JP2000191580A - Production of benzoic acid derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially advantageously obtain the subject derivative in a high yield in high selectivity by reacting a specific aromatic compound with carbon monoxide and a specified hydroxy compound in the presence of both a prescribed catalyst and a base. SOLUTION: (A) An aromatic compound of the formula Ar-X [Ar is an aryl; and X is a halogen (F, Cl Br or I), trifluoromethanesulfonate, a 1-4C alkylsulfonate or a (substituted) arylsulfonate] is reacted with (B) carbon monoxide, (C) a hydroxy compound of the formula R1OH (R1 is H, an aryl or a 1-10C alkyl) in the presence of both (D) a palladium complex compound of formula I (Ar1 and Ar2 are each aryl; and L is a phosphine ligand) e.g. [3,5-bis(trifluoromethyl)benzoato]3',5'-bis(trifluoromethyl)phenyl-bis (triphenylphosphine) palladium (II)} and (E) a base to give the objective derivative of formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method for producing benzoic acid or benzoic acid esters useful as an intermediate for producing pharmaceuticals, agricultural chemicals, various functional materials, and the like.

[0001]

2. Description of the Related Art It has been known that a benzoic acid derivative can be obtained by a reaction of inserting carbon monoxide into an aromatic halide.

JP-A-64-47 discloses an organic chloride having a chlorine atom on a ring, which is formed by using a palladium compound and a phosphine compound as catalysts in the presence of carbon monoxide in the presence of a base.
It is disclosed that a carboxylic acid can be obtained by reacting at a reaction temperature of 50 ° C to 300 ° C, and bis (diphenylphosphino) butane is exemplified as a phosphine compound.

As a method for producing bis (trifluoromethyl) benzoic acid, 3,5-bis (trifluoromethyl) bromobenzene is used as a starting material and 3,5-bis (trifluoromethyl) benzoic acid is produced by a Grignard reaction. Methods for producing acids are known [Bull. Soc.
Chim. France. , (1962), 587-9.
3].

Japanese Patent Application Laid-Open No. 9-67297 discloses that
3,5-bis (trifluoromethyl) bromobenzene, carbon monoxide and water or methanol are reacted in the presence of a catalyst comprising palladium acetate and triphenylphosphine and triethylamine to give 3,5-bis (trifluoromethyl ) It describes that benzoic acids and their esters can be obtained.

[0005]

Problems to be Solved by the Invention Japanese Patent Application Laid-Open No. 9-67297
According to the method disclosed in Japanese Patent Application Laid-Open Publication No. H06-27, relatively good results are obtained in both selectivity and yield, but a relatively large amount of palladium is deposited during the reaction because the palladium catalyst precipitates as catalyst-inactive palladium black and the actual catalyst concentration decreases. The compound had to be used. When a trifluoromethyl group is present on the benzene ring, a dehalogenation reaction proceeds as a side reaction,
The yield of the desired benzoic acid has been reduced, and the by-products have made purification of the product difficult.

[0006]

In view of the above-mentioned problems, the present inventors have intensively studied a method capable of industrially easily producing bis (trifluoromethyl) benzoic acid in large quantities. As a result, when halogeno-bis (trifluoromethyl) benzene is reacted with carbon monoxide and water or alcohols in the presence of a base, bis (trifluoromethyl) benzoic acids are produced. The inventors have found that the use of a specific catalyst significantly improves the yield and the selectivity, and that it is possible to remarkably reduce the precipitation of a metal which is likely to occur when another noble metal catalyst is used.

That is, the present invention relates to a compound represented by the general formula (1) Ar-X (1) wherein Ar is an aryl group, X is a halogen (fluorine, chlorine, bromine or iodine), a trifluoromethanesulfonate group, To an alkylsulfonate group or a substituted or unsubstituted arylsulfonate group), carbon monoxide and R ¹ OH (2) in the presence of a catalyst and a base. R ¹ is hydrogen, an aryl group, or a group having 1 to 10 carbon atoms.
Which represents an alkyl group represented by the general formula (3):

[0008]

Embedded image (Wherein, Ar and R ¹ are the same as described above), which is a method for producing a benzoic acid derivative represented by the following general formula (4):

[0009]

Embedded image (Wherein Ar ¹ and Ar ² each independently represent an aryl group, and L each independently represents a phosphine ligand). This is a method for producing a benzoic acid derivative using a palladium complex compound represented by the following formula:

Hereinafter, the present invention will be described in detail.

The aromatic compound represented by the general formula (1) used in the present invention may have a substituent other than the group represented by X as long as it is inert in the method of the present invention. A compound in which a halogen, a trifluoromethanesulfonate group, an alkylsulfonate group having 1 to 4 carbon atoms, or a substituted or unsubstituted arylsulfonate group is bonded to an aromatic group which may be present. Practically preferred are halides whose raw materials are easily available. Halogen is fluorine, chlorine, bromine or iodine, with bromine or iodine being more preferred.

The aromatic group may be a carbocyclic group such as a phenyl group or a naphthyl group, or a heterocyclic group such as a pyridyl group or a quinolyl group. The aromatic group may have a substituent. Group) represented by the general formula (5)

[0013]

Embedded image (Wherein each R ² is independently a trifluoromethyl group,
Trifluoromethyloxy group, halogen (representing fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, 1 to 1 carbon atom
4 represents an alkoxy group or an alkoxycarbonyl group having 2 to 5 carbon atoms, and n represents 0 or an integer of 1 to 5. ) Is preferable. Examples of the alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, n
-Propyl group, i-propyl group, n-butyl group, alkoxy group having 1 to 4 carbon atoms, for example, methoxy group,
Examples of the ethoxy group, n-propoxy group, i-propoxy group, and alkoxycarbonyl group having 2 to 5 carbon atoms include a methoxycarbonyl group, an ethoxycarbonyl group,
-Propoxycarbonyl group and i-propoxycarbonyl group.

The aromatic compound represented by the general formula (1) has an alkyl group, an alkoxy group, a halogen (different from X) or a trifluoromethyl group exemplified above as R, and X is bromine. Or those having an iodine atom are more preferable. Specific examples of those having an alkyl group include 2-, 3- or 4-bromotoluene, 2
-, 3- or 4-bromoethylbenzene, 2-, 3-
Or 2-, such as 4-bromo-isopropylbenzene,
Examples thereof include 3- or 4-bromo n-butylbenzene, and 2-, 3- or 4-bromomethoxybenzene,
-, 3- or 4-bromoethoxybenzene, 2-3
-Or 4-bromo n-propoxybenzene, 2, 3
-Or 4-bromoisopropoxybenzene, 2-3
-Or 4-bromo n-butoxybenzene, 2-,
Examples thereof include, but are not limited to, 3- or 4-bromochlorobenzene, and compounds in which bromine is substituted with iodine.

Further, as the aromatic compound represented by the general formula (1), halogeno- (trifluoromethyl) benzene, halogeno-bis (trifluoromethyl) benzene or hydrogen on the benzene ring of these compounds is halogen. Compounds substituted with atoms are preferred.

Specifically, 2-trifluoromethylphenyl bromobenzene, 3-trifluoromethylphenyl bromobenzene having one trifluoromethyl group,
4-trifluoromethylphenylbromobenzene, 2,3-bis (trifluoromethyl) phenylbromobenzene having two trifluoromethyl groups, 2,4-bis (trifluoromethyl) phenylbromobenzene, 2,
5-bis (trifluoromethyl) phenylbromobenzene, 2,6-bis (trifluoromethyl) phenylbromobenzene, 3,4-bis (trifluoromethyl) phenylbromobenzene, 3,5-bis (trifluoromethyl) Examples thereof include phenylbromobenzene and compounds in which bromine is substituted with iodine, but is not limited thereto.

Further, aromatic compounds having a halogen other than X include 2-chloro-3- (trifluoromethyl) bromobenzene, 2-fluoro-3- (trifluoromethyl) bromobenzene, 2-fluoro-4 -(Trifluoromethyl) bromobenzene, 3-fluoro-5-
(Trifluoromethyl) bromobenzene, 2-bromo-
6- (trifluoromethyl) bromobenzene, 4-chloro-2- (trifluoromethyl) bromobenzene, 4-
Fluoro-2- (trifluoromethyl) bromobenzene, 2-chloro-6- (trifluoromethyl) bromobenzene, 4-fluoro-3- (trifluoromethyl) bromobenzene, 1-chloro-4- (trifluoromethyl ) Bromobenzene, 2-fluoro-6- (trifluoromethyl) bromobenzene, 2-fluoro-5- (trifluoromethyl) bromobenzene, 2-chloro-4-
(Trifluoromethyl) bromobenzene, 4-chloro-
Examples thereof include, but are not limited to, 3- (trifluoromethyl) bromobenzene, 4-chloro-2- (trifluoromethyl) bromobenzene, and compounds in which bromine is substituted with iodine.

Of these, 3,5-bis (trifluoromethyl) bromobenzene or 3,5-bis (trifluoromethyl) iodobenzene, or hydrogen of the benzene nucleus of these, is remarkable because the usefulness of the product is remarkable. Is more preferably 2-chloro-3,5-bis (trifluoromethyl) bromobenzene substituted with halogen. In this case, when the former two are used as starting materials, 3,5-bis (trifluoromethyl) benzoic acid or its ester is obtained, and from the latter, 2-chloro-3,5-bis (trifluoromethyl) benzoic acid is obtained. Or an ester thereof.

When the method of the present invention is applied to an aromatic compound represented by the general formula (1), generally, a halogen or trifluoromethanesulfonate group bonded to an aromatic ring, an alkylsulfonate group having 1 to 4 carbon atoms, a substituted or unsubstituted Only a substituted arylsulfonate group or the like is converted into a carboxyl group, and a product having the substituent represented by R unchanged is obtained. Compounds having a plurality of different halogens on the aromatic ring generally react preferentially in the order of iodine, bromine, chlorine, and fluorine, but may differ depending on the position and type of substituent on the ring.

The hydroxy compound represented by the general formula (2) R ¹ OH (2) (wherein R ¹ represents hydrogen or an alkyl group having 1 to 10 carbon atoms)
An alkyl group having 0 straight or branched chain, specifically, for example, a methyl group, an ethyl group, an n-propyl group, i
so-propyl group, n-butyl group, iso-butyl group,
Examples include alcohols and water having a sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, n-decyl group, and the like. it can. Therefore, specific examples of the hydroxy compound represented by the general formula (2) in the present invention include, for example, water, methanol, ethanol, n
-Propyl alcohol, iso-propyl alcohol,
n-butyl alcohol, iso-butyl alcohol, s
Examples include ec-butyl alcohol, tert-butyl alcohol, n-pentyl alcohol, n-hexyl alcohol, n-heptyl alcohol, n-octyl alcohol, n-nonyl alcohol, and n-decyl alcohol.

The amount of water or alcohol used in the present invention may be 1 mol or more per 1 mol of the aromatic compound represented by the general formula (1). It is preferable to add the compound in a slightly excessive amount in order to cause the compound to react at a higher conversion rate and to function as a solvent.

Examples of the base in the present invention include tertiary amines such as triethylamine, tripropylamine, tributylamine, triallylamine, N, N-dimethylaniline, N, N-diethylaniline, pyridine and N-methylmorpholine; Examples thereof include acetates such as sodium and potassium acetate, and inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

The amount of the base used in the present invention is usually 1.0 to 10.0 mol, preferably 1.0 to 5.0 mol per 1 mol of the aromatic compound represented by the general formula (1). Moles, more preferably 1.0 to 3.0 moles. If the amount is less than 1.0 mol, the reaction does not proceed sufficiently, which causes a decrease in yield, which is economically disadvantageous,
Further, the load on the post-treatment process for removing or recovering the unreacted aromatic compound represented by the general formula (1) is not preferable. Further, even if it is used in an amount of more than 10.0 mol, there is almost no change in the yield of the target benzoic acid ester, and only a large amount of the excessively added base remains unreacted, which is economical. It is not preferable because it is disadvantageous and a load is applied to a post-treatment step for removing unreacted base.

The catalyst of the present invention has the general formula (4)

[0025]

Embedded image (In the formula, Ar ¹ and Ar ² each independently represent an aryl group, and L represents a phosphine ligand.)

The aryl groups represented by Ar ¹ or Ar ² in the general formula (4) are each independently a group represented by the general formula (5)

[0027]

Embedded image (Wherein each R ² is independently a trifluoromethyl group,
Trifluoromethyloxy group, halogen (representing fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, 1 to 1 carbon atom
4 represents an alkoxy group or an alkoxycarbonyl group having 2 to 5 carbon atoms, and n represents 0 or an integer of 1 to 5. ) Is an aryl group represented by

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.

The aryl group represented by the general formula (5) in the palladium complex compound represented by the general formula (4) includes a phenyl group, o-, m- and p-tolyl groups in both Ar ¹ and Ar ^2. 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, and trifluoromethyl group having one trifluoromethyl group, including a phenyl group having a hydrocarbon alkyl group 2,3-bis (trifluoromethyl) phenyl, 2,4-bis (trifluoromethyl) phenyl, 2,5-bis (trifluoromethyl) phenyl, 2,6-bis (Trifluoromethyl) phenyl group, 3,4-bis (trifluoromethyl)
Preferred examples include a phenyl group and a 3,5-bis (trifluoromethyl) phenyl group.

Furthermore, among these, those aryl groups represented by Ar ¹ in the general formula (4) complex compound represented by a certain bis (trifluoromethyl) phenyl group are preferred, whereas, in Ar ² Preferably, the aryl group represented is a phenyl group, a trifluoromethylphenyl group or a bis (trifluoromethyl) phenyl group,
More preferably, it is a trifluoromethylphenyl group or a 3,5-bis (trifluoromethyl) phenyl group.

The phosphine ligand represented by L in the palladium complex compound represented by the general formula (4) is not particularly limited, but may be represented by the general formula (6): P (R ³ ) ₃ (6) (R ³ Represents a phenyl group (aryl group) which may have a substituent independently, and represents an alkyl group having 1 to 6 carbon atoms.). Where R
^It is preferable that each ³ is independently 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. Also,
The phosphine ligand represented by L is triphenylphosphine, tri-o-tolylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine or tri-
N-butylphosphine and the like are preferred, and triphenylphosphine is particularly preferred.

General formula (4) suitable for use in the present invention
As the palladium compound represented by

[0033]

Embedded image (Tol represents an o-, m- or p-tolyl group).

The palladium complex compound used in the present invention 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 high-purity substances are easily obtained, and storage is also easy, so that it is easy to handle even in industrial use.

The method for producing the palladium complex compound used in the present invention is not particularly limited, but is described in the literature (J. Am. Chem. S.
oc., Vol. 117, No. 15, 4305 (1995)) and the methods exemplified below. A benzoic acid represented by the general formula (7) Ar-COOH (7) (where Ar is the same as above) and a general formula (1) Ar-X (1) (where Ar is With the proviso that Ar of the general formula (7)
At the same time, the same is not necessary), an aromatic compound represented by the formula (1), a solvent, a palladium compound, phosphine serving as a phosphine ligand, and a basic substance are charged. As the solvent, when the melting point is low, an aromatic compound represented by the general formula (1) can be used, and for example, aliphatic hydrocarbons such as pentane, hexane, heptane, octane, benzene, toluene,
Aromatic hydrocarbons such as xylene, diethyl ether,
Ethers such as 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 (DMF) , N, N-dimethylacetamide (DMA
c) and the like, dimethyl sulfoxide (DMS
O), sulfur-containing compounds such as 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 ratio of each material used as a raw material is not particularly limited, but in order to make effective use of palladium, the general formula (1)
It is preferable to use at least one equivalent of the aromatic compound represented by the formula and benzoic acid represented by the formula (7), 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 (4). If necessary, it can be purified by recrystallization.

The reaction of the present invention may be carried out without a solvent or in a solvent. When using a solvent,
For example, aliphatic hydrocarbons such as pentane, hexane, heptane, and octane; aromatic hydrocarbons such as benzene, toluene, and xylene; diethyl ether, dioxane, tetrahydrofuran (THF), ethers such as ethylene glycol dimethyl ether; acetone; Ketones such as methyl ethyl ketone and methyl isobutyl ketone; nitriles such as acetonitrile; tertiary amines such as pyridine; N, N-dimethylformamide (DM
Commonly used compounds such as F), acid amides such as N, N-dimethylacetamide (DMAc), and sulfur-containing compounds such as dimethylsulfoxide (DMSO) and sulfolane can be used. However, when a solvent is used, the volume of the whole reaction system increases, a larger-scale reactor is required, and the production amount per batch decreases. In the present invention, water or alcohol is used as a reactant, and since these can also function as a solvent, it is not particularly necessary to use another solvent.

The amount of the palladium complex compound used in the method of the present invention is usually 0.00001 to 0.5 mol, preferably 0.00005 as a metal per 1 mol of the aromatic compound represented by the general formula (1). To 0.1 mol, more preferably 0.0001 to 0.1 mol. 0.0000
Less than 1 mole is not preferred because the reaction progresses slowly and is not practical, and more than 0.5 mole is not preferable because there is no problem in terms of reaction but it is economically disadvantageous.

In the reaction system, a compound represented by the general formula (6) P (R ³ ) ₃ (6) (wherein R ³ is each independently an aryl group, having 1 to 1 carbon atoms)
6 represents an alkyl group. ) Or the general formula (8) (R ⁴ ) ₂ PQP (R ⁴ ) ₂ (8) (wherein R ⁴ is independently an aryl group, having 1 to 1 carbon atoms)
6 represents an alkyl group, and Q represents a divalent organic group. It is preferable to separately add the phosphine represented by the formula (1). Here, R ³ and R ⁴ may each independently be 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, and an n-butyl group. preferable. Q is-(CH ₂ ) _m- (m is 2 to 8
Alkylene group).

Accordingly, the phosphines include triphenylphosphine, tri-o-tolylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, methyldiphenylphosphine, tri-n-butylphosphine, 1,1'- Bis (diphenylphosphino) ferrocene (dppf), 1,4-bis (diphenylphosphino) butane (dppb), 1,3-bis (diphenylphosphino) propane (dppp) or 1,2-bis (diphenylphosphino) ) Ethane (dppe) and the like are preferred, and triphenylphosphine and dppb are particularly preferred.

In the method of the present invention, the phosphine added to the reaction system separately from the palladium complex compound is 0.1 mol to 100 mol, preferably 50 mol or less, more preferably 20 mol or less, per 1 mol of palladium metal. Is more preferable. Even if it is used more than 100 moles, there is almost no change in the reaction rate, the yield and the like, and it is only economically disadvantageous and is not preferable.

In the present invention, coexistence of a phosphine in the reaction system in addition to the palladium complex compound represented by the general formula (4) is effective in reducing the amount of the palladium complex compound used. It is also effective in reducing the appearance of an undesired phenomenon that palladium metal precipitates on the way and lowers the effective concentration of the catalyst.

The amount of the base used in the present invention is usually 10.0 to 1.0 mol, preferably 5.0 to 1.0 mol per 1 mol of the aromatic compound represented by the general formula (1). Mole, more preferably 3.0 to 1.0 mole. If the amount is less than this range, the reaction does not proceed sufficiently, which causes a reduction in yield and is economically disadvantageous. Further, removal or recovery of unreacted aromatic halide represented by the general formula (1) Therefore, a load is applied to the post-processing step, which is not preferable. In addition, even when used in an amount larger than this range, there is almost no change in the yield of the target benzoic acid esters, and the excessively added base remains unreacted and remains in a large amount, which is economically disadvantageous. In addition, it is not preferable because removal of unreacted base places a burden on the post-treatment step.

Next, the implementation of the manufacturing method of the present invention will be described. After charging the aromatic compound represented by the general formula (1), water or alcohols, a palladium complex compound and a base, and if necessary, a solvent and / or phosphine into the reactor, the reactor is closed, and the inside of the system is cooled. The reaction is carried out under normal pressure or under pressure after substituting with carbon monoxide. The carbon monoxide pressure is usually from normal pressure to 30 kg / cm ² , preferably from 1 to 20 kg / cm ² .
kg / cm ^2, more preferably preferably set to 2 to 10 kg / cm ^2. When the temperature is lower than this range, the reaction does not proceed sufficiently and causes a decrease in yield, which is economically disadvantageous, or a problem that the reaction speed is reduced and it takes a long time to complete the reaction. May occur, which is not preferred. In addition, even if it is higher than this range, there is almost no change in the reaction rate or the yield of the desired benzoic acid or benzoic acid ester represented by the general formula (3), and there are problems such as safety of the reaction apparatus. It is not preferable because it occurs.

The reaction temperature in the present invention is usually
The temperature is 30 ° C to 200 ° C, preferably 50 ° C to 180 ° C, and more preferably 60 ° C to 150 ° C. If the temperature is lower than this range, the reaction does not proceed sufficiently, causing a decrease in yield, and is economically disadvantageous, or
In some cases, the reaction rate is reduced and a long time is required until the reaction is completed. If the temperature is higher than this range, decomposition or the like may occur during the reaction, which causes a decrease in yield, which is economically disadvantageous, and a post-treatment step for removing decomposition products and the like. This is not preferable because the load is imposed on it.

[0049]

Next, the present invention will be described in detail with reference to examples of the production method, 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) Stainless steel with a capacity of 500 ml Autoclave 3,5
-Bis (trifluoromethyl) bromobenzene 65.3
g, 100 ml of tetrahydrofuran, palladium acetate 5
0.0 g, triphenylphosphine 175.5 g, 3,
57.6 g of 5-bis (trifluoromethyl) benzoic acid,
60.8 g of 25% aqueous ammonia was charged. Nitrogen substitution was performed twice, and when stirring was started at a nitrogen pressure of 3 kg / cm ² , the internal temperature rose to about 50 ° C. After that, the oil bath temperature was set to 120
C. and started heating. After about 2 hours, the internal temperature becomes 95.
When the temperature reached 6 ° C, the oil bath was removed and the system was cooled. Water 2
After adding 00 ml and toluene 600 ml, the mixture was stirred for several tens of minutes under ice cooling. The obtained treatment liquid was subjected to suction filtration, the organic layer of the filtrate was separated, washed twice with a saturated saline solution, dried over anhydrous magnesium sulfate, and concentrated by distilling off volatile components. The solid precipitated in the early stage of concentration was filtered off, further concentrated, and then concentrated.
Hexane was added and cooled, and the precipitated solid was separated by filtration to obtain a crude product 1.
87.5 g were obtained. The crude product was recrystallized from toluene to obtain 143.0 g of pale yellow crystals.

[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] [3,5-bis (trifluoromethyl) benzoato] 3′-trifluoromethylphenylbis (triphenylphosphine) palladium (II) was synthesized in a 500 ml stainless steel autoclave.
25.0 g of 3-trifluoromethylbromobenzene, 75 ml of tetrahydrofuran, 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 were prepared and prepared. By performing the same operation as in Example 1, 32.3 g of the objective [3,5-bis (trifluoromethyl) benzoato] 3'-trifluoromethylphenylbis (triphenylphosphine) palladium (II) was obtained.

[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, 12H)

Example 1 200 g of 3,5-bis (trifluoromethyl) bromobenzene and 145 of triethylamine were placed in a 500 ml stainless steel autoclave.
g, and 100 ml of tetrahydrofuran, and [3,5-bis (trifluoromethyl) benzoato]
3 ', 5'-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II) 2.87
g, 1.79 g of triphenylphosphine and 100 of water
g was added. After the reactor was sealed, stirring was started, and the atmosphere was replaced with nitrogen three times and further replaced with carbon monoxide three times. The initial pressure of carbon monoxide was set at 4 kg / cm ² and heating was started. One hour later, when the internal temperature reaches 100 ° C., the internal pressure is increased to 8 kg / cm.
Adjusted to ² . During the reaction, internal temperature 100 ℃, internal pressure 8kg / c
m ² was maintained.

After 12.5 hours, heating was stopped and the reactor was cooled. When the internal temperature became 50 ° C. or less, the internal gas was purged, the internal pressure was reduced to normal pressure, and nitrogen replacement was performed three times to complete the reaction.

The reaction solution was transferred to a 1000 ml beaker, and while stirring, 55 g of concentrated sulfuric acid was added dropwise from a separating funnel under ice cooling. After the completion of the dropwise addition, 50 ml of tetrahydrofuran and 100 ml of water were added, and after stirring for a while, the obtained solution was transferred to a separating funnel, and the organic layer was separated.

A stirrer, a dropping funnel and a T-shaped tube with a condenser were attached to a 2000 ml three-necked flask.
0 ml of warm water was added. Use an oil bath to raise the temperature of the hot water to 85.
C., and the above organic layer was added dropwise thereto using a dropping funnel. Since a mixture of tetrahydrofuran-water distills out a little after the start of the addition, the bath temperature and the like were adjusted while maintaining the balance between the addition amount and the distillate amount. After the addition of all
When the distillation of tetrahydrofuran was stopped and the liquid temperature and the vapor temperature started to rise, the oil bath was removed and the system was cooled to room temperature. After suction filtration of the formed precipitate, the obtained crystals were washed with water and then with toluene. After drying under reduced pressure, the desired 3,5-bis (trifluoromethyl) benzoic acid 12
8.9 g were obtained.

Example 2 200 g of 3,5-bis (trifluoromethyl) bromobenzene and triethylamine 1 were placed in a 500 ml stainless steel autoclave.
Then, 1.43 g of [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II) and 0 .4
5 g and 100 g of water were added. Thereafter, the same operation as in Example 1 was performed to obtain 130 g of 3,5-bis (trifluoromethyl) benzoic acid.

Example 3 150 g of 3,5-bis (trifluoromethyl) bromobenzene and triethylamine 11 were placed in a 500 ml stainless steel autoclave.
4.0 g and 75 g of toluene were mixed, and [3,
5-bis (trifluoromethyl) benzoato] 3 ', 5'
2.71 g of -bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II) and 200 g of water were added. Thereafter, the same operation as in Example 1 was performed to obtain 3,5-bis (trifluoromethyl) benzoic acid 8
4.0 g were obtained.

Example 4 A stainless steel autoclave having a capacity of 500 ml was mixed with 154 g of 3-trifluoromethylbromobenzene and 145 g of triethylamine, and [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5 ′. -Bis (trifluoromethyl) phenylbis (triphenylphosphine) palladium (II)
3.77 g, 0.898 g of triphenylphosphine and 100 g of water were added. Thereafter, the same operation as in Example 1 was performed to obtain 119 g of 3-trifluoromethylbenzoic acid.

[0061]

Industrial Applicability Benzoic acid derivatives and trifluoromethylbenzoic acid derivatives, which are compounds useful as intermediates for manufacturing pharmaceuticals, agricultural chemicals, various functional materials, and the like, can be easily and efficiently produced.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // C07B 61/00 300 C07B 61/00 300 (72) Inventor Satoshi Narizuka 2805 Imafuku Nakadai, Kawagoe-shi, Saitama Address: Central Glass Co., Ltd., Chemical Research Laboratory (72) Inventor Joe Morino, 2805, Imafukunakadai, Kawagoe-shi, Saitama Prefecture Central Glass Co., Ltd., Chemical Laboratory (72) Inventor, Makoto Koide 2805, Imafukunakadai, Kawagoe-shi, Saitama 4G069 AA15 BA27A BA27B BC72A BC72B BE26A BE37A 4H006 AA02 AC48 BA25 BA48 BA69 BE40 BJ50 BS30 4H039 CA66 CD10 CD20 CF30 CL25

Claims (13)

[Claims] (1) Ar—X (1) wherein Ar is an aryl group, X is a halogen (fluorine, chlorine, bromine or iodine), a trifluoromethanesulfonate group, and an alkyl group having 1 to 4 carbon atoms. An aromatic compound represented by a sulfonate group or a substituted or unsubstituted arylsulfonate group) is reacted with carbon monoxide in the presence of a catalyst and a base to obtain a compound represented by the general formula (2) R ¹ OH (2) (where R ¹ is hydrogen , An aryl group or 1 to 10 carbon atoms
Wherein the hydroxy compound is represented by the general formula (3): (Wherein Ar and R ¹ are the same as described above), which is a method for producing a benzoic acid derivative represented by the following general formula (4): (Wherein Ar ¹ and Ar ² each independently represent an aryl group, and L each independently represents a phosphine ligand). A method for producing a benzoic acid derivative using a palladium complex compound represented by the following formula: 2. Ar is a compound represented by the general formula (5). (Wherein R ² is a trifluoromethyl group, a trifluoromethyloxy group, a halogen (refers to fluorine, chlorine, bromine or iodine), a nitro group, an acetyl group, a cyano group, an alkyl group having 1 to 4 carbon atoms, An alkoxy group of Formulas 1 to 4,
Represents an alkoxycarbonyl group having 2 to 5 carbon atoms, and n is 0
Or, represents an integer of 1 to 5. The method for producing a benzoic acid derivative according to claim 1, which is an aryl group represented by the formula: 3. An aromatic compound represented by the general formula (1):
The method for producing a benzoic acid derivative according to claim 2, which is an aromatic compound having at least one trifluoromethyl group. 4. The hydroxy compound represented by the general formula (2) R ¹ OH (2) (wherein R ¹ represents hydrogen or an alkyl group having 1 to 10 carbon atoms) is water. 3. The method for producing benzoic acid according to any one of 3. 5. The aryl groups represented by Ar ¹ or Ar ² in the general formula (4) are each independently a group represented by the general formula (5): (Wherein R ² is a trifluoromethyl group, a trifluoromethyloxy group, a halogen (refers to fluorine, chlorine, bromine or iodine), a nitro group, an acetyl group, a cyano group, an alkyl group having 1 to 4 carbon atoms, An alkoxy group of Formulas 1 to 4,
Represents an alkoxycarbonyl group having 2 to 5 carbon atoms, and n is 0
Or, represents an integer of 1 to 5. The method for producing a benzoic acid derivative according to any one of claims 1 to 4, which is an aryl group represented by the formula: 6. The method for producing a benzoic acid derivative according to claim ¹ , wherein the aryl group represented by Ar ¹ in the general formula (4) is a bis (trifluoromethyl) phenyl group. 7. The aryl group represented by Ar ² in the general formula (4) is a phenyl group, a trifluoromethylphenyl group or a bis (trifluoromethyl) phenyl group.
7. The method for producing a benzoic acid derivative according to any one of items 1 to 6. 8. An aryl group represented by Ar ² in the general formula (4) is a 3-trifluoromethylphenyl group or 3,5
The method for producing a benzoic acid derivative according to any one of claims 1 to 6, which is a -bis (trifluoromethyl) phenyl group. 9. A phosphine ligand represented by L in the general formula (4) is a compound represented by the general formula (6): P (R ³ ) ₃ (6) (wherein R ³ is independently an aryl group, The benzoic acid derivative according to any one of claims 1 to 6, which is a phosphine ligand represented by the following formula: 10. A compound according to claim 1, wherein R ^{3 in} formula (6) is independently selected from phenyl, o-tolyl, m-tolyl, p-tolyl, methyl and ethyl. 7. The method for producing a benzoic acid derivative according to any one of items 1 to 6. 11. The method for producing a benzoic acid derivative according to claim 1, wherein both L in the general formula (4) are triphenylphosphine. 12. The palladium complex compound represented by the general formula (4) is [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-bis (trifluoromethyl) phenyl-bis (triphenyl) (Phosphine) palladium (II) or [3,5-bis (trifluoromethyl) benzoato]
The method for producing a benzoic acid derivative according to any one of claims 1 to 6, wherein the method is 3'-bis (trifluoromethyl) phenyl-bis (triphenylphosphine) palladium (II). 13. A method of converting 3,5-bis (trifluoromethyl) bromobenzene or 3,5-bis (trifluoromethyl) iodobenzene to [3,5-bis (trifluoromethyl) benzoato] 3 ′, 5′-. Bis (trifluoromethyl) phenyl-bis (triphenylphosphine) palladium (II) or [3,5-bis (trifluoromethyl) benzoato] 3'-bis (trifluoromethyl) phenyl-bis (triphenylphosphine) palladium (I
A method for producing 3,5-bis (trifluoromethyl) benzoic acid, comprising reacting I) with carbon monoxide and water in the presence of a base.