JP6512424B2 - Process for producing E-olefin - Google Patents

Description

  The present invention relates to an intermediate for producing chemical products such as pharmaceuticals, agricultural chemicals, liquid crystal materials and the like, and to a method for producing a compound having an E-olefin structure useful as a drug substance.

  E-olefin derivatives often exhibit excellent properties in the fields of medicine, agricultural chemicals and liquid crystal materials, and are useful compounds. In particular, in liquid crystal materials, E-olefin derivatives are known to exhibit higher clearing points, relatively low viscosities and large elastic constants than the corresponding saturated compounds, and are extremely important compounds. Generally, E-olefin derivatives are isomerized using an E-olefin derivative and a composition of the corresponding Z-olefin derivative (hereinafter referred to as "E / Z-olefin composition") using arylsulfinic acids as a catalyst. It manufactures through the process of raising the ratio of the E-olefin derivative in E / Z-olefin composition by reaction (nonpatent literature 1, 2). Also, since arylsulfinic acid is known to be unstable, it is generally purchased and stored as the corresponding arylsulfinic acid salt, and when used, reacted with an acid such as hydrochloric acid in the reaction system Produces and uses fresh arylsulfinic acid. Under the present circumstances, after mixing an E / Z-olefin composition, a sulfinate, an acid, and a solvent at room temperature, the process of heating to predetermined reaction temperature is generally used (patent document 1, nonpatent Document 1 and Non-patent Document 2).

In the current method, it is possible to isomerize the ratio of E-olefin derivative to Z-olefin derivative (E form / Z form) at a relatively high ratio, but after the isomerization reaction, E / Z-olefin composition In order to remove the Z-olefin derivative remaining in the product, it is necessary to repeat many purification operations, resulting in the deterioration of the yield and the cost increase. Therefore, for effective utilization of resources and cost reduction, development of a production method that can obtain an E-olefin derivative at a higher ratio is required.

Japanese Patent Application Publication No. 2012-528798

H. Nozaki, Y. Nishikawa, M. Kawanishi, R. Noyori, Tetrahedron, 23, 2173 (1967) T. W. Gibson, P. Strassburger, J. Org. Chem., 41, 791 (1976)

  It is an object of the present invention to provide an E / Z-olefin derivative composition in which the ratio of E-olefin derivative to Z-olefin derivative (E form / Z form) is higher E / E in the isomerization reaction with sulfinic acid acting on the composition. An object of the present invention is to provide a method for producing a Z-olefin derivative composition.

As a result of examining various reaction conditions in order to solve the above problems, the inventors of the present invention have found that the temperature at which the arylsulfinic acid acts on the E / Z-olefin derivative composition is extremely important. It came to completion.
That is, the present invention is an olefin in which an arylsulfinic acid is caused to act on a composition containing an E-olefin derivative and a Z-olefin derivative under heating, and the content of the E-olefin derivative in the olefin derivative is 80% by mass or more Provided is a method of making a derivative composition.

  The ratio of the E-olefin derivative to the Z-olefin derivative (E form / Z form) is obtained by isomerizing the E / Z-olefin derivative composition by acting the arylsulfinic acid using the production method of the present invention. It is very useful because a higher composition can be obtained and the target E-olefin derivative can be obtained at a higher ratio than conventional methods.

  The production method of the present invention is an olefin derivative production method characterized in that an arylsulfinic acid is allowed to act under heating in a reaction in which an arylsulfinic acid is caused to act on an E / Z-olefin derivative composition to isomerize it. .

  The olefin derivative having "-CH = CH-" in the structure has stereoisomers of E-form and Z-form, and usually, when the olefin derivative is produced, it is obtained as a mixed composition of E-form and Z-form. . The "E / Z-olefin composition" in the present invention is a composition containing an E-olefin derivative and a Z-olefin derivative which is an isomer of the E-olefin derivative.

  The arylsulfinic acid used is

A compound represented by (wherein R represents a hydrogen atom, a chlorine atom, a bromine atom, a methyl group, a methoxy group or a nitro group) is preferable, and it is particularly preferable that R is a hydrogen atom. Also, although the purchased arylsulfinic acid may be allowed to act on the E / Z-olefin derivative composition as it is, the arylsulfinic acid generated by causing the acid to act on the corresponding arylsulfinic acid salt is rapidly E / Z- It is preferred to act on the olefin derivative composition.

  Arylsulfinate is

(Wherein R represents a hydrogen atom, a chlorine atom, a bromine atom, a methyl group, a methoxy group or a nitro group, and X represents a sodium ion, a potassium ion or a lithium ion); Particularly preferred is a hydrogen atom.

  The acid used to cause the acid to act on the arylsulfinate is preferably hydrogen chloride, sulfuric acid, acetic acid, trifluoroacetic acid or an aqueous solution thereof, and more preferably hydrochloric acid or acetic acid. Also, as a method of producing and acting arylsulfinic acid, 1. A method of mixing an E / Z-olefin derivative composition, an arylsulfinate and a solvent, adding an acid under heating, and acting the generated arylsulfinic acid, 2. A method of mixing an E / Z-olefin derivative composition, an acid and a solvent, adding an aqueous arylsulfinate solution under heating to act on the generated arylsulfinic acid, or The E / Z-olefin derivative composition is dissolved in a solvent and heated, and an aqueous solution containing arylsulfinic acid formed by adding an acid to arylsulfinic acid salt in another reaction vessel is added to the above solution under heating Or a method of dissolving an E / Z-olefin derivative composition in a solvent and heating and simultaneously adding an aqueous solution of arylsulfinate and an acid under heating to form arylsulfinic acid to act. Is preferred. Above 1. ~ 3. When adding an acid, an aqueous solution of arylsulfinic acid or an aqueous solution of an acid to arylsulfinic acid salt under heating, these may be added all at once or in several portions and added little by little.

  When the reaction substrate has an acidic functional group such as a carboxyl group, it is not essential to add an acid separately when the acid is allowed to act. When the reaction substrate has an acidic functional group, for example, an E / Z-olefin derivative composition having an acidic functional group is dissolved in a solvent and heated, and an aqueous solution of arylsulfinate is added under heating to form an arylsulfin The acid is generated to act.

  In the present invention, in order to cause the arylsulfinic acid to act on the E / Z-olefin derivative composition under heating, the temperature is preferably higher than room temperature. Specifically, 30 ° C. or higher is preferable, 40 ° C. or higher is preferable, a temperature from 45 ° C. to reflux of the solvent is more preferable, and a temperature from 70 ° C. to reflux of the solvent is particularly preferable. The temperature conditions are under heating when acting the arylsulfinic acid on the E / Z-olefin derivative composition, and it is sufficient if the temperature is higher than room temperature. The temperature condition may be changed by raising the

In the production method of the present invention, it is important to carry out the reaction under heating when the isomerized Z-olefin derivative and the arylsulfinic acid first contact in the reaction system. In the conventional method, the E / Z-olefin composition, the sulfinate, the acid and the solvent are mixed at room temperature, so that the reaction when the Z-olefin derivative and the arylsulfinic acid are in contact is not heated. Although it does, in the present invention, the Z-olefin derivative and the arylsulfinic acid do not contact in the unheated state.
As the solvent to be used, any solvent may be used as long as it causes the reaction to proceed suitably, but aromatic solvents such as toluene, benzene and xylene, saturated hydrocarbon solvents such as hexane, heptane and cyclohexane, dichloromethane and chloroform Chlorinated solvents such as carbon tetrachloride, 1,2-dichloroethane and 1,1,2,2-tetrachloroethane, and ether solvents such as tetrahydrofuran, diethyl ether, diisopropyl ether and t-butyl methyl ether are preferable, and toluene, Particularly preferred are xylene, hexane and 1,2-dichloroethane. These solvents may be mixed and used as needed.

The olefin derivative is not particularly limited as long as it is a compound having "-CH = CH-" in the structure, and for example, an alkyl group (one or two or more CH ₂ groups in the alkyl group is And may be substituted with -O-, -CH = CH-, -CO-, -OCO-, -COO- or -C≡C-, such that the oxygen atom is not directly adjacent, one of the alkyl groups Or a compound having a chain structure based on a carbon skeleton, such as two or more hydrogen atoms optionally substituted by a halogen atom, or a cyclohexylene group (one present in this group) Of -CH ₂ -or non-adjacent two or more -CH _2- may be replaced by -O- or -S-), a phenylene group (one -CH present in this group) = Or 2 or more non-adjacent -CH = replaced by -N = And a hydrogen atom present in this group may be substituted by a fluorine atom), a naphthyl group (one —CH = present in this group, or two or more non-adjacent — CH = may be replaced by —N =, and a hydrogen atom present in this group may be substituted by a fluorine atom), preferably a compound having a cyclic structure based on a carbon skeleton such as . In an olefin derivative, it may have one "-CH = CH-", and may have two or more "-CH = CH-".

  As olefin derivatives, stereoisomers of E-form and Z-form exist. In the present invention, when the olefin derivative has two or more "-CH = CH-", for example, an olefin derivative in which all "-CH = CH-" represents an E form, "-CH = CH-" Depending on whether "-CH = CH-" represents E-form or Z-form, such as an olefin derivative in which "E-form" and "Z-form" and "-CH = CH-" all represent a Z-form. , And multiple isomers exist. In the present invention, an E-olefin derivative refers to a compound in which all "-CH = CH-" in the olefin derivative represents an E-form, and a Z-olefin derivative is one or more "-CH" in the olefin derivative. "= CH-" represents a compound representing Z form.

  A Z-olefin derivative having one or more cyclic structures in the compound is represented by the general formula (1)

(Wherein, R ¹ and R ² each independently represent a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a cyano group, a carboxy group or an alkyl group having 1 to 15 carbon atoms, 1 -CH ₂ -or 2 or more non-adjacent -CH ₂ -present in each is independently -O-, -S-, -COO-, -OCO-, -CO-,- CH = CH— or —C≡C—, which may be replaced, or —S ¹ —R ³ ,
S ¹ is a single bond or at least one type of linking group selected from the group consisting of an alkylene group having 1 to 4 carbon atoms,
R ³ represents a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a cyano group, a carboxy group, a methanesulfonyloxy group, a p-toluenesulfonyloxy group or a trifluoromethanesulfonyloxy group,
A ¹ and A ² are each independently (a) 1,4-cyclohexylene group (one -CH _2- present in this group or two or more non-adjacent -CH _2- is- It may be replaced by O- or -S-))
(B) 1,4-phenylene group (one -CH = present in this group or two or more non-adjacent -CH = may be replaced by -N =, present in this group Hydrogen atoms may be substituted with fluorine atoms)
(C) Naphthalene-2,6-diyl group, 1,2,3,4-tetrahydronaphthalene-2,6-diyl group or decahydronaphthalene-2,6-diyl group (naphthalene-2,6-diyl group or One —CH = or two or more non-adjacent —CH = present in the 1,2,3,4-tetrahydronaphthalene-2,6-diyl group may be replaced by —N =, The hydrogen atom present in these groups may be substituted by a fluorine atom.)
A group selected from the group consisting of
Z ¹ and Z ² each independently represent a single bond or a linear alkylene group having 1 to 10 carbon atoms, and one —CH ₂ — or _two non-adjacent groups present in the alkylene group Each of the above -CH ₂ -may be independently replaced by -O-, -S-, -COO-, -OCO-, -CO-, -CH = CH- or -C≡C-, Z ^The hydrogen atom present in ¹ and Z ² may be substituted by a fluorine atom,
m ¹ and n ¹ each independently represent an integer of 0 to 5, while m ¹ + n ¹ represents 1 to 5,
Y ¹ is

(The black dot in the formula represents an atom directly bonded to Y ¹ in A ¹ , A ² , Z ¹ , Z ² , R ¹ and R ^2. )
Has a structure,
When a plurality of A ¹ and A ² exist, they may be the same or different, and when a plurality of Z ¹ and Z ² exist, they may be the same or different. It is preferable that it is a compound represented by these.

The compound represented by the general formula (1) is useful, for example, as a compound used as a liquid crystal composition for a liquid crystal display device and an intermediate for synthesizing the compound. In the general formula (1), each of A ¹ and A ² independently is a trans-1,4-cyclohexylene group or an unsubstituted naphthalene-2,6-diyl group to reduce the viscosity of the liquid crystal composition. Or an unsubstituted 1,4-phenylene group is preferred, and in order to enhance the miscibility with other liquid crystal components, a trans-1,4-cyclohexylene group or an unsubstituted 1,4-phenylene group Is preferred.

When a compound having a positive Δε is produced using a compound represented by the general formula (1), A ¹ and A ² are each independently to increase Δε.

Is preferred,

Is more preferred.

When a compound having a negative Δε is produced using the compound represented by the general formula (1), each of A ¹ and A ² independently has the following structure.

  In order to improve the long-term reliability of the liquid crystal display device, it is preferable not to contain a nitrogen atom.

In the general formula (1), R ¹ and R ² are each an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, or 1 to 6 carbon atoms in order to reduce the viscosity of the liquid crystal composition. It preferably represents 12 alkoxy groups or alkenyloxy groups having 2 to 12 carbon atoms, and is preferably an alkyl group having 1 to 8 carbon atoms or an alkenyl group having 2 to 8 carbon atoms, and has 1 carbon atom. Particularly preferred is an alkyl group of 5 to 5 or an alkenyl group of 2 to 5 carbon atoms. Moreover, it is preferable that it is linear. Preferably, at least one of R ¹ and R ² is a methanesulfonyloxy group, a p-toluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, a hydroxyl group, a trifluoromethoxy group, or a carboxy group.

When producing a compound in which Δε is positive, either one of R ^{1 and} R ² is preferably a fluorine atom, a cyano group, -CF ₃ or -OCF ₃ in order to increase Δε, and the viscosity is lowered. In order to cause this, a fluorine atom is preferable.

^{Z 1} and ^{Z 2} in the general formula (1) are each independently, _-CH 2 in order to increase the miscibility with reduction and other liquid components of viscosity _{O -, - OCH 2 -,} - CF 2 O-, -OCF _2- , -CF = CF-, -C≡C- or a single bond is preferred, and -CF ₂ O-, -OCF _2- , -CH ₂ CH ₂ -or a single bond More preferred is a single bond, and a single bond or —CF ₂ O— is preferred to exhibit a large Δε. Z ¹ and Z ² directly bonded to Y ¹ preferably represent a linear alkylene group having 1 to 10 carbon atoms or a single bond, and a linear alkylene group having 1 to 4 carbon atoms or a single bond It is preferred to represent a bond.

  Among the compounds represented by the general formula (1), compounds represented by the following general formula (1a), general formula (1b), general formula (1c), general formula (1d) or general formula (1e) It is preferable that it is a compound chosen from the group which consists of.

( ^Wherein , A ^1a2 and Z ^1a2 have the same meaning as A ² and Z ² in the general formula (1),
R ^1a1 represents an alkyl group having 1 to 15 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkyl group are each independently —CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
R ^1a2 represents an alkyl group having 1 to 8 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkyl group are each independently —CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
W ^1a1 represents a single bond or a linear alkylene group having 1 to 4 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkylene group is Each independently may be replaced by -O-, -S-, -COO-, -OCO-, -CO-, or -C≡C-, and the hydrogen atom present in W ^1a1 is substituted by a fluorine atom May be done,
Y ^1a2 represents a single bond or -CH = CH-,
n ^1a1 represents an integer of 1 to 5; )

^{(Wherein, A 1b1, A 1b2, Z} 1b1 and ^{Z 1b2} is the formula in ^{(1), A 1, A} 2, represents the same meaning as ^{Z 1} and ^{Z 2,}
R ^{1 b 1} and R ^{1 b 2} each independently represent an alkyl group having 1 to 8 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkyl group is And each independently may be replaced by -CH = CH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO-,
W ^{1 b 1} and W ^{1 b 2} each independently represent a single bond or a linear alkylene group having 1 to 4 carbon atoms, and one —CH ₂ — or _two non-adjacent groups present in the alkylene group The above -CH ₂ -may be independently replaced by -O-, -S-, ^-COO- , ^-OCO- , -CO-, or ^-C−C- , ^respectively , in W ^{1 b 1} and W ^{1 b} 2 The hydrogen atom present in may be substituted by a fluorine atom,
Y ^1b2 and ^{Y 1b3} represent each independently a single bond or -CH = CH-,
m ^{1 b 1} and n ^{1 b 1} each independently represent an integer of 0 to 5, while m ^{1 b 1} + n ^{1 b} 1 represents 1 to 5. )

(Wherein, A ^1c2 and Z ^1c2 have the same meaning as A ² and Z ² in the general formula (1),
A ^1c3

Represents a group selected from
R ^1c1 represents an alkyl group having 1 to 15 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkyl group are each independently —CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
R ^1c2 represents a fluorine atom, a trifluoromethoxy group or a cyano group,
n ^1c1 represents an integer of 1 to 5; )

^{(Wherein, A 1d2} and ^{A 1d3} has the same meaning as ^{A 2} in the general formula ^(1), Z ^{1d2, Z 1d3} and ^{Z 1d4} has the same meaning as ^{Z 2} in the general formula (1),
R ^1d1 represents an alkyl group having 1 to 15 carbon atoms, and one -CH ₂ -or two or more non-adjacent -CH _2- present in the alkyl group are each independently -CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
R ^1d2 represents an alkyl group having 1 to 8 carbon atoms, and one —CH ₂ — or non-adjacent two or more —CH ₂ — present in the alkyl group are each independently —CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
W ^1d1 represents a linear alkylene group having 4 to single bond or a carbon atoms, one -CH 2 present in the alkylene group _- or nonadjacent two or more -CH 2 _- is Each independently may be replaced by -O-, -S-, -COO-, -OCO-, -CO-, or -C≡C-, and the hydrogen atom present in W ^1d1 is substituted by a fluorine atom May be done,
Y ^1d2 represents a single bond or -CH = CH-,
n 1 ^{d 1} and n 1 ^{d 2} each independently represent an integer of 0 to 4. )

( ^Wherein , A ^1e2 and Z ^1e2 have the same meanings as A ² and Z ² in the general formula (1),
R ^1e1 represents an alkyl group having 1 to 15 carbon atoms, and one -CH ₂ -or two or more non-adjacent -CH _2- present in the alkyl group are each independently -CH ₂ CHCH-, -C≡C-, -O-, -S-, -COO-, -OCO- or -CO- may be substituted,
R ^1e2 is a hydroxyl group, a hydroxymethyl group, a bromomethyl group, a chloromethyl group, a methanesulfonyloxymethyl group, a toluenesulfonyloxymethyl group, a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group or

(Black dot in the formula represents a carbon atom of A ^1e2, R ^1e3 represents. Alkyl group or a hydrogen atom having 1 to 5 carbon atoms) represent,
n 1 ^e 1 represents an integer of 1 to 4; )
Specific examples of preferred compounds are shown below, but the present invention is not limited thereto. In general formula (1a), each compound represented by the following general formula (1a-1)-general formula (1a-23) is preferable.

( ^Wherein , R ^1a1 , Z ^1a2 and R ^1a2 have the same meaning as R ^1a1 , Z ^1a2 and R ^1a2 in the general formula (1a).)

( ^Wherein , R ^1a1 , Z ^1a2 and R ^1a2 have the same meaning as R ^1a1 , Z ^1a2 and R ^1a2 in the general formula (1a).)

( ^Wherein , R ^1a1 , Z ^1a2 and R ^1a2 have the same meaning as R ^1a1 , Z ^1a2 and R ^1a2 in the general formula (1a).)

( ^Wherein , R ^1a1 , Z ^1a2 and R ^1a2 have the same meaning as R ^1a1 , Z ^1a2 and R ^1a2 in the general formula (1a).)

( ^Wherein , R ^1a1 , Z ^1a2 and R ^1a2 have the same meaning as R ^1a1 , Z ^1a2 and R ^1a2 in the general formula (1a).)
In general formula (1b), each compound represented by the following general formula (1b-1)-general formula (1b-10) is preferable.

^{(Wherein, R 1b1} and ^{R 1b2} is the formula in ^(1b), the same meanings as ^{R 1b1} and ^{R 1b2)}

^{(Wherein, R 1b1} and ^{R 1b2} is the formula in ^(1b), the same meanings as ^{R 1b1} and ^{R 1b2)}
In general formula (1c), each compound represented by the following general formula (1c-1)-general formula (1c-65) is preferable.

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2 Z 1c1} and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1, R 1c2, Z} 1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^1c1, R ^{1c2, Z} 1c2 and ^{A 1c3.)}

^{(Wherein, R 1c1,} R ^1c2 and ^{A 1c3} is the formula in ^(1c), the same meanings as R ^{1c1, R 1c2} and ^{A 1c3.)}
In general formula (1d), each compound represented by the following general formula (1d-1)-general formula (1d-35) is preferable.

(Wherein, R ^1d1 , R ^1d2 and Z ^1d2 have the same meanings as R ^1d1 , R ^1d2 and Z ^1d2 in the general formula (1d).)

(Wherein, R ^1d1 , R ^1d2 and Z ^1d2 have the same meanings as R ^1d1 , R ^1d2 and Z ^1d2 in the general formula (1d).)

(Wherein, R ^1d1 , R ^1d2 and Z ^1d2 have the same meanings as R ^1d1 , R ^1d2 and Z ^1d2 in the general formula (1d).)
In general formula (1e), each compound represented by the following general formula (1e-1)-general formula (1e-13) is preferable.

( ^Wherein , R ^1e1 , R ^1e2 and Z ^1e2 have the same meaning as R ^1e1 , R ^1e2 and Z ^1e2 in the general formula (1e))
The isomer of the Z-olefin derivative represented by the general formula (1) as an E-olefin derivative has Y ¹ in the general formula (1)

(The black dot in the formula represents an atom directly bonded to Y ¹ in A ¹ , A ² , Z ¹ , Z ² , R ¹ and R ^2. )
It represents a structure. Further, in the general formula (1), when R ¹ , R ² , Z ¹ and Z ² are a group having “—CH = CH—”, it is preferable that R ¹ , R ² , Z ¹ and Z ^{2 be} in the group "-CH = CH-" represents all E-forms.

  According to the method of the present invention, the mass ratio (E form / Z form) of E-olefin derivative to the mass of Z-olefin derivative is 80/20 or more, that is, the content of E-olefin derivative in olefin derivative is 80 mass% It can be raised above. The mass ratio of the E-olefin derivative to the mass of the Z-olefin derivative is preferably higher, preferably (E form / Z form) = 85/15 or more, and more preferably 90/10 or more. . The mass ratio (E form / Z form) of the E-olefin derivative to the mass of the Z-olefin derivative can be quantified by gas chromatography.

  Even if purification of the E / Z-olefin derivative composition is performed to remove the Z-olefin derivative remaining in the E / Z-olefin derivative composition after the isomerization reaction and obtain the target E-olefin derivative Good. The purification method may, for example, be chromatography, recrystallization, distillation, sublimation, reprecipitation, adsorption, liquid separation and the like. When a refining agent is used, silica gel, alumina, activated carbon, activated clay, celite, zeolite, mesoporous silica, carbon nano-horn, carbon nanohorn, bincho charcoal, charcoal, graphene, ion exchange resin, acid clay, silicon dioxide, diatomaceous earth, as a refining agent Perlite, cellulose, organic polymers, porous gels and the like can be mentioned. There is a problem that when such purification is repeated, the isolation yield of the E-olefin derivative decreases, but according to the method of the present invention, the isomerization reaction causes the E-olefin derivative to have a weight relative to the mass of the Z-olefin derivative. As the mass ratio can be further increased, the number of purifications can be reduced, and the yield of the E-olefin derivative can be improved.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.
The following abbreviations are used below.
Et: Ethyl group Pr: n-Propyl group Br: Bromo group For gas chromatography analysis, the following conditions were carried out.
Sample preparation: 1 mass% acetone solution column introduction amount: 1 μL
Device: GC 2010 (Shimadzu Corporation)
Column: J & W DB-17MS (30m x 0.25μm x 0.25mm)
Carrier gas: Nitrogen column pressure: (122 kPa), column flow rate: 1.06 mL / min, average velocity: 30.0 cm / sec
Split ratio: 50: 1
Injection temperature: 300 ° C, Detector temperature: (FID) 320 ° C
Column temperature setting: 100 ° C (1 min) → 10 ° C / min → 300 ° C (14 min)
EXAMPLE 1 Preparation of 1-Ethoxy-2,3-difluoro-4- [trans-4-((E) -1-propenyl) cyclohexylmethoxy] benzene Using Hydrochloric Acid as Acid

  E / Z olefin composition of 1-ethoxy-2,3-difluoro-4- [trans-4- (1-propenyl) cyclohexylmethoxy] benzene (81.5 g, E form / Z form = 6/94), benzene Sodium sulfinate (6.5 g) and toluene (200 mL) were mixed at room temperature and then heated to an internal temperature of 45 ° C. After adding 10% by mass hydrochloric acid (28.7 g) at an internal temperature of 45 ° C., the mixture was heated to an internal temperature of 85 ° C. over 15 minutes. The reaction mixture was analyzed by gas chromatography to find that E form / Z form = 87/13. The reaction solution is cooled to room temperature, water (100 mL) is added and the mixture is separated, and the organic layer is washed successively with water (100 mL), saturated aqueous sodium carbonate solution (100 mL) and saturated brine (100 mL), and anhydrous sodium sulfate Was added and dried. After filtering off sodium sulfate, the solution is concentrated and purified by silica gel column chromatography to obtain 1-ethoxy-2,3-difluoro-4- [trans-4- (1-propenyl) cyclohexylmethoxy] benzene E. / Z olefin composition (76.2 g, 93% yield, E form / Z form = 87/13) was obtained.

  Comparative Example 1 Preparation of 1-Ethoxy-2,3-difluoro-4- [trans-4-((E) -1-propenyl) cyclohexylmethoxy] benzene by Conventional Method

  E / Z olefin composition of 1-ethoxy-2,3-difluoro-4- [trans-4- (1-propenyl) cyclohexylmethoxy] benzene (1.0 g, E form / Z form = 6/94), benzene After sodium sulfinate (78 mg), toluene (2.5 mL) and 10% by mass hydrochloric acid (360 mg) were mixed at room temperature, the mixture was heated to an internal temperature of 85 ° C. and further stirred for 3 hours. The reaction mixture was analyzed by gas chromatography to find that E form / Z form = 78/22.

  EXAMPLE 2 Preparation of 1-ethoxy-2,3-difluoro-4- [trans-4-((E) -1-propenyl) cyclohexylmethoxy] benzene using acetic acid as acid

  E / Z olefin composition of 1-ethoxy-2,3-difluoro-4- [trans-4- (1-propenyl) cyclohexylmethoxy] benzene (89.7 g, E form / Z form = 6/94), benzene Sodium sulfinate (7.1 g) and toluene (225 mL) were mixed at room temperature and then heated to an internal temperature of 95 ° C. Acetic acid (45 mL) was slowly added at an internal temperature of 95 ° C, and the mixture was further stirred at 95 ° C for 3 hours. After cooling to room temperature, water (225 mL) is added and separated, and the organic layer is washed successively with water (225 mL), saturated aqueous sodium carbonate solution (225 mL) and saturated brine (225 mL), and anhydrous sodium sulfate is added It was dry. After filtering off sodium sulfate, the solution is concentrated and purified by silica gel column chromatography to obtain 1-ethoxy-2,3-difluoro-4- [trans-4- (1-propenyl) cyclohexylmethoxy] benzene E. / Z olefin composition (87.4 g, yield 97%, E form / Z form = 90/10) was obtained.

  EXAMPLE 3 Preparation of trans, trans-4- (4-Ethoxy-2,3-difluorophenyloxymethyl) -4 ‘-((E) -1-propenyl) bicyclohexyl

The isomerization reaction was carried out under the same conditions as in Example 2. The trans, trans-4- (4-ethoxy-2,3-difluorophenyloxymethyl) -4 ′-(1-propenyl) bicyclohexyl E was prepared. / Z olefin composition (48.6 g, yield 98%, E form / Z form = 83/17) was obtained.

  Example 4 Preparation of 1-Ethoxy-2,3-difluoro-4-((E) -2- (trans-4-propylcyclohexyl) vinyl) -benzene

  E / Z olefin composition of 1-ethoxy-2,3-difluoro-4-((E) -2- (trans-4-propylcyclohexyl) vinyl) -benzene (14.3 g, E form / Z form = 23 / 77), sodium benzenesulfinate (1.1 g) and toluene (45 mL) were mixed and heated to a temperature at which the solvent refluxed. After adding acetic acid (10 mL) under reflux, the mixture was further stirred for 2 hours. The reaction mixture was analyzed by gas chromatography to find that E form / Z form = 92/8. The subsequent treatment is carried out in the same manner as in Example 2 and E / Z olefin of 1-ethoxy-2,3-difluoro-4-((E) -2- (trans-4-propylcyclohexyl) vinyl) -benzene The composition (13.4 g, yield 94%, E form / Z form = 92/8) was obtained.

  Example 5 Preparation of trans-4-((E) -2- (trans-4-propylcyclohexyl) vinyl) propylcyclohexane

  E / Z olefin composition of trans-4- (2- (trans-4-propylcyclohexyl) vinyl) propylcyclohexane (10.0 g, E form / Z form = 12/88), acetic acid (10 mL) and toluene (30 mL) ) Were mixed and heated to 75.degree. Under heating, an aqueous solution of sodium benzenesulfinate (0.59 g) dissolved in water (3 mL) was added dropwise, and the mixture was stirred at a temperature at which the organic solvent refluxes for 5 hours. The reaction mixture was analyzed by gas chromatography to find that E form / Z form = 92/8. The subsequent treatments are carried out in the same manner as described in Example 2, and the E / Z olefin composition of trans-4-((E) -2- (trans-4-propylcyclohexyl) vinyl) propylcyclohexane ( 9.6 g, yield 96%, E form / Z form = 92/8) was obtained.

  Example 6 Preparation of 1,4-bis (4- (3- (E) -penten-1-yl) phenyl) -2,3-difluorobenzene

E / Z olefin composition of 1,4-bis (4- (3-penten-1-yl) phenyl) -2,3-difluorobenzene (95.3 g, E, E form / E, Z form / Z, Z body = 8/40/52), 11.7 g of sodium benzenesulfinate and toluene (475 mL) were mixed and heated to 95 ° C. While heating, acetic acid (45 mL) was added and stirred at 95 ° C. for additional 5 hours. The reaction solution was analyzed by gas chromatography to be E, E form / E, Z form / Z, Z form = 74/25/1. The subsequent treatment is carried out analogously to the method described in Example 2, E / I of 1,4-bis (4- (3- (E) -penten-1-yl) phenyl) -2,3-difluorobenzene. A Z-olefin body composition (96.7 g, quantitative yield, E, E form / E, Z form / Z, Z form = 74/25/1) was obtained.

  Example 7 Preparation of 2- (4- (3- (E) -Penten-1-yl) phenyl) -5,6,7-trifluoronaphthalene

Using 2- (4- (3-penten-1-yl) phenyl) -5,6,7-trifluoronaphthalene (5 g, E form / Z form = 13/87) as a starting material, the subsequent steps are carried out It carried out similarly to Example 6. The reaction mixture was analyzed by gas chromatography to find that E form / Z form = 90/10.

  Example 8 Preparation of trans-4- (1- (E) -propenyl) cyclohexanecarboxylic acid

  trans-4- (1-propenyl) cyclohexanecarboxylic acid (15 g, E form / Z form = 3/97) is dissolved in toluene (60 mL), sodium benzenesulfinate (9.5 g) at 90 ° C. The aqueous solution dissolved in 20 mL) was added slowly. After stirring at 90 ° C. for 3 hours, the reaction solution was analyzed by gas chromatography to be E / Z = 82/18.

  Example 9 Preparation of 4- (3- (E) -Penten-1-yl) bromobenzene

  4- (3-Penten-1-yl) bromobenzene (10 g, E form / Z form = 7/93) was used as a starting material, and the subsequent steps were carried out in the same manner as Example 1. The reaction solution was analyzed by gas chromatography to find that E form / Z form = 82/18.

Claims (4)

The isomerization reaction when a composition containing an E-olefin derivative and a Z-olefin derivative is contacted with an arylsulfinic acid for the first time is the following i) to iv)
i) A composition containing an E-olefin derivative and a Z-olefin derivative, an arylsulfinate and a solvent are mixed, and an acid is added under heating to produce an arylsulfinic acid, and ii) an E-olefin derivative and Z- A composition containing an olefin derivative, an acid and a solvent are mixed, and an aqueous solution of arylsulfinate is added under heating to generate an arylsulfinic acid, and iii) a composition containing an E-olefin derivative and a Z-olefin derivative and The solvents are mixed, and an aqueous solution of arylsulfinate and an arylsulfinic acid formed from an acid are added under heating, or an aqueous solution of arylsulfinate and an acid are simultaneously added under heating to form an arylsulfinic acid to form an arylsulfinic acid. Iv) E-olefin derivative having an acidic functional group Beauty Z- olefin derivatives mixed composition and a solvent containing, generate arylsulfinate added under heating arylsulfinate salt aqueous solution is performed by a method selected from the action,
The isomerized Z-olefin derivative is represented by the general formula (1)

(Wherein, R ¹ and R ² each independently represent a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a cyano group, a carboxy group or an alkyl group having 1 to 15 carbon atoms, 1 -CH ₂ -or 2 or more non-adjacent -CH ₂ -present in each is independently -O-, -S-, -COO-, -OCO-, -CO-,- CH = CH— or —C≡C—, which may be replaced, or —S ¹ —R ³ ,
S ¹ is a single bond or at least one type of linking group selected from the group consisting of an alkylene group having 1 to 4 carbon atoms,
R ³ represents a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, a cyano group, a carboxy group, a methanesulfonyloxy group, a p-toluenesulfonyloxy group or a trifluoromethanesulfonyloxy group,
A ¹ and A ² are each independently (a) 1,4-cyclohexylene group (one -CH _2- present in this group or two or more non-adjacent -CH _2- is- It may be replaced by O- or -S-))
(B) 1,4-phenylene group (one -CH = present in this group or two or more non-adjacent -CH = may be replaced by -N =, present in this group Hydrogen atoms may be substituted with fluorine atoms)
(C) Naphthalene-2,6-diyl group, 1,2,3,4-tetrahydronaphthalene-2,6-diyl group or decahydronaphthalene-2,6-diyl group (naphthalene-2,6-diyl group or One —CH = or two or more non-adjacent —CH = present in the 1,2,3,4-tetrahydronaphthalene-2,6-diyl group may be replaced by —N =, The hydrogen atom present in these groups may be substituted by a fluorine atom.)
A group selected from the group consisting of
Z ¹ and Z ² each independently represent a single bond or a linear alkylene group having 1 to 10 carbon atoms, and one —CH ₂ — or _two non-adjacent groups present in the alkylene group Each of the above -CH ₂ -may be independently replaced by -O-, -S-, -COO-, -OCO-, -CO-, -CH = CH- or -C≡C-, Z ^The hydrogen atom present in ¹ and Z ² may be substituted by a fluorine atom,
m ¹ and n ¹ each independently represent an integer of 0 to 5, while m ¹ + n ¹ represents 1 to 5,
Y ¹ is

(The black dot in the formula represents an atom directly bonded to Y ¹ in A ¹ , A ² , Z ¹ , Z ² , R ¹ and R ^2. )
Represents
When a plurality of A ¹ and A ² exist, they may be the same or different, and when a plurality of Z ¹ and Z ² exist, they may be the same or different. )
The manufacturing method of the olefin derivative composition whose content of the E-olefin derivative in an olefin derivative which is a compound represented by these is 80 mass% or more. The process according to claim 1, wherein the temperature at which the arylsulfinic acid is allowed to act is 45 ° C or higher. The sulfinate used is

The compound according to claim 1 or 2, wherein R represents a hydrogen atom, a chlorine atom, a bromine atom, a methyl group, a methoxy group or a nitro group, and X represents a sodium ion, a potassium ion or a lithium ion. The manufacturing method as described in any one. The production method according to any one of claims 1 to 3, wherein the acid used is hydrogen chloride, sulfuric acid, acetic acid, trifluoroacetic acid or an aqueous solution thereof.