WO2018116836A1 - Method for producing polymerizable compound - Google Patents

Abstract

The purpose of the present invention is to provide a method for industrially advantageously producing a high-purity polymerizable compound. The method of the present invention is for producing a polymerizable compound represented by formula (I), and includes a step in which a composition containing a halogenated compound represented by formula (II) is subjected to a dehydrohalogenation reaction in an organic solvent in the presence of an aqueous layer containing a basic compound.

Description

Method for producing polymerizable compound

The present invention is a method for producing a polymerizable compound that can be used for the preparation of an optical film capable of uniform polarization conversion in a wide wavelength range.

A retardation plate used in various devices such as a flat panel display device includes a ¼ wavelength plate that converts linearly polarized light into circularly polarized light, a ½ wavelength plate that converts a polarization vibration plane of linearly polarized light by 90 degrees, and the like. There is. These retardation plates can accurately give a phase difference of 1 / 4λ or 1 / 2λ of a light wavelength to a specific monochromatic light.
However, the conventional retardation plate has a problem that polarized light output through the retardation plate is converted into colored polarized light. This is because the material constituting the retardation plate has wavelength dispersion with respect to the retardation, and distribution occurs in the polarization state for each wavelength for white light that is a composite wave in which light rays in the visible light range are mixed. This is because it is impossible to adjust the input light to polarization having a phase difference of 1 / 4λ or 1 / 2λ in all wavelength regions.
In order to solve such a problem, various studies have been made on a broadband retardation plate capable of giving a uniform retardation to light in a wide wavelength range, that is, a so-called reverse wavelength dispersion plate.

On the other hand, along with the advancement and widespread use of portable information terminals such as mobile personal computers and mobile phones, it has been required to keep the thickness of flat panel display devices as thin as possible. As a result, it is also required to reduce the thickness of the retardation plate that is a constituent member.
As a method for thinning, a method of producing a retardation plate by applying a polymerizable composition containing a low molecular weight polymerizable compound to a film substrate to form an optical film is the most effective method in recent years. It is said that. Therefore, many developments of a polymerizable compound capable of forming an optical film having excellent reverse wavelength dispersion or a polymerizable composition using the same are carried out.

For example, in Patent Document 1, it is possible to form an optical film excellent in reverse wavelength dispersion, and it is easy to apply to a substrate with a low melting point suitable for processing, and exhibit a liquid crystallinity. A polymerizable compound and a polymerizable composition that are widely available and can be synthesized at low cost have been proposed.
For example, Patent Document 2 proposes a polymerizable compound that exhibits a discotic nematic phase and is easy to manufacture.

International Publication No. 2014/010325 JP 2009-227667 A

Here, as a compound that gives an optical film excellent in performance such as reverse wavelength dispersion, the present inventors have the following formula (I):

[In formula (I), the meaning of symbols and subscripts indicating the chemical structure will be described later. The polymerizable compound represented by the formula ("polymerizable compound (I)") was noted. However, according to the study by the present inventors, it was sometimes difficult to produce the polymerizable compound in a sufficiently high yield even using a conventional production method. For example, when a desired polymerizable compound is prepared by a conventional production method, impurities in a halogen-containing compound used for the synthesis of the polymerizable compound, halogen-containing compounds mixed as impurities in other raw material compounds, or salts are associated with the reaction. Although it is presumed to be due to the influence of by-products generated in this way, it has been clarified by the present inventors that a halogenated form of a polymerizable compound may be produced.

The present invention has been made under such circumstances, and an object thereof is to provide a method for producing a highly pure polymerizable compound in an industrially advantageous manner.

The present inventors diligently studied to solve the above problems. As a result, the present inventors can dehydrohalogenate a halogenated product produced as a by-product at any stage of the synthesis process of the polymerizable compound (I), thereby allowing the polymerizable compound ( The idea was that the yield of I) could be increased. Further, as a result of further studies, the present inventors have selected a predetermined halogenated compound as the starting compound of the polymerizable compound (I) and obtained a dehydrohalogenation reaction with the halogenated compound. As a result, it was found that a polymerizable compound (I) having a small halogenated mixture ratio (ie, high purity) can be produced. And the present inventors came to complete this invention through these examinations.
Thus, according to the present invention, the following method for producing a polymerizable compound is provided.

[1] A method for producing a polymerizable compound represented by the following formula (I),
A production method comprising a step of subjecting a composition containing a halogenated compound represented by the following formula (II) to a dehydrohalogenation reaction in an organic solvent in the presence of an aqueous layer containing a basic compound.
[In the formula (I), Ar is any one of groups represented by the following formulas (Ar-1) to (Ar-4);

E ¹ and E ² each independently represent —CR ¹¹ R ¹² —, —S—, —NR ¹¹ —, —CO—, or —O—, and each of R ¹¹ and R ¹² independently represents Represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms,
Rc is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a carboxyl group, or a carbon group having 1 to 6 carbon atoms. Fluoroalkyl group, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, N, N-dialkylamino group having 2 to 12 carbon atoms, carbon number An N-alkylsulfamoyl group having 1 to 6 carbon atoms or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms;
p0 is an integer from 0 to 2,
D ¹ and D ² each independently represents an aromatic hydrocarbon ring group that may have a substituent, or an aromatic heterocyclic group that may have a substituent,
Z ¹ and Z ² are each independently a single bond, —O—CH ₂ —, —CH ₂ —O—, —C (═O) —O—, —O—C (═O) —, — C (═O) —S—, —S—C (═O) —, —NR ¹³ —C (═O) —, —C (═O) —NR ¹³ —, —CF ₂ —O—, —O —CF ₂ —, —CH ₂ —CH ₂ —, —CF ₂ —CF ₂ —, —O—CH ₂ —CH ₂ —O—, —CH═CH—C (═O) —O—, —O— _{C (= O) -CH = CH} -, - CH 2 -CH 2 -C (= O) -O -, - O-C (= O) -CH 2 -CH 2 -, - CH 2 -CH 2 - O—C (═O) —, —C (═O) —O—CH ₂ —CH ₂ —, —CH═CH—, —N═CH—, —CH═N—, —N═C (CH ₃ )-, -C (CH ₃ ) = N-, -N = N-, or -C≡C- R ¹³ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms,
A ¹ , A ² , B ¹ and B ² each independently represent a cyclic aliphatic group which may have a substituent, or an aromatic group which may have a substituent,
Y ¹ , Y ² , L ¹ and L ² are each independently a single bond, —O—, —CO—, —CO—O—, —O—CO—, —NR ¹⁴ —CO—, —CO —NR ¹⁴ —, —O—CO—O—, —NR ¹⁴ —CO—O—, —O—CO—NR ¹⁴ —, or —NR ¹⁴ —CO—NR ¹⁵ —, wherein R ¹⁴ and R ¹⁵ are Each independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
R ¹ and R ² each independently represents a hydrogen atom, a methyl group, or a chlorine atom,
a and d each independently represents an integer of 1 to 20,
b and c are each independently 0 or 1,
When a plurality of Rc are present, they may be the same or different. ]

[In Formula (II), X ¹ represents a halogen atom;
G represents an organic group,
R ¹ and a represent the same meaning as the formula (I). ]

[2] The production method according to [1], wherein the halide represented by the formula (II) is a halide represented by the following formula (III).

[In the formula (III), Q is represented by the following formula (III-1) or the following formula (III-2);

[In Formula (III-1) and Formula (III-2), R ² represents the same meaning as in Formula (I), and X ² in Formula (III-2) represents a halogen atom. ]
X ¹ represents the same meaning as in the formula (II),
Ar, Z ¹ , Z ² , A ¹ , A ² , B ¹ , B ² , Y ¹ , Y ² , L ¹ , L ² , R ¹ , and a to d have the same meaning as in the formula (I). To express. ]

[3] The production method according to [2], wherein X ¹ and X ² are chlorine atoms.

[4] The production method according to [1], wherein the halide represented by the formula (II) is a halide represented by the following formula (IV).

[In formula (IV), FG ¹ represents a hydroxyl group, a carboxyl group or an amino group,
R ¹ , Y ¹ , B ¹ and a represent the same meaning as in the formula (I),
X ¹ represents the same meaning as in the formula (II). ]

[5] The production method according to [4], wherein X ¹ is a chlorine atom.

[6] The production method according to [4] or [5], wherein the FG ¹ is a hydroxyl group.

[7] The production according to any one of [4] to [6], wherein the composition is a mixture containing a halide represented by the formula (IV) and a compound represented by the following formula (V): Method.

[In Formula (V), R ¹ , Y ¹ , B ¹ , FG ¹ and a represent the same meaning as in Formula (IV). ]

[8] The proportion of the halogenated compound represented by the formula (IV) in the total of the halogenated compound represented by the formula (IV) and the compound represented by the formula (V) is 0.01% by mass or more. The production method according to [7], which is 5% by mass or less.

[9] The production method according to [1], wherein the halide represented by the formula (II) is a halide represented by the following formula (VI).

[In Formula (VI), FG ² represents a hydroxyl group, a carboxyl group, or an amino group,
R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , a and b represent the same meaning as in the formula (I),
X ¹ represents the same meaning as in the formula (II). ]

[10] The production method according to [9], wherein X ¹ is a chlorine atom.

[11] The FG ² is a carboxyl group,
The production method according to [9] or [10], wherein b is 1.

[12] The production according to any one of [9] to [11], wherein the composition is a mixture containing a halide represented by the formula (VI) and a compound represented by the following formula (VII): Method.

[In the formula (VII), R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , FG ² , a and b represent the same meaning as in the formula (VI). ]

[13] The proportion of the halogenated compound represented by the formula (VI) in the total of the halogenated compound represented by the formula (VI) and the compound represented by the formula (VII) is 0.01% by mass or more. The production method according to [12], which is 5% by mass or less.

[14] Any one of [1] to [13], wherein D ¹ and D ² are each independently any one of groups represented by the following formulas (d-1) to (d-8): The manufacturing method as described in.

[In the formulas (d-1) to (d-8), Rd represents a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, 6 alkylsulfonyl groups, carboxyl groups, fluoroalkyl groups having 1 to 6 carbon atoms, alkoxy groups having 1 to 6 carbon atoms, thioalkyl groups having 1 to 6 carbon atoms, N-alkylamino groups having 1 to 6 carbon atoms, carbon An N, N-dialkylamino group having 2 to 12 carbon atoms, an N-alkylsulfamoyl group having 1 to 6 carbon atoms, or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms,
p1 is an integer from 0 to 5, p2 is an integer from 0 to 4, p3 is an integer from 0 to 3, and p4 is an integer from 0 to 2,
Rf represents a hydrogen atom or a methyl group,
When a plurality of Rd are present, they may be the same or different from each other. ]

[15] The production method according to any one of [1] to [13], wherein Ar is any one of groups represented by the following formulas (Ar-5) to (Ar-9).

[In the formulas (Ar-5) to (Ar-9), E ¹ , Rc, and p0 represent the same meaning as described above,
Rd is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a carboxyl group, or a carbon group having 1 to 6 carbon atoms. Fluoroalkyl group, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, N, N-dialkylamino group having 2 to 12 carbon atoms, carbon number An N-alkylsulfamoyl group having 1 to 6 carbon atoms or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms;
p1 represents an integer of 0 to 5, p2 represents an integer of 0 to 4, p3 represents an integer of 0 to 3,
When a plurality of Rc and Rd are present, they may be the same or different from each other. ]

According to the present invention, it is possible to provide a method for producing a highly pure polymerizable compound in an industrially advantageous manner.

Hereinafter, the present invention will be described in detail. In the present invention, “may have a substituent” means “unsubstituted or has a substituent”. In addition, when an organic group such as an alkyl group or aromatic hydrocarbon ring group contained in the general formula has a substituent, the number of carbons of the organic group having the substituent does not include the number of carbons of the substituent And For example, when the aromatic hydrocarbon ring group having 6 to 20 carbon atoms has a substituent, the carbon number of the aromatic hydrocarbon ring group having 6 to 20 carbon atoms does not include the carbon number of such a substituent. Shall.

Here, the method for producing a polymerizable compound of the present invention is used for producing the above-described polymerizable compound (I). More specifically, the method for producing a polymerizable compound of the present invention comprises a composition comprising a halogenated compound represented by formula (II) (“halogenated compound (II)”) dissolved in an organic solvent. A method for producing a polymerizable compound (I), comprising a step of subjecting to a dehydrohalogenation reaction in the presence of an aqueous layer containing at least one basic compound.

And according to the manufacturing method of the polymeric compound of this invention, the ratio of the halogenated body which occupies in the product finally obtained by dehydrohalogenating the halogenated substance (II) is reduced. The yield of the polymerizable compound (I) can be increased.
Therefore, according to the production method of the present invention, the highly pure polymerizable compound (I) can be advantageously produced industrially.

(1) Polymerizable compound (I)
Here, the polymerizable compound (I), which is a target product of the production method of the present invention, is a compound used for the production of an optical film. And if polymeric compound (I) is used, the optical film excellent in various characteristics, such as reverse wavelength dispersion, can be produced. The polymerizable compound (I) is a compound represented by the following formula (I).

In the formula (I), a and d are each independently an integer of 1 to 20, preferably an integer of 2 to 12, more preferably an integer of 4 to 8, and b and c are each Independently, 0 or 1, with 1 being preferred.

Ar is any one of groups represented by the following formulas (Ar-1) to (Ar-4).

Here, in the formulas (Ar-1) to (Ar-4), p0 is an integer of 0 to 2, and preferably 0 or 1.

Rc is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a carboxyl group, or a carbon group having 1 to 6 carbon atoms. Fluoroalkyl group, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, N, N-dialkylamino group having 2 to 12 carbon atoms, carbon number An N-alkylsulfamoyl group having 1 to 6 carbon atoms or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms is represented.
In each of the formulas (Ar-1) to (Ar-4), when there are a plurality of Rc (that is, when p0 is 2), the plurality of Rc may be the same or different from each other. May be.

Examples of the halogen atom for Rc include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Among these, a fluorine atom, a chlorine atom, and a bromine atom are preferable.

Examples of the alkyl group having 1 to 6 carbon atoms of Rc include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, and hexyl group. An alkyl group having 1 to 4 carbon atoms is preferable, and a tert-butyl group and a methyl group are particularly preferable. The alkyl group of Rc described above is preferably a chain alkyl group.

Examples of the alkylsulfinyl group having 1 to 6 carbon atoms of Rc include methylsulfinyl group, ethylsulfinyl group, propylsulfinyl group, isopropylsulfinyl group, butylsulfinyl group, isobutylsulfinyl group, sec-butylsulfinyl group, tert-butylsulfinyl group, Examples thereof include a pentylsulfinyl group and a hexylsulfinyl group. An alkylsulfinyl group having 1 to 4 carbon atoms is preferable, an alkylsulfinyl group having 1 to 2 carbon atoms is more preferable, and a methylsulfinyl group is particularly preferable.

Examples of the alkylsulfonyl group having 1 to 6 carbon atoms of Rc include methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylsulfonyl group, butylsulfonyl group, isobutylsulfonyl group, sec-butylsulfonyl group, tert-butylsulfonyl group, Examples thereof include a pentylsulfonyl group and a hexylsulfonyl group, preferably an alkylsulfonyl group having 1 to 4 carbon atoms, more preferably an alkylsulfonyl group having 1 to 2 carbon atoms, and particularly preferably a methylsulfonyl group.

Examples of the fluoroalkyl group having 1 to 6 carbon atoms of Rc include a fluoromethyl group, a trifluoromethyl group, a fluoroethyl group, a pentafluoroethyl group, a heptafluoropropyl group, a nonafluorobutyl group, and the like. A fluoroalkyl group having 4 carbon atoms is preferred, a fluoroalkyl group having 1 to 2 carbon atoms is more preferred, and a trifluoromethyl group is particularly preferred.

Examples of the alkoxy group having 1 to 6 carbon atoms of Rc include methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, etc. An alkoxy group having 1 to 4 carbon atoms is preferable, an alkoxy group having 1 to 2 carbon atoms is more preferable, and a methoxy group is particularly preferable.

Examples of the thioalkyl group having 1 to 6 carbon atoms of Rc include methylthio group, ethylthio group, propylthio group, isopropylthio group, butylthio group, isobutylthio group, sec-butylthio group, tert-butylthio group, pentylthio group, hexylthio group and the like. A thioalkyl group having 1 to 4 carbon atoms is preferable, a thioalkyl group having 1 to 2 carbon atoms is more preferable, and a methylthio group is particularly preferable.

Examples of the N-alkylamino group having 1 to 6 carbon atoms of Rc include N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino. Group, N-sec-butylamino group, N-tert-butylamino group, N-pentylamino group, N-hexylamino group, and the like. N-alkylamino group having 1 to 4 carbon atoms is preferable, One to two N-alkylamino groups are more preferred, and an N-methylamino group is particularly preferred.

Examples of the N, N-dialkylamino group having 2 to 12 carbon atoms of Rc include N, N-dimethylamino group, N-methyl-N-ethylamino group, N, N-diethylamino group, N, N-dipropylamino group Group, N, N-diisopropylamino group, N, N-dibutylamino group, N, N-diisobutylamino group, N, N-dipentylamino group, N, N-dihexylamino group, etc. An N, N-dialkylamino group having 8 carbon atoms is preferred, an N, N-dialkylamino group having 2 to 4 carbon atoms is more preferred, and an N, N-dimethylamino group is particularly preferred.

Examples of the N-alkylsulfamoyl group having 1 to 6 carbon atoms of Rc include N-methylsulfamoyl group, N-ethylsulfamoyl group, N-propylsulfamoyl group, N-isopropylsulfamoyl group, N-butylsulfamoyl group, N-isobutylsulfamoyl group, N-sec-butylsulfamoyl group, N-tert-butylsulfamoyl group, N-pentylsulfamoyl group, N-hexylsulfamoyl group A C 1-4 N-alkylsulfamoyl group is preferred, a C 1-2 N-alkylsulfamoyl group is more preferred, and an N-methylsulfamoyl group is particularly preferred.

Examples of the N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms of Rc include N, N-dimethylsulfamoyl group, N-methyl-N-ethylsulfamoyl group, N, N-diethylsulfamoyl group. Group, N, N-dipropylsulfamoyl group, N, N-diisopropylsulfamoyl group, N, N-dibutylsulfamoyl group, N, N-diisobutylsulfamoyl group, N, N-dipentylsulfamoyl Group, N, N-dihexylsulfamoyl group and the like, N, N-dialkylsulfamoyl group having 2 to 8 carbon atoms is preferable, and N, N-dialkylsulfamoyl group having 2 to 4 carbon atoms is preferable. More preferred is an N, N-dimethylsulfamoyl group.

Among the above, Rc is a halogen atom, tert-butyl group, methyl group, cyano group, nitro group, carboxyl group, methylsulfonyl group, trifluoromethyl group, methoxy group, methylthio group, N-methylamino group, N, N-dimethylamino group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, or methylsulfinyl group is preferable.

In formulas (Ar-1) to (Ar-4), E ¹ and E ² are each independently —CR ¹¹ R ¹² —, —S—, —NR ¹¹ —, —CO—, or —O—. R ¹¹ and R ¹² each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Examples of the alkyl group having 1 to 4 carbon atoms in R ¹¹ and R ¹² include methyl group, ethyl group, n-propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group and the like. An alkyl group having 1 to 2 carbon atoms is preferable, and a methyl group is more preferable.

E ¹ and E ² are preferably each independently —S—, —C (═O) —, —NH—, or —N (CH ₃ ) —.

In formulas (Ar-1) to (Ar-4), D ¹ and D ² each independently represents an aromatic hydrocarbon ring group which may have a substituent, or a substituent. Represents a good aromatic heterocyclic group.

Specifically, examples of the aromatic hydrocarbon ring group for D ¹ and D ² include a phenyl group, a naphthyl group, an anthracenyl group, a phenanthrenyl group, a pyrenyl group, and a fluorenyl group.
Among these, as the aromatic hydrocarbon ring group, a phenyl group and a naphthyl group are preferable.

Examples of the aromatic heterocyclic group of D ¹ and D ² include a phthalimide group, a 1-benzofuranyl group, a 2-benzofuranyl group, an acridinyl group, an isoquinolinyl group, an imidazolyl group, an indolinyl group, a furazanyl group, an oxazolyl group, Razinyl group, oxazolopyridinyl group, oxazolopyridazinyl group, oxazolopyrimidinyl group, quinazolinyl group, quinoxalinyl group, quinolyl group, cinnolinyl group, thiadiazolyl group, thiazolyl group, thiazolopyrazinyl group, thia Zolopyridyl group, thiazolopyridazinyl group, thiazolopyrimidinyl group, thienyl group, triazinyl group, triazolyl group, naphthyridinyl group, pyrazinyl group, pyrazolyl group, pyranonyl group, pyranyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, Pyrrolyl group, Fe Ntridinyl group, phthalazinyl group, furanyl group, benzo [c] thienyl group, benzoisoxazolyl group, benzisothiazolyl group, benzimidazolyl group, benzoxazolyl group, benzothiadiazolyl group, benzothiazolyl group, benzothienyl group Benzotriazinyl group, benzotriazolyl group, benzopyrazolyl group, benzopyranonyl group, dihydropyranyl group, tetrahydropyranyl group, dihydrofuranyl group, tetrahydrofuranyl group and the like.
Among these, aromatic heterocyclic groups include furanyl group, thienyl group, oxazolyl group, thiazolyl group, benzothiazolyl group, benzoxazolyl group, 1-benzofuranyl group, 2-benzofuranyl group, benzothienyl group, thiazolopyridyl group Groups are preferred.

The aromatic hydrocarbon ring group and aromatic heterocyclic group of D ¹ and D ² are a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, a carbon number 1-6 alkylsulfonyl groups, carboxyl groups, fluoroalkyl groups having 1-6 carbon atoms, alkoxy groups having 1-6 carbon atoms, thioalkyl groups having 1-6 carbon atoms, N-alkylamino groups having 1-6 carbon atoms Substituted with an N, N-dialkylamino group having 2 to 12 carbon atoms, an N-alkylsulfamoyl group having 1 to 6 carbon atoms, or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms. Also good.
In addition, the aromatic hydrocarbon ring group and the aromatic heterocyclic group may have one or more substituents selected from the above-described substituents. And when it has a some substituent, a plurality of substituents may mutually be same or different.

D ¹ and D ² substituent halogen atoms, alkyl groups having 1 to 6 carbon atoms, alkyl sulfinyl groups having 1 to 6 carbon atoms, alkylsulfonyl groups having 1 to 6 carbon atoms, fluoroalkyl groups having 1 to 6 carbon atoms An alkoxy group having 1 to 6 carbon atoms, a thioalkyl group having 1 to 6 carbon atoms, an N-alkylamino group having 1 to 6 carbon atoms, an N, N-dialkylamino group having 2 to 12 carbon atoms, and 1 to 6 carbon atoms N-alkylsulfamoyl groups, and N, N-dialkylsulfamoyl groups having 2 to 12 carbon atoms, and preferred examples thereof include a halogen atom of Rc, an alkyl group having 1 to 6 carbon atoms, An alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a fluoroalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a thioalkyl group having 1 to 6 carbon atoms, and 1 to N-alkylamino group, C2-C12 N, N-dialkylamino group, C1-C6 N-alkylsulfamoyl group, and C2-C12 N, N-dialkylsulfamoyl group Specific examples of groups and preferred examples thereof are the same as those listed.

D ¹ and D ² are preferably each independently any group represented by the following formulas (d-1) to (d-8).

In formulas (d-1) to (d-8), Rd represents a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, or 1 to 6 carbon atoms. Alkylsulfonyl group, carboxyl group, fluoroalkyl group having 1 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, carbon number It represents an N, N-dialkylamino group having 2 to 12 carbon atoms, an N-alkylsulfamoyl group having 1 to 6 carbon atoms, or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms. P1 is an integer from 0 to 5, p2 is an integer from 0 to 4, p3 is an integer from 0 to 3, and p4 is an integer from 0 to 2. Among them, p1, p3, and p4 are 0 Alternatively, it is preferably 1, and p2 is preferably an integer of 0 to 3. Rf represents a hydrogen atom or a methyl group.
In each of the formulas (d-1) to (d-8), when there are a plurality of Rd (that is, when p1, p2, p3 or p4 is 2 or more), the plurality of Rd are the same as each other. It may be different or different.

Rd halogen atom, alkyl group having 1 to 6 carbon atoms, alkylsulfinyl group having 1 to 6 carbon atoms, alkylsulfonyl group having 1 to 6 carbon atoms, fluoroalkyl group having 1 to 6 carbon atoms, 1 to 6 carbon atoms An alkoxy group, a thioalkyl group having 1 to 6 carbon atoms, an N-alkylamino group having 1 to 6 carbon atoms, an N, N-dialkylamino group having 2 to 12 carbon atoms, and an N-alkylsulfamoyl group having 1 to 6 carbon atoms Groups, and N, N-dialkylsulfamoyl groups having 2 to 12 carbon atoms, and preferred examples thereof include halogen atoms of Rc, alkyl groups having 1 to 6 carbon atoms, and alkylsulfinyl groups having 1 to 6 carbon atoms. An alkylsulfonyl group having 1 to 6 carbon atoms, a fluoroalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a thioalkyl group having 1 to 6 carbon atoms, an N-alkyl group having 1 to 6 carbon atoms Specific examples of N group, N, N-dialkylamino group having 2 to 12 carbon atoms, N-alkylsulfamoyl group having 1 to 6 carbon atoms, and N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms And the same thing as what was listed as a suitable example is mentioned.

Rd is preferably a halogen atom, methyl group, cyano group, nitro group, carboxyl group, trifluoromethyl group, methoxy group, methylthio group, N, N-dimethylamino group, or N-methylamino group.

In addition, D ¹ and D ² are each independently a group represented by the formula (d-1), (d-3), or (d-7). This is particularly preferable in terms of optical characteristics and cost.

In the above formula (I), Ar ¹ is more preferably any one of groups represented by the following formulas (Ar-5) to (Ar-9).

In the formulas (Ar-5) to (Ar-9), E ¹ , Rc, Rd and p0 to p3 have the same meaning as described above, and preferred examples thereof are also the same as described above.

Here, specific examples of Ar ¹ are shown in the following formulas (ar-1) to (ar-94).

In the above formula (I), Z ¹ and Z ² are each independently a single bond, —O—CH ₂ —, —CH ₂ —O—, —C (═O) —O—, — O-C (= O) - , - C (= O) -S -, - S-C (= O) -, - NR 13 -C (= O) -, - C (= O) -NR 13 - _{, -CF 2 -O -, - O} -CF 2 -, - CH 2 -CH 2 -, - CF 2 -CF 2 -, - O-CH 2 -CH 2 -O -, - CH = CH-C ( ═O) —O—, —O—C (═O) —CH═CH—, —CH ₂ —CH ₂ —C (═O) —O—, —O—C (═O) —CH ₂ —CH ₂ —, —CH ₂ —CH ₂ —O—C (═O) —, —C (═O) —O—CH ₂ —CH ₂ —, —CH═CH—, —N═CH—, —CH═ N-, -N = C (CH ₃ )-, -C (CH ₃ ) = N-, -N = N- or -C≡C-. R ¹³ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. Examples of the alkyl group having 1 to 6 carbon atoms in R ¹³ include a methyl group, an ethyl group, a propyl group, and an isopropyl group. .
Among these, Z ¹ is preferably —CO—O—. Z ² is preferably —O—CO—.

Further, A ¹ and A ² are each independently a cyclic aliphatic group which may have a substituent or an aromatic group which may have a substituent. Among them, A ¹ and A ² are preferably substituted is also good cyclic aliphatic group.

In addition, the cycloaliphatic group which may have a substituent is an unsubstituted divalent cycloaliphatic group or a divalent cycloaliphatic group having a substituent. The divalent cycloaliphatic group is a divalent aliphatic group having a cyclic structure and usually having 5 to 20 carbon atoms.
Specific examples of the divalent cycloaliphatic group represented by A ¹ and A ² include cyclopentane-1,3-diyl group, cyclohexane-1,4-diyl group, 1,4-cycloheptane-1,4-diyl. Groups, cycloalkanediyl groups having 5 to 20 carbon atoms such as cyclooctane-1,5-diyl group; carbon numbers such as decahydronaphthalene-1,5-diyl group and decahydronaphthalene-2,6-diyl group ˜20 bicycloalkanediyl groups and the like.

The aromatic group which may have a substituent is an unsubstituted divalent aromatic group or a divalent aromatic group having a substituent. The divalent aromatic group is a divalent aromatic group having an aromatic ring structure and usually having 2 to 20 carbon atoms.
Specific examples of the divalent aromatic group for A ¹ and A ² include 1,4-phenylene group, 1,4-naphthylene group, 1,5-naphthylene group, 2,6-naphthylene group, 4,4 ′ A bivalent aromatic hydrocarbon ring having 6 to 20 carbon atoms such as a biphenylene group; a furan-2,5-diyl group, a thiophene-2,5-diyl group, a pyridine-2,5-diyl group, a pyrazine And a divalent aromatic heterocyclic group having 2 to 20 carbon atoms such as a -2,5-diyl group.

Furthermore, examples of the substituent for the divalent cyclic aliphatic group and the divalent aromatic group of A ¹ and A ² include halogen atoms such as a fluorine atom, a chlorine atom and a bromine atom; a methyl group, an ethyl group and the like. Examples thereof include an alkyl group having 1 to 6 carbon atoms; an alkoxy group having 1 to 5 carbon atoms such as a methoxy group and an isopropoxy group; a nitro group; a cyano group; The cycloaliphatic group and the aromatic group may have at least one substituent selected from the above-described substituents. In addition, when it has two or more substituents, each substituent may be the same or different.

When b and / or c is 1, L ¹ and L ² are each independently a single bond, —O—, —CO—, —CO—O—, —O—CO—, —NR ^14. —CO—, —CO—NR ¹⁴ —, —O—CO—O—, —NR ¹⁴ —CO—O—, —O—CO—NR ¹⁴ —, or —NR ¹⁴ —CO—NR ¹⁵ —. . Here, R ¹⁴ and R ¹⁵ are each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. Among these, L ¹ and L ² are preferably each independently —O—, —CO—O—, or —O—CO—.
Examples of the alkyl group having 1 to 6 carbon atoms of R ¹⁴ and R ¹⁵ include a methyl group, an ethyl group, a propyl group, and an isopropyl group.

When b and / or c is 1, B ¹ and B ² are each independently a cyclic aliphatic group which may have a substituent, or an aromatic which may have a substituent. It is a family group. Among these, B ¹ and B ² are preferably aromatic groups that may have a substituent.

Here, the cycloaliphatic group which may have a substituent is an unsubstituted divalent cycloaliphatic group or a divalent cycloaliphatic group having a substituent. The divalent cycloaliphatic group is a divalent aliphatic group having a cyclic structure and usually having 5 to 20 carbon atoms.
Specific examples of the divalent cycloaliphatic group of B ¹ and B ² include the same as those exemplified as the divalent cycloaliphatic group of A ¹ and A ² .

The aromatic group which may have a substituent is an unsubstituted divalent aromatic group or a divalent aromatic group having a substituent. The divalent aromatic group is a divalent aromatic group having an aromatic ring structure and usually having 2 to 20 carbon atoms.
Specific examples of the divalent aromatic group for B ¹ and B ² include the same examples as those exemplified as the divalent aromatic group for A ¹ and A ² .

Further, as the substituent for the divalent cycloaliphatic group and divalent aromatic group of B ¹ and B ² , substitution of the divalent cycloaliphatic group and divalent aromatic group of A ¹ and A ² Examples thereof are the same as those exemplified as the group.

Y ¹ and Y ² are each independently a single bond, —O—, —CO—, —CO—O—, —O—CO—, —NR ¹⁴ —CO—, —CO—NR ¹⁴ —. , —O—CO—O—, —NR ¹⁴ —CO—O—, —O—CO—NR ¹⁴ —, or —NR ¹⁴ —CO—NR ¹⁵ —. Here, R ¹⁴ and R ¹⁵ are each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. Among these, Y ¹ and Y ² are preferably each independently —O—, —CO—O—, or —O—CO—.
Examples of the alkyl group having 1 to 6 carbon atoms of R ¹⁴ and R ¹⁵ include a methyl group, an ethyl group, a propyl group, and an isopropyl group.

R ¹ and R ² are each independently a hydrogen atom or a methyl group. R ¹ is preferably the same as R ^2, and both R ¹ and R ² are more preferably hydrogen atoms.

In addition, from the viewpoint of obtaining an optical film or the like excellent in reverse wavelength dispersion, the polymerizable compound (I) preferably has a substantially symmetrical structure with Ar as the center. Specifically, in the polymerizable compound (I), R ¹ , a and b are the same as R ² , d and c, respectively, and —Y ¹ — [B ¹ -L ¹ ] _b —A ¹ — Z ¹ -(*) and (*)-Z ² -A ^2- [L ² -B ² ] _c -Y ^2- have a symmetrical structure with the side (*) that is bonded to Ar as the center of symmetry. Is preferred.
Note that “having a symmetric structure with (*) as the center of symmetry” means, for example, —CO—O — (*) and (*) — O—CO— or —O — (*) and (*). It means having a structure such as —O—, —O—CO — (*) and (*) — CO—O—.

(2) Halogenated compound (II)
In the production method of the present invention, at any stage of synthesizing the above-described polymerizable compound (I), the composition containing the halogenated compound (II) is subjected to a dehydrohalogenation reaction to give the halogenated compound (II). ) To desorb hydrogen halide.
In the present invention, the “composition containing the halogenated compound (II)” refers to the halogenated compound (II) itself or a dehydrohalide of the halogenated compound (II) and the halogenated compound (II). Means a mixture containing

And the halogenated substance (II) used as the object of dehydrohalogenation reaction is a compound represented by following formula (II).

In the formula (II), X ¹ represents a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom, and a chlorine atom is preferred.
R ¹ and a have the same meaning as in formula (I).

Here, G is an organic group, preferably an organic group having 5 to 80 carbon atoms and having at least one aromatic ring. Examples of the aromatic ring include an aromatic hydrocarbon ring and an aromatic heterocyclic ring.
Examples of the aromatic hydrocarbon ring include a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyrene ring, and a fluorene ring.
Among these, as the aromatic hydrocarbon ring, a benzene ring and a naphthalene ring are preferable.
Examples of the aromatic heterocycle include 1H-isoindole-1,3 (2H) -dione ring, 1-benzofuran ring, 2-benzofuran ring, acridine ring, isoquinoline ring, imidazole ring, indole ring, oxadi Azole ring, oxazole ring, oxazolopyrazine ring, oxazolopyridine ring, oxazolopyridazyl ring, oxazolopyrimidine ring, quinazoline ring, quinoxaline ring, quinoline ring, cinnoline ring, thiadiazole ring, thiazole ring, thiazolopyrazine ring , Thiazolopyridine ring, thiazolopyridazine ring, thiazolopyrimidine ring, thiophene ring, triazine ring, triazole ring, naphthyridine ring, pyrazine ring, pyrazole ring, pyranone ring, pyran ring, pyridine ring, pyridazine ring, pyrimidine ring, pyrrole Ring, phenanthridine ring, Razine ring, furan ring, benzo [c] thiophene ring, benzoisoxazole ring, benzoisothiazole ring, benzimidazole ring, benzooxadiazole ring, benzoxazole ring, benzothiadiazole ring, benzothiazole ring, benzothiophene ring, benzo Examples thereof include a triazine ring, a benzotriazole ring, a benzopyrazole ring, a benzopyranone ring, a dihydropyran ring, a tetrahydropyran ring, a dihydrofuran ring, and a tetrahydrofuran ring.
Among these, aromatic heterocycles include benzothiazole ring, benzoxazole ring, 1-benzofuran ring, 2-benzofuran ring, benzothiophene ring, 1H-isoindole-1,3 (2H) -dione ring, thiophene ring A furan ring, a benzo [c] thiophene ring, an oxazole ring, a thiazole ring, an oxadiazole ring, a pyran ring, a benzoisoxazole ring, a thiadiazole ring, a benzooxadiazole ring, and a benzothiadiazole ring.

The halogenated compound (II) is not particularly limited as long as it can be used as a raw material compound of the polymerizable compound (I). For example, the above-described formula (III), ( IV) and halogenated compounds represented by (VI) (referred to as “halogenated compound (III)”, “halogenated compound (IV)” and “halogenated compound (VI)”, respectively)). These halides can be synthesized by a known synthesis reaction. The halogenated compound (III) can be produced as a by-product when the polymerizable compound (I) is prepared by a known method, for example.

(2-1) Halogenated compound (III)
The halide (III) is a compound represented by the following formula (III).

In the formula (III), Q represents a group represented by the following formula (III-1) or the following formula (III-2).

[In formula (III-1) and formula (III-2), R ² represents the same meaning as in formula (I). X ² in formula (III-2) represents a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom, and a chlorine atom is preferred. ]

Ar, Z ¹ , Z ² , A ¹ , A ² , B ¹ , B ² , Y ¹ , Y ² , L ¹ , L ² , R ¹ and a to d have the same meaning as in the formula (I). X ¹ represents the same meaning as in the formula (II).

Halogenated compound (III) is a compound that differs from polymerizable compound (I) only in at least one terminal structure. Therefore, if the halogenated compound (III) is dehydrohalogenated to form a carbon-carbon double bond at the terminal, the polymerizable compound (I) is converted into a dehydrohalogenated product of the halogenated compound (III). Obtainable.
As the halide (III), more specifically, halogenated compounds represented by the following formulas (IIIa), (IIIb), and (IIIc) (respectively, “halogenated compound (IIIa)”, “halogen” (Referred to as "Chemical Form (IIIb)" and "Halogenated Form (IIIc)"), and mixtures thereof. In addition, the abundance ratio of the halogenated product (IIIa), the halogenated product (IIIb), and the halogenated product (IIIc) in the mixture is not particularly limited.

In the formulas (IIIa) to (IIIc), a, d, R ¹ , R ² , X ¹ and X ² have the same meaning as described above. Ar is any of the groups represented by the above formulas (Ar-1) to (Ar-4).

(2-2) Halogenated compound (IV)
The halide (IV) is a compound represented by the following formula (IV).

In formula (IV), FG ¹ represents a hydroxyl group, a carboxyl group or an amino group, and preferably a hydroxyl group. R ¹ , Y ¹ , B ¹ and a represent the same meaning as in the formula (I), and X ¹ represents the same meaning as in the formula (II).

Then, when the halogenated compound (IV) is dehydrohalogenated, a compound represented by the following formula (V) (“compound (V)”) is obtained as a dehydrohalogenated product of the halogenated compound (IV). be able to.

In formula (V), R ¹ , Y ¹ , B ¹ , FG ¹ and a represent the same meaning as in formula (IV).

In the dehydrohalogenation reaction, a mixture containing the halide (IV) and the compound (V) can be used as the composition containing the halide (IV). By subjecting such a mixture to a dehydrohalogenation reaction, the halogenated compound (IV) in the mixture can be converted into the compound (V), whereby the compound (V) having a high purity can be obtained. The ratio of the halide (IV) and the compound (V) in the mixture is not particularly limited, but the ratio of the halide (IV) in the total of the halide (IV) and the compound (V) is It is preferable that it is 0.01 mass% or more and 5 mass% or less, 0.5 mass% or more and 5 mass% or less are more preferable, and 2 mass% or more and 5 mass% or less are still more preferable.

The above-mentioned polymerizable compound (I) can be synthesized by using the obtained compound (V) and combining known synthetic reactions. That is, the polymerizable compound (I) uses the compound (V), and various documents (for example, MARCH'S ADVANCED ORGANIC CHEMISTRY (WILEY), Sandler Karo “Functional Group Organic Compound Synthesis Method” by Naoki Inamoto (Sasakawa Shoten)) can be synthesized with reference to the method described.

(2-3) Halogenated compound (VI)
The halide (VI) is a compound represented by the following formula (VI).

In formula (VI), FG ² represents a hydroxyl group, a carboxyl group or an amino group, and a carboxyl group is preferred. R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , a and b represent the same meaning as in the formula (I), and X ¹ represents the same meaning as in the formula (II).

When the halogenated compound (VI) is dehydrohalogenated, a compound represented by the following formula (VII) (“compound (VII)”) is obtained as a dehydrohalogenated product of the halogenated compound (VI). be able to.

In formula (VII), R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , FG ² , a and b represent the same meaning as in formula (VI).

In the dehydrohalogenation reaction, a mixture containing the halide (VI) and the compound (VII) can be used as the composition containing the halide (VI). By subjecting such a mixture to a dehydrohalogenation reaction, the halogenated compound (VI) in the mixture can be converted into the compound (VII) to obtain the compound (VII) with high purity. The ratio of the halogenated compound (VI) to the compound (VII) in the mixture is not particularly limited, but the ratio of the halogenated compound (VI) in the total of the halogenated compound (VI) and the compound (VII) is The content is preferably 0.01% by mass or more and 5% by mass or less, more preferably 0.5% by mass or more and 5% by mass or less, and further preferably 1.5% by mass or more and 5% by mass or less.

Using the obtained compound (VII), the polymerizable compound (I) can be synthesized by combining known synthetic reactions. That is, the polymerizable compound (I) uses the compound (VII), and various documents (for example, MARCH'S ADVANCED ORGANIC CHEMISTRY (WILEY), Sandler Karo “Functional Group Organic Compound Synthesis Method” by Naoki Inamoto (Sasakawa Shoten)) can be synthesized with reference to the method described.

(3) Dehydrohalogenation reaction Here, the dehydrohalogenation reaction is performed in an organic solvent in the presence of an aqueous layer containing at least one basic compound.

(3-1) Organic solvent The organic solvent to be used is not particularly limited as long as it can dissolve the halide (II) and is inert to the reaction. For example, ester solvents such as ethyl acetate, propyl acetate and butyl acetate; ketone solvents such as cyclopentanone, methyl ethyl ketone, diethyl ketone and methyl isobutyl ketone; dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, chlorobenzene, Halogenated hydrocarbon solvents such as o-dichlorobenzene; ether solvents such as diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, cyclopentyl methyl ether and tetrahydrofuran; aliphatic carbonization such as n-pentane, n-hexane and n-heptane Hydrogen solvents; aromatic hydrocarbon solvents such as benzene, toluene and xylene; alicyclic hydrocarbon solvents such as cyclopentane and cyclohexane; nitrogen-containing compounds such as nitromethane, nitrobenzene and acetonitrile Hydrocarbon solvents; and the like.
These solvents can be used alone or in combination of two or more.
Among these, a mixed solvent of an ester solvent and a nitrogen-containing hydrocarbon solvent, a ketone solvent and a nitrogen-containing solvent from the viewpoint of obtaining a desired product with good solubility and high yield of the halogen (II). A mixed solvent with a hydrocarbon solvent is preferable, a mixed solvent of an ester solvent and a nitrogen-containing hydrocarbon solvent is more preferable, and a mixed solvent of ethyl acetate and acetonitrile is particularly preferable.
Here, in the case of using a mixed solvent of an ester solvent and a nitrogen-containing hydrocarbon solvent, the mixing ratio of both is usually 1: 1 to 4: 1 by volume ratio of the ester solvent and the nitrogen-containing hydrocarbon solvent. The ratio is preferably 2: 1 to 3: 1.

(3-2) Aqueous layer containing basic compound As the basic compound, inorganic basic compounds and organic basic compounds can be used. From the viewpoint of efficiently proceeding with the dehydrohalogenation reaction, it is preferable to use at least an inorganic basic compound as the basic compound, and it is more preferable to use an inorganic basic compound and an organic basic compound in combination. .
The water used for the water layer is preferably water that does not contain impurities, such as distilled water.

The inorganic basic compound is not particularly limited. For example, metal carbonate, metal hydrogencarbonate, metal hydroxide, etc. are mentioned.
Examples of the metal carbonate include alkali metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate; magnesium carbonate; alkaline earth metal carbonates such as calcium carbonate and barium hydroxide;
Examples of the metal hydrogen carbonate include alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; magnesium hydrogen carbonate; alkaline earth metal hydrogen carbonates such as calcium hydrogen carbonate;
Examples of the metal hydroxide include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; magnesium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide;
These inorganic basic compounds can be used singly or in combination of two or more.
Among these, metal carbonates are preferable, alkali metal carbonates are more preferable, and sodium carbonate is more preferable from the viewpoints of availability and ease of handling.

The amount of the inorganic basic compound used is not particularly limited, but to increase the yield of the dehydrohalide and to eliminate the neutralization step after the reaction, with respect to 1 equivalent of the halide (II), It is preferably 1 to 3 equivalents, more preferably 1.5 to 2.5 equivalents.
The concentration of the inorganic basic compound in the aqueous layer is not particularly limited, but is 0.5 to 2. in order to increase the yield of dehydrohalide and to omit the neutralization step after the reaction. 5 mol / L is preferable, and 0.5 to 1.5 mol / L is more preferable.

Examples of organic basic compounds include heterocyclic compounds such as pyridine, picoline, collidine, lutidine, and 4- (dimethylamino) pyridine; tertiary amines such as triethylamine, N, N-diisopropylethylamine, and N, N-dimethylaniline; Etc.
Among these, a tertiary amine is preferable and triethylamine is more preferable from the viewpoint of increasing the yield of the dehydrohalide.
The amount of the organic basic compound used is not particularly limited, but is preferably 1 to 3 equivalents, more preferably 1.2 to 2 equivalents, per 1 equivalent of the halide (II).

(3-3) Conditions for dehydrohalogenation reaction The reaction is preferably carried out in an inert atmosphere such as argon or nitrogen.
The reaction temperature is usually −10 ° C. to + 80 ° C., preferably 10 ° C. to 70 ° C., more preferably 20 ° C. to 60 ° C.
Although depending on the reaction scale and the like, the reaction time is several minutes to 24 hours, preferably 0.5 to 10 hours.
The progress of the reaction can be confirmed by known analytical means (for example, thin layer chromatography, high performance liquid chromatography, gas chromatography).

After completion of the reaction, normal post-treatment operations in organic synthetic chemistry are performed, and the reaction product is purified by a known separation / purification means such as a distillation method, a column chromatography method, or a recrystallization method, if desired. The dehydrohalogenated product (for example, the target polymerizable compound (I)) can be isolated.
Specifically, after removing the aqueous layer (aqueous phase) from the solution after the reaction, the organic layer (organic phase) is washed with water, and then a poor solvent such as an alcohol solvent is added to the organic layer to precipitate crystals. Thus, the target polymerizable compound (I) and the like can be isolated efficiently.
The structure of the target product can be identified and confirmed by using analytical means such as NMR spectrum, IR spectrum, and mass spectrum.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited by the following examples.

Synthesis Example 1 Synthesis of Compound 1

Compound 1

Step 1: Synthesis of Intermediate A

In a 4-necked reactor equipped with a thermometer, 20.0 g (164 mmol) of 3,5-dimethylphenol was dissolved in 500 ml of acetonitrile in a nitrogen stream. To this solution, 23.4 g (246 mmol) of magnesium chloride and 58.1 g (574 mmol) of triethylamine were added and stirred at 25 ° C. for 30 minutes, and then 14.8 g (492 mmol) of paraformaldehyde was added and stirred at 75 ° C. for 3 hours. . After completion of the reaction, the reaction solution was cooled to 30 ° C., 600 ml of 1M hydrochloric acid was added, and the mixture was extracted with 800 ml of diethyl ether. The diethyl ether layer was washed with 300 ml of saturated aqueous sodium hydrogen carbonate solution and 300 ml of saturated brine, and then dried over anhydrous magnesium sulfate. After filtering off magnesium sulfate, diethyl ether was distilled off under reduced pressure using a rotary evaporator to obtain a white solid. This white solid was purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10 (volume ratio)) to obtain 17.7 g of intermediate A as a white solid (yield: 71.9 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 11.95 (s, 1H), 10.22 (s, 1H), 6.61 (s, 1H), 6.53 (s, 1H) 2.54 (s, 3H), 2.30 (s, 3H).

Step 2: Synthesis of Intermediate B

In a 4-necked reactor equipped with a thermometer, 12.0 g (79.9 mmol) of the intermediate A synthesized in Step 1 above was dissolved in 105 ml of dimethylacetamide in a nitrogen stream. To this solution, 11.0 g (79.9 mmol) of potassium carbonate was added and the temperature was raised to 80 ° C., and then 13.3 g (79.9 mmol) of ethyl bromoacetate was added over 30 minutes. The solution was stirred at 80 ° C. for 1 hour, then heated to 130 ° C. and further stirred for 1 hour. Thereafter, the reaction solution was cooled to 30 ° C., 300 ml of 1M hydrochloric acid was added, and the mixture was extracted with 120 ml of methyl isobutyl ketone. The methyl isobutyl ketone layer was dried over sodium sulfate, and the sodium sulfate was filtered off. Then, methyl isobutyl ketone was distilled off under reduced pressure using a rotary evaporator to obtain a pale yellow solid. This pale yellow solid was dissolved in 500 ml of ethanol. To this solution, 12.0 g (214 mmol) of potassium hydroxide was added and stirred at 80 ° C. for 1 hour. After completion of the reaction, ethanol was distilled off under reduced pressure using a rotary evaporator to obtain a pale yellow solid. This pale yellow solid was dissolved in 300 ml of water, and then this solution was washed with 300 ml of toluene and 300 ml of heptane. 2M sulfuric acid aqueous solution was added to this solution to adjust the pH to 3, and then the precipitated solid was collected by filtration, and the collected solid was vacuum-dried to obtain 12.3 g of Intermediate B as a white solid (yield: 80.9 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 13.42 (brs, 1H), 7.69 (d, 1H, J = 1.0 Hz), 7.30 (s, 1H), 6. 98 (s, 1H), 2.48 (s, 3H), 2.41 (s, 3H).

Step 3: Synthesis of Intermediate C

In a 4-necked reactor equipped with a thermometer, 12.0 g (63.1 mmol) of the intermediate B synthesized in Step 2 above and 14.5 g (94.6 mmol) of 2,5-dimethoxyaniline in chloroform were added to chloroform. Dissolved in 120 g. To this solution, a mixed solution of 13.3 g (69.4 mmol) of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 120 g of chloroform was added and stirred at 25 ° C. for 3 hours. After completion of the reaction, chloroform was distilled off under reduced pressure using a rotary evaporator to obtain a pale yellow oily substance. To this pale yellow oily substance, a mixed solution of 200 ml of 1M hydrochloric acid, 200 ml of water and 100 ml of methanol was added and stirred at 25 ° C. The precipitated white solid was collected by filtration, and the collected solid was vacuum-dried to obtain 16.7 g of Intermediate C as a white solid (yield: 81.2 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 8.28 (d, 1 H, J = 3.0 Hz), 7.56 (d, 1 H, J = 1.0 Hz), 7.26 (s 1H), 7.22 (s, 1H), 6.94 (s, 1H), 6.86 (d, 1H, J = 9.0 Hz), 6.64 (dd, 1H, J = 3.0 Hz) 9.0 Hz), 3.97 (s, 3H), 3.81 (s, 3H), 2.51 (s, 3H), 2.49 (s, 3H).

Step 4: Synthesis of Intermediate D

In a four-necked reactor equipped with a thermometer, 16.0 g (49.2 mmol) of the intermediate C synthesized in Step 3 above was dissolved in 200 ml of toluene in a nitrogen stream. To this solution, 12.1 g (23.0 mmol) of 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane was added and heated to reflux for 4 hours. After completion of the reaction, the reaction solution was cooled to 30 ° C., 400 ml of 1M aqueous sodium hydroxide solution was added, and the mixture was extracted with 500 ml of toluene. 500 ml of toluene was distilled off under reduced pressure from the obtained toluene layer with a rotary evaporator, and then 500 ml of heptane was added. The precipitated yellow solid was collected by filtration, and the collected solid was vacuum-dried to obtain 14.7 g of intermediate D as a yellow solid (yield: 87.5 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 10.45 (s, 1 H), 9.13 (d, 1 H, J = 3.0 Hz), 7.82 (d, 1 H, J = 1) 0.0 Hz), 7.18 (s, 1H), 6.93 (s, 1H), 6.91 (d, 1H, J = 9.0 Hz), 6.77 (dd, 1H, J = 3.0 Hz) 9.0 Hz), 3.97 (s, 3H), 3.83 (s, 3H), 2.51 (s, 3H), 2.46 (s, 3H).

Step 5: Synthesis of Intermediate E

In a four-necked reactor equipped with a thermometer, 13.2 g (38.6 mmol) of the intermediate D synthesized in Step 4 above, 220 g of water, and 11.9 g (212 mmol) of potassium hydroxide were added to ice. Stir in the cold. To the obtained mixture, 29.2 g (88.8 mmol) of potassium ferricyanide and 12 g of methanol were added, and the mixture was heated to 60 ° C. and stirred for 6 hours. After completion of the reaction, the reaction solution was cooled to 30 ° C., the precipitated yellow solid was collected by filtration, and the collected solid was vacuum dried to obtain 10.2 g of Intermediate E as a yellow solid (yield: 76. 8 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.65 (d, 1H, J = 1.0 Hz), 7.21 (s, 1H), 6.91 (s, 1H), 6. 84 (d, 1H, J = 8.5 Hz), 6.76 (d, 1H, J = 8.5 Hz), 4.04 (s, 3H), 3.97 (s, 3H), 2.51 ( s, 3H), 2.46 (s, 3H).

Step 6: Synthesis of Intermediate F

In a 4-necked reactor equipped with a thermometer, 72 g of pyridine hydrochloride was added to 7.2 g (21.2 mmol) of the intermediate E synthesized in Step 5 in a nitrogen stream, and the mixture was stirred at 180 ° C. for 4 hours. After completion of the reaction, the reaction solution was cooled to 30 ° C., and then 300 g of water was added. The precipitated solid was collected by filtration and washed with 30 g of water, 30 g of toluene, and 30 g of hexane. The obtained solid was vacuum-dried to obtain 6.38 g of intermediate F as a yellow solid (yield: 96.6 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, DMSO-d6, TMS, δ ppm): 9.91 (s, 1H), 9.59 (brs, 1H), 7.76 (d, 1H, J = 1.0 Hz), 7 .36 (s, 1H), 6.99 (s, 1H), 6.79 (d, 1H, J = 8.5 Hz), 6.74 (d, 1H, J = 8.5 Hz), 2.53 (S, 3H), 2.43 (s, 3H).

Step 7: Synthesis of Intermediate G

In a nitrogen stream, 104.77 g (0.95 mol) of hydroquinone, 100 g (0.73 mol) of 6-chlorohexanol, 500 g of distilled water, and 100 g of orthoxylene were added to a three-necked reactor equipped with a condenser and a thermometer. . While stirring the whole volume, 35.15 g (0.88 mol) of sodium hydroxide was further added in small portions over 20 minutes so that the temperature of the contents did not exceed 40 ° C. After completion of the addition of sodium hydroxide, the contents were heated and reacted for 10 hours under reflux conditions (92 ° C.).
After completion of the reaction, the temperature of the reaction solution was lowered to 80 ° C., 200 g of distilled water was added, and then the reaction solution was cooled to 10 ° C. to precipitate crystals. The precipitated crystals were separated into solid and liquid by filtration, and the obtained crystals were washed with 150 g of distilled water to obtain 203.0 g of brown crystals. When analyzed using a part of the brown crystals, the loss on drying was 36.3% by mass. As a result of analysis by high performance liquid chromatography, the ratio (molar ratio) of the monoetherified product to the dietherified product contained in the brown crystals was (monoetherified product / dietherified product), which was 92.0 / 8.0. . In a three-necked reactor equipped with a condenser with a Dean-Stark tube and a thermometer, 157 g of brown crystals obtained previously (after solid-liquid separation and washing with distilled water) in a nitrogen stream, 500 g of toluene, 2 , 6-Di-t-butyl-p-cresol 1.05 g (4.76 mmol) was added, and the whole volume was stirred to obtain a solution. The obtained solution was heated and water was removed from the Dean-Stark tube under reflux conditions to dehydrate the system. Thereafter, the solution was cooled to 80 ° C., 4.57 g (47.6 mmol) of methanesulfonic acid was added, and the mixture was again heated to reflux conditions (110 ° C.). Next, 47.98 g (0.666 mol) of acrylic acid was dropped into the solution over 2 hours, and water produced was removed to perform a dehydration reaction. Stirring was continued for 2 hours after the acrylic acid was dropped. Next, the reaction solution was cooled to 30 ° C., 500 g of distilled water was added, and the whole volume was stirred and allowed to stand. The organic layer was separated, and 400 g of 5% brine was added to the obtained organic layer for liquid separation. The organic layer was separated, 10 g of activated carbon was added to the obtained organic layer, the whole volume was stirred at 25 ° C. for 30 minutes, and then the activated carbon was removed by filtration. To the obtained filtrate was added 1.05 g (4.76 mmol) of 2,6-di-t-butyl-p-cresol, 350 g of toluene was distilled off under reduced pressure, and the solution was concentrated. To the resulting concentrated liquid, 300 g of n-heptane was added dropwise over 30 minutes to precipitate crystals, which were then cooled to 5 ° C. as they were. The crystals were separated by filtration, and the obtained crystals were washed with a mixed solution of 66.7 g of toluene and 133.3 g of n-heptane. Next, the crystals were added to 144 g of toluene and heated to 40 ° C. to dissolve the crystals. To the resulting solution, 216 g of n-heptane was added dropwise over 1 hour to precipitate crystals, which were then cooled to 5 ° C. as they were. The crystals were collected by filtration, and the obtained crystals were washed with a mixed solution of 72 g of toluene and 144 g of n-heptane, and dried in vacuo to give intermediate G (4- (6-acryloyloxy-hex-) as a white solid. 1-yloxy) phenol) was obtained in an amount of 86.4 g (yield based on 6-chlorohexanol: 58 mol%). Further, the obtained white solid was purified by silica gel column chromatography (toluene: ethyl acetate =: 95: 5 (volume ratio, the same applies hereinafter)) to increase the purity to 99.5% by mass or more.
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, DMSO-d6, TMS, δ ppm): 8.87 (s, 1H), 6.72 (d, 2H, J = 9.0 Hz), 6. 65 (d, 2H, J = 9.0 Hz), 6.32 (dd, 1H, J = 1.5 Hz, 17.5 Hz), 6.17 (dd, 1H, J = 10.0 Hz, 17.5 Hz) 5.93 (dd, 1H, J = 1.5 Hz, 10.0 Hz), 4.11 (t, 2H, J = 6.5 Hz), 3.83 (t, 2H, J = 6.5 Hz), 1.56-1.72 (m, 4H), 1.31-1.47 (m, 4H).

Step 8: Synthesis of Intermediate H

To a three-necked reactor equipped with a thermometer, 17.98 g (104.42 mmol) of trans, -1,4-cyclohexanedicarboxylic acid and 180 ml of tetrahydrofuran (THF) were added in a nitrogen stream. To this, 6.58 g (57.43 mmol) of methanesulfonyl chloride was added, and the reactor was immersed in a water bath to adjust the internal temperature of the reaction solution to 20 ° C. Next, 6.34 g (62.65 mmol) of triethylamine was added dropwise over 10 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the dropwise addition, the whole volume was further stirred at 25 ° C. for 2 hours.
To the obtained reaction solution, 638 mg (5.22 mmol) of 4- (dimethylamino) pyridine and 13.80 g (52.21 mmol) of the intermediate G synthesized in the previous Step 7 were added, and the reactor was placed in a water bath again. The temperature inside the reaction solution was adjusted to 15 ° C. by immersion. Thereto, 6.34 g (62.65 mmol) of triethylamine was added dropwise over 10 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the addition, the whole volume was further stirred at 25 ° C. for 2 hours. After completion of the reaction, 1000 ml of distilled water and 100 ml of saturated brine were added to the reaction solution, and extracted twice with 400 ml of ethyl acetate. The organic layer was collected and dried over anhydrous sodium sulfate, and then sodium sulfate was filtered off. After the solvent was distilled off from the filtrate under reduced pressure using a rotary evaporator, the obtained residue was purified by silica gel column chromatography (toluene: THF = 9: 1) to obtain 14.11 g of Intermediate H as a white solid. (Yield: 65.0 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, DMSO-d ₆ , TMS, δ ppm): 12.12 (s, 1H), 6.99 (d, 2H, J = 9.0 Hz), 6.92 (d, 2H, J = 9.0 Hz), 6.32 (dd, 1 H, J = 1.5 Hz, 17.5 Hz), 6.17 (dd, 1 H, J = 10.0 Hz, 17.5 Hz), 5.93 (dd, 1H, J = 1.5 Hz, 10.0 Hz), 4.11 (t, 2H, J = 6.5 Hz), 3.94 (t, 2H, J = 6.5 Hz), 2.48-2.56 (M, 1H), 2.18-2.26 (m, 1H), 2.04-2.10 (m, 2H), 1.93-2.00 (m, 2H), 1.59-1 .75 (m, 4H), 1.35 to 1.52 (m, 8H)

Step 9: Synthesis of Intermediate I

In a nitrogen stream, 104.77 g (0.9515 mol) hydroquinone, 100 g (0.7320 mol) 6-chlorohexanol, 500 ml distilled water, and 100 ml o-xylene were placed in a three-necked reactor equipped with a condenser and a thermometer. added. While stirring the whole volume, 35.15 g (0.8784 mol) of sodium hydroxide was further added in small portions over 20 minutes so that the internal temperature of the reaction solution did not exceed 40 ° C. After completion of the addition of sodium hydroxide, the contents were heated and reacted for 12 hours under reflux conditions (96 ° C.).
After completion of the reaction, the internal temperature of the reaction solution was lowered to 80 ° C., 200 ml of distilled water was added, and then the reaction solution was cooled to 10 ° C. to precipitate crystals. The precipitated crystals were separated into solid and liquid by filtration, and the obtained crystals were washed with 500 ml of distilled water and vacuum-dried to obtain 123.3 g of brown crystals.
As a result of analyzing the brown crystals by high performance liquid chromatography, the content ratio (molar ratio) of the compounds contained in the brown crystals was (hydroquinone / intermediate I / byproduct I = 1.3 / 90.1 / 8. 1).

Step 10: Synthesis of Intermediate J

In a three-necked reactor equipped with a condenser with a Dean-Stark tube and a thermometer, 15.3 g of brown crystals synthesized in the previous step 9 in a nitrogen stream, 70 ml of toluene, 2,6-di-t-butyl- 202 mg (0.921 mmol) of p-cresol was added and the whole volume was stirred. The whole volume was heated to 80 ° C., 10.0 g (92.15 mol) of 3-chloropropionic acid and 885 mg (9.21 mmol) of methanesulfonic acid were added, and dehydration was performed while removing generated water under reflux conditions (110 ° C.). The reaction was carried out for 2 hours. After completion of the reaction, the reaction solution internal temperature was lowered to 30 ° C., 70 ml of distilled water was added, and the whole volume was stirred and allowed to stand. The organic layer was separated, and 35 ml of distilled water was added to the obtained organic layer for liquid separation. The organic layer was separated, and 1.4 g of activated carbon was added to the obtained organic layer. The whole volume was stirred at 25 ° C. for 30 minutes, and then filtered to remove the activated carbon.
After adding 202 mg (0.921 mmol) of 2,6-di-t-butyl-p-cresol to the obtained filtrate, the solvent was distilled off from the filtrate under reduced pressure using a rotary evaporator. The obtained residue was purified by silica gel column chromatography (toluene: tetrahydrofuran =: 95: 5) to obtain 11.0 g of intermediate J as a white solid (total yield of steps 9 to 10: 40. 0 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 6.78 (d, 2H, J = 9.0 Hz), 6.76 (d, 2H, J = 9.0 Hz), 4.91 (s 1H), 4.14 (t, 2H, J = 6.5 Hz), 3.89 (t, 2H, J = 6.5 Hz), 3.76 (t, 2H, J = 6.5 Hz), 2 .79 (t, 2H, J = 6.5 Hz), 1.65-1.79 (m, 4H), 1.41-1.50 (m, 4H)

Step 11: Synthesis of Intermediate K

In a nitrogen stream, 12.50 g (72.60 mmol) of trans-1,4-cyclohexanedicarboxylic acid and 80 ml of THF were added to a three-necked reactor equipped with a thermometer. Thereto, 4.35 g (37.97 mmol) of methanesulfonyl chloride was added, and the reactor was immersed in an ice-water bath to adjust the internal temperature of the reaction solution to 5 ° C. Subsequently, 4.03 g (39.83 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 5 to 10 ° C. After completion of the dropwise addition, the whole volume was further stirred at 5 to 10 ° C. for 2 hours.
To the obtained reaction solution, 440 mg (3.60 mmol) of 4-dimethylaminopyridine and 10.9 g (36.24 mmol) of the intermediate J synthesized in the previous Step 10 were added, and the reactor was immersed again in an ice-water bath. The internal temperature of the reaction solution was 5 ° C. Thereto, 4.03 g (39.83 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 5 to 10 ° C. After completion of the dropwise addition, the ice-water bath was removed and the whole volume was adjusted to 25 ° C. Stir for another 2 hours. After completion of the reaction, 700 ml of distilled water and 70 ml of saturated brine were added to the reaction solution, and extracted twice with 250 ml of ethyl acetate. The organic layer was collected and dried over anhydrous sodium sulfate, and then sodium sulfate was filtered off. After the solvent was distilled off from the filtrate under reduced pressure using a rotary evaporator, the obtained residue was purified by silica gel column chromatography (chloroform: tetrahydrofuran = 97: 3) to obtain 9.30 g of Intermediate K as a white solid. (Yield: 56.4 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, DMSO-d ₆ , TMS, δ ppm): 12.12 (s, 1H), 6.99 (d, 2H, J = 9.0 Hz), 6.92 (d, 2H, J = 9.0 Hz), 4.07 (t, 2H, J = 6.5 Hz), 3.94 (t, 2H, J = 6.5 Hz), 3.79 (t, 2H, J = 6.5 Hz) 2.81 (t, 2H, J = 6.5 Hz), 2.47-2.56 (m, 1H), 2.18-2.27 (m, 1H), 2.01-2.11 ( m, 2H), 1.93-2.01 (m, 2H), 1.65-1.74 (m, 2H), 1.57-1.65 (m, 2H), 1.34-1. 52 (m, 8H)

Step 12: Synthesis of intermediate L

In a three-necked reactor equipped with a thermometer, 4.0 g (12.8 mmol) of the intermediate F synthesized in Step 6 above was added to 160 ml of THF in a nitrogen stream, and then cooled to 0 ° C. To this solution, 6.44 g (15.4 mmol) of intermediate H synthesized in Step 8 above, 156 mg (1.28 mmol) of 4-dimethylaminopyridine and 1.94 g (15.4 mmol) of N, N′-diisopropylcarbodiimide And stirred at room temperature for 1 hour. After completion of the reaction, 200 ml of water was added to the reaction solution and extracted with 400 ml of ethyl acetate. The obtained ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. After concentration by a rotary evaporator, the obtained residue was purified by silica gel column chromatography (toluene: ethyl acetate = 90: 10) to obtain 1.29 g of intermediate L as a skin-colored solid (yield: 14. 1 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.53 (d, 1H, J = 1.0 Hz), 7.21 (s, 1H), 7.10 (d, 1H, J = 9) 0.0Hz), 6.98-7.01 (m, 4H), 6.94 (s, 1H), 6.88 (d, 2H, J = 9.0 Hz), 6.41 (dd, 1H, J = 1.5 Hz, 17.5 Hz), 6.13 (dd, 1 H, J = 10.5 Hz, 17.5 Hz), 5.82 (dd, 1 H, J = 1.5 Hz, 10.5 Hz), 4. 18 (t, 2H, J = 7.0 Hz), 3.95 (t, 2H, J = 6.5 Hz), 2.53 (s, 3H), 2.47 (s, 3H), 2.32- 2.43 (m, 4H), 1.67-1.82 (m, 10H), 1.45-1.56 (m, 4H).

Step 13: Synthesis of Compound 1 In a four-necked reactor equipped with a thermometer, 1.13 g (1.58 mmol) of the intermediate L synthesized in Step 12 above was added to 30 ml of chloroform in a nitrogen stream. To this solution, 864 mg (1.90 mmol) of intermediate K synthesized in the previous Step 11 and 19.8 mg (0.16 mmol) of 4-dimethylaminopyridine were added, and the mixture was cooled to 0 ° C. Thereafter, 239 mg (1.90 mmol) of N, N′-diisopropylcarbodiimide was added to this solution, and the mixture was stirred at room temperature for 1.5 hours.
After completion of the reaction, the reaction solution was filtered using a filter medium pre-coated with silica gel, concentrated under reduced pressure, and 50 ml of methanol was added to the resulting residue. The precipitated white solid was collected by filtration, and the collected solid was vacuum-dried to obtain 1.23 g of Compound 1 as a white solid (yield: 67.6 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.53 (d, 1H, J = 1.0 Hz), 7.23 (s, 2H), 7.21 (s, 1H), 7. 001 (d, 2H, J = 9.0 Hz), 6.995 (d, 2H, J = 9.0 Hz), 6.94 (s, 1H), 6.89 (d, 4H, J = 9.0 Hz) ), 6.40 (dd, 1H, J = 1.5 Hz, 17.5 Hz), 6.13 (dd, 1H, J = 10.5 Hz, 17.5 Hz), 5.82 (dd, 1H, J = 1.5Hz, 10.5Hz), 4.18 (t, 2H, J = 6.5Hz), 4.15 (t, 2H, J = 7.0Hz), 3.95 (t, 4H, J = 6) .5Hz), 3.76 (t, 2H, J = 6.5Hz), 2.84 (tt, 1H, J = 3.5Hz, 11.5Hz), 2.79 (t 2H, J = 6.5 Hz), 2.59-2.73 (m, 3H), 2.54 (s, 3H), 2.44-2.48 (m, 5H), 2.32-2. 38 (m, 6H), 1.66-1.87 (m, 16H), 1.41-1.54 (m, 8H).

Synthesis Example 2 Synthesis of Compound 2

In a four-necked reactor equipped with a thermometer, 798 mg (2.56 mmol) of the intermediate F synthesized in Step 6 of Synthesis Example 1 was added to 30 ml of chloroform in a nitrogen stream. To this solution, 2.57 g (5.64 mmol) of intermediate K synthesized in Step 11 of Synthesis Example 1 and 31.3 mg (0.26 mmol) of 4-dimethylaminopyridine were added and cooled to 0 ° C. Thereafter, 776 mg (6.15 mmol) of N, N′-diisopropylcarbodiimide was added to this solution and stirred at room temperature for 2 hours.
After completion of the reaction, the reaction solution was filtered using a filter medium pre-coated with silica gel, concentrated under reduced pressure, and 50 ml of methanol was added to the resulting residue. The precipitated white solid was collected by filtration, and the collected solid was vacuum-dried to obtain 2.16 g of Compound 2 as a white solid (yield: 71.1 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.53 (d, 1H, J = 1.0 Hz), 7.23 (s, 2H), 7.21 (s, 1H), 7. 00 (d, 2H, J = 9.0 Hz), 6.995 (d, 2H, J = 9.0 Hz), 6.94 (s, 1H), 6.89 (d, 4H, J = 9.0 Hz) ), 4.15 (t, 4H, J = 7.0 Hz), 3.95 (t, 4H, J = 6.5 Hz), 2.84 (tt, 1H, J = 3.5 Hz, 11.5 Hz) 2.79 (t, 4H, J = 6.5 Hz), 2.59-2.73 (m, 3H), 2.54 (s, 3H), 2.42-2.47 (m, 5H) 2.32-2.38 (m, 6H), 1.66-1.87 (m, 16H), 1.41-1.54 (m, 8H).

(Synthesis Example 3) Synthesis of Compound 3

Step 1: Synthesis of Intermediate M

A three-necked reactor equipped with a condenser and a thermometer was charged with 104.77 g (0.9515 mol) of hydroquinone, 100 g (0.7320 mol) of 6-chlorohexanol, 500 ml of distilled water and 100 ml of o-xylene in a nitrogen stream. added. While stirring the whole volume, 35.15 g (0.8784 mol) of sodium hydroxide was further added little by little over 20 minutes so that the internal temperature of the reaction solution did not exceed 40 ° C. After completion of the addition of sodium hydroxide, the contents were heated and reacted for 12 hours under reflux conditions (96 ° C.).
After completion of the reaction, the internal temperature of the reaction solution was lowered to 80 ° C., 200 ml of distilled water was added, and then the reaction solution was cooled to 10 ° C. to precipitate crystals. The precipitated crystals were separated into solid and liquid by filtration, and the obtained crystals were washed with 500 ml of distilled water and vacuum-dried to obtain 123.3 g of brown crystals.
The brown crystals were purified by silica gel column chromatography (chloroform: methanol =: 90: 10) to obtain 20 g of intermediate M as a white solid (yield: 13 mol%).

Step 2: Synthesis of intermediate GG

In a three-necked reactor equipped with a condenser and a thermometer, in a nitrogen stream, intermediate M synthesized in Step 1 above: 20 g (95.12 mmol), N, N-diisopropylethylamine 12.3 g (95.95). 12 mmol) was dissolved in 500 ml of tetrahydrofuran. The solution was cooled in an ice bath and 5.16 g (57.01 mmol) of acryloyl chloride was slowly added dropwise while controlling the temperature to be 10 ° C. or lower. After completion of the dropping, the reaction was performed for 2 hours in an ice bath. After completion of the reaction, the reaction solution was poured into 1 liter of 0.1N hydrochloric acid aqueous solution and extracted twice with 300 ml of ethyl acetate. The obtained ethyl acetate layer was washed with 300 ml of saturated brine. Thereafter, the ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was removed by filtration. Ethyl acetate was distilled off by a rotary evaporator to obtain a pale yellow solid. The pale yellow solid was purified by silica gel column chromatography (toluene: ethyl acetate =: 95: 5) to obtain 5.6 g of a white solid (crude intermediate GG) containing intermediate GG (yield: 37). Mol%).
When the obtained solid was analyzed by HPLC, the following intermediate GG ′, which is a halogenated product of intermediate GG, was included in a ratio of 2.1% by mass in the total of intermediate GG and intermediate GG ′. It was.

 

Step 3: Synthesis of mixture N

In a nitrogen stream, 10.0 g (47.83 mmol) of trans-1,4-cyclohexanedicarboxylic acid dichloride, 84 ml of cyclopentyl methyl ether (CPME) and 31 ml of THF were added to a three-necked reactor equipped with a thermometer. Thereto was added 12.04 g of the crude intermediate GG synthesized in the previous step 2, and the reactor was immersed in an ice bath to adjust the internal temperature of the reaction solution to 0 ° C. Next, 4.83 g (47.83 mmol) of triethylamine was slowly added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 10 ° C. or lower. After completion of the dropwise addition, the whole volume was further stirred for 1 hour while maintaining the temperature at 10 ° C or lower.
30 ml of distilled water was added to the obtained reaction solution. The reaction solution was heated to 50 ° C., washed (hydrolyzed) for 2 hours, and the aqueous layer was extracted. Further, 30 ml of distilled water was added to the obtained organic layer, and the whole volume was washed (hydrolyzed) at 50 ° C. for 2 hours, and the aqueous layer was extracted. The obtained organic layer was cooled to 40 ° C., and further washed with 50 ml of a buffer solution (pH: 5.5) composed of acetic acid and sodium acetate at a concentration of 1 mol / liter, and then the buffer solution was extracted. . The obtained organic layer was further washed with 30 ml of distilled water, and then the aqueous layer was extracted.
To the obtained organic layer, 220 ml of n-hexane was added and then cooled to 0 ° C. to precipitate crystals. Thereafter, the precipitated crystals were collected by filtration. The filtrate was washed with n-hexane and then vacuum-dried to obtain 16.78 g of a mixture N as a white solid.
The obtained crystals were analyzed by HPLC, and the monoester and diester were quantified with a calibration curve. As a result, the target monoester was 11.49 g (27.45 mmol), and the diester was 5.29 g. (7.96 mmol) was found to be contained. The obtained crystals were analyzed by 13C-NMR (DMF-d7), and the content of cyclohexanedicarboxylic acid was calculated and found to be below the detection limit. When the mol content was calculated from the respective composition ratios, the monoester content was 77.52 mol% and the diester content was 22.48 mol%.

Step 4: Synthesis of Compound 3 In a four-necked reactor equipped with a thermometer, 524 mg (1.68 mmol) of Intermediate F synthesized in Step 6 of Synthesis Example 1 was added to 30 ml of chloroform in a nitrogen stream. To this solution, 2.26 g of the mixture N synthesized in the previous Step 3 and 20.5 mg (0.17 mmol) of 4-dimethylaminopyridine were added and cooled to 0 ° C. Thereafter, 509 mg (4.04 mmol) of N, N′-diisopropylcarbodiimide was added to this solution and stirred at room temperature for 1.5 hours.
After completion of the reaction, the reaction solution was filtered using a filter medium precoated with silica gel. After adding 80 ml of methanol to the obtained solution, it was cooled to 0 ° C. to precipitate crystals. Thereafter, the precipitated crystals were collected by filtration. The filtrated product was washed with methanol and then vacuum-dried to obtain 1.56 g of solid (crude compound 3) (yield: 83.4 mol%).
When the obtained solid was analyzed by HPLC, Compound 1, which is a halogenated compound of Compound 3, was contained at a ratio of 1.5 mass% in the total of Compound 3 and Compound 1.

(Synthesis Example 4) Synthesis of Compound 4

Step 1: Synthesis of intermediate O

In a four-necked reactor equipped with a thermometer, 15.0 g (102 mmol) of 2-thenoyl chloride and 15.7 g (102 mmol) of 2,5-dimethoxyaniline were dissolved in 150 g of chloroform in a nitrogen stream. To this solution, 20.7 g (205 mmol) of triethylamine was added and stirred at 60 ° C. for 2 hours. After completion of the reaction, 150 g of water was added, followed by extraction with 300 ml of chloroform. From the resulting chloroform layer, 300 ml of chloroform was distilled off under reduced pressure using a rotary evaporator, and then 300 ml of heptane was added. The precipitated pale yellow solid was collected by filtration, and the collected solid was vacuum-dried to obtain 23.4 g of Intermediate O as a pale yellow solid (yield: 86.7 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 8.45 (s, 1H), 8.20 (d, 1H, J = 3.0 Hz), 7.61 (dd, 1H, J = 1) .0 Hz, 3.5 Hz), 7.54 (dd, 1 H, J = 1.0 Hz, 5.0 Hz), 7.13 (dd, 1 H, J = 3.5 Hz, 5.0 Hz), 6.83 ( d, 1H, J = 9.0 Hz), 6.61 (dd, 1H, J = 3.0 Hz, 9.0 Hz), 3.89 (s, 3H), 3.81 (s, 3H).

Step 2: Synthesis of intermediate P

In a four-necked reactor equipped with a thermometer, 21.0 g (79.8 mmol) of the intermediate O synthesized in Step 1 was dissolved in 300 ml of toluene in a nitrogen stream. To this solution, 19.4 g (47.7 mmol) of 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane was added and heated to reflux for 4 hours. After completion of the reaction, the reaction solution was cooled to 30 ° C., 1000 ml of 1M aqueous sodium hydroxide solution was added, and the mixture was extracted with 1000 ml of toluene. Toluene was distilled off under reduced pressure from the obtained toluene layer with a rotary evaporator to obtain an oily substance. The obtained oily substance was purified by silica gel column chromatography (toluene: ethyl acetate = 90: 10) to obtain 21.2 g of intermediate P as an orange oily substance (yield: 95.2 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 9.71 (s, 1H), 8.88 (s, 1H), 7.52 (dd, 1H, J = 1.0 Hz, 5.0 Hz ), 7.47 (dd, 1H, J = 1.0 Hz, 4.0 Hz), 7.09 (dd, 1H, J = 4.0 Hz, 5.0 Hz), 6.86 (d, 1H, J = 9.0 Hz), 6.70 (dd, 1H, J = 3.0 Hz, 9.0 Hz), 3.89 (s, 3H), 3.78 (s, 3H).

Step 3: Synthesis of Intermediate Q

In a nitrogen stream, 21.0 g (75.3 mmol) of the intermediate P synthesized in Step 2 above, 350 g of water, and 24.6 g (438 mmol) of potassium hydroxide were added to a four-necked reactor equipped with a thermometer and iced. Stir in the cold. After adding 65.7 g (200 mmol) of potassium ferricyanide and 20 g of methanol to the obtained mixture, the mixture was heated to 25 ° C. and stirred for 15 hours. After completion of the reaction, the precipitated yellow solid was collected by filtration, and the collected solid was vacuum-dried to obtain 10.2 g of Intermediate Q as a yellow solid (yield: 46.1 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (400 MHz, CDCl ₃ , TMS, δ ppm): 7.67 (dd, 1 H, J = 1.2 Hz, 3.6 Hz), 7.46 (dd, 1 H, J = 1.2 Hz, 5. 2 Hz), 7.11 (dd, 1 H, J = 3.6 Hz, 5.2 Hz), 6.82 (d, 1 H, J = 8.8 Hz), 7.30 (d, 1 H, J = 8.8 Hz) ) 4.02 (s, 3H), 3.95 (s, 3H).

Step 4: Synthesis of Intermediate R

In a 4-necked reactor equipped with a thermometer, 6.30 g (23.2 mmol) of the intermediate Q synthesized in Step 3 above was dissolved in 150 ml of toluene in a nitrogen stream, and then cooled to 0 ° C. To this solution, 139 ml (139 mmol) of 1M boron tribromide dichloromethane solution was added and stirred for 1 hour. After completion of the reaction, the reaction solution was added to 500 ml of water, and the precipitated solid was collected by filtration. The obtained solid was vacuum-dried to obtain 5.37 g of intermediate R as a yellow solid (yield: 93.2 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, DMSO-d6, TMS, δ ppm): 9.82 (s, 1H), 9.48 (s, 1H), 7.83 (dd, 1H, J = 1.0 Hz, 5. 0 Hz), 7.78 (dd, 1 H, J = 1.0 Hz, 3.5 Hz), 7.23 (dd, 1 H, J = 3.5 Hz, 5.0 Hz), 6.74 (d, 1 H, J = 8.5 Hz), 6.68 (d, 1H, J = 8.5 Hz).

Step 5: Synthesis of intermediate S

To a three-necked reactor equipped with a thermometer, 2.50 g (10.1 mmol) of the intermediate R synthesized in Step 4 above was added to 100 ml of THF in a nitrogen stream, and then cooled to 0 ° C. To this solution, 5.05 g (12.1 mmol) of intermediate H synthesized in Step 8 of Synthesis Example 1, 123 mg (1.01 mmol) of 4-dimethylaminopyridine and 1.52 g (12.12) of N, N′-diisopropylcarbodiimide. 1 mmol) was added and stirred at room temperature for 1 hour. After completion of the reaction, 100 ml of water was added to the reaction solution and extracted with 300 ml of ethyl acetate. The obtained ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. After concentration with a rotary evaporator, 80 ml of methanol was added to the resulting residue. The precipitated flesh-colored solid was collected by filtration, and the collected solid was vacuum-dried to obtain 1.49 g of a flesh-colored solid containing Intermediate S as a main component (yield: 22.8 mol%). The obtained solid was used in the next step without further purification.

Step 6: Synthesis of Compound 4 In a four-necked reactor equipped with a thermometer, 1.30 g (2.00 mmol) of the intermediate S synthesized in Step 5 above was added to 30 ml of chloroform in a nitrogen stream. To this solution, 1.09 g (2.40 mmol) of intermediate K synthesized in Step 11 of Synthesis Example 1 and 24.5 mg (0.20 mmol) of 4-dimethylaminopyridine were added and cooled to 0 ° C. Thereafter, 303 mg (2.40 mmol) of N, N′-diisopropylcarbodiimide was added to the solution, and the mixture was stirred at room temperature for 1.5 hours.
After completion of the reaction, the reaction solution was filtered using a filter medium pre-coated with silica gel, concentrated under reduced pressure, and 50 ml of methanol was added to the resulting residue. The precipitated white solid was collected by filtration, and the collected solid was vacuum-dried to obtain 2.01 g of compound 4 as a white solid (yield: 89.4 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.63 (dd, 1 H, J = 1.0 Hz, 3.5 Hz), 7.50 (dd, 1 H, J = 1.0 Hz, 5. 0 Hz), 7.17 (s, 2H), 7.11 (dd, 1H, J = 3.5 Hz, 5.0 Hz), 6.994 (d, 2H, J = 9.0 Hz), 6.988 ( d, 2H, J = 9.0 Hz), 6.88 (d, 4H, J = 9.0 Hz), 6.40 (dd, 1H, J = 1.5 Hz, 17.5 Hz), 6.12 (dd 1H, J = 10.0 Hz, 17.5 Hz), 5.82 (dd, 1 H, J = 1.5 Hz, 10.0 Hz), 4.17 (t, 2H, J = 6.5 Hz), 4. 13 (t, 2H, J = 7.0 Hz), 3.93 (t, 4H, J = 6.5 Hz), 3.76 (t, 2H, J = 6.5 Hz) 2.79 (tt, 1H, J = 3.5 Hz, 11.5 Hz), 2.58-2.71 (m, 5H), 2.41-2.46 (m, 2H), 2.29- 2.34 (m, 6H), 1.62-1.89 (m, 16H), 1.40-1.52 (m, 8H).

Synthesis Example 5 Synthesis of Compound 5

In a 4-necked reactor equipped with a thermometer, 526 mg (2.11 mmol) of the intermediate R synthesized in Step 4 of Synthesis Example 4 was added to 20 ml of chloroform in a nitrogen stream. To this solution were added 2.11 g (4.64 mmol) of intermediate K synthesized in Step 11 of Synthesis Example 1 and 25.8 mg (0.21 mmol) of 4-dimethylaminopyridine, and the mixture was cooled to 0 ° C. Thereafter, 639 mg (5.06 mmol) of N, N′-diisopropylcarbodiimide was added to this solution, and the mixture was stirred at room temperature for 1.5 hours.
After completion of the reaction, the reaction solution was filtered using a filter medium pre-coated with silica gel, concentrated under reduced pressure, and 50 ml of methanol was added to the resulting residue. The precipitated white solid was collected by filtration, and the collected solid was vacuum-dried to obtain 1.77 g of compound 5 as a white solid (yield: 74.7 mol%).
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.64 (dd, 1 H, J = 1.0 Hz, 3.5 Hz), 7.52 (dd, 1 H, J = 1.0 Hz, 5. 0 Hz), 7.18 (s, 2H), 7.13 (dd, 1H, J = 3.5 Hz, 5.0 Hz), 6.993 (d, 2H, J = 9.0 Hz), 6.987 ( d, 2H, J = 9.0 Hz), 6.88 (d, 4H, J = 9.0 Hz), 4.14 (t, 4H, J = 7.0 Hz), 3.94 (t, 4H, J = 6.5 Hz), 3.76 (t, 4H, J = 6.5 Hz), 2.79 (tt, 1H, J = 3.5 Hz, 11.5 Hz), 2.58-2.71 (m, 7H), 2.42-2.45 (m, 2H), 2.29-2.35 (m, 6H), 1.63-1.89 (m, 16H), 1.41- .54 (m, 8H).

Synthesis Example 6 Synthesis of Compound 6

In a nitrogen stream, 524 mg (1.68 mmol) of the intermediate R synthesized in Step 4 of Synthesis Example 4 was added to 30 ml of chloroform in a four-necked reactor equipped with a thermometer. To this solution, 2.81 g of the mixture N synthesized in Step 3 of Synthesis Example 3 and 25.5 mg (0.21 mmol) of 4-dimethylaminopyridine were added and cooled to 0 ° C. Thereafter, 633 mg (5.02 mmol) of N, N′-diisopropylcarbodiimide was added to this solution and stirred at room temperature for 1 hour.
After completion of the reaction, the reaction solution was filtered using a filter medium precoated with silica gel. 70 ml of methanol was added to the resulting solution, and then cooled to 0 ° C. to precipitate crystals. Thereafter, the precipitated crystals were collected by filtration. The filtrate was washed with methanol and then vacuum-dried to obtain 1.77 g of a solid (crude compound 6) (yield: 80.6 mol%).
When the obtained solid was analyzed by HPLC, Compound 4 which is a halide of Compound 6 was contained at a ratio of 1.4% by mass in the total of Compound 6 and Compound 4.

(Synthesis Example 7) Synthesis of Compound 7

In a nitrogen stream, 4.15 g (19.87 mmol) of transcyclohexanedicarboxylic acid dichloride was dissolved in 30 g of cyclopentylmethyl ether and 11.5 g of tetrahydrofuran in a three-necked reactor equipped with a cooler and a thermometer. After this solution was cooled in an ice bath, 5.0 g of the crude intermediate GG obtained in Step 2 of Synthesis Example 3 was added and dissolved. Under an ice bath, 2.01 g (19.87 mmol) of triethylamine was controlled to be 10 ° C. or lower and slowly dropped into this solution. After completion of the dropwise addition, the whole volume was returned to 25 ° C. and further stirred for 1 hour. Distilled water (80 ml) was added to the resulting reaction solution, and the mixture was washed at 50 ° C. for 4 hours, and then the aqueous layer was extracted. The organic layer was further washed five times with 150 ml of a buffer solution (pH: 5.5) composed of acetic acid and sodium acetate having a concentration of 1.0 mol / liter, and then the buffer solution was extracted. The organic layer was further washed with 100 ml of distilled water and separated. To the obtained organic layer, 400 ml of n-hexane was added to precipitate crystals, and the precipitated crystals were collected by filtration. The obtained crystals were purified by silica gel column chromatography (toluene: ethyl acetate =: 70: 30) to obtain 3.56 g of a white solid (crude compound 7) containing compound 7 (yield: 45 mol%). ).
When the obtained solid was analyzed by HPLC, the following compound 7 ′, which is a halide of compound 7, was contained at a ratio of 1.8 mass% in the total of compound 7 and compound 7 ′.

Synthesis Example 8 Synthesis of Mixture 7 In a three-necked reactor equipped with a cooler and a thermometer, in a nitrogen stream, 4.15 g (19.87 mmol) of transcyclohexanedicarboxylic acid dichloride 30 g of cyclopentyl methyl ether and tetrahydrofuran 11 Dissolved in 5 g. After this solution was cooled in an ice bath, 5.0 g of the crude intermediate GG obtained in Step 2 of Synthesis Example 3 was added and dissolved. Under an ice bath, 2.01 g (19.87 mmol) of triethylamine was controlled to be 10 ° C. or lower and slowly dropped into this solution. After completion of the dropwise addition, the whole volume was returned to 25 ° C. and further stirred for 1 hour. Distilled water (15 ml) was added to the resulting reaction solution, washed at 50 ° C. for 4 hours, and then the aqueous layer was extracted. The organic layer was further washed five times with 25 g of a buffer solution (pH: 5.5) composed of acetic acid and sodium acetate having a concentration of 1.0 mol / liter, and then the buffer solution was extracted. The organic layer was further washed with 15 ml of distilled water and separated. To the resulting organic layer, 60 g of 60% hexane was added to precipitate crystals. The resulting solution was cooled to 0 ° C. and stirred for 1 hour. Thereafter, the precipitated crystals were collected by filtration to obtain 7.25 g of a solid (mixture 7). When the obtained solid was quantitatively analyzed by HPLC, it contained 5.5 g in total of Compound 7 and Compound 7 ′, which is a halogenated form of Compound 7, and 1.74 g of diester. Furthermore, when the composition of the obtained solid was analyzed by HPLC, Compound 7 ′, which is a halide of Compound 7, was contained at a ratio of 1.5 mass% in the total of Compound 7 and Compound 7 ′. .

Example 1 Dehydrochlorination Reaction of Compound 1 In a four-necked reactor equipped with a thermometer, in a nitrogen stream, the compound synthesized in Synthesis Example 1 1: 1.0 g (0.871 mmol), triethylamine 132 mg (1 .31 mmol) was dissolved in a mixed solvent of 30 ml of ethyl acetate and 15 ml of acetonitrile. To this solution, 1.5 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, an aqueous sodium carbonate solution was extracted, and the resulting organic layer was further washed with 30 ml of water. 70 ml of methanol was added to the organic layer to precipitate a solid. The obtained solid was dried with a vacuum dryer to obtain 913 mg of a white solid.
When the obtained solid was analyzed by HPLC, the peak of Compound 1 which was a halide was completely disappeared, and it was found that Compound 1 was converted to Compound 3.
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.53 (d, 1H, J = 1.0 Hz), 7.23 (s, 2H), 7.21 (s, 1H), 6. 999 (d, 2H, J = 9.0 Hz), 6.995 (d, 2H, J = 9.0 Hz), 6.94 (s, 1H), 6.89 (d, 4H, J = 9.0 Hz) ), 6.40 (dd, 2H, J = 1.5 Hz, 17.5 Hz), 6.12 (dd, 2H, J = 10.5 Hz, 17.5 Hz), 5.82 (dd, 2H, J = 1.5Hz, 10.5Hz), 4.18 (t, 4H, J = 7.0Hz), 3.95 (t, 4H, J = 6.5Hz), 2.84 (tt, 1H, J = 3) .5Hz, 12.0Hz), 2.59-2.75 (m, 3H), 2.54 (s, 3H), 2.47 (s, 3H), 2.42-2 46 (m, 2H), 2.31-2.41 (m, 6H), 1.69-1.87 (m, 16H), 1.41-1.57 (m, 8H).

Example 2 Dehydrochlorination Reaction of Compound 2 In Example 1, Compound 1: 1.0 g (0.871 mmol) was changed to Compound 2: 1.0 g (0.843 mmol) synthesized in Synthesis Example 2. Except for this, the same operation as in Example 1 was performed. As a result, 887 mg of a white solid was obtained.
When the obtained solid was analyzed by HPLC, the peak of Compound 2 which was a halogenated compound disappeared completely, and Compound 2 was converted to Compound 3.
The structure of the target product was identified by ¹ H-NMR.

Example 3 Dehydrochlorination Reaction of Crude Compound 3 In Example 1, except that Compound 1: 1.0 g (0.871 mmol) was changed to Crude Compound 3: 1.0 g synthesized in Synthesis Example 3, The same operation as in Example 1 was performed. As a result, 952 mg of a white solid was obtained.
When the obtained solid was analyzed by HPLC, the peak of Compound 1 as a halogenated product disappeared completely, and Compound 1 was converted to Compound 3.
The structure of the target product was identified by ¹ H-NMR.

(Example 4) Dehydrochlorination reaction of Compound 4 In Example 1, Compound 1: 1.0 g (0.871 mmol) was changed to Compound 4: 1.0 g (0.920 mmol) synthesized in Synthesis Example 4. Except for this, the same operation as in Example 1 was performed. As a result, 902 mg of white solid was obtained.
When the obtained solid was analyzed by HPLC, the peak of Compound 4 as a halogenated compound disappeared completely, and Compound 4 was converted to Compound 6.
The structure of the target product was identified by ¹ H-NMR. ¹ H-NMR spectrum data is shown below.

¹ H-NMR (500 MHz, CDCl ₃ , TMS, δ ppm): 7.63 (dd, 1 H, J = 1.0 Hz, 3.5 Hz), 7.51 (dd, 1 H, J = 1.0 Hz, 5. 0 Hz), 7.18 (s, 2H), 7.12 (dd, 1H, J = 3.5 Hz, 5.0 Hz), 6.993 (d, 2H, J = 9.0 Hz), 6.987 ( d, 2H, J = 9.0 Hz), 6.88 (d, 4H, J = 9.0 Hz), 6.40 (dd, 2H, J = 1.5 Hz, 17.5 Hz), 6.12 (dd 2.H, J = 10.0 Hz, 17.5 Hz), 5.82 (dd, 2H, J = 1.5 Hz, 10.0 Hz), 4.17 (t, 4H, J = 6.5 Hz), 3. 94 (t, 4H, J = 6.5 Hz), 2.79 (tt, 1H, J = 3.5 Hz, 11.5 Hz), 2.58-2. 1 (m, 3H), 2.42-2.45 (m, 2H), 2.31-2.36 (m, 6H), 1.66-1.89 (m, 16H), 1.42- 1.54 (m, 8H).

Example 5 Dehydrochlorination Reaction of Compound 5 In Example 1, Compound 1: 1.0 g (0.871 mmol) was changed to Compound 5 synthesized in Synthesis Example 5: 1.0 g (0.890 mmol). Except for this, the same operation as in Example 1 was performed. As a result, 914 mg of white solid was obtained.
When the obtained solid was analyzed by HPLC, the peak of Compound 5 which was a halogenated product disappeared completely, and Compound 5 was converted to Compound 6.
The structure of the target product was identified by ¹ H-NMR.

Example 6 Dehydrochlorination Reaction of Crude Compound 6 In Example 1, except that Compound 1: 1.0 g (0.871 mmol) was changed to Crude Compound 6 synthesized in Synthesis Example 6: 1.0 g, The same operation as in Example 1 was performed. As a result, 965 mg of a white solid was obtained.
When the obtained solid was analyzed by HPLC, the peak of Compound 4 as a halogenated compound disappeared completely, and Compound 4 was converted to Compound 6.
The structure of the target product was identified by ¹ H-NMR.

(Example 7) Dehydrochlorination reaction of intermediate J Intermediate J synthesized in Step 10 of Synthesis Example 1 in a nitrogen stream in a four-necked reactor equipped with a thermometer: 1.0 g (3. 32 mmol) and 505 mg (4.99 mmol) of triethylamine were dissolved in a mixed solvent of 40 ml of ethyl acetate and 20 ml of acetonitrile. To this solution, 9.0 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, the aqueous sodium carbonate solution was extracted, and the obtained organic layer was further washed with 20 ml of 0.5N hydrochloric acid aqueous solution. Subsequently, it was washed twice with 50 ml of distilled water. To the obtained ethyl acetate layer, 200 ml of n-hexane was added to precipitate a solid. The solid was collected by filtration and dried with a vacuum dryer to obtain 0.77 g of a white solid. When the obtained solid was analyzed by HPLC, the peak of intermediate J, which is a halogenated product, disappeared completely, indicating that intermediate J was converted to intermediate GG. This intermediate GG can be used for the synthesis of a predetermined polymerizable compound (I).

Example 8 Dehydrochlorination Reaction of Intermediate K Intermediate K synthesized in Step 11 of Synthesis Example 1 in a nitrogen stream in a four-necked reactor equipped with a thermometer: 1.0 g (2. 20 mmol) and 334 mg (3.30 mmol) of triethylamine were dissolved in a mixed solvent of 40 ml of ethyl acetate and 20 ml of acetonitrile. To this solution, 8.0 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, the aqueous sodium carbonate solution was extracted, and the obtained organic layer was further washed with 20 ml of 0.5N hydrochloric acid aqueous solution. Subsequently, it was washed twice with 50 ml of distilled water. To the obtained ethyl acetate layer, 200 ml of n-hexane was added to precipitate a solid. The solid was collected by filtration and dried with a vacuum dryer to obtain 0.82 g of a white solid. When the obtained solid was analyzed by HPLC, the peak of intermediate K, which was a halogenated product, disappeared completely, indicating that intermediate K was converted to the following compound K ′. This compound K ′ can be used for the synthesis of a predetermined polymerizable compound (I).

(Example 9) Dehydrochlorination reaction of crude intermediate GG In a four-necked reactor equipped with a thermometer, in a nitrogen stream, crude intermediate GG synthesized in Step 2 of Synthesis Example 3 above: 1.0 g, 505 mg (4.99 mmol) of triethylamine was dissolved in a mixed solvent of 40 ml of ethyl acetate and 20 ml of acetonitrile. To this solution, 9.0 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, the aqueous sodium carbonate solution was extracted, and the obtained organic layer was further washed with 20 ml of 0.5N hydrochloric acid aqueous solution. Subsequently, it was washed twice with 50 ml of distilled water. To the obtained ethyl acetate layer, 200 ml of n-hexane was added to precipitate a solid. The solid was collected by filtration and dried with a vacuum dryer to obtain 0.92 g of a white solid. When the obtained solid was analyzed by HPLC, it was found that the intermediate GG ′ was converted to the intermediate GG because the peak of the intermediate GG ′, which was a halide, had completely disappeared. This intermediate GG can be used for the synthesis of a predetermined polymerizable compound (I).

(Example 10) Dehydrochlorination reaction of crude compound 7 In a four-necked reactor equipped with a thermometer, crude compound 7 synthesized in the previous synthesis example 7 in a nitrogen stream: 1.0 g (2.20 mmol), 334 mg (3.30 mmol) of triethylamine was dissolved in a mixed solvent of 40 ml of ethyl acetate and 20 ml of acetonitrile. To this solution, 8.0 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, the aqueous sodium carbonate solution was extracted, and the obtained organic layer was further washed with 20 ml of 0.5N hydrochloric acid aqueous solution. Subsequently, it was washed twice with 50 ml of distilled water. To the obtained ethyl acetate layer, 200 ml of n-hexane was added to precipitate a solid. The solid was collected by filtration and dried with a vacuum dryer to obtain 0.89 g of a white solid. When the obtained solid was analyzed by HPLC, the peak of compound 7 ′, which was a halogenated product, was completely disappeared. Thus, it was found that compound 7 ′ was converted to compound 7. This compound 7 can be used for the synthesis of a predetermined polymerizable compound (I).

Example 11 Dehydrochlorination Reaction of Mixture 7 In a four-necked reactor equipped with a thermometer, 7.25 g of the mixture 7 synthesized in Synthesis Example 7 above in a nitrogen stream, and 2.0 g of triethylamine (19. 71 mmol) was dissolved in a mixed solvent of 200 ml of ethyl acetate and 100 ml of acetonitrile. To this solution, 50 ml of a 1 mol / L sodium carbonate aqueous solution was added and stirred at 50 ° C. for 4 hours. After completion of the reaction, an aqueous sodium carbonate solution was extracted, and the obtained organic layer was further washed with 110 ml of 0.5N hydrochloric acid aqueous solution. Subsequently, it was washed twice with 100 ml of distilled water. The obtained ethyl acetate layer was concentrated to 100 ml with a rotary evaporator. To this ethyl acetate layer, 500 ml of n-hexane was added to precipitate a solid. The solid was collected by filtration and dried with a vacuum dryer to obtain 6.58 g of a white solid. When the obtained solid was analyzed by HPLC, the peak of compound 7 ′, which was a halogenated product, was completely disappeared. Thus, it was found that compound 7 ′ was converted to compound 7. This compound 7 can be used for the synthesis of a predetermined polymerizable compound (I).

According to the present invention, it is possible to provide a method for producing a highly pure polymerizable compound in an industrially advantageous manner.

Claims (15)

1. A method for producing a polymerizable compound represented by the following formula (I),
   A production method comprising a step of subjecting a composition containing a halogenated compound represented by the following formula (II) to a dehydrohalogenation reaction in an organic solvent in the presence of an aqueous layer containing a basic compound.
   

   

   [In the formula (I), Ar is any one of groups represented by the following formulas (Ar-1) to (Ar-4);
   

   

   E ¹ and E ² each independently represent —CR ¹¹ R ¹² —, —S—, —NR ¹¹ —, —CO—, or —O—, and each of R ¹¹ and R ¹² independently represents Represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms,
   Rc is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a carboxyl group, or a carbon group having 1 to 6 carbon atoms. Fluoroalkyl group, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, N, N-dialkylamino group having 2 to 12 carbon atoms, carbon number An N-alkylsulfamoyl group having 1 to 6 carbon atoms or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms;
   p0 is an integer from 0 to 2,
   D ¹ and D ² each independently represents an aromatic hydrocarbon ring group that may have a substituent, or an aromatic heterocyclic group that may have a substituent,
   Z ¹ and Z ² are each independently a single bond, —O—CH ₂ —, —CH ₂ —O—, —C (═O) —O—, —O—C (═O) —, — C (═O) —S—, —S—C (═O) —, —NR ¹³ —C (═O) —, —C (═O) —NR ¹³ —, —CF ₂ —O—, —O —CF ₂ —, —CH ₂ —CH ₂ —, —CF ₂ —CF ₂ —, —O—CH ₂ —CH ₂ —O—, —CH═CH—C (═O) —O—, —O— _{C (= O) -CH = CH} -, - CH 2 -CH 2 -C (= O) -O -, - O-C (= O) -CH 2 -CH 2 -, - CH 2 -CH 2 - O—C (═O) —, —C (═O) —O—CH ₂ —CH ₂ —, —CH═CH—, —N═CH—, —CH═N—, —N═C (CH ₃ )-, -C (CH ₃ ) = N-, -N = N-, or -C≡C- R ¹³ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms,
   A ¹ , A ² , B ¹ and B ² each independently represent a cyclic aliphatic group which may have a substituent, or an aromatic group which may have a substituent,
   Y ¹ , Y ² , L ¹ and L ² are each independently a single bond, —O—, —CO—, —CO—O—, —O—CO—, —NR ¹⁴ —CO—, —CO —NR ¹⁴ —, —O—CO—O—, —NR ¹⁴ —CO—O—, —O—CO—NR ¹⁴ —, or —NR ¹⁴ —CO—NR ¹⁵ —, wherein R ¹⁴ and R ¹⁵ are Each independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
   R ¹ and R ² each independently represents a hydrogen atom, a methyl group, or a chlorine atom,
   a and d each independently represents an integer of 1 to 20,
   b and c are each independently 0 or 1,
   When a plurality of Rc are present, they may be the same or different. ]
   

   

   
   [In Formula (II), X ¹ represents a halogen atom;
   G represents an organic group,
   R ¹ and a represent the same meaning as the formula (I). ]
2. The production method according to claim 1, wherein the halide represented by the formula (II) is a halide represented by the following formula (III).
   

   

   [In the formula (III), Q is represented by the following formula (III-1) or the following formula (III-2);
   

   

   [In Formula (III-1) and Formula (III-2), R ² represents the same meaning as in Formula (I), and X ² in Formula (III-2) represents a halogen atom. ]
   X ¹ represents the same meaning as in the formula (II),
   Ar, Z ¹ , Z ² , A ¹ , A ² , B ¹ , B ² , Y ¹ , Y ² , L ¹ , L ² , R ¹ , and a to d have the same meaning as in the formula (I). To express. ]
3. Wherein X ¹ and X ² is a chlorine atom, a manufacturing method of claim 2.
4. The production method according to claim 1, wherein the halide represented by the formula (II) is a halide represented by the following formula (IV).
   

   

   [In formula (IV), FG ¹ represents a hydroxyl group, a carboxyl group or an amino group,
   R ¹ , Y ¹ , B ¹ and a represent the same meaning as in the formula (I),
   X ¹ represents the same meaning as in the formula (II). ]
5. The production method according to claim 4, wherein X ¹ is a chlorine atom.
6. The production method according to claim 4 or 5, wherein the FG ¹ is a hydroxyl group.
7. The production method according to any one of claims 4 to 6, wherein the composition is a mixture comprising a halide represented by the formula (IV) and a compound represented by the following formula (V).
   

   

   [In Formula (V), R ¹ , Y ¹ , B ¹ , FG ¹ and a represent the same meaning as in Formula (IV). ]
8. The proportion of the halide represented by the formula (IV) in the total of the compound represented by the formula (IV) and the compound represented by the formula (V) is 0.01% by mass or more and 5% by mass. The manufacturing method of Claim 7 which is the following.
9. The production method according to claim 1, wherein the halide represented by the formula (II) is a halide represented by the following formula (VI).
   

   

   [In Formula (VI), FG ² represents a hydroxyl group, a carboxyl group, or an amino group,
   R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , a and b represent the same meaning as in the formula (I),
   X ¹ represents the same meaning as in the formula (II). ]
10. The production method according to claim 9, wherein X ¹ is a chlorine atom.
11. The FG ² is a carboxyl group;
    The manufacturing method according to claim 9 or 10, wherein b is 1.
12. The production method according to any one of claims 9 to 11, wherein the composition is a mixture containing a halide represented by the formula (VI) and a compound represented by the following formula (VII).
    

    

    [In the formula (VII), R ¹ , Y ¹ , B ¹ , L ¹ , A ¹ , FG ² , a and b represent the same meaning as in the formula (VI). ]
13. The proportion of the halogenated compound represented by the formula (VI) in the total of the halogenated compound represented by the formula (VI) and the compound represented by the formula (VII) is 0.01% by mass or more and 5% by mass. The manufacturing method of Claim 12 which is the following.
14. The production method according to any one of claims 1 to 13, wherein D ¹ and D ² are each independently any one of groups represented by the following formulas (d-1) to (d-8): .
    

    

    [In the formulas (d-1) to (d-8), Rd represents a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, 6 alkylsulfonyl groups, carboxyl groups, fluoroalkyl groups having 1 to 6 carbon atoms, alkoxy groups having 1 to 6 carbon atoms, thioalkyl groups having 1 to 6 carbon atoms, N-alkylamino groups having 1 to 6 carbon atoms, carbon An N, N-dialkylamino group having 2 to 12 carbon atoms, an N-alkylsulfamoyl group having 1 to 6 carbon atoms, or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms,
    p1 is an integer from 0 to 5, p2 is an integer from 0 to 4, p3 is an integer from 0 to 3, and p4 is an integer from 0 to 2,
    Rf represents a hydrogen atom or a methyl group,
    When a plurality of Rd are present, they may be the same or different from each other. ]
15. The production method according to any one of claims 1 to 13, wherein Ar is any one of groups represented by the following formulas (Ar-5) to (Ar-9).
    

    

    [In the formulas (Ar-5) to (Ar-9), E ¹ , Rc, and p0 represent the same meaning as described above,
    Rd is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a carboxyl group, or a carbon group having 1 to 6 carbon atoms. Fluoroalkyl group, alkoxy group having 1 to 6 carbon atoms, thioalkyl group having 1 to 6 carbon atoms, N-alkylamino group having 1 to 6 carbon atoms, N, N-dialkylamino group having 2 to 12 carbon atoms, carbon number An N-alkylsulfamoyl group having 1 to 6 carbon atoms or an N, N-dialkylsulfamoyl group having 2 to 12 carbon atoms;
    p1 represents an integer of 0 to 5, p2 represents an integer of 0 to 4, p3 represents an integer of 0 to 3,
    When a plurality of Rc and Rd are present, they may be the same or different from each other. ]