1, 4-cineole derivatives and intermediates thereof, herbicides containing said derivatives as active ingredients, methods for using herbicides, and methods for preparing agrochemical compositions

Abstract

The present invention provides a 1, 4-cineole derivative represented by the following general formula (1), (1 '), (2), (2'), (3) or (3 '), which exhibits excellent herbicidal activity, an intermediate thereof, and a herbicide comprising the derivative as an active ingredient. In general formulae (1), (1 '), (2), (2'), (3) and (3 '), R1 to R3, X and W each represent a predefined group described in the description: [Chemical Formula 1].

Description

Technical Field

[0001] This invention relates to 1,4-cineole derivatives and intermediates thereof, herbicides containing said derivatives as active ingredients and exhibiting excellent control effects against harmful weeds in agricultural and horticultural fields and non-agricultural land, as well as methods of using said herbicides and methods of preparing pesticide compositions. Background Technology

[0002] The use of herbicides is crucial for protecting useful crops such as rice, wheat, corn, soybeans, cotton, and sugar beets from weeds and for increasing yields.

[0003] In recent years, in farmland where crops and weeds coexist, there has been a growing demand for selective herbicides that can kill weeds selectively while avoiding phytotoxicity to crops. From the perspective of preventing environmental pollution and reducing economic costs such as transportation and spraying, there is a need for formulations that demonstrate highly effective herbicides at the lowest possible dosage.

[0004] Incidentally, 1,4-cineole derivatives exhibiting similar herbicidal activity to the present invention include cinmethylin derivatives reported in Patent Document 1 and Non-Patent Document 1, as well as those containing a 1,4-cineole ring reported in Non-Patent Document 2. However, no compounds have been found to have a substituent at the C5 position of the 1,4-cineole ring (here, the carbon atom in the 1,4-cineole ring connected to the methyl group is defined as the C1 position).

[0005] Citation List

[0006] Patent documents

[0007] Patent Document 1: EP0081893A

[0008] Non-patent literature

[0009] Non-patent literature 1: Journal of Agricultural and Food Chemistry, Vol.58, 2010, pp.10147-10155

[0010] Non-patent literature 2: Journal of Pesticide Science, Vol.48, 2023, pp.11-16 Summary of the Invention

[0011] Technical problems to be solved

[0012] The purpose of this invention is to provide a 1,4-cineole derivative and its intermediates, as well as a herbicide with excellent herbicidal activity.

[0013] The purpose of this invention is to provide a method for using a herbicide and a method for preparing a pesticide composition.

[0014] Technical solutions to solve technical problems

[0015] Through in-depth research to solve the above problems, the inventors of this invention discovered that 1,4-cineole derivatives represented by the following general formulas (1), (1'), (2), (2'), (3) or (3') exhibit excellent herbicidal activity, and thus completed this invention.

[0016] In other words, the inventors of this invention have discovered that the above-mentioned problems can be solved by the following solutions.

[0017] [1] 1,4-Cephalophyllin derivatives represented by the following general formulas (1), (1'), (2), (2'), (3) or (3') (which may be referred to as “compounds of the present invention” in this specification).

[0018] [Chemical Formula 1]

[0019]

[0020] (In general formulas (1), (1'), (2), (2'), (3) and (3'), R 1Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and a C7-C11 aralkyl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, carboxyl groups or C1-C6 alkoxycarbonyl groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 aralkyloxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), benzoyl C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl groups.

[0021] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy group, a C3-C6 ring, or a halogenated alkyl group. Alkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and aryl groups (which may be monosubstituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups). (Substituted or multisubstituted), heterocyclic rings (which can be monosubstituted or multisubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be monosubstituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be monosubstituted or multisubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 alkenyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C2-C6 alkynyl groups, C1 -C6 alkyl carbonyloxy group, C1-C6 alkoxy carbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl sulfonyloxy group, C1-C6 haloalkyl sulfonyloxy group, C3-C6 cycloalkyl sulfonyloxy group, aryl sulfonyloxy group (which can be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), aminosulfonyloxy group (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups or aryl groups).Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2 and R 3 At least one of them is a substituent other than a hydrogen atom. These two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms together can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur and nitrogen atoms, and the formed rings can have one or more substitutions.

[0022] X independently represents oxygen atom, sulfur atom, and CR atom. 4 R 5 or NR 6 .

[0023] R 4 and R 5 Each can be used independently to represent a hydrogen atom or a C1-C6 alkyl group.

[0024] R 6 It represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0025] W can independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkoxy group, or an aryl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and phenoxy C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups). The following groups can be substituted with halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C7-C11 aralkyloxy groups, C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), and C7-C11 aralkyloxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups). Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic C1-C6 alkoxy groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, C3-C6 cycloalkylsulfonyloxy groups, and arylsulfonyloxy groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups).

[0026] [2] According to the 1,4-cineole derivative described in [1], wherein

[0027] R 1 Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C7-C11 aralkyl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 alkyl group). -C6 haloalkoxy group, carboxyl group or C1-C6 alkoxycarbonyl group, monosubstituted or polysubstituted; heterocyclic C1-C6 alkyl group (which may be monosubstituted or polysubstituted by halogen atom, C1-C6 alkyl group or C1-C6 haloalkyl group); phenoxy C1-C6 alkyl group (which may be monosubstituted or polysubstituted by halogen atom, C1-C6 alkyl group or C1-C6 haloalkyl group); C7-C11 aralkyloxy C1-C6 alkyl group (which may be monosubstituted or polysubstituted by halogen atom, C1-C6 alkyl group or C1-C6 haloalkyl group); benzoyl C1-C6 alkyl group (which may be monosubstituted or polysubstituted by halogen atom, C1-C6 alkyl group or C1-C6 haloalkyl group); or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group.

[0028] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). (Multi-substituted), C1-C6 alkoxy group, C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), aryl group (which can be mono- or poly-substituted by a halogen atom). Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups Groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 olefinic groups, C2-C6 alkynyloxy groups, C1-C6 alkylcarbonyloxy groups, C1-C6 alkylthiocarbonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, or carbamoyloxy groups (which may be mono- or polysubstituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substitutions.

[0029] X independently represents oxygen atom, sulfur atom, and CR atom. 4 R 5 or NR 6 ,

[0030] R 4 and R 5 Each can independently represent a hydrogen atom or a C1-C6 alkyl group.

[0031] R 6 This indicates a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0032] W can independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The following groups can be substituted or multisubstituted: C7-C11 aralkyl groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyl oxy groups or C1-C6 haloalkylsulfonyl oxy groups.

[0033] [3] According to the 1,4-cineole derivative described in [1], wherein

[0034] R 1 Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C7-C11 aralkyl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 alkyl halogroups, C1-C6 alkoxy groups, C1-C6 alkyl halogroups, carboxyl groups, or C1-C6 alkoxycarbonyl groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), phenoxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), C7-C11 aralkyloxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl groups.

[0035] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, C1-C...). 6. Alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or multiple-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or multiple-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl groups (which can be mono- or multiple-substituted by halogen atoms, cyano groups, etc.). C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following groups may be substituted with or be monosubstituted or polysubstituted C1-C6 alkyl alkyl groups, C2-C6 olefinic groups, C2-C6 alkynyl alkyl groups, C1-C6 alkyl carbonyl alkyl groups, C1-C6 alkyl sulfonyl alkyl groups, or carbamoyl alkyl groups (which may be monosubstituted or polysubstituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may also be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0036] X independently represents an oxygen atom, CR 4 R 5 or NR 6 ,

[0037] R 4 and R 5Each represents a hydrogen atom independently.

[0038] R 6 Represents the hydroxyl group, and

[0039] W represents, independently, a hydrogen atom, an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a C1-C6 haloalkylsulfonyloxy group.

[0040] [4] A synthetic intermediate represented by the following general formulas (1a), (1a'), (2a), (2a'), (3a) or (3a'), used to prepare a 1,4-cineole derivative represented by any one of [1] to [3] of general formula (1), (1'), (2), (2'), (3) or (3'):

[0041] [Chemical Formula 2]

[0042]

[0043] (In the general formulas (1a), (1a'), (2a), (2a'), (3a) and (3a'),

[0044] R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0045] R 2a and R 3aEach of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 haloalkoxy group), a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy group, or a C3-C6 alkoxy group. Cycloalkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and aryl groups (which may be mono- or polysubstituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups). (Substitution or multiple substitution), heterocyclic rings (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 alkenyl groups, C2-C6 alkenoxy groups, C2-C6 alkynyl groups, C2-C6 alkynoxy groups, C 1-C6 alkyl carbonyloxy group, C1-C6 alkoxy carbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl sulfonyloxy group, C1-C6 haloalkyl sulfonyloxy group, C3-C6 cycloalkyl sulfonyloxy group, aryl sulfonyloxy group (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), aminosulfonyloxy group (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups).Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2a and R 3a At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2a and R 3a , with R 2a and R 3a The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0046] X a Each independently represents an oxygen atom, a sulfur atom, and a CR atom. 4a R 5a or NR 6a ,

[0047] R 4a and R 5a Each can independently represent a hydrogen atom or a C1-C6 alkyl group.

[0048] R 6a This represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0049] W aEach of these groups independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkoxy group, and an aryl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups are mono- or polysubstituted; heterocyclic rings (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); C7-C11 aralkyl groups (which can be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups); heterocyclic C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); phenoxy C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms). Atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C7-C11 arylalkyloxy groups, C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, ... phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups), heterocyclic oxy groups (which can be single or multiple substitution The following groups are substituted for halogen atoms, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic C1-C6 alkoxy groups (which may be substituted for halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C1-C6 alkylsulfonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, C3-C6 cycloalkylsulfonyloxy groups or arylsulfonyloxy groups (which may be substituted for halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups (single or multiple substitutions)).

[0050] [5] According to the synthetic intermediate described in [4], wherein

[0051] R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0052] R 2a and R 3a Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). (Multi-substituted), C1-C6 alkoxy group, C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), aryl group (which can be mono- or poly-substituted by a halogen atom). Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups Groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 olefinic groups, C2-C6 alkynyloxy groups, C1-C6 alkylcarbonyloxy groups, C1-C6 alkylthiocarbonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, or carbamoyloxy groups (which may be mono- or polysubstituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2a and R 3aAt least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0053] X a Each independently represents an oxygen atom, a sulfur atom, and a CR atom. 4 R 5 or NR 6 ,

[0054] R 4a and R 5a Each can independently represent a hydrogen atom or a C1-C6 alkyl group.

[0055] R 6a This indicates a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0056] W aEach of these elements independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic ring (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The following groups can be substituted or multisubstituted: C7-C11 aralkyl groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyl oxy groups or C1-C6 haloalkylsulfonyl oxy groups.

[0057] [6] According to the synthetic intermediate described in [4], wherein

[0058] R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0059] R 2a and R 3aEach of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, C1- C6 alkyl groups or C1-C6 haloalkyl groups (mono- or poly-substituted), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms, Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following groups may be mono- or poly-substituted: C1-C6 alkyl alkoxy groups, C2-C6 alkoxy groups, C2-C6 alkynoxy groups, C1-C6 alkyl carbonyl oxy groups, C1-C6 alkyl sulfonyl oxy groups, or carbamoyl oxy groups (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2a and R 3a At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0060] X a Each independently represents an oxygen atom, CR 4 R 5 or NR 6 ,

[0061] R 4aand R 5a Each represents a hydrogen atom independently.

[0062] R 6a Represents the hydroxyl group, and

[0063] W a Each can independently represent a hydrogen atom, an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a C1-C6 haloalkylsulfonyloxy group.

[0064] [7] Herbicides, which contain:

[0065] The 1,4-cineole derivative according to any one of [1] to [3] is used as the active ingredient.

[0066] [8] The herbicide according to [7] is used on agricultural land, pasture, lawn or non-agricultural land.

[0067] [9] The method of using the herbicide according to [7] includes:

[0068] Apply an effective amount of the 1,4-cineole derivative to at least one of the following: stems and leaves of weeds, soil, and water.

[0069]

[10] A method for preparing a pesticide composition, the method comprising:

[0070] The step of mixing the herbicide according to [7] with at least one selected from diluents or surfactants.

[0071] Beneficial effects of the present invention

[0072] According to the present invention, 1,4-cineole derivatives and intermediates thereof, as well as herbicides with excellent herbicidal activity, can be provided.

[0073] The novel 1,4-cineole derivatives of the present invention, represented by the above general formulas (1), (1'), (2), (2'), (3) or (3'), exhibit excellent herbicidal activity.

[0074] According to the present invention, methods for using herbicides and methods for preparing pesticide compositions can be provided. Detailed Implementation

[0075] The 1,4-cineole derivatives related to the compounds of the present invention, the intermediates of the present invention, and herbicides containing the derivatives as active ingredients will now be described in detail.

[0076] The present invention relates to 1,4-cineole derivatives represented by the following general formulas (1), (1'), (2), (2'), (3) or (3').

[0077] [Chemical Formula 3]

[0078]

[0079] (In general formulas (1), (1'), (2), (2'), (3) and (3'), R 1 Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and a C7-C11 aralkyl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, carboxyl groups or C1-C6 alkoxycarbonyl groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 aralkyloxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), benzoyl C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl groups.

[0080] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 haloalkoxy group), a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy group, or a C3-C6 alkoxy group. Cycloalkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and aryl groups (which may be mono- or polysubstituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups). (Substitution or multiple substitution), heterocyclic rings (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 alkenyl groups, C2-C6 alkenoxy groups, C2-C6 alkynyl groups, C2-C6 alkynoxy groups, C 1-C6 alkyl carbonyloxy group, C1-C6 alkoxy carbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl sulfonyloxy group, C1-C6 haloalkyl sulfonyloxy group, C3-C6 cycloalkyl sulfonyloxy group, aryl sulfonyloxy group (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), aminosulfonyloxy group (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups).Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2 and R 3 At least one of them is a substituent other than a hydrogen atom. These two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms together can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur and nitrogen atoms, and the formed ring can have one or more substituents.

[0081] X independently represents oxygen atom, sulfur atom, and CR atom. 4 R 5 or NR 6 .

[0082] R 4 and R 5 Each can be used independently to represent a hydrogen atom or a C1-C6 alkyl group.

[0083] R 6 It represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0084] W can independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkoxy group, or an aryl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and phenoxy C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups). (Identical atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups monosubstituted or polysubstituted), C7-C11 arylalkyloxy groups, C1-C6 alkyl groups (which can be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be monosubstituted or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic oxy groups (which can be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups). Substituting halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups; heterocyclic C1-C6 alkoxy groups (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); C1-C6 alkylsulfonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, C3-C6 cycloalkylsulfonyloxy groups, or arylsulfonyloxy groups (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups).

[0085] The present invention relates to synthetic intermediates represented by the following general formulas (1a), (1a'), (2a), (2a'), (3a) or (3a'), for the preparation of 1,4-cineole derivatives represented by general formulas (1), (1'), (2), (2'), (3) or (3').

[0086] [Chemical Formula 4]

[0087]

[0088] (In the general formulas (1a), (1a'), (2a), (2a'), (3a) and (3a'), R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0089] R 2a and R 3aEach of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 haloalkoxy group), a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy group, or a C3-C6 alkoxy group. Cycloalkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and aryl groups (which may be mono- or polysubstituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups). (Substitution or multiple substitution), heterocyclic rings (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 alkenyl groups, C2-C6 alkenoxy groups, C2-C6 alkynyl groups, C2-C6 alkynoxy groups, C 1-C6 alkyl carbonyloxy group, C1-C6 alkoxy carbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl thiocarbonyloxy group, C1-C6 alkyl sulfonyloxy group, C1-C6 haloalkyl sulfonyloxy group, C3-C6 cycloalkyl sulfonyloxy group, aryl sulfonyloxy group (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), aminosulfonyloxy group (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups).Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2 and R 3 At least one of them is a substituent other than a hydrogen atom. These two adjacent substituents, R 2a and R 3a , with R 2a and R 3a The bonded carbon atoms together can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur and nitrogen atoms, and the formed ring can have one or more substituents.

[0090] X a Each independently represents an oxygen atom, a sulfur atom, and a CR atom. 4a R 5a or NR 6a .

[0091] R 4a and R 5a Each can be used independently to represent a hydrogen atom or a C1-C6 alkyl group.

[0092] R 6a It represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0093] W aEach of these groups independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkoxy group, and an aryl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups are mono- or polysubstituted; heterocyclic rings (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); C7-C11 aralkyl groups (which can be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups); heterocyclic C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); phenoxy C1-C6 alkyl groups (which can be mono- or polysubstituted by halogen atoms). Atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C7-C11 arylalkyloxy groups, C1-C6 alkyl groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, ... phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 arylalkyloxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups), heterocyclic oxy groups (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be single or multiple substitutions of halogen atoms, cyano groups), heterocyclic oxy groups (which can be single or multiple substitution The following groups are allowed to be substituted: alkyl group, nitro group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group, or C1-C6 haloalkoxy group (single or multiple substitutions); heterocyclic C1-C6 alkoxy group (which may be single or multiple substitutions of halogen atom, C1-C6 alkyl group, or C1-C6 haloalkyl group); C1-C6 alkylsulfonyloxy group, C1-C6 haloalkylsulfonyloxy group, C3-C6 cycloalkylsulfonyloxy group, or arylsulfonyloxy group (which may be single or multiple substitutions of halogen atom, cyano group, nitro group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group, or C1-C6 haloalkoxy group).

[0094] In the 1,4-cineole derivatives of the present invention represented by the above general formulas (1), (1'), (2), (2'), (3) or (3') and the synthetic intermediates represented by the above general formulas (1a), (1a'), (2a), (2a'), (3a) or (3a'), R 2 R 3 W, R 2 R 3a or W a Examples of halogen atoms represented, or halogen atoms used as substituents, include fluorine, chlorine, bromine, and iodine. The number of halogen atoms used as substituents can be one, two, or more, and in the case of two or more halogen atoms, the halogen atoms can be the same or different. The substitution position of the halogen atom can be any position in the group substituted by that halogen atom.

[0095] By R 1 R 2 R 3 R 4 R 5 R 6 W, R 2a R 3a R 4a R 5a R 6a or W a The C1-C6 alkyl group represented, or the C1-C6 alkyl group used as a substituent, can be straight-chain or branched, and examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, sec-butyl groups, tert-butyl groups, n-pentyl groups, neopentyl groups, 2-pentyl groups, 3-pentyl groups, tert-pentyl groups, n-hexyl groups, isohexyl groups, 2-hexyl groups, and 3-hexyl groups. The number of C1-C6 alkyl groups used as substituents can be one or more, and in the case of two or more, the C1-C6 alkyl groups can be the same or different. The substitution position of the C1-C6 alkyl group can be any position in the group substituted by the C1-C6 alkyl group.

[0096] By R 1 R 2 R 3 W, R 2a R 3a or W aThe C1-C6 haloalkyl group represented, or the C1-C6 haloalkyl group used as a substituent, can be straight-chain or branched, and examples include monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 2-chloroethyl, trichloromethyl, 1-fluoroethyl, 2-fluoroethyl, 6-fluorohexyl, and monobromomethyl groups. The number of C1-C6 haloalkyl groups used as substituents can be one, two, or more; in the case of two or more, the C1-C6 haloalkyl groups can be the same or different. The substitution position of the C1-C6 haloalkyl group can be any position in the group substituted by that C1-C6 haloalkyl group.

[0097] By R 1 R 2 R 3 W, R 2a R 3a or W a The C2-C6 alkenyl groups can be straight-chain or branched, and examples include vinyl groups, 1-propenyl groups, 2-propenyl groups, 1-butenyl groups, 2-butenyl groups, 3-butenyl groups, 1-methyl-2-propenyl groups, 2-methyl-2-propenyl groups, 1-pentenyl groups, 2-pentenyl groups, 3-pentenyl groups, 4-pentenyl groups, 1-methyl-2-butenyl groups, 2-methyl-2-butenyl groups, 1-hexenyl groups, 2-hexenyl groups, 3-hexenyl groups, 4-hexenyl groups, and 5-hexenyl groups.

[0098] By R 2 R 3 R 2a Or R 3a The C2-C6 alkenyloxy group can be straight-chain or branched, and examples include vinyloxy groups, 1-propenyloxy groups, 2-propenyloxy groups, 1-butenyloxy groups, 2-butenyloxy groups, 3-butenyloxy groups, 1-methyl-2-propenyloxy groups, 2-methyl-2-propenyloxy groups, 1-pentenyloxy groups, 2-pentenyloxy groups, 3-pentenyloxy groups, 4-pentenyloxy groups, 1-methyl-2-butenyloxy groups, 2-methyl-2-butenyloxy groups, 1-hexenyloxy groups, 2-hexenyloxy groups, 3-hexenyloxy groups, 4-hexenyloxy groups, and 5-hexenyloxy groups.

[0099] By R 1 R 2 R 3 W, R 2a R 3a or W aThe C2-C6 ynyl group can be straight-chain or branched, and examples include ethynyl group, 1-propynyl group, propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2-methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentynyl group, 1-hexynyl group, and 1,1-dimethyl-2-butynyl group.

[0100] By R 2 R 3 R 2a Or R 3a The C2-C6 alkynoxy group can be straight-chain or branched, and examples include acetylenoxy group, 1-propynoxy group, propynoxy group, 1-butynoxy group, 2-butynoxy group, 3-butynoxy group, 1-methyl-2-propynoxy group, 2-methyl-3-butynoxy group, 1-pentynoxy group, 2-pentynoxy group, 3-pentynoxy group, 4-pentynoxy group, 1-methyl-2-butynoxy group, 2-methyl-3-pentynoxy group, 1-hexynoxy group, and 1,1-dimethyl-2-butynoxy group.

[0101] By R 1 R 2 R 3 W, R 2a R 3a or W a The C3-C6 cycloalkyl groups represented include cyclopropyl groups, 1-methylcyclopropyl groups, 2-methylcyclopropyl groups, 2,2-dimethylpropyl groups, cyclobutyl groups, cyclopentyl groups, and cyclohexyl groups.

[0102] By R 1 R 2 R 3 W, R 2a R 3a or W a The C3-C6 cycloalkyl and C1-C6 alkyl groups can be straight-chain or branched, and examples include cyclopropylmethyl, cyclopropylethyl, 1-methylcyclopropylmethyl, 2-methylcyclopropylmethyl, 2,2-dimethylcyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl groups.

[0103] By R 2 R 3 R 2a Or R 3aExamples of C3-C6 cycloalkyl C1-C6 alkoxy groups include cyclopropylmethoxy, cyclopropylethoxy, 1-methylcyclopropylmethoxy, 2-methylcyclopropylmethoxy, 2,2-dimethylcyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, and cyclohexylmethoxy.

[0104] By R 1 The C1-C6 alkoxy-C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methoxymethyl groups, ethoxymethyl groups, n-propoxymethyl groups, isopropoxymethyl groups, n-butoxymethyl groups, sec-butoxymethyl groups, tert-butoxymethyl groups, 1-pentoxymethyl groups, 1-hexyloxymethyl groups, 2-methoxyethyl groups, 2-ethoxyethyl groups, 2-isopropoxyethyl groups, 2-isobutoxyethyl groups, 3-methoxypropyl groups, 2-methoxypropyl groups, and 2-methoxy-1-methylethyl groups.

[0105] By R 1 R 2 R 3 W, R 2a R 3a or W a The aryl group referred to is a monocyclic or polycyclic aromatic group, and examples of such groups include phenyl groups, 1-naphthyl groups, and 2-naphthyl groups.

[0106] By R 1 R 2 R 3 W, R 2a R 3a or W a Examples of heterocyclic rings include 2-pyridyl groups, 3-pyridyl groups, 4-pyridyl groups, 2-thienyl groups, 3-thienyl groups, 2-furanyl groups, 3-furanyl groups, 2-pyrimidinyl groups, 4-pyrimidinyl groups, 5-pyrimidinyl groups, 6-pyrimidinyl groups, 2-tetrahydrofuranyl groups, and 3-tetrahydrofuranyl groups.

[0107] By R 1 R 2 R 3 W, R 2a R 3a or W a The C7-C11 aralkyl groups can be straight-chain or branched, and examples include benzyl groups, 1-phenylethyl groups, 2-phenylethyl groups, 1-phenylpropyl groups, 2-phenylpropyl groups, 3-phenylpropyl groups, 1-phenyl-2-methylpropyl groups, 1-phenylbutyl groups, and 1-phenylpentyl groups.

[0108] By R 1 R 2 R 3 W, R 2a R 3a or W a The heterocyclic C1-C6 alkyl groups represented can be straight-chain or branched, and examples include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furfuryl, 3-furfuryl, 2-pyrimidinylmethyl, 4-pyrimidinylmethyl, 5-pyrimidinylmethyl, 6-pyrimidinylmethyl, 4-pyrazolylmethyl, 2-tetrahydrofurfuryl, 3-tetrahydrofurfuryl, and isoxazol-4-yl-methyl.

[0109] By R 1 , W or W a The phenoxy C1-C6 alkyl group can be straight-chain or branched, and examples include phenoxymethyl group, 2-phenoxyethyl group, 2-phenoxypropyl group, 3-phenoxypropyl group, 2-phenoxybutyl group, 3-phenoxybutyl group and 4-phenoxybutyl group.

[0110] By R 1 , W or W a The C7-C11 arylalkoxy C1-C6 alkyl groups can be straight-chain or branched, and examples include benzyloxymethyl, 1-phenylethoxymethyl, 2-phenylethoxymethyl, 1-phenylpropoxymethyl, 2-phenylpropoxymethyl, 3-phenylpropoxymethyl and benzyloxyethyl groups.

[0111] By R 1 The C1-C6 alkoxy group can be straight-chain or branched, and examples include methoxymethoxymethyl group, ethoxymethoxymethyl group, n-propoxymethoxymethyl group, isopropoxymethoxymethyl group, n-butoxymethoxymethyl group, sec-butoxymethoxymethyl group, tert-butoxymethoxymethyl group, 1-pentoxymethoxymethyl group, 1-hexyloxymethoxymethyl group, 1-ethoxyethoxymethyl group, 1-methoxyethoxymethyl group and 2-methoxyethoxymethyl group.

[0112] By R 1 The benzoyl C1-C6 alkyl group represented can be straight-chain or branched, and examples include benzoylmethyl group, 1-phenyl-1-oxopropyl group and 1-phenyl-2-oxopropyl group.

[0113] By R 2 R 3R 6 W, R 2a R 3a R 6a or W a The C1-C6 alkoxy group represented, or the C1-C6 alkoxy group used as a substituent, can be straight-chain or branched, and examples include methoxy groups, ethoxy groups, n-propoxy groups, isopropoxy groups, n-butoxy groups, isobutoxy groups, sec-butoxy groups, and tert-butoxy groups. The number of C1-C6 alkoxy groups used as substituents can be one or two or more, and in the case of two or more, the individual C1-C6 alkoxy groups can be the same or different. The substitution position of the C1-C6 alkoxy group can be any position of the group it substituted for.

[0114] By R 2 R 3 W, R 2a R 3a or W a The C1-C6 haloalkoxy group represented, or the C1-C6 haloalkoxy group used as a substituent, can be straight-chain or branched, and examples include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloroethoxy, trichloromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, and 6-fluorohexyloxy. The number of C1-C6 haloalkoxy groups used as substituents can be one, two, or more, and in the case of two or more, the individual C1-C6 haloalkoxy groups can be the same or different. The substitution position of the C1-C6 haloalkoxy group can be any position of the group it substituted for.

[0115] By R 2 R 3 W, R 2a R 3a or W a Examples of C7-C11 aralkyloxy groups include benzyloxy groups, 1-phenylethoxy groups, 2-phenylethoxy groups, 1-phenylpropoxy groups, 2-phenylpropoxy groups, 3-phenylpropoxy groups, 1-phenyl-2-methylpropoxy groups, 1-phenylbutoxy groups, and 1-phenylpentoxy groups.

[0116] By R 2 R 3 W, R 2a R 3a or W aThe heterocyclic C1-C6 alkoxy groups represented can be straight-chain or branched, and examples include 2-pyridylmethoxy groups, 3-pyridylmethoxy groups, 4-pyridylmethoxy groups, 2-thienylmethoxy groups, 3-thienylmethoxy groups, 2-furanylmethoxy groups, 3-furanylmethoxy groups, 2-pyrimidinylmethoxy groups, 4-pyrimidinylmethoxy groups, 5-pyrimidinylmethoxy groups, 6-pyrimidinylmethoxy groups, 2-tetrahydrofuranyloxy groups, and 3-tetrahydrofuranyloxy groups.

[0117] By R 2 R 3 W, R 2a R 3a or W a The C1-C6 alkoxy group can be straight-chain or branched, and examples include methoxymethoxy group, ethoxymethoxy group, 1-ethoxyethoxy group, n-propoxymethoxy group, isopropoxymethoxy group, n-butoxymethoxy group, sec-butoxymethoxy group, tert-butoxymethoxy group, 1-pentoxymethoxy group and 1-hexyloxymethoxy group.

[0118] By R 2 R 3 R 2a Or R 3a Examples of C1-C6 alkyl carbonyloxy groups include acetoxy groups, ethyl carbonyloxy groups, n-propyl carbonyloxy groups, isopropyl carbonyloxy groups, n-butyl carbonyloxy groups, isobutyl carbonyloxy groups, sec-butyl carbonyloxy groups, tert-butyl carbonyloxy groups, 1-pentyl carbonyloxy groups, and 1-hexyl carbonyloxy groups.

[0119] By R 2 R 3 R 2a Or R 3a Examples of C1-C6 alkoxycarbonyloxy groups include methoxycarbonyloxy groups, ethoxycarbonyloxy groups, n-propoxycarbonyloxy groups, isopropoxycarbonyloxy groups, n-butoxycarbonyloxy groups, sec-butoxycarbonyloxy groups, and tert-butoxycarbonyloxy groups.

[0120] By R 2 R 3 R 2a Or R 3aExamples of C1-C6 alkylthiocarbonyloxy groups include methylthiocarbonyloxy group, ethylthiocarbonyloxy group, n-propylthiocarbonyloxy group, isopropylthiocarbonyloxy group, n-butylthiocarbonyloxy group, sec-butylthiocarbonyloxy group, tert-butylthiocarbonyloxy group, 1-pentylthiocarbonyloxy group and 1-hexylthiocarbonyloxy group.

[0121] By R 2 R 3 R 2a Or R 3a Examples of C1-C6 alkylthiocarbonyl groups include methylthiocarbonyl groups, ethylthiocarbonyl groups, n-propylthiocarbonyl groups, isopropylthiocarbonyl groups, n-butylthiocarbonyl groups, sec-butylthiocarbonyl groups, tert-butylthiocarbonyl groups, 1-pentylthiocarbonyl groups, and 1-hexylthiocarbonyl groups.

[0122] By R 2 R 3 W, R 2a R 3a or W a Examples of C1-C6 alkylsulfonyloxy groups include methylsulfonyloxy groups, ethylsulfonyloxy groups, n-propylsulfonyloxy groups, isopropylsulfonyloxy groups, n-butylsulfonyloxy groups, isobutylsulfonyloxy groups, sec-butylsulfonyloxy groups, tert-butylsulfonyloxy groups, and n-pentylsulfonyloxy groups.

[0123] By R 2 R 3 W, R 2a R 3a or W a Examples of C1-C6 haloalkylsulfonyloxy groups include monofluoromethylsulfonyloxy, difluoromethylsulfonyloxy, trifluoromethylsulfonyloxy, monochloromethylsulfonyloxy, trichloromethylsulfonyloxy, and 2,2,2-trifluoroethylsulfonyloxy.

[0124] By R 2 R 3 W, R 2a R 3a or W a Examples of C3-C6 cycloalkylsulfonyloxy groups include cyclopropylsulfonyloxy, 1-methylcyclopropylsulfonyloxy, 2-methylcyclopropylsulfonyloxy, 2,2-dimethylpropylsulfonyloxy, cyclobutylsulfonyloxy, cyclopentylsulfonyloxy, and cyclohexylsulfonyloxy.

[0125] By R2 R 3 W, R 2a R 3a or W a The arylsulfonyloxy group referred to is a monocyclic or polycyclic aromatic sulfonyloxy group, and examples of such groups include phenylsulfonyloxy groups, 1-naphthylsulfonyloxy groups, and 2-naphthylsulfonyloxy groups.

[0126] By R 6 Or R 6a Examples of C1-C6 alkylamino groups include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, and tert-butylamino.

[0127] By R 1a Examples of the three C1-C6 alkylsilyl groups may be the same or different, including trimethylsilyl groups, triethylsilyl groups, triisopropylsilyl groups, dimethylisopropylsilyl groups, diethylisopropylsilyl groups, dimethylhexylsilyl groups, tert-butyldimethylsilyl groups, and ditert-butylmethylsilyl groups.

[0128] By W or W a The heterocyclic oxy groups represented include 2-pyridyloxy groups, 3-pyridyloxy groups, 4-pyridyloxy groups, 2-thienyloxy groups, 3-thienyloxy groups, 2-furanyloxy groups, 3-furanyloxy groups, 2-pyrimidinyloxy groups, 4-pyrimidinyloxy groups, 5-pyrimidinyloxy groups, 6-pyrimidinyloxy groups, 2-tetrahydrofuranyloxy groups, and 3-tetrahydrofuranyloxy groups.

[0129] The C1-C6 alkoxycarbonyl group used as a substituent can be straight-chain or branched, and examples include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, and tert-butoxycarbonyl. The number of C1-C6 alkoxycarbonyl groups used as substituents can be one, two, or more, and in the case of two or more, the individual C1-C6 alkoxycarbonyl groups can be the same or different. The substitution position of the C1-C6 alkoxycarbonyl group can be any position of the substituent within the C1-C6 alkoxycarbonyl group.

[0130] Among the 1,4-cineole derivatives represented by the above general formulas (1), (1'), (2), (2'), (3) or (3'),

[0131] R 1Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C7-C11 aralkyl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 alkyl group). C1-C6 alkyl-haloalkoxy groups, carboxyl groups, or C1-C6 alkoxycarbonyl groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl-haloalkoxy groups), phenoxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl-haloalkoxy groups), C7-C11 aralkyloxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl-haloalkoxy groups), benzoyl C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl-haloalkoxy groups), or C1-C6 alkoxy C1-C6 alkyl groups.

[0132] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). (Multi-substituted), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms). Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups Groups (which may be mono- or polysubstituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 olefinic groups, C2-C6 alkynyloxy groups, C1-C6 alkylcarbonyloxy groups, C1-C6 alkylthiocarbonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, or carbamoyloxy groups (which may be mono- or polysubstituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0133] X independently represents oxygen atom, sulfur atom, and CR atom. 4 R 5 or NR 6 ,

[0134] R 4 and R 5 Each can independently represent a hydrogen atom or a C1-C6 alkyl group.

[0135] R 6 This indicates a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0136] W can independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The following groups can be substituted or multisubstituted: C7-C11 aralkyl groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyl oxy groups or C1-C6 haloalkylsulfonyl oxy groups.

[0137] More preferably, in 1,4-cineole derivatives represented by general formulas (1), (1'), (2), (2'), (3) or (3'),

[0138] R 1 Each of these groups independently represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C1-C6 alkoxy C1-C6 alkyl group, an aryl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C7-C11 aralkyl group (which can be substituted by a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group). C1-C6 alkyl halogroups, C1-C6 alkoxy groups, C1-C6 alkyl halogroups, carboxyl groups, or C1-C6 alkoxycarbonyl groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), phenoxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), C7-C11 aralkyloxy C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 alkyl halogroups), or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl groups.

[0139] R 2 and R 3Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, C1-C...). 6. Alkyl groups or C1-C6 haloalkyl groups (single or multiple substitutions), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or multiple-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or multiple-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl groups (which can be mono- or multiple-substituted by halogen atoms, cyano groups, etc.). C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following groups may be substituted with or be monosubstituted or polysubstituted C1-C6 alkyl alkyl groups, C2-C6 olefinic groups, C2-C6 alkynyl alkyl groups, C1-C6 alkyl carbonyl alkyl groups, C1-C6 alkyl sulfonyl alkyl groups, or carbamoyl alkyl groups (which may be monosubstituted or polysubstituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may also be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0140] X independently represents an oxygen atom, CR 4 R 5 or NR 6 ,

[0141] R 4 and R 5Each represents a hydrogen atom independently.

[0142] R 6 Represents the hydroxyl group, and

[0143] W represents, independently, a hydrogen atom, an aryl group (which may be mono- or poly-substituted by a halogen atom, cyano group, nitro group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group, or C1-C6 haloalkoxy group), or a C1-C6 haloalkylsulfonyloxy group.

[0144] As a preferred aspect, among the 1,4-cineole derivatives represented by general formulas (1), (1'), (2), (2'), (3) or (3'),

[0145] R 1 Each of the following is preferably represented independently: a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C7-C11 aralkyl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 haloalkyl group). C6 alkoxy groups or C1-C6 haloalkoxy groups, mono- or poly-substituted, heterocyclic C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or benzoyl C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and

[0146] More preferably, it represents C2-C6 alkenyl groups, C2-C6 alkynyl groups, C3-C6 cycloalkyl C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), and phenoxy C1-C6 alkyl groups (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups).

[0147] R 2 and R 3 Each of the following is preferably represented independently: hydrogen atom, halogen atom, hydroxyl group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C7-C11 aralkyloxy group (which may be mono- or poly-substituted by halogen atom, cyano group, nitro group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group), heterocyclic C1-C6 alkoxy group (which may be mono-substituted by halogen atom, C1-C6 alkyl group or C1-C6 haloalkyl group). (or multiple substitutions), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms). C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), and heterocyclic C1-C6 alkyl groups. The radical group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C2-C6 olefin group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 haloalkylsulfonyloxy group, or a carbamoyloxy group (which may be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group, or an aryl group, and the C1-C6 alkyl group may be bonded to each other via alkylene groups to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0148] R 2 More preferably, it represents a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C7-C11 arylalkyloxy group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), a C1-C6 alkoxy group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 arylalkyl group). The following are possible substitutions for different ring types: alkoxy groups or C1-C6 haloalkoxy groups (mono- or poly-substituted), heterocyclic rings (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), C2-C6 alkenoxy groups, C2-C6 alkynoxy groups, C1-C6 alkyl carbonyloxy groups, C1-C6 haloalkyl sulfonyloxy groups, or carbamoyloxy groups (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may also be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R. 3 More preferably, it represents a hydrogen atom, and

[0149] R 2More preferably, it represents a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkoxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), and R 3 A more preferred representation is a hydrogen atom.

[0150] X is independently preferred to represent oxygen atoms, CR 4 R 5 or NR 6 .

[0151] R 4 and R 5 More preferably, it represents a hydrogen atom.

[0152] R 6 Preferably, it represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0153] More preferably, it represents a hydroxyl group.

[0154] W, independently and preferably, represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), or a C3-C6 cycloalkyl C1-C6 alkyl group (which may be halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). 6. Haloalkyl groups (mono- or poly-substituted), aryl groups (which can be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic rings (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, or C1-C6 alkyl groups). C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic C1-C6 alkyl groups (which may be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), phenoxy groups (which may be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic The oxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group), a C1-C6 alkylsulfonyloxy group or a C1-C6 haloalkylsulfonyloxy group, more preferably a hydrogen atom, an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group) or a C1-C6 haloalkylsulfonyloxy group.

[0155] In the synthetic intermediate (the intermediate of the present invention) represented by general formula (1a), (1a'), (2a), (2a'), (3a) or (3a') used to prepare 1,4-cineole derivatives represented by general formula (1), (1'), (2), (2'), (3) or (3'), R 2a R 3a X a R 4a R 5a R 6a and W a Examples of preferred groups include R in 1,4-cineole derivatives represented by general formulas (1), (1'), (2), (2'), (3) or (3').2 R 3 X, R 4 R 5 R 6 Groups that are the same as the preferred group of W.

[0156] Preferably, in the synthetic intermediate (the intermediate of the present invention) represented by the general formula (1a), (1a'), (2a), (2'), (3) or (3') for preparing 1,4-cineole derivatives represented by general formula (1), (1'), (2'), (3'), or (3'),

[0157] R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0158] R 2a and R 3aEach of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). Substitution), C1-C6 alkoxy group, C3-C6 cycloalkyl group (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl group (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl group (which can be mono- or poly-substituted by halogen atoms, Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (mono- or poly-substituted), heterocyclic rings (which may be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which may be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups Groups (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C2-C6 olefinic groups, C2-C6 alkynyloxy groups, C1-C6 alkylcarbonyloxy groups, C1-C6 alkylthiocarbonyloxy groups, C1-C6 haloalkylsulfonyloxy groups, or carbamoyloxy groups (which may be mono- or poly-substituted with C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl group portion may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0159] X a Each independently represents an oxygen atom, a sulfur atom, and a CR atom. 4 R 5 or NR 6 ,

[0160] R 4a and R 5a Each can independently represent a hydrogen atom or a C1-C6 alkyl group.

[0161] R 6a This indicates a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), and

[0162] W a Each of these elements independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic ring (which may be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The following groups can be substituted or multisubstituted: C7-C11 aralkyl groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyl oxy groups or C1-C6 haloalkylsulfonyl oxy groups.

[0163] More preferably, in the synthetic intermediates (intermediates of the present invention) represented by general formulas (1a), (1a'), (2a), (2'), (3) or (3') used to prepare 1,4-cineole derivatives represented by general formulas (1), (1'), (2), (2'), (3) or (3'),

[0164] R 1a Each can independently represent a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different.

[0165] R 2a and R 3a Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, C1- C6 alkyl groups or C1-C6 haloalkyl groups (mono- or poly-substituted), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms, Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following groups may be mono- or poly-substituted: C1-C6 alkyl alkoxy groups, C2-C6 alkoxy groups, C2-C6 alkynoxy groups, C1-C6 alkyl carbonyl oxy groups, C1-C6 alkyl sulfonyl oxy groups, or carbamoyl oxy groups (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2a and R 3a At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents.

[0166] X a Each independently represents an oxygen atom, CR 4 R 5 or NR 6 ,

[0167] R 4a and R 5a Each represents a hydrogen atom independently.

[0168] R 6a Represents the hydroxyl group, and

[0169] W a Each can independently represent a hydrogen atom, an aryl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group) or a C1-C6 haloalkylsulfonyloxy group.

[0170] Representative examples of 1,4-cineole derivatives represented by general formula (1) or (1') are listed in Table 1 below, representative examples of 1,4-cineole derivatives represented by general formula (2) or (2') are listed in Table 2 below, and representative examples of 1,4-cineole derivatives represented by general formula (3) or (3') are listed in Table 3 below, but the compounds are not limited thereto. Compounds include those containing optical isomers, E isomers, and Z isomers. Compound numbers will be referenced below.

[0171] The following labels in the table represent the corresponding functional groups.

[0172] “H” represents a hydrogen atom, “Me” represents a methyl group, “Et” represents an ethyl group, “n-Pr” represents a n-propyl group, “i-Pr” represents an isopropyl group, “c-Pr” represents a cyclopropyl group, “n-Bu” represents a n-butyl group, “i-Bu” represents an isobutyl group, “t-Bu” represents a tert-butyl group, “c-Pen” represents a cyclopentyl group, “n-Hex” represents a n-hexyl group, “c-Hex” represents a cyclohexyl group, “Ph” represents a phenyl group, “Bn” represents a benzyl group, “=" represents a double bond and “≡” represents a triple bond.

[0173] In Table 1, “stereochemistry at the C-5 position” refers to the optical isomerism observed in 1,4-cineole derivatives represented by general formula (1) or (1') when focusing on the C5 position (where the carbon atom substituted with a methyl group is labeled as the C1 position).

[0174] [Table 1]

[0175]

[0176] Table 1

[0177]

[0178] [Table 2] Table 1 - Continued

[0179]

[0180] [Table 3]

[0181] Table 1 - Continued

[0182]

[0183] [Table 4]

[0184] Table 1 - Continued

[0185]

[0186] [Table 5]

[0187] Table 1 - Continued

[0188]

[0189] [Table 6]

[0190] Table 1 - Continued

[0191]

[0192] [Table 7]

[0193] Table 1 - Continued

[0194]

[0195] [Table 8]

[0196] Table 1 - Continued

[0197]

[0198] [Table 9]

[0199] Table 1 - Continued

[0200]

[0201] [Table 10]

[0202] Table 1 - Continued

[0203]

[0204] [Table 11]

[0205] Table 1 - Continued

[0206]

[0207] [Table 12]

[0208] Table 1 - Continued

[0209]

[0210] [Table 13]

[0211] Table 1 - Continued

[0212]

[0213] [Table 14]

[0214] Table 1 - Continued

[0215]

[0216] [Table 15]

[0217] Table 1 - Continued

[0218]

[0219] [Table 16]

[0220] Table 1 - Continued

[0221]

[0222] [Table 17]

[0223] Table 1 - Continued

[0224]

[0225] [Table 18]

[0226] Table 1 - Continued

[0227]

[0228] [Table 19]

[0229] Table 1 - Continued

[0230]

[0231] [Table 20]

[0232] Table 1 - Continued

[0233]

[0234] [Table 21]

[0235] Table 1 - Continued

[0236]

[0237] [Table 22]

[0238] Table 1 - Continued

[0239]

[0240] [Table 23]

[0241] Table 1 - Continued

[0242]

[0243] [Table 24]

[0244] Table 1 - Continued

[0245]

[0246] [Table 25]

[0247] Table 1 - Continued

[0248]

[0249] [Table 26]

[0250] Table 1 - Continued

[0251]

[0252] [Table 27]

[0253] Table 1 - Continued

[0254]

[0255] [Table 28]

[0256] Table 1 - Continued

[0257]

[0258] [Table 29]

[0259] Table 1 - Continued

[0260]

[0261] [Table 30]

[0262] Table 1 - Continued

[0263]

[0264] [Table 31]

[0265] Table 1 - Continued

[0266]

[0267] [Table 32]

[0268] Table 1 - Continued

[0269]

[0270] [Table 33]

[0271] Table 1 - Continued

[0272]

[0273] [Table 34]

[0274] Table 1 - Continued

[0275]

[0276] [Table 35]

[0277] Table 1 - Continued

[0278]

[0279] [Table 36]

[0280] Table 1 - Continued

[0281]

[0282] [Table 37]

[0283] Table 1 - Continued

[0284]

[0285] [Table 38]

[0286] Table 1 - Continued

[0287]

[0288] [Table 39]

[0289] Table 1 - Continued

[0290]

[0291] [Table 40]

[0292] Table 1 - Continued

[0293]

[0294] [Table 41]

[0295] Table 1 - Continued

[0296]

[0297] [Table 42]

[0298] Table 1 - Continued

[0299]

[0300] [Table 43]

[0301] Table 1 - Continued

[0302]

[0303] [Table 44]

[0304] Table 1 - Continued

[0305]

[0306] [Table 45]

[0307] Table 1 - Continued

[0308]

[0309] [Table 46]

[0310] Table 1 - Continued

[0311]

[0312] [Table 47]

[0313] Table 1 - Continued

[0314]

[0315] [Table 48]

[0316]

[0317] Table 2

[0318]

[0319] [Table 49]

[0320] Table 2 - Continued

[0321]

[0322] [Table 50]

[0323] Table 2 - Continued

[0324]

[0325] [Table 51]

[0326] Table 2 - Continued

[0327]

[0328] [Table 52]

[0329] Table 2 - Continued

[0330]

[0331] [Table 53]

[0332] Table 2 - Continued

[0333]

[0334] [Table 54]

[0335] Table 2 - Continued

[0336]

[0337] [Table 55]

[0338] Table 2 - Continued

[0339]

[0340] [Table 56]

[0341] Table 2 - Continued

[0342]

[0343] [Table 57]

[0344] Table 2 - Continued

[0345]

[0346] [Table 58]

[0347] Table 2 - Continued

[0348]

[0349] [Table 59]

[0350]

[0351] Table 3

[0352]

[0353] [Table 60]

[0354] Table 3 - Continued

[0355]

[0356] [Table 61]

[0357] Table 3 - Continued

[0358]

[0359] [Table 62]

[0360] Table 3 - Continued

[0361]

[0362] [Table 63]

[0363] Table 3 - Continued

[0364]

[0365] [Table 64]

[0366] Table 3 - Continued

[0367]

[0368] [Table 65]

[0369] Table 3 - Continued

[0370]

[0371] [Table 66]

[0372] Table 3 - Continued

[0373]

[0374] [Table 67]

[0375] Table 3 - Continued

[0376]

[0377] [Table 68]

[0378] Table 3 - Continued

[0379]

[0380] [Table 69]

[0381] Table 3 - Continued

[0382]

[0383] [Table 70]

[0384] Table 3 - Continued

[0385]

[0386] [Table 71]

[0387] Table 3 - Continued

[0388]

[0389] [Table 72]

[0390] Table 3 - Continued

[0391]

[0392] [Table 73]

[0393] Table 3 - Continued

[0394]

[0395] [Table 74]

[0396] Table 3 - Continued

[0397]

[0398] [Table 75]

[0399] Table 3 - Continued

[0400]

[0401] [Table 76]

[0402] Table 3 - Continued

[0403]

[0404] [Table 77]

[0405] Table 3 - Continued

[0406]

[0407] [Table 78]

[0408] Table 3 - Continued

[0409]

[0410] [Table 79]

[0411] Table 3 - Continued

[0412]

[0413] [Table 80]

[0414] Table 3 - Continued

[0415]

[0416] Representative examples of synthetic intermediates represented by general formulas (1a), (1a'), (2a), (2a'), (3a) or (3a') include compounds in which R is present in Tables 1 to 3. 1 Compounds substituted with hydrogen atoms, trimethylsilyl groups, triethylsilyl groups, triisopropylsilyl groups, dimethylisopropylsilyl groups, diethylisopropylsilyl groups, dimethylhexylsilyl groups, tert-butyldimethylsilyl groups, or ditert-butylmethylsilyl groups.

[0417] Next, the method for preparing the 1,4-cineole derivatives represented by the above general formulas (1), (1'), (2), (2'), (3), or (3') of the present invention will be described in detail, but the present invention is not limited to this method. For the reactor, the reaction can be carried out using a magnetic stirrer, a mechanical stirrer, or even a microwave synthesis apparatus.

[0418] [Preparation Method 1]

[0419] [Chemical Formula 5]

[0420]

[0421] Step-1 is the step of preparing diol derivative (5) by subjecting the γ-terpene represented by formula (4) to an oxidation reaction. The γ-terpene represented by formula (4) is known and can be obtained from Tokyo Chemical Industry Co., Ltd. and the like.

[0422] Examples of oxidation methods in this step include methods using oxidants such as osmium tetroxide, potassium osmium tetrate, lead tetraacetate, potassium permanganate, sodium periodate, ruthenium chloride, iodine, and silver acetate, as well as oxidation in the presence of re-oxidants such as potassium ferricyanide, N-methylmorpholine N-oxide, or tert-butyl hydroperoxide. In oxidation methods, osmium tetroxide and potassium osmium tetrate are preferred for good yields.

[0423] This reaction can be carried out in the presence of a base, and examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilamide lithium, hexamethyldisilamide sodium, and hexamethyldisilamide potassium. The amount of base to be used is in the range of 0.01 equivalents to 10 equivalents relative to γ-terpene (4) without adversely affecting the progress of the reaction, but in order to obtain the target compound in good yield, the amount of base to be used is more preferably in the range of 0.05 equivalents to 5 equivalents.

[0424] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of such solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, hydrochloric acid, acetic acid, and mixtures thereof.

[0425] Depending on the oxidant and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 100°C, with a preferred range of -20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0426] In this step, the two isomers can also be obtained by performing asymmetric reactions using asymmetric ligands such as (DHQ)2PHAL or (DHQD)2PHAL, respectively.

[0427] [Preparation Method 2]

[0428] [Chemical Formula 6]

[0429]

[0430] (R 7 This refers to C1-C6 alkyl groups, C1-C6 haloalkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C1-C6 alkoxy C1-C6 alkyl groups. Aryl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), heterocyclic rings (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C7-C11 aralkyl groups (which can be mono- or poly-substituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, carboxyl groups, etc.). The following are listed as substituted groups: alkyl groups (or C1-C6 alkoxycarbonyl groups, monosubstituted or polysubstituted), heterocyclic C1-C6 alkyl groups (which may be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), phenoxy C1-C6 alkyl groups (which may be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 arylalkyloxy C1-C6 alkyl groups (which may be monosubstituted or polysubstituted by halogen atoms, C1-C6 alkyl groups, or...). (C1-C6 haloalkyl groups, mono- or poly-substituted), benzoyl C1-C6 alkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl groups, or triC1-C6 alkylsilyl groups, which can be the same or different, and Y is a leaving group such as a halogen atom, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, or p-toluenesulfonyloxy group.)

[0431] By R 7 The C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, sec-butyl groups, tert-butyl groups, n-pentyl groups, neopentyl groups, 2-pentyl groups, 3-pentyl groups, tert-pentyl groups, n-hexyl groups, isohexyl groups, 2-hexyl groups, and 3-hexyl groups.

[0432] By R 7The C1-C6 haloalkyl groups represented can be straight-chain or branched, and examples include monofluoromethyl groups, difluoromethyl groups, trifluoromethyl groups, 2,2,2-trifluoroethyl groups, 2-chloroethyl groups, trichloromethyl groups, 1-fluoroethyl groups, 2-fluoroethyl groups, 6-fluorohexyl groups, and monobromomethyl groups. The number of C1-C6 haloalkyl groups as substituents can be one or two or more, and in the case of two or more, the individual C1-C6 haloalkyl groups can be the same or different. The substitution position of the C1-C6 haloalkyl groups can be any position of the group substituted by the C1-C6 haloalkyl group.

[0433] By R 7 The C2-C6 alkenyl groups can be straight-chain or branched, and examples include vinyl groups, 1-propenyl groups, 2-propenyl groups, 1-butenyl groups, 2-butenyl groups, 3-butenyl groups, 1-methyl-2-propenyl groups, 2-methyl-2-propenyl groups, 1-pentenyl groups, 2-pentenyl groups, 3-pentenyl groups, 4-pentenyl groups, 1-methyl-2-butenyl groups, 2-methyl-2-butenyl groups, 1-hexenyl groups, 2-hexenyl groups, 3-hexenyl groups, 4-hexenyl groups, and 5-hexenyl groups.

[0434] By R 7 The C2-C6 ynyl group can be straight-chain or branched, and examples include ethynyl group, 1-propynyl group, propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2-methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentynyl group, 1-hexynyl group, and 1,1-dimethyl-2-butynyl group.

[0435] By R 7 Examples of C3-C6 cycloalkyl groups include cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, 2,2-dimethylpropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0436] By R 7 The C3-C6 cycloalkyl and C1-C6 alkyl groups can be straight-chain or branched, and examples include cyclopropylmethyl, cyclopropylethyl, 1-methylcyclopropylmethyl, 2-methylcyclopropylmethyl, 2,2-dimethylcyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl groups.

[0437] By R 7The C1-C6 alkoxy-C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methoxymethyl groups, ethoxymethyl groups, n-propoxymethyl groups, isopropoxymethyl groups, n-butoxymethyl groups, sec-butoxymethyl groups, tert-butoxymethyl groups, 1-pentoxymethyl groups, 1-hexyloxymethyl groups, 2-methoxyethyl groups, 2-ethoxyethyl groups, 2-isopropoxyethyl groups, 2-isobutoxyethyl groups, 3-methoxypropyl groups, 2-methoxypropyl groups, and 2-methoxy-1-methylethyl groups.

[0438] By R 7 The aryl group referred to is a monocyclic or polycyclic aromatic group, and examples of such groups include phenyl groups, 1-naphthyl groups, and 2-naphthyl groups.

[0439] By R 7 Examples of heterocyclic rings include 2-pyridyl groups, 3-pyridyl groups, 4-pyridyl groups, 2-thienyl groups, 3-thienyl groups, 2-furanyl groups, 3-furanyl groups, 2-pyrimidinyl groups, 4-pyrimidinyl groups, 5-pyrimidinyl groups, 6-pyrimidinyl groups, 2-tetrahydrofuranyl groups, and 3-tetrahydrofuranyl groups.

[0440] By R 7 The C7-C11 aralkyl groups can be straight-chain or branched, and examples include benzyl groups, 1-phenylethyl groups, 2-phenylethyl groups, 1-phenylpropyl groups, 2-phenylpropyl groups, 3-phenylpropyl groups, 1-phenyl-2-methylpropyl groups, 1-phenylbutyl groups, and 1-phenylpentyl groups.

[0441] By R 7 The heterocyclic C1-C6 alkyl groups represented can be straight-chain or branched, and examples include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furfuryl, 3-furfuryl, 2-pyrimidinylmethyl, 4-pyrimidinylmethyl, 5-pyrimidinylmethyl, 6-pyrimidinylmethyl, 4-pyrazolylmethyl, 2-tetrahydrofurfuryl, 3-tetrahydrofurfuryl, and isoxazol-4-yl-methyl.

[0442] By R 7 The phenoxy C1-C6 alkyl group can be straight-chain or branched, and examples include phenoxymethyl group, 2-phenoxyethyl group, 2-phenoxypropyl group, 3-phenoxypropyl group, 2-phenoxybutyl group, 3-phenoxybutyl group and 4-phenoxybutyl group.

[0443] By R 7The C7-C11 arylalkoxy C1-C6 alkyl groups can be straight-chain or branched, and examples include benzyloxymethyl, 1-phenylethoxymethyl, 2-phenylethoxymethyl, 1-phenylpropoxymethyl, 2-phenylpropoxymethyl, 3-phenylpropoxymethyl and benzyloxyethyl groups.

[0444] By R 7 The C1-C6 alkoxy group can be straight-chain or branched, and examples include methoxymethoxymethyl group, ethoxymethoxymethyl group, n-propoxymethoxymethyl group, isopropoxymethoxymethyl group, n-butoxymethoxymethyl group, sec-butoxymethoxymethyl group, tert-butoxymethoxymethyl group, 1-pentoxymethoxymethyl group, 1-hexyloxymethoxymethyl group, 1-ethoxyethoxymethyl group, 1-methoxyethoxymethyl group and 2-methoxyethoxymethyl group.

[0445] By R 7 The three C1-C6 alkylsilyl groups represented may be the same or different, including trimethylsilyl groups, triethylsilyl groups, triisopropylsilyl groups, dimethylisopropylsilyl groups, diethylisopropylsilyl groups, dimethylhexylsilyl groups, tert-butyldimethylsilyl groups, and ditert-butylmethylsilyl groups.

[0446] Examples of halogen atoms represented by Y include fluorine, chlorine, bromine, and iodine.

[0447] Step-2 is the step of preparing olefin derivative (7) by reacting a diol derivative represented by formula (5) (hereinafter also referred to as substrate (5) or diol (5)) with a compound represented by formula (6) (hereinafter also referred to as reaction substrate (6)) in the presence of a base.

[0448] This reaction can be carried out in the presence of a base, and examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilamide lithium, hexamethyldisilamide sodium, and hexamethyldisilamide potassium. The base can be used in an amount ranging from 0.1 equivalents to 5 equivalents relative to the substrate (5) without adversely affecting the reaction process, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents. The reaction substrate (6) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (5) without adversely affecting the reaction process, and in order to obtain the target compound in good yield, the reaction substrate (6) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably, from 1.1 equivalents to 1.5 equivalents.

[0449] In this reaction, the target compound can be obtained in good yield by using a re-oxidizing agent, and examples of re-oxidizing agents that can be used include N-methylmorpholine oxide, trimethylamine oxide, tert-butyl hydroperoxide, and potassium ferricyanide. The re-oxidizing agent can be used in an amount ranging from 0.1 equivalents to 20 equivalents relative to the substrate (5) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the re-oxidizing agent is preferably used in an amount ranging from 1 equivalent to 10 equivalents, and more preferably, 1.5 equivalents to 5 equivalents.

[0450] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0451] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0452] In this step, the two isomers can also be obtained by using 1S,2R-(5) and 1R,2S-(5) as substitutes for the diol (5) with their respective retained stereochemistry.

[0453] [Preparation Method 3]

[0454] [Chemical Formula 7]

[0455]

[0456] (R 7 It has the same meaning as above.

[0457] Step 3 is the step of preparing the epoxy derivative (8) by subjecting the olefin derivative represented by formula (7) (hereinafter also referred to as substrate (7)) to an oxidation reaction. The resulting epoxy derivative (8) is a mixture of 1S,6S-(8) and 1R,6R-(8) and can be easily separated and purified by column chromatography or the like.

[0458] Examples of oxidants to be used in the reaction include peroxides such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, tert-butyl hydroperoxide, sodium periodate, and OXONE, EI DuPont (trade name; containing potassium persulfate), N-chlorosuccinimide, N-bromosuccinimide, tert-butyl hypochlorite, sodium hypochlorite, and oxygen. Hydrogen peroxide and m-chloroperoxybenzoic acid are preferred among the oxidants for good yield. The oxidant can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (7) without adversely affecting the reaction process, and for obtaining the target compound in good yield, the oxidant is preferably used in an amount ranging from 0.5 equivalents to 5 equivalents, and more preferably, 1 equivalent to 3 equivalents.

[0459] This invention can be carried out in the presence of a catalyst to synthesize the target compound in good yield. Examples of catalysts to be used in the reaction include molybdenum oxide, boric acid, triferric (acetylacetone) and sodium tungstate. Among the catalysts, sodium tungstate is preferred for good yield. The catalyst can be used in an amount ranging from 0.01 mol% to 30 mol% relative to the substrate (7) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the catalyst is preferably used in an amount ranging from 0.1 mol% to 10 mol%, and more preferably, in the range of 0.5 mol% to 1 mol% relative to the substrate (7).

[0460] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of solvents that can be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; water; and mixtures thereof.

[0461] Depending on the oxidant and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of -10°C to 50°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0462] In this step, the two isomers can also be obtained by using two isomeric olefin derivatives (7) that replace the olefin derivative (7) with their respective stereochemistry, which are obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials in step-2.

[0463] [Preparation Method 4]

[0464] [Chemical Formula 8]

[0465]

[0466] (R 7 It has the same meaning as above.

[0467] Step 4 is the step of preparing 1,4-cineole derivative (9) by using an acid ring-opening epoxy derivative represented by formula (8) (hereinafter also referred to as substrate (8)) and simultaneously performing intramolecular cyclization.

[0468] Examples of acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, p-pyridinium p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanate, metaiodic acid, hexafluorophosphate, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The acid can be used in amounts ranging from 0.1 equivalents to 5 equivalents relative to the substrate (8) without adversely affecting the progress of the reaction, and preferably in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably from 1 equivalent to 1.5 equivalents, in order to obtain the target compound in good yield.

[0469] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of such solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, hydrochloric acid, acetic acid, and mixtures thereof.

[0470] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0471] In this step, each isomer can be obtained by using each isomer of epoxy derivative (8) in place of the epoxy derivative (8) with its retained stereochemistry. Each isomer of epoxy derivative (8) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2 and-3.

[0472] [Preparation Method 5]

[0473] [Chemical Formula 9]

[0474]

[0475] (R 7 It has the same meaning as above.

[0476] Step 5 is the step of preparing the ketone derivative (10) by subjecting the 1,4-cineole derivative represented by formula (9) (hereinafter also referred to as substrate (9)) to an oxidation reaction.

[0477] Examples of oxidation reactions to be used in the reaction include Swern oxidation using dimethyl sulfoxide and oxaloyl chloride or triethylamine, PCC oxidation or PDC oxidation using pyridinium chlorochromate or pyridinium dichromate, and oxidation using Dess-Martin oxidants. Oxidation of periodinane, 2-iodobenzoic acid (IBX), etc., using TPAP oxidation with tetrapropylammonium perruthenate, oxidation using nitroxy groups such as 2,2,6,6-tetramethylpiperidin-1-oxy radical (TEMPO), 2-azaadamantane-N-oxy radical (AZADO) and 2-hydroxy-2-azaadamantane (AZADOL), oxidation using high-valent iodine such as iodophenyldiacetic acid (PIDA), 1-acetoxy-1,2-benziodo-3(1H)-one (ABX) and 1-(tert-butylperoxy)-1,2-benziodo-3-one, and oxidation using N-tert-butylbenzylthionyl chloride. The oxidant can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (9) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the oxidant is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0478] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of solvents that can be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; water; and mixtures thereof.

[0479] Depending on the oxidant and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0480] In this step, each isomer can be obtained by using each isomer of 1,4-cineole derivative (9) in place of the 1,4-cineole derivative (9) with its retained stereochemistry. Each isomer of 1,4-cineole derivative (9) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3 and-4.

[0481] [Preparation Method 6]

[0482] [Chemical Formula 10]

[0483]

[0484] (R 4 R 5 and R 7 It has the same meaning as above.

[0485] Step 6 is the step of preparing olefin derivative (12) by subjecting the ketone derivative represented by formula (10) (hereinafter also referred to as substrate (10)) to a Wittig reaction with phosphonium ylide (11) (hereinafter also referred to as reaction substrate (11)).

[0486] The reaction substrate (11) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (10) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (11) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0487] This reaction can be carried out in the presence of a base, and examples of bases that can be used include alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, sodium hexamethyldisilamide, potassium hexamethyldisilamide, and lithium hexamethyldisilamide. The base can be used in an amount ranging from 0.1 equivalents to 5 equivalents relative to the substrate (10) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0488] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; halogen solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0489] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0490] In this step, each isomer can be obtained by using each isomeric ketone derivative (10) in place of the ketone derivative (10) with its retained stereochemistry. Each isomeric ketone derivative (10) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4 and-5.

[0491] [Preparation Method 7]

[0492] [Chemical Formula 11]

[0493]

[0494] (R 6 and R 7 It has the same meaning as above.

[0495] Step 7 is the step of preparing an imine derivative (14) by reacting a ketone derivative represented by formula (10) with an amine compound represented by formula (13) (hereinafter also referred to as reaction substrate (13)).

[0496] The amine compound (13) to be used in this reaction can also be used as a salt, and examples of salts that can be used include hydrochloride, sulfate and carbonate.

[0497] The reaction substrate (13) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (10) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (13) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0498] This reaction can be carried out in the presence of an acid or a base. Examples of acids that can be used include hydrochloric acid, sulfuric acid, and acetic acid. Examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilaminolithium. The acid or base may be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (10) without adversely affecting the course of the reaction, and in order to obtain the target compound in good yield, the acid or base is preferably used in amounts ranging from 0.5 equivalents to 5 equivalents, and more preferably, from 1 equivalent to 3 equivalents.

[0499] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; halogen solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0500] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0501] In this step, each isomer can be obtained by using each isomeric ketone derivative (10) in place of the ketone derivative (10) with its retained stereochemistry. Each isomeric ketone derivative (10) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4 and-5.

[0502] [Preparation Method 8]

[0503] [Chemical Formula 12]

[0504]

[0505] (R 7 R has the same meaning as Y, as described above. 8 This refers to C1-C6 alkyl groups, C1-C6 haloalkyl groups, C7-C11 aralkyl groups (which may be mono- or polysubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which may be mono- or polysubstituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C1-C6 alkoxy-C1-C6 alkyl groups, C1-C6 alkyl carbonyl groups, C1-C6 alkoxy carbonyl groups, C1-C6 alkyl thiocarbonyl groups, C1-C6 alkyl thiocarbonyl groups, C1-C6 alkyl sulfonyl groups, or C1-C6 haloalkyl sulfonyl groups.

[0506] By R 8 The C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, sec-butyl groups, tert-butyl groups, n-pentyl groups, neopentyl groups, 2-pentyl groups, 3-pentyl groups, tert-pentyl groups, n-hexyl groups, isohexyl groups, 2-hexyl groups, and 3-hexyl groups.

[0507] By R 8 The C1-C6 haloalkyl groups represented can be straight-chain or branched, and examples include monofluoromethyl groups, difluoromethyl groups, trifluoromethyl groups, 2,2,2-trifluoroethyl groups, 2-chloroethyl groups, trichloromethyl groups, 1-fluoroethyl groups, 2-fluoroethyl groups, and 6-fluorohexyl groups.

[0508] By R 8The C7-C11 aralkyl groups can be straight-chain or branched, and examples include benzyl groups, 1-phenylethyl groups, 2-phenylethyl groups, 1-phenylpropyl groups, 2-phenylpropyl groups, 3-phenylpropyl groups, 1-phenyl-2-methylpropyl groups, 1-phenylbutyl groups, and 1-phenylpentyl groups.

[0509] By R 8 The heterocyclic C1-C6 alkyl groups represented can be straight-chain or branched, and examples include 2-pyridylmethyl groups, 3-pyridylmethyl groups, 4-pyridylmethyl groups, 2-thienylmethyl groups, 3-thienylmethyl groups, 2-furfuryl groups, 3-furfuryl groups, 2-pyrimidinylmethyl groups, 4-pyrimidinylmethyl groups, 5-pyrimidinylmethyl groups, 6-pyrimidinylmethyl groups, 2-tetrahydrofurfuryl groups, and 3-tetrahydrofurfuryl groups.

[0510] By R 8 The C1-C6 alkoxy-C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methoxymethyl groups, ethoxymethyl groups, n-propoxymethyl groups, isopropoxymethyl groups, n-butoxymethyl groups, sec-butoxymethyl groups, tert-butoxymethyl groups, 1-pentoxymethyl groups, 1-hexyloxymethyl groups, 2-methoxyethyl groups, 2-ethoxyethyl groups, 2-isopropoxyethyl groups, 2-isobutoxyethyl groups, 3-methoxypropyl groups, 2-methoxypropyl groups, and 2-methoxy-1-methylethyl groups.

[0511] By R 8 Examples of C1-C6 alkyl carbonyl groups include acetyl, ethyl carbonyl, n-propyl carbonyl, isopropyl carbonyl, n-butyl carbonyl, isobutyl carbonyl, sec-butyl carbonyl, tert-butyl carbonyl, 1-pentyl carbonyl, and 1-hexyl carbonyl.

[0512] By R 8 Examples of C1-C6 alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, sec-butoxycarbonyl, and tert-butoxycarbonyl.

[0513] By R 8 Examples of C1-C6 alkyl thiocarbonyl groups include methyl thiocarbonyl groups, ethyl thiocarbonyl groups, n-propyl thiocarbonyl groups, isopropyl thiocarbonyl groups, n-butyl thiocarbonyl groups, sec-butyl thiocarbonyl groups, tert-butyl thiocarbonyl groups, 1-pentyl thiocarbonyl groups, and 1-hexyl thiocarbonyl groups.

[0514] By R 8Examples of C1-C6 alkyl thiothiocarbonyl groups include methyl thiothiocarbonyl groups, ethyl thiothiocarbonyl groups, n-propyl thiothiocarbonyl groups, isopropyl thiothiocarbonyl groups, n-butyl thiothiocarbonyl groups, sec-butyl thiothiocarbonyl groups, tert-butyl thiothiocarbonyl groups, 1-pentyl thiothiocarbonyl groups, and 1-hexyl thiothiocarbonyl groups.

[0515] By R 8 Examples of C1-C6 alkyl sulfonyl groups include methanesulfonyl groups, ethanesulfonyl groups, n-propanesulfonyl groups, isopropanesulfonyl groups, n-butanesulfonyl groups, isobutanesulfonyl groups, sec-butanesulfonyl groups, tert-butanesulfonyl groups, and n-pentanesulfonyl groups.

[0516] By R 8 Examples of C1-C6 haloalkylsulfonyl groups include monofluoromethanesulfonyl groups, difluoromethanesulfonyl groups, trifluoromethanesulfonyl groups, monochloromethanesulfonyl groups, trichloromethanesulfonyl groups, and 2,2,2-trifluoroethanesulfonyl groups.

[0517] Step-8 is the step of preparing 1,4-cineole derivative (16) by reacting a compound represented by formula (15) (hereinafter also referred to as reaction substrate (15)) with the hydroxyl group at the 5-position of the 1,4-cineole derivative represented by formula (9).

[0518] The reaction substrate (15) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (9) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (15) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0519] This reaction can be carried out in the presence of a base, and examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilamide sodium, hexamethyldisilamide potassium, and hexamethyldisilamide lithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (9) without adversely affecting the course of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0520] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0521] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0522] In this step, each isomer can be obtained by using each isomer of 1,4-cineole derivative (9) in place of the 1,4-cineole derivative (9) with its retained stereochemistry. Each isomer of 1,4-cineole derivative (9) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4 and-5.

[0523] [Preparation Method 9]

[0524] [Chemical Formula 13]

[0525]

[0526] (R 7 It has the same meaning as above.

[0527] Step 9 is the step of reacting the 1,4-cineole derivative represented by formula (9) with vinyl ethyl ether (17) (hereinafter also referred to as reaction substrate (17)) in the presence of an acid catalyst to prepare the ether derivative represented by formula (18).

[0528] The reaction substrate (17) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (9) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (17) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0529] The acid that can be used in this reaction can be an organic acid or an inorganic acid such as hydrochloric acid, sulfuric acid, acetic acid, p-toluenesulfonic acid, or pyridinium salt of p-toluenesulfonic acid. The acid can be used in an amount ranging from 0.001 equivalents to 1 equivalent relative to the substrate (9) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the acid is preferably used in an amount ranging from 0.005 equivalents to 0.5 equivalents, and more preferably, from 0.05 equivalents to 0.1 equivalents.

[0530] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0531] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0532] In this step, each isomer can be obtained by using each isomer of 1,4-cineole derivative (9) in place of the 1,4-cineole derivative (9) with its retained stereochemistry. Each isomer of 1,4-cineole derivative (9) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4 and-5.

[0533] [Preparation Method 10]

[0534] [Chemical Formula 14]

[0535]

[0536] (R 4 and R 5 It has the same meaning as above.

[0537] Step 10 is the step of preparing 1,4-cineole derivative (20) by reducing the olefin derivative represented by formula (19). The obtained 1,4-cineole derivative (20) is a mixture of 5R-(20) and 5S-(20) and can be easily separated and purified by column chromatography or the like.

[0538] The reduction methods used in this reaction may include methods using reducing agents such as zinc powder, reduced iron, tin powder, stannous chloride, or titanium chloride; methods using hydrogen donors such as hydrazine in the presence of Raney nickel; methods for catalytic hydrogen reduction in the presence of catalysts such as Raney nickel, palladium on carbon, palladium hydroxide, platinum oxide, or rhodium carbide; or methods for catalytic hydrogen transfer reduction.

[0539] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogen solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, ethyl propionate, ethyl butyrate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0540] Depending on the reaction conditions, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0541] In this step, each isomer can be obtained by using each isomeric olefin derivative (19) in place of the olefin derivative (19) with its retained stereochemistry. Each isomeric olefin derivative (19) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4,-5,-6 and-15.

[0542] [Preparation Method 11]

[0543] [Chemical Formula 15]

[0544]

[0545] (R 7 It has the same meaning as above. R 9 This indicates a C1-C6 alkyl sulfonyl group, a C1-C6 haloalkyl sulfonyl group, or a p-toluenesulfonyl group.

[0546] By R 9 Examples of C1-C6 alkyl sulfonyl groups include methanesulfonyl groups, ethanesulfonyl groups, n-propylsulfonyl groups, isopropylsulfonyl groups, n-butylsulfonyl groups, isobutylsulfonyl groups, sec-butylsulfonyl groups, tert-butylsulfonyl groups, and n-pentylsulfonyl groups.

[0547] By R 9 Examples of C1-C6 haloalkylsulfonyl groups include monofluoromethanesulfonyl groups, difluoromethanesulfonyl groups, trifluoromethanesulfonyl groups, monochloromethanesulfonyl groups, trichloromethanesulfonyl groups, and 2,2,2-trifluoroethanesulfonyl groups.

[0548] Step 11 is the step of preparing 1,4-cineole derivative (21) by reacting the ketone derivative represented by formula (10) with a sulfonating agent.

[0549] Examples of sulfonating agents to be used in this reaction include methanesulfonyl chloride, methanesulfonyl bromide, methanesulfonic anhydride, trifluoromethanesulfonyl fluoride, trifluoromethanesulfonyl chloride, trifluoromethanesulfonyl bromide, trifluoromethanesulfonic anhydride, 1-(trifluoromethylsulfonyl)imidazolium, 4-nitrophenyltrifluoromethanesulfonate, 1-(trifluoromethanesulfonyl)-1H-benzotriazole, N-phenylbis(trifluoromethanesulfonamide), trifluoromethanesulfonylaniline, N-(2-pyridyl)bis(trifluoromethanesulfonamide), 2-[N,N-bis(trifluoromethanesulfonyl)amino]-5-chloropyridine, p-toluenesulfonyl chloride, 1-(p-toluenesulfonyl)imidazolium, and p-toluenesulfonic anhydride. The sulfonating agent can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (10) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the sulfonating agent is preferably used in an amount ranging from 0.5 equivalents to 5 equivalents, and more preferably, from 1 equivalent to 3 equivalents.

[0550] This reaction can be carried out in the presence of a base. Examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilaminolithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (10) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 5 equivalents, and more preferably, from 1 equivalent to 3 equivalents.

[0551] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0552] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0553] In this step, each isomer can be obtained by using each isomeric ketone derivative (10) in place of the ketone derivative (10) with its retained stereochemistry. Each isomeric ketone derivative (10) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4 and-5.

[0554] [Preparation Method 12]

[0555] [Chemical Formula 16]

[0556]

[0557] (R 7 and R 9 It has the same meaning as above. R 10 This refers to C1-C6 alkyl groups, C1-C6 haloalkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and aryl groups (which can be halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following are substituted groups: alkyl group (or C1-C6 haloalkoxy group, mono- or polysubstituted), heterocyclic ring (which may be mono- or polysubstituted by a halogen atom, C1-C6 alkyl group, or C1-C6 haloalkoxy group), C7-C11 aralkyl group (which may be mono- or polysubstituted by a halogen atom, cyano group, nitro group, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group, or C1-C6 haloalkoxy group), or heterocyclic C1-C6 alkyl group (which may be mono- or polysubstituted by a halogen atom, C1-C6 alkyl group, or C1-C6 haloalkyl group). M represents ZnZ, Sn(R 11 3. B(OR) 11 )2 or MgZ (Z represents a halogen atom, and R 11 Represents a hydrogen atom, a C1-C6 alkyl group, or a C3-C6 cycloalkyl group, and R 11They can be the same or different, and each can be independent. In B(OR) 11 In )2, R 11 They can bond together to form 5-membered or 6-membered rings.

[0558] By R 10 The C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, sec-butyl groups, tert-butyl groups, n-pentyl groups, neopentyl groups, 2-pentyl groups, 3-pentyl groups, tert-pentyl groups, n-hexyl groups, isohexyl groups, 2-hexyl groups, and 3-hexyl groups.

[0559] By R 10 The C1-C6 haloalkyl groups represented can be straight-chain or branched, and examples include monofluoromethyl groups, difluoromethyl groups, trifluoromethyl groups, 2,2,2-trifluoroethyl groups, 2-chloroethyl groups, trichloromethyl groups, 1-fluoroethyl groups, 2-fluoroethyl groups, 6-fluorohexyl groups, and monobromomethyl groups.

[0560] By R 10 The C2-C6 alkenyl groups can be straight-chain or branched, and examples include vinyl groups, 1-propenyl groups, 2-propenyl groups, 1-butenyl groups, 2-butenyl groups, 3-butenyl groups, 1-methyl-2-propenyl groups, 2-methyl-2-propenyl groups, 1-pentenyl groups, 2-pentenyl groups, 3-pentenyl groups, 4-pentenyl groups, 1-methyl-2-butenyl groups, 2-methyl-2-butenyl groups, 1-hexenyl groups, 2-hexenyl groups, 3-hexenyl groups, 4-hexenyl groups, and 5-hexenyl groups.

[0561] By R 10 The C2-C6 ynyl group can be straight-chain or branched, and examples include ethynyl group, 1-propynyl group, propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2-methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentynyl group, 1-hexynyl group, and 1,1-dimethyl-2-butynyl group.

[0562] By R 10 Examples of C3-C6 cycloalkyl groups include cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, 2,2-dimethylpropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0563] By R10 The C3-C6 cycloalkyl and C1-C6 alkyl groups can be straight-chain or branched, and examples include cyclopropylmethyl, cyclopropylethyl, 1-methylcyclopropylmethyl, 2-methylcyclopropylmethyl, 2,2-dimethylcyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl groups.

[0564] By R 10 The aryl group referred to is a monocyclic or polycyclic aromatic group, and examples of such groups include phenyl groups, 1-naphthyl groups, and 2-naphthyl groups.

[0565] By R 10 Examples of heterocyclic rings include 2-pyridyl groups, 3-pyridyl groups, 4-pyridyl groups, 2-thienyl groups, 3-thienyl groups, 2-furanyl groups, 3-furanyl groups, 2-pyrimidinyl groups, 4-pyrimidinyl groups, 5-pyrimidinyl groups, 6-pyrimidinyl groups, 2-tetrahydrofuranyl groups, and 3-tetrahydrofuranyl groups.

[0566] By R 10 The C7-C11 aralkyl groups can be straight-chain or branched, and examples include benzyl groups, 1-phenylethyl groups, 2-phenylethyl groups, 1-phenylpropyl groups, 2-phenylpropyl groups, 3-phenylpropyl groups, 1-phenyl-2-methylpropyl groups, 1-phenylbutyl groups, and 1-phenylpentyl groups.

[0567] By R 10 The C1-C6 alkyl groups represented can be straight-chain or branched, and examples include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furfuryl, 3-furfuryl, 2-pyrimidinylmethyl, 4-pyrimidinylmethyl, 5-pyrimidinylmethyl, 6-pyrimidinylmethyl, 4-pyrazolylmethyl, 2-tetrahydrofurfuryl, and 3-tetrahydrofurfuryl.

[0568] Examples of halogen atoms represented by Z include chlorine, bromine, and iodine.

[0569] By R 11 The C1-C6 alkyl groups represented can be straight-chain or branched, and examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, sec-butyl groups, tert-butyl groups, n-pentyl groups, neopentyl groups, 2-pentyl groups, 3-pentyl groups, tert-pentyl groups, n-hexyl groups, isohexyl groups, 2-hexyl groups, and 3-hexyl groups.

[0570] By R 11Examples of C3-C6 cycloalkyl groups include cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, 2,2-dimethylpropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0571] Step 12 is the step of preparing an olefin derivative (23) by reacting an organometallic reagent (22) (hereinafter also referred to as reaction substrate (22)) with a group at the 5-position of a 1,4-cineole derivative represented by formula (21) (hereinafter also referred to as substrate (21)).

[0572] The reaction substrate (22) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (21) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (22) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0573] This reaction can be carried out in the presence of a base. Examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilaminolithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (21) without adversely affecting the course of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0574] Examples of catalysts to be used in this reaction include copper compounds, tin compounds, palladium compounds, and palladium black, with palladium compounds being preferred. Examples of palladium compounds include palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium nitrate, palladium oxide, dichlorobis(triphenylphosphine)palladium, tetra(triphenylphosphine)palladium, palladium cyanide, dichlorobis(tri-o-tolylphosphine)palladium, dichlorobis(tricyclohexylphosphine)palladium, bis(dibenzylideneacetone)palladium, tri(dibenzylideneacetone)dipalladium, bis(acetylacetone)palladium, dichloro-(1,5-cyclooctadiene)-palladium, dichlorodiaminepalladium, tetraamminepalladium nitrate, tetraaminopalladium tetrachloride, dichlorodipyridinepalladium, dichloro(2,2'-bipyridyl)palladium, dichloro(phenanthroline)palladium, and dichlorodiphenylaminepalladium. [1,2-bis(diphenylphosphine)ethane]palladium, dichloro[1,3-bis(diphenylphosphine)propane]palladium, dichloro[1,4-bis(diphenylphosphine)butane]palladium, dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium, allyl palladium(II) chloride dimer, allyl chloride-[1,3-bis-(diisopropylphenyl)-imidazol-2-ylidene]palladium, phenylallyl chloride-[1,3-bis-(diisopropylphenyl)-imidazol-2-ylidene]palladium, and dichloro-[1,3-bis(diisopropylphenyl)imidazolium-2-ylidene]-(3-chloropyridyl)palladium. Among metal catalysts, palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium, and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium are preferred for good yields. The amount of catalyst to be used is in the range of 0.001 mol% to 50 mol% relative to the substrate (21) without adversely affecting the reaction process, and in order to obtain the target compound in good yield, the catalyst is preferably used in the range of 0.01 mol% to 30 mol%, and more preferably in the range of 0.1 mol% to 10 mol%.

[0575] Palladium catalysts can be used alone or in combination with tertiary phosphine. Specific examples of tertiary phosphine include triphenylphosphine, tri(o-methylphenyl)phosphine, trimethylphosphine, triethylphosphine, tripropylphosphine, triisopropylphosphine, tributylphosphine, triisobutylphosphine, tri(tert-butyl)phosphine, trinepentylphosphine, tricyclohexylphosphine, trioctylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-bis(diphenylphosphino)ferrocene, 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, tri(hydroxymethyl)phosphine, 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, and 2-(dicyclohexylphosphino)-2',4',6'-triisopropyl-1,1'-biphenyl. Among tertiary phosphines, triphenylphosphine, 1,1'-bis(diphenylphosphino)ferrocene and 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl are preferred for good yields.

[0576] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0577] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0578] In this step, each isomer can be obtained by using each isomer of 1,4-cineole derivative (21) in place of the 1,4-cineole derivative (21) with its retained stereochemistry. Each isomer of 1,4-cineole derivative (21) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4,-5 and-11.

[0579] [Preparation Method 13]

[0580] [Chemical Formula 17]

[0581]

[0582] (R 7 and R 10 It has the same meaning as above.

[0583] Step 13 is the step of preparing 1,4-cineole derivative (24) by reducing the olefin derivative represented by formula (23). The obtained 1,4-cineole derivative (24) is a mixture of 5R-(24) and 5S-(24), and can be easily separated and purified by column chromatography or the like.

[0584] The reduction methods used in this reaction may include methods using reducing agents such as zinc powder, reduced iron, tin powder, stannous chloride, or titanium chloride; methods using hydrogen donors such as hydrazine in the presence of Raney nickel; methods for catalytic hydrogen reduction in the presence of catalysts such as Raney nickel, palladium on carbon, palladium hydroxide, platinum oxide, or rhodium carbide; or catalytic hydrogen transfer reduction methods.

[0585] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0586] Depending on the reaction conditions, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0587] In this step, each isomer can be obtained by using each isomeric olefin derivative (23) that replaces the olefin derivative (23) with its retained stereochemistry. Each isomeric olefin derivative (23) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, step-3, step-4, step-5, step-11 and step-12.

[0588] [Preparation Method 14]

[0589] [Chemical Formula 18]

[0590]

[0591] (R 2a and R 3a It has the same meaning as above. R 12 (These can be the same or different and represent three C1-C6 alkylsilyl groups.)

[0592] Can be the same or different from R 12Examples of triC1-C6 alkylsilyl groups include trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, dimethylisopropylsilyl group, diethylisopropylsilyl group, dimethylhexylsilyl group, tert-butyldimethylsilyl group and ditert-butylmethylsilyl group.

[0593] Step 14 is the step of preparing an alcohol derivative represented by formula (26) by deprotecting a silyl ether derivative represented by formula (25) (hereinafter also referred to as substrate (25)) in the presence of an acid or fluoride ion.

[0594] Examples of acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, p-pyridinium p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanate, metaiodic acid, hexafluorophosphate, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The acid can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (25) without adversely affecting the progress of the reaction, and preferably in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably from 1 equivalent to 1.5 equivalents, in order to obtain the target compound in good yield.

[0595] Examples of fluoride ions to be used in this reaction include potassium fluoride, cesium fluoride, hydrofluoric acid and its salts, and tetrabutylammonium fluoride. Fluoride ions can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (25) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, fluoride ions are preferably used in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0596] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0597] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0598] In this step, each isomer can be obtained by using each isomer of silyl ether derivative (25) in place of the silyl ether derivative (25) with its retained stereochemistry. Each isomer of silyl ether derivative (25) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as starting materials to perform steps-2, steps-3, steps-4 and steps-8, or steps-2, steps-3, steps-4 and steps-8, or steps-2, steps-3, steps-4 and steps-9, or steps-2, steps-3, steps-4, steps-5, steps-11, steps-12 and steps-13.

[0599] [Preparation Method 15]

[0600] [Chemical Formula 19]

[0601]

[0602] (X a and R 12 It has the same meaning as above.

[0603] Step 15 is the step of preparing the alcohol derivative represented by formula (28) by deprotecting the silyl ether derivative represented by formula (27) (hereinafter also referred to as substrate (27)) in the presence of acid or fluoride ions.

[0604] Examples of acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, p-pyridinium p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanate, metaiodic acid, hexafluorophosphate, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The acid can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (27) without adversely affecting the progress of the reaction, and preferably in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably from 1 equivalent to 1.5 equivalents, in order to obtain the target compound in good yield.

[0605] Examples of fluoride ions to be used in this reaction include sodium fluoride, potassium fluoride, cesium fluoride, hydrofluoric acid and its salts, and tetrabutylammonium fluoride. Fluoride ions can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (27) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, fluoride ions are preferably used in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0606] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0607] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0608] In this step, each isomer can be obtained by using each isomer of silyl ether derivative (27) in place of the silyl ether derivative (27) with its retained stereochemistry. Each isomer of silyl ether derivative (27) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, steps-3, steps-4, steps-5 and steps-6, or steps-2, steps-3, steps-4, steps-5 and steps-7.

[0609] [Preparation Method 16]

[0610] [Chemical Formula 20]

[0611]

[0612] (W a and R 12 It has the same meaning as above.

[0613] Step 16 is the step of preparing an alcohol derivative represented by formula (30) by deprotecting a silyl ether derivative represented by formula (29) (hereinafter also referred to as substrate (29)) in the presence of an acid or fluoride ion.

[0614] Examples of acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, p-pyridinium p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanate, metaiodic acid, hexafluorophosphate, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The acid can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (29) without adversely affecting the progress of the reaction, and preferably in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably from 1 equivalent to 1.5 equivalents, in order to obtain the target compound in good yield.

[0615] Examples of fluoride ions to be used in this reaction include sodium fluoride, potassium fluoride, cesium fluoride, hydrofluoric acid and its salts, and tetrabutylammonium fluoride. Fluoride ions can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (29) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, fluoride ions are preferably used in amounts ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0616] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0617] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0618] In this step, each isomer can be obtained by using each isomer of silyl ether derivative (29) in place of the silyl ether derivative (29) with its retained stereochemistry. Each isomer of silyl ether derivative (29) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4,-5,-11 and-12.

[0619] [Preparation Method 17]

[0620] [Chemical Formula 21]

[0621]

[0622] (R 1 R 2a R 3a (And Y has the same meaning as above.)

[0623] Step-17 is the step of preparing 1,4-cineole derivative (32) by reacting an alcohol derivative of formula (26) (hereinafter also referred to as substrate (26)) with a compound represented by formula (31) (hereinafter also referred to as reaction substrate (31)).

[0624] The reaction substrate (31) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (26) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (31) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0625] This reaction can be carried out in the presence of a base. Examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilaminolithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (26) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0626] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0627] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0628] In this step, each isomer can be obtained by using each isomer of alcohol derivative (26) as a substitute for alcohol derivative (26) with its retained stereochemistry. Each isomer of alcohol derivative (26) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, steps-3, steps-4, steps-5, steps-6, steps-15 and steps-10, or steps-2, steps-3, steps-4, steps-8 and steps-14, or steps-2, steps-3, steps-4, steps-9 and steps-14, or steps-2, steps-3, steps-4, steps-5, steps-11, steps-12, steps-13 and steps-14.

[0629] [Preparation Method 18]

[0630] [Chemical Formula 22]

[0631]

[0632] (R 1 X a (And Y has the same meaning as above.)

[0633] Step-18 is the step of preparing 1,4-cineole derivative (33) by reacting an alcohol derivative represented by formula (28) (hereinafter also referred to as substrate (28)) with a compound represented by formula (31).

[0634] The reaction substrate (31) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (28) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (31) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0635] This reaction can be carried out in the presence of a base, and examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilamide sodium, hexamethyldisilamide potassium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilamide lithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (28) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0636] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0637] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0638] In this step, each isomer can be obtained by using each isomer of alcohol derivative (28) as a substitute for alcohol derivative (28) with its retained stereochemistry. Each isomer of alcohol derivative (28) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, steps-3, steps-4, steps-5, steps-6 and steps-15, or steps-2, steps-3, steps-4, steps-5, steps-7 and steps-15.

[0639] [Preparation Method 19]

[0640] [Chemical Formula 23]

[0641]

[0642] (R 1 W a (And Y has the same meaning as above.)

[0643] Step-19 is the step of preparing 1,4-cineole derivative (34) by reacting an alcohol derivative (hereinafter also referred to as substrate (30)) represented by formula (30) with a compound represented by formula (31).

[0644] The reaction substrate (31) can be used in an amount ranging from 0.5 equivalents to 5 equivalents relative to the substrate (30) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the reaction substrate (31) is preferably used in an amount ranging from 1 equivalent to 3 equivalents, and more preferably in the range of 1.1 equivalents to 1.5 equivalents.

[0645] This reaction can be carried out in the presence of a base, and examples of bases that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, and N-methylimidazolium; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilamide sodium, hexamethyldisilamide potassium, diisopropylaminolithium, trimethylsilyllithium, and hexamethyldisilamide lithium. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (30) without adversely affecting the course of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0646] Any solvent that is harmless to the reaction may be used as the solvent in this reaction, and examples of solvents that may be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0647] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0648] In this step, each isomer can be obtained by using each isomer of alcohol derivative (30) instead of alcohol derivative (30) with its retained stereochemistry. Each isomer of alcohol derivative (30) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, step-3, step-4, step-5, step-11, step-12 and step-16.

[0649] [Preparation Method 20]

[0650] [Chemical Formula 24]

[0651]

[0652] (R 7 It has the same meaning as above.

[0653] Step 20 is the step of preparing an alcohol derivative represented by formula (35) by deprotecting an ether derivative represented by formula (18) (hereinafter also referred to as substrate (18)) in the presence of an acid.

[0654] Examples of acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, p-pyridinium p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanate, metaiodic acid, hexafluorophosphate, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The acid can be used in amounts ranging from 0.1 equivalents to 10 equivalents relative to the substrate (18) without adversely affecting the progress of the reaction, and preferably in amounts ranging from 0.5 equivalents to 5 equivalents, and more preferably from 1 equivalent to 3 equivalents, in order to obtain the target compound in good yield.

[0655] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0656] Depending on the acid and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0657] In this step, each isomer can be obtained by using each isomer of ether derivative (18) as a substitute for ether derivative (18) with its retained stereochemistry. Each isomer of ether derivative (18) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2, step-3, step-4, step-9, step-14 and step-17.

[0658] [Preparation Method 21]

[0659] [Chemical Formula 25]

[0660]

[0661] (R 7 It has the same meaning as above. Z' represents a halogen atom.

[0662] Examples of halogen atoms represented by Z' include fluorine, chlorine, bromine, and iodine.

[0663] Step 21 is the step of preparing the 1,4-cineole derivative represented by formula (36) by halogenating the alcohol derivative represented by formula (35) (hereinafter also referred to as substrate (35)).

[0664] Examples of halogenating agents to be used in this reaction include fluorinating agents such as DAST, bromide trifluoride, and cesium fluoride; chlorinating agents such as chlorine, thionyl chloride, oxalyl chloride, phosphorus pentachloride, phosphoryl chloride, N-chlorosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, and trichloroisocyanuric acid; brominating agents such as bromine, dibromo thionyl chloride, oxalyl bromide, phosphorus pentabromoide, phosphoryl bromide, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, and dibromoisocyanuric acid; and iodizing agents such as iodine, N-iodosuccinimide, 1,3-diiodo-5,5-dimethylhydantoin, and N-iodo-o-sulfonylbenzoimide. The halogenating agent can be used in amounts from 0.1 equivalents to 10 equivalents relative to the substrate (35) without adversely affecting the course of the reaction, and in order to obtain the target compound in good yield, the halogenating agent is preferably used in amounts from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0665] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0666] Depending on the halogenating reagent used and the reaction conditions, the reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, with a preferred range of 20°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0667] In this step, each isomer can be obtained by using each isomer of alcohol derivative (35) as a substitute for alcohol derivative (35) with its retained stereochemistry. Each isomer of alcohol derivative (35) is obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by performing an asymmetric reaction in step-1 as raw materials to perform steps-2,-3,-4,-9,-14,-17 and-20.

[0668] [Preparation Method 22]

[0669] [Chemical Formula 26]

[0670]

[0671] (R 7 (Z has the same meaning as above.)

[0672] Step 22 is the step of preparing 1,4-cineole derivative (37) by reacting an olefin derivative represented by formula (7) (hereinafter also referred to as substrate (7)) with a halogenating agent to induce intramolecular cyclization.

[0673] Examples of halogenating agents to be used in this reaction include chlorinating agents such as chlorine, thionyl chloride, oxaloyl chloride, phosphorus pentachloride, phosphoryl chloride, N-chlorosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, and trichloroisocyanuric acid; brominating agents such as bromine, dibromo thionyl chloride, oxaloyl bromide, phosphorus pentabromoide, phosphoryl bromide, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, and dibromoisocyanuric acid; and iodizing agents such as iodine, N-iodosuccinimide, 1,3-diiodo-5,5-dimethylhydantoin, and N-iodo-o-sulfonylbenzoimide. Among the halogenating agents, chlorine, N-chlorosuccinimide, bromine, N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, iodine, and N-iodosuccinimide are preferred for good yield. The halogenating agent can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (7) without adversely affecting the reaction process, and in order to obtain the target compound in good yield, the halogenating agent is preferably used in an amount ranging from 0.5 equivalents to 5 equivalents, and more preferably, from 1 equivalent to 3 equivalents.

[0674] In this reaction, the target compound can be synthesized in good yield by adding an additive. Examples of additives to be used in this reaction include triphenylphosphine, 4-dimethylaminopyridine, sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate. Among the additives, triphenylphosphine is preferred for good yield. The additive can be used in an amount ranging from 0.01 mol% to 60 mol% relative to the substrate (7) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the additive is preferably used in an amount ranging from 0.05 mol% to 50 mol% relative to the substrate (7), more preferably from 0.1 mol% to 30 mol%, and even more preferably from 1 mol% to 10 mol%.

[0675] This reaction can be carried out in the absence of a solvent or in the presence of a solvent. Any solvent that is harmless to the reaction can be used as the solvent, and examples of solvents that can be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0676] Depending on the halogenating reagent and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of -10°C to 50°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0677] In this step, the two isomers can also be obtained by using two isomeric olefin derivatives (7) that replace the olefin derivative (7) with their respective stereochemistry. The two isomeric olefin derivatives (7) are obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by carrying out the asymmetric reaction in step-1 as raw materials to carry out step-2.

[0678] [Preparation Method 23]

[0679] [Chemical Formula 27]

[0680]

[0681] (R 7(Z has the same meaning as above.)

[0682] Step 23 is the step of preparing olefin derivative (38) by reacting the 1,4-cineole derivative represented by formula (37) (hereinafter also referred to as substrate (37)) with a base.

[0683] Examples of bases to be used in this reaction include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 2-methylpyridine, 2,6-dimethylpyridine, pyrazine, imidazole, N-methylimidazolium, 1,8-diazabicyclo[5.4.0]undecene, 7-methyl-1,5,7-triazabicyclo[4 [4.0]dec-5-ene and 1,5,7-triazabicyclo[4.4.0]dec-5-ene; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amino, butyllithium, tert-butyllithium, sec-butyllithium, diisopropylaminolithium, trimethylsilyllithium, hexamethyldisilaminosodium, hexamethyldisilaminopotassium, diisopropylaminolithium, trimethylsilyllithium and hexamethyldisilaminolithium. Among the bases, potassium tert-butoxide, sodium hydride and 1,8-diazabicyclo[5.4.0]undecene are preferred for good yield. The base can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (37) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the base is preferably used in an amount ranging from 0.5 equivalents to 3 equivalents, and more preferably, from 1 equivalent to 1.5 equivalents.

[0684] This reaction is preferably carried out in a solvent. Any solvent that is harmless to the reaction can be used as a solvent, and examples of suitable solvents include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0685] Depending on the base and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of 0°C to 100°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0686] In this step, the two isomers can also be obtained by using two isomeric olefin derivatives (37) that replace the 1,4-cineole derivative (37) with their respective stereochemistry. The two isomeric olefin derivatives (37) are obtained by using 1S,2R-(5) and 1R,2S-(5) obtained by carrying out the asymmetric reaction in step-1 as raw materials to carry out steps-2 and step-22.

[0687] [Preparation Method 24]

[0688] [Chemical Formula 28]

[0689]

[0690] (Z has the same meaning as above.)

[0691] Step 24 is the step of preparing 1,4-cineole derivative (39) by reacting a diol derivative represented by formula (5) (hereinafter also referred to as substrate (5)) with a halogenating agent to induce intramolecular cyclization.

[0692] Examples of halogenating agents to be used in this reaction include chlorinating agents such as chlorine, thionyl chloride, oxaloyl chloride, phosphorus pentachloride, phosphoryl chloride, N-chlorosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, and trichloroisocyanuric acid; brominating agents such as bromine, dibromo thionyl chloride, oxaloyl bromide, phosphorus pentabromoide, phosphoryl bromide, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, and dibromoisocyanuric acid; and iodizing agents such as iodine, N-iodosuccinimide, 1,3-diiodo-5,5-dimethylhydantoin, and N-iodo-o-sulfonylbenzoimide. In terms of good yield, chlorine, N-chlorosuccinimide, bromine, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, iodine, and N-iodosuccinimide are preferred among the halogenating agents. The halogenating agent can be used in an amount ranging from 0.1 equivalents to 10 equivalents relative to the substrate (5) without adversely affecting the reaction process, and in order to obtain the target compound in good yield, the halogenating agent is preferably used in an amount ranging from 0.5 equivalents to 5 equivalents, and more preferably, from 1 equivalent to 3 equivalents.

[0693] In this reaction, the target compound can be synthesized in good yield by adding additives. Examples of additives to be used in this reaction include triphenylphosphine, 4-dimethylaminopyridine, sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate. Among the additives, triphenylphosphine and 4-dimethylaminopyridine are preferred for good yield. The additives can be used in amounts ranging from 0.01 mol% to 60 mol% relative to the substrate (5) without adversely affecting the progress of the reaction, and in order to obtain the target compound in good yield, the additives are preferably used in amounts ranging from 0.05 mol% to 50 mol% relative to the substrate (5), more preferably from 0.1 mol% to 30 mol%, and even more preferably from 1 mol% to 10 mol%.

[0694] This reaction can be carried out in the absence of a solvent or in the presence of a solvent. Any solvent that is harmless to the reaction can be used as the solvent, and examples of solvents that can be used include: aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, isopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, and mixtures thereof.

[0695] Depending on the halogenating reagent and reaction conditions used, the reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, with a preferred range of -10°C to 50°C for good yield. After the reaction is complete, the target compound can be obtained by conventional post-processing operations, and if necessary, the target compound can be purified by column chromatography or recrystallization.

[0696] In this step, the two isomers can also be obtained by using 1S,2R-(5) and 1R,2S-(5) as substitutes for the diol derivative (5) with their respective stereochemistry, 1S,2R-(5) and 1R,2S-(5) as starting materials by carrying out an asymmetric reaction in step-1.

[0697] If necessary, through melting point, infrared absorption spectroscopy, 1 H-NMR, 13 The compounds and intermediates of this invention were analyzed, confirmed, and identified by C-NMR, mass spectrometry, X-ray structural analysis, etc.

[0698] The compounds of the present invention can be prepared by any organic synthesis method, not limited to the methods described above.

[0699] This invention relates to herbicides containing compounds of the present invention as active ingredients (hereinafter also referred to as "herbicides of the present invention").

[0700] The herbicide of the present invention is preferably used on agricultural land, pasture, lawn or non-agricultural land.

[0701] Examples of agricultural land include fields, paddy fields, orchards, fallow land, and uncultivated land.

[0702] As shown in the test examples below, the compounds of the present invention exhibit excellent herbicidal activity and can be used to control a variety of weeds, including those found in rice cultivation and dryland farming. Specific examples of weeds are as follows.

[0703] Specifically, the compounds of this invention can control a variety of harmful weeds, such as Gramineae weeds like barnyard grass (Echinochloa crus-galli), rice barnyard grass (Echinochloa oryzicola), sorghum barnyard grass (Echinochloacrus-galli var. Formosensis), crabgrass (Digitaria ciliaris, Digitaria sanguinalis, Digitaria ischaem, Digitaria adscendens, Digitaria microbachne, or Digitaria horizontalis), foxtail grass (Setaria viridis), foxtail grass (Setaria faberi), golden foxtail grass (Setaria lutescens), goosegrass (Eleusine indica), wild oat (Avena fatua), rock grass (Sorghum halepense), creeping icegrass (Aropyron repens), plantain (Brachiaria plantaginea), and millet (Panicum maximum). purpurascens, Panicum dichotomiflorum, Leptochloa chinensis, Leptochloa panicea, Poa annua, Alopecurus aequalis, Alopecurus myosuroides, Agropyron tsukushiense, Brachiaria platyphylla, Cenchrusechinatus, Lolium multiflorum, Cynodon dactylon, Beckmannia syzigache, Bromus catharticus, Leersia japonica, Leersia sayanuka, Lolium rigidum, Paspalum distichum, and Phleum pretense;Cyperaceae weeds include Cyperus iria, Cyperus rotundus, Cyperus esculentus, Scirpus hotarui, Cyperus serotinus, Eleocharis acicularis, Eleocharis kuroguwai, Cyperus flaccidus, Kyllinga brevifolia, and Scirpus juncoides; Alismataceae weeds include Sagittaria pygmaea, Sagittaria trifolia, and Alismatacanaliculatum; Pontderiaceae weeds include Monochooria vaginalis, Heterantheralimosa, and Monochooria kosakowii); Linderniaceae weeds such as Lindernia pyxidaria; Plantaginaceae weeds such as Plantago asiatica, Gratiola japonica, Dopatrium junceum, and Veronica polita; Lythraceae weeds such as Rotala india and Ammannia multiflora; Elatinaceae weeds such as Elatine triandra; Malvaceae weeds such as Abutiol theophrsti and Sidaspinosa;Compositae weeds, such as Xanthium strumarim, Ambrosia elatior, Breea serosa, Galinsoga ciliata, Matricaria chamomilla, Taraxacum officinale, Erigeron canadensis, Bidens frondosa, Bidens pilosa, Bidens tripartita, Gnaphalium affine, and Senecio vulgaris; Lamiaceae weeds, such as oleander (Lamium amplexinale weber); Solanaceae weeds, such as Solanum nigrum and Datura stramonium; Amaranthaceae weeds. Weeds of the following families include: * **Polygonaceae weeds** such as *Amaranthus viridis*, *Chenopodium album*, *Kochia scoparia*, and *Amaranthus hybridus*; *Polygonaceae weeds** such as *Polygonum lapathifolium*, *Polygonum persicaria*, *Polygonum convolvulus*, *Polygonum aviculare*, *Persicaria longiseta*, and *Persicarianepalensis*; *Crpurea weeds** such as *Cardamine flexuosa*, *Capsella bursapastoris*, *Brassica juncea*, and *Rorippa indica*; *Convolvulaceae weeds** such as *Ipomoea*. purpurea), field bindweed (Convolvulus sarvensis), split-leaved morning glory (Ipomoea hederacea), short-haired calyx (Calystegia pubescens), and orange-red morning glory (Ipomoea coccinea);Portulacaceae weeds, such as Portulaca aleracea; Fabaceae weeds, such as Cassia obtusifolia, Aeschynomene indica, Sesbania exaltata, Trifolium repens, and Vicia sativa; Caryophyllaceae weeds, such as Stellaria media, Stellaria neglecta, and Stellaria uliginosa; Euphorbiaceae weeds, such as Euphorbia helioscopia and Acalypha australis; Commelinaceae weeds, such as Commelina communis and Murdannia. keisak); Potamogetonaceae weeds such as Potamogeton distinctus; Araceae weeds such as Spirodela polyrhiza; Cucurbitaceae weeds such as Sicyos angulatus; Rubiaceae weeds such as Galium spurium; Apiaceae weeds such as Oenanthe javanica; Violaceae weeds such as Viola mandshuria; Onagraceae weeds such as Ludwigia epilobioides and Oenothera odorata; Oxalidaceae weeds Weeds of the Equisetaceae family, such as Oxalis corniculata; and horsetail (Equisetum arvense).Leaf-like nematode family weeds (Zygnemataceae weeds, such as Spirogyra sp.). Therefore, the compounds of this invention can be effectively used to control harmful weeds in the cultivation of the following useful crops: rice (Oryzasativa L.), maize (Zea mays), soybean (Glycine max), cotton (Gossypium spp.), wheat (Triticum spp.), barley (Hordeum vulgare), rye (Secalecereale), oats (Avena sativa), sorghum (Sorghum bicolor), rapeseed (Brassica napus), sunflower (Helianthus annuus), sugar beet (Beta Vulgaris), sugarcane (Saccharum officinarum), Japanese zoysia (Zoysia japonicaa), peanut (Arachis hypogaea), diembryoflavum (Linum usitatissmum), tobacco (Nicotiana tabacum), and Coffea spp. (coffee genus).

[0704] The application of the herbicide of this invention is not limited to the aforementioned weeds and crops.

[0705] If necessary, the compounds of this invention can be mixed with other herbicides, various insecticides, acaricides, nematicides, fungicides (fungicides, bactericides, antiviral agents, plant resistance inducers), bird repellents, plant growth regulators, plant toxicity reducers (safeties), fertilizers, soil conditioners, synergists, etc., during formulation or spraying, or they can be mixed during spraying and used as tank mixes.

[0706] In particular, when the compounds of the present invention are mixed with another herbicide and applied, the amount of herbicide to be used can be reduced, and labor can be reduced. Furthermore, it is anticipated that the target range (weed spectrum) of the herbicide application will be broadened due to the synergistic effect of the two agents, and consequently, a stronger effect can be obtained due to the synergistic effect of the two agents. At this time, various known herbicides or phytotoxicity reducers (safeners) can also be used in combination.

[0707] Among the optional ingredients, representative examples of herbicides are shown below, but are not limited to.

[0708] (1) Compounds that exhibit herbicidal activity by interfering with plant hormone activity, such as phenoxy compounds, including 2,4-D, 2,4-D-butoxy (butotyl), 2,4-D-butyl ester, 2,4-D-dimthylammonium, 2,4-D-diolamine, 2,4-D-ethyl ester, 2,4-D-ethylhexyl ester, and 2,4-D-isobutyl ester. obutyl), 2,4-D-isoctyl ester, 2,4-D-isopropyl ester, 2,4-D-isopropylammonium, 2,4-D-sodium salt, 2,4-D-isopropanolammonium, 2,4-D-trolamine, 2,4-DB, 2,4-D-butyl butyrate DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-Dcholinesalt, dichlorprop, dichlorprop-butoxyethyl ), 2,4-dimethylammonium propionate, dichlorprop-isoctyl propionate, dichlorprop-potassium propionate, dichlorprop-P propionate, dichlorprop-P-dimethylammonium propionate, dichlorprop-P-potassium propionate, 2,4-D sodium propionate (dichlorprop-P-sodium), MCPA, MCPA-butotyl, MCPA-dimethylammonium, MCPA-2-ethylhexyl, MCPA-potassium, MCPA-sodium, MCPA-thioetyl, MCPB, MCPB-ethyl, MCPB-sodium, 2-methyl-4-chloropropionic acid (me Mecoprop, methyl 4-chloropropionic acid-butoxyethyl ester (mecoprop-butotyl), sodium 2-methyl 4-chloropropionic acid (mecoprop-sodium), high-2-methyl 4-chloropropionic acid (mecoprop-P), high-2-methyl 4-chloropropionic acid-butoxyethyl ester (mecoprop-P-butotyl), high-2-methyl 4-chloropropionic acid-dimethylammonium (mecoprop-P-dimethylammonium), high-2-methyl 4-chloropropionic acid-2-ethylhexyl ester (mecoprop-P-2-ethylhexyl), high-2-methyl 4-chloropropionic acid-potassium ester (mecoprop-P-potassium), naphthylpropylamine (naproanilid) e) Clomeprop and HIA-1; aromatic carboxylic acid compounds, such as 2,3,6-TBA, dicamba, dicamba-butotyl, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-potassium, dicamba... - Sodium dicamba (dicamba-sodium), picloram, picloram-dimethylammonium, picloram-isooctyl, picloram-potassium, picloram-triisopropanolammonium, picloram-triisopropylammonium, picloram-trolamine (tricolopyr),Ciclopyr-butotyl, triclopyr-triethylammonium, clopyralid, clopyralid-olamine, clopyralid-potassium, clopyralid-triisopropanolammonium, aminopyralid, aminocyclopyrachlor, aminocyclopyrachlor, halauxifen, florpyrauxifen, halauxifen-methyl, and DAS-534; and other compounds, such as chlormequat chloride. (naptalam), naptalam-sodium, benzolin, benzolin-ethyl, quinclorac, quinmerac, diflufenzopyr, diflufenzopyr-sodium, fluroxypyr, fluroxypyr-2-butoxy-1-methylethyl, fluroxypyr-meptyl, chlorflurenol, chlorflurenol-methyl, clacyfos, fluchloraminopyr, and indolauxipyr.

[0709] (2) Compounds that exhibit herbicidal activity by inhibiting plant photosynthesis, such as urea compounds, including chlorotoluron, diuron, fluometuron, linuron, isoproturon, metobenzuron, tebuthiuron, dimefuron, isouron, karbutilate, methabenztiazuron, and methoxyfenozide. xuron, metoburomuron, monolinuron, neburon, siduron, terbumeton, and trietazine; triazine compounds, such as simazine, atrazine, atratone, simetryn, prometryn, dimethametryn, hexazinone, metribuzin, and teretazine. Terbuthylazine, cyanazine, ametryn, cybutryne, terbutryn, propazine, metamitron, and prometon; uracil compounds, such as bromacil, bromacyl-lithium, lenacil, and terbacil; aniline compounds, such as propanil and cypromid; ammonia Carbamate compounds, such as swep, desmedipham, and phenmedipham; hydroxybenzonitrile compounds, such as bromooxynil, bromooxynil-octanoate, bromooxynil-heptanoate, ioxynil, ioxynil-octanoate, ioxynil-potassium, and ioxynil-sodium;Other compounds, such as pyridate, bentazone, bentazone-sodium, amicabazone, methazole, pentanochlor, and phenmedipham.

[0710] (3) Quaternary ammonium compounds, which are believed to become free radicals in plants and produce reactive oxygen species, thus exhibiting immediate herbicidal effects, such as paraquat and diquat.

[0711] (4) Compounds that inhibit chlorophyll biosynthesis in plants and exhibit herbicidal activity by abnormally accumulating photo-enhancing peroxides in the plants, such as diphenyl ether compounds, including nitrofen, chlomethoxyfen, bifenox, acifluorfen, acifluorfen-sodium, fomesafen, fomesafen-sodium, oxyfluorfen, lactoferrin, and aclofen. Nifen), ethoxyfen-ethyl, fluoroglycofen-ethyl, and fluoroglycofen; cyclic imide compounds such as chlorphthalim, flumioxazin, flumiclorac, flumiclorac-pentyl, cinidon-ethyl, fluthiacet-methyl, and EK-5385; and other compounds such as oxadiazine. adiargyl), oxadiazon, sulfurtrazone, carfentrazone-ethyl, thidiazimin, pentoxazone, azafenidin, isopropazole, pyraflufen-ethyl, benzfendizone, butafenacil, saflufenacil, fluazolate, flu... Profluazol, flufenpyr-ethyl, bencarbazone, tiafenacil, pyrachlonil, cyclopyranil, epyrifenacil, trifludimoxazin, flufenoximacil, HNPC-B4047, IR-6396, EK-5498, SYN-523, and compounds described in WO2008 / 008763 (FMC).

[0712] (5) Compounds that inhibit the biosynthesis of pigments such as carotenoids in plants and exhibit herbicidal activity characterized by whitening effects, such as pyridazinone compounds, such as norflurazon, chloridazon, and metflurazon; pyrazole compounds, such as pyrazolynate, pyrazoxyfen, benzofenap, toramezone, pyrasulfotole, tolpyralate, and triazolesulfonate. Tripyrasulfone, fenpyrazone, and bipyrazone; and other compounds such as amitrol, fluridone, flurtamone, diflufenican, methoxyphenone, clonazolone, sulcotrione, mesotrione, tembotrione, and other herbicides. Tefuryltrione, fenquinotrione, lancotrione, dioxopyritrione, benquitrione, cyclopyrimorate, isoxaflutole, difenzoquat, difenzoquat-metilsulfate, isoxachlortole, benzobicyclon, bicyclopyron, picolinafen, beflubutamid, beflubutamid-M, ketospiradox, ketospiradox-potassium, iptriazopyrid, flusulfinam, broclozone, pyraquinate, and in JP2012 / 2571 (Sumitomo) Compounds described in Chemical Company Limited.

[0713] (6) Compounds that inhibit fatty acid biosynthesis and exhibit herbicidal activity in plants, such as aryloxyphenoxypropionic acid compounds, including diclofop-methyl, diclofop, pyriphenop-sodium, fluazifop-butyl, fluazifop, fluazifop-P, fluazifop-P-butyl, haloxyfop, haloxyfop-etotyl, haloxyfop-P, haloxyfop-P-methyl, quizalofop-ethyl, quizalofop-P, quizalofop-ethyl, quizalofop-P-tefuryl, and cyhalofop-butyl. ofop-butyl, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, metamifop-propyl, metamifop, clodinafop-propargyl, propaquizafop, HNPC-A8169 and SYP-1924; cyclohexanedione compounds, such as alloxydim-sodium, alloxydim, clethodim, sethoxydim, tralkoxydim, butroxydim, tepraloxydim, profoxydim and cycloxydim; phenylpyrazoline compounds, such as pinoxaden.

[0714] (7) Compounds that exhibit herbicidal activity by inhibiting the biosynthesis of amino acids in plants, such as sulfonylurea compounds, including chlorimuron-ethyl, chlorimuron, sulfometuron-methyl, sulfometuron, primisulfuron-methyl, primisulfuron, bensulfuron-methyl, bensulfuron, chlorsulfuron, and methylsulfuron. Metsulfuron-methyl, metsulfuron, cinosulfuron, pyrazosulfuron-ethyl, pyrazosulfuron, flazasulfuron, rimsulfuron, nicosulfuron, imazosulfuron, flucetosulfuron, cyclosulfamuron, prosulfuron on), flupyrsulfuron-methyl-sodium, flupyrsulfuron, triflusulfuron, triflusulfuron-methyl, halosulfuron-methyl, halosulfuron, thifensulfuron-methyl, thifensulfuron-methyl, ethoxysulfuron, cyclo Oxasulfuron, ethametsulfuron, ethametsulfuron-methyl, iodosulfuron, iodosulfuron-methyl-sodium, sulfosulfuron, triasulfuron, tribensulfuron-methyl, tribensulfuron, tritosulfuron, foramsulfuronTrifloxysulfuron, trifloxysulfuron-sodium, mesosulfuron-methyl, mesosulfuron, orthosulfamuron, amidosulfuron, azimsulfuron, propyrisulfuron, metazosulfuron, methiopyrsulfuron, monosulfuron - Monosulfuron-methyl, orsosulfuron, iofensulfuron, and iofensulfuron-sodium; triazolopyrimidine sulfonamide compounds, such as flumetsulam, metosulam, diclosulam, cloransulam-methyl, floraulam, penoxsulam, and pyroxsulam; imidazolinone compounds, such as imazapyr. Imidacloprid-isopropylammonium, imazethapyr, imazethapyr-ammonium, imazaquin, imazaquin-ammonium, imazamox, imazamox-ammonium, imazamethabenz, imazamethabenz-methyl, and imazapic; pyrimidinyl salicylic acid compounds, Examples include sodium pyrithiobac, bispyribac, pyriminobac-methyl, pyribenzoxim, pyriftalid, pyrimisulfan, and triafamone; sulfonylaminocarbonyl triazoline compounds, such as flucarbazone, flucarbazone-sodium, and propoxycarbazone-sodium.Propoxycarbazone and thiencarbazone-methyl; and other compounds such as glyphosate, glyphosate-sodium, glyphosate-potassium, glyphosate-ammonium, glyphosate-isopropylammonium, and glyphosate-trimethyl sulfide. The following are listed as potential drug derivatives: glyphosate-sesquisodim, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, bilanafos, bilanafos-sodium, and cinmethylin.

[0715] (8) Compounds that exhibit herbicidal activity by inhibiting plant cell division, such as dinitroaniline compounds, including trifluralin, oryzalin, nitralin, pendimethalin, ethalfluralin, benfluralin, prodiamine, butralin, and dinitramine; amide compounds, including bensulide, napropamide, napropamide-M, propyzamide, and pronamide; organophosphorus compounds, including amiprofos-methyl, butamifos, anilofos, and piperophos; phenylamino Carbamate compounds, such as propham, chlorpropham, barban, and carbetamide; cumylamine compounds, such as daimuron, cumyluron, bromobutide, and methyldymron; and other compounds, such as asulam, asulam-sodium, dithiopyr, thiazopyr, chlorthal-dimethyl, chlorthal, diphenamid, flamprop-M-methyl, flamprop-M, and flamprop-M-isopropyl.

[0716] (9) Compounds that exhibit herbicidal activity by inhibiting plant protein or lipid biosynthesis, such as chloroacetamide compounds, including alachlor, metazachlor, butachlor, pretilachlor, metolachlor, S-metolachlor, thenylchlor, pethoxamid, acetochlor, propachlor, dimethenamide, dimethenamide-P, propisochlor, and dimethachlor; thiocarbamate compounds, such as molinate, dimepiperate, pyributicarb, EPTC, butylate, vernolate, and glyphosate. Cycloate, prosulfocarb, esprocarb, thiobencarb, diallate, tri-allate, and orbencarb; and other compounds such as etobenzanid, mefenacet, flufenacet, tridiphane, cafenstrole, fentrazamide, ipfencarbazone, oxaziclomefone, indanofan, benfuresate, pyroxasulfone, fenoxasulfone, methiozolin, dalapon, dalapon-sodium, TCA-sodium, and trichloroacetic acid.

[0717] (10) Compounds that exhibit herbicidal activity by inhibiting cellulose biosynthesis in plants, such as dichlobenil, triaziflam, indaziflam, flupoxam and isoxaben.

[0718] (11) Other herbicides, such as isoxaflutole, tetflupyrolimet, dimesulfazet, rimisoxafen, MSMA, DSMA, CMA, endothall, endothall-dipotassium, endothall-sodium, endothall-mono(N,N-Dimethylalkylammonium), ethofumesate, sodium chlorate, geranic acid, nonanoic acid, fosamine, fosamine-ammonium, acrolein, ammonium aminosulfonate sulfamate), borax, chloroacetic acid, sodium chloroacetate, ammonia nitrile, formarsine, dimethylarsine, sodium dimethylarsate, dinoterb, dinoterb-ammonium, dinoterb-diolamine, dinoterb-acetate, DNOC, ferrous sulfate, flupropanate, flupropanate-sodium, mefluidide, mefluidide-diolamine, metam, metam-ammonium, metam-potassium, metam-sodium, methylisothiocyanate, pentachlorophenol, sodium pentachlorophenoxide, pentachlorophenol laurate), quinoclamine, sulfuric acid, urea sulfate, zanthinosin, herbimycin, unguinol, metatyrosine, sarmentine, thaxtomin A, mevalocidin, alpha-limonene, pyribambenz-propyl, pyribambenz-isopropyl The following compounds are included: pyriflubenzoxime, cypyrafluone, JS-913, KHG-23844, H-9201, SIOC-0163, SIOC-0171, SIOC-0172, SIOC-0285, SIOC-0426, SIOC-H-057, ZJ-0166, ZJ-1835, ZJ-0453, ZJ-0777, ZJ-0862, and compounds described in WO2008 / 096398 (Kumiai Chemical Industry Co., Ltd.).

[0719] (12) Those that exhibit herbicidal activity by parasitizing plants, such as Xanthomonas campestris, Epicoccosirus nematosorus, Epicoccosirus nematosperus, Exserohilum monoseras, and Drechsrela monoceras.

[0720] When the compounds of the present invention are used as herbicides, they can be used on their own, and they can also be used as formulations. In formulations, suitable carriers, adjuvants, surfactants, binders, stabilizers, etc., as described in the *Pesticide Formulation Guide* (edited by the Pesticide Science Society of Japan Application Method Research Group, published by the Japan Plant Protection Society, 1997) can be mixed in.

[0721] Herbicides containing the compounds of the present invention can be formulated in any commonly used form, but not limited to, granules, microparticles, fine particles, wettable powders, water-dispersible granules (dry flowables), emulsifiable concentrates, soluble powders, suspension concentrates (flowables), liquid formulations, ductile powders, coarse powders, drift-free (DL) powders, flowable dust, oil solutions, microencapsulated suspensions, pastes, and jumbo formulations.

[0722] In formulations, any carrier commonly used in agrochemicals, whether solid or liquid, may be used. Such carriers are not limited to a specific type, but specific examples include the following: Examples of solid carriers include mineral powders (kaolin, bentonite, clay, montmorillonite, talc, diatomaceous earth, mica, vermiculite, quartz, calcium carbonate, apatite, silica, quicklime, silica sand, Japanese acid clay, zeolite, sepiolite, crushed expanded perlite powder, volcanic ash microparticles, alumina balloons, and microspheres composed of phenolic resin, epoxy resin, polyacrylonitrile, or polyurethane); plant powders (soybean flour, wheat flour, wood flour, tobacco powder, starch, and crystalline cellulose); polymers (petroleum resins, polyvinyl chloride, and ketone resins); alumina; silicates; glucose; sucrose; lactose; sugar polymers; ammonium sulfate; sodium chloride; potassium chloride; urea; highly dispersible silicic acid; and waxes.

[0723] Examples of liquid carriers include, for example, water; alcohols (methanol, ethanol, n-propanol, isopropanol, butanol, ethylene glycol, and benzyl alcohol); aromatics (toluene, benzene, xylene, ethylbenzene, and methylnaphthalene); ethers (diethyl ether, ethylene oxide, dioxane, and tetrahydrofuran); ketone solvents (acetone, methyl ethyl ketone, cyclohexanone, methyl isobutyl ketone, and isophorone); esters (ethyl acetate, butyl acetate, ethylene glycol acetate, and amyl acetate); amides (dimethylformamide and dimethylacetamide, etc.); nitriles (acetonitrile, propionitrile, and acrylonitrile); sulfoxides (dimethyl sulfoxide); alcohol ethers (ethylene glycol monomethyl ether and ethylene glycol monoethyl ether); aliphatic or alicyclic hydrocarbons (n-hexane and cyclohexane); industrial gasoline (petroleum ether and solvent naphtha); and petroleum fractions (paraffin, kerosene, and light oil, etc.).

[0724] When herbicides are formulated into emulsifiable concentrates, wettable powders, and flow agents, various surfactants are added for emulsification, dispersion, dissolution, wetting, foaming, lubrication, and application purposes. Examples of such surfactants include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, polyoxyethylene dehydrated sorbitol alkyl esters, polyoxyethylene alkyl aryl ethers, polyoxyethylene-polyoxypropylene block polymers, and polyoxyethylene styrene phenyl ethers; anionic surfactants such as alkylbenzene sulfonates, alkyl sulfosuccinates, alkyl sulfates, polyoxyethylene alkyl sulfates, aryl sulfonates, alkyl naphthalene sulfonates, polyoxyethylene styrene phenyl ether sulfates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, and polycarboxylate salts; cationic surfactants such as alkylamines (laurylamine and stearyltrimethylammonium chloride), polyoxyethylene alkylamines, alkylpyridinium salts, alkyl trimethylammonium salts, and alkyl dimethylammonium salts; and amphoteric surfactants such as carboxylic acids (betaine type) and sulfate salts, but the invention is not limited thereto.

[0725] In addition to these, a variety of auxiliaries and additives can be used, such as polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), gum arabic, polyvinyl acetate, sodium alginate, gelatin, tragacanth gum, dextrin, hydroxypropyl methylcellulose (HPMC), and methylcellulose (MC).

[0726] Preferred application methods for herbicides containing compounds of the present invention as active ingredients include soil application, water surface application, and foliar application, with particularly excellent results obtained when applied before weed germination to the early seedling stage.

[0727] The amount of the compound of the present invention to be applied as a herbicide varies depending on the application location, application time, target weeds, crops planted, etc., and generally, the amount of active ingredient is from about 0.001 kg per hectare (ha) to about 10 kg per hectare (ha), and about 0.01 kg per hectare (ha) to about 1 kg per hectare (ha) is suitable.

[0728] The present invention also relates to a method of using the herbicide of the present invention, comprising applying an effective amount of the compound of the present invention to at least one selected from the stems and leaves of weeds, soil and water surface.

[0729] There are no particular restrictions on weeds, and they include, for example, the weeds mentioned above.

[0730] The preferred soil is agricultural land such as farmland or paddy fields, which are typically used for growing crops and horticultural plants.

[0731] The water surface can be the water surface in the submerged soil.

[0732] There are no particular limitations on the treatment steps. Examples of treatment steps include spraying an effective amount of the compound of the present invention onto at least one selected from the stems and leaves of weeds, soil, and water surfaces.

[0733] Furthermore, the present invention relates to a method for preparing a pesticide composition, comprising mixing a herbicide containing the compound of the present invention as an active ingredient with at least one selected from diluents and surfactants.

[0734] There are no particular limitations on diluents, and examples include: natural minerals such as clay, quartz, calcite, sepiolite, dolomite, chalk, kaolin, pyrophyllite, sericite, halloysite, metamorphic kaolinite, wood-based clay, gaerome clay, terracotta stone, zeolite, diatomite, shirasu, mica, talc, pumice, lithium montmorillonite, zeolite, and diatomaceous earth; and calcined products of natural minerals such as calcined clay, perlite, shirasu balls, vermiculite, and cascade clay. Palladium clay and calcined diatomaceous earth; inorganic salts such as magnesium carbonate, calcium carbonate, sodium carbonate, sodium bicarbonate, ammonium sulfate, sodium sulfate, magnesium sulfate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, and potassium chloride; sugars such as glucose, fructose, sucrose, and lactose; polysaccharides such as starch, powdered cellulose, and dextrin; organic substances such as urea, urea derivatives, benzoic acid, and benzoates; plant-based materials such as wood flour, corn cobs, walnut shells, and tobacco stems; as well as fly ash, white carbon, and water.

[0735] There are no particular limitations on the surfactants used, and examples include the same surfactants described above in herbicide formulations.

[0736] There are no particular limitations on the method of mixing herbicides containing compounds of the present invention as active ingredients with at least one selected from diluents and surfactants, and known methods can be used.

[0737] [Example]

[0738] The present invention will be described in more detail below with reference to the synthesis examples, formulation examples and test examples of the compounds and intermediates of the present invention, but the present invention is not limited thereto.

[0739] The compounds obtained in the following synthetic examples 3 to 5, 8 to 13, 15, 16, 18 to 21, 24, 25, 28, 29, 31, 32, 35, 37, 40, 45, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76, 77, 80 to 102 and 104 to 391 are compounds of the present invention, while the compounds obtained in other synthetic examples are intermediates of the present invention.

[0740] Synthesis Example 1

[0741] Synthesis of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one

[0742] A solution (5 mL) of (1R,2S,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (466 mg, 1.55 mmol) in dichloromethane was added with pyridinium chlorochromate (689 mg, 3.10 mmol) and diatomaceous earth (1.34 g), followed by stirring at room temperature (25°C) for 19 hours. The reaction mixture was filtered and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 361 mg, 78%).

[0743] ¹H NMR(400MHz, CDCl3)δ0.06(s,3H),0.07(s,3H),0.90(s,9H),1.05(d,J=6.8Hz,3H),1.06(d,J=6.8Hz,3H),1.47(s,3H),1.65(dd,J=13.4,2.4 Hz,1H),2.02(dd,J=13.4,6.8Hz,1H),2.03(d,J=17.2Hz,1H),2.15(sept,J=6.8Hz,1H),2.23(d,J=17.2Hz,1H),3.93(dd,J=6.8,2.4Hz,1H).

[0744] Synthesis Example 2

[0745] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hepta-2-ol

[0746] To a tetrahydrofuran solution (9 mL) of methyltriphenylphosphonium bromide (629 mg, 1.58 mmol), 1.00 mL of 1.59 mol / L hexane solution (1.59 mmol) was added, followed by stirring at 0°C for 1 hour. (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hep-2-one (262 mg, 0.878 mmol) was added to the reaction mixture, followed by stirring at 0°C for 2 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give crude tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hep-2-yl)oxy)dimethylsilane.

[0747] To a tetrahydrofuran solution (7 mL) of the crude product of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hept-2-yl)oxy)dimethylsilane, tetrabutylammonium fluoride (1.04 mL, 1 mol / L tetrahydrofuran solution, 1.04 mmol) was added, followed by stirring at room temperature for 18 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 96 mg, 60%).

[0748] ¹H NMR(400MHz, CDCl3)δ1.07(d,J=6.8Hz,3H), 1.09(d,J=6.8Hz,3H), 1.44(s,3H), 1.50-1.65(m,2H), 2.08(dd,J=13.2,6.8Hz,1H), 2.20(m,2H), 2.29(dt,J=16.0,2.8Hz,1H), 3.80-3.88(m,1H), 4.75(t,J=2.4Hz,1H), 4.84(t,J=2.4Hz,1H).

[0749] Synthesis Example 3

[0750] Synthesis of (1R,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-2-methylene-7-oxabicyclo[2.2.1]heptane (2-72)

[0751] To a dimethylformamide solution (1.4 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hepta-2-ol (80.0 mg, 0.439 mmol), sodium hydride (55% dispersed in mineral oil, 29.0 mg, 0.658 mmol) was added, followed by stirring at 0°C for 1 hour. To the reaction mixture, 2-methylbenzyl bromide (0.059 mL, 0.44 mmol) was added, followed by stirring at room temperature for 14 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 119 mg, 95%).

[0752] ¹H NMR(400MHz, CDCl3)δ1.08(d,J=6.8Hz,3H),1.11(d,J=6.8Hz,3H),1.49(s,3H),1. 82(dd,J=12.4,2.8Hz,1H),1.92(dd,J=12.4,6.8Hz,1H),2.13-2.29(m,3H),2.32(s ,3H),3.61(dd,J=6.8,2.8Hz,1H),4.37(d,J=12.4Hz,1H),4.55(d,J=12.4Hz,1H), 4.74(t,J=2.4Hz,1H),4.83(t,J=2.4Hz,1H),7.13-7.22(m,3H),7.30-7.34(m,1H).

[0753] Synthesis Example 4

[0754] Synthesis of (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-2-methylene-7-oxabicyclo[2.2.1]heptane (2-88)

[0755] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthesis Example 3 were performed to give the colorless liquid title compound (64% yield).

[0756] ¹H NMR (400MHz, CDCl3) δ1.08(d,J=6.8Hz,3H),1.11(d,J=6.8Hz,3H),1.40(s,3H),1.82(dd,J=1 2.4,2.8Hz,1H),1.95(dd,J=12.4,6.8Hz,1H),2.14-2.31(m,3H),3.65(dd,J=6.8,2.8Hz,1H), 4.50(d,J=12.8Hz,1H),4.60(d,J=12.8Hz,1H),4.75(t,J=2.4Hz,1H),4.84(t,J=2.4Hz,1H),6 .98-7.05(m,1H),7.13(td,J=7.2,0.8Hz,1H),7.22-7.29(m,1H),7.45(td,J=7.2,1.6Hz,1H).

[0757] Synthesis Example 5

[0758] Synthesis of (1R,4S,5R)-1-isopropyl-4-methyl-2-methylene-5-(2-methylphenoxy)-7-oxabicyclo[2.2.1]heptane (2-62)

[0759] To a toluene solution (0.3 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hepta-2-ol (51.0 mg, 0.280 mmol), tripotassium phosphate (139 mg, 0.655 mmol), cuprous iodide (5.3 mg, 0.028 mmol), 4-pyridopyridine (49.8 mg, 0.336 mmol), and 2-iodotoluene (0.035 mL, 0.28 mmol) were added, followed by stirring at 140°C for 23 hours. Hexane was added to the reaction mixture, the solid was filtered through filter paper, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (yield 77.3 mg, 100%).

[0760] ¹H NMR (400MHz, CDCl3) δ1.07(d,J=6.8Hz,3H),1.08(d,J=6.8Hz,3H),1.59(s,3 H),1.77(dd,J=12.4,2.8Hz,1H),2.14-2.23(m,2H),2.25(s,3H),2.29-2.41 (m,2H),4.31(dd,J=6.8,2.8Hz,1H),4.83(t,J=2.4Hz,1H),4.89(t,J=2.4Hz ,1H),6.69(d,J=8.0Hz,1H),6.84(td,J=8.0,0.8Hz,1H),7.06-7.17(m,2H).

[0761] Synthesis Example 6

[0762] Synthesis of tert-butyl(((1S,2R,4R,5S)-5-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hept-2-yl)oxy)dimethylsilane

[0763] A solution (1.7 mL) of (1R,2S,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (175 mg, 0.582 mmol) in dichloromethane was added to pyridinium p-toluenesulfonate (11.8 mg, 0.0465 mmol) and vinyl ether (50.4 mg, 0.699 mmol), followed by stirring at room temperature for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 172 mg, 79%).

[0764] ¹H NMR(400MHz, CDCl3)δ0.051(s,3H),0.054(s,3H),0.89(s,9H),0.95-1.03(m,6H), 1.196(t,J=7.2Hz,1.5H),1.198(t,J=7.2Hz,1.5H),1.25-1.37(m,8H),1.84-1.98 (m,1H),2.00-2.10(m,1H),2.61-2.69(m,1H),3.41-3.52(m,1H),3.56-3.69(m,1H ),3.80-3.87(m,1.5H),4.00(ddd,J=8.4,3.2,1.2Hz,0.5H),4.63(q,J=7.6Hz,1H).

[0765] Synthesis Example 7

[0766] Synthesis of (1S,2R,4R,5S)-5-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0767] A solution (5 mL) of tert-butyl(((1S,2R,4R,5S)-5-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hept-2-yl)oxy)dimethylsilane (172 mg, 0.462 mmol) in tetrahydrofuran was added to tetrabutylammonium fluoride (0.69 mL, 1 mol / L tetrahydrofuran solution, 0.69 mmol), and the mixture was stirred at room temperature for 22 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 113 mg, 95%).

[0768] ¹H NMR(400MHz, CDCl3)δ0.99(d,J=6.8Hz,3H),1.00(t,J=6.8Hz,3H),1.02(d,J=6.8Hz,3H),1 .19(t,J=6.8Hz,1.5H),1.20(t,J=6.8Hz,1.5H),1.30-1.34(m,1H),1.35(s,1.5H),1.36(s ,1.5H),1.40-1.56(m,2H),1.89-2.09(m,2H),2.70-2.77(m,1H),3.41-3.52(m,1H),3.55- 3.67(m,1H),3.74-3.86(m,1.5H),4.01(ddd,J=8.4,3.2,1.2Hz,0.5H),4.60-4.66(m,1H).

[0769] Synthesis Example 8

[0770] Synthesis of (1R,2S,4S,5R)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (1-208)

[0771] A solution (2 mL) of (1S,2R,4R,5S)-5-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (113 mg, 0.437 mmol) in dimethylformamide was added, followed by stirring at 0°C for 1 hour. 2-Methylbenzyl bromide (0.059 mL, 0.44 mmol) was added to the reaction mixture, followed by stirring at room temperature for 7 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 158 mg, 100%).

[0772] ¹H NMR(400MHz, CDCl3)δ0.98-1.06(m,6H),1.15-1.22(m,3H),1.24-1.29(m,4H),1.32-1.38(m,1H) ),1.40(s,1.5H),1.41(s,1.5H),1.84-1.99(m,1H),2.01-2.13(m,1H),2.32(s,3H),2.57-2.66( m,1H),3.38-3.53(m,1H),3.54-3.67(m,2H),3.81-3.88(m,0.5H),4.00-4.06(m,0.5H),4.39(d, J=12.4Hz,1H),4.57(d,J=12.4Hz,1H),4.59-4.68(m,1H),7.13-7.22(m,3H),7.32-7.36(m,1H).

[0773] Synthesis Example 9

[0774] Synthesis of (1R,2S,4S,5R)-2-(1-ethoxyethoxy)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane (1-213)

[0775] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthesis Example 8 were performed to obtain the colorless liquid title compound (yield 49%).

[0776] ¹H NMR(400MHz, CDCl3)δ0.97-1.05(m,6H),1.17(t,J=7.2Hz,1.5H),1.19(t,J=7.2Hz,1.5H),1 .23-1.28(m,3H),1.33-1.38(m,1H),1.408(s,1.5H),1.413(s,1.5H),1.47-1.54(m,1H),1. 85-1.99(m,1H),2.01-2.13(m,1H),2.63(dd,J=12.8,6.8Hz,1H),3.38-3.52(m,1H),3.54-3 .68(m,2H),3.80-3.87(m,0.5H),4.00-4.06(m,0.5H),4.35-4.67(m,3H),6.97-7.49(m,4H).

[0777] Synthesis Example 10

[0778] Synthesis of (1R,2S,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-ol (1-24)

[0779] A solution (1 mL) of tetrahydrofuran containing (1R,2S,4S,5R)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (133 mg, 0.367 mmol) was added to a solution of 3N hydrochloric acid (0.24 mL), and the mixture was stirred at room temperature for 3 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 98.2 mg, 92%).

[0780] ¹H NMR (400MHz, CDCl3) δ1.02(d,J=6.8Hz,3H),1.03(d,J=6.8Hz,3H),1.19(dd,J=13 .2,3.6Hz,1H),1.39(s,3H),1.46-1.55(m,2H),1.99-2.14(m,2H),2.32(s,3H),2 .64(dd,J=12.8,6.8Hz,1H),3.64(dd,J=6.8,2.4Hz,1H),4.12-4.18(m,1H),4.39 (d,J=12.4Hz,1H),4.58(d,J=12.4Hz,1H),7.12-7.22(m,3H),7.30-7.35(m,1H).

[0781] Synthesis Example 11

[0782] Synthesis of (1R,2S,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (1-30)

[0783] The same reaction and treatment as in Synthetic Example 10 were performed using (1R,2S,4S,5R)-2-(1-ethoxyethoxy)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane instead of (1R,2S,4S,5R)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane to obtain the colorless liquid title compound (50% yield).

[0784] ¹H NMR (400MHz, CDCl3) δ1.02(d,J=6.8Hz,3H),1.03(d,J=6.8Hz,3H),1.21(dd,J=13.2,3.6Hz, 1H),1.41(s,3H),1.48-1.55(m,2H),2.01-2.2.16(m,2H),2.67(dd,J=12.8,6.8Hz,1H),3.69 (dd,J=6.8,2.0Hz,1H),4.13-4.20(m,1H),4.53(d,J=12.8Hz,1H),4.64(d,J=12.8Hz,1H),6. 99-7.05(m,1H),7.13(td,J=7.2,0.8Hz,1H),7.22-7.30(m,1H),7.55(td,J=7.2,2.0Hz,1H).

[0785] Synthesis Example 12

[0786] Synthesis of (1R,2S,4S,5R)-2-fluoro-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (1-2)

[0787] A solution (3 mL) of (1R,2S,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-ol (98.7 mg, 0.400 mmol) in dichloromethane was added with pyridine (0.38 mL, 5.0 mmol) and DAST (0.22 mL, 1.7 mmol), and the oil bath temperature was set to 45°C. The mixture was then stirred under reflux for 21 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, followed by extraction with dichloromethane. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 44.5 mg, 38%).

[0788] ¹H NMR(400MHz, CDCl3)δ1.00(d,J=6.8Hz,3H),1.02(d,J=6.8Hz,3H),1.42(s,3 H),1.44-1.61(m,2H),1.95-2.18(m,2H),2.33(s,3H),2.51-2.59(m,1H),3. 69(dd,J=6.8,2.4Hz,1H),4.40(d,J=12.0Hz,1H),4.59(d,J=12.0Hz,1H),4. 83(dddd,J=58.4,9.2,2.4,1.6Hz,1H),7.13-7.23(m,3H),7.31-7.35(m,1H).

[0789] Synthesis Example 13

[0790] Synthesis of (1R,2S,4S,5R)-2-fluoro-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane (1-5)

[0791] The same reaction and treatment as in Synthetic Example 12 were performed using (1R,2S,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hep-2-ol instead of (1R,2S,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hep-2-ol to obtain the colorless liquid title compound (yield 32%).

[0792] ¹H NMR(400MHz,CDCl3)δ1.00(dd,J=6.8,0.8Hz,3H),1.01(dd,J=6.8,0.8Hz,3H),1.43(s,3 H),1.44-1.62(m,2H),1.97-2.15(m,2H),2.52(ddd,J=12.8,6.8,3.6Hz,1H),3.72(dd,J =6.8,2.8Hz,1H),4.53(d,J=12.4Hz,1H),4.63(d,J=12.4Hz,1H),4.90(ddq,J=58.4,9.2 ,1.2Hz,1H),6.99-7.08(m,1H),7.10-7.17(m,1H),7.23-7.30(m,1H),7.41-7.49(m,1H).

[0793] Synthesis Example 14

[0794] Synthesis of (1S,2R,4R)-4-isopropyl-1,5-dimethyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0795] A methanol solution (5 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-methylene-7-oxabicyclo[2.2.1]hepta-2-ol (95.0 mg, 0.522 mmol) was added to palladium on carbon (20.0 mg, 55 wt% water), and the mixture was stirred at room temperature under hydrogen atmosphere for 4 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 86.8 mg, 91%).

[0796] ¹H NMR(400MHz, CDCl3)δ0.83-0.93(m,3H),0.94-01.04(m,6H),1.24-1.55(m,1H),1.36(s,2H),1.40(s, 1H),1.50-1.70(brs,1H),1.73-2.20(m,4.33H),2.38(dd,J=13.8,6.4Hz,0.67H),3.65-3.70(m,1H).

[0797] Synthesis Example 15

[0798] Synthesis of (1S,2R,4R)-4-isopropyl-1,5-dimethyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (1-83)

[0799] A solution (1 mL) of (1S,2R,4R)-4-isopropyl-1,5-dimethyl-7-oxabicyclo[2.2.1]hepta-2-ol (43.0 mg, 0.233 mmol) in dimethylformamide was added, followed by the addition of sodium hydride (55% dispersed in mineral oil, 15.0 mg, 0.344 mmol), and the mixture was stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.028 mL, 0.209 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 12 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 60.2 mg, 100%).

[0800] ¹H NMR(400MHz, CDCl3)δ0.85-1.06(m,9H),1.41(s,2.16H),1.44(s,0.84H),1.49-1 .91(m,3H),2.01-2.21(m,2H),2.25-2.32(m,1H),2.32(s,3H),3.47(dd,J=6.8,2 .4Hz,0.28H),3.50(dd,J=6.8,2.4Hz,0.72H),4.37(d,J=12.4Hz,0.28H),4.39(d ,J=12.4Hz,0.72H),4.55(d,J=12.4Hz,1H),7.13-7.22(m,3H),7.31-7.36(m,1H).

[0801] Synthesis Example 16

[0802] Synthesis of (1S,2R,4R)-2-((2-fluorobenzyl)oxy)-4-isopropyl-1,5-dimethyl-7-oxabicyclo[2.2.1]heptane (1-92)

[0803] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthetic Example 15 were performed to obtain the colorless liquid title compound (yield 92%).

[0804] ¹H NMR(400MHz, CDCl3)δ0.82-1.05(m,9H),1.41(s,2.01H),1.44(s,0.99H),1.47-1.53(m,0.67H),1.6 3-1.91(m,2.66H),1.99-2.20(m,1.67H),2.25-2.32(dd,J=13.2,6.4Hz,1H),3.49(dd,J=6.8,2.4Hz ,0.33H),3.52(dd,J=6.8,2.4Hz,0.67H),4.50(d,J=12.8Hz,1H),4.59(d,J=12.8Hz,0.33H),4.60(d ,J=12.8Hz,0.67H),7.00(t,J=8.8Hz,1H),7.08-7.15(m,1H),7.20-7.28(m,1H),7.41-7.48(m,1H).

[0805] Synthesis Example 17

[0806] Synthesis of (1R,4S,5R)-5-hydroxy-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one

[0807] To a tetrahydrofuran solution (6 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (177 mg, 0.593 mmol), tetrabutylammonium fluoride (0.89 mL, 1 mol / L tetrahydrofuran solution, 0.89 mmol) was added, followed by stirring at room temperature for 16 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a white solid (yield 96.2 mg, 88%).

[0808] Melting point: 175°C to 181°C; ¹H NMR (400MHz, CDCl₃) δ 1.05 (d, J = 6.8 Hz, 3H), 1.07 (d, J = 6.8 Hz, 3H), 1.53 (s, 3H), 1.58 (d, J = 6.8 Hz, 1H), 1.64–1.70 (m, 2H), 2.11–2.28 (m, 3H), 3.94–4.00 (m, 1H).

[0809] Synthesis Example 18

[0810] Synthesis of (1R,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-one (2-3)

[0811] A solution (2 mL) of (1R,4S,5R)-5-hydroxy-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (47.9 mg, 0.260 mmol) in dimethylformamide was added, followed by stirring at 0°C for 1 hour. 2-Methylbenzyl bromide (0.052 mL, 0.39 mmol) was added to the reaction mixture, followed by stirring at room temperature for 12 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 74.9 mg, 100%).

[0812] ¹H NMR (400MHz, CDCl3) δ1.07(d,J=6.8Hz,3H),1.08(d,J=6.8Hz,3H),1.57(s,3H),1.83(dd,J=14.0,2.8Hz,1H),1.98(dd,J=14.0,6.8Hz,1H),2.0 1-2.26(m,3H),2.34(s,3H),3.69(dd,J=6.4,2.8Hz,1H),4.41(d,J=12. 4Hz,1H),4.59(d,J=12.4Hz,1H),7.10-7.25(m,3H),7.29-7.33(m,1H).

[0813] Synthesis Example 19

[0814] Synthesis of (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (2-9)

[0815] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthetic Example 18 were performed to obtain the colorless liquid title compound (100% yield).

[0816] ¹H NMR(400MHz, CDCl3)δ1.06(d,J=6.8Hz,3H),1.07(d,J=6.8Hz,3H),1.58(s,3H),1. 83(dd,J=11.2,2.8Hz,1H),2.00(dd,J=9.2,6.8Hz,1H),2.04-2.27(m,3H),3.73(d d,J=6.8,2.8Hz,1H),4.53(d,J=12.4Hz,1H),4.63(d,J=12.4Hz,1H),7.00-7.07(m ,1H),7.14(td,J=7.2,0.8Hz,1H),7.25-7.32(m,1H),7.43(td,J=7.2,1.6Hz,1H).

[0817] Synthesis Example 20

[0818] Synthesis of (1R,4S,5R,E)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-one oxime (2-191)

[0819] A mixture of (1R,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-one (80.5 mg, 0.279 mmol) in ethanol (4 mL) and water (1 mL) was added with hydroxylamine hydrochloride (29.1 mg, 0.419 mmol) and sodium acetate (45.8 mg, 1.10 mmol), and the oil bath was set to 110°C. The mixture was then stirred under heating and reflux for 31 hours. The reaction mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 43.5 mg, 51%).

[0820] ¹H NMR(400MHz, CDCl3)δ1.11(d,J=7.2Hz,3H),1.12(d,J=7.2Hz,3H),1.54(s,3H), 1.58(s,1H),1.84(dd,J=12.8,2.8Hz,1H),2.08(dd,J=12.8,2.8Hz,1H),2.26(se pt,J=7.2Hz,1H),2.33(s,3H),2.36(s,2H),3.62(dd,J=6.8,2.8Hz,1H),4.39(d, J=12.4Hz,1H),4.57(d,J=12.4Hz,1H),7.14-7.24(m,3H),7.30(d,J=7.2Hz,1H).

[0821] Synthesis Example 21

[0822] Synthesis of (1R,4S,5R,E)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one oxime (2-197)

[0823] The same reaction and treatment as in Synthetic Example 20 were performed using (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one instead of (1R,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]hepta-2-one to obtain the colorless liquid title compound (yield 33%).

[0824] ¹H NMR(400MHz, CDCl3)δ1.11(d,J=6.8Hz,6H),1.55(s,3H),1.58(s,1H),1.84(dd,J=12 .8,2.4Hz,1H),2.08(dd,J=12.8,2.4Hz,1H),2.26(sept,J=6.8Hz,1H),2.38(s,2H),3 .67(dd,J=6.8,2.8Hz,1H),4.51(d,J=12.4Hz,1H),4.61(d,J=12.4Hz,1H),7.00-7.0 6(m,1H),7.14(td,J=7.2,2.0Hz,1H),7.24-7.31(m,1H),7.43(td,J=7.2,2.0Hz,1H).

[0825] Synthesis Example 22

[0826] Synthesis of tert-butyl(((1S,2R,4R,5S)-4-isopropyl-5-methoxy-1-methyl-7-oxabicyclo[2.2.1]hept-2-yl)oxy)dimethylsilane

[0827] A solution (3 mL) of (1R,2S,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (274 mg, 0.912 mmol) in dimethylformamide was added, followed by stirring at 0°C for 2 hours. Iodomethane (0.33 mL, 5.3 mmol) was added to the reaction mixture. The mixture was then stirred at room temperature for 26 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 289 mg, 100%).

[0828] ¹H NMR(400MHz, CDCl3)δ0.05(s,6H),0.89(s,9H),0.97(d,J=6.8Hz,3H),0.98(d,J=6.8Hz,3H),1.30(s,3H),1.20-1.36(m,2H),1.86(dd,J=12.8, 5.2Hz,1H),2.05(sept,J=6.8Hz,1H),2.60(dd,J=12.8,7.2Hz,1H),3.27(s,3H),3.57(ddd,J=7.2,3.2,1.2Hz,1H),3.84(dd,J=7.2,2.4Hz,1H).

[0829] Synthesis Example 23

[0830] Synthesis of (1S,2R,4R,5S)-4-isopropyl-5-methoxy-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0831] A solution (9 mL) of tert-butyl(((1S,2R,4R,5S)-4-isopropyl-5-methoxy-1-methyl-7-oxabicyclo[2.2.1]hept-2-yl)oxy)dimethylsilane (289 mg, 0.918 mmol) in tetrahydrofuran was added to tetrabutylammonium fluoride (1.38 mL, 1 mol / L tetrahydrofuran solution, 1.38 mmol), and the mixture was stirred at room temperature for 20 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a white solid (yield 130 mg, 71%).

[0832] Melting point: 118°C to 122°C;¹H NMR (400MHz, CDCl₃) δ 0.99 (d, J = 6.8 Hz, 3H), 1.00 (d, J = 6.8 Hz, 3H), 1.30 (s, 3H), 1.23–1.30 (m, 1H), 1.45–1.53 (m, 1H), 1.54–1.59 (m, 1H), 1.86 (dd, J = 12.8, 9.6 Hz, 1H), 2.04 (sept, J = 6.8 Hz, 1H), 2.70 (dd, J = 13.6, 7.2 Hz, 1H), 3.27 (s, 3H), 3.57 (ddd, J = 9.6, 3.6, 1.2 Hz, 1H), 3.77–3.82 (m, 1H).

[0833] Synthesis Example 24

[0834] Synthesis of (1S,2R,4R,5S)-4-isopropyl-5-methoxy-1-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (1-151)

[0835] A solution (1 mL) of (1S,2R,4R,5S)-4-isopropyl-5-methoxy-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (65.1 mg, 0.325 mmol) in dimethylformamide was added, followed by the addition of sodium hydride (55% dispersed in mineral oil, 21.0 mg, 0.481 mmol), and the mixture was stirred at 0°C for 2 hours. 2-Methylbenzyl bromide (0.052 mL, 0.39 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 24 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 81.0 mg, 82%).

[0836] ¹H NMR(400MHz, CDCl3)δ0.99(d,J=6.8Hz,6H),1.28(dd,J=12.8,3.2Hz,1H),1.37( s,3H),1.45-1.53(m,1H),1.86(dd,J=12.8,9.6Hz,1H),2.08(sept,J=6.8Hz,1H) ,2.32(s,3H),2.56(dd,J=12.8,6.8Hz,1H),3.26(s,3H),3.57-3.62(m,2H),4.37 (d,J=12.4Hz,1H),4.57(d,J=12.4Hz,1H),7.12-7.22(m,3H),7.31-7.36(m,1H).

[0837] Synthesis Example 25

[0838] Synthesis of (1S,2R,4R,5S)-2-((2-fluorobenzyl)oxy)-4-isopropyl-5-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptane (1-156)

[0839] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthesis Example 24 were performed to obtain the colorless liquid title compound (100% yield).

[0840] ¹H NMR(400MHz, CDCl3)δ0.99(d,J=6.8Hz,6H),1.30(dd,J=12.8,3.2Hz,1H),1.43(s,3H),1.46-1.52(m,1 H),1.88(dd,J=12.8,9.2Hz,1H),2.08(sept,J=6.8Hz,1H),2.60(dd,J=12.8,6.8Hz,1H),3.27(s,3H), 3.60(ddd,J=9.2,3.2,2.0Hz,1H),3.65(dd,J=7.2,2.4Hz,1H),4.51(d,J=12.8Hz,1H),4.62(d,J=12.8 Hz,1H),6.99-7.05(m,1H),7.13(td,J=7.2,1.6Hz,1H),7.22-7.29(m,1H),7.46(td,J=7.2,1.6Hz,1H).

[0841] Synthesis Example 26

[0842] Synthesis of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane

[0843] To a tetrahydrofuran solution (7 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (352 mg, 1.18 mmol), lithium bis(trimethylsilyl)amino (1.76 mL, 1 mol / L tetrahydrofuran solution, 1.76 mmol) was added, followed by stirring for 2 hours. N-phenylbis(trifluoromethylsulfonamide) (630 mg, 1.76 mmol) was added to the reaction mixture, followed by stirring at room temperature for 30 minutes. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give crude (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate.

[0844] A 1:1 mixture (5 mL) of 1,2-dimethoxyethane and dichloromethane of the crude product of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethane was added to potassium carbonate (1.34 g, 9.75 mmol) and phenylboronic acid (87.0 mg, 0.715 mmol), and argon was bubbled into the mixture for 5 min. Tetra(triphenylphosphine)palladium (150 mg, 0.130 mmol) was added to the reaction mixture, followed by stirring at room temperature for 17 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 187 mg, 44%).

[0845] ¹H NMR(400MHz, CDCl3)δ0.05(s,3H),0.06(s,3H),0.84(d,J=6.8Hz,3H),0.90(s,9H),1.08(d,J=6.8Hz,3H),1.55(s ,3H),1.64-1.71(m,1H),1.97-2.06(m,1H),2.33-2.45(m,1H),3.86-3.96(m,1H),5.98(s,1H),7.18-7.62(m,5H).

[0846] Synthesis Example 27

[0847] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0848] A methanol solution (3.5 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane (316 mg, 0.882 mmol) was added to palladium on carbon (47.0 mg, 55 wt% water), and the mixture was stirred at room temperature under hydrogen atmosphere for 21 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 217 mg, 100%).

[0849] ¹H NMR(400MHz, CDCl3)δ0.91(d,J=6.4Hz,3H),0.93(d,J=6.4Hz,3H),1.26-1.33(m ,1H),1.47(s,3H),1.58(s,1H),1.65(dd,J=13.2,6.8Hz,1H),2.06(sept,J=6.4 ,Hz,1H),2.14(t,J=12Hz,1H),2.53(dd,J=13.2,6.4Hz,1H),3.32-3.40(m,1H), 3.95(d,J=6.4Hz,1H),7.17-7.35(m,3H),7.38-7.45(m,1H),7.48-7.56(m,1H).

[0850] Synthesis Example 28

[0851] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-2-((2-methylbenzyl)oxy)-5-phenyl-7-oxabicyclo[2.2.1]heptane (1-313)

[0852] A solution (1.5 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hepta-2-ol (109 mg, 0.441 mmol) in dimethylformamide was added to sodium hydride (55% dispersed in mineral oil, 28.9 g, 0.662 mmol), and the mixture was stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.050 mL, 0.37 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 16 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 55.0 mg, 40%).

[0853] ¹H NMR(400MHz, CDCl3)δ0.90(d,J=7.2Hz,3H),0.95(d,J=7.2Hz,3H),1.51-1.60( m,1H),1.53(s,3H),1.63(dd,J=12.8,6.0Hz,1H),2.05-2.19(m,2H),2.34(s,3H ),2.39(dd,J=12.8,6.0Hz,1H),3.35-3.43(m,1H),3.78(d,J=6.0Hz,1H),4.44( d,J=12.8Hz,1H),4.60(d,J=12.8Hz,1H),7.11-7.33(m,8H),7.36-7.41(m,1H).

[0854] Synthesis Example 29

[0855] Synthesis of (1S,2R,4R)-2-((2-fluorobenzyl)oxy)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]heptane (1-322)

[0856] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthetic Example 28 were performed to obtain the colorless liquid title compound (68% yield).

[0857] ¹H NMR(400MHz, CDCl3)δ0.89(d,J=6.8Hz,3H),0.95(d,J=6.8Hz,3H),1.51-1.58(m, 1H),1.53(s,3H),1.64(dd,J=13.2,6.4Hz,1H),2.04-2.19(m,2H),2.42(dd,J=13. 2,6.8Hz,1H),3.39(ddd,J=11.2,6.4,1.6Hz,1H),3.82(dd,J=6.8,3.6Hz,1H),4.5 7(d,J=12.4Hz,1H),4.66(d,J=12.4Hz,1H),6.89-7.35(m,8H),7.46-7.55(m,1H).

[0858] Synthesis Example 30

[0859] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hept-5-en-2-ol

[0860] A solution (7 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane (233 mg, 0.650 mmol) in tetrahydrofuran was added to tetrabutylammonium fluoride (0.98 mL, 1 mol / L tetrahydrofuran solution, 0.98 mmol), and the mixture was stirred at room temperature for 29 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 97.3 mg, 61%).

[0861] ¹H NMR(400MHz, CDCl3)δ0.84(d,J=6.8Hz,3H),1.07(d,J=6.8Hz,3H),1.48-1.70(m,2H),1.61(s,3H),2.15-2 .23(m,1H),2.43(sept,J=6.8Hz,1H),3.95(ddd,J=10.1,6.4,1.6Hz,1H),6.00(s,1H),7.21-7.34(m,5H).

[0862] Synthesis Example 31

[0863] Synthesis of (1R,4S,5R)-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-2-phenyl-7-oxabicyclo[2.2.1]hept-2-ene (3-175)

[0864] A solution of dimethylformamide (1 mL) was added to (1S,2R,4R)-4-isopropyl-1-methyl-5-phenyl-7-oxabicyclo[2.2.1]hept-5-en-2-ol (50.0 mg, 0.205 mmol), followed by the addition of sodium hydride (55% dispersed in mineral oil, 13.4 mg, 0.307 mmol), and the mixture was stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.030 mL, 0.22 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 15 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 48.3 mg, 68%).

[0865] ¹H NMR(400MHz, CDCl3)δ0.85(d,J=6.8Hz,3H),1.09(d,J=6.8Hz,3H),1.64(s,3H),1.86(dd,J=12.0,2.4Hz,1H),1.97(dd,J=12.0,6.4Hz,1H),2.3 5(s,3H),2.43(sept,J=6.8Hz,1H),3.68(dd,J=6.4,1.6Hz,1H),4.45(d,J=12.4Hz,1H),4.63(d,J=12.4Hz,1H),5.97(s,1H),7.11-7.35(m,9H).

[0866] Synthesis Example 32

[0867] Synthesis of (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-2-phenyl-7-oxabicyclo[2.2.1]hept-2-ene (3-177)

[0868] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthesis Example 31 were performed to obtain the colorless liquid title compound (yield 54%).

[0869] ¹H NMR(400MHz, CDCl3)δ0.85(d,J=6.8Hz,3H),1.09(d,J=6.8Hz,3H),1.65(s,3H),1. 84-1.91(m,1H),1.88(dd,J=12.8,9.2Hz,1H),2.43(sept,J=6.8Hz,1H),3.72(dd,J =6.0,1.6Hz,1H),4.59(d,J=12.8Hz,1H),4.68(d,J=12.8Hz,1H),5.98(s,1H),7.02 (t,J=8.0Hz,1H),7.13(t,J=7.2Hz,1H),7.18-7.36(m,6H),7.48(td,J=7.2Hz,1H).

[0870] Synthesis Example 33

[0871] Synthesis of tert-butyl(((1R,4S,5R)-1-isopropyl-4-methyl-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]dioxacyclopentane]-5-yl)oxy)dimethylsilane

[0872] A toluene solution (5 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (120 mg, 0.402 mmol) was added to ethylene glycol (0.11 mL, 2.01 mmol) and p-toluenesulfonic acid monohydrate (7.0 mg, 0.040 mmol), followed by stirring under heat and reflux for 21 hours. Triethylamine was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 95.6 mg, 69%).

[0873] ¹H NMR(400MHz, CDCl3)δ0.049(s,3H),0.051(s,3H),0.87(d,J=6.8Hz,3H),0.89(s,9H),1.01(d,J=6.8Hz,3H),1.32(s,3 H),1.46(dd,J=13.6,2.4Hz,1H),1.62(d,J=11.2Hz,1H),1.81(d,J=11.2Hz,1H),2.30-2.41(m,2H),3.75-3.99(m,5H).

[0874] Synthesis Example 34

[0875] Synthesis of (1R,4S,5R)-1-isopropyl-4-methyl-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]dioxacyclopentane]-5-ol

[0876] A solution (3 mL) of tert-butyl(((1R,4S,5R)-1-isopropyl-4-methyl-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]dioxacyclopentane]-5-yl)oxy)dimethylsilane (95.6 mg, 0.279 mmol) in tetrahydrofuran was added, followed by stirring at room temperature (25°C) for 18 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 53.0 mg, 83%).

[0877] ¹H NMR(400MHz, CDCl3)δ0.88(d,J=6.8Hz,3H),1.00(d,J=6.8Hz,3H),1.39(s,3H),1.44(dd,J=14.4,1.6Hz,1H),1.55(d,J=10.0Hz,1H),1.6 8(d,J=13.2Hz,1H),1.86(d,J=13.2Hz,1H),2.39(sept,J=6.8Hz,1H),2.50(dd,J=14.4,6.8Hz,1H),3.77-3.85(m,2H),3.87-4.02(m,3H).

[0878] Synthesis Example 35

[0879] Synthesis of (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]dioxacyclopentane](1-936)

[0880] A solution (1 mL) of (1R,4S,5R)-1-isopropyl-4-methyl-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-[1,3]dioxacyclopentane]-5-ol (53.0 mg, 0.232 mmol) in dimethylformamide was added to sodium hydride (55% dispersed in mineral oil, 15.0 mg, 0.348 mmol), and the mixture was stirred at 0°C for 1 hour. 2-Fluorobenyl bromide (0.033 mL, 0.28 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature (25°C) for 17 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (71.3 mg, 92%).

[0881] ¹H NMR(400MHz, CDCl3)δ0.89(d,J=6.8Hz,3H),1.03(d,J=6.8Hz,3H),1.44(s,3H),1.64(dd,J=13.2 ,2.4Hz,1H),1.66(d,J=12.8Hz,1H),1.83(d,J=12.8Hz,1H),2.34-2.45(m,2H),3.64(dd,J=6.8, 2.4Hz,1H),3.75-3.81(m,1H),3.88-3.99(m,3H),4.53(d,J=12.8Hz,1H),4.62(d,J=12.8Hz,1H) ,7.00-7.05(m,1H),7.13(dt,J=7.2,0.8Hz,1H),7.23-7.29(m,1H),7.45(dt,J=8.0,1.2Hz,1H).

[0882] Synthesis Example 36

[0883] Synthesis of (1S,2R,4R)-4-isopropyl-5,5-dimethoxy-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0884] To a methanol solution (3 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hepta-2-one (120 mg, 0.402 mmol), trimethyl orthoformate (0.21 mL, 2.01 mmol) and p-toluenesulfonic acid monohydrate (15.0 mg, 0.0789 mmol) were added, followed by stirring under heat and reflux for 2 hours. Triethylamine was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 49.9 mg, 54%).

[0885] ¹H NMR(400MHz, CDCl3)δ0.97(d,J=6.8Hz,3H),1.01(d,J=6.8Hz,3H),1.35(dd,J=14.0,1.6Hz,1H),1.39(s,3H),1.53(d,J=9.6Hz,1H),1.70(d,J=13.2 Hz,1H),1.87(d,J=13.2Hz,1H),2.36(sept,J=6.8Hz,1H),2.44(dd,J=14. 0,6.8Hz,1H),3.28(s,3H),3.40(s,3H),3.73(ddd,J=9.6,6.8,1.6Hz,1H).

[0886] Synthesis Example 37

[0887] Synthesis of (1R,4S,5R)-5-((2-fluorobenzyl)oxy)-1-isopropyl-2,2-dimethoxy-4-methyl-7-oxabicyclo[2.2.1]heptane (1-935)

[0888] A solution (1 mL) of (1S,2R,4R)-4-isopropyl-5,5-dimethoxy-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (49.9 mg, 0.217 mmol) in dimethylformamide was added to sodium hydride (55% dispersed in mineral oil, 14.0 mg, 0.321 mmol), and the mixture was stirred at 0°C for 1 hour. 2-fluorobenzyl bromide (0.031 mL, 0.26 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature (25°C) for 16 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (62.7 mg, 85%).

[0889] ¹H NMR(400MHz, CDCl3)δ0.98(d,J=6.8Hz,3H),1.04(d,J=6.8Hz,3H),1.44(s,3H),1.56(dd,J=13.6,2.8Hz,1 H),1.68(d,J=12.8Hz,1H),1.87(d,J=12.8Hz,1H),2.30(dd,J=13.6,6.8Hz,1H),2.36(sept,J=6.8Hz,1H), 3.25(s,3H),3.37(s,3H),3.58(dd,J=6.8,2.8Hz,1H),4.52(d,J=13.2Hz,1H),4.62(d,J=13.2Hz,1H),7.0 2(ddd,J=9.6,7.2,0.8Hz,1H),7.13(dt,J=7.6,0.8Hz,1H),7.23-7.29(m,1H),7.45(dt,J=7.6,1.6Hz,1H).

[0890] Synthesis Example 38

[0891] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-ol

[0892] To a 1,2-dimethoxyethane solution (2.2 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate (230 mg, 0.643 mmol), potassium carbonate (133 mg, 0.962 mmol) and 3-thiopheneboronic acid (91.0 mg, 0.711 mmol) were added, and argon was bubbled into the mixture for 5 minutes. Tetra(triphenylphosphine)palladium (148 mg, 0.128 mmol) was added to the reaction mixture, followed by stirring at room temperature (25°C) for 29 hours. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give crude tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane.

[0893] A solution (4.8 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane in tetrahydrofuran was added to tetrabutylammonium fluoride (0.72 mL, 1 mol / L tetrahydrofuran solution, 0.72 mmol), and the mixture was stirred at room temperature (25°C) for 18 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 89.3 mg, 55%).

[0894] ¹H NMR(400MHz, CDCl3)δ0.95(d,J=6.8Hz,3H),1.10(d,J=6.8Hz,3H),1.55(d, J=8.0Hz,1H),1.58-1.64(m,1H),1.60(s,3H),2.04(dd,J=12.4,6.4Hz,1H), 2.43(sept,J=6.8Hz,1H),3.91(t,J=8.0,6.4Hz,1H),6.04(s,1H),7.06(dd, J=5.2,1.2Hz,1H),7.12(dd,J=2.8,1.2Hz,1H),7.30(dd,J=5.2,2.8Hz,1H).

[0895] Synthesis Example 39

[0896] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hepta-2-ol

[0897] A methanol solution (1 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-ol (61.8 mg, 0.247 mmol) was added to palladium hydroxide (12.0 mg, 50 wt% water), and the mixture was stirred at room temperature (25°C) under hydrogen atmosphere for 17 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 53.8 mg, 86%).

[0898] ¹H NMR(400MHz, CDCl3)δ0.97(d,J=6.8Hz,3H),0.98(d,J=6.8Hz,3H),1.34(dt,J=14.0,2.0Hz,1H ),1.46(s,3H),1.59(dd,J=14.0,6.4Hz,1H),1.59-1.70(m,1H),2.04(sept,J=6.8Hz,1H),2.4 1(dd,J=12.8,11.6Hz,1H),2.44(dd,J=14.0,6.8Hz,1H),3.42(ddd,J=11.6,6.4,2.4Hz,1H),3 .85-3.92(m,1H),6.96(dd,J=5.2,1.6Hz,1H),6.98-7.02(m,1H),7.27(dd,J=5.2,2.8Hz,1H).

[0899] Synthesis Example 40

[0900] Synthesis of (1S,2R,4R)-2-((2-fluorobenzyl)oxy)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]heptane (1-928)

[0901] A solution (1 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-(thiophen-3-yl)-7-oxabicyclo[2.2.1]hepta-2-ol (53.8 mg, 0.213 mmol) in dimethylformamide was added to sodium hydride (55% dispersed in mineral oil, 13.9 mg, 0.319 mmol), and the mixture was stirred at 0°C for 1 hour. 2-fluorobenzyl bromide (0.030 mL, 0.25 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature (25°C) for 15 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (52.8 mg, 69%).

[0902] ¹H NMR(400MHz, CDCl3)δ0.97(d,J=6.8Hz,3H),0.99(d,J=6.8Hz,3H),1.51(s,3H),1.53-1.61(m,2H) ,2.09(sept,J=6.8Hz,1H),2.13(dd,J=12.8,11.6Hz,1H),2.34(dd,J=13.6,6.8Hz,1H),3.45(ddd, J=11.6,6.4,2.0Hz,1H),3.74(dd,J=6.8,2.8Hz,1H),4.54(d,J=12.8Hz,1H),4.63(d,J=12.8Hz,1 H),6.93-7.06(m,3H),7.14(td,J=7.2,0.8Hz,1H),7.24-7.29(m,2H),7.48(dt,J=7.2,1.6Hz,1H).

[0903] Synthesis Example 41

[0904] Synthesis of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-((trimethylsilyl)ethynyl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane

[0905] To a tert-butylamine solution (1.8 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate (233 mg, 0.542 mmol), trimethylsilylacetylene (0.38 mL, 2.7 mmol), cuprous iodide (10.0 mg, 0.0542 mmol), and tetrakis(triphenylphosphine)palladium (62.6 mg, 0.0542 mmol) were added, followed by stirring at room temperature (25°C) for 22 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (163 mg, 79%). ¹HNMR(400MHz, CDCl3)δ0.04(s,3H),0.05(s,3H),0.19(s,9H),0.89(s,9H),1.15(d,J=6.8Hz,3H),1.16(d,J=6.8Hz,3H),1.38(dd, J=11.6,2.0Hz,1H),1.47(s,3H),2.00(dd,J=11.6,6.4Hz,1H),2.19(sept,J=6.8Hz,1H),3.87(dd,J=6.4,2.0Hz,1H),6.27(s,1H).

[0906] Synthesis Example 42

[0907] Synthesis of (1S,2R,4R)-4-isopropyl-1-methyl-5-[(trimethylsilyl)ethynyl]-7-oxabicyclo[2,2,1]hept-5-en-2-ol

[0908] A solution (1.4 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-((trimethylsilyl)ethynyl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane (163 mg, 0.428 mmol) in tetrahydrofuran was added to hydrochloric acid (3N aqueous solution, 0.29 mL, 0.87 mmol), and the mixture was stirred at room temperature (25°C) for 4 hours. Water was added to the reaction mixture, which was then extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (92.8 mg, 100%).

[0909] ¹H NMR(400MHz, CDCl3)δ0.19(s,9H),1.15(d,J=6.8Hz,6H),1.37(dd,J=12.8,1.2Hz,1H),1.53(s ,3H),2.12(dd,J=12.8,6.4Hz,1H),2.19(sept,J=7.6Hz,1H),3.86-3.89(m,1H),6.27(s,1H).

[0910] Synthesis Example 43

[0911] Synthesis of (1S,2R,4R)-5-ethynyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-ol

[0912] A methanol solution (9.7 mL) of (1S,2R,4R)-4-isopropyl-1-methyl-5-[(trimethylsilyl)ethynyl]-7-oxabicyclo[2.2.1]hept-5-en-2-ol (259 mg, 0.970 mmol) was added with potassium carbonate (0.201 mg, 1.46 mmol), and the mixture was stirred at room temperature (25°C) for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound (145 mg, 78%) as a colorless liquid.

[0913] ¹H NMR (400MHz, CDCl3) δ1.14(d,J=5.6Hz,3H),1.15(d,J=5.6Hz,3H),1.37(dd,J=10.0,1.2Hz,1H),1.54(s,3H),1. 64(s,1H),2.08(dd,J=10.0,5.6Hz,1H),2.21(sept,J=5.6Hz,1H),3.38(s,1H),3.87-3.89(m,1H),6.35(s,1H).

[0914] Synthesis Example 44

[0915] Synthesis of (1S,2R,4R)-5-ethyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0916] To a methanol solution (3.0 mL) of (1S,2R,4R)-5-ethynyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-ol (150 mg, 0.753 mmol), palladium hydroxide (29.0 mg, 50 wt% water) was added, followed by stirring at room temperature (25°C) under hydrogen atmosphere for 2 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 94.0 mg, 63%).

[0917] ¹H NMR (400MHz, CDCl3) δ0.79-1.04(m,11H),1.16-1.22(m,0.3H),1.27-1.34(m,0.7H),1.36(s,2.1H),1.39(s,0.9H),1.46-1.68(m,3H),1. 78(dd,J=14.0,6.4Hz,0.3H),1.98(sept,J=6.8Hz,0.7H),2.17(sept,J=6.8Hz,0.3H),2.32(dd,J=14.0,6.8Hz,0.7H),3.62-3.71(m,1H).

[0918] Synthesis Example 45

[0919] Synthesis of (1R,4S,5R)-2-ethyl-1-isopropyl-4-methyl-5-((2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptane (1-123)

[0920] A solution (1.0 mL) of (1S,2R,4R)-5-ethyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (48.0 mg, 0.242 mmol) in dimethylformamide was added to sodium hydride (55% dispersed in mineral oil, 16.0 mg, 0.367 mmol), followed by stirring at 0°C for 1 hour. 2-Methylbenzyl bromide (0.031 mL, 0.23 mmol) was added to the reaction mixture, followed by stirring at room temperature (25°C) for 39 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (64.0 mg, 92%). ¹H NMR(400MHz, CDCl3)δ0.77-1.06(m,11H),1.42(s,2.1H),1.45(s,0.9H),1.51-1.71(m,3H), 1.80-1.92(m,1.3H),2.05(sept,J=6.8Hz,0.7H),2.16-2.26(m,1H),2.32(s,2.1H),2.33(s ,0.9H),3.48(dd,J=6.4,2.8Hz,0.3H),3.49(dd,J=6.4,2.8Hz,0.7H),4.37(d,J=12.4Hz,1H ),4.54(d,J=12.4Hz,0.7H),4.55(d,J=12.4Hz,0.3H),7.13-7.21(m,3H),7.31-7.36(m,1H).

[0921] Synthesis Example 46

[0922] Synthesis of (1R,4S,5R)-2-ethyl-5-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane (1-126)

[0923] Using 2-fluorobenzyl bromide instead of 2-methylbenzyl bromide, the same reaction and treatment as in Synthetic Example 28 were performed to obtain the colorless liquid title compound (yield 71%).

[0924] ¹H NMR(400MHz, CDCl3)δ0.80-1.06(m,11H),1.43(s,2.1H),1.46(s,0.9H),1.50-1.7 0(m,3H),1.81-1.93(m,1.3H),2.05(sept,J=6.8Hz,0.7H),2.16-2.28(m,1H),3.51 -3.54(m,1H),4.50(d,J=12.8Hz,0.7H),4.51(d,J=12.8Hz,0.3H),4.55(d,J=12.8H z,1H),6.99-7.04(m,1H),7.10-7.15(m,1H),7.22-7.28(m,1H),7.44-7.48(m,1H).

[0925] Synthesis Example 47

[0926] Synthesis of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(prop-1-en-2-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane

[0927] To a 1,2-dimethoxyethane solution (2.2 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate (280 mg, 0.650 mmol), potassium carbonate (135 mg, 0.977 mmol) and 2-isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentane (0.14 mL, 0.74 mmol) were added, and argon was bubbled into the mixture for 5 minutes. Tetra(triphenylphosphine)palladium (150 mg, 0.130 mmol) was added to the reaction mixture, followed by stirring at room temperature (25°C) for 25 hours. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (yield 159 mg, 76%).

[0928] ¹H NMR (400MHz, CDCl3) δ0.04(s,3H),0.05(s,3H),0.90(s,9H),0.98(d,J=6.8Hz,3H),1.08(d,J=6.8Hz,3H),1.49(s,3H),1.56(dt,J=11.6,2. 0Hz,1H),1.76(dd,J=11.6,6.4Hz,1H),1.87(s,3H),2.36(sept,J=6.8Hz,1H),3.81(dd,J=6.4,2.0Hz,1H),4.83-4.89(m,2H),5.90(s,1H).

[0929] Synthesis Example 48

[0930] Synthesis of (1S,2R,4R)-4,5-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0931] A methanol solution (2.0 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(prop-1-en-2-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane (159 mg, 0.493 mmol) was added to palladium on carbon (31.9 mg, 55 wt% water), and the mixture was stirred at room temperature (25°C) under hydrogen atmosphere for 17 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 76.1 mg, 73%).

[0932] ¹H NMR(400MHz, CDCl3)δ0.91(d,J=6.8Hz,3H),0.92(d,J=6.8Hz,3H),1.00-1.05(m,1H),1.06(d,J=6.8Hz,3H),1.07(d,J=6.8Hz,3H),1.35(s ,3H),1.30-1.45(m,1H),1.49-1.54(m,2H),1.76-1.87(m,2H),1.98(sept,J=6.8Hz,1H),2.23(dd,J=14.0,6.8Hz,1H),3.63-3.71(m,1H).

[0933] Synthesis Example 49

[0934] Synthesis of (1S,2R,4R)-2-[(2-fluorobenzyl)oxy]-4,5-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane (1-133)

[0935] A solution (1.2 mL) of (1S,2R,4R)-4,5-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (76.1 mg, 0.358 mmol) in dimethylformamide was added to sodium hydride (60% dispersed in mineral oil, 21.5 mg, 0.538 mmol), and the mixture was stirred at 0°C for 1 hour. 2-fluorobenzyl bromide (0.052 mL, 0.43 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature (25°C) for 17 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (97.2 mg, 81%).

[0936] ¹H NMR(400MHz, CDCl3)δ0.89(d,J=6.8Hz,3H),0.91(d,J=6.8Hz,3H),1.00-1.05(m,1H),1.05(d,J=7.2Hz, 3H),1.07(d,J=7.2Hz,3H),1.33(sept,J=7.2Hz,1H),1.40(s,3H),1.69-1.84(m,3H),1.99(sept,J=6.8 Hz,1H),2.12(dd,J=13.2,6.8Hz,1H),3.51(dd,J=6.8,2.8Hz,1H),4.49(d,J=13.2Hz,1H),4.58(d,J=13 .2Hz,1H),7.00(t,J=7.2Hz,1H),7.11(t,J=7.2Hz,1H),7.20-7.28(m,1H),7.45(dt,J=7.2,1.6Hz,1H).

[0937] Synthesis Example 50

[0938] Synthesis of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(2-methylprop-1-en-2-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane

[0939] To a 1,2-dimethoxyethane solution (2.2 mL) of (1R,4S,5R)-5-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate (280 mg, 0.650 mmol), potassium carbonate (135 mg, 0.977 mmol) and 4,4,5,5-tetramethyl-2-(2-methyl-1-propenyl)-1,3,2-dioxaborane (0.15 mL, 0.74 mmol) were added, and argon was bubbled into the mixture for 5 minutes. Tetra(triphenylphosphine)palladium (150 mg, 0.130 mmol) was added to the reaction mixture. The mixture was then stirred at room temperature (25°C) for 19 hours. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 164 mg, 75%).

[0940] ¹H NMR(400MHz, CDCl3)δ0.04(s,3H),0.05(s,3H),0.89(s,9H),1.02(d,J=6.8Hz,3H),1.07(d,J=6.8Hz,3H),1.41(dd,J=11.6,2.0Hz,1H),1 .50(s,3H),1.71-1.79(m,1H),1.75(s,3H),1.83(s,3H),2.09(sept,J=6.8Hz,1H),3.84(dd,J=6.0,2.0Hz,1H),5.57(s,1H),5.73(s,1H).

[0941] Synthesis Example 51

[0942] Synthesis of (1S,2R,4R)-5-isobutyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol

[0943] A methanol solution (1.9 mL) of tert-butyl(((1S,2R,4R)-4-isopropyl-1-methyl-5-(2-methylprop-1-en-2-yl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl)oxy)dimethylsilane (164 mg, 0.487 mmol) was added to palladium on carbon (32.8 mg, 55 wt% water), and the mixture was stirred at room temperature (25°C) under hydrogen atmosphere for 17 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 84.4 mg, 77%).

[0944] ¹H NMR(400MHz, CDCl3)δ0.88(d,J=6.8Hz,3H),0.90(d,J=6.8Hz,3H),0.92-0.98(m,2H ),1.01(d,J=6.8Hz,3H),1.04(d,J=6.8Hz,3H),1.22-1.29(m,1H),1.33(dt,J=14.0, 1.6Hz,1H),1.37(s,3H),1.45-1.56(m,2H),1.85(dd,J=12.4,10.8Hz,1H),1.97(sep t,J=6.8Hz,1H),2.00-2.11(m,1H),2.32(dd,J=13.6,6.8Hz,1H),3.63-3.72(m,1H).

[0945] Synthesis Example 52

[0946] Synthesis of (1S,2R,4R)-2-((2-fluorobenzyl)oxy)-5-isobutyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane (1-915)

[0947] A solution (1.2 mL) of (1S,2R,4R)-5-isobutyl-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]hepta-2-ol (84.4 mg, 0.373 mmol) in dimethylformamide was added to sodium hydride (60% dispersed in mineral oil, 22.4 mg, 0.560 mmol), and the mixture was stirred at 0°C for 2 hours. 2-fluorobenzyl bromide (0.055 mL, 0.45 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature (25°C) for 15 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (elution: ethyl acetate / n-hexane) to give a colorless liquid title compound (97.7 mg, 79%).

[0948] ¹H NMR(400MHz, CDCl3)δ0.87(d,J=6.8Hz,3H),0.89(d,J=6.8Hz,3H),0.96-1.03(m,2H),1.02(d,J=6.8Hz,3H),1. 05(d,J=6.8Hz,3H),1.26(ddd,J=12.8,9.2,2.4Hz,1H),1.43(s,3H),1.47-1.58(m,2H),1.84(t,J=12.4Hz,1H) ,1.99-2.11(m,2H),2.26(dd,J=12.8,6.8Hz,1H),3.53(dd,J=6.8,2.4Hz,1H),4.50(d,J=12.8Hz,1H),4.60(d, J=12.8Hz,1H),6.98-7.05(m,1H),7.12(td,J=7.2,1.6Hz,1H),7.21-7.28(m,1H),7.46(td,J=7.2,1.6Hz,1H).

[0949] Synthesis Example 53

[0950] Synthesis of ...

Claims

1. A 1,4-cineole derivative represented by the following general formula (1), (1'), (2), (2'), (3) or (3'): [Chemical Formula 1] ###0001### (in general formulae (1), (1'), (2), (2'), (3) and (3'), R1 represents a hydrogen atom or a methyl group, R2 represents a hydrogen atom or a methyl group, R3 represents a hydrogen atom or a methyl group, R4 represents a hydrogen atom or a methyl group, R5 represents a hydrogen atom or a methyl group, R6 represents a hydrogen atom or a methyl group, R7 represents a hydrogen atom or a methyl group, ​ ​ R 1 each independently represents a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C2-C6alkenyl group, a C2-C6alkynyl group, a C3-C6cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C3-C6cycloalkyl C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C1-C6alkoxy C1-C6alkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C1-C6alkoxy group, a C1-C6halogenated alkoxy group, a carboxyl group or a C1-C6alkoxycarbonyl group, a heterocyclic C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a phenoxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyloxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a benzoyl C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, or a C1-C6alkoxy C1-C6alkoxy C1-C6alkyl group, R 2 and R 3 each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkenyloxy group, a C2-C6 alkynyl group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, a C1-C6 haloalkylsulfonyloxy group, a C3-C6 cycloalkylsulfonyloxy group, an arylsulfonyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, an aminosulfonyloxy group which can be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group or an aryl group,Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2 and R 3 At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents. X each independently represents an oxygen atom, a sulfur atom, CR 4 R 5 or NR 6 , R 4 and R 5 each independently represents a hydrogen atom or a C1-C6 alkyl group, R 6 represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group or an anilino group (which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group), and W each independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a phenoxy C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyloxy C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a phenoxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic oxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkylsulfonyloxy group, a C1-C6 haloalkylsulfonyloxy group, a C3-C6 cycloalkylsulfonyloxy group or an arylsulfonyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group.

2. The 1,4-cineole derivative according to claim 1, wherein R 1 each independently represents a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C2-C6alkenyl group, a C2-C6alkynyl group, a C3-C6cycloalkyl C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C1-C6alkoxy C1-C6alkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C1-C6alkoxy group, a C1-C6halogenated alkoxy group, a carboxyl group or a C1-C6alkoxycarbonyl group, a heterocyclic C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a phenoxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyloxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a benzoyl C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, or a C1-C6alkoxy C1-C6alkoxy C1-C6alkyl group, R 2 and R 3 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C2-C6 alkenyloxy group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 haloalkylsulfonyloxy group or a carbamoyloxy group which can be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group or an aryl group, and the C1-C6 alkyl groups can be bonded to each other via an alkylene group to form a 3-, 4-, 5- or 6-membered ring, R 2 and R 3 at least one of R 2 and R 3 is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 together with the carbon atoms to which they are bonded, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from the group consisting of oxygen atoms, sulfur atoms, and nitrogen atoms, and the formed ring can have 1 or more substituents, X each independently represents an oxygen atom, a sulfur atom, CR 4 R 5 or NR 6 , R 4 and R 5 each independently represents a hydrogen atom or a C1-C6alkyl group, R 6 represents a hydroxyl group, a C1-C6alkyl group, a C1-C6alkoxy group, an amino group, a C1-C6alkylamino group, an aminocarbonylamino group or an anilino group (which can be mono- or poly-substituted by halogen atoms, C1-C6alkyl groups or C1-C6haloalkyl groups), and W can independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), a C3-C6 cycloalkyl C1-C6 alkyl group (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group), an aryl group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic ring (which can be mono- or poly-substituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The following groups can be substituted or multisubstituted: C7-C11 aralkyl groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic C1-C6 alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), phenoxy groups (which can be substituted or multisubstituted by halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups or C1-C6 haloalkoxy groups), heterocyclic alkyl groups (which can be substituted or multisubstituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C1-C6 alkylsulfonyl oxy groups or C1-C6 haloalkylsulfonyl oxy groups.

3. The 1,4-cineole derivative according to claim 1, wherein... R 1 each independently represents a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C2-C6alkenyl group, a C2-C6alkynyl group, a C3-C6cycloalkyl C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C1-C6alkoxy C1-C6alkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6alkyl group, a C1-C6halogenated alkyl group, a C1-C6alkoxy group, a C1-C6halogenated alkoxy group, a carboxyl group or a C1-C6alkoxycarbonyl group, a heterocyclic C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a phenoxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, a C7-C11aralkyloxy C1-C6alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6alkyl group or a C1-C6halogenated alkyl group, or a C1-C6alkoxy C1-C6alkoxy C1-C6alkyl group, R 2 and R 3 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a C2-C6 alkenyloxy group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 haloalkylsulfonyloxy group or a carbamoyloxy group which can be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group or an aryl group, and the C1-C6 alkyl groups can also be bonded to each other via an alkylene group to form a 3-, 4-, 5- or 6-membered ring, R 2 and R 3 at least one of R 2 and R 3 is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , together with the carbon atom to which they are bonded, can form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from an oxygen atom, a sulfur atom and a nitrogen atom, and the formed ring can have 1 or more substituents, X each independently represents an oxygen atom, CR 4 R 5 or NR 6 , R 4 and R 5 each independently represents a hydrogen atom, R 6 represents a hydroxyl group, and W represents, independently, a hydrogen atom, an aryl group (which may be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a C1-C6 haloalkylsulfonyloxy group.

4. A synthetic intermediate represented by the following general formulas (1a), (1a'), (2a), (2a'), (3a) or (3a'), used for preparing the 1,4-cineole derivative represented by any one of general formulas (1), (1'), (2), (2'), (3) or (3') according to any one of claims 1 to 3: [Chemical Formula 2] (In the general formulas (1a), (1a'), (2a), (2a'), (3a) and (3a'), R 1a each independently represents a hydrogen atom or a tri(Ci-C6alkyl)silyl group, which can be the same or different, R 2a and R 3a each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkenyloxy group, a C2-C6 alkynyl group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, a C1-C6 haloalkylsulfonyloxy group, a C3-C6 cycloalkylsulfonyloxy group, an arylsulfonyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, an aminosulfonyloxy group which can be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group or an aryl group,Furthermore, the C1-C6 alkyl groups can be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings, or carbamoyloxy groups (which can be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups can also be bonded together via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), and R, 2a and R 3a At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2a and R 3a , with R 2a and R 3a The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents. X a each independently represents an oxygen atom, a sulfur atom, CR 4a R 5a or NR 6a , R 4a and R 5a each independently represents a hydrogen atom or a C1-C6alkyl group, R 6a represents a hydrogen atom, a hydroxyl group, a C1-C6alkyl group, a C1-C6alkoxy group, an amino group, a C1-C6alkylamino group, an aminocarbonylamino group or an anilino group (which can be mono- or poly-substituted by a halogen atom, a C1-C6alkyl group or a C1-C6haloalkyl group), and W a each independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a phenoxy C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyloxy C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a phenoxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic oxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkylsulfonyloxy group, a C1-C6 haloalkylsulfonyloxy group, a C3-C6 cycloalkylsulfonyloxy group or an arylsulfonyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group.

5. The synthetic intermediate according to claim 4, wherein... R 1a each independently represents a hydrogen atom or a tri(Ci-C6alkyl)silyl group, which can be the same or different, R 2a and R 3a each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkoxy C1-C6 alkoxy group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkoxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C2-C6 alkenyloxy group, a C2-C6 alkynyloxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 haloalkylsulfonyloxy group or a carbamoyloxy group which can be mono- or poly-substituted with a C1-C6 alkyl group, a C3-C6 cycloalkyl group or an aryl group, and said C1-C6 alkyl groups can be bonded to each other via an alkylene group to form a 3-, 4-, 5- or 6-membered ring, R 2a and R 3a at least one of which is a substituent other than a hydrogen atom, the two adjacent substituents, R 2 and R 3 , and R 2 and R 3 together with the carbon atoms to which they are bonded, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from the group consisting of oxygen atoms, sulfur atoms, and nitrogen atoms, and the formed ring can have 1 or more substituents, X a each independently represents an oxygen atom, a sulfur atom, CR 4 R 5 or NR 6 , R 4a and R 5a each independently represents a hydrogen atom or a C1-C6alkyl group, R 6a represents a hydroxyl group, a C1-C6alkyl group, a C1-C6alkoxy group, an amino group, a C1-C6alkylamino group, an aminocarbonylamino group or an anilino group (which can be mono- or poly-substituted by halogen atoms, C1-C6alkyl groups or C1-C6haloalkyl groups), W a each independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, an aryl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic ring which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C7-C11 aralkyl group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic C1-C6 alkyl group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a phenoxy group which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group or a C1-C6 haloalkoxy group, a heterocyclic oxy group which can be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, a C1-C6 alkylsulfonyloxy group or a C1-C6 haloalkylsulfonyloxy group.

6. The synthetic intermediate of claim 4, wherein R 1a each independently represents a hydrogen atom or a tri(Ci-C6alkyl)silyl group, which can be the same or different, R 2a and R 3a Each of these elements independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C7-C11 aralkyloxy group (which can be mono- or poly-substituted by a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group), or a heterocyclic C1-C6 alkoxy group (which can be mono- or poly-substituted by a halogen atom, C1- C6 alkyl groups or C1-C6 haloalkyl groups (mono- or poly-substituted), C1-C6 alkoxy groups, C3-C6 cycloalkyl groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), C3-C6 cycloalkyl C1-C6 alkoxy groups (which can be mono- or poly-substituted by halogen atoms, C1-C6 alkyl groups or C1-C6 haloalkyl groups), aryl groups (which can be mono- or poly-substituted by halogen atoms, Cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups (single or multiple substitutions), heterocyclic rings (which can be single or multiple substitutions of halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), and C7-C11 aralkyl groups (which can be single or multiple substitutions of halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, or C1-C6 alkoxy groups). The following groups may be mono- or poly-substituted: C1-C6 alkyl alkoxy groups, C2-C6 alkoxy groups, C2-C6 alkynoxy groups, C1-C6 alkyl carbonyl oxy groups, C1-C6 alkyl sulfonyl oxy groups, or carbamoyl oxy groups (which may be mono- or poly-substituted by C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or aryl groups, and the C1-C6 alkyl groups may be bonded to each other via alkylene groups to form 3-membered, 4-membered, 5-membered, or 6-membered rings), R 2a and R 3a At least one of them is a substituent other than a hydrogen atom, and the two adjacent substituents, R 2 and R 3 , with R 2 and R 3 The bonded carbon atoms can form 3- to 6-membered carbon rings or 3- to 6-membered heterocyclic rings with 1 to 4 independent heteroatoms selected from oxygen, sulfur, and nitrogen atoms, and the formed ring can have one or more substituents. X a each independently represents an oxygen atom, CR 4 R 5 or NR 6 , R 4a and R 5a each independently represents a hydrogen atom, R 6a represents a hydroxyl group, and W a each independently represents a hydrogen atom, an aryl group (which can be mono- or poly-substituted with a halogen atom, a cyano group, a nitro group, a C1-C6alkyl group, a C1-C6haloalkyl group, a C1-C6alkoxy group or a C1-C6haloalkoxy group) or a C1-C6haloalkylsulfonyloxy group.

7. Herbicides, which include: The 1,4-cineole derivative according to any one of claims 1 to 3 is used as the active ingredient.

8. The herbicide according to claim 7, which is used on agricultural land, pasture, lawn or non-agricultural land.

9. The method of using the herbicide according to claim 7, the method comprising: applying an effective amount of the 1,4-eudesmol derivative to at least one selected from the group consisting of stems and leaves of weeds, soil, and water surface.

10. A method of preparing a pesticide composition, the method comprising: a step of mixing the herbicide according to claim 7 with at least one selected from the group consisting of a diluent or a surfactant.

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