JP2001039919A - Production of 2,3-dihydroxybenzoic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce 2,3-dihydroxybenzoic acid useful as an intermediate for an agrochemical and medicine under a mild reaction condition in a short reaction time, high selectivity and high yield by carboxylating a disodium salt of catechol with carbon dioxide in the coexistence of the catechol. SOLUTION: A disodium salt of catechol is carboxylated with carbon dioxide in the coexistence of the catechol to provide the objective 2,3-dihydroxybenzoic acid. The disodium salt of the catechol can be obtained by reacting the catechol with sodium hydroxide or lower alcoholates of sodium in water or an organic solvent (e.g. a lower alcohol, toluene and xylene). The carboxylation reaction is preferably carried out at >=105 deg.C, and the amount of the used catechol is preferably >=0.5 time (by weight), especially 0.8-2.5 times as much as the amount of the disodium salt of the catechol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 2,3-dihydroxybenzoic acid, and more particularly to an effective method for producing 2,3-dihydroxybenzoic acid with high purity and high yield.

[0002]

2. Description of the Related Art A method of producing benzoic acids by forming phenols and alkali metal bicarbonate in a reactor and then reacting with carbon dioxide is known as the merase method. For example, in J.I. Org. Chem. ,
vol. 19, p. In 510, (1954), catechol is reacted at 225 ° C. under 82 to 136 atm of carbon dioxide under pressure for 4 hours, and the catechol is obtained at a yield of 72%.
3-Dihydroxybenzoic acid is obtained. However, it is described in the literature that if this reaction is continued for 8 hours, 2,3-dihydroxyterephthalic acid which is an overreaction product is obtained in a yield of 81%. It can be said that there is a great problem in the selectivity between 2,3-dihydroxybenzoic acid and 2,3-dihydroxyterephthalic acid as a by-product.

[0003] Also, Org. Synth. , II, p. 5
57 (1943), resorcinol merases
Carboxylation in aqueous solution
2,4-Dihydroxybenzoic acid is obtained with a yield of 7 to 60%. When the present inventors applied this method to catechol, it was confirmed that approximately the same amount of 3,4-dihydroxybenzoic acid was formed together with the target product, 2,3-dihydroxybenzoic acid (described in Comparative Examples described later). ). From this fact m
It can be said that the erase method has a problem in regioselectivity of carboxylation.

A method for obtaining benzoic acids by reacting an alkali metal salt of a phenol with carbon dioxide is disclosed in Ko.
Known as the lbe-Schmitt method,
There is an advantage that generation of regioisomers is suppressed as compared with the sse method. For example, in J.I. Amer. Chem. S
oc. , Vol. 72, p. 621, (1950), the reaction between catechol disodium salt and carbon dioxide is carried out without solvent at 145 ° C. under 58 atm of carbon dioxide under pressure for 43 hours to give 2,3-dihydroxybenzoic acid 58%. In the yield. However, this method has a drawback that the reaction is a solid reaction, the reaction results are not stable, and a long-term reaction is required under severe reaction conditions to stably improve the reaction results.

[0005]

SUMMARY OF THE INVENTION The present invention relates to a method for producing 2,3-dihydroxybenzoic acid using a disodium salt of catechol as a raw material. An object is to improve low selectivity and low yield, and achieve mild reaction conditions, short reaction time, high selectivity, and improvement in reaction yield.

[0006]

DISCLOSURE OF THE INVENTION The present invention relates to a process for producing 2,3-dihydroxybenzoic acid, which comprises a method for preparing Ko in a liquid phase.
The lbe-Schmitt method was studied. As a result, they have found that the carboxylation of catechol disodium salt in the presence of catechol can solve various problems of the prior art at once, and have completed the present invention.

That is, the present invention relates to a method for carboxylating a disodium salt of catechol with carbon dioxide, wherein the carboxylation is carried out in the presence of catechol.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The disodium salt of catechol, which is a raw material of the production method of the present invention, can be produced by reacting catechol with sodium hydroxide or sodium lower alcoholate in water or an organic solvent. The organic solvent referred to here is a lower alcohol, toluene, xylene, etc.
Any organic solvent which is inert to the reaction may be used. The amount of sodium hydroxide or lower alcoholate to be used may be at least 2.0 times the molar amount of catechol, but it is preferably 2.0 to 2.4 times the molar amount from the viewpoint of economy.

Next, the aqueous or organic solvent suspension of the disodium salt of catechol is distilled off under normal pressure or reduced pressure to remove water or the organic solvent. Catechol is added to the obtained disodium salt of catechol, and carboxylation is performed with carbon dioxide.

The amount of catechol to be added can be arbitrarily selected within a range of at least 0.5 times the weight of the disodium salt of catechol.
Five times the weight is desirable. The reaction temperature for carboxylation may be at least 105 ° C., which is the melting point of catechol.

The reaction rate can be increased by increasing the carbon dioxide pressure, but in the present invention, a pressure of 5 atm or more is sufficient. A reactor is charged with catechol-disodium salt and catechol, and after raising the temperature to the reaction temperature, carbon dioxide is injected thereinto and kept for 2 to 3 hours from the time when absorption is no longer observed. There is no problem even if carboxylation is carried out by a method in which carbon dioxide is injected and the temperature is raised to the above reaction temperature.

After completion of the reaction, the reaction mixture is cooled to 60 ° C. or lower, and the reaction mixture is mixed with water to dissolve catechol and 2,3-dihydroxybenzoic acid in the form of a sodium salt in the aqueous phase. The pH is adjusted to a range of 7 to 11 to extract and collect catechol. The catechol collected here is
It can be reused as the next reaction solvent and raw material. Then, the aqueous phase is adjusted to pH = 3 or less and subjected to acid precipitation, whereby the target product, 2,3-dihydroxybenzoic acid, can be obtained as crystals.

[0013]

EXAMPLES The method of the present invention will be described more specifically with reference to the following examples, but the present invention is not limited thereto. Quantification and purity analysis of catechol, 2,3-dihydroxybenzoic acid and 3,4-dihydroxybenzoic acid were performed by HPLC, and the analysis conditions were as follows. (HPLC analysis conditions) Detection wavelength: 254 nm Column: YMC-A-312 Solvent: acetonitrile / buffer solution = 15/85 (volume ratio) The buffer solution is an aqueous solution composed of 1 mM phosphate and 4 mM potassium phosphate.

Flow rate: 0.7 ml / min. Internal standard substance: benzyl alcohol

Example 1 In a stainless steel autoclave having an inner volume of 100 ml,
5.6 g of disodium salt of catechol (36.3 mmol)
l) and charged catechol 5.0 g (45.4 mmol), was injected CO ₂ to 14atm after CO ₂ substitution.
The temperature was raised while stirring, and heating and stirring were continued for 6 hours after the temperature reached 160 ° C. After cooling to 40 ° C. and releasing the pressure, the reaction mass was
The resulting mixture was mixed with concentrated hydrochloric acid to adjust the pH to 8, and catechol was extracted with 30 ml of chloroform. Then the aqueous phase at 5 ° C
The pH was adjusted to 1 with concentrated hydrochloric acid while stirring under cooling, and the precipitated crystals of 2,3-dihydroxybenzoic acid were collected by filtration.
From the chloroform extract, 5.65 g of catechol was recovered as white crystals by removing the solvent and drying under reduced pressure. The result of quantitative analysis of the obtained catechol was 98 in purity.
%, 50.3 mmol. The acid precipitated crystals were dried under reduced pressure to yield 4.56 g. From quantitative analysis, the purity of 2,3-dihydroxybenzoic acid was 99.0.
%. From these results, the yield of 2,3-dihydroxybenzoic acid from the disodium salt of catechol was 80.7%, and the recovery of catechol was 9%.
6%.

Example 2 The same operation as in Example 1 was carried out except that the reaction was carried out at a CO ₂ pressure of ₂ atm before the temperature was raised. Gauge pressure is maximum 8
atm was indicated. As a result, the yield of 2,3-dihydroxybenzoic acid from catechol-disodium salt was 79.6.
%, The purity was 99.0%, and the recovery of catechol was 97%.

Comparative Example 1 (merasse method) In a stainless steel autoclave having an inner volume of 100 ml, 3.0 g (27.2 mmol) of catechol, 11.4 g (136 mmol) of sodium hydrogen carbonate, and 3 parts of ion-exchanged water were used.
0 ml, and after CO ₂ displacement, CO ₂
After press-fitting, the temperature was raised to 150 ° C. and reacted for 6 hours. 40 ℃
After cooling and releasing the pressure, concentrated hydrochloric acid was added to the reaction mass to adjust the pH to 1
Then, chloroform extraction was performed to obtain 17.24 g of an organic phase. From the HPLC analysis, 1.95 g of catechol, 2,3-
A result was obtained which contained 0.72 g of dihydroxybenzoic acid and 0.64 g of 3,4-dihydroxybenzoic acid. The conversion rate of catechol was 35%, the yield of 2,3-dihydroxybenzoic acid was 17.3%, and the yield of 3,4-dihydroxybenzoic acid was 1
This corresponds to 5.4%.

Comparative Example 2 (Kolbe-Schmitt)
Method) catechol monosodium salt 4.8 g (36.3 mm
ol), except that the same operation as in Example 1 was performed. As a result, the yield of 2,3-dihydroxybenzoic acid was 0.9%.

Comparative Example 3 (Kolbe-Schmitt)
Method) Except not adding catechol, the same operation as in Example 1 was attempted. However, the reaction mass at the end of the reaction had a black carbide appearance, and the subsequent treatment was impossible.

[0020]

According to the method of the present invention, 2,3-
Since the dihydroxybenzoic acid can be obtained with high selectivity and high yield in a relatively short time, the production method of the present invention is industrially very useful.

Claims (3)

[Claims] 1. A method for carboxylating a disodium salt of catechol with carbon dioxide, wherein the carboxylation is carried out in the coexistence of catechol. 2. The method according to claim 1, wherein the carboxylation reaction is performed at a temperature of 105 ° C. or higher. 3. The use amount of catechol is at least 0.5 times by weight based on the disodium salt of catechol.
Or the method of 2.