JP2013241401A - Production method of liquid crystal compound, and intermediate thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a highly versatile production method with which a compound being useful as a functional material like a liquid crystal material or the like and having a linking group -CFO-, is conveniently and efficiently obtainable.SOLUTION: In a production method of a compound represented by formula (5), a compound represented by formula (3) and a compound represented by formula (4) are made to react with each other. X-(A)-Z-A-CFY(3). HO-(A)-Z-(A)-Z-(A)-R(4). X-(A)-Z-A-CFO-(A)-Z-(A)-Z-(A)-R(5).

Description

The present invention relates to a simple and efficient method for producing a compound having a —CF ₂ O— linking group useful as a liquid crystal compound.

Liquid crystal elements include mobile devices such as mobile phones and PDAs, display devices for office automation equipment such as copiers and personal computer monitors, display devices for home appliances such as liquid crystal televisions, clocks, calculators, measuring instruments, automotive meters, It is used for applications such as cameras, and various performances such as a wide operating temperature range, a low operating voltage, high-speed response, and chemical stability are required.
In such a liquid crystal element, a material exhibiting a liquid crystal phase is used, but there is no compound that satisfies all of the above characteristics alone, and a liquid crystal compound or a non-liquid crystal compound having excellent characteristics has not been present. By mixing a plurality of liquid crystal compositions, a liquid crystal composition satisfying the required performance was obtained.

In addition, in various properties required for the compound used in the liquid crystal composition as described above, it has excellent compatibility with other liquid crystal materials or non-liquid crystal materials, is chemically stable, and is used for a liquid crystal element. In this case, it is important to have a high speed response over a wide temperature range and a low voltage drive.
In relation to this, Patent Documents 1 to 4 describe derivatives having —CF ₂ O— as a linking group.

The manufacturing method of Patent Document 1 has a problem that the number of steps is long.

The manufacturing method of Patent Document 2 has a problem of using a highly corrosive fluorine reagent and using a sulfur compound that requires countermeasures against odor.

The manufacturing method of Patent Document 3 has a problem that the structure at the left end is largely limited by the raw material used.

The method described in Patent Document 4 has a problem that it is necessary to use CHF ₂ Br which is difficult to handle because of gas.

JP 2005-505632 A Special table 2003-525286 JP 2000-95715 A JP 2003-261478 A

The present invention can be obtained easily and efficiently a compound with useful -CF 2 _O-linking group as a liquid crystal material such as functional materials, and it is an object of versatility to provide high manufacturing method.

  As a result of intensive studies to solve the above-described problems, the present inventors have found that the target product can be obtained simply and at a high yield by using the following production method.

This invention provides the manufacturing method of the compound represented by following formula (5) with which the compound represented by following formula (3) and the compound represented by following formula (4) are made to react.
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
HO- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (4)
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (5)
The symbols in the formula have the following meanings.
R ^{2 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group. It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
A ⁴ , A ⁵ , A ⁶ , A ⁷ and A ⁸ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1, 2,3,4-tetrahydro-2,6-naphthylene group, decahydro-2,6-naphthylene group, or 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ^{4 is a} single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, any hydrogen atom in the group may be substituted with a fluorine atom.
Z ⁵ and Z ^{6 are} each independently a single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or It may be substituted with a thioetheric sulfur atom, one —CH ₂ CH ₂ — may be substituted with —COO— or —OCO—, and any hydrogen atom in the group is substituted with a fluorine atom May be.
o, p, q, and r: 0 or 1 independently of each other. However, p + q + r is 1 or more.
Y ¹ : chlorine atom, bromine atom or iodine atom.
X ² : fluorine atom, chlorine atom, bromine atom or iodine atom.

Moreover, this invention makes the compound represented by the said Formula (5) obtained by the said manufacturing method react with the compound represented by the following formula (6), and the compound represented by the following formula (7). A manufacturing method is also provided.
R ^1- (A ¹ ) _l -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ³ -M (6)
R ^1- (A ¹ ) ₁ -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ^3- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (7)
The symbols in the formula have the following meanings.
R ^{1 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
A ¹ , A ² and A ³ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1,2,3,4- A tetrahydro-2,6-naphthylene group, a decahydro-2,6-naphthylene group, or a 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ¹ , Z ² and Z ^{3 are} each independently a single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is ethereal It may be substituted with an oxygen atom or a thioetheric sulfur atom, one —CH ₂ CH ₂ — may be substituted with —COO— or —OCO—, and any hydrogen atom in the group is a fluorine atom May be substituted.
l, m and n: 0 or 1 independently of each other.
M: a boron atom, a silicon atom or a metal atom, or a group containing at least one of them.
Other symbols have the same meaning as the same symbols described above.

Moreover, this invention also provides the manufacturing method of the compound represented by following formula (3) with which the compound represented by following formula (1) and the compound represented by following formula (2) are made to react.
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -X ¹ (1)
CF ₂ Y ¹ Y ² (2)
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
The symbols in the formula have the following meanings.
X ¹ : hydrogen atom, bromine atom or iodine atom.
Y ² : chlorine atom, bromine atom or iodine atom.
Other symbols have the same meaning as the same symbols described above.

  Moreover, this invention processes the compound represented by said Formula (1) with a base, Then, it is dripped at the compound represented by said Formula (2), The manufacturing method of the compound represented by said Formula (3) Also provide.

As the production method, a method in which A ⁵ is a 1,4-phenylene group in which one or both of the 2-position and the 6-position are substituted with a fluorine atom is preferable.

Further, the production method is, X ² is a chlorine atom, a method o is 0 are preferred.

Moreover, this invention provides the manufacturing method of the compound represented by following formula (7) with which the compound represented by following formula (51) and the compound represented by following formula (6) are made to react.
Cl- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (51)
R ^1- (A ¹ ) _l -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ³ -M (6)
R ^1- (A ¹ ) ₁ -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ^3- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (7)
The symbols in the formula have the same meaning as the same symbols in the formula (5), formula (6) and formula (7).

Moreover, this invention provides the compound represented by following formula (3).
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
The symbol in a formula shows the same meaning as the same symbol in said Formula (3).

As the compound represented by the formula (3), those in which X ² is a chlorine atom and o is 0 are preferable.

According to the present invention, it is possible to obtain a compound with useful -CF 2 _O-linking group as a liquid crystal material and the like functional material easily and efficiently, can be versatile to provide a high manufacturing method.
In addition, the present invention can provide an intermediate useful in such a production method.

The present invention will be described.
Hereinafter, the compound represented by the formula (1) may be referred to as “compound (1)”, and the compounds represented by other formulas may also be denoted in the same manner.

<R ¹ and R ² >
In the compounds (4), (5), (6) and (7), R ¹ and R ² have the same meaning as described above. Moreover, the substitution of a fluorine atom and the substitution of an etheric oxygen atom or a thioetheric sulfur atom may be performed simultaneously on the aliphatic hydrocarbon group.

Hereinafter, an alkyl group substituted with at least one of an etheric oxygen atom, a thioetheric sulfur atom and a fluorine atom is referred to as a “substituted alkyl group”.
An alkenyl group substituted with at least one of an etheric oxygen atom, a thioetheric sulfur atom and a fluorine atom is referred to as a “substituted alkenyl group”.

Examples of the monovalent aliphatic hydrocarbon group include an alkyl group, an alkenyl group, and an alkynyl group, and among them, an alkyl group or an alkenyl group is preferable.
Examples of the substituted alkyl group include an alkoxy group, an alkoxyalkyl group, an alkylthio group, an alkylthioalkyl group, a fluoroalkyl group, a fluoroalkoxy group, a fluoroalkoxyalkyl group, and a fluoroalkylthio group.
Examples of the substituted alkenyl group include an alkenyloxy group, an alkenyloxyalkyl group, an alkenylthio group, an alkenylthioalkyl group, a fluoroalkenyl group, and a fluoroalkenyloxy group.

Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group.
Examples of the alkoxy group include methoxy group, ethoxy group, propoxy group, butoxy group, pentoxy group, hexyloxy group, heptyloxy group, octyloxy group and the like.
Examples of the alkoxyalkyl group include methoxymethyl group, ethoxymethyl group, propoxymethyl group, methoxyethyl group, ethoxyethyl group, propoxyethyl group, methoxypropyl group, ethoxypropyl group, propoxypropyl group and the like.
Examples of the alkylthio group include a methylthio group, an ethylthio group, a propylthio group, a butylthio group, a pentylthio group, a hexylthio group, a heptylthio group, and an octylthio group.
Alkylthioalkyl groups include methylthiomethyl, ethylthiomethyl, propylthiomethyl, butylthiomethyl, methylthioethyl, ethylthioethyl, propylthioethyl, methylthiopropyl, ethylthiopropyl, propylthio A propyl group etc. are mentioned.
Examples of the alkenyl group include a vinyl group, 1-propenyl group, 1-butenyl group, 1-pentenyl group, 3-butenyl group, and 3-pentenyl group.
Examples of the alkenyloxy group include an allyloxy group.
Fluoroalkyl groups include trifluoromethyl, fluoromethyl, 2-fluoroethyl, difluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, 2 -Fluoroethyl group, 3-fluoropropyl group, 4-fluorobutyl group, 5-fluoropentyl group and the like can be mentioned.
Fluoroalkoxy groups include fluoromethoxy group, trifluoromethoxy group, difluoromethoxy group, pentafluoroethoxy group, 1,1,2,2-tetrafluoroethoxy group, heptafluoropropoxy group, 1,1,2,3, Examples include 3,3-hexafluoropropoxy group.
Examples of the fluoroalkoxyalkyl group include a trifluoromethoxymethyl group.
As the fluoroalkenyl group, 2-fluoroethenyl group, 2,2-difluoroethenyl group, 1,2,2-trifluoroethenyl group, 3-fluoro-1-butenyl group, 4-fluoro-1-butenyl group Etc.
Examples of the fluoroalkylthio group include a trifluoromethylthio group, a difluoromethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 2,2,2-trifluoroethylthio group, and the like.

R ¹ and R ² are each independently a hydrogen atom, halogen atom, cyano group, alkyl group, alkenyl group, alkoxy group, alkoxyalkyl group, alkylthio group, alkylthioalkyl group, alkenyl group, alkenyloxy group, A group selected from the group consisting of an alkenylthio group, a fluoroalkyl group, a fluoroalkoxy group, a fluoroalkoxyalkyl group, a fluoroalkyl group and a fluoroalkenylthio group is preferred.

R ¹ is less susceptible to reactivity and side reactions, so a hydrogen atom, a fluorine atom, a cyano group, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, and a substitution having 1 to 10 carbon atoms An alkyl group or a substituted alkenyl group having 2 to 10 carbon atoms is more preferable, an alkyl group having 1 to 5 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms or a fluoro having 2 to 5 carbon atoms. An alkenyl group is more preferable, an alkyl group having 1 to 5 carbon atoms or an alkenyl group having 2 to 5 carbon atoms is more preferable, and an alkyl group having 1 to 5 carbon atoms is still more preferable.

R ² is less susceptible to reactivity and side reactions, so a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 1 10 substituted alkyl groups or substituted alkenyl groups having 2 to 10 carbon atoms are more preferred, such as hydrogen atom, fluorine atom, chlorine atom, cyano group, alkyl group having 1 to 5 carbon atoms, alkenyl group having 2 to 5 carbon atoms, carbon More preferred are a fluoroalkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms or a fluoroalkoxy group having 1 to 5 carbon atoms, a fluorine atom, a cyano group, an alkyl group having 1 to 5 carbon atoms, and 2 to 2 carbon atoms. More preferably, an alkenyl group having 5 carbon atoms, a fluoroalkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, or a fluoroalkoxy group having 1 to 5 carbon atoms. Even more preferred are 5 alkyl groups, C 1-5 alkoxy groups or C 1-5 fluoroalkoxy groups. Here, as the fluoroalkoxy group, —OCF ₂ CF ₃ or —OCF ₃ is preferable, and —OCF ₃ is particularly preferable.

^{<A 1 ,A 2 ,A 3 ,A 4} ,A 5 ,A 6 ,A 7 OyobiA ^8>
In the compound (1) and the compounds (3) to (7), A ^{1 to} A ⁸ have the same meaning as described above.

  Here, substitution of a halogen atom, a cyano group or an alkyl group having 1 to 10 carbon atoms and substitution of a nitrogen atom or an oxygen atom may be performed simultaneously on the same group. For a group containing such a substitution, the term “substituted” is added to the front of each ring group name, for example, “substituted 1,4-phenylene group”, “substituted trans-1,4-cyclohexylene group”, etc. May be called. The halogen atom here is preferably a chlorine atom or a fluorine atom.

When A ^{1 to} A ⁸ are 1,4-phenylene groups and further have a halogen atom as a substituent, the number of halogen atoms substituted by one 1,4-phenylene group is 1 to 4, Among these, one or two is preferable. When it is a trans-1,4-cyclohexylene group and further has a halogen atom as a substituent, the number of halogen atoms to be substituted is preferably 1 to 4. The halogen atom may be bonded to the 1st or 4th carbon atom of the cyclohexylene group.
Examples of the 1,4-phenylene group substituted with a nitrogen atom include 2,5-pyrimidinylene group and 2,5-pyridinylene group.
Examples of the substituted trans-1,4-cyclohexylene group substituted with an etheric oxygen atom or a thioetheric sulfur atom include 2,5-dioxa-trans-1,4-cyclohexylene group, 2,5-dithia-trans-1, 4-cyclohexylene group etc. are mentioned.

As A ^{1 to} A ⁸ , trans-1,4-cyclohexylene group, 2,6-naphthylene group, 1,4-phenylene group, substituted trans-1,4-cyclohexane are used because of reactivity and availability of raw materials. Hexylene, substituted 2,6-naphthylene, and substituted 1,4-phenylene groups are preferred.
Among them, as A ^{1 to} A ⁸ , trans-1,4-cyclohexylene group, 2,6-naphthylene group, 2,6-naphthylene group substituted with one or two fluorine atoms, 1,4- A phenylene group and a 1,4-phenylene group substituted with one or two fluorine atoms are particularly preferred.
A ⁵ is preferably a substituted naphthalene-2,6-diyl group or a substituted 1,4-phenylene group, or a 1,4-phenylene group in which one or both of the 2-position and the 6-position are substituted with a fluorine atom or It is more preferable that one or both of the 1-position and the 3-position is a naphthylene group substituted with a fluorine atom, and a 2,6-difluoro-1,4-phenylene group is particularly preferable.

Here, these cyclic groups have bonds at the 1-position and 4-position.
In the present specification, when a ring group is substituted, the smaller position is the right side and the larger position is the left side. For example, when A ¹ in the compound (7) is a 1,4-phenylene group, the side bonded to Z ¹ is the 1st position, and the side bonded to R ¹ is the 4th position.

<Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ and Z ⁶ >
In the compound (1) and the compounds (3) to (7), Z ^{1 to} Z ⁶ have the same meaning as described above.

Here, the substitution of a fluorine atom and the substitution of an etheric oxygen atom or a thioetheric sulfur atom may be performed simultaneously on the same group. A group having such substitution may be referred to with the word “substitution”. Examples of the divalent aliphatic hydrocarbon group include an alkylene group, an alkenylene group, and an alkynylene group, and among them, an alkylene group is preferable.
The substituted alkylene _{group, -CF 2 CF 2 -, -} CF 2 CH 2 -, - CH 2 CF 2 -, - CHFCH 2 -, - CH 2 CHF -, - CF 2 CHF -, - CHFCF 2 -, - CH ₂ O—, —OCH ₂ —, —CH ₂ S—, —SCH ₂ —, —CF ₂ O—, —OCF ₂ —, —CF ₂ CF ₂ CF ₂ CF ₂ —, —OCF ₂ CF ₂ O— _{, -C 2 H 4 CF 2 O-} , and the like.
Further, when Z ¹ to Z ⁶ is a single bond, the group present on both sides of each of the groups meant binding directly. For example, when Z ¹ is a single bond and l and m are 1, A ¹ and A ² are directly bonded. Further, when Z ¹ , Z ² , Z ³ and Z ⁴ are single bonds and l, m, n and o are 0, R ¹ and A ⁵ are directly bonded.

Z ^{1 to} Z ⁶ are preferably a single bond, an alkylene group having 1 to 4 carbon atoms, a fluorine-substituted alkylene group corresponding to the group, or an —O-substituted alkylene group from the viewpoint of ease of synthesis and the like.
Among these, a single bond, —CH ₂ CH ₂ —, or —CF ₂ CF ₂ — is preferable.

<L, m, n, o, p, q and r>
In the compounds (1) and (3) to (7), l, m, n, o, p, q and r have the same meaning as described above.
Here, since the liquid crystal physical properties of the compound (7) are considered to be good, l + m + n + o + p + q + r is preferably 2 to 4, and more preferably 2 or 3. Moreover, it is preferable that p + q + r is 1 or 2. In addition, l + m + n + o is preferably 1 to 3, and more preferably 1 or 2.

<Other symbols>
In the compound (1), X ¹ has the same meaning as described above. X ¹ is preferably a hydrogen atom because more objectives can be obtained with respect to the amount of raw material charged.
In the compound (1), the compound (3) and the compound (5), X ² has the same meaning as described above. X ² is preferably a chlorine atom, a bromine atom or an iodine atom, and a chlorine atom is particularly preferred because the selectivity and atomic efficiency of the reaction are particularly good.
In the compounds (2) and (3), Y ¹ has the same meaning as described above. Y ¹ is preferably a bromine atom from the viewpoint of availability of raw materials and reactivity of the resulting compound.
In the compound (2), Y ² has the same meaning as described above. Y ² is preferably a bromine atom in view of availability of raw materials.
In the compound (6), M has the same meaning as described above. M is preferably a group derived from boric acid or a borate ester, BF ₃ ⁻ , SiR ³ , SnR ³ , MgBr, MgCl, ZnCl or ZnBr, and among them, derived from boric acid (B ( OH) ₂ ) is preferred. R ³ is an alkyl group having 1 to ³ carbon atoms.

The manufacturing method of the present invention will be described by dividing the process.
In the following, gas chromatography is “GC”, N, N-dimethylformamide is “DMF”, tetrahydrofuran is “THF”, dimethyl sulfoxide is “DMSO”, N, N-dimethylacetamide is “DMAc”, dimethyl glycol May be written as “DMG”.

<First step>
In this step, the compound (1) and the compound (2) are reacted to produce the compound (3).
Here, the compound (1) as a starting material is available as a commercial product. Moreover, it can obtain by the method described in the book of organic synthesis, such as a new experimental chemistry course (Maruzen Co., Ltd. publication).
Compound (2) is available as a commercial product.

  The reaction conditions of the first step can be carried out by allowing a base to act on compound (1) at a low temperature and mixing compound (2) in a solvent.

  As the solvent, it is desirable to use an aromatic compound, an aliphatic hydrocarbon, an alicyclic hydrocarbon, an aliphatic ether compound, a cyclic ether compound, or an aprotic polar solvent. For example, as an aromatic compound, benzene, toluene, and chlorobenzene are preferable. As the aliphatic hydrocarbon, hexane and heptane are preferable. As the alicyclic hydrocarbon, cyclohexane is preferable. As the aliphatic ether compound, diethyl ether, DMG, methyl tert-butyl ether, and diethylene glycol dimethyl ether are preferable. As the cyclic ether compound, THF and dioxane are preferable. As the aprotic polar solvent, DMF, DMSO, acetonitrile, and DMAc are preferable. The reaction can also be carried out by mixing the solvent. The solvent is preferably THF.

About the usage-amount of a solvent, what is necessary is just the quantity which can implement reaction safely and stably. Preferably it is the range of 0.5-20 times amount by mass with respect to compound (1).
The reaction temperature should just be temperature which can stir favorably. Although it depends on the structure of the compound, a range of -100 ° C to 0 ° C is preferred.

  As for the usage-amount of a compound (2), an equivalent or more is preferable with respect to a compound (1), More preferably, it exists in the range of 1.0-1.8 equivalent.

As the base, alkyl lithium, alkali metal amide, alkali metal alkoxide, and alkaline earth metal amide compound are preferable. More preferably, n-butyl lithium, sec-butyl lithium, and diisopropyl lithium amide are preferable.
The amount of the base used is preferably 0.9 equivalent or more with respect to the compound (1). More preferably, it is the range of 0.95-1.25 equivalent with respect to compound (1).

  As a 1st process, after processing a compound (1) with a base, the method of dripping at a compound (2) is preferable.

<Second step>
In this step, the compound (3) and the compound (4) are reacted to produce the compound (5).

  0.5-2.0 equivalent is preferable with respect to compound (3), and, as for the usage-amount of a compound (4), More preferably, it exists in the range of 0.8-1.2 equivalent.

  The reaction conditions for the second step can be carried out by mixing compound (3) and compound (4) in the absence of a solvent or in a solvent.

  Compound (4) can be obtained by preparing a boronic acid derivative by reacting a Grignard reagent prepared from halobenzene with trialkyl borate and oxidizing it with a peroxide such as hydrogen peroxide or peracetic acid. It is also available as a commercial product.

  As the solvent, it is desirable to use aromatic compounds, aliphatic hydrocarbons, alicyclic hydrocarbons, aliphatic ether compounds, cyclic ether compounds, aprotic polar solvents, and protic polar solvents. For example, as the aromatic compound, benzene, toluene, chlorobenzene, and bromobenzene are preferable. As the aliphatic hydrocarbon, hexane and heptane are preferable. As the alicyclic hydrocarbon, cyclohexane is preferable. As the aliphatic ether compound, diethyl ether, DMG, methyl tert-butyl ether, and diethylene glycol dimethyl ether are preferable. As the cyclic ether compound, THF and dioxane are preferable. As the aprotic polar solvent, DMF, DMSO, acetonitrile, and DMAc are preferable. The reaction can be carried out in a state where the solvent is mixed or separated. Protic polar solvents include methanol, ethanol, n-propanol, iso-propyl alcohol, n-butanol, sec-butanol, iso-butanol, monohydric alcohols such as tert-butanol, ethylene glycol, propylene glycol, diethylene glycol. Such a dihydric alcohol is preferred.

  When the reaction is performed in a phase separated state, a phase transfer catalyst may be used. As the phase transfer catalyst, alkyl ammonium salts and crown ethers are preferable.

About the usage-amount of a solvent, what is necessary is just the quantity which can implement reaction safely and stably. Preferably it is the range of 0-20 times amount by mass with respect to compound (1).
The reaction temperature should just be temperature which can stir favorably. Although it depends on the structure of the compound, the range of 10 ° C to 200 ° C is preferable.

The second step is preferably performed under basic conditions. As the base to be used, alkali metal hydride, alkali metal hydroxide, alkali metal carbonate, and alkali metal alkoxide are preferable.
The amount of the base used is preferably 0.8 to 1.6 equivalents relative to compound (4).

<Third step>
In this step, the compound (5) and the compound (6) are reacted to produce the compound (7).

  0.5-2.0 equivalent is preferable with respect to compound (5), and, as for the usage-amount of a compound (6), More preferably, it exists in the range of 0.8-1.2 equivalent.

  The reaction conditions for the third step can be carried out by mixing compound (5) and compound (6) in the absence of a solvent or in a solvent.

  Compound (6) can be obtained by allowing a Trialkyl borate to act on a Grignard reagent prepared from halobenzene, and is also commercially available.

  As the solvent, it is desirable to use aromatic compounds, aliphatic hydrocarbons, alicyclic hydrocarbons, aliphatic ether compounds, cyclic ether compounds, aprotic polar solvents, and proton solvents. For example, as the aromatic compound, benzene, toluene, chlorobenzene, and bromobenzene are preferable. As the aliphatic hydrocarbon, hexane and heptane are preferable. As the alicyclic hydrocarbon, cyclohexane is preferable. As the aliphatic ether compound, diethyl ether, DMG, methyl tert-butyl ether, and diethylene glycol dimethyl ether are preferable. As the cyclic ether compound, THF and dioxane are preferable. As the aprotic polar solvent, DMF, DMSO, acetonitrile, and DMAc are preferable. The reaction can be carried out in a state where the solvent is mixed or separated.

About the usage-amount of a solvent, what is necessary is just the quantity which can implement reaction safely and stably. Preferably it is the range of 0-20 times amount by mass with respect to compound (5).
The reaction temperature should just be temperature which can stir favorably. Although it depends on the structure of the compound, the range of 10 ° C to 200 ° C is preferable.

The third step is preferably performed under basic conditions. As the base to be used, alkali metal hydride, alkali metal hydroxide, alkali metal carbonate, and alkali metal alkoxide are preferable.
The amount of the base used is preferably 0.8 to 4 equivalents relative to compound (6).

The third step is preferably carried out using a catalyst. As the catalyst to be used, a transition metal atom alone or a catalyst containing them is preferable. More preferably, nickel, palladium or platinum atoms alone or at least one of them is preferred.
The amount of the catalyst used is preferably in the range of 0.0005 equivalents to 0.2 equivalents relative to compound (6).

<Compound (3)>
About a compound (3), it can manufacture using said 1st process. Further, according to the method described in Chemische Berichte 1988, 121, 1329-1340, the corresponding benzaldehyde derivative can be fluorinated and then halogenated at the benzyl position.

  Hereinafter, the present invention will be described more specifically with reference to examples. The following examples are intended to illustrate the present invention without limiting the present invention.

A compound of the following formula (7a) was produced. In this compound (7), o = p = 1, l = m = n = q = r = 0, R ¹ is an n-propyl group, R ² is a fluorine atom, and Z ^{1 to} Z ⁶ are all This corresponds to a single bond, A ⁴ is a 1,4-phenylene group, and A ⁵ and A ⁶ are both 2,6-difluoro-1,4-phenylene groups.

[First step]

Under a nitrogen atmosphere, 233 mL of butyl lithium 1.6 mol / l hexane solution was added dropwise to 50.06 g of compound (1a) and 300 mL of THF at −70 ° C., followed by aging for 1 hour. The obtained crude oil was added dropwise to a mixture of 82.04 g of compound (2a) and 300 mL of THF at -70 ° C. After aging for 1 hour, the resulting crude oil was poured into a 5% aqueous sodium hydroxide solution, 300 mL of hexane was added, and the organic phase was washed twice with 300 mL of water. The crude oil obtained was concentrated to obtain 89.00 g of compound (3a). The product was directly used in the next step without purification.
In addition, the measurement result of various spectrum data strongly supported the structure of the corresponding compound.
_{^{1 H NMR (CDCl 3, δ}} ): 7.03 (d, 2H, Ar).
¹⁹ F NMR (CDCl ₃ , δ): −41.78 (2F, t, CF ₂ O), −108.35 (2F, m, Ar).

[Second step]

Under a nitrogen stream, 10.02 g of the compound (3a), 6.20 g of the compound (4a), 5.97 g of potassium carbonate, and 12 mL of DMF were heated and stirred at 100 ° C. for 4 hours. 20 mL of hexane was added to the obtained crude oil, and the organic phase was washed with 10 mL of 5% hydrochloric acid, 10 mL of 5% aqueous sodium bicarbonate, and 10 mL of water, and dried. The resulting crude oil was purified by silica chromatography and recrystallization to obtain 3.11 g of compound (5a).
In addition, the measurement result of various spectrum data strongly supported the structure of the corresponding compound.
¹ H NMR (CDCl ₃ , δ): 7.05 (d, 2H, Ar), −6.94 (d, 2H, Ar).
¹⁹ F NMR (CDCl ₃ , δ): −62.43 (2F, t, CF ₂ O), −109.10 (2F, m, Ar), −132.74 (2F, m, Ar), −163 .28 (1F, m, Ar).

[Third step]

Under nitrogen stream, compound (5a) 3.05 g, compound (6a) 1.49 g, potassium carbonate 3.93 g, [Pd (PPh ₃ ) ₄ ] 115.4 mg, 2-dicyclohexylphosphino-2 ′, 6 ′ dimethoxy Biphenyl 79.0 mg, DMG 11 mL, and water 17 mL were stirred for 5 hours under heating and reflux conditions. The resulting crude oil was extracted with 30 mL of hexane, and the organic phase was washed with 10 mL of 5% hydrochloric acid, 10 mL of 5% aqueous sodium bicarbonate, and 10 mL of water, and concentrated. The obtained crude oil was purified by silica chromatography and recrystallization to obtain 2.89 g of compound (7a).
In addition, the measurement result of various spectrum data strongly supported the structure of the corresponding compound.
¹ H NMR (CDCl ₃ , δ): 7.47 (d, 2H, Ar), 7.28 (d, 2H, Ar), 7.20 (d, 2H, Ar), 6.99 (m, 2H) , Ar), 2.64 (t, 2H, benzyl), 1.68 (td, 2H, CH 2), 0.97 (m, 3H, CH 3).
¹⁹ F NMR (CDCl ₃ , δ): −58.86 (2F, t, CF ₂ O), −105.90 (2F, m, Ar), −127.78 (2F, m, Ar), −158 .51 (1F, m, Ar).

In addition, a compound represented by the following formula (7b) was also produced. In this compound (7), o = p = q = 1, l = m = n = r = 0, R ¹ and R ² are all n-propyl groups, and Z ^{1 to} Z ⁶ are all simple. Bond, A ⁴ is 1,4-phenylene group, A ⁵ is 2,6-difluoro-1,4-phenylene group, A ⁶ is 2,6-naphthylene group, A ⁷ is trans-1,4-cyclohexylene It corresponds to the compound that is the group.

[Second step]

Under a nitrogen stream, 20.03 g of the compound (3a), 23.27 g of the compound (4b), 12.00 g of potassium carbonate, and 60 ml of ethylene glycol were heated and stirred at 110 ° C. for 9 hours. 60 ml of hexane was added to the resulting crude oil, and the organic phase was washed with 15 ml of 5% hydrochloric acid, 15 ml of 5% aqueous sodium bicarbonate solution and 15 ml of water and dried. The obtained crude oil was purified by silica chromatography and recrystallization to obtain 10.06 g of compound (5b).
In addition, the measurement result of various spectrum data strongly supported the structure of the corresponding compound.
¹ H NMR (CDCl ₃ , δ): 7.76 (d, 1H, Np), 7.74 (d, 1H, Np), (d, 1H, Np), 7.65 (m, 1H, Np) 7.64 (d, 1H, Np), 7.40 (dd, 1H, Np), 7.34 (dd, 1H, Np), 7.02 (d, 2H, Ar), 2.62 (tt , 1H, Cy), 1.61-1.04 ( m, 13H, Cy and CH 2), 0.92 (t, 3H, CH 3)
¹⁹ F NMR (CDCl ₃ , δ): −60.81 (2F, m, CF ₂ O), −108.91 (2F, m, Ar).

[Third step]

Under a nitrogen stream, compound (5b) 4.52 g, compound (6a) 1.55 g, potassium carbonate 4.10 g, [Pd (PPh ₃ ) ₄ ] 115.7 mg, 2-dicyclohexylphosphino-2 ′, 6′- Dimethoxybiphenyl 88.6 mg, DMG 12 ml, and water 18 ml were stirred for 5 hours under heating and reflux conditions. The resulting crude oil was extracted with 30 ml of toluene, and the organic phase was washed with 10 ml of 5% hydrochloric acid, 10 ml of 5% aqueous sodium bicarbonate and 10 ml of water and concentrated. The resulting crude oil was purified by silica chromatography and recrystallization to obtain 3.25 g of compound (7b).
In addition, the measurement result of various spectrum data strongly supported the structure of the corresponding compound.
¹ H NMR (CDCl ₃ , δ): 7.77 (br, 1H, Np), 7.74 (br, 1H, Np), 7.70 (br, 1H, Np), 7.61 (br, 1H) , Np), 7.48 (br, 1H, Np), 7.45 (m, 1H, Np), 7.39 (d, 1H, Ar), 7.26 (d, 1H, Ar), 7. 17 (d, 1H, Ar) , 2.61 (m, 3H, benzyl and CH), 1.98-0.89 (br, 21H, Cy, CH 2 and CH 3).
¹⁹ F NMR (CDCl ₃ , δ): −60.55 (2F, t, CF ₂ O), −11.95 (2F, td, Ar).
Phase sequence: C 83.5 ° C. N 242.7 I
C: Crystal, N: Nematic phase, I: Isotropic phase

Claims (9)

The manufacturing method of the compound represented by following formula (5) with which the compound represented by following formula (3) and the compound represented by following formula (4) are made to react.
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
HO- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (4)
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (5)
The symbols in the formula have the following meanings.
R ^{2 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group. It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
A ⁴ , A ⁵ , A ⁶ , A ⁷ and A ⁸ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1, 2,3,4-tetrahydro-2,6-naphthylene group, decahydro-2,6-naphthylene group, or 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ^{4 is a} single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, any hydrogen atom in the group may be substituted with a fluorine atom.
Z ⁵ and Z ^{6 are} each independently a single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or It may be substituted with a thioetheric sulfur atom, one —CH ₂ CH ₂ — may be substituted with —COO— or —OCO—, and any hydrogen atom in the group is substituted with a fluorine atom May be.
o, p, q, and r: 0 or 1 independently of each other. However, p + q + r is 1 or more.
Y ¹ : chlorine atom, bromine atom or iodine atom.
X ² : fluorine atom, chlorine atom, bromine atom or iodine atom. A method for producing a compound represented by the following formula (7), wherein the compound represented by the formula (5) obtained in claim 1 is reacted with a compound represented by the following formula (6).
R ^1- (A ¹ ) _l -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ³ -M (6)
R ^1- (A ¹ ) ₁ -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ^3- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (7)
The symbols in the formula have the following meanings.
R ^{1 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
A ¹ , A ² and A ³ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1,2,3,4- A tetrahydro-2,6-naphthylene group, a decahydro-2,6-naphthylene group, or a 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ¹ , Z ² and Z ^{3 are} each independently a single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is ethereal It may be substituted with an oxygen atom or a thioetheric sulfur atom, one —CH ₂ CH ₂ — may be substituted with —COO— or —OCO—, and any hydrogen atom in the group is a fluorine atom May be substituted.
l, m and n: 0 or 1 independently of each other.
M: a boron atom, a silicon atom or a metal atom, or a group containing at least one of them.
Other symbols have the same meaning as the same symbols in claim 1. The manufacturing method of the compound represented by following formula (3) with which the compound represented by following formula (1) and the compound represented by following formula (2) are made to react.
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -X ¹ (1)
CF ₂ Y ¹ Y ² (2)
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
The symbols in the formula have the following meanings.
A ⁴ and A ⁵ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1,2,3,4-tetrahydro-2 , 6-naphthylene group, decahydro-2,6-naphthylene group, or 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ^{4 is a} single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, any hydrogen atom in the group may be substituted with a fluorine atom.
o: 0 or 1.
X ¹ : hydrogen atom, bromine atom or iodine atom.
X ² : fluorine atom, chlorine atom, bromine atom or iodine atom.
Y ¹ : chlorine atom, bromine atom or iodine atom.
Y ² : chlorine atom, bromine atom or iodine atom.   The manufacturing method of Claim 3 which is dripped at the compound represented by the said Formula (2), after processing the compound represented by the said Formula (1) with a base. The production method according to any one of claims 1 to 4, wherein A ⁵ is a 1,4-phenylene group in which one or both of the 2-position and the 6-position are substituted with a fluorine atom. The manufacturing method in any one of Claims 1-5 whose X < ² > is a chlorine atom and o is 0. The manufacturing method of the compound represented by following formula (7) with which the compound represented by following formula (51) and the compound represented by following formula (6) are made to react.
Cl- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (51)
R ^1- (A ¹ ) _l -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ³ -M (6)
R ^1- (A ¹ ) ₁ -Z ^1- (A ² ) _m -Z ^2- (A ³ ) _n -Z ^3- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ O- (A ⁶ ) _p -Z ^5- (A ⁷ ) _q -Z ^6- (A ⁸ ) _r -R ² (7)
The symbols in the formula have the following meanings.
R ^{1 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
R ^{2 is a} hydrogen atom, a halogen atom, a cyano group, or a monovalent aliphatic hydrocarbon group having 1 to 20 carbon atoms, and one or more —CH ₂ — in the group is an etheric oxygen atom or thioetheric group. It may be substituted with a sulfur atom, and any hydrogen atom in the group may be substituted with a fluorine atom.
A ¹ , A ² , A ³ , A ⁴ , A ⁵ , A ⁶ , A ⁷ and A ⁸ : independently of each other, a trans-1,4-cyclohexylene group, a 1,4-cyclohexenylene group, 2,6-naphthylene group, 1,2,3,4-tetrahydro-2,6-naphthylene group, decahydro-2,6-naphthylene group, or 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ¹ , Z ² , Z ³ , Z ⁵ and Z ^{6 are} each independently a single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH in the group ₂ -may be substituted with an etheric oxygen atom or a thioetheric sulfur atom, and one -CH ₂ CH ₂ -may be substituted with -COO- or -OCO-, The hydrogen atom may be substituted with a fluorine atom.
Z ^{4 is a} single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, any hydrogen atom in the group may be substituted with a fluorine atom.
l, m, n, o, p, q and r: 0 or 1 independently of each other. However, p + q + r is 1 or more.
M: a boron atom, a silicon atom or a metal atom, or a group containing at least one of them. A compound represented by the following formula (3).
X ^2- (A ⁴ ) _o -Z ⁴ -A ⁵ -CF ₂ Y ¹ (3)
The symbols in the formula have the following meanings.
A ⁴ and A ⁵ : independently of each other, trans-1,4-cyclohexylene group, 1,4-cyclohexenylene group, 2,6-naphthylene group, 1,2,3,4-tetrahydro-2 , 6-naphthylene group, decahydro-2,6-naphthylene group, or 1,4-phenylene group. One or two ═CH— present in the group may be substituted with a nitrogen atom, and one or two —CH ₂ — may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, one or more hydrogen atoms in the group may be substituted with a halogen atom, a cyano group, or an alkyl group having 1 to 10 carbon atoms.
Z ^{4 is a} single bond or a divalent aliphatic hydrocarbon group having 1 to 4 carbon atoms, and one or more —CH ₂ — in the group is substituted with an etheric oxygen atom or a thioetheric sulfur atom. In addition, any hydrogen atom in the group may be substituted with a fluorine atom.
o: 0 or 1.
Y ¹ : chlorine atom, bromine atom or iodine atom.
X ² : fluorine atom, chlorine atom, bromine atom or iodine atom. The compound according to claim 8, wherein X ² is a chlorine atom and o is 0.