JP2007045744A - Manufacturing method of 2-benzylphenols - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for readily manufacturing a 2-benzylphenol compound with good efficiency and selectivity. <P>SOLUTION: The manufacturing method of the compound represented by formula 2 (wherein R<SB>1</SB>-R<SB>9</SB>are each a hydrogen atom, an alkyl group or the like and two of them may be linked together to form a ring) comprises causing a compound represented by formula 1 (wherein X is a halogen atom) to react in the presence of a dehydrohalogenation agent. Thus, the 2-benzylphenol compound substantially containing no isomers is selectively and efficiently manufactured by simple operations under mild conditions without using a special reaction apparatus. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for efficiently and selectively producing a 2-benzylphenol compound substantially free of isomers.

  Conventionally, as a method for producing a 2-benzylphenol compound, for example, a method in which 2-benzyloxyphenylmagnesium bromide and benzaldehyde are condensed and then deprotection and dehydroxylation are simultaneously performed by catalytic reduction is known. (See Patent Documents 1 and 2). However, in this method, it is essential that 2-bromophenol is used as a starting material, and a protective group is bonded thereto, followed by Grignard reaction, followed by deprotection, and the operation is complicated in multiple steps. It is difficult to handle due to the use of unstable metallic magnesium, and there are many cases where dedicated high-pressure reaction equipment is required for catalytic reduction, and matters that should be taken to ensure safety in each of these processes There are problems such as a large amount of isomers and the generation of isomers.

Japanese Patent Laid-Open No. 2001-08239 WO02 / 28872

  There has been a demand for a new method for efficiently and selectively producing a 2-benzylphenol compound that solves the above-mentioned drawbacks of the conventional techniques.

  In view of the above situation, the present inventors have conducted extensive research on a method for easily and efficiently producing 2-benzylphenol compounds, and as a result, surprisingly, α-halocyclohexanone compounds and benzaldehyde compounds are condensed. The 2-benzylidene-6-halocyclohexanone compound easily obtained by reacting in the presence of a dehydrohalogenating agent was found to solve the above problems, and the present invention was completed based on this finding. It came.

  The method of the present invention provides a method for easily and efficiently selectively producing a 2-benzylphenol compound. According to the method of the present invention, for example, a 2-benzylidene-6-halocyclohexanone compound easily obtained by condensing an α-halocyclohexanone compound and a benzaldehyde compound in the presence of an acid catalyst as a raw material, lithium salt or acetic acid By reacting in the presence of a dehydrohalogenating agent such as a salt, the target 2-benzylphenol compound can be selectively and efficiently operated under mild conditions without using a special reaction apparatus. Can be manufactured.

  Hereinafter, the present invention will be described in detail.

  The present invention solves the above-mentioned problems by providing the inventions described in the following items [1] to [8].

[1] General formula (1)

(In the formula, X represents a halogen atom, and R ₁ , R ₂ , R ₃ and R ₄ may be the same or different, and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, or a trialkyl. A silyl group, an alkoxy group, a trialkylsilyloxy group, a hydroxyalkyl group, an alkoxyalkyl group, a carboxyl group or a metal salt thereof, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkylcarbonylamino group, a nitro group, or a substituent. A phenyl group, a phenoxy group, or a heteroaryl group which may have, and _{two of} R ₁ , R ₂ , R ₃ , and R ₄ may be bonded to form a ring; R ₅ , R _{6, R 7, R 8,} R 9 , which may be the same or different, each independently, a hydrogen atom, an alkyl group, a cyclic alkyl group, alkenyl Group, cyclic alkenyl group, alkynyl group, trialkylsilyl group, hydroxyl group, alkoxy group, trialkylsilyloxy group, hydroxyalkyl group, alkoxyalkyl group, carboxyl group or metal salt thereof, alkoxycarbonyl group, amino group, alkylamino A phenyl group, a phenoxy group, or a heteroaryl group which may have a group, an alkylcarbonylamino group, a halogen atom, a nitro group, or a substituent, and R ₅ , R ₆ , R ₇ , R ₈ , R Two of ₉ may combine to form a ring.)

A 2-benzylidene-6-halocyclohexanone compound represented by the general formula (2) is reacted in the presence of a dehydrohalogenating agent.

(In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)

The manufacturing method of 2-benzylphenol compound represented by these.

[2] General formula

(In the formula, X represents a halogen atom, and R ₁ , R ₂ , R ₃ and R ₄ may be the same or different, and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, or a trialkyl. A silyl group, an alkoxy group, a trialkylsilyloxy group, a hydroxyalkyl group, an alkoxyalkyl group, a carboxyl group or a metal salt thereof, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkylcarbonylamino group, a nitro group, or a substituent. A phenyl group, a phenoxy group, or a heteroaryl group which may have, and _{two of} R ₁ , R ₂ , R ₃ and R ₄ may be bonded to form a ring.

An α-halocyclohexanone compound represented by the general formula (4)

(In the formula, R ₅ , R ₆ , R ₇ , R ₈ and R ₉ may be the same or different and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, an alkenyl group, or a cyclic alkenyl group. , Alkynyl group, trialkylsilyl group, hydroxyl group, alkoxy group, trialkylsilyloxy group, hydroxyalkyl group, alkoxyalkyl group, carboxyl group or metal salt thereof, alkoxycarbonyl group, amino group, alkylamino group, alkylcarbonylamino A phenyl group, a phenoxy group or a heteroaryl group which may have a group, a halogen atom, a nitro group, or a substituent, and two of R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are bonded To form a ring.)

The benzaldehyde compound represented by general formula (1) obtained by condensing in the presence of an acid catalyst.

（式中、Ｘ、Ｒ_１、Ｒ_２、Ｒ_３、Ｒ_４、Ｒ_５、Ｒ_６、Ｒ_７、Ｒ_８、Ｒ_９は、前記と同じ意味を示す。）

(In the formula, X, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)

A 2-benzylidene-6-halocyclohexanone compound represented by the general formula (2) is reacted in the presence of a dehydrohalogenating agent.

(In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)

The manufacturing method of 2-benzylphenol compound represented by these.

[3] The method for producing a 2-benzylphenol compound according to any one of [1] to [2], wherein the dehydrohalogenating agent is a lithium salt or an acetate salt.

[4] The method for producing a 2-benzylphenol compound according to any one of [1] to [2], wherein the dehydrohalogenating agent is lithium chloride, lithium carbonate, or sodium acetate.

[5] The method for producing a 2-benzylphenol compound according to any one of [1] to [4], wherein the reaction is performed in a temperature range of 100 to 200 ° C.

[6] The 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) is 2-benzylidene-6-chlorocyclohexanone, 2- (4-methylbenzylidene) -6-chlorocyclohexanone, 2- (4 -Chlorobenzylidene) -6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -6-chlorocyclohexanone, or 2- (4-fluorobenzylidene) -6-chlorocyclohexanone, any of [1] to [5] A process for producing a 2-benzylphenol compound according to claim 1.

[7] The cyclohexanone compound represented by the general formula (3) is α-chlorocyclohexanone, α-chloro-4-methylcyclohexanone, or α-chloro-4-methoxycyclohexanone, [2] to [5] The manufacturing method of 2-benzylphenol compound in any one.

[8] Any of [2] to [5], wherein the benzaldehyde compound represented by the general formula (4) is benzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde, 4-chlorobenzaldehyde, or 4-fluorobenzaldehyde. A process for producing a 2-benzylphenol compound according to claim 1.

  Hereinafter, the present invention will be described in detail.

  The method of the present invention is characterized in that a 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) is reacted in the presence of a dehydrohalogenating agent such as a lithium salt or acetate. It is a selective manufacturing method of 2-benzylphenol represented by Formula (2).

First, the 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) used as a raw material for the method of the present invention will be described.
X in General formula (1) shows halogen atoms, such as a chlorine atom and a bromine atom.

In the general formula (1), R ₁ , R ₂ , R ₃ and R ₄ may be the same or different and are each independently a hydrogen atom; for example, methyl group, ethyl group, n-propyl Group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group, etc. In the case of 6, it is abbreviated as “C1 to C6.” A linear or branched C1 to C6 alkyl group (the alkyl group is, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc.) Cyclic C1-C6 alkyl group; for example, tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group, t-butyldimethylsilyl group; for example, methoxy group, ethoxy group, n-pro A linear or branched C1-C6 alkoxy group such as a poxy group or an isopropoxy group; for example, a tri (linear or branched C1-C6 alkyl) silyloxy group such as a trimethylsilyloxy group or a t-butyldimethylsilyloxy group; For example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, linear or branched (C1-C6 alkoxy)-such as methoxymethyl group, methoxyethyl group, ethoxyethyl group (C1-C6 alkyl) group; for example, linear or branched C1-C6 haloalkyl group such as fluoromethyl group, difluoromethyl group, trifluoromethyl group; nitro group; phenyl group; phenoxy group; pyridyl group, thienyl group, A heteroaryl group such as a furanyl group; may have a substituent such as a cyclopropyl group; Cyclic C1-C6 alkyl group such as cyclobutyl group, cyclopentyl group, cyclohexyl group (the cyclic alkyl group is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, linear or branched C1-C6 alkyl group such as t-butyl group, n-pentyl group, n-hexyl group; cyclic C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; Tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group and t-butyldimethylsilyl group; for example, linear or branched such as methoxy group, ethoxy group, n-propoxy group and isopropoxy group A C1-C6 alkoxy group; for example, a trimethylsilyloxy group, a t-butyldimethylsilyloxy group, (Linear or branched C1-C6 alkyl) silyloxy group; For example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; For example, methoxymethyl group, methoxyethyl group, ethoxyethyl group, etc. A linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group; for example, a linear or branched C1-C6 haloalkyl group such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group; a nitro group A phenyl group; a phenoxy group; a heteroaryl group such as a pyridyl group, a thienyl group, and a furanyl group; ); For example, tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group, t-butyldimethylsilyl group; for example, straight chain such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc. Chain or branched C1-C6 alkoxy group; for example, tri (straight or branched C1-C6 alkyl) silyloxy group such as trimethylsilyloxy group, t-butyldimethylsilyloxy group; for example, hydroxymethyl group, hydroxyethyl group, etc. A linear or branched C1-C6 hydroxyalkyl group; for example, a linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as a methoxymethyl group, a methoxyethyl group, an ethoxyethyl group; a nitro group A phenyl group (the phenyl group is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n Linear or branched C1-C6 alkyl group such as butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc. Cyclic C1-C6 alkyl group; for example, tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group, t-butyldimethylsilyl group; hydroxyl group; for example, methoxy group, ethoxy group, n-propoxy group A linear or branched C1-C6 alkoxy group such as an isopropoxy group; for example, a tri (straight or branched C1-C6 alkyl) silyloxy group such as a trimethylsilyloxy group or a t-butyldimethylsilyloxy group; A linear or branched C1-C6 hydroxyalkyl group such as a hydroxymethyl group, a hydroxyethyl group; A linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as methoxymethyl group, methoxyethyl group, ethoxyethyl group; halogen atom; nitro group; phenyl group; phenoxy group; pyridyl group, thienyl Group, a heteroaryl group such as a furanyl group; may have a substituent such as; a phenoxy group (the phenoxy group includes, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n- Linear or branched C1-C6 alkyl group such as butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc. Cyclic C1-C6 alkyl group; for example, tri (linear or branched C1-C6 alkyl) such as trimethylsilyl group, t-butyldimethylsilyl group, etc. ) Silyl group; hydroxyl group; linear or branched C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc .; for example, trimethylsilyloxy group, t-butyldimethylsilyloxy A tri (linear or branched C1-C6 alkyl) silyloxy group such as a group; for example, a linear or branched C1-C6 hydroxyalkyl group such as a hydroxymethyl group or a hydroxyethyl group; for example, a methoxymethyl group or a methoxyethyl group Straight chain or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as ethoxyethyl group; halogen atom; nitro group; phenyl group; phenoxy group; heteroaryl such as pyridyl group, thienyl group, furanyl group A substituent such as a group; ); Heteroaryl groups such as pyridyl group, thienyl group, furanyl group (the heteroaryl group is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group) Linear or branched C1-C6 alkyl group such as butyl group, n-pentyl group, n-hexyl group; cyclic C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; A tri (linear or branched C1-C6 alkyl) silyl group such as a t-butyldimethylsilyl group; a hydroxyl group; for example, a linear or linear group such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group Branched C1-C6 alkoxy group; for example, tri (directly) such as trimethylsilyloxy group, t-butyldimethylsilyloxy group, etc. Or branched C1-C6 alkyl) silyloxy group; for example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, straight chain such as methoxymethyl group, methoxyethyl group, ethoxyethyl group, etc. Chain or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group; halogen atom; nitro group; phenyl group; phenoxy group; heteroaryl group such as pyridyl group, thienyl group, furanyl group; It may be.)

In the general formula (1), R ₅ , R ₆ , R ₇ , R ₈ and R ₉ may be the same or different and are each independently a hydrogen atom; for example, a methyl group, an ethyl group, Linear or branched C1-C6 alkyl group such as n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group (the alkyl group is Cyclic C1-C6 alkyl groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; for example, tri (straight or branched C1-C6 alkyl) silyl groups such as trimethylsilyl group, t-butyldimethylsilyl group; For example, a linear or branched C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc .; for example, trimethylsilyloxy group, t-butyl Tri (linear or branched C1-C6 alkyl) silyloxy group such as rudimethylsilyloxy group; for example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, methoxymethyl group A linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as a methoxyethyl group or an ethoxyethyl group; for example, a linear or branched group such as a fluoromethyl group, a difluoromethyl group or a trifluoromethyl group A branched C1-C6 haloalkyl group; a nitro group; a phenyl group; a phenoxy group; a heteroaryl group such as a pyridyl group, a thienyl group, and a furanyl group; and a substituent such as a cyclopropyl group and a cyclobutyl group. A cyclic C1-C6 alkyl group such as a cyclopentyl group, a cyclohexyl group, etc. Linear or branched C1-C6 alkyl such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group, etc. Group: cyclic C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; for example, tri (linear or branched C1-C6 alkyl) silyl such as trimethylsilyl group, t-butyldimethylsilyl group A group; for example, a linear or branched C1-C6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, and an isopropoxy group; for example, a tri (trimethyl (siloxy) group, a t-butyldimethylsilyloxy group, Linear or branched C1-C6 alkyl) silyloxy group; for example, linear or branched, such as hydroxymethyl group, hydroxyethyl group, etc. Branched C1-C6 hydroxyalkyl group; for example, linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as methoxymethyl group, methoxyethyl group, ethoxyethyl group; for example, fluoromethyl group, difluoro A linear or branched C1-C6 haloalkyl group such as a methyl group or a trifluoromethyl group; a nitro group; a phenyl group; a phenoxy group; a heteroaryl group such as a pyridyl group, a thienyl group, or a furanyl group; May be. ); For example, linear or branched C1-C6 alkenyl group such as vinyl group, 1-propenyl group, 2-propenyl group (the alkenyl group is cyclic C1 such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group) -C6 alkyl group; for example, tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group, t-butyldimethylsilyl group; for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc. A linear or branched C1-C6 alkoxy group; for example, a tri (linear or branched C1-C6 alkyl) silyloxy group such as a trimethylsilyloxy group, t-butyldimethylsilyloxy group; Linear or branched C1-C6 hydroxyalkyl groups, such as ethyl groups; for example, methoxymethyl A linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as a methoxyethyl group or an ethoxyethyl group; for example, a linear or branched group such as a fluoromethyl group, a difluoromethyl group or a trifluoromethyl group A branched C1-C6 haloalkyl group; a nitro group; a phenyl group; a phenoxy group; a heteroaryl group such as a pyridyl group, a thienyl group, a furanyl group; and the like; and a substituent such as an ethynyl group, 1 -Linear or branched C1-C6 alkynyl group such as propynyl group, 2-propynyl group (the alkynyl group is a cyclic C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; A tri (linear or branched C1-C6 alkyl) silyl group such as a group, t-butyldimethylsilyl group; Linear or branched C1-C6 alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group; for example, tri (linear or branched) such as trimethylsiloxy group, t-butyldimethylsilyloxy group C1-C6 alkyl) silyloxy group; for example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, linear or branched such as methoxymethyl group, methoxyethyl group, ethoxyethyl group Branched (C1-C6 alkoxy)-(C1-C6 alkyl) group; for example, linear or branched C1-C6 haloalkyl group such as fluoromethyl group, difluoromethyl group, trifluoromethyl group; nitro group; phenyl group; phenoxy A substituent; a heteroaryl group such as a pyridyl group, a thienyl group, or a furanyl group; It may have. ); For example, a cyclic C1-C6 alkenyl group such as a cyclopropenyl group, 1-cyclobutynyl group, 2-cyclobutynyl group (the alkenyl group is a cyclic C1-C6 such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group). An alkyl group; for example, a tri (linear or branched C1-C6 alkyl) silyl group such as a trimethylsilyl group or a t-butyldimethylsilyl group; for example, a methoxy group, an ethoxy group, an n-propoxy group, or an isopropoxy group, Linear or branched C1-C6 alkoxy group; for example, tri (linear or branched C1-C6 alkyl) silyloxy group such as trimethylsilyloxy group, t-butyldimethylsilyloxy group; for example, hydroxymethyl group, hydroxyethyl group A linear or branched C1-C6 hydroxyalkyl group, such as Linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) groups such as xymethyl group, methoxyethyl group, ethoxyethyl group; for example, straight chain such as fluoromethyl group, difluoromethyl group, trifluoromethyl group, etc. Chain or branched C1-C6 haloalkyl group; nitro group; phenyl group; phenoxy group; heteroaryl group such as pyridyl group, thienyl group, furanyl group; , T-butyldimethylsilyl group, tri (linear or branched C1-C6 alkyl) silyl group; hydroxyl group; for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc. C1-C6 alkoxy group; for example, tri (linear or linear) such as trimethylsilyloxy group, t-butyldimethylsilyloxy group, etc. Branched C1-C6 alkyl) silyloxy group; for example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, linear chain such as methoxymethyl group, methoxyethyl group, ethoxyethyl group Or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group; carboxyl group or metal salt thereof; halogen atom; nitro group; phenyl group (the phenyl group is, for example, methyl group, ethyl group, n-propyl group) , Isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group, etc., linear or branched C1-C6 alkyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group Cyclic C1-C6 alkyl groups such as cyclohexyl group; for example, trimethylsilyl group, t-butyldimethyl Tri (linear or branched C1-C6 alkyl) silyl group such as rusilyl group; hydroxyl group; linear or branched C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc. For example, tri (linear or branched C1-C6 alkyl) silyloxy group such as trimethylsilyloxy group and t-butyldimethylsilyloxy group; for example, linear or branched C1_1 such as hydroxymethyl group and hydroxyethyl group; C6 hydroxyalkyl group; for example, a linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as a methoxymethyl group, a methoxyethyl group, an ethoxyethyl group; a carboxyl group or a metal salt thereof; a halogen atom; Nitro group; phenyl group; phenoxy group; heteroaryl such as pyridyl group, thienyl group, furanyl group A substituent such as a group; Phenoxy group (the phenoxy group is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group) Linear or branched C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc .; cyclic C1-C6 alkyl group such as trimethylsilyl group, t-butyldimethylsilyl group, etc. (Straight chain or branched C1-C6 alkyl) silyl group; hydroxyl group; straight chain or branched C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group; for example, trimethylsilyloxy A tri (straight or branched C1-C6 alkyl) silyloxy group, such as a group, t-butyldimethylsilyloxy group; For example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, linear or branched (C1-C6 alkoxy)-such as methoxymethyl group, methoxyethyl group, ethoxyethyl group (C1-C6 alkyl) group; carboxyl group or metal salt thereof; halogen atom; nitro group; phenyl group; phenoxy group; even if it has a substituent such as a heteroaryl group such as pyridyl group, thienyl group, furanyl group A heteroaryl group such as pyridyl group, thienyl group, furanyl group (the heteroaryl group is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, linear or branched C1-C6 alkyl group such as t-butyl group, n-pentyl group, n-hexyl group; cyclopropyl group, A cyclic C1-C6 alkyl group such as a butyl group, a cyclopentyl group, a cyclohexyl group; a tri (linear or branched C1-C6 alkyl) silyl group such as a trimethylsilyl group or a t-butyldimethylsilyl group; a hydroxyl group; Straight chain or branched C1-C6 alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group; for example, tri (linear or linear) such as trimethylsilyloxy group and t-butyldimethylsilyloxy group Branched C1-C6 alkyl) silyloxy group; for example, linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, linear chain such as methoxymethyl group, methoxyethyl group, ethoxyethyl group Or a branched (C1-C6 alkoxy)-(C1-C6 alkyl) group; carboxy Or a metal salt thereof; a halogen atom; a nitro group; a phenyl group; a phenoxy group; a substituent such as a heteroaryl group such as a pyridyl group, a thienyl group, or a furanyl group. ).

Specific examples of the 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) that can be used in this reaction include 2-benzylidene-6-chlorocyclohexanone, 2- (2-methylbenzylidene)- 6-chlorocyclohexanone, 2- (2-ethylbenzylidene) -6-chlorocyclohexanone, 2- (2-n-propylbenzylidene) -6-chlorocyclohexanone, 2- (2-i-propylbenzylidene) -6-chlorocyclohexanone 2- (2-n-butylbenzylidene) -6-chlorocyclohexanone, 2- (2-n-hexylbenzylidene) -6-chlorocyclohexanone, 2- (2-cyclohexylbenzylidene) -6-chlorocyclohexanone, 2- (2-Phenylbenzylidene) -6-chlorocyclohex Non, 2- (2-benzylbenzylidene) -6-chlorocyclohexanone, 2- (2-pyridylbenzylidene) -6-chlorocyclohexanone; 2- (2-thienylbenzylidene) -6-chlorocyclohexanone, 2- (2-furyl) Benzylidene) -6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -6-chlorocyclohexanone, 2- (2-ethoxybenzylidene) -6-chlorocyclohexanone, 2- (2-n-propoxybenzylidene) -6-chloro Cyclohexanone, 2- (2-i-propoxybenzylidene) -6-chlorocyclohexanone, 2- (2-n-butoxybenzylidene) -6-chlorocyclohexanone, 2- (2-n-hexyloxybenzylidene) -6-chloro Cyclohexanone, 2- (2-cycl Hexyloxybenzylidene) -6-chlorocyclohexanone, 2- (2-phenoxybenzylidene) -6-chlorocyclohexanone; 2- (2-benzyloxybenzylidene) -6-chlorocyclohexanone, 2- (3-methylbenzylidene) -6 -Chlorocyclohexanone, 2- (3-ethylbenzylidene) -6-chlorocyclohexanone, 2- (3-n-propylbenzylidene) -6-chlorocyclohexanone, 2- (3-i-propylbenzylidene) -6-chlorocyclohexanone, 2- (3-n-butylbenzylidene) -6-chlorocyclohexanone, 2- (3-n-hexylbenzylidene) -6-chlorocyclohexanone, 2- (3-cyclohexylbenzylidene) -6-chlorocyclohexanone, 2 -(3-Phenylbenzili Den) -6-chlorocyclohexanone, 2- (3-benzylbenzylidene) -6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -6-chlorocyclohexanone, 2- (3-ethoxybenzylidene) -6-chlorocyclohexanone, 2- (3-n-propoxybenzylidene) -6-chlorocyclohexanone, 2- (3-i-propoxybenzylidene) -6-chlorocyclohexanone, 2- (3-n-butoxybenzylidene) -6-chlorocyclohexanone, 2- (3-n-hexyloxybenzylidene) -6-chlorocyclohexanone, 2- (3-cyclohexyloxybenzylidene) -6-chlorocyclohexanone, 2- (3-phenoxybenzylidene) -6-chlorocyclohexanone, 2- ( 3-Benzyloxybenzili ) -6-chlorocyclohexanone, 2- (4-methylbenzylidene) -6-chlorocyclohexanone, 2- (4-ethylbenzylidene) -6-chlorocyclohexanone, 2- (4-n-propylbenzylidene) -6-chloro Cyclohexanone, 2- (4-i-propylbenzylidene) -6-chlorocyclohexanone, 2- (4-n-butylbenzylidene) -6-chlorocyclohexanone, 2- (4-n-hexylbenzylidene) -6-chlorocyclohexanone 2- (4-cyclohexylbenzylidene) -6-chlorocyclohexanone, 2- (4-phenylbenzylidene) -6-chlorocyclohexanone, 2- (4-benzylbenzylidene) -6-chlorocyclohexanone, 2- (4- Methoxybenzylidene) -6-chlorocyclohexa 2- (4-ethoxybenzylidene) -6-chlorocyclohexanone, 2- (4-n-propoxybenzylidene) -6-chlorocyclohexanone, 2- (4-i-propoxybenzylidene) -6-chlorocyclohexanone, 2- (4-n-butoxybenzylidene) -6-chlorocyclohexanone, 2- (4-n-hexyloxybenzylidene) -6-chlorocyclohexanone, 2- (4-cyclohexyloxybenzylidene) -6-chlorocyclohexanone, 2 -(4-phenoxybenzylidene) -6-chlorocyclohexanone, 2- (4-benzyloxybenzylidene) -6-chlorocyclohexanone, 2- (4-methylthiobenzylidene) -6-chlorocyclohexanone, 2- (4-ethylthiobenzylidene) ) -6-Chlorocyclohex Sanone, 2- (4-n-propylthiobenzylidene) -6-chlorocyclohexanone, 2- (4-i-propylthiobenzylidene) -6-chlorocyclohexanone, 2- (4-n-butylthiobenzylidene) -6 Chlorocyclohexanone, 2- (4-i-butylthiobenzylidene) -6-chlorocyclohexanone, 2- (2 ′, 3-dimethylbenzylidene) -6-chlorocyclohexanone, 2- (2 ′, 4-dimethylbenzylidene) -6 -Chlorocyclohexanone, 2- (2 ', 6-dimethylbenzylidene) -6-chlorocyclohexanone, 2- (3', 4-dimethylbenzylidene) -6-chlorocyclohexanone, 2- (3 ', 4-dimethylbenzylidene)- 6-chlorocyclohexanone, 2- (2 ′, 3-dimethoxybenzylidene) -6-chloro Cyclohexanone, 2- (2 ′, 4-dimethoxybenzylidene) -6-chlorocyclohexanone, 2- (2 ′, 6-dimethoxybenzylidene) -6-chlorocyclohexanone, 2- (3,4-dimethoxybenzylidene) -6-chloro Cyclohexanone, 2- (3,4-dimethoxybenzylidene) -6-chlorocyclohexanone, 2-benzylidene-3-methyl-6-chlorocyclohexanone, 2-benzylidene-4-methyl-6-chlorocyclohexanone, 2-benzylidene-5 Methyl-6-chlorocyclohexanone, 2-benzylidene-6-chloro-6-methylcyclohexanone, 2-benzylidene-3-ethyl-6-chlorocyclohexanone, 2-benzylidene-4-ethyl-6-chlorocyclohexanone, 2-benzylidene- 5-Eth Lucyclohexanone, 2-benzylidene-3-cyclopentylcyclohexanone, 2-benzylidene-4-cyclopentylcyclo-6-chlorohexanone, 2-benzylidene-5-cyclopentyl-6-chlorocyclohexanone, 2-benzylidene-3-cyclohexyl-6-chloro Cyclohexanone, 2-benzylidene-4-cyclohexyl-6-chlorocyclohexanone, 2-benzylidene-5-cyclohexyl-6-chlorocyclohexanone, 2-benzylidene-3-trimethylsilyl-6-chlorocyclohexanone, 2-benzylidene-4-trimethylsilyl-6 -Chlorocyclohexanone, 2-benzylidene-5-trimethylsilyl-6-chlorocyclohexanone, 2-benzylidene-3-methoxy-6-chlorocyclohexanone 2-benzylidene-4-methoxy-6-chlorocyclohexanone, 2-benzylidene-5-methoxy-6-chlorocyclohexanone, 2-benzylidene-3-trimethylsilyloxy-6-chlorocyclohexanone, 2-benzylidene-4-trimethylsilyloxy -6-chlorocyclohexanone, 2-benzylidene-5-trimethylsilyloxy-6-chlorocyclohexanone, 2-benzylidene-3-hydroxymethyl-6-chlorocyclohexanone, 2-benzylidene-4-hydroxymethyl-6-chlorocyclohexanone, 2 -Benzylidene-5-hydroxymethyl-6-chlorocyclohexanone, 2-benzylidene-3-methoxymethyl-6-chlorocyclohexanone, 2-benzylidene-4-methoxymethyl-6-chlorocyclohex Non, 2-benzylidene-5-methoxymethyl-6-chlorocyclohexanone, 2-benzylidene-3-phenyl-6-chlorocyclohexanone, 2-benzylidene-4-phenyl-6-chlorocyclohexanone, 2-benzylidene-5-phenyl- 6-chlorocyclohexanone, 2-benzylidene-3-phenoxy-6-chlorocyclohexanone, 2-benzylidene-4-phenoxy-6-chlorocyclohexanone, 2-benzylidene-5-phenoxy-6-chlorocyclohexanone, 2-benzylidene-3- Pyridyl-6-chlorocyclohexanone, 2-benzylidene-4-pyridyl-6-chlorocyclohexanone, 2-benzylidene-5-pyridyl-6-chlorocyclohexanone, 2-benzylidene-3-thienyl-6-chlorocyclo Hexanone, 2-benzylidene-4-thienyl-6-chlorocyclohexanone, 2-benzylidene-5-thienyl-6-chlorocyclohexanone, 2-benzylidene-3-furanyl-6-chlorocyclohexanone, 2-benzylidene-4-furanyl-6 -Chlorocyclohexanone, 2-benzylidene-5-furanyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-methylcyclo-6-chlorohexanone, 2- (2-methoxybenzylidene) -4-methyl-6- Chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-methyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-ethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4- Ethyl-6-chlorosi Lohexanone, 2- (2-methoxybenzylidene) -5-ethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-cyclopentyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-cyclopentyl -6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-cyclopentyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-cyclohexyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-cyclohexyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-cyclohexyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-trimethylsilyl-6-chlorocyclohexanone, -(2-methoxybenzylidene-4-trimethylsilyl-6-chlorocyclohexanone, 2- (2-methoxy) benzylidene) -5-trimethylsilyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-methoxy-6- Chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-methoxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-methoxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3- Trimethylsilyloxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-trimethylsilyloxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-trimethylsilyloxy-6-chlorocyclohexanone, 2 -(2 -Methoxybenzylidene) -3-hydroxymethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-hydroxymethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-hydroxymethyl-6 Chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-methoxymethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-methoxymethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene)- 5-methoxymethyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-phenyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-phenyl-6-chlorocyclohexanone, 2- (2 -Methoxybenz Den) -5-phenyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-phenoxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-phenoxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-phenoxy-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-pyridyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-pyridyl-6-chloro Cyclohexanone, 2- (2-methoxybenzylidene) -5-pyridyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-thienyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-thienyl -6-chlorocyclohexanone, -(2-methoxybenzylidene) -5-thienyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -3-furanyl-6-chlorocyclohexanone, 2- (2-methoxybenzylidene) -4-furanyl-6 Chlorocyclohexanone, 2- (2-methoxybenzylidene) -5-furanylcyclo-6-chlorohexanone; 2- (3-methoxybenzylidene) -3-methyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4- Methyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-methyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-ethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene ) -4-Ethyl-6-chlorocyclohex Non, 2- (3-methoxybenzylidene) -5-ethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-cyclopentyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-cyclopentyl -6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-cyclopentyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-cyclohexyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-cyclohexyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-cyclohexyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-trimethylsilyl-6-chlorocyclohexanone, 2- (3 − Methoxybenzylidene) -4-trimethylsilyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-trimethylsilyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-methoxy-6-chlorocyclohexanone, 2 -(3-methoxybenzylidene) -4-methoxy-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-methoxy-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-trimethylsilyloxy- 6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-trimethylsilyloxy-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-trimethylsilyloxy-6-chlorocyclohexanone, 2- (3- Metoki Benzylidene) -3-hydroxymethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-hydroxymethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5-hydroxymethyl-6-chlorocyclohexanone 2- (3-methoxybenzylidene) -3-methoxymethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-methoxymethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -5 Methoxymethyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-phenyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-phenyl-6-chlorocyclohexanone, 2- (3-methoxy Benzylidene) 5-phenyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-phenoxy-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-phenoxy-6-chlorocyclohexanone, 2- (3- Methoxybenzylidene) -5-phenoxy-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-pyridyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-pyridyl-6-chlorocyclohexanone, 2 -(3-methoxybenzylidene) -5-pyridyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-thienyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-thienyl-6 Chlorocyclohexanone, 2- (3- Methoxybenzylidene) -5-thienyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -3-furanyl-6-chlorocyclohexanone, 2- (3-methoxybenzylidene) -4-furanyl-6-chlorocyclohexanone, 2 -(3-methoxybenzylidene) -5-furanyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-methyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-methyl-6- Chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-methyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-ethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4- Ethyl-6-chlorocyclohexanone, 2 (4-methoxybenzylidene) -5-ethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-cyclopentyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-cyclopentyl-6-chloro Cyclohexanone, 2- (4-methoxybenzylidene) -5-cyclopentyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-cyclohexyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-cyclohexyl -6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-cyclohexyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-trimethylsilyl-6-chlorocyclohexanone, 2- (4-methoxy Benzylidene) -4-trimethylsilyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-trimethylsilyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-methoxy-6-chlorocyclohexanone, 2- (4-Methoxybenzylidene) -4-methoxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-methoxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-trimethylsilyloxy-6 -Chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-trimethylsilyloxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-trimethylsilyloxy-6-chlorocyclohexanone, 2- (4-methoxy Benjiri Den) -3-hydroxymethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-hydroxymethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-hydroxymethyl-6-chlorocyclohexanone 2- (4-methoxybenzylidene) -3-methoxymethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-methoxymethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5 Methoxymethyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-phenyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-phenyl-6-chlorocyclohexanone, 2- (4-methoxy Benzylidene) -5-Fe 6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-phenoxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-phenoxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) ) -5-phenoxy-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-pyridyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-pyridyl-6-chlorocyclohexanone, 2- ( 4-methoxybenzylidene) -5-pyridyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-thienyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-thienyl-6-chlorocyclohexanone , 2- (4-Methoxy Benzylidene) -5-thienyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -3-furanyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -4-furanyl-6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -5-furanyl-6-chlorocyclohexanone, 2- (2-fluorobenzylidene) -6-chlorocyclohexanone, 2- (3-fluorobenzylidene) -6-chlorocyclohexanone, 2- (4-fluoro Benzylidene) -6-chlorocyclohexanone, 2- (2-chlorobenzylidene) -6-chlorocyclohexanone, 2- (3-chlorobenzylidene) -6-chlorocyclohexanone, 2- (4-chlorobenzylidene) -6-chlorocyclohexanone, 2- (2-Bromo Benzylidene) -6-chlorocyclohexanone, 2- (3-bromobenzylidene) -6-chlorocyclohexanone, 2- (4-bromobenzylidene) -6-chlorocyclohexanone, 2- (2-iodobenzylidene) -6-chlorocyclohexanone, 2- (3-iodobenzylidene) -6-chlorocyclohexanone, 2- (4-iodobenzylidene) -6-chlorocyclohexanone, 2- (2-nitrobenzylidene) -6-chlorocyclohexanone, 2- (3-nitrobenzylidene) -6-chlorocyclohexanone, 2- (4-nitrobenzylidene) -6-chlorocyclohexanone, 2- (2-vinylbenzylidene) -6-chlorocyclohexanone, 2- (3-vinylbenzylidene) -6-chlorocyclohexanone, 2- (4-vinyl benze Den) -6-chlorocyclohexanone, 2- (2-ethynylbenzylidene) -6-chlorocyclohexanone, 2- (3-ethynylbenzylidene) -6-chlorocyclohexanone, 2- (4-ethynylbenzylidene) -6-chlorocyclohexanone, etc. And a compound (6-bromocyclohexanone compound) in which the chloro group (6-chloro) at the 6-position of these compounds is replaced by a bromo group (6-bromocyclohexanone compound), preferably 2-benzylidene- 6-chlorocyclohexanone, 2- (4-methylbenzylidene) -6-chlorocyclohexanone, 2- (4-chlorobenzylidene) -6-chlorocyclohexanone, 2- (4-methoxybenzylidene) -6-chlorocyclohexanone, 2- ( 4-Fluorobenzylidene) -6-chlorocycle And the like can be given hexanone.

  Subsequently, this reaction will be described.

  Any dehydrohalogenating agent used in this reaction may be used as long as it can be dehydrohalogenated from the 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1). For example, lithium salt and acetate can be exemplified.

  Therefore, specific examples of the dehydrochlorinating agent that can be used in this reaction include lithium salts such as lithium chloride, lithium bromide, lithium fluoride, lithium iodide, lithium carbonate, lithium sulfate; lithium acetate, sodium acetate. And acetates such as potassium acetate and cesium acetate. These dehydrohalogenating agents may be used alone or in an arbitrary ratio.

  These dehydrohalogenating agents are known compounds.

  In this reaction, the molar ratio of the dehydrohalogenating agent used is any molar ratio relative to the 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1). The dehydrohalogenating agent is in the range of 0.1 to 100.0 mol, preferably 1.0 to 10.0 mol, relative to 1 mol of the 2-benzylidene-6-halocyclohexanone compound represented by (1). More preferably, the range of 1.5-5.0 mol can be illustrated.

  This reaction is preferably carried out using a solvent so that the reaction proceeds smoothly. The solvent that can be used in this reaction is not particularly limited as long as it does not inhibit the reaction. Examples thereof include amides such as dimethylformamide and dimethylacetamide; ethers such as phenyl ether and anisole; aromatic hydrocarbons such as mesitylene and xylene. Alcohols such as 2-ethyl-1-hexanol and ethylene glycol; aprotic polar solvents such as tetramethylurea, hexamethylphosphoric triamide (HMPA) and propylene carbonate; aliphatics such as pentane and n-hexane Hydrocarbons; aromatic nitro compounds such as nitrobenzene and 4-nitrotoluene; aromatic halogen compounds such as chlorobenzene and o-dichlorobenzene. Preferably, amides such as dimethylformamide and dimethylacetamide are used, and dimethylformamide is particularly preferable as a solvent. A solvent can be used individually or as a mixed solvent of arbitrary mixing ratios.

  The amount of the solvent may be an amount that can sufficiently stir the reaction system. Usually, the amount of the solvent is 0.05 with respect to 1 mol of the 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1). It may be in the range of -10 l, preferably 0.5-2 l.

  Although the reaction temperature of this reaction can illustrate the range of 0 degreeC-the reflux temperature of the solvent to be used, Preferably it is the range of 100 degreeC-280 degreeC, More preferably, the range of 150 degreeC-200 degreeC is good.

  The reaction time of this reaction is not particularly limited, but preferably 1 hour to 30 hours from the viewpoint of byproduct suppression.

  According to this reaction, a 2-benzylphenol compound represented by the general formula (2) is produced with high selectivity under mild conditions without using a special reaction apparatus. The obtained 2-benzylphenol compound represented by the general formula (2) is a useful compound as an intermediate raw material for medical and agricultural chemicals.

  The 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) used in the method of the present invention is a known compound or, for example, an α-halocyclohexanone compound represented by the general formula (3) And a benzaldehyde compound represented by the general formula (4) can be easily obtained by condensation in the presence of an acid catalyst.

  The α-halocyclohexanone compound represented by the general formula (3) will be described.

R ₁ , R ₂ , R ₃ , R ₄ in the general formula (3) have the same meaning as described above. Specific examples of the α-halocyclohexanones represented by the general formula (3) that can be used in the condensation reaction include α-chlorocyclohexanone, 2-chloro-2-methylcyclohexanone, and 2-chloro-3-methyl. Cyclohexanone, 2-chloro-4-methylhecycloxanone, 2-chloro-5-methylhecycloxanone, 2-chloro-2-ethylcyclohexanone, 2-chloro-3-ethylcyclohexanone, 2-chloro-4- Ethylcyclohexanone, 2-chloro-5-ethylcyclohexanone, 2-chloro-2-cyclopentylcyclohexanone, 2-chloro-3-cyclopentylcyclohexanone, 2-chloro-4-cyclopentylcyclohexanone, 2-chloro-5-cyclopentylcyclohexanone, 2- Chloro-2-cyclohexyl Cyclohexanone, 2-chloro-3-cyclohexylcyclohexanone, 2-chloro-4-cyclohexylcyclohexanone, 2-chloro-5-cyclohexylcyclohexanone, 2-chloro-2-trimethylsilylcyclohexanone, 2-chloro-3-trimethylsilylcyclohexanone, 2-chloro -4-trimethylsilylcyclohexanone, 2-chloro-5-trimethylsilylcyclohexanone, 2-chloro-2-methoxycyclohexanone, 2-chloro-3-methoxycyclohexanone, 2-chloro-4-methoxycyclohexanone, 2-chloro-5-methoxycyclohexanone 2-chloro-2-trimethylsilyloxycyclohexanone, 2-chloro-3-trimethylsilyloxycyclohexanone, 2-chloro-4-trimethyl Loxycyclohexanone, 2-chloro-5-trimethylsilyloxycyclohexanone, 2-chloro-2-hydroxymethylcyclohexanone, 2-chloro-3-hydroxymethylcyclohexanone, 2-chloro-4-hydroxymethylcyclohexanone, 2-chloro-5- Hydroxymethylcyclohexanone, 2-chloro-2-methoxymethylcyclohexanone, 2-chloro-3-methoxymethylcyclohexanone, 2-chloro-4-methoxymethylcyclohexanone, 2-chloro-5-methoxymethylcyclohexanone, 2-chloro-2- Phenylcyclohexanone, 2-chloro-3-phenylcyclohexanone, 2-chloro-4-phenylcyclohexanone, 2-chloro-5-phenylcyclohexanone, 2-chloro-2-phenoxy Clohexanone, 2-chloro-3-phenoxycyclohexanone, 2-chloro-4-phenoxycyclohexanone, 2-chloro-5-phenoxycyclohexanone, 2-chloro-2-pyridylcyclohexanone, 2-chloro-3-pyridylcyclohexanone, 2- Chloro-4-pyridylcyclohexanone, 2-chloro-5-pyridylcyclohexanone, 2-chloro-2-thienylcyclohexanone, 2-chloro-3-thienylcyclohexanone, 2-chloro-4-thienylcyclohexanone, 2-chloro-5-thienyl Compounds such as cyclohexanone, 2-chloro-2-furanylcyclohexanone, 2-chloro-3-furanylcyclohexanone, 2-chloro-4-furanylcyclohexanone, 2-chloro-5-furanylcyclohexanone, and The (2-bromo) compound (2-bromocyclohexanone compound) in which the chloro group (2-chloro) at the α-position (the 2-position) is replaced with a bromo group can be exemplified, and these compounds include, for example, Linear or branched C1-C6 alkyl such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group, etc. Group: cyclic C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; for example, tri (linear or branched C1-C6 alkyl) silyl such as trimethylsilyl group, t-butyldimethylsilyl group A group; for example, a linear or branched C1-C6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group; , Tri (linear or branched C1-C6 alkyl) silyloxy group such as trimethylsilyloxy group, t-butyldimethylsilyloxy group; for example, linear or branched C1-C6 hydroxy such as hydroxymethyl group, hydroxyethyl group, etc. Alkyl group; for example, linear or branched (C1-C6 alkoxy)-(C1-C6 alkyl) group such as methoxymethyl group, methoxyethyl group, ethoxyethyl group; phenyl group; phenoxy group; pyridyl group, thienyl group, It may have a substituent such as a heteroaryl group such as a furanyl group; Preferred examples of the α-halocyclohexanone compound represented by the general formula (3) include compounds in which the α-position (the 2-position) is chloro. Specifically, for example, α-chlorocyclohexanone, α -Chloro-4-methylcyclohexanone, α-chloro-4-methoxycyclohexanone and the like can be mentioned.

  Subsequently, the benzaldehyde compound represented by the general formula (4) will be described.

R ₅ , R ₆ , R ₇ , R ₈ , R ₉ in the general formula (4) have the same meaning as described above. Specific examples of the benzaldehyde compound represented by the general formula (4) that can be used in the condensation reaction include benzaldehyde, 2-methylbenzaldehyde, 3-methylbenzaldehyde, 4-methylbenzaldehyde, 2-ethylbenzaldehyde, 3- Ethylbenzaldehyde, 4-ethylbenzaldehyde, 2-cyclopentylbenzaldehyde, 3-cyclopentylbenzaldehyde, 4-cyclopentylbenzaldehyde, 2-cyclohexylbenzaldehyde, 3-cyclohexylbenzaldehyde, 4-cyclohexylbenzaldehyde, 2-trimethylsilylbenzaldehyde, 3-trimethylsilylbenzaldehyde, 4- Trimethylsilylbenzaldehyde, 2-hydroxybenzaldehyde, 3-hydroxybenzal Hydride, 4-hydroxybenzaldehyde, 2-methoxybenzaldehyde, 3-methoxybenzaldehyde, 4-methoxybenzaldehyde, 2-trimethylsilyloxybenzaldehyde, 3-trimethylsilyloxybenzaldehyde, 4-trimethylsilyloxybenzaldehyde, 2-hydroxymethylbenzaldehyde, 3 -Hydroxymethylbenzaldehyde, 4-hydroxymethylbenzaldehyde, 2-methoxymethylbenzaldehyde, 3-methoxymethylbenzaldehyde, 4-methoxymethylbenzaldehyde, 2-phenylbenzaldehyde, 3-phenylbenzaldehyde, 4-phenylbenzaldehyde, 2-phenoxybenzaldehyde, 3 -Phenoxybenzaldehyde, 4-phenoxybenzaldehyde, 2 Pyridylbenzaldehyde, 3-pyridylbenzaldehyde, 4-pyridylbenzaldehyde, 2-thienylbenzaldehyde, 3-thienylbenzaldehyde, 4-thienylbenzaldehyde, 2-furanylbenzaldehyde, 3-furanylbenzaldehyde, 4-furanylbenzaldehyde, 2-fluorobenzaldehyde 3-fluorobenzaldehyde, 4-fluorobenzaldehyde, 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-iodobenzaldehyde, 3-iodobenzaldehyde 4-iodobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4 -Nitrobenzaldehyde, 2-vinylbenzaldehyde, 3-vinylbenzaldehyde, 4-vinylbenzaldehyde, 2-ethynylbenzaldehyde, 3-benzaldehyde, 4-ethynylbenzaldehyde and the like, and these compounds include, for example, methyl group A linear or branched C1-C6 alkyl group such as ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n-hexyl group; Cyclic C1-C6 alkyl groups such as propyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; for example, tri (linear or branched C1-C6 alkyl) silyl group such as trimethylsilyl group, t-butyldimethylsilyl group; , Methoxy group, ethoxy group, n-propoxy A linear or branched C1-C6 alkoxy group such as a group or an isopropoxy group; for example, a tri (linear or branched C1-C6 alkyl) silyloxy group such as a trimethylsilyloxy group or a t-butyldimethylsilyloxy group; A linear or branched C1-C6 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group; for example, a linear or branched (C1-C6 alkoxy)-(such as methoxymethyl group, methoxyethyl group, ethoxyethyl group)-( C1-C6 alkyl) group; phenyl group; phenoxy group; heteroaryl group such as pyridyl group, thienyl group, furanyl group; Preferred examples of the benzaldehyde compound represented by the general formula (4) include benzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde, 4-chlorobenzaldehyde, and 4-fluorobenzaldehyde.

  The α-halocyclohexanone compound represented by the general formula (3) and the benzaldehyde compound represented by the general formula (4) are known compounds, or compounds that can be produced by a known method or a method analogous thereto. It is.

  In this condensation reaction, the reaction proceeds at any molar ratio of the α-halocyclohexanone compound represented by the general formula (3) and the benzaldehyde compound represented by the general formula (4). The benzaldehyde represented by the general formula (4) is 0.1 to 10.0 mol, preferably 0.33 to 3.0 mol per 1 mol of the α-halocyclohexanone represented by the formula (3). The range of can be illustrated.

  Subsequently, the acid catalyst used in this reaction will be described.

Specific examples of the base that can be used in the condensation reaction include organic sulfonic acids such as p-toluenesulfonic acid, methanesulfonic acid, and benzenesulfonic acid; acetic acid, propionic acid, trifluoroacetic acid, fluoro Organic acids typified by carboxylic acids such as acetic acid, lactic acid and amino acids; inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid; Lewis such as aluminum chloride, boron trifluoride-tetrahydrofuran complex (BF ₃ -THF complex) and polyphosphoric acid In addition, solid acids and the like can be exemplified, but it is preferable to use an organic sulfonic acid such as p-toluenesulfonic acid, methanesulfonic acid, and benzenesulfonic acid. It is particularly preferable to use it.

  The molar ratio of the base used in this reaction is usually in the range of 0.01 to 5.0 mol, preferably 0.1 to 3.0 mol, with respect to 1 mol of the raw material compound represented by the general formula (3). Can be illustrated.

  This condensation reaction can be sufficiently performed without a solvent, but can also be performed using a solvent. Solvents that can be used for this reaction are not particularly limited as long as they do not inhibit the reaction. For example, water; aromatic hydrocarbons such as toluene, xylene and chlorobenzene; nitriles such as acetonitrile and propionitrile; methanol, ethanol, Alcohols such as ethylene glycol; Amides such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone; Aprotic polar solvents such as tetramethylurea, hexamethylphosphoric triamide (HMPA), propylene carbonate; Dichloromethane, chloroform Halogenated aliphatic hydrocarbons such as ether ether solvents such as diethyl ether, tetrahydrofuran and dioxane; and aliphatic hydrocarbons such as pentane and n-hexane. From the viewpoint of reactivity, aromatic hydrocarbons such as toluene, xylene and chlorobenzene are preferably used, and toluene is particularly preferable. A solvent can be used individually or as a mixed solvent of arbitrary mixing ratios.

  The amount of the solvent may be an amount that can sufficiently stir the reaction system. Usually, the amount of the solvent is 0.05 to 10 l, preferably 0. It may be in the range of 5 to 2 l.

  Although the reaction temperature of this condensation reaction can illustrate the range of 0 degreeC-the reflux temperature of the solvent to be used, Preferably the range of 100 to 115 degreeC is good.

  Although the reaction time of the condensation reaction is not particularly limited, it is preferably 1 hour to 100 hours from the viewpoint of suppressing by-products.

  Next, although the Example is given and the manufacturing method of this invention compound is demonstrated concretely, this invention is not limited at all by these Examples.

Example 1: Production of 2-benzylidene-6-chlorocyclohexanone Into a 50 ml eggplant-shaped flask equipped with a mechanical stirrer, Dean-Stark ring, reflux tube, 1.38 g (13 mmol) of benzaldehyde, 5.15 g (39 mmol) of α-chlorocyclohexanone. ), 0.2 g (1.2 mmol) of p-toluenesulfonic acid, and then 20 ml of toluene were added, and the mixture was stirred at reflux for 9 hours. After cooling to room temperature, toluene was distilled off under reduced pressure to obtain 5.76 g of a dark red oil. The purity of the desired product in this oil was 59.9% by high performance liquid chromatography. This was used in the next step without purification.

Example 2: Production of 2-benzylphenol Into a 50 ml eggplant type flask equipped with a magnetic stirrer and a reflux tube, 5.76 g of crude 2-benzylidene-6-chlorocyclohexanone prepared in Example 1, 1.1 g of lithium chloride ( 26 mmol) and then 13 ml of dimethylformamide were added and the mixture was stirred at 160 ° C. for 6 hours. After cooling to room temperature, 50 ml of water and 30 ml of toluene were added to the system for liquid separation, and the aqueous phase was further extracted with 20 ml of toluene. The toluene phases were combined and extracted twice with 60 ml of 10% aqueous sodium hydroxide. Next, 35% hydrochloric acid was added to the aqueous phase until the system became acidic, followed by extraction with 30 ml of ethyl acetate. The ethyl acetate phase was washed with water and then with saturated brine. The ethyl acetate phase was dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off under reduced pressure. 1.1 g of red oil was obtained. The target product in this oil contained 0.73 g when analyzed by the internal standard method using high performance liquid chromatography. The yield based on benzaldehyde was 30.3%.

Example 3: Preparation of 2- (4-chlorobenzylidene) -6-chlorocyclohexanone In a 100 ml four-necked flask equipped with a mechanical stirrer, Dean-Stark ring, reflux tube and thermometer, 5.6 g of p-chlorobenzaldehyde ( 40 mmol), 15.9 g (120 mmol) of α-chlorocyclohexanone, 0.6 g (3.5 mmol) of p-toluenesulfonic acid and then 50 ml of toluene were added, and the mixture was stirred at reflux for 6 hours. After cooling to room temperature, toluene was distilled off under reduced pressure to obtain 19.3 g of black-red oil. The purity of the desired product in this oil was 52.3% by high performance liquid chromatography. This was used in the next step without purification.

Example 4: Preparation of 2- (4-chlorobenzyl) phenol Crude 2- (4-chlorobenzylidene) -6-chlorocyclohexanone prepared in Example 3 in a 50 ml eggplant-shaped flask equipped with a magnetic stirrer and reflux tube 5.0 g, 0.85 g (20 mmol) of lithium chloride and then 10 ml of dimethylformamide were added, and the mixture was stirred at 160 ° C. for 4 hours. After cooling to room temperature, 50 ml of water and 50 ml of toluene were added to the system for liquid separation. The toluene phase was extracted with 100 ml of 10% aqueous sodium hydroxide, and the aqueous phase was further washed with toluene. Next, 35% hydrochloric acid was added to the aqueous phase until the system became acidic, followed by extraction with 30 ml of ethyl acetate. The ethyl acetate phase was washed with water and then with saturated brine. The ethyl acetate phase was dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off under reduced pressure. 0.4 g of red crystals was obtained. The desired product in the crystals was 68.6% by high performance liquid chromatography.

Example 5: Preparation of 2- (4-chlorobenzyl) phenol The crude 2- (4-chlorobenzylidene) -6-chloro prepared in Example 3 was placed in a 10 ml test tube flask equipped with a magnetic stirrer and reflux tube. 1.0 g of cyclohexanone, 0.55 g (4 mmol) of sodium acetate trihydrate and 2 ml of dimethylformamide were added, and the mixture was stirred at 155 ° C. for 3 hours. The desired product in this reaction solution was 20.3% by high performance liquid chromatography.

Example 6: Preparation of 2- (4-methoxybenzylidene) -6-chlorocyclohexanone In a 100 ml four-necked flask equipped with a mechanical stirrer, Dean-Stark ring, reflux tube and thermometer, 5.4 g of p-anisaldehyde ( 40 mmol), 15.9 g (120 mmol) of α-chlorocyclohexanone, 0.6 g (3.5 mmol) of p-toluenesulfonic acid and then 50 ml of toluene were added, and the mixture was stirred at reflux for 9 hours. The purity of the target product in this reaction solution was 69.0% by high performance liquid chromatography. This was used in the next step without purification after toluene was distilled off under reduced pressure.

Example 7: Preparation of 2- (4-methoxybenzyl) phenol The crude 2- (4-methoxybenzylidene) -6-chlorocyclohexanone prepared in Example 6 was added to a 50 ml eggplant-shaped flask equipped with a magnetic stirrer and a reflux tube. 6.0 g, 2.04 g (48 mmol) of lithium chloride, and then 12 ml of dimethylformamide were added and stirred at 160 ° C. for 5 hours. After cooling to room temperature, 50 ml of water and 50 ml of toluene were added to the system for liquid separation. The toluene phase was extracted twice with 50 ml of 10% aqueous sodium hydroxide solution, and the aqueous phase was further washed with toluene. Next, 35% hydrochloric acid was added to the aqueous phase until the system became acidic, followed by extraction with 50 ml of ethyl acetate. The ethyl acetate phase was washed with water and then with saturated brine. The ethyl acetate phase was dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off under reduced pressure. 0.5 g of red oil was obtained. The target product in the crystals was 71.0% by high performance liquid chromatography.

Example 8: Preparation of 2- (4-methoxybenzyl) phenol The crude 2- (4-methoxybenzylidene) -6-chlorocyclohexanone prepared in Example 6 was added to a 50 ml eggplant-shaped flask equipped with a magnetic stirrer and a reflux tube. 5.0 g, 2.96 g (40 mmol) of lithium carbonate, and then 30 ml of dimethylformamide were added, followed by stirring at 150 ° C. for 2 hours and further at 170 ° C. for 4 hours. After cooling to room temperature, 50 ml of water and 50 ml of ethyl acetate were added to the system for liquid separation. The ethyl acetate phase was washed with water and then with saturated brine. The ethyl acetate phase was dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off under reduced pressure. The desired product in this residue was 6.3% by high performance liquid chromatography.

Claims (8)

General formula (1)

(In the formula, X represents a halogen atom, and R ₁ , R ₂ , R ₃ and R ₄ may be the same or different, and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, or a trialkyl. A silyl group, an alkoxy group, a trialkylsilyloxy group, a hydroxyalkyl group, an alkoxyalkyl group, a carboxyl group or a metal salt thereof, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkylcarbonylamino group, a nitro group, or a substituent. A phenyl group, a phenoxy group, or a heteroaryl group which may have, and _{two of} R ₁ , R ₂ , R ₃ , and R ₄ may be bonded to form a ring; R ₅ , R _{6, R 7, R 8,} R 9 , which may be the same or different, each independently, a hydrogen atom, an alkyl group, a cyclic alkyl group, alkenyl Group, cyclic alkenyl group, alkynyl group, trialkylsilyl group, hydroxyl group, alkoxy group, trialkylsilyloxy group, hydroxyalkyl group, alkoxyalkyl group, carboxyl group or metal salt thereof, alkoxycarbonyl group, amino group, alkylamino A phenyl group, a phenoxy group, or a heteroaryl group which may have a group, an alkylcarbonylamino group, a halogen atom, a nitro group, or a substituent, and R ₅ , R ₆ , R ₇ , R ₈ , R Two of ₉ may combine to form a ring.)
A 2-benzylidene-6-halocyclohexanone compound represented by the general formula (2) is reacted in the presence of a dehydrohalogenating agent.

(In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)
The manufacturing method of 2-benzylphenol compound represented by these. General formula (3)

(In the formula, X represents a halogen atom, and R ₁ , R ₂ , R ₃ and R ₄ may be the same or different, and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, or a trialkyl. A silyl group, an alkoxy group, a trialkylsilyloxy group, a hydroxyalkyl group, an alkoxyalkyl group, a carboxyl group or a metal salt thereof, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkylcarbonylamino group, a nitro group, or a substituent. A phenyl group, a phenoxy group, or a heteroaryl group which may have, and _{two of} R ₁ , R ₂ , R ₃ and R ₄ may be bonded to form a ring.
An α-halocyclohexanone compound represented by the general formula (4)

(In the formula, R ₅ , R ₆ , R ₇ , R ₈ and R ₉ may be the same or different and each independently represents a hydrogen atom, an alkyl group, a cyclic alkyl group, an alkenyl group, or a cyclic alkenyl group. , Alkynyl group, trialkylsilyl group, hydroxyl group, alkoxy group, trialkylsilyloxy group, hydroxyalkyl group, alkoxyalkyl group, carboxyl group or metal salt thereof, alkoxycarbonyl group, amino group, alkylamino group, alkylcarbonylamino A phenyl group, a phenoxy group or a heteroaryl group which may have a group, a halogen atom, a nitro group, or a substituent, and two of R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are bonded To form a ring.)
The benzaldehyde compound represented by general formula (1) obtained by condensing in the presence of an acid catalyst.

(In the formula, X, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)
A 2-benzylidene-6-halocyclohexanone compound represented by formula (2) is dehydrohalogenated in the presence of a dehydrohalogenating agent:

(In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ have the same meaning as described above.)
The manufacturing method of 2-benzylphenol compound represented by these. The method for producing a 2-benzylphenol compound according to any one of claims 1 to 2, wherein the dehydrohalogenating agent is a lithium salt or an acetate salt. The method for producing a 2-benzylphenol compound according to any one of claims 1 to 2, wherein the dehydrohalogenating agent is lithium chloride, lithium carbonate, or sodium acetate. The method for producing a 2-benzylphenol compound according to any one of claims 1 to 4, wherein the dehydrohalogenation is performed in a temperature range of 100 to 200 ° C. The 2-benzylidene-6-halocyclohexanone compound represented by the general formula (1) is 2-benzylidene-6-chlorocyclohexanone, 2- (4-methylbenzylidene) -6-chlorocyclohexanone, 2- (4-chlorobenzylidene). 6) Chlorocyclohexanone, 2- (4-methoxybenzylidene) -6-chlorocyclohexanone, or 2- (4-fluorobenzylidene) -6-chlorocyclohexanone. The manufacturing method of 2-benzylphenol compound. The cyclohexanone compound represented by the general formula (3) is α-chlorocyclohexanone, α-chloro-4-methylcyclohexanone, or α-chloro-4-methoxycyclohexanone according to any one of claims 2 to 5. A method for producing a 2-benzylphenol compound. The benzaldehyde compound represented by the general formula (4) is benzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde, 4-chlorobenzaldehyde, or 4-fluorobenzaldehyde. The manufacturing method of 2-benzylphenol compound.