7 Hz), 3.22 (2H, t, J = 7.8 Hz), 5.04 - 5.14 (2H, m), 5.19 (1H, tq-like, J = ~7, ~1.3 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 5.01, 15.37, 16.10, 17.70, 25.71, 26.68, 26.96, 39.65, 43.84, 122.44, 124.27, 126.35, 131.39, 133.39, 135.47 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 91, 107, 123 (base peak), 139, 155, 177, 195, 221, 263, 289.

[0271] Example 25 Synthesis of (6Z,9Z)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene [wherein in general formula (B), R = (Z)-3,7-dimethyl-2,6-octadienyl group, X = I, and the geometric isomerism of the double bond at the 9-position is Z]

[0272] [Chemical formula]

[0273] Under a nitrogen atmosphere, a mixture of 100 mg (89.5% GC) of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in the same manner as in Example 19 above, 450 mg of sodium iodide, and 10 ml of acetone was heated and refluxed at 60 - 65 °C for 7 hours, and then 10 ml of 2-butanone was added and stirred at 80 - 85 °C for 3 hours. After cooling the reaction mixture, it was concentrated under reduced pressure. The residue was a 68.6:31.4 mixture of the starting material (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene and the target product (6Z,9Z)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene. This was used as the starting material for the next step as a crude product.

[0274] (6Z,9Z)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene [Chemical formula]

[0275] C 15H 25 I GC-MS (EI, 70 eV): 41, 55, 69 (base peak), 91, 107, 123, 149, 177, 195, 219, 236, 262, 289, 332 (M + )。 [[ID=۸]]

[0276] Synthesis of Example 26 (E)-8-chloro-2,6-dimethyl-2,5-octadiene [when R = 3-methyl-2-butenyl group, X = Cl in the general formula (B), and the geometric isomerism of the double bond at the 5th position is E]

[0277]

Chemical formula

[0278] Under a nitrogen atmosphere, a mixture of 10.2 g of (Z)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl=phenyl=sulfone synthesized in Example 12 above (~80% GC, 95.7% Z), 0.96 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 300 ml of tetrahydrofuran was stirred while being ice-cooled, and 60 ml of a 1.0 M lithium triethylborohydride-tetrahydrofuran solution was added dropwise over 15 minutes. After stirring the reaction mixture for 65 minutes while ice-cooled, 100 g of a 12.5% aqueous sodium hydroxide solution and then 26.0 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 4.19 g of the target product (E)-8-chloro-2,6-dimethyl-2,5-octadiene (78.3 - 100% GC, yield 77%) was obtained.

[0279] (E)-8-chloro-2,6-dimethyl-2,5-octadiene

Chemical formula

[0280] C 10 H 17 Cl Colorless oil IR (D-ATR): ν = 2969, 2915, 2857, 1450, 1376, 1324, 1294, 1247, 1150, 1105, 984, 933, 831, 726, 660 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.63 (3H, s-like), 1.65 (3H, s-like), 1.69 (3H, q-like, J =~1 Hz), 2.44 (2H, t-like, J =~7.5 Hz), 2.70 (2H, t, J = 7.1 Hz), 3.57 (2H, t, J = 7.3 Hz), 5.06 - 5.11 (1H, m), 5.19 - 5.23 (1H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 15.76, 17.71, 25.66, 27.07, 42.63, 43.18, 122.66, 126.62, 130.91, 131.83 ppm。 GC-MS (EI, 70 eV): 41, 53, 67, 81, 93, 109 (base peak), 121, 137, 157, 172 (M + )。

[0281] Synthesis of Example 27 (Z)-8-chloro-2,6-dimethyl-2,5-octadiene [when R = 3-methyl-2-butenyl group, X = Cl, and the geometric isomerism of the double bond at the 5th position is Z in the general formula (B)]

[0282]

Chemical formula

[0283] Under a nitrogen atmosphere, a mixture of 3.75 g of (E)-(1-chloro-7-methyl-3,6-octadien-3-yl)methyl=phenyl=sulfone synthesized in Example 12 above (~80% GC, 100% E), 0.35 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride and 120 ml of tetrahydrofuran was stirred while cooling with ice, and 22 ml of a 1.0 M lithium triethylborohydride-tetrahydrofuran solution was added dropwise over 10 minutes. After the reaction mixture was stirred for 2 hours while cooling with ice, 80 g of a 12.5% aqueous sodium hydroxide solution and then 9.50 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 1.58 g of the target product (Z)-8-chloro-2,6-dimethyl-2,5-octadiene (93.3 - 97.2% GC, 82.0 - 58.3% Z, yield 76%) was obtained.

[0284] (Z)-8-chloro-2,6-dimethyl-2,5-octadiene

Chemical formula

[0285] C 10 H 17 Cl Colorless oil IR (D-ATR): ν = 2968, 2928, 2914, 2877, 1445, 1377, 1318, 1297, 1242, 1103, 825, 725, 659 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.64 (3H, s-like), 1.69 (3H, q-like, J = ~1.1 Hz), 1.72 (3H, q-like, J = ~1.3 Hz), 2.53 (2H, t, J = 7.5 Hz), 2.70 (2H, t, J = 7.3 Hz), 3.54 (2H, t, J = 7.5 Hz), 5.05 - 5.10 (1H, m), 5.25 - 5.31 (1H, t-like, J = ~7 Hz) ppm. 13C-NMR(125MHz, CDCl3): δ = 17.71, 23.14, 25.67, 27.02, 35.22, 42.62, 122.69, 126.63, 130.87, 131.83 ppm. GC-MS(EI, 70eV): 41, 53, 67, 81, 93, 109 (base peak), 121, 157, 172 (M + ).

[0286] Example 28 Synthesis of (E)-8-bromo-2,6-dimethyl-2,5-octadiene [when R = 3-methyl-2-butenyl group, X = Br in general formula (B), and the geometric isomerism of the double bond at the 5th position is E]

[0287]

Chemical formula

[0288] Under a nitrogen atmosphere, a mixture of 2.70 g (84.6% GC) of (E)-8-chloro-2,6-dimethyl-2,5-octadiene synthesized in Example 26 above, 5.0 g of bromoethane, 0.200 g of sodium bromide, and 10 ml of N-methyl-2-pyrrolidone was stirred for 11 hours while heating and refluxing at 60 - 70 °C. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, 2.66 g (80.7% GC, yield 81%) of the target product (E)-8-bromo-2,6-dimethyl-2,5-octadiene was obtained. This had sufficient purity and was used as a raw material for the next step as a crude product.

[0289] (E)-8-bromo-2,6-dimethyl-2,5-octadiene

Chemical formula

[0290] C 10 H 17 Br Colorless oil IR (D-ATR): ν = 2969, 2914, 2857, 1697, 1447, 1376, 1311, 1266, 1211, 1137, 1104, 984, 933, 893, 831, 759, 655 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.63 (3H, s-like), 1.65 (3H, q-like, J = 1.2 Hz), 1.69 (3H, q-like, J = ~1.3 Hz), 2.53 (2H, t, J = 7.7 Hz), 2.70 (2H, t, J = 7.2 Hz), 3.43 (2H, t, J = 7.6 Hz), 5.06 - 5.13 (1H, m), 5.18 - 5.24 (1H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 15.62, 17.71, 25.66, 27.06, 31.62, 42.89, 122.60, 126.60, 131.72, 131.85 ppm。 GC-MS (EI, 70 eV): 41, 53, 67, 81, 93, 109 (base peak), 121, 137, 203, 216 (M + )。

[0291] Example 29 Synthesis of (Z)-8-bromo-2,6-dimethyl-2,5-octadiene [wherein in general formula (B), R = 3-methyl-2-butenyl group, X = Cl, and the geometric isomerism of the double bond at the 5-position is Z]

[0292]

Chemical Structure

[0293] Under a nitrogen atmosphere, a mixture of 1.47 g of (Z)-8-chloro-2,6-dimethyl-2,5-octadiene synthesized in Example 27 above (93.3% GC, 82.0% Z), 10.2 g of bromoethane, 0.220 g of sodium bromide and 10 ml of N-methyl-2-pyrrolidone was heated to 80 - 90 °C and stirred vigorously for 9 hours while refluxing violently. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 1.49 g of the target product (Z)-8-bromo-2,6-dimethyl-2,5-octadiene (91.1 - 94.4% GC, 51.8 - 73.0% Z, yield 76%) was obtained.

[0294] (Z)-8-bromo-2,6-dimethyl-2,5-octadiene

Chemical formula

[0295] C 10 H 17 Br Colorless oil IR(D-ATR): ν = 2969, 2928, 2914, 2857, 1445, 1377, 1308, 1268, 1210, 1127, 1102, 889, 825, 652 cm -1 . 1 1H-NMR(500 MHz, CDCl3): δ = 1.64(3H, s-like), 1.69(3H, q-like, J = ~1.1 Hz), 1.72(3H, q-like, J = ~1.2 Hz), 2.63(2H, t, J = 7.6 Hz), 2.70(2H, t, J = 7.1 Hz), 3.40(2H, t, J = 7.6 Hz), 5.05 - 5.12(1H, m), 5.28(1H, t-like, J = ~7.5 Hz) ppm. 13 13C-NMR(125 MHz, CDCl3): δ = 17.73, 22.94, 25.67, 27.02, 30.79, 35.48, 122.62, 127.19, 131.72, 131.86 ppm. GC-MS (EI, 70 eV): 41, 53, 67, 81, 93, 109 (base peak), 121, 137, 203, 216 (M + ).

[0296] Example 30 Synthesis of (1E,4E)-7-chloro-5-methyl-1-phenyl-1,4-heptadiene [wherein in general formula (B), R = (E)-cinnamyl group, X = Cl, and the geometric isomerism of the double bond at the 4-position is E]

[0297]

Chemical formula

[0298] Under a nitrogen atmosphere, a mixture of 3.00 g (95.6% Z) of (3Z,6E)-(1-chloro-7-phenyl-3,6-heptadien-3-yl)methyl = p-tolyl = sulfone synthesized in Example 14 above, 0.24 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 85 ml of tetrahydrofuran was stirred while cooling with ice, and 8.50 ml of a 1.7 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After stirring the reaction mixture for 2 hours while cooling with ice, 50 g of a 12.5% aqueous sodium hydroxide solution and then 5.80 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and it was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 1.59 g (93.5 - 97.8% GC, 75.2 - 80.3% EE, yield 92%) of the target product (1E,4E)-7-chloro-5-methyl-1-phenyl-1,4-heptadiene was obtained.

[0299] (1E,4E)-7-chloro-5-methyl-1-phenyl-1,4-heptadiene

Chemical formula

[0300] C 14 H 17 Cl Colorless oil IR (D-ATR): ν = 3081, 3058, 3025, 2961, 2914, 1947, 1874, 1800, 1648, 1599, 1577, 1494, 1447, 1385, 1324, 1293, 1246, 1207, 1150, 1129, 964, 910, 838, 742, 692, 657 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.69 (3H, s-like), 2.50 (2H, t, J = 7.3 Hz), 2.94 (2H, t-like, J = ~7 Hz), 3.62 (2H, t, J = 7.3 Hz), 5.36 (1H, tq, J = 7.3, 1.3 Hz), 6.19 (1H, dt, J = 15.9, 6.4 Hz), 6.41 (1H, dt, J = 15.9, 1.6 Hz), 7.18 - 7.22 (1H, m), 7.26 - 7.32 (2H, m), 7.32 - 7.37 (2H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 15.74, 31.39, 42.55, 43.07, 124.79, 125.96, 126.90, 128.45, 128.64, 129.93, 132.68, 137.67 ppm。 GC-MS (EI, 70 eV): 39, 51, 65, 77, 91, 103, 115, 129 (base peak), 142, 157, 169, 184, 205, 220 (M + )。

[0301] Synthesis of Example 31 (1E,4E)-7-bromo-5-methyl-1-phenyl-1,4-heptadiene [when R = (E)-cinnamyl group, X = Br in general formula (B), and the geometric isomerism of the double bond at the 4th position is E]

[0302]

Chemical formula

[0303] Under a nitrogen atmosphere, a mixture of 200 mg (75.2% GC) of (1E,4E)-7-chloro-5-methyl-1-phenyl-1,4-heptadiene synthesized in Example 30 above, 170 mg of sodium bromide, and 6 ml of N-methyl-2-pyrrolidone was stirred for 9 hours while heating to 40 to 50 °C. The reaction mixture was used as it was in the next step.

[0304] (1E,4E)-7-Bromo-5-methyl-1-phenyl-1,4-heptadiene

Chemical formula

[0305] C 14 H 17 Br GC-MS (EI, 70 eV): 39, 53, 77, 91, 115, 129, 143, 157 (base peak), 171, 185, 207, 221, 235, 249, 264 (M + ).

[0306] Synthesis of Example 32 (E)-1-chloro-3-methyl-3-dodecene [when R = n-octyl group, X = Cl in the general formula (B), and the geometric isomerism of the double bond at the 3-position is E]

[0307]

Chemical formula

[0308] Under a nitrogen atmosphere, a mixture of 1.27 g of (Z)-(1-chloro-3-dodecen-3-yl)methyl = p-tolyl = sulfone (~100% Z) synthesized in Example 15 above, 100 mg of 1,3-bis(diphenylphosphino)propane palladium(II) chloride and 40 ml of tetrahydrofuran was stirred while cooling with ice, and 3.62 ml of a 1.7 M lithium triethylborohydride-tetrahydrofuran solution was injected over 2 minutes. After stirring the reaction mixture for 30 minutes under ice-cooling, 21.0 g of a 12.5% aqueous sodium hydroxide solution and then 2.44 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and it was extracted with diethyl ether. After the usual post-treatment operations of washing, drying and concentration from the diethyl ether solution, and then purification by silica gel column chromatography, 630 mg of the target product (E)-1-chloro-3-methyl-3-dodecene (92.8% by GC, yield 78%) was obtained.

[0309] (E)-1-chloro-3-methyl-3-dodecene

Chemical Structure

[0310] C 13 H 25 Cl Colorless oil IR (D-ATR): ν = 2957, 2925, 2854, 1455, 1379, 1324, 1245, 1150, 919, 725, 661 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 0.88 (3H, t, J = 7.0 Hz), 1.22 - 1.37 (12H, m), 1.62 (3H, s-like), 1.99 (2H, q-like, J =~7 Hz), 2.43 (2H, t, J = 7.4 Hz), 3.57 (2H, t, J = 7.4 Hz), 5.23 (1H, tq, J = 7.2, 1.3 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 14.10, 15.70, 22.67, 27.94, 29.27, 29.30, 29.50, 29.60, 31.88, 42.70, 43.29, 128.28, 130.75 ppm. GC-MS (EI, 70 eV): 41, 55, 69 (base peak), 81, 97, 117, 132, 153, 165, 188, 216 (M + )

[0311] Example 33 Synthesis of (Z)-1-chloro-3-methyl-3-dodecene [where R = n-octyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is Z in the general formula (B)]

[0312]

Chemical formula

[0313] Under a nitrogen atmosphere, a mixture of 1.28 g of (E)-(1-chloro-3-dodecen-3-yl)methyl = p-tolyl = sulfone synthesized in Example 15 above (~100% E), 100 mg of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 40 ml of tetrahydrofuran was stirred while being ice-cooled, and 3.70 ml of a 1.7 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After stirring the reaction mixture for 85 minutes while ice-cooled, 23.1 g of a 12.5% aqueous sodium hydroxide solution and then 2.70 g of 35% aqueous hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture, and it was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 660 mg of the target product (Z)-1-chloro-3-methyl-3-dodecene (99.6% GC, 100% E, yield 88%) was obtained.

[0314] (Z)-1-chloro-3-methyl-3-dodecene

[0315]

Chemical formula

[0316] C 13 H 25 Cl Colorless oil IR (D-ATR): ν = 2958, 2925, 2854, 1457, 1378, 1296, 1241, 1079, 833, 723, 660 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 0.88 (3H, t, J = 7.0 Hz), 1.22 - 1.37 (12H, m), 1.71 (3H, q, J = 1.3 Hz), 1.99 (2H, q-like, J =~7 Hz), 2.50 (2H, t, J = 7.5 Hz), 3.53 (2H, t, J = 7.5 Hz), 5.29 (1H, tq, J = 7.3, 0.6 Hz) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 14.11, 22.67, 23.16, 27.94, 29.29, 29.36, 29.52, 29.88, 31.88, 35.20, 42.72, 128.97, 130.61 ppm。 GC-MS (EI, 70 eV): 41, 55, 69 (base peak), 81, 97, 117, 132, 153, 165, 188, 216 (M + )。

[0317] Example 34 Synthesis of (E)-8-chloro-2,6-dimethyl-1,5-octadiene [when R = 3-methyl-3-butenyl group, X = Cl, and the geometric isomerism of the double bond at the 3-position is E in general formula (B)]

[0318]

Chem.

[0319] Under a nitrogen atmosphere, a mixture of 1.65 g of (Z)-(8-chloro-2-methyl-1,5-octadien-6-yl)methyl=phenyl=sulfone (>96.4% Z) synthesized in Example 13 above, 0.155 g of 1,3-bis(diphenylphosphino)propane palladium(II) chloride, and 50 ml of tetrahydrofuran was stirred while cooling with ice, and 9.50 ml of a 1.0 M lithium triethylborohydride-tetrahydrofuran solution was injected over 5 minutes. After the reaction mixture was stirred for 2 hours under ice-cooling, 16.0 g of a 12.5% aqueous sodium hydroxide solution and then 4.20 g of 35% hydrogen peroxide solution were added dropwise. Water was added to the reaction mixture and it was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, followed by purification by silica gel column chromatography, 0.830 g of the target product (E)-8-chloro-2,6-dimethyl-1,5-octadiene (84.9 - 91.5% GC, yield 97%) was obtained.

[0320] (E)-8-chloro-2,6-dimethyl-1,5-octadiene

[0321]

Chemical formula

[0322] C 10 H 17 Cl Colorless oil IR (D-ATR): ν = 3074, 2966, 2935, 2857, 1650, 1451, 1385, 1374, 1325, 1294, 1247, 1150, 1092, 888, 726, 660 cm -1 。 1H-NMR(500 MHz, CDCl3): δ = 1.64 (3H, s-like), 1.72 (3H, s-like), 2.01 - 2.07 (2H, m), 2.12 - 2.19 (2H, m), 2.44 (2H, t-like, J = ~7 Hz), 3.56 (2H, t, J = 7.3 Hz), 4.68 (1H, br.s-like), 4.71 (1H, br.s-like), 5.23 (1H, tq, J = 6.9, 1.3 Hz) ppm。 13 C-NMR(125 MHz, CDCl3): δ = 15.74, 22.45, 26.16, 37.51, 42.61, 43.22, 109.96, 127.42, 131.21, 145.54 ppm。 GC-MS (EI, 70 eV): 27, 39, 55, 67, 81 (base peak), 91, 105, 117, 130, 144, 157, 172 (M + )。

[0323] Example 35 Synthesis of (E)-8-bromo-2,6-dimethyl-1,5-octadiene [where R = 3-methyl-3-butenyl group, X = Br in general formula (B), and the geometric isomerism of the double bond at the 3-position is E]

[0324]

Chemical formula

[0325] Under a nitrogen atmosphere, a mixture of 0.700 g (91.5% GC) of (E)-8-chloro-2,6-dimethyl-1,5-octadiene synthesized in Example 34 above, 3.53 g of bromoethane, 0.150 g of sodium bromide, and 10 ml of N-methyl-2-pyrrolidone was heated to 75 - 80 °C and stirred vigorously for 3 hours while refluxing. After cooling the reaction mixture, water was added and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, 0.830 g (68.5% GC, yield 71%) of the crude target product (E)-8-bromo-2,6-dimethyl-1,5-octadiene was obtained. The 1The isomer ratio determined by 1H-NMR analysis was as follows: the target product (E)-8-bromo-2,6-dimethyl-1,5-octadiene: the isomer in which the double bond at the 1-position had moved to the 2-position, (E)-8-bromo-2,6-dimethyl-2,5-octadiene: the isomer in which the double bond at the 5-position had moved exo, 8-bromo-2-methyl-6-methylene-1-octene = 75.4:18.5:6.1.

[0326]

Chem.

[0327] (E)-8-bromo-2,6-dimethyl-1,5-octadiene

[0328]

Chem.

[0329] C 10 H 17 Br Colorless oil IR (D-ATR): ν = 3074, 2968, 2932, 2857, 1697, 1649, 1500, 1447, 1402, 1385, 1375, 1311, 1296, 1267, 1209, 1137, 888, 655 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.63 (3H, s-like), 1.72 (3H, s-like), 2.01 - 2.07 (2H, m), 2.12 - 2.18 (2H, m), 2.53 (2H, t-like, J = ~7.5 Hz), 3.42 (2H, t, J = 7.5 Hz), 4.67 (1H, br.s-like), 4.71 (1H, br.s-like), 5.23 (1H, tq, J = 6.9, 1.3 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 15.60, 22.45, 26.16, 31.70, 37.48, 42.87, 109.98, 127.41, 132.01, 145.52 ppm. GC-MS (EI, 70 eV): 27, 41, 55, 67, 81 (base peak), 95, 109, 121, 137, 149, 161, 174, 190, 203, 216 (M + ).

[0330] (E)-8-Bromo-2,6-dimethyl-2,5-octadiene

[0331] [Chemical formula]

[0332] C 10 H 17 Br GC-MS (EI, 70 eV): 27, 41, 53, 67, 81, 93, 109 (base peak), 121, 137, 149, 161, 175, 187, 201, 216 (M + ).

[0333] 8-Bromo-2-methyl-6-methylene-1-octene

[0334] [Chemical formula]

[0335] C 10 H 17 Br GC-MS (EI, 70 eV): 27, 41, 53, 67, 81 (base peak), 95, 109, 121, 137, 160, 173, 188, 201.

[0336] Example [Synthesis of 3-methyl-1,3-butadiene compound having a substituent at the 4-position represented by the following general formula (A)]

[0337] [Chemical formula]

[0338] Example 36 Synthesis of (3E,6E)-α-farnesene [when R = (E)-3,7-dimethyl-2,6-octadienyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is E] (1)

[0339]

Chemical formula

[0340] Under a nitrogen atmosphere, a mixture of 1.00 g (92.0% GC, 80.9% EE-α) of (6E,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 20 above, 655 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 20 mg of 2,6-di-t-butyl-p-cresol (BHT), and 16 ml of dimethylformamide was stirred at room temperature for 19 hours. Water was added to the reaction mixture and extracted with n-hexane. After the usual washing, drying, and concentration post-treatment operations from the n-hexane solution, 440 mg of the crude product of the target (3E,6E)-α-farnesene was obtained. This crude product was combined with the crude product obtained in the next example and purified (as follows).

[0341] Example 37 Synthesis of (3E,6E)-α-farnesene [when R = (E)-3,7-dimethyl-2,6-octadienyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is E] (2)

[0342]

Chemical formula

[0343] Under a nitrogen atmosphere, a mixture of 230 mg of (6E,9E)-12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene (77.8% GC, 66.7% EE-α) synthesized in Example 24 above, 130 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 20 mg of 2,6-di-t-butyl-p-cresol (BHT), and 4 ml of dimethylformamide was stirred at room temperature for 15 hours. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. After the usual washing, drying, and concentration post-treatment operations on the diethyl ether solution, 170 mg of the crude product of the target (3E,6E)-α-farnesene was obtained. This crude product was combined with the crude product obtained in the previous example (above) and purified by silica gel column chromatography to obtain 380 mg of the target (3E,6E)-α-farnesene (80.6% NMR, yield 46%).

[0344] As a result of detailed spectral analysis, this was a mixture of isomers of the target (3E,6E)-α-farnesene, E-β-isomer (Z)-β-farnesene, and (3E,6E)-3,7,11-trimethyl-1,3,6,11-dodecatetraene in which the double bond at the 10th position had moved to the 11th position, in a ratio of 80.6:12.1:7.3.

[0345] (3E,6E)-α-farnesene

[0346]

Chemical Structure

[0347] C 15 H 24 Colorless oil IR(D-ATR): ν = 3089, 2968, 2925, 2856, 1640, 1442, 1377, 988, 892 cm -1 。 11H-NMR (500 MHz, CDCl3): δ = 1.60 (3H, s-like), 1.64 (3H, s-like), 1.68 (3H, q-like, J = 1.1 Hz), 1.76 (3H, q-like, J = 1.1 Hz), 1.96 - 2.02 (2H, m), 2.04 - 2.11 (2H, m), 2.83 (2H, t, J = 7.3 Hz), 4.93 (1H, d, J = 10.7 Hz), 5.08 - 5.16 (2H, m), 5.09 (1H, dd, J = 17.4, 0.6 Hz), 5.46 (1H, t-like, J = 7.3 Hz), 6.37 (1H, dd, J = 17.4, 10.7 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 11.65, 16.10, 17.68, 25.69, 26.64, 27.21, 39.64, 110.53, 122.00, 124.21, 131.43, 131.86, 133.70, 135.77, 141.52 ppm. GC-MS (EI, 70 eV): 41, 55, 67, 79, 93 (base peak), 107, 119, 133, 147, 161, 175, 189, 204 (M + ).

[0348] Example 38 Synthesis of (3Z,6E)-α-farnesene [when R = (E)-3,7-dimethyl-2,6-octadienyl group in the general formula (A) and the geometric isomerism of the double bond at the 3-position is Z]

[0349]

Chemical formula

[0350] Under a nitrogen atmosphere, a mixture of 1.15 g (80.6% GC) of (6E,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 21 above, 728 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 20 mg of 2,6-di-t-butyl-p-cresol (BHT), and 13 ml of dimethylformamide was stirred at room temperature for 16 hours. Water was added to the reaction mixture, and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, followed by purification by silica gel column chromatography, 560 mg (81.3% NMR, yield 85%) of the target product (3Z,6E)-α-farnesene was obtained.

[0351] (3Z,6E)-α-farnesene

[0352]

Chemical Structure

[0353] C 15 H 24 Colorless oil IR(D-ATR): ν = 3090, 2969, 2926, 2857, 1644, 1441, 1377, 987, 901 cm -1 。 1 1H-NMR(500 MHz, CDCl3): δ = 1.60 (3H, s-like), 1.64 (3H, s-like), 1.68 (3H, q-like, J = 1.2 Hz), 1.82 (3H, q-like, J = 1.2 Hz), 1.94 - 2.02 (2H, m), 2.02 - 2.13 (2H, m), 2.87 (2H, t, J = 7.4 Hz), 5.06 - 5.16 (3H, m), 5.20 (1H, d-like, J = 17.2 Hz), 5.36 (1H, t-like, J = 7.4 Hz), 6.81 (1H, ddd, J = 17.2, 10.9, 1.0 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 16.08, 17.67, 19.74, 25.68, 26.33, 26.64, 39.63, 113.46, 122.33, 124.22, 129.73, 131.41, 131.89, 133.64, 135.65 ppm. GC-MS (EI, 70 eV): 41, 55, 67, 79, 93 (base peak), 107, 119, 135, 147, 161, 175, 189, 204 (M + )。

[0354] Example 39 Synthesis of (3E,6Z)-α-farnesene [when R = (Z)-3,7-dimethyl-2,6-octadienyl group in the general formula (A) and the geometric isomerism of the double bond at the 3-position is E]

[0355]

Chemical formula

[0356] Under a nitrogen atmosphere, a mixture of 760 mg (83.0% GC) of (6Z,9E)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 22 above, 520 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 20 mg of 2,6-di-t-butyl-p-cresol (BHT), and 8 ml of dimethylformamide was stirred at room temperature for 23 hours. Water was added to the reaction mixture and extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, followed by purification by silica gel column chromatography, 210 mg (85.4% NMR, yield 93%) of the target (3E,6Z)-α-farnesene was obtained.

[0357] As a result of detailed spectral analysis, this was a mixture of isomers of the target (3E,6Z)-α-farnesene, the Z-β-isomer (Z)-β-farnesene, and (3E,6Z)-3,7,11-trimethyl-1,3,6,11-dodecatetraene in which the double bond at the 10-position had moved to the 11-position, in a ratio of 85.4:6.8:7.8.

[0358] (3E,6Z)-α-farnesene

[0359]

Chem.

[0360] C 15 H 24 IR (D-ATR): ν = 3089, 2967, 2927, 2857, 1791, 1640, 1447, 1376, 988, 892 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, q-like, J = ~1 Hz), 1.69 (3H, s-like), 1.70 (3H, q-like, J = ~1 Hz), 1.76 (3H, q-like, J = ~1 Hz), 2.02 - 2.12 (4H, m), 2.84 (2H, t-like, J = 7.3 Hz), 4.93 (1H, d, J = 10.7 Hz), 5.09 (1H, d-like, J = 17.4 Hz), 5.08 - 5.18 (2H, m), 5.44 (1H, t-like, J = 7.4 Hz), 6.37 (1H, dd, J = 17.4, 10.8) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 11.64, 17.63, 23.36, 25.72, 26.52, 27.08, 31.98, 110.55, 122.77, 124.17, 131.67, 131.90, 133.63, 135.95, 141.52 ppm。 GC-MS (EI, 70 eV): 41, 55, 69, 81, 93 (base peak), 107, 119, 133, 147, 161, 175, 189, 204 (M + )。

[0361] Example 40 Synthesis of (3Z,6Z)-α-farnesene [where R = (Z)-3,7-dimethyl-2,6-octadienyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is Z] (1)

[0362]

Chem.

[0363] Under a nitrogen atmosphere, a mixture of 1.82 g (88.3% GC) of (6Z,9Z)-12-bromo-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 23 above, 1.144 g of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 20 mg of 2,6-di-t-butyl-p-cresol (BHT), and 20 ml of dimethylformamide was stirred at room temperature for 22 hours. Water was added to the reaction mixture, and the mixture was extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, and then purification by silica gel column chromatography, 913 mg (93% NMR, yield 84%) of the target product (3Z,6Z)-α-farnesene was obtained.

[0364] (3Z,6Z)-α-farnesene

[0365]

Chemical formula

[0366] C 15 H 24 IR (D-ATR): ν = 3090, 2968, 2927, 2857, 1808, 1643, 1441, 1376, 986,833 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.62 (3H, q-like, J = ~1 Hz), 1.68 - 1.72 (3H, m), 1.69 (3H, s-like), 1.81 (3H, q-like, J = ~1 Hz), 2.05 - 2.14 (4H, m), 2.87 (2H, t-like, J = 7.4 Hz), 5.06 - 5.17 (3H, m), 5.20 (1H, d-like, J = 17.2 Hz), 5.34 (1H, t-like, J = 7.4 Hz), 6.80 (1H, ddd, J = 17.4, 10.8, 0.9 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 17.63, 19.75, 23.37, 25.71, 26.21, 26.53, 31.96, 113.50, 123.11, 124.19, 129.79, 131.66, 131.90, 133.60, 135.83 ppm. GC-MS (EI, 70 eV): 41, 55, 69, 81, 93 (base peak), 107, 119, 133, 147, 161, 175, 189, 204 (M + )

[0367] BHT was added as a stabilizer to this product, and the sample tube sealed with nitrogen was stored in a refrigerator (-20 °C). After 3 years and 1 month, the 1 1H-NMR spectrum of the sample was re-measured, and the purity at the time of synthesis was maintained. It was found that the target product synthesized by the production method of the present invention can withstand long-term storage and does not decompose in a short period as described in some documents.

[0368] Example 41 Synthesis of (3Z,6Z)-α-farnesene [when R = (Z)-3,7-dimethyl-2,6-octadienyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is Z] (2)

[0369]

Chemical formula

[0370] Under a nitrogen atmosphere, a mixture of 700 mg (≈94.8% GC) of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in Example 19 above, 2.22 g of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), and 20 mg of 2,6-di-t-butyl-p-cresol (BHT) was heated at 60 - 80 °C for 2 hours. Then, an additional 2.22 g of DBU was added, and the mixture was stirred at 80 °C for 1.5 hours. The reaction mixture was poured into 10% hydrochloric acid and extracted with diethyl ether. After the usual post-treatment operations of washing, drying, and concentration from the diethyl ether solution, followed by separation and purification using silica gel column chromatography, 120 mg (60.0% GC, isomer purity 70.6%) and 0.27 g (43.8% GC, isomer purity ≈40.0%) of the target product (3Z,6Z)-α-farnesene (yield of only the target isomer 41%, total isomer yield 86%) were obtained.

[0371] As a result of detailed spectral analysis, this product was found to be a mixture of isomers of the target product (3Z,6Z)-α-farnesene, an isomer (2E,4E,6Z)-3,7,11-trimethyl-2,4,6,10-dodecatetraene having a conjugated triene structure in which the two double bonds at the 1- and 3-positions have moved to the 2- and 4-positions, and an isomer (3Z,5E)-3,7,11-trimethyl-1,3,5,10-dodecatetraene having a conjugated triene structure in which the double bond at the 6-position has moved to the 5-position. It was shown that under severe conditions of strong heating under basic conditions using a chloride intermediate with X = Cl in the hydrogen halide HX elimination step, a side reaction of the migration of the double bond of the target product to the conjugated side may occur.

[0372] (2E,4E,6Z)-3,7,11-trimethyl-2,4,6,10-dodecatetraene

[0373]

Chemical Structure

[0374] C 15 H 24 GC-MS (EI, 70 eV): 41, 55, 77, 93, 107 (base peak), 119, 135, 147, 161, 175, 189, 204 (M + ). 2D-NOESY: A correlation of NOE (Nuclear Overhauser Effect) was observed between the signals of the hydrogen atoms bonded to the carbon atoms at the positions indicated by the double-sided arrows in the following chemical formula.

[0375] [Chemical formula]

[0376] (3Z,5E)-3,7,11-Trimethyl-1,3,5,10-dodecatetraene

[0377] [Chemical formula]

[0378] C 15 H 24 GC-MS (EI, 70 eV): 41, 55, 77, 93, 107 (base peak), 119, 135, 148, 161, 175, 189, 204 (M + ).

[0379] 2D-NOESY: A correlation of NOE (Nuclear Overhauser Effect) was observed between the signals of the hydrogen atoms bonded to the carbon atoms at the positions indicated by the double-sided arrows in the following chemical formula.

[0380] [Chemical formula]

[0381] Example 42 Synthesis of (3Z,6Z)-α-farnesene [in the general formula (A), R = (Z)-3,7-dimethyl-2,6-octadienyl group, when the geometric isomerism of the double bond at the 3-position is Z] (3)

[0382]

Chemical formula

[0383] Under a nitrogen atmosphere, a mixture of 700 mg (≈89.5% GC) of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene synthesized in the same manner as in Example 19 above, 1.00 g of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 5 mg of 2,6-di-t-butyl-p-cresol (BHT), and 7.2 ml of toluene was stirred at 70 - 80 °C for 5 hours. Then, 1.00 g of DBN was added, and the mixture was stirred at 60 °C for 5 hours. 10 ml of dimethylformamide (DMF) was added to the reaction mixture, and the mixture was stirred at 60 - 80 °C for 5 hours. The reaction mixture was poured into 2% sulfuric acid and extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, 180 mg (≈95% NMR, crude yield 66%) of the target product (3Z,6Z)-α-farnesene was obtained.

[0384] Example 43 Synthesis of (3Z,6Z)-α-farnesene [in the general formula (A), R = (Z)-3,7-dimethyl-2,6-octadienyl group, when the geometric isomerism of the double bond at the 3-position is Z] (4)

[0385]

Chemical formula

[0386] Under a nitrogen atmosphere, a mixture of (6Z,9Z)-12-chloro-2,6,10-trimethyl-2,6,9-dodecatriene and (6Z,9Z)-(12-iodo-2,6,10-trimethyl-2,6,9-dodecatriene) synthesized in Example 25 above in a ratio of 68.6:31.4, 260 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 5 mg of 2,6-di-t-butyl-p-cresol (BHT), and 10 ml of dimethylformamide (DMF) was heated while raising the internal temperature from 40 °C to 80 °C over 6 hours. Then, an additional 260 mg of DBN was added, and the mixture was stirred at 80 - 85 °C for 5 hours. After cooling the reaction mixture, it was poured into 2% sulfuric acid and extracted with n-hexane. After the usual post-treatment operations of washing, drying, and concentration from the n-hexane solution, 90 mg of the target product (3Z,6Z)-α-farnesene (~90% NMR, quantitative crude yield) was obtained.

[0387] Example 44 Synthesis of (E)-β-ocimene [when R = 3-methyl-2-butenyl group in the general formula (A) and the geometric isomerism of the double bond at the 3-position is E]

[0388]

Chemical formula

[0389] Under a nitrogen atmosphere, a mixture of 1.24 g (80.7% GC) of the crude (E)-8-bromo-2,6-dimethyl-2,5-octadiene synthesized in Example 28 above, 1.04 g of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 40 mg of 2,6-di-t-butyl-p-cresol (BHT), and 20 ml of dimethylformamide (DMF) was stirred at room temperature for 23 hours. The reaction mixture was poured into 2% sulfuric acid and extracted with n-pentane. After the usual post-treatment operations of washing, drying, and concentration from the n-pentane solution, and then purification by silica gel column chromatography, the target product (E)-β-ocimene (78.7% GC, yield 55%) was obtained.

[0390] (E)-β-ocimene

[0391]

Chemical formula

[0392] C 10 H 16 Colorless oil IR (D-ATR): ν = 3090, 3006, 2972, 2926, 2858, 1791, 1640, 1606, 1442, 1376, 1105, 1075, 989, 892, 866, 831 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.64 (3H, s-like), 1.70 (3H, d-like, J = ~1 Hz), 1.77 (3H, q-like, J = ~1 Hz), 2.83 (2H, t, J = 7.4 Hz), 4.93 (1H, d, J = 10.9 Hz), 5.09 (1H, d-like, J = 17.4 Hz), 5.10 - 5.15 (1H, m), 5.46 (1H, t-like, J = 7.4 Hz), 6.38 (1H, dd, J = 10.9, 17.4 Hz) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 11.63, 17.73, 25.66, 27.31, 110.56, 122.16, 131.76, 132.16, 133.69, 141.51 ppm。 GC-MS (EI, 70 eV): 41, 53, 67, 79, 93 (base peak), 105, 121, 136 (M + )。

[0393] Example 45 Synthesis of (Z)-β-ocimene [when R = 3-methyl-2-butenyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is Z]

[0394]

Chemical formula

[0395] Under a nitrogen atmosphere, a mixture of 300 mg (73.0% GC) of (Z)-8-bromo-2,6-dimethyl-2,5-octadiene synthesized in Example 29 above, 250 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 5 mg of 2,6-di-t-butyl-p-cresol (BHT), and 5 ml of dimethylformamide (DMF) was stirred at room temperature for 22 hours. The reaction mixture was poured into 2% sulfuric acid and extracted with n-pentane. After the usual post-treatment operations of washing, drying, and concentration from the n-pentane solution, and then purification by silica gel column chromatography, 110 mg (73.6% GC, yield 59%) of the target product (E)-β-ocimene was obtained.

[0396] (Z)-β-ocimene

[0397]

Chemical Structure

[0398] C 10 H 16 Colorless oil IR (D-ATR): ν = 3090, 2971, 2927, 2858, 1644, 1594, 1440, 1377, 1158, 1106, 987, 901, 860, 828 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.64 (3H, s), 1.70 (3H, q-like, J = ~1.2 Hz), 1.82 (3H, q-like, J = ~1.2 Hz), 2.86 (2H, t-like, J = ~7.2 Hz), 5.07 - 5.14 (2H, m), 5.22 (1H, d-like, J = ~17 Hz), 5.35 (1H, t, J = 7.6 Hz), 6.81 (1H, ddd, J = 1.0, 10.9, ~17 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 17.71, 19.73, 25.67, 26.45, 113.50, 122.49, 129.64, 131.94, 132.05, 133.61 ppm. GC-MS (EI, 70 eV): 39, 53, 67, 79, 93 (base peak), 105, 121, 136 (M + ).

[0399] Example 46 Synthesis of (1E,4E)-5-methyl-1-phenyl-1,4,6-heptatriene [wherein in general formula (A), R = (E)-cinnamyl group and the geometric isomerism of the double bond at the 4-position is E]

[0400]

Chemical formula

[0401] Under a nitrogen atmosphere, 260 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN) was added to the reaction mixture of (1E,4E)-7-bromo-5-methyl-1-phenyl-1,4-heptadiene synthesized in Example 31 above, and the mixture was stirred at 40 °C for 70 minutes. The reaction mixture was poured into 2% sulfuric acid and extracted with diethyl ether. After the usual post-treatment operations of washing, drying, and concentration from the diethyl ether solution, and then purification by silica gel column chromatography, the target product (1E,4E)-5-methyl-1-phenyl-1,4,6-heptatriene was attempted to be obtained. The target product was extremely unstable, and during purification, the double bonds at the 4- and 6-positions completely isomerized to the following conjugated triene compound, (1E,3E,5E)-5-methyl-1-phenyl-1,3,5-heptatriene, with the double bonds moving to the 3- and 5-positions in a short time.

[0402]

Chemical formula

[0403] (1E,3E,5E)-5-methyl-1-phenyl-1,3,5-heptatriene

[0404]

Chemical formula

[0405] C 14 H 16 1 1H-NMR (500 MHz, CDCl3): δ = 1.78 (3H, d, J = 7.3 Hz), 1.81 (3H, s-like), 5.65 (1H, q, J = 7.2 Hz), 6.32 (1H, dd, J = 15.3, 10.1 Hz), 6.39 (1H, d, J = 15.3 Hz), 6.54 (1H, d, J = 15.6), 6.84 (1H, dd, J = 15.6, 10.1 Hz), 7.17 - 7.23 (1H, m), 7.27 - 7.34 (2H, m), 7.37 - 7.42 (2H, m) ppm. GC-MS (EI, 70 eV): 39, 51, 65, 77, 91, 105, 128, 141, 154, 169 (base peak), 184 (M + ).

[0406] Example 47 Synthesis of (E)-3-methyl-1,3-dodecadiene [when R = n-octyl group in the general formula (A) and the geometric isomerism of the double bond at the 3-position is E]

[0407]

Chemical formula

[0408] Under a nitrogen atmosphere, while stirring a mixture of 300 mg (92.8% GC) of (E)-1-chloro-3-methyl-3-dodecene synthesized in Example 32 above, 5 mg of 2,6-di-t-butyl-p-cresol (BHT), and 3 ml of tetrahydrofuran (THF) under ice-cooling, a mixture of 200 mg of potassium tert-butoxide and 2 ml of THF was injected. While raising the reaction mixture to room temperature and stirring, 200 mg of potassium tert-butoxide was added, and stirring was continued for another 3 hours. The reaction mixture was poured into dilute hydrochloric acid and extracted with diethyl ether. After the usual post-treatment operations of washing, drying, and concentration from the diethyl ether solution, followed by purification by silica gel column chromatography, 252 mg (92.7% GC, yield 93%) of the target product (E)-3-methyl-1,3-dodecadiene was obtained.

[0409] (E)-3-methyl-1,3-dodecadiene

[0410] [Chemical formula]

[0411] C 13 H 24 Colorless oil IR (D-ATR): ν = 3090, 2956, 2925, 2855, 1643, 1467, 1388, 1378, 1083, 988, 891, 721 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 0.88 (3H, t, J = 7.0 Hz), 1.22 - 1.41 (12H, m), 1.73 (3H, s-like), 2.12 (2H, q-like, J = 7.4 Hz), 4.92 (1H, d, J = 10.7 Hz), 5.08 (1H, d-like, J = 17.2 Hz), 5.49 (1H, t, J = 7.2 Hz), 6.37 (1H, ddd, J = 17.3, 10.7, 0.6 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 11.62, 14.10, 22.67, 28.22, 29.29, 29.38, 29.50 (2C), 31.88, 110.24, 133.62, 133.78, 141.68 ppm. GC-MS (EI, 70 eV): 41, 55, 68 (base peak), 81, 95, 109, 123, 137, 151, 165, 180 (M + ).

[0412] Example 48 Synthesis of (Z)-3-methyl-1,3-dodecadiene [when R = n-octyl group in general formula (A) and the geometric isomerism of the double bond at the 3-position is Z]

[0413] [Chemical formula]

[0414] Under a nitrogen atmosphere, a mixture of 300 mg (99.6% GC) of (Z)-1-chloro-3-methyl-3-dodecene synthesized in Example 33 above, 10 mg of 2,6-di-t-butyl-p-cresol (BHT), 395 mg of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) and 3 ml of dimethylformamide (DMF) was stirred at 50 °C for 1 hour and at 85 - 90 °C for 2.5 hours. Further, 520 mg of DBU was added and the mixture was stirred at 90 °C for 10 hours. After cooling the reaction mixture, it was poured into dilute hydrochloric acid and extracted with diethyl ether. After the usual post-treatment operations of washing, drying and concentration from the diethyl ether solution, followed by purification by silica gel column chromatography, 250 mg of the target product (Z)-3-methyl-1,3-dodecadiene (~100% GC, quantitative yield) was obtained.

[0415] (Z)-3-methyl-1,3-dodecadiene

[0416]

Chemical Structure

[0417] C 13 H 24 Colorless oil IR (D-ATR): ν = 3090, 2957, 2925, 2855, 1645, 1461, 1378, 1082, 987, 900, 721 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 0.89 (3H, t, J = 7.0 Hz), 1.22 - 1.40 (12H, m), 1.81 (3H, dd, J = 2.4, 1.1 Hz), 2.15 (2H, q-like, J =~7.4 Hz), 5.07 (1H, dt, J = 1.7, 10.7 Hz), 5.17 (1H, d-like, J = 17.4 Hz), 5.39 (1H, t, J = 7.7 Hz), 6.78 (1H, ddd, J = 17.4, 10.7, 0.9 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 14.10, 19.76, 22.66, 27.34, 29.28, 29.32, 29.49, 29.87, 31.88, 113.07, 131.63, 132.02, 133.80 ppm. GC-MS (EI, 70 eV): 41, 55, 68 (base peak), 81, 95, 109, 123, 137, 151, 165, 180 (M + ).

[0418] Example 49 Synthesis of (E)-α-ocimene [when R = 3-methyl-3-butenyl group in the general formula (A) and the geometric isomerism of the double bond at the 3-position is E]

[0419]

Chemical formula

[0420] Under a nitrogen atmosphere, a mixture of 820 mg (68.5% GC) of the crude (E)-8-bromo-2,6-dimethyl-1,5-octadiene synthesized in Example 35 above, 645 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), 40 mg of 2,6-di-t-butyl-p-cresol (BHT), and 15 ml of dimethylformamide (DMF) was stirred at room temperature for 20 hours. The reaction mixture was poured into 2% sulfuric acid and extracted with n-pentane. After the usual post-treatment operations of washing, drying, and concentration from the n-pentane solution, and then purification by silica gel column chromatography, 270 mg (75.6% GC, yield 58%) of the target product (E)-α-ocimene was obtained.

[0421] (E)-α-ocimene

[0422]

Chemical formula

[0423] C 10 H 16 Colorless oil IR (D-ATR): ν = 3088, 3005, 2970, 2933, 2858, 1649, 1607, 1444, 1388, 1375, 1087, 989, 890 cm -1 。 1 ¹H-NMR (500 MHz, CDCl₃): δ = 1.73 (3H, s-like), 1.75 (3H, s-like), 2.09 (2H, t-like, J =~7.8 Hz), 2.28 (2H, q-like, J = 7.8 Hz), 4.69 - 4.71 (1H, m), 4.72 - 4.74 (1H, m), 4.93 (1H, d-like, J = 10.7 Hz), 5.09 (1H, d-like, J = 17 Hz), 5.49 (1H, t-like, J =~7 Hz), 6.37 (1H, dd, J = 11.0, 17.3 Hz) ppm。 13 ¹³C-NMR (125 MHz, CDCl₃): δ = 11.67, 22.44, 26.42, 37.33, 110.09, 110.51, 132.58, 134.08, 141.49, 145.39 ppm。 GC-MS (EI, 70 eV): 27, 39, 53, 65, 81 (base peak), 93, 107, 121, 136 (M + )。

[0424] Synthesis Example <Synthesis of Primary Allyl Sulfone Diene Compound (C) Having a Substituent at the 4-Position Represented by the Following General Formula (C)>

[0425]

Chemical Formula

[0426] Synthesis Example 3 Synthesis of (3E / Z,6Z)-(7,11-Dimethyl-1,3,6,10-dodecatetraen-3-yl)methyl = p-tolyl = sulfone [When R = (Z)-3,7-dimethyl-2,6-octadienyl group in General Formula (C) and the geometric isomerism of the double bond at the 3-position is a mixture of E / Z] (1)

[0427]

Chemical Formula

[0428] Under a nitrogen atmosphere, a mixture of 530 mg of (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone and (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone synthesized in the same manner as in Example 9 above in a ratio of 76.9:23.1( 1 A mixture of 80 mg of 2,6-di-t-butyl-p-cresol (BHT) and 15 ml of tetrahydrofuran (THF) was stirred under ice-cooling, and 175 mg of potassium tert-butoxide was added. The reaction mixture was stirred at room temperature for 18 hours. As a result of GC analysis of the reaction mixture, in addition to the desired HCl elimination reaction, the elimination of undesired p-toluenesulfinic acid also proceeded, giving a complex mixture.

[0429] Synthesis Example 4 (3E / Z,6Z)-(7,11-Dimethyl-1,3,6,10-dodecatetraen-3-yl)methyl = p-tolyl = sulfone [When R = (Z)-3,7-dimethyl-2,6-octadienyl group in the general formula (C) and the geometric isomerism of the double bond at the 3-position is a mixture of E / Z] Synthesis (2)

[0430]

Chemical formula

[0431] Under a nitrogen atmosphere, a mixture of 530 mg of (3E,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone and (3Z,6Z)-(1-chloro-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl = p-tolyl = sulfone synthesized in the same manner as in Example 9 above in a ratio of 76.9:23.1( 1A mixture of 250 mg of the mixture (H-NMR), 80 mg of 2,6-di-t-butyl-p-cresol (BHT) and 2 ml of toluene was stirred at room temperature, and 480 mg of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) was added. The reaction mixture was stirred at room temperature for 1.5 hours, at 40 °C for 3 hours, and further 4 ml of toluene was added and stirred at 60 °C for 5 hours. As a result of GC analysis of the reaction mixture, in the desired HCl elimination reaction, the raw material remained with a conversion rate of 15%, and isolation and purification of the desired product were not carried out.

[0432] Synthesis Example 5 Synthesis of (3Z,6E)-(7,11-dimethyl-1,3,6,10-dodecatetraen-3-yl)methyl=phenyl=sulfone [when R = (E)-3,7-dimethyl-2,6-octadienyl group in the general formula (C) and the geometric isomerism of the double bond at the 3-position is Z]

[0433] [Chemical formula]

[0434] Under a nitrogen atmosphere, a mixture of 180 mg (~93% NMR) of (3Z,6E)-(1-bromo-7,11-dimethyl-3,6,10-dodecatrien-3-yl)methyl=phenyl=sulfone synthesized in Example 10 above, 20 mg of 2,6-di-t-butyl-p-cresol (BHT), 52 mg of 1,5-diazabicyclo[4.3.0]-5-nonene (DBN), and 2 ml of dimethylformamide (DMF) was stirred at room temperature for 11 hours. Since the progress of the reaction was slow, 520 mg of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) was further added to the reaction mixture and stirred at 50 °C for 5 hours. As a result of GC analysis of the reaction mixture, the desired product was formed, but many by-products containing C 33 H 44 hydrocarbons were generated, so isolation and purification of the desired product were not carried out.

[0435] (3Z,6E)-(7,11-dimethyl-1,3,6,10-dodecatetraen-3-yl)methyl=phenyl=sulfone

[0436] [Chemical formula]

[0437] GC-MS (EI, 70 eV): 41, 77, 105, 133 (base peak), 159, 203, 275, 344 (M + ).

[0438] From the synthesis examples which are the above-described examples and comparative examples, among the synthesis routes from the primary allyl sulfone compound (D) to the 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position, (I) The method via the halide compound (B), that is, (I)-(1) By the reductive cleavage or reductive removal of the arenesulfonyl group W at the allyl position of the primary allyl sulfone compound (D) to obtain the halide compound (B), (I)-(2) By the elimination of hydrogen halide HX from the halide compound (B) to obtain the target 4-alkyl-3-methyl-1,3-butadiene compound (A) [Chemical formula] is (II) The method via the primary allyl sulfone diene compound (C), that is, (II)-(1) By the elimination of hydrogen halide HX from the primary allyl sulfone compound (D) to obtain the primary allyl sulfone diene compound (C), (II)-(2) By the reductive removal of the arenesulfonyl group W of the primary allyl sulfone diene compound (C) to obtain the target 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position [Chemical formula] was demonstrated to be more suitable as compared with.

Claims

1. The following general formula (D): 【Chemical 1】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, X represents a halogen atom, and W represents an arenesulfonyl group.) By the reductive removal reaction of the arenesulfonyl group W of the primary allyl sulfone compound represented by the following general formula (B): 【Chemical Formula 2】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, and X represents a halogen atom.) A step of obtaining a halide compound represented by the following general formula (A): By the elimination reaction of hydrogen halide HX of the halide compound represented by the above general formula (B), the following general formula (A): 【Chemical Formula 3】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds.) A step of obtaining a 3-methyl-1,3-butadiene compound having a substituent at the 4-position represented by the following general formula (A): A method for producing a 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position, comprising at least the above steps.

2. The following general formula (D): 【Chemical 4】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, X represents a halogen atom, and W represents an arenesulfonyl group.) A primary allyl sulfone compound represented by the following general formula (A):

3. The following general formula (E): 【Chemical Formula 5】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, X represents a halogen atom, and W represents an arenesulfonyl group.) By the allyl rearrangement reaction of the arenesulfonyl group of the secondary allyl sulfone compound represented by the following general formula (D): 【Chemical Formula 6】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, X represents a halogen atom, and W represents an arenesulfonyl group.) A step of obtaining a primary allyl sulfone compound represented by the following general formula (D): A method for producing a primary allyl sulfone compound (D), comprising at least the above steps.

4. The following general formula (E): 【Chemical Formula 7】 (In the formula, R represents a linear, branched or cyclic hydrocarbon group having 1 to 20 carbon atoms and optionally containing one or more unsaturated bonds, X represents a halogen atom, and W represents an arenesulfonyl group.) A secondary allyl sulfone compound represented by the following general formula (A):

5. The method for producing a 3-methyl-1,3-butadiene compound (A) having a substituent at the 4-position according to claim 1, wherein R is a 3,7-dimethyl-2,6-octadienyl group or a 3-methyl-2-butenyl group.

6. The primary allyl sulfone compound according to claim 2, wherein R is a 3,7-dimethyl-2,6-octadienyl group or a 3-methyl-2-butenyl group.

7. The secondary allyl sulfone compound according to claim 4, wherein R is a 3,7-dimethyl-2,6-octadienyl group or a 3-methyl-2-butenyl group.

8. The following general formula (B') 【Chemical Formula 8】 (In the formula, R' represents a 3,7-dimethyl-2,6-octadienyl group or a 3-methyl-2-butenyl group, and X represents a halogen atom.) A halide compound represented by the formula.

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