WO2016072366A1

WO2016072366A1 - Butyrolactone compound, and production method

Info

Publication number: WO2016072366A1
Application number: PCT/JP2015/080805
Authority: WO
Inventors: 裕一後藤; 雅久遠藤; 軍孫
Original assignee: 日産化学工業株式会社
Priority date: 2014-11-04
Filing date: 2015-10-30
Publication date: 2016-05-12
Also published as: JP6760075B2; TWI696613B; TW201623270A; JPWO2016072366A1; KR102508578B1; KR20170081201A; CN107108540B; CN107108540A

Abstract

Provided are: a novel production method for inexpensively producing, in high yield, a photopolymerizable compound used in liquid crystal display elements or the like; and a novel intermediate compound. In a method for producing a compound represented by formula (1), a compound represented by formula (A) is reacted with a compound represented by formula (C), under acidic conditions, in the presence of metallic tin or a tin-containing compound. In a method for producing a compound represented by formula (2-A), the compound represented by formula (1) is reacted with a compound represented by formula (D), in the presence of a base. Also provided are the compound represented by formula (1) and the compound represented by formula (2-A). (In the formulae: n represents 1 or 2; J¹ and J² represent halogens; R represents a C1-6 alkyl group; Y¹ represents -SO₂-R²; and R represents a hydrocarbon group.)

Description

Butyrolactone compound and production method

The present invention relates to a method for producing a compound having a butyrolactone ring, and a novel intermediate compound used therein.

In a liquid crystal display element of a method (also referred to as a vertical alignment (VA) method) in which liquid crystal molecules aligned perpendicular to a substrate are responded by an electric field, a voltage is applied to the liquid crystal molecules during the manufacturing process. Some of them include a step of irradiating ultraviolet rays.
In such a vertical alignment type liquid crystal display element, a photopolymerizable compound is added to a liquid crystal composition in advance and used together with a vertical alignment film such as polyimide to irradiate ultraviolet rays while applying a voltage to a liquid crystal cell. A PSA (Polymer sustained Alignment) type liquid crystal display (PSA) that increases the response speed of liquid crystal is known. (See Patent Document 1 and Non-Patent Document 1)

Usually, the direction in which the liquid crystal molecules tilt in response to an electric field is controlled by protrusions provided on the substrate or slits provided on the display electrode, but a photopolymerizable compound is added to the liquid crystal composition, By irradiating ultraviolet rays while applying voltage to the liquid crystal cell, a polymer structure in which the tilted direction of the liquid crystal molecules is stored is formed on the liquid crystal alignment film. It is said that the response speed of the liquid crystal display element is faster than the method of controlling the above.
It has also been reported that the response speed of the liquid crystal display element is increased by adding a photopolymerizable compound to the liquid crystal alignment film instead of the liquid crystal composition (SC-PVA liquid crystal display) (non-patented). Reference 2).
As the additive photopolymerizable compound, several polymerizable compounds are known (see Patent Documents 2 to 6).

Japanese Unexamined Patent Publication No. 2003-307720 Japanese Unexamined Patent Publication No. 2008-239873 Japanese Unexamined Patent Publication No. 2011-84477 Japanese Unexamined Patent Publication No. 2012-240945 Japanese special table 2013-509457 gazette British Patent Application GB 2297549A

Photopolymerizable compounds have heretofore been manufactured using expensive compounds as raw materials. Therefore, as a raw material for electronic equipment that requires cost reduction, there has been a problem in its supplyability. Therefore, there is a need for a novel production method that can produce a photopolymerizable compound at low cost.

An object of the present invention is to solve the problems of the prior art described above.
Specifically, an object of the present invention is to provide a novel production method and a novel intermediate for producing a photopolymerizable compound used in a liquid crystal display element at a low cost and in a high yield.

In order to achieve the above object, the present inventors use an expensive raw material selected from a hydroxyphenyl group and a hydroxynaphthyl group in the final step by using a γ-butyrolactone compound substituted with a hydroxyalkyl group as an intermediate. We thought that it would be possible, and repeated examination.
As a result, it has been found that the intermediate can be obtained from an inexpensive unsaturated heterocyclic compound in a single step with a good yield, and that the storage stability of the intermediate is good, which is extremely advantageous industrially. It was. Moreover, it discovered that the photopolymerizable compound useful in a liquid crystal display element could be manufactured using the said intermediate body.

The present invention is based on such knowledge and has the following gist.
1. In the formula (1), the compound represented by the following formula (A) and the compound represented by the following formula (C) are reacted in the presence of metal tin or a tin-containing compound under acidic conditions. A method for producing the represented compound.

(In the formula, n represents 1 or 2.)

(Wherein J ¹ represents a halogen atom, and R represents an alkyl group having 1 to 6 carbon atoms.)

(In the formula, n represents the above meaning.)

2. A compound represented by the following formula (1) and a compound represented by the following formula (D) are reacted in the presence of a base, and then obtained when R ¹ in the formula (2) is a halogen atom. A method for producing a compound represented by the following formula (3), wherein a reaction product is reacted with a metal halide.

(In the formula, n represents 1 or 2.)

(Wherein J ² represents a halogen atom, Y ¹ represents —SO ₂ —R ² , and R ² represents a hydrocarbon group.)

(In the formula, n represents 1 or 2, R ¹ represents OY ^{1 or} a halogen atom, Y ¹ represents —SO ₂ —R ² , and R ² represents a hydrocarbon group.)

3. The manufacturing method of the compound represented by following formula (3) by making the compound represented by following formula (2) react with the compound represented by following formula (E).

(In the formula, n represents 1 or 2, R ¹ represents OY ¹ , chlorine, bromine or iodine, Y ¹ represents —SO ₂ —R ² , and R ² represents a hydrocarbon group.)

(In the formula, Ar ₁ is a divalent group represented by the following formula (4), (5) or (6)).

(In the formula (4), (5) or (6), each X independently represents a halogen atom, an alkoxy group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, or 1 to 6 carbon atoms. 6 represents a substituent selected from a haloalkoxy group and a cyano group, m ₁ to m ₆ each independently represents an integer of 0 to 4, and m ₇ and m ₈ each independently represents 0 to 3 (It is an integer, and when the number of X is 2 or more, Xs may be the same or different.)

(In the formula, n and Ar ₁ represent the above meanings.)

4). A compound represented by the following formula (1).

(In the formula, n represents 1 or 2.)

5. A compound represented by the following formula (2).

According to the present invention, a compound represented by the formula (3) having a divalent organic group having an aromatic ring having at least one halogen substituent and two α-methylene-γ-butyrolactone groups, A novel production method for producing at low cost and in a high yield, and a compound represented by formula (1) and a novel intermediate of the compound represented by formula (2) used in the production method and the like A compound is provided.
The compound represented by the formula (3) obtained by the production method of the present invention is highly oriented when used as a polymerizable compound in a liquid crystal display element, particularly as a polymerizable compound added to a liquid crystal alignment film material. It has immobilization ability, and storage stability in varnish is improved, and further solubility in liquid crystal is improved.

<Compound represented by Formula (1)>
As represented by the following scheme, the present invention comprises an unsaturated heterocyclic compound represented by the following formula (A) and a compound represented by the following formula (C) in the presence of metal tin or a tin-containing compound. It is a manufacturing method of the compound represented by Formula (1) by making it react on acidic conditions.

In the formula, n represents 0 or 1, J ¹ represents a halogen atom, and R represents an alkyl group having 1 to 6 carbon atoms.
J ¹ is preferably chlorine, bromine or iodine, and preferably chlorine or bromine.
R is preferably an alkyl group having 1 to 5 carbon atoms, which may be linear or branched, but is preferably linear. In particular, a methyl group or an ethyl group is preferable.

The compound represented by the formula (A) is a known compound and can be obtained commercially. The compound represented by the formula (C) is also a known compound and can be obtained commercially.

Examples of metal tin or tin-containing compounds include tin compounds such as tin powder, anhydrous tin chloride, tin chloride dihydrate, and tin chloride pentahydrate. In particular, anhydrous tin chloride or tin chloride dihydrate is preferred.

As the acid, an inorganic acid aqueous solution such as hydrochloric acid, sulfuric acid or phosphoric acid, an acidic resin such as Amberlyst®15, or an organic acid such as p-toluenesulfonic acid, acetic acid or formic acid can be used. Hydrochloric acid, sulfuric acid or acetic acid is particularly preferable.

As the acrylic acid derivative which is the above compound (C), 2- (chloromethyl) acrylic acid, 2- (chloromethyl) methyl acrylate, 2- (chloromethyl) ethyl acrylate, 2- (bromomethyl) acrylic acid 2- (Bromomethyl) methyl acrylate, 2- (bromomethyl) ethyl acrylate, and the like are preferable, and 2- (bromomethyl) acrylic acid or 2- (bromomethyl) ethyl acrylate is particularly preferable.

The amount of the compound (C) used is preferably 1.0 to 1.2 equivalents relative to 1 equivalent of the unsaturated heterocyclic compound, which is the compound represented by the formula (A), and 1.1 to 1. Two equivalents are more preferred.

The above reaction is carried out under acidic conditions, and the pH in the reaction is preferably 1 to 3, more preferably 1 to 2.

In the above reaction, the use of a solvent is preferable, and a solvent that is stable and inert and does not interfere with the reaction is preferable. For example, water, ethers (Et ₂ O, i-Pr ₂ O), TBME (tert-butyl methyl ether), CPME (cyclopentyl methyl ether), tetrahydrofuran, dioxane, etc.) can be used. These solvents can be appropriately selected in consideration of the ease of reaction and the like, and can be used singly or in combination of two or more. Tetrahydrofuran or water is preferable.

The reaction temperature is not particularly limited, but is usually 0 to 100 ° C., preferably 20 to 70 ° C.
The reaction time is usually 1 to 100 hours, preferably 1 to 12 hours.

The α-methylene-γ-butyrolactone compound (1) obtained as described above is purified by silica gel column chromatography after the reaction, after adding a base to the reaction solution to remove excess acid. The purity can be increased.

Solvents used for silica gel column chromatography used for purification are not particularly limited, but include, for example, hydrocarbons such as hexane, heptane, and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane, and chlorobenzene; And ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate; mixed solutions thereof; and the like. Preferably, it is a mixed liquid of esters such as ethyl acetate and hydrocarbons such as hexane or heptane.

<Compound represented by Formula (2)>
When the compound represented by the formula (1) obtained above and the compound represented by the formula (D) are reacted in the presence of a base, and R ¹ in the formula (2) is a halogen atom, The compound represented by the formula (3) is produced by reacting the obtained reaction product with a metal halide.

This will be explained below. As shown in the following scheme, the hydroxy group of the compound represented by the formula (1) obtained above is a sulfonic acid halide which is a compound represented by the formula (D). By making it react, it can be converted into a leaving group.

In the formula, n represents the same meaning as described above, J ² represents a halogen atom, Y ¹ represents —SO ₂ —R ² , and R ² represents a hydrocarbon group. Examples of J ² include chlorine, bromine and iodine.

As the hydrocarbon group for R ² , a linear or branched C _1-12 alkyl group, a C _3-12 cycloalkyl group, a C _2-12 haloalkyl group, ^a benzyl group _optionally substituted with R ^a , or Examples thereof include a phenyl group which may be substituted with ^Ra .
As R ^a , halogen, C _1-6 alkyl group, C _1-6 haloalkyl group, C _3-6 cycloalkyl group, C _1-6 alkoxy group, C _1-6 alkoxy C _1-6 alkyl group, C _{1 And} a substituent selected from a _-6 haloalkoxy group, NO ₂ , CN, a formyl group, and a phenyl group. A methyl group or an ethyl group is preferable.

The reaction between compound (1) and compound (D) is preferably carried out in the presence of a base. The base is preferably used in an amount of 1.2 to 10 equivalents, more preferably 1.2 to 3 equivalents, relative to compound (1).
Examples of bases include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride; pyridine, 4-dimethylaminopyridine, triethylamine, tributylamine , Organic bases such as N, N-dimethylaniline and 1,8-diazabicyclo [5.4.0] -7-undecene; Among them, bases such as 4-dimethylaminopyridine, pyridine and triethylamine can be used. Pyridine or triethylamine is preferable.

In the above reaction, the use of a solvent is preferable, and a solvent that is stable and inert and does not interfere with the reaction is used. For example, ketones such as acetone and methyl ethyl ketone; aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.); ethers (Et ₂ O, i-Pr ₂ O, TBME, CPME, tetrahydrofuran, dioxane, etc.); Aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.); halogenated hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.); lower fatty acid esters (methyl acetate) , Ethyl acetate, butyl acetate, methyl propionate, etc.) can be used. These solvents can be appropriately selected in consideration of the ease of reaction and the like, and can be used singly or in combination of two or more. Tetrahydrofuran is preferable.

The reaction temperature is not particularly limited, but is usually 0 to 100 ° C., preferably 40 to 70 ° C. The reaction time is usually 1 to 100 hours, preferably 1 to 12 hours.

The compound (2-A) obtained above can be highly purified by purifying with silica gel column chromatography after the reaction.

Solvents used for silica gel column chromatography are not particularly limited, but include, for example, hydrocarbons such as hexane, heptane and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and chlorobenzene; diethyl ether, tetrahydrofuran, Ethers such as 1,4-dioxane; esters such as ethyl acetate; mixed solutions thereof; and the like. Preferably, a mixture of an ester such as ethyl acetate and a hydrocarbon such as hexane or heptane is used. is there.

When obtaining the compound of the formula (2) in which R1 in the formula (2) is a halogen atom, the compound represented by the formula (2-A) obtained above is preferably combined with a metal halide in a solvent. By reacting, a compound represented by the formula (2-B) in which —OY ¹ is converted to halogen can be obtained.

(Wherein J ³ represents a halogen atom, and Y ¹ represents the above meaning.)

As the metal halide, sodium iodide, potassium iodide, sodium bromide, potassium bromide and the like can be used. The amount of the metal halide to be used is preferably 1 to 2 mol, more preferably 1 to 1.2 mol, relative to 1 mol of compound (2-A).

As a solvent for this reaction, a solvent that is stable under reaction conditions, inert and does not interfere with the reaction is used. For example, ketones such as acetone and methyl ethyl ketone; aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.); ethers (Et ₂ O, i-Pr ₂ O, TBME, CPME, tetrahydrofuran, dioxane, etc.); Aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.); halogenated hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.); lower fatty acid esters (methyl acetate) , Ethyl acetate, butyl acetate, methyl propionate, etc.) can be used. These solvents can be appropriately selected in consideration of the ease of reaction and the like, and can be used singly or in combination of two or more. Acetone is preferred.

The reaction temperature is not particularly limited, but is usually 0 to 100 ° C., preferably 30 to 45 ° C. The reaction time is usually 1 to 100 hours, preferably 1 to 12 hours.

As described above, the compound represented by the formula (2-B) can be highly purified by purifying it by silica gel column chromatography after the reaction.

In the reaction for obtaining the compound (2-B) from the above compound (2-A), Y ¹ in OY ¹ in the compound (2-A) is − A compound that is SO ₂ —R ² and R ² is ^a phenyl group optionally substituted by R ^a is preferred.

<Compound represented by Formula (3)>
The compound represented by formula (2) obtained above is reacted with an aromatic compound having a phenolic hydroxyl group represented by formula (E) in the presence of a base, as shown in the following scheme. Thus, a polymerizable compound represented by the formula (3) can be obtained.

In the above formula, Ar ₁ is a divalent group represented by the following formula (4), (5) or (6). In formula (4), (5) or (6), each X independently represents a halogen atom, an alkoxy group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, or 1 to 6 carbon atoms. And m ₁ to m ₆ are each independently an integer of 0 to 4, and m ₇ and m ₈ are each independently an integer of 0 to 3. When X is 2 or more, Xs may be the same or different. Examples of the halogen atom include fluorine, chlorine, bromine and the like.
X is preferably a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, or the like. m ₁ to m ₆ are preferably 0 to 1. m _{7 and} m ₈ are preferably 0 to 1.

As the base, inorganic bases such as sodium hydride, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, lithium carbonate and cesium carbonate can be used. Preferably, it is sodium carbonate or potassium carbonate.

・ Additives can be used for the purpose of accelerating the reaction rate. As additives, potassium iodide, sodium iodide, quaternary ammonium salts, crown ethers and the like can be used.

In the above reaction, the use of a solvent is preferable, and a stable and inert solvent that does not hinder the reaction is used. For example, ketones such as acetone and methyl ethyl ketone; aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.); ethers (Et ₂ O, i-Pr ₂ O, TBME, CPME, tetrahydrofuran, dioxane, etc.), Aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.); halogenated hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.); lower fatty acid esters (methyl acetate) , Ethyl acetate, butyl acetate, methyl propionate, etc.); nitriles (acetonitrile, propionitrile, butyronitrile, etc.); These solvents can be appropriately selected in consideration of the ease of reaction and the like, and can be used singly or in combination of two or more. Preferred are aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.).

The reaction temperature is not particularly limited, but is usually 40 to 200 ° C, preferably 40 to 150 ° C. The reaction time is usually 20 to 100 hours, preferably 20 to 60 hours.

The compound (3) obtained as described above can be highly purified by purifying by slurry washing, recrystallization, silica gel column chromatography and the like after the reaction.

The solvent used for washing is not particularly limited. For example, hydrocarbons such as hexane, heptane and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and chlorobenzene; diethyl ether, tetrahydrofuran, 1,4 -Ethers such as dioxane; esters such as ethyl acetate; ketones such as acetone or methyl ethyl ketone; alcohols such as methanol or ethanol and 2-propanol; mixtures thereof; Preferred are alcohols such as methanol, ethanol and 2-propanol.

The solvent used for recrystallization is not particularly limited as long as the compound (3) dissolves during heating and precipitates during cooling. For example, hydrocarbons such as hexane, heptane and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and chlorobenzene; ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate Ketones such as acetone and methyl ethyl ketone; alcohols such as methanol, ethanol and 2-propanol; and mixtures thereof. Tetrahydrofuran, toluene, methanol, ethanol, 2-propanol, hexane, heptane or a mixture thereof is preferable.

<Compound represented by Formula (E)>
The compound represented by the formula (E) as a raw material can be obtained as a commercial product. As shown below, an aryl halide [2-A] and an organometallic reagent [3-A] It can be obtained by carrying out a cross coupling reaction (Suzuki-Miyaura reaction) using a metal catalyst in the presence of a base.

In the above formula, X, m ₁ and m ₂ represent the above meanings, Hal represents Br, I or OTf (Tf is a paratoluenesulfonyl group), and M represents B (OH) ₂ or 4, 4, 5, Represents 5-tetramethyl-1,3,2-dioxaborolan-2-yl.

The amount of the aryl halide [2-A] and boronic acid derivative [3-A] used in the cross-coupling reaction is not particularly limited, but the boronic acid derivative is equivalent to 1 equivalent of the halogenated aryl [2-A]. It is preferable to use 1.0 to 1.5 equivalents of [3-A]. Further, 1.0 to 1.5 equivalents of aryl halide [2-A] may be used per 1 equivalent of boronic acid derivative [3-A].

As the metal catalyst used in the above coupling reaction, it is preferable to use a metal complex and a ligand. However, if the reaction proceeds without a ligand, the ligand may not be used. As metal complexes, those having various structures can be used, but palladium complexes and nickel complexes are preferably used. As the metal complex, a low-valent palladium complex or nickel complex is preferably used, and a zero-valent complex having tertiary phosphine or tertiary phosphite as a ligand is particularly preferable. In addition, an appropriate precursor that can be easily converted into a zero-valent complex in the reaction system can also be used.

Furthermore, in the reaction system, a complex containing no tertiary phosphine or tertiary phosphite as a ligand is mixed with a tertiary phosphine or tertiary phosphite, and the tertiary phosphine or tertiary phosphite is converted into a ligand. It is also possible to generate a low valence complex. Examples of the tertiary phosphine or tertiary phosphite include triphenylphosphine, tri-o-tolylphosphine, diphenylmethylphosphine, phenyldimethylphosphine, 1,2-bis (diphenylphosphino) ethane, 1,3-bis ( And diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,1′-bis (diphenylphosphino) ferrocene, trimethyl phosphite, triethyl phosphite, triphenyl phosphite and the like. Complexes containing a mixture of two or more of these ligands are also preferably used.

As the metal catalyst, it is also preferable to use a combination of a palladium complex or nickel complex that does not contain tertiary phosphine or tertiary phosphite, a complex containing tertiary phosphine or tertiary phosphite, and the above-described ligand. It is an aspect. Examples of palladium complexes and nickel complexes that do not contain the tertiary phosphine or tertiary phosphite used in combination include bis (benzylideneacetone) palladium, tris (benzylideneacetone) dipalladium, bis (acetonitrile) dichloropalladium, and bis (benzo Nitrile) dichloropalladium, palladium acetate, palladium chloride, palladium chloride-acetonitrile complex, palladium-activated carbon, nickel chloride, nickel iodide and the like. Examples of the complex containing tertiary phosphine or tertiary phosphite include dimethylbis (triphenylphosphine) palladium, dimethylbis (diphenylmethylphosphine) palladium, (ethylene) bis (triphenylphosphine) palladium, tetrakis (triphenyl). Phosphine) palladium, bis (triphenylphosphine) dichloropalladium, [1,3-bis (diphenylphosphino) propane] nickel (II) dichloride, [1,2-bis (diphenylphosphino) ethane] nickel (II) dichloride Etc. These are not limited to those described above.
These palladium complexes and nickel complexes may be used in so-called catalytic amounts. Generally, 20 mol% or less is sufficient relative to the substrate, and usually 10 mol% or less.

Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate; methylamine, dimethyl Amine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, isopropylamine, diisopropylamine, triisopropylamine, butylamine, dibutylamine, tributylamine, diisopropylethylamine, pyridine, imidazole, quinoline, collidine, etc. And the like; sodium acetate, potassium acetate, lithium acetate; and the like can also be used.

In the above reaction, the use of a solvent is preferable, and a stable and inert solvent that does not hinder the reaction is used. For example, water, alcohols, amines, aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.), ethers (Et ₂ O, i-Pr ₂ O, TBME, CPME, tetrahydrofuran, dioxane, etc.), Aliphatic hydrocarbons (pentane, hexane, heptane, petroleum ether, etc.), aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.), halogenated hydrocarbons (chloroform) , Dichloromethane, carbon tetrachloride, dichloroethane, etc.), lower fatty acid esters (methyl acetate, ethyl acetate, butyl acetate, methyl propionate, etc.), nitriles (acetonitrile, propionitrile, butyronitrile, etc.) and the like can be used. These solvents can be appropriately selected in consideration of the ease of reaction and the like, but the above solvents can be used singly or in combination of two or more.

The reaction temperature is not particularly limited, but is usually −90 to 200 ° C., preferably −50 to 150 ° C., more preferably 40 to 120 ° C. The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 40 hours, and more preferably 0.5 to 24 hours.

The biphenyl compound [4-A] obtained as described above can be highly purified by purifying by slurry washing, recrystallization, silica gel column chromatography and the like after the reaction.

The solvent used for the slurry washing is not particularly limited. For example, hydrocarbons such as hexane, heptane and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and chlorobenzene; diethyl ether, tetrahydrofuran, 1, Ethers such as 4-dioxane; esters such as ethyl acetate; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and propionitrile; alcohols such as methanol, ethanol and 2-propanol; a mixture thereof; Etc.

The solvent used for recrystallization is not particularly limited as long as the biphenyl compound [4-A] dissolves upon heating and precipitates upon cooling. For example, hydrocarbons such as hexane, heptane and toluene; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and chlorobenzene; ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate Ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and propionitrile; alcohols such as methanol, ethanol and 2-propanol; and mixtures thereof. Preferred is ethyl acetate, tetrahydrofuran, toluene or hexane. By such a method, various compounds (E) can be produced.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the interpretation of the present invention is not limited by these examples. In addition, the analyzers and analysis conditions employed in the examples are as follows.
HPLC analyzer: LC-20A system (manufactured by Shimadzu Corporation)
Column: Inertsil ODS-3 (4.6 mmΦ × 250 mm, manufactured by GL Sciences Inc.)
Detector: UV detection (wavelength 220 nm)
Eluent: acetonitrile / 0.1 wt% phosphoric acid aqueous solution (30/70, v / v, 0-10 min) → (80/20, v / v, 15-25 min)

Example 1:

To a mixed solution of THF (tetrahydrofuran) (300.0 g), 1N hydrochloric acid (33.9 g) and bromomethacrylic acid ethyl ester (75.7 g, 392 mmol) was added stannous chloride dihydrate (88.5 g, 392 mmol). ) Was dissolved, and 3,4-dihydro-2H-pyran (30.0 g, 357 mmol) was added dropwise at 25-30 ° C. over 30 minutes. Thereafter, the temperature was raised to 64 ° C. and stirred for 7 hours to obtain a reaction mixture containing 5- (4-hydroxybutyl) -3-methylenedihydrofuran-2 (3H) -one.

Next, the obtained reaction solution was cooled to 25 ° C., triethylamine (120.0 g, 1186 mmol) was added, and the formed white salt was removed by filtration. Subsequently, the obtained filtrate was concentrated to obtain 5- (4-hydroxybutyl) -3-methylenedihydrofuran-2 (3H) -one. (58.8 g, yield 96.9%)

Example 2

Stannous chloride dihydrate (106.2 g, 471 mmol) was dissolved in a mixed solution of THF (300.0 g), 1N hydrochloric acid (33.9 g) and bromomethacrylic acid ethyl ester (90.9 g, 471 mmol). Then, 2,3-dihydrofuran (30.0 g, 428 mmol) was added dropwise at 25-30 ° C. over 30 minutes. Thereafter, the temperature was raised to 64 ° C. and the mixture was stirred for 6 hours to obtain a reaction mixture containing 5- (3-hydroxypropyl) -3-methylenedihydrofuran-2 (3H) -one.
Next, the obtained reaction liquid was cooled to 25 ° C., triethylamine (142.8 g, 1411 mmol) was added, and the formed white salt was removed by filtration. Subsequently, the obtained filtrate was concentrated to obtain 5- (3-hydroxypropyl) -3-methylenedihydrofuran-2 (3H) -one. (43.5 g, yield 65.1%)

When the compound obtained in Example 1 is used as a starting material, for example, it can be derived into the following compounds. In the following formulae, Ms represents a methanesulfonyl group, I represents an iodine atom, and Ts represents a p-toluenesulfonyl group.

Example 3

To a mixed solution of THF (303.5 g), triethylamine (21.7 g, 214 mmol) and 5- (4-hydroxybutyl) -3-methylenedihydrofuran-2 (3H) -one (30.4 g, 178 mmol) was added methane. Sulfonyl chloride (24.5 g, 213 mmol) was added dropwise at 0 ° C. over 30 minutes. Thereafter, the mixture was stirred for 5 hours to obtain a reaction mixture containing 4- (4-methylene-5-oxotetrahydrofuran-2-yl) butylmethanesulfonate.
Next, the obtained reaction solution was heated to 25 ° C., and the produced white salt was removed by filtration. Subsequently, the obtained filtrate was concentrated to obtain 4- (4-methylene-5-oxotetrahydrofuran-2-yl) butylmethanesulfonate. (41.1 g, yield 92.8%)

Example 4:

Acetone (100.0 g), sodium iodide (7.2 g, 48 mmol) and 4- (4-methylene-5-oxotetrahydrofuran-2-yl) butylmethanesulfonate (10.0 g, 40 mmol) were added at 25-30 ° C. Then, the mixture was stirred at 45 ° C. for 6 hours to obtain a reaction mixture containing 5- (4-iodobutyl) -3-methylenedihydrofuran-2 (3H) -one.
The resulting reaction mixture was then concentrated, diluted with ethyl acetate (100.0 g) and washed twice with 10 wt% aqueous sodium sulfite (100.0 g). It was then washed with water (100.0 g) and the organic layer was concentrated to give 5- (4-iodobutyl) -3-methylenedihydrofuran-2 (3H) -one. (41.1 g, yield 71.0%)

Example 5:

To a mixed solution of p-toluenesulfonyl chloride (33.6 g, 176 mmol) and pyridine (200.0 g), 5- (4-hydroxybutyl) -3-methylenedihydrofuran-2 (3H) -one (20.0 g, 118 mmol) was added dropwise at 20-30 ° C. over 10 minutes. Thereafter, the mixture was stirred for 2 hours to obtain a reaction mixture containing 4- (4-methylene-5-oxotetrahydrofuran-2-yl) butyl-4-methylbenzenesulfonate.
Next, diethyl ether (200.0 g) and water (200.0 g) were added to the resulting reaction mixture and washed with water, and then the aqueous layer was separated and discarded. Thereafter, 1N hydrochloric acid (200.0 g) was added and washed three times, and then the organic layer was concentrated to give 4- (4-methylene-5-oxotetrahydrofuran-2-yl) butyl-4-methylbenzenesulfone. I got a nat. (14.5 g, yield 38.0%)

The following compounds were synthesized by the reaction shown in Example 6 using the compound obtained in Example 5 as a starting material.
The analysis apparatus and analysis conditions employed in Example 6 use UV detection (wavelength 265 nm) as a detector, and acetonitrile / 0.2 wt% ammonium acetate aqueous solution (70/30 (0− The above HPLC analysis was used except that 5 min) → 85/15 (10-30 min)) [v / v] was used.

Example 6:

To a mixed solution of dimethylformamide (100.0 g), 3-fluoro [1,1′-biphenyl] -4,4′-diol (5.0 g, 25 mmol) and potassium carbonate (7.5 g, 54 mmol), 4- (4-Methylene-5-oxotetrahydrofuran-2-yl) butyl-4-methylbenzenesulfonate (19.1 g, 59 mmol) was added dropwise at 20-30 ° C. over 10 minutes. Thereafter, the mixture was stirred at 60 ° C. for 20 hours and at 80 ° C. for 27 hours, and 4,4′-bis (4- (3-methylenetetrahydrofuran-2 (3H) -one-5-yl) butoxy) -3-fluoro- A reaction mixture containing biphenyl was obtained.

Next, water (167.0 g) was added to the obtained reaction mixture, and after filtration, the filtrate was recovered. Next, THF (167.0 g) was added to the filtrate to dissolve it, and then insoluble matters were removed again by filtration. Thereafter, heptane (67.0 g) was added to the filtrate to precipitate crystals. The precipitated crystals were filtered and dried to obtain 4,4′-bis (4- (3-methylenetetrahydrofuran-2 (3H) -on-5-yl) butoxy) -3-fluoro-biphenyl. (6.7 g, yield 53.5%) (HPLC purity; 91%)

The compound having an α-methylene-γ-butyrolactone group represented by the formula (3) obtained by the production method of the present invention is used in a wide range of fields such as a photopolymerizable compound used in a liquid crystal display device. . Moreover, the compound represented by Formula (1) and the compound represented by Formula (2) are used as an intermediate of the compound represented by Formula (3).

It should be noted that the entire contents of the specification, claims, and abstract of Japanese Patent Application No. 2014-224511 filed on November 4, 2014 are incorporated herein as the disclosure of the specification of the present invention. Is.

Claims

A compound represented by the following formula (A) and a compound represented by the following formula (C) are reacted in the presence of metallic tin or a tin-containing compound under acidic conditions (1) The manufacturing method of the compound represented by these.

(In the formula, n represents 1 or 2.)

(Wherein J 1 represents a halogen atom, and R represents an alkyl group having 1 to 6 carbon atoms.)

(In the formula, n represents the above meaning.)
A compound represented by the following formula (1) and a compound represented by the following formula (D) are reacted in the presence of a base, and then obtained when R 1 in the formula (2) is a halogen atom. A method for producing a compound represented by the following formula (3), wherein a reaction product is reacted with a metal halide.

(In the formula, n represents 1 or 2.)

(Wherein J 2 represents a halogen atom, Y 1 represents —SO 2 —R 2 , and R 2 represents a hydrocarbon group.)

(In the formula, n represents 1 or 2, R 1 represents OY 1 or a halogen atom, Y 1 represents —SO 2 —R 2 , and R 2 represents a hydrocarbon group.)
The manufacturing method of the compound represented by following formula (3) by making the compound represented by following formula (2) react with the compound represented by following formula (E).

(In the formula, n represents 1 or 2, R 1 represents OY 1 , chlorine, bromine or iodine, Y 1 represents —SO 2 —R 2 , and R 2 represents a hydrocarbon group.)

(In the formula, Ar 1 represents a divalent group represented by the following formula (4), (5) or (6)).

(In the formulas (4), (5) and (6), each X independently represents a halogen atom, an alkoxy group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, or 1 to 6 carbon atoms. 6 represents a substituent selected from a haloalkoxy group and a cyano group, m 1 to m 6 each independently represents an integer of 0 to 4, and m 7 and m 8 each independently represents 0 to 3 (It is an integer, and when the number of X is 2 or more, Xs may be the same or different.)

(In the formula, n and Ar 1 represent the above meanings.)
A compound represented by the following formula (1).

(In the formula, n represents 1 or 2.)
A compound represented by the following formula (2).

(In the formula, n represents 1 or 2, R 1 represents OY 1 , chlorine, bromine or iodine, Y 1 represents —SO 2 —R 2 , and R 2 represents a hydrocarbon group.)
The production method according to claim 1, wherein the reaction conditions are acidic conditions having a pH of 1 to 2.
The production method according to claim 1 or 6, wherein the amount of the compound represented by the formula (C) is 2.0 to 2.5 equivalents relative to 1 equivalent of the compound represented by the formula (A). .
The production method according to claim 1, 6 or 7, wherein the amount of metal tin or tin-containing compound used is 2 to 4 equivalents relative to 1 equivalent of the compound represented by formula (A).