JPH1087559A - Production of p-hydroxybenzoic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve the yield of p-hydroxy benzoic acid to be >=33%, while maintaining the selectivity of the acid in a reaction of an alkali metal salt of phenol with carbon dioxide in DMSO high in selectivity of the acid among various aprotic polar solvents. SOLUTION: This method for producing p-hydroxybenzoic acid by mixing dimethylsulfoxide, phenol and 0.9-1.1 molar fold sodium hydroxide relative to the phenol, or their aqueous solutions, then removing water by a distillation to generate a complex consisting of 1mol alkali metal salt of phenol and 2mols DMSO and reacting carbon dioxide with the complex at <=90 deg.C, is constituted by sufficiently reacting carbon dioxide with the raw material complex, then heat-treating the product at 90-120 deg.C temperature in a state of removing the carbon dioxide to the outside of the system, and then introducing carbon dioxide again for reacting at <=90 deg.C.

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 When an alkali metal salt of phenol is reacted with carbon dioxide in an aprotic polar solvent, p-hydroxybenzoic acid is formed together with salicylic acid using either sodium salt of phenol or potassium salt of phenol as a raw material. Hirao et al., And are disclosed in Journal of the Society of Organic Synthesis, 24, 1051, (1966) and French Patent No. 1,506,291 (1966). In addition, Japanese Patent Publication No. 44-019851 and European Patent No. 478197 (1992) also disclose similar reaction examples. In particular, when a sodium salt of phenol is a raw material, p-hydroxybenzoic acid is hardly produced in a solvent-free, protic solvent or a non-polar solvent, so that a Kolbe-Schmidt reaction is used from a sodium salt of phenol by using This method is significant in that p-hydroxybenzoic acid can be synthesized. In these examples,
Phenol potassium salt or phenol sodium salt as phenol alkali metal salt, dimethylformamide (hereinafter abbreviated as DMF), hexamethyl phosphoro (tri) amide (hereinafter abbreviated as HMPA) or dimethyl sulfoxide as aprotic polar solvent (Hereinafter abbreviated as DMSO). DMSO in these examples
When the reaction results were obtained by using phenol as the reaction solvent, the yield was 15 to 23% when the potassium salt of phenol or the sodium salt of phenol was used at 100 ° C., and the selectivity was 83 to 94%.
To obtain p-hydroxybenzoic acid. On the other hand, when DMF was used as the reaction solvent, the yield was 34% when the potassium salt of phenol was used at 180 ° C., and the para / ortho selectivity was 8%.
6% yields p-hydroxybenzoic acid.

[0003] As another solvent using an aprotic polar solvent, there is an example using phosphine oxide in JP-A-4-169546. For example, when a potassium salt of phenol or tributylphosphine oxide is used, the yield is reduced. P-Hydroxybenzoic acid was obtained at a rate of 45% and a selectivity of 82%.

[0004] In experiments conducted by the inventors, even when an alkali metal salt of phenol was reacted with carbon dioxide in an aprotic polar solvent, the yield of p-hydroxybenzoic acid was 50%.
The reaction stopped at less than%. For example, when DMSO is used as the aprotic polar solvent, when the reaction temperature is 70 ° C. and the carbon dioxide pressure is reacted with carbon dioxide under the conditions of normal pressure to 2.5 kPa, the yield of p-hydroxybenzoic acid is increased. Was saturated at around 33%.

[0005]

The yield of p-hydroxybenzoic acid produced by utilizing the Kolbe-Schmidt reaction remains at a low level. As described above, by performing the Kolbe-Schmidt reaction in an aprotic polar solvent, there is an advantage that p-hydroxybenzoic acid can be synthesized using a sodium salt of phenol as a raw material.
The yield of hydroxybenzoic acid, as with other reaction conditions, has hardly reached a satisfactory level.

An object of the present invention is to improve the selectivity of p-hydroxybenzoic acid in the reaction of an alkali metal salt of phenol with carbon dioxide in DMSO, which has a high selectivity for p-hydroxybenzoic acid even in aprotic polar solvents. While alive,
The purpose is to improve the yield.

[0007]

DISCLOSURE OF THE INVENTION DMSO, phenol,
After mixing an aqueous solution of sodium hydroxide equivalent to phenol, water is removed by distillation to obtain a DMSO solution of complex (A) comprising 1 mol of an alkali metal salt of phenol and 2 mol of DMSO. When carbon dioxide is reacted therewith, p-hydroxybenzoic acid is produced. In this reaction, the raw material complex reacts with carbon dioxide to form monosodium p-hydroxybenzoate, and at the same time, deprives the remaining raw material complex (A) of sodium to disodium p-hydroxybenzoate, DMSO, and carbon dioxide. A new complex (B) is formed. On the other hand, the raw material complex (A) deprived of sodium releases phenol to form a carbon dioxide-inactive complex (C) with the raw material complex (A). Therefore, even if the reaction proceeds smoothly, only 1/3 mole of the complex (B) of disodium p-hydroxybenzoate is produced from 1 mole of the starting complex (A), and the remaining phenol component is inactive. It remains in the system in the form of complex (C). Here, the complex (A), the complex (B), and the complex (C) are compounds represented by the following formula.

[0008]

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However, when the complex (B) of p-hydroxybenzoic acid is heated at a temperature of 80 ° C. or more in a condition of a small amount of carbon dioxide, 1 mol of sodium is gradually released, and the complex is changed to monosodium p-hydroxybenzoate. It has been found that the released sodium reacts with the inactive complex (C) to regenerate the raw material complex (A).

On the other hand, p-hydroxybenzoic acid monosodium salt cannot be obtained by intense heating at, for example, 120 ° C. or more because a reaction of decomposing phenol and carbon dioxide is present in a DMSO solution. Can break through.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the present invention, dimethyl sulfoxide, phenol and phenol are mixed with 0.9 to 1.1 mole times of sodium hydroxide or an aqueous solution thereof, and then water is removed by distillation to remove phenol alkali. A complex consisting of 1 mole of a metal salt and 2 moles of dimethyl sulfoxide is formed and reacted with carbon dioxide at a temperature of 90 ° C. or lower to sufficiently react carbon dioxide with the starting complex when producing p-hydroxybenzoic acid. After that, it is important to perform heat treatment in a temperature range of 90 to 120 ° C. in a state where carbon dioxide is removed outside the system, and to introduce carbon dioxide again and react at 90 ° C. or less.

With carbon dioxide removed outside the system, 90-
It is possible to perform not only one step of heat treatment in a temperature range of 120 ° C., introduction of carbon dioxide again and reaction at 90 ° C. or lower, but also plural times.

The pressure when reacting with carbon dioxide is preferably 0.05 to 5 kPa, and more preferably 0.1 to 3 kPa.

The reaction time with carbon dioxide is preferably 0.5 to 10 hours, more preferably 2 to 5 hours.

[0015] 90-
The time for heat treatment in the temperature range of 120 ° C. is 10
Minutes to 5 hours, more preferably 30 minutes to 3 hours.
Time.

[0016]

[Embodiments] Embodiments will be described with reference to embodiments.

[0017]

[Example 1] (Second Kolbe-Schmidt reaction after heat treatment at 120 ° C) 15.31 g (0.161 mol) of 99.0% phenol, 12.96 g (0.161 mol) of 19.0 N aqueous sodium hydroxide solution, and 202 g of DMSO can be distilled under reduced pressure. Placed in a 300 ml glass flask. The reaction liquid was stirred with a magnetic stirrer. After all the raw materials were charged, heating and concentration under reduced pressure were started. The pressure was gradually increased from about 5 kPa while observing the state of distillation, and was finally fixed at 2.5 kPa. 1.5 hours after the start of operation, the boiling point of DMSO (2.5 kPa, 83 ゜
C) (distillate 80.24 g), but 34.84 g after the distilling temperature reaches the boiling point, in order to more reliably remove water.
Concentration under reduced pressure was continued until distillation.

109.90 g of this solution was charged into a SUS 500 ml autoclave equipped with a stirring bar / blade, a temperature sensor, a pressure gauge, and a pipe for carbon dioxide, and the inside of the apparatus was replaced with nitrogen and carbon dioxide. . 2.5M in carbon dioxide
The pressure was increased to Pa, and the charged liquid was allowed to absorb carbon dioxide until it was saturated. Then, the mixture was stirred at a carbon dioxide pressure of 2.5 MPa and a liquid temperature of 70 ° C. for 4 hours. After releasing the gas in the autoclave and returning to normal pressure and performing nitrogen replacement, the temperature was raised to about 120 ° C over 30 minutes,
In this state, the mixture was stirred for 2 hours. When the liquid temperature of the reaction solution dropped to 50 ° C or less, carbon dioxide gas was charged to 2.5 MPa, and carbon dioxide was absorbed into the charged solution until the carbon dioxide was saturated.Then, at a carbon dioxide pressure of 2.5 MPa and a liquid temperature of 70 ° C. Stir for 4 hours. Then, carbon dioxide was released and the reaction was stopped by purging with nitrogen. Take out the reaction solution and add 0.16mol of mineral acid, pH3
Neutralization to ~ 4, high performance liquid chromatography (hereinafter,
HPLC). As a result of the HPLC analysis,
The yields were 37.0%, 4.7%, 0.36% for p-hydroxybenzoic acid, salicylic acid, and 4-hydroxyisophthalic acid, respectively, and the conversion of the starting phenol was 42.1%.

[0019]

Comparative Example 1 (1 time of Kolbe-Schmidt reaction, no heat treatment) 15.30 g (0.161 mol) of 99.0% phenol, 12.95 g (0.160 mol) of 19.0 N aqueous sodium hydroxide solution, and 300 ml of glass capable of performing vacuum distillation of DMSO 202 g Placed in flask. The reaction liquid was stirred with a magnetic stirrer. After all the raw materials were charged, heating and concentration under reduced pressure were started. The pressure was gradually increased from about 5 kPa while observing the state of distillation, and was finally fixed at 2.5 kPa. One hour after the start of operation, the boiling point of DMSO (2.5 kPa, 83 ° C)
(Distillate 71.72 g), but concentration was continued under reduced pressure until the distilling temperature reached the boiling point to further distill 34.59 g in order to more reliably remove water. The residual liquid after dehydration was 123.74 g. The residual solution was analyzed for water by the Karl Fischer method and found to be 296 ppm (1.3 mol% based on the sodium salt of phenol).

121.00 g of this prepared solution was charged into a SUS 500 ml-autoclave vessel equipped with a stirring rod / agitating blade, a temperature sensor, a pressure gauge, and a pipe for carbon dioxide, and the inside of the apparatus was replaced with nitrogen and then carbon dioxide. did. With carbon dioxide
The mixture was pressurized to 2.5 MPa, and carbon dioxide was absorbed into the charged solution until the carbon dioxide was saturated. Then, the mixture was stirred at a carbon dioxide pressure of 2.5 MPa and a liquid temperature of 70 ° C. for 8 hours. As a result of HPLC analysis of the reaction solution, the yields of p-hydroxybenzoic acid, salicylic acid and 4-hydroxyisophthalic acid were 32.8%, 3.6% and 0.2%, respectively, and the conversion of the starting phenol was 36.6%.

[0021]

After mixing DMSO, phenol, and sodium hydroxide or an aqueous solution thereof in an amount of 0.9 to 1.1 mol times with respect to phenol, water is removed by distillation, and 1 mol of phenol alkali metal salt and 2 mol of DMSO are mixed. In the method of producing p-hydroxybenzoic acid by producing a complex consisting of and reacting carbon dioxide at a temperature of 90 ° C. or less, and after sufficiently reacting carbon dioxide with the starting complex,
With the carbon dioxide removed outside the system, heat treatment is performed in a temperature range of 90 to 120 ° C., and carbon dioxide is again introduced and reacted, thereby improving the conversion of the reaction and the yield of p-hydroxybenzoic acid. Can be done.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07F 1/06 C07F 1/06

Claims (5)

[Claims] 1. A mixture of dimethyl sulfoxide, phenol, and sodium hydroxide or an aqueous solution thereof in an amount of 0.9 to 1.1 mol times with respect to phenol, and then removing water by distillation to obtain 1 mol of phenol alkali metal salt. When a complex consisting of 2 moles of dimethyl sulfoxide is formed and reacted with carbon dioxide at a temperature of 90 ° C. or less to produce p-hydroxybenzoic acid, the raw material complex is sufficiently reacted with carbon dioxide, A heat treatment at a temperature in the range of 90 to 120 ° C. in a state where is removed outside the system, and introducing carbon dioxide again to react at 90 ° C. or less. 2. The method according to claim 1, wherein the carbon dioxide is removed from the system in a state of 90 to 90.
The method for producing p-hydroxybenzoic acid according to claim 1, wherein the step of performing heat treatment in a temperature range of 120 ° C, introducing carbon dioxide again and reacting at 90 ° C or lower is performed once or plural times. . 3. The pressure at the time of reacting with carbon dioxide,
The p according to claim 1 or 2, wherein the p is 0.05 to 5 kPa.
-A method for producing hydroxybenzoic acid. 4. The time when reacting with carbon dioxide is as follows:
The method for producing p-hydroxybenzoic acid according to any one of claims 1 to 3, wherein the time is 0.5 to 10 hours. 5. The method for producing p-hydroxybenzoic acid according to claim 1, wherein the time of the heat treatment in the temperature range of 90 to 120 ° C. is 10 minutes to 5 hours.