JP2996780B2 - Method for separating fluoro-substituted benzaldehyde - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for separating a fluoro-substituted benzaldehyde, and more particularly, to a method useful as an intermediate for pesticides and pharmaceuticals from a mixture of a fluoro-substituted benzyl halide, a fluoro-substituted benzaldehyde and a fluoro-substituted benzoic acid. The present invention relates to a method for separating high-purity fluoro-substituted benzaldehyde.

[0002]

2. Description of the Related Art In recent years, fluoro-substituted benzaldehydes have attracted attention as important synthetic intermediates for pharmaceuticals, agricultural chemicals and the like. As a general method for producing a fluoro-substituted benzaldehyde, a fluoro-substituted toluene is halogenated in a side chain,
There is known a method of separating and purifying benzal halides from the reaction product mixture and hydrolyzing them. Since side-chain halides produced as intermediates in this method have close boiling points, a high-stage rectification column is used to separate only benzal halides from other side-chain halides by rectification with high purity. Therefore, this method was not suitable especially in the field of fine chemicals where relatively small-scale production of fluoro-substituted benzaldehyde is required.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the conventional method and to obtain a desired fluoro-substituted benzaldehyde from a mixture of fluoro-substituted benzaldehyde, fluoro-substituted benzyl halide and fluoro-substituted benzoic acid. Is to provide a method for separating the compound with high purity and high yield.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for separating a fluorosubstituted benzaldehyde with a high yield from a mixture of a fluorosubstituted benzyl halide, a fluorosubstituted benzaldehyde and a fluorosubstituted benzoic acid. , Surprisingly, the general formula

[0005]

Embedded image It was confirmed that the fluorosubstituted benzaldehyde can be separated with high purity by the method shown in (1). That is, a fluoro-substituted benzaldehyde can be obtained in high purity and high yield from a mixture of side chain halides (meaning benzyl halide, benzal halide, benzotrihalide) without isolating and purifying benzal halides. The present invention has been completed.

The method for separating a fluoro-substituted benzyl halide according to the present invention comprises treating a mixture of a fluoro-substituted benzyl halide, a fluoro-substituted benzaldehyde and a fluoro-substituted benzoic acid with an aqueous alkali solution to separate the fluoro-substituted benzoic acid as an alkali metal salt. Ammonia water is added to the remaining mixture of the fluoro-substituted benzyl halide and the fluoro-substituted benzaldehyde to form an oil containing a Schiff base, and further hydrolyzed with a mineral acid to convert the fluoro-substituted benzylamine into its mineral acid salt. Extracting into a layer and separating the fluoro-substituted benzaldehyde.

Hereinafter, the method for separating a fluoro-substituted benzaldehyde of the present invention will be described in detail. The mixture of fluoro-substituted benzyl halide, fluoro-substituted benzaldehyde and fluoro-substituted benzoic acid used as a raw material in the present invention may be one in which a benzene nucleus of each compound has a fluoro atom optionally substituted in the range of 1 to 5, In addition to the fluoro atom, a halogen atom such as a chlorine atom or a bromine atom may be introduced as a substituent.

[0008] Such a raw material mixture can be usually obtained by hydrolyzing a reaction product mixture obtained by side-halogenating a nuclear fluorine-substituted toluene derivative. Specific examples of the nuclear fluorine-substituted toluene derivative include monofluorotoluenes such as 2-fluorotoluene, 3-fluorotoluene, and 4-fluorotoluene; 2,4 -difluorotoluene; 2,3-difluorotoluene; Difluorotoluenes such as difluorotoluene, 3,5-difluorotoluene, 2,5-difluorotoluene, 2,6-difluorotoluene, 2,3,4 -trifluorotoluene, 3,4,5-trifluorotoluene, 2 , 4,5-
Trifluorotoluenes such as trifluorotoluene,
2,3,5,6 -tetrafluorotoluene, 2,3
Examples thereof include tetrafluorotoluenes such as 4,5 -tetrafluorotoluene and pentafluorotoluene. Further, the raw material mixture used in the present invention may be a mixture obtained by separately mixing a fluoro-substituted benzyl halide, a fluoro-substituted benzaldehyde and a fluoro-substituted benzoic acid.

By treating the above mixture with an aqueous alkali solution, first, the fluoro-substituted benzoic acid becomes an alkali metal salt and is removed by transferring to an aqueous layer. As the aqueous alkali solution to be used, for example, an aqueous solution of sodium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium hydroxide, potassium carbonate, potassium hydrogen carbonate or the like is used. The remaining fluoro-substituted benzyl chlorides and fluoro-substituted benzaldehydes are reacted with aqueous ammonia to convert the fluoro-substituted benzyl halides into fluoro-substituted benzylamine, which is condensed with the fluoro-substituted benzaldehyde to obtain a Schiff base. In this case, when the fluoro-substituted benzaldehyde is present in excess, unreacted fluorobenzaldehyde remains, but reacted with excess ammonia, the general formula

[0010]

It was confirmed that a compound represented by the following formula was formed. This compound is easily converted to a fluoro-substituted aldehyde by hydrolysis, and there is no problem if this compound is formed as a by-product.

The concentration of aqueous ammonia used in the above reaction is 3 to 20% by weight, preferably 5 to 10% by weight. The reaction is carried out at room temperature to 100 ° C., more preferably at 50 ° C.
It is carried out while heating at 80 ° C. The molar ratio of aqueous ammonia to fluoro-substituted benzyl halides is at least 20
The molar amount is not more than 2 times, preferably 5 to 15 times. When the Schiff base obtained by the above operation is hydrolyzed with a mineral acid, it becomes a fluoro-substituted benzaldehyde and a fluoro-substituted benzylamine.The fluoro-substituted benzylamine is dissolved in the aqueous layer as its mineral acid salt. Precipitate as an oil. The obtained fluoro-substituted benzaldehydes can be easily recovered by liquid separation or solvent extraction.

The mineral acids used at this time include hydrochloric acid, sulfuric acid and the like. Among them, the use of hydrochloric acid is preferable, and the amount of use is equivalent or more, preferably 1 to 6 equivalents. The concentration of hydrochloric acid is used at 1 to 35% by weight, preferably 2 to 10% by weight. On the other hand, with respect to fluoro-substituted benzylamines, the aqueous layer can be easily and highly purified by treating the aqueous layer with a base such as sodium hydroxide.

[0013]

According to the method of the present invention, that is, using a mixture of a fluoro-substituted benzyl halide, a fluoro-substituted benzaldehyde and a fluoro-substituted benzoic acid as a raw material, the operation according to the above formula 1 of the present invention is not considered in the conventional method. Fluorobenzaldehydes can be separated in high purity and high yield, which has not been obtained. Further, according to the method of the present invention, a fluoro-substituted benzaldehyde can be separated from a hydrolyzed mixture thereof with high purity and high yield without isolating and purifying benzal halides from side chain halides. Further, the present invention provides not only fluorosubstituted benzaldehydes,
The fluoro-substituted benzoic acid and fluoro-substituted benzylamine produced in each step also have the feature that they can be separated with high purity, and are excellent as a method for separating these compounds.

[0014]

EXAMPLES The method for separating a fluoro-substituted benzaldehyde of the present invention will be described below in detail with reference to examples. (Production Example 1) 4-fluorotoluene (1.0 mol) was added to 9
At 0 to 160 ° C., treatment with 2 moles of bromine, 4-fluorobenzyl bromide: 4-fluorobenzalbromide: 4-fluorobenzotribromide = 4.
A composition having a weight ratio of 2: 91.3: 4.5 was obtained. Next, the composition was reacted with water using zinc oxide as a catalyst to obtain a hydrolysis reaction solution.

(Example 1) (Separation of 4-fluorobenzaldehyde) In a 500 ml four-necked flask equipped with a stirrer, a thermometer, and a reflux condenser, the concentration of the hydrolysis reaction solution obtained in Production Example 1 was 2.72. 120% by weight of sodium hydroxide solution was added, and 4-fluorobenzoic acid was separated as a salt to obtain 96.1 g of a mixture of 4-fluorobenzyl bromide and 4-fluorobenzaldehyde (hereinafter, referred to as mixture A). Next, 5 was equipped with a stirrer, a thermometer, and a reflux condenser.
110 ml of 7% aqueous ammonia in a 00 ml four-necked flask
(0.44 mol as NH ₃ ), and while maintaining the temperature of the flask at 70 to 75 ° C., the mixture A obtained above,
96.1 g was added all at once and reacted for 3 hours. After completion of the reaction, the mixture was allowed to stand for a while, and the separated oil layer was separated. Separately, 319.6 g (0.81 mol as HCl) of 9.3% by weight hydrochloric acid was charged into a 500 ml four-necked flask equipped with a stirrer, a thermometer and a reflux condenser, and the oil layer separated as described above was poured into the flask. Was added and stirred at room temperature for 1 hour. In this way, a reaction solution separated into two layers was obtained. To this, 90 g of toluene was added, liquid separation was performed, and 90 g of toluene was again added to the aqueous layer.
Was added thereto, and the mixture was extracted and separated. The oil layer was taken out, combined with the above oil layer, dried and distilled under reduced pressure to obtain 74.1 g of 4-fluorobenzaldehyde. This was 76.8% in a yield based on 4-fluorobenzal bromide.

(Production Example 2) 4-fluorotoluene (5.
0 mol) at 105 ° C. with 1.05 moles of chlorine to give 4-fluorobenzyl chloride: 4-fluorobenzal chloride: 4-fluorobenzotrichloride = 21.7: 68.5: 9. 0.7 (weight ratio) was obtained. Next, the composition was reacted with water using zinc oxide as a catalyst to obtain a hydrolysis reaction solution.

(Example 2) (Separation of 4-fluorobenzaldehyde) 1000 ml equipped with a stirrer, thermometer and reflux condenser
In a four-necked flask, 256.8 m of a sodium hydroxide solution having a concentration of 2.72% by weight was added to the hydrolysis reaction solution obtained in Production Example 2.
l, 4-fluorobenzoic acid is separated as a salt and 4
165 g of a mixture of -fluorobenzyl halide and 4-fluorobenzaldehyde (hereinafter, referred to as mixture B )
Obtained. Next, a 7% aqueous ammonia solution was placed in a 1000 ml four-necked flask equipped with a stirrer, a thermometer, and a reflux condenser.
2.6 ml (3.0 mol as NH ₃ ) was charged, and while maintaining the temperature of the flask at 70 to 75 ° C., 165 g of the mixture B was added at once, and the mixture was reacted for 8 hours. After completion of the reaction, the mixture was allowed to stand for a while, and the separated oil layer was separated. Separately, in a 1000 ml four-necked flask equipped with a stirrer, a thermometer, and a reflux condenser, 671.6 g of 9.3% by weight hydrochloric acid (H
(1.71 mol as Cl) was added thereto, and the oil layer separated as described above was added thereto, followed by stirring at room temperature for 4 hours.
A reaction mixture separated into two layers was thus obtained. To this, 115 g of toluene was added, liquid separation was performed, 115 g of toluene was again added to the aqueous layer, liquid separation was performed, and the oil layer was taken out and combined with the above-mentioned oil layer and dried. Thereafter, the mixture was distilled under reduced pressure at 21 mmHg to obtain 95.0 g of 4-fluorobenzaldehyde as a fraction having a boiling point of 75 ° C. This corresponds to a yield of 74.4% based on 4-fluorobenzal chloride.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Tatsuo Sugiyama 2256 Nakanosato, Fujikawa-cho, Anbara-gun, Shizuoka Pref. Ihara Chemical Industry Co., Ltd. (56) References JP-A-4-5262 (JP, A) JP-A-48 JP-A-96532 (JP, A) JP-A-64-56652 (JP, A) JP-A-62-446 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 47/55 C07C 45/80 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A mixture comprising a fluoro-substituted benzyl halide, a fluoro-substituted benzaldehyde, and a fluoro-substituted benzoic acid is treated with an aqueous alkali solution to separate the fluoro-substituted benzoic acid as an alkali metal salt thereof. Aqueous ammonia is added to the mixture of benzaldehyde to form an oil containing Schiff base, and further hydrolyzed with a mineral acid to extract the fluorosubstituted benzylamine as its mineral acid salt into the aqueous layer to separate the fluorosubstituted benzaldehyde. A method for separating a fluoro-substituted benzaldehyde, comprising: