JPH1087558A - Method for producing p-hydroxybenzoic acid - Google Patents

Abstract

[PROBLEMS] To improve the yield of p-hydroxybenzoic acid. When an alkali metal salt of phenol and carbon dioxide are reacted in an aprotic polar solvent, an alkali metal salt of a compound which is less acidic than phenol is coexisted in the reaction system.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the production of p-hydroxybenzoic acid, which is useful as a raw material for medicines, agricultural chemicals or liquid crystal polymers.

[0002]

2. Description of the Related Art p-Hydroxybenzoic acid is industrially produced from an alkali metal salt of phenol and carbon dioxide by a Kolbe-Schmidt reaction. However, in that case, the alkali metal salt is limited to the potassium salt. p-
Most of the patents for the production of hydroxybenzoic acid also use a potassium salt of phenol as a raw material. This is because salicylic acid, which is an isomer of p-hydroxybenzoic acid, generally becomes a main product when a sodium salt of phenol is used as a raw material. In fact, this has become an industrial process for salicylic acid.

[0003] On the other hand, when an alkali metal salt of phenol is reacted with carbon dioxide in an aprotic polar solvent, p-hydroxybenzoic acid is produced together with salicylic acid together with salicylic acid using either phenol sodium salt or phenol potassium salt as a raw material. Is found by Hirao et al., Journal of the Society of Organic Synthesis, 24, 1051, (1966).
And French Patent 1,506,291 (1966)
Are disclosed. In addition, Japanese Patent Publication No. 44-0198
No. 51 and EP 478197 (199)
2) also discloses a similar reaction example. In these examples, potassium salt of phenol or sodium salt of phenol is used as the alkali metal salt of phenol, and dimethylformamide, hexamethylphosphoro (tri) amide or dimethylsulfoxide is used as the aprotic polar solvent. The yield of hydroxybenzoic acid is more than 20% at a reaction temperature of 100 ° C.

On the other hand, in the case of aprotic polar solvents other than dimethylformamide, hexamethyl phosphoro (tri) amide or dimethyl sulfoxide, EP 47819 is used.
No. 7 (1992) discloses an example using phosphine oxide. When sodium salt of phenol or triethylphosphine oxide is used, the yield is 30% and the selectivity is 90%.
To obtain p-hydroxybenzoic acid.

In experiments conducted by the inventors, the yield of p-hydroxybenzoic acid was 50% when an alkali metal salt of phenol was reacted with carbon dioxide in an aprotic polar solvent.
The reaction stopped at less than%. For example, when dimethyl sulfoxide is used as the aprotic polar solvent, the reaction temperature is 70 ° C., and the carbon dioxide pressure is from normal pressure to 2.5.
When reacted with carbon dioxide under the conditions of MPa, the reaction was saturated when the yield of p-hydroxybenzoic acid was around 33%.

[0006]

As described above, when the Kolbe-Schmidt reaction is carried out in an aprotic polar solvent, p-
Hydroxybenzoic acid is produced, but it is hard to say that the yield of p-hydroxybenzoic acid has reached a sufficient level. In particular, under the reaction conditions of high selectivity of 100 ° C. or lower, improvement of the yield of p-hydroxybenzoic acid still remains as an important issue.

An object of the present invention is to increase the yield of p-hydroxybenzoic acid to 33% or more even at a reaction temperature of 100 ° C. or less in the reaction between an alkali metal salt of phenol and carbon dioxide in an aprotic polar solvent. To make it happen.

[0008]

That is, the present invention relates to an alkali metal salt of a compound which is less acidic than phenol when the alkali metal salt of phenol is reacted with carbon dioxide in an aprotic polar solvent. And p-hydroxybenzoic acid.

[0009]

DETAILED DESCRIPTION OF THE INVENTION As the inventors proceeded with the study of the Kolbe-Schmidt reaction between an alkali metal salt of phenol and carbon dioxide in an aprotic polar solvent, the formation of p-hydroxybenzoic acid was reduced. It was found that the reason why the reaction stopped at a low yield was that the alkali metal salt of phenol as a raw material disappeared due to inactivation by the product.

When the reaction is carried out in an aprotic polar solvent, the resulting p-hydroxybenzoic acid is in the form of a dialkali metal salt. One of the two alkali metals of the product was deprived of the starting alkali metal salt of phenol during the formation of p-hydroxybenzoic acid. In other words, when 1 mole of p-hydroxybenzoic acid is formed, 1 mole of the alkali metal phenol salt of the raw material is converted into phenol which is inert to the reaction with carbon dioxide.

On the other hand, from the results of various experiments conducted by the inventors, it has been found that in the reaction of an alkali metal salt of phenol with carbon dioxide, the reaction is inhibited when a compound having an active proton such as an amine or an alcohol coexists. ing. Similar inhibition occurs for phenols produced by the formation of p-hydroxybenzoic acid, as they also have active protons. Further, when the reaction is carried out in an aprotic polar solvent, the reaction is saturated when the yield of p-hydroxybenzoic acid is around 33%. Since the Kolbe-Schmidt reaction hardly proceeds when phenol is added in an equimolar amount with the alkali metal salt of phenol, it was found that 1 mole of phenol inactivates 1 mole of phenol alkali metal salt as a raw material.

From the above findings, it is presumed that if the phenol alkali metal salt as a raw material can be regenerated by any method, the conversion of the raw material and the yield of p-hydroxybenzoic acid will be improved. However, as a means of regenerating the raw material phenol alkali metal salt, when reacting phenol alkali metal salt and carbon dioxide in an aprotic polar solvent, the reaction system is less acidic than phenol, preferably the alkali When the metal salt is reacted with carbon dioxide at a reaction temperature of 70 ° C. and a carbon dioxide pressure of 1.5 MPa for 4 hours, the alkali metal salt of the compound which does not react with carbon dioxide by 1.5% or more is coexisted. It has been found that the yield of p-hydroxybenzoic acid is improved with the conversion of.

[0013] To the inventors' knowledge, including the above patents,
In the reaction to synthesize p-hydroxybenzoic acid from a metal salt of phenol and carbon dioxide, for the purpose of improving the conversion,
There is no example in which the reaction was carried out in the presence of an alkali metal salt of a compound which is less acidic than phenol and whose metal salt does not react with carbon dioxide by 1.5% or more. JP-A-5-1863
No. 90 discloses an example in which a potassium salt of 2,4,6-trimethylphenol is used for the synthesis of p-hydroxybenzoic acid. In the rearrangement reaction of potassium salt, p-
It synthesizes hydroxybenzoic acid and does not synthesize p-hydroxybenzoic acid from an alkali metal salt of phenol and carbon dioxide in an aprotic polar solvent.

The coexisting alkali metal salt compound must be a compound having a lower acidity than phenol. Alkali metal salts of compounds that are more acidic than phenol,
Even if it is added, the exchange of phenol and alkali metal hardly occurs, so that the effect of the addition cannot be expected. Also. It is preferable that the alkali metal salt to be added does not easily react with carbon dioxide or decompose itself during the reaction between the alkali metal salt of phenol and carbon dioxide. Preferably, at a reaction temperature of 70 ° C. and a carbon dioxide pressure of 1.5 MPa, 4
An alkali metal salt which does not react with carbon dioxide by 1.5% or more when reacted for an hour is added. The metal salts represented by the general formulas (I) and (II) are preferably used as those satisfying the above conditions. Since the metal salt of the general formula (I) is an alkali metal salt of a phenol having an alkyl group at all of the ortho and para positions of the hydroxyl group, it does not react with carbon dioxide. The metal salt of the general formula (II) is a metal salt of a phenol having a carboxyl group at the ortho-position of the hydroxyl group, such as a dialkali metal salt of a derivative of salicylic acid. When the substituent at the para- or ortho-position of the hydroxyl group is hydrogen, it may react with carbon dioxide to form a derivative of 4-hydroxyisophthalic acid. Then, since the alkali metal salt of phenol reacts preferentially, if the supply and heating of carbon dioxide are stopped when the reaction between the alkali metal salt of phenol and carbon dioxide is saturated, the derivative of 4-hydroxyisophthalic acid can be obtained. Production is kept below 1.5%. The compound represented by the general formula (II) has two alkali metal ions in one molecule, one for a hydroxyl group and one for a carboxyl group. Since only the alkali metal ion of the phenolic hydroxyl group is involved, the preparation of the alkali metal salt requires two equivalents of the alkali metal hydroxide.

The amount of the alkali metal salt of the acid to be added is not particularly limited. However, if the amount is too large, it is uneconomical. If the amount is too small, the effect is reduced. The salt is preferably 0.1 to 2 equivalents, more preferably 0.5 to 2 equivalents.

The method of charging the alkali metal salt to be coexisted is not particularly limited. For example, an alkali metal salt to be allowed to coexist is separately prepared, and may be charged in a solution or slurry of an alkali metal salt of phenol and an aprotic polar solvent, or a predetermined amount of an alkali metal hydroxide or phenol as an acid. May be added to a solution or slurry of an aprotic polar solvent containing, followed by dehydration to prepare a metal salt of an acid added simultaneously with the alkali metal salt of phenol.

As the aprotic polar solvent used in the present invention, dimethylsulfoxide, dimethylformamide or dimethylacetamide is preferably used, and its use amount is preferably at least twice as much as phenol.

The reaction temperature is preferably from 50 to 120 ° C.

Further, the carbon dioxide pressure is 0.05 to 5
MPa is preferred, and more preferably 0.1 to 3MPa.
a.

[0020]

[Embodiments] Embodiments will be described with reference to embodiments. In Examples and Comparative Examples, the following chemicals were used.

Dimethyl sulfoxide: Merck special grade, dimethylformamide: Kanto chemical special grade Phenol: Kanto chemical special grade and Katayama chemical first grade 2,4,6-trimethylphenol: Tokyo Chemical Special grade 2,6-di-tert-butyl-4-methylphenol ： Tokyo Chemical First Class and Special Class

[0022]

[Reference Example 1] 94.11 g of phenol (1.
00mol) and 289.83g of 4N sodium hydroxide aqueous solution (1.00mo
l) was added. The phenol alkaline aqueous solution was concentrated under reduced pressure using an evaporator to obtain a wet solid content of 147.90 g.
0.28 g (0.3%) when concentrated under reduced pressure using an evaporator
Of phenol was distilled off. The wet solid was vacuum-dried with a vacuum pump at 70 ° C. until the mass became constant, to obtain 116.20 g (theoretical amount: 115.74 g) of sodium salt of phenol. At the time of drying, when the wetness disappeared on the way, the solid content was pulverized in a mortar to increase the drying efficiency and to make it easier to handle in the subsequent Kolbe-Schmidt reaction. The phenolic sodium was white and did not color if stored tightly closed. 2,4,6-Trimethylphenol sodium salt (TMP.Na) was prepared in the same manner from 6.18 g (0.045 mol) of the corresponding phenol, and 7.06 g
A green colored solid (theoretical 7.02 g) was obtained.

[0023]

Example 1 In a 200 ml glass container equipped with a stirrer for a magnetic stirrer, a thermometer, a reflux tube, a balloon containing carbon dioxide and a nozzle for supplying carbon dioxide, the sodium salt of phenol prepared in Reference Example 1 was used. 5.00
g (0.043 mol) and 7.06 g (0.045 mol) of sodium salt of 2,4,6-trimethylphenol were added. After the inside of the apparatus was replaced with carbon dioxide, 65 ml of dimethylformamide was added. And put the carbon dioxide nozzle in the charge liquid,
After absorbing carbon dioxide under normal pressure until saturated, the carbon dioxide nozzle was raised from the liquid surface and stirred at a liquid temperature of 95 ° C for 16 hours. Thereafter, unreacted carbon dioxide in the reaction solution was released with nitrogen while heating to 95 ° C. to stop the reaction. After cooling to near room temperature, the reaction mixture was analyzed by HPLC (High Performance Liquid Chromatography).
Diluted. As a result of HPLC analysis, the yields of p-hydroxybenzoic acid, salicylic acid, and 4-hydroxyisophthalic acid were 42.6%, 15.4%, 1.3%, respectively, and the conversion of phenol was
59.5%.

[0024]

Example 2 In a SUS 500 ml autoclave equipped with a stirring rod, stirring blade and a temperature sensor, 5.00 g (0.043mo
l), 7.83 g (0.043 mol) of disodium salt of salicylic acid,
70 ml of dimethylformamide was charged, and the inside of the apparatus was purged with nitrogen. After pressurizing to 500 kPa with carbon dioxide and absorbing carbon dioxide to the charged liquid until saturation, the carbon dioxide pressure is 300 to 5
The mixture was stirred at 00 kPa and a liquid temperature of 70 ° C. for 5 hours. Thereafter, without waiting for cooling, unreacted carbon dioxide in the reaction solution was released with nitrogen to stop the reaction. After cooling to near room temperature, the reaction solution was analyzed by HPLC in the same manner as in Example 1. HPLC
As a result of the analysis, p-hydroxybenzoic acid, salicylic acid, 4
-The yield of hydroxyisophthalic acid is 53.0% and 15.
The conversion of phenol was 0%, 0.03%, and 68.0%.

[0025]

Example 3 10.53 g (0.112 mol) of phenol, 24.93 g of 2,6-di-tert-butyl-4-methylphenol (0.
113mol), 50% sodium hydroxide aqueous solution 17.92g (0.224mo
l), 200 g of dimethyl sulfoxide equipped with a thermometer and a magnetic stirrer, 300 ml-
It was placed in a three-necked flask and dehydrated by vacuum concentration. The pressure was gradually increased from about 5 kPa while observing the state of distillation, and finally fixed at 2.5 kPa. About 1.5 hours after the start of operation, the boiling point of dimethyl sulfoxide (2.5 kP
a, 83 ° C), but distillation was continued after the distilling temperature reached the boiling point until 26 g of distillate was still obtained in order to more reliably remove water. The total amount of distillate was 95 g. When the water content of this alkali metal salt preparation was measured by Karl Fischer, the water content was 125 ppm. The weight of this preparation was 155.51 g.

This prepared solution was charged into a SUS 500 ml autoclave equipped with a stirring rod, a stirring blade and a temperature sensor. After the inside of the apparatus was replaced with nitrogen and carbon dioxide, the pressure was increased to 1.5 MPa with carbon dioxide, and carbon dioxide was absorbed into the charged liquid until the carbon dioxide was saturated.
The mixture was stirred at 70 ° C for 5 hours. Thereafter, without waiting for cooling, unreacted carbon dioxide in the system was released with nitrogen to stop the reaction. After cooling to near room temperature, the reaction solution
HPLC analysis was performed in the same manner. As a result of the HPLC analysis,
The yields of p-hydroxybenzoic acid, salicylic acid and 4-hydroxyisophthalic acid were 41.5%, 4.3% and 0.3%, respectively, and the conversion of phenol was 46.1%.

[0027]

EXAMPLE 4 10.54 g (0.112 mol) of phenol, salicylic acid
7.73 g (0.056 mol), 17.85 g of 50% aqueous sodium hydroxide solution
(0.223 mol) and 240 g of dimethyl sulfoxide were placed in a 300-ml three-necked flask equipped with a thermometer and a magnetic stirrer and capable of performing a vacuum distillation operation, and dehydrated by vacuum concentration. The pressure was gradually increased while watching the state of distillation from about 5 kPa, and was finally fixed at 2.4 kPa. Approximately 1.5 hours after the start of the operation, the boiling point of dimethyl sulfoxide (2.5 kPa, 83 ° C) was reached, but in order to ensure the removal of water, even after the distillation temperature reached the boiling point, still 20 g of distilling was performed. Distillation was continued until a minute appeared. The total amount of distillate was 151 g. The weight of the preparation solution of this alkali metal salt is 122.60 g.
Met.

This prepared liquid was charged into a SUS 500 ml autoclave equipped with a stirring rod, stirring blade and a temperature sensor. After the inside of the apparatus was replaced with nitrogen and then carbon dioxide, the pressure was increased to 2.5 MPa with carbon dioxide, and carbon dioxide was absorbed into the charged liquid until the carbon dioxide was saturated.
The mixture was stirred at 70 ° C for 4 hours. Thereafter, without waiting for cooling, unreacted carbon dioxide in the system was released with nitrogen to stop the reaction. After cooling to near room temperature, the reaction solution
HPLC analysis was performed in the same manner. As a result of the HPLC analysis,
The yields of p-hydroxybenzoic acid, salicylic acid and 4-hydroxyisophthalic acid were 42.8%, 8.7% and 0.1%, respectively, and the conversion of phenol was 51.6%.

[0029]

Example 5 Phenol 10.53 g (0.112 mol), salicylic acid
15.38 g (0.112 mol), 50% aqueous sodium hydroxide solution 26.61
g (0.332 mol) and 220 g of dimethyl sulfoxide in Example 4
Preparation of an alkali metal salt and Kolbe-Schmidt reaction were carried out in the same manner as described above. As a result of HPLC analysis, the yields of p-hydroxybenzoic acid, salicylic acid and 4-hydroxyisophthalic acid were 61.3%, 9.6% and 0.1%, respectively, and the conversion of phenol was 71.1%.

[0030]

Comparative Example 1 The phenol sodium salt prepared by the procedure of Reference Example 1 was 5.00 g (0.043 mol) and dimethylformamide 65 m
l was placed in a 200 ml glass container equipped with a magnetic stirrer stirrer, a thermometer, a reflux tube, a balloon containing carbon dioxide, and a nozzle for supplying carbon dioxide.
The Kolbe-Schmidt reaction was carried out in the same manner as described above. HPL
As a result of C analysis, p-hydroxybenzoic acid, salicylic acid,
The yields of 4-hydroxyisophthalic acid were 33.6% and 1
The conversion of phenol was 0.4%, 0.1%, and 44.0%.

[0031]

Comparative Example 2 Preparation of an alkali metal salt and Kolbeschmidt reaction were carried out in the same manner as in Example 4 from 15.25 g (0.162 mol) of phenol, 12.861 g (0.161 mol) of a 50% aqueous sodium hydroxide solution and 201 g of dimethyl sulfoxide. . HPL
As a result of C analysis, p-hydroxybenzoic acid, salicylic acid,
The yield of 4-hydroxyisophthalic acid is 31.9%,
The conversion of phenol was 2.8%, 0.1% and 34.9%.

[0032]

According to the present invention, when an alkali metal salt of phenol and carbon dioxide are reacted in an aprotic polar solvent, p-hydroxybenzoic acid can be obtained by coexisting an alkali metal salt of a compound having a lower acidity than phenol in the reaction system. Can be improved.

Claims (6)

[Claims] (1) When reacting an alkali metal salt of phenol with carbon dioxide in an aprotic polar solvent, a reaction system is made to coexist in the reaction system with an alkali metal salt of a compound which is less acidic than phenol. A method for producing hydroxybenzoic acid. 2. An alkali metal salt coexisting in the reaction, when reacted at a reaction temperature of 70 ° C. and a carbon dioxide pressure of 1.5 MPa for 4 hours, does not react with carbon dioxide by 1.5% or more. A method for producing p-hydroxybenzoic acid according to claim 1. 3. The method according to claim 1, wherein the alkali metal salt coexisting in the reaction is represented by the following general formula (I) or general formula (II).
Or the method for producing p-hydroxybenzoic acid according to 2. Embedded image 4. The phenol alkali metal salt is a phenol sodium or potassium salt.
The method for producing p-hydroxybenzoic acid according to any one of the above. 5. The process for producing p-hydroxybenzoic acid according to claim 1, wherein the amount of the alkali metal salt added to the reaction is 0.1 to 5 equivalents of the alkali metal salt of phenol. Method. 6. The p-hydroxybenzoic acid according to claim 1, wherein the aprotic polar solvent is dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and the amount thereof is at least twice as much as phenol. Method for producing acid.