JP2003267911A - Method for producing 2-fluorobenzoic acid derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new and advantageous method for the production of a 2-fluorobenzoic acid derivative. <P>SOLUTION: The method for the production of a 2-fluorobenzoic acid derivative expressed by general formula (1) (R is a ≤20C straight, branched or cyclic alkyl, alkenyl, alkoxy or alkenyloxy which may be substituted with a 1-10C alkoxy group) comprises the reaction of the corresponding 3-fluorobenzene derivative with s-butyllithium and the reaction of the product with carbon dioxide. The 2-fluorobenzoic acid derivative is easily produced in an improved yield by the method from a compound easily available at a low cost. The produced 2-fluorobenzoic acid derivative is extremely useful as a production intermediate for a liquid crystal compound for liquid crystal display use. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to electronic materials, medical and agricultural chemicals,
Particularly useful as a synthetic intermediate for liquid crystal materials for electro-optical displays
The present invention relates to a novel method for producing a 2-fluorobenzoic acid derivative.

[0002]

2. Description of the Related Art 2-Fluorobenzoic acid derivatives, particularly 2-fluorobenzoic acid in which the 4-position is substituted with an alkyl group, etc., are useful as intermediates for the production of various electronic materials, pharmaceuticals, agricultural chemicals, etc.
As a production method, there is a description as a production intermediate of a liquid crystal compound in JP-A-3-503637. In this publication, alkynes are coupled to 2-fluoro-4-bromobenzonitrile, then an alkynyl group is catalytically reduced to an alkyl group, and a cyano group is hydrolyzed to give 4-alkyl-2.
-A method for obtaining fluorobenzoic acid is disclosed. However, this method has many problems such that the starting material 2-fluoro-4-bromobenzonitrile is expensive, the yield in the coupling step is low, and the alkyne is difficult to obtain. It was hard to say.

Further, in German Laid-Open Patent Publication No. 3939116, 3-fluorobenzene derivative having a liquid crystal skeleton is reacted with n-butyllithium to lithiate 4-position to react with dry ice to 4-substituted-2. -There is a description that fluorobenzoic acid is obtained as a synthetic intermediate. But this way,
The selectivity and yield of the reaction are extremely low, and the practicality is poor. Therefore, 4-alkyl-2-fluorobenzoic acid and other 4
It has been desired to develop a method for producing a -substituted-2-fluorobenzoic acid derivative at high yield and at low cost.

[0004]

The problem to be solved by the present invention is to provide a method for producing a 4-substituted-2-fluorobenzoic acid derivative at a high yield and at a low cost.

[0005]

Means for Solving the Problems As a result of intensive studies for solving the above problems, the present inventors have found that the general formula (I)

[Chemical 3] (In the formula, R represents a linear, branched, or cyclic alkyl group having 20 or less carbon atoms, an alkenyl group, an alkoxyl group, or an alkenyloxy group, and these groups have 1 to 1 carbon atoms.
It may be substituted with 0 alkoxyl group. ) A method for producing a 2-fluorobenzoic acid derivative represented by the general formula
(II)

[0006]

[Chemical 4] (In the formula, R represents the same meaning as in formula (I).) A method for producing a fluorobenzene derivative, which comprises reacting s-butyllithium with carbon dioxide and then reacting with carbon dioxide To do.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the production method of the present invention, the reaction is carried out in a solvent, and the solvent is tetrahydrofuran (THF), cyclic ethers such as 1,4-dioxane, diethyl ether, dibutyl ether, diisopropyl. Ethers (IPE), chain ethers such as dimethoxyethane (DME), hexane, pentane, heptane, saturated hydrocarbons such as petroleum ether, benzene, toluene, aromatic hydrocarbons such as xylene can be used, These may be used alone or as a mixture, but cyclic ethers such as THF are preferable.

The reaction is usually carried out by cooling to room temperature or lower, but during the reaction with s-butyllithium, 0 to -100 ° C is preferable, and -30 ° C to -80 ° C is more preferable. Next, at the time of reaction with carbon dioxide, 0 to -100 ° C is preferable, and -20 ° C to -8
0 ° C. is more preferable.

The production method of the present invention is characterized in that the fluorobenzene derivative of the general formula (II) is reacted with s-butyllithium and then with carbon dioxide. The obtained benzoic acid is used as a lithium salt. If present, it is preferably treated with acid, if desired.

In the production method of the present invention, 2 of the general formula (I)
The -fluorobenzoic acid derivative is preferable for producing a compound in which R represents an alkyl group, and particularly preferable for producing a compound having a linear alkyl group having 1 to 10 carbon atoms.

The fluorobenzene derivative of the general formula (II) used as a raw material can be easily produced and obtained from 3-fluorobromobenzene which is inexpensive and easily available. For example,
In the case of 3-fluoro-1-alkylbenzene, a Grignard reagent prepared from 3-fluorobromobenzene is reacted with N, N-dimethylformamide (DMF), and the resulting 3-fluorobenzaldehyde is reacted with an alkyl Wittig reagent. And then catalytically reduced. Alternatively, it can also be obtained by reacting 3-fluorobromobenzene and 1-alkynes in the presence of a transition metal catalyst, and then catalytically reducing the same. Other fluorobenzene derivatives represented by the general formula (II) can be easily obtained by the same or similar production method.

Various useful liquid crystal compounds can be produced by using the benzoic acid derivative of the general formula (I) thus obtained as an intermediate. For example, after reacting (I) with thionyl chloride or oxalic acid dichloride to give an acid chloride, or (I) directly in the presence of a condensing agent such as dicyclohexylcarbodiimide, by reacting with 4-substituted phenols, various A liquid crystal ester compound which is a phenyl derivative of 2-fluorobenzoate can be obtained, and these are very useful as a constituent material of a liquid crystal composition.

For example, a compound in which R is a propyl group in the general formula (I) is used as an intermediate and a 4-substituted phenol is used.
4-Propyl-2-fluorobenzoic acid obtained by reacting with 3,5-difluoro-4-cyanophenol 3,5-difluoro-4
-Cyanophenyl (A)

[Chemical 5] Is a useful compound that has a melting point of 69 ° C. and can be improved in various characteristics by adding it to a liquid crystal composition, especially a liquid crystal composition for STN, to drastically reduce its driving voltage.

[0014]

The present invention will be further described below by showing Examples of the present invention. However, the present invention is not limited to these examples.

(Example) Preparation of 2-fluoro-4-propylbenzoic acid 24.1 g of 3-fluoropropylbenzene (0.174 mol) was dissolved in 240 mL of dry THF and cooled to -78 ° C. 200 mL (0.192 mol) of s-butyllithium (0.96 M cyclohexane solution) was added dropwise under stirring in an argon atmosphere at a rate such that the internal temperature was kept at -60 ° C or lower. After the dropping was completed, the mixture was stirred at the same temperature for 1 hour, and then carbon dioxide was blown thereinto at -60 ° C or lower. After the carbon dioxide absorption and heat generation were not confirmed, 10% hydrochloric acid was added dropwise, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and dried, and the crude crystals obtained by distilling off the solvent under reduced pressure were washed with n-hexane and further dried under reduced pressure to give a melting point of 124 to 125 ° C. 22.8 g of white crystals of 2-fluoro-4-propylbenzoic acid were obtained. (Yield 72%)

Comparative Example In the examples, n-butyllithium (1.6M n-hexane solution) was used instead of s-butyllithium.
Except for using 120 mL (0.192 mol), white crystals of 2-fluoro-4-propylbenzoic acid (melting point 124-125 ° C) were prepared in the same manner.
However, the yield was 8.0 g. (23% yield)

[0017]

EFFECTS OF THE INVENTION According to the production method of the present invention, a 2-fluorobenzoic acid derivative can be easily produced at a higher yield than ever before using an inexpensive and easily available compound as a raw material. The obtained 2-fluorobenzoic acid derivative is extremely useful as a production intermediate for liquid crystal compounds used for liquid crystal displays.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Shigenori Nara             3-18-22 Mimomi, Narashino, Chiba Prefecture Iiyo Heights             201 (72) Inventor Hiroshi Yoshino             4-24-13 Higashisugano, Ichikawa City, Chiba Prefecture F-term (reference) 4H006 AA02 AC46 BB11 BB15 BB25                       BC10 BJ30 BM30 BM71 BS30

Claims (2)

[Claims] 1. A compound represented by the general formula (I): (In the formula, R represents a linear, branched, or cyclic alkyl group having 20 or less carbon atoms, an alkenyl group, an alkoxyl group, or an alkenyloxy group, and these groups have 1 to 1 carbon atoms.
It may be substituted with 0 alkoxyl group. ) A method for producing a 2-fluorobenzoic acid derivative represented by the general formula
(II) [Chemical formula 2] (In the formula, R represents the same meaning as in the general formula (I).) The 3-fluorobenzene derivative represented by the formula is reacted with s-butyllithium, and then with carbon dioxide. . 2. The production method according to claim 1, wherein R represents a linear alkyl group having 1 to 10 carbon atoms.