Processes for preparing 3-isopropenyl-6-heptenal compound and 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound, and intermediate therefor

Abstract

To provide a process for efficiently and industrially preparing 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compounds such as 6-isopropenyl-3-methyl-3,9-decadienyl acetate and 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, without oxidation reaction, in order to supply a sufficient amount of an active substance required for biological or agricultural activity tests and / or for practical application or use and the like.SOLUTION: The present invention provides a process for preparing a 3-isopropenyl-6-heptenal compound (2), the process comprising: subjecting a 3-isopropenyl-6-heptenoate ester compound represented by the general formula (1) in the figure to a reduction reaction with a reducing agent to obtain a compound represented by the general formula (2) in the figure. In the formulas, R1 represents a hydrogen atom or a methyl group, and R2 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a 3-isopropenyl-6-heptenal compound and a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound, as well as to a 3-isopropenyl-6-methyl-6-heptenoic acid ester compound which is an intermediate therefor and a method for producing the same. [Background technology]

[0002] Insect sex pheromones are usually biologically active substances that allow females to attract males, and they have a high attractant activity even in small amounts. Sex pheromones are widely used as a means of predicting insect infestations and confirming geographical spread (invasion into a specific area), as well as for pest control. As means of pest control, the following methods are widely used: mass trapping, lure and kill (or attract and kill), lure and infect (or attract and infect), and mating disruption. Since only a very small amount of sex pheromone can be extracted from one insect, it is difficult to use naturally derived sex pheromones for mating disruption, etc., and there is a strong demand for artificial and industrial production of the required amount of sex pheromone raw material for basic research and further applications.

[0003] California red scale The red scale insect (Aonidiella aurantii) is a pest that is widely distributed throughout the world and attacks citrus fruits. California red scale As the sex pheromone, (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate has been reported (Non-Patent Document 1 below). As 6-isopropenyl-3-methyl-3,9-decadienyl acetate, there are 4 isomers: (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate, (3E,6R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate, (3Z,6S)-6-isopropenyl-3-methyl-3,9-decadienyl acetate, and (3E,6S)-6-isopropenyl-3-methyl-3,9-decadienyl acetate. California red scale It has been reported that it is also attracted by a mixture of these 4 isomers (Non-Patent Document 1). As a method for synthesizing (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate, for example, using (S)-(+)-carvone as a raw material, (R)-3-isopropenyl-6-heptenal is led through 9 steps including an oxidation reaction using hydrogen peroxide, and then through 3 steps including a Wittig reaction, and (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate is obtained by gas-liquid chromatography (GLC) separation (Non-Patent Document 2 below).

[0004] White peach scale (The white peach scale insect, scientific name: Pseudaulacaspis pentagona) is a pest that is widely distributed throughout the world and damages fruit trees such as peaches and tea. White peach scale As the sex pheromone, (3Z,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate has been reported (Non-Patent Document 3 below). As 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, there are 4 isomers: (3Z,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, (3E,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, (3Z,6S)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, and (3E,6S)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate. White peach scale is also attracted by a mixture of (3Z,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, which is its sex pheromone, and (3E,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, which is an isomer of the sex pheromone (Patent Document 1 below). As a method for synthesizing (3Z,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, for example, (R)-(+)-limonene is subjected to ozonolysis, followed by a Wittig reaction and a hydrolysis reaction of an acetal to yield (R)-3-isopropenyl-6-methyl-6-heptenal, and then (3Z,6R)-6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate is synthesized by a 4-carbon chain elongation reaction including a Wittig reaction and propionylation (Non-Patent Document 3 below).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

[0007] However, in Non-Patent Document 2, an oxidation reaction using hydrogen peroxide with respect to (S)-(+)-carboxylic acid is carried out. Since the oxidation reaction may cause an explosion, it is difficult to carry out industrially. Further, nine steps are required to derive the intermediate (R)-3-isopropenyl-6-heptenal from the raw material (S)-(+)-carboxylic acid, and the total yield of the nine steps is as low as 12%. Furthermore, the total yield until synthesizing (R)-6-isopropenyl-3-methyl-3,9-decadienyl acetate from the raw material (S)-(+)-carboxylic acid is also as low as 5.3%. In Non-Patent Document 3, in the oxidation reaction of (R)-(+)-limonene, since corrosive and highly toxic ozone is used, it is difficult to carry out industrially.

[0008] Thus, in the conventional production methods, it was considered very difficult to industrially produce a sufficient amount of 6-isopropenyl-3-methyl-3,9-decadienyl acetate and 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate.

[0009] The present invention has been made in view of the above circumstances, and in order to supply a sufficient amount of the original substance necessary for biological or agricultural activity tests and / or actual applications or uses, etc., it eliminates the need for an oxidation reaction and efficiently and industrially produces 6-isopropenyl-3-methyl-3,9-decadienyl acetate and 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate, etc., 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compounds. The purpose is to provide a method.

[0010] Another object of the present invention is to provide a method for producing 3-isopropenyl-6-heptenal and 3-isopropenyl-6-methyl-6-heptenal, which are intermediates useful for producing these compounds.

[0011] Furthermore, an object of the present invention is also to provide a 3-isopropenyl-6-methyl-6-heptenoic acid ester compound, which is a useful intermediate for producing 3-isopropenyl-6-methyl-6-heptenal.

Means for Solving the Problems

[0012] As a result of intensive studies to solve the above problems, the present inventors have found that a 3-isopropenyl-6-heptenoic acid ester compound can be subjected to a reduction reaction with a reducing agent to obtain a 3-isopropenyl-6-heptenal compound. Further, the present inventors have found that 6-isopropenyl-3-methyl-3,9-decadienyl acetate and 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate can be obtained industrially using the 3-isopropenyl-6-heptenal compound as an intermediate. Furthermore, the present inventors have found that the above 3-isopropenyl-6-heptenoic acid ester compound can be efficiently and industrially obtained without performing an oxidation reaction by subjecting it to a Wittig reaction of a 4-pentenyltriphenylphosphonium halide compound and a 2-propanone compound having a protected hydroxyl group, followed by a deprotection reaction and then a Johnson-Claisen rearrangement reaction, leading to the present invention.

[0013] According to one aspect of the present invention, the following general formula (1):

Chemical formula

Chemical formula

[0014] In another aspect of the present invention, a method for producing the above 3-isopropenyl-6-heptenal compound (2) and subjecting the 3-isopropenyl-6-heptenal compound (2) to a four-carbon chain extension reaction including a Wittig reaction using an ethyltriphenylphosphonium halide compound and ethylene oxide to obtain a 6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3):

Chemical formula

Chemical formula

[0015] In another aspect of the present invention, the following general formula (5):

Chemical formula

Chemical formula

[0016] In still another aspect of the present invention, the following general formula (5):

Chemical formula

Chemical formula

Chemical formula

[0017] Furthermore, in another aspect of the present invention, the following general formula (1'):

Chemical formula

[0018] According to the present invention, it is possible to provide a method for efficiently and industrially producing a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound, which eliminates the need for an oxidation reaction that is difficult to carry out industrially in terms of safety, economy, and environmental impact. Further, according to the present invention, it is possible to provide a method for producing a 3-isopropenyl-6-heptenal compound, which is a useful intermediate in the production of a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound. Furthermore, according to the present invention, it is possible to provide a 3-isopropenyl-6-methyl-6-heptenoic acid ester compound, which is a useful intermediate in the production of a 3-isopropenyl-6-methyl-6-heptenal compound. [Embodiments for Carrying Out the Invention]

[0019] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited thereto. In the chemical formulas of the intermediates, reagents, and target compounds in the present specification, there may be some that have isomers with different substitution positions in terms of structure, or stereoisomers such as enantiomers or diastereoisomers. However, unless otherwise specified, each chemical formula represents all of these isomers in any case. Further, these isomers may be present alone or as a mixture.

[0020] As described below, the present inventors considered the synthetic plans for the target compounds of the present invention, namely, a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4), a 6-isopropenyl-3-methyl-3,9-decadienol compound (3), a 3-isopropenyl-6-heptenal compound (2), and a 3-isopropenyl-6-methyl-6-heptenoic acid ester compound (1). [Chemical formula]

[0021] In the reaction formula of the above retrosynthetic analysis, the open arrow represents a transform in retrosynthetic analysis. Also, X represents a halogen atom, and R 1 represents a hydrogen atom or a methyl group, R 2 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 3 represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R 4 represents a protecting group for a hydroxyl group.

[0022] (Step F’) 6-Isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4), which is one of the target products of the present invention, is considered to be synthesized by subjecting 6-isopropenyl-3-methyl-3,9-decadienol compound (3) to an esterification reaction.

[0023] The above general formula (4) represents a (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4a), a (3E,6R)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4b), a (3Z,6S)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4c), a (3E,6S)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4d), or a combination of two or more thereof. [Chemical formula]

[0024] The above general formula (3) represents a (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3a), a (3E,6R)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3b), a (3Z,6S)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3c), a (3E,6S)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3d), or a combination of two or more thereof.

Chemical formula

[0025] (Step E’) The 6-isopropenyl-3-methyl-3,9-decadienol compound (3), which is another target compound of the present invention, is considered to be synthesized by subjecting the 3-isopropenyl-6-heptenal compound (2) to a carbon chain elongation reaction with four carbons including Wittig using an ethyltriphenylphosphonium halide compound represented by the general formula (9) and ethylene oxide (10).

[0026] The above general formula (2) represents an (R)-3-isopropenyl-6-heptenal compound represented by the following general formula (2a), an (S)-3-isopropenyl-6-heptenal compound represented by the following general formula (2b), or a combination thereof.

Chemical formula

[0027] (Step D’) The 3-isopropenyl-6-heptenal compound (2), which is another target of the present invention, is considered to be synthesized by selectively reducing the ester of the 3-isopropenyl-6-heptenoic acid ester compound (1) to an aldehyde, that is, by subjecting the 3-isopropenyl-6-heptenoic acid ester compound (1) to a reduction reaction with a reducing agent.

[0028] The above general formula (1) represents an (R)-3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1a), an (S)-3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1b), or a combination thereof.

Chemical formula

[0029] Next, the synthesis plan of the 3-isopropenyl-6-heptenoic acid ester compound (1), which is an intermediate used in the present invention, was considered.

[0030] (Step C’) The 3-isopropenyl-6-heptenoic acid ester compound (1) can be considered to be synthesized by subjecting the 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with the orthoacetic acid ester compound (11).

[0031] The above general formula (8) represents a (Z)-2-methyl-2,6-heptadienol compound represented by the following general formula (8a), an (E)-2-methyl-2,6-heptadienol compound represented by the following general formula (8b), or a combination thereof.

Chemical formula

[0032] (Step B’) The 2-methyl-2,6-heptadienol compound (8) can be considered to be synthesized by subjecting the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position to a deprotection reaction.

[0033] The above formula (7) represents a (Z)-2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following formula (7a), an (E)-2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following formula (7b), or a combination thereof.

Chemical formula

[0034] (Engineering A’) The 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position can be synthesized by subjecting the 4-pentenyltriphenylphosphonium halide compound (5) and the 2-propanone compound (6) having a protected hydroxyl group to a Wittig reaction.

[0035] Considering the reaction formula of the above retrosynthetic analysis, the chemical reaction formula according to one embodiment of the present invention is shown as follows. The following steps A to F respectively correspond to steps A' to F' in the reaction formula of the retrosynthetic analysis described above. [Chemical formula]

[0036] That is, by selectively reducing the ester of the 3-isopropenyl-6-heptenoic acid ester compound (1) to an aldehyde, it becomes possible to synthesize the 3-isopropenyl-6-heptenal compound (2) (the above step D), and thereby, simply, the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) (the above step E) and the 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) (the above step F) can be obtained.

[0037] The above steps A to F as embodiments of the present invention will be described in detail below. First, step D of synthesizing the target compound of the present invention, 3-isopropenyl-6-heptenal compound (2), step E of synthesizing 6-isopropenyl-3-methyl-3,9-decadienol compound (3), and step F of synthesizing the target compound of the present invention, 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) will be described in this order. Thereafter, step A of synthesizing 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, step B of synthesizing 2-methyl-2,6-heptadienol compound (8), and step C of synthesizing 3-isopropenyl-6-heptenoate compound (1) will be described.

[0038] The above steps D to F and steps A to C as embodiments of the present invention will be described in detail below. [1] Step D The following describes step D of synthesizing 3-isopropenyl-6-heptenal compound (2). As shown in the following chemical reaction formula, for example, the 3-isopropenyl-6-heptenoate compound (1) obtained in step C described in detail below is subjected to a reduction reaction with a reducing agent to reduce the ester of the 3-isopropenyl-6-heptenoate compound (1) to obtain it.

Chemical formula

[0039] First, the 3-isopropenyl-6-heptenoate compound represented by the following general formula (1) will be described.

Chemical formula

[0040] The 3-isopropenyl-6-heptenoic acid ester compound (1) may exist as the (R)-3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1a) and the (S)-3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1b). These isomers may be single or a mixture, but California red scale and White peach scale it is preferable that (1a) having the same skeleton as the natural sex pheromone possessed by the female of

Chemical formula

[0041] R 1 represents a hydrogen atom or a methyl group, and R 2 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Examples of the monovalent hydrocarbon group include linear or branched saturated hydrocarbon groups such as methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group and 1-methylethyl group; and linear or branched unsaturated hydrocarbon groups such as vinyl group, 1-propenyl group, 2-propenyl group, 2-methyl-1-propenyl group, ethynyl group, propynyl group and 1-butynyl group, and hydrocarbon groups that are isomers thereof may also be used. Further, a part of the hydrogen atoms of these monovalent hydrocarbon groups may be substituted with a methyl group, an ethyl group or the like. An appropriate one can be selected from these monovalent hydrocarbon groups in consideration of the reactivity and / or ease of availability in the subsequent reaction.

[0042] Specific examples of the 3-isopropenyl-6-heptenoic acid ester compound (1) include 3-isopropenyl-6-heptenoic acid methyl esters such as methyl 3-isopropenyl-6-heptenoate, ethyl 3-isopropenyl-6-heptenoate, and propyl 3-isopropenyl-6-heptenoate; 3-isopropenyl-6-methyl-6-heptenoic acid ester compounds (1') such as methyl 3-isopropenyl-6-methyl-6-heptenoate, ethyl 3-isopropenyl-6-methyl-6-heptenoate, and propyl 3-isopropenyl-6-methyl-6-heptenoate. Among the 3-isopropenyl-6-heptenoic acid ester compounds (1), the 3-isopropenyl-6-methyl-6-heptenoic acid ester compound (1') in which R 1 is a methyl group, as shown below, is White peach scale useful from the viewpoint of being usable as an intermediate for the production of the female sex pheromone of

Chemical formula

[0043] R 2 is as defined in the above general formula (1).

[0044] Next, the 3-isopropenyl-6-heptenal compound represented by the following general formula (2) will be described.

Chemical formula

[0045] The 3-isopropenyl-6-heptenal compound (2) may exist as an (R)-3-isopropenyl-6-heptenal compound represented by the following general formula (2a) and an (S)-3-isopropenyl-6-heptenal compound represented by the following general formula (2b). These isomers may be alone or a mixture, but California red scale and White peach scale it is preferable that (2a) having the same skeleton as the natural sex pheromone of the female of

Chemical formula

[0046] R 1 is as defined by the above general formula (1).

[0047] Specific examples of the 3-isopropenyl-6-heptenal compound (2) include 3-isopropenyl-6-heptenal and 3-isopropenyl-6-methyl-6-heptenal.

[0048] The 3-isopropenyl-6-heptenal compound (2) can be synthesized by selectively reducing the ester group of the 3-isopropenyl-6-heptenoic acid ester compound (1) which is a substrate to an aldehyde. The reduction reaction of the ester group is carried out by using a reducing agent, in a solvent or without a solvent, with heating or cooling as necessary.

[0049] In the reduction reaction of the ester group, alcohol may be by-produced due to over-reduction. Therefore, in this reduction reaction, among the conditions of the reduction reaction described below, the optimal conditions that can suppress the by-production of alcohol due to over-reduction and can selectively obtain the 3-isopropenyl-6-heptenal compound (2) in a good yield can be selected. Examples of the optimal conditions include using sodium = t-butoxide and diisobutylaluminum hydride to prepare sodium diisobutyl t-butoxyaluminum in the reaction system and using this as a reducing agent, using tetrahydrofuran as a solvent, setting the reaction temperature to 10 °C or lower, or combining at least two of them, etc.

[0050] Examples of the reducing agent in the reduction reaction include, for example, hydrogen; boron compounds such as borane, alkyl borane, and dialkyl borane; metal hydrides such as dialkyl silane, ester silane, alkyl aluminum, dialkyl aluminum, sodium hydride, lithium hydride, potassium hydride, and calcium hydride; and complex hydride salts such as sodium borohydride, lithium borohydride, potassium borohydride, calcium borohydride, sodium aluminum hydride, sodium diisobutyl alkoxy aluminum hydride, potassium diisobutyl alkoxy aluminum hydride, lithium diisobutyl alkoxy aluminum hydride, lithium aluminum hydride, sodium trimethoxyborohydride, lithium trimethoxyaluminum hydride, lithium diethoxyaluminum hydride, lithium tri-t-butoxyaluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride, lithium triethylborohydride, diisobutyl aluminum hydride, and diisobutyl alkoxy, and alkoxy or alkyl derivatives of the complex hydride salts. However, from the viewpoints of reaction conditions, ease of post-treatment, ease of isolation of the product, etc., diisobutyl aluminum hydride, sodium diisobutyl alkoxy aluminum hydride, potassium diisobutyl alkoxy aluminum hydride, and lithium diisobutyl alkoxy aluminum hydride are preferred. It is preferable to use those prepared in the reaction system for sodium diisobutyl alkoxy aluminum hydride, potassium diisobutyl alkoxy aluminum hydride, and lithium diisobutyl alkoxy aluminum hydride. Examples of the preparation method include, for example, mixing diisobutyl aluminum hydride and the corresponding alkoxy metal salt at an arbitrary ratio. Particularly preferred examples of the reducing agent that suppresses over-reduction to alcohol and enables aldehyde to be obtained in good yield include sodium diisobutyl t-butoxyaluminum hydride, potassium diisobutyl t-butoxyaluminum hydride, and lithium diisobutyl t-butoxyaluminum hydride.

[0051] The amount of the reducing agent used in the reduction reaction varies depending on the reducing agent used and / or reaction conditions, etc. Generally, it is preferably 0.5 mol to 1,000,000 mol, more preferably 0.9 to 200 mol, per 1 mol of the 3-isopropenyl-6-heptenoic acid ester compound (1).

[0052] As the solvent used in the reduction reaction, although it also depends on the type of the reducing agent used, water; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, ethylene glycol monomethyl ether and diethylene glycol monomethyl ether; nitriles such as acetonitrile; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide are preferred. One type of the solvent or, if necessary, two or more types may be used. Further, a commercially available solvent can be used. The amount of the solvent used is preferably 10 g to 10,000 g per 1 mol of the 3-isopropenyl-6-heptenoic acid ester compound (1).

[0053] The reaction temperature of the reduction reaction is preferably -78°C to the boiling point temperature of the solvent, more preferably -78°C to 50°C. The reaction time of the reduction reaction can be arbitrarily set, but it is desirable in terms of yield to complete the reaction by tracking the reaction with gas chromatography (GC) and / or thin layer chromatography (TLC), and it is usually about 0.5 to 72 hours.

[0054] When the 3-isopropenyl-6-heptenal compound (2) obtained by the above method has sufficient purity, it may be used in the next step as a crude product, or it may be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0055] [2] Step E Hereinafter, Step E for synthesizing the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) will be described. The 6-isopropenyl-3-methyl-3,9-decadienol compound (3) can be obtained by subjecting the 3-isopropenyl-6-heptenal compound (2) obtained in the above Step D to a 4-carbon chain extension reaction including a Wittig reaction using an ethyltriphenylphosphonium halide compound (9) and ethylene oxide (10), as shown in the following reaction formula.

Chemical formula

[0056] First, the ethyltriphenylphosphonium halide compound represented by the following general formula (9) will be described.

Chemical formula

[0057] X represents a halogen atom, preferably a chlorine atom, a bromine atom or an iodine atom.

[0058] Commercially available ethyltriphenylphosphonium halide compounds (9) can be used. Alternatively, the ethyltriphenylphosphonium halide compound (9) can also be prepared by reacting an ethyl halide compound represented by the following general formula (12) with triphenylphosphine (PPh3) in a solvent according to the reaction formula shown below.

Chemical formula

[0059] X in the general formula (12) is as defined in the general formula (9) above.

[0060] When preparing the ethyltriphenylphosphonium halide compound (9) according to the above reaction formula, a metal halide and / or a quaternary onium salt may be added to accelerate the reaction. Examples of the metal halide include lithium iodide, sodium iodide, potassium iodide, lithium bromide, sodium bromide, and potassium bromide. Examples of the quaternary onium salt include tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylphosphonium bromide, tetraethylammonium iodide, tetrabutylammonium iodide, and tetrabutylphosphonium iodide.

[0061] Also, when preparing the ethyltriphenylphosphonium halide compound (9), one or more bases selected from hydrogen carbonate salts such as lithium hydrogen carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate; carbonate salts such as lithium carbonate, sodium carbonate, and potassium carbonate; hydroxide salts such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; and organic bases such as triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine, quinoline, pyrrolidine, piperidine, collidine, lutidine, and morpholine may be added to make the reaction solution basic.

[0062] As the solvent used for preparing the ethyltriphenylphosphonium halide compound (9), the same solvent as that in the Wittig reaction described below can be used. The amount of the solvent is preferably 10 g to 10,000 g per 1 mol of the ethyl halide compound (12).

[0063] The reaction temperature in the preparation of ethyltriphenylphosphonium halide compound (9) may vary depending on the reaction conditions, but it is preferably carried out at -10°C to 180°C, more preferably 0°C to 160°C, and even more preferably 10°C to 140°C. The reaction time in the preparation of ethyltriphenylphosphonium halide compound (9) can be arbitrarily set, but it is desirable in terms of yield to follow the reaction by gas chromatography (GC) or thin-layer chromatography (TLC) until the reaction is completed, and it is usually about 0.5 to 60 hours.

[0064] Next, the 6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3) will be described.

Chemical formula

[0065] The 6-isopropenyl-3-methyl-3,9-decadienol compound (3) can exist as a (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3a), a (3E,6R)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3b), a (3Z,6S)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3c), and a (3E,6S)-6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3d). These isomers may be present alone or as a mixture of two or more, but California red scale and White peach scale it is preferable that (3a) having the same skeleton as the natural sex pheromone of the female of [species name] is included.

Chemical formula

[0066] R 1 is as defined in the above general formula (1).

[0067] The Wittig reaction refers to a chemical reaction in which an alkene is synthesized from a carbonyl compound using a phosphorous ylide called a Wittig reagent. Hereinafter, regarding the 4-carbon chain elongation reaction including the Wittig reaction, when R 1 is a hydrogen atom, the number of carbon atoms will be taken as an example for explanation. When R 1 is CH3, the number of carbon atoms in the part having R 1 will increase by 1 carbon atom. Examples of the 4-carbon chain elongation reaction including the Wittig reaction include the following reaction pathways 1 and 2.

[0068] In the method shown in reaction pathway 1, a base is allowed to act on an ethyltriphenylphosphonium halide compound (9) having 2 carbon atoms (C2) to prepare an ylide (13), and the prepared ylide (13) is reacted with ethylene oxide (10) having 2 carbon atoms (C2) to prepare 3-triphenylphosphoniobutoxide (14) having a 4-carbon skeleton (C4) (C2 + C2 = C4). A base is allowed to act on the prepared 3-triphenylphosphoniobutoxide (14) to convert it to a phosphorous ylide (15), and then, by the Wittig reaction of the phosphorous ylide (15) and a 3-isopropenyl-6-heptenal compound (2) having 10 carbon atoms (C10), a 6-isopropenyl-3-methyl-3,9-decadienol compound (3) having 14 carbon atoms (C14) is synthesized (C4 + C10 = C14).

[0069] In the method shown in Reaction Route 2, a base is allowed to act on an ethyltriphenylphosphonium halide compound (9) having two carbons (C2) to prepare an ylide (13). The prepared ylide (13) is reacted with a 3-isopropenyl-6-heptenal compound (2) having ten carbons (C10) to prepare a betaine intermediate (16) having a twelve-carbon skeleton (C12) (C2 + C10 = C12). A base is allowed to act on the prepared betaine intermediate (16) to convert it to a β-oxide phosphorous ylide (17). Thereafter, the β-oxide phosphorous ylide (17) is reacted with ethylene oxide (10) having two carbons (C2) to synthesize a 6-isopropenyl-3-methyl-3,9-decadienol compound (3) having fourteen carbons (C14) (C12 + C2 = C14). The synthesis method of Reaction Route 2 is generally known as a three-dimensional Wittig reaction or a SCOOPY (α-Substitution plus Carbonyl Olefination via β-Oxide Phosphorous Ylides) reaction (see, for example, Non-Patent Document 4 above).

[0070] Among these synthesis methods, considering economy, reactivity, and yield, one suitable for industrial production methods may be selected. From the perspective of yield, Reaction Route 1 is preferred.

Chemical formula

Chemical formula

[0071] First, Reaction Route 1 will be described in detail below. The preparation of the ylide (13) from the ethyltriphenylphosphonium halide compound (9) having two carbons (C2) is carried out by adding a base to the ethyltriphenylphosphonium halide compound (9) in a solvent, optionally with heating or cooling. Examples of the base used for preparing the ylide (13) include metal 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, and potassium t-amyloxide; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride, and dimsylsodium; metal amides such as sodium amide, lithium amide, lithium diisopropylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium dicyclohexylamide; and metal hydrides such as sodium hydride, potassium hydride, and calcium hydride. These bases may be used alone or in combination of two or more, and can be selected in consideration of the type of substrate and / or reactivity and / or selectivity. The amount of the base used is preferably 0.7 mol to 5 mol per 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0072] As the solvent used for preparing the ylide (13), the same solvent as that in the Wittig reaction described below can be used. The amount of the solvent is preferably 10 g to 10,000 g per 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0073] The reaction temperature in the preparation of the ylide (13) is preferably -78°C to 50°C, more preferably -78°C to 35°C. The reaction time in the preparation of the ylide (13) is preferably 5 minutes to 18 hours, more preferably 5 minutes to 10 hours from the viewpoint of reagent stability.

[0074] Next, ethylene oxide (10) having two carbons (C2) is added to the prepared ylides (13) in a solvent to increase the carbon number by two carbons, whereby 3-triphenylphosphoniobutoxide (14) having a four-carbon skeleton (C4) can be prepared. The amount of ethylene oxide (10) used in the two-carbon carbon number increasing reaction is preferably 0.6 mol to 5 mol with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0075] As the solvent in the two-carbon carbon number increasing reaction, the same solvent as that in the Wittig reaction described later can be used. The amount of the solvent is preferably 10 g to 10,000 g with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0076] The reaction temperature in the two-carbon carbon number increasing reaction is preferably -78°C to 50°C, more preferably -78°C to 35°C. The reaction time in the two-carbon carbon number increasing reaction is preferably 5 minutes to 18 hours, more preferably 5 minutes to 10 hours from the viewpoint of reagent stability.

[0077] Next, a base is added to the 3-triphenylphosphoniobutoxide (14) obtained by the two-carbon carbon number increasing reaction in a solvent, if necessary, under heating or cooling, whereby it can be converted into phosphorus ylide (15). The type and amount of the base, the solvent, and the reaction temperature and reaction time used in the preparation of phosphorus ylide (15) from 3-triphenylphosphoniobutoxide (14) are the same as the conditions described in the preparation of the above ylides (13).

[0078] Finally, 3-isopropenyl-6-heptenal compound (2) having ten carbons (C10) is added to the prepared phosphorus ylide (15) under cooling or heating conditions, if necessary, to carry out a Wittig reaction, whereby 6-isopropenyl-3-methyl-3,9-decadienol compound (3) having fourteen carbons (C14) can be synthesized. The amount of the 3-isopropenyl-6-heptenal compound (2) used in the Wittig reaction is preferably 0.1 mol to 5 mol with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9). Examples of the solvent in the Wittig reaction include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; chlorinated solvents such as methylene chloride, chloroform and trichloroethylene; aprotic polar solvents such as N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide and hexamethylphosphoric triamide; nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol and t-butyl alcohol. One type of the solvent or, if necessary, two or more types thereof may be used. Also, commercially available solvents can be used. The amount of the solvent is preferably 10 g to 10,000 g with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0079] The reaction temperature of the Wittig reaction is preferably -78°C to 50°C, more preferably -50°C to 35°C. The reaction time of the Wittig reaction can be arbitrarily set, but it is desirable from the viewpoint of yield to complete the reaction by tracking the reaction with gas chromatography (GC) and / or thin layer chromatography (TLC), and it is usually about 0.5 to 24 hours.

[0080] Next, reaction route 2 will be described in detail below. The preparation of the ylide (13) from the ethyltriphenylphosphonium halide compound (9) having 2 carbons (C2) is carried out by adding a base to the ethyltriphenylphosphonium halide compound (9) in a solvent, with heating or cooling as necessary. Regarding the method for preparing the ylide (13), the base used, the amount of the base used, the solvent, and the reaction temperature and reaction time are the same as the conditions described for the preparation of the above ylide (13).

[0081] Next, a betaine intermediate (16) having a 12-carbon skeleton (C12) can be prepared by adding a 3-isopropenyl-6-heptenal compound (2) having 10 carbons (C10) to the prepared ylide (13) in a solvent to increase the carbon number by 10. The amount of the 3-isopropenyl-6-heptenal compound (2) used in the preparation of the betaine intermediate is preferably 0.1 mol to 5 mol with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0082] Examples of the solvent used in the preparation of the betaine intermediate include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; aprotic polar solvents such as N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and hexamethylphosphoric triamide; nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, and t-butyl alcohol. One type of the solvent or, if necessary, two or more types may be used. Also, commercially available solvents can be used. The amount of the solvent is preferably 10 g to 10,000 g with respect to 1 mol of the ethyltriphenylphosphonium halide compound (9).

[0083] The reaction temperature in the preparation of the betaine intermediate is preferably from -78°C to 50°C, more preferably from -78°C to 20°C. The reaction time in the preparation of the betaine intermediate can be arbitrarily set, but is usually about 0.001 to 24 hours.

[0084] Next, a base is added to the prepared betaine intermediate (16) to prepare β-oxidolinylidene (17). The type and amount of the base used, the solvent, and the reaction temperature and reaction time in the preparation of β-oxidolinylidene (17) are the same as the conditions described in the preparation of the above-mentioned ylidene (13).

[0085] Finally, by performing a two-carbon chain elongation reaction of adding ethylene = oxide (10) to the prepared β-oxidolinylidene (17) in a solvent, a 6-isopropenyl-3-methyl-3,9-decadienol compound (3) having 14 carbons (C14) can be synthesized. The amount of ethylene = oxide (10) used, the solvent, and the reaction temperature and reaction time are the same as the conditions described in the preparation of the above-mentioned 3-triphenylphosphoniobutoxide (14).

[0086] When the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) obtained by the above method has sufficient purity, it may be used in the next step as a crude product, but it may also be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0087] [3] Step F Hereinafter, Step F for synthesizing a 6-isopropenyl-3-methyl-3,9-decadienyl = carboxylate compound (4) will be described. The 6-isopropenyl-3-methyl-3,9-decadienyl = carboxylate compound (4) can be obtained by subjecting the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) obtained in the above Step E to an esterification reaction, as shown by the following reaction formula. [Chemical formula]

[0088] The 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4) will be described.

Chemical formula

[0089] The 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) may exist as a (3Z,6R)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4a), a (3E,6R)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4b), a (3Z,6S)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4c), and a (3E,6S)-6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following formula (4d). These isomers may be alone or a mixture of two or more, but California red scale and White peach scale it is preferable that (4a) having the same skeleton as the natural sex pheromone of the female of is included.

Chemical formula

[0090] R 1 is as defined in the above general formula (1). R 3 represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Examples of the monovalent hydrocarbon group include linear or branched saturated hydrocarbon groups such as methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, and 1-methylethyl group; and linear or branched unsaturated hydrocarbon groups such as vinyl group, 1-propenyl group, 2-propenyl group, 2-methyl-1-propenyl group, ethynyl group, propynyl group, and 1-butynyl group. Hydrocarbon groups that are isomers of these may also be used. Further, a part of the hydrogen atoms of these monovalent hydrocarbon groups may be substituted with a methyl group, an ethyl group, or the like. From among these monovalent hydrocarbon groups, an appropriate one can be selected in consideration of the reactivity and / or ease of availability in subsequent reactions.

[0091] Specific examples of the 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) include 6-isopropenyl-3-methyl-3,9-decadienyl acetate, 6-isopropenyl-3-methyl-3,9-decadienyl propionate, 6-isopropenyl-3,9-dimethyl-3,9-decadienyl acetate, and 6-isopropenyl-3,9-dimethyl-3,9-decadienyl propionate.

[0092] As the esterification reaction, known methods for producing esters can be applied, for example, (i) reaction with an acylating agent, (ii) reaction with a carboxylic acid, (iii) transesterification reaction, (iv) a method in which the hydroxyl group of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) is converted into a leaving group and then reacted with a carboxylic acid, and the like.

[0093] (i) Reaction with an acylating agent In the reaction with an acylating agent, a method in which the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) is reacted in a single solvent or a mixed solvent of two or more solvents in the order of an acylating agent, a base, or in the reverse order, or simultaneously with an acylating agent and a base can be applied. Examples of acylating agents include acyl halides such as acyl chlorides and acyl bromides; carboxylic acid mixed acid anhydrides such as carboxylic acid anhydrides, carboxylic acid trifluoroacetic acid mixed acid anhydrides, carboxylic acid methanesulfonic acid mixed acid anhydrides, carboxylic acid trifluoromethanesulfonic acid mixed acid anhydrides, carboxylic acid benzenesulfonic acid mixed acid anhydrides, and carboxylic acid p-toluenesulfonic acid mixed acid anhydrides; and carboxylic acid p-nitrophenyl and the like. Specific examples of acyl chlorides include acetyl chloride, propionyl chloride, crotonoyl chloride, benzoyl chloride and the like. Examples of carboxylic acid anhydrides include acetic anhydride and propionic anhydride and the like. The amount of the acylating agent used is preferably in the range of 1 mol to 500 mol, more preferably 1 mol to 50 mol, and still more preferably 1 mol to 5 mol, per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0094] Examples of the base used in the reaction with the acylating agent include N,N-diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, 2-ethylpyridine, 4-dimethylaminopyridine and the like. The amount of the base used is preferably 1 mol to 500 mol per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0095] As the solvent used in the reaction with an acylating agent, the above base may be used as a solvent, or chlorinated solvents such as methylene chloride, chloroform and trichloroethylene; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and 1,4-dioxane; nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and n-butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide. The solvent may be used singly or, if necessary, two or more kinds thereof may be used. Further, a commercially available solvent can be used. The amount of the solvent used is preferably 10 g to 1,000,000 g per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0096] In the reaction using an acylating agent such as a carboxylic anhydride, a carboxylic mixed anhydride and p-nitrophenyl carboxylate, the reaction can also be carried out under an acid catalyst instead of a base. Examples of the acid catalyst include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid; organic acids such as oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) isopropoxide and titanium(IV) oxide. The acid catalyst may be used alone or, if necessary, two or more types may be used. Also, a commercially available acid catalyst can be used. The amount of the acid catalyst used in the reaction with acylating agents such as carboxylic anhydrides, mixed carboxylic anhydrides, and p-nitrophenyl carboxylates is preferably from 0.0001 mol to 100 mol.

[0097] The reaction temperature in the reaction with the acylating agent can be appropriately selected depending on the type of the acylating agent used and / or the reaction conditions. Generally, it is preferably from -50 °C to the boiling point temperature of the solvent, and more preferably from -20 °C to room temperature (5 °C to 35 °C, the same hereinafter). The reaction time in the reaction with the acylating agent can be arbitrarily set, but it is preferably optimized by tracking the progress of the reaction using gas chromatography (GC) or thin layer chromatography (TLC). Usually, it is preferably from 5 minutes to 240 hours.

[0098] (ii) Reaction with carboxylic acid The reaction with the carboxylic acid is a dehydration reaction between the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) and the carboxylic acid, and it is generally carried out in the presence of an acid catalyst.

[0099] Specific examples of the carboxylic acid in the reaction between the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) and the carboxylic acid include linear saturated carboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid, and caproic acid; branched saturated carboxylic acids such as isobutyric acid, isovaleric acid, 4-methylpentanoic acid, 2-methylbutanoic acid, and pivalic acid; linear unsaturated carboxylic acids such as acrylic acid, crotonic acid, and 3-butenoic acid; branched unsaturated carboxylic acids such as methacrylic acid, senecioic acid, tiglic acid, angelic acid, 3-methyl-4-pentenoic acid, and 4-methyl-4-pentenoic acid; and aromatic carboxylic acids such as benzoic acid. The amount of the carboxylic acid used is preferably from 1 mol to 500 mol, more preferably from 1 mol to 50 mol, and still more preferably from 1 mol to 5 mol per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0100] When using the reaction of 6-isopropenyl-3-methyl-3,9-decadienol compound (3) with a carboxylic acid, an acid catalyst may be used. The acid catalyst is the same as the acid catalyst used in the reaction with the above-mentioned acylating agent. The amount of the acid catalyst used is preferably 0.0001 mol to 100 mol, more preferably 0.001 mol to 1 mol, and still more preferably 0.01 mol to 0.05 mol per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0101] The solvent used in the reaction of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) with the carboxylic acid and its amount used are the same as those of the solvent used in the reaction with the above-mentioned acylating agent and its amount used. The reaction temperature of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) with the carboxylic acid can be appropriately selected according to the reaction conditions. Generally, -50°C to the boiling point temperature of the solvent is preferred, and room temperature to the boiling point temperature of the solvent is more preferred. Also, a reaction may be carried out while removing the generated water out of the reaction system by azeotropy using a solvent containing hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene. In this case, water may be distilled off while refluxing at the boiling point of the solvent under normal pressure, or water may be distilled off at a temperature lower than the boiling point under reduced pressure. The reaction time in the reaction with the carboxylic acid can be arbitrarily set, but it is preferably optimized by tracking the progress of the reaction using gas chromatography (GC) or thin-layer chromatography (TLC). Usually, 5 minutes to 240 hours is preferred.

[0102] (iii) Transesterification reaction The transesterification reaction is carried out by reacting the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) with an alkyl carboxylate in the presence of a catalyst and removing the generated alcohol. As the alkyl carboxylate, a primary alkyl ester of a carboxylic acid is preferred, and from the viewpoints of price and / or ease of progress of the reaction, etc., methyl carboxylate, ethyl carboxylate, and n-propyl carboxylate are more preferred. Examples of the carboxylic acid include the same compounds as the carboxylic acid in the esterification reaction that reacts with the carboxylic acid. The usage amount of the alkyl carboxylate is preferably 1 mol to 500 mol, more preferably 1 mol to 50 mol, and still more preferably 1 mol to 5 mol with respect to 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0103] Examples of the catalyst used in the transesterification reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; organic acids such as oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; bases such as sodium methoxide, sodium ethoxide, potassium t-butoxide, and 4-dimethylaminopyridine; salts such as sodium cyanide, potassium cyanide, sodium acetate, potassium acetate, calcium acetate, tin acetate, aluminum acetate, aluminum acetoacetate, and alumina; Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) isopropoxide, and titanium(IV) oxide. One type of the catalyst or, if necessary, two or more types may be used. Further, a commercially available catalyst can be used. The usage amount of the catalyst is preferably 0.0001 mol to 100 mol, more preferably 0.001 mol to 1 mol, and still more preferably 0.01 mol to 0.05 mol with respect to 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0104] The transesterification reaction may be carried out without a solvent, using the alkyl carboxylate itself as the reaction reagent as the solvent, or a solvent may be additionally used. In the case of no solvent, since operations such as unnecessary concentration and solvent recovery are not required, it is preferably carried out without a solvent. Examples of the solvent used in the transesterification reaction include hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; and ethers such as diethyl ether, dibutyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, and 1,4-dioxane. One type of the solvent may be used, or two or more types may be used as required. Also, commercially available solvents can be used. The amount of the solvent used is preferably 10 g to 1,000,000 g with respect to 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0105] The reaction temperature in the transesterification reaction can be selected as an appropriate reaction temperature depending on the type of the alkyl carboxylate used and / or the reaction conditions, and is usually carried out under heating. From the viewpoint of the ease of progress of the reaction, etc., the reaction is carried out near the boiling points of the lower alcohols having 1 to 3 carbon atoms and low boiling points generated by the transesterification reaction, that is, methanol, ethanol, 1-propanol, etc., and it is preferable to carry out the reaction while distilling off the generated lower alcohol. The alcohol may be distilled off at a temperature lower than the boiling point under reduced pressure. The reaction time in the transesterification reaction can be arbitrarily set, but it is advisable to track and optimize the progress of the reaction using gas chromatography (GC) or thin layer chromatography (TLC), and usually 5 minutes to 240 hours is preferable.

[0106] (iv) A method of converting the hydroxyl group of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) into a leaving group and then reacting it with a carboxylic acid In the method of converting the hydroxyl group of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) into a leaving group and then reacting it with a carboxylic acid, for example, the hydroxyl group of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) is converted into a leaving group selected from halogen atoms such as chloride, bromide, and iodide; alkanesulfonyloxy groups such as methanesulfonate and trifluoromethanesulfonate; and arenesulfonyloxy groups such as benzenesulfonate and p-toluenesulfonate, and then, in a solvent and in the presence of a base, these are reacted with a carboxylic acid. Examples of the carboxylic acid include the same compounds as the carboxylic acid in the reaction with the above carboxylic acid. The amount of the carboxylic acid used is preferably 1 mol to 500 mol, more preferably 1 mol to 50 mol, and even more preferably 1 mol to 5 mol per 1 mol of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3).

[0107] Regarding the solvent used in the method of converting the hydroxyl group of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) into a leaving group and then reacting it with a carboxylic acid, the amount of the solvent used, the base and the amount of the base used, and the reaction time and reaction temperature, they are the same as those of the solvent used in the reaction of the 6-isopropenyl-3-methyl-3,9-decadienol compound (3) with an acylating agent (the above (i)), the amount of the solvent used, the base and the amount of the base used, and the reaction time and reaction temperature.

[0108] Instead of reacting the carboxylic acid in a solvent in the presence of a base, carboxylates such as sodium carboxylate, lithium carboxylate, potassium carboxylate, and ammonium carboxylate may be used. The amount of the carboxylate used is the same as the amount of the carboxylic acid used in the esterification reaction for reacting with the carboxylic acid.

[0109] When the 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) obtained by the above method has sufficient purity, it may be used in the next step as a crude product, or it may be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0110] [4] Step A Hereinafter, Step A for synthesizing the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position will be described. The 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position can be obtained by converting the 4-pentenyltriphenylphosphonium halide compound (5) to a phosphorus ylide (18) with a base and then subjecting the phosphorus ylide (18) to a Wittig reaction with the 2-propanone compound (6) having a protected hydroxyl group, as shown in the following reaction formula.

Chemical formula

[0111] The 4-pentenyltriphenylphosphonium halide compound represented by the following general formula (5) will be described.

Chemical formula

[0112] R 1 is as defined in the above general formula (1). Ph represents a phenyl group. X is as defined in the above general formula (9).

[0113] Specific examples of the 4-pentenyltriphenylphosphonium halide compound (5) include 4-pentenyltriphenylphosphonium chloride, 4-pentenyltriphenylphosphonium bromide, 4-pentenyltriphenylphosphonium iodide, 4-methyl-4-pentenyltriphenylphosphonium chloride, 4-methyl-4-pentenyltriphenylphosphonium bromide, and 4-methyl-4-pentenyltriphenylphosphonium iodide, etc.

[0114] The 4-pentenyltriphenylphosphonium halide compound (5) can be prepared by reacting a 4-pentenyl halide compound represented by the following general formula (19) with triphenylphosphine (PPh3) in a solvent according to the reaction formula shown below.

Chemical formula

[0115] According to the above reaction formula, when preparing the 4-pentenyltriphenylphosphonium halide compound (5), a metal halide and / or a quaternary onium salt may be added to accelerate the reaction. Examples of the metal halide include lithium iodide, sodium iodide, potassium iodide, lithium bromide, sodium bromide, and potassium bromide, etc. Examples of the quaternary onium salt include tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylphosphonium bromide, tetraethylammonium iodide, tetrabutylammonium iodide, and tetrabutylphosphonium iodide, etc.

[0116] In addition, when preparing the 4-pentenyltriphenylphosphonium halide compound (5), if the reaction system becomes acidic, isomers in which the terminal double bond migrates to the inside may be by-produced. In order to suppress this isomerization, one or more bases selected from hydrogen carbonate salts such as lithium hydrogen carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate; carbonate salts such as lithium carbonate, sodium carbonate, and potassium carbonate; hydroxide salts such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; and organic bases such as triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine, quinoline, pyrrolidine, piperidine, collidine, lutidine, and morpholine are added to make the reaction solution basic. From the viewpoints of economy and / or suppression of isomerization, it is particularly preferable to use potassium carbonate.

[0117] As the solvent used for the preparation of the 4-pentenyltriphenylphosphonium halide compound (5), the same solvent as that used in the preparation of the phosphorus ylide (18) and the Wittig reaction described below can be used. The amount of the solvent is preferably 10 g to 10,000 g per 1 mol of the 4-pentenyltriphenylphosphonium halide compound (5).

[0118] The reaction temperature in the preparation of the 4-pentenyltriphenylphosphonium halide compound (5) depends on the reaction conditions, but is preferably carried out at -10°C to 180°C, more preferably 0°C to 160°C, and even more preferably 10°C to 140°C. The reaction time in the preparation of the 4-pentenyltriphenylphosphonium halide compound (5) can be arbitrarily set, but it is desirable from the viewpoint of yield to follow the reaction by gas chromatography (GC) or thin-layer chromatography (TLC) until the reaction is completed, and it is usually about 0.5 to 60 hours.

[0119] The 2-propanone compound having a protected hydroxyl group represented by the following general formula (6) will be described.

Chemical formula

[0120] R 4 represents a protective group for a hydroxyl group. As the protective group, an appropriate one can be selected from known protective groups for hydroxyl groups that are stable during the intended reaction, post-treatment, and storage, and are also easily deprotected. An appropriate protective group R 4 includes, for example, oxyalkyl groups such as methoxymethyl group, 2-methoxyethoxymethyl group, benzyloxymethyl group, p-methoxybenzyloxymethyl group, 2,2,2-trichloroethoxymethyl group, 1-ethoxyethyl (EE) group, and tetrahydropyranyl (THP) group, and oxyalkyl groups that are isomers thereof may also be used. Also, a part of the hydrogen atoms in these protective groups may be substituted with a methyl group, an ethyl group, or the like. Other protective groups include, for example, acyl groups such as acetyl group, propionyl group, butyryl group, isobutyryl group, propioloyl group, acryloyl group, and benzoyl, and trialkylsilyl groups such as trimethylsilyl (TMS) group, triethylsilyl group, triisopropylsilyl group, and t-butyldimethylsilyl group; and monoalkyldiarylsilyl groups such as t-butyldiphenylsilyl group. Acyl groups or silyl groups that are isomers thereof may also be used. Also, a part of the hydrogen atoms in these acyl groups and silyl groups may be substituted with a methyl group, an ethyl group, or a halogen atom. Examples of the halogen atom include chlorine atom, bromine atom, and iodine atom. The protective group R 4 is preferably a tetrahydropyranyl group, 1-ethoxyethyl group, or trimethylsilyl group from the viewpoints of reactivity and / or economy. When the protective group R 4 is a trimethylsilyl group, a deprotection reaction may occur during the Wittig reaction. However, since the next step is a deprotection reaction, even if the deprotection reaction occurs, there is no problem.

[0121] The 2-propanone compound (6) having a protected hydroxyl group may be a commercially available product or may be prepared from hydroxyacetone according to a known method.

[0122] The 2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following general formula (7) will be described.

Chemical formula

[0123] R 1 is as defined in the above general formula (1), and R 4 is as defined in the above general formula (6).

[0124] The 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position may include a (Z)-2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following general formula (7a) and an (E)-2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following general formula (7b). These isomers may be alone or in a mixture.

[0125]

Chemical formula

[0126] The Wittig reaction is carried out by adding a base to a 4-pentenyltriphenylphosphonium halide compound (5) in a solvent to prepare a phosphorus ylide (18), and then adding a 2-propanone compound (6) having a protected hydroxyl group under cooling or heating conditions as necessary. Examples of the base used for preparing the phosphonium ylide (18) include metal 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, and potassium t-amyloxide; organometallic reagents such as methyl lithium, ethyl lithium, n-butyl lithium, methyl magnesium chloride, and dimsyl sodium; metal amides such as sodium amide, lithium amide, lithium diisopropylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium dicyclohexylamide; and metal hydrides such as sodium hydride, potassium hydride, and calcium hydride. These bases may be used alone or in combination of two or more thereof, and can be selected in consideration of the type of substrate and / or reactivity and / or selectivity. The amount of the base used for preparing the phosphonium ylide reagent is preferably 0.7 mol to 5 mol per 1 mol of the 4-pentenyltriphenylphosphonium halide compound (5). As the solvent used for preparing the phosphonium ylide reagent, the same solvent as that in the Wittig reaction described below can be used. The reaction temperature in the preparation of the phosphonium ylide (18) is preferably -78°C to 50°C, more preferably -78°C to 35°C. The reaction time in the preparation of the phosphonium ylide (18) is preferably 5 minutes to 18 hours, more preferably 5 minutes to 10 hours from the viewpoint of reagent stability.

[0127] The amount of the 2-propanone compound (6) having a protected hydroxyl group used in the Wittig reaction is preferably 0.6 mol to 5 mol per 1 mol of the 4-pentenyltriphenylphosphonium halide compound (5).

[0128] Examples of solvents in the Wittig reaction include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; aprotic polar solvents such as N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and hexamethylphosphoric triamide; nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, and t-butyl alcohol. The solvent may be used singly or, if necessary, in combination of two or more. Also, commercially available solvents can be used. The amount of the solvent is preferably 10 g to 10,000 g per 1 mol of the 4-pentenyltriphenylphosphonium halide compound (5).

[0129] The reaction temperature of the Wittig reaction is preferably -78°C to 50°C, more preferably -50°C to 35°C. The reaction time of the Wittig reaction 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) and / or thin layer chromatography (TLC), and it is usually about 0.5 to 24 hours.

[0130] When the protected 2-methyl-2,6-heptadiene compound (7) having a hydroxyl group at the 1-position obtained in the Wittig reaction has sufficient purity, it may be used in the next step as a crude product, or it may be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0131] [5] Step B The following describes Step B for synthesizing the 2-methyl-2,6-heptadienol compound (8). As shown by the following reaction formula, the 2-methyl-2,6-heptadienol compound (8) can be obtained by subjecting the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, obtained in the above Step A, to a deprotection reaction.

Chemical formula

[0132] The 2-methyl-2,6-heptadienol compound (8) represented by the following general formula (8) will be described.

Chemical formula

[0133] R 1 is as defined in the above general formula (1).

[0134] The 2-methyl-2,6-heptadienol compound (8) may exist as a (Z)-2-methyl-2,6-heptadienol compound represented by the following general formula (8a) and an (E)-2-methyl-2,6-heptadienol compound represented by the following general formula (8b). These isomers may be alone or a mixture.

[0135]

Chemical formula

[0136] For the deprotection reaction, appropriate conditions may be selected according to the type of the protecting group in the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position. For example, when the protecting group is an oxyalkyl group such as a methoxymethyl group, a deprotection reaction by solvolysis using an acid or the like can be applied. Further, for example, when the protecting group is an acyl group, a deprotection reaction by solvolysis using an acid or a base can be applied. Further, for example, when the protecting group is a silyl group such as a t-butyldimethylsilyl group, in addition to a deprotection reaction by solvolysis using an acid, a deprotection reaction using fluoride ions can also be applied.

[0137] In the case of the deprotection reaction using an acid, the 2-methyl-2,6-heptadienol compound (8) can be synthesized by adding an acid and, if necessary, water or a solvent to the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position and cooling or heating. Examples of the acid used in the deprotection reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid or salts thereof; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid or salts thereof; Lewis acids such as lithium tetrafluoroborate, boron trifluoride, boron trichloride, boron tribromide, aluminum trichloride, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, tin dichloride, titanium tetrachloride, titanium tetrabromide, and trimethylsilyl iodide; oxides such as alumina, silica, and titania; and minerals such as montmorillonite. From the viewpoints of economy and / or reactivity, acetic acid can be cited as a preferred example of the acid. One type of the acid or, if necessary, two or more types may be used. Further, a commercially available acid can be used. From the perspective of economy, it is preferable to use a small amount of the acid, and it can be arbitrarily set as long as a practically sufficient reaction rate can be obtained. However, relative to 1 mol of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, it is preferably 0.00001 mol to 10,000 mol, more preferably 0.0001 mol to 1,000 mol, and even more preferably 0.001 mol to 100 mol.

[0138] When water is used in the deprotection reaction using the acid, the amount of water is preferably 1 mol to 10,000 mol, more preferably 1 mol to 1,000 mol, and even more preferably 1 mol to 500 mol relative to 1 mol of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position. Further, the reaction may be carried out while removing the alcohol generated by the deprotection reaction out of the reaction system by a method such as distillation.

[0139] Examples of the solvent in the deprotection reaction using the acid include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; ketones such as acetone and methyl ethyl ketone; aprotic polar solvents such as N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), and hexamethylphosphoric triamide (HMPA); nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, and t-butyl alcohol. One type of the solvent or two or more types may be used as necessary. Further, commercially available solvents can be used. The amount of the solvent is preferably 10 g to 10,000 g relative to 1 mol of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position.

[0140] The reaction temperature of the deprotection reaction using the acid depends on the reaction conditions, but is preferably -78°C to 160°C, more preferably -50°C to 140°C, and even more preferably -30°C to 120°C. The reaction time of the deprotection reaction using the acid can be arbitrarily set, but it is desirable from the viewpoint of yield to follow the reaction using gas chromatography (GC) and / or thin layer chromatography (TLC) to complete the reaction, and it is usually about 0.5 to 24 hours.

[0141] In the case of the deprotection reaction using a base, the 2-methyl-2,6-heptadienol compound (8) can be synthesized by adding a base and, if necessary, water or a solvent to the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, and cooling or heating. Examples of the base used in the deprotection reaction include alkoxides such as sodium methoxide, sodium ethoxide, lithium methoxide, lithium ethoxide, potassium methoxide, and potassium ethoxide; and hydroxide salts such as sodium hydroxide, lithium hydroxide, potassium hydroxide, and barium hydroxide. From the viewpoints of economy and / or reactivity, sodium hydroxide can be cited as a preferred example of the base. One type of the base or, if necessary, two or more types may be used. Also, a commercially available base can be used. The amount of the base used is preferably small from the viewpoint of economy and can be arbitrarily set as long as a practically sufficient reaction rate is obtained. However, relative to 1 mol of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, it is preferably 0.00001 mol to 10,000 mol, more preferably 0.0001 mol to 1,000 mol, and even more preferably 0.001 mol to 100 mol.

[0142] When water is used in the deprotection reaction using the base, the amount of water is preferably 1 to 10,000 moles, more preferably 1 to 1,000 moles, and still more preferably 1 to 500 moles, per mole of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position.

[0143] Examples of the solvent in the deprotection reaction using the base include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; ketones such as acetone and methyl ethyl ketone; aprotic polar solvents such as N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), and hexamethylphosphoric triamide (HMPA); nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, and t-butyl alcohol. The solvent may be used alone or, if necessary, two or more solvents may be used in combination. Also, commercially available solvents can be used. Here, in the selection of the base and the solvent, it is considered that the same conditions are obtained in the reaction system when alkoxides are used as the base in a solvent containing water and when hydroxide salts are used as the base in a solvent containing alcohols. The amount of the solvent is preferably 10 g to 10,000 g per mole of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position.

[0144] The reaction temperature of the deprotection reaction using the base depends on the reaction conditions, but is preferably -78°C to 160°C, more preferably -50°C to 140°C, and still more preferably -30°C to 120°C. The reaction time of the deprotection reaction using the base can be arbitrarily set, but it is desirable from the viewpoint of yield to monitor the reaction using gas chromatography (GC) and / or thin layer chromatography (TLC) to complete the reaction, and it is usually about 0.5 to 24 hours.

[0145] When the protecting group is a silyl group and the deprotection reaction is carried out with fluoride ions, the 2-methyl-2,6-heptadienol compound (8) can be synthesized by adding a reagent serving as a fluoride ion source and, if necessary, a solvent to the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, and cooling or heating. Also, a deprotection reaction can be carried out in combination with the acid described in the deprotection reaction with an acid.

[0146] Examples of the reagent serving as a fluoride ion source include inorganic acids such as hydrofluoric acid; amine complexes such as pyridine·nHF and triethylamine·nHF; inorganic salts such as cesium fluoride, potassium fluoride, lithium tetrafluoroborate (LiBF4), and ammonium fluoride; and organic salts such as tetrabutylammonium fluoride (TBAF). One kind or, if necessary, two or more kinds of the reagent serving as the fluoride ion source may be used. Also, a commercially available reagent can be used as the fluoride ion source. The amount of the reagent used in the deprotection reaction with fluoride ions is preferably in the range of 0.1 mol to 500 mol, more preferably 0.1 mol to 50 mol, per 1 mol of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position.

[0147] The solvent, the amount of the solvent used, the reaction time, and the reaction temperature in the deprotection reaction with fluoride ions are the same as those of the solvent, the amount of the solvent used, the reaction time, and the reaction temperature in the deprotection reaction with an acid of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position.

[0148] When the 2-methyl-2,6-heptadienol compound (8) obtained by the deprotection reaction has sufficient purity, it may be used in the next step as a crude product, or it may be purified by appropriately selecting from the usual purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0149] In the above step A, the 4-pentenyltriphenylphosphonium halide compound (5) is converted to a phosphorus ylide (18) by a base, and then the obtained phosphorus ylide (18) is subjected to a Wittig reaction with the 2-propanone compound (6) having a protected hydroxyl group, whereby a 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position is obtained. In this step A, following the Wittig reaction, a deprotection reaction occurs under the Wittig reaction conditions, and thus a 2-methyl-2,6-heptadienol compound (8) can be obtained without subjecting to the above step B. Therefore, when a deprotection reaction occurs following the Wittig reaction, or when a deprotection reaction occurs for a part of the 2-methyl-2,6-heptadienol compound (8) or the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, a mixture of the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position and the 2-methyl-2,6-heptadienol compound (8) is obtained. Whether a deprotection reaction occurs following the Wittig reaction depends on, for example, the type of the deprotecting group.

[0150] [6] Step C Hereinafter, step C for synthesizing the 3-isopropenyl-6-heptenoic acid ester compound (1) will be described. The 3-isopropenyl-6-heptenoic acid ester compound (1) can be obtained by subjecting the 2-methyl-2,6-heptadienol compound (8) obtained in the above step B to a Johnson–Claisen rearrangement reaction with the orthoacetic acid ester compound (11) as shown in the following reaction formula.

Chemical formula

[0151] The Johnson–Claisen rearrangement reaction is carried out by adding an acid to a 2-methyl-2,6-heptadienol compound (8) and an orthoacetate (11), and heating in a solvent or without a solvent as necessary. Examples of the acid in the Johnson–Claisen rearrangement reaction include mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; organic acids such as acetic acid, propionic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, boron trifluoride, boron trichloride, boron tribromide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) isopropoxide, and titanium(IV) oxide. From the viewpoints of reactivity and / or economy, propionic acid can be cited as a preferred example of the acid. One type of the acid or, if necessary, two or more types may be used. Further, a commercially available acid can be used. The amount of the acid used is preferably small from the viewpoint of economy, and can be arbitrarily set as long as a practically sufficient reaction rate is obtained. However, it is preferably 0.00001 mol to 10,000 mol, more preferably 0.0001 mol to 100 mol, per 1 mol of the 2-methyl-2,6-heptadienol compound (8) as the substrate.

[0152] The orthoacetate compound (11) represented by the following general formula (11) will be described. CH3C(OR 2 )3(11) R in the orthoacetate 2 is as defined in the above general formula (1). The amount of the orthoacetate used is preferably 1 mol to 10,000 mol, more preferably 1 mol to 100 mol, per 1 mol of the 2-methyl-2,6-heptadienol compound (8) from the viewpoint of economy.

[0153] As solvents in the Johnson–Claisen rearrangement reaction, for example, ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene, and cumene; chlorinated solvents such as methylene chloride, chloroform, and trichloroethylene; ketones such as acetone and methyl ethyl ketone; aprotic polar solvents such as N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), and hexamethylphosphoric triamide (HMPA); nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol, and t-butyl alcohol can be mentioned. One type of the solvent or, if necessary, two or more types may be used. Also, commercially available solvents can be used. From the viewpoints of economy and reactivity, it is preferable to carry out the reaction without a solvent.

[0154] The reaction temperature of the Johnson–Claisen rearrangement reaction depends on the reaction conditions, but is preferably -78°C to 300°C, more preferably 0°C to 300°C, and even more preferably 0°C to 200°C. The reaction time of the Johnson–Claisen rearrangement reaction can be arbitrarily set, but it is desirable from the viewpoint of yield to track the reaction using gas chromatography (GC) and / or thin-layer chromatography (TLC) to complete the reaction, and it is usually about 1 to 100 hours.

[0155] In the above step B, the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position is subjected to a deprotection reaction to obtain a 2-methyl-2,6-heptadienol compound (8). In this step B, following the deprotection reaction, a rearrangement reaction occurs under the deprotection reaction conditions, whereby the 3-isopropenyl-6-heptenoic acid ester compound (1) can be obtained without subjecting it to the above step C. Therefore, following the deprotection reaction, when a rearrangement reaction occurs, resulting in a rearrangement reaction for a part of the 3-isopropenyl-6-heptenoic acid ester compound (1) or the 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position, a mixture of the 2-methyl-2,6-heptadienol compound (8) and the 3-isopropenyl-6-heptenoic acid ester compound (1) is obtained. Whether or not a rearrangement reaction occurs following the deprotection reaction depends, for example, on the type of protecting group.

[0156] When the 3-isopropenyl-6-heptenoic acid ester compound (1) obtained by the above method has sufficient purity, it may be used in the next step as a crude product, or it may be purified by appropriately selecting from ordinary purification methods in organic synthesis such as distillation or various chromatographies. From the viewpoint of industrial economy, distillation is particularly preferred.

[0157] As described above, a method for producing the 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) efficiently and industrially is provided, which eliminates the need for an oxidation reaction that is difficult to implement industrially in terms of safety, economy, and environmental load. Also provided is a method for producing the 3-isopropenyl-6-heptenal compound (2) which is a useful intermediate thereof. Further provided is the 3-isopropenyl-6-methyl-6-heptenoic acid ester compound (1') which is a useful intermediate in the production of the 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4).

Example

[0158] Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the following examples. In the following, unless otherwise specified, "purity" refers to the area percentage obtained by gas chromatography (GC) analysis, and "production ratio" refers to the relative ratio of the area percentages obtained by GC analysis. Also, "yield" refers to the yield calculated based on the area percentage obtained by GC analysis. In each example, the reaction was monitored according to the following GC conditions. GC conditions: GC: Shimadzu Corporation capillary gas chromatograph GC-2014, column: DB-5, 0.25 μm x 0.25 mmφ x 30 m, carrier gas: He (1.55 mL / min), detector: FID, column temperature: 100 °C rising at 10 °C / min to 230 °C. The yield was calculated according to the following formula considering the purity (%GC) of the raw materials and products. 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 "crude yield" refers to the yield calculated without purification.

[0159] Example 1 Synthesis of 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = THP) having a protected hydroxyl group at the 1-position

[0160]

Chemical formula

[0161] Under a nitrogen atmosphere, 4-pentenyl halide compound (19: R 1=(H, X = Br) (223.55 g: 1.50 mol), triphenylphosphine (PPh3) (491.79 g: 1.87 mol), and dimethylformamide (DMF) (306 g) were charged, and the mixture was stirred at 100 °C for 12 hours to prepare 4-pentenyltriphenylphosphonium = halide compound (5: R 1 =H, X = Br), and then the internal temperature was cooled to room temperature (20 - 25 °C), and tetrahydrofuran (THF) (1080 g) was added. The internal temperature was cooled to 0 - 5 °C, potassium t-butoxide (t-BuOK) (176.87 g: 1.57 mol) was added, and the mixture was stirred for 1 hour. Then, the internal temperature was cooled to 0 °C, and 2-propanone compound (6: R 4 =THP) (282.00 g: 1.37 mol) was added dropwise over 100 minutes, and the solution was stirred at a temperature of 10 - 15 °C for 1 hour. Then, pure water (750 g) was added to the reaction solution, and the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations by normal washing and concentration, hexane (900 g) was added to the obtained solution, and the mixture was stirred for 30 minutes. Then, by filtration and concentration, a crude product (487.44 g) of the target 2-methyl-2,6-heptadiene compound (7: R 1 =H, R 4 =THP) having a protected hydroxyl group at the 1-position was obtained. The crude yield was 85.57%.

[0162] 2-Methyl-2,6-heptadiene compound (7: R 1 =H, R 4 =THP) having a protected hydroxyl group at the 1-position IR (D-ATR): ν = 3077, 2941, 2871, 2851, 1641, 1253, 1441, 1376, 1353, 1321, 1262, 1201, 1183, 1158, 1134, 1118, 1078, 1053, 1023, 979, 908, 870, 816, 642 cm -1 。 1H-NMR(500 MHz, CDCl3): 1.48 - 1.73 (5H, m), 1.76 - 1.77 (3H, m), 1.77 - 1.89 (1H, m), 2.05 - 2.18 (4H, m), 3.47 - 3.53 (1H, m), 3.84 - 3.90 (1H, m), 4.05 - 4.12 (2H, m), 4.58 (1H, t-like, J = 3.5 Hz), 4.93 - 5.03 (2H, m), 5.36 (1H, t-like, J = 6.9 Hz), 5.76 - 5.84 (1H, m) ppm. 13 C-NMR(125 MHz, CDCl3): δ = 19.49, 21.70, 25.74, 27.07, 30.64, 34.02, 62.12, 65.36, 97.48, 114.67, 126.75, 132.19, 138.27. GC-MS(EI, 70 eV): 29, 41, 55, 67, 85, 97, 109, 126, 138, 155, 168, 181, 195, 210.

[0163] Example 2 Synthesis of 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = TMS) having a protected hydroxyl group at the 1-position

[0164]

Chemical formula

[0165] Under a nitrogen atmosphere, the reactor was charged with 4-pentenyl halide compound (19: R 1 = H, X = Br) (271.26 g: 1.80 mol), triphenylphosphine (PPh3) (495.73 g: 1.89 mol), and dimethylformamide (DMF) (630 g), and stirred at 100 °C for 12 hours to obtain 4-pentenyltriphenylphosphonium halide compound (5: R 1(where H, X = Br) was prepared, and then the internal temperature was cooled to room temperature (50 - 60 °C), and tetrahydrofuran (THF) (1296 g) was added. The internal temperature was cooled to 0 - 5 °C, potassium tert-butoxide (t-BuOK) (208.20 g: 1.85 mol) was added, and the mixture was stirred for 1 hour. Then, the internal temperature was cooled to 0 - 5 °C, and a 2-propanone compound (6: R 4 = THP) (242.02 g: 1.64 mol) was added dropwise over 180 minutes, and the solution was stirred at a solution temperature of 10 - 15 °C for 1 hour. Then, pure water (900 g) was added to the reaction solution, and the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was post-treated by normal washing and concentration. Hexane (1500 g) was added to the obtained solution, and the mixture was stirred for 30 minutes. Then, by filtration and concentration, a crude product (207.41 g) of the target 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = TMS) and 2-methyl-2,6-heptadienol compound (8: R 1 = H) was obtained. The crude yield of the crude product was 45.30%. A part of the above crude product was purified to isolate the 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = TMS) having a protected hydroxyl group at the 1-position, and various spectral data thereof were measured. The results are shown below.

[0166] 2-Methyl-2,6-heptadiene compound (7:: R having a protected hydroxyl group at the 1-position 1 = H, R 4 = TMS) IR (D-ATR): ν = 3079, 2958, 2918, 2852, 1641, 1436, 1380, 1251, 1069, 992, 961, 912, 879, 841, 747, 685 cm -1 . 1H-NMR (500 MHz, CDCl3): δ = 0.13 (9H, s), 1.74 (3H, s-like), 2.06 - 2.16 (4H, m), 4.11 (2H, s), 4.94 - 5.04 (2H, m), 5.24 (1H, t-like, J = 6.8 Hz), 5.77 - 5.85 (1H, m) ppm. 13 C-NMR (125 MHz, CDCl3): δ = -0.43, 21.14, 27.03, 34.03, 61.19, 114.67, 126.44, 134.74, 138.31 ppm. GC-MS (EI, 70 eV): 27, 41, 59, 73, 93, 108, 127, 143, 157, 169, 183, 198.

[0167] Example 3 Synthesis of 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = EE) having a protected hydroxyl group at the 1-position

[0168]

Chemical formula

[0169] Under a nitrogen atmosphere, the reactor was charged with 4-pentenyl halide compound (19: R 1 = H, X = Br) (271.26 g: 1.80 mol), triphenylphosphine (PPh3) (476.84 g: 1.82 mol), and dimethylformamide (DMF) (630 g), and stirred at 100 °C for 24 hours to prepare 4-pentenyltriphenylphosphonium halide compound (5: R 1 = H, X = Br). Then, the internal temperature was cooled to room temperature (50 - 60 °C), and tetrahydrofuran (THF) (1602 g) was added. The internal temperature was cooled to 0 - 5 °C, potassium t-butoxide (t-BuOK) (212.25 g: 1.89 mol) was added, and stirred for 1 hour. Then, the internal temperature was cooled to 0 - 5 °C, and 2-propanone compound (6: R 4(241.63 g: 1.64 mol) of EE was added dropwise over 100 minutes, and the solution was stirred for 1 hour at a solution temperature of 10 - 15°C. Thereafter, pure water (900 g) was added to the reaction solution, stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations by normal washing and concentration. Hexane (1500 g) was added to the resulting solution and stirred for 30 minutes. Thereafter, by filtration and concentration, a crude product (337.69 g) of the target 2-methyl-2,6-heptadiene compound (7: R 1 =H, R 4 =EE) having a protected hydroxyl group at the 1-position was obtained. By subjecting this crude product to vacuum distillation, a purified 2-methyl-2,6-heptadiene compound (7: R 1 =H, R 4 =EE) (252.38 g: 1.23 mol) having a protected hydroxyl group at the 1-position was obtained. The yield calculated from all fractions including the fore-fraction was 83.03%.

[0170] 2-Methyl-2,6-heptadiene compound (7: R 1 =H, R 4 =EE) IR (D-ATR): ν = 3078, 2976, 2916, 1641, 1443, 1378, 1337, 1273, 1130, 1098, 1059, 1032, 985, 929, 912 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.20 (3H, t, J = 7.1 Hz), 1.31 (3H, d, J = 5.4 Hz), 1.64 - 1.76 (3H, m), 2.06 - 2.20 (4H, m), 3.46 - 3.68 (2H, m), 3.97 - 4.09 (2H, m), 4.69 (1H, q, J = 5.4 Hz), 4.92 - 5.03 (2H, m), 5.34 - 5.44 (1H, m), 5.74 - 5.85 (1H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 15.31, 19.73, 21.74, 27.11, 33.99, 60.22, 63.56, 98.80, 114.70, 128.44, 132.38, 138.20 ppm. GC-MS (EI, 70 eV): 29, 45, 55, 73, 83, 93, 109, 126, 137, 152, 169, 183, 198.

[0171] Example 4 Synthesis of 2-methyl-2,6-heptadiene compound (7: R 1 = CH3, R 4 = EE) having a protected hydroxyl group at the 1-position

[0172]

Chemical formula

[0173] Under a nitrogen atmosphere, a reactor was charged with 4-pentenyl halide compound (19: R 1 = CH3, X = Br) (90.00 g: 0.54 mol), triphenylphosphine (PPh3) (143.32 g: 0.55 mol), potassium carbonate (11.22 g: 0.08 mol) and dimethylformamide (DMF) (189.35 g), and stirred at 80°C for 24 hours to prepare 4-pentenyltriphenylphosphonium halide compound (5: R 1 = CH3, X = Br). Then, the internal temperature was cooled to room temperature (50 - 60°C), and tetrahydrofuran (THF) (486.90 g) was added. The internal temperature was cooled to 0 - 5°C, potassium t-butoxide (t-BuOK) (61.36 g: 0.55 mol) was added, and the mixture was stirred for 1 hour. Then, at an internal temperature of 0 - 5°C, 2-propanone compound (6: R 4 = EE) (73.69 g: 0.49 mol) having a protected hydroxyl group was added dropwise over 55 minutes, and the solution was stirred at a temperature of 10 - 15°C for 19 hours. Then, pure water (270.5 g) was added to the reaction solution, and the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations by normal washing and concentration, hexane (1500 g) was added to the obtained solution, and the mixture was stirred for 30 minutes. Then, by filtration and concentration, the target 2-methyl-2,6-heptadiene compound (7: R 1 = CH3, R 4A crude product (157.82 g) of =EE) was obtained. By subjecting this crude product to distillation under reduced pressure, a purified 2-methyl-2,6-heptadiene compound (7: R 1 =CH3, R 4 =EE) (89.79 g: 0.37 mol) having a protected hydroxyl group at the 1-position was obtained. The yield after purification was 75.20%.

[0174] 2-Methyl-2,6-heptadiene compound (7: R 1 =CH3, R 4 =EE) IR (D-ATR): ν = 3075, 2974, 2935, 1743, 1711, 1687, 1650, 1445, 1376, 1338, 1274, 1130, 1097, 1086, 1059, 1030, 983, 946, 930, 886 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.20 (3H, t, J = 7.1 Hz), 1.31 (3H, d, J = 5.4 Hz), 1.71 (3H, s), 1.75 - 1.76 (3H, m), 2.01 - 2.11 (2H, m), 2.16 - 2.21 (2H, m), 3.45 - 3.72 (2H, m), 3.97 - 4.11 (2H, m), 4.66 - 4.71 (3H, m), 5.27 - 5.42 (1H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 15.30, 19.73, 21.73, 22.39, 25.89, 37.89, 60.21, 63.58, 98.81, 110.00, 128.68, 132.16, 145.32 ppm. GC-MS (EI, 70 eV): 29, 45, 57, 73, 93, 107, 123, 140, 156, 168, 183, 197, 213.

[0175] Example 5 Synthesis of 2-methyl-2,6-heptadienol compound (8: R 1 =H)

[0176]

Chemical formula

[0177] Under a nitrogen atmosphere, into a reactor were charged the protected 2-methyl-2,6-heptadiene compound having a hydroxyl group at the 1-position obtained according to Example 1 (7: R 1 =H, R 4 =THP) (517.00 g: 1.287 mol), p-toluenesulfonic acid (p-TsOH) (33.24 g: 0.19 mol), and methanol (MeOH) (1287 g). The mixture was stirred at room temperature (20 - 25°C) for 22 hours and 30 minutes. Then, sodium bicarbonate (21.62 g) and pure water (10 g) were added, and the mixture was stirred for 30 minutes. The reaction solution was concentrated. Then, hexane (500 g) and pure water (800 g) were added, and the mixture was stirred for 30 minutes, and the organic layer was separated. The organic layer was concentrated. Then, p-toluenesulfonic acid (33.24 g: 0.19 mol) and methanol (1287 g) were charged, and the mixture was stirred at room temperature (20 - 25°C) for 5 hours and 30 minutes. Then, soda ash (50 g) and pure water (50 g) were added, and the mixture was stirred for 30 minutes. The reaction solution was concentrated. Then, hexane (1000 g) and pure water (1000 g) were added, and the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was post-treated by normal washing and concentration to obtain a crude product (221.90 g) of the target 2-methyl-2,6-heptadienol compound (8: R 1 =H). The crude yield was 60.33%.

[0178] 2-Methyl-2,6-heptadienol compound (8: R 1 =H) IR (D-ATR): ν = 3325, 3079, 2969, 2920, 1641, 1439, 1416, 1378, 1321, 1246, 1005, 949, 912, 845, 761, 641 cm -1 . 1H-NMR(500MHz,CDCl3): 1.66(1H, s-like), 1.78 - 1.79(3H, m), 2.03 - 2.16(4H, m), 4.10(2H, s), 4.94 - 5.03(2H, m), 5.28(1H, t-like, J = 6.9Hz), 5.74 - 5.82(1H, m) ppm。 13 C-NMR(125MHz,CDCl3): δ = 21.20, 26.95, 33.93, 61.40, 114.91, 127.53, 134.77, 138.19 ppm。 GC-MS(EI, 70eV): 29, 43, 57, 67, 79, 93, 108, 126。

[0179] Example 6 Synthesis of 2-methyl-2,6-heptadienol compound (8: R 1 = H)

[0180]

Chemical Structure

[0181] Under a nitrogen atmosphere, into a reactor were charged the protected 2-methyl-2,6-heptadiene compound (7: R 1 = H, R 4 = EE) (200 g: 0.965 mol) obtained according to Example 3, acetic acid (AcOH) (57.9 g: 0.965 mol), pure water (434.25 g), and tetrahydrofuran (THF) (434.25 g). The mixture was stirred for 3 hours and 20 minutes while distilling off the fraction at an internal temperature of 80 - 85°C. The reaction solution was cooled to 30 - 40°C, pure water (675.5 g) and hexane (675.5 g) were added, and the mixture was stirred for 30 minutes, and then the organic layer was separated. The separated organic layer was subjected to post-treatment operations such as normal washing and concentration to obtain a crude product (126.00 g) of the target 2-methyl-2,6-heptadienol compound (8: R 1 = H). The crude yield was 96.30%.

[0182] Example 7 2-methyl-2,6-heptadienol compound (8: R1 Synthesis of =CH3

[0183]

Chemical formula

[0184] Under a nitrogen atmosphere, into a reactor, a protected 2-methyl-2,6-heptadiene compound having a hydroxyl group at the 1-position obtained according to Example 4 (7: R 1 =CH3, R 4 =EE) (88.00 g: 0.363 mol), acetic acid (AcOH) (21.78 g: 0.363 mol), pure water (163.35 g), and tetrahydrofuran (THF) (163.35 g) were charged, and the mixture was stirred for 4 hours and 35 minutes while distilling off fractions at an internal temperature of 80 to 85°C. The reaction solution was cooled to 30 to 40°C, pure water (250.00 g) and hexane (250.00 g) were added, the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations such as normal washing and concentration to obtain a crude product (52.09 g) of the target 2-methyl-2,6-heptadienol compound (8: R 1 =CH3). By subjecting this crude product to distillation under reduced pressure, a purified 2-methyl-2,6-heptadienol compound (8: R 1 =CH3) (33.65 g: 0.23 mol) was obtained. The yield calculated from all fractions including the fore-run was 72.73%.

[0185] 2-Methyl-2,6-heptadienol compound (8: R 1 =CH3) IR (D-ATR): ν = 3319, 3074, 2968, 2935, 2917, 1650, 1448, 1375, 1337, 1006, 948, 887 cm -1 . 11H-NMR (500 MHz, CDCl3): 1.52 (1H, s), 1.71 (3H, s-like), 1.78 - 1.79 (3H, m), 2.01 - 2.07 (2H, m), 2.16 - 2.20 (2H, m), 4.11 (2H, s), 4.65 - 4.72 (2H, m), 5.28 (1H, t-like, J = 7.1 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 21.20, 22.42, 25.74, 37.89, 61.45, 110.18, 127.82, 134.60, 145.37 ppm. GC-MS (EI, 70 eV): 29, 43, 55, 67, 75, 84, 93, 107, 122, 132, 140.

[0186] Example 8 Synthesis of 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 = H, R 2 = Et)

[0187]

Chemical formula

[0188] Under a nitrogen atmosphere, into a reactor were charged the 2-methyl-2,6-heptadienol compound (8: R 1 = H) (60 g: 0.456 mol) obtained according to Example 6, the orthoacetic acid ester compound (11: R 2 = Et) (527.84 g: 3.192 mol) and propionic acid (4.5 g: 0.06 mol). The mixture was stirred at an internal temperature of 140 °C for 2 hours. Then, while distilling ethanol from the reaction solution, the internal temperature was raised to 150 - 160 °C and stirred for 6 hours. Then, the internal temperature was cooled to 30 - 40 °C, sodium bicarbonate (30 g) and pure water (600 g) were added, stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations such as normal washing, drying, and concentration to obtain the target 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 = H, R 2=Obtained a crude product (169.76 g) of (Et). By subjecting this crude product to distillation under reduced pressure, a purified 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 =H, R 2 =Et) (69.32 g: 0.33 mol) was obtained. The yield calculated from all fractions including the fore-fraction was 80.70%.

[0189] 3-Isopropenyl-6-heptenoic acid ester compound (1: R 1 =H, R 2 =Et) IR (D-ATR): ν = 3077, 2979, 2932, 1737, 1642, 1445, 1370, 1338, 1252, 1157, 1113, 1036, 995, 910, 895, 636, 559 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.22 (3H, t, J = 7.1 Hz), 1.45 (2H, q, J = 7.6 Hz), 1.65 (3H, s-like), 1.90 - 2.06 (2H, m), 2.34 (2H, d, J = 8.0 Hz), 2.60 (1H, quin, J = 7.5 Hz), 4.09 (2H, q, J = 7.1 Hz), 4.73 - 4.78 (2H, m), 4.92 - 5.01 (2H, m), 5.74 - 5.82 (1H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 14.20, 18.44, 31.23, 31.99, 39.20, 43.17, 60.15, 112.30, 114.59, 138.34, 145.79, 172.53 ppm. GC-MS (EI, 70 eV): 29, 41, 55, 69, 81, 93, 108, 122, 142, 155, 167, 181, 196.

[0190] Example 9 Synthesis of 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 =CH3, R 2 =Et)

[0191]

Chemical formula

[0192] Under a nitrogen atmosphere, into a reactor were charged 2-methyl-2,6-heptadienol compound (8: R 1 =CH3) (30 g: 0.206 mol) obtained according to Example 7 and orthoacetic acid ester compound (11: R 2 =Et) (167.10 g: 1.030 mol). While maintaining the internal temperature at 100°C, propionic acid (2.06 g: 0.28 mol) was added dropwise over 5 minutes, and the kettle temperature was raised to 140°C. Then, while distilling ethanol from the reaction solution, the kettle temperature was raised to 150 - 160°C, and the mixture was stirred for 7 hours and 30 minutes. Thereafter, the internal temperature was cooled to 20°C, sodium bicarbonate (12.6 g), pure water (206 g) and hexane (100 g) were added, and the mixture was stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations such as normal washing, drying, and concentration to obtain a crude product (128.26 g) of the target 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 =CH3, R 2 =Et). By subjecting this crude product to distillation under reduced pressure, a purified 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 =CH3, R 2 =Et) (30.20 g: 0.129 mol) was obtained. The yield calculated from all fractions including the fore-fraction was 68.93%.

[0193] 3-Isopropenyl-6-heptenoic acid ester compound (1: R 1 =CH3, R 2 =Et) IR (D-ATR): ν = 3075, 2979, 2936, 1737, 1648, 1446, 1373, 1261, 1177, 1147, 1035, 889 cm -1 . 1H-NMR (500 MHz, CDCl3): δ = 1.22 (3H, t, J = 7.3 Hz), 1.44 - 1.57 (2H, m), 1.65 (3H, s-like), 1.70 (3H, s), 1.87 - 1.97 (2H, m), 2.35 (2H, d, J = 7.7 Hz), 2.57 (1H, quin-like, J = 7.4 Hz), 4.10 (2H, q, J = 7.1 Hz), 4.65 - 4.69 (2H, m), 4.73 - 4.78 (2H, m) ppm. 13 C-NMR (125 MHz, CDCl3): δ = 14.21, 18.50, 22.43, 30.74, 35.16, 39.25, 43.33, 60.15, 109.87, 112.27, 145.53, 145.90, 172.54 ppm. GC-MS (EI, 70 eV): 29, 41, 55, 69, 81, 93, 107, 122, 142, 154, 167, 182, 196, 210.

[0194] Example 10 Synthesis of 3-isopropenyl-6-heptenal compound (2: R 1 = H)

[0195]

Chemical Structure

[0196] Under a nitrogen atmosphere, sodium t-butoxide (t-BuONa) (20.28 g: 0.21 mol) and tetrahydrofuran (THF) (50 g) were charged into the first reactor and stirred at 0 °C for 15 minutes. To the reaction solution, a hexane solution of diisobutylaluminum hydride (DIBAL) (200.2 mL: 0.20 mol) was added dropwise over 105 minutes, and then the mixture was stirred at room temperature (20 - 25 °C) for 2 hours. In the second reactor, under a nitrogen atmosphere, the 3-isopropenyl-6-heptenoate compound (1: R 1 = H, R 2=(Et)(32.24 g: 0.154 mol) and THF (50 g) were charged and cooled to -5 to 0 °C. The solution prepared in the first reactor was added dropwise to this reaction solution over 6 hours and 15 minutes, and the mixture was stirred at 0 to 5 °C for 4 hours. Thereafter, 20% aqueous hydrochloric acid solution (68.50 g) and pure water (300 g) were added, and the organic layer was separated. The separated organic layer was concentrated to obtain the crude product (27.70 g) of the target 3-isopropenyl-6-heptenal compound (2: R 1 =H). The crude yield was 75.97%.

[0197] 3-Isopropenyl-6-heptenal compound (2: R 1 =H) IR (D-ATR): ν = 3076, 2975, 2928, 2858, 2720, 1726, 1642, 1441, 1416, 1377, 996, 897 cm -1 -1. 1 1H-NMR (500 MHz, CDCl3): δ = 1.41 - 1.54 (2H, m), 1.65 (3H, s-like), 1.92 - 2.06 (2H, m), 2.37 - 2.47 (2H, m), 2.66 - 2.72 (1H, m), 4.77 - 4.82 (2H, m), 4.93 - 5.02 (2H, m), 5.73 - 5.81 (1H, m), 9.65 (1H, t, J = 2.3 Hz) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 18.59, 31.10, 32.15, 40.88, 47.36, 112.68, 114.87, 138.07, 145.49, 202.22 ppm. GC-MS (EI, 70 eV): 27, 41, 55, 69, 81, 95, 108, 123, 137, 151.

[0198] Example 11 Synthesis of 3-isopropenyl-6-heptenal compound (2: R 1 =CH3)

[0199]

Chemical formula

[0200] Under a nitrogen atmosphere, sodium t-butoxide (t-BuONa) (12.51 g: 0.13 mol) and tetrahydrofuran (THF) (125 g) were charged into the first reactor, and the mixture was stirred at 0 to 5 °C for 15 minutes. A hexane solution of diisobutylaluminum hydride (DIBAL) (121.08 mL: 0.12 mol) was added dropwise to the reaction solution over 105 minutes, and then the mixture was stirred at room temperature (20 to 25 °C) for 3 hours. Into the second reactor, under a nitrogen atmosphere, the 3-isopropenyl-6-heptenoic acid ester compound (1: R 1 =CH3, R 2 =Et) (20.00 g: 0.09 mol) obtained according to Example 9 and THF (125 g) were charged, and the mixture was cooled to -5 to 0 °C. The solution prepared in the first reactor was added dropwise to this reaction solution over 4 hours and 15 minutes, and the mixture was stirred at 0 to 5 °C for 4 hours. Then, 20% aqueous hydrochloric acid solution (38.08 g), pure water (100 g) and hexane (100 g) were added, and the organic layer was separated. The separated organic layer was post-treated by ordinary washing, drying, and concentration to obtain a crude product (16.00 g) of the target 3-isopropenyl-6-heptenal compound (2: R 1 =CH3). The crude yield was 81.55%.

[0201] 3-Isopropenyl-6-heptenal compound (2: R 1 =CH3) IR (D-ATR): ν = 3074, 2969, 2936, 2720, 1726, 1647, 1447, 1375, 1070, 1021, 890 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.47 - 1.55 (2H, m), 1.66 (3H, s-like), 1.70 (3H, s), 1.89 - 1.99 (2H, m), 2.38 - 2.48 (2H, m), 2.66 (1H, quin, J = 7.3 Hz), 4.65 - 4.71 (2H, m), 4.77 - 4.82 (2H, m), 9.65 (1H, t-like, J = 2.5 Hz) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 18.64, 22.40, 30.90, 35.04, 41.05, 47.41, 110.11, 112.65, 145.25, 145.61, 202.22 ppm. GC-MS (EI, 70 eV): 29, 41, 55, 69, 81, 97, 107, 122, 137, 151, 165.

[0202] Example 12 Synthesis of 6-isopropenyl-3-methyl-3,9-decadienol compound (3: R 1 = H)

[0203]

Chemical formula

[0204] Under a nitrogen atmosphere, the reactor was charged with ethyltriphenylphosphonium halide compound (9: X = Br) (5.79 g, 0.016 mol) and tetrahydrofuran (THF) (76 g), and cooled to 0 - 5 °C. To the reaction solution, a hexane solution of n-butyllithium (n-BuLi) (5.89 ml: 0.016 mol) was added dropwise over 15 minutes, and then stirred for 15 minutes to prepare ylide (13). To the reaction solution, ethylene oxide (10) (0.69 g: 0.016 mol) was added dropwise over 30 minutes, and then stirred at 15 - 20 °C for 1 hour to prepare 3-triphenylphosphoniobutoxide (14). The reaction solution was cooled to -20 - -15 °C, and a hexane solution of n-butyllithium (n-BuLi) (5.15 ml: 0.014 mol) was added dropwise over 10 minutes, and then stirred for 15 minutes to prepare phosphorus ylide (15). The reaction solution was cooled to -60 - -50 °C, and the 3-isopropenyl-6-heptenal compound (2: R obtained according to Example 10 1=H)(2.12 g: 0.013 mol) was added dropwise over 10 minutes. Then, the internal temperature was raised to room temperature (20 - 25 °C) and stirred for 3 hours. Pure water (110 g) was added to the reaction solution, stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations by normal drying and concentration to obtain a crude product (3.52 g) of the target 6-isopropenyl-3-methyl-3,9-decadienol compound (3:R 1 =H). The crude yield was 92.31%.

[0205] 6-Isopropenyl-3-methyl-3,9-decadienol compound (3:R 1 =H) IR (D-ATR): ν = 3341, 3074, 2966, 2927, 1642, 1441, 1375, 1185, 1044, 995, 909, 890, 641, 559 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.31 - 1.49 (2H, m), 1.59 - 1.71 (7H, m), 1.88 - 2.16 (5H, m), 2.21 - 2.35 (2H, m), 3.59 - 3.67 (2H, m), 4.66 - 4.77 (2H, m), 4.91 - 5.01 (2H, m), 5.14 - 5.27 (1H, m), 5.75 - 5.83 (1H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 15.76, 17.98, 18.44, 23.35, 31.58, 32.00, 32.09, 32.11, 35.16, 42.60, 47.14, 47.15, 59.60, 60.52, 111.70, 111.85, 114.27, 114.35, 126.80, 126.98, 131.46, 131.48, 138.83, 138.92, 147.13, 147.42 ppm. GC-MS (EI, 70 eV): 29, 41, 55, 67, 81, 93, 107, 121, 135, 149, 163, 177, 193, 208.

[0206] Example 13 6-Isopropenyl-3-methyl-3,9-decadienol compound (3:R1 Synthesis of =CH3

[0207] [Chemical formula]

[0208] Under a nitrogen atmosphere, the reactor was charged with ethyltriphenylphosphonium halide compound (9: X = Br) (5.35 g, 0.014 mol) and tetrahydrofuran (THF) (70.08 g), and cooled to 0 - 5°C. To the reaction solution, a hexane solution of n-butyllithium (n-BuLi) (5.10 ml: 0.014 mol) was added dropwise over 8 minutes, and then stirred for 15 minutes to prepare ylide (13). To the reaction solution, ethylene oxide (10) (0.63 g: 0.014 mol) was added dropwise over 4 minutes, and then stirred at 15 - 20°C for 1 hour to prepare 3-triphenylphosphoniobutoxide (14). The reaction solution was cooled to -5 - 0°C, and a hexane solution of n-butyllithium (n-BuLi) (4.50 ml: 0.013 mol) was added dropwise over 8 minutes, and then stirred for 15 minutes to prepare phosphorus ylide (15). The reaction solution was cooled to -5 - 0°C, and the 3-isopropenyl-6-heptenal compound (2: R 1 =CH3) (2.00 g: 0.011 mol) obtained according to Example 11 was added dropwise over 20 minutes. Then, the internal temperature was raised to room temperature (20 - 25°C) and stirred for 3 hours. Pure water (101 g) was added to the reaction solution, stirred for 30 minutes, and the organic layer was separated. The separated organic layer was subjected to post-treatment operations by normal drying and concentration. Hexane (101 g) was added to the obtained solution and stirred for 30 minutes. Then, filtration and concentration were performed to obtain a crude product (2.89 g) of the target 6-isopropenyl-3-methyl-3,9-decadienol compound (3: R 1 =CH3). The crude yield was 67.34%.

[0209] 6-isopropenyl-3-methyl-3,9-decadienol compound (3: R 1 =CH3) IR (D-ATR): ν = 3340, 3072, 2966, 2932, 1646, 1448, 1374, 1185, 1102, 1043, 1005, 887 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.37 - 1.54 (3H, m), 1.60 - 1.71 (9H, m), 1.84 - 2.14 (5H, m), 2.21 - 2.34 (2H, m), 3.59 - 3.67 (2H, m), 4.64 - 4.77 (4H, m), 5.14 - 5.28 (1H, m) ppm。 13 13C-NMR (125 MHz, CDCl3): δ = 15.77, 18.02, 18.49, 22.48, 22.50, 23.35, 30.75, 30.85, 32.04, 32.13, 35.18, 35.49, 35.52, 42.62, 47.34, 59.64, 60.53, 109.56, 109.63, 111.65, 111.81, 126.79, 126.98, 131.48, 131.50, 145.99, 146.09, 147.22, 147.52 ppm。 GC-MS (EI, 70 eV): 29, 41, 55, 69, 81, 93, 107, 121, 133, 149, 163, 177, 191, 207, 222。

[0210] Example 14 Synthesis of 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 = H, R 3 = CH3)

[0211]

Chemical Structure

[0212] Under a nitrogen atmosphere, into a reactor, the 6-isopropenyl-3-methyl-3,9-decadienol compound (3: R) obtained according to Example 12 1=(H)(1.84 g: 0.009 mol), acetic anhydride (Ac2O) (1.54 g: 0.013 mol), pyridine (2.49 g: 0.031 mol) and acetonitrile (MeCN) (1.84 g) were charged and stirred at room temperature (20 - 25 °C) for 18 hours. Pure water (10 g) and hexane (10 g) were added to the reaction solution, stirred for 30 minutes, and the organic layer was separated. The separated organic layer was post-treated by normal washing, drying, and concentration to obtain the crude product (2.13 g) of the target 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 =H, R 2 =CH3). By subjecting this crude product to vacuum distillation, the purified 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 =H, R 3 =CH3) (8) (1.68 g: 0.007 mol) was obtained. The distillation yield after vacuum distillation was 77.78%.

[0213] 6-Isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 =H, R 3 =CH3) IR (D-ATR): ν = 3074, 2968, 2926, 1742, 1642, 1442, 1364, 1237, 1041, 995, 909, 890 cm -1 . 1 1H-NMR (500 MHz, CDCl3): δ = 1.36 - 1.50 (2H, m), 1.60 - 1.72 (6H, m), 1.88 - 2.10 (8H, m), 2.21 - 2.36 (2H, m), 4.07 - 4.13 (2H, m), 4.66 - 4.77 (2H, m), 4.91 - 5.01 (2H, m), 5.12 - 5.21 (1H, m), 5.75 - 5.83 (1H, m) ppm. 1313C-NMR (125 MHz, CDCl3): δ = 16.22, 18.43, 20.99, 21.03, 23.57, 31.24, 31.59, 31.90, 31.97, 32.13, 38.61, 46.87, 47.04, 62.69, 63.05, 111.53, 111.67, 114.26, 114.28, 125.69, 126.41, 131.13, 131.25, 138.93, 138.96, 147.08, 147.18, 171.07, 171.11 ppm. GC-MS (EI, 70 eV): 29, 43, 55, 67, 81, 93, 107, 121, 135, 147, 161, 175, 190, 207, 222, 235, 250.

[0214] Example 15 Synthesis of 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 = CH3, R 3 = CH2CH3)

[0215] [Chemical formula]

[0216] Under a nitrogen atmosphere, into a reactor were charged 6-isopropenyl-3-methyl-3,9-decadienol compound (3: R 1 = CH3) (1.10 g: 0.005 mol) obtained according to Example 13, pyridine (0.95 g: 0.012 mol), and toluene (1.10 g). While maintaining the internal temperature at 0 to 10 °C, propionyl chloride (0.58 g, 0.063 mol) was added dropwise over 2 minutes, and the mixture was stirred for 3 hours. A mixed solution of sodium bicarbonate (0.07 g) and pure water (2 g) was added to the reaction solution, and the mixture was stirred for 30 minutes, and then the organic layer was separated. The separated organic layer was subjected to post-treatment operations such as normal washing, drying, and concentration to obtain the target 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4: R 1 = CH3, R 3The crude product (1.37 g) of ( =CH2CH3) was obtained. By subjecting this crude product to column purification, the purified 6-isopropenyl-3-methyl-3,9-decadienyl = carboxylate compound (4:R 1 =CH3, R 2 =CH2CH3) (1.33 g: 0.005 mol) was obtained. The yield after purification was 96.00%.

[0217] 6-Isopropenyl-3-methyl-3,9-decadienyl = carboxylate compound (4:R 1 =CH3, R 3 =CH2CH3) IR (D-ATR): ν = 3073, 2968, 2935, 1740, 1646, 1450, 1375, 1348, 1182, 1084, 887 cm -1 。 1 1H-NMR (500 MHz, CDCl3): δ = 1.12 (3H, q-like, J = 7.2 Hz), 1.39 - 1.57 (2H, m), 1.60 - 1.71 (9H, m), 1.85 - 2.10 (5H, m), 2.27 - 2.36 (2H, m), 4.64 - 4.74 (4H, m), 5.12 - 5.21 (1H, m) ppm. 13 13C-NMR (125 MHz, CDCl3): δ = 9.09, 9.12, 16.24, 18.46, 22.51, 23.57, 27.57, 30.65, 30.71, 31.28, 32.01, 32.15, 35.51, 38.68, 47.06, 47.23, 62.55, 62.92, 109.54, 109.57, 111.48, 111.62, 125.67, 126.35, 131.21, 131.34, 146.09, 147.16, 147.27, 174.43, 174.45 ppm. GC-MS (EI, 70 eV): 29, 41, 57, 81, 107, 121, 133, 148, 175, 189, 204, 222, 249, 263, 278.

Claims

1. A 3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1): 【Chemical 1】 (wherein, R １ represents a hydrogen atom or a methyl group, and R ２ represents a monovalent hydrocarbon group having 1 to 10 carbon atoms.) is subjected to a reduction reaction with a reducing agent to obtain a 3-isopropenyl-6-heptenal compound represented by the following general formula (2): 【Chemical 2】 (wherein R １ is as defined above.) A step of obtaining a 3-isopropenyl-6-heptenal compound A method for producing a 3-isopropenyl-6-heptenal compound (2), comprising at least the above step.

2. The method for producing a 3-isopropenyl-6-heptenal compound (2) according to Claim 1, and the 3-isopropenyl-6-heptenal compound (2) is subjected to a carbon chain elongation reaction containing a Wittig reaction using an ethyltriphenylphosphonium halide compound and ethylene oxide to obtain a 6-isopropenyl-3-methyl-3,9-decadienol compound represented by the following general formula (3): 【Chemical 3】 (wherein R １ is as defined above.) A step of obtaining a 6-isopropenyl-3-methyl-3,9-decadienol compound The obtained 6-isopropenyl-3-methyl-3,9-decadienol compound (3) is subjected to an esterification reaction to obtain a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound represented by the following general formula (4): [Chemical Formula 4] (wherein, R １ is as defined above, and R ３ represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 10 carbon atoms.) A step of obtaining a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound A method for producing a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4), comprising at least the above steps.

3. A 4-pentenyltriphenylphosphonium halide compound (5) represented by the following general formula (5): 【Chemical Formula 5】 (In the formula, R １ represents a hydrogen atom or a methyl group, Ph represents a phenyl group, and X represents a halogen atom.) is subjected to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6): 【Chemical Formula 6】 (wherein, R ４ represents a protecting group for a hydroxyl group.) to obtain a 2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following general formula (7): 【Chemical Formula 7】 (wherein, R １ and R ４ are as defined above.) A step of obtaining a 2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position The obtained 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position is subjected to a deprotection reaction to obtain a 2-methyl-2,6-heptadienol compound represented by the following general formula (8): 【Chemical 8】 (wherein, R １ is as defined above.) A step of obtaining a 2-methyl-2,6-heptadienol compound The obtained 2-methyl-2,6-heptadienol compound (8) is subjected to a Johnson-Claisen rearrangement reaction with an orthoacetate compound to obtain the 3-isopropenyl-6-heptenoic acid ester compound (1). The method for producing a 3-isopropenyl-6-heptenal compound (2) according to Claim 1, further comprising the above steps.

4. A 4-pentenyltriphenylphosphonium halide compound (5) represented by the following general formula (5): 【Chemical Formula 9】 (wherein, R １ represents a hydrogen atom or a methyl group, Ph represents a phenyl group, and X represents a halogen atom.) The 4-pentenyltriphenylphosphonium=halide compound (5) represented by the following is subjected to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6): 【Chemical 10】 (In the formula, R ４ represents a protecting group for a hydroxyl group.) A step of subjecting the compound to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6), and here, following the Wittig reaction, a deprotection reaction occurs, whereby the following general formula (8): 【Chemical 11】 (wherein, R １ is as defined above.) A 2-methyl-2,6-heptadienol compound represented by the following is obtained, A step of obtaining the 3-isopropenyl-6-heptenoic acid ester compound (1) by subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetic acid ester compound The method for producing the 3-isopropenyl-6-heptenal compound (2) according to claim 1, further comprising the above steps.

5. The following general formula (5): 【Chemical 12】 (wherein, R １ represents a hydrogen atom or a methyl group, Ph represents a phenyl group, and X represents a halogen atom.) The 4-pentenyltriphenylphosphonium=halide compound (5) represented by the following is subjected to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6): 【Chemical 13】 (wherein, R ４ represents a hydroxyl-protecting group.) By subjecting the compound to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6), the following general formula (7): 【Chemical 14】 (wherein R １ and R ４ are as defined above.) A step of obtaining a 2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following is obtained, By subjecting the obtained 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position to a deprotection reaction, the following general formula (8): 【Chemical Formula 15】 (wherein, R １ is as defined above.) A step of obtaining a 2-methyl-2,6-heptadienol compound represented by the following is obtained, A step of obtaining the 3-isopropenyl-6-heptenoic acid ester compound (1) by subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetic acid ester compound The method for producing the 6-isopropenyl-3-methyl-3,9-decadienyl=carboxylate compound (4) according to claim 2, further comprising the above steps.

6. The following general formula (5): 【Chemical 16】 (wherein, R １ represents a hydrogen atom or a methyl group, Ph represents a phenyl group, and X represents a halogen atom.) The 4-pentenyltriphenylphosphonium=halide compound (5) represented by the following is subjected to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6): 【Chemical 17】 (In the formula, R ４ represents a protecting group for a hydroxyl group.) A step of subjecting the compound to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6), and here, following the Wittig reaction, a deprotection reaction occurs, whereby the following general formula (8): 【Chemical Formula 18】 (wherein, R １ is as defined above.) A 2-methyl-2,6-heptadienol compound represented by the following is obtained, Subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetate compound to obtain the 3-isopropenyl-6-heptenoic acid ester compound (1); The method for producing a 6-isopropenyl-3-methyl-3,9-decadienyl carboxylate compound (4) according to claim 2, further comprising:

7. The following general formula (5): 【Chemical Formula 19】 (wherein, R １ represents a hydrogen atom or a methyl group, Ph represents a phenyl group, and X represents a halogen atom.) Subjecting the 4-pentenyltriphenylphosphonium halide compound (5) represented by to a Wittig reaction with a 2-propanone compound having a protected hydroxyl group represented by the following general formula (6): 【Chemical 20】 (wherein, R ４ represents a protecting group for a hydroxyl group.) To obtain a 2-methyl-2,6-heptadiene compound having a protected hydroxyl group at the 1-position represented by the following general formula (7): 【Chemical 21】 (wherein R １ and R ４ are as defined above.) Subjecting the obtained 2-methyl-2,6-heptadiene compound (7) having a protected hydroxyl group at the 1-position to a deprotection reaction to obtain a 2-methyl-2,6-heptadienol compound (8) represented by the following general formula (8): Subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetate compound to obtain a 3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1): 【Chemical 22】 (wherein R １ is as defined above.) Subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetate compound to obtain a 3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1): Subjecting the obtained 2-methyl-2,6-heptadienol compound (8) to a Johnson-Claisen rearrangement reaction with an orthoacetate compound to obtain a 3-isopropenyl-6-heptenoic acid ester compound represented by the following general formula (1): 【Chemical 23】 (wherein, R １ is as defined above, and R ２ represents a monovalent hydrocarbon group having 1 to 10 carbon atoms.) To obtain a 3-isopropenyl-6-heptenoic acid ester compound represented by: The method for producing a 3-isopropenyl-6-heptenoic acid ester compound (1) comprising at least:

8. The following general formula (1'): 【Chemical 24】 (In the formula, R ２ represents a monovalent hydrocarbon group having 1 to 10 carbon atoms.) A 3-isopropenyl-6-methyl-6-heptenoic acid ester compound represented by:

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