JP2022169148A - Method for producing α-trifluoromethylstyrene compound - Google Patents

Abstract

To provide a method that can produce an α-trifluoromethylstyrene compound (2) by a process suitable for industrial production.SOLUTION: This invention relates to a method for producing an α-trifluoromethylstyrene compound (2) including the step in which, in the presence of an organic transition metal catalyst including a transition metal selected from nickel, palladium, platinum, rhodium, ruthenium and cobalt, an organometallic phenyl compound (1) is reacted with 2-chloro-3,3,3-trifluoro-1-propene. [In the formula, each symbol is as described in the specifications].SELECTED DRAWING: None

Description

The present invention relates to a method for producing an α-trifluoromethylstyrene compound.

An α-trifluoromethylstyrene compound is a useful compound as a synthetic intermediate for pharmaceuticals, agricultural chemicals, etc. (Patent Document 1).
As a method for producing an α-trifluoromethylstyrene compound, for example, Patent Document 1 discloses that 3,5-dichlorophenylboronic acid and 2-bromo-3,3,3-trifluoromethyl-1-propene are combined with dichlorobis The reaction in the presence of (triphenylphosphine)palladium(II) and potassium carbonate to synthesize 1,3-dichloro-5-(1-trifluoromethylvinyl)benzene is disclosed.
Further, in Patent Document 2, a Grignard reagent prepared from 3,5-dichloro-1-bromobenzene and magnesium is reacted with ethyltrifluoroacetate to give 3′,5′-dichloro-2,2,2- 1,3-Dichloro-5-(1-trifluoromethylvinyl)benzene can be synthesized by obtaining trifluoroacetophenone and then reacting the compound with methyltriphenylphosphonium iodide in the presence of potassium tert-butoxy. disclosed.

Furthermore, in Non-Patent Document 1, 2-chloro-3,3,3-trifluoro-1-propene and various substituted phenylboronic acids are reacted in the presence of various palladium catalysts to give α-tri Synthesizing fluoromethylstyrene compounds is disclosed. Among them, the reaction with dichlorobis(triphenylphosphine)palladium (II) in the presence of the following ligand (1-(2-methoxyphenyl)-2-(dicyclohexylphosphino)pyrrole) gives a relatively good yield. It is disclosed that it can be manufactured.

WO2005/085216 WO2010/125130

Tetrahedron, 72 (2016), 5684-5690

However, in the method of Patent Document 1, the starting material, 2-bromo-3,3,3-trifluoro-1-propene, is a hazardous substance (H341: Suspected of causing hereditary disease). The method is not a safe manufacturing method.
In addition, in the method of Patent Document 2, triphenylphosphine oxide is by-produced together with the desired product in the above Wittig reaction, and it is difficult to remove this triphenylphosphine oxide. Furthermore, since it is a two-step production, it cannot be said to be a simple method.
Furthermore, in the method of Non-Patent Document 1, the ligand is difficult to obtain and expensive, so the method is not satisfactory in terms of cost and raw material availability.
Thus, neither method can be said to be an industrially suitable method.

An object of the present invention is to provide a method for producing an α-trifluoromethylstyrene compound by a method suitable for industrial production.

The present inventors have made intensive studies to solve the above problems. We have found that the desired α-trifluoromethylstyrene compound can be produced in a safe, inexpensive, and simple manner by reacting it with a specific organometallic phenyl compound without producing by-products that are difficult to remove. I have perfected my invention.

That is, the present invention is as follows.
[1] Organometallic phenyl compound (1) and 2-chloro-3,3,3-trifluoro in the presence of an organotransition metal catalyst comprising a transition metal selected from nickel, palladium, platinum, rhodium, ruthenium and cobalt. -A method for producing an α-trifluoromethylstyrene compound (2), comprising a step of reacting with 1-propene.

[In the formula,
M is a borono group (-B(OH) ₂ ), its ester group or its amide group, -BF ₃ M ¹ (wherein M ¹ represents an alkali metal), -B(OR ^a ) ₃ M ² (wherein R ^a represents a C _1-6 alkyl group and M ² represents an alkali metal), —MgX ¹ (wherein X ¹ represents a halogen atom), —SiX ² ₃ (wherein X ² independently represents a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group or Ar), —ZnX ³ (wherein X ³ is a halogen atom or represents Ar), or -SnX ⁴ ₃ (wherein X ⁴ independently represents a halogen atom, a C _1-4 alkyl group or Ar);
X represents a halogen atom;
R ¹ and R ² each independently represent a hydrogen atom or a substituent, at least one of which is a substituent;
Ar is

where * represents the binding site with M. ]

[2] The production method according to [1] above, wherein the organic transition metal catalyst is an organic palladium complex.
[3] The production method according to [1] above, wherein the organic transition metal catalyst is a complex containing an N-heterocyclic carbene ligand.
[4] The production method according to any one of [1] to [3] above, wherein the organic transition metal catalyst is added to the reaction system or prepared in the reaction system.

[5] The production method according to any one of [1] to [4] above, wherein M in the organometallic phenyl compound (1) is a borono group or an ester group thereof, and the reaction is carried out in the presence of a base. .

According to the production method of the present invention, the α-trifluoromethylstyrene compound (2) can be produced in a safe, inexpensive, and convenient manner without producing by-products that are difficult to remove. It is a very useful method suitable for industrial production.

Definitions of groups used in the present specification are described in detail below. Unless otherwise stated, the groups have the following definitions.

In this specification, compounds represented by formulas are indicated by adding formula numbers to "compounds". For example, the compound represented by formula (1) is shown as "compound (1)".
In the present specification, a numerical range represented by "-" or "-" means a numerical range whose lower limit or upper limit is the number before and after "-" or "-".
In the present specification, when the element symbol "C" is assigned a numerical range with numbers before and after "-" and is attached to the name of any group, the numbers before and after "-" are the lower limit or an arbitrary group having an integer number of carbon atoms as the upper limit, respectively. For example, an alkyl group having 1 to 3 carbon atoms is sometimes indicated as a "C _1-3 alkyl group", which means -CH ₃ , -C ₂ H ₅ , -C ₃ H ₇ and the like, respectively. is shown. The same applies to other groups.

As used herein, "alkali metal" means lithium, sodium and potassium.

As used herein, "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

As used herein, the term “C _1-4 alkyl group” means a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms. The “C _1-4 alkyl group” includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, preferably a C _1-2 alkyl group.

As used herein, a “C _1-4 alkoxy group” means a group represented by the formula R ¹¹ O— (wherein R ¹¹ represents a C _1-4 alkyl group). The “C _1-4 alkoxy group” includes methoxy, ethoxy, propoxy, isopropoxy, butyloxy, isobutyloxy, sec-butyloxy and tert-butyloxy.

As used herein, a “C _1-4 haloalkyl group” means a group in which one or more hydrogen atoms in the “C _1-4 alkyl group” are substituted with halogen atoms. Examples of "C _1-4 haloalkyl group" include fluoromethyl, 2-fluoroethyl, 3-fluoropropyl, 4-fluorobutyl, trifluoromethyl, difluoromethyl, perfluoroethyl, perfluoropropyl, chloromethyl, 2-chloroethyl , bromomethyl, 2-bromoethyl, iodomethyl, 2-iodoethyl and the like, with trifluoromethyl being preferred.

As used herein, the “C _1-4 haloalkoxy group” means a group in which one or more hydrogen atoms in the “C _1-4 alkoxy group” are substituted with halogen atoms. Examples of the "C _1-4 haloalkoxy group" include bromomethoxy, 2-bromoethoxy, 3-bromopropoxy, 4-bromobutoxy, iodomethoxy, 2-iodoethoxy, 3-iodopropoxy, 4-iodobutoxy, fluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, tribromomethoxy, trichloromethoxy, trifluoromethoxy, difluoromethoxy, perfluoroethoxy, perfluoropropoxy, perfluoroisopropoxy, 1,1,2,2- Tetrafluoroethoxy, 2-chloro-1,1,2-trifluoroethoxy.

As used herein, “C _3-8 cycloalkyl group” means a cyclic saturated hydrocarbon group having 3 to 8 carbon atoms. The “C _3-8 cycloalkyl group” includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

As used herein, “C _6-10 aryl group” means a hydrocarbon group having 6 to 10 carbon atoms and having aromaticity. The “C _6-10 aryl group” includes phenyl, 1-naphthyl and 2-naphthyl, with phenyl being preferred.

In the present specification, a “C _7-14 aralkyl group” means a “C _1-4 alkyl group” substituted with a “C _6-10 aryl group”. The “C _7-14 aralkyl group” includes benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, (1-naphthyl)methyl, (2-naphthyl)methyl and the like. , benzyl are preferred.

As used herein, the term “C _3-8 cycloalkyloxy group” means a group represented by the formula R ¹² O— (wherein R ¹² represents a C _3-8 cycloalkyl group). . The “C _3-8 cycloalkyloxy group” includes cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and cyclooctyloxy.

As used herein, a “C _6-10 aryloxy group” means a group represented by the formula R ¹³ O— (wherein R ¹³ represents a C _6-10 aryl group). The “C _6-10 aryloxy group” includes phenoxy, 1-naphthyloxy and 2-naphthyloxy, with phenoxy being preferred.

As used herein, a “C _7-14 aralkyloxy group” means a group represented by the formula R ¹⁴ O— (wherein R ¹⁴ represents a C _7-14 aralkyl group). The "C _7-14 aralkyloxy group" includes benzyloxy, 1-phenylethyloxy, 2-phenylethyloxy, 3-phenylpropyloxy, 4-phenylbutyloxy, (1-naphthyl)methyloxy, (2- naphthyl)methyloxy and the like, with benzyloxy being preferred.

As used herein, the term "C _1-4 alkyl-carbonyl group" refers to a group represented by the formula R ¹⁵ C(O)- (wherein R ¹⁵ represents a C _1-4 alkyl group) means. The “C _1-4 alkyl-carbonyl group” includes acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 3-methylbutanoyl, 2-methylbutanoyl, 2,2-dimethylpropanoyl.

As used herein, the term "C _1-4 alkoxy-carbonyl group" refers to a group represented by the formula R ¹⁶ OC(O)- (wherein R ¹⁶ represents a C _1-4 alkyl group). means. The “C _1-4 alkoxy-carbonyl group” includes methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, tert-butyloxycarbonyl.

The manufacturing method of the present invention will be described in detail below.
The production method of the present invention comprises an organometallic phenyl compound (1) in the presence of an organotransition metal catalyst containing a transition metal selected from nickel, palladium, platinum, rhodium, ruthenium and cobalt and in the absence of an oxidizing agent. and 2-chloro-3,3,3-trifluoro-1-propene.

[In the formula,
M is a borono group (-B(OH) ₂ ), its ester group or its amide group, -BF ₃ M ¹ (wherein M ¹ represents an alkali metal), -B(OR ^a ) ₃ M ² (wherein R ^a represents a C _1-6 alkyl group and M ² represents an alkali metal), —MgX ¹ (wherein X ¹ represents a halogen atom), —SiX ² ₃ (wherein X ² independently represents a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group or Ar), —ZnX ³ (wherein X ³ is a halogen atom or represents Ar), or -SnX ⁴ ₃ (wherein X ⁴ independently represents a halogen atom, a C _1-4 alkyl group or Ar);
X represents a halogen atom;
R ¹ and R ² each independently represent a hydrogen atom or a substituent, at least one of which is a substituent;
Ar is

where * represents the binding site with M. ]
In the above formula, X ¹ is preferably a bromine atom, a chlorine atom or an iodine atom, more preferably a bromine atom or a chlorine atom, particularly preferably a bromine atom.
^In the above formula, X2 is preferably a methoxy group, an ethoxy group or a fluoro group.
^In the above formula, X3 is preferably a chloro group or Ar.
^In the above formula, X4 is preferably an alkyl group, particularly preferably a butyl group.
The "ester group of borono group" represented by M includes the following groups.

[In the formula, * represents a bonding position with a benzene ring, and R ^b represents a C _1-6 alkyl group (preferably methyl or ethyl). ]
The "amide group of borono group" represented by M includes the following groups.

[In the formula, * has the same meaning as described above. ]
“-B(OR ^a ) ₃ M ² ” represented by M is specifically represented as follows.

[Each symbol in the formula has the same meaning as described above. ]
R ^a is preferably methyl, ethyl or isopropyl.
“—B(OR ^a ) ₃ M ² ” may be the following group such that three R ^a are attached.

[Each symbol in the formula has the same meaning as described above. ]
When M is a borono group, it may be a trimer as follows.

[In the formula, * has the same meaning as described above. ]
M is preferably a borono group or an ester group thereof, more preferably a borono group.

X is preferably a fluorine atom or a chlorine atom, more preferably a chlorine atom.

The "substituent" represented by R ¹ or R ² includes a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a C _1-4 haloalkyl group, a C _1-4 haloalkoxy group, and a cyano group. , nitro group, formyl group, C _3-8 cycloalkyl group, C _6-10 aryl group, C _7-14 aralkyl group, C _3-8 cycloalkyloxy group, C _6-10 aryloxy group, C _7-14 1 to 3 groups are selected from an aralkyloxy group, a C _1-4 alkyl-carbonyl group, a C _1-4 alkoxy-carbonyl group and the like. Preferably, 1 to 3 are selected from halogen atoms and cyano groups.
R ¹ is preferably a hydrogen atom or a halogen atom, more preferably a hydrogen atom or a chlorine atom.
R ² is preferably a hydrogen atom, a halogen atom or a cyano group, more preferably a hydrogen atom, a fluorine atom, a chlorine atom or a cyano group.

The organometallic phenyl compound (1) used in the present invention is preferably an organometallic phenyl compound (1) in which M is a borono group or an ester group thereof (hereinafter also referred to as a phenylboronic acid compound).
More preferred are phenylboronic acid compounds in which R ¹ is a hydrogen atom or a halogen atom and R ² is a hydrogen atom, a halogen atom, or a cyano group.
More preferred are phenylboronic acid compounds in which R ¹ is a hydrogen atom or a chlorine atom and R ² is a hydrogen atom, a fluorine atom, a chlorine atom or a cyano group.

As the organometallic phenyl compound (1), a commercially available product may be used, or it may be produced by a method known per se.

2-Chloro-3,3,3-trifluoro-1-propene used in the present invention is a gas with a boiling point of about 15° C. and is commercially available.
The amount of 2-chloro-3,3,3-trifluoro-1-propene to be used is generally 0.1-100 mol, preferably 0.5-10 mol, per 1 mol of organometallic phenyl compound (1). Mole.

The reaction between organometallic phenyl compound (1) and 2-chloro-3,3,3-trifluoro-1-propene is carried out in the presence of an organotransition metal catalyst.
The organotransition metal catalysts used in the present invention are organotransition metal catalysts containing a transition metal selected from nickel, palladium, platinum, rhodium, ruthenium and cobalt. The transition metal is preferably selected from nickel and palladium.
Suitable organotransition metal catalysts include organonickel complexes and organopalladium complexes.
The organonickel complexes and organopalladium complexes may be added to the reaction system as reagents or may be prepared in the reaction system.

The organic palladium complex is a zero-valent palladium complex; a zero-valent palladium complex produced in a reaction system from a II-valent palladium complex; A complex obtained by mixing with at least one compound (ligand) can be mentioned.

Examples of the zerovalent palladium complex include Pd ₂ (dba) ₃ (dba is dibenzylideneacetone), Pd ₂ (dba) ₃ chloroform complex, Pd ₂ (dba) ₃ benzene complex, Pd(dba) ₂ , Pd(COD ) ₂ (COD is cycloocta-1,5-diene), Pd(DPPE) (DPPE is 1,2-bisdiphenylphosphinoethane), Pd(PCy ₃ ) ₂ (Cy is a cyclohexyl group), Pd(Pt-Bu ₃ ) ₂ (t-Bu is t-butyl group), Pd(PPh ₃ ) ₄ (Ph is phenyl group) and the like.

IIvalent palladium complexes include, for example, palladium chloride, palladium bromide, palladium acetate, bis(acetylacetonato)palladium(II), dichloro(η ⁴ -1,5-cyclooctadiene)palladium(II), or these and complexes in which phosphine ligands such as triphenylphosphine and N-heterocyclic carbene ligands such as 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene are coordinated. These divalent palladium complexes are reduced, for example, by reducing species (phosphine, zinc, organometallic reagents, etc.) coexisting in the reaction system and converted to zerovalent palladium complexes.

The above zerovalent palladium complex or the zerovalent palladium complex produced by reduction in the reaction system from the IIvalent palladium complex is a diketone, phosphine, diamine, bipyridyl, N-heterocyclic It can also be converted into a zerovalent palladium complex that participates in the reaction by acting with a compound (ligand) such as carbene. It is not always clear how many of these ligands are coordinated to the zerovalent palladium complex in the reaction system. The zerovalent palladium complex produced in the reaction system preferably has high stability, and preferably has a ligand such as phosphine, diamine, bipyridyl, N-heterocyclic carbene.

Examples of diketones include β-diketones such as acetylacetone, 1-phenyl-1,3-butanedione and 1,3-diphenylpropanedione.
Preferred phosphines are trialkylphosphines. Specific examples of trialkylphosphine include tricyclohexylphosphine, triisopropylphosphine, tri-t-butylphosphine, triadamantylphosphine, tricyclopentylphosphine, di-t-butylmethylphosphine, and tribicyclo[2,2,2]octylphosphine. , tri(C _3-20 alkyl)phosphines such as trinorbornylphosphine. In addition to this, bidentate ligands such as 1,2-bis(dicyclohexylphosphino)ethane are also effective.
Diamines include tetramethylethylenediamine, 1,2-diphenylethylenediamine, and the like.
N-heterocyclic carbenes include 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, 1,3-dimesitylimidazol-2-ylidene, 1,3-dicyclohexylimidazol-2-ylidene , 1,3-diisopropylimidazol-2-ylidene, 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene, 1,3-dimesitylimidazolidin-2-ylidene and the like.
Among these ligands, phosphines and N-heterocyclic carbenes are preferred, trialkylphosphines and N-heterocyclic carbenes are preferred, and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene is particularly preferred. preferable. Since 2-chloro-3,3,3-trifluoro-1-propene is less reactive than other fluorine-containing olefins, it is bulky and has high electron-donating ability like N-heterocyclic carbene. The desired α-trifluoromethylstyrene compound (2) can be obtained with a higher yield by using a palladium complex having a group.
Palladium complexes having such N-heterocyclic carbene ligands include [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride. preferable.

The organic nickel complex is a zero-valent nickel complex; a zero-valent nickel complex generated in a reaction system from a II-valent nickel complex; or selected from the group consisting of diketones, phosphines, diamines, bipyridyls and N-heterocyclic carbenes. A complex obtained by mixing with at least one compound (ligand) can be mentioned.

Examples of the zerovalent nickel complex include Ni(COD) ₂ , Ni(CDD) ₂ (CDD is cyclodeca-1,5-diene), and Ni(CDT) ₂ (CDT is cyclodeca-1,5,9-triene). , Ni(VCH) ₂ (VCH is 4-vinylcyclohexene), Ni(CO) ₄ , (PCy ₃ ) ₂ Ni—N≡N—Ni(PCy ₃ ) ₂ , Ni(PPh ₃ ) ₄ and the like.

Examples of divalent nickel complexes include nickel chloride, nickel bromide, nickel acetate, bis(acetylacetonato)nickel (II) which may be coordinated with water molecules or solvents, or phosphines such as triphenylphosphine and these. Complexes in which ligands and N-heterocyclic carbene ligands such as 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene are coordinated are included. These II-valent nickel complexes are reduced, for example, by reducing species (phosphine, zinc, organometallic reagents, etc.) coexisting in the reaction system and converted to zero-valent nickel complexes.

The zero-valent nickel complex produced by reduction in the reaction system from the above-mentioned zero-valent nickel complex or II-valent nickel complex acts with ligands added as necessary in the reaction system to participate in the reaction. It can also be converted into a valent nickel complex. It is not always clear how many of these ligands are coordinated to the zero-valent nickel complex in the reaction system. The zerovalent nickel complex produced in the reaction system preferably has high stability, and preferably has a ligand such as phosphine, diamine, bipyridyl and N-heterocyclic carbene.

Examples of diketones include β-diketones such as acetylacetone, 1-phenyl-1,3-butanedione and 1,3-diphenylpropanedione.
Preferred phosphines are trialkylphosphines and triarylphosphines. Specific examples of trialkylphosphine include tricyclohexylphosphine, triisopropylphosphine, tri-t-butylphosphine, triadamantylphosphine, tricyclopentylphosphine, di-t-butylmethylphosphine, and tribicyclo[2,2,2]octylphosphine. , tri(C _3-20 alkyl)phosphines such as trinorbornylphosphine. Specific examples of triarylphosphines include tri(monocyclic aryl)phosphines such as triphenylphosphine, trimesitylphosphine and tri(o-tolyl)phosphine. Besides these, bidentate ligands such as 1,2-bis(dicyclohexylphosphino)ethane and 1,1'-bis(diphenylphosphino)ferrocene are also effective. Among these, triphenylphosphine, tricyclohexylphosphine, tri-t-butylphosphine and triisopropylphosphine are preferred.
Diamines include tetramethylethylenediamine, 1,2-diphenylethylenediamine, and the like.
N-heterocyclic carbenes include 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, 1,3-dimesitylimidazol-2-ylidene, 1,3-dicyclohexylimidazol-2-ylidene , 1,3-diisopropylimidazol-2-ylidene, 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene, 1,3-dimesitylimidazolidin-2-ylidene and the like.
Among these ligands, phosphines and N-heterocyclic carbenes are preferred, trialkylphosphines and N-heterocyclic carbenes are preferred, and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene is particularly preferred. preferable. Since 2-chloro-3,3,3-trifluoro-1-propene is less reactive than other fluorine-containing olefins, it is bulky and has high electron-donating ability like N-heterocyclic carbene. The desired α-trifluoromethylstyrene compound (2) can be obtained with a higher yield by using a nickel complex having a group.

The organic transition metal catalyst is preferably an organic palladium complex or an organic nickel complex, more preferably an organic palladium complex, still more preferably an N-heterocyclic carbene, from the viewpoint of yield, selectivity and catalyst durability. It is an organic palladium complex containing ligands.
The amount of the organic transition metal catalyst used is not particularly limited, but is usually about 0.0001 to 1 mol, more preferably about 0.001 to 0.2 mol, per 1 mol of the organometallic phenyl compound (1). More preferably, it is about 0.01 to 0.2 mol.

When a ligand is added to the reaction system, the amount of the ligand used is usually about 0.0002 to 2 mol, preferably 0.02 to 2 mol, per 1 mol of the organometallic phenyl compound (1). It is about 0.4 mol. The molar ratio of the added ligand to the organic transition metal catalyst is usually 0.5/1 to 10/1, preferably 1/1 to 4/1.

When the organometallic phenyl compound (1) is a phenylboronic acid compound, a phenylsilicon compound, or a phenyltin compound, the reaction with 2-chloro-3,3,3-trifluoro-1-propene is carried out in the presence of a base. may
The base used here includes hydroxide compounds such as lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide; lithium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate. , carbonate compounds such as magnesium carbonate, calcium carbonate, barium carbonate, and cesium carbonate; phosphate compounds such as lithium phosphate, sodium phosphate, and potassium phosphate; acetic acid such as lithium acetate, sodium acetate, magnesium acetate, and calcium acetate Salt compounds; alkoxides such as lithium methoxide, lithium-t-butoxide, sodium methoxide, sodium-t-butoxide, potassium-t-butoxide, fluoride salts such as cesium fluoride, potassium fluoride, tetrabutylammonium fluoride etc. The amount of the base to be used is generally about 0.01 to 10 mol, more preferably about 1 to 3 mol, per 1 mol of the organometallic phenyl compound (1).
When the organic transition metal catalyst is an organic palladium complex, the reaction proceeds without the presence of a base.

The reaction between the organometallic phenyl compound (1) and 2-chloro-3,3,3-trifluoro-1-propene is usually carried out in a solvent.
The solvent used in the present invention is not particularly limited as long as it does not adversely affect the reaction. Examples include aromatic hydrocarbon solvents such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and cyclohexane. Ether-based solvents such as tetrahydrofuran (THF), dioxane, diethyl ether, glyme, and diglyme; Nitrile-based solvents such as acetonitrile, propionitrile, dimethylcyanamide, t-butylnitrile; and water can be used. . These may be used in combination of two or more. Among them, ether solvents such as dioxane and THF are preferred.
The amount of the solvent to be used is usually 0.1 to 100 times the volume of the organometallic phenyl compound (1).

The reaction is the addition (blowing) of 2-chloro-3,3,3-trifluoro-1-propene to a mixture of organometallic phenyl compound (1), organotransition metal catalyst and solvent (and optionally base). It is preferable to carry out by
The reaction is usually carried out in the range of -50°C to 200°C, preferably in the range of 0°C to 150°C.
The reaction is preferably carried out under pressure, preferably 0.01 MPa to 10 MPa, more preferably 0.01 MPa to 0.2 MPa.
Although the reaction time depends on the reaction temperature and reaction pressure, it is usually 0.1 to 36 hours, preferably 0.5 to 2 hours.
Completion of the reaction can be confirmed by liquid chromatography, gas chromatography, NMR, or the like.

After completion of the reaction, the target α-trifluoromethylstyrene compound (2) is isolated from the reaction mixture by separation means such as concentration, crystallization, recrystallization, distillation, solvent extraction, fractional distillation, and chromatography in accordance with conventional methods. and/or can be purified.

The container for the reaction of the organometallic phenyl compound (1) and 2-chloro-3,3,3-trifluoro-1-propene is not particularly limited as long as it does not adversely affect the reaction. can be used. Since the present invention handles 2-chloro-3,3,3-trifluoro-1-propene in a gaseous state under reaction conditions, an airtight pressure vessel is preferable. In addition, since a compound generated as the reaction progresses may react with the metal of the reaction vessel and become a reaction inhibitor, a vessel lined with a resin such as PFA or glass-lined is preferable.

Thus obtained α-trifluoromethylstyrene compound (2) is reacted with compound (3) according to the method described in WO2005/085216, for example, to give compound (4). and then lead to compound (5), which is useful as an insecticide.

[In the formula, R ³ represents an alkyl group, a halogen atom, etc., R ⁴ represents an optionally substituted alkyl group, etc., X ⁵ represents a halogen atom, and n represents an integer of 0 to 4. , and other symbols are as defined above. ]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
Nuclear magnetic resonance spectra (NMR) were measured using JNM-AL300 manufactured by JEOL Ltd. ¹ H-NMR was measured at 300 MHz with tetramethylsilane as a reference, and ¹⁹ F-NMR was measured at 283 MHz with CCl ₃ F as a reference. Mass spectrometry (GC-MS) was determined by the electron ionization method (EI) using a gas chromatograph mass spectrometer (GCMS-QP5000V2) manufactured by Shimadzu Corporation.

Example 1
[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride (67.9 mg, 0.1 mmol), 3,5-dichlorophenylboronic acid (190 .1 mg, 1 mmol) and sodium bicarbonate (168.0 mg, 0.2 mmol) in 1,4-dioxane/water mixture (4:1, 2.5 mL) were prepared in an autoclave (5 ml volume). After nitrogen replacement, 2-chloro-3,3,3-trifluoro-1-propene (1.82 g, 14 mmol) was added. The reaction solution was stirred at 100° C. for 2 hours. After completion of heating, 1,4-bis(trifluoromethyl)benzene (214 mg, 1 mmol) was added as an internal standard for ¹⁹ F-NMR, and it was confirmed that a coupling product was obtained with a yield of 61%. .
¹ H-NMR (CDCl ₃ ) δ = 7.40 (d, 1H, H _Ar ), 7.34 (d, 2H, H _Ar ), 6.05 (d, 1H, C=CH ₂ ), 5.83 (d, 1H, C= _CH2 ).
19F-NMR (CDCl ₃ ) δ = -64,8 (s, 3F, CF ₃ ).
GC-MS (EI): [M]+ 240

According to the production method of the present invention, the α-trifluoromethylstyrene compound (2) can be produced in a safe, inexpensive, and convenient manner without producing by-products that are difficult to remove. It is a very useful method suitable for industrial production.

Claims (5)

organometallic phenyl compound (1) and 2-chloro-3,3,3-trifluoro-1- in the presence of an organotransition metal catalyst comprising a transition metal selected from nickel, palladium, platinum, rhodium, ruthenium and cobalt A method for producing α-trifluoromethylstyrene compound (2), comprising a step of reacting with propene.

[In the formula,
M is a borono group (-B(OH) ₂ ), its ester group or its amide group, -BF ₃ M ¹ (wherein M ¹ represents an alkali metal), -B(OR ^a ) ₃ M ² (wherein R ^a represents a C _1-6 alkyl group and M ² represents an alkali metal), —MgX ¹ (wherein X ¹ represents a halogen atom), —SiX ² ₃ (wherein X ² independently represents a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group or Ar), —ZnX ³ (wherein X ³ is a halogen atom or represents Ar), or -SnX ⁴ ₃ (wherein X ⁴ independently represents a halogen atom, a C _1-4 alkyl group or Ar);
X represents a halogen atom;
R ¹ and R ² each independently represent a hydrogen atom or a substituent, at least one of which is a substituent;
Ar is

where * represents the binding site with M. ] 2. The production method according to claim 1, wherein the organic transition metal catalyst is an organic palladium complex. 2. The production method according to claim 1, wherein the organic transition metal catalyst is a complex containing an N-heterocyclic carbene ligand. The production method according to any one of claims 1 to 3, wherein the organic transition metal catalyst is added to the reaction system or prepared in the reaction system. 5. The production method according to any one of claims 1 to 4, wherein M in the organometallic phenyl compound (1) is a borono group or an ester group thereof, and the reaction is carried out in the presence of a base.