JP2000229912A - Production of cinnamic acid derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a cinnamic acid derivative in high yield by reacting a halogenated aromatic compound with an acrylic acid derivative using a palladium complex compound as a catalyst. SOLUTION: (B) a halogenated aromatic compound [e.g. 2- trifluoromethylbromobenzene] is reacted with (B) an acrylic acid derivative, preferably at 50-180 deg.C using (A) a palladium complex compound represented by formula I [Ar1 is an aryl represented by formula II (R1 is trifluoromethyl; and (n) is 1-3); Ar2 is an aryl represented by formula III (R2 is trifluoromethyl, a halogen, nitro, acetyl or the like; and (m) is 0-4); L is a phosphine ligand], e.g. [3,5-bis(trifluoromethyl)benzoato]3',5'-bis(trifluoromethyl)phenylbis( triphenylphosphine)-palladium (II) as a catalyst. In the above reaction, the amount of Pd in the component A is preferably 0.0001-1 mol% based on the component B and the ratio of the components B:A is preferably (1:0.7) to (1.3) molar ratio.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a cinnamic acid derivative, and more particularly to a method for producing a cinnamic acid derivative from a halogenated aromatic compound and an acrylic acid derivative using a novel palladium-phosphine complex compound as a catalyst. On how to do it.

[0002]

It is already known that olefins can be arylated by brominated aromatic compounds in the presence of a palladium catalyst, a phosphine ligand and a base (RF. Hec).
k, Org. React. 27, 345-391 (1982)).

In this method, palladium has an oxidation value of 0.
And +2 valent palladium compounds such as palladium (I
It is known that I) halides and palladium (II) carboxylate, and palladium complex compounds, for example, palladium complex compounds such as PdX ₂ L ₂ and PdL ₄ can be used. Here, X represents a halogen atom, and L represents a ligand such as triphenylphosphine, tri (o-tolyl) phosphine, or tri (p-anisyl) phosphine.

Alkylation of alkenes using chlorinated aromatic compounds can also be performed in the presence of bidentate phosphine ligands (Y. Ben-David et al., Organometallic).
s 11, 1995 (1992)), and that it is possible to use lipophilic aliphatic phosphines such as tricyclohexylphosphine (Japanese Patent Application Laid-Open No. 09-509420).

[0005]

SUMMARY OF THE INVENTION The present invention provides a method for arylating acrylates with a halogenated aromatic compound in the presence of a catalyst and a base, using a novel catalyst.

[0006]

An object of the present invention is to use a palladium complex compound having a trifluoromethyl group as a phenyl group of a benzoato group of a complex compound represented by [(Ph3P) 2PdPh (PhCOO)] as a catalyst. It is solved by.

That is, the present invention relates to a method for producing a cinnamic acid derivative from a halogenated aromatic compound (halogen is chlorine, bromine or iodine) and an acrylic acid derivative in the presence of a palladium catalyst. (1)

[0008]

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Wherein Ar ¹ is a group represented by the general formula (2)

[0010]

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(Wherein, R ¹ represents a trifluoromethyl group, and n represents an integer of 1 to 3), and Ar ² represents a general formula (3)

[0012]

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(Wherein R ² is independently a trifluoromethyl group, a trifluoromethyloxy group, a halogen (refers to fluorine, chlorine, bromine or iodine), a nitro group, an acetyl group, a cyano group, L represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or an alkoxycarbonyl group having 2 to 5 carbon atoms, and m represents an integer of 0 to 4). Independently represents a phosphine ligand. ), Which is a palladium complex compound represented by the following formula:

Hereinafter, the palladium complex compound according to the present invention will be described. Specific examples of the aryl group represented by the general formula (2) include a 2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group, and a 4-trifluoromethylphenyl group having one trifluoromethyl group. A 2,3-bis (trifluoromethyl) phenyl group, a 2,4-bis (trifluoromethyl) phenyl group, a 2,5-bis (trifluoromethyl) phenyl group having two trifluoromethyl groups, A 6,6-bis (trifluoromethyl) phenyl group, a 3,4-bis (trifluoromethyl) phenyl group, a 3,5-bis (trifluoromethyl) phenyl group, and the like.

Of these, a trifluoromethyl group is
Aryl groups are preferred, and a 3,5-bis (trifluoromethyl) phenyl group is more preferred.

Therefore, as the complex compound represented by the general formula (1),

[0017]

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(Wherein, R ² , m and L have the same meanings as in the general formula (1)).

[0019]

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(Wherein R ² , m and L have the same meanings as in formula (1)).

The substituent of the aryl group represented by the general formula (3) is trifluoromethyl group, trifluoromethyloxy group, halogen (refers to fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group. Group, 1-4 carbon atoms
An alkyl group, an alkoxy group having 1 to 4 carbon atoms, and 2 carbon atoms
To 5 alkoxycarbonyl groups, and the aryl group is 0
It has up to 4 substituents.

Examples of the alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, an n-propyl group and an i-propyl group, and examples of the alkoxy group having 1 to 4 carbon atoms include a methoxy group and an ethoxy group. Group, n-propoxy group, i-
Examples of the propoxy group and the alkoxycarbonyl group having 2 to 5 carbon atoms include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, and an i-propoxycarbonyl group.

Further, as the aryl group represented by the general formula (3), an aryl group having at least one trifluoromethyl group is preferable.

As an example of the aryl group represented by the general formula (3), a trifluoromethyl group such as a 2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group or a 4-trifluoromethylphenyl group may be used. Aryl group having one trifluoromethoxy group such as 2-trifluoromethoxyphenyl group, 3-trifluoromethoxyphenyl group, and 4-trifluoromethoxyphenyl group; 2-fluorophenyl group, 3-fluoro Aryl group having one fluorine such as phenyl group and 4-fluorophenyl group; chlorine such as 2-chlorophenyl group, 3-chlorophenyl group and 4-chlorophenyl group
Aryl group having one bromine such as 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group; 2-iodophenyl group, 3-iodophenyl group, 4-iodophenyl group, etc. An aryl group having one iodine; a nitro group such as a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group
Aryl group having one acetyl group such as 2-acetylphenyl group, 3-acetylphenyl group, 4-acetylphenyl group; 2-cyanophenyl group, 3-cyanophenyl group, 4-cyanophenyl group Aryl groups having one cyano group such as 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group,
Aryl group having one alkyl group such as 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group; 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-ethoxyphenyl Group having one alkoxy group such as a group, 3-ethoxyphenyl group or 4-ethoxyphenyl group; 2-methoxycarbonylphenyl group, 3-methoxycarbonylphenyl group, 4-methoxycarbonylphenyl group, 2-ethoxycarbonylphenyl And aryl groups having one alkoxy group such as a 3-ethoxycarbonylphenyl group and a 4-ethoxycarbonylphenyl group.

The aryl group represented by the general formula (3) can have two or more substituents and can be in any combination. One of the substituents is trifluoromethyl. An aryl group which is a group is preferable, for example, a 2-chloro-3- (trifluoromethyl) phenyl group, a 2-fluoro-3- (trifluoromethyl) phenyl group, a 2-fluoro-4- (trifluoromethyl) phenyl Group, 3-fluoro-5- (trifluoromethyl) phenyl group, 2-bromo-6- (trifluoromethyl) phenyl group, 4-chloro-2- (trifluoromethyl) phenyl group, 4-fluoro-2- (Trifluoromethyl)
Phenyl group, 2-chloro-6- (trifluoromethyl)
Phenyl group, 4-fluoro-3- (trifluoromethyl) phenyl group, 1-chloro-4- (trifluoromethyl) phenyl group, 2-fluoro-6- (trifluoromethyl) phenyl group, 2-fluoro-5 -(Trifluoromethyl) phenyl group, 2-chloro-4- (trifluoromethyl) phenyl group, 4-chloro-3- (trifluoromethyl) phenyl group, 4-chloro-2- (trifluoromethyl) phenyl group 2-methyl-3- (trifluoromethyl) phenyl group, 3-methyl-5- (trifluoromethyl) phenyl group, 2-methyl-4- (trifluoromethyl) phenyl group, 4,5-dimethyl- 2- (trifluoromethyl) phenyl group, 2-methyl-5- (trifluoromethyl) phenyl group, 5,6-dimethyl-2
-(Trifluoromethyl) phenyl group, 2-methyl-5
-(Trifluoromethyl) phenyl group, 4-methyl-3
-(Trifluoromethyl) phenyl group, etc .; 2-methoxy-4- (trifluoromethyl) phenyl group, 2-ethoxy-4- (trifluoromethyl) phenyl group, 4-ethoxy-2- (trifluoromethyl) phenyl Group, 4-
Methoxy-2- (trifluoromethyl) phenyl group, 2
-Methoxy-5- (trifluoromethyl) phenyl group; 2-trifluoromethoxyphenyl group, 3-trifluoromethoxyphenyl group, 4-trifluoromethoxyphenyl group; 2-nitro-3- (trifluoromethyl) Phenyl group, 2-nitro-4- (trifluoromethyl) phenyl group, 4-nitro-2- (trifluoromethyl) phenyl group, 3-nitro-5- (trifluoromethyl) phenyl group, 2-nitro-5 -(Trifluoromethyl) phenyl group, 4-nitro-3- (trifluoromethyl) phenyl group and the like; 2-cyano-5- (trifluoromethyl) phenyl group, 2-cyano-4- (trifluoromethyl) phenyl Group, 4-fluoro-3-cyano-5
(Trifluoromethyl) phenyl group, 4-cyano-3-
(Trifluoromethyl) phenyl group, 2-chloro-5-
Cyano-3- (trifluoromethyl) phenyl group, 4-
A cyano-2- (trifluoromethyl) phenyl group and the like;
2-amino-6- (trifluoromethyl) phenyl group,
2-amino-5- (trifluoromethyl) phenyl group,
2-amino-4- (trifluoromethyl) phenyl group,
2-amino-3- (trifluoromethyl) phenyl group,
A 3-amino-6- (trifluoromethyl) phenyl group,
A 3-amino-5- (trifluoromethyl) phenyl group,
4-amino-2- (trifluoromethyl) phenyl group,
4-amino-3- (trifluoromethyl) phenyl group,
4-amino-2- (trifluoromethyl) phenyl group,
Examples thereof include a 3-amino-5- (trifluoromethyl) phenyl group, but are not limited thereto.

The aryl group represented by the general formula (3) is more preferably an aryl group having two or more trifluoromethyl groups.

The aryl group having only two trifluoromethyl groups includes 2,3-bis (trifluoromethyl) phenyl group and 2,4-bis (trifluoromethyl)
Phenyl group, 2,5-bis (trifluoromethyl) phenyl group, 2,6-bis (trifluoromethyl) phenyl group, 3,4-bis (trifluoromethyl) phenyl group,
3,5-bis (trifluoromethyl) phenyl group and the like.

Further, examples of the aryl group having a substituent described above include a 2,3,4-tris (trifluoromethyl) phenyl group, a 2,4,5-tris (trifluoromethyl) phenyl group, and a 2,3,4-tris (trifluoromethyl) phenyl group. , 5-tris (trifluoromethyl) phenyl group, 1,3,5-tris (trifluoromethyl) phenyl group, 3,4,5-tris (trifluoromethyl) phenyl group, 2,3,4,6- Tetrakis (trifluoromethyl) phenyl group, 1-bromo-
2,3,4-tris (trifluoromethyl) phenyl group, 2-bromo-4,5,6-tris (trifluoromethyl) phenyl group and the like; 3,5-dichloro-4,6-bis (trifluoromethyl ) Phenyl group, 2-chloro-
3,5-bis (trifluoromethyl) phenyl group, 2-
Methoxy-3,5-bis (trifluoromethyl) phenyl group, 2-bromo-3,5-bis (trifluoromethyl) phenyl group, 2-nitro-4,6-bis (trifluoromethyl) phenyl group, 5 , 6-Dichloro-1,3-
Bis (trifluoromethyl) phenyl group, 4-chloro-
Examples thereof include a 3,5-bis (trifluoromethyl) phenyl group, but are not limited thereto.

In the compound represented by the general formula (1), L
The phosphine ligand represented by is not particularly limited,
Formula (4), P (R ³ ) 3 (4) (wherein R ³ independently represents a phenyl group which may have a substituent, or an alkyl group having 1 to 6 carbon atoms). Phosphine ligand. Here, R ³ is each independently unsubstituted or a phenyl group substituted by an alkyl group having 1 to 6 carbon atoms, or an alkyl group having a branched chain having 1 to 6 carbon atoms. Specifically, it is preferably a group selected from a phenyl group, an o-tolyl group, an m-tolyl group, a p-tolyl group, a methyl group, an ethyl group, an n-butyl group and the like. The phosphine ligand represented by L is triphenylphosphine, tris (o-
Tolyl) phosphine, tris (m-tolyl) phosphine, tris (p-tolyl) phosphine or tris (n
-Butyl) phosphine and the like are preferable, and triphenylphosphine is particularly preferable.

This novel compound is crystalline, is soluble in many organic solvents, and is stable. It is stable in air at room temperature.

Because of these physical and chemical properties, the isolation operation is easy, so that a high-purity substance is easily obtained, and storage is easy, so that it is easy to handle even in industrial use. is there.

The method for producing the complex compound of the present invention is not particularly limited, but is exemplified below. General formula (5) for hermetically sealed containers

[0033]

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(Wherein R 1 represents a trifluoromethyl group, and n represents an integer of 1 to 3), and benzoic acid represented by the general formula (6):

[0035]

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(Wherein, X represents a halogen (fluorine, chlorine, bromine or iodine), a trifluoromethanesulfonate group, an alkylsulfonate group having 1 to 4 carbon atoms, or a substituted or unsubstituted arylsulfonate group;
Are the same as in the general formula (1)), a solvent, a palladium compound, phosphine which is a phosphine ligand, and a basic substance. As the solvent, when the melting point is low, an aromatic compound represented by the general formula (6) can be used, and for example, aliphatic hydrocarbons such as pentane, hexane, heptane, octane, benzene, toluene, xylene and the like. Aromatic hydrocarbons, ethers such as diethyl ether, dioxane, tetrahydrofuran (THF) and ethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; nitriles such as acetonitrile; tertiary amines such as pyridine; N, N-dimethylformamide (DM
F), acid amides such as N, N-dimethylacetamide (DMAc), sulfur-containing compounds such as dimethylsulfoxide (DMSO) and sulfolane, water and the like can be used.

As the basic substance, ammonia, triethylamine, tripropylamine, tributylamine,
Triallylamine, N, N-dimethylaniline, N, N
Tertiary amines such as diethylaniline, pyridine and N-methylmorpholine; acetates such as sodium acetate and potassium acetate; and inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate. Can be.

As the palladium compound, palladium acetate, palladium chloride, palladium bromide and the like are preferred.

The proportion of each of the starting materials used is not particularly limited, but in order to make effective use of palladium, the general formula (6)
It is preferable to use at least one equivalent of the aromatic compound represented by the formula and benzoic acid represented by the formula (5), and to use at least two equivalents of the phosphine. Other solvents and the like may be used in appropriate amounts.

The container may or may not be pressurized and may or may not be agitated. Normally 50 ~
Heating to about 150 ° C. accelerates the progress of the reaction. After a predetermined time has elapsed, the container is cooled and the contents are taken out. An extraction solvent is appropriately added to the contents to separate a solid content, and a volatile component is distilled off to obtain a desired complex compound represented by the general formula (1). If necessary, it can be purified by recrystallization.

In the above production method, the compound represented by the general formula (5)
By performing substantially the same treatment under substantially the same reaction conditions without using the benzoic acid represented by the general formula (7),

[0042]

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(Wherein R ² , X and m are the same symbols as in the general formula (6), and L is the same as the symbol in the general formula (4)). The complex compound, the benzoic acid represented by the general formula (5), the solvent and the base described above are charged into a container, heated if necessary, and subjected to the same purification method as described above to be represented by the general formula (1). A complex compound is obtained.

The palladium complex compound according to the present invention includes, for example, [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenylbis (trifluoromethyl) Phenylphosphine)
Palladium (II) and [3,5-bis (trifluoromethyl) benzoato] 3′-trifluoromethylphenylbis (triphenylphosphine) palladium (II).

The amount of palladium can be selected so that the proportion thereof relative to the halogenated aromatic compound used is 0.0001 to 1 mol%, preferably 0.005 to 0.05 mol%.

Next, the production method of the present invention will be described in detail. The acrylic acid derivative used in the present invention is, for example, a compound represented by the general formula (8).

[0047]

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Wherein R is CN or COR ⁴ , wherein R ⁴ is OH, aryl of _{OC 6-10} , alkyl of _{OC 1-20} , NH ₂ , NH-C _6-10 Aryl, NHC
Alkyl of _1-20 , aryl of _{NC 6-10} , N- (C _1-20
R ′ is H, C _1-10 alkyl, C _1-10 alkyl, C _6-10 aryl or N- (C _1-20 alkyl) _{2
6-2 0} aryl or R.

In the general formula (8), R is such that R ⁴ is OH,
O-C _1-20 alkyl, particularly preferably OH, OC
_It is preferably COR ⁴ which is an alkyl of _1-10 . Specifically, methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, n-butyl acrylate, sec-butyl acrylate, t-acrylate
-Butyl, pentyl acrylate, octyl acrylate,
Cyclohexyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, n-butyl methacrylate, sec-butyl methacrylate, t-butyl methacrylate, pentyl methacrylate, octyl methacrylate, cyclohexyl methacrylate, etc. Is mentioned.

The halogenated aromatic compound used in the present invention is a compound represented by the general formula (9).

[0051]

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[0052] wherein, Y is chlorine, bromine or iodine, R ⁵ is a C _6-10 - aryl, alkyl C _{1-2 0,} C
^{N, S-R 6, CO} -OR 6, -F, CF 3, -OCF 3,
An OR ⁶ or NR ⁶ _2, provided that R ⁶ is hydrogen, alkyl aryl or C _1-20 of C _6-10, p is 1 or 2, q is 1 to 5, p + q is 2 ~ 6.

[0053] In the general formula (9), R ⁵ is preferably CF _3, OR ⁶ or NR ⁶ _2, provided that R ⁶ is an alkyl phenyl or C _1-10, R ⁵ is more preferably CF ₃ It is. p is preferably 1.

[0054] As the halogenated aromatic compound represented by the general formula (9) is preferably at least one R ⁵ is CF _3, and more preferably at least two are CF _3. Such aromatic compounds include a substituted phenyl group represented by the general formula (3) and Y (bromine)
Can be exemplified. Particularly preferred are those having only one trifluoromethyl group, such as 2-trifluoromethylbromobenzene, 3-trifluoromethylbromobenzene, 4-trifluoromethylbromobenzene, or 2-trifluoromethylbromobenzene. The compounds having only 2,3-bis (trifluoromethyl) bromobenzene, 2,4-bis (trifluoromethyl) bromobenzene, 2,5-bis (trifluoromethyl) bromobenzene, 2,6-bis (trifluoromethyl) bromobenzene Bis (trifluoromethyl) bromobenzene, 3,4-bis (trifluoromethyl) bromobenzene, and 3,5-bis (trifluoromethyl) bromobenzene are exemplified.

The molar ratio of the halogenated aromatic compound to the acrylic acid derivative can be arbitrarily selected. The molar ratio is preferably in the range from 1: 0.7 to 1: 3, particularly preferably from 1: 0.8 to 1: 1.5. When two halogen atoms represented by Y are active in the reaction, twice the amount of the acrylic acid derivative is used.

Suitable inorganic bases for the process according to the invention are, for example, alkali metal and alkaline earth metal salts of weak acids, preferably alkali metal and alkaline earth metal acetates, bicarbonates, and / or It is a carbonate. The use of sodium acetate and sodium carbonate is particularly preferred. The ratio of halogenated aromatic compound to base is preferably 0.5.
3 to 2, particularly preferably 0.4 to 1.3, the equivalent of base being used per mole of halogenated aromatic compound.

The method according to the invention is, for example, 50-180.
It can be carried out at a temperature in the range of ° C. Preferred temperatures are in the range from 80 to 150 ° C., particularly preferred are temperatures in the boiling range of the solvent used. The process of the invention is usually carried out at atmospheric pressure. However, it can also be carried out under reduced or elevated pressure. The application of pressure is particularly suitable when it is desired to carry out at the reaction temperature at which the individual components of the reaction mixture will boil at atmospheric pressure. The process of the invention is generally carried out under a protective gas such as nitrogen and stirring.

Suitable solvents are, for example, hydrocarbons such as toluene, ethers such as tetrahydrofuran, and polar aprotic solvents such as N-methyl-pyrrolidone, dimethylformamide, N, N-dimethylacetonitrile or dimethylsulfoxide.

Using the method of the present invention, for example, the general formula (1)
It is possible to produce the cinnamic acid derivative of 0). However, in the above formula, the symbols used have the same meanings as in formulas (8) and (9).

[0060]

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The inorganic salt formed with the cinnamic acid derivative according to the process of the present invention can be separated, for example, by simple filtration (with or without suction). It is also possible to allow the salt to settle out and decant the rest of the reaction mixture.

Embodiments of the present invention will be described below. A halogenated aromatic compound, an acrylic acid derivative, an inorganic base, a palladium complex compound according to the present invention, and optionally a solvent are charged into a reactor and stirred. The order of preparation may be arbitrary.
The reactor is heated to a predetermined temperature, 50-200 ° C., preferably 80
Heat to １５０150 ° C. and cool to room temperature after no further progress of the reaction is observed.

The reaction mixture is poured into water, the aqueous phase is separated and extracted with an organic solvent (eg ether), washed with water or saturated saline solution and dried, and the solvent is distilled off. Obtain the product. If necessary, this is recrystallized or rectified to obtain a high-purity cinnamic acid derivative.

[0064]

The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[Preparation Example 1] [3,5-bis (trifluoromethyl) benzoato] Synthesis of 3 ', 5'-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II) In a stainless steel autoclave 65.3 g of 3,5-bis (trifluoromethyl) bromobenzene, 100 ml of tetrahydrofuran, 50.0 g of palladium acetate, 175.5 g of triphenylphosphine, 57.6 g of 3,5-bis (trifluoromethyl) benzoic acid, 25% 60.8 g of aqueous ammonia was charged. Nitrogen replacement is performed twice, the stirring is started at a nitrogen pressure of 3 kg / cm ² , and the internal temperature becomes about 50 ° C.
Rose. Thereafter, the oil bath temperature was set to 120 ° C. and heating was started. About 2 hours later, when the internal temperature reached 95.6 ° C, the oil bath was removed and the system was cooled. 200 ml of water and 600 ml of toluene were added to the reaction solution, and the mixture was stirred for several minutes. The obtained treatment liquid was subjected to suction filtration, the organic layer (upper layer) of the filtrate was separated, washed twice with a saturated saline solution, dried over anhydrous magnesium, and concentrated by evaporation of volatile components. The solid precipitated at the initial stage of concentration was separated by filtration, and the filtrate was further concentrated. Then, n-hexane was added and the mixture was cooled, and the precipitated solid was filtered to obtain 187.5 g of a crude product. The crude product was recrystallized from toluene to give pale yellow crystals.
3.0 g were obtained.

[3,5-bis (trifluoromethyl) benzoato] 3 ', 5'-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II) Melting point: 168-170 ° C (decomp.) IR (KBr: cm ^-1 ): 3060,2926,1637,1437,1321,1277,1173,
1127,748,697,518 ¹ H-NMR (reference substance: TMS solvent: CDCl ₃ ): δ ppm 6.97 (s, 1
H), 7.09 (s, 2H), 7.20-7.32 (m, 18H), 7.40-7.50 (m, 12H), 7.
53 (s, 2H), 7.62 (s, 1H) ³¹ P-NMR (reference substance: 85% H ₃ PO ₄ solvent: CDCl ₃ ): δppm 2
5.73 (s).

[Preparation Example 2] In a stainless steel autoclave, 32.5 g of 3,5-bis (trifluoromethyl) bromobenzene, 75 ml of tetrahydrofuran, 25.0 g of palladium acetate, 87.3 g of triphenylphosphine,
38.0 g of 25% aqueous ammonia (9.
5g) was charged. Perform nitrogen replacement twice and increase nitrogen pressure to 3k
When stirring was started at g / cm 2, the internal temperature rose. Thereafter, the oil bath temperature was set at 105 ° C., and heating was started. About 1.
Eight hours later, when the internal temperature reached 97 ° C., the oil bath was removed and the system was cooled. 200 ml of toluene was added to the reaction solution, and the mixture was stirred for several minutes. The obtained treatment solution was subjected to suction filtration, and the residue was washed with a small amount of n-hexane and dried to obtain 72.10 g of pale green crystals.

Bromo [3,5-bis (trifluoromethyl) phenyl] bis (triphenylphosphine) palladium (II) 7 obtained above in a stainless steel autoclave.
0.0 g, 39.1 g of 3,5-bis (trifluoromethyl) benzoic acid and 150 ml of tetrahydrofuran were added. After charging 20.5 g of 25% aqueous ammonia, nitrogen replacement was performed twice, stirring was started at a nitrogen pressure of 3 kg / cm ² , the oil bath temperature was set to 100 ° C., and heating was started. After about 2 hours, the oil bath was removed and cooled. To the reaction solution were added 500 ml of toluene, 150 ml of 25% aqueous ammonia, and 200 ml of water, and the mixture was stirred for several minutes. The upper organic layer was separated, washed twice with water and once with a saturated saline solution, dried over anhydrous magnesium sulfate, evaporated to remove volatile components, and concentrated to obtain 75.3 g of pale yellow crystals. IR and ¹ H-N of the crystal
The MR is the same as the crystal ([3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II)) obtained in Example 1. Met.

[Preparation Example 3] [3,5-bis (trifluoromethyl) benzoato] 3'-trifluoromethylphenylbis (triphenylphosphine) palladium (II)
In a stainless steel autoclave, 25.0 g of 3-trifluoromethylbromobenzene and 75 of tetrahydrofuran were added.
ml, 25 g of palladium acetate, 87.3 g of triphenylphosphine, 38 g of 25% aqueous ammonia, and 57.5 g of 3,5-bis (trifluoromethyl) benzoic acid,
The same operation as in Example 1 was performed to obtain 32.3 g of [3,5-bis (trifluoromethyl) benzoato] 3′-trifluoromethylphenylbis (triphenylphosphine) palladium (II).

[3,5-bis (trifluoromethyl) benzoato] 3'-trifluoromethylphenylbis (triphenylphosphine) palladium (II) ¹ H-NMR (reference substance: TMS solvent: CDCl ₃ ): δ ppm 6.47 (dd,
J = 7.3,7.8Hz, 1H), 6.77 (d, J = 7.3Hz, 1H), 6.80 (brs, 1H), 6.
95 (d, J = 7.8Hz, 1H), 7.24-7.30 (m, 18H), 7.40-7.46 (m, 12
H).

Example 1 Synthesis of 3,5-bis (trifluoromethyl) cinnamic acid n-butyl ester
In a nitrogen flask, 29.3 g of 3,5-bis (trifluoromethyl) bromobenzene, 15.4 g of n-butyl acrylate and the palladium complex obtained in Example 1 ([3,5- Bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II)) 210 mg, N, N-dimethylacetamide 7
0 ml was added. While stirring, it was heated using an oil bath.
After reacting at 110 ° C. for about 1 hour, it was cooled to room temperature. The reaction solution was poured into ice water and extracted with ether. After separating the organic layer, the mixture was washed three times with water, twice with saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure using an evaporator to obtain a brown solid as a residue. This was recrystallized from n-hexane to obtain 22.3 g of a crystal. N-butyl 3,5-bis (trifluoromethyl) cinnamate: Melting point: 47-48 ° C. ¹ H-NMR: (Reference substance: TMS solvent: CDCl ₃ ) δ ppm 0.975 (t, J = 7.3 Hz, 3H), 1.38-1.50 (m, 2H), 1.66-
1.75 (m, 2H), 4.25 (t, J = 6.6Hz, 2H) 6.57 (d, J = 16Hz, 1H), 7.7
0 (d, J = 16 Hz, 1H), 7.86 (s, 1H), 7.93 (s, 2H).

Example 2 Synthesis of n-butyl 3-trifluoromethylcinnamate 9.02 g of anhydrous sodium acetate was placed in a 200 ml flask, and 22.5 g of 3-trifluoromethylbromobenzene and acrylic acid were added under a nitrogen stream. N-butyl acid 15.4
g and the palladium complex obtained in Example 1 ([3,5
-Bis (trifluoromethyl) benzoato] 3 ', 5'
55.1 mg of -bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II)) and 70 ml of N, N-dimethylacetamide were added. While stirring, it was heated using an oil bath. After reacting at 110 ° C. for about 40 hours, it was cooled to room temperature. The reaction solution was poured into ice water and extracted with ether. After separating the organic layer, the organic layer is washed with water.
The extract was washed twice, successively twice with a saturated saline solution, and then dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure by an evaporator, the obtained residue was purified by silica gel chromatography to obtain 21.5 g of the title compound as an oil.

Example 3 Synthesis of 3-trifluoromethylcinnamic acid In a stainless steel autoclave, 56.3 g of 3-trifluoromethylbromobenzene, 19.8 g of acrylic acid, 50.6 g of triethylamine and obtained in Example 1 were obtained. Palladium complex ([3,5-bis (trifluoromethyl)
Benzoato] 3 ', 5'-bis (trifluoromethyl)
Phenylbis (triphenylphosphine) palladium (I
I)) 137.7 mg and tetrahydrofuran 100
ml. Nitrogen substitution was performed twice, and the nitrogen pressure was increased to 2.5.
Stirring was started at kg / cm ² and the internal temperature was adjusted to 1 using an oil bath.
The reaction was performed while adjusting to 10 ° C. After about 8 hours, the oil bath was removed and cooled. The reaction solution was poured into ice water, adjusted to pH 1 by adding concentrated hydrochloric acid, and extracted with ether. After separating the organic layer, the mixture was washed three times with water, twice with saturated saline, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure using an evaporator, the obtained residue was recrystallized from n-hexane / ethyl acetate to obtain 41.7 g of the title compound as colorless crystals. Melting point: 135-137 ° C

[0074]

According to the production method of the present invention, a cinnamic acid derivative can be produced at a high yield from an aromatic compound and an acrylic acid derivative by using a novel palladium complex compound.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat ゛ (Reference) C07F 15/00 C07F 15/00 C

Claims (19)

[Claims] 1. A method for producing a cinnamic acid derivative from a halogenated aromatic compound (halogen is chlorine, bromine or iodine) and an acrylic acid derivative in the presence of a palladium catalyst, wherein the palladium catalyst has the general formula (1) Formula 1 (Wherein, Ar ¹ is a group represented by the general formula (2): (Wherein, R ¹ represents a trifluoromethyl group, and n is 1 to
Represents an integer of 3. Represents an aryl group represented by Ar)
² is a general formula (3) (Wherein R ² is independently a trifluoromethyl group, a trifluoromethyloxy group, a halogen (fluorine,
Chlorine, bromine or iodine), a nitro group, an acetyl group, a cyano group, an alkyl group having 1 to 4 carbon atoms,
4 represents an alkoxy group or an alkoxycarbonyl group having 2 to 5 carbon atoms, and m represents an integer of 0 to 4. ), And L independently represents a phosphine ligand. A) a palladium complex compound represented by the formula: 2. The process according to claim 1, wherein the palladium catalyst used is in an amount of 0.0001 to 1 mol% of palladium, based on the halogenated aromatic compound. 3. An acrylic acid derivative represented by the general formula (8): Wherein R is CN or COR ⁴ , where R ⁴ is O
H, aryl of _{OC 6-10} , alkyl of _{OC 1-20} , N
H _2, aryl NH-C _6-10, alkyl of NH-C _1-20, aryl of N-C _6-10, N- (alkyl C _1-20)
-C _6-10 aryl or N- (C _1-20 alkyl) ₂
In and, R 'is H, A method according to claim 1 or 2, characterized in that an acrylic acid derivative represented by C _1-10 alkyl, aryl, or R a C _{6 -20).} 4. A halogenated aromatic compound represented by the general formula (9): Wherein Y is chlorine, bromine or iodine, and R ⁵ is C
_6-10 - aryl, alkyl C _{1-2 0,} CN, S-
^{R 6, CO-OR 6,} -F, CF 3, an -OCF _3, OR ⁶ or NR ⁶ _2, provided that R ⁶ is hydrogen, alkyl aryl or C _1-20 of C _6-10, p Is 1 or 2, q is 1 to 5, and p + q is 2 to 6. ), Wherein the molar ratio of the halogenated aromatic compound to the acrylic acid derivative is 1: 0.
4. The method according to claim 1, wherein the range is from 7 to 1: 3. 5. The method according to claim 1, wherein in the halogenated aromatic compound represented by the general formula (9), at least one of R ⁵ is CF ₃ . 6. The halogenated aromatic compound represented by the general formula (9), wherein R ⁵ is CF ₃ , Y is bromine, and n is 1 or 2. The method described in Crab. 7. The method according to claim 1, wherein the method is carried out at a temperature in the range from 50 to 180 ° C. 8. The method according to claim 1, wherein the method is carried out with stirring under a protective gas. 9. The method according to claim 1, wherein the aryl group represented by the general formula (2) is a bis (trifluoromethyl) phenyl group. 10. The method according to claim 1, wherein the aryl group represented by the general formula (2) is a 3,5-bis (trifluoromethyl) phenyl group. 11. An aryl group represented by the general formula (3):
The method according to any one of claims 1 to 10 ² of at least one is a trifluoromethyl group. 12. The method according to claim 1, wherein the aryl group represented by the general formula (3) is a phenyl group, a trifluoromethylphenyl group or a bis (trifluoromethyl) phenyl group. 13. An aryl group represented by the general formula (3):
The method according to any one of claims 1 to 12, which is a 3-trifluoromethylphenyl group or a 3,5-bis (trifluoromethyl) phenyl group. 14. The aryl group represented by the general formula (3) is a phenyl group, a 3-trifluoromethylphenyl group or a 3,5-bis (trifluoromethyl) phenyl group. 14. The method according to claim 1, wherein the represented aryl group is a 3,5-bis (trifluoromethyl) phenyl group. 15. A phosphine ligand represented by L is a compound represented by the general formula (4): P (R ³ ) ₃ (4) wherein R ³ is independently a phenyl group which may have a substituent; The method according to any one of claims 1 to 14, wherein the phosphine ligand is represented by the following formula: 16. R ³ is independently a phenyl group, o-
The method according to any one of claims 1 to 15, wherein the group is a group selected from a tolyl group, an m-tolyl group, a p-tolyl group, a methyl group, an ethyl group, and an n-butyl group. 17. The method according to claim 1, wherein both L are triphenylphosphine. 18. The palladium catalyst is [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II). 18. The method according to any of 17. 19. The method according to claim 1, wherein the palladium catalyst is [3,5-bis (trifluoromethyl) benzoato] 3′-trifluoromethylphenylbis (triphenylphosphine) palladium (II). the method of.