JP5365232B2 - Method for producing vinyl-substituted aryl compound using microreactor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing various vinyl-substituted aryl compounds producing in a higher efficiency and stable yield not depending on substrate materials and as a result, useful for an industrial scale production. <P>SOLUTION: The method for producing the vinyl-substituted aryl compound expressed by general formula [IV]: Ar-CR<SP>1</SP>=CR<SP>2</SP>-Z comprises a first process of reacting a halogenated aromatic compound expressed by general formula [I]: Ar-X with an organo-lithium reagent to prepare a lithilated aromatic compound expressed by general formula [II]: Ar-Li; and a second process of coupling the lithilated aromatic compound expressed by the general formula [II] with a &beta;-vinyl compound expressed by general formula [III]: Y-CR<SP>1</SP>=CR<SP>2</SP>-Z in the presence of a catalytic amount of a palladium compound and performs the first and second reactions by using a microreactor. In the general formulae [I] to [IV], Ar is an aryl which may have a substituent; X is a halogen atom; Y is a halogen atom or trifluoromethane sulfonyloxy; Z is an aryl which may have a substituent or 1C-10C linear, branched or cyclic alkyl; and R<SP>1</SP>and R<SP>2</SP>are each independently H or 1C-6C linear, branched or cyclic alkyl. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to a method for producing a vinyl-substituted aryl compound, and more specifically, uses a microreactor for a vinyl-substituted aryl compound useful as a synthetic intermediate for pharmaceuticals, agricultural chemicals, liquid crystal materials, organic electroluminescence (organic EL) materials, and the like. Thus, the present invention relates to a method for producing with high efficiency and stable yield.

  A compound having an aryl skeleton is a compound useful as a synthetic intermediate for various chemical products. Among them, vinyl-substituted aryl compounds have functions such as fine chemicals such as pharmaceuticals and agricultural chemicals, liquid crystals, organic electroluminescence (organic EL), etc. It is one of the important compounds as synthetic intermediates for functional materials.

  As a method for producing these vinyl-substituted aryl compounds, specifically, for example, an aryl metal compound composed of, for example, magnesium, boron, silicon, zinc, tin, or an art complex thereof, and a vinyl compound such as alkenyl halide or alkenyl triflate, A method of cross-coupling in the presence of a catalytic amount of an organometallic compound such as nickel or palladium is known (for example, Non-Patent Document 1). However, most of the above aryl metal compounds need to be prepared via transmetalation of an aryl lithium compound synthesized from an aryl halide as a raw material and an organolithium reagent, which makes the process complicated. In addition, since a stoichiometric amount of a metal reagent is required for the transmetalation, the production cost is likely to increase, and in the case of a toxic metal, it takes effort to completely remove the metal. There is a problem that such a defect has a problem that its use on an industrial scale is naturally limited because the surface is easily surfaced as the production scale increases.

  On the other hand, the lithium compound and a vinyl compound such as alkenyl halide are directly cross-coupled in the presence of an organometallic compound such as palladium or ruthenium without passing through the transmetalation of the lithium compound, thereby producing a vinyl. Methods for synthesizing substituted aryl compounds and vinyl-substituted alkyl compounds are known (for example, Non-Patent Document 2). In this method, in the case of a reaction using a stoichiometric amount of palladium or ruthenium, the target compound is stably obtained in a good yield regardless of the substrate, but palladium or ruthenium is used for a catalytic amount. In the case of the conventional reaction (catalytic reaction), there was a problem that the yield varied considerably and it was difficult to stably obtain the target compound.

  On the other hand, recently, as one of process engineering, researches for performing a synthesis reaction using a microreactor having advantages such as easy reaction design are being actively conducted. For example, the present inventor has proposed a method in which a halogen compound and a lithium reagent are reacted using a microreactor to obtain a lithium compound, and the lithium compound is subsequently continuously reacted with an electrophilic compound using a microreactor. (Patent Document 1). In addition, the present inventors use a microreactor to lithiate (monolithiate) one of the halogen groups of an o-dihaloaromatic compound, to perform electrophilic substitution of the monolithiated compound, A method of continuously performing a step of lithiating a (remaining) halogen group and a step of electrophilic substitution of the lithiated product using a microreactor has been proposed (Patent Document 2). However, the reaction using the microreactor described in the above document is a reaction between a lithium compound and an electrophilic compound, and not only a cross-coupling reaction with a vinyl compound such as an alkenyl halide is taken into consideration. It is not assumed that the reaction with the compound is carried out in the presence of a catalyst such as palladium.

  For this reason, various vinyl-substituted aryl compounds useful as synthetic intermediates such as fine chemicals and functional materials can be produced more efficiently and with a stable yield regardless of the substrate, and thus on an industrial scale. Development of a method for producing the vinyl-substituted aryl compound useful for the production of

JP 2006-241065 A JP 2008-195639 A

Diederich, F .; Stang, P. J., Eds.Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 1998. J. Org. Chem., 44, 14 (1979)

  The object of the present invention is to produce a desired vinyl-substituted aryl compound by using a microreactor in a simpler manner and in a shorter time than conventional methods, that is, with high efficiency and a stable yield regardless of the substrate. It is to provide a possible method.

（式中、Ａｒは、置換基を有していてもよいアリール基を表し、Ｘは、ハロゲン原子を表す。）で示されるハロゲン化芳香族化合物と有機リチウム試薬とを反応させ、一般式［ II ］

（式中、Ａｒは上記に同じ。）で示されるリチオ化された芳香族化合物を得る第１の工程と、
触媒量のパラジウム化合物の存在下、上記一般式［ II ］で示されるリチオ化された芳香族化合物と一般式［ III ］

（式中、Ｒ^１及びＲ^２は夫々独立して、水素原子又は炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基を表し、Ｙは、ハロゲン原子又はトリフルオロメタンスルホニルオキシ基を表し、Ｚは、置換基を有していてもよいアリール基又は炭素数１〜１０の直鎖状、分枝状若しくは環状のアルキル基を表す。）で示されるβ−ビニル化合物とをカップリングさせる第２の工程と、
を含み、
上記第１及び第２の工程を、マイクロリアクターを用いて行うことを特徴とする一般式［ IV ］

（式中、Ｒ^１、Ｒ^２、Ａｒ及びＺは上記に同じ。）で示されるビニル置換アリール化合物の製造方法である。 The present invention relates to general formula [I]

(In the formula, Ar represents an aryl group which may have a substituent, and X represents a halogen atom.) A halogenated aromatic compound represented by formula (II) is reacted with an organolithium reagent, and the general formula [ II]

A first step of obtaining a lithiated aromatic compound represented by (wherein Ar is the same as above);
In the presence of a catalytic amount of a palladium compound, the lithiated aromatic compound represented by the above general formula [II] and the general formula [III]

(In the formula, R ¹ and R ² each independently represents a hydrogen atom or a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, and Y represents a halogen atom or a trifluoromethanesulfonyloxy group. Z represents an aryl group which may have a substituent or a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms) and a β-vinyl compound represented by A second step of ringing;
Including
The general formula [IV], wherein the first and second steps are performed using a microreactor.

(Wherein R ¹ , R ² , Ar and Z are the same as above).

  According to the production method of the present invention, if a reaction is carried out using a microreactor in the presence of a catalytic amount of a palladium compound, the target vinyl can be obtained with high efficiency by a simple operation and with a stable yield regardless of the substrate. It becomes possible to produce a substituted aryl compound. Further, if a catalytic amount of a palladium compound used in the production method of the present invention is mixed with a compound capable of coordinating with palladium in a microreactor and then supplied to the coupling reaction system in the second step, a higher yield can be obtained. Thus, the intended vinyl-substituted aryl compound can be produced. Furthermore, since the production method of the present invention can be carried out even at room temperature, it is a useful method that does not require a special cooling (heating) device, and can be a production method advantageous for production on an industrial scale.

It is a figure which shows the schematic diagram of the reaction apparatus containing the microreactor used in Example 1 with reaction conditions. It is a figure which shows the internal structure of the T-shaped micromixer used in Examples 1-3. It is a figure which shows the schematic diagram of the reaction apparatus containing the microreactor used in Example 2 with reaction conditions. It is a figure which shows the schematic diagram of the reaction apparatus containing the microreactor used in Example 3 with reaction conditions.

  Specific examples of the “aryl group” in the “aryl group optionally having substituent (s)” represented by Ar in the general formulas [I], [II] and [IV] include, for example, a phenyl group, pyridyl Group, naphthyl group, quinolyl group, isoquinolyl group, naphthyridinyl group, anthryl group and the like, among which phenyl group is preferable.

  The “substituent” in the “aryl group optionally having substituent (s)” represented by Ar in the general formulas [I], [II] and [IV] is a first step described below (halogen-lithium). The reaction is not particularly limited as long as it does not adversely affect the exchange reaction) and the second step (coupling reaction). Specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n -Butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2- Dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohex C 1-6 linear, branched or cyclic such as syl group, 2-methylpentyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclohexyl group Alkyl groups such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, cyclobutoxy, n-pentyloxy, isopentyloxy Group, sec-pentyloxy group, tert-pentyloxy group, neopentyloxy group, 2-methylbutoxy group, 1,2-dimethylpropoxy group, 1-ethylpropoxy group, cyclopentyloxy group, n-hexyloxy group, iso Hexyloxy group, sec-hexyloxy group, tert-hexyloxy group, neohexylo Straight chain or branched chain having 1 to 6 carbon atoms such as xyl group, 2-methylpentyloxy group, 1,2-dimethylbutoxy group, 2,3-dimethylbutoxy group, 1-ethylbutoxy group, cyclohexyloxy group, etc. Or a cyclic alkoxy group, for example, a phenyl group etc. are mentioned. Moreover, it is a case where the said substituent is introduce | transduced into two adjacent carbon atoms, Comprising: These two substituents may have an oxygen atom or a sulfur atom in a chain | strand C3-C6 fat In the case of forming an aromatic ring, examples of the group formed by combining these substituents include trimethylene group, tetramethylene group, oxydimethylene group (oxyethylene group), thiodimethylene group (thioethylene group), and oxytrimethylene. Group, thiotrimethylene group, dioxymethylene group, dithiomethylene group, dioxydimethylene group (dioxyethylene group), dithiodimethylene group (dithioethylene group), etc. And an alkylene group which may be present.

  As Ar in the general formulas [I], [II] and [IV], "an aryl group having no substituent", that is, an "unsubstituted aryl group" is preferable, and among them, "phenyl having no substituent" “Group”, that is, “unsubstituted phenyl group” is more preferable.

  Specific examples of the halogen atom represented by X in the general formula [I] include a chlorine atom, a bromine atom and an iodine atom, among which a chlorine atom and a bromine atom are preferable, and among them, a bromine atom is more preferable. .

  Specific examples of the halogen atom represented by Y in the general formula [III] include a chlorine atom, a bromine atom and an iodine atom, among which a bromine atom and an iodine atom are preferable, and among them, a bromine atom is more preferable. .

  Y in the general formula [III] is more preferably a halogen atom.

  Specific examples of the “aryl group” in the “aryl group optionally having substituents” represented by Z in the general formulas [III] and [IV] include, for example, a phenyl group, a pyridyl group, and a naphthyl group. Quinolyl group, isoquinolyl group, naphthyridinyl group, anthryl group and the like, among which phenyl group is preferable.

  The “substituent” in the “aryl group optionally having substituent (s)” represented by Z in the general formulas [III] and [IV] has an adverse effect on the second step (coupling reaction) described later. Although it is not particularly limited as long as it does not range, specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group , Cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl Group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group, 2-methylpentyl group, 1,2-dimethylbutyl , 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclohexyl group, etc., a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, such as methoxy group, ethoxy group, n-propoxy group, iso Propoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, cyclobutoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, tert-pentyloxy group, neopentyl Oxy group, 2-methylbutoxy group, 1,2-dimethylpropoxy group, 1-ethylpropoxy group, cyclopentyloxy group, n-hexyloxy group, isohexyloxy group, sec-hexyloxy group, tert-hexyloxy group, Neohexyloxy group, 2-methylpentyloxy group, 1,2-dimethyl Butoxy group, 2,3-dimethylbutoxy group, 1-ethylbutoxy group, a linear 1 to 6 carbon atoms such as a cyclohexyl group, branched or cyclic alkoxy groups such as phenyl group and the like. Moreover, it is a case where the said substituent is introduce | transduced into two adjacent carbon atoms, Comprising: These two substituents may have an oxygen atom or a sulfur atom in a chain | strand C3-C6 fat In the case of forming an aromatic ring, examples of the group formed by combining these substituents include trimethylene group, tetramethylene group, oxydimethylene group (oxyethylene group), thiodimethylene group (thioethylene group), and oxytrimethylene. Group, thiotrimethylene group, dioxymethylene group, dithiomethylene group, dioxydimethylene group (dioxyethylene group), dithiodimethylene group (dithioethylene group), etc. And an alkylene group which may be present.

  The linear, branched or cyclic alkyl group having 1 to 10 carbon atoms represented by Z in the general formulas [III] and [IV] may have an oxygen atom or a sulfur atom in the chain. Specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert- Hexyl group, neohexyl group, 2-methylpentyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group Cyclohexyl group, n-heptyl group, isoheptyl group, sec-heptyl group, tert-heptyl group, neoheptyl group, cycloheptyl group, n-octyl group, isooctyl group, sec-octyl group, tert-octyl group, neooctyl group, 2 -Ethylhexyl group, cyclooctyl group, n-nonyl group, isononyl group, sec-nonyl group, tert-nonyl group, neononyl group, cyclononyl group, n-decyl group, isodecyl group, sec-decyl group, tert-decyl group, Neodecyl group, cyclodecyl group, hexahydroindanyl group, decahydronaphthyl group, spiro [4,4] nonyl group, spiro [4,5] decyl group, norbornyl group, adamantyl group, methoxymethyl group, ethoxyethyl group, propoxy Propyl group, methylthiomethyl group, ethyl Oechiru group, propyl thio propyl group, tetrahydrofuryl group, and the like.

  Z in the general formulas [III] and [IV] is preferably an "aryl group optionally having a substituent", and among them, an "aryl group having no substituent", that is, an "unsubstituted aryl group" "Is more preferable, and among them, a" phenyl group having no substituent ", that is, an" unsubstituted phenyl group "is more preferable.

Specific examples of the linear, branched or cyclic alkyl group having 1 to 6 carbon atoms represented by R ¹ and R ² in the general formulas [III] and [IV] include, for example, a methyl group and an ethyl group. , N-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group, 2-methylpentyl group, Examples include 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclohexyl group and the like.

As R ¹ and R ² in the general formulas [III] and [IV], a hydrogen atom is more preferable.

（式中、ｐ個のＲ^３は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｐは０〜５の整数を表し、Ｗは炭素原子又は窒素原子を表し、Ｘは上記に同じ。なお、隣接する２つのＲ^３は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるハロゲン化ベンゼン誘導体又はハロゲン化ピリジン誘導体、一般式［ VI ］

（式中、ｑ個のＲ^４は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｑは０〜７の整数を表し、Ｕ^１及びＵ^２は、共に炭素原子を表すか又はＵ^１及びＵ^２の何れか一方が窒素原子を表す場合は他方が炭素原子を表し、Ｖ^１及びＶ^２は、共に炭素原子を表すか又はＶ^１及びＶ^２の何れか一方が窒素原子を表す場合は他方が炭素原子を表し、Ｘは上記に同じ。なお、隣接する２つのＲ^４は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるハロゲン化ナフタレン誘導体、ハロゲン化キノリン誘導体、ハロゲン化イソキノリン誘導体又はハロゲン化ナフチリジン誘導体、或いは一般式［ VII ］

（式中、ｒ個のＲ^５は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｒは０〜９の整数を表す。なお、隣接する２つのＲ^５は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるハロゲン化アントラセン誘導体等が挙げられる。 Next, the compound used in the present invention will be described. The halogenated aromatic compound represented by the general formula [I] used in the present invention does not adversely affect the first step (halogen-lithium exchange reaction) and the second step (coupling reaction) described later. A halogenated benzene derivative, a halogenated pyridine derivative, a halogenated naphthalene derivative, a halogenated quinoline derivative, a halogenated isoquinoline derivative, or a halogenated naphthyridine derivative, which may have a substituent and has a halogen atom substituted on the aromatic ring , Halogenated anthracene derivatives and the like. Specific examples of the halogenated aromatic compound represented by the general formula [I] include, for example, the general formula [V].

(In the formula, each p ³ R ³ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, p represents an integer of 0 to 5, W represents a carbon atom or a nitrogen atom, X is the same as above, and two adjacent R ³ are bonded to each other. A halogenated benzene derivative or a halogenated pyridine derivative, which may form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain together with the carbon atom), General formula [VI]

(Wherein q R ^{4 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, q represents an integer of 0 to 7, U ¹ and U ² both represent a carbon atom, or when either U ¹ or U ² represents a nitrogen atom, the other represents Represents a carbon atom, and V ¹ and V ² both represent a carbon atom, or when either V ¹ or V ² represents a nitrogen atom, the other represents a carbon atom, and X is the same as above. Two adjacent R ^{4 s} may form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. ) Halogenated naphthalene derivatives, halogenated quinoline derivatives, halogenated isoquinolines Derivatives or halogenated naphthyridine derivatives, or the general formula [VII]

(Wherein r R ^{5 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, and r represents an integer of 0 to 9. Note that two adjacent R ^{5 s} have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. An optionally substituted aliphatic ring having 3 to 6 carbon atoms may be formed.) And the like.

Specific examples of the linear, branched or cyclic alkyl group having 1 to 6 carbon atoms represented by R ³ , R ⁴ and R ⁵ in the general formulas [V], [VI] and [VII] include For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group 2-methylpentyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclohexyl group, etc. Can be mentioned.

Specific examples of the linear, branched or cyclic alkoxy group having 1 to 6 carbon atoms represented by R ³ , R ⁴ and R ⁵ in the general formulas [V], [VI] and [VII] include For example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, cyclobutoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, tert-pentyloxy group, neopentyloxy group, 2-methylbutoxy group, 1,2-dimethylpropoxy group, 1-ethylpropoxy group, cyclopentyloxy group, n-hexyloxy group, isohexyloxy Group, sec-hexyloxy group, tert-hexyloxy group, neohexyloxy group, 2-methylpentyloxy Si group, 1,2-dimethylbutoxy group, 2,3-dimethylbutoxy group, 1-ethylbutoxy group, cyclohexyloxy group and the like.

  As p in the general formula [V], an integer of 0 to 3 is preferable, and 0 is more preferable.

  As W in general formula [V], a carbon atom is preferable.

  Q in the general formula [VI] is preferably an integer of 0 to 5, more preferably an integer of 0 to 3, and more preferably 0.

U ¹ , U ² , V ¹ and V ² in the general formula [VI] are all carbon atoms, or any one is preferably a nitrogen atom, and more preferably all are carbon atoms.

  As r in the general formula [VII], an integer of 0 to 7 is preferable, an integer of 0 to 5 is more preferable, an integer of 0 to 3 is more preferable, and 0 is particularly preferable.

In the general formulas [V], [VI] and [VII], “adjacent two Rs (two R ^{3 s} , two R ^{4 s} or two R ^{5 s} ) represented by R ³ , R ⁴ and R ⁵ are these In the chain may have an oxygen or sulfur atom in the chain and may form an aliphatic ring having 3 to 6 carbon atoms. Specific examples of the “aliphatic ring” include cyclopentane ring, cyclohexane ring, tetrahydrofuran ring, tetrahydropyran ring, tetrahydrothiophene ring, tetrahydrothiofuran ring, 1,3-dioxacyclopentane ring, 1,3- Examples include a dioxacyclohexane ring and a 1,4-dioxacyclohexane ring. In addition, the carbon number of the carbon atom which comprises these aliphatic rings means the carbon number containing the two carbon atoms which comprise the aromatic ring condensed with the said aliphatic ring.

  Specific examples of the halogenated benzene derivative and the halogenated pyridine derivative represented by the general formula [V] include, for example, chlorobenzene, bromobenzene, iodobenzene, chlorotoluene, bromotoluene, iodotoluene, chloroxylene, bromoxylene, iodoxylene, Chloromesitylene, bromomesitylene, iodomesitylene, chlorocumene, bromocumene, iodocumene, chlorocymene, bromocymene, iodocymene, chlorohexylbenzene, bromohexylbenzene, iodohexylbenzene, chloromethoxybenzene, bromomethoxybenzene, iodomethoxybenzene, chlorohexyloxybenzene, Bromohexyloxybenzene, iodohexyloxybenzene, chloroindane, bromoindane, iodoindane, black Chroman, bromochroman, iodochroman, chloroisochroman, bromoisochroman, iodoisochroman, chlorothiochroman, bromothiochroman, iodothiochroman, chloromethylenedioxybenzene, bromomethylenedioxybenzene, iodomethylenedioxybenzene, etc. Halogenated benzene derivatives such as chloropyridine, bromopyridine, iodopyridine, chloromethylpyridine, bromomethylpyridine, iodomethylpyridine, chlorodimethylpyridine, bromodimethylpyridine, iododimethylpyridine, chlorotrimethylpyridine, bromotrimethylpyridine, iodotrimethylpyridine , Chloroethylpyridine, bromoethylpyridine, iodoethylpyridine, chloroisopropylpyridine, bromoisopropyl Halogenated pyridine derivatives such as pyridine, iodoisopropylpyridine, chlorohexylpyridine, bromohexylpyridine, iodohexylpyridine, chloromethoxypyridine, bromomethoxypyridine, iodomethoxypyridine, chlorohexyloxypyridine, bromohexyloxypyridine, iodohexyloxypyridine, etc. Among them, for example, chlorobenzene, bromobenzene, iodobenzene, chlorotoluene, bromotoluene, iodotoluene, chloroxylene, bromoxylene, iodoxylene, chloromesitylene, bromomesitylene, iodomesitylene, chlorocumene, bromocumene, iodocumene, chlorocymene, bromocymene , Iodocymene, chlorohexylbenzene, bromohexylbenzene, iodohexyl Benzene, chloromethoxybenzene, bromomethoxybenzene, iodomethoxybenzene, chlorohexyloxybenzene, bromohexyloxybenzene, iodohexyloxybenzene, chloroindane, bromoindane, iodoindane, chlorochroman, bromochroman, iodochroman, chloroisochroman, Halogenated benzene derivatives such as bromoisochroman, iodoisochroman, chlorothiochroman, bromothiochroman, iodothiochroman, chloromethylenedioxybenzene, bromomethylenedioxybenzene, iodomethylenedioxybenzene, among which chlorobenzene, Unsubstituted halogenated benzene derivatives such as bromobenzene and iodobenzene are more preferred. Preferred. In addition, the bonding position of the halogen atom in the halogenated benzene derivative and the halogenated pyridine derivative is not particularly limited, and the halogen atom may be bonded to any carbon atom as long as it is a carbon atom on the aromatic ring, Furthermore, the bonding position of the substituent in the halogenated benzene derivative and the halogenated pyridine derivative is not particularly limited, and the substituent is bonded to any carbon atom as long as it is a carbon atom to which no halogen atom is bonded. Also good. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited to these examples. These halogenated benzene derivatives and halogenated pyridine derivatives are commercially available. Or those synthesized by conventional methods may be used as appropriate.

（式中、Ｒ^３、ｐ及びＷは上記に同じ。）で示される、置換基を有していてもよいフェニル基又はピリジル基であるものに相当する。 As a reminder, in the above general formula [I], the halogenated benzene derivative and the halogenated pyridine derivative represented by the above general formula [V] are such that Ar in the general formula [I] is represented by the general formula [VIII].

(Wherein R ³ , p and W are the same as above), which corresponds to a phenyl group or a pyridyl group which may have a substituent.

  Specific examples of the halogenated naphthalene derivative, halogenated quinoline derivative, halogenated isoquinoline derivative and halogenated naphthyridine derivative represented by the general formula [VI] include, for example, chloronaphthalene, bromonaphthalene, iodonaphthalene, chloromethylnaphthalene, bromomethylnaphthalene. , Iodomethylnaphthalene, chlorodimethylnaphthalene, bromodimethylnaphthalene, iododimethylnaphthalene, chlorotrimethylnaphthalene, bromotrimethylnaphthalene, iodotrimethylnaphthalene, chloroethylnaphthalene, bromoethylnaphthalene, iodoethylnaphthalene, chloroisopropylnaphthalene, bromoisopropylnaphthalene, iodo Isopropyl naphthalene, chlorohexyl naphthalene, bromohexyl naphthalene, iodine Halogenated naphthalene derivatives such as dohexylnaphthalene, chloromethoxynaphthalene, bromomethoxynaphthalene, iodomethoxynaphthalene, chlorohexyloxynaphthalene, bromohexyloxynaphthalene, iodohexyloxynaphthalene, such as chloroquinoline, bromoquinoline, iodoquinoline, chloromethylquinoline , Bromomethylquinoline, iodomethylquinoline, chlorodimethylquinoline, bromodimethylquinoline, iododimethylquinoline, chlorotrimethylquinoline, bromotrimethylquinoline, iodotrimethylquinoline, chloroethylquinoline, bromoethylquinoline, iodoethylquinoline, chloroisopropylquinoline, bromo Isopropyl quinoline, iodoisopropyl quinoline, chlorohexyl quinoline Halogenated quinoline derivatives such as bromohexylquinoline, iodohexylquinoline, chloromethoxyquinoline, bromomethoxyquinoline, iodomethoxyquinoline, chlorohexyloxyquinoline, bromohexyloxyquinoline, iodohexyloxyquinoline, such as chloroisoquinoline, bromoisoquinoline, iodo Isoquinoline, chloromethylisoquinoline, bromomethylisoquinoline, iodomethylisoquinoline, chlorodimethylisoquinoline, bromodimethylisoquinoline, iododimethylisoquinoline, chlorotrimethylisoquinoline, bromotrimethylisoquinoline, iodotrimethylisoquinoline, chloroethylisoquinoline, bromoethylisoquinoline, iodoethylisoquinoline, Chloroisopropyl isoquinori , Bromoisopropylisoquinoline, iodoisopropylisoquinoline, chlorohexylisoquinoline, bromohexylisoquinoline, iodohexylisoquinoline, chloromethoxyisoquinoline, bromomethoxyisoquinoline, iodomethoxyisoquinoline, chlorohexyloxyisoquinoline, bromohexyloxyisoquinoline, iodohexyloxyisoquinoline, etc. Isoquinoline derivatives such as chloronaphthyridine, bromonaphthyridine, iodonaphthyridine, chloromethylnaphthyridine, bromomethylnaphthyridine, iodomethylnaphthyridine, chlorodimethylnaphthyridine, bromodimethylnaphthyridine, iododimethylnaphthyridine, chlorotrimethylnaphthyridine, bromotrimethylnaphthyridine, iodotri Methylnaphthyridine, chloroethylnaphthyridine, bromoethylnaphthyridine, iodoethylnaphthyridine, chloroisopropylnaphthyridine, bromoisopropylnaphthyridine, iodoisopropylnaphthyridine, chlorohexylnaphthyridine, bromohexylnaphthyridine, iodohexylnaphthyridine, chloromethoxynaphthyridine, bromomethoxynaphthyridine, iodomethoxynaphthyridine Halogenated naphthyridine derivatives such as chlorohexyloxynaphthyridine, bromohexyloxynaphthyridine, iodohexyloxynaphthyridine, etc., among which chloronaphthalene, bromonaphthalene, iodonaphthalene, chloromethylnaphthalene, bromomethylnaphthalene, iodomethylnaphthalene, chloro Dimethylnaphtha , Bromodimethylnaphthalene, iododimethylnaphthalene, chlorotrimethylnaphthalene, bromotrimethylnaphthalene, iodotrimethylnaphthalene, chloroethylnaphthalene, bromoethylnaphthalene, iodoethylnaphthalene, chloroisopropylnaphthalene, bromoisopropylnaphthalene, iodoisopropylnaphthalene, chlorohexylnaphthalene, Halogenated naphthalene derivatives such as bromohexylnaphthalene, iodohexylnaphthalene, chloromethoxynaphthalene, bromomethoxynaphthalene, iodomethoxynaphthalene, chlorohexyloxynaphthalene, bromohexyloxynaphthalene, iodohexyloxynaphthalene and the like are preferable, among which chloronaphthalene and bromonaphthalene No iodonaphthalene More preferably a halogenated naphthalene derivative, more preferably bromonaphthalene even further therein. Further, the bonding position of the halogen atom in the halogenated naphthalene derivative, halogenated quinoline derivative, halogenated isoquinoline derivative and halogenated naphthyridine derivative is not particularly limited, and the halogen atom is a carbon at the 1st to 8th positions on the aromatic ring. It may be bonded to any carbon atom as long as it is an atom, and the bonding position of the substituent in the halogenated naphthalene derivative, halogenated quinoline derivative, halogenated isoquinoline derivative and halogenated naphthyridine derivative is not particularly limited. The substituent may be bonded to any carbon atom as long as it is a 1st to 8th carbon atom to which no halogen atom is bonded. In addition, said specific example is an example to the last, Comprising: The compound which concerns on the manufacturing method of this invention is not limited at all by these examples, These halogenated naphthalene derivatives, halogenated quinoline derivatives, halogenated isoquinoline derivatives As the halogenated naphthyridine derivative, a commercially available product may be used, or a product synthesized by a conventional method may be used as appropriate.

（式中、Ｒ^４、ｑ、Ｕ^１、Ｕ^２、Ｖ^１及びＶ^２は上記に同じ。）で示される、置換基を有していてもよいナフチル基、キノリル基、イソキノリル基又はナフチリジニル基であるものに相当する。 As a precaution, in the above general formula [I], the halogenated naphthalene derivative, halogenated quinoline derivative, halogenated isoquinoline derivative and halogenated naphthyridine derivative represented by the above general formula [VI] ] In general formula [IX]

(Wherein R ⁴ , q, U ¹ , U ² , V ¹ and V ² are the same as above), which may have a substituent, a naphthyl group, quinolyl group, isoquinolyl group or naphthyridinyl group Is equivalent to

  Specific examples of the halogenated anthracene derivative represented by the general formula [VI] include, for example, chloroanthracene, bromoanthracene, iodoanthracene, chloromethylanthracene, bromomethylanthracene, iodomethylanthracene, chlorodimethylanthracene, bromodimethylanthracene, iododimethyl. Anthracene, chlorotrimethylanthracene, bromotrimethylanthracene, iodotrimethylanthracene, chloroethylanthracene, bromoethylanthracene, iodoethylanthracene, chloroisopropylanthracene, bromoisopropylanthracene, iodoisopropylanthracene, chlorohexylanthracene, bromohexylanthracene, iodohexylanthracene, Chloromethoxyanthra Halogenated anthracene derivatives such as cene, bromomethoxyanthracene, iodomethoxyanthracene, chlorohexyloxyanthracene, bromohexyloxyanthracene, iodohexyloxyanthracene, and the like. Among them, unsubstituted halogen such as chloroanthracene, bromoanthracene, and iodoanthracene Anthracene derivatives are preferable, and among them, bromoanthracene is more preferable. In addition, the bonding position of the halogen atom in these halogenated anthracene derivatives is not particularly limited, and the halogen atom may be bonded to any carbon atom as long as it is a 1- to 10-position carbon atom on the aromatic ring. Further, the bonding position of the substituent in the halogenated anthracene derivative is not particularly limited, and the substituent is bonded to any carbon atom as long as it is a 1- to 10-position carbon atom to which no halogen atom is bonded. It may be. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited by these examples. These halogenated anthracene derivatives are either commercially available or are usually used. What was synthesize | combined by the method should just be used suitably.

（式中、Ｒ^５及びｒは上記に同じ。）で示される、置換基を有していてもよいアントリル基であるものに相当する。 As a reminder, in the general formula [I], the halogenated anthracene derivative represented by the general formula [VII] is such that Ar in the general formula [I] is represented by the general formula [X].

(Wherein R ⁵ and r are the same as above), which is an anthryl group which may have a substituent.

  The amount of the halogenated aromatic compound used is usually 0.5 to 10 equivalents, preferably 0.5 to the β-vinyl compound represented by the general formula [III] used in the second step described later. 5 equivalents, more preferably 0.8-3 equivalents. When the amount is less than 0.5 equivalent, the coupling reaction in the second step to be described later does not proceed sufficiently. On the other hand, the use of a halogenated aromatic compound in an amount exceeding 10 equivalents impairs economy. This is not desirable because it causes problems. In addition, the usage-amount of the said halogenated aromatic compound said here is general formula [II] produced by reaction with this halogenated aromatic compound and the organolithium reagent mentioned later in the 1st process of the microreactor mentioned later. The apparent equivalent when the lithiated aromatic compound represented by (2) reacts with the β-vinyl compound in the micromixer of the second step, in other words, the micromixer of the second step of the microreactor described later In which the β-vinyl compound and the lithiated aromatic compound represented by the general formula [II] formed by lithiation of the halogenated aromatic compound are defined as apparent equivalents. .

  In the production method of the present invention, the halogenated aromatic compound represented by the general formula [I] used in the present invention is required to be liquid or used in a solution state. Therefore, when the halogenated aromatic compound represented by the general formula [I] is not liquid, it is necessary to dissolve it in an organic solvent that is inert to the reaction in at least the first and second steps described later. Further, even when the halogenated aromatic compound represented by the general formula [I] is a liquid, a liquid halogenated aromatic compound having a high viscosity is used, or a halogenated aromatic compound having high reactivity is used. In some cases, when it is difficult to use a liquid halogenated aromatic compound as it is, it is desirable to dilute it appropriately in an organic solvent. Specific examples of the organic solvent include aliphatic hydrocarbon solvents such as n-pentane, n-hexane, cyclohexane, n-heptane, n-octane, isooctane, and petroleum ether, benzene, toluene, xylene, and mesitylene. , Aromatic hydrocarbon solvents such as ethylbenzene, ether solvents such as dimethyl ether, diethyl ether, methyl-tert-butyl ether, cyclopentyl methyl ether, tetrahydrofuran (THF), dimethoxyethane, dioxane, N, N-dimethylformamide, N, Examples include amide solvents such as N-dimethylacetamide and N-methylpyrrolidone, and sulfoxide solvents such as dimethyl sulfoxide, among which n-pentane, n-hexane, cyclohexane, n-heptane, n-octane and isooctane. Aliphatic hydrocarbon solvents such as benzene, toluene, xylene, mesitylene, ethylbenzene, and other aromatic hydrocarbon solvents, dimethyl ether, diethyl ether, methyl-tert-butyl ether, cyclopentyl methyl ether, tetrahydrofuran (THF), dimethoxyethane, Ether solvents such as dioxane are preferable, and ether solvents such as dimethyl ether, diethyl ether, methyl-tert-butyl ether, cyclopentyl methyl ether, tetrahydrofuran (THF), dimethoxyethane, and dioxane are more preferable. In addition, these organic solvents may be used alone or in combination of two or more, and the mixing ratio when using two or more in combination can be arbitrarily determined.

  In these organic solvents, the molar concentration of the halogenated aromatic compound solution represented by the general formula [I], that is, the molar concentration of the solution supplied to the microreactor described later is usually 0.01 to 20 mol / L, preferably Is suitably used so as to be 0.02 to 10 mol / L, more preferably 0.05 to 5 mol / L. In addition, when it is less than 0.01 mol / L, the amount of the organic solvent is relatively increased, and the flow rate in the microreactor described later is excessively large (the flow rate is too high). IV] is not desirable because the yield of the vinyl-substituted aryl compound represented by the formula [IV] is small and the productivity is lowered.

  As the organolithium reagent used in the present invention, a conventionally known organolithium reagent can be used. Specifically, for example, methyllithium, ethyllithium, propyllithium, butyllithium, pentyllithium, hexyllithium, methoxymethyllithium And alkyllithium such as ethoxymethyllithium, among which methyllithium, ethyllithium, n-propyllithium, isopropyllithium, n-butyllithium, isobutyllithium, sec-butyllithium, tert-butyllithium, n-pentyllithium, n-Hexyllithium is preferred, and n-butyllithium is more preferred. These organolithium reagents may be used alone or in combination of two or more, and the mixing ratio when using in combination of two or more can be arbitrarily determined. As these organolithium reagents, commercially available ones are sufficient.

  The amount of the organolithium reagent used varies depending on the type of the halogenated aromatic compound represented by the general formula [I] to be used, but is usually 0.5 to 10 equivalents relative to the halogenated aromatic compound, preferably Is 0.5 to 5 equivalents, more preferably 0.8 to 3 equivalents. When the amount is less than 0.5 equivalent, the halogen-lithium exchange reaction in the first step described later does not proceed sufficiently. On the other hand, when an amount of the organic lithium reagent exceeding 10 equivalent is used, for example, an alkoxy group is substituted. This is not desirable because problems such as progress of o-lithiation of the halogenated aromatic compound and loss of economic efficiency occur. The amount of the organolithium reagent used here refers to the apparent equivalent during the reaction between the halogenated aromatic compound represented by the general formula [I] and the organolithium reagent, in other words, the microreactor described later. In the micromixer of the first step, it is defined as an apparent equivalent when the halogenated aromatic compound represented by the general formula [I] reacts with the organolithium reagent.

  If the organolithium reagent is commercially available, it is usually in a solution state and can be used as it is. However, the amount of the organolithium reagent used and the halogenation represented by the above general formula [I] can be used. It is desirable to determine the molar concentration of the organolithium reagent in consideration of the molar concentration of the aromatic compound solution. For this reason, when determining the molar concentration of the organolithium reagent supplied to the microreactor described later, the commercially available organolithium reagent is at least an organic solvent inert to the reaction in the first and second steps described later. A diluted one may be used. Specific examples of the organic solvent used for the dilution include organic solvents similar to the organic solvent used for bringing the halogenated aromatic compound represented by the above general formula [I] into a solution state. Preferred specific examples include aliphatic hydrocarbon solvents such as n-pentane, n-hexane, cyclohexane, n-heptane, n-octane and isooctane. Further, the amount used may be appropriately adjusted according to the molar concentration of the organolithium reagent described later.

  The molar concentration of the organolithium reagent, that is, the molar concentration of the solution supplied to the microreactor described later, is indicated by the amount of the organolithium reagent used relative to the halogenated aromatic compound represented by the general formula [I], the general formula [I]. It may be determined in consideration of the molar concentration of the solution of the halogenated aromatic compound, the flow rate (flow rate) of the organolithium reagent in the microreactor, etc., for example, usually 0.01 to 20 mol / L, preferably 0. It is 02-10 mol / L, More preferably, it is 0.05-5 mol / L. In addition, when it is less than 0.01 mol / L, the amount of the organic solvent is relatively increased, and the flow rate in the microreactor described later is too large (the flow rate is too high), so that the productivity is reduced. This is undesirable because it causes problems.

（式中、ｓ個のＲ^６は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｓは０〜５の整数を表し、Ｊは炭素原子又は窒素原子を表し、Ｒ^１、Ｒ^２及びＹ上記に同じ。なお、隣接する２つのＲ^６は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるビニルベンゼン誘導体（スチレン誘導体）若しくはビニルピリジン誘導体、一般式［ XII ］

（式中、ｔ個のＲ^７は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｔは０〜７の整数を表し、Ｑ^１及びＱ^２は、共に炭素原子を表すか又はＱ^１及びＱ^２の何れか一方が窒素原子を表す場合は他方が炭素原子を表し、Ｔ^１及びＴ^２は、共に炭素原子を表すか又はＴ^１及びＴ^２の何れか一方が窒素原子を表す場合は他方が炭素原子を表し、Ｒ^１、Ｒ^２及びＹ上記に同じ。なお、隣接する２つのＲ^７は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるビニルナフタレン誘導体、ビニルキノリン誘導体、ビニルイソキノリン誘導体若しくはビニルナフチリジン誘導体、又は一般式［ XIII ］

（式中、ｕ個のＲ^８は夫々独立して、炭素数１〜６の直鎖状、分枝状若しくは環状のアルキル基、炭素数１〜６の直鎖状、分枝状若しくは環状のアルコキシ基又はフェニル基を表し、ｕは０〜９の整数を表し、Ｒ^１、Ｒ^２及びＹ上記に同じ。なお、隣接する２つのＲ^８は、これらが結合している炭素原子と共に、鎖中に酸素原子又は硫黄原子を有していてもよい炭素数３〜６の脂肪族環を形成していてもよい。）で示されるビニルアントラセン等のアリールビニル化合物、或いは一般式［ XIV ］

（式中、Ｚ’は、炭素数１〜１０の直鎖状、分枝状若しくは環状のアルキル基を表し、Ｒ^１、Ｒ^２及びＹ上記に同じ。）で示されるアルキルビニル化合物が挙げられる。 The β-vinyl compound represented by the general formula [III] used in the present invention is an aryl vinyl compound or an alkyl vinyl compound in which a halogen atom or a trifluoromethanesulfonyloxy group is substituted at the β-position of the vinyl group, The vinyl group of the compound and / or the aryl group of the compound may have a substituent as long as the second step (coupling reaction) described later is not adversely affected. Specific examples of the β-vinyl compound represented by the general formula [III] include, for example, the general formula [XI].

(In the formula, each s R ⁶ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. an alkoxy group or a phenyl group, s represents an integer of 0 to 5, J represents a carbon atom or a nitrogen atom, R ^1, R ² and Y same as above. in addition, two R ⁶ adjacent, these A benzene derivative (styrene) which may form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which is bonded. Derivatives) or vinylpyridine derivatives, general formula [XII]

(Wherein t R ^{7 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, t represents an integer of 0 to 7, Q ¹ and Q ² both represent a carbon atom, or when either Q ¹ or Q ² represents a nitrogen atom, the other represents Represents a carbon atom, and T ¹ and T ² both represent a carbon atom, or when ^one of T ¹ and T ² represents a nitrogen atom, the other represents a carbon atom, R ¹ , R ² and Y Note that two adjacent R ⁷ together with the carbon atom to which they are bonded form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain. Vinyl naphthalene derivatives, vinyl quinoline derivatives, and vinyl isoquinoline Derivatives or vinylnaphthyridine derivatives, or a general formula [XIII]

(In the formula, each of u R ⁸ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, u represents an integer of 0 to 9, and R ¹ , R ² and Y are the same as described above, and two adjacent R ^{8 s} are chained together with the carbon atom to which they are bonded. Or an aryl vinyl compound such as vinyl anthracene represented by the general formula [XIV], which may form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom therein.

(Wherein, Z ′ represents a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, and R ¹ , R ² and Y are the same as described above). .

Specific examples of the linear, branched or cyclic alkyl group having 1 to 6 carbon atoms represented by R ⁶ , R ⁷ and R ⁸ in the general formulas [XI], [XII] and [XIII] include For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group 2-methylpentyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclohexyl group, etc. Is mentioned.

Specific examples of the linear, branched or cyclic alkoxy group having 1 to 6 carbon atoms represented by R ⁶ , R ⁷ and R ⁸ in the general formulas [XI], [XII] and [XIII] include For example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, cyclobutoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, tert-pentyloxy group, neopentyloxy group, 2-methylbutoxy group, 1,2-dimethylpropoxy group, 1-ethylpropoxy group, cyclopentyloxy group, n-hexyloxy group, isohexyloxy Group, sec-hexyloxy group, tert-hexyloxy group, neohexyloxy group, 2-methylpentylio Xyl group, 1,2-dimethylbutoxy group, 2,3-dimethylbutoxy group, 1-ethylbutoxy group, cyclohexyloxy group and the like can be mentioned.

  As s in general formula [XI], the integer of 0-3 is preferable, and 0 is more preferable especially.

  As J in general formula [XI], a carbon atom is preferable.

  As t in the general formula [XII], an integer of 0 to 5 is preferable, an integer of 0 to 3 is more preferable, and 0 is more preferable among them.

Q ¹ , Q ² , T ¹ and T ² in the general formula [XII] are all carbon atoms, or any one is preferably a nitrogen atom, and more preferably all are carbon atoms.

  As u in the general formula [XIII], an integer of 0 to 7 is preferable, an integer of 0 to 5 is more preferable, an integer of 0 to 3 is more preferable, and 0 is particularly preferable.

Formula [XI], [XII] and ^R 6, ^{R 7} and "two adjacent R represented by ^{R 8} (two ^R 6, two ^{R 7} or two ^{R 8)} in [XIII], these In the chain may have an oxygen or sulfur atom in the chain and may form an aliphatic ring having 3 to 6 carbon atoms. Specific examples of the “aliphatic ring” include cyclopentane ring, cyclohexane ring, tetrahydrofuran ring, tetrahydropyran ring, tetrahydrothiophene ring, tetrahydrothiofuran ring, 1,3-dioxacyclopentane ring, 1,3- Examples include a dioxacyclohexane ring and a 1,4-dioxacyclohexane ring. In addition, the carbon number of the carbon atom which comprises these aliphatic rings means the carbon number containing the two carbon atoms which comprise the aromatic ring condensed with the said aliphatic ring.

  The linear, branched or cyclic alkyl group having 1 to 10 carbon atoms represented by Z ′ in the general formula [XIV] may have an oxygen atom or a sulfur atom in the chain, For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, n-pentyl group, isopentyl group, sec-pentyl Group, tert-pentyl group, neopentyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, cyclopentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, Neohexyl group, 2-methylpentyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, cyclo Xyl group, n-heptyl group, isoheptyl group, sec-heptyl group, tert-heptyl group, neoheptyl group, cycloheptyl group, n-octyl group, isooctyl group, sec-octyl group, tert-octyl group, neooctyl group, 2 -Ethylhexyl group, cyclooctyl group, n-nonyl group, isononyl group, sec-nonyl group, tert-nonyl group, neononyl group, cyclononyl group, n-decyl group, isodecyl group, sec-decyl group, tert-decyl group, Neodecyl group, cyclodecyl group, hexahydroindanyl group, decahydronaphthyl group, spiro [4,4] nonyl group, spiro [4,5] decyl group, norbornyl group, adamantyl group, methoxymethyl group, ethoxyethyl group, propoxy Propyl group, methylthiomethyl group, ethylthioethyl Group, propylthiopropyl group, tetrahydrofuryl group and the like.

  Specific examples of the vinylbenzene derivative (styrene derivative) and the vinylpyridine derivative represented by the general formula [XI] include, for example, β-chlorostyrene, β-bromostyrene, β-iodostyrene, β-trifluoromethanesulfonyloxystyrene, β -Chloromethylstyrene, β-bromomethylstyrene, β-iodomethylstyrene, β-trifluoromethanesulfonyloxymethylstyrene, β-chlorodimethylstyrene, β-bromodimethylstyrene, β-iododimethylstyrene, β-trifluoromethanesulfonyloxy Dimethylstyrene, β-chlorotrimethylstyrene, β-bromotrimethylstyrene, β-iodotrimethylstyrene, β-trifluoromethanesulfonyloxytrimethylstyrene, β-chloroethylstyrene, β-bromoethyl Styrene, β-iodoethyl styrene, β-trifluoromethanesulfonyloxyethyl styrene, β-chloroisopropyl styrene, β-bromoisopropyl styrene, β-iodoisopropyl styrene, β-trifluoromethanesulfonyloxy isopropyl styrene, β-chlorohexyl styrene, β-bromohexylstyrene, β-iodohexylstyrene, β-trifluoromethanesulfonyloxyhexylstyrene, β-chloromethoxystyrene, β-bromomethoxystyrene, β-iodomethoxystyrene, β-trifluoromethanesulfonyloxymethoxystyrene, β- Chlorohexyloxystyrene, β-bromohexyloxystyrene, β-iodohexyloxystyrene, β-trifluoromethanesulfonyloxyhexyloxy Styrene, β-chloro-α-methylstyrene, β-bromo-α-methylstyrene, β-iodo-α-methylstyrene, β-trifluoromethanesulfonyloxy-α-methylstyrene, β-chloro-β-methylstyrene, Vinylbenzene derivatives (styrene derivatives) such as β-bromo-β-methylstyrene, β-iodo-β-methylstyrene, β-trifluoromethanesulfonyloxy-β-methylstyrene, such as β-chlorovinylpyridine, β-bromovinyl Pyridine, β-iodovinylpyridine, β-trifluoromethanesulfonyloxyvinylpyridine, β-chlorovinylmethylpyridine, β-bromovinylmethylpyridine, β-iodovinylmethylpyridine, β-trifluoromethanesulfonyloxyvinylmethylpyridine, β- Chlorovinyldimethyl Pyridine, β-bromovinyldimethylpyridine, β-iodovinyldimethylpyridine, β-trifluoromethanesulfonyloxyvinyldimethylpyridine, β-chlorovinyltrimethylpyridine, β-bromovinyltrimethylpyridine, β-iodovinyltrimethylpyridine, β-trifluoro L-methanesulfonyloxyvinyltrimethylpyridine, β-chlorovinylethylpyridine, β-bromovinylethylpyridine, β-iodovinylethylpyridine, β-trifluoromethanesulfonyloxyvinylethylpyridine, β-chlorovinylisopropylpyridine, β-bromovinylisopropyl Pyridine, β-iodovinylisopropylpyridine, β-trifluoromethanesulfonyloxyvinylisopropylpyridine, β-chlorovinylhexylpyri , Β-bromovinylhexylpyridine, β-iodovinylhexylpyridine, β-trifluoromethanesulfonyloxyvinylhexylpyridine, β-chlorovinylmethoxypyridine, β-bromovinylmethoxypyridine, β-iodovinylmethoxypyridine, β-trifluoro L-methanesulfonyloxyvinylmethoxypyridine, β-chlorovinylhexyloxypyridine, β-bromovinylhexyloxypyridine, β-iodovinylhexyloxypyridine, β-trifluoromethanesulfonyloxyvinylhexyloxypyridine, β-chloro-α-methylvinyl Pyridine, β-bromo-α-methylvinylpyridine, β-iodo-α-methylvinylpyridine, β-trifluoromethanesulfonyloxy-α-methylvinylpyridine, β-chloro-β Vinylpyridine derivatives such as -methylvinylpyridine, β-bromo-β-methylvinylpyridine, β-iodo-β-methylvinylpyridine, β-trifluoromethanesulfonyloxy-β-methylvinylpyridine, etc. -Chlorostyrene, β-bromostyrene, β-iodostyrene, β-trifluoromethanesulfonyloxystyrene, β-chloromethylstyrene, β-bromomethylstyrene, β-iodomethylstyrene, β-trifluoromethanesulfonyloxymethylstyrene, β -Chlorodimethylstyrene, β-bromodimethylstyrene, β-iododimethylstyrene, β-trifluoromethanesulfonyloxydimethylstyrene, β-chlorotrimethylstyrene, β-bromotrimethylstyrene, β-iodotrimethylstyrene , Β-trifluoromethanesulfonyloxytrimethylstyrene, β-chloroethylstyrene, β-bromoethylstyrene, β-iodoethylstyrene, β-trifluoromethanesulfonyloxyethylstyrene, β-chloroisopropylstyrene, β-bromoisopropylstyrene, β -Iodoisopropyl styrene, β-trifluoromethanesulfonyloxyisopropyl styrene, β-chlorohexyl styrene, β-bromohexyl styrene, β-iodohexyl styrene, β-trifluoromethanesulfonyloxyhexyl styrene, β-chloromethoxy styrene, β-bromo Methoxystyrene, β-iodomethoxystyrene, β-trifluoromethanesulfonyloxymethoxystyrene, β-chlorohexyloxystyrene, β-bromohexyl Oxystyrene, β-iodohexyloxystyrene, β-trifluoromethanesulfonyloxyhexyloxystyrene, β-chloro-α-methylstyrene, β-bromo-α-methylstyrene, β-iodo-α-methylstyrene, β- Such as trifluoromethanesulfonyloxy-α-methylstyrene, β-chloro-β-methylstyrene, β-bromo-β-methylstyrene, β-iodo-β-methylstyrene, β-trifluoromethanesulfonyloxy-β-methylstyrene, etc. Vinylbenzene derivatives (styrene derivatives) are preferable, and among them, unsubstituted vinylbenzene derivatives (styrene derivatives) such as β-chlorostyrene, β-bromostyrene, β-iodostyrene, β-trifluoromethanesulfonyloxystyrene are more preferable, Among them, β-bu More preferred is lomostyrene. Further, the bonding position of the vinyl group with respect to the aromatic ring in these vinylbenzene derivatives (styrene derivatives) and vinylpyridine derivatives is not particularly limited, and the vinyl group is bonded to any carbon atom as long as it is a carbon atom on the aromatic ring. Further, the bonding position of the substituent on the aromatic ring in the vinylbenzene derivative (styrene derivative) and vinylpyridine derivative is not particularly limited, and the substituent may be a carbon atom to which no vinyl group is bonded. For example, it may be bonded to any carbon atom. Furthermore, these vinylbenzene derivatives (styrene derivatives) and vinylpyridine derivatives are not limited to either (E) isomer or (Z) isomer, and any of (E) isomer and (Z) isomer It may be a derivative. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited to these examples. These vinylbenzene derivatives (styrene derivatives) and vinylpyridine derivatives are commercially available. May be used as appropriate, or those synthesized by conventional methods may be used as appropriate.

（式中、Ｒ^６、ｓ及びＪは上記に同じ。）で示される、置換基を有していてもよいフェニル基又はピリジル基であるものに相当する。 As a precautionary note, in the above general formula [III], the vinylbenzene derivative (styrene derivative) and the vinylpyridine derivative represented by the above general formula [XI] are represented by the formula [III] wherein Z is represented by the general formula [III]. XV]

(Wherein R ⁶ , s and J are the same as above), which is a phenyl group or a pyridyl group which may have a substituent.

Specific examples of the vinylnaphthalene derivative, vinylquinoline derivative, vinylisoquinoline derivative and vinylnaphthyridine derivative represented by the general formula [XII] include, for example, β-chlorovinylnaphthalene, β-bromovinylnaphthalene, β-iodovinylnaphthalene, β- Trifluoromethanesulfonyloxyvinylnaphthalene, β-chlorovinylmethylnaphthalene, β-bromovinylmethylnaphthalene, β-iodovinylmethylnaphthalene, β-trifluoromethanesulfonyloxyvinylmethylnaphthalene, β-chlorovinyldimethylnaphthalene, β-bromovinyldimethyl Naphthalene, β-iodovinyldimethylnaphthalene, β-trifluoromethanesulfonyloxyvinyldimethylnaphthalene, β-chlorovinyltrimethylnaphthalene, β-bromovinyl Limethylnaphthalene, β-iodovinyltrimethylnaphthalene, β-trifluoromethanesulfonyloxyvinyltrimethylnaphthalene, β-chlorovinylethylnaphthalene, β-bromovinylethylnaphthalene, β-iodovinylethylnaphthalene, β-trifluoromethanesulfonyloxyvinylethyl Naphthalene, β-chlorovinylisopropylnaphthalene, β-bromovinylisopropylnaphthalene, β-iodovinylisopropylnaphthalene, β-trifluoromethanesulfonyloxyvinylisopropylnaphthalene, β-chlorovinylhexylnaphthalene, β-bromovinylhexylnaphthalene, β-iodo Vinylhexylnaphthalene, β-trifluoromethanesulfonyloxyvinylhexylnaphthalene, β-chlorovinylmethoxynaphthalene Talene, β-bromovinylmethoxynaphthalene, β-iodovinylmethoxynaphthalene, β-trifluoromethanesulfonyloxyvinylmethoxynaphthalene, β-chlorovinylhexyloxynaphthalene, β-bromovinylhexyloxynaphthalene, β-iodovinylhexyloxynaphthalene, β-trifluoromethanesulfonyloxyvinylhexyloxynaphthalene, β-chloro-α-methylvinylnaphthalene, β-bromo-α-methylvinylnaphthalene, β-iodo-α-methylvinylnaphthalene, β-trifluoromethanesulfonyloxy-α- Methyl vinyl naphthalene, β-chloro-β-methyl vinyl naphthalene, β-bromo-β-methyl vinyl naphthalene, β-iodo-β-methyl vinyl naphthalene, β-trifluoromethanesulfonyl Vinylnaphthalene derivatives such as xyl-β-methylvinylnaphthalene, such as β-chlorovinylquinoline, β-bromovinylquinoline, β-iodovinylquinoline, β-trifluoromethanesulfonyloxyvinylquinoline, β-chlorovinylmethylquinoline, β- Bromovinylmethylquinoline, β-iodovinylmethylquinoline, β-trifluoromethanesulfonyloxyvinylmethylquinoline, β-chlorovinyldimethylquinoline, β-bromovinyldimethylquinoline, β-iodovinyldimethylquinoline, β-trifluoromethanesulfonyloxyvinyl Dimethylquinoline, β-chlorovinyltrimethylquinoline, β-bromovinyltrimethylquinoline, β-iodovinyltrimethylquinoline, β-trifluoromethanesulfonyloxyvinyl trime Luquinoline, β-chlorovinylethylquinoline, β-bromovinylethylquinoline, β-iodovinylethylquinoline, β-trifluoromethanesulfonyloxyvinylethylquinoline, β-chlorovinylisopropylquinoline, β-bromovinylisopropylquinoline, β-iodo Vinylisopropylquinoline, β-trifluoromethanesulfonyloxyvinylisopropylquinoline, β-chlorovinylhexylquinoline, β-bromovinylhexylquinoline, β-iodovinylhexylquinoline, β-trifluoromethanesulfonyloxyvinylhexylquinoline, β-chlorovinylmethoxy Quinoline, β-bromovinylmethoxyquinoline, β-iodovinylmethoxyquinoline, β-trifluoromethanesulfonyloxyvinylmethoxyquinoline, β-chlorovinylhexyloxyquinoline, β-bromovinylhexyloxyquinoline, β-iodovinylhexyloxyquinoline, β-trifluoromethanesulfonyloxyvinylhexyloxyquinoline, β-chloro-α-methylvinylquinoline, β-bromo-α -Methylvinylquinoline, β-iodo-α-methylvinylquinoline, β-trifluoromethanesulfonyloxy-α-methylvinylquinoline, β-chloro-β-methylvinylquinoline, β-bromo-β-methylvinylquinoline, β- Vinylquinoline derivatives such as iodo-β-methylvinylquinoline, β-trifluoromethanesulfonyloxy-β-methylvinylquinoline, such as β-chlorovinylisoquinoline, β-bromovinylisoquinoline, β-iodovinylisoquinoline, β-trifluoro Methanesulfonyloxyvinylisoquinoline, β-chlorovinylmethylisoquinoline, β-bromovinylmethylisoquinoline, β-iodovinylmethylisoquinoline, β-trifluoromethanesulfonyloxyvinylmethylisoquinoline, β-chlorovinyldimethylisoquinoline, β-bromovinyldimethylisoquinoline , Β-iodovinyldimethylisoquinoline, β-trifluoromethanesulfonyloxyvinyldimethylisoquinoline, β-chlorovinyltrimethylisoquinoline, β-bromovinyltrimethylisoquinoline, β-iodovinyltrimethylisoquinoline, β-trifluoromethanesulfonyloxyvinyltrimethylisoquinoline, β -Chlorovinylethylisoquinoline, β-bromovinylethylisoquinoline, β-iodovinylethyl Isoquinoline, β-trifluoromethanesulfonyloxyvinylethylisoquinoline, β-chlorovinylisopropylisoquinoline, β-bromovinylisopropylisoquinoline, β-iodovinylisopropylisoquinoline, β-trifluoromethanesulfonyloxyvinylisopropylisoquinoline, β-chlorovinylhexylisoquinoline, β-bromovinylhexylisoquinoline, β-iodovinylhexylisoquinoline, β-trifluoromethanesulfonyloxyvinylhexylisoquinoline, β-chlorovinylmethoxyisoquinoline, β-bromovinylmethoxyisoquinoline, β-iodovinylmethoxyisoquinoline, β-trifluoromethanesulfonyl Oxyvinylmethoxyisoquinoline, β-chlorovinylhexyloxyisoquinoline , Β-bromovinylhexyloxyisoquinoline, β-iodovinylhexyloxyisoquinoline, β-trifluoromethanesulfonyloxyvinylhexyloxyisoquinoline, β-chloro-α-methylvinylisoquinoline, β-bromo-α-methylvinylisoquinoline, β- Iodo-α-methylvinylisoquinoline, β-trifluoromethanesulfonyloxy-α-methylvinylisoquinoline, β-chloro-β-methylvinylisoquinoline, β-bromo-β-methylvinylisoquinoline, β-iodo-β-methylvinylisoquinoline , Β-trifluoromethanesulfonyloxy-β-methylvinylisoquinoline derivatives such as β-chlorovinylnaphthyridine, β-bromovinylnaphthyridine, β-iodovinylnaphthyridine, β Trifluoromethanesulfonyloxyvinylnaphthyridine, β-chlorovinylmethylnaphthyridine, β-bromovinylmethylnaphthyridine, β-iodovinylmethylnaphthyridine, β-trifluoromethanesulfonyloxyvinylmethylnaphthyridine, β-chlorovinyldimethylnaphthyridine, β-bromovinyldimethyl Naphthyridine, β-iodovinyldimethylnaphthyridine, β-trifluoromethanesulfonyloxyvinyldimethylnaphthyridine, β-chlorovinyltrimethylnaphthyridine, β-bromovinyltrimethylnaphthyridine, β-iodovinyltrimethylnaphthyridine, β-trifluoromethanesulfonyloxyvinyltrimethylnaphthyridine, β-chlorovinylethylnaphthyridine, β-bromovinylethylnaphthyridine, β-iodo Vinylethylnaphthyridine, β-trifluoromethanesulfonyloxyvinylethylnaphthyridine, β-chlorovinylisopropylnaphthyridine, β-bromovinylisopropylnaphthyridine, β-iodovinylisopropylnaphthyridine, β-trifluoromethanesulfonyloxyvinylisopropylnaphthyridine, β-chlorovinylhexyl Naphthyridine, β-bromovinylhexylnaphthyridine, β-iodovinylhexylnaphthyridine, β-trifluoromethanesulfonyloxyvinylhexylnaphthyridine, β-chlorovinylmethoxynaphthyridine, β-bromovinylmethoxynaphthyridine, β-iodovinylmethoxynaphthyridine, β-trifluoro Lomethanesulfonyloxyvinylmethoxynaphthyridine, β-chlorovinylhexyloxy Naphthyridine, β-bromovinylhexyloxynaphthyridine, β-iodovinylhexyloxynaphthyridine, β-trifluoromethanesulfonyloxyvinylhexyloxynaphthyridine, β-chloro-α-methylvinylnaphthyridine, β-bromo-α-methylvinylnaphthyridine, β -Iodo-α-methylvinylnaphthyridine, β-trifluoromethanesulfonyloxy-α-methylvinylnaphthyridine, β-chloro-β-methylvinylnaphthyridine, β-bromo-β-methylvinylnaphthyridine, β-iodo-β-methylvinyl And vinyl naphthyridine derivatives such as naphthyridine, β-trifluoromethanesulfonyloxy-β-methylvinylnaphthyridine, and the like. Among them, for example, β-chlorovinylnaphthalene, β-bromovinylnaphthalene, β- Dovinylnaphthalene, β-trifluoromethanesulfonyloxyvinylnaphthalene, β-chlorovinylmethylnaphthalene, β-bromovinylmethylnaphthalene, β-iodovinylmethylnaphthalene, β-trifluoromethanesulfonyloxyvinylmethylnaphthalene, β-chlorovinyldimethylnaphthalene , Β-bromovinyldimethylnaphthalene, β-iodovinyldimethylnaphthalene, β-trifluoromethanesulfonyloxyvinyldimethylnaphthalene, β-chlorovinyltrimethylnaphthalene, β-bromovinyltrimethylnaphthalene, β-iodovinyltrimethylnaphthalene, β-trifluoromethane Sulfonyloxyvinyltrimethylnaphthalene, β-chlorovinylethylnaphthalene, β-bromovinylethylnaphthalene, β-iodovinyl Tylnaphthalene, β-trifluoromethanesulfonyloxyvinylethylnaphthalene, β-chlorovinylisopropylnaphthalene, β-bromovinylisopropylnaphthalene, β-iodovinylisopropylnaphthalene, β-trifluoromethanesulfonyloxyvinylisopropylnaphthalene, β-chlorovinylhexylnaphthalene , Β-bromovinylhexylnaphthalene, β-iodovinylhexylnaphthalene, β-trifluoromethanesulfonyloxyvinylhexylnaphthalene, β-chlorovinylmethoxynaphthalene, β-bromovinylmethoxynaphthalene, β-iodovinylmethoxynaphthalene, β-trifluoromethane Sulfonyloxyvinylmethoxynaphthalene, β-chlorovinylhexyloxynaphthalene, β-bromovinylhexyl Oxynaphthalene, β-iodovinylhexyloxynaphthalene, β-trifluoromethanesulfonyloxyvinylhexyloxynaphthalene, β-chloro-α-methylvinylnaphthalene, β-bromo-α-methylvinylnaphthalene, β-iodo-α-methylvinyl Naphthalene, β-trifluoromethanesulfonyloxy-α-methylvinylnaphthalene, β-chloro-β-methylvinylnaphthalene, β-bromo-β-methylvinylnaphthalene, β-iodo-β-methylvinylnaphthalene, β-trifluoromethanesulfonyl Vinyl naphthalene derivatives such as oxy-β-methylvinylnaphthalene are preferred, among which β-chlorovinylnaphthalene, β-bromovinylnaphthalene, β-iodovinylnaphthalene, β-trifluoromethanesulfonyloxyvinyl Unsubstituted vinylnaphthalene derivatives are more preferred such as Futaren,
Among them, β-bromovinylnaphthalene is more preferable. Further, the bonding position of the vinyl group with respect to the aromatic ring in these vinyl naphthalene derivatives, vinyl quinoline derivatives, vinyl isoquinoline derivatives and vinyl naphthyridine derivatives is not particularly limited, and the vinyl group is a carbon atom at the 1st to 8th positions on the aromatic ring. As long as it is bonded to any carbon atom, and the bonding position of the substituent on the aromatic ring in the vinyl naphthalene derivative, vinyl quinoline derivative, vinyl isoquinoline derivative and vinyl naphthyridine derivative is not particularly limited. The group may be bonded to any carbon atom as long as it is a 1st to 8th carbon atom to which no vinyl group is bonded. Furthermore, these vinyl naphthalene derivatives, vinyl quinoline derivatives, vinyl isoquinoline derivatives and vinyl naphthyridine derivatives are not limited to either the (E) isomer or the (Z) isomer, and the (E) isomer and (Z) Any derivative of the body can be used. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited to these examples. These vinyl naphthalene derivatives, vinyl quinoline derivatives, vinyl isoquinoline derivatives, and vinyl naphthyridines are not limited thereto. As the derivative, a commercially available derivative may be used, or a derivative synthesized by a conventional method may be appropriately used.

（式中、Ｒ^７、ｔ、Ｑ^１、Ｑ^２、Ｔ^１及びＴ^２は上記に同じ。）で示される、置換基を有していてもよいナフチル基、キノリル基、イソキノリル基又はナフチリジニル基であるものに相当する。 As a precaution, in the general formula [III], the vinyl naphthalene derivative, vinylquinoline derivative, vinylisoquinoline derivative and vinylnaphthyridine derivative represented by the general formula [XII] , General formula [XVI]

(Wherein R ⁷ , t, Q ¹ , Q ² , T ¹ and T ² are the same as above), which may have a substituent, a naphthyl group, quinolyl group, isoquinolyl group or naphthyridinyl group Is equivalent to

  Specific examples of the vinyl anthracene derivative represented by the general formula [XIII] include, for example, β-chlorovinylanthracene, β-bromovinylanthracene, β-iodovinylanthracene, β-trifluoromethanesulfonyloxyvinylanthracene, β-chlorovinylmethyl. Anthracene, β-bromovinylmethylanthracene, β-iodovinylmethylanthracene, β-trifluoromethanesulfonyloxyvinylmethylanthracene, β-chlorovinyldimethylanthracene, β-bromovinyldimethylanthracene, β-iodovinyldimethylanthracene, β-trifluoro L-methanesulfonyloxyvinyldimethylanthracene, β-chlorovinyltrimethylanthracene, β-bromovinyltrimethylanthracene, β-iodovinyltrimethyl Anthracene, β-trifluoromethanesulfonyloxyvinyltrimethylanthracene, β-chlorovinylethylanthracene, β-bromovinylethylanthracene, β-iodovinylethylanthracene, β-trifluoromethanesulfonyloxyvinylethylanthracene, β-chlorovinylisopropylanthracene, β-bromovinylisopropylanthracene, β-iodovinylisopropylanthracene, β-trifluoromethanesulfonyloxyvinylisopropylanthracene, β-chlorovinylhexylanthracene, β-bromovinylhexylanthracene, β-iodovinylhexylanthracene, β-trifluoromethanesulfonyl Oxyvinylhexylanthracene, β-chlorovinylmethoxyanthracene, β-butyl Movinylmethoxyanthracene, β-iodovinylmethoxyanthracene, β-trifluoromethanesulfonyloxyvinylmethoxyanthracene, β-chlorovinylhexyloxyanthracene, β-bromovinylhexyloxyanthracene, β-iodovinylhexyloxyanthracene, β-trifluoromethane Sulfonyloxyvinylhexyloxyanthracene, β-chloro-α-methylvinylanthracene, β-bromo-α-methylvinylanthracene, β-iodo-α-methylvinylanthracene, β-trifluoromethanesulfonyloxy-α-methylvinylanthracene, β-chloro-β-methylvinylanthracene, β-bromo-β-methylvinylanthracene, β-iodo-β-methylvinylanthracene, β-trifluorometa And vinyl anthracene derivatives such as N-sulfonyloxy-β-methylvinylanthracene, among others, unsubstituted β-chlorovinylanthracene, β-bromovinylanthracene, β-iodovinylanthracene, β-trifluoromethanesulfonyloxyvinylanthracene, etc. The vinyl anthracene derivative is preferable, and among these, β-bromovinylanthracene is more preferable. Further, the bonding position of the vinyl group with respect to the aromatic ring in these vinyl anthracene derivatives is not particularly limited, and the vinyl group is bonded to any carbon atom as long as it is a carbon atom at the 1-position to the 10-position on the aromatic ring. Further, the bonding position of the substituent on the aromatic ring in the vinyl anthracene derivative is not particularly limited, and the substituent is any carbon atom at the 1-position to the 10-position to which the vinyl group is not bonded. It may be bonded to a carbon atom. Furthermore, these vinylanthracene derivatives are not limited to either the (E) isomer or the (Z) isomer, and may be any derivatives of the (E) isomer and the (Z) isomer. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited to these examples. These vinyl anthracene derivatives are commercially available or are ordinary methods. Those synthesized by the above may be used as appropriate.

（式中、Ｒ⁸及びｕは上記に同じ。）で示される、置換基を有していてもよいアントリル基であるものに相当する。 As a precaution, the vinyl anthracene derivative represented by the above general formula [XIII] in the above general formula [III] is such that Z in the general formula [III] is represented by the general formula [XVII].

(Wherein R ⁸ and u are the same as above), which is an anthryl group which may have a substituent.

  Specific examples of the alkyl vinyl compound represented by the general formula [XIV] include, for example, 1-chloropropylene, 1-bromopropylene, 1-iodopropylene, 1-trifluoromethanesulfonyloxypropylene, 1-chloro-1-butene, 1 -Bromo-1-butene, 1-iodo-1-butene, 1-trifluoromethanesulfonyloxy-1-butene, 1-chloro-3-methyl-1-butene, 1-bromo-3-methyl-1-butene, 1-iodo-3-methyl-1-butene, 1-trifluoromethanesulfonyloxy-3-methyl-1-butene, 1-chlorovinylcyclopentane, 1-bromovinylcyclopentane, 1-iodovinylcyclopentane, 1- Trifluoromethanesulfonyloxyvinylcyclopentane, 1-chlorovinylcyclohexane 1-bromovinylcyclohexane, 1-iodovinylcyclohexane, 1-trifluoromethanesulfonyloxyvinylcyclohexane, 1-chloro-1-methylpropylene, 1-bromo-1-methylpropylene, 1-iodo-1-methylpropylene, 1- Such as trifluoromethanesulfonyloxy-1-methylpropylene, 1-chloro-2-methylpropylene, 1-bromo-2-methylpropylene, 1-iodo-2-methylpropylene, 1-trifluoromethanesulfonyloxy-2-methylpropylene, etc. An alkyl vinyl compound is mentioned. Further, these alkyl vinyl compounds are not limited to either the (E) isomer or the (Z) isomer, and may be any derivatives of the (E) isomer and the (Z) isomer. The above specific examples are merely examples, and the compounds according to the production method of the present invention are not limited by these examples. These alkyl vinyl compounds are commercially available or are ordinary methods. Those synthesized by the above may be used as appropriate.

  In the production method of the present invention, the β-vinyl compound represented by the general formula [III] used in the present invention is required to be liquid or used in a solution state. Therefore, when the β-vinyl compound represented by the general formula [III] is not liquid, it is necessary to dissolve it in an organic solvent that is inert to the reaction in the second step described later. Further, even when the β-vinyl compound represented by the general formula [III] is a liquid, when using a highly viscous β-vinyl compound, or when using a highly reactive β-vinyl compound, If it is difficult to use a liquid β-vinyl compound as it is, it is desirable to dilute it appropriately in an organic solvent. Specific examples of the organic solvent include organic solvents similar to the organic solvent used for bringing the halogenated aromatic compound represented by the above general formula [I] into a solution state. Preferred specific examples and More preferred specific examples also include a preferred organic solvent and a more preferred organic solvent used for bringing the halogenated aromatic compound represented by the above general formula [I] into a solution state.

  The molar concentration of the β-vinyl compound, that is, the molar concentration of the solution supplied to the microreactor described later, is the amount of the lithiated aromatic compound represented by the general formula [II] relative to the β-vinyl compound, the general formula [ II] may be determined in consideration of the molar concentration of the solution of the lithiated aromatic compound represented by the formula (II) and the flow rate (flow rate) of the β-vinyl compound in the microreactor, for example, usually 0.01 to 20 mol. / L, preferably 0.02 to 10 mol / L, more preferably 0.05 to 5 mol / L. In addition, when it is less than 0.01 mol / L, the amount of the organic solvent is relatively increased, and the flow rate in the microreactor described later is excessively large (the flow rate is too high). IV] is not desirable because the yield of the vinyl-substituted aryl compound represented by the formula [IV] is small and the productivity is lowered.

  As the palladium compound used in the present invention, conventionally known, for example, a commercially available homogeneous zero-valent or divalent palladium compound can be used. Specifically, for example, tetrakis (triphenylphosphine) palladium, Zero-valent palladium compounds such as bis (tri-tert-butylphosphine) palladium, bis (tricyclohexylphosphine) palladium, bis (dibenzylideneacetone) palladium, palladium acetate, palladium trifluoroacetate, bis (acetonitrile) palladium dichloride, bis Bivalent palladium compounds such as (acetylacetonato) palladium, allyl palladium chloride, bis (triphenylphosphine) palladium dichloride, bis (triphenylphosphine) palladium diacetate are mentioned, among others Bis (tri-tert-butylphosphine) palladium which is a divalent palladium compound, bis (tricyclohexylphosphine) palladium, and palladium acetate which is a divalent palladium compound are preferred, among which bis (tri-tert-butylphosphine) palladium, More preferred is palladium acetate. As described later, a mixture of a divalent palladium compound such as palladium acetate and a compound capable of coordinating with palladium such as triphenylphosphine, tri-tert-butylphosphine, and tricyclohexylphosphine It is also possible to use it as a compound (mixed palladium compound). In such a case, a premixed material outside the microreactor may be used, but a mixture of a palladium compound and a compound capable of coordinating to palladium It is desirable to use what was performed in a microreactor.

  The use amount of the palladium compound, that is, the use amount of palladium in the palladium compound in terms of mole, is 1 mol of the β-vinyl compound represented by the general formula [III] used in the second step described later. Usually, it is 0.001 to 20 mol%, preferably 0.01 to 20 mol%, more preferably 0.1 to 20 mol%. When the amount is less than 0.001 mol%, the coupling reaction in the second step described later does not proceed sufficiently. On the other hand, when a palladium compound in an amount exceeding 20 mol% is used, there is a problem that the economy is impaired. This is undesirable because it occurs. In addition, the usage-amount of the said palladium compound said here is, when it makes it contact the beta-vinyl compound shown by general formula [III], and the said palladium compound in a micromixer, as mentioned later, The apparent mol% in terms of palladium at the time of the reaction between the β-vinyl compound and the palladium compound, in other words, the reaction between the β-vinyl compound and the palladium compound in the micromixer of the second step of the microreactor described later. When the palladium compound is dissolved in advance in the solution of the β-vinyl compound represented by the general formula [III], which is defined by the apparent mol% in terms of palladium when, or the β-vinyl compound coexists. When a palladium compound and a compound capable of coordinating to palladium are mixed in a solution, It is defined by the mol% of the palladium in terms of the palladium compound in a solution.

  Apart from the β-vinyl compound solution represented by the general formula [III], the palladium compound is dissolved in an inert organic solvent as described above, and the molar concentration of the palladium compound is adjusted. An appropriately adjusted solution may be prepared, and the β-vinyl compound and the palladium compound may be brought into contact in the micromixer of the second step of the microreactor described later, or represented by the general formula [III]. A solution prepared by dissolving a commercially available palladium compound in a β-vinyl compound solution may be supplied into the micromixer in the second step, but the palladium compound and the compound capable of coordinating to palladium are mixed. When using a compound as a palladium compound (mixed palladium compound), it is preferable to use a compound mixed in a microreactor. That's right. That is, in the microreactor, a step of mixing a palladium compound and a compound capable of coordinating with palladium (ligand mixing step) is provided, and the solution after the ligand mixing step is placed in the micromixer of the second step. It is preferable to supply. As described above, when a compound obtained by mixing a palladium compound and a compound capable of coordinating with palladium in a microreactor is used for a coupling reaction, a commercially available palladium compound is used as it is for a coupling reaction. Thus, an improvement in the yield of the target vinyl-substituted aryl compound represented by the above general formula [IV] can be expected. As a mixture of a palladium compound and a compound capable of coordinating to palladium, a compound in which the palladium compound and a compound capable of coordinating to palladium are simply mixed, a part or all of palladium of the palladium compound A compound in which a compound capable of coordinating with palladium is coordinated is considered, and any compound in any state is included in the present invention. In addition, the above “coordinated state” means a state in which a compound capable of coordinating to palladium is simply coordinated to palladium in the palladium compound, or a compound capable of coordinating to palladium on zero-valent palladium. It also includes the state in which is coordinated. Such mixing is performed in the presence of a β-vinyl compound, and a mixed solution of a palladium compound, a compound capable of coordinating with palladium, and a β-vinyl compound is supplied into the micromixer in the second step. However, if a so-called β-vinyl compound is required for the β-vinyl compound, there is no need to prepare a microtube for circulating only the solution dissolved in the organic solvent. It is preferable in that it can be realized.

  When a palladium compound and a compound capable of coordinating with palladium are mixed and supplied to the reaction system (coupling reaction) in the second step, specific examples of the palladium compound used include palladium acetate and the like. The bivalent palladium compound of these is mentioned. On the other hand, specific examples of the compound capable of coordinating with palladium include phosphine compounds such as triphenylphosphine, tri-tert-butylphosphine, and tricyclohexylphosphine. Among them, tri-tert-butylphosphine is preferable. . The amount of the compound capable of coordinating to palladium (phosphine compound) used when mixing the palladium compound and the compound capable of coordinating to palladium is determined by the amount of the palladium compound used, and specifically, It is 1.0-20 equivalent normally with respect to palladium in a palladium compound, Preferably it is 1.5-10 equivalent, More preferably, it is 1.8-8 equivalent. If the amount is less than 1.0 equivalent, the target mixed palladium compound cannot be efficiently prepared. On the other hand, if a compound capable of coordinating to palladium in an amount exceeding 20 equivalent (phosphine compound) is used, the economy is impaired. This is undesirable because it causes problems such as these. In addition, the usage-amount of the compound (phosphine compound) which can be coordinated to the said palladium said here is defined by the equivalent in palladium conversion in a palladium compound.

  In the production method of the present invention, the palladium compound used in the present invention is required to be a liquid or to be used in a solution state. It is necessary to dissolve in an organic solvent inert to the reaction in the second step. Specific examples of the organic solvent include organic solvents similar to the organic solvent used for bringing the halogenated aromatic compound represented by the above general formula [I] into a solution state. Preferred specific examples and More preferred specific examples also include a preferred organic solvent and a more preferred organic solvent used for bringing the halogenated aromatic compound represented by the above general formula [I] into a solution state. Moreover, since the compound (phosphine compound) which can be coordinated to palladium used when mixing with a palladium compound is also a solid in most cases, with respect to the reaction in the second step and the ligand mixing step described later. It must be dissolved in an inert organic solvent. The organic solvent inactive to the reaction in the second step and the ligand mixing step mentioned here can be the same organic solvent used for dissolving the palladium compound.

  The molar concentration of the palladium compound, that is, the molar concentration of the solution of the palladium compound supplied to the microreactor described later, is the amount of the β-vinyl compound represented by the general formula [III], the molar concentration of the solution of the vinyl compound, and β -It may be determined in consideration of the flow rate (flow rate) of the vinyl compound in the microreactor, for example, usually 0.0001 to 5 mol / L, preferably 0.001 to 3 mol / L, more preferably 0.01 to 1 mol / L. When the amount is less than 0.0001 mol / L, the amount of the organic solvent is relatively large, the flow rate in the microreactor described later is too large (the flow rate is too high), and the efficiency is not good. This is undesirable because it occurs.

  In the production method of the present invention, as will be described later, a reaction stop step may be included as a further step as necessary, and a reaction stop solution is used in the reaction stop step. Specific examples of the reaction stop solution include polar protic organic solvents such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol and the like, such as water. And aqueous solvents such as ammonium chloride aqueous solution and hydrochloric acid aqueous solution. Among them, alcoholic organic solvents such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol are preferable. Methanol is more preferred. Moreover, these reaction stop solutions may be used individually or in combination of 2 or more types, respectively, and the mixing ratio at the time of using 2 or more types in combination can be defined arbitrarily.

  The amount of the reaction stop solution used is not particularly limited as long as the reaction solution after the second step (after the coupling reaction) described later can be post-treated, and may be arbitrarily adjusted. The reaction stop solution may be used as it is without being diluted with an inert organic solvent as described above.

  In the production method of the present invention, the organolithium reagent used in the first step described later and the lithiated aromatic compound represented by the general formula [II] produced in the first step described later are activated. For example, a chelating agent such as tetramethylethylenediamine or hexamethylphosphoric triamide can be added. The amount of the chelating agent used is usually 0.01 to 10 equivalents, preferably 0.1 to 5 equivalents, more preferably 0.8 to 3 equivalents with respect to the organolithium reagent and the lithiated aromatic compound. is there. The amount of the chelating agent used here refers to an apparent equivalent at the time of contact between the organolithium reagent or the lithiated aromatic compound and the chelating agent, in other words, the first amount of the microreactor described later. In the process micromixer, the organolithium reagent or the lithiated aromatic compound is brought into contact with the chelating agent, and the chelating agent is defined as an apparent equivalent when chelating the metal lithium.

  Next, the microreactor used in the present invention will be described. The microreactor according to the production method of the present invention is a micro part composed of a mixing part for contacting and mixing a plurality of liquids, a so-called micro mixer, and a reaction part connected to the rear part of the mixing part, a so-called tube reactor. Means a flow-type reactor, the minimum length of the cross section of the flow path in the mixing section is from several μm to several thousand μm, and the equivalent diameter of the reaction section is from several μm to several thousand μm. Accordingly, the minimum length and equivalent diameter of the channel cross section can be selected as appropriate. The equivalent diameter referred to here means a diameter when the cross section of the flow path is converted into a circle.

  The shape of the cross section of the flow path in the mixing section in the microreactor, so-called micromixer, is not particularly limited, and may be appropriately selected according to the purpose. More specifically, for example, a circle, a rectangle, a semicircle, a triangle, and the like can be given. Further, the liquid can be divided and circulated in a plurality of flow paths inside. Further, the length and shape of the flow path (circulation) direction in the reaction part of the microreactor, so-called tube reactor, are not particularly limited, and the flow rate and reaction of the liquid sent to the microreactor as will be described later. It can be appropriately selected according to time and the like. Furthermore, by using a plurality of the above microreactors connected together or using an apparatus incorporating a plurality of microreactors, the process according to the production method of the present invention may further include another process (reaction).

  A microreactor can be installed in a thermostat such as a thermostat, or a heating or cooling device can be installed near the flow path, or another flow installed near the flow path. The reaction temperature in each step to be described later may be controlled by adopting and adopting a heat medium or a refrigerant in the passage.

  A micromixer usually has a microchannel (microchannel) with an equivalent diameter of several mm or less, preferably smaller than 1000 μm, and is defined as a device that initiates a reaction by contacting and mixing in the microchannel. It is a reaction apparatus for carrying out the reaction in a steady state using a flow reactor or a static micromixer (static micromixer). The static micromixer is a device represented by a mixer having a fine flow path for mixing, as described in, for example, WO 96/30113, 3. Mixer described in Chapter 3, W. Ehrfeld, V. Hessel, H. Lowe, published by Wiley-VCH.

  In such a microreactor, since the flow path is microscale and the liquid flow rate is small, it is necessary to consider a laminar flow dominant flow instead of a turbulent flow dominant in a batch reactor. At this time, a stable interface is formed between the liquids (fluids), and the reaction occurs while contacting and mixing only by molecular diffusion through the interface. Since the reaction occurs at the interface between the laminar flows as described above, the specific surface area (surface area per unit volume of the liquid (fluid) involved in the reaction) is increased, and the reaction efficiency is increased. In addition, since the width of the flow path is small, the heat exchange efficiency is high and the temperature control during the reaction can be precisely performed. In addition, in the microreactor, the reaction is performed in a normal flow state. Another characteristic is that the reaction can be controlled by the time (residence time) that the compounds involved in the reaction stay in the tube reactor.

  As the microreactor according to the production method of the present invention, a microreactor equipped with a conventionally known micromixer or a commercially available microreactor can be used. Specific examples of commercially available micromixers and microreactors include, for example, a single mixer and a caterpillar mixer manufactured by Institute, Fleet, Microtechnique Mainz (IMM), a microglass reactor manufactured by Microglass, Cytos manufactured by YMC, and Yamatake. YM-1 / YM-2 mixer manufactured by Shimadzu, mixing tee and tee (T-shaped connector) manufactured by Shimadzu GLC, IMT chip reactor manufactured by Micro Chemical Co., Ltd., Micro High Mixer developed by Toray Engineering, Micro manufactured by Hitachi Plant Technology Examples include a mixing server, a T-shaped micromixer manufactured by Sanko Seiki Kogyo Co., Ltd., and any of them can be used in the present invention. For the manufacturing method of the present invention, a newly designed and prototyped product can be used.

  As described above a little, the minimum structural unit of the microreactor used in the present invention is a mixing part (micromixer) and a reaction part (tube called tube reactor), and the microreactor includes at least two micromixers. It is a microreactor that can connect two or more tube reactors and perform two or more steps. In the flow reaction, it is necessary to construct a reaction apparatus incorporating a microreactor. In that case, the apparatus configuration includes a microreactor including a micromixer and a tube reactor, and a feed pump for supplying a solution of a raw material or a reagent to the microreactor. , Thermostats such as thermostats and circulation circulators, heat exchangers for temperature adjustment, temperature sensors, flow sensors, pressure sensors for measuring pressure in pipes, product tanks for storing product solutions, etc. .

The micromixer used in the present invention preferably has a small channel for mixing a liquid compound or a compound dissolved in an organic solvent with each other. Inside the micromixer, the reaction is started by contact and mixing, and at the same time, heat is generated by the reaction. For this reason, the conventional Kenic static mixer with a large channel cross-sectional area cannot obtain sufficient mixing performance in the mixing reaction due to the large channel size, and also has a slow heating capability for the amount of heat generated during the reaction. Although it is sufficient and distinguished from the micromixer used in the present invention, even a simple T-shaped channel tee that mixes two substreams provides sufficient mixing performance and heat removal capability. Can be used as a micromixer in the present invention. When the reaction is performed by mixing two substreams, the cross-sectional area of the substream is usually determined by the cross-sectional area of the flow path of the mixer to be used. The flow path of the micro-mixer of the present invention is usually 100μm ² ~16mm ^2, preferably 1000 .mu.m ² to 4 mm ^2, more preferably 10000 ² to 2 mm ^2, particularly preferably has a cross-sectional area of 100000 ² ~ 1 mm ^2.

  A tube called a tube reactor connected as a reaction part to the rear part of the micromixer that is a mixing part has a function of removing reaction heat generated by diffusion and mixing of compounds. The smaller the inner diameter of the tube, the shorter the diffusion distance and the greater the reaction rate.Therefore, it not only works to shorten the reaction time, but also increases the heat exchange capacity and generates a large amount of heat. It also works favorably with the reactions involved. However, the smaller the inner diameter of the tube, the greater the pressure loss when the liquid flows. Therefore, the pump and tube to be used must have a special high pressure resistance specification, and the liquid flow rate is limited. The structure of the mixer is also limited, resulting in inconvenience. For this reason, the tube in the present invention has an equivalent diameter of usually 100 μm to 4000 μm, preferably 250 μm to 3000 μm, more preferably 300 μm to 2000 μm, and particularly preferably 500 μm to 1500 μm.

  The material of the microreactor, that is, the material of the micromixer and the tube reactor is not particularly limited, and may be appropriately selected according to demands such as heat resistance, pressure resistance, solvent resistance, and processability. Specifically, for example, metals such as stainless steel, titanium, copper, nickel and aluminum, glass, photuran glass, various ceramics, peak resin, plastic, silicon, tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer (PFA) Teflon (registered trademark) resin and the like can be suitably used.

The method for producing the microreactor is not particularly limited, and may be appropriately selected depending on the purpose. The microreactor is manufactured by a microfabrication technique. Specific examples of the microfabrication technique suitable for the microreactor include the following.
(A) LIGA technology combining X-ray lithography and electroplating (b) High aspect ratio photolithography method using EPON SU8 (c) Mechanical micro cutting (micro drill that rotates a drill with a drill diameter of micro order at high speed Processing)
(D) High aspect ratio processing method of silicon by Deep RIE (e) Hot Emboss processing method (f) Stereolithography method (g) Laser processing method (h) Ion beam method The microreactor used in the present invention is one of the above-described micro processings A technique may be used and is not particularly limited.

（式中、Ａｒ、Ｘ、Ｙ、Ｚ、Ｒ^１及びＲ^２は上記に同じ。） Each step according to the production method of the present invention and the conditions of the microreactor in the step will be described. The reaction formula [A] will be described below in order as an example of the process according to the production method of the present invention.

(In the formula, Ar, X, Y, Z, R ¹ and R ² are the same as above.)

  In the production method of the present invention, at least a halogenated aromatic compound represented by the above general formula [I] is reacted with an organolithium reagent to obtain a lithiated aromatic compound represented by the above general formula [II]. A microreactor comprising a first step and a second step of coupling the lithiated aromatic compound obtained in the first step and the β-vinyl compound represented by the general formula [III]. It is characterized by performing using. The palladium compound used in the second step may be a commercially available one, but a mixture of a palladium compound and a compound capable of coordinating with palladium (mixed palladium compound) is used. A step of mixing a palladium compound and a compound capable of coordinating with palladium (ligand mixing step) is provided in the microreactor, and the ligand mixing step is further added to the first and second steps. When using a microreactor, the mixed solution can be supplied as it is to the reaction system of the second step, and by using the mixture just before this use, the target general formula [IV] It is preferable because the yield of the vinyl-substituted aryl compound represented by is improved. Furthermore, the reaction solution after the coupling (after the second step) can be used, for example, if the target vinyl-substituted aryl compound represented by the general formula [IV] does not decompose. A batch-type process may be used in which a post-treatment operation is performed from a tube reactor (tube) into a container such as a flask filled with the above-mentioned reaction stop solution, but the reaction solution is further added to the first and second steps. It is preferable to perform a reaction stopping step of treating with a reaction stopping solution using a microreactor because the processing operation can be performed safely at room temperature and the operation itself is easy.

  First and second steps in the microreactor, and the flow rate of the liquid fed to the mixing section (micromixer) in the ligand mixing step and / or the reaction stopping step that is appropriately performed as necessary (liquid feeding speed) ) Is appropriately selected depending on the size, shape, length, temperature, etc. of the flow path. Specifically, for example, a T-shaped micromixer (inner diameter Φ250 μm, 500 μm) which is one type of micromixer and an inner diameter Φ1000 μm. When a tube is used in combination, it is usually 0.01 mL / min to 100 mL / min, preferably 0.05 mL / min to 50 mL / min, more preferably 0.1 mL / min to 30 mL / min, and particularly preferably 0.8 mL / min. The range is from 2 mL / min to 20 ml / min. The flow rate supplied to the microreactor having a plurality of each compound used in the present invention may be the same flow rate or a different flow rate. It is desirable to determine in consideration of the molar concentration of the compound and the number of equivalents of the compounds. Moreover, although the pump for liquid feeding can be used in any of the liquid feeding pumps used industrially, the model which does not produce pulsation at the time of liquid feeding is preferable, and specifically, for example, a plunger pump, a gear pump, a rotary pump , Diaphragm pumps, syringe pumps and the like.

  In the microreactor, the reaction is initiated by mixing by molecular diffusion through the interface between the liquid compound or the compound dissolved in an organic solvent. Energy for promoting mixing may be added. Mixing can be changed from laminar flow control to turbulent flow control depending on the flow velocity and the shape of the reactor (three-dimensional shape of the contact portion between fluids, shape of the flow path, etc., wall roughness). They may be mixed in either laminar flow or turbulent flow.

  Specifically, the reaction temperature in the microreactor in the first and second steps of the present invention is usually −78 ° C. to 60 ° C., preferably −30 ° C. to 50 ° C., more preferably −20 ° C. to 40 ° C. It is. In the production method of the present invention, for example, the reaction in the first step (halogen-lithium exchange reaction) proceeds even at a low temperature usually carried out in a batch reaction such as -78 ° C. Since the reaction proceeds promptly even at about room temperature and side reactions such as homocoupling are suppressed, a special cooling (heating) device is not required. The temperature range is preferred. Moreover, the reaction temperature in the microreactor in the ligand mixing step is specifically usually -78 ° C to 60 ° C, preferably -30 ° C to 50 ° C, more preferably -20 ° C to 40 ° C. The ligand mixing step, which is a step of mixing a palladium compound and a compound capable of coordinating with palladium, normally does not require a special cooling (heating) device because the reaction proceeds efficiently even at room temperature. A temperature range of 40 ° C. is preferred. Furthermore, specifically, the treatment temperature in the microreactor in the reaction stopping step is usually −78 ° C. to 60 ° C., preferably −30 ° C. to 50 ° C., more preferably −20 ° C. to 40 ° C. In batch-type processing, heat generation during post-processing becomes a problem, but in the production method of the present invention, heat treatment during post-processing can be suppressed by processing the reaction solution in a microreactor as a reaction stopping step. Therefore, a temperature range of −20 ° C. to 40 ° C. that does not require a special cooling device is preferable.

  The reaction time in each step of the present invention starts mixing in the compound or reagent mixing part (micromixer) described above, and passes through a reaction part (tube called a tube reactor) connected to the rear part of the mixing part. It is expressed by the residence time until it is supplied from the outlet of the reaction section to the mixing section of the next step or discharged from the reaction section. More specifically, the reaction time of the first step is such that the mixing of the halogenated aromatic compound represented by the general formula [I] and the organic lithium reagent is started in the micromixer of the first step, It is expressed by the residence time until it is mixed with the raw material of the next reaction (β-vinyl compound represented by the general formula [III]) in the micromixer of the second step through the tube connected to the rear part of the mixer. The The reaction time of the second step is the same as that of the lithiated aromatic compound and palladium compound represented by the general formula [II] and β-vinyl represented by the general formula [III] in the micromixer of the second step. Mixing with the compound begins until it is discharged from the outlet through the tube connected to the back of the micromixer, or until mixed with the reaction stop solution in the micromixer in the reaction stop process. Expressed in time. Furthermore, the reaction time of the ligand mixing step is such that mixing of the palladium compound and the compound capable of coordinating with palladium is started in the micromixer of the ligand mixing step, and a tube connected to the rear part of the micromixer is connected. It is expressed by the residence time until it is supplied to the raw material for the next reaction (lithiated aromatic compound represented by the general formula [II]) in the micromixer of the second step. Furthermore, the processing time of the reaction stop step is such that the reaction solution and the reaction stop solution of the second step start mixing in the micro mixer of the reaction stop step, and pass through a tube connected to the rear part of the micro mixer. It is represented by the residence time until it is discharged from the outlet. Further, the total reaction time is represented by the sum of the reaction time of the first step and the reaction time of the second step, or when the reaction stop step is included, the reaction time of the first step It is expressed as the sum of the reaction time of the second step and the processing time of the reaction stop step. In the present invention, the reaction time can be adjusted by changing the flow rate of the compound, reagent, etc. supplied to the microreactor. However, the micromixer is often set in advance with a flow rate range suitable for mixing. It is desirable to set the reaction time by a method of changing the length of the tube and the equivalent diameter so as to obtain an appropriate residence time according to the flow rate of the solution of the compound, reagent, etc. supplied to the reactor. The residence time in the microreactor may vary depending on parameters such as the reactivity of the halogenated aromatic compound, the organolithium reagent and the β-vinyl compound, their molar concentration, the reaction temperature, and the type of palladium compound.

  Since the first step (halogen-lithium exchange reaction) according to the present invention is a very fast reaction, and the lithium intermediate produced often has low thermal stability, the residence time in the first step is usually 0. .001 seconds to 60 seconds, preferably 0.01 seconds to 30 seconds. This is because if the reaction time is too short, the reaction does not proceed sufficiently, and if the reaction time is too long, the decomposition of the lithiated aromatic compound represented by the general formula [II] tends to proceed.

  The residence time in the second step (coupling reaction) according to the present invention is usually 0.1 second to 60 seconds, preferably 1 second to 30 seconds. If the reaction time is too short, the reaction does not proceed sufficiently. Conversely, if the reaction time is too long, the decomposition from the vinyl-substituted aryl compound represented by the general formula [IV] tends to proceed.

  The residence time in the ligand mixing step according to the present invention is usually 0.1 to 60 seconds, preferably 0.5 to 30 seconds. If the mixing time is too short, the mixture of the palladium compound and the compound capable of coordinating to palladium is not sufficient. Conversely, if the mixing time is too long, the yield of the vinyl-substituted aryl compound represented by the general formula [IV] is improved. Because it becomes difficult to expect.

  The residence time in the reaction stopping step according to the present invention is usually 0.2 seconds or longer, preferably 0.2 seconds to 120 seconds. This is because the post-processing does not proceed sufficiently if the processing time is too short.

  In the present invention, when the reaction is carried out in the flow channel of the microreactor, the micro flow channel acts as a micro reaction field, and high-speed and efficient diffusion and mixing occur. For this reason, the present invention can efficiently produce the vinyl-substituted aryl compound represented by the general formula [IV] with high yield and high selectivity. In the micromixer in the first step, the flow path cross-sectional minimum length of the mixing part (micromixer) in the microreactor is usually 100 μm to 1000 μm, preferably 100 μm to 800 μm, more preferably 100 μm to 500 μm, In the micromixer in the step, usually 100 μm to 1000 μm, preferably 100 μm to 950 μm, more preferably 100 μm to 800 μm. In the micromixer in the ligand mixing step, usually 100 μm to 1000 μm, preferably 100 μm to 800 μm, more preferably. Is 100 μm to 500 μm, and is usually 100 μm to 1000 μm, preferably 100 μm to 950 μm, more preferably 100 μm to 800 μm in the micromixer in the reaction stopping step. In the present invention, the micromixer in the first step, if necessary, the minimum length of the cross section of the micromixer in the ligand mixing step, the micromixer in the second step, and if necessary, further stopping the reaction. It is preferable to make it smaller than the micromixer in the process. In the micromixer in the second step and the reaction stopping step, it is preferable that the magnitude relationship of the minimum length of the cross section of the flow path be as small as possible within the range where the increase in pressure loss does not become a problem.

  The flow path length of the reaction section (tube called tube reactor) in the microreactor is appropriately adjusted depending on the reaction time (residence time) and flow rate of the reaction solution in the microreactor. In the tube of the process (halogen-lithium exchange reaction), it is usually 10 mm to 5000 mm, preferably 10 mm to 1000 mm, and in the tube of the second step, it is usually 10 mm to 5000 mm, preferably 10 mm to 3000 mm. In the process tube, it is usually 10 mm to 5000 mm, preferably 10 mm to 1000 mm, and in the reaction stop process tube, it is usually 50 mm to 5000 mm.

  In the present invention, the progress of the reaction can be monitored using various known analytical instruments. The reaction rate can be confirmed by, for example, high performance liquid chromatography, capillary gas chromatography or the like. It is also possible to monitor the reaction online by tracking changes in absorbance using an online FT-IR spectrometer or an online NIR spectrometer.

  The vinyl-substituted aryl compound represented by the above general formula [IV] thus obtained can be isolated by a known method. For example, extraction by distillation using an organic solvent, distillation, recrystallization using an organic solvent or water or a mixed solution of an organic solvent and water, or column chromatography, etc. may be performed by a method alone or in combination as appropriate. It is possible to purify.

  The vinyl-substituted aryl compound represented by the above general formula [IV] obtained by the method described so far can be used as a synthetic intermediate for pharmaceuticals, agricultural chemicals, liquid crystal materials, organic electroluminescence (organic EL) materials and the like. However, it is not limited to these uses.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited at all by these examples. The reaction rate of the vinyl-substituted aryl compound represented by the general formula [IV], which is the target product, the residual rate of the raw material compound, and the by-product formation rate are determined from the area ratio with the standard substance by gas chromatography (GC). It is obtained by calculating and performing quantitative analysis.

Example 1 Synthesis of (E) -stilbene by a microreactor using palladium acetate as a palladium compound Synthesis of phenyllithium by n-butyllithium and bromobenzene, followed by palladium acetate (Pd (OAc) ₂ ) as a catalyst The reaction with (E) -β-bromostyrene was performed using the microreactor shown in FIG. 1 to synthesize (E) -stilbene.
Three T-shaped micromixers (M1, M2 and M3; stainless steel T-shaped micromixers manufactured by Sanko Seiki Kogyo Co., Ltd .; Fig. 2) and three tube reactors (R1, R2 and R3; stainless steel manufactured by GL Sciences Inc.) Microreactor composed of tubes (outer diameter 1/16 inch (1.58 mm), inner diameter 1000 μm)) and four tube reactors for precooling (P1, P2, P3 and P4; stainless steel manufactured by GL Sciences Inc.) A reactor composed of a tube (outer diameter 1/16 inch (1.58 mm), inner diameter 1000 μm)) was immersed in a water bath and set at 24 ° C. The solutions supplied from the four tube reactors (P1, P2, P3, and P4) for pre-cooling are all sucked up into gas tight syringes, and then each of them at a predetermined flow rate using a Harvard syringe pump. It was supplied to the micromixer in the process. The residence time was adjusted by changing the length of the tube reactors (R1, R2, and R3) without changing the liquid flow rate (liquid feeding speed).
In the T-shaped micromixer M1 (inner diameter 250 μm) in the first step, a THF solution (0.10 M) of bromobenzene obtained by diluting bromobenzene (manufactured by Wako Pure Chemical Industries, Ltd.) with THF is added from the tube reactor P1. Each n-hexane solution (0.50 M) of n-butyllithium obtained by diluting a commercially available n-hexane solution (manufactured by Kanto Chemical Co., Inc.) of 2.60 Mn-butyllithium with n-hexane was supplied from the tube reactor P2. The solution was fed at a flow rate of 0 mL / min (0.30 mmol / min) and 0.6 mL / min (0.30 mmol / min). For the T-shaped micromixer M2 (inner diameter 500 μm) in the second step, commercially available β-bromostyrene (manufactured by Wako Pure Chemical Industries, Ltd.) is used in advance (LJ Dolby, C. Wilkins, TG Frey, J. Org). Chem. 1966, 31, 1110.) (E) -β-bromostyrene and palladium acetate (Pd (OAc) ₂ ) (Aldrich) diluted or dissolved in THF (E) -β -THF solution of bromostyrene and palladium acetate ((E) -β-bromostyrene; 0.133M, palladium acetate; 13.3 mM) was added from the tube reactor P3 to 1.5 mL / min ((E) -β-bromo (Styrene; 0.20 mmol / min, palladium acetate; 0.020 mmol / min). A methanol solution (neat) was fed from the tube reactor P4 at a flow rate of 1.5 mL / min to the T-shaped micromixer M3 (inner diameter 500 μm) in the reaction stopping step. The residence time in the tube reactor R1 (length 32.5 cm) is 4.3 seconds, the residence time in the tube reactor R2 (length 50 cm) is 4.6 seconds, and the residence time in the tube reactor R3 (length 50 cm) is 3. It was 6 seconds. In addition, the tube reactors (P1, P2, P3, and P4) for pre-cooling were all 100 cm long. In this way, the reaction solution containing the vinyl-substituted aryl compound represented by the general formula [IV] discharged from the outlet of R3, that is, (E) -stilbene, is the solution for the first few minutes until the reaction becomes stable. Discard and collect the subsequent solution in a sampling tube for 30 seconds, then standardize the solution collected in the sampling tube with GC (CBP1 column; 0.25 mm × 25 m, starting temperature 50 ° C., heating rate 10 ° C./min). Quantitative analysis was performed by an internal standard method using substances, and the reaction rate of this reaction was determined. As a result of analysis, (E) -stilbene (GC retention time; 21.8 minutes) was obtained in a yield of 78% (based on (E) -β-bromostyrene). In addition, (E) -β-bromostyrene (GC retention time: 14.7 minutes (yield; 0% ((E) -β-bromostyrene standard))) as a raw material and biphenyl (by-product) ( GC retention time; 17.4 minutes (yield; 9% (based on bromobenzene))), 1,4-diphenyl-1,3-butadiene (GC retention time; 25.3 minutes (yield; 4% (( The determination of E) -β-bromostyrene standard))) was also determined from GC in the same manner.

Example 2 Synthesis of (E) -stilbene by microreactor using bis (tri-tert-butylphosphine) palladium as palladium compound Synthesis of phenyllithium with n-butyllithium and bromobenzene, followed by bis (tri-tert - to carry out the reaction with butyl phosphine) palladium ^{_{(Pd (t Bu 3 P)}} 2) was used as the catalyst (E)-.beta.-bromostyrene, using the microreactor shown in Fig. 3, (E) - stilbene Synthesized.
Three T-shaped micromixers (M1, M2, and M3; stainless steel T-shaped micromixers manufactured by Sanko Seiki Kogyo Co., Ltd .; Fig. 2) and tube reactors (R1, R2, and R3; stainless tubes manufactured by GL Sciences Inc.) (Reactor 1/16 inch (1.58 mm), inner diameter 1000 μm)) and four tube reactors for pre-cooling (P1, P2, P3 and P4; stainless steel tube manufactured by GL Sciences Inc.) (Outer diameter 1/16 inch (1.58 mm), inner diameter 1000 μm)) was embedded in a water bath and set to 24 ° C. The solutions supplied from the four tube reactors (P1, P2, P3, and P4) for pre-cooling are all sucked up into gas tight syringes, and then each of them at a predetermined flow rate using a Harvard syringe pump. It was supplied to the micromixer in the process. The residence time was adjusted by changing the length of the tube reactors (R1, R2, and R3) without changing the liquid flow rate (liquid feeding speed).
In the T-shaped micromixer M1 (inner diameter 250 μm) in the first step, a THF solution (0.10 M) of bromobenzene obtained by diluting bromobenzene (manufactured by Wako Pure Chemical Industries, Ltd.) with THF is added from the tube reactor P1. Each n-hexane solution (0.50 M) of n-butyllithium obtained by diluting a commercially available n-hexane solution (manufactured by Kanto Chemical Co., Inc.) of 2.60 Mn-butyllithium with n-hexane was supplied from the tube reactor P2. The solution was fed at a flow rate of 0 mL / min (0.30 mmol / min) and 0.6 mL / min (0.30 mmol / min). For the T-shaped micromixer M2 (inner diameter 500 μm) in the second step, commercially available β-bromostyrene (manufactured by Wako Pure Chemical Industries, Ltd.) is used in advance (LJ Dolby, C. Wilkins, TG Frey, J. Org). . Chem. 1966, 31, 1110. purified according) (E)-.beta.-bromostyrene and bis (tri -tert- butylphosphine) palladium ^{_{(Pd (t Bu 3 P)}} 2) ( manufactured by Aldrich) and the THF (E) -β-bromostyrene and palladium acetate in THF ((E) -β-bromostyrene; 0.133M, bis (tri-tert-butylphosphine) palladium; 6.67 mM) From the tube reactor P3, 1.5 mL / min ((E) -β-bromostyrene; 0.20 mmol / min, bis (tri-tert-butylphosphine) palladium; 0 It was fed at a flow rate of 010mmol / min). A methanol solution (neat) was fed from the tube reactor P4 at a flow rate of 1.5 mL / min to the T-shaped micromixer M3 (inner diameter 500 μm) in the reaction stopping step. The residence time in tube reactor R1 (length 32.5 cm) is 4.3 seconds, the residence time in tube reactor R2 (length 12.5 cm) is 1.2 seconds, and the residence time in tube reactor R3 (length 50 cm) is 3.6 seconds. In addition, the tube reactors (P1, P2, P3, and P4) for pre-cooling were all 100 cm long. In this way, the reaction solution containing the vinyl-substituted aryl compound represented by the general formula [IV] discharged from the outlet of R3, that is, (E) -stilbene, is the solution for the first few minutes until the reaction becomes stable. Discard and collect the subsequent solution in a sampling tube for 30 seconds, then standardize the solution collected in the sampling tube with GC (CBP1 column; 0.25 mm × 25 m, starting temperature 50 ° C., heating rate 10 ° C./min). Quantitative analysis was performed by an internal standard method using substances, and the reaction rate of this reaction was determined. As a result of analysis, (E) -stilbene (GC retention time; 21.8 minutes) was obtained in a yield of 74% (based on (E) -β-bromostyrene). In addition, (E) -β-bromostyrene (GC retention time: 14.7 minutes (yield; 0% ((E) -β-bromostyrene standard))) as a raw material and biphenyl (by-product) ( GC retention time; 17.4 minutes (yield; 2% (based on bromobenzene))), 1,4-diphenyl-1,3-butadiene (GC retention time; 25.3 minutes (yield; 1% (( The determination of E) -β-bromostyrene standard))) was also determined from GC in the same manner.

Example 3 Synthesis of (E) -stilbene by a microreactor using a mixture of a palladium compound and a compound capable of coordinating palladium using a microreactor Synthesis of phenyllithium by n-butyllithium and bromobenzene, And subsequent reaction with (E) -β-bromostyrene using as a catalyst a mixed palladium compound prepared by reacting palladium acetate (Pd (OAc) ₂ ) with tri-tert-butylphosphine ( ^t Bu ₃ P) Was performed using the microreactor shown in FIG. 4 to synthesize (E) -stilbene.
Three T-shaped micromixers (M1, M2 and M3; stainless steel T-shaped micromixers manufactured by Sanko Seiki Kogyo Co., Ltd .; Fig. 2) and three tube reactors (R1, R2 and R3; stainless steel manufactured by GL Sciences Inc.) Microreactor composed of tubes (outer diameter 1/16 inch (1.58 mm), inner diameter 1000 μm)) and four tube reactors for precooling (P1, P2, P3 and P4; stainless steel manufactured by GL Sciences Inc.) A reactor composed of a tube (outer diameter 1/16 inch (1.58 mm), inner diameter 1000 μm)) was immersed in a water bath and set at 24 ° C. The solutions supplied from the four tube reactors (P1, P2, P3, and P4) for pre-cooling are all sucked up into gas tight syringes, and then each of them at a predetermined flow rate using a Harvard syringe pump. It was supplied to the micromixer in the process. The residence time was adjusted by changing the length of the tube reactors (R1, R2, and R3) without changing the liquid flow rate (liquid feeding speed).
In the T-shaped micromixer M1 (inner diameter 250 μm) in the first step, a THF solution (0.10 M) of bromobenzene obtained by diluting bromobenzene (manufactured by Wako Pure Chemical Industries, Ltd.) with THF is added from the tube reactor P1. An n-hexane solution (0.50 M) of n-butyllithium obtained by diluting a commercially available n-hexane solution (manufactured by Kanto Chemical Co., Inc.) of 2.60 Mn-butyllithium with n-hexane was supplied from the tube reactor P2 to each 6. The solution was fed at a flow rate of 0 mL / min (0.60 mmol / min) and 1.2 mL / min (0.60 mmol / min). For the T-shaped micromixer M2 (inner diameter 250 μm) in the ligand mixing step, commercially available β-bromostyrene (manufactured by Wako Pure Chemical Industries, Ltd.) is used in advance (LJ Dolby, C. Wilkins, TG Frey, J. (E) -β-bromostyrene and palladium acetate (Pd (OAc) ₂ ) (manufactured by Aldrich) purified according to Org. Chem. 1966, 31, 1110.) were diluted or dissolved in THF (E)- A THF solution of (β-bromostyrene and palladium acetate ((E) -β-bromostyrene; 0.133M, palladium acetate; 6.67 mM) was added from the tube reactor P3 to commercially available tri-tert-butylphosphine (manufactured by Aldrich). ) In THF with a solution of tri-tert-butylphosphine dissolved in THF (0.025M) from the tube reactor P4 at 3.0 mL / min ((E) -β Bromostyrene; 0.40 mmol / min, palladium acetate; 0.020mmol / min), was fed at a flow rate of 1.6mL / min (0.040mmol / min). Residence time in tube reactor R1 (length 32.5 cm) is 2.1 seconds, residence time in tube reactor R2 (length 12.5 cm) is 1.3 seconds, residence time in tube reactor R3 (length 200 cm) is It was 8.0 seconds. In addition, the tube reactors (P1, P2, P3, and P4) for pre-cooling were all 100 cm long. In this way, the reaction solution containing the vinyl-substituted aryl compound represented by the general formula [IV] discharged from the outlet of R3, that is, (E) -stilbene, is the solution for the first few minutes until the reaction becomes stable. Discard and collect the subsequent solution in a sampling tube for 30 seconds while quenching the reaction with 1.5 mL of methanol (neat), then use GC to standardize the solution collected in the sampling tube (CBP1 column; 0.25 mm × 25 m) Then, quantitative analysis was performed by an internal standard method using a standard substance at a starting temperature of 50 ° C. and a heating rate of 10 ° C./min) to obtain the reaction rate of this reaction. As a result of analysis, (E) -stilbene (GC retention time; 21.8 minutes) was obtained in a yield of 95% (based on (E) -β-bromostyrene). In addition, (E) -β-bromostyrene (GC retention time: 14.7 minutes (yield; 0% ((E) -β-bromostyrene standard))) as a raw material and biphenyl (by-product) ( GC retention time; 17.4 minutes (yield; 8% (based on bromobenzene))), 1,4-diphenyl-1,3-butadiene (GC retention time; 25.3 minutes (yield; 0% (( The determination of E) -β-bromostyrene standard))) was also determined from GC in the same manner.

  From the results of Examples 1 to 3, not only can the halogen-lithium exchange reaction, which is the first step, and the coupling reaction, which is the second step, be performed continuously, but in a normal batch reaction, After preparing the aryllithium compound by once performing a reaction (halogen-lithium exchange reaction) at a low temperature such as −78 ° C., it was necessary to perform a coupling reaction in the next step. It has been found that energy costs for production can be saved. In addition, if a mixture of a ligand compound and a compound capable of coordinating with palladium is supplied to the reaction system in the second step so as to include a ligand mixing step, the intended vinyl-substituted aryl can be obtained. It was found that the yield of the compound was improved. Furthermore, if a reaction stopping step is included, the work time required for the post-treatment can be eliminated, and it can be seen that this is an excellent manufacturing method from the viewpoint of improving productivity. Therefore, the present invention is a production method that can be expected to produce various vinyl-substituted aryl compounds with high efficiency and a stable yield.

  The production method of the present invention can produce vinyl-substituted aryl compounds useful as synthetic intermediates such as pharmaceuticals, agricultural chemicals, liquid crystal materials, and organic electroluminescence (organic EL) materials with high efficiency and stable yield. It can be a production method useful for production on a target scale.

Claims (24)

Formula [I]

(In the formula, Ar represents an aryl group which may have a substituent, and X represents a halogen atom.) A halogenated aromatic compound represented by formula (II) is reacted with an organolithium reagent, and the general formula [ II]

A first step of obtaining a lithiated aromatic compound represented by (wherein Ar is the same as above);
In the presence of a catalytic amount of a mixed palladium compound, the lithiated aromatic compound represented by the general formula [II] and the general formula [III]

(In the formula, R ¹ and R ² each independently represents a hydrogen atom or a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, and Y represents a halogen atom or a trifluoromethanesulfonyloxy group. Z represents an aryl group which may have a substituent or a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms) and a β-vinyl compound represented by A second step of ringing;
Including
The general formula [IV], wherein the first and second steps are performed using a microreactor.

(Wherein R ¹ , R ² , Ar and Z are the same as above) , wherein the mixed palladium compound is a compound capable of coordinating with the palladium compound and palladium; Wherein the mixed palladium compound obtained by the ligand mixing step is supplied to the reaction system of the second step. A method for producing a vinyl-substituted aryl compound . The manufacturing method according to claim 1, wherein the first and second steps are performed continuously. Furthermore, the manufacturing method of Claim 1 which includes the process (henceforth a reaction stop process) which processes the reaction solution after the said coupling with reaction stop liquid. The manufacturing method according to claim 3 , wherein the reaction stopping step is performed continuously in a microreactor together with the first and second steps. The minimum channel cross-sectional length of the mixing unit in the first step of the microreactor is 100 μm to 1000 μm, and the minimum channel cross-sectional length of the mixing unit in the second step of the microreactor is 100 μm to The manufacturing method according to claim 1 which is 1000 micrometers. The minimum channel cross-sectional length of the mixing unit in the first step of the microreactor is 100 μm to 1000 μm, and the minimum channel cross-sectional length of the mixing unit in the second step of the microreactor is 100 μm to 1000 μm. The manufacturing method according to claim 1 , wherein the minimum length of the flow path cross section of the mixing portion in the ligand mixing step of the microreactor is 100 μm to 1000 μm. The minimum channel cross-sectional length of the mixing unit in the first step of the microreactor is 100 μm to 1000 μm, and the minimum channel cross-sectional length of the mixing unit in the second step of the microreactor is 100 μm to 1000 μm. The manufacturing method according to claim 4 , wherein the minimum length of the flow path cross section of the mixing portion in the reaction stop process of the microreactor is 100 μm to 1000 μm. The minimum channel cross-sectional length of the mixing unit in the first step of the microreactor is 100 μm to 1000 μm, and the minimum channel cross-sectional length of the mixing unit in the second step of the microreactor is 100 μm to 1000 μm. Yes, the minimum cross-sectional length of the mixing section in the ligand mixing step of the microreactor is 100 μm to 1000 μm, and the minimum cross-sectional length of the flow path of the mixing section in the reaction stopping step of the microreactor is The manufacturing method according to claim 4 which is 100 micrometers-1000 micrometers. The residence time in the first step of the microreactor is 0.001 second to 60 seconds, and the residence time in the second step of the microreactor is 0.1 second to 60 seconds. The manufacturing method as described in. The residence time in the first step of the microreactor is 0.001 second to 60 seconds, the residence time in the second step of the microreactor is 0.1 second to 60 seconds, and the microreactor The production method according to claim 1 , wherein a residence time in the ligand mixing step of the reactor is 0.1 second to 60 seconds. The residence time in the first step of the microreactor is 0.001 second to 60 seconds, the residence time in the second step of the microreactor is 0.1 second to 60 seconds, and the microreactor The production method according to claim 4 , wherein the residence time in the reaction stopping step of the reactor is 0.2 seconds to 120 seconds. The residence time in the first step of the microreactor is 0.001 second to 60 seconds, the residence time in the second step of the microreactor is 0.1 second to 60 seconds, The production time according to claim 4 , wherein the residence time in the ligand mixing step is 0.1 second to 60 seconds, and the residence time in the reaction stop step of the microreactor is 0.2 seconds to 120 seconds. Method. The manufacturing method according to claim 1, wherein the first and second steps are performed in a temperature range of -20 ° C to 40 ° C. The manufacturing method of Claim 1 which performs the said 1st and 2nd process and a ligand mixing process in the temperature range of -20 degreeC-40 degreeC. The manufacturing method of Claim 4 which performs the said 1st and 2nd process and reaction stop process in the temperature range of -20 degreeC-40 degreeC. The manufacturing method of Claim 4 which performs the said 1st and 2nd process, a ligand mixing process, and a reaction stop process in the temperature range of -20 degreeC-40 degreeC. The production method according to claim 1, wherein the mixed palladium compound is at least one selected from the group consisting of zero-valent and divalent mixed palladium compounds. The production method according to claim 1, wherein the mixed palladium compound is at least one selected from the group consisting of bis (tri-tert-butylphosphine) palladium and bis (tricyclohexylphosphine) palladium. The mixture of palladium compound, The method according to claim 1 which is bis (tri -tert- butylphosphine) palladium. The production method according to claim 1 , wherein the palladium compound is palladium acetate and the compound capable of coordinating with the palladium is tri-tert-butylphosphine. In the general formulas [I], [II] and [IV], the aryl group which may have a substituent represented by Ar is represented by the general formula [VIII].

(In the formula, each p ³ R ³ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, p represents an integer of 0 to 5, W represents a carbon atom or a nitrogen atom, and two adjacent R ^{3 s} are in the chain together with the carbon atom to which they are bonded. Or an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in general formula [IX].

(Wherein q R ^{4 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, q represents an integer of 0 to 7, U ¹ and U ² both represent a carbon atom, or when either U ¹ or U ² represents a nitrogen atom, the other represents Represents a carbon atom, and V ¹ and V ² both represent a carbon atom, or when ^one of V ¹ and V ² represents a nitrogen atom, the other represents a carbon atom, and two adjacent R ⁴ May form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. Or general formula [X]

(Wherein r R ^{5 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, and r represents an integer of 0 to 9. Note that two adjacent R ^{5 s} have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. The production method according to claim 1, which may be an aliphatic ring having 3 to 6 carbon atoms. The aryl group optionally having a substituent represented by Z in the general formulas [III] and [IV] is represented by the general formula [XV].

(In the formula, each s R ⁶ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, s represents an integer of 0 to 5, J represents a carbon atom or a nitrogen atom, and the two adjacent R ⁶ atoms together with the carbon atom to which they are bonded together in the chain Or an aliphatic ring having 3 to 6 carbon atoms, which may have an oxygen atom or a sulfur atom, in general formula [XVI]

(Wherein t R ^{7 s} are each independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, t represents an integer of 0 to 7, Q ¹ and Q ² both represent a carbon atom, or when either Q ¹ or Q ² represents a nitrogen atom, the other represents It represents a carbon atom, T ¹ and T ^2, when both representing either a nitrogen atom or T ¹ and T ² represents a carbon atom representing the other carbon atom. in addition, two adjacent R ⁷ May form an aliphatic ring having 3 to 6 carbon atoms which may have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. Or general formula [XVII]

(In the formula, each of u R ⁸ is independently a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms, a linear, branched or cyclic group having 1 to 6 carbon atoms. Represents an alkoxy group or a phenyl group, and u represents an integer of 0 to 9. Note that two adjacent R ^{8 s} have an oxygen atom or a sulfur atom in the chain together with the carbon atom to which they are bonded. The production method according to claim 1, which may be an aliphatic ring having 3 to 6 carbon atoms. The aryl group optionally having a substituent represented by Ar in the general formulas [I], [II] and [IV] is a phenyl group, and Z in the general formulas [III] and [IV] The production method according to claim 1, wherein the aryl group which may have a substituent shown is a phenyl group. The production method according to claim 1, wherein the amount of the mixed palladium compound used is 0.001 mol% to 20 mol% with respect to 1 mol of the β-vinyl compound represented by the general formula [III].

Images