JPH11171802A - Process for producing alkylbiphenyl derivatives and intermediates thereof - Google Patents

Abstract

(57) Abstract: A method for efficiently producing an alkylbiphenyl derivative by reducing a vinylbiphenyl derivative, and a novel vinylbiphenyl derivative as a raw material thereof. A vinyl biphenyl derivative is reduced to a general formula: [Wherein R ² represents a hydrogen atom or the like, and R ³ represents a formula-(X ¹ ) _p- (CH ₂ CH ₂ ) _q- (X ² ) _r- (CHR′CHR ″) _s -Z (formula Wherein X ¹ and X ² independently represent a single bond or -CH _2- ,
R ′ and R ″ are the same or different and are a hydrogen atom or an alkyl group, Z is a hydrogen atom, p is an integer of 0 to 10, and q, r and s are each independently an integer of 0 or 1. A represents a halogen atom, m represents an integer of 0 to 2, B represents a halogen atom or the like, and n represents an integer of 0 to 2.] It can be advantageously manufactured.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a liquid crystal material,
The present invention also relates to an industrially suitable production method of an alkylbiphenyl derivative useful as an intermediate material for fine chemicals such as pharmaceuticals and agricultural chemicals, and a novel production intermediate thereof.

[0002]

2. Description of the Related Art As a method for producing an alkylbiphenyl derivative, a method for converting a substituent already present on an alkylbiphenyl skeleton into a desired substituent is known.
A method in which a hydroxyiminomethyl group is converted to a cyano group by dehydration [Zh. Org. Khim. , Vol. 20, p. 1305 (1
984)], but this method requires a large number of steps to reach the alkylbiphenyl skeleton, and requires a large amount of metal hydroxide, which is expensive to dispose of. Comes with difficulties. Further, as a synthesis method by coupling between aryl groups, a method of dehalogenocoupling in the presence of triphenylphosphine and a reducing metal has been reported [JP-A-6-65153.
This method is not industrially advantageous because, for example, it is necessary to use a large excess of zinc powder, and homocoupling occurs and the selectivity of the reaction is not sufficient. Further, an organometallic compound, that is, an arylborane (European Patent Application Publication (EPA) 690046) and an arylsilane (Japanese Patent Application Laid-Open No. 6-239770) are prepared by converting a halobenzene into an organometallic compound in the presence of a palladium complex catalyst or a heavy metal such as manganese. There is known a method of coupling with an arylmagnesium [JP-A-8-109143] and the like. However, these methods use expensive raw materials and special catalysts, emit metal hydroxides that require a lot of disposal costs, and have many problems in industrial practice such as the yield is not always good. Holding a point.
Further, a method of synthesizing an alkylbiphenyl derivative for dehydrogenating an adduct obtained by a Diels-Alder reaction is known. As an example, a method by an addition reaction of a cinnamate with butadiene [Japanese Patent Laid-Open No. 9-87238] No.] can be given. However, all of these methods involve a large number of steps and a reaction with a low yield, which is not suitable for industrial practice. Further, as a method utilizing the Gomberg-Bachmann reaction, a method for synthesizing cyanobiphenyls in which alkylaniline (or cyanoaniline) is converted into a diazonium salt and coupled with benzonitrile (or alkylbenzene) [Japanese Patent Application Laid-Open No. 50-137963] is known. Are known. However, in these reactions, three isomers are generated due to the difference in the coupling position, and a large amount of tar-like substances are produced as by-products, so that the production rate of the desired cyanobiphenyls is low. Also, the separation of each isomer is difficult and not suitable for industrial practice.

[0003]

SUMMARY OF THE INVENTION In view of the above, it is an object of the present invention to provide a method for industrially producing a high-purity alkylbiphenyl derivative in a high yield and a novel intermediate for the production. is there.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, by subjecting a vinyl biphenyl derivative to reduction, a high-purity target alkyl biphenyl derivative can be obtained in good yield. As a result of further research, the present invention was completed. There has been no known method for producing an alkylbiphenyl derivative according to the method of the present invention, and the vinylbiphenyl derivative, which is a raw material of the method of the present invention, is a novel substance. That is, the present invention relates to (1) the general formula [I]

Embedded image [Wherein, R ¹ is a group represented by the formula-(X ¹ ) _p- (Y ¹ ) _q- (X ² ) _r- (Y ² ) _s -Z (X ¹ and X ^{2 each} independently represent a single bond or -CH _2- Y
¹ is

Embedded image Z represents a hydrogen atom or an alkyl group, and Z represents a hydrogen atom, a halogen atom, an aryl group which may be substituted, or a saturated hydrocarbon group. p is an integer of 0 to 10,
q, r and s each independently represent an integer of 0 or 1. )
Wherein R ² represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or a saturated hydrocarbon group, and A represents a halogen atom. m represents an integer of 0 to 2, and when m is 2, A may be different. B
Represents a halogen atom, an alkyl group optionally having a halogen atom, an alkoxy group optionally having a halogen atom, an acyl group, an alkoxycarbonyl group or a cyano group. n represents an integer of 0 to 2, and when n is 2, B
May be different. Wherein the vinyl biphenyl derivative represented by the general formula [I
I]

[0005]

Embedded image [Wherein R ³ is a group represented by the formula-(X ¹ ) _p- (CH ₂ CH ₂ ) _q- (X ² ) _r- (CHR′CHR ″) _s -Z (X ¹ , X ² , Z, R ′ , R ″, p, q, r and s are
The meaning is as defined above. ) Is represented by R ² , A, m,
B and n are as defined above. And a novel biphenyl derivative represented by the general formula [I], which is a raw material compound of the method of the present invention.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula [I], R ¹ is a group represented by the formula-(X ¹ ) _p- (Y ¹ ) _q- (X ² ) _r- (Y ² ) _s -Z (X ¹ and X ² independently represents a single bond or —CH ₂ —;
¹ is

Embedded image Z represents a hydrogen atom or an alkyl group, and Z represents a hydrogen atom, a halogen atom, an aryl group which may be substituted, or a saturated hydrocarbon group. p is an integer of 0 to 10,
q, r and s independently represent an integer of 0 or 1. And specific examples thereof include a hydrogen atom, a halogen atom, an aryl group which may be substituted, and a hydrocarbon group which may have an aryl group. Examples of the halogen atom represented by R ¹ include, for example, fluorine, chlorine, bromine, and iodine. Examples of the optionally substituted aryl group include, for example, a phenyl group, a 1-naphthyl group, and an alkyl-substituted phenyl group (for example, 4- Methylphenyl, 2-ethylphenyl, 3-isopropylphenyl, etc., alkoxy-substituted phenyl group (3-methoxyphenyl, etc.), halogen-substituted phenyl group (eg, 4-chlorophenyl, etc.), 4-methyl-
Examples thereof include a phenyl group or a naphthyl group having or not having a substituent such as a 1-naphthyl group.

The hydrocarbon group which may have an aryl group includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl,
_C1-13 alkyl or cycloalkyl groups such as cyclopentyl, hexyl, 3-methylpentyl, cyclohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, such as benzyl, 1-phenylethyl, 2-phenylethyl, _C7-10 aralkyl groups such as 3-phenylpropyl, for example vinyl, 1-
Propenyl, 1-butenyl, 2-methyl-1-propenyl, 1-pentenyl, 1,3-pentadienyl, 1-hexenyl, 1-cyclohexenyl, 1-heptenyl,
-C such as -octenyl, 3-nonenyl, 9-decenyl
_2-12 alkenyl group, for example C _8-10 phenyl-substituted alkenyl group such as styryl, such as ethynyl, 1-propynyl, 1-butynyl, 1-pentynyl, C _2-12 alkynyl groups such as 1-heptynyl, e.g. phenylethynyl, etc. A C _8-10 phenyl-substituted alkynyl group such as 3-
And C _4-12 alkenyl groups such as methyl-3-penten-1-yl.

In the above general formulas [I] and [II], R
² represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or a saturated hydrocarbon group. Examples of the halogen atom represented by R ² include, for example, fluorine, chlorine, bromine, and iodine. Examples of the optionally substituted aryl group include, for example, a phenyl group, a 1-naphthyl group, and an alkyl-substituted phenyl group (for example, 4- Methylphenyl,
2-ethylphenyl, 3-isopropylphenyl, etc.), alkoxy-substituted phenyl group (3-methoxyphenyl, etc.), halogen-substituted phenyl group (eg, 4-chlorophenyl, etc.), 4-methyl-1-naphthyl group, etc. A phenyl group or a naphthyl group or the like with or without a saturated hydrocarbon group such as methyl,
Ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl, octyl, nonyl,
C such as decyl, undecyl, dodecyl, tridecyl
_Examples thereof include a _1-13 alkyl group and a cycloalkyl group. In the general formula [II], R ³ represents a hydrogen atom, a halogen atom, an aryl group which may be substituted, or a saturated hydrocarbon group which may have an aryl group. Examples of the halogen atom represented by R ³ include, for example, fluorine, chlorine, bromine, and iodine. Examples of the optionally substituted aryl group include, for example, a phenyl group, a 1-naphthyl group, and an alkyl-substituted phenyl group (for example, 4- Substitution such as methylphenyl, 2-ethylphenyl, 3-isopropylphenyl), alkoxy-substituted phenyl group (eg, 3-methoxyphenyl), halogen-substituted phenyl group (eg, 4-chlorophenyl), 4-methyl-1-naphthyl group Examples of the saturated hydrocarbon group which may have an aryl group such as a phenyl group or a naphthyl group having or not having a group include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, Cyclopentyl, hexyl, 3-methylpentyl,
A C _1-13 alkyl or cycloalkyl group such as cyclohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, such as benzyl,
And C _7-10 aralkyl groups such as 1-phenylethyl, 2-phenylethyl, and 3-phenylpropyl.

In the general formulas [I] and [II], A represents a halogen atom such as fluorine, chlorine, bromine and iodine. In the above general formulas [I] and [II], B is a halogen atom such as fluorine, chlorine, bromine and iodine, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, te
alkyl groups such as rt-butyl, for example, haloalkyl groups such as trifluoromethyl, for example, alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, for example, haloalkoxy groups such as difluoromethoxy, 2-chloroethoxy, for example, acetyl, propionyl, Examples thereof include aliphatic acyl groups such as butyryl and the like, aromatic acyl groups such as benzoyl and p-chlorobenzoyl, and alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and isopropoxycarbonyl, and cyano groups.

The reduction in the method of the present invention can be carried out by homogeneous hydrogenation with an acetic acid catalyst or catalytic hydrogenation with a solid catalyst under normal pressure or pressure, or hydrogenation with diimide. Homogeneous hydrogenation using an acetic acid catalyst can be performed, for example, using chlorotris (triphenylphosphine) rhodium (I), chlorohydridotris (triphenylphosphine) ruthenium (II), hydridecarbonyltris (triphenylphosphine) iridium (I), Pentacyanocobalt (II) acetic acid, allene-tricarbonylchromium acetic acid, bis (cyclopentadienyl) dicarbonyltitanium and the like are used. The reaction temperature is usually -20 to 250C, preferably 0 to 4C.
0 ° C. The hydrogen pressure is appropriately selected from 1 to 300 atm in a range suitable for the reaction to be performed. The amount of catalyst used is
The molar ratio of the vinyl biphenyl derivative represented by the general formula [I] is 0.001 to 0.5, preferably 0.005 to 0.5.
0.05.

The catalytic hydrogenation with a solid catalyst is carried out by using a platinum-based catalyst such as platinum (IV) oxide, activated carbon with platinum or platinum black, a palladium-based catalyst such as activated carbon with palladium or barium carbonate with palladium, Raney nickel W- 1-8, nickel catalysts such as Urushibara nickel, cobalt catalysts such as reduced cobalt, copper catalysts such as reduced copper, chromium catalysts such as copper-chromium oxide, zinc-chromium oxide, rhodium with asbestos, colloid Rhodium-based catalysts such as rhodium, ruthenium oxide, ruthenium-based catalysts such as ruthenium-carbon, iridium with asbestos,
This is performed using an iridium-based catalyst such as colloid iridium. If necessary, hexachloroplatinic (IV) acid or the like as a co-catalyst, acids such as sulfuric acid, hydrochloric acid, acetic acid or the like, or bases such as sodium hydroxide or triethylamine as a promoter can be added. For control of the reaction, catalyst poisons such as pyridine and quinoline can be added as necessary. The hydrogen pressure of the reaction is from normal pressure to 300 atm, and the higher pressure is higher, the reaction is completed in a shorter time. However, from the viewpoint of operability, it is preferably from normal pressure to 50 atm, and the reaction temperature is −
The reaction can be carried out at 50 ° C to 350 ° C, but preferably 10 ° C to 50 ° C from the viewpoint of suppressing side reactions. The amount of the catalyst used is 0.5 to 150% of the vinyl biphenyl derivative [I].
1.0 to 10% in terms of weight and operability
Weight.

When the reduction in the process of the present invention is carried out by catalytic hydrogenation, it can be carried out without a solvent, but water, aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, benzene, toluene , Aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chlorobenzene, alcohols such as methanol, ethanol and ethylene glycol, ketones such as acetone and methyl ethyl ketone, diethyl ether and tetrahydrofuran , Dioxane, 1,2-dimethoxyethane, ethers such as 2-methoxyethyl ether, acids such as acetic acid and propionic acid, acid anhydrides such as acetic anhydride, esters such as ethyl acetate, dimethylformamide, dimethylacetamide Which amides, nitriles such as acetonitrile, or can be carried out in a solvent selected from these a mixture of two or more. The amount of the solvent used is 0.5 to 50% of the vinyl biphenyl derivative [I].
Double weight, preferably 1 to 20 times weight.

After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, the reaction solution can be filtered to remove the catalyst, and the filtrate can be concentrated to obtain a product. If necessary, the product can be purified by distillation, column chromatography, recrystallization or the like (Example 1).
23). The diimide used as a reducing agent in the method of the present invention can be obtained by oxidation of hydrazine, decomposition of azodicarboxylate, elimination reaction from N-sulfonylhydrazide, and the like. When this is used, the temperature of the reduction reaction is -20
To 120 ° C., and the required amount of the diimide is 2.0 to 20 times the molar amount of the vinyl biphenyl derivative [I]. As the solvent, water, methanol, ethanol, acetonitrile, or the like can be used.

The vinyl biphenyl derivative represented by the general formula [I], which is a raw material of the method of the present invention, is a novel compound,
General formula [1]

Embedded image [Wherein, A, m, B and n have the same meaning as described above. ]
Can be synthesized by using the methylbiphenyl derivative represented by

That is, the methylbiphenyl derivative represented by the general formula [1] is, for example, a compound represented by the general formula [i]

Embedded image [Wherein, A and m are as defined above. And a general formula (ii)

Embedded image [Wherein B and n have the same meanings as described above], and can be obtained by reacting with benzenes (see Reference Examples 1 to 12 and JP-A-9-176104).

Process for producing vinyl biphenyl derivative [I]

Embedded image

[0017]

Embedded image

[0018]

Embedded image

In each of the above formulas, X,
Y and W represent chlorine, bromine or iodine. R ¹ ,
R ² , A, m, B and n are as defined above. R ⁴ represents a lower alkyl group or a phenyl group. R ⁵
Represents a lower alkyl group which may be substituted with fluorine or a phenyl group. R ⁶ represents a lower alkyl group or a phenyl group. In the production method and the method, a benzyl halide derivative represented by the general formula [2] can be obtained by a halogenation reaction of a methylbiphenyl derivative represented by the general formula [1].

Examples of the halogenating agent used in the present halogenation reaction include chlorinating agents such as chlorine, sulfuryl chloride and N-chlorosuccinimide, bromine, N-bromosuccinimide, N-bromophthalimide and 1,3-dibromo-5. ,
Brominating agents such as 5-dimethylhydantoin and trichlorobromomethane, and iodinating agents such as tert-butyl hypoiodite are exemplified. Methyl biphenyl derivative [1]
Is usually 0.80 equivalent or more, preferably 0.90 to 1.3 equivalent. This halogenation reaction can be performed without solvent, but water, pentane, hexane, heptane, cyclohexane, aliphatic hydrocarbons such as methylcyclohexane, benzene, toluene, aromatic hydrocarbons such as xylene, dichloromethane, Halogenated hydrocarbons such as 1,2-dichloroethane and chlorobenzene, alcohols such as methanol, ethanol and ethylene glycol, ketones such as acetone and methyl ethyl ketone, diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and 2- Ethers such as methoxyethyl ether; acids such as acetic acid and propionic acid; esters such as ethyl acetate; amides such as dimethylformamide and dimethylacetamide; nitriles such as acetonitrile; It can be carried out in a solvent selected from mixtures of more. The amount of the solvent used is 0.50 to 50 times the weight of the methylbiphenyl derivative [1], preferably 1.0 to 50 times.
20 times the weight.

The halogenation reaction is carried out by light irradiation or a peroxide such as benzoyl peroxide or tert-butyl peroxide;
Good results can be obtained by adding a radical initiator such as 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2,2'-azobis (isobutyronitrile). The amount of the peroxide or the radical initiator used for the methylbiphenyl derivative [1] is as follows:
Usually, the molar ratio is 0.005 to 0.2%, preferably 0.01.
~ 0.1. The reaction temperature of this halogenation reaction is usually 30 to 170 ° C, preferably 50 to 90 ° C, and the reaction is usually completed in 10 minutes to 12 hours. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, pour the reaction solution into water and separate the organic layer, or extract with an extraction solvent such as toluene, ethyl acetate, ethyl ether, or 1,2-dichloroethane, and separate and concentrate the organic layer to obtain the product. Can be. If necessary, the product can be purified by distillation, column chromatography, recrystallization, or the like (Reference Examples 13 to 24).

In the production method, the benzylphosphonium salt represented by the general formula [3] can be obtained by reacting a benzyl halide derivative [2] with a phosphine derivative represented by the general formula [a]. Examples of the phosphine derivative [a] include trimethylphosphine, triethylphosphine, tripropylphosphine, tributylphosphine, and triphenylphosphine. This phosphonium salt formation reaction can be performed without solvent, but pentane, hexane, heptane, cyclohexane, aliphatic hydrocarbons such as methylcyclohexane,
Aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chlorobenzene, alcohols such as methanol, ethanol and ethylene glycol, ketones such as acetone and methyl ethyl ketone, and diethyl Ether, tetrahydrofuran, dioxane, 1,2-
Ethers such as dimethoxyethane and 2-methoxyethyl ether; acids such as acetic acid and propionic acid; esters such as ethyl acetate; amides such as dimethylformamide and dimethylacetamide; nitriles such as acetonitrile; It can be carried out in a solvent selected from the above mixture. The amount of the solvent used is 0.50 to 50 times the weight of the benzyl halide derivative [2].

For the benzyl halide derivative [2],
The charging ratio of the phosphine derivative [a] is usually 0.50 to
It is 3.0 moles, preferably 0.90 to 1.2 moles. The reaction temperature of the present phosphonium salt formation reaction is usually 3
The reaction temperature is 0 to 250 ° C, preferably 50 to 150 ° C, and the reaction is usually completed in 1 to 24 hours. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, it can be obtained by filtering the precipitated crystals after cooling and, if necessary, purifying them by washing with a solvent or recrystallization (Reference Examples 25 to 36). In the production method, the vinyl biphenyl derivative [I] can be obtained by an olefination reaction in which a benzylphosphonium salt [3] is reacted with a carbonyl compound represented by the general formula [b] in the presence of a base. As the carbonyl compound [b] in the present olefination reaction, benzaldehyde, 1
Aromatic aldehydes such as naphthalene carbaldehyde, 3-chlorobenzaldehyde and 4-methylbenzaldehyde, formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde, 2-methylbutanal, hexanal, heptanal, Cyclohexanecarbaldehyde, octanal, nonanal,
Decanal, undecanal, dodecanal, C _1-14 saturated aliphatic aldehydes such as tridecanal, phenylacetaldehyde, C _8-11 saturated aliphatic aldehydes having an aryl group such as 3-phenylpropionaldehyde,
Acrylaldehyde, propynal, crotonaldehyde, 2-pentenal, 3-methyl-2-butenal,
2-hexenal, 2,4-hexadienal, 2-heptenal, 2-octenal, 2-octynal, 2
- nonenal, 4-decenal, C _3-13 unsaturated aliphatic aldehydes such as 10 Undesenaru, cinnamaldehyde, C _9-11 unsaturated aliphatic aldehydes having an aryl group such as phenyl propargyl aldehyde, acetophenone, propiophenone, benzophenone And saturated or unsaturated aliphatic ketones such as acetone, ethyl ketone, methyl vinyl ketone, and 3-butyn-2-one. These carbonyl compounds [b] are known and easily available,
It can be synthesized by the method described in the literature [Reagents for Organic Synthesis, Vol. 4, p. 97 (1974)]. The charging ratio of the carbonyl compound [b] is 0.70 to 4.0 times mol, preferably 0.90 to 2.0 times mol of the benzylphosphonium salt [3].

In the present olefination reaction, aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, aromatic hydrocarbons such as benzene, toluene and xylene, methanol, ethanol,
Alcohols such as ethylene glycol, ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and 2-methoxyethyl ether; amides such as dimethylformamide and dimethylacetamide; dimethylsulfoxide; hexamethylphosphoramide; liquid The reaction can be performed in a solvent selected from ammonia or a mixture of two or more of these.
The amount of the solvent used is the same as that of the benzylphosphonium salt [3].
The weight is 0 to 50 times the weight, preferably 2.0 to 10 times the weight. The amount of the carbonyl compound [b] charged in the present olefination reaction is 0.70 to 4.0 times, preferably 0.90 to 1.3 times the mol of the benzylphosphonium salt [3]. This olefination reaction is performed in the presence of a base. Examples of the base used include alcoholates such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organometallic compounds such as methyllithium, butyllithium and phenyllithium; and inorganic bases such as lithium hydride, sodium hydride and sodium amide. And organic bases such as DBN. The charge ratio of the base was 0.1% of the benzylphosphonium salt [3].
It is 70 to 2 moles, preferably 0.90 to 1.2 moles.

In carrying out the present olefination reaction, first, a benzylphosphonium salt [3] is reacted with the above-mentioned base to give a compound of the general formula [7]

Embedded image [Wherein A, m, B, n and R ⁴ have the same meanings as described above], which is a reaction for obtaining benzylidenephosphorane (phosphorane formation reaction). In this phosphorane formation reaction, a base is added little by little to a mixture of a benzylphosphonium salt [3] and a solvent, or conversely, a mixture of a benzylphosphonium salt [3] with a powder or a solvent is added to a solution of the base. It may be performed according to a conventional method. In the present phosphorane-forming reaction, in order to suppress the decomposition of benzylidenephosphorane [7] to be formed, the above addition is usually carried out under cooling at a temperature of -100 to 60 ° C, preferably -40 to 20 ° C.
Performed at a temperature of ° C.

The condensation reaction for producing the vinyl biphenyl derivative [I] is carried out by mixing benzylidenephosphorane [7] produced by the phosphorane-forming reaction with the carbonyl compound [b]. The condensation reaction is usually carried out under cooling, usually at -40 to 60.
C., preferably at a temperature of 0 to 40C. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, by pouring the reaction solution into water or acidic water and separating the organic layer, or extracting with an extraction solvent such as toluene, ethyl acetate, ethyl ether, or 1,2-dichloroethane, separating and concentrating the organic layer, Also,
If necessary, it can be obtained by purification by distillation, column chromatography, recrystallization or the like (Examples 24 to 44). In the production method, the benzylphosphonate derivative represented by the general formula [4] can be obtained by reacting the benzyl halide derivative [2] with the phosphite derivative represented by the general formula [c]. Examples of the phosphite derivative [c] include trimethyl phosphite, triethyl phosphite, tris (2,2,2-trifluoroethyl) phosphite, tribenzyl phosphite, and triphenyl phosphite.

The present phosphite formation reaction can be carried out without a solvent, but aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, aromatic hydrocarbons such as benzene, toluene and xylene, Halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chlorobenzene, alcohols such as methanol, ethanol and ethylene glycol, ketones such as acetone and methyl ethyl ketone, diethyl ether, tetrahydrofuran and dioxane;
Ethers such as 1,2-dimethoxyethane and 2-methoxyethyl ether, acids such as acetic acid and propionic acid,
Esters such as ethyl acetate, dimethylformamide,
The reaction can be carried out in a solvent selected from amides such as dimethylacetamide, nitriles such as acetonitrile, or a mixture of two or more of these. The amount of the solvent used is 0.50 to 50 times the weight of the benzyl halide derivative [2]. For the benzyl halide derivative [2]
The charging ratio of the phosphite derivative [c] is usually 0.50.
The molar ratio is from 3.0 to 3.0 times, preferably from 0.90 to 1.2 times. The reaction temperature of the present phosphite formation reaction is usually 30 to
The reaction temperature is 250 ° C, preferably 50 to 150 ° C, and the reaction is usually completed in 1 to 24 hours.

After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, it can be obtained by evaporating low-boiling components from the reaction mixture under reduced pressure after cooling, and, if necessary, purifying the product by distillation, recrystallization or column chromatography (Reference Examples 37 to 37).
48). In the production method, the vinyl biphenyl derivative [I] can be obtained by a vinylation reaction in which a benzylphosphonate derivative [4] and a carbonyl compound [b] are reacted in the presence of a base. The charge ratio of the carbonyl compound [b] is 0.70 to 4.0 times mol, preferably 0.90 to 4.0 times the benzylphosphonate derivative [4].
It is 2.0 times mol. This vinylation reaction includes aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane, and methylcyclohexane; aromatic hydrocarbons such as benzene, toluene, and xylene; alcohols such as methanol, ethanol, and ethylene glycol; and diethyl ether. , Tetrahydrofuran, dioxane, 1,2-
In a solvent selected from dimethoxyethane, ethers such as 2-methoxyethyl ether, amides such as dimethylformamide and dimethylacetamide, dimethylsulfoxide, hexamethylphosphoramide, liquid ammonia, or a mixture of two or more of these. It can be carried out. The amount of the solvent to be used is 1.0 to 50 times, preferably 2.0 to 10 times the weight of the benzylphosphonate derivative [4].

This vinylation reaction is carried out in the presence of a base. As the base used, sodium methoxide,
Examples thereof include alcoholates such as sodium ethoxide and potassium tert-butoxide; organometallic compounds such as methyllithium, butyllithium and phenyllithium; and inorganic bases such as lithium hydride, sodium hydride and sodium amide. The charge ratio of the base is 0.70 to 2 times, preferably 0.90 to 1.2 times the mol of the benzylphosphonate derivative [4]. When carrying out the present vinylation reaction, first, a benzylphosphonate derivative [4]
And a base described above to obtain a phosphonate carbanion (anionization reaction). The anionization reaction is carried out using a benzylphosphonate derivative [4]
A conventional method may be used, such as adding the base little by little to the solution of the above, or conversely adding the benzylphosphonate derivative [4] or a solution thereof to the solution of the base. In this anionization reaction, the above addition is usually carried out under cooling, usually at -40 to 60, in order to suppress the decomposition of the generated phosphonate carbanion.
C., preferably at a temperature of -10 to 20C. The condensation reaction to produce the vinyl biphenyl derivative [I] in the next step is performed by mixing the phosphonate carbanion formed by the anionization reaction with the carbonyl compound [b]. This condensation reaction is carried out under cooling, usually at -40 to 60 ° C, preferably at 0 to 60 ° C.
Performed at a temperature of ４０40 ° C.

In this vinylation reaction, a mixture of a benzylphosphonate derivative [4] and a carbonyl compound [b] is added to a solution of a base, or a mixture of the benzylphosphonate derivative [4] and a carbonyl compound [b] is added. By adding a base to the solution of the mixture, the anionization reaction and the condensation reaction can be performed in parallel. The reaction temperature in this case is usually −40 to 80 ° C., preferably 20 to 70 ° C.
° C. In this case, the reaction is usually performed using a batch-type stirred tank reactor, but the accumulation and retention of heat-unstable phosphonate carbanions are performed using a multi-stage continuous stirred tank reactor. It is also industrially preferable to avoid this. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method.
For example, the reaction solution is poured into water or acidic water, the organic layer is separated or extracted with a solvent such as toluene, ethyl acetate, ethyl ether, or 1,2-dichloroethane, and the organic layer is separated and concentrated to obtain a product. be able to. If necessary, the product can be obtained by purifying the product by distillation, column chromatography, recrystallization, or the like (Examples 45 to 65).

In the production method, the benzal halide derivative represented by the general formula [5] can be obtained by a halogenation reaction of a methylbiphenyl derivative [1]. Examples of the halogenating agent used in the present halogenation reaction include chlorinating agents such as chlorine, sulfuryl chloride, N-chlorosuccinimide, bromine, N-bromosuccinimide, N-bromophthalimide, 1,3-dibromo-5,5- Brominating agents such as dimethylhydantoin and trichlorobromomethane; and iodinating agents such as tert-butyl hypoiodite. The charging ratio of the halogenating agent to the methylbiphenyl derivative [1] is usually 1.6 equivalents or more, preferably 1.8 equivalents.
~ 2.6 equivalents. This halogenation reaction can be performed without solvent, but water, pentane, hexane, heptane, cyclohexane, aliphatic hydrocarbons such as methylcyclohexane, benzene, toluene, aromatic hydrocarbons such as xylene, dichloromethane, Halogenated hydrocarbons such as 1,2-dichloroethane and chlorobenzene,
Alcohols such as methanol, ethanol and ethylene glycol; ketones such as acetone and methyl ethyl ketone; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and 2-methoxyethyl ether; acids such as acetic acid and propionic acid And esters such as ethyl acetate, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, or a mixture of two or more of these. The amount of the solvent used is 0.50 to 0.5% of the methylbiphenyl derivative [1].
The weight is 50 times, preferably 1.0 to 30 times the weight.

The halogenation reaction is carried out by light irradiation or a peroxide such as benzoyl peroxide or tert-butyl peroxide;
Good results can be obtained by adding a radical initiator such as 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2,2'-azobis (isobutyronitrile). The amount of the peroxide or the radical initiator used for the methylbiphenyl derivative [1] is as follows:
The molar ratio is usually 0.005 to 0.3, preferably 0.01 to 0.3.
It is 0.15. The reaction temperature of this halogenation reaction is usually 30 to 170 ° C, preferably 50 to 90 ° C, and the reaction time is usually 10 minutes to 12 hours. After completion of the reaction, the benzal halide derivative [5], which is a dihalogenated product,
It can be separated from other reaction products (monohalogen compound, trihalogen compound) and unreacted raw materials by a conventional method. For example, it can be obtained by evaporating the solvent from the reaction mixture under reduced pressure after cooling and, if necessary, purifying the product by distillation, column chromatography or recrystallization (Reference Examples 49 to 60). In the production method, the general formula [6]
Can be obtained by hydrolyzing a benzal halide derivative [5].

The present hydrolysis reaction can be carried out without a solvent. However, water, aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, and aromatic hydrocarbons such as benzene, toluene and xylene. , Dichloromethane, 1,2-dichloroethane, halogenated hydrocarbons such as chlorobenzene, methanol,
Alcohols such as ethanol and ethylene glycol,
Ketones such as acetone and methyl ethyl ketone, diethyl ether, tetrahydrofuran, dioxane, 1,2
Ethers such as dimethoxyethane and 2-methoxyethyl ether; acids such as acetic acid and propionic acid; esters such as ethyl acetate; amides such as dimethylformamide and dimethylacetamide; nitriles such as acetonitrile; It can be carried out in a solvent selected from a mixture of more than one species. The amount of the solvent used is 0.50 to 50 times the weight of the benzal halide derivative [5],
Preferably it is 1.0 to 20 times the weight. By performing the hydrolysis reaction in the presence of an acid or a base, effects such as shortening the reaction time and improving the yield can be obtained. As the acid, sulfuric acid, hydrochloric acid, inorganic acids such as hydrobromic acid, formic acid,
Organic acids such as acetic acid. Examples of the base include inorganic bases such as potassium hydroxide, sodium hydroxide, and potassium carbonate, and organic bases such as triethylamine. The amount of the acid or base used is 0.10 to 1.0 mol of the benzal halide derivative [5], and a large excess may be used in some cases. The reaction temperature of the present hydrolysis reaction is usually -10 to 200C, preferably 20 to 100C.
And the reaction time is usually 10 minutes to 24 hours. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, it can be obtained by filtering the precipitated crystals after cooling or, if necessary, purifying the product by distillation, column chromatography or recrystallization (Reference Examples 61 to 72).

In the production method, the vinyl biphenyl derivative [I] can be obtained by a Wittig reaction in which a benzaldehyde derivative [6] is reacted with a phosphonium salt represented by the general formula [d] in the presence of a base. Phosphonium salts [d] are described in the literature [Org. React., Vol. 14, 270
Page (1965)] or can be produced by the method described. The charging ratio of the phosphonium salt [d] is 0.70 to 4.0 times mol, preferably 0.90 to 1.3 times mol of the benzaldehyde derivative [6]. This Wittig reaction is carried out using aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, aromatic hydrocarbons such as benzene, toluene and xylene, methanol, ethanol,
Alcohols such as ethylene glycol, ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and 2-methoxyethyl ether; amides such as dimethylformamide and dimethylacetamide; dimethylsulfoxide; hexamethylphosphoramide; liquid The reaction can be performed in a solvent selected from ammonia or a mixture of two or more kinds. The amount of the solvent used is 1.0 to 50% of the benzaldehyde derivative [6].
Double weight, preferably 2.0 to 30 times weight.

The Wittig reaction is carried out in the presence of a base. Examples of the base used include alcoholates such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organometallic compounds such as methyllithium, butyllithium and phenyllithium; and inorganic bases such as lithium hydride, sodium hydride and sodium amide. And organic bases such as DBN. The charge ratio of the base was 0.70 to 2.70 for the phosphonium salt [d].
The molar amount is 0 times, preferably 0.90 to 1.2 times. When the present Wittig reaction is carried out, first, a phosphonium salt [d] is reacted with the above base to obtain a compound represented by the general formula [e] (R ⁶ ) ₃ P = CR ¹ R ² [e] wherein R ¹ , R ² and R ⁶ have the same meanings as described above] (iridination reaction). This iridation reaction may be carried out according to a conventional method such as adding a base little by little to a mixture of a phosphonium salt [d] and a solvent, or conversely adding a phosphonium salt [d] to a solution of a base. In the present ylide-forming reaction, the addition is usually carried out under cooling at a temperature of -100 to 60C, preferably at a temperature of -40 to 20 in order to suppress the decomposition of the generated phosphorus ylide [e].
Performed at a temperature of ° C.

The condensation reaction to produce the vinyl biphenyl derivative [I] is carried out by mixing phosphorus ylide [e] and a benzaldehyde derivative [6]. This condensation reaction is carried out at a temperature of usually -40 to 60C, preferably 0 to 40C under cooling. After completion of the reaction, the product can be isolated from the reaction mixture by a conventional method. For example, the reaction solution is poured into water or acidic water, the organic layer is separated or extracted with a solvent such as toluene, ethyl acetate, ethyl ether, or 1,2-dichloroethane, and the organic layer is separated and concentrated to obtain a product. be able to. Further, if necessary, the product can be obtained by purifying the product by distillation, column chromatography, recrystallization, or the like (Examples 66 to 83).

[0037]

The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. The vinyl biphenyl derivative [I] used as a raw material
Are described in Tables 5, 7 and 10 below. Example 1 (Production example of alkylbiphenyl derivative [II]) 4.50 g (18.2 mmol) of 4 '-(1-pentenyl) biphenyl-4-carbonitrile ([I] -1) was added to ethyl acetate 6
It was dissolved in 5.0 ml, and 0.30 g of 5% palladium carbon was added thereto. The mixture was stirred under a hydrogen stream at normal pressure and normal temperature. After the completion of hydrogen absorption, the catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the product 4.20.
g was obtained. This was purified by silica gel column chromatography (hexane: toluene = 1: 1) to give a purity of 96.6%.
(High performance liquid chromatography) 4'-pentylbiphenyl-4-carbonitrile [[Table 1], [II] -1]
3.29 g were obtained (yield 72.5%). IR νCN (NaCl, cm
^-1 ) 2227.1.

Examples 2 to 23 Reduction of vinyl biphenyl derivative [I] was carried out in the same manner as in Example 1 except that the raw material was changed to another vinyl biphenyl derivative [I] and the catalyst was changed to another catalyst. Examples of the production of the alkylbiphenyl derivative [II] according to Examples 2-2
No. 3 is described in [Table 1] together with Example 1.
In Table 1, Ph represents a phenyl group, Me represents a methyl group, Et represents an ethyl group, Pr represents a propyl group, and Bu represents a butyl group. The catalyst is 5% palladium on carbon, platinum (IV) oxide, and Raney nickel W-2.

[0039]

[Table 1]

Reference Examples 1 to 3 (Synthesis examples of methyl biphenyl derivative [1]) 97 g (1.1 mol) of isopentyl alcohol (3-methyl-1-butanol) and 83 g of sodium nitrite
To the mixture (1.2 mol), 120 ml of concentrated hydrochloric acid was added dropwise over 60 minutes while maintaining the temperature at 0 to 5 ° C with stirring. After stirring was continued for 10 minutes, the layers were separated, and the oil layer was washed with saturated aqueous sodium hydrogen carbonate to obtain a crude isopentyl nitrite product. Next, this was dissolved in 722 g (7 mol) of benzonitrile,
While maintaining the temperature at 5 to 70 ° C., the solution
A mixture of 107 g (1.0 mol) of toluidine and 309 g (3 mol) of benzonitrile was added over 2 hours.
Subsequently, distillation was carried out under reduced pressure to obtain 145 g of a fraction having a boiling point of 155 to 170 ° C./5 mmHg after distilling off benzonitrile. The distillate was analyzed by gas chromatography to find that its components were 4'-methylbiphenyl-2-carbonitrile,
4'-methylbiphenyl-3-carbonitrile and 4 '
-Methylbiphenyl-4-carbonitrile, the contents of which were 48%, 12% and 24%, respectively (yield: 3%).
6%, 9%, 18%). The fraction was further fractionated by a precision fractionator to separate the isomers. Each of the obtained isomer fractions (purity 97% or more (gas chromatography)) was recrystallized from methanol to give 4'-methylbiphenyl-4-
Carbonitrile [Table 2], [1] -1, boiling point 173-
174 ° C / 5mmHg, melting point 111.0 ° C, IR νCN (KBr, c
m ^-1 ) 2222.3, ¹ H-NMR (CDCl ₃ , δ ppm) 2.409 (3H, s) 7.
3 ■ 7.8 (8H, m)] and 4′-methylbiphenyl-2-carbonitrile [[Table 2], [1] -2], boiling point 155-1
56 ° C./5 mmHg, melting point 53.2 ° C., IR νCN (KBr, cm ⁻¹ ) 2222.1, ¹ H-NMR (CDCl ₃ , δ ppm) 2.421 (3H, s) 7.3 ■ 7.8 (8
H, m)], 4'-methylbiphenyl-3-carbonitrile
[[Table 2], [1] -3], boiling point 169-170 ° C / 5m
mHg, melting point 76.4 ° C., IR νCN (KBr, cm ⁻¹ ) 2226.1, ¹ H-NMR (CDCl ₃ , δ ppm) 2.400 (3H, s) 7.2 ■ 7.8 (8
H, m).

Reference Examples 4 to 12 Methyl biphenyl derivatives [1] were prepared in the same manner as in Reference Examples 1 to 3, except that the raw materials were changed to other toluidines [i] and to other benzenes [ii]. ] Together with Reference Examples 1 to 3 are shown in [Table 2]. In [Table 2],
Me represents a methyl group.

[Table 2]

Reference Example 13 (Synthesis example of benzyl halide derivative [2]) 200 g (1.03 mol) of 4'-methylbiphenyl-4-carbonitrile [[Table 2], [1] -1] was added to 1,2-dichloroethane The solution was dissolved in 1600 ml and 8.20 g (50.0 mmol) of 2,2'-azobis (isobutyronitrile) was added. While stirring, 166 g (1.04 mol) of bromine was added dropwise over 1 hour and 40 minutes while maintaining the reaction temperature at 80 ° C. Thereafter, the mixture was stirred at 80 ° C. for 5 hours and left at room temperature overnight. Transfer the reaction to a separatory funnel,
After water washing, liquid separation was performed. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 284 g of a product. This was recrystallized from toluene and hexane to give 46.6% purity (high performance liquid chromatography) of 4'-bromomethylbiphenyl-4.
-183 g of carbonitrile [Table 3], [2] -1, was obtained (yield 65.2%). This was recrystallized two more times using toluene and hexane. The purity of the crystal was 99.4% (high performance liquid chromatography), and the melting point was 107.2 to 108.2 ° C. ¹ H-NMR (CDCl ₃ , δ ppm) 4.55 (s, 2H), 7.30-7.80
(M, 8H).

Reference Examples 14 to 24 The same procedure as in Reference Example 13 was repeated except that the raw material was changed to another methylbiphenyl derivative [1] and the halogenating agent was changed to another halogenating agent. 2]
Are shown in Table 3 together with Reference Example 13 as Reference Examples 14 to 24. In Table 3, Me represents a methyl group, halogenating agent represents sulfuryl chloride, bromine, N-bromosuccinimide, and tert-butyl hypoiodite.

[Table 3]

Reference Example 25 (Synthesis example of benzylphosphonium salt [3]) 21.8 g (80.1 mmol) of 4'-bromomethylbiphenyl-4-carbonitrile [[Table 3], [2] -1] was added to xylene 80.0 The solution was dissolved in 80 ml at 80 ° C., and 21.0 g (80.1 mmol) of triphenylphosphine was added thereto. After this 2
After stirring for 8 hours, 80.0 ml of xylene was added, and the mixture was left overnight at room temperature. The precipitated powder was collected by filtration, washed with 80.0 ml of toluene and 80.0 ml of hexane, dried under reduced pressure, and dried at a purity of 98.4% (high performance liquid chromatography) 4- (4-cyanophenyl) benzyltriphenylphosphonium bromide [[Table 4],
[3] -1] 39.3 g was obtained (91.8% yield). 233.6-239.4 ° C. IR νCN (NaCl Nujol, cm ⁻¹ ) 2217.4. ¹ H-NMR (DMSO-d ₆ , δ ppm) 5.29 (d, 2H), 7.12 (dd, 2H),
7.66-8.00 (m, 21H).

Reference Examples 26 to 36 Reference Example 2 was repeated except that the raw material was changed to another benzyl halide derivative [2] and another phosphine derivative [a].
Synthesis examples of benzylphosphonium salt [3] performed in the same manner as in Example 5 are described in Table 4 together with Reference Example 25 as Reference Examples 26 to 36. In Table 4, Ph is a phenyl group, Me
Represents a methyl group, Et represents an ethyl group, Pr represents a propyl group, and Bu represents a butyl group. The phosphine derivative [a] represents triphenylphosphine, represents trimethylphosphine, represents triethylphosphine, represents tripropylphosphine, and represents tributylphosphine.

[0046]

[Table 4]

Example 24 (Production example of vinyl biphenyl derivative [I] by olefination reaction of benzylphosphonium salt [3] in the production method) 4- (4-cyanophenyl) benzyltriphenylphosphonium bromide [[Table 4] , [3] -1] 21.4 g (40.0
mmol) was suspended in 80.0 ml of dry tetrahydrofuran, and 25.0 ml of a 1.60 M solution of butyllithium in tetrahydrofuran was added thereto while stirring under a nitrogen stream.
The solution was added dropwise in 15 minutes while maintaining the temperature at 55 ° C. After stirring at 0 ° C for 30 minutes, a solution of 2.88 g (40.0 mmol) of butyraldehyde and 10.0 ml of tetrahydrofuran was added to the solution at 0 ° C over 5 minutes. Thereafter, the temperature was raised to room temperature and left overnight. 40.0 ml of water,
40.0 ml of ether was added to the reaction solution, and the mixture was separated. The ether layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 17.6 g of a product. This was purified by silica gel column chromatography (hexane: toluene = 1: 1) and purified.
97.4% (high performance liquid chromatography) of 4 '-(1-
Pentenyl) biphenyl-4-carbonitrile [[Table 5], [I] -1] 7.89 g was obtained (yield 79.8%). IR νCN (KBr, cm ^-1 ) 2229.0. ¹ H-NMR (CDCl ₃ , δ ppm) 0.93-1.01 (3H), 1.42-1.5
8 (2H), 2.19-2.44 (2H), 5.68-5.79, 6.24-6.47, 7.41-
7.73 (10H).

Examples 25 to 44 The same procedures as in Example 24, except that the starting material was changed to another benzylphosphonium salt [3], another carbonyl compound [b] was used, and the base was changed to another base. The synthesis example of the vinyl biphenyl derivative [I] performed in Example 25 together with the benzylphosphonium salt [3], the carbonyl compound [b] and the base used in Table 4 used as raw materials was used in Example 25.
The results are shown in Table 5 together with Example 24.
In Table 5, Ph represents a phenyl group, Me represents a methyl group, Et represents an ethyl group, Pr represents a propyl group, and Bu represents a butyl group. The base is butyl lithium, sodium methoxide,
Represents potassium tert-butoxide.

[0049]

[Table 5]

Reference Example 37 (Synthesis example of benzylphosphonate derivative [4]) 21.8 g (80.1 mmol) of 4'-bromomethylbiphenyl-4-carbonitrile [[Table 3], [2] -1] and triethylphosphonate A mixture of 13.3 g (80.0 mmol) of phyte was
The mixture was stirred at 91 ° C. under reflux for 16 hours. The low-boiling components were distilled off from the reaction solution under reduced pressure to obtain 27.0 g of a product. This was purified by silica gel column chromatography (toluene) to give a purity of 9
8.2% (high performance liquid chromatography) of diethyl 4-
19.5 g of (4-cyanophenyl) benzylphosphonate [[Table 6], [4] -1] was obtained (yield 73.9%). 73.4-76.0 ° C. IR νCN (NaCl Nujol, cm ^-1 ) 2225.2. ¹ H-NMR (CDCl ₃ , δ ppm) 1.28 (t, 6H), 3.21 (d, 2
H), 4.06 (dq, 4H), 7.40-7.74 (8H).

Reference Examples 38 to 48 A benzylphosphonate derivative prepared in the same manner as in Reference Example 37 except that the raw material was replaced with another benzyl halide derivative [2] and another phosphite derivative [c] was used. The synthesis examples of [4] were used together with the benzyl halide derivative [2] of [Table 3] used as a raw material and the phosphite derivative [c] used as reference materials as Reference Examples 38 to 48 [Table 6].
It describes in. In Table 6, Me represents a methyl group, Et represents an ethyl group, and Ph represents a phenyl group. The phosphite derivative [c] represents triphenyl phosphite, represents trimethyl phosphite, represents triethyl phosphite, and represents tris (2,2,2-trifluoroethyl) phosphite.

[0052]

[Table 6]

Example 45 (Production Example of Vinyl Biphenyl Derivative [I] by Vinylation Reaction of Benzylphosphonate Derivative [4] in Production Method) 1.60 g of sodium hydride (60% oil, 40.0 mmol)
l) was suspended in 80.0 ml of dry tetrahydrofuran. While stirring under a nitrogen stream, diethyl 4- (4-cyanophenyl) benzylphosphonate [[Table 6], [4]
-1] 13.2 g (40.1 mmol), butyraldehyde 2.88 g (40.0 mmol) and tetrahydrofuran 50.
0 ml of the solution was added in 15 minutes, keeping at 55-60 ° C.
After stirring at 55-60 ° C. for 30 minutes, the reaction solution was added with 40.0 m of water.
l, 40.0 ml of ether was added at 0-5 ° C, and the mixture was separated. The ether layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 9.70 g of a product. This was subjected to silica gel column chromatography (hexane: toluene = 1: 1).
To obtain 5.57 g of 4 '-(1-pentenyl) biphenyl-4-carbonitrile [[Table 7], [I] -1] having a purity of 98.2% (high performance liquid chromatography). Rate 56.1%). IR νCN (KBr, cm ^-1 ) 2229.0.

Examples 46 to 65 The starting materials were changed to other benzylphosphonate derivatives [4].
A benzylphosphonate derivative obtained by using a production example of a vinyl biphenyl derivative [I] in the same manner as in Example 45 except that the base was replaced with another base instead of the other carbonyl compound [b] was used as a raw material. [4], along with the carbonyl compound [b] and the base used,
Table 5 together with Example 45 are shown in Table 7. [Table 7]
Medium, Ph is a phenyl group, Me is a methyl group, Et is an ethyl group, Pr
Represents a propyl group, and Bu represents a butyl group. The base is sodium hydride, sodium methoxide, and potassium tert-butoxide.

[0055]

[Table 7]

Reference Example 49 (Synthesis Example of Benzal Halide Derivative [5]) 52.5 g (272 mmol) of 4'-methylbiphenyl-4-carbonitrile [[Table 2], [1] -1] was added to 230 ml of ethyl acetate.
1,2'-azobis (isobutyronitrile)
5.04 g (30.7 mmol) were added. A suspension of 100 g (350 mmol) of 1,3-dibromo-5,5-dimethylhydantoin in 1450 ml of ethyl acetate was added thereto at a reaction temperature of 75 ° C.
And added in 35 minutes. Thereafter, the mixture was stirred at 77 ° C. for 3 hours and left at room temperature overnight. Low boiling components were distilled off from the reaction solution under reduced pressure to obtain 152 g of a product. 880 ml of toluene was added thereto, and the mixture was stirred under reflux and filtered while hot. The filtrate was concentrated under reduced pressure to obtain 93.7 g of 4'-dibromomethylbiphenyl-4-carbonitrile [[Table 8], [5] -1] (yield 9).
8.2%).

Reference Examples 50 to 60 A benzal halide derivative was prepared in the same manner as in Reference Example 49 except that the raw material was changed to another methylbiphenyl derivative [1] and the halogenating agent was changed to another halogenating agent. The synthesis examples of [5] are referred to as Reference Examples 50 to 60 and Reference Example 49.
The results are shown in [Table 8]. In Table 8, Me represents a methyl group. The halogenating agent is sulfuryl chloride,
Represents bromine, represents 1,3-dibromo-5,5-dimethylhydantoin, and represents tert-butyl hypoiodite.

[0058]

[Table 8]

Reference Example 61 (Synthesis example of benzaldehyde derivative [6]) 4'-dibromomethylbiphenyl-4 obtained in Reference Example 49
-Carbonitrile [[Table 8], [5] -1] 93.7 g
(267 mmol), a mixture of 524 ml of water and 600 ml of acetic acid were stirred at 84 ° C. for 2 hours and then left at room temperature overnight. The precipitated crystals were collected by filtration and recrystallized from 300 ml of toluene to give 4'-purity of 97.7% (high performance liquid chromatography).
Formyl biphenyl-4-carbonitrile [[Table 9],
[6] -1] 39.6 g was obtained (yield 71.5%). 153.0-153.8 ° C. IR νCN (KBr, cm ^-1 ) 2224.2. ¹ H-NMR (DMSO-d ₆ , δ ppm) 7.96-8.10 (m, 8H), 10.0
9 (s, 1H). Reference Examples 62 to 72 Examples of synthesis of benzaldehyde derivatives [6] performed in the same manner as in Reference Example 61 except that the raw materials were changed to other benzal halide derivatives [5] are referred to as Reference Examples 62 to 72. It is described in [Table 9]. In Table 9, Me represents a methyl group.

[0060]

[Table 9]

Example 66 (Production Example of Vinyl Biphenyl Derivative [I] by Wittig Reaction of Benzaldehyde Derivative [6] in Production Method) 12.0 g of butyltriphenylphosphonium bromide (3
0.1 mmol) was suspended in 60.0 ml of dry tetrahydrofuran, and 20.0 ml of a 1.60 M solution of butyllithium in tetrahydrofuran was added thereto while stirring under a nitrogen stream, and the reaction temperature was kept at 0 to 5 ° C. while cooling. Dropped in minutes. 0 ° C
After stirring for 30 minutes, 4'-formylbiphenyl-4-carbonitrile [[Table 9], [6] -1] 6.21
g (30.0 mmol) and 58.0 ml of tetrahydrofuran in
C. and added in 5 minutes. Thereafter, the temperature was raised to room temperature and left overnight. 90.0 ml of water and 80.0 ml of ether were added to the reaction solution to carry out liquid separation. The ether layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 14.9 g of a product. This was purified by silica gel column chromatography (hexane: toluene = 1: 1), and 4 '-(1-pentenyl) biphenyl- having a purity of 97.9% (high-performance liquid chromatography) was used.
5.56 g of 4-carbonitrile [[Table 10], [I] -1]
Was obtained (yield 75.0%). IR νCN (KBr, cm ^-1 ) 2229.0. Examples 67 to 83 The same procedures as in Example 66 were carried out, except that the raw material was changed to another benzaldehyde derivative [6], another phosphonium salt [d] was used, and the base was changed to another base. Examples 67 to 8 were prepared by synthesizing the vinyl biphenyl derivative [I] together with the benzaldehyde derivative [6], the phosphonium salt [d] and the base used in Table 9 which were used as raw materials.
No. 3 is described in [Table 10] together with Example 66.
In Table 10, Ph represents a phenyl group, Me represents a methyl group, Et represents an ethyl group, Pr represents a propyl group, and Bu represents a butyl group. Also,
Base is butyllithium, sodium methoxide,
Represents sodium hydride.

[0062]

[Table 10]

[0063]

According to the present invention, by reducing the vinyl biphenyl derivative, the target alkyl biphenyl derivative having high purity can be obtained in good yield. Therefore, the method of the present invention is an industrially suitable method for industrially producing an alkyl biphenyl derivative. In addition, the novel vinyl biphenyl derivative, which is a production intermediate of the method of the present invention, is useful as a liquid crystal material itself and as an intermediate material for fine chemicals such as pharmaceuticals and agricultural chemicals.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 43/225 C07C 43/225 C 49/782 49/782 49/80 49/80 255/50 255/50 // C07B 61 / 00 300 C07B 61/00 300

Claims (3)

[Claims] 1. A compound of the general formula [I] [Wherein, R ¹ is a group represented by the formula-(X ¹ ) _p- (Y ¹ ) _q- (X ² ) _r- (Y ² ) _s -Z (X ¹ and X ^{2 each} independently represent a single bond or -CH _2- Y
¹ is Alternatively, Z represents an alkyl group, and Z represents a hydrogen atom, a halogen atom, an aryl group which may be substituted, or a saturated hydrocarbon group. p represents an integer of 0 to 10, and q, r and s each independently represent an integer of 0 or 1. R ² represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or a saturated hydrocarbon group, and A represents a halogen atom. m represents an integer of 0 to 2;
When A is 2, A may be different. B is a halogen atom, an alkyl group optionally having a halogen atom, an alkoxy group optionally having a halogen atom, an acyl group,
It represents an alkoxycarbonyl group or a cyano group. n is 0
And n is an integer of 2 and B may be different when n is 2. Wherein the vinyl biphenyl derivative represented by the general formula [II] is subjected to reduction. [Wherein, R ³ is a group represented by the formula-(X ¹ ) _p- (CH ₂ CH ₂ ) _q-
(X ² ) _r- (CHR′CHR ″) _s -Z (X ¹ , X ² , Z,
R ′, R ″, p, q, r and s have the same meanings as described above), and R ² , A, m, B and n have the same meanings as above. For producing alkyl biphenyl derivatives. 2. The method according to claim 1, wherein the reduction is catalytic reduction. 3. A compound of the general formula [I] [Wherein, R ¹ is a group represented by the formula-(X ¹ ) _p- (Y ¹ ) _q- (X ² ) _r- (Y ² ) _s -Z (X ¹ and X ^{2 each} independently represent a single bond or -CH _2- Y
¹ is Alternatively, Z represents an alkyl group, and Z represents a hydrogen atom, a halogen atom, an aryl group which may be substituted, or a saturated hydrocarbon group. p represents an integer of 0 to 10, and q, r and s each independently represent an integer of 0 or 1. R ² represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or a saturated hydrocarbon group, and A represents a halogen atom. m represents an integer of 0 to 2;
When A is 2, A may be different. B is a halogen atom, an alkyl group optionally having a halogen atom, an alkoxy group optionally having a halogen atom, an acyl group,
It represents an alkoxycarbonyl group or a cyano group. n is 0
And n is an integer of 2 and B may be different when n is 2. ] The vinyl biphenyl derivative represented by these.