JPH0859525A - Production of trans-difluoroethylene compound - Google Patents

Abstract

PURPOSE: To produce a trans-difluoroethylene compound suitable for a liquid crystal in high yield at a low cost by passing a readily available halogenated cyclohexane compound as a raw material through a lithium compound in three steps. CONSTITUTION: This method for producing a trans-difluoroethylene compound of formula 1 (A<2> is trans-1,4-disubstituted cyclohexylene; A<1> is A<2> , etc.; A<3> is a 1,4-disubstituted cyclohexenylene, etc.; A<4> is A<1> ; Y<1> is COO, OCO, C≡C, etc.; Y<2> is Y<1> ; (m) is 0 or 1; R<1> is an alkyl, etc.; R<2> is R<1> ; X is Cl, etc.; (n) is 0 or 1) comprises reacting a halogenated cyclohexane compound of formula 2 with a lithium compound, providing a lithium compound of formula 3, then reacting the resultant compound with trifluoroethylene, affording a compound of formula 4 and further reacting the prepared compound of formula 4 with a lithium compound of formula 6. When an electron-transfer agent is present in the system in the reaction in the first stage, the trans-isomer of the lithium compound of formula 3 is stabler than the cis-isomer thereof. Thereby, the trans-isomer of the compound of formula 1 is a main product. As a result, an inexpensive mixture of the cis- with the trans-isomers can be used as the raw material.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing a trans-difluoroethylene compound.

[0002]

2. Description of the Related Art As a conventional method for producing a trans-difluoroethylene compound, the present inventors have disclosed in JP-A-06-409.
As described in No. 67, a method of obtaining a target difluoroethylene compound using chlorotrifluoroethylene as a starting material is known.

[0003]

The method described in Japanese Patent Laid-Open No. 06-40967 requires a low temperature of -100 ° C. when lithiating chlorotrifluoroethylene with n-butyllithium. There was a drawback. In addition, there is a drawback that the process becomes long, such that CF ₂ = CF-Si (CH ₃ ) ₃ is produced by using CF ₂ = CFCl.

[0004]

The present invention provides a novel manufacturing method to solve the above-mentioned problems. That is, the general formula
(2) R ^1- (A ¹ ) _m -Y ¹ -A ² -X (2) (In the formula, A ² is a trans-1,4-disubstituted cyclohexylene group, which may be unsubstituted or substituted. One or two or more halogen atoms as a group, which may have a cyano group, A ¹ is a trans-1,4-di-substituted cyclohexylene group,
1,4-disubstituted cyclohexenylene group or 1,4-disubstituted phenylene group, which is unsubstituted or as a substituent
It may have one or two or more halogen atoms or a cyano group, and one or more CH groups present in this group may be substituted with a nitrogen atom, and 1
Or two or more CH ₂ groups may be substituted with an oxygen atom or a sulfur atom, and Y ¹ is -COO-, -OCO-, -C≡C.
_{-, - CH 2 CH 2 -} , - CH = CH-, -OCH 2 -, - CH 2 O- or a single bond, m represents 0 or 1, R ¹ is an alkyl group having 1 to 10 carbon atoms Shows a halogen atom, a cyano group, in the case of an alkyl group, an oxygen atom may be inserted between the carbon-carbon bond or between the carbon-carbon bond between this group and the ring,
Further, a part of the carbon-carbon bond may be a double bond or a triple bond, and the one CH ₂ group may be substituted with a carbonyl group, and also in the group. A part or all of hydrogen atoms may be replaced by fluorine atoms, and X is a chlorine atom, a bromine atom or an iodine atom), and a halogenated cyclohexane compound represented by the general formula ( 3) R ^1- (A ¹ ) _m -Y ¹ -A ² -Li (3) lithium compound, and then reacted with tetrafluoroethylene to give a compound of the general formula (4) R ^1- (A ¹ ) _m -Y ¹ -A ² -CF = CF ₂ (4) A trifluoroethylene compound represented by the formula (6) R ^2- (A ⁴ ) _n -Y ² -A ³ -Li (6) (wherein , A ³ is a 1,4-di-substituted cyclohexenylene group or 1,
A 4-di-substituted phenylene group is shown, A ⁴ is a trans-1,4-di-substituted cyclohexylene group, a 1,4-di-substituted cyclohexenylene group or a 1,4-di-substituted phenylene group, and these groups are Each unsubstituted or one as a substituent or
It may have 2 or more halogen atoms or cyano groups, and 1 or 2 or more CH present in these groups
The group may be substituted with a nitrogen atom, and one or more CH ₂ groups may be substituted with an oxygen atom or a sulfur atom, and Y ² is -COO-, -OCO-,-. C≡C-, -CH ₂
CH _2- , -CH = CH-, -OCH _2- , -CH ₂ O- or represents a single bond,
n represents 0 or 1, R ² represents an alkyl group having 1 to 10 carbon atoms, a halogen atom or a cyano group, and in the case of an alkyl group, a carbon atom between a carbon-carbon bond or between this group and a ring. An oxygen atom may be inserted between the carbon bonds, and
A part of the carbon-carbon bond may be a double bond or a triple bond, and one CH ₂ group may be substituted with a carbonyl group, and a hydrogen atom in the group may be substituted. A part or all of which may be substituted with a fluorine atom) is reacted with a lithium compound represented by the following general formula (1) R ^1- (A ¹ ) _m -Y ¹ -A ² -CF = Provided is a method for producing a trans-difluoroethylene compound, which comprises obtaining a trans-difluoroethylene compound represented by CF-A ³ -Y ^2- (A ⁴ ) _n -R ² (1).

Further, when the halogenated cyclohexane compound is reacted with lithium metal, an electron transfer agent is used, and the electron transfer agent is an aromatic hydrocarbon or condensation of two or more rings. A production method characterized in that it is an aromatic hydrocarbon having a ring, and the electron transfer agent is naphthalene or biphenyl or 2,6-di-t-butylnaphthalene or 2,7-di-t-butylnaphthalene or Provided is a manufacturing method characterized by being 4,4'-di-t-butylbiphenyl or anthracene.

In the present invention, the reaction proceeds as follows.

In the present invention, since A ² is a trans-1,4-di-substituted cyclohexylene group, this reaction with CF ₂ = CF ₂ is different from the case where A ² is a 1,4-di-substituted phenylene group. In this case, the replacement with one occurs preferentially. This is compound (4) and CF
₂ = CF ₂ is different in reactivity with CF ₂ , so that a compound having a desired substituent on only one side of CF ₂ = CF ₂ is first obtained. Therefore, an asymmetric difluoroethylene compound can be easily obtained.

Further, in order to insert a substituent at the trans position on the opposite side of the difluoroethylene moiety, the following reaction is carried out.

Since A ³ of this compound (6) is a 1,4-di-substituted cyclohexenylene group or a 1,4-di-substituted phenylene group, lithiation is easy. In this case, the electron transfer agent may or may not be added.

In the above formula, A ² is a trans-1,4-di-substituted cyclohexylene group, which is unsubstituted or has one or more halogen atoms or cyano groups as substituents. May be. A ³ is a 1,4-di-substituted cyclohexenylene group or a 1,4-di-substituted phenylene group, A ¹ ,
A ⁴ is a trans-1,4-di-substituted cyclohexylene group, a 1,4-di-substituted cyclohexenylene group or a 1,4-di-substituted phenylene group, which are either unsubstituted or have one substituent Alternatively, it may have two or more halogen atoms and a cyano group, and one or two or more CH groups present in this group may be substituted with a nitrogen atom, and
One or more CH ₂ groups may be substituted with an oxygen atom or a sulfur atom.

Further, Y ¹ and Y ² are independently of each other -COO-, -O.
_{CO-, -C≡C -, - CH 2} CH 2 -, - CH = CH -, - OCH 2 -, - shows a CH ₂ O- or a single bond. m and n are 0 or 1. R ¹ , R ²
Are independently of each other an alkyl group having 1 to 10 carbon atoms, a halogen atom or a cyano group, and in the case of an alkyl group, carbon-
An oxygen atom may be inserted between carbon bonds or between carbon-carbon bonds between this group and the ring, and part of the carbon-carbon bonds may be double or triple bonds. Further, one of the CH ₂ groups may be substituted with a carbonyl group, and some or all of hydrogen atoms in the group may be substituted with fluorine atoms. X is a chlorine atom, a bromine atom or an iodine atom.

In the manufacturing method of the present invention, as a first step, the halogenated cyclohexane compound represented by the general formula (2) is reacted with lithium metal to obtain a lithium compound represented by the general formula (3). At this time, by reacting in the presence of an electron transfer agent, the cooling temperature can be made higher than before and a high yield can be obtained, so that the manufacturing process becomes easy.

This electron transfer agent is an aromatic hydrocarbon compound, and one that generates an anion (organic lithio compound) of an organic halogen compound through electron transfer from lithium metal is used. Generally, a compound having two or more aromatic rings or a condensed ring is used. Specific examples include naphthalene, biphenyl, 2,6-di-t-butylnaphthalene, 2,7-di-t-butylnaphthalene, 4,4'-di-t-butylbiphenyl, anthracene, etc., preferably Naphthalene, biphenyl and 4,4'-di-t-butylbienyl.

The amount of the electron transfer agent used is 0.01 times to 3 times, preferably 0.1 times to 2 times the mol of the halogenated cyclohexane compound (2). The amount of lithium metal used is 1 with respect to the halogenated cyclohexane compound.
The molar amount is 10 to 10 times, preferably 1 to 2 times.

The reaction solvent is preferably a hydrocarbon solvent or an ether solvent, and particularly preferably n-hexane, diethyl ether, tetrahydrofuran or a mixed solvent thereof. The solvent is used in an amount of 2 times to 50 times, preferably 5 times to 30 times the weight of the halogenated cyclohexane compound. The reaction temperature is preferably -80 ° C to 25 ° C, particularly preferably -80 ° C to -50 ° C.

Then, as a second step, the lithium compound (3) obtained in the above reaction is isolated and purified,
By reacting with tetrafluoroethylene, a trifluoroethylene compound represented by the general formula (4) is obtained. The amount of tetrafluoroethylene used is 1 to 10 times, preferably 1 to 2 times the mol of the halogenated cyclohexane compound. The reaction temperature is preferably -80 ° C to 25 ° C, particularly preferably -80 ° C to -50 ° C.

In the present invention, as described above, since the ring A ² substituted with lithium is a trans-1,4-di-substituted cyclohexylene group, the case where A ² is a 1,4-di-substituted phenylene group is On the contrary, in the reaction with CF ₂ = CF ₂ , substitution on one side of the same occurs preferentially. This is because the reactivity of the compound (4) with CF ₂ = CF ₂ is different, and a compound having a desired substituent on only one side of CF ₂ = CF ₂ is first obtained. Therefore, an asymmetric difluoroethylene compound can be easily obtained.

Then, a trifluoroethylene compound (4)
Can be reacted with a separately prepared lithium compound represented by the general formula (6) to obtain a difluoroethylene compound represented by the general formula (1).

The reaction solvent is preferably a hydrocarbon solvent, an ether solvent, an amine solvent or a mixed solvent thereof. As the hydrocarbon type, petroleum ether, n-pentane and n-hexane are particularly preferable. As the ether solvent, diethyl ether, tetrahydrofuran and dimethoxyethane are particularly preferable. As the amine solvent, triethylamine, N, N, N ′, N′-tetramethylethylenediamine, and hexamethylphosphoramide are particularly preferable.

The amount of the solvent used is 2 times to 50 times, preferably 5 times to 10 times the weight of the trifluoroethylene compound (4). The reaction temperature is preferably -80 ° C to 40 ° C, particularly preferably -50 ° C to 30 ° C.

Therefore, in this method, the target compound can be produced in a high yield in 3 steps from the easily available halogenated cyclohexane compound. In addition, since the lithium compound obtained in the first step is more stable in the trans form than in the cis form, the halogenated cyclohexane compound as the starting material can be used for the trifluoro compound obtained in the second step from either the cis form or the trans form. Is the main trans-compound. Therefore, as the raw material, an inexpensive mixture of cis and trans isomers can be used.

Specific structures of the final compounds produced by this method include the following compounds. As typical compounds thereof, there are the following compounds as compounds having two rings. R ¹ -A ² -CF = CF-A ³ -R ² (7)

More specifically, the compound of the general formula (7) includes the following compounds. In the following description, not only the compound represented by the general formula (7) but also “-Ph-” is 1,
Represents a 4-disubstituted phenylene group, "-Cy-" is trans-1,4
Represents a di-substituted cyclohexylene group, and “-Ch-” represents a 1,4-di-substituted cyclohexenylene group, preferably a 4-substituted cyclohexen-1-yl group. R ¹ -Cy-CF = CF-Ph-R ² (7A)

[0024]

Embedded image

Further, as a compound in which a 1,4-di-substituted phenylene group is replaced with a 1,4-di-substituted cyclohexenylene group, there are the following compounds. R ¹ -Cy-CF = CF-Ch-R ² (7B)

[0026]

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Further, there are the following compounds as a compound in which the 1,4-disubstituted phenylene group is a phenylene group in which some hydrogen atoms are replaced by fluorine atoms. In the chemical formulas below, "-PhF-" represents a 1,4-disubstituted-fluorophenylene group. R ¹ -Cy-CF = CF-PhF-R ² (7C)

[0028]

[Chemical 3]

Further, as a compound having three rings, there are the following compounds. R ¹ -A ¹ -Cy-CF = CF-A ³ -R ² (8) R ¹ -Cy-CF = CF-A ³ -A ⁴ -R ² (9)

More specifically, the compounds represented by the general formulas (8) and (9) include the following compounds. R ¹ -Ph-Cy-CF = CF-Ph-R ² (8A) R ¹ -Cy-CF = CF-Ph-Ph-R ² (9A)

R ¹ -Ph-Cy-CF = CF-Ch-R ² (8B) R ¹ -Cy-Cy-CF = CF-Ph-R ² (8C) R ¹ -Cy-Cy-CF = CF- Ch-R ² (8D) R ¹ -Ch-Cy-CF = CF-Ph-R ² (8E) R ¹ -Ch-Cy-CF = CF-Ch-R ² (8F) R ¹ -PhF-Cy- CF = CF-Ph-R ² (8G) R ¹ -PhF-Cy-CF = CF-Ch-R ² (8H) R ¹ -Ph-Cy-CF = CF-PhF-R ² (8I) R ^1- Cy-Cy-CF = CF-PhF-R ² (8J) R ¹ -Ch-Cy-CF = CF-PhF-R ² (8K) R ¹ -Cy-CF = CF-Ph-Cy-R ² (9B ) R ¹ -Cy-CF = CF-Ph-Ch-R ² (9C) R ¹ -Cy-CF = CF-Ch-Ph-R ² (9D) R ¹ -Cy-CF = CF-Ch-Cy- R ² (9E) R ¹ -Cy-CF = CF-Ch-Ch-R ² (9F) R ¹ -Cy-CF = CF-PhF-Ph-R ² (9G) R ¹ -Cy-CF = CF- PhF-Cy-R ² (9H) R ¹ -Cy-CF = CF-PhF-Ch-R ² (9I)

In addition, in the case of a 3-ring compound, there are the following compounds in which Y ¹ and Y ² between the rings are changed to other than a single bond.

R ¹ -Ph-C ≡ C-Ph-CF = CF-Cy-R ² (10A) R ¹ -Ph-CH ₂ CH ₂ -Ph-CF = CF-Cy-R ² (10B) R ¹ -Ph-OCH ₂ -Ph-CF = CF-Cy-R ² (10C) R ¹ -Ph-CH ₂ O-Ph-CF = CF-Cy-R ² (10D) R ¹ -Ph-COO-Ph- CF = CF-Cy-R ² (10E) R ¹ -Ph-OCO-Ph-CF = CF-Cy-R ² (10F) R ¹ -Ph-C ≡ C-Cy-CF = CF-Ph-R ² (10G) R ¹ -Ph-CH ₂ CH ₂ -Cy-CF = CF-Ph-R ² (10H) R ¹ -Ph-OCH ₂ -Cy-CF = CF-Ph-R ² (10I) R ^1- Ph-CH ₂ O-Cy-CF = CF-Ph-R ² (10J) R ¹ -Ph-COO-Cy-CF = CF-Ph-R ² (10K) R ¹ -Ph-OCO-Cy-CF = CF-Ph-R ² (10L) R ¹ -Ph-C ≡ C-Cy-CF = CF-Ch-R ² (10M) R ¹ -Ph-CH ₂ CH ₂ -Cy-CF = CF-Ch-R ² (10N) R ¹ -Ph-OCH ₂ -Cy-CF = CF-Ch-R ² (10O) R ¹ -Ph-CH ₂ O-Cy-CF = CF-Ch-R ² (10P) R ^1- Ph-COO-Cy-CF = CF-Ch-R ² (10Q) R ¹ -Ph-OCO-Cy-CF = CF-Ch-R ² (10R)

Further, as a compound having four rings, there are the following compounds. R ¹ -A ¹ -Cy-CF = CF-A ³ -A ⁴ -R ² (11) More specifically, the compound of the general formula (11) includes the following compounds. R ¹ -Ph-Cy-CF = CF-Ph-Ph-R ² (11A)

R ¹ -Ph-Cy-CF = CF-Ch-Ch-R ² (11B) R ¹ -Ph-Cy-CF = CF-Ph-Cy-R ² (11C) R ¹ -Ph-Cy- CF = CF-Ph-Ch-R ² (11D) R ¹ -Ph-Cy-CF = CF-Ch-Ph-R ² (11E) R ¹ -Ph-Cy-CF = CF-Ch-Cy-R ² (11F) R ¹ -Cy-Cy-CF = CF-Ch-Ch-R ² (11G) R ¹ -Cy-Cy-CF = CF-Ph-Cy-R ² (11H) R ¹ -Cy-Cy- CF = CF-Ph-Ch-R ² (11I) R ¹ -Cy-Cy-CF = CF-Ch-Ph-R ² (11J) R ¹ -Cy-Cy-CF = CF-Ch-Cy-R ² (11K) R ¹ -Ch-Cy-CF = CF-Ch-Ch-R ² (11L) R ¹ -Ch-Cy-CF = CF-Ph-Cy-R ² (11M) R ¹ -Ch-Cy- CF = CF-Ph-Ch-R ² (11N) R ¹ -Ch-Cy-CF = CF-Ch-Ph-R ² (11O) R ¹ -Ch-Cy-CF = CF-Ch-Cy-R ² (11P) R ¹ -Ph-Cy-CF = CF-PhF-Ph-R ² (11Q) R ¹ -Ph-Cy-CF = CF-PhF-Cy-R ² (11R) R ¹ -Ph-Cy- CF = CF-PhF-Ch-R ² (11S) R ¹ -Cy-Cy-CF = CF-PhF-Ph-R ² (11T) R ¹ -Cy-Cy-CF = CF-PhF-Cy-R ² (11U) R ¹ -Cy-Cy-CF = CF-PhF-Ch-R ² (11V) R ¹ -Ch-Cy-CF = CF-PhF-Ph-R ² (11W) R ¹ -Ch-Cy- CF = CF-PhF-Cy-R ² (11X) R ¹ -Ch-Cy-CF = CF-PhF-Ch-R ² (11Y)

In addition, in the case of a 4-ring compound, there are the following compounds in which Y ¹ and Y ² between the rings are changed to other than a single bond.

R ¹ -Ph-Cy-CF = CF-Ph-C ≡ C-Ph-R ² (12A) R ¹ -Ph-Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-R ² ( 12B) R ¹ -Ph-Cy-CF = CF-Ph-CH ₂ O-Ph-R ² (12C) R ¹ -Ph-Cy-CF = CF-Ph-OCH ₂ -Ph-R ² (12D) R ¹ -Ph-Cy-CF = CF-Ph-OCO-Ph-R ² (12E) R ¹ -Ph-Cy-CF = CF-Ph-COO-Ph-R ² (12F) R ¹ -Cy-Cy- CF = CF-Ph-C ≡ C-Ph-R ² (12G) R ¹ -Cy-Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-R ² (12H) R ¹ -Cy-Cy-CF = CF-Ph-CH ₂ O-Ph-R ² (12I) R ¹ -Cy-Cy-CF = CF-Ph-OCH ₂ -Ph-R ² (12J) R ¹ -Cy-Cy-CF = CF- Ph-OCO-Ph-R ² (12K) R ¹ -Cy-Cy-CF = CF-Ph-COO-Ph-R ² (12L) R ¹ -Ch-Cy-CF = CF-Ph-C ≡C- Ph-R ² (12M) R ¹ -Ch-Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-R ² (12N) R ¹ -Ch-Cy-CF = CF-Ph-CH ₂ O-Ph -R ² (12O) R ¹ -Ch-Cy-CF = CF-Ph-OCH ₂ -Ph-R ² (12P) R ¹ -Ch-Cy-CF = CF-Ph-OCO-Ph-R ² (12Q ) R ¹ -Ch-Cy-CF = CF-Ph-COO-Ph-R ² (12R)

In addition, a 1,4-disubstituted phenylene group of A ³ , 1,4-
Di-substituted cyclohexenylene group, or the hydrogen atom of 1,4-di-substituted phenylene group of A ¹ , A ⁴ , trans-1,4-di-substituted cyclohexylene group, 1,4-di-substituted cyclohexenylene group A part of the CH group may be replaced with a nitrogen atom, a part of the CH group may be replaced with a nitrogen atom, or a part of the CH ₂ group may be replaced with an oxygen atom or a sulfur atom. Examples of this include the following compounds.

[0039]

[Chemical 4]

The compound as described above which can be produced by this method can be made into a liquid crystal composition by mixing it with another liquid crystal material or a non-liquid crystal material, so that the liquid crystal composition can have a low viscosity. When used as an element, high-speed response becomes possible.

The method of introducing an acyl group into R ¹ and R ² of the compound represented by the general formula (1) can be carried out by the general formula in which R ¹ and R ² are hydrogen atoms.
The Friedel-Crafts reaction between the compound (1) and an acyl halide may be used. In addition, the method of introducing a cyano group is represented by the general formula in which R ¹ and R ² are bromine atoms or iodine atoms.
The compound (1) may be reacted with CuCN.

Further, a method of introducing a vinylidene group (-C = C-) into Y ¹ of the compound of the general formula (1) is carried out by the general formula (R ¹ and R ² is a chlorine atom, a bromine atom or an iodine atom). A coupling reaction between the compound of 1) and an alkenyl grinder compound may be used. Further, a method of introducing an ethylidene group (-C≡C-) into Y ¹ of the compound of the general formula (1) can be carried out by using a compound of the general formula (1) in which R ¹ and R ² are bromine atom or iodine atom, and alkynyl. A coupling reaction with a lithium compound may be used.

[0043]

【Example】

Example 1 [First Step] Preparation of trans-4-n-propylcyclohexyllithium In a 1000 ml four-necked flask, 50 g (0.188 mol) of 4,4′-di-t-butylbiphenyl and tetrahydrofuran (THF) were added.
00 ml was added and cooled to 0 ° C. Under an argon gas atmosphere, 2.6 g (0.37 mol) of lithium metal and 0.1 g of bromine were added, and the mixture was stirred at the same temperature for 3 hours.

Next, after confirming that the reaction liquid was deep blue, it was cooled to -70 ° C. and 15.1 g (0.094 mol) of 1-chloro-4-n-propylcyclohexane (cis / trans = 2/1) )
A solution dissolved in 50 ml of THF was added dropwise with stirring at -50 ° C or lower over 30 minutes. Further, the mixture was stirred at -70 ° C for 30 minutes.

[Second Step] Synthesis of 2- (trans-4-n-propylcyclohexyl) -1,1,2-trifluoroethylene THF of trans-4-n-propylcyclohexyllithium prepared in the first step 18.8 g (0.188 mol) of tetrafluoroethylene was blown into the solution at -50 ° C or lower over 15 minutes. Furthermore, after reacting at -78 ° C for 30 minutes, the temperature was raised to -10 ° C, 200 ml of 1N hydrochloric acid was added, and the organic layer was separated. The aqueous layer was extracted with n-hexane, washed with water together with the organic layer, dried, the solvent was distilled off under normal pressure, and the low boiling point was distilled off under reduced pressure. The obtained crude liquid was purified by distillation under reduced pressure to obtain 11.6 g (yield 60%) of 2- (trans-4-n-propylcyclohexyl) -1,1,2-trifluoroethylene. nC ₃ H ₇ -Cy-CF = CF ₂

[Third Step] Separately, a 300 ml four-necked flask was charged with 6.02 g (25.2 mmol) of 4-chloroiodobenzene and 30 ml of dry ether and cooled to -78 ° C. Next, 17 ml (27.8 m) of n-BuLi n-hexane solution (1.63 mol / l) was added.
mol), and was added dropwise over 15 minutes. After stirring at -78 ° C for 1 hour, N, N, N ', N'-tetramethylethylenediamine (TME
DA) 3.8 ml (25.5 mmol) was added, and 2- (trans-4-n-propylcyclohexyl) -1,1, obtained in the second step, was further added.
A mixed solution of 1.3 g (6.31 mmol) of 2-trifluoroethylene and 10 ml of dry ether was added dropwise over 15 minutes.

The temperature was further raised to room temperature, and after reacting for 1 hour, 1N
100 ml of hydrochloric acid was added, and the organic layer was separated. The aqueous layer was extracted with n-hexane, and the organic layer was washed with water and dried, the solvent was distilled off, the crude liquid obtained was purified by silica gel column chromatography, and the obtained solid was re-purified from methanol. Crystallize to give (E) -1- (4-chlorophenyl) -2- (trans
1.03 g (yield 55%) of 4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. _{n-C 3 H 7 -Cy-} CF = CF-Ph-Cl

[0048]

[Chemical 5]

The analysis results of this compound are shown below. ¹⁹ F NMR (CDCl ₃ ) δppm from CFCl ₃ -154.4ppm (d, d, J _FF = 119.3Hz, J _FH = 29.9Hz) -161.4ppm (d, d, J _FF = 119.3Hz, J _FH = 6.6Hz ) MS m / e 298 (M +)

Example 2 In the third step of Example 1, 5.59 g (25.2%) of 4-fluoroiodobenzene was used instead of 4-chloroiodobenzene.
mmol), except that the reaction is carried out in the same manner as in Example 1, (E)-
0.80 g (yield 45%) of 1- (4-fluorophenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-F

[0051]

[Chemical 6]

Example 3 In the third step of Example 1, 7.13 g (25.2 g) of 4-bromoiodobenzene was used instead of 4-chloroiodobenzene.
mmol), except that the reaction is carried out in the same manner as in Example 1, (E)-
0.88 g of 1- (4-bromophenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene (yield
41%). nC ₃ H ₇ -Cy-CF = CF-Ph-Br

[0053]

[Chemical 7]

The following compounds can be obtained in the same manner as in Examples 1-3. Lithiation of CH ₃ -Cy-Cl to CH _3-
Cy-Li was prepared and obtained from I-Ph-Cl after reacting with CF ₂ = CF ₂ .
It is reacted with Li-Ph-Cl, produce _{CH 3 -Cy-CF = CF-} Ph-Cl. C ₂
Lithiation from H ₅ -Cy-Cl to produce C ₂ H ₅ -Cy-Li, CF ₂ = CF
After reacting with ₂ , react with Li-Ph-Cl to give C ₂ H ₅ -Cy-CF = CF-Ph
-Manufacture Cl. Lithiation from nC ₄ H ₉ -Cy-Cl to nC ₄ H ₉ -Cy-
Producing Li, reacting with CF ₂ = CF _2, and then reacting with Li-Ph-Cl to produce nC ₄ H ₉ -Cy-CF = CF-Ph-Cl.

CF ₃ -Cy-Cl was lithiated to produce CF ₃ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-Cl to give CF.
₃ -Cy-CF = CF-Ph-Cl manufactured. Lithiated from nC ₃ H ₇ O-Cy-Cl to produce nC ₃ H ₇ O-Cy-Li, reacted with CF ₂ = CF _2, and then Li-P
It is reacted with h-Cl, producing _{nC 3 H 7 O-Cy-} CF = CF-Ph-Cl. CH
₂ = CHCH ₂ -Cy-Cl to produce CH ₂ = CHCH ₂ -Cy-Li by lithiation, react with CF ₂ = CF _2, and then react with Li-Ph-Cl to give CH ₂ =
CHCH ₂ -Cy-CF = CF-Ph-Cl manufactured. After lithiation from CH ₃ C≡C-Cy-Cl to produce CH ₃ C≡C-Cy-Li, after reacting with CF ₂ = CF ₂ ,
It is reacted with Li-Ph-Cl, produce _{CH 3 C≡C-Cy-CF =} CF-Ph-Cl. nC ₃ H ₇ -Cy-Cl was lithiated to produce nC ₃ H ₇ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then reacted with Li-PhF-Cl to produce nC ₃
Manufactured H ₇ -Cy-CF = CF-PhF-Cl.

[0056]

Embedded image

CH ₃ -Cy-Cl was lithiated to produce CH ₃ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-F to produce CH
₃ -Cy-CF = CF-Ph-F manufactured. Lithiation from CH ₃ -Cy-Cl
CH ₃ -Cy-Li was produced, reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-Br to produce CH ₃ -Cy-CF = CF-Ph-Br. nC ₃ H ₇ O-Cy-Cl
Manufactures _{nC 3 H 7 O-Cy-} Li with lithiated from, after the reaction with CF ₂ = CF _2, is reacted with _{Li-Ph-F, nC 3} H 7 O-Cy-CF = CF-Ph-
Manufacture F. Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-Cy
-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Ph-Br to produce nC ₃ H ₇ O-Cy-CF = CF-Ph-Br.

Example 4 In the third step of Example 1, 6.20 g (2%) of 4-n-propyliodobenzene was used instead of 4-chloroiodobenzene.
(5.2 mmol) The reaction was performed in the same manner as in Example 1 except that
1.06 of (E) -1- (4-n-propylphenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene
g (yield 49%) was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-C ₃ H ₇ (n)

[0059]

[Chemical 9]

The following compounds can be obtained in the same manner as in Example 4. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy-L
i was prepared and obtained from I-Ph-C ₃ H ₇ (n) after reacting with CF ₂ = CF ₂ .
CH ₃ -Cy-CF = CF-Ph-C ₃ H by reacting with Li-Ph-C ₃ H ₇ (n)
Manufactured ₇ (n). Lithiation of C ₂ H ₅ -Cy-Cl to C ₂ H ₅ -Cy-Li
And reacting with CF ₂ = CF ₂ and then reacting with Li-Ph-C ₃ H ₇ (n) to give C ₂ H ₅ -Cy-CF = CF-Ph-C ₃ H ₇ (n). Manufacturing.

Lithiation from nC ₄ H ₉ -Cy-Cl to nC ₄ H ₉ -Cy-
After producing Li, reacting with CF ₂ = CF ₂ and then reacting with Li-Ph-C ₃ H ₇ (n), nC ₄ H ₉ -Cy-CF = CF-Ph-C ₃ H ₇ (n) Manufactured. CF ₃ -Cy-C
Lithiation of l yields CF ₃ -Cy-Li, which is reacted with CF ₂ = CF ₂ and then with Li-Ph-C ₃ H ₇ (n) to produce CF ₃ -Cy-CF = CF-Ph -
Manufactured C ₃ H ₇ (n).

Lithiation from nC ₃ H ₇ O-Cy-Cl to give nC ₃ H ₇ O-
Cy-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Ph-C ₃ H ₇ (n) to produce nC ₃ H ₇ O-Cy-CF = CF-Ph-C ₃ H ₇ Manufactured (n). CH
₂ = CHCH ₂ -Cy-Cl was lithiated to produce CH ₂ = CHCH ₂ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-C ₃ H ₇ (n), CH ₂ = CHCH ₂ -Cy-CF = CF-Ph-C ₃ H ₇ (n) was produced.

Example 5 In the third step of Example 1, 5.06 g (25.2%) of 4-ethoxybromobenzene was used instead of 4-chloroiodobenzene.
mmol), except that the reaction is carried out in the same manner as in Example 1, (E)-
1.03 g (yield 53%) of 1- (4-ethoxyphenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. _{n-C 3 H 7 -Cy-} CF = CF-Ph-OC 2 H 5

[0064]

[Chemical 10]

Example 6 In the third step of Example 1, the reaction was performed in the same manner as in Example 1 except that 6.07 g (25.2 mmol) of 4-trifluoromethoxybromobenzene was used instead of 4-chloroiodobenzene, (E) -1- (4-trifluoromethoxyphenyl)-
1.06 g (yield 49%) of 2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-OCF ₃

[0066]

[Chemical 11]

The following compounds can be obtained in the same manner as in Examples 5 and 6. Lithiation of CH ₃ -Cy-Cl to CH _3-
Cy-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Ph-OC ₂ H ₅ obtained from I-Ph-OC ₂ H ₅ to react with CH ₃ -Cy-CF = CF-Ph. -OC ₂ H ₅
Manufactured. C ₂ H ₅ -Cy-Cl is lithiated to produce C ₂ H ₅ -Cy-Li, which is reacted with CF ₂ = CF ₂ and then with Li-Ph-OC ₂ H ₅ to give C ₂
Manufactured H ₅ -Cy-CF = CF-Ph-OC ₂ H ₅ . Lithiation is performed from CF ₃ -Cy-Cl to produce CF ₃ -Cy-Li, and after reacting with CF ₂ = CF ₂ , Li-Ph-OC
It is reacted with ₂ H _5, producing _{CF 3 -Cy-CF = CF-} Ph-OC 2 H 5.

Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-
Cy-Li was produced, reacted with CF ₂ = CF _2, and then reacted with Li-Ph-OC ₂ H ₅ to produce nC ₃ H ₇ O-Cy-CF = CF-Ph-OC ₂ H ₅ . CH ₃ -Cy
CH ₃ -Cy-Li is produced by lithiation from -Cl, reacted with CF ₂ = CF _2, and then reacted with Li-Ph-OCF ₃ to produce CH ₃ -Cy-CF = CF-Ph-OC.
Production of F _3.

Example 7 Example 1 was repeated except that 5.31 g (25.2 mmol) of 4- (2-methyl-1-propenyl) bromobenzene was used instead of 4-chloroiodobenzene in the third step of Example 1. The same reaction was carried out to obtain (E) -1- [4- (2-methyl-1-propenyl) phenyl] -2- (trans-4-n-propylcyclohexyl)-
0.80 g (yield 40%) of 1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-CH = C (CH ₃ ) ₂

[0070]

[Chemical 12]

Example 8 Example 1 was repeated except that 4.91 g (25.2 mmol) of 1-methyl-2- (4-bromophenyl) acetylene was used instead of 4-chloroiodobenzene in the third step of Example 1. The same reaction is performed and (E) -1- [4- (propyl-1-in) phenyl]-
0.97 g (yield 51%) of 2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-C≡CCH ₃

[0072]

[Chemical 13]

The following compounds can be obtained in the same manner as in Examples 7 and 8. Lithiation of CH ₃ -Cy-Cl to CH _3-
Cy-Li was produced, reacted with CF ₂ = CF _2, and then I-Ph-CH = C (CH ₃ ) ₂
From Li-Ph-CH = C (CH ₃ ) ₂ obtained from CH ₃ -Cy-CF = CF
Producing _{-Ph-CH = C (CH 3} ) 2. Lithiation of C ₂ H ₅ -Cy-Cl to C ₂
After producing H ₅ -Cy-Li and reacting with CF ₂ = CF ₂ , Li-Ph-CH = C (C
H _{3) 2} and reacted, producing _{C 2 H 5 -Cy-CF =} CF-Ph-CH = C (CH 3) 2.

Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-
Cy-Li was produced, reacted with CF ₂ = CF _2, and then Li-Ph-CH = C (CH ₃ ) ₂
To produce nC ₃ H ₇ O-Cy-CF = CF-Ph-CH = C (CH ₃ ) ₂ . Lithiation of CH ₃ -Cy-Cl to produce CH ₃ -Cy-Li,
After reacting with CF ₂ = CF ₂ , Li-Ph-C ≡ obtained from I-Ph-C≡C-CH ₃
Is reacted with C-CH _3, produce _{CH 3 -Cy-CF = CF-} Ph-C ≡C-CH 3.

Lithiation is performed from CF ₃ -Cy-Cl to produce CF ₃ -Cy-Li, which is reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-C ≡C-CH ₃ to give CF _3- Manufactured Cy-CF = CF-Ph-C≡C-CH ₃ . nC ₃ H ₇ O-Cy
Lithiation from -Cl to produce nC ₃ H ₇ O-Cy-Li, CF ₂ = CF
After reacting with ₂ , react with Li-Ph-C ≡ C-CH ₃ to give nC ₃ H ₇ O-
Manufactured Cy-CF = CF-Ph-C≡C-CH ₃ .

Example 9 In a 300 ml three-necked flask equipped with a cooling tube, 0.10 g of CuCN was added.
(1.1mmol) and anhydrous dimethyl sulfoxide (DMSO) 50m
l was added and heated to 90 ° C. to dissolve. Then, under stirring,
(E) -1- (4-bromophenyl) -2- (obtained in Example 3
A solution of 0.40 g of trans-4-n-propylcyclohexyl) -1,2-difluoroethylene in DMSO is added dropwise. Then further
After stirring at 150 ° C for 1 hour, the mixture was cooled to room temperature.

Pour 200 ml of water, extract with methylene chloride,
The organic layer was washed with saturated brine, dried, filtered, the solvent was evaporated, and the obtained solid was purified by silica gel column chromatography to give (E) -1- (4-cyanophenyl) -2. 0.29 g (yield 85%) of-(trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-CN

[0078]

Embedded image

The following compounds can be obtained in the same manner as in Example 9. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy-L
i is produced, reacted with CF ₂ = CF _2, and then reacted with Li-Ph-Br to produce CH ₃ -Cy-CF = CF-Ph-Br, reacted with CuCN,
Manufactured CH ₃ -Cy-CF = CF-Ph-CN. Lithiation of nC ₃ H ₇ O-Cy-Cl to produce nC ₃ H ₇ O-Cy-Li, reaction with CF ₂ = CF ₂
Is reacted with -Ph-Br, to produce a _{nC 3 H 7 O-Cy-} CF = CF-Ph-Br, is reacted with CuCN, the _{nC 3 H 7 O-Cy-} CF = CF-Ph-CN Manufacturing. Lithiation of CH ₂ = CHCH ₂ -Cy-Cl to CH ₂ = CHCH ₂ -Cy-L
i is produced and reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-Br to produce CH ₂ = CHCH ₂ -Cy-CF = CF-Ph-Br, reacted with CuCN and CH ₂ = CHCH ₂ -Cy-CF = CF-Ph-CN manufactured.

Example 10 In the third step of Example 1, 5.52 g (25.2 mmol) of 4- (2,2-difluorovinyl) bromobenzene was used in place of 4-chloroiodobenzene, and the same procedure as in Example 1 was performed. To (E) -1- [4- (2,2-difluorovinyl) phenyl]-
0.95 g (yield 46%) of 2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-CH = CF ₂

[0081]

[Chemical 15]

Example 11 In the third step of Example 1, 7.23 g of 4-[(E) -1,2-difluoro-2-trifluoromethylvinyl)] bromobenzene was used instead of 4-chloroiodobenzene. (25.2mmol)
Using (E) -1- [4-[(E) -1,
2-Difluoro-2-trifluoromethylvinyl)] phenyl] -2- (trans-4-n-propylcyclohexyl) -1,2-
1.12 g (yield 45%) of difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-CF = CFCF ₃

[0083]

Embedded image

Example 12 The procedure of Example 1 was repeated except that 6.0 g (25.2 mmol) of 4- (2,2-difluorovinyloxy) bromobenzene was used in place of 4-chloroiodobenzene in the third step of Example 1. In the same manner, (E) -1- [4- (2,2-difluorovinyloxy) phenyl] -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene (0.88 g ( Yield 41%). nC ₃ H ₇ -Cy-CF = CF-Ph-OCH = CF ₂

[0085]

[Chemical 17]

The following compounds can be obtained in the same manner as in Examples 10-12. Lithiation from CH ₃ -Cy-Cl
CH ₃ -Cy-Li was produced, reacted with CF ₂ = CF _2, and then I-Ph-CH = CF ₂
Reacted with Li-Ph-CH = CF ₂ obtained from CH ₃ -Cy-CF = CF-Ph-
Manufactured CH = CF ₂ . Lithiation of C ₂ H ₅ -Cy-Cl to C ₂ H ₅ -Cy-Li
To produce C ₂ H ₅ -Cy-CF = CF-Ph-CH = CF ₂ by reacting with CF ₂ = CF ₂ and then with Li-Ph-CH = CF ₂ . nC ₃ H ₇ O-Cy-Cl
To produce nC ₃ H ₇ O-Cy-Li, and after reacting with CF ₂ = CF ₂ , reacted with Li-Ph-CH = CF ₂ to produce nC ₃ H ₇ O-Cy-CF = CF
-Manufactured Ph-CH = CF ₂ .

Li obtained from I-Ph-CF = CFCF ₃ after lithiation from CH ₃ -Cy-Cl to produce CH ₃ -Cy-Li, which was reacted with CF ₂ = CF _2.
-Ph-CF = CFCF ₃ and _{reacted, CH 3 -Cy-CF = CF} -Ph-CF = CFCF 3
Manufactured. CH ₃ to produce CH ₃ -Cy-Li with lithiated from _{-Cy-Cl, CF 2 = CF} 2 and after the reaction, I-Ph-OCH = obtained from CF ₂ Li-Ph-OC
It is reacted with H = CF _2, producing _{CH 3 -Cy-CF = CF-} Ph-OCH = CF 2. nC ₃ H ₇ O-Cy-Cl was lithiated to produce nC ₃ H ₇ O-Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-CF = CFCF ₃ to produce nC ₃ producing _{H 7 O-Cy-CF =} CF-Ph-CF = CFCF 3.

Example 13 In the third step of Example 1, the reaction was carried out using 7.08 g (25.2 mmol) of 4- (trans-4-n-propylcyclohexyl) iodobenzene instead of 4-chloroiodobenzene. , (E) -1- [4- (trans
1.22 g (yield 50%) of 4-n-propylcyclohexyl) phenyl] -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-Cy-C ₃ H ₇ (n)

[0089]

Embedded image

The following compounds can be obtained in the same manner as in Example 13. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy
Manufactures -Li, after the reaction with CF ₂ = CF _2, is reacted with _{Li-Ph-Cy-C 3} H 7 obtained from _{I-Ph-Cy-C 3} H 7 (n) (n), CH ₃ -Cy-CF = CF-P
Manufactured h-Cy-C ₃ H ₇ (n). Lithiation from nC ₃ H ₇ O-Cy-Cl
nC ₃ H ₇ O-Cy-Li was produced, reacted with CF ₂ = CF _2, and then Li-Ph-Cy
-C ₃ H ₇ (n), nC ₃ H ₇ O-Cy-CF = CF-Ph-Cy-C ₃ H
Manufactured ₇ (n).

F-Cy-Cl was lithiated to produce F-Cy-Li, which was reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-Cy-C ₃ H ₇ (n) to give F-Cy-Li. Cy-CF = CF-Ph-Cy-C ₃ H ₇ (n) was produced. nC ₃ H ₇ -Cy-Cl was lithiated to produce nC ₃ H ₇ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-Cy-C ₂ H ₅ to produce nC ₃ H ₇ -Cy-CF = CF-Ph
-Manufactured Cy-C ₂ H ₅ .

Example 14 In the third step of Example 1, 4-bromo-4'-n-propylbiphenyl was used in place of 4-chloroiodobenzene.
The reaction was carried out using 6.93 g (25.2 mmol), and the reaction was carried out in the same manner as in Example 1 to obtain (E) -1- (4-n-propylbiphenyl) -2- (trans-4-n-propylcyclohexyl)- 1.25 g (yield 52%) of 1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-Ph-C ₃ H ₇ (n)

[0093]

[Chemical 19]

The following compounds can be obtained in the same manner as in Example 14. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy
-Li was produced, reacted with CF ₂ = CF _2, and then reacted with Li-Ph-Ph-C ₃ H ₇ (n) obtained from I-Ph-Ph-C ₃ H ₇ (n) to obtain CH 2. ₃ -Cy-CF = CF-P
Manufactured h-Ph-C ₃ H ₇ (n). Lithiation from nC ₃ H ₇ O-Cy-Cl
nC ₃ H ₇ O-Cy-Li was produced, reacted with CF ₂ = CF _2, and then Li-Ph-Ph
-C ₃ by reacting H ₇ and _{(n), nC 3 H 7} O-Cy-CF = CF-Ph-Ph-C 3 H
Manufactured ₇ (n).

F-Cy-Cl was lithiated to produce F-Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-Ph-C ₃ H ₇ (n) to produce F-Cy-Li. Cy-CF = CF-Ph-Ph-C ₃ H ₇ (n) was produced. nC ₃ H ₇ -Cy-Cl was lithiated to produce nC ₃ H ₇ -Cy-Li, which was reacted with CF ₂ = CF ₂ and then with Li-Ph-Ph-C ₂ H ₅ to produce nC ₃ H ₇ -Cy-CF = CF-Ph
-Manufactured Ph-C ₂ H ₅ . Lithiation from nC ₃ H ₇ -Cy-Cl to nC ₃ H ₇
-Cy-Li was produced, reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-Ph-F to produce nC ₃ H ₇ -Cy-CF = CF-Ph-Ph-F.

Example 15 Under an argon atmosphere, 0.015 g (0.6 mmol) of magnesium and 10 ml of dry THF were placed in a 100 ml three-necked flask equipped with a reflux tube. Then add 1 drop of 1-bromopropane,
4-methylphenethyl bromide 0.12 g (0.6 mmol) in THF 5 ml
The solution dissolved in was added dropwise. After the dropwise addition was completed, the mixture was refluxed for another hour and then allowed to cool to room temperature.

Separately, under argon atmosphere, with a reflux tube
(E) -1-obtained in Example 3 in a 00 ml three-necked flask.
(4-Bromophenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene 0.2 g (0.58 mmol) and 1,3-bis (diphenylphosphino) propanedichloronickel [NiCl ₂ ( dppp)] 5m of dry THF solution containing 0.01g
1 was put therein, and the above solution was added dropwise thereto using a dropping funnel.

After the dropping, the mixture was further stirred at room temperature for 24 hours,
20 ml of water was added. Further, 20 ml of 20% hydrochloric acid was added to separate the organic layer, which was washed with water and dried, and then the solvent was distilled off. The obtained crude product was purified by silica gel column chromatography to obtain (E) -1- [4- (4-methylphenethyl) phenyl] -2- (trans-4-n-propylcyclohexyl) -1, 0.14 g (yield 61%) of 2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-CH ₃

[0099]

Embedded image

Example 16 In Example 15, 1-bromo-2- (4-methylphenyl) ethene was replaced with 0.12 instead of 4-methylphenethyl bromide.
The reaction was performed in the same manner as in Example 15 except that g (0.6 mmol) was used, and (E) -1- [4- (2-p-methylphenylethenyl) phenyl] -2- (trans-4-n- Propylcyclohexyl) -1,2-
0.12 g (yield 55%) of difluoroethylene was obtained. _{n-C 3 H 7 -Cy-} CF = CF-Ph-CH = CH-
Ph-CH ₃

[0101]

[Chemical 21]

The following compounds can be obtained in the same manner as in Examples 15 and 16. Lithiation is performed from CH ₃ -Cy-Cl to produce CH ₃ -Cy-Li, which is reacted with CF ₂ = CF ₂ and then Li
It is reacted with -Ph-Br, to produce _{CH 3 -Cy-CF = CF-} Ph-Br, Br
-CH ₂ CH ₂ -Ph-CH ₃ reacted with CH ₃ -Cy-CF = CF-Ph-CH ₂ CH ₂ -P
Manufactured h-CH ₃ . nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-Cy-CF = CF-P
h-Br was prepared and reacted with Br-CH ₂ CH ₂ -Ph-CH ₃ to produce nC ₃ H ₇ O-
Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-CH ₃ was produced. From nC ₃ H ₇ -Cy-Cl
nC ₃ H ₇ -Cy-CF = CF-Ph-Br was produced and Br-CH ₂ CH ₂ -Ph-OC ₃ H ₇
nC ₃ H ₇ -Cy-CF = CF-Ph-CH ₂ CH ₂ -Ph-OC ₃ H
Manufactured ₇ (n).

CH ₃ -Cy-CF = CF-Ph-Br was prepared from CH ₃ -Cy-Cl, reacted with Br-CH = CH-Ph-CH _3, and CH ₃ -Cy-CF = CF-Ph. -CH
= CH-Ph-CH ₃ manufactured. nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-Cy-CF =
CF-Ph-Br was prepared and reacted with Br-CH = CH-Ph-CH ₃ to produce nC ₃
Producing _{H 7 O-Cy-CF =} CF-Ph-CH = CH-Ph-CH 3. nC ₃ H ₇ -Cy-Cl to produce _{nC 3 H 7 -Cy-CF =} CF-Ph-Br from, Br-CH = CH-Ph -OC 3 H
Reaction with ₇ (n) nC ₃ H ₇ -Cy-CF = CF-Ph-CH = CH-Ph-OC ₃ H
Manufactured ₇ (n).

Example 17 In the third step of Example 1, instead of 4-chloroiodobenzene, 6.83 g (2%) of 4-bromo-4'-methyltolan was added.
(5.2 mmol) The reaction was performed in the same manner as in Example 1 except that
1.10 g (46% yield) of (E) -1- [4- (2-p-toluylethynyl) phenyl] -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. . _{nC 3 H 7 -Cy-CF =} CF-Ph-C≡C-Ph-CH 3

[0105]

[Chemical formula 22]

The following compounds can be obtained in the same manner as in Example 17. Lithiation from CH ₃ -Cy-Cl to produce CH ₃ -Cy-Li, reaction with CF ₂ = CF ₂ followed by Li-Ph-C
≡C-Ph-CH ₃ reacted with CH ₃ -Cy-CF = CF-Ph-C ≡C-Ph-C
Manufacture H ₃ . nC ₃ H ₇ O-Cy-Cl was used to prepare nC ₃ H ₇ O-Cy-Li, which was reacted with CF ₂ = CF ₂ and then reacted with Li-Ph-C ≡ C-Ph-CH ₃ to produce nC ₃ H ₇ O-Cy-Cl. ₃ H ₇ O-Cy-CF = CF-Ph-C ≡ C-Ph-CH ₃ produced. nC ₃ H ₇
NC ₃ H ₇ -Cy-Li was produced from -Cy-Cl, and after reacting with CF ₂ = CF ₂ ,
Reaction with Li-Ph-C ≡ C-Ph-OC ₂ H ₅ , nC ₃ H ₇ -Cy-CF = CF-
Manufactured Ph-C≡C-Ph-OC ₂ H ₅ .

Example 18 The reaction was performed in the same manner as in Example 1 except that 7.66 g (25.2 mmol) of 4-iodophenyltetrahydropyranyl ether was used in place of 4-chloroiodobenzene in the third step of Example 1. , By finally treating with acid,
0.72 of (E) -1- (4-hydroxyphenyl) -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene
g (yield 41%) was obtained.

Then, the obtained (E) -1- (4-hydroxyphenyl) -2- (trans-4-n-propylcyclohexyl)-
0.30 g (1.07 mmol) of 1,2-difluoroethylene, 0.15 g of potassium carbonate and 10 ml of acetone were added, and further, 0.20 g of α-bromo-p-xylene was added at room temperature. After refluxing for 4 hours, the mixture was cooled, filtered, the solvent was evaporated, and the obtained crude crystals were purified by silica gel column chromatography to obtain (E) -1- [4- (4-methylbenzyloxy). ) Phenyl] -2-
0.40 g (yield 90%) of (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-OCH ₂ -Ph-CH ₃

[0109]

[Chemical formula 23]

Example 19 (E) -1- (4-hydroxyphenyl) -obtained in Example 18
2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene 0.30 g (1.07 mmol) was dissolved in 10 ml of methylene chloride, 0.09 g of pyridine was added at room temperature, and the mixture was cooled to 0 ° C. 0.17 g of p-toluic acid chloride was added.

After stirring at room temperature for 1 hour and cooling, diluted hydrochloric acid was added, the mixture was filtered, and the solvent was distilled off to obtain crude crystals, which were purified by silica gel column chromatography to obtain (E) -1-
0.34 g (yield 80%) of [4- (4-methylbenzoyloxy) phenyl] -2- (trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ph-OCO-Ph-CH ₃

[0112]

[Chemical formula 24]

In the same manner as in Examples 18 and 19, the following
You can get a compound. CH₃-Lithiation from Cy-Cl
CH₃-Cy-Li is manufactured and CF₂= CF₂ After reacting with CH₃-CyCF = CF-
Ph-OH, Br-CH₂-Ph-CH₃ CH₃-Cy-CF =
CF-Ph-OCH₂-Ph-CH ₃ Manufactured. n-C₃H₇O-Cy-Cl to Lithio
N-C₃H₇O-Cy-Li is manufactured and CF₂= CF₂ After reacting with n-
C₃H₇O-Cy-CF = CF-Ph-OH, Br-CH₂-Ph-CH₃ React with
, N-C₃H₇O-Cy-CF = CF-Ph-OCH₂-Ph-CH₃ Manufactured.

Lithiation from nC ₃ H ₇ -Cy-Cl to nC ₃ H ₇ -Cy-
After producing Li and reacting with CF ₂ = CF ₂ , nC ₃ H ₇ -Cy-CF = CF-Ph-O
H and reacted with Br-CH ₂ -Ph-OCH ₃ to give nC ₃ H ₇ -Cy-CF = C
Manufactured F-Ph-OCH ₂ -Ph-OCH ₃ . After lithiation from nC ₃ H ₇ -Cy-Cl to produce nC ₃ H ₇ -Cy-Li, after reacting with CF ₂ = CF ₂ , nC ₃ H ₇
-Cy-CF = CF-Ph-OH, react with Br-CH ₂ -Ph-F, n-
Producing _{C 3 H 7 -Cy-CF =} CF-Ph-OCH 2 -Ph-F.

Lithiation of CH ₃ -Cy-Cl to produce CH ₃ -Cy-Li, reaction with CF ₂ = CF ₂ , then CH ₃ -CyCF = CF-Ph-OH,
Reacted with ClCO-Ph-CH ₃ , CH ₃ -Cy-CF = CF-Ph-OCO-Ph-C
Manufacture H ₃ . nC ₃ nC obtained from _{H 7 O-Cy-Cl 3} H 7 O-Cy-CF = CF-P
Reacting h-OH with ClCO-Ph-CH ₃ to give nC ₃ H ₇ O-Cy-CF = CF
-Manufactured Ph-OCO-Ph-CH ₃ .

NC ₃ H ₇ -Cy-CF = CF-Ph obtained from nC ₃ H ₇ -Cy-Cl
-OH was reacted with ClCO-Ph-OCH ₃ to give nC ₃ H ₇ -Cy-CF = CF-
Manufactured Ph-OCO-Ph-OCH ₃ . nC ₃ H ₇ -C obtained from nC ₃ H ₇ -Cy-Cl
y-CF = CF-Ph-OH is reacted with ClCO-Ph-F to give nC ₃ H ₇ -C
Manufactured y-CF = CF-Ph-OCO-Ph-F.

Example 20 Example 1 was repeated except that 6.3 g (25.2 mmol) of 1-iodo-4-n-propyl-1-cyclohexene was used in place of 4-chloroiodobenzene in the third step of Example 1. The reaction is performed in the same manner as in (E) -1- (4-n-propyl-1-cyclohexene
-1-yl) -2- (trans-4-n-propylcyclohexyl)
0.98 g (yield 50%) of -1,2-difluoroethylene was obtained. nC ₃ H ₇ -Cy-CF = CF-Ch-C ₃ H ₇ (n)

[0118]

[Chemical 25]

The following compounds can be obtained in the same manner as in Example 20. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy
-Li was produced, reacted with CF ₂ = CF _2, and then reacted with Li-Ch-C ₃ H ₇ (n) obtained from I-Ch-C ₃ H ₇ (n) to produce CH ₃ -Cy- CF = CF-Ch-C ₃ H ₇
Manufactured (n). C ₂ H ₅ -Cy-Cl is lithiated to produce C ₂ H ₅ -Cy-Li, which is reacted with CF ₂ = CF ₂ and then reacted with Li-Ch-C ₃ H ₇ (n) to give C ₂ H ₅ -Cy-CF = CF-Ch-C ₃ H ₇ (n) manufactured. After lithiation from CF ₃ -Cy-Cl to produce CF ₃ -Cy-Li, after reacting with CF ₂ = CF ₂ ,
By reacting with Li-Ch-C ₃ H ₇ (n), CF ₃ -Cy-CF = CF-Ch-C ₃ H
Manufactured ₇ (n).

Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-
Cy-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Ch-C ₃ H ₇ (n) to produce nC ₃ H ₇ O-Cy-CF = CF-Ch-C ₃ H ₇ Manufactured (n). n-
Lithiation of C ₃ H ₇ -Cy-Cl to produce nC ₃ H ₇ -Cy-Li, CF
₂ = After reacting with CF ₂ , react with Li-Ch-CH ₃ to give nC ₃ H ₇ -Cy-
Manufactured CF = CF-Ch-CH ₃ . Lithiation from nC ₃ H ₇ -Cy-Cl to n-
C ₃ H ₇ -Cy-Li was produced, reacted with CF ₂ = CF _2, and then Li-Ch-C ₄ H
₉ is reacted (n), and producing _{nC 3 H 7 -Cy-CF =} CF-Ch-C 4 H 9 (n).

Example 21 In the third step of Example 1, 2-iodo-5-n-propylpyrimidine was used in place of 4-chloroiodobenzene.
The reaction was performed in the same manner as in Example 1 except that 6.25 g (25.2 mmol) was used, and (E) -1- (5-n-propylpyrimidin-2-yl) -2- (
0.87 g (yield 45%) of trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. In the chemical formula below, "-Py-" represents a pyrimidine-2,5-diyl group. nC ₃ H ₇ -Cy-CF = CF-Py-C ₃ H ₇ (n)

[0122]

[Chemical formula 26]

The following compounds can be obtained in the same manner as in Example 21. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy
-Li was produced, reacted with CF ₂ = CF _2, and then reacted with Li-Py-C ₃ H ₇ (n) obtained from I-Py-C ₃ H ₇ (n) to produce CH ₃ -Cy- CF = CF-Py-C ₃ H ₇
Manufactured (n). To produce a C ₂ H ₅ -Cy-Li with lithiated from C ₂ H ₅ -Cy-Cl, after the reaction with CF ₂ = CF _2, is reacted with _{Li-Py-C 3 H 7} (n), C ₂ H ₅ -Cy-CF = CF-Py-C ₃ H ₇ (n) produced. After lithiation from CF ₃ -Cy-Cl to produce CF ₃ -Cy-Li, after reacting with CF ₂ = CF ₂ ,
By reacting with Li-Py-C ₃ H ₇ (n), CF ₃ -Cy-CF = CF-Py-C ₃ H
Manufactured ₇ (n).

Lithiation from nC ₃ H ₇ O—Cy—Cl to nC ₃ H ₇ O—
Cy-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Py-C ₃ H ₇ (n) to produce nC ₃ H ₇ O-Cy-CF = CF-Py-C ₃ H ₇ Manufactured (n). n-
Lithiation of C ₃ H ₇ -Cy-Cl to produce nC ₃ H ₇ -Cy-Li, CF
₂ = After reacting with CF ₂ , react with Li-Py-CH ₃ to give nC ₃ H ₇ -Cy-
Manufactured CF = CF-Py-CH ₃ . Lithiation from nC ₃ H ₇ -Cy-Cl to n-
C ₃ H ₇ -Cy-Li was produced, reacted with CF ₂ = CF _2, and then Li-Py-C ₄ H
₉ is reacted (n), and producing _{nC 3 H 7 -Cy-CF =} CF-Py-C 4 H 9 (n).

In the chemical formula below, “-Pi-” is pyridine-2,5-
Represents a diyl group. In the same manner, nC ₃ H ₇ -Cy-Cl was lithiated to produce nC ₃ H ₇ -Cy-Li, and after reacting with CF ₂ = CF ₂ , ₂ -chloroiodobenzene was used instead of 2- Iodine-5-n
- using propyl pyridine, was obtained from _{I-Pi-C 3 H 7} (n) Li
-Pi-C ₃ H ₇ (n) to react with nC ₃ H ₇ -Cy-CF = CF-Pi-C ₃ H
Manufactured ₇ (n). Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-
Cy-Li was produced and reacted with CF ₂ = CF ₂ and then with Li-Pi-C ₃ H ₇ (n) to produce nC ₃ H ₇ O-Cy-CF = CF-Pi-C ₃ H ₇ Manufactured (n).

Example 22 In the third step of Example 1, 2-chloro-5-n-propyldioxane was replaced by 4-chloroiodobenzene.
The reaction was performed in the same manner as in Example 1 except that 6.45 g (25.2 mmol) was used, and (E) -1- (5-n-propyldioxan-2-yl) -2- (
0.84 g (yield 41%) of trans-4-n-propylcyclohexyl) -1,2-difluoroethylene was obtained. In the chemical formula below, "-Do-" represents a dioxane-2,5-diyl group. nC ₃ H ₇ -Cy-CF = CF-Do-C ₃ H ₇ (n)

[0127]

[Chemical 27]

The following compounds can be obtained in the same manner as in Example 22. Lithiation of CH ₃ -Cy-Cl to CH ₃ -Cy
-Li was produced, reacted with CF ₂ = CF _2, and then reacted with Li-Do-C ₃ H ₇ (n) obtained from I-Do-C ₃ H ₇ (n) to produce CH ₃ -Cy- CF = CF-Do-C ₃ H ₇
Manufactured (n). To produce a C ₂ H ₅ -Cy-Li with lithiated from C ₂ H ₅ -Cy-Cl, after the reaction with CF ₂ = CF _2, is reacted with _{Li-Do-C 3 H 7} (n), C ₂ H ₅ -Cy-CF = CF-Do-C ₃ H ₇ (n) manufactured. After lithiation from CF ₃ -Cy-Cl to produce CF ₃ -Cy-Li, after reacting with CF ₂ = CF ₂ ,
By reacting with Li-Do-C ₃ H ₇ (n), CF ₃ -Cy-CF = CF-Do-C ₃ H
Manufactured ₇ (n).

Lithiation from nC ₃ H ₇ O-Cy-Cl to nC ₃ H ₇ O-
Cy-Li is produced and reacted with CF ₂ = CF ₂ and then with Li-Do-C ₃ H ₇ (n) to produce nC ₃ H ₇ O-Cy-CF = CF-Do-C ₃ H ₇ Manufactured (n). n-
Lithiation of C ₃ H ₇ -Cy-Cl to produce nC ₃ H ₇ -Cy-Li, CF
₂ = After reacting with CF ₂ , react with Li-Do-CH ₃ to give nC ₃ H ₇ -Cy-
Manufactured CF = CF-Do-CH ₃ . Lithiation from nC ₃ H ₇ -Cy-Cl to n-
To produce a C ₃ H ₇ -Cy-Li, after the reaction with _{CF 2 = CF 2, Li-} Do-C 4 H
₉ is reacted (n), and producing _{nC 3 H 7 -Cy-CF =} CF-Do-C 4 H 9 (n).

[0130]

According to the production method of the present invention, the reaction is carried out as follows. (A ^{1 to} A ⁴ , R ¹ , R ² , Y ¹ , Y ² , m and n have the above meanings)

Since the compound can be produced by such a reaction, the target compound can be produced inexpensively in a high yield in 3 steps from an easily available halogenated cyclohexane compound. In the reaction in the second step, the substitution on one side of the reaction occurs preferentially. This is because the reactivity of the produced compound with CF ₂ = CF ₂ is much higher in the latter case.

That is, in the present invention, since the ring A ² substituted with lithium is a trans-1,4-disubstituted cyclohexylene group, unlike the case where A ² is a 1,4-disubstituted phenylene group,
During the reaction with CF ₂ = CF ₂ , substitution on one side occurs preferentially. Therefore, after this reaction, it is not necessary to separate and purify the trifluoroethylene compound (4) from the compound in which two molecules are substituted, so that the productivity is extremely good. Therefore, the production of the asymmetric compound becomes easy.

The lithium compound obtained by the lithium / electron transfer agent system is more stable in the trans form than in the cis form, and therefore, the halogenated cyclohexane compound as the starting material may be in the cis form or the trans form. The main product of the cyclohexane ring of the obtained difluoroethylene compound is the trans form. Therefore, as the raw material, an inexpensive mixture of cis and trans isomers can be used.

The present invention can be applied in various ways within a range that does not impair the effects of the present invention. In addition, the compound produced by the production method of the present invention can be used for the production of another compound by another reaction.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display location C07C 41/30 43/192 43/225 C 7419-4H 67/343 69/773 253/14 255 / 46 255/50 255/54 255/55 255/57 C07D 239/26 319/06 C09K 19/30 9279-4H

Claims (4)

[Claims] ^1. A compound represented by the general formula (2) R ^1- (A ¹ ) _m -Y ¹ -A ² -X (2) (wherein A ² is a trans-1,4-di-substituted cyclohexylene group, It may be unsubstituted or may have 1 or 2 or more halogen atoms as a substituent, a cyano group, A ¹ is a trans-1,4-di-substituted cyclohexylene group,
1,4-disubstituted cyclohexenylene group or 1,4-disubstituted phenylene group, which is unsubstituted or as a substituent
It may have one or two or more halogen atoms or a cyano group, and one or more CH groups present in this group may be substituted with a nitrogen atom, and 1
Or two or more CH ₂ groups may be substituted with an oxygen atom or a sulfur atom, and Y ¹ is -COO-, -OCO-, -C≡C.
_{-, - CH 2 CH 2 -} , - CH = CH-, -OCH 2 -, - CH 2 O- or a single bond, m represents 0 or 1, R ¹ is an alkyl group having 1 to 10 carbon atoms Shows a halogen atom, a cyano group, in the case of an alkyl group, an oxygen atom may be inserted between the carbon-carbon bond or between the carbon-carbon bond between this group and the ring,
Further, a part of the carbon-carbon bond may be a double bond or a triple bond, and the one CH ₂ group may be substituted with a carbonyl group, and also in the group. A part or all of hydrogen atoms may be replaced by fluorine atoms, and X is a chlorine atom, a bromine atom or an iodine atom), and a halogenated cyclohexane compound represented by the general formula ( 3) R ^1- (A ¹ ) _m -Y ¹ -A ² -Li (3) lithium compound, and then reacted with tetrafluoroethylene to give a compound of the general formula (4) R ^1- (A ¹ ) _m -Y ^1- A ² -CF = CF ₂ (4) A trifluoroethylene compound represented by the following formula (6) R ^2- (A ⁴ ) _n -Y ² -A ³ -Li (6) (wherein , A ³ is a 1,4-di-substituted cyclohexenylene group or
1,4-di-substituted phenylene group, A ⁴ is a trans-1,4-di-substituted cyclohexylene group, a 1,4-di-substituted cyclohexenylene group or a 1,4-di-substituted phenylene group. Each of the groups may be unsubstituted or may have one or more halogen atoms or cyano groups as substituents, and one or more CH atoms present in these groups may be present.
The group may be substituted with a nitrogen atom, and one or more CH ₂ groups may be substituted with an oxygen atom or a sulfur atom, and Y ² is -COO-, -OCO-,-. C≡C-, -CH ₂
CH _2- , -CH = CH-, -OCH _2- , -CH ₂ O- or represents a single bond,
n represents 0 or 1, R ² represents an alkyl group having 1 to 10 carbon atoms, a halogen atom or a cyano group, and in the case of an alkyl group, a carbon atom between a carbon-carbon bond or between this group and a ring. An oxygen atom may be inserted between the carbon bonds, and
A part of the carbon-carbon bond may be a double bond or a triple bond, and one CH ₂ group may be substituted with a carbonyl group, and a hydrogen atom in the group may be substituted. A part or all of which may be substituted with a fluorine atom) is reacted with a lithium compound represented by the following general formula (1) R ^1- (A ¹ ) _m -Y ¹ -A ² -CF = A method for producing a trans-difluoroethylene compound, which comprises obtaining a trans-difluoroethylene compound represented by CF-A ³ -Y ^2- (A ⁴ ) _n -R ² (1). 2. The method for producing a trans-difluoroethylene compound according to claim 1, wherein an electron transfer agent is used when the halogenated cyclohexane compound is reacted with lithium metal. 3. The method for producing a trans-difluoroethylene compound according to claim 2, wherein the electron transfer agent is an aromatic hydrocarbon having two or more rings or an aromatic hydrocarbon having a condensed ring. 4. The electron transfer agent is naphthalene, biphenyl, 2,
The trans-difluoroethylene compound according to claim 3, which is 6-di-t-butylnaphthalene, 2,7-di-t-butylnaphthalene, 4,4′-di-t-butylbiphenyl or anthracene. Manufacturing method.