JP2003335766A - Method for producing dibenzoyltartaric acid and acid anhydride thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide methods for industrially advantageously producing dibenzoyltartaric acid and acid anhydride thereof with no formation of byproducts including benzoic acid and sulfur dioxide gas needing troublesome after-treatment. <P>SOLUTION: The method for producing the dibenzoyltartaric anhydride comprises carrying out a reaction between tartaric acid, benzoyl chloride and benzotrichloride in an organic solvent. The method for producing the dibenzoyltartaric acid comprises hydrolyzing the resultant dibenzoyltartaric anhydride. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing dibenzoyl tartaric acid and its acid anhydride, which are important compounds for use as optical resolving agents for various racemic amines and for various organic synthetic intermediates. .

[0002]

2. Description of the Related Art As a method for producing dibenzoyltartaric acid or its acid anhydride from tartaric acid as a raw material, the following methods have been proposed so far. That is, the first method is a method of reacting tartaric acid with benzoyl chloride to produce dibenzoyl tartaric anhydride, and hydrolyzing the dibenzoyl tartaric anhydride to produce dibenzoyl tartaric acid, for example, D-tartaric acid. A method of producing dibenzoyl D-tartaric acid anhydride by reacting benzoyl chloride with a 3-fold molar amount thereof, and hydrolyzing this to produce dibenzoyl D-tartaric acid has been proposed (for example, CL Butl
ar and Leonard H. Cretcher, J. Am. Chem. Soc., 55
(1933), p2605 etc.).

However, in this first method, a 3-fold molar amount of benzoyl chloride is used with respect to tartaric acid, and an excess 1-fold molar amount of benzoyl chloride that is not consumed in the benzoylation reaction becomes a dibenzoyltartaric acid anhydride. When consumed, it produces a one-fold molar amount of benzoic acid. Therefore, when manufacturing dibenzoyl tartaric anhydride, of course,
When dibenzoyltartaric acid anhydride is hydrolyzed to produce dibenzoyltartaric acid, benzoic acid produced as a by-product must be separated and removed, and the benzoic acid produced as a by-product should be recovered and reused. However, a post-treatment such as purification is required, but the process therefor is complicated and not economical.

As a second method, there is a method of reacting tartaric acid with benzoyl chloride and thionyl chloride to produce dibenzoyl tartaric anhydride, and hydrolyzing the dibenzoyl tartaric anhydride to produce dibenzoyl tartaric acid. For example, a method has been proposed in which tartaric acid is reacted with twice the molar amount of benzoyl chloride in the presence of thionyl chloride to produce dibenzoyl tartaric anhydride, and this is hydrolyzed to produce dibenzoyl tartaric acid. (For example,
Hungarian Patent No. 191,051 specification).

However, in the second method, since thionyl chloride is used in addition to benzoyl chloride, it is disadvantageous in terms of production cost, and there is a problem that a facility for treating the generated sulfur dioxide gas is required. is there.

[0006]

Therefore, the present inventors have solved various problems that were unavoidable in the above-mentioned conventional methods, and have a troublesome post-treatment such as benzoic acid and sulfur dioxide gas. As a result of diligent studies on a method capable of industrially advantageously producing dibenzoyltartaric acid and its acid anhydride without generation of by-products, the object was achieved by reacting tartaric acid with benzoyl chloride and benzotrichloride. The inventors have found out what can be done and have completed the present invention.

Accordingly, an object of the present invention is to industrially advantageously produce dibenzoyl tartaric acid and its acid anhydride without the generation of by-products such as benzoic acid and sulfur dioxide gas which require a troublesome post-treatment. Another object of the present invention is to provide a method for producing dibenzoyl tartaric acid and its acid anhydride.

[0008]

That is, the present invention is a method for producing dibenzoyl tartaric anhydride by reacting tartaric acid with benzoyl chloride and benzotrichloride in an organic solvent to obtain dibenzoyl tartaric anhydride. Further, the present invention is a method for producing dibenzoyl tartaric acid, wherein dibenzoyl tartaric acid anhydride is obtained by hydrolyzing dibenzoyl tartaric acid anhydride obtained by reacting tartaric acid with benzoyl chloride and benzotrichloride in an organic solvent.

In the present invention, the tartaric acid used as a raw material may be L-tartaric acid which is an optically active substance, or D-tartaric acid, and further, these L-tartaric acid and D-tartaric acid can be used. It may be a mixture (racemic form or the like). As the tartaric acid, a commercially available one may be used, or a tartaric acid synthesized by a known method may be used.

In the present invention, the reaction of tartaric acid with benzoyl chloride and benzotrichloride may be carried out by adding a mixture of benzoyl chloride and benzotrichloride to tartaric acid in an organic solvent, or in an organic solvent. It is also possible to first add one of benzoyl chloride and benzotrichloride to tartaric acid, and then add the other of benzoyl chloride and benzotrichloride. Preferably, tartaric acid is reacted with benzoyl chloride, and then benzotrichloride is added and reacted.

In the reaction of tartaric acid with benzoyl chloride and benzotrichloride, the reaction ratio of tartaric acid with benzoyl chloride and benzotrichloride is such that the addition amount of benzoyl chloride is 0.1 to tartaric acid.
8 to 1.5 times molar amount, preferably 1.0 to 1.2 times molar amount, and the addition amount of benzotrichloride is 0.8 to 1.5 times.
The molar amount is 1.5 times, preferably 1.0 to 1.2 times. Regarding the amount of benzoyl chloride added, if it is less than 0.8 times the molar amount, tartaric acid as an unreacted raw material remains and the yield decreases. On the contrary, if it exceeds 1.5 times the molar amount, unreacted benzoyl chloride remains. And not economical. When the amount of benzotrichloride added is less than 0.8 times the molar amount, tartaric acid as an unreacted raw material remains and the yield decreases, and benzoic acid is mixed into the product to deteriorate the product quality. On the contrary, when the amount is more than 1.5 times the molar amount, the excessive amount of benzotrichloride is decomposed at the end of the reaction to cause coloring of the product dibenzoyltartaric acid, which is not preferable.

In the present invention, an organic solvent is used in the reaction of tartaric acid with benzoyl chloride and benzotrichloride. As the organic solvent, halogenated hydrocarbons and aromatic hydrocarbons are preferable, and specifically, trichloroethylene. , Tetrachloroethylene, chlorobenzene,
Dichlorobenzene, toluene, xylene and the like are preferably used, and trichloroethylene, tetrachloroethylene, chlorobenzene, dichlorobenzene and xylene are preferable. With regard to these organic solvents, only one kind thereof may be used alone, or two or more kinds may be mixed and used as a mixed solvent.

Further, in the present invention, the benzoylation reaction may be carried out without a catalyst, but a Lewis acid catalyst may be added as a catalyst during the reaction, and the reaction is carried out by adding the catalyst. The advantage is that the speed is increased and the reaction time can be shortened. Examples of Lewis acid-based catalysts added for this purpose include ferric chloride, aluminum chloride, antimony pentachloride, titanium chloride, zinc chloride, tin chloride, and boron trifluoride. From the viewpoint of activity and the amount of by-products produced, ferric chloride is preferable. With regard to these Lewis acid catalysts, one type thereof may be used alone, or two or more types may be used as a mixture.

The reaction conditions in the benzoylation reaction of the present invention may be the same as those of a usual reaction of this type,
The reaction temperature is preferably 70 to 150 ° C., more preferably 80 to 130 ° C. When the reaction temperature is lower than 70 ° C., the reaction rate becomes slow and it takes a long time to complete the reaction. If the temperature is higher than 150 ° C., tartaric acid as a raw material or dibenzoyl tartaric acid anhydride as a product is thermally decomposed and the yield is reduced. During this benzoylation reaction, dibenzoyl tartaric acid anhydride is produced and hydrogen chloride gas is by-produced.The hydrogen chloride gas may be subjected to detoxification treatment such as alkali neutralization treatment, It may be introduced into a hydrochloric acid absorption tower for treatment and taken out as a by-product hydrochloric acid.

Next, dibenzoyl tartaric acid can be produced by hydrolyzing the dibenzoyl tartaric acid anhydride obtained by the above benzoylation reaction. Regarding the hydrolysis reaction of this dibenzoyl tartaric anhydride,
It can be carried out in the same manner as the usual hydrolysis reaction of acid anhydride, and for example, the method described in the specification of Japanese Patent No. 3,208,971 can be suitably applied.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION Preferred embodiments of the method of the present invention will be specifically described below based on Examples.

Example 1 143.0 g (88.1 m) of tetrachloroethylene was placed in a reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device.
l) and 60.0 g (0.400 mol) of L-tartaric acid were added, and then 0.24 g (1.5 mmol) of ferric chloride as a catalyst was added. While maintaining the reaction temperature at 120 to 130 ° C. under stirring, first chlorination. 62.6 g (0.445 mol) of benzoyl and then 86.5 g (0.443 mol) of benzotrichloride were added dropwise at a rate of 0.52 g / min and 0.48 g / min, respectively.
After the dripping of these benzoyl chloride and benzotrichloride was completed, the reaction mixture was aged for 0.5 hours at the reaction temperature.

Thereafter, the reaction mixture was cooled to room temperature, and the precipitated crystals were filtered and washed with tetrachloroethylene to obtain 123.2 g (0.362) of dibenzoyl L-tartaric anhydride.
Mol) was obtained. The hydrogen chloride gas produced as a by-product in the process of the benzoylation reaction was introduced into an exhaust gas abatement system and neutralized.

The obtained dibenzoyl L-tartaric acid anhydride was analyzed by liquid chromatography (LC). As a result, the LC purity of dibenzoyl L-tartaric acid anhydride was 99.3%.
The yield of dibenzoyl L-tartaric acid anhydride was 90.5% based on the raw material L-tartaric acid.

Example 2 141.0 g (86.9 m) of tetrachloroethylene was placed in a reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device.
l) and 60.0 g (0.400 mol) of L-tartaric acid, then 0.24 g (1.5 mmol) of ferric chloride as a catalyst was added, and benzoyl chloride was added while maintaining the reaction temperature at 115 to 130 ° C. with stirring. A mixture of 62.6 g (0.445 mol) and 86.6 g (0.443 mol) of benzotrichloride was added to 0.
The mixture was added dropwise at a rate of 54 g / min, and after completion of the addition of this mixture, the reaction mixture was aged for 1.0 hour at the reaction temperature.

Thereafter, the reaction mixture was cooled to room temperature, and the precipitated crystals were filtered and washed with tetrachloroethylene to obtain 134.1 g of dibenzoyl L-tartaric acid anhydride (including the attached liquid). The hydrogen chloride gas produced as a by-product in the process of the benzoylation reaction was introduced into an exhaust gas abatement system and neutralized.

Next, 240.0 g (13.3%) of water was placed in a reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device.
And 30.0 g (0.326 mol) of toluene,
The above-mentioned dibenzoyl L-tartaric acid anhydride was added thereto and mixed, and the reaction temperature was raised to 80 ° C. with stirring to react for 2.0 hours, and then the reaction mixture was cooled to room temperature to remove dibenzoyl L-tartaric acid. Precipitation was performed, and the obtained reaction mixture was filtered and dried to obtain 126.3 g (0.3% of dibenzoyl L-tartaric acid).
46 mol) was obtained.

The dibenzoyl L-tartaric acid thus obtained was analyzed by liquid chromatography (LC). As a result, dibenzoyl L-tartaric acid was analyzed.
The tartaric acid has an LC purity of 99.8% and a water content of 1.8.
The yield of benzoyl L-tartaric acid was 0% by weight, and the yield of raw material was L.
-It was 86.6% based on tartaric acid.

Example 3 A reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device was charged with 142.8 g (98.1 m) of trichlorethylene.
l) and 60.0 g (0.400 mol) of L-tartaric acid were added, and then 0.24 g (1.5 mmol) of ferric chloride as a catalyst was added, while maintaining the reaction temperature at 80 to 90 ° C. under stirring.
First, 56.2 g (0.400 mol) of benzoyl chloride and then 78.2 g (0.400 mol) of benzotrichloride were sequentially added dropwise at a rate of 0.45 g / min, and after the addition of these benzoyl chloride and benzotrichloride was completed, the reaction was carried out. The mixture was aged at reaction temperature for 2.0 hours.

Thereafter, the reaction mixture was cooled to room temperature, the precipitated crystals were filtered, washed with trichlorethylene and dried to obtain 111.0 g of dibenzoyl L-tartaric anhydride.
(0.326 mol) was obtained. The hydrogen chloride gas produced as a by-product in the process of the benzoylation reaction was introduced into an exhaust gas abatement system and neutralized.

The obtained dibenzoyl L-tartaric acid anhydride was analyzed by liquid chromatography (LC). As a result, the LC purity of dibenzoyl L-tartaric acid anhydride was 99.9%.
The yield of dibenzoyl L-tartaric acid anhydride was 81.5% based on the starting L-tartaric acid.

Example 4 In a reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device, 51.6 g (59.9 ml) of para-xylene and L-
60.0 g (0.400 mol) of tartaric acid was charged, then 0.018 g (0.11 mmol) of ferric chloride as a catalyst was added, and while maintaining the reaction temperature at 110 to 130 ° C. under stirring, 62.4 g of benzoyl chloride ( 0.444 mol), and then 86.4 g (0.442 mol) of benzotrichloride were added dropwise at a rate of 0.52 g / min and 0.41 g / min, respectively, and after the addition of these benzoyl chloride and benzotrichloride was completed, the reaction mixture was added. Was maintained at the reaction temperature for 3.0 hours for aging.

Thereafter, the reaction mixture was cooled to room temperature, the precipitated crystals were filtered, washed with para-xylene, and dried to give 117.1 g (0.344) of dibenzoyl L-tartaric anhydride.
Mol) was obtained. The hydrogen chloride gas produced as a by-product in the process of the benzoylation reaction was introduced into an exhaust gas abatement system and neutralized.

The obtained dibenzoyl L-tartaric acid anhydride was analyzed by liquid chromatography (LC). As a result, the LC purity of dibenzoyl L-tartaric acid anhydride was 99.9%.
The yield of dibenzoyl L-tartaric acid anhydride was 86.0% based on the starting L-tartaric acid.

Example 5 In a reaction vessel equipped with a condenser, an exhaust gas removing device, and a heating device, 51.6 g (59.9 ml) of para-xylene and L- were added.
60.0 g (0.400 mol) of tartaric acid was charged, 0.06 g (0.44 mmol) of ferric chloride as a catalyst was then added, and 62.4 g of benzoyl chloride (while maintaining the reaction temperature at 120 to 130 ° C. under stirring). 0.444 mol), then 86.4 g (0.442 mol) of benzotrichloride, respectively.
42 g / min and 0.48 g / min were added dropwise, and after completion of the addition of these benzoyl chloride and benzotrichloride,
The reaction mixture was aged maintaining the reaction temperature for 2.0 hours.

Then, the reaction mixture was cooled to room temperature, and the precipitated crystals were filtered and washed with para-xylene to obtain 108.2 g (0.318 mol) of dibenzoyl L-tartaric anhydride. The hydrogen chloride gas produced as a by-product in the process of the benzoylation reaction was introduced into an exhaust gas abatement system and neutralized.

The obtained dibenzoyl L-tartaric acid anhydride was analyzed by liquid chromatography (LC). As a result, the LC purity of dibenzoyl L-tartaric acid anhydride was 99.0%.
The yield of dibenzoyl L-tartaric acid anhydride was 79.5% based on the raw material L-tartaric acid.

[0033]

INDUSTRIAL APPLICABILITY According to the present invention, byproducts such as benzoic acid and sulfur dioxide gas, which require a troublesome post-treatment, are not generated, and various racemic amines are used as optical resolving agents and various organic syntheses. It is possible to industrially advantageously produce dibenzoyltartaric acid and its acid anhydride, which are important compounds for applications such as intermediates.

Continued front page    (72) Inventor Tomotake Asawa             Nippon Light Metal, 161, Kambara, Kambara-cho, Anbara-gun, Shizuoka Prefecture             Kambara Manufacturing Co., Ltd. (72) Inventor Toshihiro Fujino             East, 9-1, Oemachi, Minato-ku, Nagoya City, Aichi Prefecture             Les Nagoya Office (72) Inventor Yoshihiro Ogita             2-2-1 Nihombashi Muromachi, Chuo-ku, Tokyo             No., Toray Co., Ltd. Tokyo business site F-term (reference) 4H006 AA02 AC46 BJ50 BS10                 4H039 CA65 CA66 CD10 CD20 CD30

Claims (6)

[Claims] 1. A method for producing dibenzoyl tartaric anhydride, which comprises reacting tartaric acid with benzoyl chloride and benzotrichloride in an organic solvent to obtain dibenzoyl tartaric anhydride. 2. The dibenzoyl according to claim 1, wherein the organic solvent is one organic solvent selected from trichloroethylene, tetrachloroethylene, chlorobenzene, dichlorobenzene, toluene and xylene, or a mixed solvent of two or more kinds. Method for producing tartaric anhydride. 3. The method for producing dibenzoyl tartaric anhydride according to claim 1, wherein tartaric acid is reacted with benzoyl chloride and then benzotrichloride is reacted. 4. The method for producing dibenzoyl tartaric acid anhydride according to claim 1, wherein the reaction is carried out in the presence of a Lewis acid catalyst. 5. The Lewis acid catalyst is ferric chloride, aluminum chloride, antimony pentachloride, titanium chloride, zinc chloride,
One or two selected from tin chloride and boron trifluoride
The method for producing dibenzoyl tartaric anhydride according to claim 4, wherein the method is a mixture of one or more kinds. 6. A method for producing dibenzoyltartaric acid, characterized by hydrolyzing the dibenzoyltartaric anhydride obtained by the method according to claim 1 to obtain dibenzoyltartaric acid.